Communicable disease epidemiology and control = Les maladies transmissibles : épidémiologie et lutte [full issue]

WORLD HEALTH OUAR I ERLY · RAPPORT TRIMES I RIEL DE SANITAIRES MONDIALES COMMUNICABLE DISEASE EPIDEMIOLOGY AND CONTROL LES MALADIES TRANSMISSIBLES: EPIDEMIOLOGIE ET LUTTE Vol. 45, No. 2/3, 1992 World Health Organization Organisation mondiale de la Sante Geneve The World Health Organi,.ation is a specialized agency of the United Nation-. with primary responsibility for international health matter .... and public health. Through this or- ganization, \Vhich Wa!) created in 1948, the health profes~ional\ of some 160 countrie.(. exchange their knowledge and experience wilh the aim of making po...,sible the attain- ment by all citi,en, of the world by the year 2000 of a level of health chat will permit them to lead a socially and economically productive life. By mean-. of direct technical cooperation ~·ith it.(. Member States, and by stimulating such cooperation among them. WHO promote .... the development of comprehcn'Sive health 'Service!), the prevention an<l control of di .... ease\. the improvement of environmental con- ditions, the development of health manpower, the coordination and development of bio- medical and health services re ... earch, and the planning an<l implementation of health pro- gramme\. The'>e broad field .... of endeavour encompas .... a wide variety of activities, .(.UCh as devel- oping sy,;tem'S of primary health care that reach the whole population of Memher coun- tries; promoting the health of mother'i an<l children: combating malnutrition; controlling malaria and other communicable disea .... e .... including tuberculosi!i. and leprosy: having achieved the eradication of \ntallpox. promoting mas .... immunization again .... t a number of other preventable <li'iea .. es; improving mental health: providing safe water supplie-.: and training health per-.unnel of all categorie'.'I. Progre!)s tov..ard..., better health throughoul the v..orld al!-.o demand'i international coop- eration in \Uch matters a'i e-;tabli'ihing intemationul standards tor hiological substance'1, pesticide!<. and phannaceutic.:als; fon11ulating cnvironmcntal health criteria: recommending international nonproprietary names for drug!); a<lrnini\tering the International Health Re- gulaliom: revi...,ing the International Cla .... sification of Diseases, lnjurie..,, and Causes of Death; and collecting and di'i-.eminating health .... rntiMical information. Further information on many aspects of WIIO's work is pre!<.ented in the Organi,.a- tion's publications. The World h£•alth statistics quarterly replaces (since IQ78) the monthly World heallh .,tati.\lin n•rwrt (published since 1907) and it-. forerunner the Epulemio/ogical and i·iral ,;fafistics report (publi'ihcd 'iincc 1947). It deal!<. with the detailed analy!i.i\ of '1elected health topic\ of current intere .... t. Starting with Vol. 41 ( 1988), the Quanerly contain,., articles in either French or English with a summary in both languages. Annual sub\cription .................................. . Sw. fr. I 00.- Price per copy ..................................... . SIN. fr. 28.- Material ji-om the Quarterly may he reproduced prm·iding due acknm-vledgement i.,· made. L'Organisation mondiale de la Sant<: (OMS). creee en 1948, e.'.t une institution 'ipC:cia- lbf'e des Nations Lnie .... a qui incombe, sur le plan international. la responsabilit<: princi- pale en matiere de questions sanitaires et de santC publique. Au .... ein de l'OMS, le~ pro- re~!)sionnels de la 'Sant<: de qud4ue 160 pays C:changent des connaissanccs et <les <lonnee~ d'expCfiencc en vue de faire accCdcr d'ici l'an 2000 tous lcs habitant\ <lu monde a un niveau <le 'Sante qui leur pcrmettc <le mener une vie .... ocialcment et Cconomi4uement pro- ductive. Grace a la cooperation technique qu'elle pratique avec se-. Etat.'. Membres ou qu'elle stimulc cntre eux, I 'OMS !<. 'emploie a promouvoir la misc sur pied <le service\ de santC complcts, la prevention et l'endiguemenc de!<. maladies, l"am<!lioratlon de l'environne- ment, le <ltveloppement des personnel~ de .santC, la coordination et le progrC-. de la re- cherche hiomCdicale et <le la recherche 'SUr le'i service .... de .... antC. ainsi que la planifica- tion et I 'execution <les programme-. de santC. Le va.'.'lte domaine oll s'exerce !'action de l'OMS comporte de .... activitC!) trt:s diver'.'le!i.: devcloppement de ... !i.Oin.s de sante primaire!) pour que routes le'i populations puis\ent y avoir acce.,: promotion de la santC maternclle et infantile; la lune contre la malnutrition; lutte contre le palu<lisme et d 'autres mala<lies tran .... mi!i.'.'lible!<., dont la tuberculose et la lepre; I 'eradication de la variole etant rtalisCc, promolion de la vaccination de ma'.'l .... e contre un certain nombre d'autre.(. maladies Cvitable\: amelioration de la -.ante rnentale: approvi'.'lionnement en eau .... aine; formation <le per .... onnels de santC de tuutes categories. II est d 'autre!i. secteurs encore ull une cooperation intematiunale ..., impose pour a'i!)Urer un mcilleur Ctat de santC a traver'i le monde et I 'OMS collabure notamment aux tJ.<.:he..., suivantes: Ctablis~ement d'etalons internationaux pour les produits biologiq_ues, le.s pesti- cides et lcs preparations pharmaceutique"; formulation de critCrc!-. <le saluhritC de l'cnvi- ronnement, re,:ummandation.s rclative'S aux denominations communes intemationalcs pour le'S !)Ubstance\ pharmaceutique!); application du Reglement .... anitairc international: revi- !-.ion de la Classification intemationalc des maladie.'., traumatismcs er causes de detCs: rassemblemcnt et diffusion d'informatio1h stati.'.tique!<. .sur la santC. On trouvera dart!<. lcs publications <le I 'OMS de plu-. amples ren .... eignement':i sur de nomhreux a!<.pccts de'S travaux de I 'Organisation. Le Rapport trinu•striel de wutfatique., .wnitaires mmulia/c.\· remplace (depub 1978) le Ramwrt de .\tatistiqlll'S sanitairn mondiales (publiC depui .... 1967) et son precurseur le Napport tpidbniolo~iquc t.'I dl'mographiquc (puhliC <lepui'S 1947). II prCsente des analy'>e!) dCtaillCes sur des ..ujet... .... ptcifi4uc'i cfinteret courant. A compter du Vol. 41 ( 1988), le Trimestriel pre!<.ente des artide-. originaux en fran<rai'S ou en anglais, accompa- gne5, d 'un rc\ume dans le, deux langues. Prix de I 'abonnement annuel ............................. . Fr.,. 100.- Le nu1nero ....................................... . rr. '.'I. 28.- La reproduction d' extra its du Trimestriel est autorisee, sous re- served' indication de la source. IX ISSN 0043 - 85 I O PRINTED IN SWITZERLAND 92/9383 - Atar S.A., Geneva - 5200 Cover design: Gilbert Auberson * T M F N Symbols used in tables Preliminary, approximate or estimated data. Data not available. Nil or magnitude negligible. 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L'Organisation mondiale de la Sante est toujours heureuse de recevoir des demandes d'autorisation de reproduire ou de traduire ses publications, en partie ou integralement. Les demandes ii cet effet et les demandes de renseignements doivent iltre adressees au Bureau des Publications, Organi- sation mondiale de la Sante, Geneve, Suisse, qui se !era un plaisir de four- nir les renseignements les plus recents sur les changements apportes au texte, les nouvelles editions prevues et les reimpressions et traductions deja disponibles. © Organisation mondiale de la Sante, 1992 Les publications de !'Organisation mondiale de la Sante beneficient de la protection prevue par les dispositions du Protocole N° 2 de la Convention universelle pour la Protection du Droit d' Auteur. Tous droits reserves. Les appellations employees dans cette publication et la presentation des donnees qui y figurent n'impliquent de la part du Secretariat de !'Organisa- tion mondiale de la Sante aucune prise de position quant au statut juridique des pays, territoires, villes ou zones, ou de leurs autorites, ni quant au trace de leurs frontieres ou limites. La mention de firmes et de produits commerciaux n'implique pas que ces firmes et produits commerciaux sont agrees ou recommandes par !'Organi- sation mondiale de la Sante de preference a d'autres. Saul erreur ou omis- sion, une majuscule initiale indique qu'il s'agit d'un nom depose. WORLD HEALTH STATISTICS QUARTERLY RAPPORT TRIMESTRIEL DE STATISTIQUES SANITAIRES MONDIALES Vol. 45, No. 2/3, 1992 COMMUNICABLE DISEASE EPIDEMIOLOGY AND CONTROL CONTENTS Page LES MALADIES TRANSMISSIBLES: EPIDEMIOLOGIE ET LUTTE SOM MAIRE Introduction .................................. . 166 [Introduction] [anglais seulement] ................. . Evaluation des mesures de lutte contre les parasitoses Evaluating measures to control intestinal parasitic infec- tions. D. A. P. Bundy, A. Hall, G. F. Medley & L. Savioli .. 168 intestinales [resume]. D. A. P. Bundy, A. Hall, G. F. Medley & L. Savioli ............................ . Ampleur de la mortalite due aux affections aigues des voies respiratoires chez les enfants de mains de 5 ans The magnitude of mortality from acute respiratory infec- tions in children under 5 years in developing countries. Michel Garenne, Caroline Ronsmans & Harry Campbell . 180 dans les pays en developpement [resume]. Michel Garenne, Caroline Ronsmans & Harry Campbell ...... . Flambees de maladies a transmission hydrique aux Waterborne disease outbreaks in the United States of America: causes and prevention. Gunther F. Craun ..... 192 Etats-Unis d'Amerique: causes et prevention [resume]. Surveillance F.-X. Meslin and control of emerging zoonoses. Cholera 1991 - an old enemy with a new face [sum- 200 mary]. Silvere Simeant. . . . . . . . . . . . . . . . . . . . . . . . . . . 218 The global epidemiology of the HIV/AIDS pandemic and its projected demographic impact in Africa. James Chin, Maria-Antonia Remenyi, Florence Morrison & Rudolfo Bulatao . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 The endemic treponematoses: not yet eradicated. A. Meheus & G. M. Antal . . . . . . . . . . . . . . . . . . . . . . . . 228 Control of pertussis in the world. Artur Galazka. . . . . . . . 238 Progress towards the global elimination of neonatal tetanus. Cynthia Whitman, Lahouari Belgharbi, Frani,ois Gasse, Carole Torel, Vittoria Mattei & Henrik Zoffmann.. 248 World malaria situation 1990. Division of Control of Tropical Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257 Human leishmaniases: epidemiology and public health aspects. P. Desjeux. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 Chagas disease: epidemiology and prospects for inter- ruption of transmission in the Americas. A. Moncayo . . . 276 Progress towards the global eradication of poliomyelitis. Harry F. Hull & Nicholas A. Ward. . . . . . . . . . . . . . . . . . . 280 The epidemiology of measles. C. John Clements, Marc Strassburg, Felicity T. Cutts & Carole Torel . . . . . . . . . . . 285 The XXth century dengue pandemic: need for surveil- lance and research. Scott B. Halstead . . . . . . . . . . . . . . . 292 Epidemiology and control of Japanese encephalitis. Akira lgarashi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Influenza - its impact and control. Y. Ghendon . . . . . . . 306 Gunther F. Craun ............................. . Surveillance et lutte contre les nouvelles zoonoses [resume]. F.-X. Meslin .......................... . C~ol~ra 1991 - vieil ennemi, nouveau visage. Silvere S1meant ..................................... . Epidemiologie du VIH/SIDA au niveau mondial et pro- jections de son impact demographique en Afrique [resume]. James Chin, Maria-Antonia Remenyi, Florence Morrison & Rudolfo Bulatao ...................... . Les treponematoses endemiques: pas encore d'eradica- tion [resume]. A. Meheus & G. M. Antal ............ . La lutte contre la coqueluche dans le monde [resume]. Artur Galazka ................................. . Progres realises vers !'eradication mondiale du teta- nos neonatal [resume]. Cynthia Whitman, Lahouari Belgharbi, Frani,ois Gasse, Carole Torel, Vittoria Mattei & Henrik Zoffmann ............................. . Situation du paludisme dans le monde, 1990 [resume]. Division de la lutte contre les maladies tropicales ..... . Les leishmanioses humaines: epidemiologie et aspects de sante publique [resume]. P. Desjeux ............. . La maladie de Chagas: epidemiologie et perspectives d'une interruption de la transmission aux Ameriques [resume]. A. Moncayo .......................... . Vers !'eradication mondiale de la poliomyelite [resume]. Harry F. Hull & Nicholas A. Ward .................. . Epidemiologie de la rougeole [resume]. C. John Clements, Marc Strassburg, Felicity T. Cutts & Carole Torel ........................................ . La pandemie de dengue du xx• siecle: besoin de surveillance et de recherche [resume]. Scott B. Hal- stead ........................................ . L'encephalite japonaise: epidemiologie et lutte [resume]. Akira lgarashi ................................. . La grippe - impact et lutte [resume]. Y. Ghendon .... . Pages 166 177 189 197 205 208 227 235 245 255 265 274 279 284 290 296 303 310 - 166 - COMMUNICABLE DISEASE EPIDEMIOLOGY AND CONTROL INTRODUCTION This issue of the World health statistics quarterly is devoted to discussions of the epidemiology and con- trol of selected communicable diseases. These dis- cussions are timely and important. Infectious and par- asitic diseases accounted for an estimated one-third of all deaths in the world in 1990, but this statistic, consi- dered by itself, hides a grim reality. In developed countries, this category of disease is responsible for only 4.4% of all deaths, while in the poorer, less developed nations where 77.1% of all deaths in the world occur annually, 44.1% of deaths are still due to infectious diseases. For children, the situation is graver still - 71.3% of all deaths in developing countries are estimated to be caused by infection.• Over the past decade, a great deal of attention has been paid, appropriately, to the previously neglected and increasingly important role of noncommunicable diseases and chronic health problems. The study of the characteristics of what has been termed the "epidemiological transition" has become a pro- minent subject of public health research.b Yet this theory, which predicts a gradual (albeit incomplete) replacement of infectious diseases as causes of death by degenerative diseases and conditions for which human beings themselves are largely respon- sible, may require modification. In fact, in many developing countries, a different model is emerging, one which is marked by a high incidence of both infectious and "post-transitional" diseases and by the resurgence of a number of infectious diseases which had been relatively well controlled or even the appearance of new ones.0 Accordingly, a modern understanding of the epidemiology of the diseases discussed in this issue of the Quarterly is emerging. Greater emphasis is being placed on the social and economic parameters which define their occurrence as it becomes more and more clear that the morbid- ity and mortality due to these infectious diseases are as much a function of the state of human development than they are of the virulence of the microorganisms which are their biological cause. A number of important issues are raised by the contributing authors to this issue. A common theme encountered in a majority of the articles is the importance of improving surveillance in order to better understand changes in the epidemiological characteristics of diseases and to better direct public health control efforts. More sensitive and more specific case definitions should be developed and standardized, as for acute respiratory infections; shifts in the age distribution of disease brought • World Health Organization. Global health situation and projections - estimates. Geneva, WHO, 1992. (Document WHO/HST/92-1 ). O Omran, A. R. Epidemiological transition: 1. Theory. In: Ross, J. A. (ed.), International encyclopedia of population. Volume 1. New York, Free Press, 1982. c Frenk, J. et al. The epidemiologic transition in Latin America. Bulletin of the Pan American Health Organization, 111: 485-496 (1991). about by partially implemented control measures should be clarified (pertussis); and geographical pockets of high risk need to be identified (tetanus, measles). Perhaps most importantly, surveillance of the impact of public health interventions on rates of morbidity and mortality should be more closely linked to their implementation_ For poliomyelitis erad- ication, for example, improved surveillance is the key to success. Surveillance systems currently being developed in conjunction with the poliomyelitis eradication effort can be used to improve surveillance of other con- ditions as well. But as surveillance improves, one should expect at least an initial increase in reported incidence. Improved data collection and reporting may be partially responsible for the growing rec- ognition of leishmaniasis and Chagas disease as important public health problems - this "surveil- lance artefact" may seem to indicate a worsening problem, but in fact it is the phenomenon of shedding light on situations which were previously hidden from view. Interestingly, most - if not all - of the problems posed by the diseases presented here have impli- cations which go far beyond those of the traditional public health sector_ The potential impact of infec- tion with the human immunodeficiency virus and the acquired immune deficiency syndrome is perhaps the most wide-ranging. In some areas where young adults, both women of child-bearing age and wage- earning males, have high rates of infection, the very fabric of society is threatened. The links between Japanese encephalitis and agriculture (rice cultiva- tion creates vector-breeding sites) and animal hus- bandry (pigs amplify disease), between leishmania- sis and agricultural irrigation projects, and between Chagas disease and migration to urban areas are also strong. Dengue, malaria and cholera are examples of resur- gent diseases. That the current epidemic of dengue can be traced to the Second World War is indicative of the impact which war, civil strife and political upheaval have frequently exerted on health. Our attention is also drawn to this problem by the authors of the article on poliomyelitis eradication_ Perhaps no disease of the 1990s is more indicative of the relationship between disease and social de- velopment than cholera. The emergence of cholera in South America for the first time in a century makes it very clear that, even though the late XXth century world is one in which transportation and communication barriers have largely disappeared, putting the countries and the peoples of the world in close touch with each other, the potential for infec- tious diseases to spread more widely and more quickly has been greatly multiplied. Focal outbreaks and confined epidemics seem to be giving way to pandemics of infectious diseases, many of which are discussed here. Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 167 - Finally, it must be reiterated that although geographical barriers are being rapidly eroded, so- cial barriers remain intact. To a large degree, the epidemiology of the infectious diseases presented here is marked by substantially higher incidence and mortality rates in populations living in relative • World Health Organization. A paradigm for health: a framework for new public health action. Geneva, WHO, 1991. (Document EB89/11). Wld hlth statist. quart., 45 (1992) poverty and in particularly vulnerable groups such as children, women and the elderly. Recognition that infectious diseases are not disappearing as rapidly as might be wished, and understanding that they continue to be responsible for a large share of human suffering, especially in the developing world, are prerequisites for the concerted public health action called for by the World Health Organization.d This issue of the Quarterly attempts to promote this recognition and understanding. - 168 - EVALUATING MEASURES TO CONTROL INTESTINAL PARASITIC INFECTIONS D. A. P. Bundy,• A. Hall,• G. F. Medley• & L. Saviolib Introduction Current estimates suggest that at least one-quarter of the world's population is chronically infected with intestinal parasites and that most of these infected people live in developing countries (1). Because of the scale of this public health problem and the limited economic and technical resources available, it is essential that control programmes be carefully designed and evaluated. The design of procedures to evaluate control measures requires a clear under- standing of the epidemiological characteristics of the infection to be controlled, and an appreciation of the epidemiological differences between helminths, protozoa and other infectious agents. For epidemiological purposes it has been suggested that all infectious agents can be separated into two groups: macroparasites, a group which mainly com- prises the helminths, and microparasites, a tax- onomically diverse group including viruses, bacteria and protozoa. The characteristic which requires this separation is the biology of helminth reproduction: while most species of helminths reproduce within their definitive hosts in the sense of producing stages which are infective to other hosts, only a very few species of intestinal helminths such as Strongy- loides and Capillaria actually multiply in number within a host; for all other species of intestinal helminths each worm in the gut of a host is a result of a separate infection event. One important con- sequence of the cumulative gain of worms is that the number of infective stages shed by that host - its infectiousness - is related to the number of worms it contains. In epidemiological terms this means that the unit of study is the individual worm. The other important consequence of the accumula- tion of worms is that the occurrence of disease is related to the intensity of infection: infections with a few worms tend to be asymptomatic but as more worms are acquired, signs and symptoms of disease are more likely to occur. In contrast with macroparasitic infections, the or- ganisms classified as microparasites both reproduce and multiply within their hosts. For intestinal proto- zoa this means that a single infectious stage can both establish an infection and then multiply so that the host in turn excretes large numbers of infectious stages. The infectiousness of a host is not therefore related directly to the degree of exposure to infec- tion, and for epidemiological purposes the individual host is the unit of study. Finally, intestinal protozoa are superficially similar to intestinal helminths in that infected people are not necessarily diseased. • WHO Collaborating Centre for the Epidemiology of Intestinal Parasitic Infections, Imperial College, London, United Kingdom. O Programme on Intestinal Parasitic Infections, Division of Com- municable Diseases, World Health Organization, Geneva. These biological characteristics of macro- and micro- parasites mean that the prevalence and intensity of infections are both important measures for evaluat- ing programmes to control intestinal helminths, while for intestinal protozoa only the prevalence is of use. The prevalence of infections with intestinal parasites is defined as the proportion of the popula- tion that is infected, while the intensity is the aver- age number of parasites within individuals in the population. The basis of any procedure to evaluate control measures is the diagnosis of infections, and the microscopical examination of faeces for the eggs or larvae of helminths and for the trophozoites or cysts of protozoa is still the most widely used and practic- able means to detect infections. This technique re- quires technical skill but is otherwise simple and inexpensive, and although it may lack in sensitivity for light infections, a diagnosis made by microscopy is usually species-specific. There are many books and manuals which provide details of microscopy and other methods to diagnose intestinal parasitic infections (2). The next two sections will deal separately, and in more detail, with the specific characteristics of the biology, epidemiology and diagnosis of intestinal helminths and protozoa which need to be under- stood if the effectiveness of measures to control infections are to be evaluated. Intestinal helminths The focus here will be on the most common in- testinal nematode parasites of humans: Ascaris lum- bricoides, Trichuris trichiura, and the two species of hookworms, Necator americanus and Ancylostoma duodenale. The distribution among hosts Intestinal helminths are neither uniformly nor randomly distributed amongst individuals in a popu- lation, but are highly aggregated so that most indi- viduals have few worms while a few people harbour disproportionately large worm burdens. This pattern of distribution is illustrated in Fig. 1 and is typical of all the major species of nematode parasites of humans. Field studies have repeatedly found that about 70% of the worms occur in 15-30% of the people. This minority of heavily infected people not only comprises the individuals most likely to suffer disease, they are also the major sources of infection in the community. Consequently, it is more impor- tant and certainly more practicable to control or eradicate morbidity due to intestinal helminths than to eradicate all infections. Morbidity and transmis- sion can be reduced by treating the most heavily infected individuals, particularly children, and the advantages of such approaches have been recently Rapp. trimest. statist. sanit. mond., 45 (1992) - 169 - FIG.1 AN EXAMPLE OF A TYPICAL DISTRIBUTION OF HELMINTHS (ASCARIS LUMBRICOIDESI IN A KOREAN COMMUNITY EXEMPLE D'UNE DISTRIBUTION TYPIQUE D'HELMINTHES (ASCARIS LUMBRICOIDESI DANS UNE COLLECTIVITE COREENNE 450 400 350 .. .; .,, : 300 "C " .c E :ii 250 I .. .; :, ~ 200 ii .!: 0 ii 150 .0 E :, 2 100 50 0 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15+ Worm burden - Charge parasitaire Source: Reference (241 - Reference (241. demonstrated by a combination of theoretical studies, practical evaluation and cost-effectiveness analysis (3, 4). These advances, together with a more critical assessment of the practicalities of delivering drugs (5, 6), have contributed to the development of control approaches aimed specifically at groups within communities which are most at risk of both infection and disease (4). Because the aim of such control measures is to reduce mean worm burdens and eliminate disease, the prevalence of infection is likely to be an inadequate means of evaluating such control programmes and it is necessary to assess changes in the intensity of infection in order to measure disease and transmission. This is necessary particularly because, as will be shown later, there is no direct relationship between the prevalence and intensity of infection. In order to appreciate this it is necessary to describe in more detail something of the variation in worm burdens that occurs among a population (7). A population of worms within a person is typically in a state of flux in which old worms die and new worms are acquired by exposure to infective stages. Some aspects of the infection processes and the establishment of worms can be assessed by moni- toring reinfection following treatment. Such studies indicate that some individuals are predisposed to heavy infections while others are consistently lightly infected. Predisposition is demonstrated by showing that the size of a worm burden acquired after treat- ment is positively associated with the intensity of infection before treatment. Such an association has been shown for all the major intestinal helminths (7), and this trend persists over at least two reinfection Wld hlth statist. quan., 45 ( 1992) periods (8). Longitudinal studies confirm that this positive association reflects a direct relationship be- tween the rate of reinfection and initial infection status. An additional, practical consequence of the aggregated distribution of parasites and of the ten- dency for some individuals to be consistently heavily infected is that a large sample size must be used to estimate mean intensity when assessing the effect of control measures. Infection in the community The aggregation of a large proportion of all worms in a small proportion of all people in a community is also seen within age groups, although the degree of aggregation varies with age and with the species of parasite. In hookworm infection, worms tend to be more aggregated among adults than among children (9), while for T. trichiura and A. lumbricoides, infec- tions tend to be more highly aggregated among children. Heavy infections may also be aggregated among families. Studies have shown that more families tend to contain individuals who are heavily infected with T. trichiura and A. lumbricoides than would be ex- pected by chance, whereas families with a mixture of both heavy and lightly infected individuals are less common than would be predicted. Studies of these parasites in Mexico and Malaysia indicate that families also exhibit a predisposition to infection. The relationship between age and prevalence shows some variation among the major intestinal hel- - 170 - minths. The peak prevalence of infections with A. lumbricoides and T. trichiura is usually reached by 5 years of age, while for hookworm infection the peak is reached in young adults (Fig. 2). For infections with A. lumbricoides a slight decline in prevalence is often observed in adulthood. For most helminth species the initial rise in the intensity of infection with age closely mirrors the rise of prevalence, but the rise in intensity occurs at a slightly slower rate (Fig. 3). The age at which the highest mean intensity of infection occurs depends on the life span of the helminth species and is independent of local rates of transmission (10). For A. lumbricoides and T. trichiura the peak intensity of infections tends to occur among children aged 5-10 years, and for hookworm the peak occurs in adult- hood. The most important differences in the relationship between age and the intensity of infections with these species become apparent after the peak inten- sity has been attained. Ascaris lumbricoides and T. trichiura exhibit a marked decline in the intensity of infection after the peak in childhood, to reach a relatively stable but low level which then persists throughout adulthood (Fig. 3). Studies of hookworm in which burdens have been counted after expulsion by antihelmintic treatment (Fig. 3) indicate that the intensity attains a peak in adulthood (9). These patterns show that the prevalence of infection with A. lumbricoides and T. trichiura may be similar in children and adults, but the children will tend to have larger worm burdens. For hookworm infec- tions, in which both the prevalence and intensity of infection show a rise with age, more adults than children will be infected and they will have larger worm burdens. The relationship between intensity and prevalence In order to explain these relationships between age and infection, it is necessary to examine the relation- ship between prevalence and intensity (Fig. 4). The non-linear relationship between the prevalence of infection with A. lumbricoides and the mean worm burden is a direct consequence of the fact that most worms are aggregated in a few hosts while most other hosts are lightly infected. This relationship holds true even when egg counts are used to es- timate worm burdens, and is characteristic of all the major intestinal nematode species. The important practical consequence of this relation- ship is that even if control measures reduce the mean worm burden, and thus the prevalence of disease, there may be little change in the prevalence of infection. Prevalence of infection can provide a reasonable estimate of the mean intensity of infec- tion when worm burdens are small: a decline in the mean worm burden from 10 to 5 worms is ac- companied by a large fall in the prevalence (Fig. 4). In contrast, where average burdens are large, a significant reduction in the intensity of infection is not reflected in a similar change in prevalence. This is particularly true for T. trichiura where worm bur- dens often range from 50 to 100 worms. This helps to explain why the prevalence of infection with A. lumbricoides often declines in line with intensity in adulthood, but the prevalence of T. trichiura does so only rarely (11 ). This adds further weight to our contention that the prevalence alone is an inad- equate measure of the status of infection with in- testinal helminths, particularly in circumstances where infections are hyperendemic. Assessing the intensity and prevalence of infection The microscopical examination of faeces for the eggs or larvae of intestinal helminths is usually diagnostic for each species of infection and provides the prevalence of infection, although the eggs of the two species of hookworms cannot be readily dis- tinguished. Determining the intensity of infections by treating people and counting the number of worms expelled is invaluable for research studies, but is not a practicable means of evaluating control pro- grammes. The reproductive biology of the parasites can intro- duce error in estimates of both the prevalence and intensity of infections. Female nematodes only pro- duce eggs when they are sexually mature and have been fertilized by males, so infections with juvenile or male worms alone will not be detected. The reported prevalence of infection will be an under- estimate of the true prevalence because infections will not be detected in some individuals. The most convenient means of estimating the inten- sity of infections is to quantify the density of eggs in faeces on the assumption that this is directly pro- portional to the number of worms in the intestine. Eggs counts are usually expressed as eggs per gram (epg) of faeces and there are several books or manuals which give details of techniques which can be applied to weighed stool specimens (2). There are several sources of variation in egg counts which can make them unreliable estimates of the intensity of infections for individuals. Firstly, male worms do not produce eggs, so it has to be assumed that control measures do not affect the sex ratio of worms. Secondly, faecal egg counts have been found to vary from day to day within indi- viduals (12). Thirdly, the fecundity of female worms is dependent on worm density (10). Finally, several studies have shown that egg counts before anti- helmintic treatment are poorly correlated with the number of worms subsequently expelled (13). Although an egg count tends to be a poor estimate of the number of worms present in an individual's gut, the use of group or sample averages overcomes some of the inherent variability and imprecision, and mean egg counts for large groups can be usefully representative of mean worm burdens. An important point is maintaining the consistency of sampling techniques throughout monitoring. For example, in- creasing the size of stool specimen examined will increase the sensitivity of sampling, and may give a false impression of an increase in prevalence of infection. Assessing the extent of morbidity in the community For many bacteria and viruses there is a close and simple correspondence between infection and dis- ease. In contrast, for most helminth infections the relationship between infection and disease is com- plex and disease is not an automatic outcome of infection. If we accept that infections with a few worms in an otherwise healthy host are asymp- tomatic and that illness is related to the intensity of infection, then it is apparent from the distribution of heavy infections that the occurrence of disease will be related to age. The relationship is complicated by Rapp. trimest. statist. sanit. mond., 45 (1992) " c c a, > 0 E I'! -~ 'iii "' :0 c. " Cl :0 ,: (.) I c a, 'C 5 ~ E 0 ;: c "' " ::; 100 90 80 70 ~ " " 60 c " .; > ·<I> o': 50 ~ " " c 40 " .; > " o': 30 20 10 0 100 90 80 70 - 171 - FIG.2 COMPARISON OF TYPICAL AGE I PREVALENCE RELATIONSHIPS COMPARAISON DE RELATIONS AGE I PREVALENCE CARACTERISTIQUES ,fa---.__ Trichuris ~ ~-~~ ·~~~~~~~~~~~~ / Ascaris 0 10 20 30 40 Age (years) - Age (annees) Source: References (29, 30) - References (29, 30). FIG.3 COMPARISON OF TYPICAL AGE/ INTENSITY RELATIONSHIPS COMPARAISON DE RELATIONS CARACTERISTIQUES AGE/ INTENSITE DE L'INFESTATION Trichuris 60 Hookworm - Ankylostome (X7) 50 40 30 20 10 0 0 10 20 30 40 Mean age (years) - Age moyen (annees) Source: References (9, 31) - References (9, 31). Wld hlth statist. quart .. 45 (19921 - 172 - FIG.4 COMPARISON OF TYPICAL PREVALENCE/ INTENSITY RELATIONSHIPS COMPARAISON DE RELATIONS CARACTERISTIQUES PREVALENCE/ INTENSITE DE L'INFESTATION 100--~~~~~~~~~~~~~~~~~~~~-- l Q) " c:: .. .; > ... 0: I ~ .. " c:: Q) .; > i:! 0.. ~ Q) " c:: Q) .; > .., 0: ? .. " c:: .. .; > Q) 0: 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 0 0 • • • .... • • .. • • • • A. lumbricoides 10 20 30 Mean worm burden - Charge parasitaire moyenne • • • • • T. trichiura 2 4 6 8 10 Mean intensity (eggs/g; OOOsl - lntensite moyenne (a,ufs/g • en milliers) 100 "T""~~~...---~---:=-~'=='"~~~~~~~~~~~.~~---:s ·•·· . ., . -:. .. 90 ··~.... • ··" ~ ... l8o ·• •-,. • • ~ .. . .~ 70 ,.J • • Q) .; ¥ ••• . l; 60 • • 1 50 .... ~ . ; 40 g • j 30 .. o: 20 • 10 ... • • • Hookworm - Ankylostome 0 .............. -...-......,...-.---,.._,--,--,,--,--~-r-"T"""~""T"""-r---r"""T-,"-,,--,--1 0.8 1 1.2 1.4 1.6 1.8 2 0 0.2 0.4 0.6 Mean intensity (eggs/g; OOOs) - lntensite moyenne (a,ufs/g - en miliers) Source: Reference (19) - Reference 119). Rapp. trimest. statist. sanit. mond., 45 (1992) - 173 - the fact that the occurrence of disease is not just related to the number of worms in a host, but is likely also to be related to the biomass of worms, to the duration of infection, and to the background health status of the host. These factors mean three things: that disease is much less common than infection, that not all people will benefit equally from treatment, and that any changes in the health status of diseased indi- viduals may be hidden when the community as a whole is studied. This failure to appreciate that helminth infections do not always cause disease, which has led to the apparent lack of effect of some control measures, may be a major reason for the failure to recognize the importance of helminth dis- ease for human health (14). There is a general acceptance of the view that very intense infections result in illness. For example, hookworms can cause severe anaemia, ascariasis can obstruct the intestine and trichuriasis can cause colitis, rectal prolapse and dysentery. However an understanding of the relationship between the inten- sity of infection and any clinical signs or symptoms has proved more elusive. This appears to be due to two main factors. Firstly, the relationship between the intensity of in- fection and the pathogenesis of disease is not linear. Studies of the anaemia associated with hookworm infection indicate that although severe anaemia occurs when there are thousands of worms, a clini- cally important degree of anaemia can be caused by a few hundred worms, the precise number depend- ing on the host's iron status (15). This relationship occurs despite a constant blood loss per worm which might be expected to lead to a linear relation- ship. Studies of the protein-losing enteropathy caused by T. trichiura also indicate a non-linear relationship with worm burden. The second reason for the lack of understanding of the relationship between the intensity of infection and disease is the difficulty of attributing the cause of morbidity and of measuring it when attributed. This is in part the classical epidemiological problem of identifying the specific cause of illness or morbid- ity in a population subject to many different causes of ill-health. For helminth infections this is exacer- bated by the absence of specific signs or symptoms. This problem has been addressed by intervention studies in which helminth infections have been treated by chemotherapy. Significant improvements in growth have been observed in children infected with hookworms, A. lumbricoides and T. trichiura (16, 17). Even more subtle consequences of infection are suggested by recent double-blind placebo trials which show significant improvement in the cognitive ability of schoolchildren moderately infected with T. trichiura (18). These results suggest that even mod- erate helminth infections may have insidious con- sequences that are unlikely to be attributed in public health statistics. In one study of a village where helminths were hyperendemic, only 2% of actual morbidity had been reported to the health author- ities (14). Some insights into the relationship between infec- tion and disease have been provided by a statistical analysis of appropriate data (19). If it is assumed that a threshold number of worms is associated with disease, then by using the relationship between the intensity and prevalence of infection (Fig. 4) it is possible to estimate the proportion of individuals W/d hlth statist. quart., 45 ( 1992) who exceed some threshold number of worms and who are likely to be ill for any given prevalence of infection (Fig. 5). One of the conclusions of this analysis is that the threshold number of worms need not be defined precisely, since the form of the re- lationship between infection and disease is relatively insensitive to the threshold value, provided the valus is relatively large. These analyses indicate that as the prevalence of infection rises, the presence of disease increases disproportionately. For example, if more than 25 A. lumbricoides are taken to cause disease, then almost half the population will suffer from disease when the prevalence of infection is 90%, but only 2% when the prevalence of infection is 70%. It is unsurprising that in areas where the prevalence of infection is stated to be "high", studies of morbidity often reach very different conclusions about the public health significance of intestinal helminths. There is obviously a need for quantitative rigour in defining the prevalence of disease, both for deter- mining the public health significance of helminths and for evaluating the effectiveness of control (19). Evaluating the control of intestinal protozoa The focus here will be on the three most common and important intestinal protozoan infections of humans in developing countries, Entamoeba his- tolytica, Giardia duodena/is and Cryptosporidium parvum, which respectively cause the diseases amoebiasis, giardiasis and cryptosporidiosis. It should be pointed out that infections with these and other species of intestinal protozoa also occur in industrialized countries in significant numbers, although infections tend to be epidemic rather than endemic and to occur within distinct social groups. The emphasis here will be on evaluating measures to control infections in developing countries. Assessing the extent of morbidity in the community Infections with intestinal protozoa are often asymp- tomatic. The reasons for this vary from species to species but are largely unknown. However the dis- tinction between infection and disease is as impor- tant for protozoa as it is for helminths, although for different reasons. Because a single cyst can result in the establishment of an infection, and because intestinal protozoa mul- tiply as well as reproduce within a host, the occur- rence of disease is not as clearly related to the intensity of infection as it is for helminths, although it has been observed that oocysts, for example of C. parvum, are excreted in large numbers during diar- rhoea. This suggests that there is a relationship between the multiplication of the parasite and the occurence of disease, but why all infections do not cause disease when there is evidence of heavy infections is unclear. Many people in developing countries show no signs or symptoms of disease when infected with in- testinal protozoa. This raises the question of the role of asymptomatic cyst passers in the transmission of disease. People who are lightly infected with a species of intestinal helminths are probably not major sources of transmission, but infection with a single protozoan cyst can lead to the excretion of many millions of cysts each day. This has led to a debate about the risks to infected individuals of treating asymptomatic infections and, if such infec- tions are not treated, the risks of infection and ~ ... :g :0 0 E .!1! II) 'C II) u c: .. .; > ... a': l > :s :0 0 E 0 8 c: .. .; > .. a': - 174 - FIG. 5 RELATIONSHIP BETWEEN PREVALENCE OF MORBIDITY AND INFECTION FOR DIFFERENT ASSUMED WORM BURDEN THRESHOLDS OF MORBIDITY RELATION ENTRE LA PREVALENCE D'UNE PARASITOSE ET L'INFESTATION POUR DIFFERENTS SEUILS DE MORBIDITE EXPRIMES PAR LA CHARGE PARASITAIRE 80 70 60 50 40 30 20 10 0 0 20 40 60 80 5 10 15 20 25 30 Prevalence of infection (%) - Prevalence de !'infestation (%) Source: Reference (19) - Reference (19). disease to other members of the community. These issues should be considered in any control pro- gramme involving chemotherapy as a tool of con- trol, but will not be dealt with here. The consistent observation of asymptomatic infec- tions raises questions about whether the organisms which parasitize asymptomatic individuals have the potential to cause disease or are inherently non- pathogenic strains, and about whether diseased people are different in some way from asymptomatic cyst passers because, for example, their immune response to infection modulates the occurrence of symptoms. These are largely theoretical questions and the differences in the biology of these or- ganisms, coupled with the gaps in our knowledge, makes generalizations difficult. However, recent de- velopments have increased our understanding of the biology and epidemiology of the three main in- testinal protozoa which cause disease in humans, and this growth in knowledge may assist in evaluat- ing control programmes. Entamoeba histolytica can invade the wall of the large intestine to cause dysentery, and organisms can be carried in the blood to distant tissues and organs where abscesses may form (20). Other indi- viduals, although infected, remain asymptomatic and only excrete cysts in their stools. There is a growing body of evidence from studies of isoenzymes, sur- face antigens, ribosomal RNA and DNA, that what was once considered to be a single species may in fact comprise two species which are morphologically indistinguishable but only one of which causes dis- ease. If this is the case and if two species are created from what is currently classified as E. histolytica, then the diagnosis of infections with E. histolytica by direct microscopy of stools will no longer be pos- sible and the epidemiology and significance of infec- tions will have to be re-evaluated. The taxonomy of what is here called Giardia duo- dena/is is disorganized: there are at least three other names in current use, including G. /amblia, G. in- testinalis and Lamblia intestinalis. Again asymp- tomatic infections occur in many individuals while in others there is disease, typically characterized by diarrhoea and malabsorption. No symptom is unique to giardiasis, but a recent definition of clinical cases may be of assistance in control programmes (21). Infections and disease both tend to be chronic and may last for several months. There is some evidence for differences between strains of G. duodena/is, but there is no clear association yet with the occurrence of disease. The epidemiology of giardiasis could however be explained by the existence of strains with differing potential to cause disease, or by the development of partial immunity which ameliorates symptoms, but does not protect from reinfection. The disease caused by C. parvum is a self-limiting watery diarrhoea with no particularly specific symp- toms, and evidence from parasitological and sero- logical surveys suggests that asymptomatic infec- tions are common (22). There are few symptoms of disease due to intestinal parasites which are characteristic or unique, and the clinical course of disease can be similar to other infectious diseases: in many parts of the world Rapp. trimest. statist. sanit. mond., 45 (1992) 100 - 175 - dysentery is more often caused by species of Shigella than by E. histolytica, while Vibrio cholerae or enterotoxigenic strains of Escherichia coli are more likely to be a cause of severe watery diarrhoea than C. parvum. Clinical judgement is not therefore a sound basis on which to assess the prevalence of disease due to intestinal protozoa, and a specific diagnostic technique should be applied for the pur- pose of evaluating control programmes. Assessing the prevalence of infections Infection with intestinal protozoa can be more dif- ficult to diagnose than infection with intestinal helminths. Most currently-used techniques either rely on seeing cysts or vegetative stages in faeces, or use specific antibodies as a means of capturing parasite antigens from faeces. A diagnosis is there- fore made indirectly and cysts, trophozoites or anti- gen can be diluted, obscured or damaged, so that infections may not be detected. Current diagnostic techniques are neither very sensitive nor very specific. Assessing the accuracy of the diagnostic test to be used in the evaluation of control pro- grammes is important if the results are to be related to the effects of control. Nevertheless the microscopical examination of faeces is still the standard and most specific means of diagnosing intestinal protozoa, even if it may lack sensitivity. Ideally both fresh faeces and samples subjected to a concentration technique should be examined: fresh faeces should be examined if only trophozoites are being passed or if a diagnosis of amoebiasis is to be made (see below), and although concentration techniques destroy trophozoites, they serve to extract cysts from faeces if they are present only in small numbers, thereby increasing the sen- sitivity of the diagnosis. The concentration technique to be used should be selected carefully, depending on the protozoan species of interest (23). Serological tests for infection have limitations. They often cannot detect very recently-acquired infections because it may take 10 days or more before anti- bodies are detectable in the blood. In addition, anti- bodies in general may persist long after the infection has resolved or been treated, although there is some evidence that different classes of antibodies may be of use in diagnosing current infections. The sero- diagnosis of parasitic diseases has recently been reviewed by Maddison (24). Serodiagnosis, as other diagnostic techniques, allows the calculation of the rate of new infections. Control programmes that reduce transmission would reduce the rate of in- crease of positive diagnoses. For long-lasting anti- bodies, this would be shown as a reduction in the seropositivity with age compared with precontrol, and for shorter-term antibodies, a reduction in the seropositivity overall. A potentially more useful and highly specific means of diagnosing intestinal protozoa lies in the use of monoclonal antibodies to detect parasite antigens in faeces. In theory an assay to detect antigens ex- pressed only by pathogenic species or strains could provide a tool to distinguish strains of parasites which cause disease. A specific and sensitive anti- gen-capture ELISA also has advantages over micro- scopy because large numbers of samples can be screened at once. This would have obvious value if a large-scale control programme were to be evaluated. Until monoclonal antibodies can be identified which are specific to pathogenic species or strains, polyva- Wld hlth statist. quart., 45 (1992) lent antiserum is generally likely to be of most use in diagnosing any intestinal protozoan infection. Yet whatever antibodies are used, sufficient controls should be used when doing such tests to control for non-specific binding as there may be antigens in faeces which may affect the performance of the assay. Like most protozoa, Entamoeba histo/ytica has tradi- tionally been diagnosed by the microscopic examin- ation of stools for cysts or trophozoites. Differentia- tion from the morphologically similar but smaller cysts of E. hartmanni requires measurement. Another problem with diagnosing infections with E. histolytica is that the parasite may not be excreted in the faeces of people with amoebic abscesses, and abscesses may develop without preceding symp- toms of diarrhoea or dysentery. Finally, if there is enough evidence to justify reclassifying E. histolytica as two separate species as discussed above, then there will be a need for tools to distinguish between the species, such as indirect fluorescence antibody tests or an ELISA. This uncertainty about what is and is not E. histolytica makes it difficult to discuss the significance of seeing cysts alone in faecal samples. Nevertheless whatever the result of the taxonomic debate, it is clear that in order to diagnose the disease amoebiasis, one must see trophozoites con- taining ingested red blood corpuscles during a microscopic examination of fresh faeces. Infections with G. duodena/is can be diagnosed ac- curately by the microscopic examination of fresh stool smears for cysts and trophozoites, which are characteristic. Microscopy has been reported to miss between 10% and 50% of infection (25), probably because cysts are known to be excreted inter- mittently, although experience at diagnosing G. duo- dena/is is likely to be an important influence on the likelihood of detecting infections. People with diarrhoea due to C. parvum usually excrete large numbers of oocysts which are easily found in faeces, but they are smaller than the cysts of G. duodena/is or species of amoeba, and do not stain with iodine, so they can be difficult to find when present only in small numbers. Concentration techniques and staining procedures may need to be applied, all of which increase the time and costs of testing faecal samples. Oocysts have been detected by using antibodies conjugated with fluorescent dyes and an ELISA has been reported, and tech- niques for diagnosing C. parvum have recently been reviewed by Casemore (23). Distribution of infections and morbidity among hosts The specific characteristics of the epidemiology of each species of intestinal protozoa are important factors to be considered when attempting to evalu- ate control programmes: the patterns of infection and disease differ considerably between species of protozoa and between different age groups within the community. For example, Fig. 6 shows that infections with G. duodena/is are more common in children living in an urban slum in Bangladesh than among adults, while the opposite is true for E. histo/ytica. Some people are consistently more likely to be infected than others, and infections generally tend to be most common in children. Giardiasis is common amongst children, travellers and people with im- - 176 - FIG.6 PREVALENCE OF INFECTION BY AGE FOR TWO INTESTINAL PROTOZOA AMONG 1 765 INHABITANTS OF AN URBAN SLUM IN BANGLADESH PREVALENCE DE L'INFESTATION PAR AGE POUR DEUX PROTOZOAIRES INTESTINAUX PARMI LES 1 765 HABITANTS D'UN BIDONVILLE DU BANGLADESH ~ " 1 " c: " .;; > . ., .t i .. " c: "' .;; > " .t 60 Age (years) - Age (annees) Source: Hall (unpublished observations - Observations non publiees). mune deficiency diseases: groups which are assumed to be immunologically naive or deficient. Repeated infections are associated with less severe symptoms or may be asymptomatic. For these reasons, host responses are believed to partially explain the observation that many infected people in developing countries do not have symptoms of dis- ease. Although risk factors for disease can reveal some- thing about the occurrence of asymptomatic infec- tions, the risk factors for infection are not necessarily the same as the risk factors for disease. Adults infected with E. histo/ytica have been found to be 10 times more likely than children to develop amoebia- sis, while adult men are 3-6 times more likely to develop amoebiasis than women (20). Distribution of infection and disease in the to person or through contaminated water supplies. There is still a debate about whether G. duodena/is is a true zoonosis, and the term "reservoir of infec- tion" may be preferable. Studies have shown that beavers can be infected with organisms which are morphologically indistinguishable from those der- ived from humans, and these animals live in water c~urses in areas of North America where there have been outbreaks of infections among campers or local inhabitants. Of more relevance to developing countries is that G. duodena/is cysts have been detected in the stools of goats and sheep in the household of infected people in Egypt (26). Animal reservoirs of potential infection should thus be con- sidered when evaluating measures to control G. duodena/is and C. parvum, but there is no evidence that E. histolytica is commonly transmitted between animals and humans. community Discussion and conclusions In developing countries intestinal protozoa are typi- cally endemic with transmission occurring all year round, perhaps with seasonal fluctuations related to temperature and rainfall. Infections are mainly associated with poor sanitation and a lack of clean water to maintain personal hygiene, although there is very little clear epidemiological data on the routes of infection. The role of animals in the transmission of intestinal protozoa varies from species to species. Although more than 40 species of animals have been found to be infected with C. parvum, and contact with ani- mals such as calves can lead to infections, it is likely that much transmission occurs directly from person This review has attemped to identify the biological and epidemiological aspects of intestinal helminth and protozoan infection which are most relevant to evaluating control approaches. It is apparent that these groups of infections share a number of characteristics: both occur in the intestine, have external transmission routes, are associated with poverty and poor sanitation, and are diagnosed by coprological methods. Despite these superficial simi- larities it is equally apparent that control of these two groups of infections requires very different ap- proaches to evaluation. In evaluating control of helminth infection it is intensity which provides the most meaningful measure of both morbidity and transmission. The most commonly used measure, Rapp. trimest. statist. sanit. mond., 45 (1992) - 177 - prevalence, may provide a misleading estimate of the success of control, particularly in those hyper- endemic communities most in need of the control programmes. Evaluating helminth intensity, how- ever, requires careful attention to the structure of the population sample examined. Evaluation of the con- trol of protozoan infections, in contrast, can usefully be achieved using prevalence measures. The com- plexity for protozoa arises from the need to dif- ferentiate pathogenic species and strains from ubiquitous harmless infections. The development of improved approaches to evalu- ating the control of intestinal parasites will involve two major areas of study. For the evaluation of helminths, greater understanding is required of the spatial distribution of infections, particularly mul- tiple-species infections, to allow more precise design of sampling procedures. For the evaluation of proto- zoan infection, the major need is for improved field procedures for differentiating pathogenic species and strains. Acknowledgements D. A. P. Bundy acknowledges support from The Wellcome Trust, A. Hall holds a Leverhulme Trust fellowship, and G. F. Medley is a Royal Society University Research Fellow. SUMMARY Intestinal parasitic infections are among the most common infections of humans in developing coun- tries, but the resources available for their control are severely limited. Careful evaluation of control measures is essential to ensure that they are cost- effective. The evaluation of the effects of control on intestinal helminths and intestinal protozoa requires an understanding of the different epidemiological patterns of these two groups of parasites. The transmission dynamics and morbidity asso- ciated with the major helminth infections (Ascaris lumbricoides, Trichuris trichiura and the hook- worms) are dependent on the size of the worm burdens. Thus the important parameter for evalu- ating the impact of control on morbidity and trans- mission is the intensity of infection, which can be assessed by determining the mean density of para- site eggs in faecal specimens. Estimation of intensity is subject to systematic errors, however, due to the complex pattern of worm burden distributions. The frequency distribution of burdens is highly over- dispersed, and individuals exhibit predisposition to particular levels of infection. Furthermore, mean in- tensity is age-dependent, in a species-specific manner, and is clustered spatially and within families. These complex patterns imply that the es- timation of intensity is exceptionally sensitive to the size and demographic structure of the population sample selected for assessment. They also have the effect that prevalence estimates, the most commonly used measures of infection in communities, can seriously mislead. Paradoxically, prevalence is least useful where infection is most common because the relationship between prevalence and intensity is most markedly non-linear when the prevalence is high. Thus in areas where control is most needed, evaluation using prevalence might suggest that con- trol had failed while evaluation by intensity would, correctly, show the measure of success. With the major protozoan infections (Entamoeba his- tolytica, Giardia duodena/is and Cryptosporidium parvum) an estimate of intensity is of little value and the central parameter for evaluation is prevalence. Prevalence does exhibit age and spatial hetero- geneity, which may be species-specific, so there remains a need to ensure a consistent sample struc- ture, although this is less critical than for the hel- minths. The major constraint on evaluating the con- trol of protozoan infections is the need to identify pathogenic species and, in some cases, pathogenic strains. Harmless commensal protozoans are ubiqui- tous and often morphologically very similar to pathogens, but their control is both unnecessary and impracticable. Species such as E. histolytica appear to exist as strains with differing pathogenicity, thus control will be cost-effective only if the focus is on pathogenic strains. Effective diagnosis is therefore central to the evaluation of the control of protozoan infections. Microscopy of faeces will usually be adequate to identify the major species, and is ap- propriate for G. duodena/is and C. parvum. Identify- ing the pathogenic strains of E. histo/ytica requires specialized laboratory methods, none of which are currently available for routine field use. RESUME Evaluation des mesures de lutte contre les parasitoses intestinales Les parasitoses intestinales comptent parmi les in- festations les plus courantes dans les pays en deve- loppement, mais les moyens dont on dispose pour les combattre sont des plus limites. Une evaluation soigneuse des mesures de lutte est essentielle pour en assurer la rentabilite. L'evaluation des effets de la lutte contre les helminthes et les protozoaires intesti- naux suppose la connaissance des differents aspects que peut revetir l'epidemiologie de ces deux grou- pes de parasites. Wld hlth statist. quart., 45 ( 1992) La dynamique de la transmission des principales helminthiases (ascaridiase, trichocephalose et ankylostomiase) et la morbidite qu'elles suscitent dependent de !'importance de la charge parasitaire. C'est done l'intensite de !'infestation, que l'on peut apprecier par la determination de la densite moyen- ne des reufs de parasites dans des echantillons de selles, qui constitue le parametre a prendre en consi- deration pour evaluer l'impact des mesures de lutte sur la morbidite et la transmission. Cependant, etant - 178 - donne que la charge parasitaire n'est pas repartie de fa~on simple, cette estimation peut etre entachee d'erreurs systematiques. La distribution de frequen- ce de la charge parasitaire est tres largement disper- see et les individus peuvent etre predisposes a une valeur particuliere de la charge infestante. De plus, l'intensite moyenne de !'infestation est liee a l'age, selon l'espece en cause, et elle presente des agre- gats dans l'espace comme au sein des familles. II resulte de cette complexite que !'estimation de l'in- tensite est exceptionnellement sensible a la taille et a la structure demographique de l'echantillon de population choisi pour !'evaluation. II peut egale- ment s'ensuivre que la prevalence estimative, qui est le parametre le plus frequemment utilise pour eva- luer l'intensite de !'infestation dans une collectivite, peut conduire a de graves erreurs d'interpretation. Paradoxalement, c'est lorsque la parasitose est tres repandue qu'elle est le mains utile, du fait que la relation entre la prevalence et l'intensite de !'infesta- tion est d'autant mains lineaire que la prevalence est plus forte. Ainsi, dans les regions ou la lutte est le plus necessaire, une evaluation basee sur la preva- lence pourrait donner a penser que les mesures de lutte ont echoue alors qu'une evaluation basee sur l'intensite permettrait d'apprecier correctement le succes obtenu. Dans le cas des principales protozooses (Entamoeba histolytica, Giardia duodena/is et Cryptosporidium parvum), l'intensite estimative n'offre guere d'interet et c'est la prevalence qui constitue le parametre important pour !'evaluation. Comme la prevalence presente une heterogeneite selon l'age et dans l'es- pace, heterogeneite qui peut etre caracteristique de l'espece, ii est necessaire de s'arranger pour que l'echantillon ait une structure uniforme, encore que ce facteur soit mains determinant que dans le cas des helminthes. Lorsqu'on cherche a evaluer les resultats de la lutte contre les protozooses, la princi- pale contrainte consiste dans la necessite d'identifier l'espece, voire la souche pathogene en cause. Les protozoaires commensaux inoffensifs sont omnipre- sents et leur morphologie est souvent tres sembla- ble a celle de leurs homologues pathogenes, mais ii est inutile et d'ailleurs impossible de les eliminer. Dans l'espece E. histolytica, par exemple, ii existe des souches plus ou mains pathogenes, aussi la lutte ne sera-t-elle rentable que si elle se concentre sur les souches veritablement pathogenes. II est done capital de disposer de moyens de diagnostic efficaces pour evaluer les resultats de la lutte contre les protozooses. L'examen d'un echantillon de selles entre lame et lamelle suffit en general pour identifier les principales especes, et ii convient bien pour G. duodena/is et C. parvum. L'identification des sou- ches pathogenes de E. histo/ytica necessite en revan- che des methodes specialisees de laboratoire qui ne sont pas actuellement utilisables en routine sur le terrain. REFERENCES- REFERENCES 1. WHO Technical Report Series, No. 749, 1987 (Prevention and control of parasitic infections: report of a WHO Expert Committee). OMS Serie de Rapports techniques, N° 749, 1987 (Lutte contre les parasitoses intestinales: rapport d'un Comite OMS d'experts). 2. WORLD HEALTH ORGANIZATION. Basic laboratory methods in medical parasitology. Geneva, WHO, 1991. 3. ANDERSON, R. M. & MEDLEY, G. F. Community control of helminth infections of man by mass and selective chemotherapy. Parasitology, 90: 629-660 (1985). 4. BUNDY, D. A. P. New initiatives in the control of helminths. Transactions of the Royal Society of Tropical Medicine and Hygiene, 84: 467-468 (1990). 5. Mon, K. E. Selective population chemotherapy in Schistosoma haematobium infection: pros and cons. In: Miller M. J. & Love E. J. (eds), Parasitic diseases: treatment and control. Boca Raton, CRC Press, 1989. 6. SAv1ou, L. ET AL. Control of morbidity due to Schistosoma haematobium on Pemba Island; selective population chemotherapy of school- children with haematuria to identify high-risk localities. Transactions of the Royal Society of Tropical Medicine and Hygiene, 83: 805-810 (1989). 7. BUNDY, D. A. P. & MEDLEY, G. F. lmmuno- epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden. Parasitology, 104: 5105-5119 (1992). 8. CHAN, L. ET AL. The effect of repeated chemo- therapy on age-related predisposition to Ascaris /umbricoides and Trichuris trichiura infection. Parasitology, 104: 371-377 (1992). 9. BRADLEY, M. ET AL. The epidemiology and popula- tion biology of Necator americanus infection in a rural community in Zimbabwe. Transactions of the Royal Society of Tropical Medicine and Hygiene, 86: 73-76 (1991 ). 10. ANDERSON, R. M. The population dynamics and epidemiology of intestinal nematode infections. Transactions of the Royal Society of Tropical Medicine and Hygiene, 80: 686-696 (1986). 11. BUNDY, D. A. P. Epidemiological aspects of Tri- churis and trichuriasis in Caribbean com- munities. Transactions of the Royal Society of Tropical Medicine and Hygiene, 80: 706-718 (1986). 12. HALL, A. Intestinal helminths of man: the inter- pretation of egg counts. Parasitology, 85: 605- 613 (1982). 13. ANDERSON, R. M. & SCHAD, G. A. Hookworm bur- dens and faecal egg counts: an analysis of the biological basis of variation. Transactions of the Royal Society of Tropical Medicine and Hygiene, 79: 812-825 (1985). 14. COOPER, E. S. & BUNDY, D. A. P. Trichuriasis. In: Mahmoud A. F. (ed.), Bailliere's clinical tropical medicine and communicable diseases. London, Bailliere Tindall, 1988. (Second edition). 15. LWAMBO, N. J. s. ET AL. A new approach to morbidity risk assessment in hookworm end- emic communities. Epidemiology and infectiorr. in press (1992). Rapp. trimest. statist. sanit. mond., 45 (1992) - 179 - 16. STEPHENSON, L. s. ET AL. Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, Trichuris tri- chiura and Ascaris lumbricoides infections. American journal of tropical medicine and hygiene, 41: 78-87 (1989). 17. COOPER, E. S. ET AL. Growth suppression in the Trichuris dysentry syndrome. European journal of clinical nutrition, 44: 138-147 (1990). 18. NOKES, C. ET AL. Geohelminth infection and aca- demic assessment in Jamaican children. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 85: 272-273 (1991). 19. GuYATT, H. L. & BUNDY, D. A. P. Estimating prevalence of morbidity due to intestinal hel- minths: prevalence of infection as an indicator of the prevalence of disease. Transactions of the Royal Society of Tropical Medicine and Hygiene, 85: 778-782 (1991). 20. MARTiNEZ-PALOMO, A. & Ruiz-PALACIOS, G. Ameo- biasis. In: Warren, K. S. & Mahmoud, A. A. F. (ed.), Tropical and geographical medicine. New York, McGraw-Hill, 1990. (Second edition). 21. HOPKINS, R. s. & JURANEK, D. D. Acute giardiasis: an improved clinical case definition for epi- demiologic studies. American journal of epi- demiology, 133: 402-407 (1991 ). · 22. CURRENT, W. L. & GARCIA, L. S. Cryptosporidiosis. Clinical microbiological reviews, 4: 325-358 (1991). 23. CASEMORE, D. P. Laboratory methods for diag- nosing cryptosporidiosis. Journal of clinical pathology, 44: 445-451 (1991 ). Wld hlth statist. quart., 45 (1992) 24. MADDISON, S. E. Serodiagnosis of parasitic dis- eases. Clinical microbiology reviews, 4: 457-469 (1991). 25. BURKE, J. A. The clinical and laboratory diagnosis of giardiasis. CRC critical reviews in clinical lab- oratory science, 8: 373-391 (1977). 26. SULLIVAN, P. S. ET AL. Illness and reservoirs as- sociated with Giardia lamblia infection in rural Egypt: the case against treatment in developing world environments of high endemicity. American journal of epidemiology, 127: 1271- 1281 (1988). 27. SEO, B. S. ET AL. Frequency distribution of Ascaris lumbricoides in rural Korea with special refer- ence on the effect of changing endemicity. Korean journal of parasitology, 17: 105-113 (1979). 28. BUNDY, D. A. P. ET AL. Predisposition to Trichuris trichiura infections in humans. Epidemiology and infection, 98: 65-71 (1987). 29. BUNDY, D. A. P. ET AL. Age-related prevalence and intensity of Trichuris trichiura infection in a St Lucian community. Transactions of the Royal Society of Tropical Medicine and Hygiene, 88: 85-94 (1987). 30. HSIEH, H. C. Studies on endemic hookworm: I. Survey and longitudinal observation in Taiwan. Japanese journal of parasitology, 19: 508-522. 31. BUNDY, D. A. P. ET AL. Population ecology of intestinal helminth infections in human com- munities. Philosophical transactions of the Royal Society of London, Series B, 321: 405-420 (1988). - 180 - THE MAGNITUDE OF MORTALITY FROM ACUTE RESPIRATORY INFECTIONS IN CHILDREN UNDER 5 YEARS IN DEVELOPING COUNTRIES Michel Garenne,• Caroline Ronsmansb & Harry Campbell° The most widespread and fatal of all acute diseases, pneumonia, is now Captain of the Men of Death. Sir William Osler, 1901. Introduction In developed countries, during the last hundred years, the evolution of mortality due to acute respir- atory infections (ARI) has been dramatic (1). At high levels of mortality, such as XIXth century Europe, ARI was the category of diseases making the largest contribution to shortening of life expectancy. Dis- eases due to ARI represented a loss of 7.5 years of life, more than all other infectious diseases (4.8 years) and diarrhoeal diseases (2.9 years). Among infants and children, ARI was the first cause of death outside the neonatal period. When life expectancy was below 45 years, 25% of all deaths in the age group 0-4 years were due to ARI, compared to only 4% when life expectancy was higher than 70 years. Recognition of pneumonia and other ARI as an important public health problem in developing coun- tries is recent. The magnitude of mortality from ARI in childhood in developing countries was docu- mented and published for the first time in the early 1960s (2). More recently, the World Health Organization (WHO) and other international agencies have made ARI one of their priorities for intervention. Increased concern about the important contribution of ARI deaths to overall mortality was raised at the World Health Assembly in 1976.d In 1983, a Technical Advisory Group on ARI was established by WHO in Geneva (3). The global programme for the control of acute respiratory infections was officially initiated in 1984 as a distinct programme under Disease Prevention and Control in WHO's Seventh General Programme of Work, covering the period 1984-1989. The central objective of the programme is to reduce mortality from ARI, in particular pneumonia. This objective is endorsed in the Declaration of the World Summit for Children, New York, 30 September 1991, which es- tablished the goal of reducing by one-third the deaths due to ARI in children under 5 years of age during the period 1990-2000. • Associate Professor of Demography, Harvard University, Center for Population and Development Studies, Cambridge, MA, United States of America. O DrPH candidate, Harvard University, Center for Population and Development Studies, Cambridge, MA, United States of America. c Consultant in Public Health (Child Health), Fife County Health Board, Scotland, United Kingdom. d World Health Organization. Official records, 233: 63-109 ( 1976). • World Health Organization. Implementation of the Global Strategy for Health for All by the Year 2000, second evaluation: and eighth report on the world health situation. Geneva, WHO, 1992. (Doc- ument A45/3). I Garenne, M. et al. AR/ mortality in a rural area of Senegal. Draft paper, 1992. The most recent WHO estimates (for 1990) indicate that out of nearly 12.9 million children under 5 who die each year in developing countries, about 4.3 million die of ARI. Of these, it is estimated that 0.8 million (18.6% of all ARI deaths) occur in the first month of life. Other estimates have indicated that about two-thirds of ARI deaths occur in the first year of life (4). The WHO estimates further state that the ARI complications of measles accounted for 0.48 million deaths (11% of ARI deaths and 55% of all measles deaths) and that the ARI complications of pertussis accounted for 0.26 million deaths (6% of ARI deaths and 72% of all pertussis deaths). Thus, ARI was estimated to be the single largest cause of death in young children, being associated with 33% of all childhood deaths in developing countries.• These estimates are based on various sources. The main sources of information have been analyses based on national cause-of-death statistics notified to WHO and extrapolations from these data to those countries which do not record cause-of-death data but have similar levels of child mortality. The aim of this article is to review and discuss the available data on mortality from ARI among children under 5 in developing countries. For this purpose, 25 studies with data on ARI deaths were reviewed. They were compared with historical data from developed coun- tries before 1965. Data and method To evaluate the relationship between proportion of ARI deaths and level of mortality in historical popu- lations, the study by Preston et al. (5) was used. The authors analysed the causes of death by age and sex in 180 data sets from 43 national populations before 1965 (a complete review of the data will be pub- lished in a separate paper: Garenne et al. forthcom- ing).1 Causes of death from ARI were coded accord- ing to the International Classification of Diseases (ICD), Sixth and Seventh Revisions. To estimate the magnitude of mortality from ARI in developing countries, a search of the MEDLINE data base from January 1980 to December 1991 was performed. The search focused on community studies of mortality from all causes and from ARI in children under 5 years in developing countries. Re- sults from 2 unpublished studies were provided by the authors (6, '). The data base revealed 21 com- munity-based longitudinal studies in 13 countries (6-26, '): only the studies with detailed causes of death for children aged < 5 years were kept for the final analysis. In 12 studies, the ascertainment of ARI deaths was part of an overall assessment of cause- specific mortality (5 in Bangladesh, 1 in Kenya, 1 in Morocco, 1 in Nigeria, 2 in Senegal, 1 in The Gambia and 1 in Guinea-Bissau). In the 9 remaining studies, the longitudinal surveillance was aimed specifically at ascertaining deaths due to ARI. The latter studies were undertaken to assess the impact on ARI- Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 181 - mortality of a community-based ARI intervention project (2 in India, 2 in Nepal, 1 in Pakistan and 1 in the United Republic of Tanzania); to assess the impact of a pneumococcal vaccine (2 in Papua New Guinea); to identify the etiological agents respon- sible for acute lower respiratory infections (ALRI) and to determine risk factors for ARI morbidity (1 in the Philippines). In addition, 2 studies based on national death regis- tration systems were included. Puffer & Serrano investigated causes of death in children from 13 regions in 8 countries in Latin America during the period 1968-1971 (27). They used the Eighth Revision of the ICD for classification of ARI deaths (28). Von Schirnding reviewed national data on mortality from ARI in South Africa for the period 1968-1985 (29). Data on ARI in children from "coloured race" were included in our analysis. Data on black children were excluded because of underreporting of deaths in this group. Causes of death were classified according to the Ninth Revision of the ICD (30). Data from these studies were compared to the historical data. Definition of ARI deaths Classification of AR/ deaths The International Classification of Diseases and Causes of Death (ICD) classifies diseases according to the biological etiology of the causes of death or, where etiology is not apparent, the anatomical local- ization. The ARI classified under "diseases of the respiratory system" in the Ninth Revison are pre- sented in Table 1. Acute bronchitis and bronchiolitis are coded under the acute respiratory infections (code 466). Influenza and pneumonia are grouped under the same subtitle (code 480-487). In addition, the fourth digit of the ICD makes it possible to specify pneumonia occurring after certain diseases, such as measles (code 484.0), whooping cough (code 484.3) and varicella (484.8). Earlier revisions of the ICD differ slightly from the Ninth Revision (28, 31). For instance, in the Eighth Revision pneumonia (480-486) was classified separately from influenza (470-474) and pneumonia after measles, varicella or pertussis was not included in the diseases of the respiratory system. In the community studies reviewed, the lack of con- sistency in the inclusion of the diseases causing death from ARI was striking. In 10 studies, deaths due to ARI were not further differentiated into upper or lower respiratory infections. ALRI, where speci- fied, mostly referred to deaths from pneumonia. ARI deaths following measles were addressed separately in 7 studies. Pertussis was considered as an ARI death in 2 studies (9, 11), while 4 studies listed pertussis as a separate cause (6, 12, 23, '). Deaths due to laryngitis and influenza were listed in 2 studies only (6, '). Varicella was mentioned in the sole Senegal study.I One study classified ARI under the heading "symptoms, signs and ill-defined dis- eases" (13). Role of pneumonia Among the diseases listed in Table 1, it is generally agreed that in developing countries, most ARI TABLE 1. ARI IN THE INTERNATIONAL CLASSIFICATION OF DISEASES, NINTH REVISION (ICD-9) TABLEAU 1. LES IRA DANS LA CLASSIFICATION INTERNATIONALE DES MALADIES, NEUVIEME REVISION (CIM-91 Diseases of the respiratory system - Maladies de l'appareil respiratoire ACUTE RESPIRATORY INFECTIONS (codes 460-466) - AFFECTIONS AIGUES DES VOIES RESPIRATOIRES (codes 460-466): (460) (461) (462) (463) (464) (465) (466) - common cold - rhume banal - acute sinusitis - sinusite aigue - acute pharyngitis - pharyngite aigue - acute tonsillitis - amygdalite aigue - acute laryngitis and tracheitis - laryngite et tracheite aigues - acute upper respiratory infections of multiple or unspecified sites - infection aigue des voies respiratoires superieures, a localisations multiples ou non precisees - acute bronchitis and bronchiolitis - bronchite et bronchiolite aigues PNEUMONIA AND INFLUENZA (codes 480-487) - PNEUMONIE ET GRIPPE (codes 480-487): (480) (481) (482-483) (484) (485) (486) (487) 484.0 484.3 484.8 484.* - viral pneumonia - pneumonie a virus - pneumoccocal pneumonia - pneumonie a pneumocoque - pneumonia due to other bacteria and other organisms - pneumonies dues a d'autres bacteries ou d'autres organismes - pneumonia in infectious diseases classified elsewhere - pneumonie au cours d'autres maladies infectieuses classees ailleurs • measles (055.1) - rougeole (055.1) • whooping cough (033) - coqueluche (033) • varicella (052) - varicelle (052) • other infectious diseases - autres maladies infectieuses - bronchopneumonia, organism unspecified - bronchopneumonie, micro-organisme non precise - pneumonia, organism unspecified - pneumonie, micro-organisme non precise - influenza - grippe Notes. Codes 470-478 include other URI diseases and chronic conditions (deviated septum and polyps and chronic upper respiratory). Codes 490-496 include chronic obstructive pulmonary disease and allied conditions (chronic bronchitis, emphysema, asthma). Codes 010-018 cover tuberculosis, including respiratory tuberculo- sis. - Les codes 470 a 478 couvrent d'autres maladies des voies respiratoires superieures (deviation de la cloison, polypes, affections chroniques). Les codes 490 a 496 couvrent des maladies pulmonaires obstructives chroniques et affections connexes (bronchite chronique, emphysema, asthme). Les codes 010 a 018 couvrent la tuberculose, y compris celle de l'appareil respiratoire. Wld h/th statist. quart., 45 (1992) - 182 - deaths among infants and children may be ascribed to pneumonia, bronchiolitis and acute obstructive laryngitis (32). However, the similarity in clinical symptoms of pneumonia and bronchiolitis have often hampered the distinction of these syndromes in developing countries and the magnitude of mor- tality due to viral bronchiolitis is not well document- ed in populations. Indirect evidence from hospital studies suggests that pneumonia is the leading cause of death from ARI in developing countries. Pneumonia is the primary cause of hospitalization for ARI, before bronchiolitis and laryngitis (33-37). Hospital-based data on case-fatality rates (CFR) by clinical syndrome vary widely. Rahman reported similar CFRs for pneumonia and bronchiolitis (CFR = 8%) among children under 5 years old in Bangladesh (33). In the United Republic of Tanzania, Mtango observed the highest CFRs in children with laryngotracheitis (CFR = 28%) and bronchiolitis (CFR = 6%), while children with pneumonia had a CFR of 3% (34). Weissenbacher observed higher CFRs for pneumonia than for other infections (CFR 5.8 vs. 2.1) (35). In addition, the risk of death is higher in children when a bacterial pathogen is identified (33, 35). Results from national registration data confirm these findings. Von Schirnding (29) found that among 3 77 4 "coloured" infants aged 0-11 months who died from ARI, 96.3% had a diagnosis of pneumonia recorded on the death certificate. Puffer & Serrano (27) also reported a majority of deaths due to pneu- monia in Latin America: among neonatal deaths from ARI, 95.1% (1 092/1148) had pneumonia; this proportion was 77% (2 591/3 359) among infants ( 1-11 months) and 69.8% (489/701) among children aged 12-59 months. In Ecuador, pneumonia accoun- ted for 59% and bronchiolitis for 28% of the 1 304 ARI deaths reported in infants in 1987 (37). Bronchiolitis may be misclassified as an upper res- piratory tract infection (URTI), as has been suggested by Bulla & Hitze (38). The authors suggest that the high proportion of deaths due to URTI reported in 9 African countries (64% of all ARI), may have been in part due to misclassification of lower respiratory tract infections (LRTI), e.g. bronchiolitis classified as URTI. In addition, bronchiolitis is often complicated with pneumonia in developing countries. Diagnosis of AR/ The validity of causes of death depends first on the validity of the diagnosis. In the case of ARI, the clinical distinction between the various syndromes remains a difficult undertaking. Inter-observer vari- ation in auscultation of the chest is frequent and ideally, definitive clinical diagnosis should be based on X-ray findings, culture of lung aspirates and measurement of blood oxygen levels (39-41). The distinction between pneumonia and bronchiolitis is particularly difficult. Clinical signs for both syn- dromes include signs of respiratory distress such as tachypnea, nasal flaring and intercostal retractions. The presence of diffuse wheezing characteristic of bronchiolitis may be difficult to recognize for non- trained observers. Wheeze can also be found in children with pneumonia. • Garenne, M. & Fontaine, 0. Assessing probable causes of deaths using a standardized questionnaire - a study in rural Senegal. Proceedings of the IUSSP seminar on morbidity and mortality, Sienna, 7-10 July 1986. Specific problems of verbal autopsies The ICD classification scheme normally requires a physician or a laboratory diagnosis. Its application to developing countries raises specific difficulties since most deaths of children occur outside hospitals. Investigators have therefore developed methods for interviewing relatives of the deceased person and have attemped to translate this information into a medical diagnosis. These procedures, called "verbal autopsies", have been reviewed recently (42). In community studies, verbal autopsies have been used systematically for more than three decades for assessing causes of death (42, 43). The quality of verbal autopsies depends upon many conditions: the design of the interview (structured, semi-structured or open interview), the time elapsed since death, the person answering the questions, the quality of the interviewer and the qualification of the persons who review and code the interviews.9 Sen- sitivity and specificity of the criteria used in verbal autopsies depend not only on their own char- acteristics but also on the capacity of the family to notice and report the symptoms. Clinical case def- initions of ALRI have been validated against con- firmed diagnoses of pneumonia, whether they were fatal or not, and may not be accurate for identifying death due to ARI. Few studies have attempted to validate clinical criteria against death from ALRI. Kalter (44) validated clinical signs reported by the mother after the death of the child in 100 children under 2 years who died from ALRI as diagnosed by a physician. Reports of cough and dyspnea before death had a sensitivity of 86% and a specificity of 47%. Including duration of symptoms improved the specificity but sensitivity decreased to 41%. Navarro (45) found that in 71 children under 5 with autopsy- proven pneumonia, 50 (70%) had clinical signs of severe or complicated pneumonia at admission. Shann (46) evaluated clinical signs among children 1-59 months of age, admitted with cough and chest in-drawing and compared those who died with those who survived. Among the clinical signs evaluated, highest specificity was achieved through identifying the severity of the chest in-drawing. Standard criteria for post-mortem diagnosis of ARI have not yet been developed. In the community studies reviewed, 7 authors provided no criteria for classifying ARI deaths. Pandey (20) defined an algo- rithm for classification of cases, but not for deaths. The ICD classification was utilized in 5 studies. Criteria for inclusion in the specific ARI categories and lists of ARI codes, however, were not provided. In Matlab (Bangladesh), 3 physicians independently assigned the ICD code after reading the post-mortem interview and an additional interview was under- taken if no consensus could be reached (9, 10). AR/ in multiple causes of death Often, ARI do not occur alone, but in association with other infections or conditions, such as malnutri- tion, diarrhoea and chronic conditions. The coding of multiple causes has been discussed extensively in other documents (47) and in particular in the ICD. Investigators usually include in causes of death dis- eases where ARI is an underlying (principal, primary) or precipitating (immediate, coprimary) cause. In the studies reviewed, some authors only considered single causes of death (19, 22) while others assumed that deaths from ALRI were always the primary or co primary cause of death (11 ). Some authors include Rapp. trimest. statist. sanit. mond., 45 (19921 - 183 - or distinguish ARI as a contributing (associated) cause (7, 21, 25, ') although the criteria used for detemining when ALRI contributes to - rather than directly causes - the death are not provided. In summary, the accuracy of available data on ARI deaths can be seriously questioned. The apparent validity of the data on ARI as underlying cause of death is probably due to the fact that pneumonia and bronchiolitis are the most common causes of death from ARI, that their clinical diagnosis has a relatively high sensitivity and specificity, and that mothers can easily recognize and accurately recall the symptoms. A more complete discussion on the validity of classification of ARI deaths will be pub- lished separately (Ronsmans et al., forthcoming). Results Most of the data available refer to underlying causes of death. These are first analysed, both for de- veloped countries and for developing countries. ARI deaths after measles and pertussis are analysed separately. AR/ mortality in European populations prior to 1965 In his analysis, Preston (1) found that the proportion of ARI deaths declined with the level of mortality, that the proportion of ARI deaths was slightly higher among children 1-4 than among infants, and that there was no difference by sex outside of infancy (Table 2). The analysis of the proportion of ARI deaths was pursued separately for children <1 and 1-4 in the European populations prior to 1965. The relationship of the percentage of ARI deaths with the level of mortality was investigated using a log-linear regres- sion, where the dependent variable was the log- arithm of the age-specific death rate (ASDR). The h % (Eo.59) = [(,qo•%(Eo.11ll + ((1-1qol*,q4*(E12-s9))]/5qo where nqx = probability of dying between ages x and x+n, and % (Ex-x+nl expected proportion of ARI deaths in age group x to x+n based on historical population. logarithmic scale was utilized to better fit the marked decline of the proportion of ARI deaths at low levels of mortality. Results were highly significant and are summarized in the following equations: Age 0-11 months: %ARI = -4.446 + 4.823*LN (ASDR_0-11) Age 12-59 months: %ARI = 14.928 + 3.387*LN (ASDR_12-59) A multivariate analysis was designed to investigate the statistical effect of four variables: level of mor- tality, regional patterns (West, North, East and South) (48), time and level of economic development (Garenne et al., forthcoming). The level of mortality was significant for both infant and child mortality. There were differences according to regional pattern, with higher proportions of ARI deaths in the East regional pattern. The proportion of ARI deaths was significantly lower after 1950 among children aged 1-4 years. This could be interpreted as the effect of antibiotics on ARI mortality. The proportion of ARI deaths was significantly lower in the more de- veloped countries at ages 1-4, but not in infancy. This again suggests a probable role of case manage- ment, which is likely to be better in more developed countries. Comparison with developing countries The data from the community studies and from the vital registrations were compared to the European experience by combining the two age groups: <1 and 1-4 years. Values of (q) and (m), the quotient of mortality (probability of dying between age O and 5 years per 1 OOO live births), and the age-specific death rates (deaths at ages 0-4 years per 1 OOO person-years at risk), are provided to allow easier comparisons of mortality levels. The expected pro- portion of deaths from ARI was computed using the regression equation from the European data. To calculate the expected proportion of ARI deaths in the age group 0-59 months, the expected proportion of ARI deaths for the age groups 0-11 months and 12-59 months were weighted by the proportion of children dying in each age group.h TABLE 2. ARI MORTALITY IN EUROPEAN POPULATIONS PRIOR TO 1965: AVERAGE OF EMPIRICAL LIFE TABLES, ACCORDING TO LEVEL OF MORTALITY TABLEAU 2. MORTALITE IRA DANS DES POPULATIONS EUROPEENNES AVANT 1965: MOYENNE DES TABLES DE MORTALITE EMPIRIQUES, SELON LE NIVEAU DE MORTALITE Age-specific death rates - Taux de deces par age Level of Average ea mortality (e0 ) 3 (years) Total/1 OOO Niveau de e0 moyenne ARl/1 OOO mortalite (e0 ) 3 (en annees) IRA/1000 Age 0-11 months - O a 11 mois <45 38.6 223.10 45.41 45-54 49.5 146.95 26.58 55-64 60.7 71.09 12.31 65-69 67.5 39.48 5.71 70-74 71.2 23.68 2.53 Age 12-59 months - 12 a 59 mois <45 38.6 36.13 9.62 45-54 49.5 20.95 4.73 55-64 60.7 6.65 1.46 65-69 67.5 2.39 0.49 70-74 71.2 1.16 0.15 3 e0 is the life expectancy at birth in years - e0 represente l'esperance de vie a la naissance, en annees. Source: Reference 11), Table 5.1 - Reference 11), tableau 5.1. W!d hlth statist. quart., 45 (1992) Percentage ARl/100 Pourcentage IRA/100 20.4 18.1 17.3 14.6 10.7 26.6 22.6 22.0 20.6 13.2 Sex ratio/100 Taux de masculinite /100 117.6 116.8 121.8 117.2 118.1 97.7 100.5 102.3 98.2 100.7 - 184 - The comparison is based on slightly different def- initions of underlying causes of death. However, the consistency of the data from developing countries with the experience of developed countries was striking (Table 3, Fig. 1). The mean proportion of ARI deaths was 18.8% and the mean of the predicted values was 17.5%. In half of the cases, the propor- tion of deaths could be predicted by the level of mortality with a maximum relative difference of 25%. Major discrepancies between observed and expected values could be explained either by the definitions used, by the proportion of unknown causes of death or by atypical regional patterns of mortality, with the exception of South Africa's coloured population, for which the observed values were much higher than expected. In studies aimed at evaluating the effect of community-based interventions on ARI mortality, data from the control areas consistently reported the highest proportional mortality from ARI (Fig. 1). At the other extreme, the very low pro- portional mortality from ARI reported by Chen et al. in Bangladesh (8) probably reflects the lack of stand- ardization for coding ARI deaths. Age pattern of mortality The proportion of deaths occurring in each age group gives a picture of the age pattern of mortality. Three age groups were selected: neonatal (0-27 TABLE 3. COMPARISON OF OBSERVED PROPORTION OF ARI DEATHS AMONG CHILDREN UNDER 5 YEARS IN DEVELOPING COUNTRIES WITH EXPECTED VALUES FROM HISTORICAL EXPERIENCE (9 community studies and 14 registration systems) TABLEAU 3. COMPARAISON DE LA PROPORTION DE DECES IRA OBSERVEE CHEZ LES ENFANTS DE MOINS DE 5 ANS DANS LES PAYS EN DEVELOPPEMENTET LES VALEURS ATTENDUES PAR EXPERIENCE HISTORIQUE (9 etudes communautaires et 14 systemes d'enregistrement) Number Mortality' (all causes) Observed Expected Ratio Study - Etude of deaths Mortalite' (toutes causes) % ARI deaths % ARI deaths observed/expected Nombre q/1 OOO m/1 OOO % deces IRA % deces IRA Rapport de deces observes attend us observes/attendus Community studies - Etudes communautaires Bangladesh 7 858 251.0 62.8 6.2 23.0 0.27 India - lnde control - temoin 161 159.5 36.6 26.2 20.2 1.30 intervention 176 118.5 26.2 18.8 18.7 1.01 Kenya 557 75.2 16.0 19.5 16.9 1.15 Morocco - Maroc 382 101.9 22.2 11.4 17.7 0.64 Nepal - Nepal surveillance 64 258.0 65.0 31.2 23.1 1.35 interventionb 74 172.3 40.0 18.8 21.2 0.89 Nepal - Nepal 2 101 341.5 94.0 22.4 24.7 0.91 Pakistan control 0 - temoin° 130 136.8 30.7 33.1 20.2 1.64 intervention 378 100.0 21.7 20.8 18.3 1.13 Senegal - Senegal 1 593 256.3 64.5 15.8 23.8 0.66 U.-R. of Tanzaniad - R.-U. de Tanzanied control - temoin 325 182.2 40.1 35.7 intervention 873 149.4 32.3 34.9 Registration systems - Systemes d'enregistrement South Africa - Afrique du Sud 1968-1973 13 810 19.5 4.0 18.6 10.5 1.76 1974-1979 11 079 16.5 3.4 18.6 10.0 1.86 1980-1985 4647 7.1 1.4 18.5 5.6 3.29 Argentina - Argentine Chaco 1 701 96.7 21.0 16.4 17.6 0.93 San Juan 2 558 88.2 19.0 16.8 17.1 0.98 Bolivia - Bolivie 4 276 138.2 31.1 32.6 19.6 1.66 Brazil - Brasil Recite 3 635 121.3 26.9 12.4 18.8 0.66 Ribeiriio 1 126 63.1 13.3 10.7 15.5 0.69 Sao Paulo 4 312 74.5 15.8 16.6 16.3 1.02 Chile-Chili 2 714 65.6 13.8 20.0 15.6 1.28 Colombia - Colombie Cali 1 627 75.9 16.2 12.5 16.7 0.75 Cartagena - Carthagene 1 255 69.0 14.6 9.8 16.4 0.59 Medellin 1348 68.4 14.5 11.5 16.4 0.70 El Salvador 2 210 126.3 28.1 11.7 19.2 0.61 Jamaica - Jama·ique 1 903 46.9 9.7 8.8 14.1 0.63 Mexico - Mexique 3 953 75.9 16.2 16.2 16.5 0.98 Mean - Moyenne 2 649 115.7 27.6 18.8 17.5 1.07 ' q = probability of dying between birth and age 5 per 1 OOO live births; m = age-specific death rate among children 0-4 years old (deaths per 1 OOO person-years at risk) - q = probabilite de deces entre la naissance et l'Age de 5 ans, par 1 OOO naissances vivantes; m = taux de mortalite par 8ge chez les enfants de O a 4 ans (deces pour 1 OOO annees/personnes a risque). b Results from first and second intervention year combined - Resultats pour les deux premieres annees d'intervention ensemble. c 3 years combined for the control and intervention area respectively - Resultats de trois annees pour les zones t8moin et d'intervention respectivement. d Control = first year in the control area. Expected values of % ARI deaths were not calculated since age-specific death rates were not provided - Temoin = premiere annee dans la zone temoin. Les valeurs attendues du % de deces IRA n'ont pas E:te calculees, car les taux de mortalite par groupe d'age n'etaient pas disponibles. Rapp. trimest. statist. sanit. mand., 45 ( 1992) - 185 - FIG.1 OBSERVED AND PREDICTED PERCENTAGE OF ARI DEATHS BY LEVEL OF MORTALITY• (8 community studies and 14 registration systems) POURCENTAGE DE DECES IRA OBSERVES ET PREVUS PAR NIVEAU DE MORTALITE• (8 etudes communautaires et 14 systemes d'enregistrement) 40 <( T rf1 Tan (c) • an I a:: - 35 " c: 1Pak (c) Bal ~ _., "' ~ • Nep1 (c) ,:, -~ 30 .., ,:, "' ~ • Ind (c) "' ~ ; 25 ,:, c: •Nep2 0 ·1:: •• • • 0 e 20 0.. I •• a: <( • s 15 " ~ ,:, • .. ,r • • "' .,:; 'io " ,:, 10 .; 0 • c: 0 • Ban "E 0 5 Cl. 0 a': 0 0 10 20 30 40 50 60 70 80 90 100 Age-specific death rate in children 0-5 years - Taux de deces par age chez les enfants de 0-5 ans a (cl refers to the control area. (i) to the intervention area - (c) indique une zone temoin, (i) une zone d'intervention. Study codes - Codes etude Ban: Bangladesh Bal: Bolivia - Bolivie Ind: India - lnde days), post-neonatal (28 days-first birthday) and early childhood (1-4 years). ARI deaths in children under 5 are usually concentrated in the age group 1-11 months (Table 4, Fig. 2). For all studies com- bined, 20.8% of ARI deaths occurred before age 1 month, 57.8% at 1-11 months and 21.5% at 12-59 months. There was a marked gradient of deaths at ages 12-59 months, ranging from low values in East regional patterns to high values in extreme South regional patterns such as Senegal. The share of neonatal mortality was more mixed, probably reflect- ing inconsistencies in definitions more than real differences. In particular, in the Indian study (18), neonatal mortality from ARI seems to have been largely overestimated. Contribution of measles to AR/ mortality As reported by various authors, a high proportion of measles deaths seem to be associated with ARI (Table 5). Proportions range from 100% in Guinea- Bissau and the Philippines to 25% in Bangladesh. Few authors, however, define in detail "measles associated with ARI". It is possible that the upper respiratory symptoms accompanying measles have been misclassified as pneumonia after measles. In Senegal, where an in-depth analysis of corn- Wld hlth statist. quan., 45 (19921 Nep: Nepal - Nepal Pak: Pakistan Tan: U.R. of Tanzania - R.U. de Tanzanie plications of measles cases was conducted, pneu- monia usually occurring in the second and third week after the onset of the symptoms accounted for 30% of measles deaths, and acute laryngitis, usually occurring in the third or fourth week, for about 2%. Other measles deaths were due mainly to diarrhoea, sometimes with an accompanying pneumonia. Measles also represents an important proportion of all ARI mortality. This proportion ranges from 1.5% in Chile to 92.5% in Guinea-Bissau, and the mean for all studies is 18.6%. This proportion depends very much on the incidence of measles and the measles immunization coverage over the period considered. In Chile, measles immunization coverage was high and few measles deaths were registered. In Guinea- Bissau, Smedman (16) reported a massive outbreak of measles in the year of the study. The two studies describing an unusually high contribution of measles to ARI (16, 25) assumed that all measles deaths were associated with ARI, which is not agreed by other authors. Contribution of pertussis to AR/ mortality According to the ICD, deaths from pertussis are classified under ARI if they are caused by pneu- - 186 - FIG. 2 AGE DISTRIBUTION OF DEATHS FROM ARI (4 longitudinal studies, 13 registration systems) REPARTITION PAR AGE DES DECES DUS AUX IRA (4 etudes longitudinales, 13 systemes d'enregistrementl 100 "' 80 c "' ..... ..... Cl) ~ "O ~.E ~ 0 c E Cl). ~ Cl) "O "O :: (/) 60 .c -'-' c: c.!! ·- c: ii:<I> <( "' Cl) E-;:; O Cl) ';-§ .c <( CO!:: 40 -8 .~ -'-' 0-<i c "O 0"' ·e-8 g_ g £·e 0 0. 20 0 cl: 0 CHIL ARG 1 IND MOR COL1 BOL BRAZ1 KEN • <1 month - <1 mois ~ 1-11 months-1·11 mois D 12·59 months - 12-59 mois Study codes - Codes etude ARG: Argentina - Argentine IND: India - lnde BOL: Bolivia - Bolivie JAM: Jamaica - Jama·ique BRAZ: Brazil - Bresil KEN: Kenya CHIL: Chile - Chili MEX: Mexico - Mexique COL: Colombia - Colombie MOR: Morocco - Maroc ELSA: El Salvador SEN: Senegal - Senegal TABLE 4. PROPORTION OF ARI DEATHS BY AGE AND STUDY, CHILDREN AGED UNDER 5 YEARS• TABLEAU 4. PROPORTION DES DECES IRA PAR AGE ET PAR ETUDE (ENFANTS DE MOINS DE 5 ANS)• Age group - Groupe d'age Country - Pays Study code - Code etude <1 month/mois 1·11 months/mois 12·59 months/mois India - lnde IND 46 (60.5) 16 (21.1) 14 (18.4) Kenya KEN 19 (19.8) 34 (35.9) 42 (44.3) Morocco - Maroc MOR 12 (24.0) 28 (56.0) 10 (20.0) Senegal - Senegal SEN 17 ( 6.8) 88 (35.1) 146 (58.2) Argentina - Argentine Chaco ARG1 54 (19.4) 183 (65.6) 42 (15.1) San Juan ARG2 88 (20.4) 306 (71.0) 37 ( 8.6) Bolivia - Bolivie BOL 308 (22.5) 727 (53.1) 334 (24.4) Brazil - Bresil Recite BRAZ1 62 (14.0) 253 (57.0) 129 (29.0) Ribeiriio BRAZ2 29 (24.2) 69 (57.4) 22 (18.4) Sao Paulo BRAZ3 184 (25.9) 421 (59.3) 105 (14.8) Chile - Chili CHIL 89 (16.4) 406 (74.9) 47 ( 8.7) Colombia - Colombie Cali COL1 54 (26.6) 107 (52.6) 42 (20.7) Cartagena - Carthagene COL2 25 (20.3) 57 (46.3) 41 (33.4) Medellin COL3 21 (13.5) 102 (65.9) 32 (20.6) El Salvador ELSA 69 (18.8) 214 (58.5) 83 (22.7) Jamaica - Jama'ique JAM 36 (21.7) 82 (49.4) 48 (28.9) Mexico - Mexique MEX 139 (21.7) 383 (59.8) 119 (18.6) All studies - Toutes etudes 1 254 (20.8) 3 491 (57.8) 1 296 (21.5) • The figures give number (percentage) of ARI deaths in each age group - Les chiffres indiquent le nombre (pourcentage) des deces IRA dans chaque groupe d'age. Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 187 - TABLE 5. CONTRIBUTION OF MEASLES TO ARI MORTALITY, SELECTED COUNTRIES, VARIOUS YEARS• TABLEAU 5. CONTRIBUTION DE LA ROUGEOLE AUX DECES IRA, DANS UN CERTAIN NOMBRE DE PAYS ET POUR DIVERSES ANNEES • Age group Number o/o measles deaths Number % ALRI' deaths (months) measles deaths associated with ARI ARI deaths due to measles Author/year/area - Auteur/annee/zone Groupe d'age Deces par % de deces rougeole Nombre % de deces IARI • (mois) rougeole associes avec les IRA de deces IRA dus a la rougeole Spika, 1989 1-59 122 (25.4) 390 (7.9) Riley, 1986 6-59 22 (63.6) 68 (20.6) Fauveau, 1990 intervention 6-35 1 (100.0) 31 (3.2) comparison - comparaison 6-35 13 (77.9) 73 (13.7) Bhatia, 1989 intervention 1-11 12 (75.0) 88 (10.2) comparison - comparaison 1-11 22 (77.3) 131 (13.0) Smedman, 1986 0-83 62 (100.0) 31 (92.5) Tupasi, 1990 0-59 11 (100.0) 18 (61.1) Garenne, 1992 0-59 78 (30.0) 250 (9.2) Mtango, 1986 0-59 421 (25.0) Puffer, 1973 Argentina - Argentine Chaco 0-59 57 (49.1) 588 (4.8) San Juan 0-59 102 (78.4) 1 072 (7.5) Bolivia - Bolivie 0-59 564 (80.1) 2 512 (18.0) Brazil - Bresil Recife 0-59 406 (84.0) 1 867 (18.3) Ribeirao 0-59 47 (91.5) 429 (10.0) Sao Paulo 0-59 162 (85.2) 2 026 (6.8) Chile - Chili 0-59 23 (82.6) 1 249 (1.5) Colombia - Colombie Cali 0-59 83 (87.9) 687 (10.6) Cartagena - Carthagene 0-59 109 (61.5) 563 (11.9) Medellin 0-59 92 (80.4) 603 (12.3) El Salvador 0-59 181 (65.2) 1 534 (7.7) Jamaica - Jama'ique 0-59 11 (45.4) 540 (9.0) Mexico - Mexique 0-59 332 (75.6) 2 011 (12.5) • Deaths from measles or ALAI as an underlying or associated cause. Pertussis deaths are not included in the ALAI deaths - oeces ayant pour cause immediate au associee la rougeole ou une IARI. Les deces dus a la coqueluche ne sont pas comptes parmi les deces IARI. ti ALAI: acute lower respiratory infection - IARI: infection aigue des voies respiratoires inferieures. mania. Only one study provided an indication of the magnitude of pneumonia among pertussis deaths. In Senegal, only 12% of all pertussis deaths were es- timated to be due to pneumonia as an immediate cause. For the other studies, we computed the ratio of all pertussis deaths to all ARI and pertussis deaths. Percentages of pertussis deaths ranged from 0.5% in Medellin (Colombia) to 28.3% in Senegal (Table 6). The studies reporting the highest pro- portions were studies where the epidemiology of pertussis was a major subject of research (12, '). However, the ratio of pertussis deaths to ARI deaths in community studies depends very much upon the epidemiology of pertussis during the study period. Interventions One way to indirectly validate the ascertainment of causes of death is to observe the changes in ARl- specific mortality rates after cause-specific inter- ventions. The community-based treatment trials showed consistent declines in overall and ARl- specific mortality rates (Fig. 3). Discussion The assessment of the magnitude of ARI mortality is hampered by several issues. Firstly, there is no standard definition of ARI. While there is a general agreement that most ARI deaths are due to pneu- monia, bronchiolitis and laryngotracheitis, other causes such as influenza may have been overlooked. Influenza was a significant cause of death in XIXth century Europe. Since most of the definitions of deaths due to ARI refer to deaths from pneumonia, the reported data should be interpreted as represent- ing primarily mortality from pneumonia. Wld hlth statist. quart., 45 ( 1992) The lack of standardization for ascertaining causes of death is another major limitation for a proper evalu- ation of the magnitude of ARI in mortality among preschool children. This involves the methods of investigating causes of deaths, e.g. verbal autopsies, the lack of sensitivity and specificity of clinical diag- noses on which most cause-of-death data in de- veloping countries are based, and the methods of recording and coding multiple causes of death. In particular, the role of ARI may be underestimated in considering only underlying causes of death. It is not surprising that the studies in which ARI was a major focus of research reported the highest proportional mortality from ARI. Whether these studies represent the true contribution of ARI to mortality, or whether the increased attention led to overestimation, is dif- ficult to ascertain. Death is generally preceded by signs of respiratory distress. Unless specific criteria for a minimum duration of these symptoms before death are defined as a prerequisite for assigning ARI as the cause, inclusion of non-specific signs of res- piratory distress may lead to overestimation of mortality from ARI. Few authors, however, defined a minimum duration of respiratory symptoms before death (6, 18, 'J. Associations of ARI with measles and pertussis de- serve particular attention, since effective measures for the control of these infections are available. Pneumonia is one of the most important com- plications of measles and has been responsible for a large proportion of measles deaths in developing countries (49, 50). Pneumonia typically occurs 2-3 weeks after the acute attack of measles and may be due to the direct effect of the measles virus or to the pulmonary superinfection following the depressive effect of the measles virus on the immune system (51, 52). Despite the absence of clear definitions, and the often lacking information on levels of im- - 188 - FIG.3 INTERVENTION EFFECTS ON MORTALITY FROM ALL CAUSES AND ARI IN CHILDREN UNDER 5 YEARS• (4 community-based intervention studies) EFFET DES INTERVENTIONS SUR LE NIVEAU DE MORTALITE ET LE POURCENTAGE DES DECES IRA CHEZ LES ENFANTS DE MOINS DE 5 ANS• (4 etudes d'intervention ii base communautaire) 40 < Tan (c) !!: Ta~ " 35 c: :, ... Pak (c) "' :, 'C "' .a, Nep (c) " •Q) 'C "' " 'C 30 c: 0 'E 0 0. 0 0: Ind (c) i1' < E 25 _g "' ,: 1ii " 'C 0 c: 0 'E 20 0 0. 0 0: 15 20 30 40 so 60 70 Age-specific death rate in children 0-5 years/1 OOO years - Taux de deces par age chez des enfants de O a 5 ans/1 OOO annees a (c) refers to the control area, and (i) to the intervention area - (c) indique une zone temoin, et (i) une zone d'intervention. Study codes - Codes etude Pak: Pakistan Ind: India - lnde Nep: Nepal - Nepal Tan: U.R. of Tanzania - R.U. de Tanzanie TABLE 6. CONTRIBUTION OF PERTUSSIS TO ARI MORTALITY, SELECTED COUNTRIES, VARIOUS YEARS• TABLEAU 6. CONTRIBUTION DE LA COQUELUCHE AUX DECES IRA, DANS UN CERTAIN NOMBRE DE PAYS ET POUR DIVERSES ANNEES• Age group Pertussis/ALRI' % Pertussis among ALAI b (months) deaths pertussis deaths Author/year/area - Auteur/an nee/zone Groupe d'age Deces par % de coqueluche parmi (mois) coqueluche/lARI' les deces IARI' + coqueluche Fauveau, 1990 intervention 1-35 4/96 (4.2) comparison - comparaison 1-35 9/159 (5.7) Omondi-Odhiambo, 1984 1-59 7/54 (13.0) Darkaoui, 1989 1-59 3/41 (7.3) Garenne, 1992 0-59 67/310 (21.6) Mtango, 1986 0-59 10/431 (2.3) Puffer, 1973 Argentina - Argentine Chaco 0-59 24/612 (3.9) San Juan 0-59 21/1093 (1.9) Bolivia - Bolivie 0-59 58/2570 (2.3) Brazil - Bresil Recife 0-59 33/1900 (1.7) Ribeirao 0-59 8/437 (1.8) Sao Paulo 0-59 36/2062 (1.7) Chile-Chili 0-59 7/1256 (0.6) Colombia - Colombie Cali 0-59 12/699 (1.7) Cartagena - Carthagene 0-59 21/584 (3.6) Medellin 0-59 3/407 (0.5) El Salvador 0-59 35/1569 (2.2) Jamaica - Jama'ique 0-59 21/561 (3.7) Mexico - Mexique 0-59 27/2038 (1.3) • Death from pertussis or ALRI as an underlying or associated cause. Measles deaths are not included in the ALRI deaths - Deces ayant pour cause immediate ou associee la coqueluche ou une IARI. Les deces dus a la rougeole ne sont pas comptes parmi les deces IARI. b ALAI: acute lower respiratory infection - IARI: Affection aigue des voies respiratoires inferieures. Rapp. trimest. statist. sanit. mond., 45 (1992) - 189 - munization coverage or the presence of major measles epidemics in the studies reviewed, the mean estimate of 16.8% of ARI deaths that can be ascribed to measles comes remarkably close to the commonly-used WHO estimate of 15%. With the current progress in world immunization against measles, this proportion has decreased to 10-12%. Ascertainment of ARI deaths due to pertussis poses more problems. Before immunization was com- monly practised in industrialized countries, major epidemics occurred every 4-6 years (53). The epi- demic pattern of pertussis makes difficult the es- tablishment of its importance in short-term sur- veillance. In verbal autopsies, a history of the typical whoop will only be elicited if specific questions are asked. In addition, very young infants show a lower frequency of paroxysms and typical whoop, com- plicating the diagnosis in this age group. The high proportion of ARI deaths attributed to pertussis in the studies in Senegal and Kenya, where deaths from pertussis were addressed with particular atten- tion, may merely reflect this fact, though the contri- bution of major epidemics during the study period cannot be excluded. Pertussis may also cause de- layed mortality through its effect on the nutritional status of the child (54). The epidemiology of pertus- sis has received less attention in developing count- ries than measles or ARI, and unless precise case definitions are developed and long-term surveillance carried out, its contribution to ARI will remain un- known. Data based on underlying causes of death suggest that, in developing countries, approximately 1 out of 6 deaths of children aged 0-4 years are due to pneumonia. This estimate matches what is known from developed countries at similar levels of mor- tality in the past. To this major underlying cause of death, one should add other ARI deaths, ARI deaths after measles, pertussis or other infectious diseases as well as in association with acute malnutrition. Without more accurate data, it seems to be difficult to give a final estimate, but the WHO figure of 1 out of 3 deaths due to - or associated with - ARI may be close to the real range of ARI proportional mor- tality in children of developing countries. ARI mortality has been declining steadily with im- proving living conditions in developed countries and has been declining very rapidly since 1950 when antibiotics became available. Perhaps the best way to estimate the current burden of ARI diseases in developing countries is to compare ARI mortality to the lowest values recorded in developed countries. This would provide a number of deaths that could be averted if the best medical technology were provided to every child. Such a comparison and the high values of ARI mortality found in many develop- ing countries indicate that more efforts should be made to better control ARI. SUMMARY This article reviews the available evidence of mor- ·tality from acute respiratory infections (ARI) among children aged under 5 years in contemporary devel- oping countries and compares the findings with European populations before 1965. In European populations before 1965, the level of mortality was found to be a determinant of the proportion of deaths due to ARI. There were marked differences according to regional patterns of mortality. Deaths from ARI played a smaller role after 1950, when the use of antibiotics became generalized. In developing countries, the role of ARI mortality seems to be similar to the European experience. The age pattern is very marked. In absolute values, ARI mortality is highest in the neonatal period and de- creases with age. In relative values, ARI mortality is highest in the postneonatal period. ARI, mainly pneumonia, accounts for about 18% of underlying causes of death in developing countries. Pneumonia and other ARI are frequent complications of measles and pertussis; ARI is also commonly found after other infections and in association with severe malnutrition. Virtually no data are available in developing countries to provide final estimates of the role of ARI in mortality of children aged under 5 years. However, the WHO figure of 1 out of 3 deaths due to - or associated with - ARI may be close to the real range of the ARl-proportional mor- tality in children of developing countries. Results are discussed in light of the definitions of ARI used in various studies, the difficulties in ascer- taining and coding multiple causes of death and the quality of data from some sources. RESUME Ampleur de la mortalite due aux affections aigues des voies respiratoires chez les enfants de moins de 5 ans dans les pays en developpement Cet article passe en revue les donnees disponibles concernant la mortalite actuelle par affection aigue des voies respiratoires (au infection respiratoire aigue - IRA) chez les enfants de mains de 5 ans dans les pays en developpement, et etablit une comparaison avec la situation en Europe avant 1965. On avait constate qu'avant cette date, dans les populations euro- peennes, le niveau de mortalite etait un determinant de la proportion de deces dus aux IRA. Les tableaux Wld hlth statist. quart., 45 (1992) de mortalite presentaient de tres nettes differences selon les regions. Le role des deces par IRA a diminue a partir de 1950, avec la generalisation de l'usage des antibiotiques. Dans les pays en developpement, le role de la mortalite par IRA parait similaire a ce qu'il etait jadis en Europe. La repartition par age est tres nette. En valeur absolue, c'est au cours de la periode neona- - 190 - tale que la mortalite par IRA est la plus forte; elle diminue ensuite avec l'age. En valeur relative, cette mortalite est plus forte durant la periode post- neonatale. Les IRA, et en particulier les pneumonies, sont la cause initiale d'environ 18% des deces dans les pays en developpement. Elles sont une complication fre- quente de la rougeole et de la coqueluche; on les rencontre frequemment aussi apres d'autres infec- tions, ou associees a la malnutrition grave. II n'y a dans les pays en developpement que tres peu de donnees qui puissent fournir des estimations finales sur le role des IRA dans la mortalite des enfants de mains de 5 ans. Toutefois, le chiffre qu'indique l'OMS - 1 deces sur 3 du ou associe aux IRA - doit etre assez proche de la realite, s'agissant de la mortalite proportionnelle par IRA chez les enfants des pays en developpement. L'analyse des resultats tient compte des definitions des IRA utilisees dans differentes etudes, des diffi- cultes a determiner les causes multiples de deces et a les coder, et de la qualite des donnees provenant de certaines sources. REFERENCES- REFERENCES 1. PRESTON, S. H. Mortality patterns in national popu- lations. New York, Academic Press, 1976. 2. GORDON, J. E. ET AL Death rates and causes of death in eleven Punjab villages: an epidemiolo- gical study. Indian journal of medical research, 49: 568-594 (1961 ). 3. A programme for controlling acute respiratory infections in children: memorandum from a WHO meeting. Bulletin of the World Health Or- ganization, 62: 47-58 (1984). 4. LEOWSKI, J. 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ET AL The effect of maternal and child health and family planning services on mortality: is prevention enough? British medical journal, 301: 103-107 (1990). 10. FAUVEAU, V. ET AL Excess female deaths among rural Bangladeshi children: an examination of cause-specific mortality and morbidity. Inter- national journal of epidemiology, 20: 729-735 (1991). 11. SPIKA, J. S. ET AL. Acute lower respiratory infec- tions: a major cause of death in children in Bangladesh. Annals of tropical paediatrics, 9: 33-39 (1989). 12. 0MONDl-0DHIAMBO, ET AL Age-specific infant and childhood mortality and causes of death. In: Van Ginneken, J. K. & Muller, A. S. (eds), Maternal and child health in rural Kenya: an epidemiologi- cal study. London, Croom Helm, 1984. 13. BRADLEY, A. K. & GILLES, H. M. Malumfashi en- demic diseases research project, XXI. Pointers to causes of death in the Malumfashi area, north- ern Nigeria. Annals of tropical medicine and parasitology, 78: 265-271 (1984). 14. CANTRELLE, P. ET AL The profile of mortality and its determinants in Senegal, 1960-1980. In: Deter- minants of mortality change and differentials in developing countries. New York, United Nations, 1986. (UN populationstudies-E. 85.Xlll.4). 15. GREENWOOD, B. M. ET AL Deaths in infancy and early childhood in a well-vaccinated, rural West African population. Annals of tropical paedia- trics, 7: 91-99 (1987). 16. SMEDMAN, L. ET AL Survival 0-6 years of age in a periurban community in Guinea-Bissau: a lon- gitudinal assessment. Annals of tropical paedia- trics, 6: 67-72 (1986). 17. MCCORD, c. & KIELMANN, A. A. A successful pro- gramme for medical auxiliaries treating child- hood diarrhoea and pneumonia. Tropical doctor, 8: 220-225 (1978). 18. BANG, A. T. ET AL Reduction in pneumonia mor- tality and total childhood mortality by means of community-based intervention trial in Gadchiroli, India. Lancet, ii: 201-206 (1990). 19. DATTA, N. ET AL Application of case management to the control of acute respiratory infections in low-birthweight infants: a feasibility study. Bulletin of the World Heath Organization, 65 ( 1 ): 77-82 (1987). DATTA, N. ET AL. La prise en charge des cas appliquee a la lutte contre les infections res- piratoires aigues chez les enfants de poids in- suffisant a la naissance: etude de faisabilite [resume). Bulletin de /'Organisation mondiale de la Sante, 65 (1): 81 (1987). 20. PANDEY, N. R. ET AL. Impact of a pilot acute respiratory infection (ARI) control programme in a rural community of the hill region of Nepal. Annals of tropical paediatrics, 9: 212-220 (1989). 21. PANDEY, N. R. ET AL Reduction in total under-five mortality in western Nepal through community- based antimicrobial treatment of pneumonia. Lancet, ii: 993-997 (1991). 22. KHAN, A. J. ET AL Acute respiratory infections in children: a case management intervention in Abbottabad district, Pakistan. Bulletin of the World Health Organization, 68: 577-585 (1990). 23. MTANGO, F. D. E. & NEUVIANS, D. Acute respiratory infections in children under five years - control project in Bagamoyo district, Tanzania. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 80: 851-858 (1986). 24. RILEY, I. D. ET AL Immunization with a polyvalent pneumococcal vaccine - effect on respiratory Rapp. trimest. statist. sanit. mond .. 45 (1992) - 191 mortality in children living in the New Guinea highlands. Archives of disease in childhood, 56: 354-357 (1981). 25. RILEY, I. D. ET AL Pneumococcal vaccine prevents death from acute lower-respiratory-tract infec- tions in Papua New Guinean children. Lancet, ii: 877-881 (1986). 26. TUPASI, T. K. ET AL Patterns of acute respiratory tract infection in children: a longitudinal study in a depressed community in Metro Manila. Re- views of infectious diseases, 12 (Supplement 8): S940-S949 (1990). 27. PUFFER, R. R. & SERRANO, C. V. Patterns of mor- tality in childhood. Washington, D.C., Pan American Health Organization, 1973. (Scientific publication No. 262). 28. WORLD HEALTH ORGANIZATION. Manual of the inter- national statistical classification of diseases, in- juries and causes of death. Eighth Revision. Geneva, WHO, 1967. ORGANISATION MONDIALE DE LA SANTE. Manuel de la classification statistique internationale des mala- dies, traumatismes et causes de deces. Huitieme revision. Geneve, OMS, 1967. 29. VON SCHIRNDING, Y. E. R. ET AL. Acute respiratory infections as an important cause of childhood deaths in South Africa. South African medical journal, 80: 79-82 (1991). 30. WORLD HEALTH ORGANIZATION. Manual of the inter- national statistical classification of diseases, in- juries and causes of death. Ninth Revision. Geneva, WHO, 1977. ORGANISATION MONDIALE DE LA SANTE. Manuel de la classification statistique internationale des mala- dies, traumatismes et causes de deces. Neu- vieme revision. Geneve, OMS, 1977. 31. WORLD HEALTH ORGANIZATION. Manual of the inter- national statistical classification of diseases, in- juries and causes of death. Seventh Revision. Geneva, WHO, 1957. ORGANISATION MONDIALE DE LA SANTE. Manuel de la classification statistique internationale des mala- dies, traumatismes et causes de deces. Septieme revision. Geneve, OMS, 1957. 32. Pio, A. ET AL The magnitude of the problem of acute respiratory infections. In: Douglas, R. M. & Kirby-Eaton, E. (eds), Acute respiratory infections in childhood. Proceedings of an international workshop. Sydney, University of Adelaide, 1985. 33. RAHMAN, M. ET AL. Acute lower respiratory tract infections in hospitalized patients with diarrhoea in Dhaka, Bangladesh. Review of infectious dis- eases, 12 (Supplement 8): S899-S906 (1990). 34. MTANGO, F. D. E. ET AL Magnitude, presentation, management and outcome of acute respiratory infections in children under the age of five in hospitals and rural health centres in Tanzania. Tropical medicine and parasitology, 40: 97-102 (1989). 35. WEISSENBACHER, M. ET AL Etiologic and clinical evaluation of acute lower respiratory tract infec- tions in young Argentinian children: an over- view. Reviews of infectious diseases, 12 (Supplement 8): S889-S898 (1990). 36. SUNAKORN, P. ET AL Epidemiology of acute res- piratory infections in young children from Thai- land. Paediatric infectious disease journal, 9: 873-877 (1990). 37. WORLD HEALTH ORGANIZATION. World health statis- tics annual. Geneva, WHO, 1989. Wld hlth statist. quart., 45 (1992) ORGANISATION MONDIALE DE LA SANTE. Annuaire de statistiques sanitaires mondiales. Geneve, OMS, 1989. 38. BULLA, A. & HITZE, K. L. Acute respiratory infec- tions: a review. Bulletin of the World Health Organization, 56 (3): 481-498 (1978). BULLA, A. & H1TZE, K. L. Panorama des infections aigues de l'appareil respiratoire (resume]. Bulletin de l'Organisation mondiale de la Sante, 56 (3): 497 (1978). 39. MULROW, C. D. ET AL Observer variability in the pulmonary examination. Journal of general in- ternal medicine, 1: 365-367 (1986). 40. STEINHOFF, M. C. Nosology and standards for ARI studies. In: Gadomski, A. G. (ed.), ALRI and child survival in developing countries. Proceedings of a workshop held in August 1989 in Washington, D.C. Baltimore, JHU Design Publications, 1990. 41. BERMAN, S. Overview of pneumonia in early in- fancy. In: Gadomski, A. G. (ed.), ALRI and child survival in developing countries. Proceedings of a workshop held in August 1989 in Washington, D.C.Baltimore, JHU Design Publications, 1990. 42. GRAY, R. H. Verbal autopsy: using interviews to determine causes of death in children. Baltimore, The Johns Hopkins University Press, 1991. (Occasional paper No. 14). 43. KIELMANN, A. A. ET AL Child and maternal health services in rural India - the Narangwal experi- ment. Baltimore, The Johns Hopkins University Press, 1983. 44. KALTER, H. D. ET AL Validation of postmortem interviews to ascertain selected causes of death in children. International journal of epidemio- logy, 19: 380-386 (1990). 45. NAVARRO, E. E. ET AL Clinicopathologic studies of children who die of acute lower respiratory tract infections: mechanism of death. Reviews of in- fectious diseases, 12 (Supplement 8): S1065- S1073 (1990). 46. SHANN, F. ET AL. Clinical signs that predict death in children with severe pneumonia. Paediatric infectious disease journal, 8: 852-855 (1989). 47. MANTON, K. G. & STALLARD, E. Recent trends in mortality analysis. New York, Academic Press, 1984. 48. COALE, A. & DEMENY, P. Regional model life tables and stable populations. Princeton, Princeton Uni- versity Press, 1966. 49. MORLEY, D. C. ET AL Measles in West Africa. West African medical journal, 16: 24-31 (1967). 50. VOORHOEVE, A. M. ET AL Agents affecting the health of mother and child in a rural area of Kenya - Ill. The epidemiology of measles. Trop- ical and geographical medicine, 29: 428-440 (1977). 51. MARKOVITZ, L. A. & N1EBURG, P. The burden of acute respiratory infection due to measles in developing countries and the potential impact of measles vaccine. Reviews of infectious diseases, 13 (Supplement 13): S555-S561 (1991). 52. DOVER, A. S. ET AL Pneumonia associated with measles. JAMA, 234: 612-614 (1975). 53. WRIGHT, P. F. Pertussis in developing countries: definition of the problem and prospects for con- trol. Reviews of infectious diseases, 13 (Supplement 16): S528-S534 (1991 ). 54. MORLEY, D. C. ET AL Whooping cough in Nigerian children. Tropical geographical medicine, 18: 169-182 (1966). - 192 - WATERBORNE DISEASE OUTBREAKS IN THE UNITED STATES OF AMERICA: CAUSES AND PREVENTION Gunther F. Craun• Introduction In the United States of America, the reporting of waterborne outbreaks is voluntary. National statis- tics, available from 1920, are compiled from informa- tion obtained from the scientific literature and state public health and environmental protection agencies. Specific diseases are reported as a result of legisla- tion or administrative rule in each state. Currently, information is provided to the federal government on the occurrence of 49 notifiable diseases, some of which may be waterborne. State and local public health agencies are primarily responsible for disease surveillance and the detection and investigation of outbreaks. The Environmental Protection Agency (EPA) and Centers for Disease Control (CDC) provide assistance when requested in the investigation of waterborne outbreaks. EPA and CDC have main· tained a collaborative waterborne disease sur· veillance programme at the federal level since 1971. Periodically, waterborne outbreak data are analysed to identify the water system deficiencies and etiolo· gical agents responsible for the outbreaks (1). This information is important to evaluate the adequacy of public health programmes, regulations, and treat- ment technologies to provide safe drinking-water. Definitions For an outbreak to be considered waterborne, acute illness affecting two or more persons with similar symptoms must be epidemiologically associated with the ingestion of water. Also included are single, well-documented cases of chemical poisoning such as infantile methemoglobinaemia associated with high nitrate concentrations. During most outbreaks, water was found to be bacteriologically or chemic- ally contaminated, but in only a few outbreaks was the etiological agent isolated from water. Reported outbreaks are primarily associated with water used or intended for drinking or domestic purposes, but outbreaks are also associated with ingestion of non· potable water. Included in the surveillance system but excluded from this analysis are waterborne out- breaks on cruise ships operating from United States ports and among swimmers, bathers, and hot-tub users, with dermal or inhalation exposure. Water systems are classified as community (systems with 25 year-round residents) or noncommunity (systems for institutions, industries, camps, parks, hotels or businesses). Outbreaks in residents without com- munity systems or persons who consume water from nonpotable sources (e.g. backpackers, camp- ers) and outbreaks in which contaminated water was ingested while swimming or bathing are classified as individual and recreational. • Research Fellow, Virginia Polytechnic Institute and State Uni: versity, Blacksburg, VA, United States of America. Statistics Since 1920, 1 702 waterborne outbreaks with 542 018 cases of illness, and 1 089 deaths have been re- ported in the United States. Almost all deaths were due to typhoid fever prior to 1940, but 9 deaths have occurred since 1971: 4 during an outbreak of diarrhoea caused by enterohaemorrhagic E. coli 0157:H7; 2 during an outbreak of shigellosis in an elderly population; and single deaths due to ac- cidental fluoride contamination of a community water system, ethylene glycol contamination of drinking-water used for haemodialysis, and high nitrate in a farm well. Three additional cases of methemoglobinaemia reported since 1971 did not result in death. During the past decade, 291 waterborne outbreaks were reported in community (43%) and non- community (33%) systems and from the ingestion of contaminated water from recreational (14%) and in- dividual (10%) water sources. For all types of sys- tems, the average frequency of occurrence was 29 outbreaks per year, which is only slightly less than reported during the previous decade and com- parable to the number reported during the 1930s and 1940s (Table 1). TABLE 1. AVERAGE NUMBER OF WATERBORNE OUTBREAKS PER VEAR, UNITED STATES OF AMERICA, 1920-1990 TABLEAU 1. NOMBRE MOVEN DE FLAMBEES DE MALADIES A TRANSMISSION HVDRIQUE PAR AN, IETATS-UNIS D'AMERIQUE, 1920-1990 Community Noncommunity All water Time period systems systems systems Peri ode Reseaux Autres Ensemble des reseaux publics reseaux d'adduction d'eau 1920-30 17.2 2.6 23.2 1931-40 12.8 8.1 30.6 1941-50 9.6 14.2 31.3 1951-60 4.1 3.9 11.1 1961-70 3.9 3.9 13.1 1971-80 12.3 16.1 32.6 1981-90 12.4 9.7 29.1 1920-90 8.9 7.1 20.2 More outbreaks are usually reported in community than in noncommunity systems. The number of out- breaks reported each decade in community systems declined until 1971. Outbreaks have also declined during the past decade. From 1981 to 1985, 186 waterborne outbreaks were reported with only 105 reported during 1986-1990. Eighty-nine out- breaks in community systems and 61 outbreaks in noncommunity systems were reported in the first half of the decade, compared with 35 and 36 outbreaks, respectively in the latter half. Although several large waterborne outbreaks occurred during the past decade, most outbreaks were in small communities. The relative size of Rapp. trimest. statist. sanit. mond., 45 (1992) - 193 - outbreaks reported in community water systems during the past decade is among the lowest of any decade since 1920 and similar to the size of out- breaks in noncommunity systems (Table 2). The TABLE 2. CASES OF WATERBORNE ILLNESS PER OUTBREAKS, UNITED STATES OF AMERICA, 1920-1990 TABLEAU 2. NOMBRE DE CAS DE MALADIES A TRANSMISSION HYDRIQUE PAR FLAMBEE EPIDEMIQUE, ETATS-UNIS D'AMERIQUE, 1920-1990 Community Noncommunity All water Time period systems systems systems Peri ode Reseaux Autres Ensemble des reseaux publics reseaux d'adduction d'eau 1920-30 513 138 400 1931-40 748 60 339 1941-50 467 57 172 1951-60 247 51 112 1961-70 1 023 111 354 1971-80 483 114 241 1981-90 290 274 225 1920-90 438 83 221 number of illnesses per outbreak in noncommunity systems during the past decade is much larger than reported during any previous period, and the magni- tude of these outbreaks indicates the potential effect on the large, travelling, transient population. Reporting It is difficult to determine whether the decline in the reported number of waterborne outbreaks in the past 5 years is due to the occurrence of fewer outbreaks or less active surveillance and reporting. Outbreaks are most likely to be reported in com- munity systems, and because less active surveillance should continue to recognize most outbreaks in these water systems, the decrease in reported out- breaks for community systems since 1985 may re- flect a decrease in outbreak occurrence. An active surveillance programme is required to detect out- breaks in noncommunity systems, especially those involving travellers. Therefore, the large decline in outbreaks observed for noncommunity water sys- tems during the same time may reflect less active su rvei I la nee. The number of reported outbreaks increased drama- tically during 1979-1983, and it can also be argued that this increase was primarily the result of im- proved surveillance and reporting, while the de- crease in reported outbreaks since 1985 reflects a less active, more typical surveillance system. The number of waterborne outbreaks reported after 1983 is comparable to that reported during a similar period just prior to 1979. This suggests that in- creases or decreases in waterborne outbreak statis- tics primarily reflect surveillance and reporting changes rather than deterioration or improvement in water systems. Many factors influence the degree to which outbreaks are recognized, investigated and reported in any single year, including interest in the problem and the capabilities for recognition and investigation at the state and local level. While it is generally agreed that waterborne outbreak reporting is incomplete, it is difficult to estimate the number of outbreaks that may go undetected or unreported. Estimates suggest that only one-half to one-third or even one-tenth of all waterborne outbreaks are detected, investigated and reported (2). Causes of outbreaks During 1981-1990, contaminated, untreated ground- water or inadequately disinfected groundwater was responsible for 43% of all reported waterborne out- breaks, and contaminated, untreated surface water or inadequately treated surface water was respon- sible for 24% of all reported outbreaks (Table 3). Contaminated groundwater has consistently been responsible for more waterborne outbreaks than contaminated surface water. In each decade since 1920, 43-56% of all outbreaks were caused by con- taminated groundwater, against 14-37% by con- taminated surface water. Contaminated, untreated TABLE 3. CAUSES OF WATERBORNE OUTBREAKS, UNITED STATES OF AMERICA, 1981-1990 TABLEAU 3. CAUSES DES FLAMBEES DE MALADIES A TRANSMISSION HYDRIQUE, ETATS-UNIS D'AMERIQUE, 1981-1990 Cause of outbreak - Cause de la flambee epidemique Untreated groundwater - Eaux souterraines non traitees Inadequate disinfection of groundwater - Eaux souterraines mal desinfectees Ingestion of contaminated water while swimming - Ingestion d'eau contaminee en nageant Inadequate disinfection of surface water - Mauvaise desinfection des eaux de surface Distribution deficiencies - Problemes de distribution Filtration deficiencies - Problemes de filtration Unknown - lnconnue Untreated surface water - Eaux de surface non traitees Miscellaneous - Divers Total W/d hlth statist. quart .• 45 (1992) Community Public 12.1 13.7 28.2 24.2 12.9 5.6 1.6 1.7 100 Percentage of outbreaks Pourcentage de flambees epidemiques Type of water system Type de reseau d'adduction d'eau Noncommunity Autre 44.3 33.0 9.3 3.1 1.0 3.1 4.1 2.1 100 All systems T ous reseaux 26.5 16.5 14.1 15.1 12.4 5.8 3.8 3.4 2.4 100 - 194 - groundwater has declined in importance as a cause of outbreaks, and inadequate or interrupted disinfec- tion has increased in importance, causing 17-27% of all outbreaks since 1971. Prior to 1971, only 2-6% of all outbreaks were caused by inadequate disinfection of groundwater. The increased occurrence of out- breaks in disinfected groundwater systems may be due to increased use of disinfection with little or no effort to reduce or eliminate sources of contamina- tion. The lack of attention to providing effective, continuous disinfection is also important. Although most outbreaks in disinfected groundwater systems during the 1980s were the result of improper chlorin- ation, several occurred in systems using iodine. Causes of outbreaks in untreated groundwater dur- ing the 1980s included: overflow or seepage of sewage into wells or springs (25%); surface runoff or flooding (13%); chemical contamination (5%); and contamination through limestone or fissured rock (4%). The investigation of most outbreaks (52%) caused by untreated groundwater was insufficient to identify a cause. In surface water systems, outbreaks now occur primarily because of inadequate or interrupted disin- fection in systems that do not provide filtration. Prior to 1971, outbreaks in surface water systems were caused most often by contaminated, untreated water. In the 1980s, a large increase also occurred in outbreaks in filtered surface water systems; in pre- vious decades, except for the 1920s, only 2-4% of all outbreaks occurred in filtered surface water systems. Proper design and operation of filtration facilities are important in preventing waterborne outbreaks. The causes of outbreaks differed in community and noncommunity systems during 1981-1990. In com- munity systems, most outbreaks were caused by inadequate disinfection of surface water (28%) and contamination of water in the distribution systems (24%), primarily through cross-connections and re- pairs of mains. In noncommunity systems, almost all outbreaks (77%) were caused by contaminated, un- treated and inadequately disinfected groundwater. Etiology Etiological agents responsible for waterborne out- breaks have changed since 1920 (Table 4). Typhoid fever is no longer a threat in the United States. Hepatitis A replaced typhoid fever in the 1960s as the most frequently identified etiology, but it has declined in importance. Since 1971, the most fre- quently identified etiology has been giardiasis. During the past decade, some 65% of waterborne giardiasis outbreaks were caused by contaminated surface water and 13% were caused by faecal con- tamination of groundwater or groundwater under the influence of surface water. Inadequate disinfec- tion of surface water when disinfection was the only treatment, and ineffective filtration or pretreatment of surface water were responsible for most out- breaks and cases of giardiasis. Giardia can be inac- tivated by disinfection but only if stringent con- ditions are met and consistently maintained (2). Although any of the identified etiological agents can be transmitted through either contaminated surface or groundwater, some agents were more frequently associated with groundwater contamination. Almost all (82%) reported outbreaks of hepatitis A were caused by contaminated groundwater. Contaminated groundwater was also responsible for 60% of the outbreaks of campylobacterosis, 48% of the out- breaks of viral gastroenteritis, 27% of the outbreaks of shigellosis, as well as for a single outbreak of amoebiasis, and 2 outbreaks of chronic gastro- enteritis. During the past decade, the etiology of acute gas- troenteritis (AGI) was not determined in almost half of the outbreaks. In outbreaks caused by contami- nated groundwater, only 38% were of a defined etiology, against 77% of outbreaks caused by surface water. In many outbreaks, the search for an etiologi- cal agent was limited or clinical specimens could not be collected in a timely manner. Although the symp- toms and incubation period suggest viral illness in some outbreaks, it is felt that outbreaks of AGI represent a combination of viral, bacterial and para- sitic etiologies. In 1984 unpasteurized milk was implicated in Brainerd, Minnesota, in an outbreak of a distinctive chronic diarrhoeal illness characterized by dramatic, urgent watery diarrhoea persisting for many months; no causative agent could be identified (3). In 1987 the first waterborne outbreak of chronic gastroenter- itis occurred; untreated well water in an Illinois restaurant was implicated as the vehicle of transmis- sion (4). Nonbloody diarrhoea with a median fre- quency of 12 stools per day persisted in 87% of patients after 6 months. No bacterial, mycobacterial, viral or parasitic agents known to be entero- pathogenic were detected in stools or well water. The well water was contaminated with coliforms. A second outbreak, also associated with untreated well water, occurred in a small Oklahoma community in 1988, but again no agent could be isolated. More research is required to help identify agents which may cause this and other unidentified waterborne illnesses, in order to assess the adequacy of current water treatment process and regulations. Although more timely investigations may help identify some agents, increased availability of laboratory pro- cedures is also needed. Outbreaks of 2 newly-recognized waterborne etiolo- gical agents were reported. Although its waterborne transmission had been suspected and it had been isolated from water (5, 6), E. coli 0157:H7 had not previously been documented as a cause of water- borne outbreaks. In 1989 an outbreak of 243 cases occurred in Cabool, Missouri, where one-third of the ill persons had bloody diarrhoea, 32 were hos- pitalized and 4 died (1). The water distribution system was identified as the likely source of con- tamination. The severity of illness associated with this organism reinforces the need to prevent water- borne outbreaks. Waterborne transmission of Cyano- bacteria (blue-green algae-like bodies) (CLB) has been identified in stool specimens from patients around the world, and its role in causing diarrhoeal illness is currently being investigated (7). An out- break in a Chicago hospital was associated with drinking-water in a building in which open-air, roof- top storage tanks were used to maintain water pres- sure. Ill persons had remissions and relapses of explosive watery diarrhoea. CLB but no ova or para- sites were found in stool specimens; no CLB were found in water samples but algae were found in a storage tank. The protozoan Cryptosporidium has only recently been recognized as a cause of diarrhoea illness in humans. Like Giardia, animals as well as humans may serve as sources of environmental contamina- tion and human infection (8). The first waterborne outbreak was reported in 1985 in a Texas community Rapp. trimest. statist. sanit. mand., 45 (1992) - 195 - with sewage-contaminated groundwater. It was also responsible for one of the largest waterborne out- breaks in the United States, affecting an estimated 13 OOO persons in Carrollton, Georgia, in 1987 (9). This community used surface water which under- went conventional treatment: coagulant feed, rapid mix, flocculation, sedimentation, filtration through anthracite sand filters, and chlorination. EPA water quality regulations were not exceeded for turbidity or coliforms and disinfection was not interrupted. Cryptosporidium oocysts identified in the water system during the outbreak most likely entered be- cause of the operational practice of stopping and later restarting the flow of water through some filters without backwashing the filter. This practice resulted in higher-turbidity water from these filters. Limited studies have been conducted, but evidence indicates that this protozoan is very resistant to O Information for comparative purposes only: EPA regulations require inactivation of 99.9% for Giardia and 99.99% for viruses. ation (2, 8). Only 90% inactivation of oocysts was found at 100 mg/I free chlorine for 2 hours contact. In comparison, 99% inactivation of Giardia occurs at about 2.5 hours at 1 mg/I, polio virus at 3 minutes at 1 mg/I, rotavirus and E. coli bacteria at less than 1 minute at 0.1 mg/I. b The occurrence of Cryptosporidium is widespread in water supplies in the United States (10). Oocysts were detected at an average concentration of 43/1001 in 55% of 257 samples collected from surface water and springs in 17 states and less than 1/1001 in 17% of 36 drinking-water samples. In comparison, an average of 3 Giardia cysts/1001 were found in 16% of the same water samples, and none were found in the drinking-water samples. No correlation was found between the occurrence of either protozoan and the current water quality indicator, coliforms. Additional research is needed to determine why so few waterborne outbreaks have been reported. En- demic cases may not be well reported, asymp- TABLE 4. ETIOLOGY OF WATERBORNE OUTBREAKS, UNITED STATES OF AMERICA, 1920-1990 TABLEAU 4. ETIOLOGIE DES FLAMBEES DE MALADIES A. TRANSMISSION HYDRIQUE, ETATS-UNIS D'AMERIOUE, 1920-1990 Time period Peri ode 1920-1940 1941-1960 1961-1970 Disease Maladie Typhoid fever - Fievre typho'ide Gastroenteritis - Gastro-enterite Shigellosis - Shigellose Amoebiasis - Amibiase Hepatitis A - Hepatite A Chemical poisoning - Intoxication chimique Subtotal - Total partial Gastroenteritis - Gastro-enterite Typhoid fever - Fievre typho'ide Shigellosis - Shigellose Hepatitis A - Hepatite A Salmonellosis - Salmonellose Chemical poisoning - Intoxication chimique Paratyphoid fever - Paratypho'ide Amoebiasis - Amibiase Tularaemia - Tularemie Leptospirosis - Leptospirose Poliomyelitis - Poliomyelite Subtotal - Total partial Gastroenteritis - Gastro-enterite Hepatitis A - Hepatite A Shigellosis - Shigellose Typhoid fever - Fievre typho'ide Salmonellosis - Salmonellose Chemical poisoning - Intoxication chimique Toxigenic E. coli - E. coli enterotoxigene Giardiasis - Giardiase Amoebiasis - Amibiase Subtotal - Total partial Wld hlth statist. quart., 45 (19921 Number of outbreaks Nombre de flambees epidemiques 372 144 10 2 1 530 265 94 25 23 4 4 3 2 2 1 1 424 39 30 19 14 9 9 4 3 3 130 Time period Peri ode 1971-1980 1981-1990 Number of Disease outbreaks Maladie Nombre de flambees epid0miques Gastroenteritis (AGI) - Gastro-enterite (AGI) 181 Giardiasis - Giardiase 39 Chemical poisoning - Intoxication chimique 38 Shigellosis - Shigellose 24 Hepatitis A - Hepatite A 16 Viral gastroenteritis - Gastro-enterite virale 12 Salmonellosis - Salmonellose 8 Typhoid fever - Fievre typho'ide 4 Campylobacterosis - Campylobacterose 3 AGI (toxigenic E. colt) - Gastro-enterite aigue (E. coli toxigene) Subtotal - Total partial Gastroenteritis (AGI) - Gastro-enterite (AGI) Giardiasis - Giardiase Shigellosis - Shigellose Chemical poisoning - Intoxication chimique Viral gastroenteritis - Gastro-enterite virale · Hepatitis A - Hepatite A Campylobacterosis - Campylobacterose Salmonellosis - Salmonellose Cryptosporidiosis - Cryptosporidiose Yersiniosis - Yersiniose Chronic gastroenteritis - Gastro-enterite chronique AGI (E. coli 0157:H7) - Gastro-enterite aigue (E. coli 0157:H7) Typhoid fever - Fievre typho'ide Dermatitis (chlorine) - Dermatite (due au chlore) AGI (cyanobacteria-like body) - Gastro-enterite aigue due aux organismes analogues a des cyanobacteries Cholera - Cholera Amoebiasis - Amibiase Subtotal - Total partial 326 128 71 22 18 15 11 10 4 2 2 2 291 - 196 - tomatic infection may be high, and protective im- munity may be important. Some oocysts in the environment may not be infective for humans, and oocysts identified in water may not be viable (cur- rent analysis cannot assess viability). Although the infective dose is thought to be low, it may not be high enough in most water systems to cause suf- ficient infection in large numbers of people. For example, 46 oocysts/1001 were detected in the Carrollton outbreak compared with only 0.5-1.7 oocysts/1001 in the water survey (8, 9). Discussion New strategies are needed to prevent waterborne outbreaks. Outbreaks have occurred in systems that have not exceeded regulations for coliforms and turbidity, and the data clearly show that disinfection has not been effective as the only treatment for surface waters. The important waterborne diseases at the turn of the century were typhoid fever and cholera. These diseases are transmitted exclusively among humans, and waterborne transmission can be prevented by protecting water sources from sew- age contamination. Since these pathogens are very susceptible to disinfection, chlorination was found to be adequate as the only treatment of some surface waters. Important waterborne diseases are now caused by protozoa which cause infection at a lower dose and are much more resistant to disinfection. Water contamination by these protozoa is not necessarily detected by coliform occurrence. In addi- tion to human reservoirs, wild and domestic animals are important primary or intermediate sources of infection by these protozoa and also by other newly- recognized etiological agents. Since it is impossible to exclude animals from watersheds, greater empha- sis must be placed on water treatment barriers. Although the protection of raw water quality is still important, it is only one barrier to the transmission of waterborne disease. It is necessary to maintain additional barriers-filtration and disinfection-to en- sure adequate margins of safety for surface-water systems. More emphasis must also be placed on the design and operation of filtration facilities if they are to be effective as part of the multiple barrier con- cept. The new EPA surface-water treatment require- ments address disinfection and filtration of surface waters (54 FR 27486-541, June 19, 1989). Adequate disinfection of groundwater should reduce the occurrence of waterborne outbreaks, particularly for small systems where intermittent contamination of wells and springs cannot be readily determined or prevented. Disinfection is not a substitute for proper development and protection of groundwater sources from contamination; it is an additional barrier for an increased level of protection. EPA has recently drafted requirements for disinfection of public water systems using groundwater. Disinfection must continue as the final barrier against waterborne disease, but concerns over the human health effects that may be associated with long-term exposures to chlorine or chlorinated by- products may require changes in disinfection tech- niques or disinfectants (11, 12). These concerns, however, must be tempered with considerations of the benefits provided by chlorination. Alternative disinfectants may be more expensive and not tech- nologically feasible for developing countries where waterborne disease may be a greater threat. Ad- ditional research is required to better define the potential risks associated with chlorine and alterna- tive disinfectants. Chlorination may be the final, but it must not be the only, barrier against transmission of waterborne pathogens. Source protection is also important for both surface and groundwater. Properly designed and operated filtration plants can make disinfection more effective by removing turbidity and substances that exert chlorine demand and by reducing micro- biological contamination. When disinfection is a part of the multiple barrier approach and not relied upon so heavily, lower concentrations of chlorine can be used, thereby lowering the levels of chlorinated by- products produced. SUMMARY National statistics on waterborne outbreaks in the United States of America show that 1 702 water- borne outbreaks with 542 018 cases of illness and 1 089 deaths have been reported. Almost all deaths prior to 1940 were due to typhoid fever; 9 deaths from other causes have occurred since 1971. During the past decade, 291 waterborne outbreaks were reported in community (43%) and noncommunity (33%) systems, and from the ingestion of contami- nated water from recreational (14%) and individual (10%) water sources. Although several large waterborne outbreaks occurred during the past decade, most were in small communities. The number of illnesses per outbreak in noncommunity systems during the past decade is much larger than that reported during any previous period, and the magnitude of these outbreaks indi- cates the potential effect on the travelling, transient population. During 1981-1990, contaminated, untreated ground- water or inadequately disinfected groundwater was responsible for 43% of all reported waterborne out- breaks, and contaminated, untreated surface water or inadequately treated surface water was respon- sible for 24% of all reported outbreaks. The use of untreated groundwater has declined in importance as a cause of outbreaks, and more outbreaks are now caused by inadequate or interrupted disinfec- tion of groundwater. The increased occurrence of outbreaks in disinfected groundwater systems may be due to (i) increased use of disinfection with little effort to reduce or eliminate sources of contamina- tion, and (ii) not providing effective, continuous dis- infection. In surface-water systems, outbreaks occur primarily because of inadequate or interrupted disinfection in systems that do not provide filtration, but a large increase in outbreaks has recently occurred in fil- Rapp. trimest. statist. sanit. mond., 45 (1992) - 197 - tered systems. In community systems, most out- breaks were caused by inadequate disinfection of surface water (28%) and contamination of water in the distribution systems (24%), primarily through cross-connections and repairs of water mains. In noncommunity systems, almost all outbreaks (77%) were caused by contaminated groundwater. Since 1971, the most frequently identified etiology was giardiasis. Inadequate disinfection of surface water when disinfection was the only treatment, and ineffective filtration or pretreatment of surface water were responsible for most outbreaks and cases of giardiasis, but 13% were caused by faecal contami- nation of groundwater or groundwater under the influence of surface water. Almost all (82%) out- breaks of hepatitis A were caused by contaminated groundwater. Contaminated groundwater was also responsible for: 60% of outbreaks of campylo- bacterosis, 48% of outbreaks of viral gastroenteritis, 27% of outbreaks of shigellosis, a single outbreak of amoebiasis, and 2 outbreaks of chronic gastro- enteritis. In 1987 the first waterborne outbreak of a distinctive chronic diarrhoeal illness characterized by dramatic, urgent, watery diarrhoea persisting for many months was reported in Illinois. Untreated well water in a restaurant was implicated as the vehicle of transmis- sion, but no causative agent could be identified. A second outbreak also associated with untreated well water occurred in 1988, but again no agent could be isolated. Outbreaks of two newly recognized waterborne etio- logical agents were reported. In 1989 an outbreak of 243 cases of E. coli 0157:H7 occurred in Cabool, Missouri, where one-third of the ill persons had bloody diarrhoea, 32 were hospitalized and 4 died. Waterborne transmission of Cyanobacteria (blue green algae-like bodies) was identified in an out- break in a Chicago hospital where open-air, roof-top storage tanks were used to maintain water pressure. The protozoan Cryptosporidium has only recently been recognized as a cause of diarrhoeal illness in humans. As with Giardia, animals as well as humans may serve as sources of environmental contamina- tion and human infection. The first waterborne out- break was reported in 1985 in a community with sewage-contaminated groundwater. One of the largest waterborne outbreaks, an estimated 13 OOO cases of cryptosporidiosis, occurred in 1987 in a community using surface water treated by an appar- ently complete filtration and disinfection process; water quality regulations were not exceeded for turbidity or coliforms and disinfection was not inter- rupted. New strategies are needed to prevent waterborne outbreaks. Outbreaks have occurred in systems that have not exceeded regulations for coliforms and turbidity, and the data clearly show that disinfection has not been effective as the only treatment for surface waters. Although the protection of raw water quality is still important, it is only one barrier to the transmission of waterborne diseases. It is necessary to maintain additional barriers-filtration and disin- fection-to ensure adequate margins of safety for surface water systems. More emphasis must also be placed on the design and operation of filtration facilities. Adequate disinfection of groundwater should reduce the occurrence of waterborne outbreaks, particularly for small systems where intermittent contamination of wells and springs cannot be readily determined or prevented. Disinfection is not a substitute for the proper development and protection of groundwater sources from contamination; it is an additional bar- rier for an increased level of protection. Disinfection is required to protect against waterborne disease transmission, and concerns for health effects which may be associated with long-term exposure to dis- infectants and disinfection by-products must be tempered with considerations of the benefits. When disinfection is part of the multiple-barrier ap- proach, lower concentrations can be used, thereby lowering levels of disinfection by-products. RESUME Flambees de maladies a transmission hydrique aux Etats-Unis d' Amerique: causes et prevention D'apres les statistiques nationales concernant les flambees de maladies a transmission hydrique aux Etats-Unis d'Amerique, 1 702 flambees, au cours desquelles ont ete enregistres 542 018 cas et 1 089 deces, ont ete signalees. Avant 1940, pratiquement tous les deces etaient dus a la fievre typho"ide; depuis 1972, 9 deces dus a d'autres maladies ont ete signales. Au cours des 10 dernieres annees, 291 flamblees de maladies a transmission hydrique ont ete signalees, 43% dans les reseaux publics d'adduction d'eau, 33% dans d'autres reseaux, 14% suite a !'ingestion d'eau polluee dans des zones de loisirs et 10% d'eau de sources privees. Plusieurs poussees importantes de maladies a trans- mission hydrique sont survenues au cours des 10 dernieres annees, mais la plupart du temps dans de petites collectivites. Dans chaque circonstance, le Wld hlth statist. quart., 45 (19921 nombre de cas enregistres dans des reseaux non publics au cours des 10 dernieres annees etait beau- coup plus important qu'au cours de toute autre periode anterieure, et !'importance des foyers donne une idee du risque encouru par les voyageurs et les personnes de passage. De 1981 a 1990, 43% des flambees de maladies a transmission hydrique notifiees etaient imputables a des eaux souterraines contaminees, non traitees ou mal desinfectees, et 24% a des eaux de surface contaminees, non traitees ou mal desinfectees. La consommation d'eaux souterraines non traitees n'est plus une cause aussi importante d'epidemies et la plupart des flambees sont desormais provoquees par une mauvaise desinfection ou une absence pas- sagere de desinfection des eaux souterraines. L'augmentation de flambees epidemiques survenant - 198 - dans des reseaux d'eaux souterraines desinfectees peut etre due i) a un recours accru de la desinfec- tion sans chercher a reduire ou eliminer les sources de pollution ou ii) a !'absence de systemes efficaces de desinfection en continu. En ce qui concerne les eaux de surface, les flambees epidemiques surviennent principalement en raison de l'insuffisance ou de !'interruption de la desinfec- tion dans des reseaux depourvus de systemes de filtration, mais une augmentation importante a re- cemment ete observee dans des reseaux dotes de systemes de filtration. Dans les reseaux publics, la plupart des flambees ont ete provoquees par une mauvaise desinfection des eaux de surface (28%) et par la contamination de l'eau des reseaux de distri- bution (24%), principalement lors de raccordements ou de la reparation des conduites d'eau. Dans les autres reseaux, la presque totalite des flambees (77%) ant ete provoquees par des eaux souterraines contaminees. Depuis 1971, c'est la giardiase qui a ete !'affection la plus frequemment observee. Une mauvaise desinfec- tion des eaux de surface - en !'absence de tout autre traitement - et lorsqu'une filtration ou un pre-traitement inefficaces des eaux de surface ant ete responsables de la plupart des flambees epide- miques et des cas de giardiase, mais 13% s'expli- quent par une contamination fecale des eaux souter- raines ou !'infiltration d'eaux de surface dans les eaux souterraines. Pratiquement toutes les flambees epidemiques d'hepatite A (82%) ant ete provoquees par des eaux souterraines contaminees. La pollution des eaux souterraines est egalement responsable de 60% des flambees de campylobacteriose, de 48% des flambees de gastro-enterite virale, de 27% des flambees de shigellose, d'une flambee d'amibiase et de 2 flambees de gastro-enterite chronique. En 1987, la premiere flambee epidemique d'une maladie diarrheique chronique d'origine hydrique caracterisee par une diarrhee aqueuse tres profuse persistant pendant plusieurs mois a ete signalee dans !'Illinois. De l'eau non traitee provenant d'un puits consommee dans un restaurant a ete mise en cause dans la transmission mais aucun agent etiolo- gique n'a pu etre identifie. Une deuxieme flambee egalement imputable a de l'eau de puits non traitee est survenue en 1988, mais la encore aucun agent n'a pu etre isole. Des flambees imputables a deux agents etiologiques a transmission hydrique recemment identifies ant ete signalees. En 1989, une flambee de 243 cas d'infection a E. coli 0157:H7 s'est produite a Cabool, dans le Missouri, ou un tiers des personnes malades presentaient des diarrhees sanglantes, 32 ant ete hospitalisees et 4 sont decedees. La transmission hydrique d'organismes analogues a des cyanobacte- ries (algues bleues) a ete relevee lors d'une flambee epidemique survenue dans un hopital de Chicago ou des reservoirs d'eau a l'air libre places sur le toit etaient utilises pour assurer une pression d'eau suffi- sante. Un protozoaire, Cryptosporidium, n'a ete reconnu comme cause de maladie diarrheique chez l'homme que tres recemment. Tout comme pour Giardia, l'animal et l'homme peuvent constituer des sources de contamination de l'environnement et d'infection humaine. La premiere flambee epidemique d'origine hydrique a ete signalee en 1985 dans une collectivite dont les eaux souterraines avaient ete contaminees par des eaux usees. Une des plus importantes flam- bees de maladie hydrique, ou l'on avait denombre quelque 13 OOO cas de cryptosporidiose, est surve- nue en 1987 dans une collectivite consommant des eaux de surface ayant subi un traitement complet de filtration et de desinfection; les valeurs-limites rela- tives a la turbidite ou aux coliformes n'avaient pas ete depassees et la desinfection n'avait pas ete interrompue. De nouvelles methodes doivent done etre mises au point pour prevenir les flambees de maladies a transmission hydrique. Certaines ant eclate dans des reseaux ou les valeurs-limites relatives aux colifor- mes OU a la turbidite n'avaient pas ete depassees et les donnees indiquent clairement que la desinfection n'a pas toujours ete efficace comme seul traitement pour les eaux de surface. Bien que la protection de la qualite de l'eau non traitee soit toujours impor- tante, elle n'est qu'une mesure de protection parmi tant d'autres contre la transmission des maladies hydriques. II est done necessaire de s'assurer des protections supplementaires - filtration et desinfec- tion - afin de garantir une marge de securite suffi- sante dans les reseaux utilisant les eaux de surface. II faudrait egalement accorder davantage d'attention a la conception et au mode de fonctionnement des systemes de filtration. Une bonne desinfection des eaux souterraines de- vrait reduire la survenue des flambees de maladies a transmission hydrique, en particulier dans les petits reseaux ou une contamination intermittente des puits ou des sources est difficile a deceler ou a prevenir. La desinfection ne saurait remplacer !'ex- ploitation judicieuse et la protection des sources d'eau souterraine de toute pollution; ce n'est qu'un element de plus pour garantir un niveau accru de protection. La desinfection est necessaire pour se premunir contre la transmission des maladies hydri- ques et !'inquietude que peuvent soulever les ris- ques d'une exposition de longue duree aux desinfec- tants et aux sous-produits de la desinfection doit etre temperee par les avantages potentiels qu'elle presente. Lorsque la desinfection s'insere dans une strategie de protection a plusieurs valets, de plus faibles concentrations de desinfectants peuvent etre utilisees, ce qui permet aussi de reduire la concen- tration des sous-produits de la desinfection. REFERENCES- REFERENCES 1. HERWALDT, B. L. ET AL. Waterborne-disease out- breaks, 1989-1990. Morbidity and mortality weekly report, 40 (SS-3): 1-13 (1991 ). 2. CRAUN, G. F. (ed.). Methods for the investigation and prevention of waterborne disease outbreaks. Cincinnati, Environmental Protection Agency, 1990. 3. OSTERHOLM, M. T. ET AL. An outbreak of a newly recognized chronic diarrhoea syndrome associ- ated with raw milk consumption. Journal of the Rapp. trimest. statist. sanit. mand., 45 (1992) - 199 - American Medical Association, 256: 484-490 (1986). 4. PARSONNET, J. ET AL Chronic diarrhoea associated with drinking untreated water. Annals of internal medicine, 110: 985-991 (1989). 5. DEV, V. J. ET AL Waterborne outbreak of Es- cherichia coli 0157. Lancet, i: 1412 (1991 ). 6. McGowEN, K. L. ET AL Escherichia coli 0157:H7 from water. Lancet, i: 967-968 (1989). 7. LONG, E. G. ET AL. Morphologic and staining char- acteristics of a cyanobacterium-like organism associated with diarrhoea. Journal of infectious diseases, 164: 199-202 (1991 ). 8. SYKORA, J. L. & CRAUN, G. F. (eds). The taxonomy, detection, epidemiology and waterborne control of cryptosporidium. Pittsburgh, University of Pittsburgh, 1989. Wld hlth statist. quart., 45 (1992) 9. HAYES, E. B. ET AL Large community outbreak of cryptosporidiosis due to contamination of a fil- tered public water supply. New England journal of medicine, 320: 1372-1376 (1989). 10. RosE, J. B. ET AL Survey of potable water sup- plies for Cryptosporidium and Giardia. Environ- mental science and technology, 25 (8): 1393- 1400 (1991 ). 11. CRAUN, G. F. Epidemiologic studies of organic micropollutants in drinking-water. In Hutzinger, 0. (ed.), The handbook of environmental chem- istry. Volume 5A: water pollution. Berlin, Spring- er-Verlag, 1991. 12. BULL, R. J. & KOPFLER, F. C. Health effects of disin- fectants and disinfection by-products. Denver, American Water Works Association, 1991. - 200 - SURVEILLANCE AND CONTROL OF EMERGING ZOONOSES F.-X. Meslin• Introduction Emerging zoonoses are defined as zoonotic diseases caused either by totally new or partially new agents, or by microorganisms previously known, but now occurring in places or in species where the disease was previously unknown. New animal diseases with an unknown host spectrum are also included in our definition. An emerging zoonosis or potentially zoonotic disease always represents a major chal- lenge to the scientific and managerial capabilities of the veterinary profession and of its medical counter- part, as the situation requires that answers to a number of essential questions be given with the least possible delay. The immediate questions are: What is the nature of the agent? What is its potential for further spread? What control measures can be taken in the human and animal populations? How can surveillance best be established in infected and noninfected coun- tries? Most human diseases which have emerged recently are zoonoses, as natural animal reservoirs represent a more frequent source of new agents than the sudden appearance of a completely new entity (1). This is especially true for viruses which have at- tracted much attention in the recent past, but also for bacterial and parasitic zoonoses with wild ver- tebrates, in particular rodents and arthropods, in- volved in their transmission cycles. During the past 5 years alone, a large number of emerging zoonoses and potentially zoonotic dis- eases have appeared worldwide, calling for the attention of veterinary services and the scientific community. Examples of these diseases can be grouped into three main categories: • Diseases associated with changing farming prac- tices, trade and consumer habits. • Diseases associated with changing environmental conditions which influence reservoirs, vector and/ or victim species population parameters. • Pathogens acquiring new properties through adaptation, mutation and recombination. Factors explaining the emergence of a zoonotic or potentially zoonotic disease are usually complex, involving mechanisms at the molecular level, such as genetic drift and shift and modifications of the immunological status of individuals and populations. • Chief, Veterinary Public Health, Division of Communicable Dis- eases, World Health Organization, Geneva. b World Health Organization. Report of a WHO consultation on epidemiological emergency in poultry and egg salmonel/osis, Geneva, 20-23 March 1989. (Document WHO/CDSNPH/89.82). Broad social and ecological considerations, such as population growth and movement, food habits, a changing environment and many other dimensions should be considered as they may play a more important role in disease emergence than the above mechanisms. Consequently, a given disease may be classified in more than one group. Diseases associated with changing farming practices, trade and consumer habits Enteric zoonotic infections The increasing international trade in live animals and foodstuffs, together with the use of modern slaughter machinery, has favoured the spread of enteric zoonotic infections in an unprecedented manner. In many countries belonging to the in- dustrialized and developing world, the incidence of foodborne infections has increased dramatically dur- ing the past few years. According to the Pan American Health Organization (PAHO), many of these diseases have increased by as much as 100% within a few years. The WHO surveillance pro- gramme for the control of foodborne infections and intoxications in Europe reports an incidence of more than 1 200 cases per million inhabitants on average. In some industrialized countries the incidence is estimated to be as high as 10% of the population. Among these infections, salmonellosis has become a major problem in food hygiene and zoonosis con- trol. New strains of pathogens may be selected and find new opportunities for their spread. Thus dif- ferent phage types of Salmonella enteritidis have become apparent as invasive, egg-transmitted agents of an increasing proportion of human salmo- nellosis in the United States of America, and in a number of European countries (2). From there, these· pathogens spread, reaching a peak of incidence in some countries, and yet continuing on a steep in- crease in others. b Outbreaks of disease and infection caused by Es- cherichia coli 0157:H7 and some other related sero- vars are increasingly reported (3, 4). These infec- tions are characterized by a high morbidity and mortality in some age groups. According to a 1987 report of the National Institutes of Health, Bethesda, United States, case-fatality rates up to 10% nation- wide and ranging from 3 to 38% were reported in elderly residents of nursing homes and children. In some outbreaks, the source of infection has been identified as food of animal origin, but the potential role of livestock (cattle, swine and poultry) as a reservoir of Shiga-like toxin producing Escherichia coli (SL TEC) needs further investigation. Trade and the New World screwworm in Africa The New World screwworm fly, larvae of which cause a well-known myiasis in mammals in Latin America, was identified for the first time outside the Rapp. trimest. statist. sanit. mond., 45 (19921 - 201 - Americas in the Libyan Arab Jamahiriya in the summer of 1988 (5). It is believed that the larvae were carried there with a consignment of infested sheep from South America. The larvae grow in wounds, eating the tissues of live animals. Massive infestation may eventually lead to the death of the host animals. This fly and its larvae also cause the most serious forms of human myiasis in the Americas (6). A screwworm eradication programme was started in the Libyan Arab Jamahiriya late in 1990. The pro- gramme, coordinated by FAQ, was based on the release of sterile male screwworm flies (7). This programme involves the air shipment of millions of sterile flies from Mexico every week for air dispersal over the infested area in the Libyan Arab Jamahiriya. This campaign led to the elimination of the fly from the Libyan Arab Jamahiriya in October 1991. The New World screwworm represented a serious threat to livestock industries in the Libyan Arab Jamahiriya and neighbouring North African coun- tries. There was also the risk that the fly or larvae could be carried across the Sahara, and that the fly would establish itself in the rest of Africa. Had animals south of the Sahara become infected, it was thought that a disaster might have resulted with the destruction of up to 80% of wild animals in Africa, in addition to serious economic losses in the livestock industries.c Import of subhuman primates and viral diseases In September 1989 numerous cynomolgus monkeys shipped from the Philippines to the United States died in a United States quarantine facility located in Reston. A virus was isolated, similar to Ebola and later called "Reston virus" (8, 9). The Ebola virus had caused major epidemics of haemorrhagic fever in southern Sudan and northern Zaire in 1976. Dur- ing these outbreaks, very high case-fatality rates were reported in humans (up to 90% in Zaire) (10). Infections with the Reston virus from the Philippines occurred in a limited number of people profession- ally exposed to infected monkeys, but no illnesses were noted in these persons (11, 12). However, as the exact virulence of this virus was unknown, strict measures were taken to limit human exposure and to prevent human infection with this new agent (13). Animal feeding practices and bovine spongiform encephalopathy Although bovine spongiform encephalopathy (BSE) is not a zoonosis, the possible implications of this disease for public health have attracted the interest of animal and human health specialists and of the general public over the last four years. The recycling of rendered ruminant tissues for incor- poration in animal feed had become an accepted practice in many countries as it represented a cheap source of protein. This practice was however more common in certain countries, especially those where vegetable proteins were not available in large quan- tities. 'Food and Agriculture Organization of the United Nations. Screw- worm information. Animal Production and Health Division. Rome, FAQ, 1989. d World Health Organization. Technical guide fo, the diagnosis. prevention and control of Rift Valley fever (RVF) in man and animals. Alexandria, WHO, 1983 (WHO/EMRO technical publication no. 8). Wtd hlth statist. quart., 45 (1992) The results of epidemiological investigations carried out in the United Kingdom, where the disease was first diagnosed in 1985, suggest that BSE occurrence on a large scale was associated with exposure to a common source of infection, consisting of cattle and calf feed or supplements prepared with meat and bone meal containing viable scrapie-like agents (14, 15). Exposure increased during the period 1981-1982 as a result of the interaction of different factors. Three factors were instrumental to the appearance of BSE: (a) the presence of endemic sheep scrapie in an area, with (b) a high number of sheep relatively to cattle, and (c) the incorporation of large quan- tities of meat and bone meal deriving from ovine tissues in cattle diet. Infections occurred following major technological changes which took place over a short period of time in a number of the rendering plants of the United Kingdom, resulting in the main- tenance of a sufficient level of infectivity in the meat and bone meal and leading to the epidemic after 4 or 5 years. Recycling of SSE-infected bovine tissues in ruminant feed played a significant role in increas- ing the magnitude of the epidemic. The use of ruminant proteins in ruminant feed was banned as soon as evidence regarding the origin of the epi- demic became available. According to the Office international des epizooties (OIE) about 35 627 cases were reported in the United Kingdom, from November 1986 to 31 August 1991. Forty-one cases have also been diagnosed in Ireland, 2 in Oman, 1 in the Falkland Islands, and, more recently, 7 in Switzerland and 4 in France. A number of cases in Ireland and the cases in Oman and in the Falklands were in cattle imported from the United Kingdom. According to the results of a com- puter simulation, the disease is expected to dis- appear from the United Kingdom by the end of this decade, as evidence now strongly suggests that horizontal transmission does not exist and maternal transmission would not play a significant role in maintaining the disease. Diseases associated with changing environ- mental conditions A large number of the zoonoses which emerged during the 1980s fall into this category, as the cycles of a number of zoonotic diseases involve vectors or host species whose population dynamics largely depend upon environmental conditions. Three examples are cited below. Dams and arthropod-borne diseases Rift Valley fever (RVF) is an arthropod-borne viral disease of animals and man known to occur cycli- cally in the eastern and southern parts of Africa. In 1977 RVF occurred for the first time north of the Sahara, in Egypt, causing major outbreaks in which at least 18 OOO people fell ill and about 600 died. The number of deaths in animals was certainly also very large but remains unknown to this day. A second outbreak, much less widespread, was ob- served in 1978, after which the disease disappeared from the area. d In 1987 the first epidemic of RVF ever reported in West Africa was notified in Rosso (Mauritania) at the border with Senegal (16). Although RVF virus had previously been isolated from arthropods and ver- tebrates in a number of West African countries, this outbreak in human beings provided the first evi- - 202 - dence in this part of the world that effective virus amplification cycles could be established in a do- mestic animal (17). Fortunately the extent of this outbreak remained limited compared to the 1977 Egyptian epidemic, but it serves as a warning of the risk which other countries may run, especially those in sub-Saharan Africa, the southern part of the Medi- terranean and the Middle East. The outbreak in Mauritania occurred on the bank of the Senegal river upstream of the N'Diama dam project. Both in the outbreak in Mauritania and in the epidemic in Egypt there seemed to be some association with a large dam project which created conditions conducive to the breeding of mosquitos. It is assumed that the availability of water attracted nomadic populations and their herds of cattle, camels and small ruminants, thus creating con- ditions for the amplification of the virus and disease occurrence. Irrigation, agricultural development and parasitic diseases Zoonotic cutaneous leishmaniasis has become a sizeable problem in central and south-west Tunisia. The disease was endemic in this part of the country until a major outbreak occurred in 1982, close to the Sidi Saad dam, shortly after the project was com- pleted. The dam, together with vast programmes of agricultural development promoting intensive sheep rearing, and, to this purpose, cultivation of grass as fodder, contributed to the proliferation of the res- ervoir species (a rodent) and vector (phlebotomes). Incidentally, the grass which was grown belonged to the same family as the wild species which con- stitutes the staple food of the rodents (18). Similar outbreaks were reported in Morocco and other African and Middle-Eastern countries. New human settlements and vampire bat rabies Vampire bat rabies is another example of a viral disease which can become a major health hazard under certain conditions. The disease in man re- cently emerged as a significant problem in relation to movements of the human population and changes in environmental conditions and domestic animal densities. The relationship between the bite of rabid bats and paralytic rabies in cattle was definitely established in 1921. The first reported outbreak of human paralytic rabies diagnosed as poliomyelitis began in 1927 and a definitive diagnosis of rabies was established in 1931 (19). From 1929 to 1982, fewer than 200 cases of human rabies following bat bites were reported to the WHO Regional Office for the Americas (in the Pan American Sanitary Bureau). In cattle, however, an average of 100 OOO animals (of a value of US$40 million) are reported to die from vampire bat rabies every year. This makes vampire bat rabies a 'World Health Organization. Report of the expert consultation on the attention of persons exposed to rabies transmitted by vampire bats, Washington, D.C., 2-5 April 1991. (Document AMRO/HPV). ' Lopez, A. R. Outbreak of vampire-transmitted human rabies in Madre de Dios and in the Tutino and Mannayaque communities, Department of Amazonas, Peru. (Submitted for publication). • World Health Organization. Report of a WHO consultation on molecular epidemiology of influenza viruses, Athens, Georgia, United States of America, 5-6 September 1986. (Document WHO/ MIMNPH/86.1). major problem for livestock production in countries from Mexico to northern Argentina. Since 1984 there has been a considerable increase in the number of reports of human deaths due to vampire bat rabies received from Peru and BraziL • Such an outbreak of vampire bat rabies in humans was carefully studied in a remote area in the north- eastern part of Peru in which pig raising was intro- duced as part of a project for rural development and discontinued when it was realized that the pigs were a threat to traditional crops. The increased exposure of people can be attributed to the decreasing number of pigs which had pre- viously represented the major source of blood for the bats and facilitated their multiplication, and not, as often suggested, to an outbreak of bat rabies spilling over to man. 1 The primitive conditions under which people were living facilitated the occurrence of bites during the night. The absence of post- exposure care led to the high death rate (4.5%) in the communities. Pathogens acquiring new properties Influenza A viruses are causing significant diseases in animals, especially in swine, horses and birds (20). In man, influenza A viruses have caused the largest pandemics of this century (in 1918, 1957 and 1968). An estimated 20 million people died worldwide during the 1918-1919 pandemic. During such epidemics incidence rates can reach as much as 70% of the population and although case fatality is usually low, mortality shows a marked increase in comparision to the expected nonepidemic rate. In the United States alone there were approximately 70 OOO and 30 OOO excess deaths in the 1957 (Asian) and 1968 (Hong Kong) pandemics respectively (21). On the basis of serology in humans and reports of an epizootic in swine coinciding with the 1918 pan- demic, it was suggested that the 1918 pandemic might have originated from swine (22). Further studies confirmed the results of earlier serological and virus isolation/characterization studies that had associated swine influenza viruses and the disease in humans (23, 24)_ However, the situation proved to be much more complicated in that influenza viruses were isolated in many different species of wild and domestic birds. It is noteworthy that all the different subtypes of in- fluenza A viruses (H1-H4 and N1-N9) are perpetu- ated in aquatic birds, in particular migrating water fowl. Wild ducks maintain 13 of the 14 HA hae- magglutinins (HAI and all 9 neuraminidase protein (NA) subtypes of influenza viruses from which the current mammalian (including human) influenza A viruses probably derive (25, 26). Studies of viruses isolated from lower mammals (i.e. swine, seals, whales, mink, etc.) provided evidence that avian influenza viruses could be transferred to mammalian species and, more alarmingly, do so with high pathogenicity.9 The availability of rapid sequencing technology has recently provided a wealth of information on the phylogenic relationship of influenza virus genes, which strongly suggests that in addition to surface glycoprotein, genes of avian origin coding for internal proteins were intro- duced into the viruses which led to the 1957-1958 and 1968-1979 pandemics (27, 28). Rapp. trimest. statist. sanit. mond., 45 (1992) - 203 - Based on these phylogenic studies, it appears most likely that new pandemic strains in humans either derived from avian influenza viruses directly by in- terspecies transfer or after reassortment with the circulating human strains. New influenza viruses spreading to horses without reassortment have been isolated in northern China. These strains have been shown to differ antigenically from those currently circulating in equines and humans. Their potential for becoming harmful for human beings needs to be carefully evaluated (29). In order to obtain an early warning of the occurrence of new virus strains and try to adapt vaccine produc- tion, a network for the surveillance of influenza in man was established in WHO in the 1960s. This network now comprises 110 laboratories in 79 countries. Unfortunately, continued surveillance and virological studies of animal influenza A viruses have remained low in the animal health and produc- tion sector of most countries. Impact of emerging zoonoses and research promotion Emerging zoonoses or potential zoonotic problems may have huge economic and social implications. Vampire bat rabies is a problem for cattle breeders in countries of Central and Latin America and the potential implications of the New World screwworm establishing itself south of the Sahara were dis- astrous, possibly endangering the wild fauna of East African countries. The economic impact of bovine spongiform encephalopathy as a cattle disease is enormous for the animal production sector in the United Kingdom. Its potential implications for public health contributed to increasing the burden for the meat sector as restrictions were enforced in the meat trade and in trade in other cattle products. A number of medicinal products prepared from bovine tissues have been banned in some BSE-infected countries and producers are now required to procure raw material from safe sources. These outbreaks of infections of a zoonotic nature or with an unknown host spectrum have in most cases contributed to the development of better control tools, diagnostics and forecasting systems. For example, the outbreak of Rift Valley fever in Rosso re-emphasized the need to develop safe and effec- tive veterinary vaccines suitable for large-scale im- munization, since the currently available inactivated and live-attenuated vaccines have major disadvan- tages for mass application. A mutagen-attenuated Rift Valley fever vaccine (30) has recently been shown to be safe and efficacious in sheep, and would represent a good vaccine candidate for mass production. The need to improve diagnostic tech- niques for disease surveillance led to the develop- ment of an ELISA which is now available for anti- body testing. Developments have also been recorded in the rabies field, such as the demonstration of the efficacy of the oral vaccination technique using a red fox bait, and vaccine for raccoon dog rabies elimination in Finland. The increasing trend in the occurrence of bat rabies in Europe has led to a better knowledge of the immunogenicity provided by current rabies vaccines against European bat lyssaviruses. The emergence of BSE has given a new thrust to research on animal and human diseases caused by Wld hlth statist. quart., 45 (1992) unconventional agents (31 ). Ongoing research on these agents responsible for spongiform en- cephalopathies, using mainly scrapie as a model, is expected to lead to the understanding of the patho- genesis of these diseases. Lessons learned from this research may even help elucidate the mechanisms of common central nervous system degenerative dis- orders such as Alzheimer's disease, myotrophic lat- eral sclerosis and Parkinson's disease (32). The above clearly shows that the challenge created by emerging zoonoses has often led to the develop- ment of new biologicals and laboratory techniques to tackle the problem. These new technologies are sometimes not available or not applied at field level and have therefore not always had the expected impact on our ability to control a number of zoonotic disease outbreaks. This is especially true for these exotic diseases which occur cyclically every 5-10 years, and for which there is no permanent and organized thrust aimed at transforming promising laboratory findings into easily transferable tech- nologies. Forecasting and early detection of emerging diseases Emerging zoonotic or potentially zoonotic problems are clearly not rare events and with the increasing human population, the related environmental changes and urbanization, as well as ever-increasing trade and travel, one can expect to see more epi- demics of such diseases. Fortunately a large proportion of the diseases falling within our definition are not caused by entirely new pathogens, but rather by known agents invading new territories or adapting to new hosts. Essential technologies for diagnosis, surveillance and control usually already exist. The situation in most cases is therefore far better than looking for the unknown. The level of active searching and sophistication nec- essary for the detection of the majority of the emer- ging zoonotic diseases is thus likely to remain within acceptable technical and economic limits. Some of the new agents and diseases which recently emerged could clearly not have been predicted. For example, although it was said that it was there to be found, the isolation of an Ebola-related virus as the cause of a disease outbreak in shipments of mon- keys imported from Asia came as a total surprise for a number of reasons. Firstly, there was no compel- . ling epidemiological evidence indicating that sub- human primates were the natural reservoirs of the known Ebola viruses; secondly, all Ebola viruses had so far been isolated in Africa; thirdly, Ebola infec- tions due to African viruses had always been assoc- iated in humans with severe haemorrhagic fevers and high case-fatality rates, whereas the Ebola- Reston virus which was fatal in monkeys did not induce illness in the few humans who were infected. Further investigation following the characterization of the Reston virus, consisting in serosurveys against different filoviruses carried out in monkey colonies in the United States and the Philippines, showed - contrary to all beliefs - that filovirus infections were not uncommon even in closed col- onies. The BSE epidemic already mentioned resulted from the combination of numerous factors, each of which taken in isolation would not have led to such an occurrence. However considering a posteriori the - 204 - resistance of the agent to most conventional chemi- cal and physical inactivating techniques, together with the factors which triggered the epidemics, the establishment of a ban on the use of all or selected ruminant tissues in cattle feed has become the key measure to halt or prevent the animal disease in scrapie- and SSE-infected countries. The perception of the level of risk associated with the use of rumi- nant tissues in animal feed and of bovine tissues as food for humans resulted in the adoption of more stringent measures which took into consideration some uncertainties, especially regarding the strength of the species barrier. Measures now taken for the prevention of the hypothetical risk for humans in the United Kingdom and the group of countries where BSE occurs sporadically are considered adequate by all experts in that field. Another lesson to be learned from this is that scrapie in sheep, which is still considered by many infected countries as a minor animal health problem, should attract more attention in the future. On the other hand, it is well known that major changes introduced into the environment may create conditions favourable to the emergence of vector- borne diseases in animals and humans,h especially when the modifications are related to water re- sources management (e.g. building of irrigation sys- tems, dams etc.). Newly-available technologies (re- mote sensing/satellite imagery) have proved useful in predicting the risk of emergence of Rift Valley fever in eastern Africa. The technique is very promis- ing and can be applied to many arboviruses on the African continent. In certain circumstances, as shown by the descrip- tion of the outbreak of cutaneous leishmaniasis, man may involuntarily create the best possible conditions for the explosion of a disease. Sometimes a new but fragile equilibrium can be established between newly-introduced human activities in the animal pro- duction field and increased populations of vectors of the disease. As suggested in some outbreaks of vampire bat rabies in Peru, it was when pig farms disappeared that the incidence of vampire bat bites and rabies cases in humans increased. "Food and Agriculture Organization of the United Nations. Effects of agricultural development on vector-borne diseases. Edited ver- sion of the working papers presented to the seventh annual meeting of the joint WHO/FAO/UNEP panel of experts on environ- mental management for vector control, 7-11 September 1987. Rome, FAQ. 1987. (Document FAO/AGLJMISC/12/87). Strengthening global surveillance of zoonoses Early detection of these problems requires that sur- veillance at the global level be reinforced. An effec- tive way to achieve this would be to strengthen the existing network of WHO collaborating centres, es- pecially those located in developing tropical coun- tries, by providing them with the appropriate techno- logy and training in pathogen agent detection and characterization. Highly-specialized laboratories are required which may only be available at the inter- national level. At the country level, even more important than good laboratory support is a surveillance system based on field staff properly trained in epidemiological tech- niques for outbreak investigation. The organization of training in field epidemiology of national veteri- nary staff involved in disease reporting is considered an essential step towards early disease detection, outbreak investigation and reporting. In order to facilitate the rapid flow of information at the global level, national surveillance systems must be linked to international scientific institutions and global epi- demiological investigation services by modern means of communication. A number of surveillance networks have already been established under WHO's aegis in the zoonoses field in some regions. For example rabies sur- veillance in Europe and the Americas is well or- ganized and foodborne infections and intoxications are monitored in Europe, although improvements are still needed regarding speed and sensitivity of the system at both national and international levels. Zoonosis surveillance systems are, however, still dangerously deficient in many places in the world, so that an emerging zoonotic problem may be un- detected for a while until it has reached such a magnitude that control requires huge efforts. Sys- tematic joint entomological, zoological and virologi- cal studies prior to the onset of projects related to water resources management in tropical countries would certainly allow for an evaluation of the risks of emergence of these diseases and the design of contingency plans for the control of the potential hazards. Along the same principles, special attention should be paid to potential zoonoses whenever human settlements are established in previously un- inhabited areas. The role of veterinarians in as- sessing potential hazard and related risks, and in detecting and controlling outbreaks is crucial, and the profession must adapt and strengthen its profici- ency to act effectively both in the field and within multidisciplinary groups. SUMMARY "Emerging zoonoses" are defined as zoonotic dis- eases caused either by apparently new agents, or by previously known microorganisms, appearing in places or in species in which the disease was pre- viously unknown. New animal diseases with an un- known host spectrum are also included in this defini- tion. Natural animal reservoirs represent a more frequent source of new agents of human disease than the sudden appeareance of a completely new agent. Factors explaining the emergence of a zoonotic or potentially zoonotic disease are usually complex, involving mechanisms at the molecular level, such as _genetic drift and shift, and modification of the immunological status of individuals and populations. Social and ecological conditions influencing popula- tion growth and movement, food habits, the en- vironment and many other factors may play a more important role than changes at the molecular level. Rapp. trimest. statist. sanit. mand., 45 ( 1992) - 205 - Diseases associated with changing farming prac- tices, trade and consumer habits. Bacterial enteric diseases due to Salmonella enteritidis and Echeri- chia coli 0:157 are examples of diseases associated with changing farming practices and consumer habits. The increasing trade in live animals for ani- mal production and research led to the introduction of the New World screwworm to the Libyan Arab Jamahiriya in 1989 and an Ebola-like virus in monkeys in quarantine facilities in the United States of America. The development of the epidemics of bovine spongiform encephalopathy (BSE) in the United Kingdom is due to multiple factors including the increasing use of ruminant proteins as feed for animals. Diseases associated with changing environmental conditions which influence reservoirs, vectors and/or victim species population parameters. Projects for the management of water resources (dams, irriga- tion) have brought Rift Valley fever to Rosso (Mauri- tania) and cutaneous leishmaniasis to countries of northern Africa. Human rabies outbreaks following contacts with infected vampire bats in Peru and Brazil are examples of changing vector and victim population parameters. Pathogens acquiring new properties through adap- tation, mutation and recombination. Recently a new type of equine influenza viruses, antigenically dif- ferent from circulating human and equine influenza strains, were detected in northern China. In general, these outbreaks have contributed to the development of better control tools, diagnostic tech- niques and forecasting systems. A large proportion of emerging zoonoses are not caused by entirely new pathogens but rather by known agents invading new territories or adapting to new hosts. Essential technologies for diagnosis, surveillance and control usually already exist. Early detection of emerging diseases requires re- inforced surveillance on a global level. This could be achieved by strengthening the existing network of WHO collaborating centres and particularly those in developing tropical countries, by providing ap- propriate technology and training in detection and characterization of pathogenic agents. Highly specialized laboratories would serve as a backup -reference resource. At country level, it is essential that field staff be properly trained in epidemiological techniques for outbreak investigation. An emerging zoonosis or potentially zoonotic disease always represents a major challenge to the scientific and managerial capabilities of the veterinary profession and its medical counterpart. The role of veterinarians in assessing potential hazard and related risks, and in detecting and controlling outbreaks is crucial, and the profession must adapt and strengthen its profici- ency to act effectively both in the field and within multidisciplinary groups. RESUME Surveillance et lutte contre les nouvelles zoonoses Par «nouvelles» zoonoses, on entend des zoonoses qui sont dues soit a des agents apparemment nou- veaux, soit a des micro-organismes dont !'existence etait deja connue mais qui apparaissent dans des lieux au dans des especes ou la maladie etait jus- qu'alors inconnue. Rentrent egalement dans cette definition de nouvelles zoonoses dont on ignore la gamme des hates capables de les heberger. L'origine de nouveaux agents causateurs de maladie humaine est plus souvent imputable a des reservoirs animaux qu'a la brusque apparition d'un agent en- tierement nouveau. Les facteurs expliquant !'appari- tion d'une maladie zoonotique ou potentiellement zoonotique sont habituellement complexes, impli- quant des mecanismes qui se situent au niveau moleculaire tels que des variations geniques mineu- res au majeures au des modifications de l'etat im- munologique d'individus et de populations. Les con- ditions sociales et ecologiques qui influent sur la croissance et le mouvement demographiques, sur les habitudes alimentaires, de meme que les facteurs ecologiques et beaucoup d'autres parametres, peu- vent jouer un role dont !'importance depasse celui des modifications intervenant au niveau moleculaire. Maladies associees a des modifications des prati- ques agricoles et commerciales et des habitudes des consommateurs. Les maladies intestinales d'origine bacterienne dues a Salmonella enteritidis et a Esche- richia coli 0:157 sont des exemples d'infections asso- ciees a des modifications affectant les pratiques agricoles et les habitudes des consommateurs. Quant a l'accroissement du commerce des animaux Wld h/th statist. quart., 45 (1992) vivants en vue de la production animale et de la recherche, ii a provoque !'introduction de Cochlio- myia hominivorax. d'origine americaine, en Jamahi- riya arabe libyenne en 1989 et celle d'un virus du genre Ebola chez les singes dans des installations de quarantaine des Etats-Unis d'Amerique. L'apparition d'epidemies d'encephalopathie bovine spongiforme (BSE) au Royaume-Uni est due a des facteurs multi- ples, dont !'utilisation croissante de proteines de ruminants dans les nourritures destinees aux ani- maux. Maladies associees a des modifications environne- mentales influant sur les reservoirs, les vecteurs et/ou les especes atteintes. Les grands travaux d'amenagement des ressources hydrauliques (barra- ges, installations d'irrigation) ant introduit la fievre de la Vallee du Rift a Rosso (Mauritanie) et la leishmaniose cutanee dans des pays d'Afrique sep- tentrionale. Les episodes de rage humaine survenus a la suite de contacts avec des vampires infectes au Perou et au Bresil fournissent une illustration des changements qui peuvent se produire dans les ca- racteristiques du vecteur et des populations attein- tes. Agents pathogenes acquerant de nouvelles proprie- tes par des mecanismes d'adaptation, de mutation et de recombinaison. En Chine septentrionale, ii a re- cemrnent ete decele un type nouveau de virus de grippe equine, dont les caracteristiques antigeniques different de celles des souches de grippe humaine et equine en circulation. - 206 - De fa~on generale, ces episodes ant contribue au perfectionnement des moyens de lutte ainsi qu'a la mise au point de techniques de diagnostic et de systemes de prevision ameliores. Une forte propor- tion des nouvelles zoonoses ne sont pas dues a des agents pathogenes entierement nouveaux, mais plu- tot a des agents deja connus qui envahissent de nouveaux territoires ou s'adaptent a des hates nou- veaux. Le plus souvent, on dispose deja des techni- ques essentielles de diagnostic, de surveillance et de lutte. Le depistage precoce de nouvelles maladies exige que la surveillance soit renforcee au niveau mondial. A cette fin, ii faudrait consolider le reseau existant des centres collaborateurs de l'OMS, en particulier de ceux qui sont implantes dans des pays tropicaux en developpement, en leur fournissant une technolo- gie appropnee et en formant leur personnel au depistage et a !'identification des agents pathogenes. Les laboratoires hautement specialises auraient un role de soutien et de reference. Au niveau des pays, ii est essentiel de bien former le personnel de terrain aux techniques d'investigation epidemiologique. Lorsqu'apparait une zoonose ou une maladie potentiellement zoonotique, elle consti- tue toujours un probleme majeur qui met a l'epreu- ve les capacites scientifiques et gestionnelles du corps veterinaire et medical. Les veterinaires jouent un role crucial dans !'evaluation des risques reels et potentiels et dans le depistage et la lutte contre les epidemies, et ils doivent s'adapter et s'armer plus efficacement pour intervenir sur le terrain comme dans le cadre d'equipes pluridisciplinaires. REFERENCES - REFERENCES 1. MORSE, s. & SCHLEUDERBERG, A. Emerging viruses: the evolution of viruses and viral diseases. Journal of infectious diseases, 162: 1-7 (1990). 2. RODRIGUEZ, D. c. ET AL International increase in Salmonella enteritidis: a new pandemic? Epi- demiology and infection, 105: 21-27 (1990). 3. MACDONALD, K. L. ET AL Escherichia coli 0157:H7 - an emerging gastrointestinal pathogen. Re- sults of a one-year prospective, population- based study. Journal of the American Veterinary Medical Association, 259 (24): 3567 (1988). 4. OSTROFF, S. M. ET AL Surveillance of Escherichia coli 1057, isolation and confirmation, United States, 1988. Morbidity and mortality weekly report, 40 (SS1) (1991). 5. 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Pendant des siecles, la maladie a sevi de maniere endemique dans cette region densement peuplee, occasionnant de temps a autre des poussees explosives qui de- passaient alors ses limites naturelles pour s'etendre a d'autres regions de l'lnde. L'annee 1817 marque un tournant dans l'histoire du cholera. Cette annee-la, une poussee epidemique d'une extreme violence se propage en 3 mois a !'ensemble de la province du Bengale, puis a toute l'lnde, a Ceylan et a la Birma- nie. Par voie de terre, mais surtout par voie mari- time, l'epidemie gagne progressivement le Siam, Malacca, Java, au elle provoque 100 OOO marts, Borneo, les Philippines, la Chine et le Japan qu'elle atteint en 1822. Vers l'ouest, !'invasion de l'Arabie puis d'Oman (1821) semble liee au debarquement d'un corps expeditionnaire anglais envoye de l'lnde vers ce pays. Remontant le golfe Persique, les val- lees du Tigre et de l'Euphrate, la maladie atteint Bagdad, la Syrie, le Caucase pour venir finalement s'eteindre sur les rives de la Mediterranee orientale: le cholera se declare en effet a Alexandrette (aujour- d'hui lskenderun, Turquie) en 1823 mais disparait completement de cette zone vers la fin de l'annee. Au cours de l'ete 1824, les derniers cas sont rappor- tes en Chine. L'epidemie etait consommee; elle lais- sait derriere elle beaucoup de marts et de desarroi mais pas de foyer endemique. La premiere pandemie sera suivie de 5 autres au cours du XIXe siecle (Tableau 1). Ces pandemies TABLEAU 1. PANDEMIES DE CHOLERA ENREGISTREES AU x1x• SIECLE TABLE 1. CHOLERA PANDEMICS RECORDED IN THE XIXth CENTURY Pandemie - Pandemic Premiere pandemie - First pandemic Deuxieme pandemie - Second pandemic Troisieme pandemie - Third pandemic Ouatrieme pandemie - Fourth pandemic Cinquieme pandemie - Fifth pandemic Sixieme pandemie - Sixth pandemic Duree Duration 1817-1823 1826-1851 1852-1859 1863-1879 1881-1896 1899-1923 presentent des caracteristiques communes. Elles sont probablement toutes causees par le vibrion cholerae decrit par Koch en 1884. On peut presque • Soumis pour publication le 7 fevrier 1992. b Renforcement des Services epidemiologiques et statistiques, Divi· sion de la Surveillance epidemiologique et Appreciation de la Situation sanitaire et de ses Tendances, Organisation mondiale de la Sante, Geneve. ' Organisation mondiale de la Sante. Cinquieme rapport du Comite de la Quarantaine internationale ii l'Assemblee mondiale de la Sante. Actes officiels, 87: 400 (1958). toujours retracer a leur origine une recrudescence de l'activite epidemique au Bengale, entrainant une nouvelle vague de cholera et !'infestation de nouvel- les zones, au provoquant, a partir de la troisieme pandemie, la recrudescence de !'infection dans des zones au elle etait restee endemique a la suite des pandemies anterieures. Les mouvements massifs de personnes jouent un role evident et souvent dramati- que dans la contagion, que ce soit le long des routes commerciales (maritimes et terrestres), a !'occasion d'un pelerinage (La Mecque sera la plaque tournante du cholera dans le monde arabe entre 1831 et 1912), au a la suite d'operations militaires. Les pandemies successives suivront toujours les memes routes car ce sont les routes que prennent les voyageurs (cotes maritimes, ports, vallees, routes caravanieres). Le developpement de la navigation a vapeur, l'ouver- ture du Canal de Suez (1869), l'avenement des che- mins de fer, favorisent d'ailleurs l'ouverture de nou- velles routes au cholera, ainsi que son extension rapide. Le cholera toutefois ne penetrera pas les terres situees a des latitudes extremes, ni celles tres protegees par leur insularite. La mortalite globale de ces 6 pandemies est impossible a preciser mais elle est enorme et se chiffre en millions de victimes. Le taux de letalite du cholera a cette epoque etait en effet tres eleve, atteignant frequemment 50% et pou- vant atteindre 70% des cas enregistres (1). Les 2e, 3e, 4e et 5e pandemies causerent des ravages etendus, atteignant progressivement la majorite des pays de l'epoque, de l'lnde au Japan en passant par I' Asie du Sud-Est, du Mayen-Orient a la Russie, et du Quebec au Chili. L'Europe de l'Ouest ne fut pas epargnee. Toutefois, cet assaut porte par le cholera au cceur des pays les plus avances de l'epoque declencherait des reactions dignes de leur creativite. Sur le plan politique, la 2e pandemie provoquerait la convocation de la premiere Conference sanitaire in- ternationale (Paris, 1851 ). Sur le plan scientifique, la contagiosite du cholera serait definitivement prou- vee et sa transmission par voie hydrique demontree (Snow, 1854). L'agent causal, Vibrio cholerae, serait identifie (Koch, 1884). A terme, !'effort de collabora- tion international suscite par la maladie culminerait avec la creation de la premiere organisation interna- tionale de sante a vocation mondiale, l'Office inter- national d'Hygiene de Paris (1907). Entre 1923, date a laquelle prend fin la 6~ pandemie, et 1965, le cholera resta localise en Orient. Durant cette periode, l'lnde rapporte d'ailleurs, a peu d'exceptions pres, entre 90% et 99% du nombre total des deces de cholera enregistres annuellement. Les quelques cas qui apparurent aux Celebes en 1937 susciterent cependant un grand interet epidemiologi- que car ils etaient de toute evidence dus au seul Vibrio cholerae El Tor qui avait ete decouvert par Gotschlich en 1905 et auquel on n'avait pas porte beaucoup d'attention jusque-la. L'opinion des experts de l'epoque etait que seul le vibrion classi- que pouvait causer des epidemies (2) et la reappari- tion de cas a Makassar (Celebes) en 1957 n'ebranla pas cette confiance.c Rapp. trimest. statist. sanit. mond., 45 ( 19921 209 - La 7• pandemie La 7e pandemie se distingue des precedentes par plusieurs aspects; d'abord son point de depart a ete les Celebes et l'agent responsable Vibrio cholerae El Tor; ensuite, la pandemie s'est developpee de ma- niere beaucoup moins explosive que les preceden- tes. Malgre la frequence, l'intensite et la rapidite des deplacements modernes, l'epidemie mit 10 ans pour atteindre l'Afrique et 30 ans pour atteindre les Ame- riques. Enfin, la letalite observee a ete incomparable- ment inferieure a celle des epidemies anterieures. En contraste, la maladie est souvent restee endemique dans les pays en developpement qu 'elle a atteints. Extension. La progression de la 7e pandemie s'est faite en 3 phases (Carte 1): de 1961 a 1966, exten- sion rapide d'est en ouest jusqu 'a l'lraq, en passant par le Bengale ou, en quelques annees, le vibrion El Tor s'est substitue en grande partie au vibrion classi- que; en 1970-1971, menace de l'Europe et attaque de l'Afrique sur 3 fronts (3); a partir de 1991, invasion du Perou (4) et extension a l'Amerique latine (5). L'apparition du cholera en Guinee (aout 1970) fut d'autant plus dramatique qu'elle fut d'abord dissi- mulee par les autorites nationales, amenant le Direc- teur general de l'OMS, fait sans precedent, a la notifier d'autorite (6). Situee a plusieurs milliers de kilometres des zones epidemiques les plus proches a l'epoque (Egypte, aout 1970) ii est vraisemblable que la Guinee ait ete infectee par les passagers de vols en provenance de pays eux-memes affectes (7) . Le cholera progressa rapidement d'ouest en est le long de la cote africaine. La plaine costale, chaude, humi- de et lagunaire, offrit un terrain de choix pour la propagation de la maladie de proche en proche, suivant les trajets normalement frequentes par les pecheurs, bateliers et commer~ants locaux. En no- vembre, franchissant d'une traite 1 OOO km en direc- tion de l'interieur, la maladie, probablement appor- tee par les passagers d'une voiture (8), atteignit Mopti (Mali). De la, le cholera se repandit a tous les pays du Sahel en suivant l'axe du fleuve Niger, puis a la Mauritanie vers l'ouest, au Nigeria, au Tchad et au Nord Cameroun vers l'est (9). En 2 ans, 29 pays africains furent atteints par la maladie, qui est restee a l'etat endemique dans ce continent depuis lors. Vingt ans plus tard (janvier 1991) !'irruption du cho- lera au Perou et son extension rapide a I' Amerique latine n'est pas sans rappeler l'epidemie africaine: l'Amerique latine, comme l'Afrique, n'avait pas connu de cas de cholera depuis le siecle dernier; le pays le premier frappe est situe a plusieurs milliers de kilometres de tout foyer endemique OU epidemi- que; par contre, de serieux problemes politiques et economiques affectent l'etat de son developpement; enfin, la diffusion initiale de l'epidemie est tres rapide: a partir du moment ou les premiers cas sont reconnus au Perou, 2 OOO km de cote sont infectes en 2 semaines; le pays voisin (Equateur) est atteint en moins de 5 semaines, et le circonvoisin (Colom- bie) en moins de 6 semaines. Apres s'etre commu- niquee encore a deux autres pays voisins (Bresil, Chili), la maladie apparait soudain au Mexique dans une petite communaute isolee et situee a 3 OOO km de la zone epidemique la plus proche. Les efforts vigoureux effectues par ce pays pour circonscrire les premiers cas ne peuvent eviter !'extension a cinq Etats mexicains en quelques semaines, puis aux pays voisins d'Amerique centrale. Le vibrion El Tor aura done boucle le tour du monde en 30 ans; au cours de cette periode, peu nombreux sont les pays situes entre le 45• degre de latitude nord et le 30• deg re de latitude sud qui n' ont pas rap po rte de cholera (Carte 2); et encore faut-il noter que, parmi ceux-ci, certains ont ete le siege d'epidemies notoi- res; d'autres ont ete proteges par leur insularite (Madagascar, Maurice, Seychelles) ou par leur eloi- gnement de la zone initiale (Botswana, Lesotho, Namibie) . FIG. 1 NOMBRE DE CAS DE CHOLERA NOTIFIES A. L'OMS, 1961-1991, PAR REGION ET PAR ANNEE NUMBER OF CASES OF CHOLERA REPORTED TO WHO, 1961-1991, BY REGION AND BY YEAR 367058 1 ~ ;~ L- 0 I I 0 I 15 10 5 0 0 g ! nl ' ! - I I I n ~ I I ~ I I I I I 1961 63 65 67 69 1971 73 75 77 79 1981 83 85 87 89 1991 ~ Afriq ue Africa Wld hlth statist. quart., 45 ( 1992) - Asie Asia ~ Ameriques Americas II Reste du monde L___J Rest of the world "' "' :, ~ · C AR TE 1 . P R O G R ES SI O N D E L A 7 ° P A N D E M IE E N TR E 19 61 E T 19 91 M A P 1 . E X P A N S IO N O F TH E S EV EN TH P A N D E M IC B ET W EE N 1 96 1 A N D 1 99 1 19 7- 1 µ 1 96 3 ' Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e x pr es si on o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f th e se cr e ta ria t o f th e W H O c o n c e rn in g th e le ga l st at us o f a n y c o u n tr y, t er rit o ry , ci ty o r a re a o r o f its a u th or iti es , o r c o n c e rn in g th e de lim ita tio n o f its fr on tie rs o r bo un da rie s - Le s de si gn at io ns u til is ee s su r ce tte c a rte e t la pr es en ta tio n de s do nn ee s qu i y fig ur en t n ' im pl iq ue nt . de la p ar t de ! 'O rg an is at io n m o n di al e de la S an te , a u cu n e p ris e de p os iti on q ua nt a u st at ut ju rid iqu e de te l o u t el p ay s, te rr ito ire , v ill e o u z o n e , o u d e se s a u to rit es , n i q ua nt a u tra ce d e se s fro nt iE !re s. N 0 ~ Q ::,- ~ "' ii:' ~· . Q c: . , ? ... "' "' "' ~ 0 C AR TE 2 . P A Y S , O U Z O N ES A . L' IN TE R IE U R D E S P A Y S , O U D E S C A S D E C H O LE R A O N T ET E N O TI FI ES ( 19 61 - 19 91 ) M A P 2 . C O U N TR IE S O R A R E A S W IT H IN C O U N TR IE S W H ER E C AS ES O F C H O LE R A H A V E B EE N R EP O R TE D , 19 61 -1 99 1 o = 0 0 0 D 0 0 0 ' \ Th e d es ig na tio ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e x pr es si on o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f th e se cr e ta ria t o f th e W H O c o n c e rn in g th e le ga l s ta tu s o f a n y c o u n tr y, t er rit or y, ci ty o r a re a o r o f its a u th or iti es , o r c o n c e rn in g th e de lim ita tio n o f its fro nt ie rs o r bo u n da rie s - Le s de si gn at io ns u til is ee s su r ce tte c a rt e e t la p re se n ta tio n de s do nn ee s qu i y f ig ur en t n 'im pl iq ue nt , de la p ar t de ! 'O rg an is a tio n m o n di at e de la S an te , a u cu n e p ris e de p os iti on q ua n t a u s ta tu t jur id iq ue d e te l o u t el p ay s, t er rit oi re . v ill e a u z o n e , o u d e se s a u to rit es , n i qu an t a u tra ce d e se s fro nt iE lre s. - 212 - Incidence. L'intensite de la 7• pandemie a ete globa- lement moderee en dehors de deux annees (1971 et 1991) qui correspondent a !'extension de la maladie a l'Afrique et a l'Amerique respectivement; en effet, le nombre total de cas rapportes annuellement a l'OMS au cours de cette pandemie a oscille le plus souvent entre 30 OOO et 60 OOO par an (Fig. 1). De 1970 a 1976 ces chiffres sont largement depasses a la suite de !'introduction du cholera en Afrique (ou ii cause plus de 70 OOO cas en 1971) et de l'impact d'une epidemie tenace en lndonesie jusqu'en 1976. De plus, l'endemisation du cholera en Afrique et la diminution constante de son incidence en Asie ame- nent en 1982 un changement historique dans la distribution geographique mondiale de la maladie; pour la premiere fois l'Asie cesse en effet d'etre le principal pourvoyeur de cas, aux depens de l'Afrique d'abord, puis de la Region des Ameriques en 1991, lorsque !'introduction du cholera au Perou provoque la flambee epidemique la plus intense de cette pan- demie: 1% de la population de ce pays fut atteinte au cours des 5 premiers mois (causant plus de 220 OOO cas). Letalite. Les taux de letalite observes dans les pays au cours de la 7• pandemie ont ete nettement infe- rieurs a ceux observes lors des pandemies prece- dentes; ils sont de plus en constante baisse, sauf en Afrique (Fig. 2). Le taux de letalite au niveau mon- dial en 1991 a ete de 3,3%. Ces donnees refletent plusieurs facteurs; d'une part une amelioration de la notification, tendant a enregistrer aujourd'hui de nombreux cas benins qui ne l'auraient pas ete autre- fois; d'autre part la moindre virulence du biotype El Tor si on la compare a celle du biotype classique; enfin et surtout une meilleure connaissance de la maladie et la capacite croissante des gouvernements a mettre en reuvre rapidement des moyens de lutte efficaces. Ainsi, ii n'est guere surprenant de consta- ter que la letalite du cholera en Afrique reste tres superieure a la moyenne mondiale. Endemicite. Le vibrion cholerae El Tor est plus resis- tant et, en particulier, plus apte a survivre dans l'environnement que le vibrion cholerae classique. Ainsi, le cholera est devenu plus ou mains endemi- que dans de nombreux pays ou !'hygiene du milieu est deficiente, !'education sanitaire peu developpee et l'acces a une quantite suffisante d'eau potable difficile, voire impossible, pour la majorite. Depuis que le cholera a ete introduit en Afrique, jamais mains de 11 pays n'ont notifie des cas a l'OMS. La capacite du biotype El Tor a survivre dans l'environ- nement a d'ailleurs ete confirmee par !'apparition, en dehors de toute epidemie, d'un foyer de cholera autochtone sur les cotes des Etats qui bordent le golfe du Mexique (70, 11). Depuis 1973, ce foyer a determine dans les Etats du Sud des Etats-Unis, !'apparition de cas sporadiques, chez des personnes ayant consomme du crabe, des crevettes ou des huitres recueillis dans les eaux du Golfe. L'existence d'un reservoir naturel a egalement ete soupi;:onnee pour expliquer !'apparition sporadique de cas de cholera au Queensland (12) ainsi que la recurrence du cholera en Sardaigne de 1973 a 1979 (13). Situation actuelle Bi/an global En 1991, d'apres les donnees disponibles a l'OMS au 16 janvier 1992, 52 pays ont notifie des cas de cholera a l'OMS (Carte 3). Parmi eux, 21 rap- portaient deja !'existence de zones infectees sur leur territoire en 1990; 26 pays ont ete nouvellement infectes, essentiellement en Amerique latine; enfin, 5 pays ont notifie seulement des cas importes. Au total, plus d'un demi-million de cas et plus de 16 OOO deces de la maladie ont ete rapportes. Le nombre de cas est superieur a la totalite de tous ceux qui ont ete rapportes au cours des 5 annees precedentes, ce qui en fait le plus eleve, et de loin, FIG. 2 " Cl ~ c " e " 0.. I " Cl "' c: " e :, 0 0.. TAUX DE LETALITE DU CHOLERA DANS LE MONDE, 1961-1991, PAR REGION ET PAR ANNEE CASE-FATALITY RATE OF CHOLERA IN THE WORLD, 1961-1991, BY REGION AND BY YEAR % 50 ~-----------------------------------~ 40 30 20 10 61 62 63 64 65 6 6 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 Afrique - Africa Asie Asia ~ Ameriques ~ Americas - Total Rapp. trimest. statist. sanit. mond., 45 (1992) "' " ' ~ 0 • Ca na da US A Bo liv ia Br az il Ch ile Co lo m bi a Ec ua do r El Sa lva do r G ua te m al a H on du ra s M ex ic o N ic ar ag ua Pa na m a Pe ru Ve ne zu el a C AR TE 3 . P A Y S , O U Z O N ES A L 'IN TE R IE U R D E S P A Y S , O U D E S C A S D E C H O LE R A O N T ET E N O TI FI ES , 1 99 1 M A P 3 . C O U N TR IE S O R Z O N ES W IT H IN C O U N TR IE S W H ER E C A S E S O F C H O LE R A W ER E R EP O R TE D , 1 99 1 • Fr an ce R om an ia • Sp ai n Uk ra in e • Ru ss ia n Fe de ra tio n A ng ol a Be ni n Bu rk in a Fa so Ca m er oo n Ch ad Co te d 'Iv oi re G ha na Li be ria N ig er N ig er ia Sa o To m e a n d Pr in ci pe To go Bu ru nd i M al aw i M oz am bi qu e R w an da U ga nd a U . R. o f T an za ni a Za m bi a o = ~ Ca s a u to ch to ne s - A ut oc ht ho no us c a se s • Ca s im po rt es s e u le m e n t- Im po rt ed c a se s o n ly 0 . b () \ () Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f t he s e cr e ta ria t o f t he W H O c o n ce rn in g th e le ga l s ta tu s o f a n y co u n tr y, t er rit or y, c ity o r a re a o r o f i ts a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f its fro nt ie rs o r bo un da rie s - Le s de si gn at io ns u til is 0e s su r ce tte c a rt e e t la pr es en ta tio n de s do nn ee s qu i y fig ur en t n 'im pl iq ue nt . de la p ar t de ! 'O rg an is at io n m o n di al e de la S an ta . a u cu n e p ris e de p os iti on q ua nt a u st at ut ju rid iqu e de te l o u t el p ay s, te rr ito ire , v ill e a u z o n e , o u d e se s a u to rit 0s , n i qu an t a u t ra ce d e se s fro nt ie re s. N . . . . w - 214 - depuis que l'OMS a ete creee en 1948. 70% des cas ant ete enregistres en Amerique latine avec plus de 300 OOO pour le seul Perou (58% des cas mondiaux). L'Afrique arrive en deuxieme position parmi les con- tinents affectes avec 19 pays touches et quelque 136 OOO cas enregistres, dont les trois quarts au Ghana, au Nigeria, au Tchad et en Zambie. En Asie, le Nepal represente les deux tiers des cas notifies par 12 pays. Le taux de letalite du cholera en 1991 a ete le plus bas jamais enregistre dans l'histoire de cette mala- die (3,3%), largement influence par le bas taux de mortalite enregistre au Perou (0,95%). II est toutefois 9 fois plus eleve en Afrique (9,3%) qu'en Amerique latine (1,1%). De meme, au sein de chaque pays, on observe generalement des differences importantes de mortalite entre les provinces. Ainsi, au Perou, le taux de letalite a ete 18 fois plus eleve en Cajamarca (4,3%) et 24 fois plus eleve a Pasco (5,6%) que dans le departement de Lima/Callao (0,23%). Ces gra- dients importants entre provinces, entre pays et entre continents refletent en grande partie des inega- lites en ce qui concerne le niveau d'education des populations, leur acces a des etablissements de sante, la qualite des soins et le degre de penetration des programmes nationaux de lutte centre les mala- dies diarrheiques aigues et centre le cholera. Bien que le cholera reste avant tout une affection associee au sous-developpement, aucun pays n'est aujourd'hui a l'abri de la maladie, etant donne l'in- tensite et la rapidite des echanges internationaux. Ainsi, les Etats-Unis ant rapporte 26 cas de cholera en 1991, soit plus qu'en aucune autre annee au cours de ce siecle; 17 de ces cas etaient en relation directe avec l'epidemie latino-americaine. Au Japan, 93 cas importes ant ete notifies, qui ant cause au mains 27 cas secondaires. Evolution de la situation dans les pays, fin 1991 Au debut decembre 1991, la situation sur les princi- paux fronts du cholera evolue de la maniere suivan- te: au Perou, 11 mois apres le debut de l'epidemie, la transmission de la maladie est encore intense, provoquant environ 500 nouveaux cas par jour, es- sentiellement dans les departements de la cote et les deux departements amazoniens du pays. L'Equateur, 10 mois apres la notification de ses premiers cas, rapporte encore plusieurs centaines de cas par se- maine. En Colombie, le troisieme pays affecte, l'epi- demie s'est repandue de maniere nettement mains rapide et mains intense que dans les 2 pays prece- dents. Une centaine de cas par semaine sont encore rapportes debut decembre. Au Bresil, la contamina- tion a ete longtemps limitee aux municipalites ama- zoniennes limitrophes du Perou. L'arrivee des pre- miers cas a Manaus, capitale de l'Amazonas, signait cependant, debut octobre, !'extension lente et mode- ree mais ineluctable de la maladie suivant le cours du fleuve. En effet, debut novembre, des cas appa- raissaient a Belem, a !'embouchure du fleuve Ama- zone, marquant la fin de la traversee ouest-est de l'Amerique du Sud par l'epidemie et pla~ant sous menace directe la region populeuse et sous- developpee du Nordeste bresilien, aussi bien que les grandes metropoles du Sud. Le Chili a rapporte 41 cas entre le 22 avril et le 22 mai 1991 et n'en a pas signale depuis. C'est le seul pays latino- americain qui ait pu juguler l'epidemie. Encore son environnement reste-t-il contamine par le V. cholerae El Tor qui continue a etre isole dans differentes parties du pays. La Bolivie, atteinte tardi- vement, n'a rapporte que 175 cas et la maladie semble peu susceptible de se repandre rapidement sur les hauts plateaux de ce pays. Au Mexique, 15 Etats sur 32, y compris le District federal, rappor- tent des cas en nombre modere. En Amerique cen- trale, le Panama, le Guatemala et le Salvador sont respectivement les pays les plus affectes du conti- nent apres le Perou et l'Equateur (14). L'epidemie y est encore en pleine evolution et continuera a exer- cer une pression sur les pays non encore atteints (Belize, Costa Rica) ou recemment touches (Hondu- ras, Nicaragua) d'Amerique centrale. En Afrique, l'epidemie la plus intense a eu lieu au Tchad (ou 2 pour 1 OOO de la population a ete affectee cette annee). Des epidemies relativement intenses ant egalement affecte la Zambie, le Ghana, le Nigeria et le Niger. Elles ant maintenant fait place a une situa- tion endemique. Le Nigeria continue a rapporter le plus grand nombre de cas pour ce continent. Tendance future II est probable que le nombre de cas et de deces en 1992 sera inferieur a celui enregistre en 1991. Toute- fois, !'introduction du cholera aux pays d' Amerique centrale qui ne l'ont pas encore, au Paraguay, au Venezuela et aux Etats du Nordeste du Bresil est a redouter en priorite. La possibilite qu'une epidemie importante se developpe a partir de ces premiers cas dependra en grande partie de l'etat de l'environne- ment dans la zone ou ils surviennent et du degre de conscientisation sanitaire de la population. Globale- ment, la letalite de la maladie continuera a decroitre, a mesure que progresse !'experience des systemes de sante et des populations en ce qui concerne le cholera. Les pays affectes en 1991 le resteront pour la plupart en 1992, les situations epidemiques faisant place a des situations endemiques d'intensite varia- ble suivant les pays consideres. Epidemiologie du cholera Beaucoup d'attitudes individuelles et collectives vis- a-vis du cholera restent influencees par le souvenir des epidemies du x1xe siecle et par le profil epide- miologique encore redoutable de la maladie jusqu'a la fin des annees 50. Ce profil a cependant change considerablement, en consequence de 3 groupes de facteurs: 1. Caracteristiques du vibrion. Le vibrion cholerae El Tor, responsable de la pandemie actuelle, a des caracteristiques differentes du vibrion cholerae classique. II est mains virulent: en phase epidemi- que, ii determine mains de cas secondaires symp- tomatiques (15) et mains de formes graves (16), amenant des taux de letalite mains eleves. En fait, la grande majorite des infections dues a El Tor passe inaper~ue. Bart (17) a pu estimer le ratio des infections par rapport aux cas a 36 pour 1 dans le cas du vibrion El Tor, a 4 pour 1 dans le cas du vibrion classique. Lars de la meme etude, la frequence des cas secondaires hospitalises etait 8 fois plus elevee avec le vibrion classique qu'avec le vibrion El Tor. Par centre El Tor est plus resistant. Sa periode d'excretion est plus longue, de 3 a 20 jours, centre 1 a 7 jours pour le vibrion classique. Resumant les travaux de huit auteurs differents, Feachem (15) indique que la mediane de la periode d'excretion rapportee par ces auteurs a ete de 2 jours pour le vibrion classique, alors qu'elle a varie de 1 a 8 jours pour El Tor. Chez des convalescents non traites, Rapp. trimest. statist. sanit. mond., 45 (1992) - 215 - Pierce (18) a meme identifie des portages de plusieurs mois. Les vrais porteurs chroniques sont toutefois exceptionnels et ne jouent pas un role appreciable dans la transmission de la mala- die (19). El Tor peut egalement survivre long- temps dans l'environnement (20); ii a souvent ete isole dans des communautes au on ne pouvait pas prouver !'existence du cholera, et dans des communautes d'ou le cholera avait disparu de- puis longtemps, meme en dehors de tout con- texte epidemique, ce qui n'a jamais ete observe avec le vibrion cholerae classique. Entin El Tor pourrait etre mains immunogenique. Alors qu'un episode initial de cholera classique confere pen- dant plusieurs annees une protection complete contre une eventuelle reinfection, Clemens (21) a trouve qu'un episode initial de cholera El Tor etait suivi d'une protection negligeable. Toutes ces caracteristiques favorisent )'apparition d'epide- mies mains dramatiques mais plus durables et plus facilement suivies d'un etat endemique. 2. Evolution des modes de vie. Depuis le XIX• siecle, l'intensite et la rapidite des echanges ant augmente de maniere extraordinaire. Oue ce soit a des fins militaires, commerciales, religieuses (pelerinage) au touristiques, le mouvement inter- national des personnes et des marchandises s'est accru dans des proportions considerables; de meme leur vitesse. Aujourd'hui, ii n'est plus un seul pays au monde qui ne soit expose en perma- nence a !'introduction du vibrion cholerique, par l'intermediaire d'un porteur asymptomatique, ou d'un aliment contamine. Que ce vibrion entraine une epidemie OU non depend du degre d'hygiene qui prevaut la ou ii est introduit. Si de nombreux pays ant realise des progres considerables dans le domaine de !'hygiene individuelle et collective, de larges segments de population dans Jes pays en developpement n'ont pas encore un acces facile a une quantite suffisante d'eau potable, ne font pas usage de moyens sanitaires d'evacuer leurs excreta et ant une hygiene corporelle et alimentaire deficiente; ce sont ces populations qui sont surtout exposees au cholera. 3. Connaissance de la pathogenie du cholera. Plus d'un siecle d'observations diverses depuis 1830 avait conduit a la conclusion que c'est essentielle- ment la deshydratation aigue consecutive a la diarrhee, lorsque celle-ci est profuse, qui peut causer la mart du patient cholerique. Vers la fin des annees 50, le reequilibrage rapide du patient avec une quantite d'eau et de sels appropries est done apparue comme la cle de la prevention de la mortalite de cette maladie. Une decennie de re- cherches intenses (1958-1968) aboutit a l'elabora- tion de formulas salines satisfaisantes tant pour la rehydratation intraveineuse que pour la rehy- dratation orale, et a !'elaboration de normes de traitement largement disseminees depuis par l'OMS. d Cette decouverte a ete un des faits mar- quants de l'histoire du cholera, permettant d'abaisser sa letalite au-dessous de 1% et debou- chant, de plus, sur la diffusion mondiale d'une therapeutique efficace et peu onereuse de la des- hydratation aigue d'origine diarrheique en gene- ral. Aujourd'hui fabriques sous differents noms par un grand nombre de pays, l'usage des sels de rehydratation s'etend a toutes les diarrhees ai- gues, en particulier chez celles de l'enfant de d Organisation mondiale de la Sante. Guide pour la Jutte contre le cholera. Geneve, OMS, 1991. (DocumentWHO/CDD/SER/80.4Rev. 2). Wld hlth statist. quart., 45 ( 19921 mains de 5 ans, qui est une des principales cau- ses de mortalite dans le Tiers-Monde. Au Perou, comme ailleurs, ii a ete possible d'observer que le gradient de letalite du cholera se superposait au gradient d'accessibilite aux services de sante, et on peut admettre aujourd'hui que la mart d'un patient cholerique est un echec du systeme de sante. Reservoir II est maintenant prouve que le V. chole'rae 01 toxi- nogene El Tor peut vivre en forme libre ou peut-etre associee, dans un reservoir aquatique natural (10). De tels reservoirs pourraient exister en maints en- droits (12, 13). Le principal reservoir de vibrions reste cependant l'homme infecte, qu'il soit malade, asymptomatique, ou mart. Le cadavre d'un choleri- que est tres contagieux et ceux qui sont charges de sa toilette sont particulierement exposes, surtout si la preparation du corps inclut la purge de l'intestin, tel que c'est la coutume dans certains pays africains. L'homme infecte est essentiellement contagieux par ses selles (qui peuvent contenir jusqu'a 109 germes par ml) et par ses vomissements. De plus, la survie du vibrion cholerae El Tor dans la sueur pendant plusieurs semaines observee par Dodin en condi- tions de laboratoire (22) a permis !'elaboration d'hypotheses plausibles de transmission de la mala- die par contage direct. Mode de transmission II est generalement admis que la dose infectieuse necessaire pour determiner un syndrome cholerique est elevee. Hornick (23) a etudie chez des volontal- res americains la dose minimum de Vibrio cholerae classique necessaire pour declencher un syndrome cholerique. Aucune modification des selles n'a ete observee tant que la dose est restee inferieure a 108 vibrions. Une dose de 1011 a ete necessaire pour provoquer une diarrhee severe de type cholerique chez 50% des sujets. Apres neutralisation de l'acidite gastrique a l'aide de 2 g de NaHC03, les doses infectieuses minimum necessaires pour produire une diarrhee et un syndrome cholerique ant ete abais- sees respectivement a 104 et 105• Avec le biotype El Tor, des doses de 103 vibrions ant ete suffisantes, apres neutralisation de l'acidite gastrique, pour de- clencher une infection symptomatique chez des vo- lontaires (24). Role de l'eau Demontree pour la premiere fois par Snow, la res- ponsabilite de l'eau dans la transmission du cholera a ete souvent signalee par la suite. Elle a meme ete consideree par plusieurs auteurs (25, 26) comme le vehicule presque exclusif de la transmission au Bangladesh. Au cours de ces dernieres annees, le role de l'eau a encore ete mis en evidence en lndonesie par Glass (27) et en Afrique du Sud par Sinclair (28). Au Perou, le milieu hydrique etait for- tement contamine; le vibrion cholerique a ete retrou- ve dans l'eau de riviere, tant a Lima qu'a lquitos, a des concentrations de 103/dl, dans les eaux du prin- cipal collecteur de Lima, a des concentrations excep- tionnelles de 105/dl et dans l'eau de mer, tant a Lima qu'a Callao, a des concentrations de 104/dl (29). Des enquetes epidemiologiques ant permis de demon- trer que, dans les villes de la cote, la consommation de l'eau du systeme d'adduction et de puits munici- - 216 - paux etait un facteur de risque. II semble cependant que le role de l'eau dans la transmission du cholera ait ete cite plus souvent parce qu'il etait plausible que parce qu'il etait demontre. Dans les annees 70, Felix et Dodin se sont eleves contre ce biais: obser- vant !'expansion rapide de l'epidemie cholerique du Niger et du Nord Nigeria au Nord Cameroun et au Tchad, Felix (8) observait « ... en saison particuliere- ment seche, avec une temperature au sol superieure a 60° au soleil et 40° a l'ombre, dans un paysage predesertique au l'eau est totalement absente, nous avons eu !'evidence que l'epidemie hydrique etait un mythe». Mais etait-ce vraiment un mythe? En tout cas, pas pour Snow. C'est le plus grand merite de Feachem (15) d'avoir patiemment demontre a quel point la pensee et les ecrits de Snow avaient ete deformes, d'une part, et combien d'auteurs, d'autre part, avaient hativement conclu au role de l'eau sans le prouver rigoureusement, omettant d'envisager au rejetant prematurement les autres mecanismes de transmission toujours possibles du cholera, meme dans un environnement hydrique. Feachem (30) identifie et resume 11 exemples d'epidemies au l'eau n'a joue aucun role, notant toutefois que la plupart de ces acces epidemiques ant eu lieu dans des pays au le niveau de vie etait eleve, et non pas en pays epidemique. Un role non negligeable peut sans doute etre assi- gne a l'eau utilisee pour arroser les cultures marai- cheres, au encore «raffraichir» les salades, fruits et legumes exposes a l'etal des marchands ambulants; dans les villes du Tiers-Monde, les eaux usees, non epurees, sont souvent rejetees dans un cours d'eau qui peut egalement constituer une source ban mar- che d'eau d'arrosage. La principale source d'approvi- sionnement de ces villes en legumes frais et salades se trouve done exposee a la contamination de l'eau qui recueille les effluents de la ville. Cette hypothese a ete retenue pour expliquer les cas de cholera apparus au Chili en 1991, essentiellement chez des personnes qui avaient consomme des crudites culti- vees dans les environs de la capitale. Le vibrion cholerique a e·te isole dans l'eau de riviere au Perou, au Chili, au Mexique, au Guatemala et au Salvador a des concentrations allant jusqu'a 103/100 ml. II a ete isole a la concentration de 105/100 ml dans de l'eau d'irrigation a Lima. La consommation de legumes arroses par des eaux usees contaminees a egale- ment ete retenue pour expliquer l'epidemique surve- nue a Jerusalem en 1970 (31). Transmission de personne a personne Beaucoup d'auteurs ant considere avec scepticisme la possibilite d'une transmission de personne a per- sonne, au lui ant accorde un role reduit (32-34). Les observations de Felix au Sahel, en 1971, et la decou- verte de la longue survie du vibrion dans la sueur, suggerent cependant l'hypothese plausible que, dans certaines circonstances, le contage direct est possible. En particulier, les rassemblements (peleri- nage, festival, fete, funerailles) de personnes qui n'ont pas une hygiene personnelle rigoureuse, soit par manque d'education, soit parce que !'absence d'eau ne le leur permet guere, peuvent favoriser le contage direct. Ainsi Coulanges & Coulanges (35) decrivent la situation observee a Goulfey (Came- roun), au 400 enfants, isoles dans leurs cases apres leur circoncision rituelle, ant echappe a l'epidemie majeure qui a frappe la communaute qui les entou- • PAHOJWHO. VII lnteramerican meeting at the ministerial level on animal health. Washington D.C., PAHO, 1991. (Document RIMSA 7/22) (anglais seulement). rait et dont ils partageaient cependant nourriture et boisson. Les auteurs y voient la preuve d'une conta- mination essentiellement interhumaine, tout en avouant que cela n'explique pas tout. En fait, s'il est plausible que des porteurs puissent transmettre !'in- fection directement dans des circonstances favori- sant les contacts personnels et sociaux rapproches, ii est douteux que le contact seul puisse expliquer le role des porteurs dans la transmission du chole- ra (36). Role des aliments L'amelioration des systemes de surveillance epide- miologique depuis 20 ans, en particulier la rapidite d'intervention en cas de suspicion de cholera, le renforcement des capacites de diagnostic bacteriolo- gique et !'utilisation plus frequente de techniques de recherche efficaces (etudes cas-temoins) ant permis de demontrer dans un nombre croissant de cas, le role des aliments dans la transmission de la mala- die. Les aliments peuvent transmettre le cholera de deux manieres: d'une part, lorsqu'ils sont souilles par des mains au de l'eau elles-memes contaminees (contamination externe), d'autre part lorsqu'ils sont eux-memes porteurs de microbes; dans cette der- niere categorie entrent les fruits de mer (crabes, crevettes, huitres, moules, palourdes, clovisses) et les poissons recueillis dans des eaux contaminees. Feachem (30) cite 9 cas demontres d'epidemies pro- voquees par la consommation de fruits de mer. D'autres exemples ant ete publies depuis, aux Etats- Unis (37) et ailleurs. En 1991, au Perou, 57% des echantillons de cebiche recueillis sur le marche de Callao et 30% de ceux recueillis sur le marche de Lima auraient ete contamines par le vibrion choleri- que. • La contamination de ce plat du rant la prepara- tion ne fait aucun doute. Toutefois, le vibrion a aussi ete isole dans l'intestin et sur les ecailles d'un poisson de consommation courante peche dans les eaux cotieres (4, 29). En Equateur, on a demontre !'association de la maladie avec la consommation de poisson cru et de fruits de mer crus. Aux Etats-Unis, au mains 14 des 16 cas de cholera autochtones notifies en 1991 ant ete causes par des aliments contamines. En plus, 5 des 10 cas importes sont survenus chez des voyageurs recemment rentres d'Equateur au i\s avaient consomme des fruits de mer crus. Dans la premiere categorie, on peut imaginer une infinite d'aliments. Seuls sont dangereux ceux qui sont manges crus au insuffisamment cuits. Le vi- brion est en effet detruit a 70° (39). II peut toutefois survivre dans la chair de crabes cuits a la vapeur pendant 25 mn au bouillis pendant 8 mn (10). La survie du vibrion au niveau des aliments contamines en laboratoire a ete etudiee par de nombreux au- teurs (40, 41) et a abouti a des resultats qui varient assez considerablement. La capacite d'un aliment contamine a transmettre la maladie depend en effet d'un grand nombre de facteurs qui ne sont pas toujours standardises dans les etudes en cause. Ainsi la dose qui a infecte !'aliment au depart, la temperature et la duree de la conservation, les con- ditions de pH et d'humidite (activite de l'eau libre dans une substance alimentaire) influent considera- blement les resultats. De plus, la resistance du vi- brion varie suivant la souche etudiee. Ainsi, suivant des etudes non publiees de l'lnstitut national de Santa de Lima (Perou), la souche peruvienne serait plus resistante a l'acidite (croissance a pH 5,0) et au chlorure de sodium (croissance dans une solution de NaCl a 4%). • A la temperature du refrigerateur (0° a Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 217 - 5°) la multiplication du vibrion est ralentie mais sa survie prolongee. Sur certains aliments tels que cuisses de grenouilles (42), crabes, huitres et crevet- tes (43), le vibrion survit mieux a -20° qu'a +4 au +7 °C. Du riz rechauffe et resservi le lendemain peut se reveler contaminant alors qu'il ne l'etait pas lors du premier repas. Au Mali, la consommation de restes de gruau de millet laisses a temperature ambiante sans etre rechauffes a ete un facteur de transmission (44). En Guinee, les aliments prepares avec une sauce tomate (pH acide) avaient mains de chance de transmettre la maladie que ceux prepares avec une sauce d'arachide (pH neutre) (45). En general, ce sont les aliments prepares a la mai- son au par de petits traiteurs artisanaux qui sont les plus exposes. Ainsi, en 1991 au Perou, aliments, glaces et rafraichissements vendus dans les rues etaient des facteurs de risque. En Equateur, on a demontre !'association de la maladie avec la con- sommation de rafraichissements distribues par des vendeurs ambulants. Les repas d'enterrement en Afrique ant ete a l'origine de plusieurs epidemies de cholera, les personnes effectuant la toilette du mart etant souvent les memes que celles qui preparent le repas offert en cette circonstance (30). En juin 1991, a Bayana Tehsil (lnde), 2 600 cas de cholera et 29 marts sont survenus chez des personnes qui s'etaient contaminees avec des aliments servis lors de 2 fetes de mariage.1 La contamination d'aliments au de boissons prepares industriellement n'est ce- pendant pas inconnue. En 1972, 25 personnes voya- geant sur un vol commercial a destination de Syd- ney (Australie) se contaminerent en mangeant un hors-d'reuvre de crevettes charge a l'escale de Bahre'in. Une personne mourut (7, 30, 46). En 1973, au Portugal, l'eau minerale naturelle d'une marque connue etait contaminee et a contribue a transmettre le cholera (47). En 1991, aux Etats-Unis, des ali- ments contamines ant ete a l'origine de 14 cas de cholera autochtone. Si 11 de ces cas etaient la consequence de la consommation de crabes achetes imprudemment sur des marches equatoriens (prepa- ration non industrielle) par des voyageurs qui les avaient rapportes (illegalement) et probablement cuits insuffisamment, 3 cas ant ete provoques par du lait de noix de coco congele importe commercia- lement de Tha'ilande. La transmission du cholera par les aliments est sans doute plus frequente qu'on a bien voulu le dire dans le passe. La mettre en evidence requiert des enquetes relativement coGteu- ses et ii est probable qu'elles resteront pour quelque temps encore l'apanage des pays qui ant les res- sources appropriees pour les realiser. Conclusion En 1991, une recrudescence mondiale du cholera a ete observee. Elle s'est surtout exercee aux depens de l'Afrique qui a rapporte 2 fois plus de cas qu'en aucune autre annee de cette 1• pandemie, et de l'Amerique latine au la maladie, qui avait disparu depuis le siecle dernier, a infecte 13 pays et fait plus de 350 OOO cas en 11 mois. La letalite enregistree en Amerique latine est sans doute la plus basse de l'histoire du cholera. En tout etat de cause, la morta- lite du cholera est tres inferieure a la mortalite des diarrhees aigues non choleriques qui, chez les seuls enfants de mains de 5 ans, causent chaque annee I National Institute of Communicable Diseases. Cholera in India, 1991. New Delhi, NICD, 1991. (Document non publie) (anglais seulement). Wld hlth statist. quan., 45 ( 1992) plus de 3,5 millions de deces dans le monde et environ 300 OOO dans les Ameriques. La gravite du cholera en 1991 ne justifie done plus !'emotion con- siderable qui a encore ete observee cette annee dans le public, et au sein des gouvernements des pays directement au indirectement exposes. De toute evi- dence, l'inconscient collectif occidental reste encore profondement marque par le souvenir des ravages que la maladie a causes en Europe et en Amerique du Nord au XIX• siecle. Le cholera cependant a change de visage. La grande majorite des personnes infectees ne presentent pas de signes cliniques; parmi les malades, le vibrion cholerique El Tor cause mains de formes graves que le vibrion cholerique classique. La conduite a tenir en cas de diarrhee aigue est aujourd'hui bien codifiee et le traitement tres efficace. II ne requiert que des produits simples, peu onereux, largement disponibles internationale- ment, et faciles a utiliser. La letalite du cholera aujourd'hui ne reflete done plus que le defaut d'ac- cessibilite (culturelle, geographique, fonctionnelle) aux services de sante et la qualite insuffisante des soins qui y sont prodigues. El Tor est toutefois plus apte que le vibrion classique a survivre dans l'envi- ronnement. Le cholera est reste, et restera, endemi- que dans la plupart des pays au les principes de !'evacuation sanitaire des excreta et des eaux usees ne sont pas generalises. II se manifestera par des cas sporadiques chez des personnes qui sont expo- sees a la maladie par leur condition personnelle (hypochloridrie gastrique au moment de !'infection, par exemple) et leur mode de vie (mauvaise hygiene corporelle et alimentaire), ainsi que par des epide- mies localisees dans une zone au l'environnement est particulierement defavorable au dans un groupe expose a une infection alimentaire. Decrit essentiel- lement comme une maladie a transmission hydrique jusqu'a la fin des annees 60, le cholera est en fait tres frequemment transmis par les aliments. Les bases theoriques d'un contage direct par la sueur ant egalement ete demontrees. L'existence d'un re- servoir naturel pour le vibrion cholerique 01 toxino- gene biotype El Tor a ete prouvee; toutefois le reservoir principal de ce germe est l'homme, qui l'elimine par ses selles. Le probleme de fond du cholera repose done essentiellement sur !'hygiene personnelle et sur l'assainissement de l'environne- ment moyennant !'evacuation sanitaire des excreta humains et l'epuration des eaux usees. La couvertu- re totale des populations dans ce domaine requiert malheureusement des investissements qui sont hors de portee des economies de la plupart des pays en developpement pour les 20 ans a venir, meme avec l'aide internationale. L'hygiene de l'eau de boisson, des aliments et des mains restera done le pilier de la prevention du cholera dans les pays en developpe- ment pour les annees a venir. La recherche du mode de transmission dominant de la maladie dans une population donnee est essentielle pour effectuer les choix strategiques qui s'imposent en matiere de prevention (48). Les pays les plus exposes au chole- ra ant encore beaucoup a faire pour renforcer leur capacite nationale en recherche epidemiologique, tel que l'a demontre l'epidemie latino-americaine. Le cholera a ete a l'origine de progres historiques dans le domaine medical; en demontrant la contagiosite du cholera, John Snow affecta definitivement la credibilite de la theorie des miasmes qui paralysait la pensee scientifique depuis des siecles et ouvrait une voie royale pour la comprehension et la preven- tion des maladies transmissibles; en recherchant un traitement approprie du patient cholerique, on a abouti a la formulation des sels de rehydratation orale, produit simple, efficace et ban marche qui trouve maintenant sa principale application dans le - 218 - traitement de la deshydratation des diarrhees aigues en general; de meme, un programme efficace de lutte nationale contre le cholera devrait amener des ameliorations dans le domaine de la surveillance epidemiologique, des maladies diarrheiques, de !'hygiene des aliments, de l'eau potable, de !'educa- tion sanitaire et ii n'est pas improbable que l'epide- mie qui a frappe l'Amerique latine soit !'occasion d'un progres historique dans le domaine de la sante dans ce continent. La franchise et la vigueur avec lesquelles les gouvernements des pays concernes ant reagi devant une maladie que, dans d'autres regions, certains continuent a dissimuler, est en tout cas de ban augure. RESUME Les caracteristiques des epidemies de cholera du XIX• siecle sont rappelees. L'extension, !'incidence et la letalite de la maladie au cours de la 7• pandemie sont decrites. La situation epidemiologique mondiale et sa tendance fin 1991 sont analysees. L'epidemio- logie du cholera est revue en soulignant les facteurs qui peuvent expliquer le profil mains dramatique du cholera aujourd'hui. Le role joue par l'eau, les ali- ments et le contage direct dans la transmission du cholera au cours des 20 dernieres annees est revu a la lumiere d'etudes recentes et avec des references specifiques a l'epidemie qui frappe l'Amerique la- tine. Dans ce dernier continent, !'emotion intense suscitee par la maladie a ete le catalyseur d'actions vigoureuses qui pourraient engendrer des progres significatifs et durables dans le domaine de la sante. SUMMARY Cholera 1991 - an old enemy with a new face The cholera epidemics of the XIXth century are described and reviewed. The extent, incidence and case-fatality rate for the disease in the seventh pan- demic are described. The global epidemiological situation and its trend at the end of 1991 are ana- lysed. A review of cholera epidemiology highlights the factors that might explain the less tragic nature of the disease today. The role of water, food and direct contagion in transmission of cholera over the last 20 years is considered in the light of recent studies and with special reference to the epidemic in Latin America, where the intense emotion aroused by the disease has prompted vigorous action that could produce significant and lasting progress in the health field. 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ET AL Epidemic cholera in Mali: high mortality and multiple routes of transmission in a famine area. Epidemiology and infection, 100: 279-289 (1988). 45. ST Louis, M. E. ET AL Epidemic cholera in West Africa: the role of food handling and high risk foods. American journal of epidemiology, 131: 719-727 (1990). 46. FELIX, H. & DoDIN, A. Epidemiologie mondiale du cholera - evolution entre 1970 et 1980. Bulletin de la Societe de pathologie exotique, 1: 17-30 (1981 ). 47. BLAKE, P. A. ET AL. Cholera in Portugal 1974 - II. Transmission by bottled mineral water, Amer- ican journal of epidemiology, 105: 344-348 (1977). 48. GLASS, R. I. ET AL Cholera in Africa: lessons in transmission and control for Latin America. Lan- cet, 338: 791-795 (1991). - 220 - THE GLOBAL EPIDEMIOLOGY OF THE HIV/AIDS PANDEMIC AND ITS PROJECTED DEMOGRAPHIC IMPACT IN AFRICA James Chin,• Maria-Antonia Remenyi,a Florence Morrison• & Rudolfo Bulataob Introduction and background The first cases of acquired immunodeficiency syn- drome (AIDS) were described in June 1981, in five unrelated homosexual men who were residents of Los Angeles, California (United States of America). During the early 1980s there were extreme mis- conceptions about AIDS, ranging from the belief that AIDS was a problem restricted to homosexual men and injecting drug users, to the concern that the very rapid spread of AIDS could wipe out total human populations within a few decades. Scientific studies carried out with almost unprecedented swift- ness during the 1980s have largely dispelled these misconceptions. The human immunodeficiency virus (HIV) was isolated and identified as the etiological agent of AIDS in 1983 and serological tests to detect antibodies to HIV became available in 1985. Sero- logical surveys of human populations have shown that by the mid-1980s HIV had spread to most major regions of the world. HIV is primarily transmitted from person to person through sexual intercourse, mainly vaginal but also anal. Like some other sexually transmitted diseases HIV can also be transmitted through blood (or trans- planted organs or tissues), and from an infected mother to her foetus/infant before, during or shortly after birth. There are no data to even suggest that HIV can be transmitted by casual contact with an infected person. Exposure to HIV, especially for per- sons with multiple sexual partners (homosexual or heterosexual) and for those who share drug injecting equipment, occurs to some extent in all countries. Data from cohort studies indicate that over 60% of HIV-infected adults will progress to AIDS within 13 years after their infection (1, 2, cJ and almost all will die within a few years after developing AIDS. It is highly probable that virtually all HIV-infected per- sons will develop AIDS and die within 15-20 years after acquiring HIV infection. A case-fatality rate of such magnitude leads inevitably to questions about the demographic impact of the millions of deaths expected during the 1990s from this growing pan- demic. The world population is currently estimated to be about 5.5 billion, and annual increases of close to 100 million are expected (3). Thus, the 0.5-1million AIDS deaths projected by WHO to occur annually by the late 1990s will have a relatively minor impact on the size of the world population over the next two • Surveillance, Forecasting and Impact Assessment Unit, Office of Research, Global Programme on AIDS, World Health Organization, Geneva. O Population, Health and Nutrition Division, World Bank, Wash- ington, D.C., United States of America. c Lee, C. A. et al. Ten year follow-up of a cohort of 111 anti-HIV seropositive haemophiliacs. Vlth international conference on AIDS, San Francisco, June 1990. (Abstract Th. C. 37). decades. However, HIV/AIDS-affected individuals are not distributed evenly throughout the world; in those areas where the spread of HIV began in the late 1970s, a marked demographic impact can be ex- pected during the next few decades. This article summarizes the status of the HIV/AIDS pandemic in the early 1990s; provides estimates and short-term projections of AIDS mortality in a hypo- thetical country of sub-Saharan Africa; projects the potential demographic impact of AIDS in a hypothe- tical country of sub-Saharan Africa; and describes the major problems associated with modelling the long-term demographic impact of this pandemic. Methods AIDS cases are officially reported to WHO's Global Programme on AIDS (GPA) in Geneva, Switzerland from Member States via WHO's Regional Offices. However, as noted in prior reviews (4, 5), official AIDS case reports, especially in developing coun- tries, present a very inaccurate picture of the actual occurrence of AIDS. Therefore, estimates of the an- nual number of AIDS cases which probably occurred were derived by use of an AIDS estimation and short-term projection model developed by WHO (6). Estimated AIDS cases and deaths up to 1992 were extrapolated from public health surveillance data and through the use of the WHO model. Estimates of HIV seroprevalence were based on available HIV serological data. For developed countries, HIV es- timates developed by national experts and/or na- tional AIDS programmes were used, and for de- veloping countries estimates by regional experts or by WHO were used_ For the first half of the 1990s, projections of AIDS cases and deaths were derived from the WHO model; beyond the mid-1990s, the potential effects of AIDS on selected demographic indicators were derived from a demographic projection model de- veloped by R Bulatao of the World Bank (7). The World Bank model was selected because it provided detailed demographic projections which fell within the general range of results obtained by other long- term projection models. The model used a hypothet- ical population of sub-Saharan Africa in which HIV spread started in the early 1980s, and a set of standardized input values for the major biological and epidemiological variables. The hypothetical pop- ulation, standardized inputs and requested outputs were developed for a workshop organized by the United Nations Population Division and WHO (8). Demographic projections in the absence of AIDS come from the World Bank model and the United Nations (3). The following standard indicators were selected to assess the potential demographic impact of AIDS in a country of sub-Saharan Africa: rate of natural increase; AIDS age-specific mortality rates; infant mortality rate; probability of dying before age Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 221 - 1 and by age 5; under-5 mortality rate; life expect- ancy at birth; and the dependency ratio (9). These indicators are defined on p. 225. Current status of the HIV/AIDS pandemic AIDS cases. While about 450 OOO AIDS cases were reported to WHO as of January 1992, WHO's es- timate of adult AIDS cases since the start of the pandemic is about 1.5 million (10). HIV infections. WHO estimates that a cumulative global total of 9-11 million adults have been infected with HIV, of whom approximately 5-7 million are men and 3-5 million are women (10). Over 2 million of those HIV infections are estimated to have occurred in the Americas - about 1 million in North America and over 1 million in Latin America, includ- ing the Caribbean. Another 0-5 million infections are estimated to have occurred in Western Europe. The highest estimated number of HIV infections is in sub-Saharan Africa, where more than 6.5 million adults may have been infected. In South and South- East Asia (primarily India, Myanmar and Thailand), there may now be over 1 million infected indi- viduals. HIV infections in most other areas are be- lieved to be relatively low as of early 1992. Progression to severe clinical disease, AIDS and death. Of the cumulative total of HIV-infected adults, close to 1.5 million are estimated to have progressed to AIDS, and close to 90% of these AIDS cases are estimated to have died. It is also estimated that over 1 million adults have developed less severe illnesses related to their infection, formerly referred to as AIDS-related conditions (ARC). At present, approximately 1 out of 3 children born to HIV-infected women in sub-Saharan Africa is esti- mated to be infected with HIV; most of these infec- ted infants are not expected to survive to their fifth birthday. WHO has estimated that close to 1 million HIV-infected children have been born worldwide since the start of the pandemic, over half of whom have developed AIDS and died. In addition, almost 2 million uninfected children have been born who are already or who will become AIDS orphans because of maternal AIDS. About 90% of children born to HIV-infected women are estimated to be in sub- Saharan Africa (11). Projected AIDS mortality up to the mid-1990s For a hypothetical country of sub-Saharan Africa, the WHO projection model estimated that between 1985 and 1989, AIDS deaths increased the crude death rate by 0.3 per 1 OOO population over what would have been expected in the absence of AIDS (3, 11); a further increase of 1.1 per 1 OOO population (about 9%) is expected by the mid-1990s. Between 1985 and 1989, AIDS added an average of about 10% to the annual death rate for those aged 15-49: by the mid-1990s, AIDS is expected to add more than 40% to that rate. Fig. 1A shows that for the age group 15-49, AIDS is expected to reverse the declining trend in mortality rates. It should be noted that these are national projections: in many urban areas a doubling or tripling of the total death rate for this age group is expected . Early in the pandemic, almost no effect on infant or child mortality was noticeable. Yet by the mid-1990s, infant mortality is expected to be 4% higher than it would be in the absence of AIDS, and the probability of dying before age 5 is expected to increase by more than 7% as a consequence of AIDS. By the mid-1990s the projected increase in AIDS mortality in children will begin to negate reductions in mor- tality achieved by child survival programmes over the past two decades (Fig. 78). To compare AIDS with the leading causes of death in children under 5, mortality estimates prepared by other WHO pro- grammes were used. (These estimates are based on general assumptions and probabilities: they are pre- sented only to show expected trends and should not be considered precise.) Estimated death rates for those under 5 from measles, malaria, diarrhoea and AIDS for a hypothetical sub-Saharan country are presented in Fig. 2. These projections show that FIG. 1 ~::, Q) 0 ESTIMATED/ PROJECTED ADULT AND CHILD MORTALITY IN A COUNTRY OF SUB-SAHARAN AFRICA MORTALITE ESTIMATIVE I PROJETEE CHEZ LES ADULTES ET CHEZ LES ENFANTS DANS UN PAYS D'AFRIQUE AU SUD DU SAHARA A. ADULT MORTALITY (15-49 YEARS) MORTALITE CHEZ LES ADULTES (DE 15 A 49 ANS) 8~~~~~~~~~~~~~~~~~~ 6 4 B. CHILD MORTALITY (PROBABILITY OF DYING BEFORE AGE 5) MORTALITE CHEZ LES ENFANTS (PROBABILITE DE DECES AVANT L'AGE DE 5 ANS) c..c.. 2 0 1986-1989 1990-1994 1980-1984 1985-1989 1990-1994 Years - Annees Years - Annees WH092666 Wld hlth statist. quart., 45 (19921 - 222 - FIG.2 · ESTIMATED I PROJECTED MORTALITY RATES IN CHILDREN UNDER 5 YEARS IN A COUNTRY OF SUBSAHARAN AFRICA TAUX DE MORTALITE ESTIMATIF I PROJETE CHEZ LES ENFANTS DE MOINS DE 5 ANS DANS UN PAYS D' AFRIOUE AU SUD DU SAHARA c !!! "'c ~"' -o- == c .,:;; "' U o oO oo o~ ~ ~ "'0 a. a. 16 12 8 4 0 • Diarrhoea Diarrhee 1988 diarrhoea is expected to remain the predominant cause of death among children; malaria will continue to be an important cause of death, while deaths due to measles will decrease as a result of the growing use of measles vaccine. These crude estimates suggest that before the middle of this decade, AIDS will cause more deaths in children of sub-Saharan Africa than either malaria or measles. Projected demographic impact Long-term projections of demographic parameters for countries of sub-Saharan Africa come primarily from the UN Population Division: however, the pro- jections currently available in UN publications were made without consideration of the effects of AIDS (3). Thus, UN projections describe a future time "in the absence of AIDS " . Demographic projections to the year 2010 that incorporate the effects of HIV/ AIDS have also been produced through the use of HIV/AIDS models. The following sections describe the selected indicators for a sub-Saharan country; present estimates and projections for the period d Defined by the United Nations as North America , Japan, all Europe, Australia , New Zealand and the former USSR. Year - Annee D Measles Rougeole 1993 1985-2010 in the absence of AIDS; and summarize the effects AIDS will have on these indicators as projected by one HIV/AIDS demographic model (7). Rate of natural increase. Rate of natural increase was selected to analyse the effect of AIDS on population size. The advantage of th is indicator as a measure of population growth is that it does not need to consi - der the effect of migration on population change - an effect hard to assess in countries with poor data collection . UN estimates suggest that sub-Saharan crude birth rates of close to 50 per 1 OOO population in 1985 will decline to about 40 by the year 2010, in the absence of AIDS. Compared with industrialized countries,d a rate of almost 40 per 1 OOO is consider- ed high . Crude death rates for sub-Saharan Africa are also expected to decrease: it is estimated that they will fall from 15.8 per 1 OOO population in 1985 to 10.2 per 1 OOO in 2010. This yields a rate of natural increase that fluctuates around 30 per 1 OOO (3%) for the entire 25-year period (Table 1). The rate of natural increase for a sub-Saharan country is projected to decrease more rapidly in the presence of AIDS. As a result of AIDS, according to the World Bank model, the growth rate is projected to decline from 3.5 to 2.4 in 2010; without AIDS, the growth rate would decline more slowly as noted above, to about 3% in 2010 (Table 1, Fig. 3A) . TABLE 1. SELECTED DEMOGRAPHIC INDICATORS FOR A HYPOTHETICAL COUNTRY OF SUB-SAHARAN AFRICA TABLEAU 1. INDICATEURS DEMOGRAPHIQUES POUR UN PAYS HYPOTHETIQUE EN AFRIOUE AU SUD DU SAHARA Demog raphic indicator lndicateurs demograph iques Rate of natural increase - Taux d'accroissement naturel Mortality rates - Taux de mortal ite Crude death - Mortalite brute Infant mortality - Mortalite infantile Under-5 mortality - Mortalite des moins de 5 ans Life expectancy at birth - Esperance de vie a la naissance Dependency ratio - Rapport de dependance World Bank Model - Modele de la Banque mond iale 1985 2010 2010 No AIDS No AIDS With AIDS Sans SIDA Sans SIDA Avec SIDA 3.5 3.0 2.4 14.8 8. 4 16.4 101 .2 61 .3 104.7 166.0 92 .0 215.3 51 .5 61 .4 47 .1 103.2 87.2 81.4 United Nations - Nations Unies 1985 20 10 No AIDS No AIDS Sans SIDA Sans SIDA 3.1 2.9 15.8 10.2 109.0 73.0 165.3 NA 50.3 58.5 94.3 88.9 Rapp. trimest. statist. sanit. mond., 45 (1992) - 223 - Age-specific mortality rates. Infant and under-5 mor- tality rates are of particular interest in assessing the pandemic's impact on children; while for adults, mortality rates for those aged 15-49 need to be examined. While there has been a decreasing trend worldwide in under-5 mortality, it remains relatively high in developing regions; among these regions the highest levels are in sub-Saharan Africa - in 1985 it was about 165 per 1 OOO compared to about 18 per 1 OOO in the most industrialized countries. The UN estimates that under-5 mortality will decline even further in future decades. Other measures of mor- tality are also expected to fall between 1985 and 2010: the crude death rate from 15.8 to 10.2, and the infant mortality rate from 109.0 to 73.0 (Table 1). In the World Bank model, the crude death rate for a hypothetical sub-Saharan country was projected to fall from 14.8 per 1 OOO population in 1985 to 8.4 per 1 OOO population in 2010 in the absence of AIDS. However with AIDS, the crude death rate was pro- jected to rise to 16.4 by 2010 - about twice the rate without AIDS (Table 1, Fig. 38). Infant mortality rates in the absence of AIDS would have been expected to fall from 101.2 in 1985 to 61.3 in 2010, but instead will remain almost unchanged by 2010 at 104.7 per 1 OOO live births. Similarly in the presence of AIDS, no decline was projected for the probability of dying by age 5; it is expected to increase from 166.0 to 215.3 between 1985 and 2010, whereas without AIDS, it was expected to decline by about 50% to 92.0 per 1 OOO live births in 2010 (Table 1, Fig. 3C). Life expectancy at birth. The use of life tables, although a more complicated procedure, allows for an analysis of the impact of AIDS on relatively young populations through examination of its effect on life expectancy at birth. To estimate the average number of years lived by a newborn subjected to prevailing mortality rates, data on deaths, survivors, probability of dying, and probability of surviving successive age intervals are needed. Age-specific mortality information can be obtained from vital registration systems, censuses or sample surveys. Where information is scarce, model life tables based on patterns of mortality current at particular points FIG.3 PROJECTED IMPACT OF AIDS ON DEMOGRAPHIC INDICATORS IN A COUNTRY OF SUBSAHARAN AFRICA PROJECTIONS DES EFFETS DU SIDA SUR LES INDICATEURS DEMOGRAPHIQUES DANS UN PAYS D'AFRIOUE AU SUD DU SAHARA .. 3 Cl "' c: " ~ :, f. I 2 " Cl "' c: 1l :;; 0.. 200 150 100 50 RATE OF NATURAL INCREASE OF POPULATION TAUX D'ACCROISSEMENT NATUREL DE LA POPULATION 1990 1990 without AIDS/sans SIDA with AIDS/avec SIDA 1995 2000 2005 Years - Annees INFANT AND CHILD MORTALITY MORTALITE INFANTO-JUVENILE CMR with AIDS/TMJ avec SIDA A 2010 •••••••••• •••• • • IMR with AIDS/TMI avec SIDA ------ ---- -----IMR without AIDS/TMI sans SIDA c 1995 2000 2005 2010 Years - Annees Wld hlth statist. quan., 4!i (19921 10 5 1990 CRUDE DEA TH RA TE TAUX BRUT DE MORTALITE with AIDS/avec SIDA 1995 2000 2005 Years - Annees LIFE EXPECTANCY AT BIRTH ESPERANCE DE VIE A LA NAISSANCE 8 2010 60-~:::::w~i~th~ou:t:A:ID:S:~:a:ns:S:l~DA~~~~~~---~ 40- with AIDS/avec SIDA 20- D 0-4-~~~~l~~~~~l~~~-l~~~----i 1990 1995 2000 2005 2010 Years - Annees - 224 - in time and for particular social and economic cir- cumstances are used to estimate life expectancy. The effect of AIDS on average length of life can be determined by comparing life expectancy at birth in situations for which AIDS is either included or excluded. The difference between the two averages represents life expectancy lost due to AIDS. The UN estimated that a sub-Saharan African was expected to live 50.3 years in 1985 - about 24 years less than a person in a developed country - but projected a rise to 58.5 years by 2010 (Table 1). Without AIDS in the hypothetical sub-Saharan country, the World Bank model projected that life expectancy at birth would increase from 51.5 years in 1985 to 61.4 years by 2010 - a difference of about 10 additional years of life. With AIDS, life expectancy is expected to decrease to 47.1 in 2010, or by more than 12 years compared to projected life expectancy in the absence of AIDS (Table 1, Fig. 30). Dependency ratio. The dependency ratio is used to analyse the economic implications of changes in age distribution: a higher dependency ratio indicates a heavier burden on persons aged 15-64. For 1985, the UN estimated a ratio of 94.3 dependents per 100 persons aged 15-64 in the sub-Saharan region. Although the ratio is expected to decline to 88.9 by 2010, it will still be about twice as high as in developed countries. This difference is explained by the high proportion of children under 15 in African countries - 45% compared with about 20% for industrialized areas - a difference that is not offset by the higher proportion of people over 65 in in- dustrialized regions. According to the World Bank model projections for a sub-Saharan country, AIDS deaths are expected to reinforce the declining trend in the dependency ratio: by the year 2010 the ratio without AIDS is projected to be 87.2 and with AIDS 81.4 (Table 1 ). This result must be interpreted cauti- ously since thousands of deaths in adults at produc- tive ages will show little effect on the dependency ratio when the size of the reference population is several million or more. An analysis of the expected number of orphans, for example, is needed to exam- ine more fully the increasing social and economic burden on certain segments of the population as a consequence of the age-specific effects of AIDS. Discussion Although estimated and long-term projections cannot be made with great precision, the general dimensions of the HIV/AIDS pandemic have been more clearly delineated now at the start of its second decade. Epidemiological data indicate that in industrialized countries, where extensive spread of HIV began in the late 1970s or early 1980s, the majority of HIV infections occurred during the first half of the 1980s. As a result, peak incidence for AIDS cases and deaths in these countries is project- ed to occur in the mid-1990s. Although a subsequent decline in cases and deaths is expected, AIDS will nevertheless remain a major disease problem in industrialized countries for the foreseeable future and will continue to have far-reaching effects on almost all sectors of human life. Heterosexual trans- mission of HIV has increased slowly but steadily in all industrialized countries during the latter half of the 1980s; the future demographic impact of HIV/ AIDS in these countries will depend on the extent of such spread during the 1990s. In industrialized countries, data for estimating demo- graphic indicators are considered reasonably reliable since they come from periodic population censuses and well established vital registration systems. In general, developing countries and especially those in sub-Saharan Africa lack routine data collection sys- tems. In these countries, demographic indicators are estimated from fragmentary information obtained by occasional censuses and sample surveys, or are derived from life tables based on prevailing mor- tality patterns. Referring to its child mortality estimates, the UN Population Division states that "The estimates for Africa are probably the least reliable. Most African countries have data from at least one or two cen- suses or surveys, but there are not enough data to evaluate their quality and to estimate trends" (12). Despite the fact that only sparse data of often ques- tionable quality are available for sub-Saharan Africa, a variety of models were designed to project the long-term effects of HIV/AIDS on this region. These models produced widely varied results, partly be- cause different values were used for model para- meters; in addition, projections were usually un- accompanied by measures of variability which made interpretation of the results more difficult. Further- more, no criteria existed to facilitate a choice among the models. The situation was discouraging to policy makers who needed to estimate the potential demo- graphic impact of the HIV/AIDS pandemic. To obtain more precise long-term projections for sub-Saharan Africa and to evaluate the reasons for the discrepant results produced by the various models, the UN Population Division and WHO's Global Programme on AIDS convened a workshop in New York in December 1989. The workshop was intended to: (a) promote technical discussions among demo- graphic modellers about differences in existing models; (b) develop a consensus for future activities with respect to modelling the AIDS pandemic and its demographic impact; and (c) initiate discussions be- tween demographic modellers and public health pro- fessionals in order to ensure that models would provide the information required for health policy formulation and implementation (8). To achieve comparability among models as far as it was possible, a set of standard inputs and outputs was developed for use by the participant modellers. The input parameters described the demographic characteristics of a hypothetical population at the beginning of the projection period and also at the end of 25 years in the absence of AIDS. The long- term demographic projections produced by the models at this workshop differed substantially for the intermediate and worst-case scenarios: for the best-case all the models indicated that the epidemic could not be sustained. The major finding was that the variations among the models were due predomi- nantly to the assumed rates of infectivity; the way models regulated selection of sexual partners within and across subgroups: and the timing of entrance into active sexual life. While it was believed that identification of those factors that explained the different outcomes produced by various models would be made easier by the use of standard inputs, in fact the differences in model data needs and the processes represented precluded a definitive com- parison (8). However, models derived from demo- graphic projections produced results closer to one another than those from the other models. It was for this reason that the projections produced by one of these latter models (the World Bank model) was used in this article (7). Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 225 - It should be emphasized that the results of any model that projects the potential demographic im- pact of HIV/AIDS in sub-Saharan Africa must be interpreted with caution not only because major p~oblems exist with regard to the reliability of the demographic data used, but also because it is ex- tremely difficult to obtain a precise mathematical representation of so complex, dynamic and inter- dependent a human problem (8). The values and ranges for many, if not most, of the major biological and behavioural variables which affect the spread of HIV and its subsequent impact on individuals and populations are not known with substantial ac- curacy. Even if it is assumed that a model can simulate the effects of HIV on populations with precision, the values used as well as the choice of parameters to be included may completely invalidate any projections produced. The values currently used for model parameters may appear to be reasonable in the absence of more comprehensive data, but some of them, e.g. HIV infectivity, could be in error by at least 10-fold while others, such as the effect of HIV on fertility patterns, have to be assumed or ignored. In addition, sub-Saharan countries differ markedly with regard to social and sexual patterns which significantly affect the spread of HIV; demo- graphic indicators also vary substantially between West and East Africa. Therefore, the projected effects of HIV/AIDS models on demographic indicators for a hypothetical sub-Saharan country over a period of 25 years cannot be considered precise: instead these projections should be viewed as initial attempts to predict the gross demographic consequences of AIDS during the next few decades. Despite the uncertainty associated with long-term projections, one group has published results from its HIV/AIDS modelling efforts which forecast " ... that in Definitions - Definitions Rate of natural increase Crude birth rate minus crude death rate Crude birth rate Annual live births x 1 OOO divided by the midyear population Crude death rate Annual deaths x 1 OOO divided by the midyear population AIDS age-specific mortality rates Annual deaths for a specific age group x 100 OOO divided by the midyear population for the specific age group Infant mortality rate Deaths of those aged <1 year x 1 OOO divided by the live births for a given year Probability of dying before age 1 (or age 5) Estimated from a cohort: = deaths to those in the cohort < 1 [or <51 x 1 OOO divided by the live births for a given year [or 5 years) - these probabilities can also be obtained from life tables <5 mortality rate Deaths to children <5 x 1 OOO divided by the population <5 Life expectancy at birth Average yeift-s of life expected for a newborn subjected to prevailing mortality conditions - for the life table population, life expectancy at birth is equivalent to the reciprocal of the crude death rate = 1 divided by annual deaths divided by the midyear population Dependency ratio Children <15 plus persons ;;,,65 x 100 divided by the population aged 15-64 Wld hlth statist. quart .• 45 (1992) Taux d'accroissement nature/ Taux brut de natalite mains taux brut de mortalite Taux brut de natalite Nombre annuel de naissances vivantes x 1 OOO divise par l'effectif de la population en milieu d'annee Taux brut de mortalite Nombre annuel de deces x 1 OOO divise par l'effectif de la population en milieu d'annee Taux de mortalite due au SIDA par age Nombre des deces annuels dans un groupe d'age particulier x 100 OOO divise par l'effectif en milieu d'annee du groupe d'age particulier Taux de mortalite infantile Deces des <1 an x 1 OOO divise par le nombre de naissances vivantes au cours d'une an nee donnee La probabilite des deces d'enfants de <1 an (ou de <5 ans) Calculee a partir d'une cohorte = nombre de deces dans la cohorte des <1 an [ou <5 ans) x 1 OOO divise par le nombre de naissances vivantes au cours d'une annee donnee [au 5 ans] - ces probabilites peuvent aussi etre extraites des ta- bles de mortalite Taux de mortalite des <5 ans Nombre des deces d'enfants de <5 ans x 1 OOO divise par l'effectifdes <5 ans Esperance de vie a Ja naissance Nombre moyen d'annees de vie attendues pour un nouveau-ne soumis aux conditions de mor- talite existantes - pour la population couverte par la table de mortalite, l'esperance de vie a la naissance equivaut a la reciproque du taux brut de mortalite = 1 divise par le nombre de deces annuels divise par l'effectif de la population en milieu d'annee Rapport de dependance Nombre d'enfants de <15 ans plus personnes de :;;.65 ans x 100 divise par l'effectif de la popula- tion de 15 a 64 ans - 226 - the worst-afflicted areas AIDS is likely to change population growth rates from positive to negative values in a few decades" (13). No complex mathe- matical model is required to predict that if the majority of adults in a given population are infected with HIV, then the majority of adults can be expected to die of AIDS within a decade or two. Such a large increase in both child deaths (as a result of mother- to-infant transmission) and adult deaths due to AIDS in a population so affected could, in a couple of decades, result in a negative population growth rate. HIV infection rates of 60-70% or greater have already been observed in relatively small groups of persons at very high risk of HIV infection, such as female prostitutes and injecting drug users. However, HIV infection rates of such magnitude are exceedingly unlikely to occur in any large general population. Analysis of HIV seroprevalence data available to WHO suggests that HIV prevalence in adults in urban areas of sub-Saharan Africa is beginning to peak at levels which range from a low of <10% to a high of about 30-40%. The highest estimated total (urban and rural) adult HIV prevalence in any sub-Saharan country, as of early 1992, is about 15-20%. Time and continued public health surveillance of HIV infections are needed to answer the critical question of how high HIV seroprevalence rates will rise before they level off and/or begin to decline. Any HIV/AIDS model, depending on its assumptions and input values, can produce results showing the vast majority of any population being HIV-infected in a few decades. Regardless of whether a negative population growth rate is a reasonable long-term scenario for any sub-Saharan country, all of the available epi- demiological and serological data indicate continu- ing increases in HIV seroprevalence levels in many rural areas of sub-Saharan Africa. Thus, during the 1990s and into the next decade, continuing increases in AIDS cases and deaths can be expected. The results of demographic models of the HIV/AIDS pan- demic in sub-Saharan Africa all project large in- creases in AIDS deaths. There is also little doubt that during the next several decades AIDS will be among the leading causes of infant and child mortality in this region. AIDS is not expected by most epi- demiologists and HIV/AIDS modellers to reverse the positive population growth rate in sub-Saharan countries over the next 20-30 years. Nevertheless, AIDS will have a profound impact on all health and social welfare systems in the region. In addition, there is a growing appreciation that AIDS will ser- iously affect social, economic and development issues that will require a concerted and coordinated response from the world community. SUMMARY The global epidemiology of HIV/AIDS has evolved to the point that the pandemic now predominantly affects heterosexuals, especially in developing coun- tries. This article summarizes the status of the HIV/ AIDS pandemic as of the early 1990s; provides es- timates and short-term projections of AIDS mortality in a hypothetical country of sub-Saharan Africa; projects the potential demographic impact of AIDS in a hypothetical sub-Saharan country; and describes the major problems associated with modelling the long-term demographic impact of this pandemic. Estimated AIDS cases and deaths up to 1992 were extrapolated from public health surveillance data and through use of the WHO model. Estimates of HIV seroprevalence were based on available HIV serological data. For developed countries, HIV es- timates developed by national experts and/or na- tional AIDS programmes were used, and for de- veloping countries estimates by regional experts were used or were prepared by WHO. For the first half of the 1990s, projections of AIDS cases and deaths were derived from the WHO model; beyond the mid-1990s, the potential effects of AIDS on selec- ted demographic indicators were derived from a demographic projection model developed by the World Bank. Although estimates and long-term projections cannot be made with great precision, the general dimensions of the HIV/AIDS pandemic have been more clearly delineated now at the start of its second decade. Epidemiological data indicate that in industrialized countries, where extensive spread of HIV began in the late 1970s or early 1980s, the majority of HIV infections occurred during the first half of the 1980s. As a result, peak incidence for AIDS cases and deaths in these countries is project- ed to occur in the mid-1990s. Although a subsequent decline in cases and deaths is expected, AIDS will nevertheless remain a major disease problem in industrialized countries for the foreseeable future and will continue to have far-reaching effects on almost all sectors of human life. Heterosexual trans- mission of HIV has increased slowly but steadily in all industrialized countries during the latter half of the 1980s; the future demographic impact of HIV/ AIDS in these countries will depend on the extent of such spread during the 1990s. The results of demographic models of the HIV/AIDS pandemic in sub-Saharan Africa all project large increases in AIDS deaths. There is little doubt that during the next decades AIDS will be among the leading causes of infant and child mortality in this region. AIDS is not expected by most epi- demiologists and HIV/AIDS modellers to reverse the positive population growth rate in sub-Saharan countries over the next 20-30 years. Nevertheless, AIDS will have a profound impact on all health and social welfare systems in the region. In addition, there is a growing appreciation that AIDS will ser- iously affect social, economic and development issues, thus requiring a concerted and coordinated response from the world community. Rapp. trimest. statist. sanit. mond., 45 (1992) - 227 - RESUME Epidemiologie du VIH/SIDA au niveau mondial et projections de son impact demographique en Afrique Dans l'etat actuel de son evolution, l'epidemiologie du VIH/SIDA au niveau mondial se caracterise par une pandemie affectant principalement les hetero- sexuels, notamment dans les pays en developpe- ment. Le present article recapitule les donnees sur la pandemie en ce debut des annees 90; ii donne des estimations et des projections a court terme de la mortalite imputable au SIDA et de l'impact demogra- phique de cette maladie dans un pays imaginaire de l'Afrique au sud du Sahara; enfin, ii expose les principaux problemes que pose la modelisation a longue echeance de l'impact demographique de la pandemie. Le nombre estimatif de cas et de deces jusqu'en 1992 a ete obtenu par extrapolation des donnees de surveillance et utilisation du modele OMS. Les esti- mations de la seroprevalence du VIH sont basees sur les donnees serologiques disponibles. En ce qui concerne les pays developpes, on a utilise les esti- mations elaborees par les experts au les program- mes nationaux de lutte contre le SIDA, tandis que pour les pays en developpement ce sont les estima- tions des experts regionaux ou de l'OMS qui ant ete utilisees. Pour la premiere moitie de la decennie actuelle, les projections des cas et des deces sont fournies par le modele OMS. Au-dela, les effets potentiels du SIDA sur un certain nombre d'indica- teurs demographiques ant ete obtenus a partir d'un modele de projection demographique mis au point par la Banque mondiale. La precision sur les estimations et les projections a long terme ne peut pas etre tres bonne, cependant l'ampleur globale de la pandemie de VIH/SIDA appa- rait desormais plus clairement au seuil de sa deuxie- me decennie. Les donnees epidemiologiques indi- quent que dans les pays industrialises, c'est vers la fin des annees 70 et le debut des annees 80 que le VIH a commence a se repandre largement, la majori- te des infections ayant ete contractees pendant la premiere moitie des annees 80. II s'ensuit que, dans ces pays, !'incidence des cas et des deces passera, selon les projections, par un maximum au milieu des annees 90. Bien qu'on s'attende ulterieurement a un recul du nombre de cas et de deces, le SIDA demeurera neanmoins une pathologie majeure dans les pays industrialises et continuera d'avoir des ef- fets incalculables sur la plupart des aspects de la vie humaine. La transmission heterosexuelle du VIH a progresse lentement mais regulierement dans tous les pays industrialises au cours de la deuxieme moitie de la decennie 80; dans ces pays, l'impact demographique futur du VIH/SIDA dependra de l'ampleur de cette propagation au cours de la decennie actuelle. Les modeles demographiquesde la pandemie de VIH/SIDA aboutissent tous a la meme prevision pour l'Afrique au sud du Sahara, a savoir une augmentation impor- tante des deces imputables au SIDA. II ne fait guere de doute qu'au cours des prochaines decennies, le SIDA comptera parmi les principales causes de mor- talite infanto-juvenile dans cette region. La plupart des epidemiologistes et des specialistes de la mode- lisation ne pensent pas que le SIDA entraine une inversion de la croissance demographique dans les pays d'Afrique au sud du Sahara au cours des 20 a 30 prochaines annees. Neanmoins, la maladie aura un profond impact sur !'ensemble des systemes de sante et de protection sociale des la region. En outre, on pense de plus en plus que le SIDA va aggraver les problemes sociaux et economiques et compromettre le developpment, d'ou la necessite d'une reaction concertee et coordonnee de la part de la communaute mondiale. REFERENCES- REFERENCES 1. Moss, A. R. & SACCHETTI, P. Natural history of HIV infection. AIDS, 3: 55-61 (1989). 2. RUTHERFORD, G. W. ET AL. Course of HIV-1 infection in a cohort of homosexual and bisexual men: an 11-year follow-up study. British medical journal, 301: 1183-1188 (1990). 3. UNITED NATIONS POPULATION DIVISION. World popula- tion prospects 1990. New York, United Nations, 1991. 4. CHIN, J. Global estimates of AIDS/HIV. AIDS, 4 (Supplement 1): S277-S283 (1990). 5. CHIN, J. & MANN, J. M. Global surveillance and forecasting of AIDS. Bulletin of the World Health Organization, 67: 1-7 (1989). CHIN, J. & MANN, J. M. SIDA: surveillance mon- diale de prevalence [resume). Bulletin de /'Organisation mondiale de la Sante, 67 (1 ): 6-7 (1989). 6. CHIN, J. & LWANGA, S. Estimation and projection of adult AIDS cases: a simple epidemiological model. Bulletin of the World Health Organiza- tion, 69 (4): 399-406 (1991). Chin, J. & Lwanga, S. Estimations et projections des cas de SIDA chez l'adulte: un modele epide- miologique simple [resume]. Bulletin de Wld hlth statist. quart., 45 ( 1992) /'Organisation mondiale de la Sante, 96 (4): 405 (1991). 7. BULATAO, R. Projecting the demographic impact of the HIV epidemic using standard parameters. In: The AIDS epidemic and its demographic con- sequences. New York, United Nations/World Health Organization, 1991. (Pub. No E.91.Xlll.5). 8. UNITED NATIONS/WORLD HEALTH ORGANIZATION. The AIDS epidemic and its demographic con- sequences. New York, United Nations/World Health Organization, 1991. (Pub. No E.91.Xlll.5). 9. SHRYOCK, H. s. &SIEGEL,J. s. Methods and materials of demography. Washington, D.C., US Govern- ment Printing Office, 1973. (Volume2). 10. CHIN, J. Global estimates of HIV infection and AIDS cases: 1991. AIDS, 5 (Supplement 2): S59- S63 (1991). 11. CHIN, J. Current and future dimensions of the HIV/AIDS pandemic in women and children. Lancet, ii: 221-224 (1990). 12. UNITED NATIONS. Mortality of children under age five. New York, United Nations, 1988. (Popula- tion Studies No. 105). 13. ANDERSON, R. M. ET AL. Nature, 352: 581-589 (1991). - 228 - THE ENDEMIC TREPONEMATOSES: NOT YET ERADICATED A Meheus• & G. M. Antal b At the beginning of this century endemic treponema- toses (yaws, bejel, pinta) were rampant in almost all areas of the tropical belt but occurred as well in some communities in the temperate zone. Typically, the endemic treponematoses were confined to underprivileged population groups in remote areas with little or no access to health care and low standards of hygiene. Disease transmission occurs early in life by direct contact with infectious lesions and, in the case of bejel, also by sharing drinking vessels. The disease persists for years and may lead to gummatous lesions and the destruction of cartilage and bone. Late pinta is less distinctive, but is marked by dis- figuring pigmentary changes. The diagnosis is made on clinical grounds but syphilis serological tests are a helpful adjunct. The causative treponemes cannot yet be distinguished from each other or from the treponeme causing venereal syphilis, neither mor- phologically nor by laboratory tests. During the 1920s and 1930s treatment campaigns against yaws using multiple-dose injections of arsenical prep- arations and bismuth were launched at hospitals or by mobile units. Results of yaws treatment were spectacular, and a system of rural dispensaries was established to consolidate the results obtained by the mobile teams. In this way, yaws control in Central Africa was the starting point for the system of basic health services (1); the treatment of yaws by injection also firmly established the success of Western-style medicine in tropical countries (2). However, as treatment was limited to clinical cases only, control was not always achieved and by 1950 it was estimated that there were 50 million cases of yaws worldwide. The acceptance by the Second World Health Assembly in 1949 of an epidemiologi- cal approach for the control of the endemic trepone- matoses set the scene for a global control pro- gramme under the technical guidance of the World Health Organization (WHO) and with material sup- port from the United Nations Children's Fund (UNICEF). Long-acting penicillin was the "magic bullet" for treatment of yaws, bejel and pinta in a single intramuscular injection. It is estimated that in the course of the worldwide campaigns against en- demic treponematoses, approximately 160 million persons were examined during initial treatment surveys and more than 300 million re-examinations were done during re-surveys. In the course of these activities, approximately 50 million persons with clinical and latent infections were treated (3, 4). The control of the endemic treponematoses thus became a major success and the burden of these diseases was drastically reduced (5, 6). From 1965 onwards, control activities were greatly reduced, while the diseases were not yet eradicated. The static rural • Programme Manager, Sexually Transmitted Diseases, Global Pro- gramme on AIDS, World Health Organization, Geneva. • Former Chief, Sexually Transmitted Diseases, Division of Com- municable Diseases, World Health Organization, Geneva. health services were often ineffective in the sur- veillance of the endemic treponematoses and in the search for and treatment of cases and contacts in the community. As endemic foci remained, the last 20 years have witnessed a resurgence of the endemic treponematoses, in particular in parts of West and Central Africa and in South-East Asia (4, 7, 8). Renewed control efforts are needed, but the lack of financial and technical resources is a major barrier to effective disease control in the most affected areas. Among other important considerations are the following: (i) because of the success of the mass campaigns in the 1950s, endemic treponematoses are thought to be fully under control; (ii) as the diseases are not fatal and are restricted to poor, remote, rural populations, they are not perceived as high-priority problems by many decision makers; (iii) there is the potential for development of resist- ance of the treponeme against long-acting penicillin; (iv) in areas where endemic treponematoses still occur, health services are inadequate or non- existent; (v) programmes aiming at a single disease are now frowned upon by the international public health establishment; (vi) the emphasis is now on establishing broad-based primary health care ser- vices in currently underserved areas of the world (9). Therefore innovative approaches are needed for re- newed control efforts against the endemic trepone- matoses (10, 11, 12). These diseases can be lastingly controlled and finally eradicated by active com- munity involvement in control activities integrated with the primary health care (PHC) services. Where PHC is inadequate, yaws control can be used as a catalyst to strengthen PHC and drastically increase the utilization of health services (13). Detailed data on endemic treponematoses were last published in 1985 (4); more recent information on the epidemiology of these diseases according to WHO region and epidemiological areas is exten- sively reviewed in this article. Africa In Mauritania, seroepidemiological studies point to the existence of a large focus of endemic syphilis (bejel) with some persistent transmission in popula- tion groups living along the Senegal River (14). In Senegal, Ridet found clinical and serological evi- dence of continued endemic syphilis (bejel) trans- mission in populations south of the Senegal River where 2.1% of the children under 15 years of age showed early clinical lesions of the disease and about 14% had serological evidence of treponemal infection - not less than 60% of these were high- titre reactors (>1:16); 70% of adults had serological evidence of past exposure to treponemal infection (15). The endemic area seemed to extend into the Rapp. trimest. statist. sanit. mond., 45 (1992) - 229 - departments of Linguere and Kedougou in Eastern Senegal where a much lower disease activity was found. According to Graitcer (unpublished report, 1985) the health services identified 1 119 cases of endemic syphilis (1980) primarily in the districts of Longa, Thies and Eastern Senegal. 60% of cases occurred in children under 15 years of age. Yaws used to be mesa- to hypoendemic in the Lower Casamance, an area adjacent to the Gambia and close to the Atlantic Ocean, but disease trans- mission in this focus may have ceased already (15). The very rare seropositivity in children could be attributed to congenital syphilis. However, yaws cases continued to be reported (Table 1) from dif- ferent areas of the country and there is no explana- tion for the reported presence of yaws in the same area where endemic syphilis is found. In Guinea hypo- and mesoendemic areas were situ- ated close to the borders with Liberia and Sierra Leone in the humid forest zone. After a mass treat- ment campaign no cases of yaws were reported until 1983, when a resurgence occurred, during which more than 1 600 active cases were reported. Since then yaws cases have continued to be detected TABLE 1. REPORTED CASES OF ENDEMIC TREPONEMATOSES, 1983-1990• TABLEAU 1. CAS DECLARES DE TREPONEMATOSES ENDEMIQUES, 1983-1990• Africa - Afrique Angola ........................... . Benin - Benin ..................... . Burkina Faso Yaws- Pian ..................... . Bejel - Bejel .................... . Burundi ........................... . Cameroon - Cameroun .............. . Central African Republicb - Republique centrafricaineb ........... . Chad -Tchad ...................... . Congob ........................... . Cote d'Ivoire Yaws- Pian ..................... . Bejel - Bejel .................... . Equatoria Guinea - Guinee equatoriale .. . Ethiopia - Ethiopie ................. . Gabonb ........................... . Ghanab ........................... . Guinea - Guinee ................... . Guinea-Bissau - Guinee-Bissau ........ . Mali .............................. . Niger ............................. . Nigeriab - Nigeria .................. . Rwandab .......................... . Senegal - Senegal .................. . Togob ............................ . Uganda - Ouganda ................. . Zaire - Zafre ....................... . Zambia - Zambie ................... . South-East Asia - Asie du Sud-Est India - lnde ....................... . Indonesia - lndonesie ............... . Thailand - Tha'ilande ................ . Western Pacific - Pacifique occidental Fiji-Fidji ......................... . Papua New Guinea - Papouasie-Nouvelle-Guinee .......... . Solomon Islands - lies Salomon ....... . Vanuatu ........................... . Viet Nam ......................... . Americas - Amerique Colombia (yaws) - Colombie (pian) ..... . Mexico (pinta) - Mexique (pinta) ....... . 1983 1984 3 895 3 327 781 485 117 102 8 041 9 226 732 674 1 629 203 1 644 18 235 16 109 585 168 5 223 1 652 3 8 9 314 525 408 70 4382 697 380 283 91 246 9160 1174 224 898 225 31 2 956 260 111 588 422 7 302 15 931 33 16C 21 833 4 041 492 22 1985 1 730 545 14 5 030 1 025 2 173 161 10 468 394 342 4 012c 161 4 95 0 1 154 19 3 5 719 25 339c 2 1 647 411 1986 1987 1988 1989 70 2 428 580 583 1 503 103 89 94 4 425 3 425 4 354 1 236 1 553 88 100 269 48 5 166 18 790 22 234 20 476 1 404 2 064 533 213 127 10 6594 415 1 687 286 18 2 404 2 1 854 157 14 136 187 614 208 2 280 927 265 380 5 639 0 11 2 070 12 92 210 3 534 59 704 875 189 21 5 729 117 0 3063 4165 446 23 94 17c 2 899 0 0 3 421 6 477 98 78 1990 17 738 4124 278 9 664 29 1 927 78 70 a In general data are compiled from country reports to WHO, consultant and research surveys - En general, les donnees sont etablies a partir de rapports de pays envoyes a l'OMS, d'enquetes de consultants et de resultats de recherches. b Infectious lesions only - Lesions infectieuses uniquement. c Provisional data - Donnees provisoires. Wld hlth statist. quart., 45 (1992) 3 Q ::, ?- tli M A P 1 . G EO G R AP H IC AL D IS TR IB U TI O N O F TH E E N D E M IC T R E P O N EM AT O SE S IN T H E E A R LY 1 99 0s C AR TE 1 . R E P A R TI TI O N G EO G R AP H IQ U E D E S TR E P O N EM AT O SE S E N D E M IQ U ES A U D E B U T D E S A N N E E S 9 0 Pi nt a ~ Y aw s- P ia n • En de m ic s yp hi lis - Sy ph ili s e n de m iq ue W H 09 25 22 Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f th e s e cr e ta ria t o f th e W HO c o n ce rn in g th e le ga l st at us o f a n y c o u n tr y, t er rit or y, c ity o r a re a o r o f its a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f its f ro nt ie rs o r bo un da rie s - Le s de si gn at io ns u til is ee s s u r ce tte c a rt e e t la pr es en ta tio n d es d on ne es q ui y f ig ur en t n 'im pl iq ue nt , de l a p ar t de ! 'O rg an is at io n m o n di al e de la S an ta , a u c u n e p ris e de p os iti on qu an t a u st at ut ju rid iq ue d e te l o u te l p ay s, te rr ito ire , v ill e o u z o n e , o u d e se s a u to rit 0s , n i q ua nt a u tr ac e de s es f ro nt ie re s. I' -) w 0 - 231 - (Table 1) indicating that yaws transm1ss1on is still present to some extent in the former endemic areas. In Liberia low-level yaws transmission was sus- pected to occur in areas close to the border with Cote d'Ivoire, namely Nimba, Grand Bed and Maryland counties; the government considered in- tensifying anti-yaws activities but was unable to do so owing to lack of financial resources. The present epidemiological situation concerning yaws is unclear and the government is in favour of an epidemiologi- cal investigation. In Cote d'Ivoire where active surveillance for the endemic treponematoses is being pursued, large numbers of cases of yaws and endemic syphilis are being reported to the Ministry of Public Health (Table 1) - about one-third are infectious lesions. One-third of the cases are reported from four rural provinces: Adzope, Gagnoa, Bondouku and Tissale. In 1991 mass treatment activities were implemented in two regions. In Ghana following the mass penicillin treatment campaign (1955-1965), static health care facilities could not control the spread of yaws in the affected populations. Consequently, active yaws cases in- creased 21-fold between 1969 and 1976 (16). The three southern regions - Ashanti, Eastern and Cen- tral - reported 80% of the yaws cases, with inci- dence rates between 400 and 500 cases per 100 OOO population. The government, in cooperation with the European Economic Community, WHO, UNICEF and USAID launched a yaws/yellow fever programme which also included BCG and tetanus vaccination activities (1981-1983). As a result, yaws was reduced to 62 cases per 100 OOO population in the most affected areas. Economic problems in Ghana have limited the continuation of yaws control activities which may result in another resurgence of the dis- ease, particularly in the most remote rural areas. The government is interested in reactivating intensified yaws control activities. Yaws appears to be still highly endemic in Togo (Table 1) where the endemic area is located in the southern region and along the borders with Ghana and Benin. Yaws prevalence rates of 2-3.5% were reported from the 5 most affected prefectures (Lacs, Vo, Yoo, Kloto and Bassar).c In Benin yaws is endemic in the provinces of Mono, Atlantique and Oueme in the south of the country. A survey in Oueme province found 1.7% of children suffering from infectious yaws lesions (17) and sero- reactor levels of 19%. About 3 OOO yaws cases are detected annually (Table 1) indicating continued yaws transmission in the affected areas. Yaws con- trol is limited to the activities of the fixed health care facilities which are often far away from the remote yaws endemic areas. An endemic syphilis (bejel) focus is suspected to exist in the north of the country. The yaws control programme in Nigeria is part of the federally operated sexually transmitted disease (STD) control programme which is now integrated with the AIDS control programme. Yaws cases con- tinue to be reported from many areas of the country, including from those areas where the disease is c World Health Organization. Yaws and other endemic treponema- toses. Report of a regional meeting, Brazzaville, 3-6 February 1986. (Unpublished document AFR/CD/58). Wld hlth statist. quart., 45 (1992) known not to exist, indicating the diminishing com- petence of medical staff to identify yaws cases. Small-scale epidemics continue to be reported from communities in the south of the country, in Bendel and Cross River States (M. 0. Alli, unpublished report, 1986) including a small outbreak close to Lagos (0. Ogunnowo, personal communication, 1988), where active surveillance is required to de- lineate and control a still simmering yaws ende- micity. A bejel endemic area still exists in the department of Oudalan in the north of Burkina Faso; Oudalan is a semi-desert area of about 10 OOO km2 with a popula- tion of approximately 50 000. This area is adjacent to the bejel-endemic area of Gao in Mali (see below). Several studies found about 7% of children between 5 and 14 years of age with early bejel lesions; up to 22% of children and 41% of adults showed serologi- cal evidence of treponemal infection. Nomadic and semi-nomadic ethnic groups (e.g. Fulani, Tuaregs, Bellahs) were most affected by bejel. There has been little change in transmission levels over the past years (18). A yaws-endemic area is located in the south-west of the country, a savannah area with approximately 1.1 million inhabitants. An epidemiological investi- gation identified the area of Gaoua as the focus of yaws transmission, with 3.9% of chfldren suffering from infectious yaws lesions and 11.6% showing serological evidence of treponemal infection (19). For most years no separate data are available for endemic syphilis (Table 1) since venereal and en- demic syphilis (bejel) are reported as a single dis- ease entity. The government sees the endemic trepo- nematoses as a public health problem but lacks resources for their definite control. There are three distinct foci of endemic syphilis in the Sahelian zone of Mali: a mesa-endemic area is situated in the Senegal river basin in the west of the country; it includes 7 districts (1.5 million in- habitants) in the regions of Kays and to the north of Koulikoro, where 19% of children aged 5-9 years were found to be infected by the treponeme. An- other focus of infection (0.6 million inhabitants) is associated with the Dogan tribe which lives on the cliffs of Bandiagara in the Mopti region in the centre of Mali (Ministry of public health, unpublished re- port, 1986). The most important bejel endemic area extends over 10 districts with 1.1 million inhabitants along the river Niger in the regions of Timbuktu and Gao. In preparation for a mass-treatment campaign, an epi- demiological study (20) confirmed bejel to be hyper- endemic in this area. More than one-fifth of the children between 5 and 14 years were found to be infected, and in more than half the infection was still active. A mass treatment campaign was imple- mented (1987-1988) in collaboration with Medecins sans frontieres. An attempt was made to evaluate different serological parameters for their efficacy in measuring the impact of mass treatment by a standard single-dose penicillin regimen on trepo- nemal endemicity in the child population (5-15 years). A comparison of two serum collections drawn randomly from the same population groups before therapy and 12 months later showed that the demonstration of the disappearance of treponemal lgM (present in active disease) by the solid-phase haemadsorption assay (SPHA) is the most sensitive indicator; but the test is complicated and costly. - 232 - However, a more practical indicator was shown to be a change in seroprevalence of high-titre VDRL reactors (>1.8, or better >1:16) among children who respond to the therapy by converting to a negative serological test (Table 2). Now, the government would like to continue and extend campaign ac- tivities. A yaws-endemic area used to exist in the districts of Bougouni and Sikasso in south-west Mali, an area bordering on Burkina Faso, Cote d'Ivoire and Guinea. The Ministry of Public Health (unpublished report, 1986) believes that yaws transmission has ceased, as no clinical cases of yaws nor any sero- reactor could be detected among children under 10 years of age. Endemic syphilis (bejel) is found among the Tuareg and Bellah in the north of Niger: there are about 800 OOO Tuaregs for whom the government conducts annual treatment clinics in several northern villages at the time the nomads congregate. Over 9 OOO bejel cases were reported in 1983; most were from the northern departments of Agadez, Arlit and Tchinta- baraden. Financial limitations curtailed these treat- ment activities and reduced the number of reported bejel cases drastically (Table 1). In 1990 medical authorities resumed treatment activities at one gath- ering place of the Tuareg and expressed their in- terest in launching a bejel control programme among the nomadic groups in the desert area. There are anecdotal reports of numerous bejel cases in the northern part of Chad where war-like con- ditions have curtailed control activities. Several thousand yaws cases are reported annually from Cameroon (Table 1). The data were reviewed recently by Louis et al. (21). Most cases occurred in south-west Cameroon which is close to the Cross River State of Nigeria and may form a common yaws-endemic area. Another yaws-endemic area is located close to the border with Gabon, Congo and the Central African Republic where itinerant pygmy populations are heavily infected. Not less than 480 yaws cases were found among 653 pygmies exam- ined (WHO/AFRO, unpublished report, 1992). Pygmy groups represent an important source of infection for the sedentary populations with which they come into contact. The health administration has no specific plan for the control of this infection. In Gabon yaws is endemic in the north (Woleu-Ntem Province) and is said to be primarily confined to itinerant pygmy groups which move freely across the border with Equatorial Guinea, Cameroon and the Congo. Reports on a recent increase of yaws in Ngounie Province have been investigated and results are awaited. Also in the Central African Republic yaws infections are predominantly found among the pygmies of the rain-forest area in the south of the country. In the course of treatment surveys carried out among pygmies in Sangha and Lobaye provinces, R. Widy- Wirski (unpublished report, 1986) identified active yaws lesions in 41% of 1 005 pygmies and more than 75% had serological evidence of active disease. An increase of reported yaws cases has been noted in recent years (Table 1). A health education cam- paign is currently being undertaken among pygmies. In Congo most yaws cases occur among the pygmies and are reported from the provinces of Likouala and Sanghia; and from the southern part of the country, Lekoumou and Kouilou. The first two areas are adjacent to the yaws-endemic areas in Cameroon, Gabon and the Central African Republic (Ministry of Public Health, unpublished report, 1985). Several surveys carried out in Likouala confirm very high rates of clinical yaws among pygmies (22). Plans have been drawn up for a yaws control pro- gramme in the north of the country. Yaws was thought to have been eliminated from Zaire since the early 1960s. However, the disruption of health care services and economic deprivation have made it difficult for the population to maintain personal hygiene and have led to an environment favourable to the transmission of the endemic trepo- nematoses. Two recent surveys identified yaws- endemic foci in Ubangi in the north-west of the country, not far from Bangui, Central African Re- public, and in the lturi forest area in the north-east of Zaire (23, 24). In the former, focus cases with infectious yaws lesions were seen in 11% of the children under 15 years of age in this sedentary population. In lturi, yaws was found at a high rate among pygmies. WHO received a request to col- laborate in the training of laboratory and other health personnel to be involved in planned yaws control activities. More than 200 yaws cases are reported annually from Rwanda (Table 1). Health authorities believe that the disease problem can be controlled by rou- tine health service activities. In Sudan yaws is suspected to be still endemic in the southern regions of Equatoria, Bahr-el-Ghazal and Upper Nile; but this area cannot be surveyed because of civil unrest. Some low-level endemicity TABLE 2. VALUE OF DIFFERENT SEROLOGICAL TESTS IN EVALUATING THE IMPACT OF A MASS TREATMENT CAMPAIGN AGAINST ENDEMIC TREPONEMATOSES, IMBUKTU REGION, MALI TABLEAU 2. RESULTATS DE DIFFERENTS TESTS SEROLOGIOUES UTILISES POUR EVALUER L'IMPACT D'UNE CAMPAGNE DE TRAITEMENT DE MASSE CONTRE LES TREPONEMATOSES ENDEMIOUES, REGION D'IMBUKTU, MALI SPHA-lgM .................................... . Qualitative VDRL - VDRL qualitatif ................ . Quantitative VDRL- VDRL quantitatif (Titre ;a, 1:8) .... . Quantitative VDRL - VDRL quantitatif (Titre ;a, 1 :16) ... . Quantitative TPHA - TPHA quantitatif (Titre ;;;, 1 :1280) .. Quantitative TPHA- TPHA quantitatif (Titre ;a, 1:10240) . 1987 % 11.5 20.1 16.0 14.1 18.7 8.2 1988 % 2.7 16.6 5.7 3.1 18.0 4.1 Ratio - Rapport 1987 1988 4.3 1.2 2.8 4.5 1.0 2.0 p <0.0001 NS <0.001 <0.001 NS 0.035 Rapp. trimest. statist. sanit. mond., 45 (1992) - 233 - of endemic syphilis exists in the Northern Region (Nuba mountains).d In Ethiopia an organized yaws campaign took place in the south and south-west of the country in the 1950s. No subsequent information on the epi- demiological situation became available until a small survey of some villages in the Wellaga and lllubabor administrative regions in the south-west of the country was carried out in 1986 as part of a viral survey programme. Not less than 68% of 227 children tested showed serological evidence of treponemal infection, and infectious yaws lesions could be observed in 10 of 200 children in one area (25). This focus may well be a part of the yaws- endemic area in Sudan. Although Angola was assumed to 'be free from yaws, it reported 70 cases of the disease in 1988 (Table 1).c A recent observation (26) of an unexplained positive syphilis serology in sera collected from 1 575 healthy black primary school children in Bloemfontein South Africa led the investigators to reflect on the possible existence of endemic syphilis in the population of the black township. Similar observations of what was believed to be endemic treponematosis had been made in black communities in Bloemfontein and the Cape Province. Two treponemal diseases which are similar to or· identical with endemic syphilis and bejel existed in Bantu populations of Botswana (dichuchwa) and Zimbabwe (njovera). Dichuchwa may still be preva- lent among the bushmen of the Kalahari desert, but njovera is no longer encountered (Latif, personal communication, 1992). Eastern Mediterranean d Yaws was reported (1955) from the lowlands be- tween the Juba and Shabelle rivers in the south of Somalia, but no studies were undertaken to confirm the existence and extent of the disease. Bejel is suspected to occur among the Bedouin in the North. In the arid areas of Hijaz and Asir in Saudi Arabia, bejel was endemic among the nomatic and semi- nomadic Bedouin. Two recent studies (27, 28) found clinical and serological evidence of possibly no longer active foci of a nonvenereal treponematosis (bejel) in the north-west and south-west of the country. In the Syrian Arab Republic the disease has virtually disappeared after an eradication campaign in the 1950s in bejel-endemic north-eastern provinces of Deir-Ezzor, Hassaka and Ragga, and surveillance ac- tivities which continued for 8 years. A seroepidemiological survey carried out in Iraq on 102 children aged 7-14 years in the Amara region demonstrated that bejel transmission has ceased in this area for some time. Moreover, information on the situation regarding bejel in the western Euphrates valley and Mosul indicates that no bejel case had been seen for the last 20-30 years. A focus of endemic syphilis was discovered recently in a remote area in the north-western part of d World Health Organization. Regional meeting on endemic trepone- matoses, Amman, Jordan 20-23 October 1986. (Unpublished docu- ment EM/CD/36-E). Wld hlth statist. quart., 45 ( 1992) Pakistan; 43 cases of infectious lesions were de- tected among 2 OOO persons. Cases tested by VDRL were found to be reactive. South-East Asia The present yaws situation in India is not entirely clear. An enquiry made into the extent of the yaws problem in Central India in 1985 showed that in at least 10 districts of 3 states (Andhra Pradesh, Orissa and Medhya Pradesh), low-level disease transmis- sion was continuing. 1 349 yaws cases were repor- ted from this area over a 21/2-year period (1983 to June 1985). Yaws endemicity appears to be associ- ated with certain tribal groups and some degrees of inaccessibility. There may be some additional pockets of endemic treponematosis in Tamil Nadu, the North-East Frontier States and Gujarat (29). In Sri Lanka few yaws cases (2 cases in 1982; 9 cases in 1983) are reported from two areas of low socioeconomic status; the north-central plains and the adjacent lower part of the hill country and an area in the south of the country (30). The disease is being kept under surveillance by anti-malaria teams which are active in this area. Yaws appears to have been eliminated from Thailand, except for the occasional small outbreaks in the border area with Malaysia. Owing to rapid mop-up operations, these epidemics could be con- tained within a short period of time. By the early 1950s the estimated total number of yaws cases was about 12 million (i.e. mean preva- lence 15%), making Indonesia the second largest focus of yaws in the world (after Africa). A WHO/ UNICEF-sponsored national yaws control pro- gramme did not rely on a vertical approach and the use of mobile field teams but established 2 500 district teams to cover all 26 yaws-endemic pro- vinces. Since its implementation yaws control ac- tivities were continued with varying intensity and changing control approaches. Yaws could be redu- ced to negligible levels indeed in 12 provinces in- cluding Java, Bali, major parts of Kalimantan and Sulawesi, but is still of considerable prevalence in the rural areas in the eastern and western parts of Kalimantan, the island of Sumatra, the Moluccas, Timar and in particular in lrian Jaya. In the latter area, yaws transmission is still quite intensive in the remote tribal areas, while among the new settlers originating from other parts of the country yaws is rarely observed. It may be estimated that since the onset of organized yaws control activities, the popu- lation living in yaws-endemic areas and therefore being exposed to yaws infection declined from 92 million to 35 million. The latest data available refer to 1984 when 15 931 infectious yaws cases were reported from 22 of the 27 provinces (31). There is little doubt that yaws still constitutes a major health problem in large parts of the popula- tion living in remote and economically depressed areas. A yaws control campaign was launched in 1991 in East Timar with support from UNICEF (Meheus, unpublished report, 1991). Western Pacific After a vertical treatment campaign in the early 1960s, yaws was considered eradicated from - 234 - Cambodia. Subsequently there were anecdotal re- ports of skin lesions believed to be yaws being seen among Cambobian refugees arriving in Thailand. In 1986 Cambodia reported 4 858 cases of clinical yaws. Considering the inadequacy of the health ser- vice infrastructure at that time and the limited dia- gnostic capabilities for this "end-of-the-road dis- ease" it may be reasonably assumed that the number of reported cases does not reflect the true extent of the disease problem. During a consultation, R. Widy-Wirski (unpublished report, 1987) observed several villages with children having active yaws lesions. He also found high seroreactor rates in both children and adults, indicating a recent resurgence of yaws transmission in certain communities. Anti- yaws activities were implemented in military secure areas of Kampong Speu, Kampong Chhang, and Siem Reap province between 1987 and 1991. During this period 1 935 yaws cases were treated. In Papua New Guinea yaws was deemed to be under control as a result of the nationwide total mass treatment campaign in the late 1950s and limited regional efforts in the late 1970s. However, various investigations since 1978 confirmed a resurgence of yaws infection in the North of the country (East & West Sepik, Karkar Island) and Papua (East New Britain, New Ireland, North Solomon) with isolated pockets of high clinical and serological prevalence being encountered often. 833 yaws cases were re- ported in 1984 (32). By 1989 the number of reported cases had quadrupled (Table 1). Of serious concern are observations from Papua New Guinea and the Solomon Islands of diminished response to treat- ment with repository penicillin and the persistence of yaws transmission despite intensive treatment of cases and contacts. The possible emergence of Treponema pertenue strains with reduced sus- ceptibility to penicillin needs to be investigated. Yaws prevalence in the Solomon Islands was the highest among the Pacific Islands. Following the WHO/UNICEF-supported national yaws treatment campaign and subsequent surveillance activities (1956-1970), yaws was thought to have been elimin- ated and transmission interrupted. In 1981 many cases of skin lesions were observed in the Western Province. A serological investigation confirmed these lesions to be due to yaws. It was speculated that yaws had been reintroduced from a yaws-endemic area in Papua New Guinea. In 1984 a mass treatment campaign was launched which examined 29 135 people and identified 4 041 active yaws cases, pre- dominantly in children. Subsequent to this cam- paign, yaws reappeared in the same area and led to a further yaws treatment campaign with the assist- ance of the New Zealand Army in 1987. 2 070 active yaws cases were detected among the 24 216 inhabitants of the yaws-endemic area (33). In response to a renewed yaws epidemic, another treat- ment campaign was carried out in 1991. Vanuatu (the former New Hebrides) continued to report yaws cases (495 cases in 1985); most were from Tanna Islands and some from Espiritu Santo. With the help of the New Zealand Army, a mass examination and treatment programme was carried out on Tanna Island in 1989. Among 18 223 people examined 464 suspected yaws cases were found, of which 23% could be serologically confirmed, bring- ing the prevalence of clinical yaws cases to less than 1% (34). Two years later a considerable number of yaws cases were again reported from Tanna Island from villages which had refused to participate in the recent control programme (W.I. van der Meijden, unpublished report, 1992) - the infection may spread again from there to the rest of the popula- tion. Americas Until the first half of this century, yaws and pinta represented an important public health problem in several countries of Latin America and the Caribbean. In most of the endemic areas, yaws and pinta were eradicated through national mass treat- ment campaigns. Unfortunately, pockets of these two endemic treponematoses still exist in remote areas of some countries (S. Talhari, unpublished report, 1988). In Suriname yaws appears to be still endemic among the black populations living in the interior of the country, where over 10% of rural schoolchildren had a positive syphilis test in 1980. Few clinical yaws cases from the interior seek care in the capital city, and civil unrest in the interior prevented the im- plementation of control activities. Low-level yaws transmission persists in Guyana where between 1979 and 1984 the leprosy service identified 36 yaws cases. In Venezuela no yaws cases have been identified for the last 15 years. The disease is regarded as being eradicated. However, between 1983 and 1985, 24 pinta cases were reported, and pinta transmis- sion is going on among Indian populations close to the border with Colombia. In Panama yaws cases have not been observed since 1980 and the disease can be regarded as having been eradicated, but the eradication of pinta is less certain. As recently as 1988 some foci of yaws were detected by R. Widy-Wirski (unpublished report, 1988) in the course of surveys for HIV infection among rural populations in Haiti. Two cases of early yaws reported in pregnant women in Martinique (35) give evidence of con- tinued low-level endemicity of this treponematosis. In Mexico pinta was endemic predominantly in the states of Guerrero, Michoacan, Chiapas and Oaxaca. In the course of a national pinta campaign, which was deactivated in 1983, over 250 OOO pinta cases were· traced and treated. In the state of Michoacan the disease is thought to have been eradicated. Active pinta surveillance is maintained in the state of Oaxaca only. While pinta does not represent a public health problem now, low-level disease transmission is continuing (Table 1) in the remote pinta-endemic areas which may offset some of the gains achieved by the control programme. Yaws is still endemic in communities along the Pacific coastal area of Colombia where an integrated active surveillance programme is operational. A dis- turbing increase in reported yaws cases has been noted in recent years (Table 1). In addition, yaws cases are reported from other endemic areas of the country. In Brazil no new yaws infections have been seen for several years. Pinta is now rarely seen among Indians in the Western Amazonas region and along the tributaries of the Rio Negro. Rapp. trimest. statist. sanit. mond., 45 (1992) - 235 - Europe The last foci of endemic syphilis were located in rural Bosnia and among Moslem Turkish farmers in Bulgaria. With the advent of penicillin therapy a mass treatment campaign was implemented in Bosnia in 1948. This campaign was the model for the epidemiological approaches applied in subsequent mass treatment campaigns against the endemic treponematoses all over the world. In surveys and resurveys 35 238 cases of endemic syphilis were treated. The campaign resulted in the eradication of the disease in 1951 (36). The little known focus in Bulgaria was also success- fully controlled by a case-treatment campaign (1958- 1962). A follow-up study confirmed that complete interruption of treponemal transmission has been achieved (37). Acknowledgement The authors wish to thank their colleagues in the Regional Offices for their collaboration in gather- ing all the information, and in particular Dr D. Barakamfitiye and Dr G. Petersen for provid- ing detailed data. SUMMARY The endemic treponematoses which comprise yaws, endemic syphilis (bejel) and pinta constitute a group of potentially disabling and disfiguring infections which primarily afflict children in tropical and sub- tropical areas. Foci where these diseases are now endemic have a patchy distribution and are typically confined to underprivileged communities living in remote rural areas, with little or no access to health services and removed from the mainstream of socio- economic development. A drastic decline in the prevalence of these infec- tions was brought about by the implementation of mass treatment campaigns with penicillin under the technical guidance of WHO and with material sup~ port from UNICEF in the 1950s and 1960s. These worldwide campaigns against the endemic trepone- matoses halted disease transmission in many areas and held the promise of complete eradication if intensive surveillance could be continued for some time with the increasing involvement of the basic health services. National campaigns were so suc- cessful that relatively low priority was given to the preparation of the rural health services for this new task. The failure of many countries to integrate active control measures into the functions of the rural health services led to the gradual build-up and extension of treponemal reservoirs and the re- surgence of foci of increased disease transmission particularly in communities where standards of hygiene and health care had remained low. In a number of former endemic foci only low-level trans- mission persisted; in a few areas disease prevalence increased dramatically to reach pre-campaign levels. The lack of technical and financial resources limited the success of renewed national control activities in the most affected areas. Today, with waning interest in these diseases con- fined to remote, and thus silent, population groups, and a decreasing ability of health staff to identify cases, data collected by countries need to be supple- mented by information from other sources in order to arrive at a more valid assessment of the situation concerning the endemic treponematoses. Central and West Africa are most severely affected by the resurgence of the endemic treponematoses. In recent years a number of countries (e.g. Ghana, Cote d'Ivoire and Mali) have launched renewed con- trol efforts, often combining yaws or endemic syphilis control with other public health pro- grammes. In Central Africa itinerant pygmy groups are still highly affected by yaws and are an impor- tant source of infection for the sedentary population with which they come into contact. In Chad, Sudan and Ethiopia, there is some evidence of persistent foci of endemic treponematoses; the epidemiological situation in Southern Africa is not well established. In the Eastern Mediterranean, bejel has been elim- inated from most areas, but foci of infection have been reported in remote villages in Pakistan, and some endemic syphilis transmission might still pre- vail in nomadic people of the Arabian peninsula. Health officials in South-East Asia and the Pacific Islands have documented remaining foci of yaws in at least 7 Member States, including several out- breaks in the Solomon Islands. Indonesia has made dramatic progress in yaws control but widely dis- persed foci of infection still persist, particularly in lrian Jaya, the Moluccas, Sumatra and Kalimantan. In the Americas, yaws incidence is very low with very small foci remaining in Suriname, Guyana, Colombia and some islands of the Caribbean. Pinta cases are still detected in Indian tribes of Mexico and the Amazon basin. RESUME Les treponematoses endemiques: pas encore d'eradication Les treponematoses endemiques qui comprennent le pian, le bejel (syphilis endemique) et la pinta consti- tuent un groupe d'infections potentiellement invali- Wld hlth statist. quart., 45 ( 19921 dantes ou defigurantes qui frappent avant tout l'en- fant dans les regions tropicales et subtropicales. Les foyers actuels d'endemie sont repartis irreguliere- - 236 - ment et se limitent generalement aux communautes defavorisees vivant dans des zones rurales reculees a l'ecart du developpement socio-economique et dans lesquelles l'acces aux services de sante est difficile ou inexistant. Les campagnes de traitement de masse menees au moyen de la penicilline avec l'appui materiel de l'UNICEF au cours des annees 50 et 60 ont entraine un declin spectaculaire de la prevalence de ces infections. Les campagnes mondiales contre les tre- ponematoses endemiques ont permis d'interrompre la transmission dans de nombreuses regions et laisse entrevoir la possibilite d'une eradication com- plete si une surveillance intensive pouvait etre main- tenue assez longtemps avec la participation crois- sante des services de sante de base. Les campagnes nationales ont connu un tel succes que la prepara- tion des services de sante ruraux a cette nouvelle tache est apparue comme mains prioritaire. Beau- coup de pays n'ayant pas integre de mesures de lutte actives aux services de sante ruraux, on a assiste a une extension et a un renforcement pro- gressifs des reservoirs a treponemes ainsi qu'a la resurgence de foyers de transmission accrue, notam- ment dans les communautes ou les normes d'hygie- ne et de soins de sante restent peu developpees. Dans plusieurs anciens foyers d'endemie, on n'ob- serve qu'une persistance de la transmission a un faible niveau, mais parfois la prevalence a augmente de fai;:on spectaculaire pour se retrouver au niveau d'avant les campagnes. Le manque de ressources techniques et financieres a limite le succes des nouvelles activites nationales de lutte dans la plupart des regions touchees. Aujourd'hui, ces maladies qui se limitent a des zones reculees et a des groupes incapables de faire entendre leur voix suscitent mains d'interet et les agents de sante savent de mains en mains les reconnaitre. Les donnees reunies par les pays doi- vent done etre completees par des informations emanant d'autres sources pour permettre une eva- luation plus precise de la situation des treponemato- ses endemiques. Les regions les plus touchees par la resurgence sont l'Afrique centrale et occidentale. Ces dernieres an- nees, plusieurs pays, par exemple le Ghana, la Cote d'Ivoire et le Mali, ont lance de nouveaux efforts de lutte en rattachant souvent la lutte contre le pian ou la syphilis endemique a d'autres programmes de sante publique. En Afrique centrale, les groupes itinerants de pygmees sont encore tres touches par le pian et constituent une importante source d'infec- tion pour la population sedentaire avec laquelle ils entrent en contact. Au Tchad, au Soudan et en Ethiopia, certaines indications temoignent de la per- sistance de foyers de treponematoses endemiques; la situation epidemiologique en Afrique australe n'est pas connue avec precision. En Mediterranee orientale, le bejel a ete elimine dans la plupart des zones, mais des foyers d'infection ont ete signales dans des villages recules du Pakistan, et ii est possi- ble que la transmission de la syphilis endemique subsiste chez les nomades de la peninsula arabique. Les responsables de la sante en Asie du Sud-Est et dans les iles du Pacifique ont fait etat de foyers de pian qui se maintiennent dans 7 Etats Membres au mains, plusieurs poussees ayant ete notamment ob- servees aux lies Salomon. L'lndonesie a fait des progres spectaculaires dans la lutte contre le pian, mais des foyers d'infection tres disperses subsistent notamment en lrian Jaya, dans les Moluques, a Sumatra et a Kalimantan. Dans les Ameriques, !'incidence du pian est tres faible et seuls des foyers reduits subsistent au Suri- name, en Guyana, en Colombia et dans certaines iles des Cara'ibes. On observe encore des cas de pinta chez des populations indiennes du Mexique et d'Amazonie. REFERENCES - REFERENCES 1. Rapport de !'Administration beige du Rwanda- Burundi, 1938. Cited in: Van Nitsen, R., Le pian. Bruxelles, lnstitut royal colonial beige, Section des sciences naturelles et medicales, 1946. (Memoires). 2. HACKETT, C. J. Private medical practice and anti- yaws campaigns in South-Eastern Nigeria 1925- 1950. Tropical doctor, 10: 129-132 (1980). 3. GuTHE, T. & W1LLCOK, R. R. Treponematoses: a world problem. WHO Chronicle, 8: 37-113 (1954). 4. ANTAL, G. M. & CAUSSE, G. The control of en- demic treponematoses. Reviews of infectious diseases, 7 (Supplement): 5220-5226 (1985). 5. WORLD HEALTH ORGANIZATION. Four decades of achievement 1948-1988. Geneva, WHO, 1988. 6. CAUSSE, G. & MEHEUS, A. Control of sexually transmitted diseases (STDs) [summary]. World health statistics quarterly, 41 (2): 100-101 (1988). CAUSSE, G. & MEHEUS, A. La lutte contre les maladies sexuellement transmissibles (MST). Rapport trimestriel de statistiques sanitaires mondiales, 41 (2): 82-102 (1988). 7. Yaws again (editorial). British medical journal, 4: 1090 (1980). 8. Endemic treponematoses. Weekly epidemiologi- cal record, 56: 241-244 (1981). Les treponematoses endemiques. Re/eve epide- miologique hebdomadaire. 56: 241-244 (1981 ). 9. HOPKINS, D. R. Control of yaws and other en- demic treponematoses: implementation of verti- cal and/or integrated programs. Reviews of in- fectious diseases, 7 (Supplement): 5338-5342 (1985). 10. MEHEUS, A. Integration of yaws control and primary health care. Reviews of infectious dis- eases, 7 (Supplement): 5284-5288 (1985). 11. DE SCHRYVER, A. & MEHEUS, A. Revue: les trepone- matoses endemiques ne sont toujours pas eradi- quees. Medecine tropicale, 49: 237-244 (1989). 12. LUGER, A. & MEHEUS, A. [Alarming spread of endemic treponematoses]. Zeitschrift fur Haut- krankheiten, 63: 463-464 (1988). (In German). 13. MEHEUS, A. Integrated disease control for yaws- affected populations. South-East Asian journal of tropical medicine and public health, 17 (Supple- ment): 84-88 (1986). 14. LEPERS, J. P. ET AL. Etude sero-epidemiologique en Mauritania (1985-1986): frequence des trepo- Rapp. trimest. statist. sanit. mond., 45 (1992) - 237 - nematoses, du virus de l'hepatite B, du virus VIH et des hemorragies virales. Bulletin de la Societe de pathologie exotique, 81: 24-31 (1988). 15. R1DET, J. ET AL A sero-epidemiological study on the endemicity of treponematoses in Senegal [summary]. Bulletin of the World Health Organ- ization, 57 (2): 327 (1979). RIDET, J. ET AL Etude sero-epidemiologique sur l'endemicite treponemique au Senegal. Bulletin de /'Organisation mondiale de la Sante, 57 (2): 315-327 (1979). 16. AGADZI, V. K. ET AL Resurgence of yaws in Ghana. Lancet, ii: 389-390 (1983). 17. BouooN, D. & Houssou, B. Le niveau de l'endemie pianique dans le sud du Benin en 1982. Annales de la Societe beige de medecine tropicale, 64: 397-402 (1984). 18. GAZ1N, P. & MEYNARD, D. Enquete clinique et serologique sur le bejel au nord du Burkina Faso. Bulletin de la Societe de pathologie exo- tique, 81: 827-831 (1988). 19. BouooN, D. ET AL Niveau de l'endemie pianique en Haute-Volta en 1981. Tropical medicine and parasitology, 36: 58-60 (1985). 20. AUTIER, P. ET AL. Etudes serologiques et cliniques sur la treponematose endemique en Republique du Mali. Annales de la Societe beige de mede- cine tropicale, 69: 319-329 (1989). 21. Louis, J. P. ET AL. Situation de l'endemie pianique dans les Etats-Membres de l'OCEAC. Bulletin de liaison et de documentation, 89-90: Jul.-Dec. (1989). 22. OsvALA, D. Efficacite de l'extencilline dans le traitement du pian et prevalence de cette en- demie dans la region de la Likouala. Bulletin de liaison et de documentation OCEAC, 73: 17-18 (1986). 23. Z1EFOR, A. ET AL. Studies on a focus of yaws in Ubangi, Zaire. Tropical medicine and parasito- logy, 36: 63-71 (1985). 24. DIETZ, W. H. ET AL Nutritional status of Et pygmies and Lese horticulturists. American Wld hlth statist. quan., 45 (1992) journal of physical anthropology, 78 (4): 509-518 (1989). 25. ZERGABACHEW ASFAW. Serologic and clinical survey of treponemal diseases in South-Western Ethiopia. Ethiopian medical journal, 26: 121-126 (1988). 26. VAN NIEKERK, c. H. ET AL. [Positive serological tests for syphilis in black primary school children in Bloemfontein]. South African medical journal, 67: 90-91 (1985). (In Afrikaans). 27. SEBAI, z. A & BAKER, T. D. Endemic syphilis (bejel) in a bedouin community in Saudi Arabia. Ain Shams medical journal, 30: 13-17 (1979). 28. PACE, J. L. Treponematoses in Arabia. Saudi medical journal, 4 (39): 211-220 (1983). 29. SEHGEL, P. N. ET AL (EDS). Yaws: prospects and strategies for eradication in India. Delhi, National Institute of Communicable Diseases, 1987. 30. JAYAKURU, G. N. Yaws in Sri Lanka. South-East Asian journal of tropical medicine and public health, 17 (Supplement): 42-48 (1986). 31. SOSROAMIDJOJO, s. ET AL. Yaws in Indonesia. South-East Asian journal of tropical medicine and public health, 17 (Supplement): 19-34 (1986). 32. TALWAT, E. Papua New Guinea: yaws problem assessed. South-East Asian journal of tropical medicine and public health, 17 (Supplement): 59-65 (1986). 33. FEGAN, D. ET AL. Yaws in the Solomon Islands. Journal of tropical medicine and hygiene, 93 (1): 52-57 (1990). 34. HARRIS, M. ET AL Yaws infection in Tanna, Vanuatu, 1989. South-East Asian journal of tropi- cal medicine and public health, 22 ( 1 ): 113-119 (1991). 35. ARSLANAGIC, N. ET AL. Eradication of endemic syphilis in Bosnia. Genitourinary medicine, 65 (1): 4-7 (1989). 36. SPIROV, G. Endemic syphilis in Bulgaria. Geni- tourinary medicine, 67 (5): 428 (1991 ). - 238 - CONTROL OF PERTUSSIS IN THE WORLD a Artur Galazkab Introduction Forty years ago a noted epidemiologist, Dr J. E. Gordon, stated that "the severity of whooping cough is much underrated both in the direct and indirect damage it causes to health, growth and resistance of young children .... Deaths are inordinately frequent among infants aged less than one year. As a world problem of preschool children, whooping cough is in the front rank of acute infections. Despite all this the disease continues to be lightly regarded by the public, and also by many physicians" (1). Many of Dr Gordon's statements are still true today. Among vaccine-preventable diseases, pertussis rivals measles and neonatal tetanus in importance and severity among young children in developing countries and is third only to measles and neonatal tetanus as a cause of death. It is estimated that pertussis is still causing some 340 OOO deaths of children in the world each year.c Pertussis is an exhausting illness that can last for several months. In the industrialized world, an es- timated 0.04% of infected children die from pertussis and its consequences, especially from pneumonia. In the developing world the case-fatality rate may reach or exceed 1-2%. Pneumonia is reported as a compli- cation for 29% of patients, being highest (34%) among infants under 6 months of age (2). Other complications, related to severe coughing attacks, range from broken blood vessels in the eyes to umbilical and inguinal hernias. Lack of oxygen and/ or increased blood pressure during coughing attacks can lead to central nervous system disorders such as convulsions, coma and encephalitis, all of which occasionally result in permanent damage. Encepha- lopathy/encephalitis is reported in 0.1-4% of patients and permanent brain damage in 0.6-2% (3). Also the prolonged coughing attacks and associated vomiting may lead to severe undernutrition. The burden on health from this preventable disease may thus be far greater than can be measured directly. Weakness of pertussis surveillance Lack of valid data on pertussis morbidity The reported pertussis incidence is likely to be an underestimate of the true incidence for many reasons. Firstly, the disease is frequently under- • This article is a shortened version of the paper presented at the Fourteenth Meeting of the Global Advisory Group on the Expanded Programme on Immunization (EPI) in Antalya, Turkey, 14-18 Oc- tober 1991. (Document EPI/GAG/91/WP.16). O Medical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. c Galazka, A. Pertussis mortality - Methods for estimation of number of deaths due to pertussis. EPI Research and Development Group Meeting, Geneva 1-2 October 1991. (Document EPI/RD/91/ WP.5 Oct.). diagnosed, particularly if the classic symptoms of paroxysmal cough and whoop have not occurred. Classic symptoms may not be present with pertus- sis, particularly in infants and older children (4). Difficulties in laboratory confirmation also contribute to underdiagnosis. These problems are compounded by reliance on a passive reporting system with its inherent weakness of underreporting. Reported data based on hospitalized cases may suffer from dis- proportionate representation of severe cases in younger children and infants. Only an estimated 5-25% of all pertussis cases are reported in the United States of America, and England & Wales (5, 6); reporting is disproportionately higher for hospitalized patients with classic, laboratory- confirmed, and hence more severe disease (5). A ninefold increase of pertussis cases was identified when an active and enhanced pertussis surveillance system was introduced in Nova Scotia, an Atlantic province of Canada, to better delineate the epi- demiology of the disease (7). Limitations in the available data on pertussis cases and deaths make comparisons between different regions or countries difficult. Such comparisons are also hampered by differences in the reliability of surveillance data, differences in completeness of reporting of pertus- sis, and differences in the quality of clinical and bacteriological diagnosis in different countries. In some developed countries pertussis is still not noti- fiable, and in some others statistics on pertussis incidence are not reliable. In many countries, the reported numbers reflect only hospitalized cases, reporting is considerably delayed and available data cannot serve as an operational tool for controlling the disease. As of March 1992, only 61% of countries in the African Region of WHO and 54% of countries in the Western Pacific Region provided data on pertussis incidence for 1990 to WHO/headquarters. Trends in pertussis morbidity Pertussis in WHO regions Although existing surveillance data cannot be con- sidered qualitatively accurate, they are useful for depicting the trends and patterns of pertussis occur- rence. Data from the EPI information system suggest clear downward trends in the number of reported cases in the Region of the Americas and the Western Pacific regions in the 1980s, less obvious decline in the African, Eastern Mediterranean and South-East Asia regions, and no clear trend in the European Region. Regional data summarize cases from sur- veillance systems of varying quality and real trends may be clouded by mixing reliable and unreliable data. The analysis of pertussis incidence in selected countries may provide more useful information. In many countries of the world, a clear downward trend can be documented (Fig. 1). Rapp. trimest. statist. sanit. mond., 45 (1992) " E .. :a .. ,:; 0 0 0 0 :? ;; 0 0. .. " c: .. " O · . ; . !: 'c )( :, .. I- I c: .!2 .; :i 0. 0 0 . 0 0 0 0 :? :;; 0. " '§ " " c: " "O ·.; .E 0. 1 7 4 78 FI G .1 R EP O RT ED P ER TU SS IS IN C ID EN C E R A TE S PE R 1 00 O OO P O PU LA TI O N IN S EL EC TE D C O U N TR IE S, B Y W H O R EG IO N, 1 97 4- 19 90 T A U X D 'IN C ID EN C E C O Q UE LU CH EU SE D EC LA RE P O U R 1 00 O OO H A B IT A N TS D A N S C ER TA IN S P A Y S, PA R R EG IO N O M S, 1 97 4- 19 90 Af ric a - A fri qu e 78 80 82 84 88 88 90 Eu ro pe Am er ic as - A m er iq ue s U ni te d St at es o f A m er ic a Et at s- U ni s d' Am er iq ue 0. 1 ' - ' - - ' - ' - - ' - - ' - - - ' - - ' - - ' - - ' - - ' - - ' - - ' - - - ' - - ' - ' ' - ' 74 78 78 80 82 84 88 88 90 So ut h- Ea st A si a As ie d u Su d- Es t Ea st er n M ed ite rr an ea n M ed ite rr an ee o rie nt al e 0. 1 ' - ' - - ' - ' - - ' - - - ' - - - ' - - - ' - - ' - - ' - - ' - - - ' - - - ' - - ' - ' ' - ' ~ 7 4 78 78 80 82 84 88 88 90 W es te rn P ac ifi c Pa ci fiq ue o cc id en ta l 1 0 0 0 ~ - - - - - - - - - - - - - ~ 10 0 10 Ja pa n - Ja po n 0. 1 f - - ,~ ~ ~ ~ ~ ~ ~ * - ~ - r - 1 '- ~ r - li < H " n n ~ ~ M u " oo 78 78 80 82 84 88 88 90 0. 1 ~ ' - ' - ' - - ' - - ' - - - ' - - - ' - - ' - - ' - - ' - - ' - - ' - - - ' - - ' - ' ~ 7 4 78 78 80 82 84 88 88 90 Ye ar s - An ne es - 240 - Pertussis in developed countries Before the introduction of widespread immunization of young children with pertussis vaccine, the inci- dence rates in Europe and the United States were very high. The reported rates per 100 OOO population ranged from 200-300 in England & Wales and Sweden, to more than 1 OOO in Denmark and Nor- way. Similarly, in the United States and Canada, prior to the introduction of pertussis vaccine in the 1940s, the annual incidence rate varied from 98 to 210 per 100 OOO population (9, d). The observations made in most countries suggest that, following the introduction and widespread use of DPT vaccine, the incidence of reported pertussis declined dramatically, initiating a trend that would continue for about 20 years. In England & Wales, the average annual number of reported cases ex- ceeded 150 OOO in the 1950s and by 1973, when vaccine acceptance was over 80%, annual noti- fications of pertussis had fallen to around 2 400 (10). Similarly in other European countries, the number of pertussis cases reported annually was reduced from 20 000-30 OOO in the 1950s in Finland or nearly 100 OOO in the late 1950s and the beginning of the 1960s in Poland, to several hundred cases in the 1970s and 1980s (8, 10). In the late 1970s and the 1980s, the situation in Europe began to differentiate. Three groups of coun- tries can be distinguished with respect to trends in pertussis incidence. The first group includes countries reporting an inci- dence rate between 10 and >100 per 100 OOO. This group includes Sweden and Italy, countries which do not routinely give pertussis vaccine to infants. In other countries of this group, DPT vaccine is used but immunization coverage is below 80% (Germany, the former USSR, Ireland, Spain, the United King- dom). It is estimated that in Germany the annual number of pertussis cases may exceed 10 OOO; this produces an incidence rate above 20 per 100 OOO. In the former USSR, the incidence rate in last four years (1988-1991) ranged from 17 to 24 per 100 OOO population. In Denmark, the incidence rate is high despite high immunization coverage; in this country, however, a special immunization schedule is used. Countries with a moderate reported incidence (be- tween 1 and 10 per 100 OOO) include Austria, Finland, Greece, Israel, Norway, the Netherlands, Portugal, Romania, Yugoslavia. In the third group, pertussis incidence is low, <1 per 100 OOO, in Hungary, Switzerland, Bulgaria, Czecho- slovakia, Poland and Turkey. In the United States, accompanying the widespread use of vaccine, the incidence rate dropped to <10 per 100 OOO population (9, d ). Further declines occurred and in the 1970s and the beginning of the 1980s the number of reported cases ranged between 1 OOO and 2 OOO, with the incidence rate between 0.5 and 1 per 100 OOO population. In the middle 1980s the number of reported cases increased to 3 000-4 OOO cases. In Canada, the incidence rate declined from 160 per 100 OOO in the 1940s to about 10 per 100 OOO in the 1970s-1980s (12). Experience in Japan, the United Kingdom and Sweden has demonstrated that stopping vaccination with pertussis vaccine or a decline of pertussis vaccine coverage in a previously highly vaccinated population resulted in resurgence of the disease. Pertussis in developing countries Trends in morbidity. In developing countries, the problem of pertussis may be many times more serious than it is in Europe and North America, for the following reasons: (i) a lower median age of incidence, as shown by studies performed in the 1960s by Morley in 17 developing countries (13); (ii) a high case-fatality ratio in young age groups; and (iii) an association with protein-energy malnutri- tion. The combination of these three factors is re- sponsible for a much higher mortality than in the industrialized countries. In developing countries surveillance systems are weak and reports are often delayed. However, even this unsatisfactory system suggests that pertussis incidence is high (Fig. 1). Several countries in Africa reported incidence rates above 100 per 100 OOO population (Angola, Liberia, Malawi) and many countries reported incidence rates between 10 and 100 per 100 OOO population. In other regions many countries have also reported an incidence rate above 10 per 100 OOO population (Bolivia in the Region of the Americas; Somalia and Yemen in the Eastern Mediterranean Region; Ban- gladesh, India and Indonesia in the South-East Asia Region; and Papua New Guinea, Philippines, Sol- omon Islands, Vanuatu and Viet Nam in the Western Pacific Region). Despite widespread underreporting, more than 80% of pertussis cases are reported from the developing countries (Table 1). The full extent and magnitude of TABLE 1. NUMBER OF REPORTED PERTUSSIS CASES AND PERTUSSIS INCIDENCE RATES PER 100 OOO POPULATION IN DEVELOPING AND DEVELOPED COUNTRIES, 1987 TABLEAU 1. NOMBRE DE CAS DE COQUELUCHE DECLARES ET TAUX D'INCIDENCE COQUELUCHEUSE POUR 100 OOO HABITANTS DANS LES PAYS EN DEVELOPPEMENT ET LES PAYS DEVELOPPES, 1987 WHO region Region OMS Developing countries Pays en developpement Number Incidence rate of cases Nombre Taux de cas d'incidence Africa - Afrique 132 596 Americas Ameriques 29 318 South-East Asia -Asie du Sud-Est 205 524 Eastern Medi- terranean - Mediter- ranee orien- tate 68 388 Europe 501 Western Pacific - Pacifique occidental 103 895 Total 540 222 27.8 7.0 16.7 19.0 1.0 8.0 14.1 Developed countries Pays developpes Number Incidence rate of cases Nombre Taux de cas d'incidence 4 649 1.8 113 902 14.6 1 200 0.8 119 751 10.1 d Brink, E. Pertussis update. Seventeenth Immunization Conference World total - Cases - Proceedings, 18-19 May 1982, Atlanta, Georgia, United States of Total mondial Cas: 659 973 Incidence rate - America. Taux d'incidence: 13.1 Rapp. trimest. statist. sanit. mond., 45 (1992) - 241 - the disease in the developing world remains un- determined. Epidemiological pattern of pertussis. Weakness, low sensitivity, and availability of data mostly from hos- pitalized cases, hamper assessing the epidemiologi- cal pattern of the disease. The cyclicity of the reported pertussis incidence can be traced in many developing countries. Increases in reported pertussis morbidity are seen every 2-4 years in the Philippines and Viet Nam; every 4- 5 years in Argentina, Costa Rica and Iraq; and every 5-6 years in Mexico and Ethiopia (Fig. 1). Whooping cough epidemics have varied in their severity, from a relatively mild village outbreak with no deaths in Thailand (14) or with a low case-fatality ratio in the outbreak in urban areas of South Africa (15), to severe outbreaks affecting large pro- portions of children under 7 years of age (Table 2) and resulting in a high mortality and complication rates (16, 18, • ). TAllLE 2. PERTUSSIS ATTACK RATES (%1 BY AGE IN THREE PERTUSSIS EPIDEMICS IN COTE D'IVOIRE, GUATEMALA AND INDONESIA TABLEAU 2. TAUX D'ATTAQUE DE LA COQUELU- CHE (%1 PAR AGE LORS DE TROIS EPIDEMIES DE COQUELUCHE EN COTE D'IVOIRE, AU GUATEMALA ET EN INDONESIE Cote d'Ivoire Guatemala Indonesia 1986' 1983' lndonesie 1978c Age in years Age en annees Attack rates in% - Taux d'attaque en% <1 59 35 50 1 46 40 2 77 45 76 3 71 47 4 63 20 81 5 61 l 6 40 63 7 63 11 8 r 65 9 10 J 10-14 2 Total 62 19 68 a Source: Galazka, A. Pertussis mortality - Methods for estimation of number of deaths due to pertussis. EPI Research and Development Group Meeting, Geneva, 1-2 October 1991. (Document EPI/RD/91/WP, 5 Oct.) 'Source: Reference (16) - Reference 1161. 'Source: Reference (17) - Reference (17). The duration of pertussis epidemics may vary con- siderably. Rural epidemics in Thailand and Cote d'Ivoire lasted 2-4 months (14, •). In Antigua, pertus- sis epidemics tend to reach their maximum fairly quickly, and then to decline slowly. Of 8 major epidemics, the maximum number of cases was reached usually within 4-5 months and the average duration was 11 months (19). In an urban outbreak in a highly immunized com- munity in Cape Town in South Africa, the incidence began to rise in June 1988, peaked in December 1988 and had returned to pre-epidemic levels by March 1989 (15). An epidemic in rural areas of the Machakos District in Kenya lasted more than a year, from April 1974 to July 1975 (18). • Sokal, D. C. et al. Rapport d'une enquete sur la coqueluche: epidemie du village de Dougba, Departement de Tingrela, R.C.I., mai-aout 1982. Organisation de coordination et de cooperation pour la lutte contre les grandes endemies, Secretariat general. B.P. 153, Bobo-Dioulasso, Haute Volta, No. 7.998/82/DOC.TECH.OCCGE. Wld hlth statist. quart., 45 ( 1992) In summary, pertussis is a disease common to children in various areas of the developing world, regardless of race, climate or geographical location. It seems that the disease occurs in more or less severe epidemics with interepidemic periods of re- duced morbility. Mortality due to pertussis Studies by Morley in Nigeria drew attention to the severity of pertussis in developing countries. Morley showed that the case-fatality ratio (CFR) due to pertussis in the llesha Hospital in Nigeria in 1957- 1961 was comparable with the one recorded at the London Hospital in 1911-1929 (13). The analysis of the evolution of pertussis mortality under the age of 15 years in England & Wales and in Antigua, showed that in the XIXth century pertus- sis death rates were about the same in Antigua as in England & Wales (Fig. 2). In England & Wales death rates began to decline by the end of the XIXth century and had fallen to 1 per 40 in the 1950s. In contrast, the rates in Antigua did not show significant changes until the mid-XXth century. In the 1950s, death rates in Antigua were several dec- ades behind those of England & Wales. Similar differences in reported incidence were observed in the Americas during 1969-1972; in North America a clear declining trend was evident while no clear pattern could be seen in Central and South America (20). Mortality due to pertussis in industrialized countries started to decline a long time before the introduction of mass immunization with DPT vaccine. One contri- buting factor was the improvement in socioeco- nomic status. Among persons of higher socioeco- nomic status, pertussis was contracted at a later age, with resultant decrease of the severity of the dis- ease (21). In the beginning of the 1980s the case- fatality ratio (CFR) of pertussis in the United States declined to 0.5%; all deaths occurred among hos- pitalized patients who were less than one year of age, had not been vaccinated and had pneu- . mania (2). In Sweden, where routine immunization against pertussis was stopped in 1979, 3 deaths were reported among 2 282 hospitalized patients in 1981-1983; the CFR being 0.1% (22). A case-fatality ratio of 0.04% was reported in England & Wales in 1976-1981 (23). Data on pertussis mortality from developing coun- tries are often based on hospital studies. These data show high CFR, from 3.3% in South Africa (24) to 10%-16% in Nigeria (13), Uganda (25), and Kenya (26). In all these studies CFR was dependent on age, with the highest ratio noted in infants. Pertussis was the fifth cause of death in children in Kenya in the 1950s (26) and the disease with its complications caused about 9% of all child deaths in western Nigerian hospitals (27). The case-fatality ratio is lower in community-based surveys and in outbreak data. It ranges from 0.3% in an urban outbreak in the immunized population in South Africa (15) to 1-3% in Kenya (18, 28), Indonesia (17), Cote d'Ivoire• and among Mexican Indians (29). There have been pertussis outbreaks with a high mortality, such as an outbreak in Guate- mala with a CFR approaching 15% (16). - 242 - FIG.2 PERTUSSIS DEATH RATES PER MILLION AT AGES UNDER 15 YEARS, ANTIGUA AND ENGLAND & WALES, 1851-1956 TAUX DE DECES PAR COQUELUCHE PAR MILLION D'HABITANTS CHEZ LES MOINS DE 15 ANS, ANTIGUA ET ANGLETERRE & GALLES, 1851-1956 1 OOO c ~ ·e :;; Q. "' .a, " ·Cl) .,, " .,, )( ::, "' I- 100 I c ~ ·e ai Q. Cl) ~ .c 1o Cl) a 10 1851 61 71 81 91 1901 11 21 31 40 50·56 Years - Annees -+- Antigua --8-- England & Wales - Angleterre & Galles Based on reference (191 -D'apres la reference (19). Immunization schedules Most countries in the world use OPT vaccine for immunization of children under 3 years. However, there are essential differences in the immunization schedules used. Usually, the primary series consists of 3 doses of OPT vaccine given during the first year of life. In the African and South-East Asia regions, most countries use the immunization schedule recommended by the EPI with 3 doses given at 6, 10 and 14 weeks; some countries used 3, 4 and 5 month schedules (Table 3). In the American Region the schedule used in the United States, with two-month intervals, is the one most frequently fol- lowed. In the European Region, immunization schedules in 74% of countries aim to complete the primary series before or at 6 months of age. The only country in Europe which has no pertussis immunization is Sweden (Fig. 3). In Germany and Italy, OPT or OT vaccines are recommended for primary immuniza- tion. In Denmark, a monovalent pertussis vaccine is used in a 3-dose schedule, at 5 and 9 weeks and 10 months of age. It should be mentioned that in 14%-18% of countries in the regions of the Americas, the Eastern Mediterranean, Europe and the Western Pacific, the third dose of OPT vaccine in the primary series is recommended at a late age, some time after 6 months. In Japan, OPT containing the acellular pertussis component is given in a 3-dose primary series in children over 24 months. In 1988, the Min- istry of Health of Japan announced that OPT im- munization could be started from 3 months , but as of 1990 only some 10% of infants under 12 months were immunized with OPT vaccine (30, 31). The booster policy also varies. Between 31% and 63% of countries in 5 WHO regions recommend a fourth dose of OPT vaccine at 12 to 24 months. In the South-East Asia Region, most of the countries achieve immunization against pertussis with only the 3 primary doses. The fifth dose of OPT vaccine is used in one-third of countries of the Americas and Western Pacific regions. In other regions this second booster dose is used infrequently. Immunization coverage with pertussis vaccines Successful immunization programmes require both effective vaccines and effective systems to deliver them. The immunization coverage with 3 doses of OPT vaccine in infants is very heterogeneous. Although in many countries the coverage rate ex- ceeded 85%, many other countries, especially in Rapp. trimest. statist. sanit. mond., 45 (1992) - 243 - FIG. 3 SCHEDULES OF IMMUNIZATION AGAINST DIPHTHERIA, TETANUS AND PERTUSSIS IN EUROPEAN COUNTRIES CALENDRIER DE LA VACCINATION ANTIDIPHTERIQUE, ANTITETANIQUE ET ANTICOQUELUCHEUSE DANS LES PAYS EUROPEENS COUNTRY Albania Austria Belgium Bulgaria Czechoslovakia Denmark Finland France Germany Greece Hungary Ireland Israel Italy Luxembourg Netherlands Norway Poland Portugal Romania Spain Sweden Switzerland Turkey United Kingdom Former USSR Yugoslavia AGE 2 4 6 8 10 12 14 16 18 20 22 24 2 4 6 8 10 12 14 16 18 • • • • • ~ ••• f'."·· ·:. .:.·._.·.··: .......... · ... ·. ·.) D t-·····.· .. j ••• - 0 . 1§1 •• • 1:.-:-:,:-:.-.) [] ~ • - • -0~ [·.··.·.·) ~ D ••• c;::;:;:J ••• =:=] f:,·-·.:-.. ·.·.:1 ~ ~~ rl ~ • • • • • - ~ ••• • - t:.··.-·. j •• - D • • • • 1,-... _:· -j !:iii~ - - :22] ~ --- • , • . ' • -: :-: :,': ~ t&l ••• • • • • D ·-· 0 0 • • • - ~ ••• • • 0 r .-·.·.,1 • • • D ~ ~ D D D ~ ••• r .......... _.· . . -. .-.·.· ·.:_.-..... -..... ·.-· ........ -..... ·. . ·.·.·.·.·.· t==:J [.· .......... ··--.· ·J ••• • D ~ 1§1 ••• l!"J.lll!l ............. _-.:_-,:-::, ' ~ [:;;! •• • • - D . D . 2 4 6 8 10 12 14 16 18 20 22 24 2 4 6 8 10 12 14 16 18 MONTHS -MOIS YEARS - ANNEES • DPT-DTC ~PER-C DDT ~Td TABLE 3. IMMUNIZATION SCHEDULES FOR DPT VACCINE, BY WHO REGION TABLEAU 3. CALENDRIER DE LA VACCINATION PAR LE DTC, PAR REGION OMS Primary 3 doses PAYS Albanie Autriche Belgique Bulgarie Tchecoslovaquie Danemark Finlande France Allemagne Grece Hongrie lrlande Israel ltalie Luxembourg Pays-Bas Norvege Pologne Portugal Roumanie Espagne Suede Suisse Turquie Royaume-Uni Ex-URSS Yougoslavie AGE WH092633 in weeks (w) o r months (m ) of age Tro is premieres doses Booster doses Rappels WH O reg ion - Region OM S Africa - Afrique Americas - Ameriques South-East Asia - Asie du Sud-Est Eastern Mediterranean - Mediterranee orientale Europe• Western Pacific b - Pacifique occidental b 6, 10, 14 w 2, 3, 4 m 6, 10, 14 s 2, 3, 4 m Age en semaines (s) ou en m ois (m ) 3, 4, 5 m 4, 5, 6 m 2, 4, 6 m 3, 5-6 7-15 m 12-24 m 3-6 years 3-6 annees Percentage of cou ntries using a given sched ule - Pourcentage de pays uti lisant un schema donne 64 36 31 19 10 57 14 57 33 64 36 9 9 30 25 30 15 45 5 11 48 15 18 63 11 23 35 23 16 48 35 a No pertuss is vaccine used in Sweden. In Denmark, m onovalent pertussis vaccine is used at 5 and 9 weeks, and 10 m onths - On ne vaccine pas centre la coqueluche en Suede. Au Oanem ark, on administre un vacc in monovalent a 5 et 9 semaines pu is a 10 m ois. b In 5 countries, the OPT booster dose g iven at schoo l entry is no . 4 dose, since no dose is give n one year after co m pletion of t he prim ary series of 3 doses - Oans 5 pays, le rappe l du OTC etfectue lo rs de l'entree a l'ecole correspond a la dose N° 4, puisqu 'on n'administre aucu ne dose un an apres l'achevement de la premiere serie de 3 doses. Wld hfth statist. quart., 45 (1992) - 244 - Africa, report a coverage rate below 50% (Map 1). Failure to reach and maintain high coverage rates with DPT vaccine in infants is due to different change in the age distribution of pertussis morbidity. The range of these changes differs depending on immunization schedules and immunization coverage MAP 1. WORLDWIDE IMMUNIZATION COVERAGE(%) WITH 3 DOSES OF OPT, 1987-1989 CARTE 1. COUVERTURE MONDIALE (%1 PAR 3 DOSES DE OTC, 1987-1989 % ~ < 50 • 50 - 80 HA> 80 The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the secretariat of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries - Les designations utilisees sur cette carte et la presentation des donnees qui y figurent n'impliquent, de la part de !'Organisation mondia1e de la Sante, aucune prise de position quant au statut juridique de tel ou tel pays, territoire, ville ou zone, ou de ses autorit0s, ni quant au trace de ses frontiElres. reasons in industrialized and developing countries. Negative attitudes towards vaccination have recently emerged in many developed countries, mainly those with a low occurrence of EPI target diseases, and pressure groups have been formed to oppose vacci- nations. These groups use media to spread their ideas in anti-vaccination campaigns' and public con- fidence in pertussis vaccination, eroded by media campaigns, is not supported by the medical profes- sion (32). In developing countries, immunization coverage with DPT3 in infants recently exceeded 80% (April 1991 ), but there are considerable differences in coverage rates between WHO regions (Africa 57%, Americas 75%, Eastern Mediterranean 80%, South-East Asia 89% and Western Pacific 94%), and between indi- vidual countries within the regions. Also within countries great differences exist in immunization coverage, with underserved urban areas, displaced population groups, nomads and refugees having the least coverage. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak manage- ment of immunization services; not using every op- portunity to immunize eligible children; and ineffec- tive information and motivation of mothers on the need to return to complete the immunization series and on the benefit and importance of immunization. The success in controlling pertussis by immunization has altered its epidemiology by reducing the likeli- hood of repetitive, casual exposure to children with pertussis and consequent reinforcement of immunity from such exposure (33). The wide use of pertussis vaccination has had several effects on the epidemio- logy of pertussis: apart from breaking off the en- demic pattern of the disease, there has been a clear I Velimirovic, B. Hostility to immunization. Fourth European Meet- ing of National Programme Managers on the EPI, St Vincent, Val d'Aosta, Italy, 21·24 May 1991. • Galazka, A. Control of pertussis in the world. Fourteenth meeting of the EPI Global Advisory Group, Antalya, Turkey, 14-18 October 1991 . (Document EPI/GAG/91/WP.16). rates.9 These observations underline the need for early immunization of infants against pertussis, as well as the importance of booster doses of pertussis- containing vaccines given to older children. There is a lack of reliable information from develop- ing countries on the influence of DPT immunization on age-specific morbidity. Data from pertussis epi- demics in Cote d'Ivoire, Guatemala and Indonesia show that the highest incidence rate was similar to that observed in industrialized countries before the introduction of mass immunization with DPT vaccine, i.e. among children aged 1-4 years (Table 2). Towards better control of pertussis in the world During the past 15 years, a successful programme on immunization has been implemented in most countries of the world. Although some investigators have challenged pertussis vaccine as ineffective, dangerous or superfluous, most experts agree that widespread use of the vaccine has resulted in enor- mous benefits.9 However, some problems have arisen in several countries in the developed world in which pertussis has been either well controlled previously or should have been (34). These problems have resulted in recrudescence or persistence of pertussis in Den- mark, Germany, Italy, Sweden, the United Kingdom and the former USSR. The indirect or underlying causes of these problems are apathy and com- placency on the part of physicians and parents, negative attitudes to immunization spread by anti- immunization pressure groups using a wide range of media, and ligitation over liability for alleged vaccine-related injuries. In the developing world, the main problem is the high drop-out rates between the first and the third dose of DPT vaccine. These immunizations are often Rapp. trimest. statist. sanit. mond. , 45 (19921 - 245 - delayed, leaving infants unprotected during the most vulnerable period of the first 6 months of life. The lack of data on the present epidemiological pattern of pertussis in the developing world makes it difficult to decide on the policy of booster doses. The 1980s witnessed significant contributions to the development and evaluation of acellular pertussis vaccine. Data from a wide variety of serological and epidemiological studies in different populations have now been accumulated and demonstrate that Japanese acellular pertussis vaccines are safe and up to 80% effective in preventing clinically signifi- cant pertussis. In the United States, the Food and Drug Administra- tion licensed the ACV for use in the fourth and fifth doses of the childhood DPT immunization schedule (35). Despite a substantial body of existing data on ACVs, however, several major questions continue to delay the use of ACVs in young infants. These questions refer mainly to the uncertainty about the overall "best estimate" of efficacy of ACV relative to existing whole-cell vaccines, and the ef- ficacy of ACVs in young infants under 6 months. Also, questions about the risk, if any, of rare but serious adverse reactions associated with ACVs have not been fully answered. Obtaining answers to these questions will be costly, logistically difficult and take several years to accomplish. Several groups, including government agencies and private manufacturers, are now planning· or carrying out efficacy field trials. There are many complex issues surrounding site selection, vaccine selection, study design, case definition and vaccination schedule. If successfully launched, the trials are ex- pected to run for approximately 3 years, to cost several million dollars, and provide results by the mid-1990s (36). SUMMARY Available data indicate that pertussis remains an important disease during infancy and childhood, par- ticularly among those who are inadequately im- munized. Over the past 15 years, successful im- munization programmes have been implemented in most countries in the world. Some problems have arisen in the industrialized world where pertussis had been well controlled previously. The underlying causes of these problems are apathy and complac- ency on the part of physicians and parents, negative attitudes to immunization spread by anti- immunization pressure groups and litigation over liability for alleged vaccine-related injures. In developing countries, immunization coverage with primary series of three doses of DPT vaccine in infants exceeds 80%, but there are considerable differences in coverage rates between regions and between and within countries. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak management of immunization services, miss- ing opportunities to immunize eligible children and ineffective information and motivation of mothers to return to complete the immunization series. To effectively control pertussis in the world, all countries should use available pertussis vaccines in immunization programmes for children. Since acellular pertussis vaccines are not generally avail- able, the widespread use of DPT vaccine containing the whole-cell pertussis component should be con- tinued. All efforts should be directed to increase or maintain high immunization coverage with DPT im- munization at the level of at least 90% in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and ideally, pertussis should be a reportable disease. More information on the present epidemiological pattern of pertussis, especially age distribution of pertussis cases in de- veloping countries, is needed to develop the policy of booster doses of DPT vaccine in children >1 year. RESUME La lutte contre la coqueluche dans le monde Les statistiques montrent que la coqueluche reste une maladie importante de la premiere et de la deuxieme enfance, en particulier chez les sujets mal immunises. Au cours des 15 annees ecoulees, la plupart des pays ant mis en place avec succes des programmes de vaccination anticoquelucheuse. Dans le monde industrialise, ou la maladie etait jusqu'ici bien maitrisee, un certain nombre de pro- blemes ant surgi. Les causes profondes en sont l'apathie et le laxisme de la part des medecins et des parents, les attitudes negatives vis-a-vis de la vacci- nation que propagent des groupes de pression op- poses a cette pratique, ainsi que les proces en dommages et inten~ts pour des sequelles imputees a la vaccination. Dans les pays en developpement, la couverture des nourrissons par les trois premieres doses de vaccin Wld hlth statist. quart., 45 ( 1992) DTC depasse 80% mais on constate des differences notables selon les regions et les pays, voire a l'inte- rieur d'un meme pays. De nombreux facteurs peu- vent expliquer que, dans certains pays en develop- pement, on ne parvienne pas a assurer ni a mainte- nir une bonne couverture vaccinale: faiblesses dans la gestion des services de vaccination, occasions manquees de vacciner des enfants en age de l'etre, enfin meres trap mal informees et motivees pour revenir faire achever la serie d'injections. Pour tous les pays du monde, la maitrise de la coqueluche passe par des programmes de vaccina- tion infantile utilisant les vaccins anticoquelucheux disponibles. Comme les vaccins acellulaires ne sont generalement pas disponibles, ii taut continuer a generaliser !'utilisation du vaccin DTC a base de cellules entieres. Taus les efforts doivent viser a - 246 - accroitre ou a maintenir une forte couverture vacci- nale par le OTC, c'est-a-dire au mains 90% dans tous les districts. II faut egalement renforcer la surveil- lance de la morbidite coquelucheuse dans tous les pays et l'ideal serait de rendre obligatoire la declara- tion de la coqueluche. ·II est necessaire de rassem- bier davantage de donnees sur la situation epide- miologique actuelle de la coqueluche, notamment en ce qui concerne la distribution par age des cas dans les pays en developpement, afin d'etendre le princi- pe du rappel chez les enfants de plus d'un an. REFERENCES - REFERENCES 1. GORDON, J. E. & HOOD, R. I. Whooping cough and its epidemiological anomalies. American journal of medical sciences, 222: 333-361 ( 1951 ). 2. CENTERS FOR DISEASE CONTROL. Pertussis surveil- lance, 1979-1981. Morbidity and mortality weekly report, 31 (25): 333-336 (1982). 3. GALAZKA, A. M. ET AL Indications and con- traindications for vaccines used in the Expanded Programme on Immunization. Bulletin of the World Health Organization. 62 (3): 357-366 (1984). 4. CHERRY, J. D. ET AL. Report of the Task Force on Pertussis and Pertussis Immunization - 1988. Pediatrics, 81 (Supplement 6): 939-984 (1988). 5. CENTERS FOR DISEASE CONTROL. Pertussis surveil- lance - United States, 1986-1988. Morbidity and mortality weekly report, 39 (4): 57-66 (1990). 6. THOMAS, M. G. Epidemiology of pertussis. Re- views of infectious diseases, 11 (2): 255-262 (1989). 7. HALPERIN, S. A. ET AL. Persistence of pertussis in an immunized population: results of the Nova Scotia Enhanced Pertussis Surveillance Pro- gramme. Journal of pediatrics, 115 (5): 686-693 (1989). 8. ADONAJLO, A. Pertussis. In: Kostrzewski, J. (ed.). Infectious diseases in Poland and their control in years 1961-1970. Warsaw, Pantswowy Zaklad Wydawnictw Lekarskich, 1973. 9. FARIZO, K. M. ET AL. Epidemiological features of pertussis in the United States, 1980-1989. (In print). 10. DEPARTMENT OF HEAL TH, WELSH OFFICE, ScornsH HOME AND HEALTH DEPARTMENT. Whooping cough - Pertussis. In: Immunization against infectious diseases 1990. London, HMSO, 1990. 11. Huov1LA, R. Whooping cough in Finland 1920- 1978. Statistical and epidemiological studies. Acta paediatrica scandinavica, (Supple- ment 298): 5-9 (1982). 12. Pertussis incidence - Canada. Weekly epi- demiological record, 61 (8): 55-58 (1986). Incidence de la coqueluche - Canada. Re/eve epidemiologique hebdomadaire. 61 (8): 55-58 (1986). 13. MORLEY, D. ET AL Whooping cough in Nigerian children. Tropical and geographical medicine, 18: 169-182 (1966). 14. Report on outbreak of pertussis in school children, Pichit Province. Weekly epidemiological surveillance report, 47: 15 (1984). 15. STREBEL, P. ET AL. An outbreak of whooping cough in a highly vaccinated urban community. Journal of tropical pediatrics, 37 (2): 71-76 (1991). 16. MATA, L. J. The children of Santa Maria Cauque: a perspective field study of health and growth. Cambridge, Mass., The Massachusetts Institute of Technology Press, 1978. 17. Outbreak of whooping cough Indonesia. Weekly epidemiological record, 59 (4): 26-27 (1984). Flambee de coqueluche - lndonesie. Re/eve epidemiologique hebdomadaire, 59 (4): 26-27 (1984). 18. VOORHOEVE, A. M. ET AL. Machakos project studies: agents affecting health of mother and child in a rural area of Kenya - IV. The epidemiology of pertussis. Tropical and geographical medicine, 30 (1): 125-139 (1978). 19. UnLEY, K. H. The epidemiology and mortality of whooping cough in the Negro over the last hundred years in Antigua, British West Indies. West Indian medical journal, 9 (2): 77-95 (1960). 20. PANAMERICAN HEALTH ORGANIZATION. Health condi- tion in the Americas, 1969-1972. PAHO scientific publication, 287: 51 (1974). 21. WRIGHT, P. F. Pertussis in developing countries - definition of the problem and prospects for con- trol. Reviews of infectious diseases, 13 (Supplement 6): 5528-5534 (1991). 22. ROMANUS, V. ET AL. Pertussis in Sweden after the cessation of general immunization in 1979. The pediatric infectious disease journal, 6 (4): 364- 371 (1987). 23. Whooping cough surveillance. Communicable disease report, 41: 3-6 (1982). 24. RAMKISSON, A. ET AL. Whooping cough - a ne- glected disease in Southern Africa. South African medical journal, 75 (12): 560-561 (1989). 25. Bw100, N. 0. Whooping cough in Uganda. Scan- dinavian journal of infectious diseases, 3: 41-43 (1971). 26. FENDALL, N. R. E. & GROUNDS, J. G. The incidence and epidemiology of diseases in Kenya - II. Some important communicable diseases. Journal of tropical medicine and hygiene, 68 (5): 113-120 (1965). 27. OMOLULU, A. Child health in Western Nigeria. West African medical journal, 14 (6): 255-268 (1965). 28. MAHIEU, J. M. ET AL. Pertussis in a rural area of Kenya: epidemiology and a preliminary report on a vaccine trial. Bulletin of the World Health Organization, 56 (5): 773-780 (1978). MAHIEU, J. M. ET AL La coqueluche dans une zone rurale du Kenya: epidemiologie et rapport preli- minaire sur un essai de vaccination [resume]. Bulletin de /'Organisation mondiale de la Sante, 56 (5): 779-780 (1978). 29. HE1MGARTNER, E. [Epidemiological and clinical ob- servations on an epidemic of whooping cough in the Mazuaha region, State of Mexico]. Revista de Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 247 - investigaci6n en salud pub/ica, 37 (2): 101-111 (1977). (In Spanish). 30. KIMURA, M. & KuNo-SAKAI, H. Current epidemio- logy of pertussis in Japan. The pediatric infec- tious disease journal, 9 (10): 705-709 (1990). 31. KIMURA, M. & KuNO-SAKAI, H. Pertussis vaccines in Japan - a clue toward understanding of Japan- ese attitude to vaccines. Journal of tropical pedi- atrics, 37 (1): 45-47 (1991). 32. CONWAY, s. P. & PHILLIPS, R. R. Morbidity in whooping cough and measles. Archives of dis- ease in childhood, 64 (10): 1442-1445 (1989). 33. MORTIMER, E. A. Pertussis and pertussis vaccines: 15 years of change. Seminars in pediatric infec- tious diseases, 2 (2): 82-90 (1991). Wld hlth statist. quart., 45 ( 1992) 34. MORTIMER, E. A. Pertussis and pertussis vaccine in the industrialized world. The Tokai journal of experimental and clinical medicine, 13 (Sup- plement): 93-96 (1988). 35. MARWICK, C. Acellular pertussis vaccines avail- able soon for fourth, fifth doses of DPT immuniz- ation. Journal of the American Medical Associa- tion, 267 (2): 207-208 (1992). 36. BERNIER, R. H. Outstanding issues in the clinical evaluation of new acellular pertussis vaccines. In: Proceedings of the Vlth international sym- posium on pertussis. Bethesda, Department of Health and Human Services, Food and Drug Administration, 1990. - 248 - PROGRESS TOWARDS THE GLOBAL ELIMINATION OF NEONATAL TETANUS Cynthia Whitman,• Lahouari Belgharbi,b Fran~ois Gasse,• Carole Torel,b Vittoria Matteib & Henrik Zoffmann• Neonatal tetanus claimed the lives of over 433 OOO infants in 1991 (Map 1). Among the six target dis- eases of the Expanded Programme on Immunization (EPI), neonatal tetanus is second only to measles as the leading killer of children. It is endemic in 90 countries throughout the world. In some of these developing nations, neonatal tetanus (NT) is respon- sible for one-half of the neonatal mortality and one- quarter of infant mortality. Even with treatment, the case-fatality ratio can approach 80-90% (1, 2). Although neonatal tetanus is a serious disease and a prevalent one, it can be effectively prevented through immunization and clean delivery practices. In 1989, in recognition of the magnitude of NT incidence as well as its preventable nature, the World Health Assembly resolved to eliminate neonatal tetanus from the globe by 1995. This goal was reaffirmed in 1991 at the World Summit for Children. Neonatal tetanus incidence Neonatal tetanus is one of the most underreported notifiable diseases. Its extensive incidence has only recently been appreciated. Because NT tends to occur in areas with poor access to health care, it often remains hidden within the community. NT strikes in the first days of life when the child is kept within the home, and it does not leave residual disabilities as identifiers of the disease's presence. Furthermore, the high case-fatality ratio and stigmas, common to many traditional belief systems or due to associations with unclean delivery practices, serve as disincentives to seeking care. Cases which do reach a health facility are often not reported by staff. Until recently, most reporting forms did not list neonatal tetanus separately from tetanus contracted at older ages. During the 1980s, more than 42 developing coun- tries, including 18 of the 25 most populous nations, undertook special community-based neonatal mor- tality surveys to determine the true incidence of NT. Conducted before immunization and clean delivery programmes were widely established, these early studies revealed that approximately 1 million children contracted NT each year, of which 800 OOO died. Mortality rates varied markedly by locale, rang- ing from O to 70 NT deaths per 1 OOO live births. Based on estimates from the survey results, routine surveillance systems could only identify 2-8% of cases during this decade (1, 2). By uncovering the magnitude of NT mortality, the community-based surveys were critically important • Medical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. • Technical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. in changing health policy makers' perceptions and in generating political support for NT control and elim- ination. The surveys are too expensive, however, to be used for routine monitoring of NT mortality. Surveillance data cannot be used to measure global trends in NT incidence either. Although 90% of countries now report NT cases separately from other forms of tetanus, routine reporting systems identi- fied only 4% of the NT cases estimated to occur in 1990. This proportion is too small to determine NT magnitude or programme impact reliably. NT's relatively stable case-fatality ratio provides the basis for understanding how mortality and incidence statistics are linked. This is particularly important as community mortality surveys measure neonatal tetanus deaths while surveillance systems report NT cases regardless of disease outcome. Because the case-fatality ratio does not vary significantly among different locations or treatment regimens, NT mor- tality is assumed to equal 85% of disease incidence. Thus, incidence and mortality can be calculated even if only one of these statistics is known. WHO has recently developed a methodology to es- timate national and global neonatal tetanus mor- tality. Each country is assigned a pre-intervention NT mortality rate, using data from the oldest nationwide community mortality survey. In the absence of a survey, countries are assigned rates based on the surveys of neighbouring countries at similar risk. This rate is multiplied by a country's annual number of live births to calculate the baseline number of NT deaths which would occur without control activities. Next, estimates of the number of deaths occurring despite disease control interventions are calculated. Using a country's most recent tetanus toxoid (TT) coverage data and assuming a vaccine efficacy of 95%, the annual number of NT deaths occurring despite immunization is estimated. This result is then subtracted from the pre-intervention estimate to determine the annual number of NT deaths pre- vented by control programmes. (The exact method- ology is available from WHO upon request.) Countries achieving over 80% coverage with either clean delivery practice or TT immunization are ex- cluded from these estimates. It is assumed that their surveillance systems are relatively well developed and accurate. For these nations, the number of NT deaths reported by the country are used. The WHO methodology is not without limitations. For example, TT efficacy may be less than 95% in many field conditions. Nevertheless, this technique provides a way to measure NT mortality that is more precise than the usual routine surveillance data and less costly than special surveys. Based on WHO estimates, TT immunization and clean delivery practice prevented over 793 OOO infant Rapp. trimest. statist. sanit. mond., 45 (1992) /\ M A P 1 . E S TI M A TE D N E O N A TA L TE TA N U S M O R TA LI TY R A TE S, 1 99 1 (p er 1 OO O liv e bi rt hs ) C AR TE 1 . T A U X E S TI M A TI F D E M O R TA LI TE P A R T E TA N O S N E O N A TA L, 1 99 1 (p ou r 1 O OO n a is sa nc es v iv an te s) R a te -T a u x 0 <1 ~ 1 - 5 [Z J-~- 5~- - - _ J Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f th e se cr e ta ria t o f th e W H O c o n ce rn in g th e le ga l st at us o f_ a n y co u n tr y, t er rit or y, c ity o r a re a o r o f its a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f its f ro nt ie rs o r bo un da rie s - Le s de si gn at io ns u til is ee s su r ce tte c a rte e t la pr E! se nt at io n de s do nn E! es q ui y f ig ur en t n 'im pl iq ue nt , de l a pa rt de l'O rg an is" a tio n m o n di al e de l a Sa ntE !, a u cu n e pr is e de po si tio n qu an t a u s ta tu t jur idi qu e de te l o u te l p ay s, t er rit oi re , v ill e o u z o n e , o u d e se s au to rit E! s, n i q ua nt a u tr ac e de s es fr on tiE !re s. N "" " (! ) - 250 deaths in 1991 (Fig. 1). Of the 433 800 infants who died of NT that year, approximately 212 OOO died in South-East Asia, 127 OOO in Africa, 46 OOO in the Western Pacific, 37 OOO in the Eastern Mediterranean and 1 300 in Europe. The Pan American Health Or- ganization, using a separate methodology to es- timate mortality, calculated that 10 570 newborns died of NT in the Region of the Americas (Table 1, Fig. 2). Focal dis,ribution of neonatal tetanus TABLE 1. ESTIMATED NEONATAL TETANUS MORTALITY RATES AND NUMBER OF DEATHS OCCURRING BY WHO REGION, DEVELOPING COUNTRIES, 1991 TABLEAU 1. TAUX ESTIMATIF DE MORTALITE PAR TETANOS NEONATAL ET NOMBRE DE DECES SURVENUS PAR REGION OMS, PAYS EN DEVELOPPEMENT,1991 Neonatal tetanus Number of mortality rate neonatal tetanus WHO region (per 1 OOO live births) deaths Region OMS Taux de mortalite Nombre de d9c8s par tetanos neonatal par tetanos neonatal (pour 1 OOO naissances vivantes) Whether survey results, routine reports or mortality estimates are examined, NT incidence is often focal. The causative organism, Clostridium tetani, is ubi- quitous in soil and animal excrement; however, it elaborates toxin only under anaerobic conditions, such as in a necrotic umbilical cord stump. NT cases consistently cluster in geographical areas and popu- lation groups where shared behaviours or the en- vironment enhance the risk of cord contamination. Africa - Afrique 5 127 056 At the global level, two regions at high risk for NT have been identified using mortality estimates. Ap- proximately 80% of the newborns who died of NT in 1991 were born in South-East Asia or Africa . Although the African Region has the highest NT mortality rate, nations in Sout-East Asia contributed almost twice as many deaths due to their immense Americas - Ameriques Eastern Mediter- ranean - Mediter- ranee orienta le Europe a South-East Asia - Asie du Sud-Est Western Pacific - Pacifique occi- dental Global (developing countries) - Total (pays en develop- pement) populations. • Turkey only - Turquie seulement. FIG. 1 10 570 2 36 558 1 343 5 211 926 2 46 427 3 433 880 ESTIMATED NEONATAL TETANUS DEATHS OCCURRING AND PREVENTED, DEVELOPING COUNTRIES, 1991 NOMBRE ESTIMATIF DE DECES DUS AU TETANOS NEONATAL SURVENUS ET EVITES DANS LES PAYS EN DEVELOPPEMENT, 1991 Global Total South-East Asia Asiedu Sud-Est Africa Afrique Eastern Mediterranean M6diterran0e orientate Americas Am9riques WHO region - Region OMS Western Pacific Pacifique occidental occurring - Oeces survenu Europe Rapp. trimest. s tatist. sanit. mond., 45 (19921 - 251 - Countries whose estimated NT mortality is greater than 1 NT death per 1 OOO live births are defined as endemic for NT. Of these 90 countries, 10% produce 80% of the world's NT deaths (Table 2, Fig. 3). They have been designated priority nations for NT elimi- nation activities. Community mortality surveys provided the first evi- dence that NT concentrated in certain areas within a country. In Egypt the risk of neonatal tetanus was found to be 5 times greater in rural than in urban areas, as was the risk in upper Egypt when com- pared to the lower Nile region. Another example is India. This country alone is responsible for 25% of the world's NT mortality. Among India 's 12 states, 3 contribute 95% of the NT deaths. Approximately 75% of this nation 's NT mortality occurs in only one state, Uttar Pradesh. More recently, a special survey in Bolivia found a decreased risk of NT in high altitude areas. Of the 430 NT cases studied, only 3 occurred in regions above 2 OOO feet despite half the country's population living above this height (da Silveira and de Quadros, unpublished manuscript, 1991 ). The Region of the Americas has identified focal areas of increased NT incidence using routine sur- veillance reports and health facility record reviews. Combined data from 11 countries revealed that 9% of districts produce 80% of the NT cases. Only 21% of the women of childbearing age in these countries live in risk areas (3) . In another study of several American countries, 50% of the NT cases were con- centrated in 5% of the districts (4). Not only does neonatal tetanus cluster in certain areas and population groups, it even recurs more frequently in certain families. Results from a study in Pakistan indicate that mothers of infants diagnosed with NT are at increased risk of having another baby contract the disease. If all women were immunized TABLE 2. COUNTRIES CONTRIBUTING 80% OF THE GLOBAL ESTIMATED NEONATAL TETANUS DEATHS, DEVELOPING COUNTRIES, 1991 TABLEAU 2. PAYS D'OU SONT ORIGINAIRES 80% DU NOMBRE ESTIMATIF DE DECES DUS AU TETANOS NEONATAL DANS LES PAYS EN DEVELOP- Country Pays India - lnde Bangladesh Indonesia - lndonesie China - Chine Nigeria - Nigeria Ethiopia - Ethiopie U.-R. Tanza nia - R. -U. de Tanzanie Zaire - Zafre Uganda - Ouganda Viet Nam Sudan - Soudan Kenya Nepal - Nepal Somalia - Soma lie Philippines Ghana Myanmar Other developing countries - Autres pays en developpement Global (developing countries) - Total (pays en develop- pement) PEMENT, 1991 Estimated number of neonatal tetanus deaths occurring Nombre estimatif de deces dus au tetanos neonatal 110 466 46 889 37 375 24 435 24 388 14 699 12 056 10 927 10 797 10 522 8 826 8 397 8 136 7 875 7 092 6 245 5 586 79 169 433 880 % global estimates % des estimations mondiales 25.1 10.7 8.5 5.6 5.6 3.3 2.7 2.5 2.5 2.4 2 1.9 1.9 1.8 1.6 1.4 1.3 18.3 100 FIG. 2 ESTIMATED NEONATAL TETANUS DEATHS OCCURRING BY WHO REGION, DEVELOPING COUNTRIES, 1991 NOMBRE ESTIMATIF DE DECES PAR TETANOS NEONATAL SURVENUS PAR REGION OMS, PAYS EN DEVELOPPEMENT, 1991 Europe 0.3% South-East Asia Asie du Sud-Est 48.8% Americas - AmE!riques 2.4% Africa - Afrique 29 .3% Western Pacific Pacifique occidental 10.7% Eastern Mediterranean M0diterranee orientale 8.4 % Total number of neonatal tetanus deaths: 433 880 Nombre total des deces par tetanos neonatal: 433 880 W/d h/th statist. quart .• 45 119921 - 252 - when their child was treated for NT, one-third of cases in this area could have been prevented (5) . The marked focality of NT is not surprising given the strong link between the disease and cord-care prac- tices. For instance, a recent case-control study in Senegal found that handwashing before delivery and application of cord dressings by a trained attendant had greater impact on the risk of NT than did the cleanliness or type of cord-cutting instrument (6) . Behaviours such as handwash ing, delivery practice, traditional birth customs and interest in immuniza- tion, are often shared among people in a g iven locale or subgroup. Because these activities also affect NT incidence, cases tend to occur more fre- quently in these populations. Medically underserved areas and livestock-raising regions are two environ- ments particularly associated with behaviours con- ducive to NT. It is important to note, however, that not every country has focal pockets of increased NT incidence. In El Salvador the rate of NT cases is similar among all districts, suggesting that risk behaviours and environmental conditions are similar throughout the country (4). Prevention strategies Immunizing women w ith tetanus toxoid (TT) and implementing clean del ivery practices can effectively prevent neonatal tetanus. Tetanus toxoid is a highly effective vaccine, costs US$0.15 per dose and can potentially reach a large number of women through existing EPI and antenatal care (ANC) infrastructures. Clean delivery practice is equally important. It helps the mother as well as the child by preventing a range of birth-related infections. Over 100 OOO women in developing countries die each year from puerperal infections. The majority of these deaths could be prevented by clean delivery practice. Tetanus toxoid immunization WHO recommends a 5-dose immunization schedule. The first dose simply primes the immune system. After a second injection, 85% of women develop protective antibody levels. When a woman becomes pregnant, these antibodies are transferred across the placenta to the embryo. With each successive TT dose, a higher proportion of women achieve protec- tive antibody levels and these last for increasing time intervals. By the fifth dose, 99% of women maintain protective antibod ies against tetanus throughout their childbearing years. High tetanus toxoid coverage in women of child- bearing age is extremely effective in preventing neonatal tetanus. For example, in the Pidie district of Indonesia, a community survey revealed an NT mor- tality rate of 32.1 deaths over 1 OOO live births. TT coverage was a mere 10%. After a mass campaign to immunize all women 10-45 years old, coverage levels increased to 84%. Two years later a follow-up survey found that only 4.9 newborns per 1 OOO live births died of NT, a reduct ion of 85% in NT mor- tality (7). At the global level, increases in TT coverage of pregnant women have progressed slowly. Between 1987 and 1991, TT immunization levels rose only 20%, a pace too gradual to eliminate NT by 1995. FIG.3 50 40 <I> Cl "' c: 30 <I> ~ :, 0 a.. <I> Cl "' c: 20 <I> " 1i; a.. 10 GLOBAL• TETANUS TOXOID IMMUNIZATION COVERAGE, 1987-1991 COUVERTURE MONDIALE8 DE LA VACCINATION ANTITENATIQUE, 1987-1991 1987 1988 1989 1990 1991 Years - Ann0es • Developing co untries only - Pays en d0veloppement seuleme nt. Rapp. trimest. statist. sanit. mond., 45 I 1992) - 253 - The EPI is much more successful at immunizing children than pregnant women. Only 43% of preg- nant women in developing countries receive a pro- tective course of TT (2 or more doses), while ap- proximately 80% of children complete an immuniza- tion schedule with 6 different antigens in their first year of life. In 1990 tetanus toxoid coverage equalled or exceeded oral polio vaccine (OPV3) coverage in less than one-third of nations. High TT coverage levels are quite attainable. Every WHO region contains at least one country whose TT coverage exceeds 96%. Globally, coverage of preg- nant women may rise sharply in the next few years as China, the world's most populous nation, em- barks on a TT immunization programme. Reported TT coverage is often inaccurate, usually underestimating true protection against neonatal tetanus. Because TT injections protect women and their future pregnancies for several years, many infants will be safe from NT even if their mother did not receive an injection during the last pregnancy. Immunization coverage surveys can measure the proportion of infants protected at birth against NT, a more precise performance indicator than routinely reported TT coverage levels. WHO recommends the periodic use of these simple coverage surveys to verify the accuracy of reported TT coverage and to measure protection at birth. At present, only 17% of women in the developing world have had their TT coverage monitored through these surveys. WHO is also developing a protocol to enable countries to measure protection at birth during routine EPI con- tacts. Clean delivery practices Neonatal tetanus is well controlled in some in- dustrialized countries through clean delivery practice alone. Over the last decade, most programmes in developing countries have concentrated on training traditional birth attendants, providing home delivery kits and educating pregnant women about the "three cleans" (clean hands, clean delivery surface and clean cord care). Operational research has shown that training of birth attendants alone can reduce death due to sepsis, asphyxia and birth trauma by 40-60%, and NT mortality by 90% (8). Only a small number of nationwide surveys are available to estimate global and regional clean de- livery coverage. Clean deliveries are defined as those with a trained attendant present. In 1991, 52% of deliveries in the developing world were assisted by a trained attendant, and 70% of women delivered at home. Half the female population in developing countries risk unclean deliveries and infants dying of NT. Clean delivery coverage varies widely by region. The Americas have the highest clean delivery coverage (86%), followed by the Asiatic countries (49%), Oceania (42%) and Africa (38%) (8). However, even developing countries with high levels of clean de- livery care may not reach the women most in need, and infants delivered in health facilities or with trained attendants are still at risk for NT through unclean cord care in the early days of life. Issues in tetanus toxoid quality At present, manufacturers in over 40 nations pro- duce tetanus toxoid. Several countries have multiple Wld hlth statist. quart., 45 (1992) TT producers within their borders, yet only the few manufacturers who supply UNICEF undergo a WHO vaccine-quality approval process. The quality of the remaining vaccine is largely unknown. An assumption critical to the success of neonatal tetanus elimination is that the TT used to immunize women is potent and of good quality. Recently, an increasing number of reports from Asia and Africa describe the failure of TT to prevent neonatal tetanus in the offspring of immunized women. For instance, in 1990 a community mortality survey undertaken in Bangladesh found a surprisingly modest decline in the number of NT deaths despite significantly increased coverage levels. Furthermore, infants born to women claiming to have been im- munized with 2 doses of TT had an NT mortality rate of 13.1 per 1 OOO live births. Based on the survey results, TT efficacy was estimated to be only 46% (Traverso, unpublished observations, 1990). Samples of the locally manufactured toxoid were sent for laboratory analysis, and a problem of sub- standard vaccine potency was discovered. The Bangladesh experience raises serious concerns about the quality of TT produced by local manu- facturers. Particularly as activities to increase TT coverage accelerate in order to eliminate NT by 1995, potent, high-quality vaccine must be ensured. WHO, in conjunction with the Centers for Disease Control (CDC), has developed a protocol to assist countries in the rapid assessment of suspected TT failures and in verifying their toxoid potency. A long-term plan is also being developed by WHO to help countries review their TT manufacturing pro- cedures and quality control practices. Priority elimination activities Clean delivery practices and TT coverage of women of childbearing age in the general population have not expanded quickly. Therefore, a first priority is to identify foci of increased NT incidence in order that staff and resources can be assigned to these high- risk areas on a priority basis. This permits a much more rapid impact on disease reduction. Over 90% of countries endemic for NT have already developed an NT action plan specifying their national elimina- tion policies. WHO has urged these nations to iden- tify their high-risk areas for NT down to the district and subdistrict level by the end of 1992. Countries can identify their high-risk areas using available incidence data. Sometimes this will include recent surveys or special studies, but for most coun- tries only routine surveillance reports are available. In this case, high-risk areas can be defined as those districts or geographical units with the highest NT incidence or where cases have recurred over the past few years. This method is used extensively in the Americas (3). The sensitivity of this method has limitations, bias- ing identifications of high-risk areas to those locales with better reporting. However, districts which report NT cases may have better staff motivation, infra- structure or access, thus making control measures operationally more feasible than the less developed areas not reporting cases. By prioritizing resources to those areas which report NT, programme man- agers should be motivated to improve their neonatal tetanus surveillaoce so that they receive greater assistance. - 254 - In areas without surveillance data, health facility records can be reviewed to identify NT cases and areas of increased incidence. Alternatively, risk can be estimated using clean delivery coverage data. Areas with the lowest proportion of clean deliveries should be prioritized for additional resources and elimination activities. A second important priority in eliminating NT is to improve the utilization of existing data. Every rou- tinely reported case of NT should be investigated at the time of diagnosis. Case investigations should include, at a minimum, the infant's address, ethnic group, delivery and cord-care history, maternal im- munization and antenatal care status. Mapping of the locations of multiple NT cases may suggest high-risk areas and groups. In addition, the inves- tigations should also help identify problems in health care access and delivery, which should assist in planning corrective activities. Because so many cases of NT never reach health facilities, NT surveillance activities must expand into the community. In Jalisco (Mexico) NT incidence varied from 1.7 per 1 OOO live births, based on hospital record reviews, to 3.7 per 1 OOO live births, found in a community survey (4). Community vital event registries need to be established throughout countries to monitor birth outcomes, maternal and neonatal deaths. In the Americas, training of mid- wives in NT surveillance has already begun in order to increase community reporting. Conclusion Neonatal tetanus is a highly fatal disease which claims the lives of over 433 OOO infants annually. Although the control strategies, TT immunization and clean delivery practice are highly effective in preventing NT, progress in reaching the general population has been slow. Risk of neonatal tetanus is intimately linked with delivery and cord-care practices so that cases cluster in certain geographical areas and groups which share common birth and immunization practices. By identifying the risk populations, elimination activities can be focused on these areas for maximum and rapid reduction of disease incidence. Case inves- tigations and community vital event registries will facilitate the identification of high-risk areas and subgroups. In addition, it is also vital to ensure that the tetanus toxoid used in any NT elimination ac- tivities is potent. The ability to target TT immunization and clean delivery practices to focal areas of increased NT incidence provides a solid basis to make the elimin- ation of neonatal tetanus a realistic target. SUMMARY Neonatal tetanus (NT) can be effectively prevented through immunization and clean delivery practices. However, NT claimed the lives of over 433 OOO in- fants in 1991. It is endemic in 90 countries through- out the world. Community-based neonatal tetanus mortality surveys helped to determine the true inci- dence of NT and revealed that, before immunization and clean delivery programmes were well es- tablished, approximately 1 million children con- tracted NT each year, of which 800 OOO died. Mor- tality rates varied markedly by locale, ranging from O to 70 NT deaths per 1 OOO live births. NT is still one of the most underreported notifiable diseases, and routine reporting systems identified only 4% of the NT cases estimated to have occurred in 1990. Based on WHO estimates, tetanus toxoid (TT) im- munization and clean delivery practices prevented over 793 OOO infant deaths in 1991. Of the 433 OOO infants who died of NT that year, approximately 212 OOO died in South-East Asia; 127 OOO in Africa; 46 OOO in the Western Pacific; 37 OOO in the Eastern Mediterranean; and 1 300 in Europe. The Pan American Health Organization, using a separate methodology to estimate mortality, calculated that 10 500 newborns died of NT in the Region of the Americas. NT consistently clusters in geographical areas and population groups where shared practices or the environment enhance the risk of cord contamination. 80% of the newborns who died of NT in 1991 were born in South-East Asia or Africa. Of the 90 countries endemic for NT, 10% produce 80% of the world's NT deaths. NT also clusters at country level. In Egypt, the risk of NT was found to be 5 times greater in rural than urban areas, as was the risk in Upper Egypt when compared to the Lower Nile region. India alone is responsible for over 20% of the world's NT mor- tality. Among India's 12 states, 3 contribute 95% of the NT deaths and approximately 75% of this na- tion's mortality occurs in only one state - Uttar Pradesh. More recently, a special survey in Bolivia found a decreased risk of NT in areas of high altitude. Not only does neonatal tetanus cluster in certain areas and population groups, it even recurs more fre- quently in certain families. Results from a study in Pakistan indicate that mothers of infants diagnosed with NT are at increased risk of having another baby contract the disease. At the global level, increases in TT coverage of pregnant women have progressed slowly. Between 1987 and 1990, TT immunization levels rose only 15%, a pace too gradual to eliminate NT by 1995. In 1990, only 43% of pregnant women in developing countries received a protective course of TT while approximately 80% of children completed an im- munization schedule with 6 different antigens in their first year of life. However, reported TT coverage is inaccurate and often underestimated. Immuniza- tion coverage surveys can measure more accurately the proportion of infants protected at birth against NT. Rapp. trimest. statist. sanit. mond., 45 (1992) - 255 - In 1991, 52% of deliveries in the developing world were assisted by a trained attendant, and 70% of women delivered at home. Half the female popula- tion in developing countries risks unclean deliveries and infants dying of NT. Clean delivery coverage varies widely by region. The Americas have the highest clean delivery coverage (86%), followed by the Asiatic countries (49%), Oceania (42%) and Africa (38%). However, even in developing countries with high levels of clean de- livery care, women most in need may not be reached and infants delivered in health facilities or with trained attendants are still at risk for NT through unclean cord care in the early days of life. An assumption critical to the success of neonatal tetanus elimination is that the TT used to immunize women is potent and of good quality. Based on a survey undertaken in Bangladesh in 1990, TT efficacy was estimated to be only 46%. Samples of the locally manufactured toxoid were sent for laboratory analysis, and a problem of substandard vaccine po- tency was discovered. In order to eliminate NT by 1995 potent, high quality vaccine must be ensured. WHO, in conjunction with the Centers for Disease Control (CDC), has de- veloped a protocol to assist countries in the rapid assessment of suspected TT failures and in verifying their toxoid potency. A long-term plan is also being developed by WHO to help countries review their TT manufacturing procedures and quality control prac- tices. The first priority for all endemic countries is to identify foci of increased NT incidence in order that staff and resources can be assigned to these high risk areas on a priority basis. Implementing inten- sified immunization activities in these areas permits a much more rapid impact on disease reduction. A second priority in eliminating NT is to improve the performance of the surveillance system in order to detect all NT cases, investigate them and implement corrective measures. RESUME Progres realises vers !'eradication mondiale du tetanos neonatal Le tetanos neonatal (TN) peut etre efficacement pre- venu par la vaccination et par des pratiques d'accou- chement hygieniques. Le TN n'en a pas mains coOte la vie a plus de 433 OOO nourrissons en 1991 et ii sevit a l'etat endemique dans 90 pays. Des enquetes a base communautaire sur la mortalite due au teta- nos neonatal ant aide a determiner !'incidence veri- table de cette maladie et ant revele qu'avant l'institu- tionnalisation des programmes de vaccination et d'accouchement hygienique, environ 1 million d'en- fants contractaient chaque annee le TN, avec 800 OOO issues fatales. Selan les regions, les taux de mortali- te variaient consideralement, dans un intervalle com- pris entre O et 70 deces dus au TN pour 1 OOO naissances vivantes. Le TN constitue toujours parmi les maladies sujettes a declaration obligatoire, une de celles qui sont le plus fortement sous-enregistrees, et l'on considere qu'en 1990 les systemes courants de notification n'ont identifie que 4% du nombre estimatif des cas. D'apres les estimations de l'OMS, la vaccination par l'anatoxine tetanique et !'application de pratiques d'accouchement hygieniques ant reussi a prevenir plus de 793 OOO deces de nourrissons en 1991. Cette an nee-la, sur les 433 OOO deces de nouveau-nes dus au TN, environ 212 OOO sont survenus en Asie du Sud-Est, 127 OOO en Afrique, 46 OOO dans la Region du Pacifique occidental, 37 OOO en Mediterranee orientale et 1 300 en Europe. Employant une metho- de differente pour !'estimation de la mortalite, !'Organisation panamericaine de la Sante a calcule que le TN avait provoque la mart de 10 500 nou- veau-nes dans la Region des Ameriques. Le TN tend a se concentrer regulierement dans des regions geographiques et parmi des groupes de population ou, soit des pratiques communes, soit des facteurs de milieu augmentent le risque de contamination du cordon ombilical. Parmi les deces Wld hlth statist. quart., 45 (19921 de nouveau-nes dus au TN en 1991, 80% sont surve- nus en Asie du Sud-Est et en Afrique. 80% des deces par TN qui se produisent dans le monde sont origi- naires de 9 pays sur les 90 ou le TN est endemique. Le TN se presente aussi par grappes au niveau des pays. En Egypte, on a constate que le risque de TN etait cinq fois plus eleve dans les zones rurales que dans les secteurs urbains et que la meme difference existait entre le risque rencontre, respectivement, en Haute-Egypte et dans la region du Bas-Nil. L'lnde a elle seule est responsable de plus de 20% de la mortalite mondiale due au TN. Sur les 12 Etats que compte l'lnde, 3 fournissent 95% du total des deces dus au TN et pres de 75% de la mortalite nationale provient d'un seul Etat: l'Uttar Pradesh. Plus recemment, une enquete speciale realisee en Bolivie a indique que le risque de TN diminuait dans les zones de haute altitude. Le tetanos du nouveau- ne ne tend pas seulement a se concentrer dans certaines regions et parmi certains groupes de popu- lation, mais ii tend aussi a revenir trapper plus frequemment certaines familles. D'apres une etude realisee au Pakistan, les meres dont les nouveau-nes ant contracte le TN risquent davantage d'avoir un autre bebe atteint de la meme maladie. A !'echelon mondial, la couverture des femmes en- ceintes par la vaccination antitetanique n'a pro- gresse que lentement. Entre 1987 et 1990, les taux de vaccination par l'anatoxine tetanique n'ont augmente que de 15%, soit a un rythme trap lent pour que le TN puisse etre elimine d'ici 1995. En 1990, 43% seulement des femmes enceintes des pays en developpement ant re~u un traitement prophylactique a l'anatoxine tetanique, tandis qu'en- viron 80% des enfants ant ete vaccines au cours de leur premiere annee de vie au moyen de six antige- nes differents. Les indications fournies sur la vacci- nation antitetanique restent cependant imprecises et - 256 - la couverture est souvent sous-estimee. Les enque- tes sur la couverture vaccinale permettent de mesu- rer avec plus d'exactitude la proportion des nourris- sons proteges contre le TN des leur naissance. En 1991, 52% des accouchements qui ant eu lieu dans des pays en developpement ant beneficie de !'assistance d'un auxiliaire qualifie et 70% des fem- mes ant accouche a domicile. On estime que la moitie des femmes vivant dans des pays en develop- pement risquent d'accoucher dans de mauvaises conditions d'hygiene et de voir leur bebe mourir du TN. La proportion des accouchements ayant lieu dans de bonnes conditions d'hygiene varie considerablement selon les regions. Cette proportion est la plus forte dans les Ameriques (86%), a la suite de quoi vien- nent les pays d'Asie (49%), d'Oceanie (42%) et d'Afri- que (38%). Meme dans les pays en developpement au cette proportion est elevee, beaucoup de femmes parmi les plus demunies peuvent rester hors d'at- teinte des prestations, et meme des bebes qui nais- sent dans des services de sante au avec l'aide d'auxiliaires qualifies risquent de contracter le TN parce que leur cordon est mal soigne pendant les premiers jours de la vie. Pour que l'on parvienne a eliminer le tetanos neona- tal, ii est indispensable que l'anatoxine tetanique employee pour la vaccination des femmes soit active et de bonne qualite. D'apres une enquete entreprise au Bangladesh en 1990, l'anatoxine n'est apparue efficace qu'a 46%. Des echantillons du produit fabri- que sur place ant ete envoyes au laboratoire pour y etre analyses et l'activite du vaccin a ete reconnue inferieure a la norme. Si l'on veut parvenir a eradiquer le TN en 1995, on doit pouvoir produire un vaccin puissant et de haute qualite. En collaboration avec les Centers for Disease Control (CDC), l'OMS a elabore un protocole destine a aider les pays a evaluer rapidement les echecs presumes de la vaccination antitetanique et a verifier l'activite de l'anatoxine. L'OMS prepare aussi un plan a long terme pour aider les pays a reexaminer leurs procedes de preparation de l'anatoxine tetani- que et leurs pratiques de contr61e de la qualite. Taus les pays d'endemicite doivent commencer par determiner les foyers au !'incidence du TN a augmente, afin d'y affecter en priorite du personnel et des ressources. En intensifiant les activites de vaccination dans ces zones a haut risque, on par- viendra a reduire beaucoup plus rapidement la mor- bidite tetanique. En second lieu, !'elimination du TN demande que l'on ameliore le systeme de surveillance afin de depister tous les cas de TN, de les etudier et d'appli- quer des mesures correctives. REFERENCES - REFERENCES 1. GALAZKA, A. ET AL Neonatal tetanus in the world and the Global Expanded Programme on Im- munization. In: Nistico, G. et al. (eds.), Pro- ceedings of the Eighth International Conference on Tetanus. Rome-Milan, Pythagora Press, 1989. 2. STANFIELD, J. P. & GALAZKA, A. Neonatal tetanus in the world today. Bulletin of the World Health Organization, 62 (4): 647-669 (1984). STANFIELD, J. P. & GALAZKA, A. Le tetanos du nou- veau-ne dans le monde d'aujourd'hui [resume). Bulletin de /'Organisation mondiale de la Sante, 62 (4): 666-667 (1984). 3. Neonatal tetanus control - defining high risk areas: the experience in the Americas. EPI News- letter, 12 (4): 3-5 (1990). 4. DA SILVEIRA, C. M. & DE QuADROS, C.A. Neonatal tetanus: countdown to 1995. World health forum, 12 (3): 289-296 (1991). 5. TRAVERSO, H. P. ET AL. Reassessment of risk factors for neonatal tetanus, Bulletin of the World Health Organization, 69 (5): 573-579 (1991). TRAVERSO, H. P. ET AL Reevaluation des facteurs de risque de tetanos neonatal [resume]. Bulletin de /'Organisation mondiale de la Sante, 69 (5): 578 (1991). 6. LEROY, 0. & GARENNE, M. Risk factors of neonatal tetanus in Senegal. International journal of epi- demiology, 20 (2): 521-526 (1991). 7. Impact of tetanus toxoid immunization, Weekly epidemiological record, 63 (40): 301-302 (1988). Impact de la vaccination par l'anatoxine tetanique. Re/eve epidemiologique hebdomadaire, 63 (40): 301-302 (1988). 8. WORLD HEALTH ORGANIZATION. Maternal mortality - A global factbook. Geneva, WHO, 1991. Rapp. trimest. statist. sanit. mond., 45 (1992) - 257 - WORLD MALARIA SITUATION 1990 Division of Control of Tropical Diseases World Health Organization, Geneva Population at risk Over 40% of the world population remained exposed to varying degrees of malaria risk in 99 countries or areas. Falciparum malaria does not exist or its rela- tive prevalence is less than 1% in 13 of these coun- tries or areas (Map 1). Of a total world population of about 5.3 billion people, 3.1 billion people (59%) live in areas free of malaria (it never existed, disappeared or was elim- inated by antimalaria campaigns and the malaria- free situation has been maintained). 1.7 billion people (32%) live in areas where endemic malaria was considerably reduced or even eliminated but transmission was reinstated and the situation is unstable or deteriorating. These latter areas include zones with the most severe malaria problems which developed following major ecological or social changes, such as agricultural or other economic exploitation of jungle areas, sociopolitical unrest, etc.; these zones comprise only about 1% of the world population. Areas where endemic malaria re- mains basically unchanged, and no national anti- malaria programme was ever implemented, are in- habited by 500 million people (9%), mainly in tropi- cal Africa. Malaria reporting to WHO Through its regional offices, WHO receives informa- tion on the number of malaria cases recorded by Member States' surveillance programmes (Table 1). Malaria cases are commonly defined as cases requir- ing treatment and which have been microscopically confirmed; in countries without microscopy facilities at peripheral level, cases are mostly diagnosed on clinical grounds. Such cases are not included in the figures quoted in this article. Accurate information on the global incidence of malaria is difficult to obtain because reporting is particularly incomplete in areas known to be highly endemic. The global incidence of malaria is estimat- ed to be nearly 120 million clinical cases each year, with nearly 300 million people carrying the parasite (Table 2). Countries in tropical Africa are estimated to have more than 80% of all clinical cases and more than 90% of all parasite carriers. In recent years, reporting of malaria cases improved in the WHO African Region although it remains fragmentary and irregular. In the other regions the total number of cases has not changed much over the last few years, although trends in individual countries vary. Of the total number of cases reported annually to WHO (excluding the African Region), 90% are from only 19 countries. Some 75% are concentrated in 9 countries (in decreasing order): India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Viet Nam, Cambodia and China. Further- more, within these countries malaria is concentrated in certain areas. Malaria mortality Severe malaria and mortality are caused by Plas- modium falciparum which is the predominant species of malaria in tropical Africa. In the rest of the world it is far less common. WHO receives very limited and irregular reports on malaria deaths. Coverage of reporting is particularly poor in "frontier areas" of economic development, such as intensified exploitation of natural resources in jungle areas, or in areas overburdened with civil war or other con- flicts, illegal trade and mass movements of refugees, and figures are therefore gross underestimates. For example, a total of 1 428 deaths were reported from the Americas in 1986, but the annual malaria mar- TABLE 1. NUMBER OF MALARIA CASES REPORTED (THOUSANDS), BY WHO REGION, 1983-1990• TABLEAU 1. NOMBRE DE CAS DE PALUDISME SIGNALES (MILLIERS), PAR REGION OMS, 1983-1990" WHO Region - Region OMS 1983 1984 1985 1986 1987 1988 Africa b., -Afriqueb,, ......................................................... 2 726 4 523 11 634 17 442 19 463 21 957 Americas - Ameriques ...................................................... 831 932 911 951 1 018 1120 South-East Asia - Asie du Sud·Est ...................................... 2 731 3 004 2 503 2 689 2 823 2 789 Europe ........................................................................... 73 62 57 47 28 24 Eastern Mediterranean - Mediterronee orientale .................. 305 335 391 611 566 602 Western Pacific - Pacifique occidental ............................... 1 839 1 410 1178 1 012 893 774 Total (excluding Africa - a !'exclusion de l'Afrique) ............. S 779 5743 S 040 S 310 S 328 S 309 • The inforfll(]non provided does not cover lhe toto/ popu/onon ot r~k in some instances. - Les informonons communiquees ne recouvrent pos, dons certoins cos, lo tota/~e de lo poptJonon exposee. • Mainly dinico//y diagnosed coses. - Essennellement des cos diognosnques /ors d' exomens c/iniques. ' Incomplete figures. - Chilfres incomplets . . . = No data ovoiloble. - Pas de donnees disponibles. W/d hlth statist. quart., 45 (1992) 1989 1990' 13 835 1 114 1 057 2 957 2 614 21 12 532 566 829 761 S 453 S 010 < D < D !::! _ .. 0 M A P 1 . E P ID E M IO LO G IC AL A S S E S S M E N T O F TH E S TA TU S O F M A LA R IA , 19 90 C AR TE 1 . E V A LU A TI O N E P ID E M IO LO G IQ U E D E L A S IT U A TI O N D U P A LU D IS M E , 1 99 0 Es tim at ed n u m be r o f c lin ic al c a se s N om br e e s tim at if de c as c lin iq ue s Ca se s re po rte d Ca s si gn al es - - - - ~ 55 o th er c o u n tr ie s 55 a u tr es p ay s 0 \ M ai n a re a s w he re m a la ria tr an sm is si on o cc u rs Pr in ci pa le s z o n e s o u ii y a tr an sm is si on d e pa lu di sm e 0 , ; 0 Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n th is m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f th e se cr e ta ria t o f th e W H O c o n ce rn in g th e le ga l st at us o f a n y co u n tr y, t er rit or y, c ity o r ar ea o r o f its a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f its fr on tie rs o r bo un da rie s - Le s de si gn at io ns u til is ee s s u r ce tte c a rt e et t a pr es en ta tio n de s do nn ee s qu i y f ig ur en t n 'im pl iq ue nt , de la p ar t d e !'O rg an is at io n m o n di al e de la S an te , a u cu n e p ris e de p os iti on q ua nt a u st at ut ju rid iqu e de te l o u te l p ay s, te rr ito ire , vil 1e o u z o n e , o u d e se s a u to rit es . n i q ua nt a u tr ac e de s es fr on ti8 re s. N (.T I O J TABLE 2. MALARIA: EPIDEMIOLOGICAL DATA, 1988-1990 TABLEAU 2. PALUDISME: DONNEES EPIDEMIOLOGIOUES, 1988-1990 Number of malaria Slide positivity rate Number of malaria cases Percentage of cases reported Taux de posttivite per 1 OOO population• P. lalciparum cases Country or area - Pays ou territoire Nombre de cos de des lames Nombre de cos Pourcentage de cos paludisme signales (%) de paludisme pour a P. lalciparum 1 OOO habitants• 1988 1989 1990 1988 1989 1990 1988 1989 1990 1988 1989 1990 CENTRAL AMERICA INCLUDING MEXICO -AMERIQUE CENTRALE Y COMPRIS LE MEXIQUE Belize ..................................................................... 2 725 3 285 3 033 12.2 16.6 17.6 16.0 18.3 16.1 3.5 2.9 1.3 Costa Rica ............................................................... 1 016 699 1151 1.0 0.6 1.0 1.3 0.9 1.4 2.7 4.4 0.4 Dominican Republic - Republique dominicaine ............. 1 072 1 275 356 0.3 0.4 0.1 0.2 0.2 0.0 99.3 97.S 93.8 El Salvador .............................................................. 9 095 9 605 9 269 4.3 5.0 4.0 2.0 2.0 2.0 2.5 0.4 0.2 Guatemala .............................................................. 52 561 42 453 41 711 12.7 12.8 13.6 15.8 11.7 11.1 4.1 2.7 2.4 Haiti- Hani ............................................................ 12 306 23 231 4 806 30.5 36.6 35.0 2.8 4.6 0.8 100.0 100.0 100.0 Honduras ................................................................ 29 737 45 922 53 095 7.1 11.7 12.7 6.7 9.9 11.7 1.4 0.8 1.2 Mexico - Mexique ................................................... 116 238 101 241 44 513 8.4 6.8 3.0 2.7 2.3 1.0 0.1 0.1 0.1 Nicaragua ............................................................... 33 047 45 982 35 785 6.7 8.8 7.7 9.4 12.3 9.2 7.8 3.7 4.4 Panama .................................................................. 1 OOO 427 381 0.2 0.1 0.1 0.5 0.2 0.2 16.1 19 .7 27.6 SOUTH AMERICA-AMERIQUE DU SUD Argentino -Argentine ............................................... 666 1 620 1 660 3.3 7.7 7.3 0.2 0.4 0.4 0.0 0.0 0.1 Bolivia - Bolivie ...................................................... 22 258 25 367 19 680 21.2 22.5 16.2 9.1 8.9 6.8 6.7 5.4 3.3 Brazil - Bresil ......................................................... 559 535 577 520 560 396 16.6 17.1 17.0 8.9 9.0 8.5 51.4 47.7 45.0 Colombia - Colombie ............................................... 100 850 100 286 99 489 19.8 18.0 20.1 5.2 4.9 4.5 32.8 33.4 35.7 Ecuador - Equateur .................................................. 53 607 23 274 71 670 16.1 16.1 19.7 9.4 3.8 11.5 25.3 28.2 30.5 French Guiano - Guyane frnn~aise ............................. 3 188 6 284 5 909 12.2 17.5 12.0 35.4 69.8 59.7 71.6 61.0 44.1 Guyana .................................................................. 35 470 20 822 22 681 d 19.6 14.5 16.8d 35.8 20.4 28.5d 68.6 59.5 56.9d Paraguay ................................................................ 2 884 S 247 1 660 3.7 5.9 1.7 0.9 1.5 0.4 0.8 0.3 3.4 Peru - Perou ........................................................... 32 359 32114 28 882d 25.8 32.1 d 4.7 4.5 3.9d 0.0 0.2 O.Sd Suriname ................................................................ 2 691 1 704 1 608 8.0 7.3 8.6 9.4 5.8 5.3 85.3 93.0 98.5 Venezuela ............................................................... 45 827 43 374 46 910 13.2 12.3 9 .4 d 3.2 2.9 lP 31.8 30.2 35.2d ASIA WEST OF INDIA-ASIE A L'OUEST DE L'INDE Afghanistan ............................................................. 378 896 257 282 317 479 36.3 43.9 43.2 49.9 28.4 34.4 0.5 0.7 0.6 Iran (Islamic Republic of) - Iran (Republique islamique d') ............................... 53 319 59175 77 470 2.4 2.5 3.5 1.3 1.4 1.8 34.3 35.8 47.6 Iraq ........................................................................ 6 883 4 963 1 832 0.5 0.2 0.4 0.3 0.1 1.6 2.5 2.8 Oman ..................................................................... 24 619 17 867 32 720 8.9 6.7 12.1 17.8 12.6 21.8 91.7 89.8 94.6 Pakistan ................................................................. 57 811 107 739 79 689 1.9 3.5 3.1 0.5 1.0 0.7 28.8 52.0 54.3 Saudi Arabia -Arabie saoudite .................................. 9 797 6 475 15 666 1.6 1.1 2.3 2.1 1.3 3.2 88.6 82.8 95.4 Syrian Arab Republic - Republique arabe syrienne ........ 105 83 107 0.1 0.1 0.0 0.0 0.0 0.0 16.9 28.0 United Arab Emirates - Emirats arabes unis ................. 3 056 2 823 3 514 4.0 3.8 4.3 2.0 1.8 2.2 38.7 36.8 41.0 Yemen - Yemen ...................................................... 11 291 11 411 11 783 12.5 12.2 14.5 1.9 1.9 1.9 89.3 100.6 94.8 MIDDLE SOUTH ASIA - ASIE CENTRALE MERIDIONALE Bangladesh ............................................................. 33 824 so 738 53 875 1.3 1.7 2.2 0.3 0.5 0.5 61.4 66.3 63.2 Bhutan ................................................................... 11 314 19162 22.1 26.7 60.7 100.4 54.3 44.0 India - lnde ............................................................ 1854 830 2 017 823 1777 253 2.5 2.8 2.6 2.4 2.6 2.2 37.1 36.7 34.7 Nepal - Nepal. ........................................................ 23 751 22 333 20 338 1.9 2.1 2.5 2.1 2.2 1.7 12.S 10.4 7.5 Sri Lanka ................................................................ 383 294 258 727 287 384 28.7 23.0 23.S 31.0 20.9 23.0 24.6 25.4 20.0 EASTERN ASIA AND OCEANIA-ASIE OE L'EST ET OCEANIE Cambodio - Cambodge ............................................ 123 796 25.2 73.S 89.6 China• - Chine' ...................................................... 93 170 88 569 86 628 0.4 0.5 0.5 0.1 0.1 0.1 13.6 12.8 9.2 East Timorh- Timor oriental h ...................................... 64 854 108.1 58.1 Indonesia' - lndonesie' ............................................ 32 471 22 802 26 018 0.5 0.3 0.4 0.2 0.1 0.2 46.0 43.8 29.3 Loo People's Democratic Republic - Republique democratique populaire lao .................... 37 724 34 637 21 499 18.7 16.0 14.3 12.2 10.9 6.5 93.9 95.3 86.3 Maloysia - Malaisie ................................................. 50 743 65 363 SO SOO 2.2 2.6 2.3 3.0 3.9 2.8 69.7 69.6 70.7 Myanmar ................................................................ 94 736 135 194 23 l67d 10.0 10.9 17.9d 2.6 3.6 0.6d 89.0 85.7 79.8d Papua New Guineo - Papouasie-Nouvelle-Guinee .......... 83 944 121 796 104 939 42.3 36.3 39.9 23.6 33.9 28.4 71.3 77.2 77.2 Philippines .............................................................. 154 943 115 542 86 172 11.4 7.8 7.3 8.8 6.4 5.4 52.2 67.0 61.7 Solomon Islands - lies Salomon ................................ 63 893 65 241 116 449 22.2 22.3 31.9 213.0 209.3 372.1 62.0 61.6 69.8 Thailand - Tha·11ande ................................................ 349 291 299 137 272 634 4.4 4.0 3.7 7.5 6.4 5.6 53.4 56.0 63.6 Vonuatu .................................................................. 26 894 25 422 28 558 29.5 26.S 32.2 179.3 169.S 194.3 74.9 66.6 65.8 Viet Nam ................................................................ 151 520 142 818 139 588 4.9 6.5 6.4 3.3 3.1 3.0 64.5 74.5 73.8 EUROPE INCLUDING TURKEY ANO THE FORMER USSR - EUROPE Y COMPRIS LA TURQUIE ET L'ANCIENNE URSS Turkey - Turquie ...................................................... 16 245 12112 8 680 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0.0 0.0 • Population in originally molorious oreos. - Hobitan~ des zones initiolement impoludees. • 1972. ' Jovo and Boli only; in 1990 (provisional data). 153 OOO coses were recorded in the other islands. - Jovo et Bali seulemen~ en 1990 (donnees prov~oires), 153 OOO cos ont ete enregisnes dons les aunes fo. • Provisional. - Prov~oire. • Microscopicolly-con~rmed cases only. - Cos con~rmes par exomen microscopique seulement . . . . = No doto ovoilable. - Pas de donnees disponibles. - 260 - tality for the Brazilian Amazon region alone has been estimated to be between 6 OOO and 10 OOO. The vast majority of malaria deaths occur in Africa; estimates vary greatly: a figure of 800 OOO deaths per year in African children has been quoted in 1991 by the WHO African Region. There are indications that mortality in children has fallen in some areas; this is 'due to the widespread use of antimalarials, to social development, and better education. Constraints The variety and complexity of technical, political, sociocultural and economic factors that come together in the transmission of malaria have demon- strated the necessity of adopting an approach which takes into account various risk factors leading to different degrees of endemicity. The various epi- demiological situations need organized control with realistic goals permitting diversification and com- plementarity in the measures that are applied in accordance with local conditions, resources and levels of development. Among the main barriers to prevention and control of the disease in areas with high transmission are: (a) inadequate sanitation and precarious living con- ditions; (b) a frequent lack of financial resources; (c) lack of knowledge about the biology, ecology and control of the vectors; (d) expansion of the agri- culture, mining and forest industries into new areas, leading to migration; and (e) inefficient or non- existent health infrastructure. Global trends The reduction in number of reported malaria cases from 9 million to 5 million between 1976 and 1984 (Fig. 1) was largely due to the control of a malaria resurgence in India. The number of cases from India has stabilized, and in China malaria incidence con- tinued to fall as a result of the successful integration of malaria control into the primary health care system. Excluding China and India, the overall ma- laria situation seems to be deteriorating. Areas par- ticularly susceptible to this deterioration include "frontier areas" in South-East Asia and South America. In the highly endemic areas of Africa, there has been little change, but epidemics have occurred in areas of lower endemicity. With regard to parasite resistance to antimalarial drugs, there are only a few countries which have not reported the resistance of P. falciparum to chloro- quine; and the rapid evolution of this resistance in Africa threatens to hamper the provision of adequate treatment in rural areas. Resistance to sulfadoxine/ pyrimethamine has developed in South-East Asia, South America and focally in Africa. In Thailand, there are indications that up to 50% of cases in certain areas no longer respond to mefloquine therapy, while sensitivity to quinine is also diminish- ing in areas of Thailand and Viet Nam. Africa In Africa north of the Sahara, the total number of cases reported has fluctuated around 1 100 during recent years. The Libyan Arab Jamahiriya and Tunisia are considered free from malaria transmis- sion, only imported cases being reported. In Egypt, only 75 cases were recorded in 1990, compared with 192 in 1989. Most of them (falciparum infections) were from a new focus (Khour Saudii) in El Faiyum Governorate. No cases were found in the focus of Terssa, in which transmission had occurred in pre- vious years. In Algeria, 109 of the 152 cases record- FIG.1 8 6 4 2 NUMBER OF MALARIA CASES REPORTED, 1964-1990 NOMBRE DE CAS DE PALUDISME NOTIFIES, 1964-1990 WORLD (excl. African Region and China) MONDE (sauf la Rt!!gion africaine et la Chine) - WORLD (excl. African Region. China and India) MONDE (sauf la At!!g,on africaine. la Chine et l'lnde) 1965 1970 1975 1980 Year-Annee 1985 .... - 1990 Rapp. trimest. statist. sanit. mand., 45 (19921 - 261 - ed in 1990 were imported. Two foci of P. vivax infections were detected: Arib locality in Ain-Defla Wilaya with 13 cases, and lhrir area in Djanet Wilaya with 29 cases. The latter is an ancient focus reacti- vated probably after importation of cases. In Morocco, the number of cases detected remained stable with 839 in 1990 compared with 830 in 1989. Of the 781 cases of local origin (all P. vivax) 52% were detected in El Kelaa Sraghna (262) and Settat (173) Provinces; 100 were recorded in Chefchaouen, 64 in Khemisset, 63 in Khenifra, 38 in Khouribga, and 23 each in Larache and Taza Provinces. Five other provinces reported 12 or fewer cases of local trans- mission. In Africa south of the Sahara, between 12 and 22 million cases per year have been reported during 1985-1989, but based on levels of endemicity it has been estimated that about 100 million clinical ma- laria cases may occur every year, and that the prevalence of infection may be in the order of 275 million parasite carriers. Africa experiences the highest levels of endemicity in the world, with very large areas classified as holoendemic (in forest or savannah at altitudes up to 1 OOO m with an average rainfall over 2 OOO mm/year). At altitudes over 1 500 m and rainfall below 1 OOO mm/year, endemicity de- creases and the potential for epidemic outbreaks increases. Marked seasonality and quasi-cyclic occurrence of heavy rains have led to epidemics or serious exacerbations of endemicity (Botswana, Burundi, Kenya, Madagascar, Rwanda, Swaziland, Zaire and Zambia). Despite the scarcity of studies on malaria mortality in Africa, it is obvious that in highly endemic areas malaria mortality is concentrated in the younger age groups. In 1969, it was estimated that malaria might be responsible for 1 million infant and child deaths per year in tropical Africa. From data collected in 1970-75, it was concluded in Kenya (Kisumu) and Nigeria (Garki) that malaria was responsible for about 20-30% of the infant mortality. A more recent study in the Gambia (1987) concluded that malaria mortality may be as high as 6.3 per 1 OOO per year in infants and 10.7 per 1 OOO per year in children 1-4 years old. In other areas of Africa, in Burkina Faso and Congo for example, much lower infant and childhood mortalities from malaria have been re- ported. The lack or shortage of trained personnel for the planning, organization, monitoring and evaluation of programmes remains one of the major constraints. The Interregional Meeting on Malaria Control in Africa held in Brazzaville in October 1991 adopted a policy aimed at: (i) the prevention and reduction of malaria mortality by providing prompt diagnosis and adequate treatment of malaria cases through the basic health services - this implies also the creation of efficient referral systems for the management of severe and complicated cases as well as for treat- ment failures; and (ii) the detection and prevention of epidemics and the selective application of vector control measures applicable to the local epi- demiological situation and where the results can be sustained. The Americas Since 1974, when only 269 OOO malaria cases were recorded (corresponding to an annual incidence of 1.34 per 1 OOO population in the originally malarious areas), the number of cases detected every year was Wld hlth statist. quart., 45 (19921 continually rising, with 1 114 OOO cases reported in 1989 (3.9 per 1 OOO population in originally mala- rious areas). In 1990, the increase seems to have come to a halt with 1 057 OOO cases recorded. More than half of the cases were registered in Brazil (53%); 25% originated from the Andean countries and 14% were from Central America. Vivax malaria continued to predominate in the Americas (67% of all infection). Its relative preva- lence was 99.9% in Mexico and 97.6% in Central America. However, P. falciparum predominates in Haiti (100%), Suriname (99%) and the Dominican Republic (94%); and the proportion of falciparum infections was 57% in Guyana, 45% in Brazil and 44% in French Guiana. 73% of all falciparum infec- tions detected in the Americas occurred in Brazil. Within each country malaria transmission is con- centrated in certain regions which made it possible to identify priority areas for antimalaria activities. Countries initiated epidemiological stratification of the malarious areas in order to adapt antimalaria measures to local conditions and existing risk fac- tors, and to make better use of the resources avail- able. Considering groups of contiguous countries with antimalaria programmes, the situation in 1990 was as follows. Central America, including Mexico. A considerable decline in the number of cases has been reported from Mexico where malaria cases rose from 18 OOO in 1976 to 134 OOO in 1984, the year with the highest incidence. In 1990, only 44 OOO cases (detected in 11 OOO localities) were reported, compared with 101 OOO (detected in 16 100 localities) in 1989. Fal- ciparum infections declined also in 1990, only 62 (compared with 150 in 1989) were recorded in rain- forest areas near the border with Belize and Guate- mala (Tabasco, Chiapas and Ouintama Rao states). In the other countries, the overall malaria incidence varied from 0.16 per 1 OOO population in malarious areas in Panama to 17 per 1 OOO in Belize. In Honduras, where cases went up from 19 OOO in 1987 to 53 OOO in 1990, the departments with high inci- dence were: Yara (13 600 cases), Choluteca (8 300), Colon (7 500), Cortes (7 200) and Valle (3 200). In Belize malaria incidence remained high, reaching 40 and 47 cases per 1 OOO in Cayo and Toledo Districts. In Guatemala, the situation hardly changed; nearly 70% of the cases came from 5 of the 22 depart- ments: El Peten, Alta Verapaz, Escuintla, lzabal and El Quiche. In Nicaragua, malaria cases declined from 46 OOO in 1989 to 36 OOO in 1990. About 60% of them were from Region II (Leon and Chinandega departments and 23 municipios). Within this region, only 6 muni- cipios reported 70% of the cases: El Viejo, Somotillo, Chichigalpa, La Reynaga, Chinandega and Leon. In the latter, the local health authorities successfully reduced malaria transmission after careful study of the local risk factors and by adapting antimalaria measures to the local conditions. In El Salvador, malaria cases decreased steadily from 96 OOO in 1980 (with 16 OOO falciparum infections) to 9 300 (with 18 falciparum infections) in 1990. The authorities in- tegrated malaria control into the general health ser- vices, basing antimalaria measures on epidemiologi- cal stratification and adapting them constantly to the evolution of the malaria situation. Panama reported the lowest number of cases in this region: 381 in - 262 - 1990 compared with 427 in 1989. The local cases were from 72 localities (<1% of the localities in malarious areas) situated in Darien Province, San Blas comarca and in eastern Panama (Bayano region). Movements of the indigenous population, importation of cases, colonization and ecological changes contribute to the persistence of transmis- sion in these areas. Caribbean. In this subregion, malaria transmission occurs only on the island of Hispaniola. In the Dominican Republic, where between 1 100 and 1 400 cases were recorded annually during 1986-1989, only 356 malaria cases were detected in 1990. A drought from January to May, traditionally rainy months, may have helped to limit the number of cases. In Haiti, malaria control is one of the priority pro- grammes delegated to the health services. All cases are falciparum infections. During the last 3 years, 31-37% of the blood specimens examined were found positive. South America (Andean subregion). 25% (267 OOO) of all cases detected in the Americas are from this region (Bolivia, Colombia, Ecuador, Peru, Venezuela); 64% of the total occurred in Colombia (nearly 100 OOO cases) and Ecuador (72 OOO). More than 25% of the cases recorded in Colombia, Ecuador and Venezuela are falciparum infections. In Colombia, 80% of all cases were detected from 74 municipios in 6 regions: Pacific Coast, Lower Cauca, Uraba, Amazon, Sarare and Magdalena Media. However, only 12% of the localities in the malarious areas provided information and there is considerable un- derregistration of malaria mortality. Epidemiological stratification of the malarious areas has been initia- ted. In Ecuador, the provinces of Esmeraldas, Manabi, Guayas and Los Rios registered 92% of all cases. They represent the new frontiers for develop- ment with agricultural colonization and mining ac- tivities. Esmeraldas continues to have the highest incidence of falciparum cases, reporting 40% of the country total. In Venezuela, reporting a total of 47 OOO cases in 1990, 57% originated from Bolivar State (mainly from rain-forest areas), 15% from Sucre State (largest proportion from Santa Fe muni- cipio), and 11% from the Federal Territory of Amazonas where cases increased by 71% compared with 1989. Most falciparum infections occur in jungle areas of the Amazon region (Federal Territory of Amazonas and Bolivar State). In Bolivia, the number of cases decreased from 25 OOO in 1989 to 20 OOO in 1990, with an even greater decrease in the fal- ciparum infections from 1 400 to 650. In Peru, inci- dence remained stable. However, there was a resur- gence of falciparum transmission (from O cases in 1988 to 131 in 1990) mainly in the region of Piura (Tum bes). South America (French Guiana, Guyana, Suriname). The coastal plains were freed from malaria during recent decades, but the disease has remained en- demic in the tropical jungle areas of the interior. The principal factor that led to a rapid deterioration of the situation during recent years is the intense mi- gration between the coastal areas and the interior as well as across the borders. French Guiana and Guyana have the highest overall incidence in the Americas, with 53 and 40 cases per 1 OOO population, respectively. Guyana is the most affected country with 23 OOO cases, 75% of all cases in this area. The highest incidence (417 per 1 OOO) was recorded in the region along the southern border with Venezuela. In French Guiana, the Oyapock and Maroni river basins (incidence 546 and 204 per 1 OOO respectively) continued to be the most affected areas. In Suriname activities were very limited due to civil disturbances. South America (Brazil). Brazil is unique in terms of the diversity of its epidemiological situations. Its total territory of more than 8.5 million km2 com- prises nearly 7 million km2 of originally malarious areas, 5 million belonging to the Amazon region. Only 15% (24 million people) of Brazil's total popula- tion live in areas with malaria transmission. In 1990, the increase in the number of cases came to a halt with 560 OOO cases recorded (578 OOO in 1989). repre- senting 53% of all cases in the Americas. The prop- ortion of falciparum infections, which was 55% in 1986, came down to 45% in 1990. Nearly 99% of all cases were detected in the Amazon region. The high incidence in this region is con- nected with activities in "frontier areas" of economic development, such as mining by garimpeiros in remote and inaccessible areas, and forest clearing followed by subsistence agriculture. Rondonia State had 33% of all cases, 10 out of the 23 municipios producing 90% of the cases. In Mato Grosso (25% of all cases) 90% of the cases were from 10 municipios with an annual incidence of 129 and more per 1 OOO population. In Para (20% of all cases), 5 municipios with the highest number of cases had an annual incidence ranging from 27 to 584 per 1 000. Outside the Amazon region there is little malaria transmission. An outbreak that developed in Faz de lguacu, Parana, was contained by remedial meas- ures carried out by the three bordering countries. In 1989 more than 1 OOO indigenous cases were detec- ted on the Brazilian side, while in 1990 only 200 cases were recorded. South America (southern cone). In this subregion (Argentina, Chile, Paraguay and Uruguay) malaria is endemic only in Paraguay and in the north of Argen- tina, the situation being strongly affected by the influx of population from southern Brazil through Paraguay. In Argentina, incidence remained stable with 1 660 cases detected in 1990 (1 620 in 1989), and in Paraguay vector control measures brought down the incidence from 5 200 cases in 1989 to 1 700 in 1990. Asia west of India Endemic malaria is absent from Bahrain, Cyprus, Israel, Jordan, Kuwait, Lebanon and Qatar. However, an episode of local transmission of vivax malaria occurred in the Kerak Lowlands of Jordan during November-December 1990. The focus was elim- inated through prompt and efficient remedial measures against the vector and mass treatment around the cases. Among the 538 OOO malaria cases reported in this region from countries where malaria is endemic, 317 OOO (59%) were recorded in Afghanistan, 80 OOO in Pakistan (15%) and 77 OOO in Iran (14%). Fal- ciparum malaria cases are most numerous in Pakistan (43 OOO) and Iran (36 OOO), although the relative prevalence of this species is more important in Yemen (98%), Saudi Arabia (95%) and Oman (95%). In Afghanistan, activities continued to be very lim- ited because of the civil conflicts. 317 OOO malaria cases were reported in 1990 compared with 247 OOO Rapp. trimest. statist. sanit. mond., 45 (1992) - 263 - in 1989. The percentage of blood specimens found positive were 43% and 42%, respectively. Falciparum infections increased from <510 during 1982-1986 to 3 300 in 1987. They declined to 1 600 in 1989, rising again to 2 800 in 1990. They represented less than 1% of the cases in 1990. In Pakistan, the number of cases decreased from 104 OOO in 1989 to 80 OOO in 1990. Gradually, the participation of the general health services in case-detection activities is improv- ing; in Sind and North-West-Frontier provinces, 42% and 47% of all blood specimens have been collected from fever cases by these services. The percentage of positive blood specimens decreased in Punjab, Sind and Baluchistan, whereas it rose sharply in the North-West-Frontier Province, from 3.6% to 6.5%. Overall, the relative prevalence of falciparum infec- tions continued to rise (54% in 1990 compared with 34% in 1987). Countrywide, it was 33% in Punjab (36% in 1989), 38% in North-West-Frontier Province (32% in 1989), 77% in Sind (74% in 1989) and 77% in Baluchistan (only 42% in 1989). An important epi- demiological feature is the influx of more than 3.5 million Afghan refugees, mainly into the North-West- Frontier Province. The majority are living in camps situated alongside local villages and the reported incidence of malaria continued to be significantly higher in these camps than in the surrounding areas. In 1990, 83 OOO malaria cases were detected in these camps with a slide positivity rate of 20% (range 4.6- 31%). 17 OOO of the cases (21%) were falciparum infections. In the Islamic Republic of Iran, malaria incidence continued to increase, with 77 OOO cases reported in 1990 compared with 59 OOO in 1989 and 53 OOO in 1988. Nearly 7 OOO cases were imported, mainly from Afghanistan. Few foci exist in the areas north of the Zagros chain. Regarding the southern slopes of the Zagros chain, malaria is less important in the west and south-west of the country. However, in the south-eastern part of the country (Hormozgan, Sistan and Baluchistan and the tropical part of Kerman provinces), prevalence is high and transmission of malaria has never been interrupted. In Oman, malaria cases increased from 18 OOO in 1989 to 33 OOO in 1990, because of heavy rains and extension of irrigation for agriculture. About one- third of the cases were recorded in Dhahira region. 95% of all cases were falciparum infections, although their proportion was only 33% in the Southern region. In the 2 main malaria strata, "coas- tal" and "foothills", prevalence rates were, re- spectively, 0.5% and 2.1% in the protected areas, and 1.8% and 7.2% in the unprotected areas. In Saudi Arabia, where malaria cases were reduced from 18 OOO in 1987 to 6 500 in 1989, heavy and early rains caused a sharp increase to 16 OOO cases in 1990. The most affected areas were Gizan (52% of the indigenous cases), the lowlands of Asir (31%) and the Western region (17%). In Yemen, malaria cases seem to have increased in recent years. In 1990, 11 OOO cases were confirmed and the slide positivity rate was 14%. This rate was at a low in 1985 with 4.6%, and increased over the years to 12% in 1989. The number of confirmed cases rose from approximately 3 OOO in 1985 to 6 OOO in 1987 and to 11 OOO in the following years. The incidence and the rates tend to be higher in the southern governorates. However, the data are in- complete and cover mainly the coastal plain areas, foothills and part of Soccotora island. Wld hlth statist. quart., 45 (1992) In the United Arab Emirates, among the 3 500 cases reported in 1990, less than 1% were of local origin, occurring sporadically in rural areas as secondary cases to imported infections. Pakistan, Oman and India are the principal source of the imported cases. In Syria, the malaria situation remained stable with 107 cases reported - 68 of them being of local origin (Tatous 45, Al Hasakeh 17, Latakia 3, Damas- cus, Edlib and Hama, 1 each). Middle South Asia Overall, there was a reduction of nearly 10% in the number of malaria cases reported, from 2.37 million in 1989 to 2.14 million in 1990. However, these figures are provisional and strongly influenced by the fact that more than 80% of all cases in this region are recorded in India. With regard to malaria mortality, the existing systems of death registration probably underestimate the number of deaths from malaria, as only parasitologically confirmed malaria cases are taken into account. Studies conducted in many endemic areas have indicated that although malaria deaths occur in fact more frequently than shown in official records, they are not such an important demographic factor as before the initiation of the malaria eradication campaign. In India, 268 malaria deaths were recorded in 1989 and 222 in 1990. In Bangladesh it is estimated that between 200 and 800 malaria deaths occur annually. In Nepal, official statistics indicate that such deaths are only sporadic. In India, 1.78 million cases were recorded in 1990, representing more than one-third of the total number of cases reported outside Africa. Compared with the 2.02 million cases in 1989, this corresponds to a reduction of 12%. The relative prevalence of falciparum infections has not varied much over the period 1986-1990, ranging between 35% and 37%. Some 27% (489 OOO) of the total cases were notified in Gujarat State, where 599 OOO cases were recorded in 1989 (30% of the total cases in India). Uttar Pradesh (99 OOO cases), Rajasthan (86 OOO cases) and Punjab (29 OOO cases) also reported a reduction of malaria incidence. However, cases increased from 11 OOO in 1989 to 12 OOO in 1990 in Delhi. In Tamil Nadu, there were 76 OOO malaria cases in 1988 and 90 OOO in 1989, from which they rose to 117 OOO in 1990 (+30%). In Haryana, only 9 200 cases were registered in 1988, but 24 OOO were detected in 1989 and 50 OOO in 1990. In Sri Lanka, malaria incidence rose sharply, from only 38 500 malaria cases in 1982 (37 OOO P. vivax, 1 500 P. falciparum) to 676 OOO (493 OOO P. vivax, 183 OOO P. falciparum) in 1987. The following regions were the most affected: Anuradhapury, Kurunegala, Puttalam, Matale, followed by Maha, Monaragala and Hambantota. Most of the falciparum infections were reported from Kurunegala, Anuradhapura, Hambantota and Puttalam. In 1987, 35% of the blood specimens examined were found positive for malaria and 27% of all cases were falciparum infections. In 1990, 287 OOO cases were recorded compared with 259 OOO in 1989. The percentage of falciparum infec- tions decreased however from 25% in 1989 to 20% in 1990. In Bangladesh, incidence continued to rise with 54 OOO cases reported in 1990 compared with 51 OOO and 34 OOO in 1989 and 1988, respectively. Almost two-thirds of all cases were falciparum infections originating mainly in Chittagong Division near the - 264 - eastern border of the country. In Nepal, the malaria situation remained stable with about 23 OOO cases reported annually during 1988-1990. The incidence of falciparum infections declined, however, from 7 500 in 1985 to 2 300 in 1989 and 1 500 in 1990. In Bhutan, malaria incidence is still high (100 per 1 OOO population). Deaths attributed to malaria numbered 14 in 1988 and 25 in 1987. In Maldives, the last indigenous falciparum cases occurred in 1976 and indigenous malaria has not been detected since 1984. Only a few imported malaria cases are recorded. Surveillance is carried out through primary health care workers and screen- ing for malaria has continued at ports of entry. Eastern Asia and Oceania Australia, Brunei Darussalam, the Democratic People's Republic of Korea, Hong Kong, Japan, Macao, Mongolia, the Republic of Korea, Singapore, large areas of China and most of Oceania are consi- dered free from malaria. These countries notify only imported cases, although a few introduced cases secondary to imported malaria occur occasionally in some of them. These foci are promptly eliminated by appropriate remedial measures. The endemic coun- tries of this region reported some 1.27 million con- firmed malaria cases in 1990, compared with 1.38 million in 1989. More than one-fifth of these were from Thailand (273 OOO), 14% came from Indonesia (179 OOO) and 11% from Viet Nam (140 OOO). These 3 countries reported nearly 50% of all cases in the region. In Thailand, the number of malaria cases decreased from 349 OOO in 1988 to 299 OOO cases in 1989, and 273 OOO in 1990. However, the relative prevalence of falciparum malaria rose from 53% to 64% during the same years. The highest incidence continued to be recorded in the border provinces of Trat (bordering Cambodia) and Tak (bordering Myanmar). Malaria cases increased by more than 70% in Trat (recording nearly one-quarter of all cases), and also in Tak; both provinces together with Chanthaburi and Kanchanaburi registered nearly 50% of all cases in Thailand. One of the major problems continues to be the increasing frequency of falciparum strains highly resistant to chloroquine and sulfadoxine/pyrimeth- amine, and to mefloquine, in the border areas of Trat and Tak. In Indonesia, surveillance activities are carried out only in Java and Bali. After a decline in the number of reported cases, from 32 OOO in 1988 to 23 OOO in 1989, incidence increased again in 1990, with more than 26 OOO cases detected (provisional data). How- ever, the proportion of falciparum cases continued to decrease, from 46% in 1988 to 44% in 1989 and 29% in 1990. Malaria control activities in the Outer Islands are limited to areas of socioeconomic impor- tance and include indoor residual insecticide spray- ing, malariometric surveys, and the provision of suppressive treatment to clinical malaria cases at health centres. About 30% of the blood specimens examined were found positive and 153 OOO malaria cases were reported. In Viet Nam, the number of malaria cases did not vary much from 1989 to 1990 when 140 OOO cases were recorded, but in the same year 1.9 million clinically diagnosed cases were registered. Between 1987 and 1990, there was an increase of 380% in severe or complicated malaria cases in the northern provinces and of 175% in the southern provinces. Mortality from malaria rose from 1 070 deaths in 1987 to 3 439 in 1989. In China, the declining trend of malaria incidence continued with 117 OOO cases reported in 1988, com- pared with 138 OOO cases in 1989; there were 904 OOO cases in 1984. Some 89% of the population live in areas where malaria is absent or has been elimin- ated, or where its incidence is 0.1 per 1 OOO popula- tion or less. Malaria incidence dropped by 23-40% in Hainan, Yunnan, Guangxi and Guizhou in South China, whereas there was a slight increase in Guangdong, Fujian and Sichuan. The number of cases for theses provinces totalled 73 OOO (62% of all cases). In Middle and East China, malaria declined to some extent in Anhui, Hubei, Henan and Hunan. A slight increase was recorded in Jiangsu, Jiangxi, Zhejiang and Shanghai. The total number of cases for these areas was 44 OOO (38% of all cases). There were only 274 malaria cases in north and north-west China. Of the total number of 117 OOO cases, 80 OOO were diagnosed by microscopy; 10% of these were falciparum infections. Indigenous falciparum malaria occurred in Hainan, Yunnan, Guangxi and Anhui. In Cambodia, the Lao People's Democratic Republic, Myanmar, Papua New Guinea and Vanuatu, the ma- laria situation has not changed significantly during the past few years. In the Solomon Islands, malaria incidence nearly doubled, from 65 OOO cases in 1989 to 117 OOO in 1990 - the highest level since 1983, corresponding to an annual incidence of 336 cases per 1 OOO popu- lation. This increase is probably due to a discontinu- ation of antimalaria activities in most provinces and general shortage of resources. In the Philippines, only 3 of the 75 provinces are nonmalarious, but some municipalities within the endemic areas are considered freed from malaria when no indigenous cases were recorded during 3 consecutive years. In 1988, the malaria programme has been integrated into the general health services and received increased financial and logistical sup- port from the government. The number of cases reported were 155 OOO in 1988, 116 OOO in 1989 and 86 OOO in 1990. In Malaysia, malaria cases decreased from 65 OOO in 1989 to 51 OOO in 1990. In the peninsula, some 90% of the population live in areas freed from malaria and the disease is only endemic in the hilly and less developed areas of the centre, the north and north- eastern part of the peninsula. As an average, some 50% of the total cases occur among the security forces, the indigenous Orang Asli, and workers in the land development schemes. In 1990, 14 OOO cases were notified. In Sarawak, transmission is limited to the border areas; in 1990, the number of cases reported was 1 200. In Sabah, 35 OOO cases were reported in 1990, compared with 48 OOO in 1989. Europe, including Turkey and the former USSR Malaria continues to be endemic (P. vivax only) in the south-east and a few other foci in Turkey and in some small foci in Azerbaijan and Tajikistan. In Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 265 - Turkey, the number of malaria cases reported de- clined continuously from 67 OOO in 1983 to 8 700 in 1990. The great majority of the cases are from Adana and south-east Anatolia. Few small foci con- tinue to exist in other provinces. Some 8 OOO import- ed cases of malaria were notified in Europe but it is thought that the actual number of imported cases is considerably higher due to underreporting. SUMMARY Malaria risk of varying degree exists in 99 countries or areas. However, falciparum malaria does not exist or its relative prevalence is less than 1% in 13 of these countries. Accurate information on the global incidence of malaria is difficult to obtain because reporting is particularly incomplete in areas known to be highly endemic. The global incidence of mal- aria is estimated to be nearly 120 million clinical cases each year, with nearly 300 million people carrying the parasite. 90% of the total number of cases reported annually to WHO are from 19 countries only. This does not include the WHO African Region where reporting of cases remains fragmentary and irregular despite im- provements in recent years. Some 75% of cases are concentrated in 9 countries (in decreasing order): India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Viet Nam, Cambodia and China. Further- more, within these countries malaria is concentrated in certain areas. Of a total world population of about 5.3 billion people, 3.1 billion (59%) live in areas free of malaria (it never existed, disappeared or was eliminated by antimalaria campaigns and the malaria-free status has been maintained). 1.7 billion people (32%) live in areas where endemic malaria was considerably re- duced or even eliminated but transmission was re- instated and the situation is unstable or deteriorat- ing. These latter areas include zones with the most severe malaria problems which developed following major ecological or social changes, such as agri- cultural or other economic exploitation of jungle areas, sociopolitical unrest, etc.; these zones com- prise only about 1% of the world population. Areas where endemic malaria remains basically unchang- ed, and no national anti malaria programme was ever implemented, are inhabited by 500 million people (9%), mainly in tropical Africa. Severe malaria and mortality are caused by Plas- modium falciparum which is the predominant species of malaria in tropical Africa. In the rest of the world it is far less common. WHO receives very limited and irregular reports on malaria deaths. The vast majority of malaria deaths occur in Africa; estimates vary greatly: a figure of 800 OOO deaths per year in African children has been quoted in 1991 by the WHO African Region. There are indications that mortality in children has fallen in some areas be- cause of the widespread use of antimalarials, of social development and of better education. Countries in tropical Africa are estimated to have more than 80% of all clinical cases and more than 90% of all parasite carriers. The shortage of per- sonnel trained for the planning, monitoring and evaluation of programmes remains one of the major constraints. The Interregional Meeting on Malaria Control in Africa held in Brazzaville in October 1991 adopted a policy aimed at: (i) the prevention and reduction of malaria mortality by providing prompt diagnosis and adequate treatment of malaria cases through the basic health services; this implies also the creation of efficient referral systems for the management of severe and complicated cases as well as for treatment failures; and (ii) the detection and prevention of epidemics and the selective ap- plication of vector control measures applicable to the local epidemiological situation and where the results can be sustained. There are only a few countries from which the resistance of P. falciparum to chloroquine has not been reported, and the rapid evolution of this resist- ance in Africa threatens to hamper the provision of adequate treatment in rural areas. Resistance to sulfadoxine/pyrimethamine has developed in South- East Asia, South America and focally in Africa. In Thailand, there are indications that up to 50% of cases in certain areas no longer respond to meflo- quine therapy, while the sensitivity to quinine is also diminishing in areas of Thailand and Viet Nam. RESUME Situation du paludisme dans le monde, 1990 II existe un risque variable de paludisme dans 99 pays ou territoires. Toutefois, le paludisme a falcipa- rum n'est present, ou du mains sa prevalence rela- tive est inferieure a 1%, que dans 13 d'entre eux. II est difficile de connaitre avec exactitude !'incidence mondiale du paludisme car, dans les regions de tres forte endemicite, la declaration est particulierement incomplete. L'incidence mondiale estimative du pa- ludisme est de pres de 120 millions de cas cliniques Wld hlth statist. quart., 45 (1992) par an et le nombre de porteurs du parasite de presque 300 millions. Dix-neuf pays declarent annuellement a l'OMS 90% a eux seuls du nombre total des cas. II n'est pas tenu compte, dans cette statistique, de la Region africaine de l'OMS ou la declaration des cas reste fragmen- taire et irreguliere malgre des ameliorations ces dernieres annees. Environ 75% des cas sont concen- - 266 - tres dans 9 pays qui sont, par ordre decroissant, l'lnde, le Bresil, !'Afghanistan, le Sri Lanka, la Tha"i- lande, l'lndonesie, le Viet Nam, le Cambodge et la Chine. En outre, les cas se regroupent dans certaines regions de ces pays. Sur une population mondiale totale d'environ 5,3 milliards de personnes, 3, 1 milliards (59%) vivent dans des zones indemnes de paludisme (soit qu'il n'ait jamais sevi, soit qu'il ait disparu ou en ait ete durablement elimine a la suite de campagnes de lutte); 1,7 milliard (32%) vivent dans des regions ou le paludisme endemique a ete considerablement re- duit, voire elimine, mais ou la transmission a repris et la situation est instable ou en voie de degradation. Dans ces regions se trouvent les zones qui connais- sent les problemes de paludisme les plus graves apparus a la suite de grands changements ecologi- ques ou sociaux, qu'il s'agisse de !'exploitation agri- cole ou autre d'etendues de foret vierge a des fins economiques, de troubles socio-politiques, etc.; ces zones representent environ 1% de la population mondiale. Les regions ou le paludisme demeure a l'etat endemique sans changement fondamental, et ou aucun programme de lutte antipaludique n'a jamais ete mis en ceuvre, comptent 500 millions d'habitants (9%) et se situent principalement en Afrique tropicale. Les cas graves ou mortels de paludisme sont dus a Plasmodium falciparum, espece qui predomine en Afrique tropicale. Dans le reste du monde, cette espece est beaucoup mains repandue. L'OMS n'est que tres incompletement et irregulierement informee des deces imputables au paludisme. C'est en Afrique que la mortalite palustre est de loin la plus impor- tante; les estimations sont tres variables: pour la Region africaine de l'OMS, on fait etat en 1991 de 800 OOO deces d'enfants par an. D'apres certaines indications, la mortalite chez l'enfant a regresse dans quelques zones grace a la tres large utilisation des antipaludiques, a !'amelioration de !'education et au developpement social. Selan les estimations, c'est en Afrique tropicale que se trouvent plus de 80% des cas cliniques et plus de 90% des porteurs du parasite. La penurie de person- nel forme a la planification, au controle et a !'evalua- tion des programmes demeure l'une des principales contraintes. La politique adoptee lors de la Reunion interregionale sur la lutte contre le paludisme en Afrique, qui s'est tenue a Brazzaville en octobre 1991, vise i) a prevenir et a reduire la mortalite paludeenne grace a un diagnostic rapide et a un traitement approprie des cas dans le cadre des services de sante de base, ce qui implique la mise en place d'un systeme d'orientation-recours efficace pour la prise en charge des cas graves ou compli- ques ainsi que des echecs therapeutiques; et ii) a reperer et a prevenir les epidemies et a mettre en reuvre de fa~on selective des mesures de lutte anti- vectorielle adaptees a la situation epidemiologique locale dans la mesure ou des resultats durables peuvent etre escomptes. II n'y a que quelques pays ou l'on n'ait pas fait etat d'une resistance de P. falciparum a la chloroquine. Au vu de !'evolution rapide de cette resistance en Afrique, on risque de ne plus pouvoir etre a meme d'assurer un traitement approprie en milieu rural. La resistance a !'association sulfadoxine/pyrimethamine a fait son apparition en Asie du Sud-Est, en Ameri- que du Sud et, par places, en Afrique. En Tha"ilande, les cas rebelles au traitement par la mefloquine pourraient atteindre 50% et la sensibilite a la quinine diminue egalement dans certains secteurs des re- gions de Tha"ilande et du Viet Nam. Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 267 - HUMAN LEISHMANIASES: EPIDEMIOLOGY AND PUBLIC HEAL TH ASPECTS P. Desjeu~ The leishmaniases are a group of globally wide- spread parasitic diseases of multifaceted clinical manifestations (cutaneous, mucocutaneous, diffuse cutaneous and visceral). They are caused by several species belonging to the genus Leishmania - a flagellate protozoa transmitted exclusively by the bite of the female of the phlebotomine sandfly. The sandfly becomes infected when taking blood from reservoir hosts, which include man or domestic and wild animals. Most leishmaniases are zoonotic and humans are infected only accidentally when exposed to the natural transmission cycle. However, in the anthroponotic forms man is believed to be the unique reservoir host. Parasite The old concept of three or four species of Leish- mania, each causing a separate clinical disease, has been disproved - at least 20 species of Leishmania are pathogenic for humans. There is no absolute correlation between Leishmania taxa and the clinical disease produced. This diversity has vast impli- cations for the control and treatment of the disease and requires the identification of the parasite in each focus. A list of these species, their geographical distribution, epidemiology and disease mani- festations are given in Boxes 1-5. The only identified vectors are sandflies of the genus Lutzomyia in the New World and Phlebotomus in the • Medical Officer, Trypanosomiases and Leishmaniases Control, Division of Control of Tropical Disease, World Health Organization, Geneva. Old World. Sandflies are 2-3 mm varicoloured in- sects, differentiated by pointed velvet wings, arched back and big dark eyes. They are abundant all year round in tropical areas and during the summer in temperate zones. More than 500 species and sub- species are known throughout the world but less than 35 have been proved to be vectors of human leishmaniasis. The haematophagous sandfly females feed all through the night but especially at dusk. However, they can also bite during the day when disturbed in their resting places. The insect absorbs the Leishmania parasite with the blood from an infected host. The parasite life cycle in the sandfly is 4-7 days, after which the parasite can be inoculated in another animal or human when the fly takes a new bloodmeal. The sandfly breeding sites remain largely unknown, although some have been identi- fied, such as rodent burrows, tree trunks and organic debris. Reservoirs Most of the leishmaniases are zoonoses of wild or domestic animals. Visceral leishmaniasis involves canines (dogs, jackals and foxes) whereas cutaneous leishmaniasis depends on rodents, sloths, mar- supials, hyraxes, primates and other mammals. A Leishmania species in a given area is usually main- tained by a single reservoir host, even if other mammals may sometimes be infected. Identification of the reservoir is a prerequisite for the selection and application of selective control methods; in case of anthroponoses, man is believed to be the unique reservoir. Box 1. Visceral leishmaniasis - Old World Leishmania species Clinical features L. infantum VL CL• L. donovani VL/PKDL a Rare manifestation. Epidemiology Vectors Zoonotic P. ariasi (ZVL) P. perfiliewi P. perniciosus P. major P. langeroni P. chinensis P. /ongiductus P. smirnovi Anthroponotic P. martini (AVL) ? P. orientalis P. argentipes P. alexandri Reservoirs Dog/fox Dog/fox Dog Dog/fox/jacka I Dog Dog/racoon dog Dog/fox/jackal Badger Man Rodent? Carnivorous? Man Man? Geographical distribution Southern Europe, North Africa Eastern Mediterranean, South-Western Asia Egypt China Azerbaijan, Georgia, Kazakhstan, Tajikistan, Turkmenistan, Ukraine (Crimea), Uzbekistan Pakistan Kazakhstan (Kzyl-Orda) East Africa Indian Subcontinent China AVL = anthroponotic visceral leishmaniasis; CL = cutaneous leishmaniasis; PKDL = post kala azar dermal leishmaniasis; VL = visceral leishmaniasis; ZVL = zoonotic visceral leishmaniasis. Wld hlth statist. quart .. 45 (1992) Leishmania species L. major l. tropica l. aethiopica a Rare manifestation. - 268 - Box 2. Cutaneous leishmaniasis - Old World Clinical features CL Epidemiology Zoonotic (ZCL) Vectors P. duboscqi P. papatasi P. salehi CL (Recidivans) Anthroponotic P. sergenti VLa (ACL) CL, DCL Zoonotic (ZCL) P. longipes P. pedifer Reservoirs Rodent: Arvicanthis spp. Meriones spp. Psammomys spp. Rhombomys opimus Tatera spp. Dog (victims?) Rattus rattus (victims?) Hyrax: Dendrohyrax spp. Heterohyrax spp. Procavia spp. Geographical distribution Arabian Peninsula Africa Kazakhstan, Tajikistan, Turkmenistan, Uzbekistan India, Pakistan South-Western Asia Eastern Mediterranean Greece India, Pakistan North Africa South-Western Asia East Africa ACL = anthroponotic cutaneous leishmaniasis; CL ZCL = zoonotic cutaneous leishmaniasis. cutaneous leishmaniasis; OCL diffuse cutaneous leishmaniasis; VL visceral leishmaniasis; Box 3. Cutaneous leishmaniasis - New World Leishmania species Clinical features Epidemiology Vectors Reservoirs Geographical distribution l. peruviana CL Zoonotic Lu. ayacuchensis Dog? Peru, "uta" (ZCL) Lu. peruensis Rodent? Ecuador? Lu. verrucarum l. amazonensis CL/DCL Zoonotic Lu. flaviscutellata Rodent Central and South VLa (ZCL) Marsupial America l. mexicana CL Zoonotic Lu. olmeca olmeca Rodent Central and South (ZCL) America • Rare manifestation. CL = cutaneous leishmaniasis; DCL = diffuse cutaneous leishmaniasis; VL = visceral feishmaniasis; ZCL = zoonotic cutaneous leishmaniasis. Leishmania species l. infantum/ chagasi l. guyanensis L. panamensis l. braziliensis a Rare manifestation. Box 4. Visceral and cutaneous leishmaniasis - New World Clinical features Epidemiology VL Zoonotic CL" (ZVL) CL Zoonotic (ZCL) CL/MCL Zoonotic (ZCL) CL/MCL Zoonotic (ZCL) Vectors Visceral leishmaniasis Lu. longipalpis Lu. evansi Cutaneous leishmaniasis Lu. umbratilis Lu. whitmani Lu. anduzei Lu. trapidoi Lu. ylephiletor Lu. panamensis Lu. gomezi sylvatic: Lu. wellcomei Lu. carrerai Lu. yucumensis Lu. 1/anosmartinsi Lu. spinicrassa semi-urban: Lu. intermedia Reservoirs Dog/fox (Lycalopex vetulus} (Cerdocyon thous} Marsupial Sloth Anteater Marsupial Sloth Procyonid Monkey Unknown? Dog/horse Geographical distribution Central and South America South America Central America· north of South America Central and South America South America CL= cutaneous leishmaniasis; MCL = mucocutaneous leishmaniasis; VL = visceral leishmaniasis; ZVL = zoonotic visceral leishmaniasis. Rapp. trimest. statist. sanit. mond., 45 (19921 M A P 1 . D IS TR IB U TI O N O F O LD W O R LD A N D N E W W O R LD V IS C ER AL L E IS H M A N IA S IS , 19 90 C AR TE 1 . R E P A R TI TI O N D E S LE IS H M AN IO SE S V IS C ER AL ES D E L ' A N C IE N E T D U N O U V E A U M O N D E , 1 99 0 W l-0 89 98 3 Th e de si gn at io ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l o n t hi s m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f t he s e cr e ta ria t o f t he W H O c o n ce rn in g th e le ga l s ta tu s o f a n y co u n tr y, te rr ito ry , c ity o r a re a o r o f i ts a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f its f ro nt ie rs o r bo un da rie s - Le s de si gn at io ns u til is ee s s u r ce tte c a rt e et l a p re se nt at io n de s do nn ee s qu i y fig ur en t n 'im pl iq ue nt , de l a p ar t de ! 'O rg an is at io n m o n di al e de la S an t0 , a u cu n e p ris e de p os iti on q ua nt a u s ta tu t jur idi qu e de t el o u t el p ay s, te rr ito ire , v ii l e o u z o n e , o u d e se s a u to rit E! s, n i q ua nt a u t ra ce d e se s fro nt i0 re s. M A P 2 . D IS TR IB U TI O N O F O LD W O R LD A N D N E W W O R LD C U TA N E O U S L E IS H M A N IA S IS , 1 99 0 C AR TE 2 . R E P A R TI TI O N D E S LE IS H M AN IO SE S C U TA N EE S D E L 'A N C IE N E T D U N O U V E A U M O N D E , 1 99 0 '' ff? [:.;:.-·. ;-j N ew W o rld - N ou ve au M on de a ~~~ ~J L. M aj o r Sp or ad ic c a se s - Ca s s po ra di qu es • ~ L . Tr op ic a o. L . A et hi op ic a ~ O ve rla p - C he va uc he m en t o c :i D \ W H 09 23 02 Th e d es ig na tio ns e m pl oy ed a n d th e pr es en ta tio n o f m a te ria l in t hi s m a p do n o t im pl y th e e xp re ss io n o f a n y o pi ni on w ha ts oe ve r o n t he p ar t o f t he s e cr e ta ria t o f t he W H O c o n ce rn in g th e le ga l s ta tu s o f a n y co u n tr y, te rr ito ry . ci ty o r ar ea o r o f its a u th or iti es , o r co n ce rn in g th e de lim ita tio n o f i ts f ro nt ie rs o r bo un da rie s - Le s d8 si gn at io n s u til is e e s su r ce tte c a rte e t la pr es en ta tio n de s do nn ee s qu i y f ig ur en t n 'im pl iq ue nt , de la p ar t de ! 'O rg an is at io n m o n di al e de la S an ta , a u cu n e p ris e de p os iti on q ua nt a u st at ut jur idi qu e de te l o u t el p ay s, te rr ito ire , v ill e o u z o n e , o u d e se s a u to rit es . n i q ua nt a u tr ac e de s es fr on tie re s. - 271 - Box 5. New species of leishmania pathogenic for humans Species L. naiffi L. shawi L. lainsoni Situation analysis Severity of the problem Reservoirs Armadillo (Dasypus novemcictus) Monkey Sloth Procyonid Rodent Morbidity/mortality. Leishmaniases are important diseases in terms of morbidity and some are severe in terms of mortality; in man the disease occurs in at least four major forms: visceral, cutaneous, muco- cutaneous and diffuse cutaneous. • Visceral leishmaniasis (VL) or "kala azar", char- acterized by irregular fever, malaise, loss of weight, splenomegaly, sometimes hepatomegaly and/or lymphadenopathies and anaemia; the mortality rate is usually 100% if untreated. After recovery, patients may develop a chronic form called "post kala azar dermal leishmaniasis" (PKDL), relevant to transmission, since the nodu- lar lesions contain abundant parasites; they usu- ally require a long and expensive treatment. • Mucocutaneous leishmaniasis (MCL) or "espun- dia", which produces an extensive destruction of oral, nasal and pharyngeal cavities with highly disfiguring lesions, mutilation of the face and suffering. • Cutaneous leishmaniasis (CL), usually a self- healing ulcer but lifelong aesthetic stigma can result from multiple lesions (sometimes more than 100) with disabling and disfiguring scars. Its most severe form, recidivans leishmaniasis, can be particularly destructive and disfiguring if un- treated. • Diffuse cutaneous leishmaniasis (DCL) occurs in individuals with defective cell-mediated immune response. Its severity is due to disseminated lesions that resemble those of lepromatous lep- rosy, which never heal spontaneously and tend to relapse after treatment. Because of the devastat- ing consequences to the patient, it is recognized as a special public health problem. Leishmaniases are a complex of clinical entities caused by several Leishmania species with various epidemiological patterns in a heterogeneous dis- tribution. The greater the variety of physical and geographical conditions, the greater the diversity of clinical and epidemiological patterns. Geographical distribution. Currently the leishma- niases, prevalent in four continents, are considered b Badaro, R. The identification of risk factors associated with the transmission of New World visceral leishmaniases. In: Research on control strategies for the leishmaniases. Proceedings of an inter- national workshop, Ottawa, Canada, 1-4 June 1987. Ottawa, IDRC, 1988. (Manuscript report 184e). 'Walton, B. Leishmaniases: a global problem. In: Research on control strategies for the leishmaniases. Proceedings of an inter- national workshop, Ottawa, Canada, 1-4 June 1987. Ottawa, IDRC, 1988. (Manuscript report 184e). Wld hlth statist. quart., 45 (1992) Vectors Lu. ayrozai Lu. paraensis Lu. whitmani Lu. ubiquitalis Human cases Brazil (Amazonas State) Brazil (Acre and Para State) Brazil (Para State) to be endemic in 82 countries (21 in the New World and 61 in the Old World) (see Maps 1 & 2). More than 90% of the visceral leishmaniasis cases in the world are reported from Bangladesh, Brazil, India and Sudan; and more than 90% of cutaneous leish- maniasis cases emanate from Afghanistan, Brazil, Iran, Saudi Arabia and the Syrian Arab Republic. The large number of endemic countries illustrates the global importance of the problem, but the problem is far greater in a few countries as indicated by prevalence data. Incidence/prevalence. A common estimate of the worldwide annual incidence is 600 OOO newly re- ported clinical cases, an overall prevalence of 12 million cases and an estimated population at risk of about 350 million (1). However, it is difficult to provide realistic estimates of those infected vs. those at risk. There is probably an even greater difference between the number of cases actually occurring and the number usually reported due to several fac tars (2). • The distribution of transmission sites within en- demic areas is often discontinuous, with sep- arate, widely scattered foci. • Numerous cases are undiagnosed, misdiagnosed or unreported, especially when patients have no access to medical facilities, when diagnostic capabilities are scarce or absent, when drugs are not permanently available or when only passive case detection is used. A study in Guatemala showed that active medical surveillance increased the number of cases reported 40-fold compared with the numbers reported in the same area by passive case detection (3). • The number of people infected but asymptomatic is much higher than the number infected and presenting with clinical illness - clinical cases are usually only the proverbial tip of the iceberg; in an area of Brazil where 7.5% of children were reported to become infected with VL each year, only 1 among 6.5 manifested the disease in the area of highest prevalence.b These data correlate with those obtained in Kenya (1 out of 5), Ethiopia (1 out of 7) and India (1 out of 10). Asymptomatic leishmania-infected persons de- velop the clinical illness more readily in certain circumstances such as co-infections with HIV or other immunosuppressive conditions. • Leishmaniasis is not a notifiable disease in 52 out of the 82 endemic countries. Although health authorities are aware of the gravity of leishmania- sis some may be reluctant to make the disease notifiable since official recognition is ac- companied by the implicit need to solve or at least alleviate the problem.c - 272 - In spite of the scarcity of reliable data it is clear that the number of cases occurring around the world is considerably greater than that officially reported, and the number of infections greater still (2). Making leishmaniasis a notifiable disease may not initially change the situation of underreporting and poor quality of the data. However, the progressive im- provement of both quantity and quality of the in- formation available will prove the relative import- ance of the disease and give support to health authorities seeking more external financial support, aiming at implementing control activities.d Increased severity Public health impact. Except for some countries such as Saudi Arabia, where cutaneous leishmaniasis is so common that it is called in Arabic "little sister", or Peru, where the prevalence of the cutaneous leishmaniasis called "uta" is so high that parents expect it to occur in their children as a childhood disease, the public health impact of the leishmani- ases has been largely underestimated, mainly be- cause of lack of awareness of its serious impact on health. During the last two decades it has become apparent that all forms of leishmaniasis are much more prevalent than had been previously suspected, both in terms of increasing incidence and geographi- cal spread. This increasing public health importance of the leishmaniases is illustrated by the following official data: e.g. Tunisia (1 300 cases in 1983, 6 OOO in 1990), and northern states of Brazil (2 OOO cases in 1980, 9 OOO in 1989).e In 1991 in eastern India (Bihar State) the situation became epidemic, 38 among 42 districts were facing the worst kala azar epidemic since the late 1970s, between 250 OOO and 300 OOO people were believed to have the disease (5 times the official data), and because of the rapid manner in which the disease is spreading, an alarming situation exists. Recent reports from the western Upper Nile (southern Sudan) speak of 40 OOO deaths due to kala azar over the past 5 years in a population of less than 1 million (4); initially the outbreak was confined to a relatively small area but is now spreading to adjoining areas. Development as a factor of increasing severity. The increased importance of the leishmaniases is due to several factors, many related to development. • New settlements in endemic areas, and coloniza- tion schemes as illustrated in Andean countries, where, to solve the problems of overpopulation and lack of land to be cultivated, people migrate from the high plateau to the low tropical plains where transmission risk is very high. • Large-scale migration of populations for occu- pational reasons, e.g. people crossing the border between Bangladesh and India, or Nepal and India, and temporary workers in countries of the Arabian peninsula. Civil strife and military oper- ations are other reasons for population moves. d Guerra, H. Role of national data centres and obligatory reporting in control programmes. In: Research on control strategies for the leishmaniases. Proceedings of an international workshop, Ottawa, Canada, 1-4 June 1987. Ottawa, IDRC, 1988. (Manuscript report 184e). • Desjeux, P. Information on the epidemiology and control of the leishmaniases by country or territory. Geneva, WHO, 1991. (Docu- ment WHO/LEISH/91.30). • Development of Qew agroindustrial projects, bringing nonimmui1e people to endemic areas (road building, oil prospecting, mining, farming, forestry development as well as tourism and military activity, guerilla warfare). Pressure on populations throughout the world pushes people into new areas where the infection is endemic, exposing many more to the natural vectors and an increased risk of infection. • Fast-growing (e.g. Kuwait City) and/or unplanned urbanization (e.g. Manaus), encompassing neigh- bouring rural areas where the zoonotic cycle occurs, and deterioration in social and economic conditions in the poor suburbs of cities, where low-income populations concentrate due to the massive rural-urban migration (e.g. Kabul). • Man-made environmental changes (building of dams, irrigation systems, wells), as in the Amazo- nian Basin, Saudi Arabia or Tunisia. Other factors • Reduction in, or termination of, campaigns of insecticide spraying for malaria control. After years of successful control, several countries now face a serious resurgence (Bangladesh, Colombia, India, Iran, Peru, Mediterranean countries, etc.). • AIDS and other immunosuppressive conditions increase the risk for leishmania-infected people to develop VL clinical illness. This has resulted in an increase in the number of VL cases in southern Europe. Another consequence is a change in the age distribution - VL was classically a childhood disease but now more than 50% of the cases are in adults. The risk of leishmania and HIV co- infection is progressively increasing in certain areas of the world where both diseases exist: in urban foci of VL such as Marseille (France), and Rio de Janeiro and Santarem (Brazil). It has also been observed in rural areas where VL has been endemic and where AIDS is now spreading (India, southern Ethiopia, north-eastern Brazil). An international registry is to be created in WHO to assess the incidence and the prevalence of HIV/leishmaniasis co-infection in areas around the world where the problem is expected to increase. • The growing importance of the leishmaniases can also be the result of a greater awareness among the population and improved case detec- tion and notification systems, especially when it is made a notifiable disease. Economic impact. When endemic diseases such as leishmaniases debilitate the population and eventu- ally erode the labour force they constitute barriers to progress. Economically, the leishmaniases are far more important than the number of cases would suggest. They are a serious threat to the health of approximately 350 million people and the costs in- volved (treatment, depletion of labour force) have caused great losses to agricultural or industrial rural development programmes. Outbreaks of leishmania- sis have caused delays in the implementation of projects, e.g. in Saudi Arabia and the Amazonian Basin in Brazil, or even brought them to a complete standstill as in Morocco, Saudi Arabia and in the tropical areas of Andean countries. In the latter, the failure of migration programmes is believed to be Rapp. trimest. statist. sanit. mond., 45 (1992) - 273 - due in part to the various diseases people had to cope with (leishmaniasis, malaria, yellow fever) in new settlement areas. The leishmaniases affect mainly people from developing countries (72 out of 82), of which 13 are among the least economically developed. Within countries, the affected classes of population are those of lowest socioeconomic status, who have minimal political influence and very limited capacity to assume the costs of the disease (diagnosis, hospitalization, treatment, etc.). Specific first-line treatment is expensive - between US$ 60 and US$ 120 for a WHO-recommended course of pentavalent antimonials to which the cost of delivery, often in remote areas, must be added; cases that do not respond to antimony may be treated with second-line drugs of much higher cost, such as amphotericin B or pentamidine. In some countries, the budget to treat the existing cases surpasses the total public health budget. For every member of a family afflicted by kala azar, the cost of treatment and the loss of wages is enormous, be- cause of a significant loss in productive working days. Frequently the patient has to face logistical difficulties: long distance to the treatment centre, poor communications, unacceptably costly or time- consuming hospitalization. This often leads to inter- rupted treatment and facilitates the appearance of resistance, which then implies the use of second-line drugs. If not treated, severe leishmaniases become chronic and debilitating, incapacitating the patients and creating a vicious circle: poverty - malnutrition - disease. It has been shown in Brazil that children suffering from malnutrition are 9 times more likely to develop classical visceral leishmaniasis.b A complete evaluation of the financial cost of leish- maniasis for patients should take into account the 'World Health Organization. Guidelines for leishmaniasis control at regional and subregional levels. Geneva, WHO, 1988. (Document WHO/LEISH/88.25). following elements: consultations, biological tests, treatment, hospitalization, suspension of working days and unavailability of service. Very few such studies are available, and they are usually incom- plete. Control Leishmaniases can be controlled by specific inter- ventions directed against the vulnerable pathways in the transmission cycles. The control measures are however dependent on the specific epidemiological characteristics of each focus ( 1, t). In all foci of leishmaniasis, passive case detection followed by treatment and case reporting should constitute the basis of a control programme and the first step towards a national strategy for control. Active medi- cal surveillance involves regular systematic screen- ing of clinically suspected cases through serological testing and parasitological diagnosis. Additional con- trol strategies (vector or reservoir host-control) de- pend on up-to-date information on the local epi- demiology: identity of vector species and animal reservoir hosts, type of disease (cutaneous or visceral, anthroponotic or zoonotic) and the antici- pated severity of the problem. Details on leishmani- ases in all endemic areas presented country by country are available in the WHO document Informa- tion on the epidemiology and control of the leishma- niases by country or territory (WHO/LEISH/91.30), recently issued in English and in French. The docu- ment includes data on parasites, proved or sus- pected vectors and reservoirs, geographical distri- bution and main foci, severity, prevalence and inci- dence, public health implications, sociocultural and economic factors in 82 countries or territories. It also reviews the main past or ongoing control activities.e The document is available free of charge from CTD/ TRY, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland. SUMMARY The leishmaniases are parasitic diseases caused by different species of Leishmania, protozoa transmitted by sandflies, haematophagous biting insects. The reservoir hosts are man (anthroponotic cycle) and domestic or wild animals (zoonotic cycle). In man the disease takes four main clinical forms: visceral, cutaneous, mucocutaneous and diffuse cutaneous. Morbidity and mortality due to leishmaniasis are on the increase. Leishmaniasis, which is now found on four continents, is endemic in 82 countries (21 in the New World and 61 in the Old). The large number of endemic countries shows the global scale of the problem, though it is particularly severe in certain countries (90% of cases of visceral leishmaniasis come from 4 countries). Annual incidence is estimated at some 600 OOO new clinical cases, officially reported, with a global preva- lence of 12 million cases and a population at risk of approximately 350 million. It is very difficult to pro- vide realistic estimates given the frequency of sub- clinical forms of visceral leishmaniasis, the large number of undiagnosed or unreported cases, the frequent absence of active screening and the fact that the leishmaniases are notifiable diseases only in a few countries (30 out of 82); nevertheless, it seems clear that official reporting of cases considerably underestimates the problem. Wld hlth statist. quart., 45 (1992) Over the last two decades, it has become clear that leishmaniasis is a growing public health problem in terms of geographical extent and incidence with the occasional severe epidemic, such as that which occurred in Sudan. This could be due to a number of factors, such as the development of agroindustrial projects and the settling of large, nonimmune popu- lations in endemic zones, large-scale migration be- tween countries, rapid and unplanned urban expan- sion, environmental changes caused by dams and irrigation, and the reduction in or termination of insecticide spraying for malaria control. In economic terms, leishmaniasis is more significant than the number of cases might suggest. Seventy of the 82 endemic countries are developing countries and 13 of them are among the least developed. The leishmaniases retard development and burden coun- tries by weakening the labour force, calling for ex- pensive treatment which often exceeds the total primary health care budget (US$ 60-120 per patient) and slowing down rural development. Individual cases of visceral or severe cutaneous leishmaniasis are heavy financial burdens because of hospitalization, treatment and loss of resources for the family, with fewer working days and reduc- tion or loss of salary. - 274 - The leishmaniases can be controlled by tackling various elements of the transmission cycle; control methods and strategies must be addressed to the epidemiological characteristics of the foci, which include the identity of the vector or vectors, animal reservoirs, the variety of the disease (cutaneous or visceral, anthroponotic or zoonotic) and the severity of the problem. In all foci; passive case detection, followed by treat- ment and notification, should be the basis of the control programme; active medical surveillance should be based on screening of clinically suspected cases through serological testing and parasitological diagnosis. More specific methods such as vector or reservoir host control should be selected on the basis of up-to-date information on the local epi- demiology. Details on leishmaniasis for the 82 countries or territories affected are available in the WHO docu- ment Information on the epidemiology and control of the leishmaniases by country or territory (WHO/ LEISH/91.30) (English and French), which also re- views the main past or ongoing control activities. The document is available, free of charge, from CTD/TRY, World Health Organization, avenue Appia, 1211 Geneva 27, Switzerland. RESUME Les leishmanioses humaines: epidemiologie et aspects de sante publique Les leishmanioses sont des maladies parasitaires causees par differentes especes de leishmania, pro- tozoaires transmis par la piqure d'insectes hemato- phages, les phlebotomes. Les hates reservoirs sont soit l'homme (cycle anthroponotique), soit des ani- maux domestiques au sauvages (cycle zoonotique). La maladie se presente chez l'homme sous quatre formes cliniques principales: viscerale, cutanee, cuta- neomuqueuse et cutaneodiffuse. Les leishmanioses revetent de plus en plus d'importance du point de vue de la morbidite et de la mortalite. Actuellement les leishmanioses, prevalentes dans quatre conti- nents, sont endemiques dans 82 pays (21 du Nou- veau monde, 61 de l'Ancien monde). Le grand nom- bre de pays endemiques illustre bien !'importance globale du probleme, qui est toutefois beaucoup plus severe dans certains pays (90% des cas de leishmaniose viscerale proviennent de quatre pays). On estime !'incidence annuelle a environ 600 OOO nouveaux cas cliniques, officiellement signales, avec une prevalence globale de 12 millions de cas et une population a risque de 350 millions de personnes environ. II est toutefois tres difficile de fournir des estimations realistes quand on sait la frequence des formes infra-cliniques de la leishmaniose viscerale, le grand nombre de cas non diagnostiques au non signales, !'absence frequente de depistage actif et enfin le faible nombre de pays ou les leishmanioses sont de declaration obligatoire (30 sur 82). Toutefois, ii apparait clairement que le nombre de cas officiel- lement signales represente une large sous- estimation du probleme. Au cours des deux dernieres decennies, ii est deve- nu de plus en plus apparent que les leishmanioses representaient, en termes de sante publique, un probleme croissant: extension geographique, aug- mentation de !'incidence avec parfois !'apparition d'epidemies tres severes, telles que celle du Soudan, et que cela pourrait etre rattache a divers facteurs tels que: le developpement de projets agro- industriels et !'implantation massive de populations non immunes en zones d'endemie, les migrations de populations a grande echelle entre les pays, !'urbani- sation rapide et non planifiee, les modifications de l'environnement (barrage, irrigation), et enfin la re- duction au l'arret des pulverisations d'insecticides dans le cadre de la lutte contre le paludisme. Economiquement, les leishmanioses sont plus im- portantes que ce que suggere le nombre de cas; 70 parmi les 82 pays endemiques sont des pays en developpement et 13 d'entre eux sont parmi les mains avances. Les leishmanioses representent un frein au develop- pement, une charge pour les pays en termes d'affai- blissement de la population active, du cout eleve du traitement qui depasse souvent, a lui seul, le budget global des soins de sante primaires (US$ 60-120 par malade) et du retard dans les programmes de deve- loppement rural. lndividuellement, les leishmanioses, viscerale ou cu- tanee severe, se traduisent par une charge financiere due a !'hospitalisation, au traitement et a la diminu- tion des ressources familiales (reduction des jour- nees de travail, diminution ou perte de salaire). Les leishmanioses peuvent etre contr61ees en s'atta- quant aux differents elements du cycle de transmis- sion; les methodes et strategies de lutte doivent etre definies en fonction des caracteristiques epidemiolo- giques des foyers, y compris l'identite du ou des vecteurs, du au des reservoirs animaux, le type de la maladie (cutanee ou viscerale, anthroponotique au zoonotique) et enfin la severite du probleme. Dans tous les foyers, la detection passive des cas, suivie de leur traitement et de la notification, doit constituer la base de tout programme de lutte; la surveillance medicale active se basera sur la suspi- cion clinique, la serologie et le diagnostic parasitolo- gique. Les methodes de lutte plus specifiques telles que la lutte contre le vecteur au le/les reservoirs animaux seront decidees sur la base d'une analyse recente de la situation epidemiologique dans chaque pays. Un document intitule Information on the epidemio- logy and control of the leishmaniases by country or territory vient de paraitre, en anglais et en franc;:ais, sous la cote WHO/LEISH/91.30. II presente, pays par pays, une mise a jour des donnees epidemiologi- ques pour les 82 pays ou territoires concernes par les leishmanioses; ii fait egalement le point des principales activites de lutte passees ou en cours. Ce document peut etre obtenu gratuitement en s'adres- sant a: CTD/TRY, Organisation mondiale de la Sante, avenue Appia, 1211 Geneve 27, Suisse. Rapp. trimest. statist. sanit. mond., 45 (1992) - 275 - REFERENCES - REFERENCES 1. WHO Technical Report Series, No. 793, 1990 (Con- trol of the leishmaniases: report of a WHO Expert Committee). OMS Serie de Rapports techniques, N° 793, 1990 (Lutte contre les leishmanioses: rapport d'un Comite OMS d'experts). 2. ASHFORD, R. W. ET AL. Estimation of population at risk of infection, and number of cases of leishma- niasis. Parasitology today, 8 (3): 104-105 (1992). Wld hlth statist. quart., 45 (1992) 3. COPELAND, H. W. ET AL. Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala. American journal of tropical medi- cine and hygiene, 43: 257-259 (1990). 4. The "killing disease" soars in South Sudan. TOR news, 37: November (1991). - 276 - CHAGAS DISEASE: EPIDEMIOLOGY AND PROSPECTS FOR INTERRUPTION OF TRANSMISSION IN THE AMERICAS A. Moncayoa Frequency and geographical distribution Chagas disease, named after the Brazilian physician Carlos Chagas who first described it in 1909, exists only on the American Continent. It is caused by a flagellate protozoan parasite, Trypanosoma cruzi, transmitted to humans by a blood-sucking triato- mine bug known popularly in the different countries as "kissing bug", "vinchuca", "barbeiro", "chipo", etc. • Chief, Trypanosomiases and Leishmaniases Control, Division of Control of Tropical Diseases, World Health Organization, Geneva. Transmission through vectors Chagas disease is a zoonosis transmitted in natural foci or ecological units within a well-defined geo- graphical environment. The ecological unit is consti - tuted by an ecotope composed of sylvatic or peri- domestic mammals and of sylvatic triatomine bugs both infected with T. cruzi. Continuous transmission is assured with or without the involvement of human beings. These conditions of transmission are present from latitude 42° N to latitude 40° S. The geographical distribution of the human T. cruzi infec- tion extends from the south of the United States of America to the south of Argentina (see Map 1). Only MAP 1. GEOGRAPHICAL DISTRIBUTION OF HUMAN T. CRUZ/ INFECTION IN THE AMERICAS CARTE 1. DISTRIBUTION GEOGRAPHIOUE DES CAS D'INFESTATION HUMAINE PART. CRUZ/ DANS 1,.ES AMERIQUES United States of America Etats-Unis d'Amerique Nicaragua .· .... · ... C9sta Rica / · Panama Colombia Colombie The designations employed and the presentati on of material on this map do not imply the expression of any opi nion whatsoever on the part at the secretariat of the WHO concerning the legal status of any country, territo ry, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries - Les designations utilis6es sur cette carte et la presentation des donnees qui y f igurent n'impliquent, de ta part de !'Organisation mondiale de la Santa, aucune prise de position quant au statut juridique de tel ou tel pays, territoire, ville ou zone, ou de ses autorites, ni quant au trace de ses frontieres. Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 277 three indigenous cases of Chagas disease have been reported in the United States. There are two stages of the human disease: the acute stage which appears shortly after the infection and the chronic stage which may last several years; the latter irreversibly affects internal organs namely the heart, oesophagus and colon, and the peripheral nervous system. After several years of a silent, asymptomatic period, 27% of those infected develop cardiac symptoms which may lead to sudden death, 6% develop diges- tive damage (mainly megaviscera), and 3% will pre- sent peripheral nervous involvement. The remaining 64% will not present any clinical symptoms. Data on the prevalence and distribution of Chagas disease have improved in quality and quantity dur- ing the 1980s as a result of the cross-sectional studies sponsored by the WHO Special programme for Research and Training in Tropical Diseases (TOR) in countries where accurate information was not available. A group of experts met in Brasilia in 1979 and devised standard protocols to carry out coun- trywide prevalence studies on human T. cruzi infec- tion and triatomine house infestation. These studies were carried out during the 1980s with the collaboration of the ministries of health of Chile, Colombia, Ecuador, Honduras, Mexico, Paraguay and Uruguay. The accurate information obtained has made possible better planning and evaluation of the national control programmes by individual countries. On the basis of these countrywide surveys it is now TABLE 1. PREVALENCE OF HUMAN T. CRUZI INFECTIONS IN LATIN AMERICA, 1980-1985 TABLEAU 1. PREVALENCE DES INFESTATIONS HUMAINES A T. CRUZI EN AMERIQUE LATINE, 1980-1985 Population at % of total risk population Country group - Groupe de pays Group I - Groupe I Argentina - Argentine ....... . Brazil - Brasil. ..................... . Chile - Chili ........................ . Ecuador - Equateur ........... . Honduras ............................. .. Paraguay ............................. .. Peru - Perou ..................... . Uruguay .............................. . Venezuela .......................... .. Group II - Groupe II Bolivia - Bolivie ............... .. Colombia - Colombie ........ . Costa Rica ........................... . Mexico - Mexique .............. . Group Ill - Groupe Ill (OOO) Population ~ risque (en milliers) 6900 41 054 1800 3823 1 824 1 475 6766 975 11 392 1 800 3 OOO 1 112 El Salvador............................ 2 146 Guatemala........................... 4 022 Nicaragua .......................... .. Panama................................. 898 %de la population totale 33 32 15 41 42 45 34 33 68 30 10 45 43 52 42 Prevalence of infected persons (000) Prevalence de !'infes- tation (en milliers) 2 640 6340 1 460 30 300 397 643 37 1 200 500 900 130 322 730 220 estimated that the overall prevalence of human T. Total... ...................................... 88 987 25 15 849 cruzi infection on the continent reaches 16 million cases. Some 90 million people, i.e. 25% of all the Source: Reference (1)- Reference (1). population of Latin America, are at risk of contract- ing Trypanosoma cruzi infection. Endemic countries The endemic countries can be divided into four groups according to several indicators such as: number of confirmed human cases, prevalence of seropositive tests in blood donors and population samples, and the presence of infected vectors and reservoirs (Table 1). The main factors on which these criteria are based are the following: magnitude of transmission, quantity and quality of the available epidemiological information, and existence or ab- sence of coordinated actions towards the control of this disease.b Group I. The countries of this group present high prevalence of human T. cruzi infection and high triatomine house infestation rates which have in- duced the national health authorities to establish control activities through vertical programmes or, more recently, within the context of primary health care (PHC) strategies. Argentina, Brazil, Chile, Ecuador, Honduras, Paraguay, Peru, Uruguay and Venezuela are included in this group. Group II. All the countries included in this group show evidence of intradomiciliary transmission, with a clear association between T. cruzi infection and electrocardiographic alterations as well as other O Beltran-Hernandez, F. Geographical distribution and prevalence of Chagas disease. Expert Committee on Chagas disease, Buenos Aires, 1989. (Document CHAIWP/89.7). Wld hlth statist. quart., 45 ( 1992) pathologies attributable to Chagas disease. No formal control programmes have yet been es- tablished in these countries. Bolivia, Colombia, Costa Rica and Mexico belong to this group. Group Ill. Countries in which there is evidence of domiciliary transmission but more accurate epi- demiological data are needed to support the evi- dence of a clear correlation between T. cruzi infec- tions and clinical pictures. In all these countries, the acute phase of Chagas disease is frequently ob- served, and recent serological data indicate that the prevalence of seropositive reactions to T. cruzi anti- gens is relatively high. El Salvador, Guatemala, Nicaragua and Panama are included in this group. Group IV. In some of the countries and territories in this group the only epidemiological evidence is the presence of infected triatomine bugs. Trinidad and Tobago and Belize have reported some human infec- tions in the past, and more recently Guyana. Chagas disease is enzootic in Antigua, Aruba, Bahamas, Belize, Cuba, Curac;:ao, Dominican Re- public, Grenada, Guadeloupe, French Guiana, Guyana, Haiti, Jamaica, Martinique, Saint Vincent, Suriname, Trinidad, Virgin Islands and the United States of America. Transmission via blood transfusion The rural/urban migration movements that occurred in Latin America in the 1970s and 1980s changed the - 278 - traditional epidemiological pattern of Chagas disease as a rural condition and transformed it into an urban infection that could be transmitted by blood trans- fusion. The figures in Table 2 show the extent of the problem in some selected cities of the continent between 1966 and 1986. While it varies between 3.0% and 63.0%, the prevalence of T. cruzi-infected blood is higher than that of hepatitis or HIV infec- tion. In Buenos Aires (Argentina), for instance, it is es- timated that more than 500 OOO transfusions are made annually. The prevalence of T. cruzi-infected blood has been estimated at 6.0%, as indicated in Table 2. This means that if blood were not screened for transfusion in this city, some 30 OOO donors could transmit the disease on the basis of 1 transfu- sion for each receptor. The transfusion of Chagas disease via blood trans- fusion is a real threat even for countries in which the disease is not transmitted by vectors such as the United States and Canada where two cases of acute Chagas disease have been recently documented (3, 4). In addition, migration of persons infected by T. cruzi to nonendemic countries poses a public health problem for the safety of blood transfusion (5). The screening test commonly used is indirect hae- magglutination (IHA) which has high specificity to avoid false negatives. Another agglutination test using latex reagents was developed recently, well defined molecular reagents are still needed in view of the very high degree of sensitivity and specificity required in blood-bank control. Some countries in Latin America have compulsory screening of samples in blood banks. Such is the case in Argentina, Bolivia, Brazil, Honduras, Uruguay and Venezuela. TABLE 2. PREVALENCE OFT. CRUZI-INFECTED BLOOD BANKS IN SELECTED COUNTRIES TABLEAU 2. PREVALENCE DES BANQUES DE SANG INFESTEES PART. CRUZIDANS UN CERTAIN NOMBRE DE PAYS Country group - Groupe de pays Group I - Groupe I Argentina - Argentine: Buenos Aires (1970) ................ .. Santiago del Estero (1966) ...... .. Cordoba (1982) .......................... . Brazil - Bresil: Brasilia (1984) ............................ . Rio (1979) .................................. .. Sao Paulo (1982) ...................... . Chile - Chili: Santiago (1983) ........................ .. Vicuna (1983) .......................... .. Ecuador - Equateur: Guayaquil (1961) ...................... . Honduras: Tegucigalpa ............................. . Paraguay: Asuncion (1972) ........................ .. Peru - Perou: Tacna (1972) .............................. . Uruguay: Endemic areas (1972) - Zones d'endemie (1972) .................. .. Venezuela: Valencia (1973) ......................... . Caracas (1973) .......................... .. Group II - Groupe II Bolivia - Bolivie: Santacruz (1983) ...................... . Colombia - Colombie ................ .. Costa Rica: San Jose .................................... . Mexico - Mexique: Queretaro (1984) ....................... . Source: Reference (2) - Reference (2). Number of % positive samples tested Nombre Pourcentage de d'E:chantillons seropositivit8 contrales 97 308 6.0 1 700 20.5 2 441 8.4 2 413 14.6 3 501 3.9 56 902 2.9 214 3.7 62 14.5 1 054 3.2 50 28.0 562 11.3 329 12.9 329 5.5 733 10.3 98 620 5.1 268 63.0 221 7.6 200 16.5 SUMMARY American trypanosomiasis, or Chagas disease, is a parasitic disease caused by the haemoflagellate pro- tozoa, Trypanosoma cruzi. The human infection occurs only in the Americas, where it is widely distributed in the periurban and rural areas of tropical and subtropical countries, from Mexico to Argentina and Chile. It is transmitted to man and other mammals mainly through insects, the triato- mine bugs. As an enzootic disease, it extends from approximately latitude 42.5°N (northern California and Maryland) to latitude 43.5°S (southern Argentina and Chile). The results of several serological surveys indicate an overall prevalence of 16-18 million infected indi- viduals. Up to 30% of those infected will develop the cardiac and/or hollow viscera irreversible lesions that characterize chronic Chagas disease. The endemic countries can be divided into four groups according to several indicators such as the number of confirmed human cases, the prevalence of seropositive tests in blood donors and population samples, the presence of infected vectors and re- servoirs, and the existence or absence of coordi- nated actions towards the control of this disease. The domestic cycle of transmission, involving man and domestic animals such as dogs, cats, and do- mestic triatomine bugs, is the one that maintains the infections in the rural and periurban areas. Some triatomine species are well adapted to human dwel- lings where human and animal reservoirs are in intimate contact. The poor socioeconomic condition of the population and the domestic nature of the vector play crucial roles in maintaining the infection at an endemic level. Rapp. trimest. statist. sanit. mond., 45 (1992) - 279 - Most cases of human infection occur in the rural areas, where they are acquired through contact with the faeces of infected triatomine bugs. But blood transfusion is increasingly considered the second most important mechanism of transmission of Chagas disease. The transmission of Chagas disease via blood trans- fusion is a threat even for countries where it is not transmitted by vectors, as is the case of the United States of America and Canada where two cases of acute Chagas disease transmitted by blood trans- fusion have been reported. In addition, migration of persons infected by T. cruzi to nonendemic countries poses a public health problem for the safety of blood transfusion. RESUME La maladie de Chagas: epidemiologie et perspective d'une interruption de la transmission aux Ameriques La trypanosomiase americaine, ou maladie de Cha- gas, est une parasitose due a un hemoflagelle, Trypanosoma cruzi. L'infestation de l'homme n'a lieu qu'aux Ameriques, ou elle est tres repandue dans les zones periurbaines et rurales des pays tropicaux et subtropicaux, du Mexique a !'Argentine et au Chili. La transmission a l'homme et aux mammiferes s'effectue principalement par l'intermediaire d'insec- tes, des punaises du genre triatome. L'enzootie s'e- tend approximativement en latitude de 42,5° N (nord de la Californie et du Maryland) a 43,5° S (sud de !'Argentine et du Chili). Plusieurs enquetes serologiques montrent que la prevalence globale de !'infestation est de 16 a 18 millions. Dans une proportion pouvant atteindre 30%, les sujets infestes voient leur etat evoluer vers la maladie de Chagas chronique caracterisee par des lesions au niveau du creur et des visceres creux. On peut diviser les pays d'endemie en quatre grou- pes en fonction de plusieurs indicateurs tels que le nombre de cas humains confirmes, la prevalence de la seropositivite chez les donneurs de sang et parmi la population, la presence de vecteurs et de reser- voirs de !'infestation, et !'existence ou !'absence d'une action coordonnee en vue de la lutte centre la maladie. C'est par un cycle domestique de transmission, im- pliquant l'homme, des animaux domestiques tels que chiens et chats ainsi que des triatomes adaptes aux conditions domiciliaires que !'infestation se per- petue dans les zones rurales et periurbaines. Certai- nes especes de triatome sont bien adaptees a !'habi- tat humain, la au l'homme et les animaux reservoirs sont en contact etroit. Les mauvaises conditions socio-economiques dans lesquelles vit la population et le caractere domestique du vecteur jouent un role capital dans la perpetuation de l'endemie. La plupart des infestations humaines se produisent dans des zones rurales au elles sont contractees par contact avec les dejections contaminees de triatomes infestes. Toutefois, on estime que le developpement de la transfusion sanguine vient au deuxieme rang pour la transmission de la maladie. La transmission transfusionelle de la maladie de Chagas constitue une menace, meme pour des pays au ii n'y a pas de transmission vectorielle, comme c'est le cas aux Etats-Unis d'Amerique et au Canada au l'on a signale deux cas de maladie de Chagas en phase aigue, consecutifs a une transfusion. En outre, la migration de personnes infectees par T. cruzi vers des pays exempts d'endemie pose un probleme de sante publique liee a la securite des dons de sang. REFERENCES- REFERENCES 1. UNDP/WORLD BANK/WHO. Special Programme for Research and Training in Tropical Diseases. Eighth Programme Report. WHO, Geneva, 1987. 2. SCHMUNIS, G. A. Chagas disease and blood trans- fusion. In: Infection, immunity and blood transfu- sion. Alan R. Liss Inc. 1985. 3. GRANT, I. H. ET AL. Transfusion-associated acute Chagas disease acquired in the United States. Annals of internal medicine, 111 (10): 849 (1989). Wld hlth statist. quart., 45 (1992) 4. NICKERSON, P. ET AL. Transfusion-associated Trypa- nosoma cruzi infection in a nonendemic area. Annals of internal medicine, 111 (10): 851 (1989). 5. KIRCHOFF, L. ET AL. American trypanosomiasis (Chagas disease) in Central American immigrants. The American journal of medicine, 82: 915 (1987). - 280 - PROGRESS TOWARDS THE GLOBAL ERADICATION OF POLIOMYELITIS Harry F. Hull• & Nicholas A. Ward• In May 1988, the World Health Assembly committed WHO to the global eradication of poliomyelitis by the year 2000. The Pan American Health Organiza- tion (PAHO) had previously committed the American Region of WHO in 1985 to the same goal by the year 1990. In 1988, the Western Pacific Region also adopt- ed the eradication of poliomyelitis as a regional goal for 1995. Substantial progress has been made to- wards these goals. This article will outline the cur- rent status of poliomyelitis in the world. Strategies for poliomyelitis eradication Safe and effective vaccines against poliomyelitis first became available in 1955 when inactivated polio vaccine (IPV) was created by a team led by Dr. Jonas Salk. The introduction of this vaccine was ac- companied by dramatic declines in the number of reported polio cases in industrialized countries. A second, more potent generation of inactivated polio vaccines became available in the late 1970s. Oral, live polio virus vaccines (OPV) were developed in several laboratories, but current vaccines use the attenuated strains of Dr. Albert Sabin. Mass cam- paigns conducted with OPV in the 1960s virtually eliminated polio from the developed nations. Because of the effectiveness of OPV in stopping the spread of wild polio viruses, OPV is the only vaccine recommended by WHO. Initially, the Expanded Pro- gramme on Immunization (EPI) recommended that all children be given 3 doses of OPV in the first year of life, but in 1984, an optional fourth dose was recommended to be given at birth in polio-endemic countries. Many countries have incorporated this fourth dose into their routine schedule. Although the primary strategy of EPI - to raise immunization coverage to the highest level possible - is effective in reducing the number of polio cases, polio eradication cannot be achieved through routine immunization alone. Polio eradication was achieved in many industrialized countries through the use of mass campaigns with OPV. Additional strategies rec- ommended by WHO for polio eradication are: 1. Improving the surveillance systems to the point where each country can detect all cases of paraly- sis which might be polio. 2. Building a global network of laboratories with the technical competence to reliably identify polio virus from specimens collected from these cases. 3. Conducting supplemental immunization activities including: national vaccination days, outbreak re- • Medical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. O Rotary International provided financial aid and volunteer vaccina- tors that were critical to the success of the programme. Other significant donors include the United States Agency for Inter- national Development, UNICEF and other intergovernmental and governmental agencies. sponse immunization, targeted mass vaccination campaigns in high risk areas (mopping up). As high levels of immunization coverage are being achieved globally, an increasing number of coun- tries are adopting these strategies. Progress towards polio eradication Since the EPI was established in 1974, immunization levels for all EPI vaccines, including OPV, have risen dramatically. In 1990, coverage data indicated that coverage with 3 doses of OPV for children at 1 year of age had risen to 85% globally (Fig. 1). This achievement was not equal in all areas of the world. Coverage levels were highest in the Western Pacific Region and the South-East Asia Region of WHO at 95% and 91% respectively. This was achieved largely on the basis of 98% coverage in China and 93% coverage in India. Coverage was lowest in the African Region at 56%. Of the 46 countries reporting coverage data in the African Region in 1990, 22 (48%) failed to achieved 70% coverage and 14 (30%) failed to achieved 50% coverage. As a consequence of the high levels of immunization achieved, the reported global incidence of polio has decreased dramatically (Fig. 2). In 1990, 16 435 cases of polio were reported, a 39% decrease from 1989 when 26 916 cases were reported. This decrease occurred despite an improvement in both the com- pleteness and timeliness of reporting at the global level. For 1990, 171 (88%) of 184 countries/areas had reported polio case counts to WHO on 1 October of the following year compared to 166 (85%) for 1989. Improvements in both timeliness and completeness of reporting at the national level have occurred as more countries improve surveillance for polio as well as for other EPI target diseases. Despite these improvements, global polio surveillance remains in- adequate. WHO estimates that 148 OOO cases of polio occurred in 1990 - a net reporting efficiency of 11%. Polio cases are based on an estimated vaccine ef- ficacy of 80% and a paralysis rate of 5 per 1 OOO. Another consequence of both increased coverage and country and regional polio eradication initiatives is that polio cases, and presumably polio viruses, are being restricted to limited areas of the world. The number of countries reporting O polio cases has steadily increased (Fig. 3). 116 countries reported O polio cases in 1990, against 74 in 1985. There was a coincident decrease in the number of countries reporting more than 10 cases of polio (64 in 1985, 29 in 1990). As a result of the Pan American Health Organiza- tion's polio eradication initiative,b polio eradication is close in North, South and Central America, and the Caribbean Basin. Following the inauguration of PAHO's initiative in 1985, the number of confirmed polio cases increased in 1986 to 920 (Fig. 4). This resulted largely from improved surveillance. In 1990, Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 281 - a total of 18 virologically confirmed polio cases were reported, despite a doubling in the number of sus- pected cases investigated. In 1990, confirmed polio cases were reported only from Mexico, Guatemala, Colombia, Ecuador and Peru. Of note is the absence of confirmed cases from Brazil, which had accounted for 67% of the regional total in 1986. As of 1 January 1992, only 9 cases of virologically confirmed polio- myelitis had been reported in the Region in 1991. These were reported from 2 countries, Colombia and Peru. The last confirmed isolation of wild polio virus in the Region was from Peru in September 1991. Countries in the Region are continuing intensive surveillance for polio cases, case investigation and outbreak response vaccination, on the assumption that undetected chains of transmission may still exist or that virus may be reintroducted from other polio-endemic regions of the world. 100 80 " Cl E 1l 60 :i 0 0. I " Cl "' c: 40 " u a; 0. 20 0 0 50 0 e .. "' u " .,, 40 !:! Jl E 0 2 I 30 0 0 e .. " .. "' u 20 10 FIG.1 GLOBAL IMMUNIZATION COVERAGE OF OPV3 IN THE FIRST YEAR OF LIFE, 1985-1990 EVOLUTION DE LA COUVERTURE VACCINALE MONDIALE PAR LE VPB3 I/ AU COURS DE LA PREMIERE ANNEE D'EXISTENCE, 1985-1990 / / / / / 1985 1986 1987 1988 1989 1990 Year-Annee FIG.2 REPORTED INCIDENCE OF ACUTE POLIOMYELITIS, 1978-1990 EVOLUTION DE L'INCIDENCE DECLAREE DE LA POLIOMYELITE AIGUE, 1978-1990 7 1978 79 80 81 82 83 84 85 86 87 88 89 1990 Year-Annee Wld hlth statist. quan., 45 (1992) - 282 - A world map of reported polio cases in 1990 is presented in Map 1. The combination of India and China accounted for 84% of the polio cases reported globally in 1990. From 1987 to 1989, India accounted for more than 60% of the polio cases reported in the world. As a result of increased coverage with 3 doses of OPV, India experienced a 68% decline in reported cases from 1988 (23 095 cases) to 1990 (7 340 cases). Some states in India are undertaking polio eradication activities including particularly mopping-up and statewide vaccination days. Despite reported immunization coverage of 98% with 3 doses of OPV, China has experienced outbreaks of "' ~ Cl. " "O " .0 E 0 z I "' " ·~ c J 8 0 .; .D E J z 120 100 80 60 40 20 0 1985 FIG. 3 NUMBER OF COUNTRIES REPORTING ZERO POLIO CASES, 1985-1990 NOMBRE DE PAYS AVANT NOTIFIE ZERO CAS DE POLIO, 1985-1990 1986 1987 1988 1989 Year- Annee Polio cases reported - Cas de polio notifies D O EZJ 1-10 D >10 ~ No report - Pas de notification FIG.4 REPORTED AND CONFIRMED POLIO CASES, AMERICAS, 1985-1990 1990 NOMBRE DE CAS DE POLIOMYELITE DECLARES OU CONFIRMES AUX AMERIQUES, 1985-1990 2 800 2 400 "' "' u " "O 2 OOO ~ .D E 0 1 600 z I "' " "' 1 200 "' u 0 .; 800 .D E J z 400 0 1985 1986 1987 1988 Years - Annees - Confirmed ConfirmE!s 1989 1990 ~ Reported DE!clarE!s Source: Pan American Hea lth Organization - Organisation panamE!ricaine de la Sante. 1991 Rapp. trimest. s tatist. sanit. mond., 45 (1992) - 283 - MAP 1. REPORTED INCIDENCE OF POLIOMYELITIS, 1990 CARTE 1. INCIDENCE DECLAREE DE LA POLIOMYELITE, 1990 Incidence 1990 Number of cases Nombre de cas D o D 1-10 ~ 11 -100 • > 100 mHH Not avai lable mm:J Non disponible Data available as of 8 January 1991 - Donnees au 8 janvier 1991 . The designations employed and the presentation of materia l on this map do not imply the expression of any opinion whatsoever on the part of the secretariat of the WHO concerning the lega l status of any country, territory, city or area or of its authorit ies, or concerning the del imitation of its fron- tiers or boundaries - Les designations utilisees sur cette carte et la presentation des donnees qui y fig urent n'impliquent, de la part de !'Organisation mondiale de la Sant0, aucune prise de position quant au statut juridique de tel ou tel pays, territoi re, ville o u zone, ou de ses autoritEls, ni quant au trace de ses frontieres. polio in both 1989 (4 623) and 1990 (5 065 cases), up from 667 in 1988. The majority of cases were reported from the rural areas to the densely-populated coastal regions. Cases were largely unvaccinated and clustered among children born outside the family planning programme and in children displaced from their home villages for economic reasons. Some, but certainly not all, of the increased number of cases can be attributed to improved surveillance. China has targeted polio eradication for 1995 under the Western Pacific Region's eradication initiative. The Philippines began a national polio eradication initiative in 1991 . Prior to the initiative, polio cases fell 75% from 1988 (344 cases) to 1990 (85 cases) . The impact of the decline in polio cases is apparent from the closure of the polio ward at the infectious diseases hospital in Manila for want of cases need- ing treatment. Polio eradication plans are being de- veloped for the other 4 polio-endemic countries in the Western Pacific Region (Cambodia, Lao P.D.R., Papua New Guinea and Viet Nam). Increased sur- veillance for polio is being initiated for the countries in the Region thought to be free of wild polio viruses. Egypt, with 565 polio cases reported in 1990, has targeted poliomyelitis for eradication by 1994. Era- dication activities were undertaken nationwide in 1991. The reported number of polio cases for Egypt in 1991 will exceed the 1990 report, largely as a result of improved case finding. With the exception of Yemen, Egypt's neighbouring countries on the Arabian peninsula are either polio-free or reporting a small number of cases. In Europe, most countries report either O or a small number of poliomyelitis cases due to wild polio virus. The exception in 1990 was the former USSR, which reported a total of 337 cases in 1990, up from 91 in 1989. This increase is due to outbreaks of polio Wld hlth statist. quart., 45 ( 1992) in the republics along the country's southern border. Because of the political and social upheaval taking place in the republics, there is concern that ad- ditional epidemics of polio and other EPI target diseases may occur. Although most of the countries of North Africa and Southern Africa are reporting either O or few cases of polio, polio remains endemic through most of the continent. Surveillance remains poor with case counts received from only 29 of the 46 countries in the African Region of WHO for 1990 (63%). Globally, 73% of the countries not submitting polio case counts for 1990 are in Africa. Political turmoil and war in Africa, as well as in other areas of the world (Afghanistan, Cambodia, Iraq and other countries), represent a major impediment to polio eradication as well as to the control of other EPI target diseases. Conclusion PAHO's polio eradication initiative has demonstrated the feasibility of eradicating polio and defining the strategies to be used. Polio eradication can be achieved globally by the combination of improved surveillance for poliomyelitis (including laboratory confirmation of cases) and effective immunization of the high-risk populations with potent, oral polio vaccine. Although improved immunization coverage with 3 doses of OPV given by routine administration can reduce the number of polio cases, polio eradica- tion will require supplemental immunization ac- tivities. These activities include national vaccination days, outbreak response vaccination and mopping- up. There has been a dramatic decrease in the number of reported polio cases and the eradication of wild polio viruses is imminent in the Region of the Americas. WHO estimates that in 1990, app- roximately 150 OOO cases of paralytic poliomyelitis occurred in the world. - 284 - SUMMARY Poliomyelitis has been virtually eliminated from the industrialized countries by mass campaigns conduc- ted with oral polio vaccine (OPV). In 1988, the World Health Assembly set the goal of global eradication of poliomyelitis by the year 2000. The current WHO strategy for eradication uses three primary activities beyond routine immunization with OPV. They are: (i) improved disease surveillance, (ii) building a global network of laboratories, and (iii) supplemental immunization strategies which include mass im- munization campaigns with OPV at the national level, and targeted campaigns at the local level. Eradication of polio from the Region of the Americas is close and may have already been achieved. In other regions, the number of reported polio cases has declined, largely as a result of high immuniza- tion coverage. As more countries implement polio eradication strategies, the number of polio cases will continue to fall until eradication is achieved. RESUME Vers l'eradication mondiale de la poliomyelite Les campagnes de masse a l'aide du vaccin antipo- liomyelitique buccal (VPB) ont permis la quasi- elimination de la poliomyelite des pays industriali- ses. En 1988, l'Assemblee mondiale de la Santa s'est fixe pour objectif d'eradiquer d'ici l'an 2000 la po- liomyelite a !'echelon mondial. La strategie actuelle- ment menee par l'OMS en vue de cette eradication repose, au-dela de la vaccination systematique par le vaccin buccal, sur trois actions fondamentales. II s'agit i) d'une surveillance meilleure de la maladie, ii) de la mise en place d'un reseau mondial de laboratoires, et iii) de strategies de vaccination corn- plementaires avec des campagnes de vaccination de masse a !'echelon national, ou visant localement des groupes determines. L'eradication de la poliomyelite de la Region des Ameriques est proche et peut-etre deja realisee. Dans les autre regions, le nombre de cas declares de poliomyelite est en recul, en grande partie grace a une forte couverture vaccinale. A mesure que les pays seront plus nombreux a mettre en place des strategies d'eradication de la poliomye- lite, le nombre de cas continuera a reculer jusqu'a !'eradication totale. Repp. trimest. stetist. senit. mond., 45 (19921 - 285 - THE EPIDEMIOLOGY OF MEASLES C. John Clements," Marc Strassburg,b Felicity T. Cutts 0 & Carole Toreld Introduction Measles infection is caused by a virus which is extraordinarily uniform wherever it occurs around the globe (1). Unlike some highly successful viruses such as poliovirus and influenza, no major strain variations appear to occur, and the genotype is stable with little evidence of geographical variation in antigens. Nonetheless, the measles virus con- tinues to cause unparalleled morbidity and mortality in many parts of the world despite the availability of a vaccine for over 20 years. Global situation Before measles vaccine became available, virtually all children contracted measles, an estimated ' Medical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. b Assistant Chief, Data Collection and Analysis, Los Angeles County Department of Health Services, United States of America . ' Senior Lecturer, Communicable Disease Epidemiology Unit, School of Hygiene and Tropical Medicine, London, United Kingdom. d Technical Officer, Expanded Programme on Immunization, World Health Organization, Geneva. 130 million cases each year. The act1v1t1es of the Expanded Programme on IIT)munization (EPI) have resulted in a dramatic increase in coverage which has contributed significantly to reducing both measles morbidity and mortality. In 1990, ap- proximately 80% of the world's children aged < 1 were reported to have received measles vaccine (Fig. 1), and it was estimated that around 2 million deaths were prevented. Despite this important progress, in 1990 45 million cases and around 1 million deaths were estimated to occur in developing countries. Thus measles is still responsible for more deaths than any other EPI target diseases. The true number dying as a result of measles may be twice the estimated 1 million if the recently documented delayed effect of the disease is taken into account. Measles ranks as one of the leading causes of childhood mortality in the world. In one community study in Kenya in 1985 (2), measles accounted for 35% of reported deaths in infants 1-12 months of age and for 40% of deaths in children 1-4 years of age. The impact of measles on the lives of millions of young children every year, particularly in developing countries, indicates the urgent need for further reduction in measles incidence. FIG. 1 100 80 " g, g 60 ~ :, 0 0.. " Cl "' E ~ 40 " 0.. 20 GLOBAL COVERAGE WITH MEASLES VACCINE, 1983-1990 COUVERTURE MONDIALE PAR LE VACCIN ANTIROUGEOLEUX, 1983-1990 1983 1984 1985 1986 1987 1988 1989 Year - Annee Source: Data officia lly reported to WHO - Declarations officielles a l'OMS. Wld hlth statist. quart., 45 ( 1992) 1990 286 - Changing epidemiology The epidemiology of measles changes as coverage increases. Even with countries placing additional efforts behind measles control, outbreaks of measles are expected to continue to occur and do not necessarily indicate programme failure (3). After reaching high coverage levels, a period of low measles incidence usually follows which may last for a number of seasons. This low incidence or "honey- moon" period may be followed by a resurgence of outbreaks of considerable size. Pockets of sus- ceptibles are capable of sustaining outbreaks due to the highly infectious nature of measles (Fig. 2). Even so, high coverage is likely to lengthen the period between epidemics. With control pro- grammes and effective surveillance systems in place, the size of the expected outbreaks can be minimized, and it is important to note that measles incidence has been greatly reduced from that of the pre- immunization era. Reported measles cases have declined since the introduction of the first measles vaccines in the 1960s (Fig. 3). Some countries, including developed and developing, experienced more than 99% reduc- tion in incidence of reported cases. However, in recent years the number of reported cases in some of those countries has temporarily increased, although still far below prevaccine era levels. Out- breaks have occurred among school-age children, for a variety of reasons. In developing countries, measles remains endemic in most areas, with the largest proportion of cases reported to occur in children under 5 years, and over one-quarter of all cases being below 9 months of age (4). Transmis- sion in some urban settings is due to a combination of factors including crowding, low coverage, uneven vaccine coverage, and migration into the cities. Transmission also occurs in both urban and rural areas in age groups wh ich are below the recom- mended age of immunization. It was previously thought that the achievement of high coverage in older children would protect young infants by herd immunity, but this has been observed infrequently due to the highly infectious nature of the measles virus. When assessing changes in measles epidemiology, it is important to distinguish between proportions, relative frequencies and absolute incidence or inci- dence rates . Changes in proportions do not always represent the situation accurately. Following a period of successful immunization in a community, two events may commonly occur - an increase in the proportion of measles cases which occur among immunized children, and an increase in the propor- tion of children who acquire measles before the scheduled age of immunization. The age at which children contract measles depends upon a variety of local circumstances. Because ma- ternal antibodies decay at variable rates in different parts of the world, different proportions of infants are protected against measles in the first few months of life. As maternal antibodies wane, the attack rates for measles increase each month to a maximum between 1 and 2 years in developing countries. A hospital -based survey from Afghanistan reported a typical picture of the age distribution of cases, with 74% of all cases occurring between 4 months and 3 years (5). Compared with the age distribution of cases in the pre-immunization era, there is now a greater propor- tion of cases occurring before 9 months of age in some developing countries (2, 4). While this does FIG. 2 0 £ "' "' <..) 6 5 " 4 -0 " .c E 0 z I 3 g e "' " "' rl 0 :;; .0 E ::, z 2 REPORTED MEASLES CASES, HONG KONG, 1965-1989 CAS DE ROUGEOLE DECLARES, HONG KONG, 1965-1989 Coverage with measles vaccine 12-23 months - Couverture par le vaccin antirougeoleux. 12-23 mois 40%· > 60% · > <······--·· 75% -· ········> <··· 80-90% .•• 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 Year - Annee Source: Data officially reported to W HO - Declarations officielles a l'OMS. Rapp. trimest. statist. sanit. mond., 45 I 1992) - 287 - FIG. 3 NUMBER OF CASES OF MEASLES REPORTED GLOBALLY, 1974-1989 NOMBRE DE CAS DE ROUGEOLE DECLARES DANS LE MONDE, 1974-1989 7 " 6 c ~ 1 " 5 .. <.> " "Cl " .c E 4 0 z I " c -~ 3 1 " 3l .. <.> 0 2 .; £> E :, z 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 Year - Annee Source: Data officially repo rted to WHO - Declarat ions officiell es a l'OMS. not represent an absolute increase in numbers, these data have served as a critical impetus for researchers to find a measles vaccine which could successfully immunize infants earlier in life. Over the next decade, it is hoped that a vaccine will be developed wh ich can be administered early in life, thus protecting infants from early attacks of measles. Protection by immunization Since the introduction of the Schwarz vaccine in the 1960s, there have been a number of opportunities to study the field efficacy of this measles vaccine strain at 9 months of age. Vaccine efficacy is typically determined by comparing the rate of measles in immunized children with that of measles in un- immunized children. Under most field conditions, the vaccine efficacy is thought to be about 85% for children receiving the vaccine at 9 months of age or older. At present it is not clear what the value would be for those measles vaccines which might be used at younger ages. If measles could be effectively controlled in a country in a relatively short period of time, the issue of duration of immunity may not play a critical role . Previously it was thought that if children were pro- tected during the first few years of their life, the usual time of peak transm ission, the likelihood of further exposure would be low. It is generally assumed that an infection with the wild measles strain confers lifelong immunity. The measles vaccine virus is an attenuated strain of the live virus, therefore there is the theoretical possibility that the antigenic properties of the vaccine strain are not equal to that of the wild virus. Recent studies, however, now show that protection from the Wld h lth statist. quart., 45 ( 1992) standard measles vaccine administered at an age when maternal antibody has been lost lasts at least 21 years (6). Some countries are now experiencing a second peak of transmission in older children and young adults (3), due mostly to "vaccine failures" (chi ldren were immunized but failed to seroconvert) and "failure to immunize " (children were never im- munized). Young people exposed during this peak in their second decade of life will need protection using a vaccine with the ability to confer immunity lasting at least 20 years. When an immune individual is exposed to the wild vi rus, an amnestic response occurs, usually with a resulting boost to antibody levels. As outbreaks of measles become rare, exposure to the wild virus will diminish, and therefore th is boosting effect by the wild virus will diminish also. The net result will be that an individual's protection against measles will be solely dependent on the long-lasting antigenicity of the vaccine. Various levels of herd immunity have been sug- gested as being necessary to interrupt transmission of measles. Mathematical models of infectious diseases have shown that once a population reaches a certain level of immunity, the remaining un- immunized individuals will be protected by the immunity of the surrounding " herd". But due to the highly infectious nature of the measles virus, the required level is thought to be very high in urban areas. It has been demonstrated that even in communities with high coverage, outbreaks can occur. In 1988, Harare (Zimbabwe) experienced an outbreak when coverage was reported to be 83% (7) . Another study from Texas (United States of America) reported a school outbreak which occurred despite a reported 99% coverage rate. This same Texas population had - 288 - a 95% level of demonstrable serological antibodies to measles (8). There are other examples of out- breaks occurring among populations with reported high coverage, such as the outbreak which occurred in Hungary in 1988 at a time when reported cover- age was 98% (9). It is difficult to ascertain with a high degree of certainty what the precise level of herd immunity is, based on such reports, since a large number of factors may have contributed to these outbreaks. Reported coverage may not have reflected the true levels of immunity in the com- munity, and there was always the possibility of measles virus being introduced from nearby areas with lower immunity. It appears that the level of coverage needed to interrupt transmission will vary with the epi- demiological situation. A rural or island population may need much lower levels of coverage to achieve herd immunity, whereas it has been demonstrated that coverage of 83% and a vaccine efficacy of around 85% were not sufficient for a city like Harare. In crowded conditions, it is likely that even 95% vaccine coverage using a vaccine whose efficacy is less than 90% will not be sufficient to interrupt transmission completely. Vaccine efficacy of measles vaccines in current use at 9 months of age is of the order of 85-95%. Thus even a coverage level of 100% would only protect 85% of immunized infants in most situations in developing countries. Additional mechanisms are needed to boost vaccine efficacy if the 1995 targets are to be reached. High-risk areas and groups As measles vaccine coverage increases, it is ex- pected that the majority of future outbreaks will probably originate from pockets of low coverage. Such pockets are not randomly distributed, but are known to occur in certain settings. Densely popu- lated urban areas are particularly at risk, where the virus may be kept circulating by numerous pockets of susceptibles, despite a relatively high overall level of coverage. The urban poor, who usually have less access to immunization services, are usually the most at risk. In addition, there may be ethnic or cultural factors which these groups face which might hinder their accepting immunization (10). Additionally, high-risk groups may include specific age groups, e.g. school children (who represent cohorts from previous years when coverage was lower and who may not have been exposed to measles infection), ethnic minorities (who may have been underserved or may have rejected immuniza- tion for cultural reasons), hospitalized children (who are at high risk of nosocomial transmission), and children in refugee camps (where crowding fa- cilitates the spread of the virus) (11). Medical settings have been the foci of a number of measles outbreaks. It is paradoxical that the im- munization clinic, the very place parents bring their children to be protected against disease, becomes the place the child acquires a life-threatening illness. A study in the United States of America confirmed that in 1984 nearly 3% of measles cases acquired their infection in a medical setting (12). A study in Cote d'Ivoire revealed that two-thirds of measles cases treated in a health centre were nosocomial in origin (13). Prevention of measles must include rou- tine immunization of children brought to clinics for any reason, and improvements in waiting areas so that patients with measles can be isolated easily. Children admitted to hospital and siblings who visit them must be immunized at the earliest opportunity. In some settings, medical personnel have been the source of measles spread. Policies requiring im- munization or proof of immunization among health workers may need to be implemented in such set- tings. The highly communicable nature of measles The highly communicable nature of measles and the explosive nature of outbreaks has been well docu- mented. One study among an unimmunized popula- tion in India (14) reported that 80% of children had been infected with measles by the time they reached 10 years of age. Among highly susceptible populations in crowded settings, the opportunity for explosive point source outbreaks is great. In one study in the United States, one infected person was believed to have transmit- ted measles to dozens of others at a sports meet- ing (15), again emphasizing the highly infectious nature of measles. In households, secondary attack rates of 80% have frequently been reported. In contrast to densely po- pulated areas, nomads and other groups in sparsely populated areas experience only sporadic disease transmission (16). However, when such peoples come together for festivals or markets, explosive outbreaks may occur, hence such occasions and gatherings should be targeted for immunization ac- tivities. There appears to be an interrelationship between continuous urban transmission and rural outbreaks. Bartlet (17) and Black (18) suggest that in an iso- lated situation, a minimum population of 400 OOO to 500 OOO susceptible individuals is required to sustain measles transmission. If this is correct, rural trans- mission is likely to be maintained by a continuous process of recontamination by cases from nearby cities. This observation underlines the importance of improving coverage not only at the country level but even at the village and community levels as well. Improved surveillance and special studies are needed to obtain better documentation of the foci of measles transmission in countries with high cover- age. Measles is a serious disease Contrary to popular belief, measles is not a benign childhood illness, but affected children are at risk of various complications with varying degrees of seriousness. Even in countries with adequate health care and healthy child populations, the complication rate can reach 10% (19). The commonest com- plications in industrialized countries are ear infection (around 5%), pneumonia (around 2.5%), diarrhoea (around 2.5%) and encephalitis (around 0.1%). The picture is significantly different in develop- ing countries where measles affects children at a younger age and many children are already experiencing a background of viral, bacterial and parasitic infections, and may in addition be mal- nourished. One community study from India showed 82% of children with measles had complica- tions (14). A study of hospitalized children in Afghanistan (20) showed 84% of children with Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 289 - measles had pneumonia, 30% had diarrhoea and 22% laryngotracheobronchitis (some had multiple complications). In a hospital study from Mexico, half the cases with complications were aged < 1, and 70% of these were malnourished (21). Due to measles complications, a large number of children become handicapped due to deafness, im- paired vision or blindness. In areas where vitamin A deficiency is a problem, children with measles may be precipitated into acute vitamin A deficiency with resulting impairment or loss of vision from xero- phthalmia. A less common but devastating complication is subacute sclerosing panencephalitis (SSPE) which develops in between 1 and 5 per 100 OOO cases and occurs several years after the initial measles infection. Mortality Measles has been called the greatest killer of children in history. The degree to which the virus inflicts death on a population varies, as there is a wide range in the reported measles case-fatality rates (CFRs). There is intercountry, interregional and even interepidemic variation in CFRs. Crowded conditions have been found to be associ- ated with higher case-fatality rates (22). Typically, large urban agglomerations present ideal conditions for measles transmission, especially among dense populations of poor who are not only under- immunized, but also experience high rates of other infectious conditions as well as reduced access to medical care. In such conditions, the CFR can be as high as 20%. The CFRs in industrialized countries are currently estimated to be less than 0.1%. This is partly due to the difference in age-specific attack rates, underlying good nutrition, supportive treatment for bacterial chest infections, and other environmental and socio- logical factors. Quantifying CFRs is difficult and may be subject to bias, in that most information is usually obtained from sources which have an unrepresentative case load. For example, hospitals tend to admit and re- port the most serious cases. Such hospitalized cases are at increased risk of dying compared to non- hospitalized cases. Recognizing such difficulties, WHO/EPI reviewed community studies of CFRs, and now uses a value of 3% as an estimate of the CFRs within one month of onset of acute measles infec- tion among persons of all ages in the developing world. Such estimates must be viewed with caution in light of some community-based studies which suggest this may be a significant underesti- mate (23), and further work is needed to refine how CFRs are calculated. For instance an outbreak in Afghanistan resulted in a CFR of 28% for all ages and a CFR of 42% for children 0-4 years. The results from this study underline the added danger of acquiring measles at a young age (24). A number of studies suggest that measles is more severe in situations where intense exposure occurs, such as "secondary" transmission (transmission from an index case to other children in the same household), crowding and outbreaks. A study in Machakos District (Kenya) (25) showed that in families with several cases of measles, secondary cases had a higher risk of dying than those who Wld hlth statist. quart., 45 (19921 were infected from outside. Older children with their increased mobility appear to have an increased op- portunity for infection outside the home and tended to have lower case-fatality rates. Another study from the Gambia showed measles mortality was strongly associated with more than five measles cases in a household (26). Intense ex- posure to measles virus may be a risk factor for death following measles. In contrast, in an industrialized country, Sutter found no difference in severity between primary and sec- ondary cases in a very different sociological setting where the overall severity of measles was much less and mortality was minimal (27). Delayed mortality In addition to well-documented complications and mortality associated with the acute illness, the long- term impact of the infection is now being re- ported (28, 29). In several African studies it has now been documented that for many months after the acute attack, there is a reduced survival rate in the affected infants. Thus it appears that those infected with measles virus who survive the acute disease have a greatly increased risk of dying after the period of the acute illness when compared with those not infected with measles (Table 1). Death TABLE 1. MORTALITY DURING 9 MONTHS OF FOLLOW-UP FOR MEASLES PATIENTS AND COMMUNITY CONTROLS, THE GAMBIA TABLEAU 1. MORTALITE AU COURS DE 9 MOIS DE SUIVI CHEZ DES MALADES A TTEINTS DE ROUGEOLE ET LEURS TEMOINS DANS LA COMMUNAUTE, GAMBIE Mortality of measles cases Mortality Mortalite chez les malades of community control 0·9 months later Delayed Mortalite chez les Age at infection Acute 1 ·9 months later temoins pris dans Age au moment En phase Tardive la communaute de !'infection aigue apres 1 a 9 mois apres O a 9 mois 3-11 months - 3-11 mois 18% 56% 3% 1-2 years - 1-2 ans 9% 13% 2% Based on reference (29) - D'apres la reference (29). may result from a variety of apparently unrelated conditions in the months following measles infec- tion. One possible explanation of these observations may be that there is a reduced cell-mediated im- mune response as a result of measles infection. Some authors postulate the persistence of measles virus to account for increased delayed mortality. The younger the age of infection, the more dramatic appears the effect of this delayed mortality phe- nomenon, emphasizing the urgent need to protect children at the youngest possible age. Based on such studies, it is now thought that the true impact of measles virus infection is much greater than is actually recorded in the number of deaths generally attributed to measles, making the control of this disease an even greater priority. To date, studies describing delayed mortality have all been conducted in Africa. It is important to confirm these observations in Asia and the Americas. - 290 - Treatment Vitamin A administered to children acutely ill with measles has been shown to reduce mortality. Re- sults from a trial in South Africa showed children treated with vitamin A had a reduced risk of dying, recovered more quickly from pneumonia and diar- rhoea and had less croup (30). In addition, symp- tomatic treatment for cases requires antibiotics to combat bacterial complications, and oral rehydration salts for dehydration following diarrhoea. Case- fatality rates can be lowered if cases reach health care facilities where appropriate care is offered early. For uncomplicated cases, supportive fluids, anti- pyretics and nutritional therapy may be required. Many children need increased food intake for four to eight weeks to recover their pre-measles nutritional status. SUMMARY Measles is a highly infectious disease which has a major impact on child survival, particularly in de- veloping countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about its epidemiology and the best strategies for administering measles vaccines. However, it is clear that tremendous progress can be made in prevent- ing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well-tried methods of treating cases. Research in the coming decade may provide more effective vaccines for use in immunization programmes. An understanding of the basic epidemiology of measles is a prerequisite for effective control measures. RESUME Epidemiologie de la rougeole La rougeole est une maladie extremement conta- gieuse qui conditionne en grande partie la survie des enfants, en particulier dans les pays en develop- pement. II est important de comprendre l'epidemio- logie de cette maladie du fait qu'elle est capable de changer rapidement avec l'accroissement de la cou- verture vaccinale. II y a encore beaucoup de progres a faire dans la connaissance de cette epidemiologie et la recherche des meilleures strategies d'adminis- tration de vaccin antirougeoleux. Toutefois, ii est evident qu'on peut faire des progres considerables dans la prevention de la morbidite et de la mortalite rougeoleuses en s'appuyant sur les connaissances existantes, en utilisant les vaccins actuels et en appliquant des therapeutiques eprouvees. II est pos- sible que les recherches de la prochaine decennie debouchent sur des vaccins plus efficaces utilisables dans les programmes de vaccination. La connais- sance des donnees fondamentales de l'epidemiolo- gie de la rougeole doit servir de base a des mesures de lutte efficaces. REFERENCES- REFERENCES 1. BLACK, F. L. Measles active and passive immunity in a worldwide perspective. In: Melnick, J. L. (ed.), Progress in medical virology. Basel, Karger, 1989. 2. SPENCER, H. c. ET AL. Impact on mortality and fa- tality of a community-based malaria control pro- gramme in Saradidi, Kenya. Annals of tropical parasitology, 81 (Supplement 1): 36-45 (1987). 3. Cuns, F. T. ET AL Principles of measles control. Bulletin of the World Health Organization, 69 ( 1 ): 1-7 (1991). Cuns, F. T. ET AL Principes de la lutte contre la rougeole. Bulletin de /'Organisation mondiale de la Sante, 69 (2): 155-162 (1991). 4. !AYLOR, W. R. ET AL Measles control efforts in urban Africa complicated by high incidence of measles in the first year of life. American journal of epidemiology, 127: 788-794 ( 1988). 5. ARYA, L. S. ET AL. Spectrum of complications of measles in Afghanistan: a study of 784 cases. Journal of tropical medicine and hygiene, 90: 117-122 (1987). 6. MILLER, C. Live measles vaccine: a 21 year follow- up. British medical journal, 295: 22-24 (1987). 7. KAMBARAMI, R. A. ET AL Measles epidemic in spite of high measles immunization coverage rates in Harare, Zimbabwe. Bulletin of the World Health Organization, 69: 213-219 (1991). KAMBARAMI, R. A. ET AL. Epidemie de rougeole a Harare, Zimbabwe, malgre des taux eleves de vaccination [resume). Bulletin de /'Organisation mondiale de la Sante, 69 (2): 218 (1991 ). 8. GUSTAFSON, T. L. ET AL Measles outbreak in a fully immunized secondary school population. New England journal of medicine, 316: 717-774 (1987). Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 291 - 9. Measles outbreak. Weekly epidemiological rec- ord, 64 (18): 137-138 (1989). Flambee de rougeole. Re/eve epidemio/ogique hebdomadaire,64 (18): 137-138 (1989). 10. CoETZEE, N. T ET AL. Measles vaccination coverage and its determinants in a rapidly growing peri- urban area. South African medical journal, 78: 733-737 (1990). 11. TOOLE, M. J. ET AL. Measles prevention and control in emergency settings. Bulletin of the World Health Organization, 67 (4): 381-388 (1989). TOOLE, M. J. ET AL Prevention de la rougeole et lutte antirougeoleuse dans les situations d'urgence [resume). Bulletin de /'Organisation mondiale de la Sante, 67 (4): 386-387 (1989). 12. DAVIS, R. M. ET AL A persistent outbreak of measles despite appropriate preventive and con- trol measures. American journal of epidemio- logy, 126: 438-449 (1987). 13. KLEIN-ZABBAN, M. L. ET AL. Frequency of noso- comial measles in a maternal and child health centre in Abidjan [summary]. Bulletin of the World Health Organization, 65 (2): 201 (1987). KLEIN-ZABBAN, M. L. ET AL Frequence des rouge- oles nosocomiales dans un centre de protection maternelle et infantile d' Abidjan. Bulletin de /'Organisation mondiale de la Sante, 65 (2): 197- 201 (1987). 14. NAIRN, J.P. ET AL. Epidemic measles in an isolated unvaccinated population, India. International journal of epidemiology, 18: 952-957 (1989). 15. CHEN, R. T. ET AL. An explosive point-source out- break in a highly vaccinated population: mode of transmission and risk factors for disease. Amer- ican journal of epidemiology, 129: 173-182 (1989). 16. LouTAN, L. & PAILLARD, S. The epidemiology of measles in a nomadic community. (In press). 17. BARTLET, M. S. Measles periodicity and com- munity size. Journal of the Royal Statistical Society, Series A: 120: 48-70 (1957). 18. BLACK, F. L. Measles endemicity in insular popula- tions: critical community size and its impli- cations. Journal of theoretical biology, 11: 207- 211 (1966). W/d hlth statist. quart .• 45 (1992) 19. Measles - United States, first 26 weeks, 1989. Morbidity and mortality weekly report, 38: 863- 871 (1990). 20. SRIVASTAVA, R. N. ET AL Morbidity and mortality of children hospitalized with medical disorders in Afghanistan. Journal of tropical pediatrics, 25: 168-172 (1979). 21. AVILA-FIGUERA, c. ET AL [Complications in children with measles]. Boletfn medico de/ hospital in- fant!/ de Mexico, 47: 520-524 (1990). (In Spanish). 22. AABY, P. Introduction to community studies of severe measles: comparative test of crowding/ exposure hypothesis. Reviews of infectious dis- eases, 10: 451 (1988). 23. AABY, P. ET AL Mortality from measles: assessing the impact. (In press). 24. WAKEHAM, P. F. Severe measles in Afghanistan. Journal of tropical pediatrics, 24: 87-88 ( 1978). 25. AABY, P. & LEEUWENBURG, J. Patterns of transmis- sion and severity of measles infection: a re- analysis of data from the Machakos area, Kenya. Journal of infectious diseases, 161: 171-174 (1990). 26. HULL, H. Increased measles mortality in house- holds with multiple cases in the Gambia, 1981. Reviews of infectious diseases, 10: 463-467 (1988). 27. SunER, R. W. ET AL Measles among the Amish: comparative study of measles severity in primary and secondary cases in households. Journal of infectious diseases, 163: 12-16 (1991). 28. AABY, P. & CLEMENTS, C. J. Measles immunization research: a review. Bulletin of the World Health Organization, 67 (4): 443-448 (1989). AABY, P. & CLEMENTS, C. J. Le point de la recherche en matiere de vaccination antirougeoleuse [resume). Bulletin de /'Organisation mondiale de la Sante, 67 (4): 446 (1989). 29. HULL, H. F. ET AL Measles mortality and vaccine efficacy in rural West Africa. Lancet, i: 972-975 (1983). 30. HussEY, G. D. & KLEIN, M. A randomized controlled trial of vitamin A in children with severe measles. New England journal of medicine, 323: 160-164 (1990). - 292 - THE XXth CENTURY DENGUE PANDEMIC: NEED FOR SURVEILLANCE AND RESEARCH Scott B. Halstead• History of dengue The evolutionary history of the dengue viruses and their involvement with human beings is obscure. Because there is a well-established zoonotic cycle in which South-East Asian subhuman primates support the efficient transmission of all four dengue ser- otypes, it is tempting to view this geographical region as the "home" of the dengue viruses (1). In Asia, the urban cycle, involving Aedes aegypti and human beings, probably started when Western trade and colonial expansion introduced the vector from Africa (2). Scientific dengue virology had to await the isolation in mice of types 1 and 2 in the 1940s (3, 4). Except for several retrospective serological studies (5, 6), epidemics before 1940 must be surmised from their clinical and epidemiological characteristics. Using these identifying features, dengue viruses appear to have spread outside their ancestral home in pandemic fashion in each of the past two cen- turies. The tip of an XVlllth century pandemic can be identified from the classic description of dengue fever in Philadelphia in 1780 by Benjamin Rush (7). The causal virus and transmitting mosquito un- doubtedly were introduced into Philadelphia by ship, an unwelcome consequence of the sugar, rum and slave trade between African, colonial American and Caribbean ports. This first pandemic produced re- ports of sporadic dengue outbreaks in the United States of America, Caribbean and South American coastal cities during the XIXth century and the first three decades of the XXth century (BJ. A second pandemic had its most obvious locus in semi-tropical northern Queensland where gold and sugar generated rapid population growth. Settlers lived in hastily constructed boom towns depending for water on rain collected from roof runoff and stored in rain barrels. The resultant Aedes aegypti populations supported continuous dengue activity in Australia from the 1870s until World War I (9). The first outbreak of a disease resembling dengue hae- morrhagic fever/dengue shock syndrome (DHF/DSS) was reported from Charters Towers and nearby towns in 1897 (10). Dengue-like epidemics were also reported from the eastern Mediterranean in the late XIXth century (11), culminating in the explosive and severe Greek epidemic of 1928 (12). Effective mos- quito control measures introduced in Greece and in many colonial cities in tropical Asia, as well as the anti-Aedes campaigns of the American hemisphere, produced a global interregnum in dengue transmis- sion in the mid-XXth century (13). Modern pandemic dengue The great XXth century pandemic grew out of ecological forces brought into play by World War II • Rockefeller Foundation, New York, United States of America. and which have continued at unprecedented levels since then. Early in the war, dengue strains were carried by combatants from South-East Asia to Japan and the Pacific Islands, including Hawaii. Little is known about the distribution of dengue serotypes prior to World War II, but there is no question that destruction of city water supplies, temporary hous- ing for war refugees, the explosive post-war growth of populations through high fertility and rural-to- urban migration, and the steady deterioration of urban environments, have led to sustained growth in density and the area occupied by Aedes aegypti. Together these factors have resulted in the endemic transmission of all four dengue serotypes in most of the Asian tropics (14). With almost no effective programmes of vector containment, absolute num- bers of dengue infections, as well as dengue infec- tion rates, have increased steadily over the past 40 years. Meanwhile, the remarkable gains achieved towards the eradication of Aedes aegypti in the American tropics have been eroded and reversed. This was followed by the introduction and spread of dengue viruses beginning in the 1960s. Where once they were absent, dengue viruses have invaded Cuba, many of the Caribbean Islands, Mexico, the United States, most of Central America, Colombia, Ecuador, Peru, Paraguay, Bolivia, Argentina and Brazil (Maps 1 & 2). By the 1990s dengue had spread north to China, including the province of Taiwan, and south to Queensland (Australia) and repeatedly eastward to nearly all of the Pacific Islands, most conspicuously Tahiti. In Africa and the Middle East, areas of epidemic activity include outbreaks in Kenya, Mozambique, Somalia and Yemen (Map 3). The haemorrhagic fever phenomenon The most important attribute of the XXth century dengue pandemic has not been its extent, but its intensity. Repeated serological studies have shown that 3 or 4 dengue serotypes have been simul- taneously or serially endemically transmitted in all of the Asian tropics, probably since at least the 1960s, and also in the American tropics with the pro- gressive spread of Aedes aegypti there beginning in the 1970s. In South-East Asia this hyperendemicity resulted in a new acute vascular permeability syn- drome, the dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Limited mainly to children, DHF/DSS results in hypovolemic shock, often complicated by severe internal haemorrhaging and a high case-fatality rate. We now know that beginning slowly in the early 1950s, children with dengue haemorrhagic fever were being hospitalized in Thailand (14). Clusters of cases were identified in Manila in 1954, and longer outbreaks in Manila in 1956 and Bangkok in 1958 (14). Absolute numbers of recorded cases of DHF/ DSS have increased dramatically since 1960 parallel- ing, but not completely concordant with, the en- demicity of two or more dengue viruses. Case attack Rapp. trimest. statist. sanit. mond., 45 (1992) - 293 - MAP 1. DISTRIBUTION OF AEDES AEGYPTI IN THE AMERICAS, 1950-1990 CARTE 1. REPARTITION D'AEDES AEGYPTIAUX AMERIOUES, 1950-1990 The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities. or concerning the delimitation of its frontiers or bouridaries - Les designations utilisees sur cette carte et la presentation des donnees qui v figurent n'i mpliquent, de la part de !'Organisation mondiale de la Sante, aucune prise de position quant au statut juridique de tel ou tel pays, territoire, ville ou zone, ou de ses autoritE!s, ni quant au trace de ses frontiElres . MAP 2. DISTRIBUTION OF DENGUE AND DHF/DSS IN THE AMERICAS, 1950-1990 CARTE 2 . REPARTITION DE LA DENGUE ET DE SES FORMES HEMORRAGIOUES AVEC SYNDROME DE CHOC AUX AMERIQUES, 1950-1990 ~ Dengue DHF/DSS Forme h0morrag ique/ syndrome de choc 3,2,1,4 The designations employed and the presentati on of material on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organizati on concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries - Les designations utitisees sur cette carte et la presentation des donnl:les qul y figurent n'impliquent, de la part de !'Organisation mondiale de la Santi:!, aucune prise de position quant au statut juridique de tel ou tel pays, territoire, ville ou zone, ou de ses autorites, ni quant au trace de ses frontii:!res. rates have shown similar dramatic increases. DHF/ DSS has spread throughout tropical Asia and is now endemic in all countries of the region with the exception of Bangladesh, India and Pakistan. Table 7 details case reports for the past 30 years. Cases and deaths are grouped by the 20-year period, 1961 - 1980, then two 5-year periods, 1981 -1985 and 1985- 1990. Cases in the latter two time-periods equal or exceed those reported during the first 20 years of epidemic DHF/DSS. Major recent extensions include the Cuban outbreak of 1981, southern China and Hainan Island (75), Sri Lanka (16), India (17), Mal- dives (S. Nimmannitya, personal communication), Wld hlth statist. quart .• 45 (1992) Tahiti (78) and Venezuela (19) in the mid- to late 1980s. Although there is limited or no reporting, there can be little doubt that the Lao People's Demo- cratic Republic and Cambodia have experienced DHF/DSS at the same high level of endemicity as neighbouring Thailand and Viet Nam. Cases reported to the Western Pacific and South- East Asia Regional Offices of the World Health Or- ganization require some comment. Notification of DHF/DSS cases to WHO by Member States is volun- tary. Largely due to the work of the interregional Technical Advisory Commitee on Dengue and Den- - 294 - MAP 3. GLOBAL DENGUE VIRUS ACTIVITY SINCE 1960 CARTE 3. ACTIVITE DU VIRUS DE LA DENGUE DANS LE MONDE DEPUIS 1960 3,2,1,4 . - 1,2 0 D Dengue, no DHF - Dengue, san s forme hE! mo rragique • DHF/DSS - Forme hem orrag ique/syndrom e de choc The designations employed and the presentation of materia! on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries - Les designa tions utilis€!es sur cette carte et la presentati on des donnees qui Y figurent n'impliquent, de la part de !'Organisation mondiale de la Sante, aucune prise de position quant au statut juridique de tel ou tel pays, territoire, ville ou zone, ou de ses autorit8s, ni quant au trace de ses frontiE!res. gue Haemorrhagic Fever which has met at frequent intervals since 1973, a case definition of DHF/DSS was adopted and guides to diagnosis, treatment and control of the disease prepared (20). The Technical Guide provided a case notification form and, as recommended, the two regions have been served by a Dengue Newsletter. The request to Member States from WHO is that hospitalized cases and deaths, shock and non-shock, be reported monthly, giving age and sex. In practice, cases are reported annually; several countries have extended their own national case reporting to include hospital outpatients. DHF/ DSS case reporting is incomplete (Cambodia, Lao P. D. R.), fails to conform to WHO case definitions (most countries) and is inflated (most countries). Few countries report DSS separately from DHF, non- shock. Many mix dengue feve r cases with DHF/DSS. Overreporting of DHF/DSS is a problem, but it is not yet known what proportion of the increase in DHF/ DSS cases is attributable to inflation in the reporting base. Distribution of DHF/DSS: implications for pathogenesis A glance at the world map (Map 3) shows hetero- geneous disease distribution. The circulation of mul- tiple dengue serotypes does not always produce DHF/DSS. This includes all of Africa and much of tropical America . Why should th is be? Observations made during the 1981 dengue outbreak in Cuba established the fact that blacks are relatively resistant to DHF/DSS (21). A resistance gene in blacks might account for the absence of reports of DHF/DSS from Africa where dengue 2 and 3 have been epidemic while type 2 is enzootic in West African subhuman primates (22, 23). What is less clear is whether a resistance gene widely distributed in tropical American populations accounts for the relative paucity of DHF/DSS in this hemisphere. Virological studies related to the Cuban epidemic and the recent sharp DHF/DSS outbreak in TABLE 1. DENGUE HAEMORRHAGIC FEVER CASES (AND DEATHS) REPORTED TO WHO REGIONAL OFFICES, 1956-1990 TABLEAU 1. CAS DE DENGUE HEMORRAGIQUE (ET DECES) DECLARES AUX BUREAUX REGIONAUX DE L'OMS, 1956-1990 Phil ippines Viet Nam China Tha iland Lao P. D.R. Cambodia Myanmar Malaysia Ch ine Thailande R.p.d. lao Cambodge M alaisie c D c D c D c D c D c D c D c D 1956-1980 25 831 2 124 325 409 6 268 36 256 2 455 236 556 5 926 30 267 1 342 5 163 330 1981 123 8 35 323 408 25 641 194 1 524 90 486 14 1982 305 31 39 806 361 22 250 159 49 3 052 36 1983 1 684 130 149 51 9 1 798 85 293 3 032 30 022 231 2 856 83 790 10 1984 2 545 89 30 498 368 69 597 451 22 14 2 323 39 702 5 1985 . 45 107 399 80 076 542 1 759 15 2 666 134 384 11 1986 687 30 46 266 511 29 030 206 365 43 2 191 111 1 403 9 1987 859 27 354 517 1 566 170 630 896 3 914 91 7 292 222 2 025 8 1988 2 922 68 85 160 826 51 510 1 259 26 926 189 1 212 27 1 181 65 1 448 2 1989 305 14 40 205 289 37 996 907 69 204 280 n. a. n.a. 1 196 52 2 401 14 1990 588 27 37 569 255 38 062 2 626 113 855 422 60 3 7 241 403 5 200 178 2 071 38 1981-1985 4 657 258 300 253 3 334 85 293 3 032 227 586 1 577 1 781 29 9 369 395 5 414 76 1986-1990 5 361 166 563 71 7 3 447 127 568 4 792 409 645 1 993 5 551 164 7 241 403 17 060 628 9 348 71 Total 35 849 2 548 1 189 379 13 049 249 117 10 279 873 787 9 496 7 332 193 7 241 403 56 696 2 365 19 925 477 Rapp. trimest. s tatist. sanit. mond., 45 ( 1992) 295 - Singapore Indonesia India Singapour lndonesie lnde c D c D c D 1956-1980 5 240 51 48982 2 676 1 500 156 1981 133 0 5909 231 1982 216 0 4 665 255 1983 205 2 13 875 491 1984 86 0 12 710 382 1985 126 2 13 875 460 1986 354 0 12 710 600 1987 436 0 22 765 1 039 1988 245 0 47 573 1 527 128 28 1989 944 0 10 362 464 1990 1 733 4 13 043 458 1981-1985 766 4 51 034 1 819 1986-1990 3 712 4 106 453 4 088 128 28 Total 9 718 59 206 469 8 583 1 628 184 Total number of cases - Nombre total de cas: 2 780 900 Total number of deaths - Nombre total de deces: 47 968 " French Polynesia - Polynesie fran~aise. Venezuela have yielded dengue 2 viruses which have been identified genetically as South-East Asian topo- types (24). This observation can be interpreted as follows: sequential dengue infections involving only American topotypes yield DHF/DSS at a low fre- quency, while sequential infections terminating with a South-East Asian topotype result in DHF/DSS at high frequency. For the moment such a topotype is called a "biotype", while acknowledging that it is unknown whether Caribbean and South-East Asian topotypes differ in crucial antigenic determinants or some biological property. The introduction of a South-East Asian "biotype" is likely to be responsible for the recent emergence of classical DHF/DSS in Maldives, Sri Lanka, Vellore and Madras in South India (J. John, personal com- munication). and New Delhi in 1988-1989. The entire Indian subcontinent has been epidemiologically si- lent since a small outbreak of DHF/DSS in Calcutta in 1963 (25) and despite the continuous circulation of 3 or 4 dengue serotypes (26). A careful search for DHF/DSS conducted in Colombo (Sri Lanka) during the 1980s yielded very few cases until the 1989-1990 outbreak (27). Nonetheless, 3 dengue serotypes were recovered from out- or inpatients with the dengue fever syndrome; sequential dengue infections were common. Unfortunately, as this article is written, the topotypes of the 1989-1990 Sri Lankan outbreak are unknown and the very extensive Indian epidemic of 1988 yielded no viruses whatsoever. More recently, a sharp outbreak of DHF/DSS in Tahiti appears to be an extension of a current South-East Asian dengue 3 pandemic. Dengue 3 has been associated with DHF/ DSS cases in Thailand since 1984 (28). Still not understood are differences between viruses which cause DHF/DSS in the presence of pre-existing dengue antibody and those which do not. If, as hypothesized, more cellular infection occurs in severe than in mild dengue, then according to the antibody-dependent infection enhancement (ADE) hypothesis, DHFJDSS might occur with either of the following: (i) a virus with enhanced ability to repli- cate in mononuclear phagocytes or (ii) a virus with antigenic attributes which optimize ADE. Recent re- search favours the second explanation. 1. In laboratory studies, any dengue virus will raise antibodies which will produce ADE with any of Wld hlth statist. quart., 45 (1992) Sri Lanka Cuba Venezuela Pacific Islands c 79 10 203 1 121 1 334 1 413 lies du Pacifique D c D c D c D 17 116143 159 0 20 2 665 40 213' 5' 61 3 325 30 116 143 159 81 5 990 70 213 5 98 116143 159 5 990 70 213 5 the 4 dengue serotypes (29). In reality only certain dengue virus types participate in antibody- enhanced disease: in South-East Asia, dengue types 2, 3 and possibly 4. The clinical course of type 1 infections is not altered by pre-existing antibody (30). 2. Cross-reactive neutralizing antibodies down- regulate the severity of secondary dengue infec- tions. This fact was established in the elegant studies of Kliks, Burke et al. (31, 32). Primary dengue infections raise neutralizing antibodies which are either highly specific (monovalent) or have heterotypic cross-reactivity. When an indi- vidual with monovalent neutralizing antibodies is infected with a second type, only infection- enhancing antibodies are present and the re- sultant infection produces a severe disease. In Kliks' study of 41 children with secondary dengue infections (32), 7 of 11 individuals with monova- lent antibody were hospitalized, whereas 28 of 30 individuals with low-level heterotypic dengue 2 neutralizing antibodies were completely asymp- tomatic. Hypotheses which might explain this phenomenon (each testable) are: (i) infecting virus pairs fail to share neutralizing epitopes, (ii) infecting virus pairs share a critical number of enhancing epitopes, or (iii) an initial infecting virus induces in its host a minimal immune response. Individuals who produce small amounts of homologous antibody also would produce little or no heterotypic antibody and would not be able to down-regulate ADE. Need for better surveillance and more research The almost unnoticed DHF/DSS outbreak in New Delhi in 1988 is a sad reflection on the readiness and competence of national and international disease surveillance systems. Without question, this was among the most important epidemiological research opportunities in the XXth century dengue pandemic. DHF/DSS was introduced abruptly into a previously unaffected area where 3 or 4 dengue viruses had been endemically transmitted for many years. An understanding of exactly what happened in India would likely answer key questions concerning the pathogenesis of DHF/DSS. Because of present epi- demiological silence, the focus of pathogenetic in- - 296 - terest now shifts to Africa where epidemiological studies of dengue infection are crucial. Understanding the pathogenesis of DHF/DSS is still a major public health challenge and a first-rate scientific problem. One of the most exciting research opportunities is to uncover the molecular bases for resistance to dengue disease severity in blacks. This discovery could unlock many secrets. This problem cries out for immediate attention. Essential to any studies is the recovery of viral strains representative of initial infecting viruses and of those producing DHF/DSS. This can be accomplished only through prospective studies in which there is careful docu- mentation of dengue clinical syndromes and the recovery and preservation of dengue strains. WHO technical advisory groups have repeatedly called for such studies and for the conservation of viral strains in regional laboratory facilities. Never before has implementation of these recommendations been so urgent. In 1980 the Bulletin of the World Health Organization published a status report on dengue haemorrhagic fever which called for improved research and im- proved surveillance by laboratories serving popula- tions in which dengue viruses were active (14). Fortunately, several crucial research questions have been answered, but these have led to a set of new research questions. Because the XXth century den- gue pandemic shows no sign of waning, an even larger portion of the world's population is at risk to DHF/DSS. It is essential to establish improved clini- cal and virological surveillance designed to answer crucial research questions, particularly in areas at risk to the introduction of dengue haemorrhagic fever. SUMMARY By the last decade of the XXth century Aedes aegypti and the 4 dengue viruses had spread to nearly all countries of the tropical world. Some 2 billion persons live in dengue-endemic areas with tens of millions infected annually. Dengue pandemics were also doc- umented in the XVlllth and XIXth centuries; they were contained by organized anti-Aedes aegypti campaigns and urban improvements. The XXth cen- tury dengue pandemic has brought with it the simultaneous circulation of multiple serotypes and in its aftermath, endemic dengue haemorrhagic fever/ dengue shock syndrome (DHF/DSS). Nearly 3 million children have been hospitalized with this syndrome in the past 3 decades, mainly in South-East Asia. Recent outbreaks of DHF/DSS in the Pacific Islands, China, India, Sri Lanka, Cuba and Venezuela are indicators of the high intensity and rapid spread of dengue transmission. The magnitude of the XXth century dengue pandemic requires urgent improve- ments in early warning surveillance by WHO Member States and the development of the capacity to study underlying mechanisms of the disease. A key research question is why does DHFJDSS not occur with all second dengue infections? Two an- swers have been suggested: (1) a human resistance gene. Data from the 1981 DHF/DSS epidemic in Cuba have demonstrated the existence in blacks of a resistance gene. The effect of such a gene in reduc- ing disease susceptibility of American and African blacks requires more study. (2) The existence of dengue "biotypes". Some, but not all biotypes may cause DHF/DSS during a second dengue infection. A South-East Asian dengue 2 biotype introduced into Cuba is thought to be responsible for the 1981 DHFJDSS epidemic. DHF/DSS did not occur with the genetically distinct Caribbean dengue 2 viruses which were in circulation in the 1970s. How does a second dengue infection cause severe disease? A recent study in Thailand suggests that when antibody residual from the first infection is able to neutralize a second virus type, even weakly, a secondary infection will occur, but its severity is down-regulated and the disease mild. When no cross-reactive neutralizing antibodies are raised, a second infection is under the influence of enhancing antibody; the resulting infection and disease are severe. The presence or absence of antigens on both the first and second virus determine disease se- verity. An alternate mechanism which could deter- mine disease severity is that South-East Asian den- gue viruses may be inherently more capable of supporting severe antibody-enhanced infection than viruses from other geographical regions. The extension of DHF/DSS to new areas always provides opportunities to study and understand dis- ease pathogenesis. Two very important elements of dengue control are lacking in most countries, namely enhanced surveillance for DHF/DSS and im- proved research which should include at least the study of pre- and post-epidemic sera and the isola- tion of viruses from serologically documented cases. RESUME La pandemie de dengue du xxe siecle: besoin de surveillance et de recherche La derniere decennie du XX• siecle a vu Aedes aegypti et les 4 virus de la dengue s'etendre a presque tous les pays du monde tropical. Ouelque 2 milliards de personnes vivent dans des regions ou la dengue est endemique, affectant chaque annee plu- sieurs dizaines de millions d'entre elles. Des pande- mies de dengue avaient deja ete observees aux XVIII• et XIX• siecles: elles ont ete endiguees grace a Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 297 - des campagnes de demoustications dirigees contre Aedes aegypti et a !'amelioration de l'urbanisme. La pandemie de dengue du xx• siecle a mis simultane- ment en circulation de multiples serotypes et, dans son sillage, la dengue endemique et sa forme he- morragique avec syndrome de choc. Pres de 3 mil- lions d'enfants presentant ce syndrome ant ete hos- pitalises au cours des 3 decennies ecoulees, princi- palement en Asie du Sud-Est. Les flambees qui ant eclate recemment dans les iles du Pacifique, en Chine, en lnde, au Sri Lanka, a Cuba et au Venezuela montrent combien la transmission de la dengue est intense et sa propagation rapide. L'ampleur de la pandemie actuelle exige qu'on ameliore de toute urgence le systeme de veille avancee mis en place par l'OMS et ses Etats Membres et qu'on se donne les moyens d'etudier la pathogenese de la maladie. Un point crucial pour la recherche est de savoir pourquoi la maladie ne se produit pas toujours apres une deuxieme infection. On a propose deux reponses: 1) !'existence d'un gene de resistance chez l'homme. Les donnees tirees de l'epidemie de 1981 qui s'est produite a Cuba ant permis de mettre en evidence !'existence d'un gene de resistance chez les Noirs. II convient d'etudier de fac;:on plus approfon- die l'effet qu'un tel gene pourrait avoir sur la reduc- tion de la sensibilite a la maladie chez les Noirs d'Amerique et d'Afrique. 2) !'existence de «biotypes» de la dengue. Certains biotypes, mais pas tous, pourraient entrainer une dengue hemorragique au un syndrome de choc apres une deuxieme infection. On pense qu'un biotype de dengue 2 originaire d'Asie du Sud-Est et introduit a Cuba est responsa- ble de l'epidemie de 1981. Les virus de la dengue 2 d'origine cara"ibe qui en sont genetiquement dis- tincts et circulaient dans les annees 1970 n'ont pas provoque la maladie. De quelle maniere une deuxieme infection par le virus de la dengue entraine-t-elle une maladie grave? Une etude recente menee en Tha"ilande incite a penser que lorsque les anticorps qui subsistent apres une premiere infection sont capables de neu- traliser, meme faiblement, un deuxieme type viral, la deuxieme infection se produit effectivement mais sa gravite est amoindrie et la maladie est benigne. S'il n'y a pas stimulation d'anticorps neutralisants don- nant lieu a des reactions croisees, la deuxieme infec- tion se trouve alors sous !'influence d'anticorps faci- litants et la maladie qui en resulte est grave. Selan !'absence au la presence des antigenes sur le pre- mier et le deuxieme virus, la maladie est plus au mains grave. La gravite de la maladie pourrait s'ex- pliquer par un autre mecanisme, a savoir que les virus d'Asie du Sud-Est pourraient etre intrinseque- ment plus enclins a provoquer une infection grave, du fait de la presence d'anticorps facilitants, que les virus originaires d'autres zones geographiques. La propagation de la dengue hemorragique et du syndrome de choc a de nouvelles regions constitue toujours une occasion d'etudier et de mieux com- prendre la pathogenese de la maladie. Dans la plu- part des pays, ii manque deux elements importants a la lutte contre la dengue, a savoir une meilleure surveillance de la forme hemorragique et de la forme avec syndrome de choc et une meilleure recherche qui devrait comporter au mains l'etude des serums pre- et post-epidemiques et l'isolement du virus sur les cas serologiquement confirmes. REFERENCES- REFERENCES 1. RUDNICK, A. Ecology of dengue viruses. Asian journal of infectious diseases, 2: 156-160 (1978). 2. SMITH, C. E. G. The history of dengue in tropical Asia and its probable relationship to the mos- quito Aedes aegypti. Journal of tropical medi- cine and hygiene, 5: 3-11 (1956). 3. HonA, S. Experimental studies on dengue - I. Isolation, identification and modification of the virus. Journal of infectious disease, 90: 1-9 (1952). 4. SABIN, A. B. & SCHLESINGER, R. w. Production of immunity to dengue with virus modified by pro- pagation in mice. Science, 101: 640-542 (1945). 5. HonA, S. ET AL. Long persistence of anti-dengue antibodies in serum of native residents of Japanese main islands. Kobe journal of medical science, 14: 149-153 (1968). 6. HALSTEAD, S. B. Etiologies of the experimental dengues of Siler and Simmons. American journal of tropical medicine and hygiene, 23: 974-982 (1974). 7. RusH, B. An account of the bilious remitting fever as it appeared in Philadelphia in the summer and autumn of the year 1780. Medical inquiries and observations (Philadelphia): 89-100 (1789). 8. HIRSCH, A. (ED.). Handbook of geographical and historical pathology. Volume I. London, New Sydenham Society, 1883. Wld hlth statist. quart., 45 (19921 9. LUMLEY, G. F. & TAYLOR, F. H. Dengue. Sydney, Australasia Medical Publishing Co., 1943. (School of Public Health Tropical Medical Ser- vice Publication No. 3). 10. HARE, F. E. The 1897 epidemic of dengue in North Queensland. Australasian medical gazette, 17: 98-107 (1898). 11. GRAHAM, H. Dengue: a study of its mode of propagation and pathology. Medical record, 61: 204-212 (1902). 12. HALSTEAD, s. B. & PAPAEVANGELOU, G. Transmis- sion of dengue 1 and 2 viruses in Greece in 1928. American journal of tropical medicine and hygiene, 29: 635-637 (1980). 13. HALSTEAD, S. B. Selective primary health care: strategies for control of disease in the develop- ing world. Dengue reviews of infectious dis- eases, 6: 251-264 (1984). 14. HALSTEAD, S. B. Dengue haemorrhagic fever - a public health problem and a field for research. Bulletin of the World Health Organization, 58 (1 ): 1-21 (1980). HALSTEAD, S. B. Dengue hemorragique - pro- bleme de sante publique et domaine de re- cherche. Bulletin de /'Organisation mondiale de la Sante, 58 (3): 375-397 (1980). 15. Ou1, F. X. ET AL. The first epidemic of dengue haemorrhagic fever in the People's Republic of - 298 - China. American journal of tropical medicine and hygiene, 44: 364-370 ( 1991 ). 16. VITARANA, T. & JAYASEKERA, N. Dengue haemor- rhagic fever outbreak in Sri Lanka. South-East Asian journal of tropical medicine and public health, 4: 682 (1990). 17. SRIVASTA, V. K. ET AL An epidemic of dengue haemorrhagic fever and dengue shock syndrome in Delhi: a clinical study. Annals of tropical pediatrics, 10: 329-334 (1990). 18. CHUNGUE, E. ET AL Dengue and dengue hae- morrhagic fever in French Polynesia: a compar- ative study of two successive epidemics. South- East Asian journal of tropical medicine and public health, 21: 680-681 (1990). 19. Dengue haemorrhagic fever in Venezuela. Pan American Health Organization epidemiology bulletin, 11: 7-9 (1990). 20. WORLD HEAL TH ORGANIZATION. Dengue haemorrhagic fever: diagnosis, treatment and control. Geneva, WHO, 1986. ORGANISATION MONDIALE DE LA SANTE. La dengue hemorragique: diagnostic, traitement et moyens de lutte. Geneve, OMS, 1987. 21. GUZMAN, M. G. ET AL Dengue haemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study. American journal of tropical medicine and hygiene, 42: 179-184 (1990). 22. GUBLER, D. J. ET AL Dengue 3 virus transmission in Africa. American journal of tropical medicine and hygiene, 35: 1280-1284 (1986). 23. CORDELUER, R. ET AL Circulation selvatique du virus dengue 2 en 1980 dans les savanes sub- soudaniennes de Cote d'Ivoire, Cahiers ORSTOM serie entomologie medicate et parasitologie, 21: 165-179 (1983). 24. Rico-HESSE, R. Molecular evolution and distribu- tion of dengue viruses type 1 and 2 in nature. Virology, 174: 479-493 (1990). 25. SARKAR, J. K., Calcutta's experience and findings in haemorrhagic fever and chikungunya fever epidemic. Japanese journal of medical science and biology, 20: 88-90 (1967). 26. CAREY, D. E. ET AL Studies on dengue in Vellore, South India. American journal of tropical medi- cine and hygiene, 15: 580-587 (1966). 27. VITARANA, T. & JAYASEKERA, N. A study of dengue in a low DHF area: Sri Lanka. Proceedings of the International Conference on Dengue/DHF. Kuala Lumpur, University of Malaysia, 1983. 28. N1sALAK, A. ET AL Severe dengue infections among children in metropolitan Bangkok, 1973- 1989: description of epidemics and characteriza- tion of virus serotypes associated with them. South-East Asian journal of tropical medicine and public health, 21: 678-679 (1990). 29. MORENS, D. & HALSTEAD, S. B. Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. Journal of general vi- rology, 71: 2909-2914 (1990). 30. BURKE, D. S. ET AL A prospective study of dengue infections in Bangkok. American journal of tropi- cal medicine and hygiene, 38: 172-180 (1988). 31. KuKs, S. C. ET AL. Evidence that maternal dengue antibodies are important in the development of dengue haemorrhagic fever in infants. American journal of tropical medicine and hygiene, 38: 411-419 (1988). 32. KuKs, S. C. ET AL Antibody-dependent enhance- ment of dengue virus growth in human mono- cytes as a risk factor for dengue haemorrhagic fever. American journal of tropical medicine and hygiene, 40: 444-451 (1989). Rapp. trimest. statist. sanit. mond., 45 (1992) - 299 - EPIDEMIOLOGY AND CONTROL OF JAPANESE ENCEPHALITIS Akira lgarashia Introduction Japanese encephalitis (JE) has been considered as a serious disease because of its high case-fatality rate and grave sequelae with neuropsychiatric disorders. The causative agent, JE virus, belongs to the family Flaviviridae which comprises approximately 60 members (1, 2). Many of the flaviviruses have been documented as medical or veterinary patho- gens (3, 4), and most of them, including JE virus, were formerly classified as group B arboviruses ac- cording to their transmission cycle in nature and antigenic cross-reactivity. Studies on JE virus in recent years were highlighted by advances in the molecular aspects. Three struc- tural proteins were identified for JE virus: membrane protein (M), core protein (C), and envelope glyco- protein (E). The E protein, which was isolated from the virion surface, was immunogenic in experi- mental animals producing neutralizing anti- bodies (5), which were protective for lethal JE virus infection in mice (6, 7). Antigenicity of the E protein was analysed by monoclonal antibodies (MCA) to identify multiple epitopes with various cross- reactivity and biological properties (8). Genomic RNA of JE virus, which is single-stranded and positive-sense, was analysed for its nucleotide (nt) sequence. The data on a wild strain, JaOArS982, revealed a total of 10 976 nt: 95 nt in the 5'- noncoding region, 10 296 nt in a long open reading frame (ORF), and 585 nt in the 3'-noncoding re- • Professor and Chairman, Department of Virology, Institute of Tropical Medicine, Nagasaki University, Japan. gion (9). The ORF was considered to be translated into a polyprotein of 3 432 amino-acids. The 5' one- fourth of the ORF comprised structural protein genes in the order of C, PreM (precursor of M), and E, whereas the remaining part of the ORF represented the nonstructural protein genes (NS1, NS2A, NS28, NS3, NS4A, NS48, NS5). The 3'-end of JE virus genomic RNA did not contain poly(A) tract but was presumed to form stem-and-loop secondary struc- ture (10). This genomic organization is essentially the same as that of other flaviviruses as represented by the yellow fever virus (11), and consistent with the sequence data on other JE virus strains. Epidemiological trends of JE The epidemic transmission cycle of JE virus in nature has been well documented, with the main vector being Cu/ex tritaeniorhynchus or related species, and swine or avians the major amplifier vertebrates. It is also known that JE and JE virus exist in many countries in East Asia, South-East Asia and South Asia. Most of these areas are favoured by a climate with sufficient temperature and precipita- tion during the monsoon season, which enables rice cultivation in watered paddy fields, while swine rais- ing is also quite common in these areas, except in Muslim countries. This environmental and socioagri- cultural background could facilitate JE virus circula- tion by providing ample vector breeding sites and abundant amplifiers. The epidemiology of JE until 1972-1975 having been described elsewhere (12), Tables 1 & 2 only cover the period 1973-1990. TABLE 1. REPORTED NUMBER OF JAPANESE ENCEPHALITIS CASES (AND DEATHS) IN CHINA, REPUBLIC OF KOREA, JAPAN, VIET NAM AND THAILAND, 1973-1990 TABLEAU 1. NOMBRE DECLA~E DE CAS (ET DE DECES) D'ENCEPHALl'f.E JAPONAISE EN CHINE, EN REPUBLIQUE DE COREE, AU JAPON, AU VIET NAM ET EN THAILANDE, 1973-1990 Year China Republic of Korea Japan Viet Nam Thailand An nee Chine Republique de Coree Japan Thailande 1973 89 478 769 (157) 70 (27) 1 914 (247) 1 784 (476) 1974 86 900 399 (10) 6 (0) 4 246 (925) 1 617 (466) 1975 89 018 743 (3) 27 (6) 913 (151) 1 622 (384) 1976 70 319 250 (0) 13 (9) 1 789 (542) 1 559 (409) 1977 66 372 550 (0) 5 (0) 2 265 (558) 1 738 (422) 1978 51 335 560 (0) 88 (21) 1 693 (280) 1 503 (356) 1979 49 287 600 (0) 86 (26) 1 688 (387) 2 082 (491) 1980 14 192 (1 793) 107 (4) 40 (15) 1 262 (210) 2 413 (447) 1981 39 985 194 23 (5) 1 095 (298) 1 562 (257) 1982 31889 1 197 21 (4) 2 709 (532) 1 540 (268) 1983 24 260 (2 486) 139 (15) 32 (8) 3 244 (600) 2 084 (371) 1984 26 259 27 (5) 2 431 (407) 1 618 (231) 1985 29 065 0 (0) 39 (8) 4935 (592) 1 980 (267) 1986 18 282 (1 587) 0 (0) 26 (3) 2 889 (515) 1 723 (231) 1987 24 390 (2 283) 3 (0) 37 (7) 3 225 (335) 1 711 (181) 1988 25 123 (2 106) 1 (0) 32 (4) 2 724 (297) 1 587 1989 17 098 (1100) 1 (0) 37 (4) 1 301 (168) 1990 38 062 (2 626) 1 (0) 54 (8) 916 (95) 1 208 (125) Sources: China - Institute of Virology, Beijing, China; other countries - WHO, Geneva. - Chine - lnstitut de Virologie, Pekin, Chine; autres pays - OMS, Geneve. Wld hlth statist. quart., 45 (19921 - 300 - TABLE 2. REPORTED NUMBER OF JAPANESE ENCEPHALITIS CASES (AND DEATHS) IN INDIA, NEPAL, SRI LANKA, MYANMAR AND BANGLADESH, 1978-1990• TABLEAU 2. NOMBRE DECLARE DE CAS (ET DE DECES) D'ENCEPHALITE JAPONAISE EN INDE, AU NEPAL, AU SRI LANKA, AU MYANMAR ET AU BANGLADESH, 1978-1990" Year India Nepal Sri Lanka Myanmar Bangladesh An nee lnde Nepal 1978 7 463 (2 755) 422 (119) (0) 422 (119) 1979 2 845 (926) 182 (46) (0) 182 (46) 1980 3 478 (1 436) 622 (231) (0) 0 (0) 2 1981 3.894 (1167) 54 (16) (0) 0 (0) 0 1982 3 515 (1 260) 843 (390) (0) 0 (0) 2 1983 1 716 (581) 243 (36) (0) 0 (0) 0 1984 3 321 (1 405) 142 (45) (0) 0 (0) 0 1985 2 490 (916) 595 (146) 441 (65) 0 (0) 0 1986 7 500 (2 617) 1 600 (420) 336 (70) 0 (0) 0 1987 3 515 (1 346) 500 (135) 766 (138) 0 (0) 0 1988 6 817 (2 407) 1 390 (400) 163 (26) 0 (0) 0 1989 6 400 (2 422) 888 (227) 293 (49) 0 (0) 4 1990 1 574 (1 291) 365 (102) 387 (43) 0 (0) 1 a Data prior to 1977 are not available for these countries - On ne dispose pas, pour ces pays, de donnees ant0rieures a 1977. Source: WHO, Geneva - OMS, Geneve. In Japan, the number of human JE cases dramati- cally decreased after the 1966 epidemic and has remained under 100 per year from 1972 until the present. Two factors may account for this reduced JE endemicity: decreased vector population and mass-vaccination of humans. The decreased vector population was not the result of a JE control pro- gramme but was caused by the wide spraying of pesticides in the rice fields by farmers to protect rice crops. However, a high level of insecticide resistance was found among Cx. tritaeniorhynchus collected in the fields after the 1980s. Resistance, especially to organophosphorus compounds, was observed for all Cx. tritaeniorhynchus strains captured in various parts of Japan (13-15). This is possibly related to the increased Cx. tritaeniorhynchus population in Japan after the 1980s (16). Serological surveillance of the blood of slaughtered swine revealed more than 80% antibody prevalence in south-eastern Japan, par- ticularly on Kyushu and Shikoku Islands. However, the number of human JE cases in Japan has been maintained at a low level, probably because of the sustained vaccination among young children (80% coverage rate), and dissociation between swine- Cu/ex cycle and human dwellings. In contrast, JE virus circulation is almost negligible in northern Hokkaido Island, although focal infection has been reported in swine farms (17). In the Republic of Korea, although the annual number of JE cases dropped from 1 OOO to 100 after 1969, 1 197 cases (with morbidity of 3.1 per 100 OOO population) were recorded in 1982. The number again decreased in 1983, and only a few cases were serologically confirmed as JE afterwards. This de- crease was also considered to be the result of mass vaccination. During the period 1955-1966, most of the cases were found among children under 14 years old, with the highest attack rate observed in the age group 4-7 years. However, the age- specific incidence showed a decreasing trend in young age groups, while it was increasing in the age group over 15 years. At the end of 1985, the vaccin- ation coverage rate was 100% in the age group 3-15 years. The Republic of Korea has been produc- ing inactivated JE vaccine from infected mouse brains, by a process similar to the one used in Japan. As is the case in Japan, organophosphorus insecticides have been used extensively in rice fields. In China, more than 20 OOO human JE cases were reported every year until 1975. In spite of the strengthening of JE control programmes, 10 000- 20 OOO JE cases are still being reported annually, with a case-fatality rate around 10%. Except for the Xintian area, the Tibet Autonomous Region and Qinghai Province, the entire country has become an epidemic area. Besides human JE, fatal equine JE is considered a great economic problem in this country. In Viet Nam, epidemics of acute encephalitis syn- drome (AES) have been spreading after the first outbreak in the North in 1965. The AES is clinically compatible with JE, and approximately 30% of the cases were serologically diagnosed as JE, either by the haemagglutination-inhibition (HI) test or by lgM- ELISA. JE virus was isolated from patients, mos- quitos, swine and wild birds. Several thousand pa- tients have been reported almost every year with significant case-fatality rates until the present. Although the disease exists both in the North and the South of the country, the epidemic season in the subtropical North extends from June to August with a peak in July, while the disease has been reported all year round in the tropical South, with a slight increase in July. Children under 9 years were the most frequently affected age group. In Thailand, the first outbreak of acute viral en- cephalitis, which occurred in 1969 in Chiang Mai Valley, northern Thailand, was shown to be associ- ated with JE virus. After this outbreak, the epidemic area gradually spread out and the number of patients increased, to exceed 2 OOO cases in 1979. Further studies in northern Thailand showed con- tinued JE virus circulation in this area together with dengue virus infection (18). Epidemics of JE occurred during the rainy season from June to August with a peak in July in the north, while seasonal variation was not clear in the south. The morbidity rate of viral encephalitis was reported to be highest in the north followed by the north-east regions, and relatively low in central and southern Thailand. However, extensive transmission of JE virus among swine was recently demonstrated (19), and 40% of encephalitis cases were serologically confirmed as JE in the southern region. Children under 14 years were most frequently affected by viral encephalitis and approximately 30% of them were serologically confirmed as JE. In India, JE cases were diagnosed in Tamil Nadu and Andhra Pradesh in 1955, and JE virus isolated from Rapp. trimest. statist. sanit. mond .. 45 (1992) - 301 - mosquitos and human specimens. Before 1970, JE was recorded only in the southern parts of India, since then cases have been recognized in various parts of the country. A large epidemic of JE occurred in 1978, with more than 7 OOO patients and a 36% case-fatality rate in West Bengal, Karnataka, Tamil Nadu, Andhra Pradesh, Assam and Uttar Pradesh. Thereafter, large JE outbreaks have been reported every year with 2 000-7 OOO cases. In southern India, children were predominantly affected, whereas in eastern and north-eastern India, adults were also affected by JE. The JE epidemiology in India is characterized by a multiplicity of possible vector species, including Anopheles and Mansoni besides Cu/ex; moreover, the avian species play a relatively important role as amplifier since the swine popula- tion is small. Also in 1978, Nepal experienced its first JE epidemic, in the southern Terai belt along the Indian border, with 422 cases and 119 deaths. The disease has been occurring every year since, with the number of cases fluctuating between 50 and 800, the case- fatality rate around 30-50%. Children 5-14 years were most frequently affected, representing 46% of total JE cases. Cases peaked in September-October after the monsoon season. Serological surveillance showed anti-JE antibodies among animals and birds as well as in 79% of human populations in endemic areas. Although the amplifier vertebrate host of JE in Nepal was not identified, swine are probably very important in spite of their relatively small population size. Cu/ex was the most abundant mosquito genus captured, with vishnui as a predominant species. Thus, the apparent increase in JE epidemics in recent years in several developing countries of Asia is a remarkable phenomenon. The underlying causes have not yet been elucidated, although in Sri Lanka, the JE epidemic was recorded in areas were rice cultivation had been newly introduced (20). It may be speculated that agricultural development, with concomitant population growth, may have resulted in accelerated JE virus transmission. JE control measures Three JE control strategies have been considered based on the transmission cycle of JE virus: (i) vector control, (ii) swine immunization, and (iii) immunization of humans. Attempts to control JE vector mosquitos by chemical insecticide spraying apparently reduced vector den- sity but the effect was transient. Insecticide spraying to control JE virus transmission was not considered cost-effective because vector breeding sites in irriga- ted rice fields cover large areas, and because of the possibility of insecticide resistance. Immunization of swine to control JE virus transmis- sion was carried out in several limited areas in Japan. Extensive swine immunization was per- formed in lki Islands, Nagasaki Prefecture, in 1972 to cover almost all the swine population. Although a control area was not set up in this study, the number of human JE cases in this island was signifi- cantly reduced in ensuing years. A similar success in swine immunization was reported after 1985 in Kumamoto Prefecture, which until then had recorded the highest number of human JE cases in Japan. In a controlled field study in Osaka Prefecture, JE virus Wld hlth statist. quart., 45 ( 19921 transmission was modified by swine vaccination. In this study, a live-attenuated ML-17 strain vaccine was used, which possessed several biological char- acteristics such as reduced mouse virulence, ab- sence of swine viraemia and limited growth in vector mosquitos (21). The following problems have been recognized in connection with swine immunization: (i) most of the swine population on farms are slaughtered around 6-8 months, requiring immunization of newly born piglets every year before the JE epidemic season; (ii) live-attenuated JE vaccine is not effective in the piglets which possess maternal antibodies until about 6 months. The latter fact has restricted the timing of swine immunization to a narrow period. This timing would be more difficult to determine in tropical areas where JE virus transmission can take place all year round. Therefore, human immunization remains the most reliable control measure for human JE at present. Current JE vaccine Human immunization with inactivated JE vaccine prepared from infected mouse brain was initiated by United States military personnel, and utilized for the JE control strategy in Japan. The first national standard for this vaccine (1954) was revised several times to remove brain materials and prevent pos- sible allergic encephalopathy. The most remarkable improvement was achieved in 1965 through purifica- tion, using ultracentrifugation or alcohol-protamine precipitation to reduce the protein nitrogen content below 0.02 mg/ml. By further technical improve- ments, the current vaccine preparation consists of almost pure virion with a protein nitrogen content <0.01 mg/ml without detectable brain materials. The efficacy of mouse brain-derived JE vaccine was demonstrated by a placebo-controlled double-blind test in China (Province of Taiwan) in 1966. The study also showed that 2 shots of the vaccine were re- quired to obtain appreciable immunity. Another placebo-controlled double-blind test was performed in Kamphanphet Province in Thailand. In this study, three groups were set up: one for Nakayama mono- valent vaccine, the second for Nakayama + Beijing-1 bivalent vaccine, and the third for placebo tetanus toxoid. The idea of a bivalent vaccine group came from the observation that some JE virus strains were better neutralized by anti-Beijing-1 immune serum than by anti-Nakayama immune serum, and vice versa. The result of this study showed that both monovalent and bivalent vaccines were equally ef- fective to prevent JE, with a 91% efficacy rate (22). Follow-up studies on the vaccinees showed that the vaccine efficacy is still observed (B. L. Innis, per- sonal communication). Studies on the vaccination history of JE patients in Japan have shown that only 4.8% had been vacci- nated, in contrast with 62.2% without vaccina- tion (23). On the other hand, the outcome of JE was not significantly related to vaccination history. This may indicate that JE vaccine is effective to block viraemia by neutralizing antibodies but cannot modify the disease outcome once the virus has invaded the central nervous system (CNS). Further evidence for the efficacy of JE vaccination is the change in age-specific JE morbidity before and after mass-vaccination in Japan. In 1955 when vaccination - 302 - was not extensively performed, children 5-9 years showed the highest morbidity, followed by the age group 1-4. In 1967, on the other hand, morbidity among these younger age groups was significantly reduced (probably because mass-vaccination was targeted to the 3-15 year group) while it increased in older age groups. Similar changes were observed in the Republic of Korea as mentioned before. The duration of the neutralizing antibodies among vaccinees was studied in JE-nonendemic Hokkaido Island, in northern Japan, which provided baseline data for establishing a JE vaccination schedule. The National Institute of Health of Japan recommends ~ injec~ions at a week's interval for primary vaccina- tion; this should be followed by a booster immuniza- tion a year later, and the immunity should then be maintained by a booster every 3-4 years. The side effects of the Nakayama strain JE vaccine observed on 60 629 250 vaccinees between 1977 and 1984 were summarized by the Vaccination-induced He~lth Damage Authorization Committee in Japan. !hts report described 13 cases with nervous system involvement (3 each encephalitis and peripheral nerve paralysis, 2 each meningitis and febrile con- vulsion, and 1 each encephalopathy, convulsive dis- orders, and other CNS involvement); 4 cases of systemic serious adverse reactions (3 shock, and 1 sudden death); 7 local adverse reactions (3 rash, 2 each of local reactions and abscess-phlegmon)· and 2 other side effects not clearly documented'. These 26 cases with side effects give a rate of 0.43 per million vaccinations which is less than the cor- responding rate for measles (6.0), BCG (1.55), OPT (0.99) and polio (0.62); it is similar to that of rubella (0.42), and higher than that of influenza vaccine (0.35). Evaluation on the potency and safety of the Japanese-made JE vaccine was performed in the United States (24). The results showed 77% sero- conversion of neutralizing antibody in the vaccinees who received 2 doses at 1-2 week intervals. The rate increased to 99% by the third dose after 6-12 months. The adverse reactions reported by this study were: local pain (18%); headache (9%); ery- thema (6%); swelling (3%); and dizziness, fatigue, somnolence, nausea, chills, fever and lower back pain (<5%). Differences among JE virus isolates and vaccine strains Classical studies on strain variation ot JE virus iso- lates were further analysed by the HI test using MCA (25), oligonucleotide fingerprinting (26) and by nt sequencing of PreM gene region of th~ viral genome (27). Cross-neutralization tests on various JE virus isolates were carried out using immune mouse sera obtained by different strains of JE vaccine. The result indicated that JE virus isolates could be separa~.~d into 2 antigenic subtypes, N_akayama and BetJing-1, as mentioned before (28). Sinc~ a single ~train was preferred for vaccine pro- duction and higher cross-neutralization was ob- served for anti-Beijing-1 serum than anti-Nakayama serum, the National Institute of Health of Japan changed the vaccine strain from the classical Nakayama to Beijing-1 in 1989. At the same time the imm~nizing dose was reduced to 0.5 ml, half the previous volume, and protein content to less than 40 µg/dose. Rationale for the development of the second generation JE vaccine Control of current JE epidemics in developing coun- tries of Asia calls for the development of a novel JE vaccine whi?~ is ine~pensive and can be prepared in large quant1t1es, whtle possessing a degree of po- tency, safety and heat-stability comparable to the current vaccine. Towards this objective, WHO has proposed to develop the second generation JE vac~ine by u_sing recombinant DNA technology. Ex- penme~ts with recombinant yeast, Escherichia co/i, baculov,rus, and vaccinia virus have succeeded in expressing the E protein gene, but the products were of low immunogenicity and unsatisfactory for a vaccine candidate. Experiments to express an E gene product with a~thentic antig~nicity were performed using recom- binant baculov1rus (29), or vaccinia virus (30). The recombinants possessing E gene together with its upstream PreM gene could express the gene product which reacted with a battery of MCA, almost in the same way as authentic E protein. Such a gene product was found on the surface of infected cells and produced neutralizing antibodies in immunized animals. ~uch a recombinant vaccinia virus pro- duc~d ~ h!gh lev~I of long-lasting neutralizing anti- ~od_,es in ,.ml"!1un1zed rabbits and conferred protect- ive 1mmun1ty in mice. Another series of recombinant "'.accinia virus expressed E gene product as a par- ticulate form which was secreted into the infected cul_ture medium and associated with M protein (31). Th,~ co~ponent induced a high level of neutralizing ant1bod1es and protective immunity in mice (32). Further research was carried out to discover dena- turati?n-re~istant, possibly linear, and neutralizing E protein ep1topes by examining cyanogen bromid- cleaved peptides. An 8Kd fragment near the C- terminal of the E protein was found to be im- munogenic in mice (33). A cDNA covering this gene fragment was expressed in recombinant Escherichia ~oli an<:J t~e pr_oduct was shown to induce protective immunity in mice (34). Recent studies in the United States have shown that when 2 cDNA clones corresponding to 5'- and 3'- half of JE virus ANA were combined together in vitro, the resulting DNA molecule could be tran- scribed into ANA. and an infective progeny virus was recovered from the cells transfected with the ANA transcript. This strategy is similar to that documented. for the yellow fever virus, and it has great potential for our understanding of the biologi- cal p_roperties. of the viral gene, such as patho- genic,ty and virulence, at a molecular level, and will eventually provide basic information and techniques to generate genetically engineered live attenuated JE vaccine. It should be mentioned that before being used for humans, extensive purification of the gene product and careful assessment of the recombinant vaccinia virus should be carried out. Conclusion JE continues to be a disease of significant public. health priority in endemo-epidemic areas in several Asian countries. Although human vaccination has Rapp. trimest. statist. sanit. mond., 45 (1992) - 303 - proved to be the most reliable JE control measure in Japan and the Republic of Korea, the amount of JE vaccine currently available is insufficient to conduct mass vaccination in several developing countries. This makes it imperative to develop the second generation JE vaccine. SUMMARY Japanese encephalitis (JE) remains endemo- epidemic in several countries in East, South-East and South Asia. The disease has been under control in Japan since the 1970s owing to mass immunization using mouse-brain-derived inactivated vaccine and to reduced vector mosquito populations. The vector density which was once reduced by wide spraying of insecticides in rice fields showed an increasing trend after the 1980s as a result of mosquito resistance. In the Republic of Korea, the number of JE cases showed a significant decrease after 1983 also be- cause of mass immunization using mouse-brain- derived vaccine. On the other hand, large out- breaks of JE continued to occur in China, Viet Nam, Thailand, India, Nepal and Sri Lanka. In China, a hamster-kidney cell-derived vaccine was developed and used for human immunization. Besides human JE, the fatal outcome of equine JE is an economic problem in China. Current JE vaccine derived from mouse brain is highly purified and its safety and efficacy have been proved by field-tests as well as laboratory experi- ments. In spite of slight antigenic differences among JE virus isolates, JE vaccine produced by a classical Nakayama strain was effective in preventing overt JE in a field study in Thailand. The technology of mouse-brain-derived inactivated JE vaccine produc- tion was transferred from Japan to India, Thailand and Viet Nam. The production of JE vaccine in these countries is still on a pilot scale and insufficient for mass-immunization of susceptible target popula- tions. In order to overcome this problem, the development of the second generation JE vaccine was proposed to provide inexpensive vaccine in large quantities. Studies on the molecular biology of JE virus clarified the entire nucleotide sequence of genomic RNA showing a similar genome organization as other flaviviruses such as yellow fever virus. Antigenic analysis on the envelope glycoprotein E by mono- clonal antibodies revealed multiple epitopes with various biological characteristics and antigenic cross-reactivity. One of the epitopes was JE virus- specific and neutralizing. Since the isolated E protein was shown to be an immunogenic and protective antigen, several studies were performed to express E-protein gene using recombinant DNA technology. Studies using recombinant baculovirus or vaccinia virus showed that the presence of the upstream PreM gene was required in order to express an E-protein gene product which possessed antigenicity almost similar to authentic E protein. Such a gene product was immunogenic to elicit neutralizing anti- bodies and conferred protection in experimental ani- mals. Another recombinant vaccinia virus construct with an entire E and PreM gene could express the inserted gene as a particulate form in the infected cell-culture fluid. Such a form of gene product could facilitate further purification which is required for further practical use. Another line of the study was directed to produce a denaturation-resistant and thus possibly a linar epitope of an E-protein gene by recombinant E. coli. The gene product obtained from SOS-PAGE gel of such recombinant could elicit neu- tralizing antibodies and conferred protection in mice. Careful studies related to potency and safety should be performed before any recombinant gene products are actually used. RESUME L'encephalite japonaise: epidemiologie et lutte L'encephalite japonaise reste a l'etat endemo- epidemique dans plusieurs pays de l'Asie de l'Est, du Sud-Est et du Sud. Au Japan, la maladie est maitrisee depuis les annees 70 grace a des campa- gnes de vaccination de masse avec un vaccin inacti- ve prepare sur cerveau de souris et a la reduction des populations de moustiques vecteurs. Le traite- ment a grande echelle des rizieres par des insectici- des a permis de reduire la densite des vecteurs, mais celle-ci recommence a croitre depuis les an- nees 80, par suite de la resistance developpee par les moustiques. En Republique de Coree, le nombre de cas d'encephalite japonaise a amorce un recul sensible a partir de 1983, egalement par suite de campagnes de vaccination de masse au moyen du vaccin prepare sur cerveau de souris. En revanche, d'importantes flambees se produisent encore en Chine. On a mis au point un vaccin prepare sur cellules renales de hamster qui est utilise pour la Wld hlth statist. quart., 45 (19921 vaccination humaine. Dans ce pays, outre les cas humains d'encephalite japonaise, l'issue fatale de l'encephalite japonaise equine pose un probleme economique. Le vaccin actuel, prepare sur cerveau de souris, est d'une tres grande purete et des essais en situation reelle, de meme que des epreuves de laboratoire, ont permis d'en affirmer l'innocuite et l'efficacite. Malgre !'existence de legeres differences antigeni- ques entre les divers isolements du virus, le vaccin produit a partir de la souche classique Nakayama a permis une prevention efficace des manifestations cliniques de l'encephalite japonaise lors d'une etude sur le terrain en Tha"ilande. Le Japan a communique sa technologie de production du vaccin inactive prepare sur cerveau de souris a l'lnde, a la Thai"lande et au Viet Nam. La production de vaccin dans ces pays en est encore a !'echelon pilote et reste insuffi- - 304 - sante pour la vaccination de masse des groupes de population sensibles. Pour resoudre le probleme, ii a ete propose de developper un vaccin de deuxieme generation qui serait produit en grande quantite et a bas prix. L'etude du virus par les methodes de la biologie moleculaire a permis de determiner en totalite la sequence nucleotidique de l'ARN genomique, et montre que le genome viral etait organise comme celui des autres flavivirus, notamment le virus ama- ril. L'analyse antigenique de la glycoproteine E d'en- veloppe a l'aide d'anticorps monoclonaux a revele la presence d'epitopes multiples biologiquement diver- sifies et mis en evidence !'existence d'une reactivite croisee. Un des epitopes etait specifique de ce virus et suscitait une activite neutralisante. Etant donne que lorsqu'elle est isolee, la proteine E est immuno- gene et protectrice, plusieurs equipes ant tente d'ex- primer le gene qui code pour cette proteine au moyen des techniques du genie genetique. Les tra- vaux portant sur l'emploi de baculovirus au de virus de la vaccine comme vecteurs d'expression ant montre que la presence du gene PreM etait necessai- re a !'expression d'une proteine E presentant une antigenicite presque analogue a celle de la protei- ne E originelle. Ce produit genique s'est revele suffi- samment immunogene pour declencher une reponse en anticorps neutralisants et conferer une protection a des animaux de laboratoire. Un autre vecteur d'expression, constitue de virus vaccinal recombi- nant porteur de la totalite des genes E et PreM, pourrait exprimer le gene insere sous forme particu- laire dans le liquide de culture cellulaire infecte. Sous cette forme, le produit genique se preterait davantage a la purification plus poussee que suppo- se !'utilisation pratique. Une autre partie de l'etude a ete consacree a la production d'un epitope resistant a la denaturation, et done vraisemblablement lineai- re, par un gene de la proteine E insere dans une E. coli recombinante. Le produit genique obtenu a partir du gel SOS-PAGE a pu susciter la formation d'anticorps neutralisants et conferer une protection a la souris. II convient d'etudier avec soin l'activite et l'innocuite de tous ces produits obtenus par genie genetique avant de pouvoir les utiliser de maniere effective. REFERENCES- REFERENCES 1. WESTAWAY, E. G. ET AL. Flaviviridae. lntervirology, 24: 183-192 (1985). 2. CALISHER, C. H. ET AL. 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Insecticidal resist- ance of Cu/ex tritaeniorhynchus (Diptera: Cul- icidae) in Japan: genetics and mechanisms of re- sistance to organophosphorous insecticides. Journal of medical entomology, 24: 595-603 (1987). 15. YASUTOMI, K. & TAKAHASHI, M. Insecticidal resist- ance of Cu/ex tritaeniorhynchus (Diptera: Cul- icidae) in Japan: a country-wide survey of resist- ance to insecticides. Journal of medical entomo- logy, 24: 604-608 (1987). 16. WATANABE, M. [Annual trend of Japanese en- cephalitis virus contamination and relation with insecticidal resistance of Cu/ex tritaeniorhynchus in Toyama Prefecture]. Life and environment 33: 33-38 (1988). (In Japanese). 17. TAKASHIMA, I. ET AL. Ecological studies of Japanese encephalitis virus in Hokkaido: interepidemic out- breaks of swine abortion and evidence for the virus to overwinter locally. American journal of tropical medicine and hygiene, 38: 420-427 (1988). 18. IGARASHI, A. ET AL. Flavivirus infections in Chiang Mai Areas, Thailand. South-East Asian journal of tropical medicine and public health, 14: 470-480 (1983). 19. BURKE, D. S. ET AL Intense transmission of Japan- ese encephalitis virus to pigs in a region free of epidemic encephalitis. JE & HFRS bulletin, 1: 17- 26 (1986). 20. V1TARANA, T. ET AL The 1985/86 Japanese en- cephalitis outbreak in Sri Lanka and the impact of new irrigation schemes. In: Tongcharoeng, P. & Kurstak, E. (eds), Virus diseases in Asia. Bangkok, Mahidol University, 1988. 21. YOSHIDA, I. ET AL. Establishment of an attenuated ML-17 strain of Japanese encephalitis virus. Bikenjournal, 24: 46-67 (1981). Rapp. trimest. statist. sanit. mond., 45 ( 1992) - 305 - 22. HOKE, C. H. ET AL Protection against Japanese en- cephalitis by inactivated vaccines. New England journal of medicine, 319: 608-614 (1988). 23. KITANO, T. [Japanese encephalitis vaccine]. Clinics and drug therapy, 9: 707-711 (1990). (In Japanese). 24. POLAND, J. D. ET AL Evaluation of the potency and safety of inactivated Japanese encephalitis vac- cine in US inhabitants. Journal of infectious diseases, 161: 878-882 (1990). 25. KOBAYASHI, Y. ET AL. Antigenic analysis of Japan- ese encephalitis virus using monoclonal anti- bodies. Infection and immunity, 44: 117-123 (1984). 26. HORI, H. [Oligonucleotide fingerprint analysis on Japanese encephalitis virus strains of different geographic origin]. Tropical medicine, 28: 179- 190 (1986). (In Japanese). 27. CHEN, W.-R. ET AL Genetic variation of Japanese encephalitis virus in nature. Journal of general virology, 71: 2951-2922 (1990). 28. OYA, A. New development of criteria on Japan- ese encephalitis vaccine requirements in Japan. JE & HFRS bulletin, 2: 11-13 (1987). 29. MATSUURA, Y. ET AL Characterization of Japanese encephalitis virus envelope protein expressed by Wld hlth statist. quart., 45 (1992) recombinant baculoviruses. Virology, 173: 67 4- 682 (1989). 30. YASUDA, A. ET AL Induction of protective im- munity in animals vaccinated with recombinant vaccinia viruses that express PreM and E gly- coproteins of Japanese encephalitis virus. Journal of virology, 64: 2788-2795 ( 1990). 31. MASON, P. W. ET AL Japanese encephalitis virus- vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infec- tion. Virology, 180: 294-305 (1991). 32. KONISHI, E. ET AL Comparison of protective im- munity elicited by recombinant vaccinia viruses that synthesize E or NS1 of Japanese encephal- itis virus. Virology, 185: 401-410 (1991). 33. SRIVASTAVA, A. K. ET AL. lmmunogenicity of pep- tides cleaved by cyanogen bromide from Japan- ese encephalitis virus envelope glycoprotein E. Acta virologica, 34: 228-238 (1990). 34. SRIVASTAVA, A. K. ET AL. Japanese encephalitis virus fusion protein with protein A expressed in Escherichia coli confers protective immunity in mice. Microbiology and immunology, 35: 863- 870 (1991). - 306 - INFLUENZA - ITS IMPACT AND CONTROL Y. Ghendon• Influenza has long been recognized as a problem in both industrialized and developing nations. During an ordinary epidemiological season, about 10% of the world's population catch influenza, i.e. some 500 million people. Influenza epidemics may spread from one end of the world to another within a few months. The spread is highly favoured by the increasing speed and pro- portions of modern intercountry travel. Once the infection has been implanted in a receptive popula- tion, factors such as humid and cold weather, indoor life and crowded public transport (which intensify the frequency of contacts) may trigger the epidemic wave. The cost of influenza Influenza A infections are a predictable cause of excess mortality. For example, in the United States of America in 1957 the Asian strain of influenza virus caused an estimated 70 OOO deaths; the Hong Kong virus that appeared in 1968 caused about 30 OOO deaths in the United States alone (1). Even without the appearance of a new virus, each year many people die as a result of influenza infection. Deaths from influenza may result from the destruc- tion of lung tissue in influenza pneumonia, but can also be due to cardiopulmonary or other chronic diseases that are exacerbated during influenza infec- tion. At least 10 OOO excess deaths have been docu- mented in the United States during each of 18 different epidemics registered from 1957 to 1985. Between 80% and 90% of the excess deaths attri- buted to pneumonia and influenza during epidemics occur among persons 65 years of age or more. During the 1987 influenza outbreak in the United Kingdom, influenza and pneumonia were respon- sible for the death of about 7 700 people, most of them in the age group over 70. However, influenza affects all age groups and the age-specific incidence rate is actually highest in children between 1 and 14 years and nearly 4 times (37%) that estimated for the population aged 60 years or more (10%) (1). Hospitalization rates are relatively uniform for ages 5-44 and highest in age groups ~5 and ;,s,65. The death rate is low in children (2.7 per 100 OOO) and highest in the over-65 age group (75.9 per 100 OOO) (2). Days lost from school and work, and hospitalizations required for complications of influenza infection, re- sult in a very high cost to society. In the United States, for example, hospitalization rates for adults with high-risk medical conditions increase two- to • Senior Virologist, Microbiology and Immunology Support Ser- vices, Division of Communicable Diseases, World Health Organiza· tion, Geneva. fivefold in different age groups during major epi- demics, reaching a maximum rate of about 800 excess hospitalizations per 100 OOO high-risk persons (1, 2); hospitalization costs exceed US$300 million for each epidemic. According to 1985 estimates of disease-burden value and costs associated with treatment, the cost of influenza was between 4 and 50 times higher than other common infectious diseases (1). It has been estimated in the United States that about 70 million people catch influenza at a cost of about US$4.5 billion during an influenza outbreak (1, 3). Vaccination could have prevented 80% of these in- fections and saved about US$2.5 billion. The 1974-1975 influenza epidemic in the United Kingdom was not one of the more severe in recent decades, but its estimated cost in loss of produc- tivity was £100 million (4). The use of influenza vaccine In spite of influenza infection being a widespread problem in many industrialized and developing countries, the existing influenza vaccines are among the least utilized. The need for annual revaccination, misconceptions about the capabilities of the vaccine - many recipients expect them to prevent all respi- ratory infections - and unanswered questions about their efficacy in high-risk persons and populations have led many physicians to conclude that vaccina- tion against influenza was not worth the effort. The needs and means of influenza control were discussed at a WHO meeting in 1986 (5) which stressed that influenza remains an important dis- ease, causing high levels of morbidity at unpredict- able intervals, usually every few years. It was rec- ognized that the vaccine cannot prevent epidemics, largely due to the emergence of antigenic variants. However, it was recommended that studies designed to assess vaccine efficacy should include their ability not only to protect the vaccinees but also to reduce the impact of influenza epidemics in the community. There is no dearth of data available on the efficacy of influenza vaccine to prevent morbidity and mor- tality (4). Studies of a large metropolitan population of non-institutionalized ambulatory elderly persons during several recent influenza epidemics in the United States have consistently shown a reduction in morbidity of approximately 70% among vaccinees when the virus inducing the outbreak and the virus used for the production of influenza vaccine are immunologically closely related. It has been estimated that 60% of residents in United States nursing homes may be affected during an outbreak, and up to 25% of patients die or develop life-threatening complications. A series of some Rapp. trimest. statist. sanit. mond., 45 (1992) - 307 - 20 published and unpublished observational studies of influenza outbreaks showed evidence of vaccine efficacy (4). Some of these studies indicated that "herd immunity" may be an important phenomenon worthy of consideration in determining the spread of influenza virus in the institutional setting. In one study nursing homes which experienced sustained spread of influenza were compared with nursing homes in which only sporadic cases occurred (5). It was found that the former had significantly lower levels of vaccination (median of 51% and 81% of residents vaccinated respectively). This suggests that herd immunity may be achieved with institutional vaccination rates in the vicinity of 80%. Who should be vaccinated? Influenza vaccines are in routine use in many coun- tries and mainly recommended for persons with chronic disease and at increased risk of influenza complications. However, only a small percentage of the high-risk groups are vaccinated. For example in the United States, 43 million persons are at risk of death from influenza by virtue of underlying ill- nesses. In reality, only 8 million receive the vaccine. In the United Kingdom, the high-risk groups include 10 million people but again, only a small proportion is vaccinated each year. It is not realistic to expect influenza vaccines to prevent the spread of the disease in the community as vaccines against measles and poliomyelitis do, but the impact of influenza epidemics can be redu- ced by vaccines made from the appropriate strains of influenza viruses and used at the right time. The priority group for influenza vaccination are those at greatest risk of influenza-related com- plications: adults and children with chronic disorders of the pulmonary or cardiovascular systems requir- ing regular medical follow-up or hospitalization dur- ing the preceding year (including children with asthma); residents of nursing homes and other chronic-care facilities housing patients of any age with chronic medical conditions. Other priority groups for influenza vaccine are those at moderate risk of influenza-related complications: other healthy persons ;,,55 years old; adults and children who have required regular medical follow- up or hospitalization during the preceding year be- cause of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, haemo- globinopathies or immunosuppression; children and teenagers (aged 6 months to 18 years) who are receiving long-term aspirin therapy and, therefore, may be at risk of contracting Reye's syndrome after an influenza infection. In addition, groups potentially capable of noso- comial transmission of influenza to high-risk per- sons: physicians, nurses and other personnel who have extensive contact with high-risk patients (e.g. primary-care and certain speciality clinicians and staff of chronic-care facilities and intensive-care units, particularly neonatal intensive-care units). Pro- viders of home care to high-risk persons (e.g. visit- ing nurses, volunteer workers) as well as all house- hold members of high-risk persons, including children, whether or not they provide care. Among the general population, influenza vaccine should be administered to all persons who wish to reduce their chances of acquiring influenza infection. Wld hlth statist. quart., 45 (19921 Persons who provide community services may be considered for vaccination to minimize the disrup- tion of essential activities during severe epidemics. Vaccine types Both inactivated and live attenuated virus vaccines are available for influenza prophylaxis (4). Inacti- vated vaccines are in routine use in many countries. In most of these countries the vaccines are recom- mended for risk groups, but in some countries vaccination is extended to mass campaigns of healthy adults or children. Cold-adapted (ea) recom- binant live attenuated virus vaccines were recently developed in several countries. Clinical studies suggest that these vaccines can afford good protec- tion in healthy children and in adults (4). Such a vaccine is used for mass immunization of adults and schoolchidren in the republics of the former USSR. Comparative studies of the efficacy of inactivated and ea live virus vaccines showed a greater efficacy of the inactivated vaccine in adults and older children, while among young children the live virus vaccine was more effective (6). Biological mechanisms of protection The strategy for influenza control must be based on the mechanisms of immunity to influenza in humans. At present, most information on these mechanisms has been obtained in animal models. It is clear that previous infection of humans with an identical strain of virus confers immunity upon later challenge and that this immunity can be both solid and long-lasting, as shown by the resistance of the population over 20-25 years to H1N1 influenza virus infection on the reappearance of this subtype in 1977, 20 years after the last H1N1 outbreak. High titres of haemagglutinin-inhibiting antibody are associated with protection against a virus with a closely related haemagglutinin (HA). Resistance to influenza infection in humans has been correlated with HA antibody in nasal washings also in the absence of serum antibody (7). On the other hand, studies of maternally transferred antibody in neonates have shown that serum antibodies alone may contribute to resistance. Cell-mediated immunity appears to be responsible for the recovery process from influenza infection (8). Since local and serum antibodies and also cytotoxic T-cells (Tc-cells) appear to be mediators of immunity to influenza infection, it is important that influenza vaccines induce all these components of immunity. Comparative studies of inactivated and ea live in- fluenza virus vaccines have shown the inactivated vaccine to induce serum lgA and lgC in most vacci- nees contrary to the live vaccine. The inactivated vaccines also induced higher titres of serum anti- bodies than the live vaccine. However, only 38% of vaccinees having received the inactivated vaccines showed a local lgA response compared with 83% of vaccinees immunized with ea live vaccine (7). Another study showed that pre-challenge local lgA, detected almost exclusively in subjects naturally in- fected or vaccinated with ea live vaccine, was asso- ciated with protection against shedding. Also low levels of nasal lgA (>1 109 2 ) suppressed viral shedding. The effect of nasal lgG was not as clearly - 308 - demonstrated but at higher levels (>41092 ) shedding was reduced (7). The ability of influenza vaccines to stimulate the Tc cell response has not been determined in unprimed humans but ea live influenza virus vaccine induces a primary Tc cell response in mice and sensitizes the lungs for a secondary Tc cell response (6, 7). Another factor influencing the efficacy of influenza vaccines is the appearance of drift variants of in- fluenza virus. One study indicates decreasing pro- tective effect of repeated vaccinations with inactiv- ated vaccine even when the vaccine viruses matched the prevailing epidemic strains. On the other hand, natural infection with live influenza virus afforded almost complete protection during successive out- breaks involving drift variants for more than 4 years (9). It is possible that the local administration of a live attenuated influenza virus vaccine which would mimic natural influenza infection provides a more long-lasting and broadly reactive immunity than the inactivated vaccine. However, the factors responsible for protection in humans need to be further eluci- dated before any clear conclusions can be drawn about the efficacy of inactivated vs. live virus vaccines. Antiviral drugs In addition to vaccines, several antivirals are effec- tive against influenza. Two drugs, amantadine and rimantadine, have shown 70-90% efficacy in protect- ing against influenza A in controlled studies (10). Influenza surveillance Influenza surveillance plays an important part in the control of influenza (11, 12). The main objectives of influenza surveillance are: • to allow the early detection of influenza outbreaks and identification of the causative agent. The early warning should permit health providers to prepare for a possible increased demand on health care services and to warn the general practitioners in order that they may carry out vaccinations among persons at risk who have not yet been vaccinated; • to permit estimates of the impact of the influenza by collection and analysis of influenza morbidity and mortality data; • to provide influenza virus isolates from outbreaks and sporadic cases for analysis of antigenic char- acteristics required for the decision about variants to include in influenza vaccines; • to detect population groups at increased risk of complications from influenza which are not cur- rently specified in recommendations for the use of influenza vaccine. The true morbidity and mortality from influenza are difficult to estimate in most countries by simply reporting influenza-like illness or acute respiratory diseases. Without laboratory confirmation, illnesses may be erroneously attributed to influenza viruses. On the other hand, diseases and deaths induced by influenza viruses without physician contact or occurring after acute symptoms have subsided will be underreported. Analysis and comparisons of the impact of influenza and benefit of influenza vaccination in different countries are also difficult because surveillance sys- tems and methods vary from country to country. The laboratory element of influenza surveillance appears to be globally both more uniform and avail- able than statistical observations. However, both lab- oratory services and capabilities to isolate and char- acterize respiratory viruses other than influenza need to be expanded in many parts of the world. In many countries influenza surveillance is based on groups of physicians (sentinel physicians) volun- teering to report weekly on the extent of influenza- like illness. The number of physicians participating in such surveillance systems ranges from about 40 to several hundred. Their interest and experience accumulated over several years result in a high degree of year-to-year consistency despite the range of symptoms presented. Using patient contacts as denominator and acute respiratory illness/influenza-like illness as numerator, a statistical model can be developed of morbidity baselines which permit the clear demonstration of epidemics that exceed the expected baseline. The approach for statistical modelling is similar to that tested by WHO (13) and used over many years in the United States (14) to assess mortality, and per- mits the definition of an epidemic threshold. Laboratory investigation of a subset of patients can be organized by providing the physicians with speci- men collection transport kits for throat or nasal swabs to be mailed to a central laboratory. A com- bination of direct antigen detection and rapid culture methods permit quick and efficient responses to the physicians. About 30-50% of specimens collected by trained surveillance physicians can be positive for influenza and other respiratory viruses including RSV. It is desirable that the surveillance system provide a measure of severity. A simple measure can be ob- tained through analysis of weekly mortality reports for an entire region or for major cities. The reports can be either influenza and pneumonia deAths (selected by a trained worker in the office receiving death certificates) or, since influenza epidemics are an almost unique event leading to excess mortality, the total number of deaths. The total number of deaths is often available sooner and more readily. After about 5 years of data collection, statistical baselines can be established and major epidemics of mortality readily detected. Another possible surveillance system is based on the collection of reports of hospital admissions for respiratory illnesses. As more hospitals install effec- tive computer systems to monitor patient admis- sions and discharges, such data may be quickly made available without jeopardizing patient privacy. Other approaches to surveillance used in certain countries include recording the number of emer- gency hospital bed services, home visits by emer- gency physicians, statistics on sales of pharmaceu- ticals, data on social security sickness claims, or absenteeism from schools or work. WHO influenza programme The emphasis of the WHO influenza programme established in 1947 is on rapid isolation and char- Rapp. trimest. statist. sanit. mond., 45 (1992) - 309 - acterization of new strains needed for effective vaccines. It is in constant communication with a network of 110 WHO-recognized national institutions for influenza designated by governments in 79 countries, and with 3 WHO collaborating centres for reference and research on influenza. Data on recent influenza activity worldwide collected through the network are published in the Weekly epi- demiological record. National institutions for influenza isolate influenza viruses and send them to the WHO collaborating centres for influenza for analysis of the antigenic characteristics, mainly of the haemagglutinin. The national laboratories make a preliminary identifica- tion of current isolates with diagnostic reagents which are updated, produced and distributed by the WHO Collaborating Center for Influenza Reference and Research at the Centers for Disease Control in Atlanta, United States. Each year, at the end of February, WHO issues the recommendations for the composition of influenza vaccines to be used in the forthcoming epidemiolo- gical season. The recommendations (15) are based on various information sources including epi- demiological data, antibody prevalence surveys, data from vaccine trials and results of studies of antigenic characteristics of influenza viruses isolated in dif- ferent countries. This programme and network of collaborating cen- tres and national institutions on influenza enable WHO to keep its Member States informed on in- fluenza occurrence and antigenic characteristics of any new variant of the virus, and to make new viruses available for vaccine production. Influenza is not a trivial disease; it kills thousands of people and puts a heavy load on national economies every year, but it can be prevented. Using vaccines and antivirals, it is possible to protect both the individuals in high-risk groups and defined subsets of the population. SUMMARY Influenza is an underestimated public health prob- lem. Epidemics spread rapidly from country to country and may affect as many as 500 million people across the world in a moderate influenza year. The disease, particularly influenza A, kills and the new influenza viruses which appeared in 1957 (Asian influenza) and 1968 (Hong Kong) are estima- ted to have caused at least 100 OOO deaths in the United States of America. Deaths from influenza also occur in years when there is no new virus; at least 10 OOO excess deaths have been documented in the United States during each of 18 different epidemics recorded from 1957 to 1985. Although most deaths are among the elderly, influenza occurs in all age groups with repercussions in schools and work places, and on hospital resources, at a high cost to society. As many as 79-80% of influenza cases can be pre- vented when the virus inducing the outbreak and the virus used in the influenza vaccine are closely re- lated. Preventing 80% of cases would correspond in the United States to a saving of US$2.5 billion. People at the greatest risk of influenza-related com- plications are adults and children with chronic dis- orders of the pulmonary or cardiovascular systems, residents of nursing homes and of facilities for patients with chronic medical conditions. Other priority groups for vaccination are those at moderate risk of influenza-related complications such as healthy elderly persons, people with chronic meta- bolic diseases, children and teenagers on long-term aspirin therapy. Groups potentially capable of trans- mitting influenza to high-risk persons should also be vaccinated. These include all health care personnel who have extensive contact with high-risk patients. Among the general population, influenza vaccine should be administered to all persons who wish to reduce their chances of acquiring influenza infection and to those providing community services, in order to minimize the disruption of essential activities during epidemics. Both inactivated and live attenuated virus vaccines are available. Comparative studies of the efficacy of Wld hlth statist. quart., 45 (1992) two vaccine types showed a greater efficacy of the inactivated vaccine in adults and older children, while among young children the live virus vaccine was more effective. The strategy for influenza control must be based on the mechanisms of immunity to influenza in humans. Most information is derived from animal studies but it is evident that in humans previous infection confers immunity upon later challenge with an identical virus and that this immunity can be both solid and long-lasting. It is possible that the local administration of a live attenuated influenza virus vaccine which would mimic natural influenza infec- tion provides a longer lasting and more broadly reactive immunity than the inactivated vaccine. How- ever, the factors responsible for protection in humans need to be further elucidated before any clear conclusion can be drawn about the efficacy of inactivated vs. live virus vaccines. In addition to vaccines, several antivirals are effective against in- fluenza. Two drugs, amantadine and rimantadine, have shown 70-90% efficacy in protecting against influenza A. Influenza surveillance plays an important part in the control of the disease. The main objectives of in- fluenza surveillance are the early detection of influenza outbreaks and the identification of the causative agent. Surveillance systems should allow for estimates of the impact of influenza on morbidity and mortality data and provide the influenza virus isolates required for deciding on influenza vaccine composition and vaccine production. Surveillance should also help detect population groups at in- creased risk of complications from influenza which are not currently specified in recommendations for the use of influenza vaccine. The emphasis of the WHO influenza programme established in 1947 is on the rapid isolation and characterization of new strains needed for effective vaccines. It is based on a network of 110 WHO- recognized national institutions for influenza des- ignated by governments in 79 countries and 3 WHO - 310 - collaborating centres for reference and research on influenza. The national laboratories isolate influenza viruses and send them to the collaborating centres for analysis of the antigenic characteristics. Each year at the end of February, WHO issues recom- mendations for the composition of influenza vaccines to be used in the forthcoming epidemiolo- gical season. The recommendations are based on various information sources including epidemiologi- cal data, antibody prevalence surveys, data from vaccine trials and results of studies of antigenic characteristics of influenza virus isolates in different countries. RESUME La grippe - impact et lutte On sous-estime la grippe en tant que probleme de sante publique. Les epidemies se propagent rapide- ment d'un pays a l'autre et au cours d'une annee moyenne, jusqu'a 500 millions de personnes peu- vent etre touchees dans le monde par la maladie. Elle peut etre mortelle, en particulier la grippe A, et les nouveaux virus qui ant fait leur apparition en 1957 (grippe asiatique) et en 1968 (Hong Kong) ant cause, selon les estimations, au mains 100 OOO deces aux Etats-Unis d'Amerique. Des deces peuvent egalement se produire les annees ou aucun nouveau virus n'apparait; aux Etats-Unis, on a ob- serve une surmortalite d'au mains 10 OOO deces lors de chacune des 18 epidemies enregistrees entre 1957 et 1985. Bien que ces deces frappent surtout les personnes agees, la grippe touche tous les groupes d'age avec les consequences que l'on sait sur la scolarite, l'activite professionnelle et les ressources hospitalieres, le coat en etant tres eleve pour la societe. Lorsque les virus responsables de la flambee et ceux qui entrent dans la composition du vaccin antigrip- pal sont tres proches, on peut eviter jusqu'a 79-80% des cas de grippe. Aux Etats-Unis, prevenir 80% des cas reviendrait a economiser US$2,5 milliards. Ce sont les adultes et les enfants porteurs d'infections pulmonaires ou cardio-vasculaires chroniques qui sont les plus exposes aux risques de complications, de meme que les pensionnaires des etablissements de soins et les malades hospitalises pour longue maladie. Parmi les autres groupes a vacciner en priorite figurent ceux qui sont exposes a un risque modere de complications comme les personnes agees en bonne sante, les personnes souffrant de troubles metaboliques chroniques, les enfants et les adolescents qui suivent un traitement au long cours par l'aspirine. II faudrait egalement vacciner les groupes qui pourraient transmettre la grippe aux personnes a haut risque. II s'agit notamment de tous les personnels soignants qui sont largement en con- tact avec les malades a haut risque. Dans la popula- tion generale, ii faudrait vacciner toutes les person- nes qui souhaitent eviter la maladie ainsi que celles qui assurent les principaux services collectifs afin de reduire au minimum la desorganisation des activites essentielles pendant les epidemies. II existe des vaccins a base de virus inactive et de virus vivant attenue. L'etude comparee de leur effica- cite respective montre que le vaccin inactive est plus efficace chez l'adulte et les grands enfants alors que, chez les jeunes enfants, c'est le virus vivant qui est le meilleur. La strategie de la lutte antigrippale doit se fonder sur le mecanisme de l'immunite vis-a-vis de la maladie. Pour l'essentiel, la connaissance qu'on en a provient d'etudes sur !'animal, mais ii est evident que, chez l'homme, une infection anterieure confere une im- munite contre une infection ulterieure par un virus identique, l'immunite pouvant etre a la fois solide et durable. II est possible que !'administration locale d'un vaccin vivant attenue, qui simulerait une infec- tion grippale naturelle, soit capable de conferer une immunite plus large et plus durable que le vaccin inactive. Toutefois, une meilleure connaissance des facteurs qui conditionnent la protection chez l'hom- me est necessaire avant qu'on puisse se prononcer sur l'efficacite respective du vaccin inactive et du vaccin vivant. Outre les vaccins, un certain nombre d'antiviraux sont efficaces contre la grippe. Deux d'entre eux, l'amantadine et la rimantadine, sont capables d'assurer une protection de 70-90% contre la grippe A. La surveillance joue un role important dans la lutte contre la grippe. Ses principaux objectifs sont la detection precoce des flambees epidemiques et !'identification de !'agent etiologique. Les systemes de surveillance doivent prendre en compte !'impact estimatif de la grippe sur les donnees de morbidite et de mortalite et fournir les isolements de virus grippaux qui sont necessaires pour decider de la composition du vaccin et de sa production. Ces systemes devraient egalement aider a mettre en evidence les groupes de population qui courent un risque accru de complications non encore prises en compte dans les recommandations pour !'utilisation du vaccin grippal. Le programme Grippe de l'OMS, cree en 1947, s'at- tache tout particulierement a l'isolement et a la caracterisation rapides des nouvelles souches en vue de la production de vaccins efficaces. II repose sur un reseau de 110 instituts nationaux de la grippe reconnus par l'OMS et designes par les gouverne- ments respectifs de 79 pays ainsi que sur 3 centres collaborateurs OMS de reference et de recherche pour la grippe. Les laboratoires nationaux isolent les virus et les expedient aux centres collaborateurs en vue d'une analyse antigenique. Fin fevrier de chaque annee, l'OMS emet des recommandations pour la composition des vaccins antigrippaux a utiliser lors de la saison epidemiologique a venir. Ces recom- mandations s'appuient sur diverses sources d'infor- mation: donnees epidemiologiques, enquetes sur la prevalence des anticorps, donnees tirees d'essais vaccinaux et resultats des travaux de laboratoire sur les caracteristiques antigeniques des virus grippaux isoles dans les divers pays. Rapp. trimest. statist. sanit. mond., 45 (1992) - 311 - REFERENCES - REFERENCES 1. USA INSTITUTE OF MEDICINE. COMMITIEE ON ISSUE AND PRIORITIES FOR NEW VACCINE DEVELOPMENT. New vaccine development, establishing priorities. 1985-87 - I. Diseases of importance in the Uni- ted States. Washington, D.C., National Academy of Sciences, 1985. 2. COUCH, R. W ET AL. Influenza: its control in person and population. Journal of infectious diseases, 153 (3): 431-440 (1986). 3. Safeguarding profits with a shot in the arm. Accountancy age: 8 June (1989). 4. SCHOENBAUM, S. C. Economic impact of influenza - The individual's perspective. American journal of medicine, 82 (Supplement 6A): 26-30 (1987). 5. Progress in the development of influenza vac- cines: Memorandum from a WHO meeting. Bulletin of the World Health Organization, 65 (3): 289-293 (1987). Progres relatifs a la mise au point des vaccins antigrippaux: Memorandum d'une Reunion de l'OMS. Bulletin de /'Organisation mondiale de la Sante, 65 (4): 465-470 (1987). 6. GHENDON, Y. Vaccination against influenza vi- ruses: current status. Advances in biotechnologi- cal processes, 14: 159-201 (1990). 7. PATRIARCA, P. ET AL Risk factors for outbreaks of influenza in nursing homes: a case-control study. American journal of epidemiology, 124 ( 1 ): 114- 119 (1986). 8. CLOVER, R. D. ET AL Comparison of heterotypic protection against influenza A[Taiwan/86 (H1N1) by attenuated and inactivated vaccines to Al Wld hlth statist. quart., 45 (1992) Chile/83-live viruses. Journal of infectious dis- eases, 163 (1): 300-304 (1990). 9. GHENDON, Y. The immune response to influenza infection. Acta virologica, 34 (3): 295-304 (1990). 10. ADA, G. L. & JONES, P. D. The immune response to influenza infection. Current topics in micro- biology and immunology. 128: 1-54 (1986). 11. HOSKINS, T. W. ET AL. Assessment of inactivated influenza A vaccine after three outbreaks of in- fluenza A at Christ's Hospital. Lancet, i: 33-35 (1979). 12. WHO Technical Report Series, No. 754, 1987. (Progress in the development and use of anti- viral drugs and interferon: report of a WHO Scientific Group). OMS Serie de Rapports techniques, N° 754, 1988 (Progres de la mise au point et de /'utilisation des antiviraux et de /'interferon: rapport d'un groupe scientifique de l'OMS). 13. GHENDON, Y. Influenza surveillance. Bulletin of the World Health Organization, 69 (5): 509-515 (1991). GHENDON, Y. Surveillance de la grippe. Bulletin de /'Organisation mondiale de la Sante, 69 (6): 649-656 (1991 ). 14. Report of WHO/GEIG meeting on the standardi- zation and improvement of influenza surveil- lance. Bulletin of the World Health Organization: (In press). 15. AssAAD, F. ET AL Use of excess mortality from respiratory diseases in the study of influenza. Bulletin of the World Health Organization, 49 (3): 219-233 (1973). WORLD HEALTH ORGANIZATION PUBLICATIONS ICD-10 International Statistical Classification of Diseases and Related Health Problems Tenth Revision NOW AVAILABLE FOR ORDERING Volume 1 Tabular List The first volume, which runs well over 1 ,OOO pages, contains the classifica- tion at the three- and four-character levels, the classification of the mor- phology of neoplasms, special tabu- lation lists for mortality and morbidity, definitions. and the nomenclature regulations. The volume also repro- duces the report of the International Conference for the Tenth Revision. which indicates the many complex considerations behind the revisions. ISBN 92 4154419 8 Sw.fr.130.-/US$117.00 """"~ ~ International () Statistical Classification of Diseases and tJ Related Health Problems \ Tenth RevlSlon ~ -· 0 (t) --- - .... IN PREPARATION Volume 2 Instruction Manual The second volume consolidates notes on certification and classifica· tion formerly included in Volume 1. supplemented by a great deal of new background information. instructions. and guidelines for users of the tabular list. Detailed explanations of the tabu- lations are complemented by exten- sive practical advice on their use. Historical information about the de· velopment of the classification, which dates back to 1893, is also included. ISBN 92 4 1 54420 1 Revised, refined, and vastly expanded in scope IN PREPARATION voiume 3 Alphabetical Index The final volume presents the de- tailed alphabetical index. Expanded introductory material is comple- mented by practical advice on how to make the best use of the index. To facilitate efficient coding, the index includes numerous diagnostic terms commonly used as synonyms for the terms officially accepted for use in the classification. ISBN 92 4 154421 X ------------------------------------- O Please send __ copies of IC0-10 Volume 1: Tabular List at Sw.fr. 130.-/US $117.00; in developing countries: Sw.fr. 91.-(1151331) O Payment enclosed ORDER FORM O Please charge to my credit card OVisa O American Express O Eurocard/Mastercard/Access Card number Expiry date Date of order Signature DSA.ICD.92 A Name Address WHO• DISTRIBUTION AND SALES• 1211 GENEVA 27 • SWITZERLAND PUBLICATIONS OF THE WORLD HEALTH ORGANIZATION 1992 WORLD HEAL TH FORUM An international journal of health development (Separate editions in Engli~h, Frenc.:h, Spa11L',,h. Arabic.:. Chinese and Rus .... ian) World h£•alth .forum i.-. a quarterly journal for pulky-maker<s, health planners, adminis- trator...,, health educator\, and public health worker<; of all kinds. It provide .... a medium for Lhe presentation and dis<.:Us'iion of new concept.-. in public health and nc\v approaches to health problem'i, and it is devoted to the improvement of health through the promo- tion of health services covering the entire population an<l the undertaking of a wide va- riety of public health mca.-.ure.\, whether or not they are !-.Upporte<l by WHO. The Fortun is the main organ of WHO\ Member States for the international exchange of health in- fomrnrion and an active inslrumenl in lechnical cooperation among developing countries. Sub'icriprion (4 number:-.) ................................. . Price per copy ...................................... . BL.:LLETIN OF THE WORLD HEALTH ORGANIZATION Sw. fr. 66.- Sw. t'r. 20.- The Uullctin i') the principal scientific organ of WHO: its role i!-. to review progres\ in medical and related .... cience~ ("update" articles) and to bring to light new knowledge by publi:-.hing original papers on .... cienli fie research in the laboratory and field. The Bulletin contain!-. original article .... in either Engli'ih or French, with a summary in the other language. One volume i!-. puhli<ihed annually, con...,i<;ting of six numbers. Subscription (6 number<;) ................................. . Price per copy ...................................... . WEEKLY EPIDEMIOLOGICAL RECORD (Bilingual: English and French) Sw. fr. 145.- Sw. fr. 25.- Prepared for lhe guidam.:e of health administration!-. and health authorities, the \t'l'l'kly eJJidemiological uuml contains notification:-. made under the International Health Regu- lations and infonnarion conceming their applkation. The Record also contain<; epidemiu- lo~ical information on communicahle di~ease<; of international importance. Annual subscription ................................... . Sw. fr. 170.- WORLD HEAL TH STATISTICS QUARTERLY The World h,,a/tl, statistin quarterly replaces (since 1978) the World health .\lati;;tit·s report (puhti .... hed 'lince 1967) and it .... forerunner the Epuh1nuolo,~ical and rital statistics rt'port (publh,hed since 1947). lt deals with the detailed analy!-.is of !-.Clcc:ted health topics of current interest. The Quarterly contain:-. articles in eitlu•r French or English with a ...,ummary in both languages. Annual !-.Uh!-.criprion ................................... . Price per cop} .................... · · · · · · · · · · · · · · · · · · · WORLD HEALTH STATISTICS ANNL'AL {Bilingual: English and French) Sw. fr. 100.- Sw. l'r. 28.- The forerunner of thi .... series was the !\nmwl l'pidemiological /'l.'/Wrl of lht' Ll'ap,m• oj ,Vatious. It wa" followed hy the A1111ual l'f)idcmio/ogiad and l'ita/ .\tati;;tin· is .... ued by the \Vorld Health Organization. Larc .... r puhlication!-.: 1987, Vital ,rati<.,tic.... and life tahle:-.. oral health and care, cau<iC<; of death (<;in!!le volume). 45.i page..... . . . . . . . . . . . . . . . . . . . . . . . Sw. fr. 90.- 1988. Vital ~tatistic .... and life tahle .... , lhe he~tlth prok· ... ...,ion" in the 198(h. cau:-.c .... of death (!-.irtgle ... oturne), 513 page'i (out of ~tock) . . . . . . . Sw. fr. 90.- 1989. Vital .... tati:-.tic .... and lift- tahle:-., lhe WHO MONICA Project. cause\ of death (!-.ingle volume), 44.\ page<; . . . . . . . . . . . . . . . . . . . . . Sw. fr. 90.- 1990. Vital :-.tari .... tic\ amJ life tahle...,, international <itati!,,rics on catt!-.C..., of di:-.ahiliry. cau .... e .... or death (<iingle volume). 447 page .... (out of .... tockJ . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sv.·. fr. 90.- 1991. Vital <.,lati<itic<; and lik table:-.. health and human development, cau\e<i or death (single volume), 371 pages. . . . . . . . . . . . . . . . . Sw. fr. 100.- PUBLICATIONS DE L'ORGANISATION MONDIALE DE LA SANTE 1992 FORUM MONDIAL DE LA SANTE Revue internationale de developpement sanitaire (Edition<; ~eparC:e<; en f'ran<.;ai<;, anglais, espagnol, arabe, chinois et ru\'iC) Forum mondial de la mnti e<;t une revue trime..,trielle destinCe aux rcsponsablcs des politiques sanitairc\, aux planiticareurs, administrateurs er C<lucareurs sanitaires. cnfin aux rravailleur .... de la !-.ante puhlique de route~ caregorie!-.. Trihune pour la presentation et la di .... c:u!-. .... ion de nou\oeaux concepts en .... ante puhlique et de nouvelles appn.K:he<; <les pro- hlfme:-. de .:,,ante. Forum !-.e c:on .... ac:re a !'amelioration de la .... ante par la prumolion <le .... ervices de <;anlC couvranl la population tuul entiCre et cl"une va~te gamme de me ... ures <le <;ante publique, qu 'elle .... :-.oient ou non \Outenue..., par I 'OMS. ll e<;I le principal organe a la di-spo-sition des Ftat~ Membres de I 'OMS pour I 'Cchange international cl 'informa- tions <;anitaires en m<:me temps qu'un instrument de cooperation technique entrc pays en dCveloppement. Ahunnement (4 numero .... ) ............................... . Le nurn6ro ....................................... . BULLETIN Fr. s. 66.- Fr. s. 20.- DE L'ORGANISATION MONDIALE DE LA SANTE Le Bull£•tin est le principal organe \cientifique de !'OMS; ii a pour rOI<: de pa%er en revue les progrCs de<; ~cience~ m<!dicale~ et apparentC:es (articles de la rubrique «Le point») er de mettre en lumiC:re le\ connais'lances nouvelles en prC:senlant dans des arti- cles originaux le\ rCMtltat~ de rec:herche\ scientifiques au laboratoire et sur le terrain. Le llulletin contient de:-. article!-. originaux en fran~ai:-. ou en anglai!-., accompagnCs d'un r6~umc! dans l"autre lang1,.1e. Un volume e ... t puhlie annuellernent, e1ant forme de .... ix nurnero!-.. Abonnement (6 numCro<;) ............................... . Le nu1116ro ....................................... . RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE (Bilingue: fran~ais et anglai!-.) Fr.,. 145.- Fr. ,. 25.- Oe~tine aux a<lrnini!-.tration\ !-.anitaire .... et aux !-.ervic:e~ de .... anre. le Nl'f,,,.,: i1,idimiologi- que llehdomadaire cuntient le~ notification<; exig<:es par le Rt:glement \;mitain: interna- tional. ainsi quc d'autres renseignements concernant l'application de ce regternent. Le Hl.'!ed contient eg:alement de:-. infonnarion!-. 6pidemiologique!-. c:oncemant lt:s maladies tran\mis .... ibles d'une importance internationale. Prix de I 'abonnement annuel .............................. . Fr.,. 170.- RAPPORT TRIMESTRIEL DE ST A TISTIQUES SANITAIRES MONUIALES Le Na1,port trime.\triel d,• slalisliqm'.\ .wnilairt's mo,u/ia!t.'.\. rcmplace (depui!-. 1978) le RapJWrt de statistique;; .mnituires mondialcs (puhli6 depui~ llJ67) el .... on pr6curseur le Rapport tpidbniologiquc l'I dhnograJJhique (publi6 depuis 1947). 11 pr6~enle des analyses dCraillCes 'iltr de<; <;Ujets spe!cifique~ d'int<:r<:t courant. Le Trimestricl pre ... ente de\ artic:les originaux en franCrais ou en anglai~. accumpagn6..., d'un re .... ume <lan.:,, k<; cleux langucs. Prix de l'ahonnement annuel 1.e nun16ro ....................................... . ANNUAIRE DE STATISTIQUES SANITAIRES MONDIALES (Bilinguc: franCrais et anglai'I) Fr.,. JOO.- Fr.:-.. 28.- Cet annuaire n:::mplace lc'i S1a11stu1m'.\ l'pidhuiologiques c't dhnogmJJhique.\ annuelle.;; publitc .... par l'Organi!,,ation mondiale de la Sante d qui avaient. elles-mernes, rernplaCC le Rapport ,,1,idtmio/ogll/U£' a111111el publiC par la SociCtl! de..., Nation ..... Puhlicatiorh rfrcntcs: 1987. Mouvemcnt de la population et tahle..., de: survie. same et soin:-. bucco-dcntaire'I, cau\e~ de dCC(:<; ( I .... c:ul \·Olume), 45.5 page!-. ..... 1988. Mouvcmcnt de la population et table" ck survie, la :-.ituation de..., profcs~ion:-. de :-.ante dan.., les annCe\ 80, cause..., de dece..., ( I ~c:ul volume). S 13 page .... (Cpui\C) .......................... . 1989. Mouvcment ck la population et rabk" de <iltr\ ie, le Projcl MONICA de I 'OMS, cau~e<; de d<:ce<; ( l <ieUI volume), 443 page~ ...................................... . I lJ90. Mouvement de la population ~t rahlcs de .... urvie. ~tatistiqucs inter- nationalt:::!-. sur le~ cau!-.cs d'incapacitC. cau~es de dCd~<; (I \cul vo- lume), 447 page .... (epui~e). . . . . . . . ........ . llJ91. Mom·ement de la population et table\ de wn·ic. la <;antC cl le developpemenr humain. c.:1usc\ de dCCC\ (I <;cul volume), 371 page'i ..................................... . Fr. S. 90.- Fr.,. 90.- Fr.,. 90.- Fr.,. 90.- Fr.,. 100.- COMMUNICABLE DISEASE EPIDEMIOLOGY AND CONTROL During the latter half of the XXth century a range of tools have been developed or brought into use to prevent and control illness, and hence premature death, due to infections with bacteria, viruses and parasites. Vaccines, antibiotics, drugs, insecticides and pesticides, sanitation, public health education, alone or in combination, have proven their efficacy. At the same time, demographic growth; increased migration, travel and trade; intensive land use; degradation of the environment; changing agricultural practices; industrial developments; the growth of urban slums - all have contributed to the rapid spread of organisms between people, countries and continents. Diseases that threatened the world a century ago, such as cholera, influenza and malaria, have been joined by new ones such as AIDS, and others may be in store for the future. This issue of the World health statistics quarterly is devoted to a selection of communicable diseases and different aspects of their prevention and control. The articles describe some of the successes and problems encountered by the WHO Expanded Programme on Immunization in their attempts to reduce childhood morbidity and mortality from measles, neonatal tetanus, pertussis and poliomyelitis. The epidemiology of dengue haemorrhagic fever, Japanese encephalitis, leishmaniasis, malaria, and the more circumscribed but persistent Chagas disease, and endemic treponematoses are dealt with in separate articles. Other features in this issue discuss the demographic impact of AIDS, the cost of influenza and new attitudes needed to deal with cholera today. Communicable disease control also entails decisions about priorities, and this· requires reliable morbidity and mortality data. The lack of such information and ways of reaching credible estimates are dealt with in several articles on specific diseases in this issue. One article discusses in greater detail the use of various data sources in evaluating the importance of acute respiratory infections. The effectiveness of disease control programmes should translate into decreasing morbidity and mortality, but some intestinal parasitic infections require an additional parameter to be accounted for, namely de,:ree of infection. Another feature shared by several articles in this issue is how environmental changes have contributed to the spread of diseases. The classic example is the association between drinking-water and cholera. To supply clean water is not a problem limited to the developing world. A review of waterbome disease outbreaks in the United States of America illustrates the difficulty of maintaining a proper water supply in modem, industrialized and economically healthy societies. Finally, as the AIDS pandemic has shown, new diseases can appear. One article on emerging zoonoses describes the relationship between animal health, agricultural practices and the risk to human populations, today and tomorrow. LES MALADIES TRANSMISSIBLES: EPIDEMIOLOGIE ET LUTTE La deuxieme partie du xxc siecle a vu la mise au point ou l'utilisation de tout un arsenal pour la Jutte contre les maladies infectieuses d'origine bacterienne, virale ou parasitaire et les deces prematures qu'elles entrainent. Les vaccins, les antibiotiques et autres medicaments, les insecticides et les pesticides en general, l'assainissement, l'education pour la sante publique, sont autant de moyens qui, seuls ou en association, ont fait la preuve de leur efficacite. D'un autre cote, la croissance demographique, l'augmentation des migrations, des deplacements et des echanges, la culture intensive, la degradation de l'environnement, l'evolution des fai;:ons culturales, le developpement industriel, et la proliferation des bidonvilles ont leur part de responsabilite dans la transmission rapide des micro-organismes entre personnes, pays et continents. Aux maladies qui menai;:aient le monde ii y a un siecle - cholera, grippe et paludisme - sont venues s'ajouter de nouvelles comme le SIDA, sans compter celles que nous reserve peut-etre l'avenir. La presente livraison du Rapport trimestrie/ de statistiques sanitaires mondiales est consacree a un certain nombre de maladies transmissibles et aux divers aspects de la lutte contre ces maladies. Les articles evoquent quelques-uns des succes et des problemes qu'a connus le Programme elargi de vaccination de l'OMS dans sa tentative de reduire la morbidite et la mortalite infanto-juvenile imputables a la rougeole, au tetanos neonatal, a la coqueluche et a la poliomyelite. Des articles distincts sont consacres a l'epidemiologie de la dengue hemorragique, de l'encephalite japonaise, de la leishmaniose, du paludisme, des treponematoses endemiques ainsi que de la maladie de Chagas, plus circonscrite, mais neanmoins toujours presente. Sont egalement traites l'impact demographique du SIDA, le cout de la grippe et les nouvelles attitudes a adopter aujourd'hui face au cholera. La lutte contre les maladies transmissibles suppose egalement des decisions quant aux priorites, d'ou la necessite de donnees fiables sur la morbidite et la mortalite. Dans les articles consacres aux differentes maladies, sont abordes les problemes que pose l'absence de telles donnees et les moyens d'obtenir des estimations credibles. Un des articles expose en detail l'utilisation de diverses sources de donnees pour evaluer l'importance des infections respiratoires aigues. L'efficacite des programmes de lutte contre la maladie doit se traduire par une diminution de la morbidite et de la mortalite, mais dans le cas de certaines parasitoses intestinales, ii faut prendre en compte un parametre supplementaire, a savoir l'intensite de I' infestation. Autre point commun a plusieurs des articles de la presente livraison: l'influence des modifications du milieu sur la propagation des maladies. Le lien entre l'eau de consommation et le cholera en est un exemple classique. L'approvisionne- ment en eau propre n'est pas un probleme limite au monde en developpement et une etude des flambees de maladies a transmission hydrique aux Etats-Unis d'Amerique souligne la difficulte d'assurer un approvisionnement convenable en eau dans nos societes industrialisees modemes en bonne sante economique. Enfin, comme la pandemie de SIDA en foumit la preuve, de nouvelles maladies peuvent faire leur apparition. Un des articles, consacre aux nouvelles zoonoses, decrit les relations entre la sante animate, les fai;:ons culturales et les risques presents et futurs qu'encourent les populations humaines.