WPRO 2901
FIRST REGIONAL SEMINAR ON METHODS OF ~PIPEMIOLOOlCAL SURIlEILLANCE AND amGRAPHICAL PATHOLOGY
Sponsored
by
the
WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR THE WESTERN PACIFIC
Manila. Philippine.
1 to 1-0 Deoember 1971
FINAL REPORT
NOT FOR SALE
PRINl'ED AND DISTRIBUTED by
the
REGIONAL OFFICE FOR THE WESTERN PACIFIC
of the World Health Organization Manila. Philippine. August 1972
.,
CONTENTS
1.
PREF'ACE •••••••••••••••••••••••••••••••••••••••••••••••••••••••••
1
2.
EMERGING CHANGES AND CHALLENGES COMMUNICABLE DISEASES
...........
2 2
2.1
Communicable diseases reported by participating oountries ................................... '" . . . . . . . . . . . . .
3.
EPIDEMIOLOGY AND DISEASE SURVEILIANCE: THE CONTINUING ASSESSMENT OF REALm IN A POPUIATION •••••••••••••••••••••••••••••••••••••••
6 6
3.1 3.2 3.3
Definition of the population The elements of communicable disease surveillance The pub11c health laboratory as a spearhead for
.............................. ......... •••••• I •••••••••
6 11
surveillanoe ..............................................
..
4.
WORLD-WIDE SURVEILIANCE OF COMMUNICABLE DISEASES
13 13 15 15 16 16
4.1 4.2 4.3
4.4 4.5 4.6 5.
Purpose and scope of ep1demiologioal surveillance The role of WHO in world-wide surveillance of communioable diseases ••.•••.••••••.••••••••••••••••••••.•• Sources of information in world-wide surveillance ••••••••• Dissemination of information ••••••.••••••••..•..•••••••.•• Limit1ng factors in international surveillance •••••••••••• The future • • • • • It • • • • • • • • • • • • • • • • • • • • • It • • • • • • • • • • • • • • • • • • • •
.........
17 17
USES OF ADVANCED LABORATORY TECHNIQUES IN EPIDEMrOLOGICAL INVESTIGA TION •.••••••••••••••••...•••.•••.••••••••••••••••••••••
5.1 5.2
Virological diagnostic methods •••••••••••••••••••••••••••• Poliomyelitis and other enterovirus infections ••••••••••••
5.3 5.4 5.5 5.6 5.7 .,
17 17 Influenza •............••...••.•.........•.•.•...••...•.... 18 Measles •.••.••••.•...........••..•.•.....••..•.•.•.•.•..•• 18 Ru'bella ........•........•........................•.•.•..•• 18 Cholera and other vibrios
Hepa ti tis and Au Antigen ...................•........•••.•. Smallpox ..............................................•...
5.8 6.
.................................
19 19 20 20 20 21
SERUM REFERENCE BANK AND REFERENCE CENTRES ••••••••••••••••••••••
6.1 6.2 7.
The WHO Serum Referenoe Bank ••••••••••••••••••••••••••••••
Reference centres
.........................................
SURVEILLANCE OF VECTORS OF MEDICAL IMPORTANCE •••••••••••••••••••
22
7.1 7.2 7.3 7.4
Speciation ....•...•....•.....•....•.•........••..•....•.•• Distribution and density ................................. .
Insecticide resistance ....•....•.•••.••...•.••.•.•.•.•.•.• Control •..••.•.•..........•.............•...•........•...•
23 23 26 26
- 11 -
CONTENTS
8.
GEOGRAPHIC PATHOLOGY AND METHOOO FOR MAPPING DISEASES ••••••••••
28
8.1
S\.lJ'rI"Dary'
and conclusions ..................................... . I~T
9.
DISCUSSION ON COMMUNICABLE DISEASES OF TOPICAL
••••••••
9.1
9·2
Eye diseases (conjunctivitis and trachoma) Respiratory diseases •.•••••.••••••••.••••••.••.•••••.•••• Intestinal diseases
...............
9. 4 9.5 9.6 9·7 9.8 9.9 9.12 9.15 10. 11.
9.3
Diphtheria •••...•.••......•.•....•.....................•. Venereal diseases .....................................•.•
.......................................
Shigellosis ............................................. . Intestinal parasites ••••••••••••••••••••••••••••••••••••• Hepat1 tis ........................................................................... .. 'l\1'berculosls ........................................................................................ ..
34 35 35 36 36 37 37 37 39 40 40
9.10 I..eprosy ................ '" ........................................... .
9.11 Vector-borne diseases ................................... . Inmunizat10n ........... "..•............•..•..•.• "..•.•.•• "
9.13 Vector control 9.14 Mapping of disease
SMON ••••••••••••••••••••• " •••••••••••••••••••••••••••••••
........................................... ..... ................ " ............... .
45 46
48
49 50
stJMrt1ARY' ................................."...................... REC~ATIONS
••••••••••••••••••••••••••••••••••••••••••••••••
53 55 60 63 58
ANNEX: ANNEX: ANNEX: ANNElC
1 2
3 4
AGENDA LIST OF WORl<:I}Il(] PAPERS •••••••• " ••••••••••••••••••••• LIST OF PARTICIPANTS S~ NEW LABORATORY METHOOO APPLICABLE TO EPIDEMIOLOGICAL INVESTIGATION AND SURVEILLANCE OF INFECT! aus DISEASES ."............................
.............................................. ................................
ANNElC ANNElC ANNElC ANNElC
ANNEX ANNEX
COMPUTER PRINTOUT OF THE SURVEY OF STEGOMYIA MOSQUlTOE:3 1971 ..." •••••••• " ••• " •• "•••• " ••• "•••••••• 6 MAPPING OF DISEA5E9 THE TASKS FOR MEDICAL BIOGRAPHY ••••••••••••••••••••• 7 ~ TIC MAPPING •••••••••••••••••••••••••••••••••••• 8 - MORBIDITY RATES OF DIPHTHERIA IN 1958 AND 1968 •••••• CASES OF DIPHTHERIA REPORTED IN COUNTRIES OF WESTERN PACIFIC REGION IN 1969 •.•••.•••...•......••. 9 REPORTED CASES OF DIPHTHERIA IN THE WESTERN PACIFIC REGION IN 1957-1970 ••••••••••••••••••••••••• 10 - MORBIDITY RATES - DIPHTHERIA IN THE WESTERN
5
.................................
84 88
101
98
•
103 104
105 106
PACIFIC REGION 1957-1969 ...............••...........
1.
PREFACE
The first WHO Regional Seminar on Methods of Epidemiofogical Surveillance and Geographical Pathology took place at the WHO Regional Office, Manila, Philippines, from 1 to 10 December 1971. The main purpose of the Seminar was to consider ways of improving surveillance methodology and promoting the use of new laboratory techniques in epidemiological investigation. It also aimed at presenting and discussing the geography of diseases and vectors. In welcoming the participants, the Regional Director, Dr Francisco J. Dy, said that surveillance meant the epidemiological study of a
disease as a dynamic process involving the ecology of the infectious agent, the host, the reservoirs and the vectors as well as the complex mechanism concerned in the spread of infection and the extent to which that spread occurs. Surveillance, therefore, provided the essential scientific basis for planning, implementing and assessing communicable disease control programmes. He also called attention to the importance of preparing geographical maps showing the distribution ~f disease and the various ecological factors affecting their distribution. Such publications were most useful and although there were some fine examples of such work in the Western Pacific Region, much more were needed. He stated that the WHO was very much interested in helping to establish and strengthen epidemiological surveillance services and was prepared to provide assistance of that kind if so requested by governments. Dr Desmond B. Travers, Assistant Director-General, Commonwealth Department of Health, Australia, was 'elected as Chairman of the Seminar, Dr C.M. Collins, Assistant Director, Division of Public Health, New Zealand as Rapporteur for the English language and Dr Ung Try, Chief, Department of Communicable Diseases and Epidemiology, Khmer Republic as Rapporteur for the French language. All participants in turn served as Vice Chaimen. The Director of the Seminar was Dr Telford Work.
This report contains brief summaries of the working papers, the discussions and the conclusions reached. It has taken into account information from the country reports presented by the partiCipants either orally or in writing. The programme of the Seminar is given in Annex 1. As a basis for discussion, five working papers were prepared by the consultants and a number of WHO publicatiOns were distributed to the participants. The list of the working papers and documents is found in Annex 2. The Seminar was attended by partiCipants from 19 countries or territories in the Western Pacific Region (see Annex 3). In addition to the four WHO consultants, two staff members from WHO headquarters, Geneva, 11 staff members from the Region and a number of observers were present.
- 2 -
Simultaneous interpretation was provided into English and French of all the work of the Seminar. 2. EMERGING CHANGES AND CHALLENGES COMMUNICABLE DISEASES
The agenda of the Seminar was focused on various methods and steps to achieve a workable disease reporting system appropriate for the countries of the Western Pacific Region. each of which has its own characteristics. Geographically, most of the countries of the Region are insular or peninsular and are bordered by oceans and seas. While this poses some problems of isolation, it is advantageous for the effective definition, control and mapping of communicable diseases. In the past half century, the pattern of communicable diseases has changed radically. In the nineteen-thirties sulfa drugs became available, diminishing the mortality and stopping the spread of many bacterial diseases. By the nineteen-fifties chemotherapeutic and antibiotic drugs were being applied on a massive scale to change the epidemiologic pictures of tuberculosis, leprosy, filariasis, yaws and other major diseases. Insecticides such as DDT and dimethyl phthalate proved speoially effective against the vectors of borne diseases such as scrub typhus, malaria and dengue. But as ep1demio mortality reoeded, other problems emerged. At present we are faced with the necessity to reassess the situation in view of the ohanged patterns of the reoognized classic diseases and the shift from devastating mortality to extensive morbidity with vitiating economic effeots from lowered human productivity, and the emergence of a host of virus disease problems that are not amenable to chemotherapy, antibiotics, available vaccines or practicable vector control measures. 2.1 Communicable diseases reported by participating countries
The communicable diseases reported by individual countries as important from the point of view of epidemiological surveillance are presented in Table 1. They differ somewhat from those reported to WHO as the eight leading communicable disease problems in each country. It seems therefore that the most prevalent diseases are not necessarily the most important in the context of epidemiological surveillance. Diseases reported as of importance to all countries were venereal diseases, tuberculosis, enteric fevers and helminthic infections, but even these differ in the kind of challenge they offer to effective surveillance. The problem of syphilis in urban1zed countries and territories such as Hong Kong, Japan and Singapore was contrasted with the threat of resurgence in Malaysia and Papua New Guinea as a result of campaigns that had eliminated the spirochaetal immunity conferred by yaws. Countries
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COMMUNICABLE DISEASES OF IMPORTANCE IN EPlDEMIOWGICAL SURVEILLANCE AS REPORTED BY COUNTRIES IN THE WESTERN PACIF1C REGION
INfECTIONS VIRAL AND RICKETTSIAL INFECTIONS BACTERIAL INFECTIONS
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- 5 such as the Philippines. which had long used BCG vaccination, presented patterns of tuberculosis and leprosy different from those found in Japan and Australia, two countries where widespread case finding had been applied. Korea reported on twenty years experience with typhoid as a major cause of morbidity and mortality while other countries lacked information either because the disease was not reportable or because there was no mechanism for establishing a diagnosis dependent upon routine public health laboratory support of a disease surveillance system. In many of the islands scattered across the PaCific, there has been a remarkable decline in tuberculosis mortality. Largely free of malaria because the anopheline mosquito vector is absent, their most serious vector-borne diseases have been filariasis, the cause of a severe recurrent fever, and elephantiasis. Through mass administration of a chemo-prophylactic drug, hetrazan, the chain of microfilaria transmission to Aedes polynesiensis mosquito vectors has been diminished and the infection virtually eliminated as an important cause of disease in American Samoa, Fiji. parts of French P0lynesia, and Western Samoa. In this area measles has long been considered the swiftest epidemic killer of small children and adults, but a recently available vaccine has turned susceptible into immune conmunit1es. Penicillin has eliminated yaws. Antibiotic therapy of pneumonia and vaccine for pertussis has lowered the infant mortality rate so that the largest segment of the population, now under 20 years of age, has a much greater life expectancy than before; this however will be challenged by cancer and heart disease. Hepatitis is the major communicable disease problem of Australia and New Zealand. Caused by at least two different viruses, serum type hepatitis can now be diagnosed by new serological techniques. Prolonged unsettled conditions have held off efforts to determine the mechanisms of the spread of plague in the Republic of Viet-Nam. The disease is a major cause of morbidity and mortality in that country and is of concern to neighbouring countries because of the danger it represents. In the Khmer Republic and Laos, malaria remains a vector-borne disease of major importance because the difficulty of access precludes a full scale eradication effort. Epidemic conjunctivitis has occurred explosively in several countries. It appears that at least some of the outbreaks in Japan are due to a new virus. Trachoma is only intermittently reported and its relative importance may have been obscured in many countries where communicable eye disease is a major problem. Such is the diversity of the communicable disease problems in nations of the Region, that it has become essential to consider methods of developing better epidemiological surveillance if they are to be attacked effectively.
- 6 3. EPIDEMIOLOGY AND DISEASE SURVEILIANCE: THE OOm'INUING ASSESSMEm' OF HEALTH IN A POPULATION
The health status of a population is comparable to that of an individual. The health of an individual is assessed by means of a thorough history and physical examination. including appropriate laboratory tests: that of a population by epidemiology. utilizing recognized public health laboratory procedures.
3.1 Definition of the population Populations differ in size. age, race, sex. distribution. ~bility and accessibility, all factors of importance to the epidemiologist. The population to be examined therefore must be defined in consideration of the applicability of epidemiologic methods and the objective of the examination. For example. if the goal is to measure an occupational disease, the group selected would be different from that chosen for the assessment of childhood diseases due to exanthemic viruses or malnutrition. Whatever the national or international objectives of surveillance may be. the epidemiological approach must begin with a defined population at the local level. The value of any disease surveillance can be no greater than the validity of the reporting from the local defined population. The reporting system at the local level is therefore fundamental to the entire surveillance process. 3.2 The elements of communioable disease surveillance Among the elements of communicable disease surveillance, the following may be considered: (a) Formal reporting f.t>rtali ty Death observations Death registration f.t>rbidity Reportable diseases Specified diseases EpidemiCS (b) Investigations Individual cases Outbreaks Laboratory studies Studies
- 7 (c) Ecological analysis Distribution of vectors Non-human vertebrates Animal diseases Cd) Social sources cif information Mass media Utilization of drugs and biological substances Characterization of population (e) Analytical systems Records Statistics Computers 3.2.1 Formal reporting
3.2.1.1 Mortality reporting' Death is a more certain fact than any other with which we have to deal. The effects range from simple grief to economic impact. Disposal of the corpse is the focal point for gathering data. In some towns a crude death rate is calculated by counting the funeral proceSSions which on a given day or in a period of time pass a point - sometimes the local health office - on the way to the cemetery. In western countries the third official certification of a person's life - after birth and marriage - is the death certificate which must be obtained before disposal of the body is permitted. This requires registration of a cause of death. If disease in the patient has not been diagnosed by a physician beforp. death, an autopsy is mandatory; the official responsible is the coroner who then reports a cause to the health authority. 3.2.1.2 Morbidity reporting. Morbidity is the measure of an illness that can be specifically identified, its severity and consequences noted, and its distribution according to geography, age and sex evaluated. If death 1s a consequence, the nature of this illness is an essential element in ~eporting mortality. The signs used to characterize illness range widely from fevers of variable temperature and duration to visible marks in such exanthemic diseases as measles or smallpox. The validity of local reporting requires qualified observation. Familiarity with specific disease manifestations, such as the diarrhoea of cholera or the stool of shigellosis, as contrasted to the necessity of sophisticated public health laboratory microbiology for diagnosis of infectious hepatitis, determines not only the extent of morbidity reporting but the confidence l~vel of the data collected.
- 8 Observers of communicable disease may range from an observant mother in a household with measles to a visiting public health official who collects and dispatches to a reference laboratory blood specimens from acutely ill or convalescent persons. Recognition of measles is relatively Simple compared to etiological diagnosis of cases of jaundice with fever in central Africa. A laboratory answer to the question of whether it is viral hepatitis or yellow fever is an essential distinction for local control and international quarantine. Diseases vary in relative importance in different places. A local outbreak of malaria, while important to the country concerned, and to the global campaign for eradication of malaria, is not of as preSSing importance as a new pocket of smallpox or yellow fever. The number of diseases to be reported varies according to the agency requiring the information - it is usually greater at the local level and smaller when only diseases of national or international concern are considered. <a) Reportable or notifiable diseases
-,
In many tropical areas, and in communities that have been devastated by epidemics in the past, reporting may be limited to only a few diseases such as cholera, smallpox, malaria and plague. A second echelon of diseases, involving slower progression, includes tuberculosis, leprosy and typhoid. Because of the universal availability of vaccine for the prevention or control of childhood diseases such as diphtheria, pertussis and tetanus, reporting of these diseases on a regular basis may be prescribed. On the other hand, with the introduction of such preventive measures through local health units capable of substantial or mass vaccination, these may become the priority diseases for a reporting system. Because of the variations found in reporting systems, the United States Public Health Service gathers and publishes reports of quarantinable diseases as they occur abroad. From indigenous and foreign disease reports has evolved the weekly reporting of 25 diseases and others of special epidemic importance. Guided by the "blue book", the Manual of Procedures for National Morbidity Reporting, each state health officer reports on these diseases early each week to the National Center for Disease ControL - There they are tabulated and analyzed. Wi thin two or three days the collated information is disseminated to the participating states, interested national governments, the World Health Organization and infectious disease professionals through publication of the Morbidity Mortality Weekly Report (MMWR). Subsequently, an annual summary is prepared which often reveals previously unrecognized communicable disease problems. At the least, it puts into perspective the occurrence of diseases which many believe to have been conquered long ago or, indeed, to have disappeared. Depending on local and national disease reporting mechanisms, most other countries issue a Similar report, at least on a monthly basis. The World Health Organization has a global reporting system. •
- 9(b) Specified diseu..
In addition to the notifiable diseases on the establiShed list, a number of other co-.unicable diseases are of interest and concern to the services responsible for surveillance. These are specified diseases, not reportable week17, but of 1IIportance in as.e.Sllent.s on a reglonal and annual baai.. A mlSlber of parasitic di.eases of a non-acute nature and low trana.i •• ibilit7 11&7 be included.. AmoD(ll; these are 88Oebiasis, toxoplaa.o.i., t.r,ypanosoaiaais, and filariasi.. As rare, exotic or unu.ual entit.ie., their presence and fluct.uat.ions are iaportant. to note. 3.2.1.3 Epidea1cs. Sources of infor.ation for these less ca.mon di.e.... are often the.individual states or special interest laboratories and inve.tiptora. EpideJl1cs are s1ll1lar17 reported. When a diseue 18 a oonetant threat, as with saallpox and rabies, or liable to pass unnot.iced, like aaoebiasis, or fOl'llerl7 of maJor iaportanoe .. with poliom;ye1iti., or newl7 recosn1zed such as Venezuelan equine encephal~litis, or newly eaerging as exeaplified b7 drug-induced malaria or cl. .-u.ociat.ed hepatiti., careful epidftl1c st.udies, proper17 publicized can often bring a situation to light in time for effective control or for the proviSion of help needed to define the extent of the problea. }.2.2 Eooloi1cal anall!is }.2.2.1 Distribution of vectors. The ecological situation in which people live significant17 influences the variety of diseases subject. to surveillance. The collection, ident.ification and surveillance of pot.ent.ial diseue vectors are maJor activities in communicable di.ease surveillance; the7 are discussed in sreater detail below. 3.2.2.2 Animal diseases. In addition to ecological evaluat.ion of vector pot.ent.ial and the IIOnitoring of the presence of zoonotic agents in wildlife reservoirs, the directed search for aniDal diseues such as anthrax in w.l.ld quadrupeds or plague in wild rodents is an exaaple of special camaunicable disease surveillance. The appearance and progression of an infect.iO\ls dise.se is lIOn!tored before it spreads to a human collllllWl1ty, thus allowing time for oontrol measures. to be set up. Susceptible sentinel an1aals "'7 also be used for such monitoring. 3.2.3 Social sources of inforaation So far we have considered sources of information on communicable dis....s that are under the control of delesated public health agencies. An effeotive surveillance programme also derives information from accesllOI'7 sources, and this often leads to aggressive epidemiologlcal inveatiptlonand the creation of a formal reporting procedure.
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3.2.3.1 Mass media. Newspaper stories about the occurrence of epidemic disease, often desoribed as of obscure etiology, have revealed the existence of epidemics in communities ranging from rural villages to large urban areas. Newspaper stories describing epidemic influenza in local populations have been primary sources of information on the progression of pandelll1c influenza through III8.IlY countries in the past. In the nineteen-forties, newspaper stories were used by poliolllYelitis res.earchers to select epidemics for the investigations which have given us moh of what is known about the epidelll1ology of poliomyelitis. 3.2.3.2 utilization of drugs and biological substances. The seasonal occurrence and seographical distribution of other types of diseases, for example, enoephalitis or yellow fever have been measured or determined by examining manufacturers' records of the sale and distribution of vaccine. In the same way, unusually large sales of antibiotics and chemotherapeutic drugs have provided indications of increases of oertain bacterial diseases or diseases of unknown etiology, for example epidemic conjunotivitis. (See also ,paragraph 9.15 on SKlH in Japan.) 3.2.3.3 Characterization of population. Epidea1cs of venereal diseases in the United States of Aaerioa have been asscoiated with teen-age high school students of certain urban social strata in recent years, constituting new epidelll1ological situations that require speoial disease control measures because of the young People's ignorance of the lIechanis.. by.nich syphilis and gonorriloeawere being transmitted. Against this urban aetting, often associated with an affluent se~ent of society, is contrasted the epidemiology of kuru among the Fore people of New Guinea where cerellOnial consumption of the flesh of dead relatives has been found to be the definitive source of infeotive virus oausing this unique, slowly progressive, inevitably fatal degenerative disease of the central nervous system. When an outbreak of infectious hepatitis occurred in Pascagoula, Mississippi, in 1961, the association with oonsumption of raw oysters from sewage-oontaminated oyster beds and the extent of the disease in the oity population were established as a result of telephonic interviews with people whose names had been selected at random from the telephone book and whoa it would otherwise have been iIIpractical to reach. 3.2.4 Analytical syste.. all the above-mentioned information sources, data of varying reliability reach the responsible health officials. The information received ~t be systematized into a fora of records that is useful to those who JlUst analyse, interpret and disseminate it. From
•
•
3.2.4.1 Records. The simplest form of surveillance is the recording of positive information. Laboratory diagnosed cases of botulism or tetanus usually do not represent all the cases occurring but do establish the existence of the problems and possibly the scurce of 1nfect1on. Bes1des providing a factual basis for recognizing the existenoe of certa1n diseases in- particular 10calit1es,- such reoorda are auffioient to enable a rural health offioer to initiate measures for the oontrol and prevention of speo1f10 diseases.
"
- 11 If infonnation is to be fed into a provincial, national or regional surveillance system, a more elaborate record system is required. However, an effective system can utilize relatively simple records. Caution must be exercised to avoid letting the details of the record system obscure its utility. Sometimes reports of the greatest significance are lost because the record system is too elaborate. Simplicity should be the byword. A new disease should emerge clearly and not be obscured in an attempt to handle too many diseases. 3.2.4.2 Statistics. Statistical analyses should also be Simple and may be limited to establishing incidence and prevalence rates. Too often there is a tendency to quantify on the basis of inadequate data. In recent years record keepers, bookkeepers, statisticians and other handlers of data have become fascinated by the diverse capabilities of the latest model computers to record, store, tabulate, analyse, calculate and recall data. But a computer can only shuffle and deal the data that is put into it. It cannot think or interpret the meaning of information or produce a surveillance system. The imaginative cOlllllWlicable disease control officer can do more with a handful of records containing valid reports of disease oOOurrence than can a roomful of record systems, statisticians and opmputer terlllinals. It still requires a trained brain to think out the Significance of the data received. 3.3 The public health laboratory as a speamead for surveillance
The epidemiological monitoring of pneumonia to signal the onset of an influenza epidemic, or the observation of characteristic exanthemata to discover outbreaks of measles and smallpox, have been given as examples of co.unicable disease reporting dependent upon observation of Clinically diagnosed cases. Reporting of ma.ny other diseases is dependent upon their identification in the public health laboratory. The laboratory thus becomes the spearhead of epidemiological investigation. Acute febrile disease of the central nervous system and poliomyelitis, are both diseases in which clinical attack rates are low relative to the actual number of persons infected. Isolation of the virus responsible or serological demonstration of a rise in antibody titre for a given etiological agent determines the specific disease to be reported. In countries where competent virus laboratories have been developed, previously unrecognized poliomyelitis has been established as a not uncommon enteric infection and paralytic disease. With the viral encephalitides, establishment of the specific virus etiology deterlllines measures of control, e.g •• rabies versus arbovirus encephalitis. Identification of pertUSSis leads to consideration of the need for an immunization programme. Venereal disease represents a combination of infections of such importance that many countries have established special laboratory testing and reporting systems for them.
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The responsible health agency may give such specialized attention to particular communicable diseases because they are either new or special problems. The special problems may require unique laboratory techniques for diagnosis. The occurrence and recognition of the etiology of a new disease may require laborator¥ expertise that transcends the resources and capability of a local or even a national laboratory. The World Health Organization has developed a system of collaborating, regional, and world reference laboratories. This network not only feeds otherwise unobtainable information on special disease problems into the international surveillance system but also provides technological support in solving puzzling diagnostiC problems and special facilities not available in stanclard laboratories. The versatility and capability of this specialized reference service is such that it is constantly in demand to assist in epidemiological studies and communicable disease surveillance activities. ).).1
Utilization
The uses to which the information acquired by an effective communicable disease surveillance system can be put inolude the investigation or implementation of control measures such as mass vaccination, vector control or application of international health regulations. The official policy of the World Health Organization with regard to an organization for epidemiological surveillance is stated in terms of actions such as: (a) data recording, data analysiS and evaluation (by physicians, hospitals, laboratories, veterinary health services, entomologists, etc.); (b) planned investigations in the field and immunological surveys; (c) immediate field investigations (motivated by inooming reports or by laboratory findings) and containment operations; (d) laboratory studies of etiological agents and their changing biological properties; (e) ecological studies and mapping the results; •
(f) dissemination of information to all those who play an active role at the various levels of surveillance; and (g) formulation of recommendations for the decision-making authority.
- 13 Thus surveillance constitutes a long-term process, continuously developing and changing, depending on the different environmental and socio-economic situations and the results of applying health measures. It forms an integral part of epidemiological activities in general. 4. v,QRID-WIDE SURVEILlANCE OF COMMUNICABLE DISEASES
The necessity f0r international surveillance of communicable disease is clear: in the world of today where mass travel and the huge volume of international commerce are corner-stones of the economy of many countries, it is in the interest of the world community to be kept constantly informed about the Gccurrence and outbreak of some of the major communicable diseases. 4.1 Purpose and scope of epidemiological surveillance
•
Any kind of information considered useful for epidemiological forecasting, planning, programme review and assessment in relation to prevention and control is relevant to surveillance activities. The feasibility of world-wide surveillance depends largely on the information that is made available by national health authorities. In order to understand the scope and limitations of international surveillance it is necessary first to review the basic activities in the national surveillance of communicable diseases. These are: (a) Bringing existing knowledge together from all sources and, in the process, establishing close co-operation for this purpose between all relevant branches of gpvernment and medical services. A typical example is the regular consultation and exchange of information between medical and veterinary services on problems concerning zoonoses, food hygiene and animal husbandry practices. Such consultations are frequently hampered by the fact that in most countries, these services are under the Jurisdiction of two different ministries, that of health and that of agriculture • (b) Establishing or impl"0ving a system of reporting of outbreaks of communicable disease. In areas with an imcomplete infrastructure of medical services, such a system may depend on laymen reporting an unusually large number of observable symptoms in a community (diarrhoea, vomitting, skin rash, fever, etc.) followed by on-thespot field inves~igations by a mobile medical team. In areas with adequate medical facilities it would depend on continuous analysis of routine reports on cases and deaths received from hospitals, health centres, and medical practitioners, and data from health laboratory services. (c) Following the trends in communicable diseases through careful consolidation of reported data of cases and deaths, for the purpose of forecasting serious outbreaks and, whenever possible, taking preventive action against them.
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- 14 (d) Conducting surveys for specific purposes by the use of serological and other laboratory examinations, questionnaires and other methods relevant to the problem at hand. These may take the form of serological surveys for pre- and post-vaccination assessment of the immune status of a population, or they may be epidemiological or entomological surveys, preceding the implementation of projects for the development of urbanization, industry and agriculture, undertaken to assess the inevitable resultant changes in local ecology and the probable effects on the transmission of infectious diseases; (e) Investigating individual cases, and in particular presumptive cases of diseases such as cholera, plague, smallpox and yellow fever covered by the International Health Regulations and other diseases of community importance such as malaria and poliomyelitis; (f) Studying animal reservoirs and vector distribution in relation to zoonoses and insect-borne diseases. The distribution of important vectors is established in order to define "receptive areas", in particular for arbovirus infections (yellow fever and dengue haemorrhagic fever) and malaria: (g) Central analysis and. consolidation of data (transforming data into information) ~nd other p.xisting knowledge and dissemination of the resulting information through periodiC epidemiological surveillance reports. These reports should be made available to the decision makers and the staff of all branches of the health services; (h) Prompt notification to the World Health Organization of the occurrence of diseases (single cases as well as outbreaks) under the International Health Regulations (IHR) 1969 and of outbreaks of other diseases of international importance: The obligation to report outbreaks of the latter diseases is governed by the World Health Assembly resoiutions WHA22.47 and 48. 1 (1) Collection and disseminatL'n of information about "infected ar!:'as" as defined by the Ir.ternaticnal Health Regulations,2 50 that countries may apply the measures indicated in the Regulations.
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1
Off. Rec. WId Hlth Org., No. 176, 23-24. •
Article I of the International Health Regulations states that an "infected area" is defined on epidellliological principles by the health administration reporting the disease and need not correspond to administrative boundaries. It is that part of its territory which, because of population characteristics, density and mobility and/or vector and animal reservoir potential, could support transmission of the reported disease.
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- 15 4.2 The role of WHO in world-wide surveillance of communicable diseases Although the World Health Organization is not the only agency responsible for the international surveillance of disease, it is the most important one in that field. WHO has access to a large amount of information partly provided by national health authorities in accordance with formal agreements, and partly supplied on a voluntary basis. The Organization consolidates all relevant information and disseminates this by appropriate means, through its headquarters and regional offices. The need for constant improvement in the quality and promptness of reporting as well as in the geographical coverage of surveillance activities is reflected in many WHO programmes. Meetings of experts are sponsored for the purpose of dealing either with specific diseases and their epidemiology or, as in the case of the Co_ittee on International Surveillance of Conmunicable Diseases, with all matters related to the International Health Regulations and surveillance in general. Improved surveillance methodology has been developed, particularly in relation to the two diseases, malaria and smallpox, for which eradication programmes sponsored by WHO already exist. Inter-regional and regional seminars, training courses, workshops and other educational activities playa. very important part in the longterm improvement of surveillance on an international scale. The same effect is expected from the many scientific and popular articles published by WHO. last but not least, the Organization maintains networks of reference laboratories in all parts of the world for viral, bacterial and parasitic diseases. These networks playa cruoial role, both direot and indireot, in international surveillanoe of oommunioable diseases. Three WHO serum referenoe banks are intended to faoilitate the use of serologioal teohniques in surveillance. 4.3 Sources of information in world-wide surveillanoe The International Health Regulations, oonstitute a formal international agreement by whioh most Member States of WlI) are bound without reservations. It stipulates that each health administration shall notify the Organization of the ooourrenoe of the diseases subJeot to the Regulations, - plague, oholera, yellow fever and smallpox. Other diseases whioh are subJeot to international surveillanoe are malaria, viral influenza, paralytio poliomyelitis, louse-borne typhus and relapsing fever. The obligation of Member States to report these diseases to WHO is governed by World Health Assembly resolutions but only outbreaks have to be reported. As the term "outbreakS" is nowhere defined oonsiderable discretion is lert to Member States as to what they should or should not report.
- 16 In addition to these formally established means of international surveillance a number of more or less informal sources are available to the Organization. Mention has already been made of an extensive network of WHO-sponsored reference laboratories in the field of viral, bacterial and parasitic infections and the serum reference banks. Data on morbidity and mortality are routinely collected on the national level and made available to WHO. Frequently however the time lag involved in this type of reporting is such that the infonnation is of no iDlDediate value in current epidemiological surveillance. Nevertheless, and despite the fact that in many countries the reporting is limited to hospitals and clinics under government control, these morbidity and mortality statistics are useful for the study of long-term trends in important conmunicable diseases. Many other sources are available such as WHO consultants, personal contacts with key personnel in the national health administrations, diplomatic channels and, at last but not least, the mass media - newspapers, radio and television. Reports· in the press frequently give the first indication of outbreaks of communicable disease in various parts of the world; they are often fairly accurate and it always pays to follow up such leads by contacting the health administrations concerned. 4.4 Dissemination of information
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On the national level epidemiological surveillance reports are prepared and issued at frequent intervals for distribution to all branches of the health services and to WHO as well. The importance of such reports cannot be over-estimated because they can be prepared only through the process of a central consolidation and assessment of all available data. National epidemiological surveillance reports are carefully studied by WHO and whenever information of more than local interest appears it is also disseminated internationally. On the international level WHO has ceased to issue a daily epidemiological radio-telegraphic bulletin but now provides the regional offices by t~lex with infonnation on the occurrence of the four diseases covered by the International Health Regulations. That information is transmitted to national health administrations upon request. The Organization's Weekly Epidemiological Record (WER), which is issued each Friday morning, contains epidemiological notes and reviews concerning diseases of international importance; it also publishes information on the application of the International Health Regulations. A series of technical guides for the surveillance of selected communicable diseases have also appeared in the WER. 4.5 Limiting factors in international surveillance
The practice of surveillance is far more complex on the international than on the national level for several reasons: (a) Because the quality and completeness of surveillance vary from country to country, great gaps are often left in the factual knowledge necessary for an assessment of the international epidemiological situation.
- 17 (b) National interests related mainly to tourism and the export trade, and sometimes expressions of the archaic social stiglll& attached to certain diseases, frequently result in the total suppression of infor.ation and a deliberate avoidance of notification. (c) WHO, as an inter-governmental organization, may report only information obtained officially from its Member States: it may not disseminate any information that it may obtain from unofficial source.
4.6 The future The present day standards of world-wide surveillance leave much to be desired. A better understanding is required of the importance of practising surveillance, nationally as well as internationally. Improvements can be achieved through staff training, better management policies applied to existing facilities and the further development of epidemiological and health laboratory services and of cOllllW1ications between different branches of the health services. In this connexion, the creation of national. epidemiological surveillance reports where these do not already exist would represent a very considerable step forward.
5. USES OF ADVANCED LABORATORY TECHNIQUES IN EPIDEMIOLOGICAL INVESTIGATION 5.1 Virological diagnostiC methods Isolation and identification of viral agents are now fairly well standardized. Cell or tissue culture is the most useful tool for this purpose. Usually three kinds ot cell cultures .are used, namely: primary or serially-propagated hu.an diplOid cells, human stable cell strain like HeLa cells, and monkey kidney cells. In addition, the suckling mouae is indispensable for isolation and identification of arbovirus, coxackie virus and so forth. Developing ohick embryos are still in use for lIOrk on influenza viruses and riokettsiae. Serologioal diagnosis is not feasible unless it i8 done on tllO serum sp8oi..ns taken respectively at the patient's acute and convalescent phases. It is very neoessary that doctors and persons in charge of epidemiologioal surveillanoe should be familiar with this prinoiple. There are many kinds of serologioal tests: those most commonly used are neutralization tests, haemagglutination tests and complement-fixation tests. Techniques are given in Annex 4. 5.2 Poliomrelitis and other enterovirus infections
In many oountries in the past ten years, poliomyel1 tis has been brought under oontrol by vacoination. In others, prinCipally in the tropics and subtropios, it is beooming an inoreasing hazard year by year. In the latter countries, it is IIIOst desirable to introduoe virus laboratory
- 18 services, where they do not already exist along with vaccination and surveillance of the disease by notification. Since the techniques of isolation and identification of poliovirus and other enteroviruses, and of titration of neutralizing antibodies against these agents are well established, there should not be much difficulty in inaugurating such services in places where a bacteriological laboratory is functioning.
5.3 Influenza Influenza is of great international importance because it often occurs as a pandemic. If an unusual amount of respiratory illness is observed, it is most important to send a report to WHO, and to ship new virus isolates or material such as throat swabs or washings to the World Influenza Centre or a regional influenza centre as soon as possible. Isolation and identification of influenza virus by inoculation into the amniotic cavity of developing chick embryos or into tissue culture (monkey kidney) are usually not difficult to perform in a standard virus laboratory, but the safest way to obtain a fine antigenic analysis of the strains isolated is to make use of the reference centres. It is important not to delay sending reports and material. The haemagglutination-inhibition test is often employed for serological diagnosis, but it is sometimes difficult to get a good result unless a current strain is used as antigen and great care is taken to eliminate any non-specific inhibitors to viral haemagglutination in serum. The complement-fixation test, using supernate of emulsion of infected allantoic membrane with a standard strain of influenza A or B virus is recommended for diagnostic purposes because it is usually group A or B specific but not strain specific; it is thus easy to determine whether a virus belongs to A or B.
5.4 Measles Since the diagnOSis of measles is easy to make on clinical grounds, virological diagnosis is required only in special circumstances. However, a sero-epidemiological study is of importance in elucidating the immunity status of the population. Age distribution of the antibody positive rates can be obtained by haemagglutination-inhibition tests and the results will provide very useful basic data for a measles vRccination programme. <'.5 Rubella
Although rubella is apt to be considered an unimportant disease in the tropiCS and subtropics, in recent years, several disastrous epidemics have occurred in those areas and have resulted in the birth of a great number of rubella rabies. Immunity against rubella is relatively low among women of child-bearing age in the tropics because climatic conditions are usually unfavourable for the spread of the virus. Epidemics are therefore rare but the possibility of their occurring increases with the growth of urbanization and international travel. It is therefore necessary to investigate the immunity status of the population by using the haemagglutinininhibition test, and to consider the possibility that immunization may be needed in the future.
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5.6 Hepatitis
and Au anti~n
Two varieties of hepatitis virus, A and B, are known. The former causes short- incubation hepatitis (epidemic or infectious hepatitis); the latter is associated with long-incubation hepatitis (serum hepatitis). Little more is yet known about virus A but it is well-established that "Australia antigen" (Au or HAA or SH antigen) relates to clinical and sub-clinical hepatitis due to virus B. Transfusion of Au antigen positive blood causes post-transfuSion hepatitis at a very high rate. Therefore, it is imperative everywhere to exclude donors with Au antigen positive blood. Various methods of Au antigen detection have been developed. Single radial immuno-diffusion and immuno-electrosyneresis are currently used for screening blood donors. The complement-fixation and immunoadherence haemagglutination tests are recommended for advanced study because they are more sensitive. Radio-immunoassay is superior, particularly to detect anti-Au antibody, but is not used routinely.
The rate of Au antigen is generally high among populations in the tropics and subtropics and it is of interest that it differs from one ethnic group to another. Some investigators consider the possibility of arthropod transmission of virus B. Certainly, accUIIIU1ated results show that virus B is transmitted not only by blood transfUsion but by feca1oral and other routes. Sero-epidemiologica1 study of Au antigen and antibody is essential for the surveillance of viral hepatitis, in addition to notification of clinically evident cases of the disease.
5.'r Smallpox In most countries of south-east ASia, smallpox has been well controlled for' quite a long time. However, vigilance is always necessary because of the existence nearby of large endemic areas. The clinical detection and recognition of the disease are comparatively simple matters. Clinical diagnOSis is a sufficient reason to report cases, but laboratory diagnosis must follow. The pertinent procedures are given in a WHO publication, "Guide to the laboratory diagnosis of smallpox for' smallpox eradication programmeS" (Geneva, 1969). Electron microscopy of material, negatively stained with phosphotungstic acid, from vesicle or pustule fluid will give a picture of characteristic virion structure of pox virus very quickly. This makes it possible to differentiate between Herpesvirus varicelae and variola virus but not between variola and vaccinia subgroup. A new method for the isolation and identification of variola virus was recently developed in Japan by Kitamura, and is to be published soon. It utilizes hyperplastiC focus formation in HeLa cells. The cultivation of the virus on HeLa cells using a flat-bottom type of microplate produces hyperplastic focus and makes it easy to identify variola virus and determine its infectivity titre. Differentiation of variola major and minor viruses is more easily done by the above method, utilizing the growth difference of the two viruses at different Ceiling temperatures, than by pock-counting in developing eggs.
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Since the immunity status of individuals is reflected most clearly by the skin reaction after vaccination, it is recommended to perform mass surveys of the illDm.mity of a population against smallpox by measuring that reaction. Reading should be done three and seven days after the inoculation of smallpox vaccine. A "take" means no immunity; immune persons show accelerated reaction of erythema on day three but none on day seven, and there are intermediate reactions.
5.8 Cholera and other vibrios Since El Tor vibrio has created a new situation during the last decade, its surveillance is of importance in this region, and laboratory investigation is indispensable for this purpose. The standard technique of isolation and identification of the cholera vibrio is well established. The El Tor vibrio can be differentiated from classical Vibrio cholerae by variations in their ability to cause haemolysis and agglutination of chick or sheep red cells and in their resistance to 50 mg-polymixim B disc (Difco) and to MurkerJee's phage IV at routine test dilution. V. parahaemolyticus is an enteropathogenic, facultatively halophilic organism encountered in bacterial food poisoning and gastroenteritis. It is relatively unknown outside of Japan, but it will certainly become important as enteropathogen among peoples who commonly consume sea foods. Therefore, further study of y. parahaemolyticus should be encouraged.
6.
SERUM REFERENCE BANK AND REFERENCE
CENI'RES
6.1 The WHO serum reference bank The role of the WHO serum reference bank is twofold. It undertakes the scientific banking of serum collections and provides a service for serological epidemiological investigations in individual countries. Serum collections will be made in each country under the auspices of the Western Pacific Regional Office. Sera are accepted and stored in the serum bank with their individual data in a retrievable form. With WHO approval, investigation of sera for antibody or other markers will be made at the serum bank or by co-operating laboratories. Some of the sera will be stored for posterity. With WHO approval, some of the serum collections may be distributed to other laboratories for specified investigations. Serological epidemiological studies to be undertaken in t he serum bank ares (1) a one-time prevalence survey of antibodies or other markers, for instance the polio-antibody study of a population, and (2) prospective or longitudinal studies on representative serum samples from the same individuals, collected at specific time intervals over a given period, for instance before and after immunization. FOr this pUrpose, it is most desirable to collect
- 21 sera from randomly selected heal thy individuals of various ages who may be considered representative of the population to be studied. A sample size of 25 in each age group (e.g., single-year groups under five years of age, five year groups up to 19 yeara of age, and broader groups thereafter) usually provides sufficient numbers for a simple appraisal of the age pattern of the sero-reactivity curve as a whole. On the other hand, sera from acutely ill and convalescent patients with a specific clinical syndrome will be collected, stored and studied for antibodies against various antigens, particularly in the case of a new epidemic. Some of the al1quots of serum should be preserved at opt1lllum temperature for study at some future time and designated Hposterity samples". They are intended for (1) multipurpose and prospective surveys of representative index groups; (2) elucidation of the etiology of undiagnosed illness or unidentified epidemics the causative agent of which will be isolated at a later date on sera taken from patients in such occasions; (3) genetic and other studies on materials from unique and disappearing population groups; and (4) future reference with regard to special genetic and biochemical markers. The quantity of serum required is about 3 ml from which 6 aliquots of 0.5 ml will usually be preserved in plastic (NUNC) tubes. Blood is taken by vacutainer type of syringe and serum is separated under ster1le oconditions. Specimens are transported from the field to the serum bank at -150 to o -196 C in liquid N2 refrigerators, with identifioation cards attaohed. After arrival at the serum bank aliquoting of eaoh serum is made and the o speoimens are stored in the super-freezer at -70 C. At the same time, data about collection of sera are processed and the results of the investigation are obtained by oomputers. The results will be sent as soon as possible to the country which has contributed to the serum oolleotion and to WHO. According to the experience of the serum bank in Prague, the whole process takes roughly four months. The serum bank also circulates information periodically about the serum collections and the studies carried out by the bank or co-operating laboratories. Some of the participants asked whether emergency aid in fighting an epidemic could be expected from the bank, but were told that the purpose of the serum bank was completely different. 6.2 Reference centres
There are three levels of WHO reference centres and a category of collaborating laboratories. They are WI{) International Reference Centres (IRC), WHO Regional Reference Centres (RRC) and National Referenoe Centres (NRC). Besides these, WHO collaborating laboratories are nominated by IRe or by WI{) for a oertain period of time, to oo-operate on tasks requiring international oollaboration.
- 22 An IRC is an institution designated by WHO to assist in the development and maintenance of high standards of work in specialized fields. An RRC is established by WHD in cOJl8ultation with the IRC. and usually one RRC for one subject exists in a region. An NRC is established by a government to provide consultant service in a particular field, and it is responsible to the government. An NRC may establish direct contact with the related RRC and. in the absence of an RRC. with an IRC. The functions of IRC or RRC in the field of microbiology are as follows: (1)
Identification and classification of micro-organisms. Maintenance of prototype strains and their distribution to selected laboratories for reference purposes. Provision of newly-isolated strains of micro-organisms to regional or other competent laboratories. Taking part in the provision of specific typing sera. Playing an active part in collaborative fields and laboratory studies set up by WHO.
(2)
(3) (4) (5)
(6) Training of research workers in its specific fields. (7) (8)
Providing aid and advice to national laboratories. Submission of an annual repOrt on the work of the centre to WHO.
In 1970, 107 WHO IRCs, 56 WHO RRCs, 2 WHO/IARC IRCs, 2 WHO/FAO IRCs, and 20 WHO/FAO reference centres were in existence.
7.
SURVEILLANCE OF VECTORS OF MEDICAL IMPORrANCE
Many of the important diseases that affect man, particularly in the tropics and subtropics, are transmitted by insects. Some of these diseases are explosive in nature and can rapidly assume epidemic proportions; wellknown examples are dengue haemorrhagic fever and yellow fever, transmitted by the StegomYia moSQuitoes, typhus fever for which the body louse is responsible, plague associated with the rat and the flea, and malaria transmitted by the anopheline mosquito. Diseases of a more chronic fonn, and which spread more slowly, are filariasis transJDi tted by IIIOsqui tos, onchocerciasis transmitted by the blackfly. trypanosomiasis by the tsetse fly, and Chagas' diseases transmitted by the reduviid bug.
- 23 Morbidity and mortality statisticB will frequently reveal w.nere these diseases exist. surveillance on the other hand oan tell us where outbreaks _y be expected. One aspect of surveillance is the presenoe of the pathogenic organ1_ in ani-lor man; another is the distribution and density of the arthropod veotor that tranBll1ts it. In most. situat.ions, these factors are in a oonstant state of flux; it is of the greatest importance therefore for public health authorities to be able to recognize trends in disease incidence, to identify the responsible elements and to place themselves in a position to deal with them. Entomological observations can play an important role in the development of such an overall surveillance prog~. Some of the most 1IIportant of these are described below. They are basically saple and can be perfonaed by all countries in the Region. Ideally, they should be under the direction of an entomolOgist. However, the maJorit.y of the obBervations recom.ended could be performed by a well-trained entomological technician. WHO would give consideration to providing additional training to suoh personnel. This type of entomological un!t should be integrated into the overall COmmunicable d1sease surveillance prosram-e. 7.1 SpeCiation
It is of prime lIIportance to be aware of the identity of the spec1es with which one is concerned. Without this information it is difficult, if not impossible. to obtain a complete understanding of the epidemiology of the disease and to plan effective, safe and economic methods of control, based upon the knowledge of the most vulnerable phase of the life cycles of the vector. General infonaation on methods that can be used to identify some of the IIOre lIIportant vectors 1s contained in a document provided to the Seminar, entitled "Vector Control in International Health". This docUlllent also provideB information on the life cycle of a number of vectors including moaquitoeB, fleas and lice. For the most part Bpeciation can be determined by orthodox taxonomic methods. However, in certain areas, for exa.ple Anopheles gambiae in Africa, subspeciation is possible· only through complex cytogenetiC procedures, requiring specialized knowledge. A similar similar situation . .y develop in studies now currently under way on the Aedes soutellaris group in the Pacific. WHO oould provide assistance in taxonomic identifications if this was required by countries in the Region. 7.2 Distribution and densitl
An equally important element in any national or international surveillance progralllll8 is related to 1IOd1tications in the d1stribution and dens! ty of vector populations. In many instances, man is. responsible by his own actions for an increased exposure to vector-borne disease. His crowing into insanitary urban conglolleratlons can result in a dangerous rise in the denaity of mosquitoes, flies and rats: the opening up of new agrioultural areas without adequate preparation can bring h1lll into contact with new animal reaervoirs of disease: the conetruction of du. and irrigation systems can result in human settlement in unfavourable ecological Situations.
- 24 Most residual 1n8ecticides have been shown to be effective asainst endophllicapeoies of aaadfl1ea. . Consequently, in parta of Iran and other oountries in the ....e geographic region, the inoidence of cutaneous leishmaniaais was drastioally reduoed with the introdUotion of ant1alaria . operations. However, in areas where such operations have been terllinated, sandflies have reappeared and diseaae transmission haa been reaumed. Ecologioal change does not always work to man's disadvantage. For example, one of the -,st' iJaportant outbreaks of dengue fever yet reoorded ooourred in Greeoe in 1928: thi8 was tranam1 tted by Aede8 &api. Investigations carried' out by WII) during the past ten years have shown that this apeoie8 of lIOaqui to i8 no longer found in the Maditerranean area. If obServations on di8tribution and density are to be of value, they II\UIt be baaed on standardized, reproduoible techniques and should be quantified as far a8 po88ible. Because of the 1IIIportanoe of Aedes aeSlpti in the Western Paoific Rec10n and beoause of the si~lioity and aoouraoy of prooedures that have been developed to obtain Aedes indices in different parts of the world, this mosquito will be taken as an ex..ple of vector surveillance. The first_thod to be oonsidered is the house index, which is simply the ratio, expressed as a percentage, between the n~ber of house a in a well-defined area on the premses of which aotual breeding plaoes of Aedes aegypti are found, and the total number of houses eXUlined in the area. The advantage of this prooedure i8 that it perllits COJDp&ri8ons to be .ade between situations that exist in one part of the world (or one oountry) with another. However, it is t1ate-consuming and reCluires a well-trained staff. The procedure oan also be applied to surveys of adult IIOSClui toes. Another valuable but simpler procedure has been designated the "single larva oolleotion method". This oan be used rapidly over a large area by a relatively untrained staff reoeiving only limited supervision. The infoI'll&tion oolleoted should inolude: (a) the nUllber of houses examined, (b) the nUilber of houses with mosquitoe8 breeding in indoor or outdoor oontainers, (c) the total nlmber of oontainers exaJlined for larvae, excluding those with no water, (d) the number of containers with larvae. The data colleoted will pena1t the following est1ates to be made: (i) the proportion of houses with breeding IDOsquitoes, (11) the proportion of potential larval habitats which are occupied, (11i) the min1J11W11 IlUIIIber of larval habitats per house occupied by Aedes aemti, and (iv) the prevalenoe of Aedes aearpti relative to other containerbreecl1ng IBOsquitoes in and around houses. The application of the _thod under field conditions, co.paring it with the conventional house index, has been well described by Sheppard, Maodonald and Tonn in the Bull. WId Hlth Org. 1969, 467-468, and copies of the reprint will be .ade available.
!2,
- 25 It should be stressed, however, that the greatest value of the technique is in determining the broad distribution of the vector and the main larvae habitats. When the initial surveys have been completed, more detailed investigations will be necessary to define the situation more accurately. Finally, there is the Breteau Index used very effectively by French workers in West Africa: this reflects the number of Aedes-positive containers per 100 houses. It has been concluded that places in West Africa with a Breteau Index exceeding 50 are at risk of yellow fever outbreaks, such as that which occurred in Senegal in 1965. These predictions were borne out by epidemics of yellow fever that occurred in Upper Volta and Togo in 1969. For assessing the adult den&ity, the biting rate is used: this is the number of Aedes aegypti taken during biting (or landing) on human bait per man hour: for the sake of uniformity, these assessments should be made at the peak of mosquito activity. Almost 7000 records of Aedes aegypti have been collected by WHO during the pass five years. These have been stored in a computer and this information can now be drawn upon as required and printouts of denSity maps can be made. Examples of these maps will be presented to the Seminar. This global survey will be continued until as complete a picture as possible is obtained of the distribution and density of this group of mosquitoes. Work on other species of arthropods, such as ticks, is proceeding in the same way. An example of the type of map which is available to governments on request is attached in its draft form. This applies only to Aedes aegypti (see Annex 5). In South-East Asia and the Western Pacific, Aedes aegypti has become extremely abundant in many cities. In Thailand, where domestic water is stored in large jars, the average house index exceeds 70 not only in Bangkok, but even in Chiengmai in the north of the country. In the Philippines, the multiplicity of containers breeding larvae has resulted in a record Breteau Index of 560 at Davao in Southern Mindanao. In Thailand and the Philippines as well as in other countries in SouthEast Asia and Western Pacific regions where dengue haemorrhagic fever has become prevalent it has been suggested that the reason may be the sheer numbers of Aedes aegypti in the houses. However, research directed towards correlating mosquito density with transmission has been inconclusive. Alarming estimates of population densities of Culex fatigans have been made in some cities of the world. For example, in one city in Burma the density was estimated to be between 45 million and 65 million per square mile, and even in rural communi ties in India, where the WHO research unit for the genetic control of mosquitoes is working, densities of between 15 000 and 20 000 mosquitoes have been found in small rural villages.
- 26 It has been observed in a number of countries in the Region where su~veys have been performed that mite-borne scrub typhus is an important and widespread disease. For countries in whicll this condition could occur, it may be impoy'tant to arrange for serological observations to be performed on a selected sample of the population. Studies on the presence and distribution of possible vectors should also be undertaken. The assistance of WHO could be requested in planning and implementing such work.
7.3 Insecticide resistance Since the first report of resistance to the modern residual insecticides, the problem has grown steadily in scope and intensity. At present, 105 species of arthropods of public health importance have been reported to have developed insecticide resistance t.o some degree. Almost every important disease vector is involved, and one can only anticipate that, as control programmes are extended, the situation will deteriorate further. Of special interest is the situation in the Central Valley of California where the mosquito vector of encephalitis is now resistant to all available insecticides. It is of the greatest importance also to note the widening distribution of rat resistance to warfarin. An outline of the present poSition on resistance has been presented in the special issue of the WlKl Chronicle on vector control, 1 copies of which were made available to participants in the seminar. WHO has developed a standard test procedure and test kit for almost every vector of public health importance. Many thousands of these have been provided to workers throughout the world and the results. which are analysed and stored in a computer, make it possible to map resistance on a world basis. The systematic use of these test kits in a surveillance programme has the advantage of revealing trends in the development of resistance, and thus helps to prevent control failures. By establishing the extent of insecticide resistance and determining cross resistance pattprns in resistant populations, one is able to determine which compounds are still effective and make recommendations for substitute materials. It is planned to prepare maps showing the distribution of reSistance; these will be overlays to the maps on distribution and density. 7.4 Control
Another important factor in the development of an overall surveillance programme is an adequate knowledge of control procedures. This is necessary in order that authorities may be in a position to deal with outbreaks as they develop. In this regard it is important to bear in mind that the control of all vectors of public health importance today is dependent upon the use of chemicals and that this situation is likely to continue for an
~o Chron., 1971, 25, 214-218.
- 'Z7 -
indefinite period of time. In retrospect, it is of value to note that the discovery of the synthetic residual insecticides had the effect of revolutionizing vector control and, as a result of their development, it became possible for the first time in the history of public health to contemplate the control, or even the eradication, of many of the maJor diseases of man. However, as already indicated, the development of resistance has tended to blunt the original optimism: it is also important to note that no single or Simple solution to the problem of resistance has yet been discovered. The only practical solution that is open to us at present is the replacement of insecticides to which resistance has developed by another of known characteristics which will control the resistance species. The present status of the control of. the major vectors of huan disease has been outlined in broad terms in the special issue of the WHO Chronicle referred to above. More detailed information on techniques that might be used in the control of vectors is to be found in the 17th Report of the WHO Expert Committee on Insecticides,l copies of which were made available to the Seminar. In this document it is shown that the most satisfactory fom of control from a long-term viewpoint is through sanitation. This is reiterated here: if source reduction, integrated with the JudiciOUS use of insectiCides, is made the basis of mosquito control, the problems of resistance and environmental control will be avoided. This may be more expensive in the short-teno, but is more satisfactory in the long run. Emphasis must also be placed on the necessity to keep airports free of mosquitoes and to 1nsist on the effective disinsect10n of incoming aircraft as a protect10n against the 1ntroduction of dangerous vectors. Details of how this can be achieved will be found in "Vector Control in Internstional Health" which has been made available to the Seminar participants. In conclusion, surveillance of human disease is a multidisciplinary undertaking. This is particularly the case as far as the vector is concerned. It involves not only ecology and taxonomy, but also genetics, physiology, chemistry and control. All these must be brought together into one entity before an accurate assessment can be made of the possibility that vector-borne diseases will recede, or increase in intenSity, and before one can acquire enough confidence to recognize and deal with a deteriorating situation. The means are at hand to stop epidemicS of vector-borne disease: it is up to vector surveillance to forewarn, and to epidemiological surveillance to decide on the line of action to be taken.
~d Hlth Org. techno Rep. Ser.,
No. 443, Annex 18.
- 28 In the past few years the occurrence of a sequence of virus diseases transmitted by arthropod vectors has made medical entomology an inseparable part of the epidemiological surveillance of communicable diseases. In the face of a vector-borne virus disease the first objective is to establish the identity of the vector, to know the situation of risk, and to introduce expeditious measures of vector control. This involves capability for the collection of arthropods, capability to identify them by genus and species, and capability to observe their breeding, mobility, distribution and biting habits and to process them for virus isolation. When the nature of the diseased cases is such that an immediate laboratory diagnosis cannot be made, it is often possible to isolate the responsible virus from the arthropod vector or non-human zoonotic reservoir as a first step in the laboratory procedure to provide the antigen which will be the basis of the laboratory study of the infection. A collecting system entailing constant search for virus-infected arthropods often turns up suspect disease agents. The etiology of a number of newly-occurring human epidemic diseases has been rapidly identified by serological screening of patient's sera against virus isolates fortuitously discovered in mosquitoes in the course of a long-term entomological surveillance programme. Once a virus-vector association has been established, such systematic collection and processing of selected vector species can provide quantitative data relevant to time of appearance, duration of presence and intensity of infectivity of the vector population. This represents the most sensitive method in the surveillance of virus disease situation involving arthropod vectors. When the vector is recognized, it can provide clues as to the source of the virus which may be useful in focusing on the area where intensive vector control is required or may lead to serological investigations to uncover the silent wild mechanism of maintenance and dissemination of the virus. The selective collection of biting mosquitoes and precipitation tests can assist in identifying the source of the vector's blood meal. It is thus apparent that personnel with entomological and virological training are essential for effective epidemiological surveillance. When such personnel have additional training in epidemiology, they can assume major responsibility in handling the surveillance system.
8.
GEOGRAPHIC PATHOLOGY AND METHODS FOR MAPPING DISEASES
The fact that geographic pathology, epidemiology and medical geography overlap to a considerable extent is not surprising since each of these is di!"€cted toward the same problem. The differences are simply differences in approach. The epidemiologist is primarily concerned with controlling disease, especially the spread of disease among populations; he is statistically oriented, in contrast to the clinician who is mainly concerned
- 29 with curing disease in individual patients. emphasis is upon the geographic environment The geographic pathologist focuses upon the disease as influenced by the place where it disciplines or subdisciplines are concerned The medical geographer's in which the disease occurs. essential nature of the occurs. All three of these with the ecology of disease.
One of the very important problems in Our efforts to relate geographic factors to the occurrence and manifestations of disease is how to handle the great accumulation of knowledge so that what is known shall be available when needed. If we were to apply available knowledge, many of the serious problems related to geographic medicine and epidemiology could be resolved. This is not so easy as it sounds, however, because first we would have to select the pertinent bits and pieces of "available knowledge" from the enormous stockpile of data, next, deter~ine their relationships with each other; only then could we attempt to fit them together so that the whole would become much more than just the sum of its parts. Our opportunities for getting important new information, if we can effective17 handle the data, are increasing at a fantastic rate now that we have aircraft and earth satellites with their multiple band sensing and recording mechanisms. For most of man's existence he has been heavily dependent on data obtained by the refleotionof eleotromagnetic energy in the narrow range of 0.4 - 0.9 microns, comprising the visible and very near infrared spectrum. The new sensing mechanisms enlarge upon this to an almost unbelievable degree. Optical-mechanical scanners that sense thermal infrared, side-looking airborne radar (SLAR), and gamma ray spectrometers, together with more conventignal recorders (cameras), extend "vision" over the enormous range of 10-0 to 10 9 microns. These devices, operating from ordinary and high altitude aircraft, and satellites are providing access to all parts of the earth at frequent intervals, and are producing enormous volumes of data. This makes it all the more urgent to develop computer systems that can select and process data, converting them to the information we need if we are to answer the preSSing questions of today -- and the further questions that will be just as pressing tomorrow. At present less than 3 per cent. of the data being accumulated by the National Aeronautics and Space Administration of the United States of America in its Earth Resources Programme is even reviewed. And of this 3 per cent., but a small fraction is actually converted to useful information. It is very unlikely that we can handle the enormous amount of data available to us without computer assistance. The greatest single obstacle to full exploitation of what computer technology has to offer medicine is the lack of a data-structuring system that allows effective input. A second major obstacle is our inability to develop a format for displaying output that will communicate pertinent information effectively in the context of the particular problem. The arrangement, manipulation, and presentation of data so that the total becomes more than the sum of its parts, is the essence of converting data into information. To the geographic
- 30 pathologist, the medical geographer. and the epidemiologist, map forms are ideal for the presentation of information because disease maps are readily adaptable to serve a variety of purposes. Disease maps can be produced in response to three general categories of questions. The first may be merely: what countries have the disease and. perhaps. how much? The answer is well suited to a dot-type or shading-type map. These maps are simple to produce and. although limited in scope, provide information that can be of great value. The second type of map presents quantitative information to answer questions about the distribution of disease within the area under consideration. Contour maps are best suited for this. The third type of map presents quantitative information on the incidence. or other disease rate or index. of a disease. the prevalence of reservoirs and vecto:'s. land usage. etc. This is obviously the most complicated kind of disease map and can be used as a research tool to help elucidate the ecology of a disease by identifying and locating the complex factors that contribute to its causality. Computer technology has progressed to the point where most tabular and narrative data having real location can be readily converted into map form. This offey's enormous advantages but also poses a great challenge; we must develop a data base appropriate for computer manipulation in order to make effective use of the computer technology and instrumentation that is becoming more and more readily available. When we have converted large amounts of epidemiological data into map form. we shall have at our disposal a much better means of evaluating the many ecological factors that contribute to disease. And with this new information we shall be able to accomplish much more epidemiological surveillance. Since the presentation of data in map form highlights those areas in which information is deficient or lacking altogether, disease maps may also stimulate the pl~duction of necessary information. The use of disease-environmental maps as a research tool is based on the assumption that coincidence in the distribution patterns of two mapped factors indicates a relationship between those factors. Of course, the association may be merely coincidental, and recognizing such a coincidence is only a first step toward detecting causal relationships. A mathematical approach to determining the probability that one or even several particular factors are causally associated with a disease is very appropriate, once the factors are known. Unfortunately. there at'e manY important factors that are still unknown, and this is where distribution maps can play thei~ greatest. but not their only role. Overlaying and visual comparison of patterns permits the detection of relationships so complex that standard mathematical methods may fail to show them. The computer/plotter can produce maps rapidly and relatively inexpensively. once the data base and appropriate programmes have been established, and the maps thus produced can be used by the geographic pathologist. epidemiologist, etc., as a research tool as well as a means
- 31 of displaying the final results of his work. Another obvious advantage of computer-produced maps is to allow presentations to be kept up to date. In the past, the relatively few available geographic atlases of disease remained unrevised for many years because of the time and expense required to produce new editions. There is a long way to go before disease data in narrative or tabular form can be converted into maps. One of the serious problems is that disease maps, except for certain dot-type ones, represent abstract statistical surfaces that must be calculated from field observational data; in this they are quite unlike road maps, political maps, topographic maps, type-of-bedrock geological maps, etc., which show the actual locations of things. It was this aspect of the problem that caused the greatest difficulty in the development of a system for computerized "mapping of disease" (KlD) (see Annex 6) and related environmental data, since we lacked a data-structuring system that would allow effective input into a computer data base. After considerable work, the concept of a data point, i.e., a bit of mappable data was developed and the minimum limits of its content were defined as follows: (1) (2) (3)
a precise LOCATION a defined disease or environmental FACTOR a specific VALUE for that factor a particular TIME reference the DATA SOURCE
(4) (5)
Characterization of the environmental factor proved to be very difficult indeed. However, a hierarchical system was developed which allowed sharp characterization of the factor to be measured and located. This system made it possible to produce data points from narrative and tabular data. In this connexion, it is pertinent to consider a basic problem -the validity of the data. There is an old Korea saying: "The water, downstream, will not be clear so long as the water, upstream, is muddy", and this is quite applicable to the manipulation of data whether by computer, or pencil, or simply as an unaided mental process. The data base is the first 11nk in the chain, and no amount of processing can convert bad data into good information. Reliable disease data are very limited indeed, and if the study is restricted to such data the task would be quite simple, mainly because there would be so little to deal with. However, there are large pools of suboptimal data, and one must make, do with these, if reasonably effeotive solutions to very pressing problems are to be developed.
- 32 The most critical part in developing any automated data processing system is to determine precisely what output (result) is aimed at. This is necessarily so because output requirements directly influence virtually eve~y step in the development of the system. The other side of the coin is input. In a sense, input is the cloth from which the garment is made; system deSign is the pattern to which it is cut; and the computer is the sewing machine. Since output is of no value unless it is put to good use, the potential user must also be considered. In developing the MOD system, output was directed primarily toward information, in map form, that would be useful to the user by: presenting quantitative aspects of disease-environmental data in relation to place and time; identifying the multiple (potentially causal) factors associated with a given disease, and their interrelationships; determining interrelationhips, if any, among several different diseases occurring together, e.g., schistosomiasis. iron deficiency, protein malnutrition and tuberculosis; evaluating the impact of the disease upon socioeconomic conditions in the area; anticipating the effects of an altered ecology on the incidence and manifestations of disease. and predicting probable variations in incidence in the foreseeable future -- on the basis of past history and trend analysis. There are three principal kinds of maps: dot-type (data point). shading-type (choropleth), and contour-type (isopleth). The first two types have been most extensively used in presenting the distribution of diseases because of their simplicity. but these kinds of maps have severe limitations. Dot-type maps are suited primarily to show whether a particular factor is present or not, i.e., to give a yes or no answer, at a particular point. Only limited quantitative information is possible, by varying dot size, shape, or colour. Shading type maps are most suited to depicting an area in which a particular characteristic does or does not eXist, e.g., a geologic structure Or a political state. They have much the same limitation in presenting quantitative aspects as do dottype maps. Contour-type maps, on the other hand, couple both qualitative and quantitative aspects of the data. at the same time indicating a real coverage. Each contour line (isopleth) connects a series of points of equal value, the group of contour lines presenting a series of distribution patterns that show amounts of involvement. Moreover, since the closeness
- 33 of lines indicates the rate of change with (geographic) distance, relationships are clearly demonstrated that might otherwise be completely overlooked with shading-type maps, since all values in a shaded area combine to pl~duce an average. Thus, shading-type maps (and to an even greater extent, dot-type maps), present quite limited information about disease and environmental relationships because of the problems involved in gr~upingdata, that often lead to marked distortion of place/quantity relationships. An exception is the special situation where, using high resolution, i.e., large scale maps, every case or small group of cases of a particular disease is precisely located by a dot. Such a technique is widely used, and very successfully, by epidemiologists. This is probably the reason why disease and environments:! maps have not been more extensively used. Contour mapping avoids the most serious of the data grouping problems; however, it makes-much greater demands of the data base in terms of completeness, and requires much more skill and energy in data manipulation and display. The major difficulty comes with interpolation and extrapolation when, as so often happens, data points are sparsely or poorly distributed or both. Fortunately, there are ways to handle this problem. As an example of just how maps could be used in epidemiological surveillance, a communicable virus disease that is dependent upon a (non-human) reservoir, an arthropod vector, and a susceptible human population is considered below. Areas in which there were potential (uninfected) reservoirs and vectors would be the regions of primary concern in epidemiologic surveillance if there were a non-immune population there. Moreover, knowledge about whether or not the areas had been previously treated with DDT, for example, would help in antiCipating certain problems in vector control. The pertinent maps that could be produced - assuming an adequate data base - and overlaid, one upon the other would show the following information: lea) (b) 2(a) (b) (c) Presence (and amount) of potential reservoirs. Presence (and amount) of infected reservoirs. Presence (and amount) of potential vectors. Presence (and amount) of infected vectors. Areas where significant resistance to insecticides might have developed, e.g., where DDT had been used in the past. Areas where living conditions and habits of the human population were conducive to effective contact with infected vectors - i.e., areas of risk with respect to infection. Presence (and numbers and protective level) of immune individuals, i.e., population areas exposed to infection but not at high risk with respect to the disease.
3(a)
(b)
- 34 4 Ecological factors pertaining to reservoirs and vectors such as: kinds and amounts of particular species of p~ants; soil characteristics; land use, including irrigation, etc.; surface water and its nature; climatic conditions, etc.
It must be emphasized that the user, not the computer system, makes the correlations between the raw data and the output map, evaluating the various factors that make the map look as it does. The computer system will not analyse the maps it produces nor will it make value judgments. 8.1 Summary and conclusions We are being inundated with data, but starved for
The problem: information.
The solution: Develop an automatic data processing system (with an adequate data base) that, in response to specific query, will retrieve, collate, and manipulate all the pertinent data to yield the best possible answer. An effective system for mapping disease and related environmental data provides the means whereby the disease panorama can be quickly and effectively presented in map form in a time context that may be either current or historic. In this context, the disease panorama is to include location of the disease at a particular time in terms of prevalence, incidence, mortality, and morbidity. But more than this, it can also include information on the nature, quantity and location of those numerous environmental factors which influence the rate of occurrence as well as the character of the disease (see also Annexes ';' and 8). 9. DISCUSSION ON COMMUNICABLE DISEASES OF TOPICAL INTEREST
When the technical presentations on epidemiological surveillance, advanced laboratory techniques for diagnosis and investigation, vector surveillance and mapping of diseases were completed, attention was directed to the communicable diseases of primary concern in the Western Pacific Region. These were considered from the point of view of the current difficulties in their surveillance and control. 9.1 Eye diseases (conjunctivitis and trachoma)
During the period August to October 1971, an epidemic of conjunctivitis was observed in China (Taiwan), Hong Kong, Japan, the Khmer Republic, Malaysia, the Philippines, the Republic of Viet-Nam ,and Singapore. 'The attack rate among schoolchildren in the greater Manila area was about
- 35 -
8 per cent. whilst that among the general population was estimated to be about 6 per cent. The attack rates among the different adult age groups showed no significant differences, and this suggested the operation of a new etiological agent to which the population had not been previously exposed. A viral agent was isolated in Bangkok, Iiong Kong, and Singapore, but no final identification of the virus is yet available. It probably does not belong to the adenoviruses. Trachoma was reported to be of widespread occurrence in Papua New Guinea but is not a major cause of blindness there. A country report from Laos referred to increased occurrence of trachoma in rural areas. 9.2 Respiratory diseases
Respiratory infections ranging from epidemic influenza to pertussis, bronchitis and pneumonia were mentioned as being commonly notified or reported voluntarily by well-informed medical men. Suspected cases of influenza can be diagnosed by the dispatch of specimens, correctly collected according to the WHO guide, to the regional reference laboratory for influenza. On receipt of positive information it may be Judged appropriate to vaccinate persons in selected occupations, infants, reconvalescents and the aged, making sure that the vaccine contains the specific antigen for the circulating type of influenza virus. This would be particularly important in countries such as Papua New Guinea where post-influenzal pneumonia has been a very important cause of mortality, probably reflecting that country's stage of socio-economic development.
9.3 Diphtheria The periodic reappearance of diphtheria, with fatal consequences, emphasized the importance of increased surveillance for this disease and of more effective efforts for early vaccination of growing populations. If diphtheria is to be completely controlled the routine i~unization schedules must be strictly adhered to, attention must be given to immunization policy in general and the coverage of the population by the health services must be improved. Epidemiological services are needed for the investigation of sporadic or generally occurring cases, the analysis of immunization levels, the rapid detection and follow-up of carriers of either toxic or non-toxic strains and the study of socio-economic factors in population subgroups in which the disease may be expected to occur. Diphtheria is reasonably well controlled 1n the countries of the Western Pacific. Between 1958 and 1968, a downward trend in morbidity rates was observed everywhere except in the Republic of Viet-Nam (see Annex 8. It is expected that th1s trend will continue but epidemic outbreaks are still possible if immunization levels are not kept high, particularly 1n the peri-urban and slum areas. Indeed, the decline 1n 1969 and 1970 is now less pronounoed in the countries whioh showed the highest reduotion in previous decade. Epidemiological surveillance is particularly needed in diphtheria during the stage of low morbidity.
- 36 In Fiji. the detection of a case of diphtheria initiates a search for carriers and contacts that utilizes large numbers of health department staff and is usually not successful 1n finding the SOurce. There was some question. particularly in regard to Papua New Guinea as to whether the occurrence of diphtheria cases was a reflection on the effectiveness of immunization. With a low diphtheria attack rate after immunization epidemics of pertussis ravage the child population showing that the DPT vaccines might have certain basic defiCiencies. It was stated that dermal diphtheroid might playa role in immunity status. The Schick test was a good indicator of the immune status of a population. Seventy-eight per cent. of children in Japan between 0-15 years of age in 1968 were Schick negative. In New Zealand. the rate ranged from 94 per cent. in a better housing area school to 76 per cent. among children of Italian and Greek immigrants. 9.4 Venereal diseases Even though consideration of gonorrhoea and syphilis was not in the programme of the Seminar. a number of problems were mentioned in connexion with changing patterns of incidence. the need for more effective surveillance. the phenomenon of the replacement of yaws by syphilis and the sensitivity of gonococci to therapeutic drugs, It was suggested that a regional reference centre for gonorrhoea strains was a necessary component of gonorrhoea surveillance. It was stated that there was no sign of a gpnorrhoea vaccine although one for syphilis was being developed and tested in the United States of America and West ~~~.
In Fiji. where yaws had been virtually eliminated by mass treatment with penicillin. congenital syphilis had not appeared as it had recently in Papua New Guinea.
9.5 Intestinal diseases It was reported that 2.5 million people had visited Hong Kong 10.1969 and ~ million in 1970. A somewhat smaller number of visitors to Singapore stayed an average of 3.5 days. The impact of enteric diseases among such great numbers of visitors and tourists emphasized the importance of better surveillance of shigellosis and typhoid as well as of cholera. It was stated that a permanent watch for cholera carriers was maintained in Hong Kong where sewage disposal for about 20 per cent. of the population consists of the manual emptying of night soil buckets. Samples of·the night soil collection are tested microbiologically. By this method it is possible to trace the premises of origin of a cholera positive stool but in the event of a cholera epidemic the overload of the laboratory would make the system impossible. In Hong Kong, also, a system of bacterial enteropathogen surveillance had been introduced. Stool specimens from hospitals or outpatient clinics were sent to Government laboratories for bacterial exaMination. A~ positives found were reported to the area health officers,
- 37 who initiated investigation without waiting for official notification from the attending physicians. In addition, the numbers of notifications of infectious diseases were published weekly in the press so that private practitioners, doctors in hospitals, etc., and the public would become more aware of the disease dangers in the community, and would be more likely to report such diseases to the health authorities when encountered.
9.6 Shigellosis Shigellosis is one of the most prevalent enteric infections in the Region. According to reports from China (Taiwan), Fiji, and Japan, Shigella dysenteriae type 1 had disappeared and the same may be the case in other countries. Instead, She flexneri and ~. sonnei have now been found to assume greater importance everywhere. Along with the changing pattern of Shigella infections, clinical symptoms have become milder. However, the emergence of resistant strains remains a problem. Surveys in the Region, have shown resistance to the more "classical"antibiotics chloramphenicol, tetracycline etc.,- to occur in 29 per cent. of She dysenteriae, 57 per cent. of~. flexneri and 72 per cent. of ~. sonnei. So far, no resistant strains to other antibiotics have been seen, but some resistant strains to kanamycin, nalidixic aCid, etc., have been reported in Japan. The reasons for the change in the epidemic type of Shigella were discussed. It was presumed that immunity, the use of drugs, environmental changes, etc., had exerted some influence but no conclusion was reached. 9.7 Intestinal paraSites
In discussions on the extent to ~hich intestinal paraSites may interfere with the utilization of ingested food, and on the inability of infected persons to work effectively even in the absence of overt disease. no hard data were offered. However the extent of the problem was evidenced by a report that in the Republic of Viet-Nam approximately 88 per cent. of people in all age groups suffered from protozoal or helminthic infections. The three main protozoal paraSites found were Entamoeba coli, Giardia lamblia and Trichomonas; ~. histolytica infection occurred in about 1.8 per cent. The three leading helminthic infections were trichuriasis (51 per cent.), ascariasis (48 per cent.), and opisthorchiasis (44 per cent.). Hookworm infection occurred in approximately 32 per cent. -- Necator 40 per cent., Ancylostoma 40 per cent. and mixed infection 20 per cent. In the southern part of Laos, schistosomiasis was a·problem on Khong Island. A 1970 survey revealed the infection rate of organisms resembling Schistosoma japonicum to be approximately 14 per cent. among the indigenous population.
9.8 Hepatitis Hepatitis has been serious in Australia and New Zealand. The morbidity rate recently reached 150 per 100 000 population in New Zealand. It was, however, believed probable that hepatitis was serious in other countries also.
- 38 Although recognized as an important disease problem in the West, infectious hepatitis is a notifiable disease in only seven countries of the region: American Samoa, Australia, French Polynesia, Khmer Republic, New Zealand, Papua New Guinea, and Philippines. The result was a serious lack of information. In the Republic of Viet-Nam arrangements for the reporting of infectious hepatitis were being established. An admission and disposition sheet was made out for each in-patient in government hospitals. These sheets were handled by automatic data processing equipment at the national level using a standardized disease nomenclature which included infectious hepatitis. Since the majority of professional level medical care was given in government hospitals and since the person coming to central health services with this complaint was usually hospitalized, the admission and disposition sheet was a useful means of gathering data. Admittedly, cases being seen by the private physician or hospital would not be detected by this system. It was recommended that infectious hepatitis come under some type of surveillance especially now that the serological approach using the Au antigen was available at least for virus B. Watch could be relatively simple. It was mentioned that in the Eastern Mediterranean Region an outbreak of infectious hepatitis had been preceded on several occasions by a rise in incidence of mixed bacterial dysenteries. A watch could be initiated among the group thus discovered to be exposed to an outbreak. After the conventional incubation period, icteric and anicteric cases could be detected using the available liver function tests at clinical laboratories. It was reported that some cases without icterus showed severe histopathological change of liver in autopsies; the symptoms of hepatitiS, whether jaundice appeared or not, were sometimes independent of the severity of liver lesion. To determine this, it would be necessary to carry out the transaminase and other liver function tests. The concern regarding "hepatitis associated antigen" (Australia antigen) carriers in nursing and laboratory staff was discussed. It was concluded that in certain localities the HAAT rate was so high that it would be impractical to displace these people from such positions. Medical administrators should rather, pay attention to careful surveillance and prevention of contacts by careful aseptic precautions and the use of disposable apparatus and equipment as much as possible. It appeared from the discussion that it was very difficult to compare morbidity data on hepatitis from different countries because of the very varying practices in morbidity and mortality reporting. In countries where this disease was studied, most fatal cases with symptoms of acute failure of the liver were attributed to viral
- 39 hepatitis. The following example was given: The fatality rate in Denmark, Germany, Austria and Czechoslovakia is approximately 0.36-0.65, but in Switzerland it is 5.2. This did not mean that the treatment was not gpod in Switzerland. or that the disease was intrinsically more severe, but that the less serious cases were not notified and therefore the case fatality rate appeared very high. Another area of interest in infectious hepatitis involved association with cooked seafoods. In the epidemiological investigation of cases of infectious hepatitis in Hong Kong, patients sometimes gave a history of having eaten shellfish, and particularly oysters, before the onset of illness. In Hong Kong, oysters were often subject to a short period of frying or cooking. There were several epidemiological reports concerning hepatitis epidemics due to eating contaminated oysters. Both hepatitis viruses A and B were known to be heat-resistant. Therefore, fried oyster should be- considered dangerous because the heat during frying did not penetrate enough to kill the virus. The same remark applied also to typhoid bacilli and other organisms. It was reported that in Japan, where the number of typhoid fever cases had decreased remarkably, those still found were concentrated in the prefectures that are famous for their production of oysters. This would indicate a close relationship between oysters and typhoid fever. The possibility was discussed that serum hepatitis might be a vector-borne infection involving mosquitoes. It was pointed out that arthropod-borne viruses must replicate within the vector before infecting the blood sucking mouth parts. Whether serum hepatitis virus could be mechanically transmitted like myxomatosis could not be established until a susceptible experimental animal, could be found. According to the human volunteer experiments done by Dr Krugman. an antigen positive blood which is diluted up to 10-7 fold could produce hepatitis in volunteers. Therefore, mosquito transmission of hepatitis virus B could theoretically be possible. Dr Krugman had recently developed a heat-killed hepatitis B virus vaccine which had been shown to be effective in a small field trial.
9.9 Tuberculosis The morbidity rates of tuberculosis were around 200 per 100 000 population in the period immediately following World War II in most countries in the Region except Australia and New Zealand. The introduction of BCG vaccination, and antituberculosis drugs, and the improvement. of nutritional and environmental conditions had resulted in a dramatic decrease of tuberculosis mortality in many countries, but it was still high and a great gap was seen in comparison to the two countries mentioned above. Particularly, the war-devastated area like Viet-Nam (Saigpn) shows a high rate of X-ray positive and bacteriOlogically positive cases. Accordingly, tuberculosis was still the biggest public health problem in most countries of the Region. In
- 40 order to aChieve effective control of tuberculosis, it was necessary to maintain thorough epidemiological surveillance in a country by measuring the extent of tuberculosis problem. This was done by notification of tuberculosis cases and deaths and by clinical and laboratory methods. To obtain an effective direct impact on the chain of tuberculosis infection it was necessary to find mycobacterium positive infectors and to render them non-infective. In this connexion, smear positive cases were the most dangerous source of infection since it had been shown that each such patient infected at least five other persons within a year. Case finding was done by mass X-ray examination and bacteriological diagnosis with microscopic as well as culture examinations. It was highly recommended to utilize microscopic examination of sputum in developing countries. A high school graduate could be specially trained in three months to carry out such examinations. The Ryukyus Islands had not conducted BCG vaccination until recently, while Japan had been carrying out an intensive BeG vaccination programme for the whole population below 30 years of age since the end of World War II. This afforded a valuable opportunity to assess the efficacy of BCG vaccination. Although the decreasing trend of the tuberculosis mortality rate in the Ryukyus was not so very , different from that in Japan, there was a much higher proportion of severe cases of tuberculosis in the former country. It was therefore to be recommended that the Ryukyu Islands, where only the middle school age group was covered at present, should expand the BCG vaccination programme to other age groups. 9.10 Leprosy
On the question whether a possible immunological deficiency among the population of Papua New Guinea would account for the considerable amount of leprosy there, it was pointed out that the very low proportion of lepromatus (3 per cent.) argued against deficiency of (cellular, i.e., delayed-type) immunological mechanisms. 9.11 Vector-borne diseases Filariasis
9.11.1
COncern was expressed about the possible introduction of filariasis into such areas as northern New Caledonia, where a potential vector, Aedes vigi1ax was present, by migrant microfilaria carriers from Tahiti or Wallis Island. This emphasized the importance of extending chemoprophylaxis for filariasis to all infected areas as had been done in American Samoa where the microfilaremia rate had been reduced to 0.78 per cent. No positive mosquitoes had been found there since 1968, though since April 1970, 1471 had been dissected from 215 catching stations in 36 villages. A four-man team carried out systematic
- 41 village-by-village surveys, locating and treating positive cases. The team also checked for anaemia, measured heights, weights and blood pressures, and checked blood sugars. It really provided a kind of epidemiological surveillance service. In French Polynesia, Bancrofti filariasis control was not based on disinsection measures. In fact, the rural modus vivendi of Aedes polynesiensis would render extremely costly at disinsection campaign covering the whole territory. Control activities were thus limited to mass chemoprophylaxis in rural areas and to active treatment of detected carriers. According to an experiment carried on during three years in the pilot area of Mcorea, this procedure had proved effective. 9.11.2 Malaria The concept of surveillance in the field of malaria implied knowledge of the clinico-pathological. parasitological and epidemiological aspects of the disease, of the various devices to screen malaria cues based on that knowledge, and of the methods used to control or eradicate the disease. Presence or history of typical malarial fevers, examination for enlarged spleens and microscopiC examination of thick blood smears were the main screening devices, but the confirmation of a malaria case was based on the microscopic examination of the blood. New immunological techniques namely, haemagglutination, fluorescent antibody, and iDIIIUnoelectrophoresis were promising screening tools in situations of disappearing malaria. Various techniques of malaria intelligence were presented. selected would depend on objectives and means available: The one
(a) Reconnaissance surveys gave a rapid idea of a malaria situation; they were usually based on knowledge of landscape epidemiology, as well as data from hospital records on malaria morbidity and mortality. (b) Malaria surveys inoluded malariometric surveys among children (parasite and spleen) in representative samples of the population, and entomological surveys. These surveys were done both before and after any malaria control scheme. (c) Pre-eradication surveys were sophisticated operations covering all factors that played a role in the epidemiology of the disease, whether relating to the vector and its biophysical environment, or to man and his socio-economic environment. They formed a basis for plans for malaria eradication and served to gather base line data for comparison after initiating attack measures. (d) Serial paraSite surveys among children and infant paraSite surveys in indicator areas were done during the early attack phase to assess the impact of insecticidal spraying on the interruption of malaria transmission. In successfUl programmes the original parasite rate would drop by 80 per cent. at the end of the first year of attack.
- 42 -
When the parasite rate had fallen below 2 per cent. under the impact of a residual campaign, malaria surveillance was established on a total coverage basis. At that point sampling surveys had become blunt epidemiological tools unable to detect and eliminate the residue of infective cases. Vigilance was considered to be an extension of surveillance after the task of eradication had been completed. However, before conSidering the type of mechanism needed in a particular area, it was extremely important to determine the degree of receptivity and vulnerability of every area and this was undertaken through surveillance. Since the principal risk arose from importation of cases, there should be adequate machinery to prevent resumption of transmission arising from imported malaria carriers. Normally the basic health services should be equipped to undertake those activities. Unfortunately however, such services were not well-developed in most of the countries of the Region. Thus a serious dilemma arose as to whether the maintenance activities should be continued through the malaria eradication service and if so for how long, or alternatively what steps should be taken to accelerate the development of basic health services and in what way. On the question of the international importation of malaria, the following potnts were made: (a) It was very difficult to enforce regulat10ns on international travellers. All that could be done was to inform appropriate officials about their arrival in a malaria-free but potentially malarious country, and make certain that, if any fever is experienced they will report to the nearest clinic or health centre for blood examination and subsequent remedial measureS. (b) As regards nationals returning from malarious countries abroad, the Department of Health could enforce any regulatiOns providing for examination for the presence of malaria parasites, and for curative measures. Vulnerable groups included overseas students, high-sea fishermen, technical missions to malarious areas, m1l1tary service or Peace Corps returnees. (c) Whatever safety measures were taken, it was very difficult to detect every imported malaria case, and unless epidemic vigilance units with a malaria expertise component existed at central and district levels the malaria fOCi, cropping up from undetected malaria cases, would be missed, thus leading to an endemic situation.
- 43 (d) A major problem was that of the importation of malaria across frontiers between one country that was eradicating malaria and one that was not. It could be resolved only by international co-operation and co-ordination, and by priority being given to the eradication of malaria in the infected areas along the frontier. In response to questions about malaria in Papua New Guinea it was reported that, so far as was known, there were no chloroquine-resistant falciparum strains r the therapy 0 f malaria was therefore quite standard in that oountry. 9.11.3 Japanese enoephalitis Epidemic Japanese B enoephalitis had been serious in Japan, Korea and Taiwan until three years previously. Researoh was oontinuing on theoverw1oter1ng of the veotor and the reservoirs of infeotion, _. -'.. because the source of these temperate zone epidemios was still not understood. The deoline in nuaber of oases had been variously attribl.lted to suooessfUl vaooination, bonus veotor oontrol fro. widely used agrioultural insecticides and ohanges in human behaviour such as that from summer outdoor evening pastimes to indoor watohing of television. No definitive or quantitative data. to support these suggestions were available, however. " .
•
The faot that oases of enoephalitis were frequently seen in paediatrio wards and fever hospitals of other countries, and the information that was aocumulating about the presenoe of veotors and the isolation of virus from IIOsqui toes in truly tropioal countries, were indioations that Japanese B enoephalitis virus transmission might occur all year round, and might possibly immunize the population by oausing repeated 1ofeotions at an early age. It was suggested that the problem deserved more intensive continuous research in oertain other countries of the Region. It was noted that the disease had formerly been oonfined to northern Taiwan, but that sinoe 1967 oases had ooourred in the southern and eastern regions. In 1969 and 1970 small amounts of attenuated (non-strain) JBe vaooine had been used in piglets, the suspeoted epidemic reservoir of the virus. Beoause of the small nUJllbers, no significant effect could be measured. Since the initiation of an immunization programme, using a killed vaCCine, in young children in Taiwan, the highest attack rate had shifted from the two to three year olds to the over-seven age group. The number of Japanese enoephalitis cases reported in Japan had fallen from 1179 in 1965 to 140 in 1970. While in Japan the decline in reported cases was attributed to the initiation of mass vaccination in 1967, the Koreans believed that the decline 10 their country was simply a cyolio phenomenon.
•
- 44 9.11.4 Haemorrhagic fevers in the region - Korean type and dengue _ were mentioned briefly. Maps were shown which indicated that Korean haemorrhagic fever cases were appearing more frequently to the south of the area where the disease was originally observed in the Republic. Since no etiological pathogen had yet been isolated and no vector identified, there were no known means of control. The Republic of Korea seemed to be the only country in the Region where this disease was recognized. No information was available on its occurrence or absence in North Korea. It was stated that Tahiti, in French Polynesia, could be added to the list of places where epidemic dengue haemorrhagic fever occurred. It seemed that, although Aedes aegypti mosquitoes had first been observed in south-east Asia 150 years before, population increases and urbanization had fostered logarithmic increases in this peridomestic mosquito, and that the consequent acceleration of the cyclic circulation of dengue viruses, starting from the original 1954 focus of the disease in Manila, had produced dengue haemorrhagic fever in many countries of the Region.
9.11.5 Plague With regard to the spread of plague in the Republic of Viet-NUl, it was stated that the most recent flare up of the disease started in 1962 when a few cases only were localized in one of the provinces near Saigon. The disease spread slowly in space as well as in time to become a really big problem in 1965. At that time efforts were concentrated on controlling plague in human beings by dusting clothes, giving vaccinations, administering streptomycin and sulfanomides, but not enough attention was given to the epidemiological study of rodents or attempts to control epizootics among rats. In 1963, and in the following years the insecure conditions in rural areas resulted in a rapid population increase in the cities where the environmental conditions were already in a critical situation after the immigration of almost one million people from the north after the 1954 Geneva agreement. The above were all considered to be relevant factors in the changes of the ecology of both rodents and fleas, changes which were crucial to the spreading of the disease. Experience had shown that the control measures now being practised could confine plague to limited areas and eventually eliminate it. After the large-scale reappearance of plague in the country in 1962 investigators identified about 25 small mammals that might be implicated in its transmission - but only six, Rattus norvegicus, !!. exulans, !!. rattus, Ba.ndicota indica, ~. Bengalensis and Suncus murinus showed evidence of infection. These investigations had ended in 1967, but since then, great ecological changes had taken place, and further investigation was needed of the effects these changes had had on the rodent and flea population.
- 45 • In the past, the gross flea index had been used as an indicator of the possible onset of human plague but it had proved necessary to find a more reliable index. The possibility of utilizing the percentage of flea-infested rats by species and rat pools was being investigated. vector surveillance had been integrated into the overall programme of plague surveillance. BaSically, the flea was an ectoparasite of the rodent host and shared the microclimate of the rodent habitat. There were several important rodent hosts each living under quite different conditions, some of which were favourable fer the flea and some not. The flea population density was, therefore, dependent on the rodent species, and data gathered from flea indices must be related to critical diffel~nces among the rodent species. In the future, studies on flea densities, critically important data on both temperature and humidity should be obtained as these two factors were interdependent ~n their effects on larva survival. The variation in the response of different species of the host animal to infection by the plague bacillus was considered to be an important consideration in plague surveillance. Even at subspecies level, there were considerable differences in susceptibil1 ty. F'or example Rattus rattus diardi, with its 90 per cent. mortality obviously could not support the infection very long. On the other hand, !!. norvegicus, with perhaps a 50 per cent. mortality presented a more serious problem. There were many important unanswered questions. FOr example, the house shrew, Suncus murinus was a common occupant of houses of plague patients. It had heavy burdens of fleas and was regularly found infected with plague. But there was no information about its response to infection nor about the time during which it could infect new flea vectors. The importation of human plague from the Republic of Viet-Nam to the United States, according to published material, had occurred only once (Dickerson 19(6). Only one case was on record of plague imported in to Europe. It was stated that the present surveillance services of the health authorities, which are assisted by AID and WHO, covered all ports from which international shipping operated. 9.12 Immunization
, •
Vaccination was not a main subject of the Seminar, but it was brought up by participants in connexion with surveillance programmes. Accordingly, a brief summary is presented in the accompanying table of the prinCipal immunizations practised. VaCCinations against smallpox, diphtheria, typhoid, cholera, and tuberculosis (BeG) are the most widely adopted in the countries of the Region.
- 46 Live attenuated poliovirus vaccine (Sabin) has been used on a mass scale in Australia, Hong Kong, Japan, New Zealand, Singapore and some Western Pacific Islands, and the results in preventing paralytic poliomyelitis have been dramatic. It has been used to a more limited extent in China (Taiwan), Philippines and the Republic of Korea. In other countries poliomyelitis is still a big problem. Malaysia had an outbreak of type 3 poliomyelitis in 1970. Therefore, sustained immunization with Sabin vaccine is necessary in these countries. Extensive immunization with influenza and Japanese encepha11tis vaccine has been carried out only in Japan. It is said that the A2 Hon" Kong influenza epidemic was relatively mild because of widespread vaccination. In Australia vaccination was restricted to persons with chronic heart and pulmonary disease and those over 65 years of age. Japanese encephalitis vaccine was also used in field trials Taiwan and the Republic of Korea. It was found to be 80 per cent. effective in Taiwan. Measles vaccination is practised only in Australia, Japan, New Zealand and some South Sea Islands. Routine rubella vaccination is carried out with a high coverage of susceptible age groups in Australia and New Zealand, but is not done in other countries. BCG vaccination is widely used against tuberculosis but the age of the target population varies from one country to another. In New Zealand and the Ryukyu Islands a mass campaign is conducted among children of 12 to 13 years of age entering secondary school, whereas in Japan, Tonga and elsewhere BCG vaccination covers all ages from the newborn through young adults. It was reported that BCG vaccination had been dropped in the South Island of New Zealand where the tuberculosis rate is low. 9.13 Vector control
The questions raised on the subject of vector control reflected in some measure the growing awareness of participants that this was a largely undeveloped area of surveillance activity in the Region. They covered not only various aspects of insecticides and insecticide reSistance, but also new measures for biological control. In some countries biting arthropods are a problem apart from being potential vectors of disease. In French Polynesia, Culicoides flies are a serious nuisance. Whether they may also transmit pathogenic viruses is unknown. Examinations of CU11coides carried out 1n California and Panama have resulted in viruses being isolated. But no adequate search for viruses pathogenic to man has been undertaken. It was re-emphasized that if insecticides were used effectively and extensively the emergence of reSistance was inevitable. The speed of emergence of resistance might be increased through the use of insecticides in agriculture. The only practical measure was to replace the insecticide to which resistance had appeared by another known to be effective. For this reason, it was of the greatest importance to carry out systematic surveillance of and testing for resistance.
,
- 47 It was reported that various researchers were being conducted by WID on the biological control of vectors. The WHO genetic control research unit in India was oarrying out an eight-year progr8.llllle on genetic manipulation as a practical means of controlling .asquitoes. Progress had been made on the use of irradiation, chemosterilization, cytoplasmic incompatibility and translooations as means for mosquito control. The last appeared to offer the greatest promise from a practical viewpoint; however none of the procedures mentioned oould be available operationally for at least 10, or even 15 years. The progress in biologioa1 oontro1 using fungi, viruses, parasites, and predators was less advanced: these methods oould not be expected to come into practical use for many years to cOile. Consequently, insecticides would remain the basic means of vector control in the foreseeable future. As a oonsequence of measures taken to deal with emergencies a number of survei11anoe programmes had been developed in different parts of the world. One example cited was the outbreaks of yellow fever that had occurred 1n West Africa three years before. Various studies had been undertaken in that general area to investigate the circulation of the virus in the natural reservoir, the distribution of the vector and the level of 1IImuni ty of the human population. Another example was the reoent outbreak of plague in Indonesia which had led to a detailed study of the natural focus of that disease. Reference was also made to the outbreaks of insectioide poisoning that had occurred in two oountries in the Eastem Mediterranean Region and had resulted in a study of the method of transporting flour and similar food by sea. Another oonsequence was that an international agreement on the separation of food from pesticides during transport had been developed. During the discussion of a proposal that a periodiC list of arthropod vector distribution should be issued, attention was drawn to what WHO had done to colleot and distribute infonnation of that kind. A circular letter had been sent in 1965 to all the oountries and territories in the Region, asking about the Aedes aeszpti situation and information thus obtained was published in~WID Bul1etin. 1 Ii was intended to send out another oircu1ar letter to enquire about the present situation. It was to be hoped that oertain oountries and territories, where the information on this JIOsqui to was still inadequate, would start a survey of Aedes aegypti. Studies of the insectioide susceptibility of this mosquito should also be undertaken to obtain baseline values helpful to investigations into any development of resistance. Mapping was an important element in three programmes with which WHO was associated. The first concemed onchocerciasis in West Afrioa. Seven countries in that area had agreed to undertake extensive action to oontro1 this disease with assistance from the United Nations Development Progr8llllte (UNDP) and other bodies. It would be neoessary to have a cOllplete map of the rivers and streams in the area and this might be done by satellite using remote sensing. The same progranne could map the river habitats of species of tsetse flies. Finally mapping of the areas where the reservoirs of yellow fever might be found was under consideration.
•
~1l. W1d H1th Org., 1967, ~, 544-546.
- 48 The importance of morbidity and mortality notification and registration in epidemiological surveillance was emphasized. The resulting statistical data were especially important for the country concerned. Unfortunately questions on morbidity were rarely included in censuses because of the adDt1nistrative cost. It was necessary to encourage and educate all medical practitioners to be alert to the possibility of encountering notifiable diseases, and to notify them when suspected. On the question of dealing with emergency situations, it was explained that WHO maintained a list of consultants in each particular field who were ready to travel to any place within 24 to 48 hours. They were usually equipped with the necessary laboratory instruments for diagnosis. Where necessary, pathological samples were sent for examination to a regional reference centre or inter-regional centre. However, the serum banks did not deal with emergency situations. 9.14 Mapping of disease The discussion on mapping of diseases centred on the following aspects. With regard to the problem of validity and compatibility of data, it was pointed out that an essential part of data processing for the production of maps, as for tabular or narrative presentations of information, was evaluation of the data leading to selection (sometimes with modifications of form) of those items best suited to the particular objective. In mapping chronic diseases or those with long incubation periods, the best possible evaluation must be made considering the geographic stability of the population. With respect to information available in already printed base maps, the importance of the influence of geochemical environment, including the type of soil, on infections was mentioned. Anthrax was considered a good example of this relationship, suitable characteristics of soil and ground water being necessary for the conversion of bacillary to spore forms. In answer to a question about the development of programmes for mapping disease in various countries of the Region and the appropriate procedures to be used, the following information was provided: Article 13 of the International Health Regulations (part 3), valid as of 1 January 1971, says: "The Organization shall review the epidemiological trends of the diseases subject to the Regulations, and shall publish such data, not less than once a year, illustrated with maps, showing infected and free areas of the world, and any other relevant information obtained from the surveillance programme of the Organization". Each country can produce its own national maps. The national atlases of diseases of India, Kenya, Tanzania and Uganda are good examples of what can be done. In the Western Pacific Region, malaria, plague and schistosomiasis are diseases in which precise mapping would be very helpful
- 49 indeed. This Regional Offioe will oonsider fo~l requests for assistanoe in prooedures for disea.e mapping if suoh prosra-es are oonsidered by the oountry to have high priority in its programme of diseaae surveillanoe and oontrol. Parti01pants were informed that in addit10n to the mater1al presented 1n the oourse of the Seminar, works on geographio pathology and medioal geography were l1sted 1n the sem1nar information bullet1n No.4. A good guide was the oomp1led SU/lllll8.ry: "Souroes of InfoI'll&tion on Medioal Geography", by Lynn S. Mul1ns. In the d1scussion on mapp1ng d1sease importance of work1ng where poss1ble with University Departments of' Geography was stressed. Several partioipants joined in a discussion of the meaning of the term statistically significant. In substance it was &&reed that levels of statistical significance were chosen arbitrarily to suit the subJeot, the situation and the individual, and that all they did was to Masure the desree of confidence in making a statement that two (or ~re) events or situations did or did not have comparabilityand/or a relationship with eaoh other. On the epidemiological surveillance of communicable diseases, the comments was made that apart from the need to ensure oompleten.ss, there was also an important need to ensure promptness of notifioations of oo..unioable diseases. Very often dootors were slow in notif7ing the diseasea and patients might have been discharged from hospitals before the notifioation reaohed the health authorities. As an example of the value of hospital reportina of new diseases or those that are not notifiable as & possible lead for the deteotion and surveillance of new disease problems, an acoount was presented of the investigation into the ooourrenoe of SMON in Japan. 9.15 SM:>N Subaoute myelo-optico-neuropathy. Sfol)N for short. is a new neurologioal disease whiOh haa emerged sinoe the middle of the n1n~teen-fiftiea in Japan. It is c11nically characterized by abdominal pain or diarrhoea or both, and an unusual paraesthesia which follows the fomer in the lower limbs.
Twenty per cent. or more of the patients have blurred vision, 3 per cent. become totally blind and 10 to 15 per cent. cannot take care of themaelves due to 1II.1I1cle weakness or visual disturbance or both. After two extensive outbreaks had occurred in Okayama, Japan in 1969, the Japanese (]overnment established a Special Researoh CoaIission. Although viral etiology had been suspected from the beginning, the Co_ission took a multidisciplinary approach and considered various aspects of neurology, neuropathology, epidemiology, microbiology, biochemistry and 80 forth. The first steps taken were to establish guidelines for clinical diagnosis
- 50 and to initiate an epidemiological survey based upon notifications of the disease from doctors allover the country. The number of registered SMJN patients had reached about 9000 (9 per 100 000 population). After two years of such multidisciplinary research it was found that a strong association existed between the disease and intake of clioquinol. Animal experiments showed that clioquinol was neurotoxic. Familial and institutional aggregation of SMON seemed to suggest its being infectious. However, after further study and analysis of the data, it was revealed that an excess intake of clioquinol was a more plausible explanation than that of intramural infection. The Japanese Government therefore banned the sale of clioquinol as of 8 September 1970. The result was a dramatic drop in new cases from 1988 in 1969 to about 10 in the period 1970 to October 1971. Most of the study group agreed that there was convincing evidence that SMDN was a non-infectious, drug-induced iatrogenic disease. However, many problems remain unsolved, e.g., why did the condition occur in Japan? 10.
SUMMARY
The effects of the growing diversity and changing patterns of communicable diseases vary according to a country's geographical, ethnic and economic situation. If we fail to give proper attention to these aspects of communicable disease problems, we will be neglecting one of the most important areas of health development. In view of the variety of communicable disease manifestations and the presently available means for their treatment, control and prevention, there is an urgent need for national health authorities to strengthen and intensify epidemiological surveillance in order to be able to recognize these diseases quickly, define them accurately and control them expeditiously. The Seminar therefore began its work by reviewing the emerging disease problems and the changing patterns of those which have long afflicted populations in the Region. Next, the objectives of epidemiological surveillance and the means of improving it were considered wi til special regard to those epidemic or endemic diseases presented by the participants as being of importance in their countries. The diseases discussed included smallpox, cholera, plague, malaria, filariasis, typhoid, pertUSSiS, pneumonia, poliOmyelitis, rubella and Japanese B encephalitis. They were examined from the points of view of early reporting, accurate definition of distribution, and assessment of existing immunity and susceptibility. Methods for reliable routine reporting of disease cases were related to the objective of the surveillance sponsor. It was agreed that to have information on a few important diseases well reported was preferable to having many diseases poorly reported or not reported at all. Dependence on accurate diagnosis was the key to validity of reports.
- 51The routine collection of data without adequate analysis and without rational action results in a surveillance system limited to the mere accumulation of information. An essential component of epidemiological surveillance is a permanent capability to respond when analysis of the data on disease occurrence calls for action. This action may take various forms and further field investigation through careful laboratory stUdy, therapeutic support of eXist1ng health care facilities, implementation of vector control or mass immunization. When surveillance detects a new disease of unknown etiology, a multidisciplinary approach should be adopted to elucidate the,nature of the disease and to develop control measures, as was done with subacute myelo-optico-neuropathy (SMON) in Japan. In former times, it was necessary to depend upon olinical diagnosis of communicable disease. This method has been reinforced and, in many oases, largely replaoed by new public health laboratory teohniques. Standardized serological teohn1ques for complement-fixation and haemagglutination tests, tissue culture systems for the isolation of a variety of viruses, fluoresoent antibody, immuno-eleotrophoresis, radio immunoassay and eleotron mioroscopy all represent the application of biolOgical and physical sciences to provide instruments for the acourate and rapid identification and serological diagnosis of etiological agents. The differing laboratory capabilities and capacity of different countries have been recognized by the World Health Organization which has established Or helped establish international, regional and national reference centres. These laboratories oan provide teohnical aSSistance in dealing with a variety of communicable disease problems. WHO has established serum banks which serve to extend effeotive epidemiological surveillance of the current immunity and susoeptibility of sampled populations to a variety of infectious pathogens, and to determine what disease agents are being transmitted in a particular area. The ~ost recent of these banks has been set up in Tokyo where, directly or through the Regional Office, arrangements can be made foroollation, storage and examination of appropriately collected sera. With the rapidly changing malaria situation other vector-borne diseases such as plague and filariasis, have assumed major importance in the Region. This situation, together with the emergence of new vector-borne viral diseases such as dengue haemorrhagic fever, and the threat of yellow fever from both eAst and west, underline the necessity for a permanent entomologioal capability in epidemiologioal surveillance. An entomological service must be able to seek out potential vectors, identify them by speoies, relate their behaviour and distribution to potential and aotual disease transmiSSion and prooess them to detect evidence of th~ir being infected by the pathogen in question. EmphasiS was placed on the growth in international air traffic and the inoreasing movements from place to place of potentially infectious persons and alien arthropod veotors and vertebrate reservoirs of disease. The responsibility of health authorities to inSist upon and oversee
- 52 disinsection of aircraft arriving in their airports from abroad - when considered necessary - was recognized as being strongly supportable and easily enforceable. The usefulness of converting disease surveillance data to map form and the value of disease mapping in the search for further information on the occurrence of communicable disease were demonstrated. The introduction of simple mapping methods such as spot, shading type or even contour lines that can be applied by any interested individual, or of computer printouts on base maps and multiple factor illumination by new remote senSing techniques, represented a new, and immeasurable advance in communicable disease research technology that can have immediate and practical results in the definition and control of infectious diseases in the Region. As a result of epidemiological surveillance carried out in various countries, it was possible to note the following changes in communicable disease situations: (1) The rapidly increasing incidence of viral hepatitis in Australia, New Zealand and some South Pacific Islands. (2) The significantly diminished numbers of microfilaria carriers and cases of filariasis due to mass administration of chemoprophylactic drugs.
(3) The shifting age and socio-economic patterns of venereal diseases such as gonorrhoea and syphilis, which may require their being transferred from special surveillance systems and put back into the overall epidemiological surveillance system. (4) Tuberculosis has long received special attention through mass X-ray screening and tuberculin testing and has now reached a point of control reqUiring that the sputum positive individual be sought as the source of infection and treated. Intestinal diseases, and particularly cholera, gastroenteritis, shigellosis and salmcnellosis, appear to be the communicable diseases of greatest prevalence and morbidity in many countries. These diseases provide a striking example of inadequate diagnostic capacity and reporting, and require renewed attention and vigilance. (6) Certain respiratory and other diseases, ranging from pandemic influenza through common pneumonias, bronchitis and childhood exanthemic diseases to an old threat, diphtheria, pose special problems in each country's surveillance system.
(5)
- 53 Direct observation of the operation of a national epidemiological surveillance system fur communicable diseases at the Disease Intelligence center of the Philippines illustrated the complexities met with in attempting to handle surveillance of a great many diseases, and the expense of collating and manipulating the data. In reviewing the panorama of an effective epidemiological surveillance system as presented during the ten days of the Seminar, it becomes apparent that there is room for much improvement in the existing system in each country. Efforts can be intensified, expertise added to and, perhaps, budgets enlarged to cover the expansion of functions and to provide some of the newly available laboratory, computer and mapping techniques. But it was emphasized many times over that the fundamental elements of any surveillance system were accurate diagnosis and reporting of individual cases of notifiable disease, backed by the irreplaceable work of the professional epidemiologist trained to analyse the accumulated data for appropriate action and response. 11. REOOMMENDATIONS
11.1 The time has come to consider implementing more intense epidemiological surveillance for communicable diseases of common concern and for specified diseases of special concern in particular countries. To do this, strong epidemiological services are needed which will set up a system of surveillance appropriate to the continuously changing and developing natural, ecological and social conditions. 11.2 The organization of epidemiological surveillance includes a basiC series of actions such as: (a) improving data recording, analysiS and evaluation;
(b) well-planned individual investigations in the field, immunological surveys and containment operations; (c) (d) ecological studies and mapping of results; dissemination of information at various levels; and
(e) formulation of recommendations for the decisionmaking authority. 11.3 The epidemiological surveillance services should be based on the teamwork of various disciplines and all branches of the health services, and should co-operate with the services of ministries of education, agriculture, economy. etc. 11.4 No purely administrative system is satisfactory for surveillance work; the latter should not be based on a structure parallel to or separate from the existing epidemiological services.
- 5411.5 More effective diagnosis and definition of communicable diseases are needed and could be achieved through increased public health laboratory capability. This will require the establishment of new facilities and the improvement of existing facilities by providing new technical equipment, further training of staff and making fuller use of WHO regional reference centres. 11.6 To make surveillance of infectious diseases more effective, and of greater benefit both to individual countries and internationally, it is reoommended that use be made of the WHO Serum Reference Bank in consultation with the Regional Office. 11.7 A more effeotive assessment of the presence and the distribution of vectors and potential vectors of communicable diseases such as plague, malaria, filariasis, dengue and Japanese B encephalitis is urgently needed and will require an adequate entomological staff supported by WHO specialists where necessary.
11.8 Insistence by national health authorities on effective disinsection of aircraft as a protection against the introduction of dangerous vectors, and on keeping airports free of mosquitoes, is an essential element of international vector control. 11.9 Disease maps are h1ghly useful in present1ng the information necessary for effective disease surveillance. The integration of ex1sting data in disease maps may reveal the areas in which information is deficient and should be obtained. Action should be initiated: (a) to develop and maintain national disease data banks that will allow rapid and effective integration of country data with relevant data from elsewhere in the Region;
(b) to stimulate and support further interest in mapping disease among the countries of this Region; (c) to support the production of disease maps by direct assistance at the country level, utilizing what amounts (and quality) of data are available there. 11.10 The preparation and publication of technical guides for the control of communicable diseases would seem to be an activity of special practical value: these guides should continue to be made available in a form suitable fer wide use. Each programme for the control of communicable diseases should be regularly evaluated. It would seem useful to make an evaiuation not only of national programmes, but also of the many seminars on communicable diseases that have been organized by WHO. 11.11 In view of the multidisciplinary team effort required for the development of more effective communicable disease surveillance, appropriate recruitment and training of epidemiolog1sts, entomologists, microbiologists, virologists, public health statisticians and other communicable disease personnel should be increased.
- 55 ANNFJe I
AGENDA WEDNESDA Y, 1 December Registration Official opening of the Seminar Introduction of the Participants Election of Chairman, Vice-Chairman and Rapporteurs Explanation of procedures "Epidemiology and Disease Surveillance: The Continuing Assessment of Health in a Population" "World-wide Surve1llance of COlIIJIUnicable D1seases" Plenary discussions Cocktail given by the Regional Director THURSDAY, 2 December "The Use of New Laboratory Techniques in Epidemiological Investigation and Surveillance" Part I Country reports FRIDAY, 3 December "The Use of New Laboratory Techniques in Epidemiological Investigation and Surve1l1ance" Part II Discussions Discussion of selected diseases "D1ptheria 1n the Western Pacific Region - Surveillance Report of A Decade" Dr B. Velirnirovio Dr R. Kono Dr R. Kono Dr r. Shigematsu Dr B. Velimirovic Dr T. Work
WHO Conference Hall DrF.J. Dy
Paper by Dr E. Roelsgaard (Presented by Dr B. Velimirovic)
WHO Lounge
- 56 Annex 1 SATURDAY, 4 December Serum Banks and Reference Centres Dr I. Shigematsu Dr R. Kono Dr R. Sansonnens
WHO Reference Services Plenary discussions FREE
SUNDAY, 5 December Recreational trip to Corregidor KlNDAY, 6 December "Geography of Diseases - Introduction" "Geographic Medicine and the Health Implications" "Ecologic Substrate for Development and Persistence of Diseases" "Production Procedures for Thematic Maps" Mapping of Diseases Use of Computers Plenary discussions TUESDAY, 7 December "Surveillance of Vectors of Medical Importance" Plenary discussions "Surveillance of Malaria" Film projection Dr M. Farid Dr A.P. Ray Mr J. Wright
Host.:
Dr J. Azurin
Dr H. Hopps
Mr H. Engeler
Dr H. Hopps
- 57 -
Annex 1 WEDNESDAY, 8 December "Non-communicable Disease Epidemiology Geographical Surveillance of Heart Disease Mortality on TaSlll8.Jlia" Dr N. McGlashan
"SM)N" Plenary discussions "Surveillance of Tuberculosis" "Geographical Characteristics of Shigella and Shigellosis" Discussion of selected diseases THURSDAY, 9 Deceaaber Discussion on the subject raised by the participants Presentation of the draft summary report and draft recommendations of the Seminar Groups discussions Field trip to Disease Intelligence Center Secretary of Health, Manila FRIDP.Y, 10 December Final discussions and conclusions Evaluation of the Seminar Closing ceremony
Dr R. Kono Dr I. Shigematsu
Dr J .C. Tao
Dr K. KObari
Guide:
Dr J. Dizon
Dr F.J. Dy
- 58 ANNEX 2
LIST OF WORKING PAPERS WPR/CD/2 Epidemiology and Disease Surveillance: The Continuing Assessment of Health in a Population The Use of New Laboratory Techniques in Epidemiological Investigation and Surveillance WHO Serum Reference Bank, Tokyo
Dr
T. Work
WPR/CD/3
Dr R. Kono
WPR/CD/4 WPR/CD/5
Dr I. Shigematsu Dr H.C. Hopps
An Operating Guide for the Users Geography of Diseases, Geographical Variations in the Occurrence of the Diseases, and Methodology of Mapping of Diseases Surveillance of Vectors of Medical Importance World-wide Surveillance of Communicable Diseases OTHER DOCUMENTS
•
WPR/CD/6 WPR/CDI7
Mr J.W. Wright Dr Erik Roelsgaard
1.
Diphtheria in the Western Pacific Region - Surveillance Report of a Decade
Dr B. Velimirovic
2.
WHO Reference Services Production Procedures for Thematic Maps Surveillance of Malaria Non-communicable Disease Epidemiology Geographical Surveillance of Heart Disease Mortality on Tasmania
Dr R. Sansonnens Mr H. Engeler Dr M. Farid Dr A. P. Ray Dr N. McGlashan
3.
4.
5.
- 59 Annex 2
6. 7. 8.
Surveillance of Tuberculosis Geograph1cal Characteristics of Shigella and Shigellosis Guide for the Collection and Transport of Virological Specimens
Dr J
.C. Tao
Dr K. Kobari Virus Unit, WKl Geneva
- 60 ANNEX
3 LIST OF PARTICIPANTS
AMERICAN SAKJA AUSTRALIA
Dr Lowell M. Wiese, Director of Medical Services Dr Desmond B. Travers, Assistant Director-General, Commonwealth Department of Health; Dr William J. Stevenson, Chief Health Officer, State Department of Health
CHINA FIJI FRENCH POLYNESIA HONG KONG JAPAN
Dr Hsu Shu-Tao, Director, Taiwan Serum and Vaccine -Laboratory
Dr E. Macu Salato, Assistant Director of Medical Services (Health) Dr Pierre Delebecque, Adjoint au Chef du Service d'Hygiene Territorial Dr Lee Shiu Hung, Principal Medical Officer (Planning), Medical and Health Department Dr Rintaro Okamoto, Assistant Chief, Quarantine Section, Public Health Bureau, Ministry of Health and Welfare; Dr Syuichi Tani, Assistant Chief, Communicable Disease Control Section, Public Health Bureau, Ministry of Health and Welfare
KHMER REPUBLIC
Dr Ung Try, Chief, Department of Communicable Diseases and Epidemiology; Dr Yit Kim Seng, Director, Public Health and Preventive Medicine
KOREA LAOS MALAYSIA NEW ZEALAND
Dr Sungwoo Lee, Chief, Public Health Section, Bureau of Public Health Dr Thao Bounseng, Medecin-Chef de la Province de Savannakhet Dr J.S. Gill, Medical Officer of Health, Public Health Institute Dr C.M. Collins, Assistant Director, Division of Public Health
- 61 l'.nnex 3 LIST OF PARTICIPANTS (continued) PAPUA NEW GUINEA PHILIPPINES RYUKYU
Dr M.A. Price, Senior Lecturer in Medicine, University of Papua New Guinea
Dr Julio P. Valera, Medical Specialist, Disease Intelligence Center Dr Chokei Yoshida, Director, Public Health Laboratory Dr RaJendra Prasad Sharma, Assistant Commissioner of Public Health Dr Penisimani L. Mapa, Medical Officer Dr Pham Quang Tuan, Chef du Service de Medecine
ISIANDS
SINGAPORE TONGA VIET-NAM WE:.;TERN
preventive SAMOA Dr Tuioti Siaosl, District Medical Officer CONSULTANTS AND TEMPORARY ADVISER Dr Huward C. Hopps, Professor of Pathology, School of Medicine, University of Missouri-Columbia Dr Reisaku Kono, Director, Central Virus Diagnostic Laboratory, National Institute of Health, Tokyo Dr Telfcr1 Work, Professor of Infectious and Tropical Diseases, School of Public Health, University of California at Los Angeles Dr' rtsuzo Shigematsu, Chief, Department of Epidemiology, Institute of Public Health, Tokyo SECRETARIAT Mr ,ToW. Wright, Chief, Vector Biology and Control Unit, WHO Headquarters Dr B. Velimirovic, Regional Adviser on Communicable Diseases and Cperational Officer, WPRO Dr K. Kobari, Regional Adviser on Communicable Diseases and Co-operating Officer, WPRO Dr J.C. Tao, Regional Adviser on Communicable Diseases and Co-operating Officer, WPRO
- 62 Annex 3 SECRETARIAT (continued) INl'ERPRETERS: Mr P. Lambert, Mr R. Aouad and Miss G. Clement
RESOURCE PERSONS
Dr M. Farid, Chief, Malaria Planning and Programme, WHO Headquarters Dr A.P. Ray, Senior Regional Malaria Adviser, WPRO Dr R. Sansonnens, Regional Adviser on Health Laboratory Services, WPRO Mr Heinrich Engeler, UN Map Production Specialist OBSERVERS
WlI)
Dr G.M. Antal, Mr G.H.W. Garner, Dr A. Tito de Morais, Dr P. Maury, Dr K.M. Patwary, Mr F. Sadek OBSERVERS
Dr Zenaida O. Ludovice, Epidemiologist and Dr Antoliano Alday, Supervising StatistiCian, Disease Intelligence Center, Philippines Professor Chamlong Harinasuta, Central Co-ord1nating Board, Regional Tropical Medicine and Public Health Project of South-East Asian Ministers of Education Organization; and Dr Santasiri Sornmani, Chief, Schistosomiasis Research Unit, Faculty of Tropical Medicine, Thailand Dr Guy Leison" Programme Director (Health), South Pacific Commission Dr N.D. McGlashan, Senior Lecturer in Geography, University of Tasmania, Australia Dr Robert Juni, Communicable Diseases Control Advisor, AID, Viet-Nam ~
- 63 ANNEX 4
SOME NEW LABORATORY MR!'OODS APPLICABLE TO EPIDEMIOLOGICAL INVESTIGATION AND SURVEILLANCE OF INFECTIOUS DISEASES
by Reisaku Kono, M.D., M.P.H. *
As described elsewhere, it is impossible to review all the newly developed laboratory techniques that are applicable to epidemiological surveillance of infectious diseases. I have made a rather arbitrary selection of several topios that are, I believe, of common interest and importance. 1. Virological diagnostic methods
The general method of isolation and identification of many viruses are shown by two flow diagrams (Annex Fig. 1-1). The laboratory diagnosis of smallpox(l) is illustrated in a separate diagram, because of its particularly importance at a time when a global eradication programme is in progress (Annex Fig. 1-2). Electronmicroscopy of negatively stained materials from eruption, vesicle fluid or pustUle fluid with phosphotungstic acid will give a picture of characteristic virion structure within a short period of time, it enables us to differentiate Herpesvirus varicelae from variola virus but d~fferentiation between variola and vaccinia subgroup remains impossible. (2) Only the following features of virus pathogenicity can give positive variola evidence which has a decisive importance for surveillance of cases in non-endemic areas.
* Director, Central Virus Diagnostic Laboratory, National Institute of Health of Japan.
- 64 Annex 4 Differential Diagnosis of Vaccinia and Variola Viruses
Host and conditions Rabbit intradermal 12 day old fertile hen I s eggs
Vaccinia virus .aJor Vesicle, pustule 35 - 37 C large pocks 2 3 mm. umbilicate~
Variola virus minor (alastrim) No response
No response
Tiny pocks (0.5 - 0.8 mm)
"
38.5 C. no change from 37 C Number of pocks reduced to 1/2 - 1/3 Plaque formation
Practically no pock formed
Tissue culture: HeLa or FL cell mono layers
Hyperplastic focus formation
Hyperplastic focus formation on HeLa cell mono layers )'re of particular value to diffe~~tiate variola virus from vaccinia virus(3. Recently, Kitamura et al.(~) developed a microplate cultivation technique, and it can be applied to differentiate V. major from V. minor by titration of infectiVity at the ceiling temperature of 38.5 C and 38.3 C for each. HeLa cell (2.0 x 105 ce11s/m1) is cultivated on the flat bottom of wells of the microplate, then the serially diluted virus is inoculated onto HeLa cell mono 1aye rs, sealed with scotch tape and incubated in a water bath regulated at 35.0, 38.3 and 38.5 C + 0.01 C for 48 hours. Wash the cell sheet with 0.1 ml/we11 of PBS (-), stain with 0.05 ml/wel1 of the Wright solution at R.T. for 20 minutes. After drying observe the plate under a dissecting microscope, and count the hyperplastic foci to get endpoint of infectivity. Effect of Temperature on the Hyperplastic Focus Formation in HeLa Cell TElllperature Variola major virus V. minor virus 35 C Complete focus formation II
.
38c Reduction of focus to 1/2 of 35 C Reduction of focus to 1/20 of 35 C
38.5 C Reduction of focus 1/5 or less of 35 C Almost nil
- 65 Annex 4 The above are the criteria for the differentiation of two viruses.
REFERENCES: (1) (2) (3)
WHO: Guide to the laboratory diagnosis of smallpox for the smallpox eradication programme, Geneva, 1969. Cruickshank, J.G. et al. (1966) Lancet, ~, 527. Kitamura, T. (1968) Virology, ~, 174-180. Kitamura, et al.: To be published.
(4) 2.
Fluorescent antibody (FA) technique
Almost two decades have passed Since Coons et al. first established the principles of the fluorescent antibody technique. Therefore, it is not a new one, but a number of improvements and refinements were devised, giving this simple and reproducible technique a degree of specificity and sensitivity which has led to its increasing application in a variety of fields. Now, the flUorescent antibody technique can be effectively applied to the surveillance of infectious diseases. Principle The fluorescent antibody technique combines histochemical and immunological methods to pinpoint specific antigen-antibody complexes on the 'surface of an organism and in tissue sections or cellular smears with the aid of fluorochrome substance conjugated to the antibody. When tissues or cells containing a particular antigen, e.g., influenza A2 virus, are stained with its specific fluorescein-conjugated antibody against influenza A2 and examined under a fluorescence microscope. only cells containing or infected with A2 virus emit fluorescence. Cells infected with influenza B virus will not fluoresce at all if the fluorescent antibody has been carefully checked for specificity and is appropriately diluted. This method is called the direct method. Another method used in the fluorescent antibody technique is the indirect method. First. an unlabelled antibody is reacted with an antigen; this antibody is called primary antibody. In the second step, the serum globulin of the antigen-antibody complex formed is stained with labelled anti-antibody (secondary antibody). If specific fluorescence is detected, we have indirect evidence of the presence of the specific antigen-antibody complex in the first step. The third method is a variation of the indirect method in which the antigen-antibody-complement is stained with fluoresceinconjugated antibody against complement (Annex Fig. 2-1, and Annex Fig. 2-2).
- 66 Annex 4 Merits of FA technigue They are (1) rapidity; (2) specificity; and (3) sensitivity. The staining procedure and microscopic examination can be completed in one to two hours. Japanese encephalitis virus antigen in human brains, rabies virus antigen in dog brains, or influenza virus antigen in nasal smears can be identified in one to two hours after the specimen is sent to the laboratory. The specificity and sensitivity of FA technique are assured if the materials used are suitable, the proper method is followed and enough controls are set up. The direct method is able to detect antigens in the order of 10- 4 \1g/mm2, and· the indirect method is 5-10 times more sensitive than the direct one, but non-specific reaction is liable to occur. Prerequisites (1) The antigenic material to be stained should not lose its reactivity during the process and should be made accessible to the antibody. The pretreatment or fixation of the preparation are necessary to assure the above condition as well as to remove fats and other interfering substances. A highly potent and specific fluorescent antibody with very weak negative charge is needed. In fluorescent antibody a ratio of fluorochrome substance to protein molecule (F/P ratio) should be approximately 1:2. be carefully controlled as regards the time and the temperature of staining, the pH of buffered saline and washing. The staining titre must be determined beforehand with a known preparation containing a sufficient amount of antigen, and the working dilution Should be 2 to 4 staining units. (4) The following controls are required to ensure the specificity. Antigens: untreated or uninfected tissue, fixed unstained tissue and tissue containing heterologous antigen. None of these should show fluorescence on microscopy. Antibody: one step or two step inhibition tests, staining with heterologous antibody or normal globulins tagged with flUorochrome.
(2)
(3) The conditions under which the reaction takes place must
.
- 67 -
Annex 4 Observation A high-pressure mercury la.p, various kinds of filters and a microscope with a dark-field condenser to which photographic equipment can be readily attached are needed. Recently, an interference f1lter effective as an exciter was developed in Denmark. This is oalled FITC filter and it makes possible the use of an ordinary low voltage tungsten bulb as light source for routine work. In other words the FITC filter will make a fluoresoence microscope unnecessary for routine. However, the fluorescenoe microscope remains of value for research purposes. Applicat10n The FA teohnique has now an unlimited application in microbiology, pathology, immunology and so forth. In prinoiple there are two ways of applying the FA method for the purpose of epidemiological surveillance. The first is serologioal identifioation of an etiological agent using group or type specific serum. Many cultured baoterial organisms oan be identified and typed by FA. The FA staining of smears of material from a patient is sufficient for the rapid diagnosis of baoterial, viral and mycoplasma infections. The second is detection and t1tration of a specific antibody in sera from patients or healthy persons. FTA-ABS is one of such examples. USEFUL REFERENCES:
(1) (2) (3)
Holborow, E.J. (1968) Ed. Blackwell, Oxford.
Standardization of illll1UIlOfluorescence.
Kawamura, A. (1969) Ed. Fluorescent antibody teChniques and their appl1oation. U. Tokyo Press, Tokyo. Beutner, E.H. (1971) Ed. Defined illlllUnofluorescent staining. Ann. N.Y. Acad. ScL, 117. Cholera and other vibrios
3.
During the last decade, El Tor vibrio has crated a new situation by revealing its pandemic propensity. An experienced bacteriologist in a standard laboratory can expect to recover V. cholerae from about ~ of properly collected specimens of cholera sU)'ol within 24 hours. Darkfield microscopy and the fluorescent antibody technique, when used judioiously, can diagnose cases within a few hours. Enrichment in alkal1ne peptone water, is essential for 1solation of v1brios, as they are comparatively scanty in the formed stool.
- 68 Annex 4 Systemic examination of pooled nightsoll or of specimens from busket latrines has proved to be more useful in special situations for surveillance of El Tor infection than for classical cholera infection. It is noted that the organism usually persists for less than three weekS in the intestinal tract of affected individuals. E1 Tor vibrios can be differentiated from the classical V. cholerae by their ability to cause haemolysis and agglutination of chick or sheep red cells and by their resistance to 50 ug-polymixin B disc (Difco) and to MukerJee's phage IV at routine test dilution. All these tests should be oarried out for proper identification (Annex Figs. 3-1, 3-2 and 3-3). parahaemolytious is the name proposed by Sakazaki et a1. (1963) for an enteropathogenic, facultatively halophilic organism encountered in Japan as the commonest causative agent of food poisoning. This vibrio is frequently isolated from diarrhoeal cases in India. There is reason to believe that y. parahaeaolyticus is an important organism in food poisoning and diarrhoea outside of Japan, particularly among peoples who habitually eat sea foods (Annex Fig. 3-4 and 3-5). USEFUL REFERENCES:
y.
(1) (2) 4.
World Health Organization (1970) Principles and practice of cholera control, Geneva, (Pub1. Hl th Paper No. 40). Sakazaki, R. et al.(1963) Jap. J. Med. Sci. Biol., Hepatitis and Au antigen ~,
161.
It has long been known that there are two varieties of hepatitis virus: virus A and virus B. Virus A causes infectious or epidemic hepatitis; and virus B is associated with serum hepatitis or homologpus serum Jaundice(l). The discovery of the Australian antigen by Blumberg et al.(2) is a great break-through in the seemingly insoluble problem of human hepatitis. During the search for precipitating lipoprotein antibodies, an antibody was detected in the serum of two frequently transfused Americans with hemophilia which gave a preCipitin line by Ouchterlony immunodiffusion technique with one of 24 test human sera. The antigen in this serum contained li t.tle or no lipoproteins. Since the reacting serum was obtained from an Australian abor~gine, the antigen was named "Australia antigen" • Okochi and Murakami (3) made the same line of study 1n which they found the same kind of antigen in a patient with ohronic myelogenous leukaemia who had also frequent transfusions and in profeSSional blood donors. This was identified as being the same as Au-antigen by Blumberg. "
- 69 Annex 4 They found in 1968 that the recipients who were transfused with Au(+) blood showed Au-antifn in their serum and often developed serum hepatitis. Prince(4 who intended to screen out hepatitis virus carrier from the blood donors started to study an almost identical method to that mentioned above. He found an appearance of new isoprecipitin in patients with serum hepatitis; when he performed precipitation between sera from hepatitis patients in various stages of illness and that from the person who had frequent blood transfusions. This was named SH antigen. Now, the antigen is called Au-antigen, HAA antigen or SH antigen. The etiological Significance of Au-antigen to serum hepatitis is now well established by human volunteer experiments of Krugmann's group(5). Annex Fig. 4-1 shows the typical examples of the human volunteer experiments. However, there are still controversies concerning the nature of Au-antigen: is it a virus or other product? As for studies of virus A there is not much progress yet. In practice, the detection method of Au antigen and antibOdy is a problem; there have been many improvements and refinements to develop a more sensitive test than the original immunodiffusion method. Table 4-1 shows the list of existing test procedures for Au-antigen and antibody. I would like to introduce two new methods which are used in Japan. One, the immune adherence hemagglutination test (IA) is rather special; the other is the coated tube method of radioimmunoassay which has recently been developed and is now becoming routine (Annex Table 4-1, Figs. 4-2, 4-3 and 4-4). The positive rate of Au-antigen is higher in patients with hepatitis and other liver diseases, or blood diseases like leukaemia and haemophilia, Down's syndrome and so on. On the other hand, it is of interest to find differences of the positive rate between races as shown in Table 4-2.
.
At any rate, screening of Au-ag positives from blood donors is of practical importance in prevention of serum hepatitis (Annex Table 4-3) . 4.1 Immune adherence hemagglutination test (IA) Principle The IA technique consists of 3 steps: the first is the reaction between antigen and antibody; the second is the reaction of antigen-antibody complex with complement (C) resulting in the formation of antigen-antibody-comp1ement complex (ag-ag-C): the third is the adherence of ag-ab-C complex to human erythrocytes, indicator cells, resulting in a positive hemagglutination pattern of human erythrocytes.
- 70 -
Annex 4 Eg,uipaent (1) (2) (3) Microtitre kit Microtitre plate vibrator Incubator at 37C
Reagents (1)
++ . Gelatine veronal buffer (GVB )
(2)
Dithiothreitol (HS-CH2-(CHOH)2-CH2-SH. M.W. 154.2) solution: 3 mg/ml in 0.04M El7l'A-GVB (2 parts of O.lM EIYrA. pH 7.5 added 3 parts of GVB) Human "0" erythrocytes suspension (1.2 x 10 GVB)
.
8 /m! in the EDrA-
Controls Positive and negative control sera should be included in each test. Pr.ooedure (1) Make two fold serial dilution of sera to be tested (inactivated at 56 c. 30 min. beforehand) from 1:8 to 1:128 with GVB in a volUllle of 0.025 ml on a microtitre plate. Add 1 drop (0.025 ml) of the diluted anti-Au containing 5 IA units and III1x well. Incubate for 60 min. at 37
(2)
(3) (4)
c.
Add.l drop (0.025 ml) of diluted (1/75 with aBV) guinea pig serUIII and mix well. Incubate for 40 min. at 37
(5) (6)
c.
Add 1 drop (0.025 ml) of human "0" erythrocytes suspension and mix well. Keep the microtitre plate quietly at room temperature for 60 min. and read the hemagglutination pattern.
(7)
- 71 Annex 4·
4.2
Radioimmunoassay (RIA):
Coated tube method
RIA is the most sensitive test for Au-antigen and antibody. At the moment there are three different methods: method of Walsh; radioisotope precipitation test (RIP); and the coated tube method (Ct-RIA). The principle of RIA is to titrate Au-ag in a serum by measuring radioactivity of the Au-ag-ab complex which is formed b,y reaction between Au-ag in serum to be tested and a known amount of radioisotope-labelled Au-ab added. rr- the titration of Au-ab is desired, "the radioisotope-labelled Au-ag is needed. The difference between three methods lies in how to separate free labelled antigen (or antibody) from the bound one. (1) The method of Walsh uses -paper chromatoelectrophoresis for the separation. In RIP the Au-ag-ab-comp1ex is separated by two steps: namely, precipitation QY adding antihuman YG gcat serum to the perfonned Au-ag..ab-complexand centrifugation to separate free fonn in the supernate and bound form in the precipitate. The coated tube method is the simplest of the three and will be used in the future. (8) One ml of a serum to be tested for Au-ag is added to Au-ab coated poiystyren tubes. Stand at room temperature for 30 minutes, and wash out throughly. Then, a known amount of 125I-Au-ab is added and the tubes allowed to stand at room temperature for two hours. Wash out unbOund 125I-Au-ab throughly and count radioactivity by Logic well-type counter. Control tubes are prepared in the same way except that they contain phosphate buffer or Au-ag and ab free serum instead of the serum to be tested. The counts of those tubes give that of the background. The tes'\; is considered positive when the count exceeds the control count plus 5 G. In order to determine Au-ab, the Au-ag coated tubes must be prepared (Annex Tables 4-4 and 4-5). REFERENCES
(1)
WID Memorandum (1970) Viral hepatitis and tests for the Australia (hepatitis-associated) antigen and antibody. Bull. WId H1th Org.,
42, 957. (2) (3) (4) (5) (6) (7)
Blumberg. B.S. (1964) Bull. N.Y. Acad. Med., 40, 377. Okochi, K. &: Murakami,
s.
(1968) Vox Sang ••
12,
374.
Prince, A.M. (1968)- Proc. nat. Acad. SCi., 60, 814. Lander. J.J. et al. (1971) New Eng. J. Mad., 285, 303 •. Okochi, K. et a1. (1971) Vox Sang., 12.332. Mayumi, M. et alo (1971) Vox Sang •• Toyoshima, S. et a1.:
..e2..
178.
(8)
To be published.
- 72 Annex 4
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- 73 -
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- 74 Annex 4
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~
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.
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- 7(. -
o
o SUBDIVISION OF VIBRIO CHOLERAE
o
SEROLOGICAL TVPING ( o-Agglu t inat ion) .
BIOLOGICAL .TVPI NG BIotype el tor Hemolysis (+) Chicken red cell agglutination(+) PolymilCin B sensitivity(-) Muker~ee's phagelV &en5ltlvity(-1
PHAGE TVPl/IX3 Phage types of V. cholerae
o1
Typ.
Form
)
log.Lwa Hikojima INba
1.2.3.4.5 Phage types of biotype eltor
o 2jso-called o 3 non-agglutinat;~.
I
vibtlos (NAG)
039
1.2.l 4. 5.6
Annex i"ig. 3-4
ISOLATION OF V. PARAHAEMOLVTICUS Stool Specimens in acute stages Stool specimens in convalescent, fish. sea water etc.
GST(gtucose-saltteepot) Broth or NaCl-Co1istin Broth
t I I
•
8-12 hrs at 37C v -!t TCaS Agar or aTa Teepor Agar
118"'24 hrs at 37 C Suspected colonies • 1
for id1ntific:ation
- 77 -
Annex 4
Annex Fig. 3-5
COLONY DIFFERENTIATION OF V, CHOLERA;' AND V,PARAHAEMOLYTICUS FROM OTHER ORAN ISMS ON TeaS AGAR
.
V. cholerae -""''''- Rather small, pale yellow V. parahaemolyticus-Large, deep blue of
green· center
V•• lglnolyUcus-Large, yellow MromonasII ---.
No growth or small, yeUow No growth or smal~ yel~ black or greenisn
ProtNS
_ I I- - _ . _ -
PseUdomonas--No growth or small colorless or pale green Enterococ:ci---No growth or sinall comp.lct yellowish white
•
Annex Fig. 4-2 Annex Fig. 4-1 WELLS IN AGAR ON MICROSCOPE SLIDE CI
-
~
;x..
.f::"
4
-..,u0
.... ·.w···AJj,··
.I'-.
=e
~
:[ )!~·~1 , i lC i "'Pt
~.~.~-<p I .
-.J
ro
0'@-$
I htsT-.._
i i i ~ . I I i t ~
i i
IN..
.,111" IG lIDS AF1III bPaSUIII
- --
"IIo_........ ~,_
_ _ .,..... - - . . ......._ 1......_ _ _ _
"A ... antigen; P
= patient's serum; C = antibody. 011
L::.
-
I
.
+
.. a slide for immuno-
This figure shows how to punch wells in agar layer electric precipitation test for Au al1tigen al1d 3mibodj'_
•
.-
- 79 -
Annex 4
• AM·MI.....n " , -. . . . --.-
Annex Fig. 4-3 Wlua '011 IIIIIAL nSTS (/oJ 'OR ANTIGEN AND 'ANTlIODY Dn'(CTIOII AIIO e.. 'CIA ANTIGIH Dn'ECTIDN ONI.Y . -• • • ~ . . . . . _ 4 . . . . . -:,...
~
_~ . . . . _ _
•
t; ....... 0 . . . . . _ _
..._
••• ~
_
:.00000000,0 00 ad A I A ("') C) l) 0.0 000000 0 OJ p 00 0 00000 0 O· O!J ()! -(C
--1 I
-
...... -
_-
.
..
. -, , " ) r, 0 0 0 - -... .,... f-) 1""\ ~ .O' ......
~--
....~ ..
-
.. , .'
t"., ~. . ... '
0 0 ,
p C
(i\ P \'J:'
B
:- .I."".... ·: ....
.
'\...1 ...... ~ r j
t .'-, '.
...
I
r. ',-.. 0 U'" '" r) c .of' , . \ .;' ..•...,:
--~
3 ---:. 8 .() f)
.. ;;.w-
()O 0.0 0 ............ ....... r100 00 000 00 0 Ot ()O, ()
t'):
--~
, .'
.
+
Sera 1, 3, 4, 8 and 9 show Au antigen positive: Sera 6, 11 and 13 Au 8'ltibody positive.
Annex Fig. 4-4
FLO'" DI AGRAM OF RAD 10 (MM UNOASSAY BY COAlED TUBE METHOD
•
•. · ....
1 ])ETfttION OIA.t·A~ • •
-.......
. f
." I0
0 228 1
IICIJJ I
0
••I
LoGrtc 101 Wall
c:•...,...
- 80 Annex 4
• Annex Table 4-1 Mill. .
or All
AlII....
au . .IEDII .....cnON . . . .If...
I.. . . .-,., .} Ilnta.
'-"""_MIa If. .kl
" ......., , - - . ........ 11Itp1•• _tiMe _ ....UM '~1••
_, ",ore O'.... r1onr ••••••••••••••••••••
, ..__ - ' U f t
el 1 _ 1. ." ..,.....'............ .:. .. 'Pple, 119. . . . Alt........ . Mh,......., - ' ". .
c-pa-a.,"'.,_ .......................'U". ,. '_ft. .....If..." ,..,.......................,,,.. I.
:
..... e' ~
....'illuwl t. I,••,"""".,..eepie ..................... 'illuw1. 110' .IIlUMe __ ....!Mt.Ma
I. rl _ _,· ..,~ .................. A"U••
01\ " . . . . ." " -•
'-,
lie........ Wd...
.........,............................... ,,,.. ---- .... "'.......... ....
....
..................................... Ia.,a.,..a.l".
- 81 -
Annex 4 Annex Table 4-2
.,
l>IS'l'RlBU'1'ION OF AUS'l'BALIA ANTIGEN IN SOME IONlIOSPITALlZED ("NORMAL") POPULATIONS Population l!:!!!cricas Eskimos Indinn!J' Athabascan IndianS', CaahlnrabM Indians, JTa.ida Indinns, ~ Ind ians. Mexioo, WI&'S.tIIUt Indiana, 5a"'Jo Indiana, ~ Indio.naJ _ _ Neeross Negroes Whitea Whites ACrica "Bantu" "Colore4" Pare Triatan Da. 0",)' • Chanaia.ns Asia.
Loca.tion
lfwDber 'teated
NWllber positive
Per cen't j;losit.1ve
,
..
lb:aa11
394 Al"'Ska.~U.S.A.~ Alo.oka V.S~. 204 Pel'll ' £19 Canada 3;5a Yucatan 1,417 Mexioo }40 U.S.A. 95 Pel'll ~102 South .DIkot& (V.SeA.) 1:50 Georgia. ~ (V.SeA.) 607 ~.il 119 Georgla, ~ (v.a.... ) 896
1 18 0 0
0 20.2 0
0.,
1 0 0 0 0
4
0.07 0.3 0 0 0 0 0 0 0
0
0
.5
2.5
100
South Atrioa South Atrioa Tanza.n1&
Triatan d& CaUr. Ghana
72 100 120 42 9~
2 0
2.8
•
Indiana Japanese Chinese Taiwanese Israelis' Jordanian. Fillipinos Fillipino. Vietnamese !:uron e Finns Lapps &. Italians Greeks Portuguese ,Q~ea.nia.
Man1la,7.X.. Vietnam Finland. Italy Creeoe Hawaii Finland.
South In41& Japan (VU1GUa) U.S.A.,Wwa Taiwan Israel Jordan Cebu,P.I.
127 1,034 100 23 '40 40 128
, )7 8
1 0 9
0.8 0 9.:> ."
764 197
0 .5 4 0
5
2.4 0.5 0
13.0 0
1.2
9
,4.6 ti.}
4.8
n..,.
212
127
924 44 4
857
0 15 1
1 0
0.1 0 0
2.2
l.B
Aborigines Maoris Melaneaiana Mioroneaia.na
Australia. New Zealand lew ClUnea. Marshall Ialu4a !ora :Bom Ja.wa.1i
1,807 166 ~9
'8 1 6 ~
2.1 2.5 2.3
Polynesians Pol)'nesi8M
474
. •
43
1
,
7.2
,.6
.. oa;noiHu tflll ... oar . . aft M . . . . . . WNW 1t7 _. (uw
»--1"1: )
I).
'I' ~ ~
Annex Table 4-4 Annex Table 4-3 Pn'l'M11CJ' or Au-3C ana ~"t1-Au-ant1l1oq In bealtl\)' 111001 4-a· ~ ... aa4 IU
COMPNIlSOII or SSIISXTIVrn IIB'tIIEEII CIlM?~ ·FDA'rIOll DR I aADI(.\tMMDBOASIAI
In Talqo, 1911. lI&'le
(OkocJd, 1m) ~ule
A ..
10.
A.-"'+)
Anti A.(+) Bo.
Au-Ac(+)
Anti Au(+)
l' -1'
101 612 40'1
5 12
4-~'
11 10.'"
4' 1"
20-2t
22 3-J ,
50-" 40 - 4' 50-" 60-
2., 2.l
"
14.1
o , 1.J
0" 0 0
Sampl. No, 1 2
RIA
eFT 512
-lndex{~,CF'
Sensitivity
, 1).1$ 2J It ,..5
15.'
60 14.J .2t 20.0 11 2'••
145 41
12.4
•
o
0
, '105
" , 4' 1t
1 1.' 1 2.2
3 4
, 1).0
o o
•• ••
5
6 7 8 9
Au- ag : detected by the immunt: ',dherence haemagglutination test Anti Au- ab : detected by the passive haemagglutination test
10
100.000 5.600 3,400 3,400 400 >750 >750 360 300 200
32 32 16
4 <4 ~
193 180 106 210 100
tQl
<4 <4
<4
>157!. 43 •Note: Figutes are different from Annex Table 4-2. This is simply due to sensitivity of test used. Immune adherence haemagglutination is superior in sensitivity than Ouchterlony technique used in Annex Table 4-2.
."
.
"
•
- 83 -
".
Annex 4
• r
Annex Table 4-5 "'_IOII AU-A; AIID AU-A» CAUIIII AHOBG II.OOD DOM()R8 ay UA ftS'I
or
~-"
.•
A\a-u.
lCWIIb.~
of
.XJ.~D•••
•
-
+
47 43
41.4
4:;.2
-
3 2
3.1 2.1
•
.- 84 .. • ANNEX 5 OOMPt7l'ER PRIlfl'Otn' OF THE SURVEY OF STEOOMYIA Jll)SQUITOES 1971
.
The following mapa represent computer printouts on reotilinear co-ordinates, overlaid by outline transparencies on Mercator's projection and on a soale of 1:5 million at the equator. The stesomyia species i8 Aedes aeppti, and. every 20th century reoord encountered 18 _pped, either by presence or absenoe (p or X), or by abundance or density. For larval infestations, House Index (per cent. of houses infested), Container index (per oent. of water-filled oontainers infested) and. Breteau Index (number of posi ti ve oontainers per 100 houses) have been put on a ooson asoendine scale from 1 to 9. If JD:>re than one type of index is obtained in the ..... reoord. the oOllputer prints the average. .The quanti taUve relationship between the three indices was determ1ned empirically from 189 records in which all three were obtained at the ..... time for the aame plaoe. It 18 planned that new data and improvements in layout will be included in a printout to appear in a year's time. Where an abundance of records around the same place produces an illegible smudge, the computer will be instructed to print only the highest figure. Some s78t.... will be developed to indioate the year, or rather the decade, in which the record was taken. Records of the presenoe or absence, and ocoasionally the abundance si.paonl, ~. atricanus, ~. vlttatua, ~. luteooephalus, and A. metaUicus are also on the oomputer. It is proposed to print these out on a scale of 1:20 milllon. of~.
•
Separate printout _pa &r4I available on reQuest, and are numbered to allow spe~1ficatlon. In speclal oircumstanoes, printouts of particular areas ~ be made on a larger 80ale, e.g., 1:2.5 million.
'.
- 85 -
. .. .!
Annex 5 Density Figure 1 2 3 4 5
House Index 1-3 4-7 8-14 15-24 25-34 35-44 45-54 55-84 85<
Container Index 1-2 3-5 6-9 10--14 15-19 20-24 25-29 ;0-39
Breteau Index 1-4 5-9 10-19 20-34 35-49 50-74 75-99 100-199 200
6 7 ~
8 9
40<
<
P present
X absent
•
•
LIST OF MAPS Seale: 1 in 5 000 000
,
v "
I ><
~
>
U1
~ 22
1. Spaln-Morocco-AIgeria 2. ltaly-Greece-Llbya 3. Black Sea 4. Egypt and Levant (ven)
5. Sudan 6. Dakar (ven) 7. Gulf of Guinea States 8. E. Nigeria, Chad 9. RCA to Uganda O. Gabon, Congo
11. Angola 12. Southwest Africa (ven) 13. South Africa (ven) 14. Mozambique-Zambia 15. Madagascar (vert)
16. Tanzania 17. 18. 19. 20.
Kenya, Ethiopia, Somalia Somalia-Yemen Arabia-Iran W. Pakistan
21. S. india (ven) 22. Nepal, India 23. Thailand, Burma 24. Talwan-Hainan-Luzon 25. Cblna -Japan
26. Malaya, S. Indo Cbl~ 27. Sabab-Mlndanao
WHO 10753
28. Java 29. Celebes 30. New Guinea
d" '"
~
31. N. Queensland 32. New South Wales 33. Solomon Islands 34. New Caledonia, Fiji
'.
.. I '.
..
"
- 87 Sample
Annex
5
. f'
•
<> p
? '3 r .!:'. I"
p p
"
o
- 88 ANNEX 6
~
MAPPING OF DISEASES
.
•
!nd.",ie ar... of B, ",alaI(!
o
Endemic GriOS of W. bancroftl
so miles
MAIN ENDEMIC AREAS OF FILARIASIS. WEST MALAYSIA,
1969
itef: Institute for Medical Research, Malaysia, Annual Report 191"9, Division of Filariasb :tesearch, Dr C.P. Ramachandran and Mr S. Gi~anandarn, pp 51-66
.
- 89 Annex 6 INF .ATE O' SCNI$TOMIASII 1$ "N51 IN ~OT ORIGI""~ DATA II-COORDINATES I
o.
~
P~OTTING ~1"1T5
MAXIMUM X • MAXIMUM Y • .-SCA~£
~, •• OOOOOO
~OTTrD VA~uES
NAV! IrEN
12.000000
MIMI~ MU~TI~I!D IV
MINIMUM • •
Y• -'0.000000 A FACTOR ~. 10 TO TH!
-10.000000
IS IS
HORIZONT'~
X-VALUE. V-'C'~E
-10.00 + YERTIC'~
0.4'44. "CALf VALUE'
012'4"'" 12.00 11.1. 10", 1.70 7 •••
12 •• '.789 12'45.7 •• 12'4,'7'9 12,.,.T.' ,214"7"
12'•••,.' 12'.'.7•• 12,.,,'8'
,."
T.O, 6.2' 1.41 •• 5. hTt
+0 +0 frO +0
z, ••
~.,.
0.46
I",
Z,II
+0
-hie -ZoOI'
-h" -, , -.,,.. -5,'0 .... 1'
..
+0 .0
+0
+10. +100
+100+2" ·2600
-11.0l'
-1.60 -9,42 -10.2'
-1.1. -6 ••,
....) +7
+0 +0
+u +0 +100 +1700
-11.'0
-1 •• " -11.19 -16.01 -1 •••• -17 . . . -11.4, -19,'1
-13.'4 +0 +100
-12.72
+400 +200
-ZO,9. -21.78 -25.01 -25.90 -a•• 71 -23,4, -24,2,
-ZO.l.
+0
-22.61
+0 +0 +0+0 +0
+'100
/ +100
+0 +D
+0 +0 +0
+100 +0
-21." -Z•• ST -29020
+0
The maps oomprising Figures 1 - 10 were all produoed using the MOD SY8tem, either by computer or 1>1 comPJter-sll111.1~ated manoeuvres. They are products of an extensive exe~ise to develop methoclology; they were not desigped to reflect a real;.Ufe situation sinoe the data upon which they are based 'are incomplete and out of date. Figure 1 - Dot-type map produced from the standard set of South Amer1c~ schistosomiasis data using the Kansas Geological Survey trend-surfaoe progrllllllle running on an IBo1 7090 computer wl th output on a line printer (outl1ne of continent lidded. manually),
- 90 Annex 6
" "
...
, . . U1l Of 't"U'o~l .. sn It .... ..,."' -'" -rJ
_6'
'l1li.,
I~ , ..,.
......
-II
-.,
-
..
."
.J.
.... .. ........ ~........
=::::,':,/~ ::::.:.:~ ........ .... .... .......... ........ • • • • • • eo .
.... -........
"'. ..
.
••• 0.0 "
• 0.0 ... "
••• 0 ••••
-, , -u
:::::::: :::: ::::~HH:~;H::::·· !::::::::::: :::::::::::::: ::::::: ::: :::::: :::1 11::H#l1:::::::: ~~~~~~~~:::: :::: ::::: ::::::: ::::::: ::::::: ::~~~~~~~~ 1111111111 11111111 0 "
::::::::::~ :::::::: ......... .......... .......... .......... .......... .......... ........ ........................... ::ii::!!:: :::::::::: :::: ... .... .. ....................-----:!!! ........ ....... 0 ••••• 0 . . . . . . . . . . .
..~
::::: :::::::::: :::::::::: ::: ~~~~~~:H~:HH~II •• :::::::::: :::::: :::: :::::: ::JJ::::IIJ1UUU :::::::: :::::::::: :::::::: ~H~!!~~HHHH :::: ••••••• •• • •••••••••• •••••••••• 1111 •• 1111111111
.... •• 0 ..........................
...
., . -n
"
"1·lil"I I I I I·I I I I I I I I ~1I1i ::: :::::::::: :::::::::: ........ : ::;::: ..........
-... .......... .... .......... .. .......... .. ...........
• • • • • • • • • e' •••••••
." ,: !~:n '"' ... • ' 1- 4
~'!.tI:e"'lC
.
If
,aO'f".tI.
Galli
stu •
1 ClGau.
/
'. of Bchis toFigur e 2 - Shadi ng-typ e map produ ced from the 8tand ard set ssing by proce 80111 iu1sda ta oute t on a line-p rinter after lly). manua ·an I!Itt 7090 (outli ne of confin ement added
- 91 Annex 6
•
I~F
RaTE OF
~C"IS'OSO_I'SII
IS
~"S.)
•• 'IN
-"0
-""
-,':
-,'
-.u
-n
-Il
-n
,. ........................ ................ .... " .. " .... " ...... . " .... "" .. " • "
......... .
.... ...... "
......
•
-. -III
" " ...•............................ " .. " " .. "" .... "" .. " .. " .......... " .... " " ..... "" .. " ..•....•.......•.............. .. .. " .... " .... "" .......... "" .. " .. " ............. "" .. ..••.••..•.••..•....•. .... . ............................. ~
. .•....•.... .... """ .. .... ,, ..
.•..•......•••.....•.••..... .... "" .... " " .. ,. .. ,." .... """ ,.""" .. ,, ",," " " ........... """ ... ,," " .... "" ..... ".- .. " .... " "" .... ,"""" .. ,." .. " .. " .... ,." " " .. """ ... "",," " .... " .. " ." .... ,. .. "" " .... " .... " ........... "" """"" .. " .. """",." .",,""" "" " " ............................................ .... ".,," " ... -" .... " .......... "" "" .. """. .... "" ....... .... .... ,.,. . . . . . . . . . . . . . . . ,. . . . ",. .. " . . . e .. " ~ ~
" ........... 0.0""" .. " .... """".· "" ..
-20
.. .... .......... .................. ............... ............. .. · ........................... ............................. .. ..... ............. ..................... ......... .. ...... ........ ...... .. ........ .. ....... . . ........•.•......................... · ............................................... . .. ....................... . .... .......................... . ·..................... ,..................... . ..
-2' -,. _. sI
:: 1 ·f' • 1 II II
(ITa ~RDI,.PEC
4 : ~i.J
Figure 3 - Aa with l'1gure 2. plus added ocean1c po1nts, to demonstrate one method of adjust1ng computer output to allow for such natural geograph1c features as a large body of water.
- 92 Annex 6
-
• -10
t
-. I
-
. I -+11
x
0-
.... I I
, -11I --)j)
"
.,'
-.X X X X
.,' .,' t
.' I -.,
--II
.,.
. I
.. I
-10
-. I
--. -.
F1gure 4 - The standard set of test data lIIach1ne using a Univel'lli ty of Miohigan oontouring prograllllle. (Contours were manual17 traoed from lineprinter output, and outline of continent added.)
-.
'- 93 Annex
6
~--~~~--~----~----~-----50
-80
~-----~--~~--~~--~------60 -40 -50 -70 Figl.lre 5 - A block cl1yram. presenting the standard set of test elata. produced by an IBM 7094 using the Un! versi ty of Mioh1pn block-cl1agram prograllllle and an off-line plotter (continent outline and grid added manually).
- 94 -
Annex
6
•
'.
Figure 6 - Manually drum contour map showing sohistosomiasis data. \181M oonventional oartopfh1o .ethods--for oomparison with Figure 7. which utllizes oomputer teohnique.. Both are based on preoisely the sue data point.. IIlld both are reasonable approximations. oonsidering the relative sJ)N"city ot the data points.
•
- 95 -
Annex 6
·
,
•
•
"
r
- 96 Armex 6
-X-+--r--
x X 10 ZO
X ZO 10
x --~-----x~------+_--
iI
•
Figure 8 - The atandard set of aohiatoaOlll1as1a data (Venezuela only) oontour mapped to illuatrate the effecta of grid size. (Since the ooarser grid lim! ta reaolution. oontour intervals are neceaaar!ly larger in the map on the left.
.;.
x
x
x
Figure 9 - '!'he standard set of (Venezuelan) achistosomiasis contour mapped to illustrate differences depending upon pattern of diatribution of data points I right-data for each province distributed over a 1/2° grid matrix veraus left data for each province grouped at its (areal) oenter.
- 97 -
·
Annex 6
f
,. I
1" , lnlec:llOft
.. I
'Itt
01
Sl."'- .....,.. fund Sllft••
"""-.om,,,,, IS
""MO'~IIII""","
......... ,I"l Wi"'''" '0'""
':
...... 0~.
10-
.
-.~
.'0--
- '"
.-"
... I
10
•
P1gure 10 - '!he atcldard ..t ot. a.ch1atoa0lll1..i. data. contour ..pped uaing a aixth-degree trend surtace (Kans.. o.ological Sul"le)") pro~ to de.onatrate the distortion that rew1 ta fraa an inappropriate method of intttrpolaticm-. o~ with PiIUN 6. (Contour line. were traoed MnU&l17 .rr. 11n..pr1nter output.)
ANNEX 7
THE TASKS FOR MEDICAL GEOGRAPHY by
Dr N.D. McGlashan
1
The ideals of Hippocrates' writing in the 4th century B.C. in which he urged close study of the environment by physicians of his day have only recently been greatly heeded. During these centuries geography and medicine have followed quite separate ways and the aetiological links between these disciplines have been ignored. In the last two or three decades, however, the situation has altered, and I wish to suggest to you by referring, only briefly, to actual practical case studies some of the main lines of medical work being undertaken by geographers in these days. 1. The administration of medical facilities
It is clear that for any public facility (be it banking, education, or clinic) to be of greatest benefit, its location, related to potential users, needs careful study. In the simplest case, this means providing a facility for a population cluster of a certain threshold size. In our world, population clusters wax and wane and transport to the public facility also may effectively increase or decrease its area of effective coverage. Studies can be made to bring together forecasts of population for a future date with expected speeds of movement along transport communication networks. Another aspect of this task is to study effects of distance upon the patient's own perception of what he considers to be ill-health. If distance or cost is very great he will tend not to seek early treatment and, at the other extreme, if medical aid is nearby and easily obtainable he also may leave his visit to the doctor until late. Those persons who travel to seek medical care most easily may be the middle-distance ones, with the scale of distance depending upon looal modes of travel. 2. Spatial definition of morbidity or mortal1ty
The simplest method of portraying disease or death is the dot map as used a century ago by John Snow and recently by our colleague, Dr Lee, in South Korea. It is easy to construct and all can understand it; and it has many valuable roles, especially where absolute case numbers are the
,. .\'
lSenior Lecturer in Geography, University of Tasmania, Australia.
- 99 -
. .
Armex 7 central interest. For some purposes, a "rate" map relating cases to population-at-risk may be preferred. This corrects any false impression of sickness cases merely replicating the-population distribution pattern. If good data are available, contour linea of death (isomorts) or of diseasecmess (is-omorbs) maybe constructed. Anotherrefinementinvolves the calculation of allowance for age and sex variations in local populations which permit geographical comparisons to be made. 3. Signifioant variations of pattern
It is not enough now to seek, from these disease maps, to interpret their patterns. It is necessary to show that the mapped distributions are not Just due to chance or random variations. One seeks to establish that, at a pre-determined significance level, the variation. away from some postulated "normal" situation. is so great as to need explanation. With large case numbers, "two standard deviations" may be an aopropriate test; with small numbers. perhaps the vcisson distribution may be used. In either case. patterns with neighbouring areas showing corroboration of each other's trend is often helpful. 4. Association in space
.-
The aim of spatial and significant definition of disease patterns is usually for comparison with another mapped pattern: perhaps a vector or physical or social geographical factor. In the simple case, compare only two maps; alternatively. use multi-factorial analysiS, probably by computer, of several variables simultaneously. This comparison. too. must be tested for statistical meaning - could it have happened by chance? If it is unlikely to have occurred by chanoe, we may (and only may) have suggested a ~elationship of some sort. Perhaps both are caused equally by a third ~actor unconsidered. This stage is not proof of a causative relationship. Rarely. however, rarely it may lead to the formulation of a new aetiological hypothesis. Often this will need testing in another discipline. 5. Diffusion in space
Lastly as a task for geographers is the problem of time/space spread of "an innovation". It may be the use of a bronze axe. a higher ladies' ~emline or an infectious hepatitis virus. Geographers have shown, for example. that certain rare climatic conditions can produce peculiar spread of airborne virus. This may throw light on incubation limits and control measures. Spread of measles through a network of human settlements has shown that particular places may typically "lag" or alternatively "lead" foci compared with nearby major population-centres. This has vast prophylactiC potential. Network analYSis may also indicate the threshold size of a community to keep a partioular disease outbreak running uninterrupted and without introduction of further contagion from outside.
- 100 r
Annex 7
Reference A number of examples of these types of geographical tasks has been collected in: MoGlashan, N.D. (Ed.) "Medical Geography Techniques and Case Studies" Methuen: IDndon. Due for publication: March 197~.
- 101 Annex 7 !
Thematic Mapping by
Mr Heinrich Engeler1
f
One of the objectives of this Seminar is to determine how maps can be more effectively used to support studies in geographic pathology and improve methods of epidemiological surveillance. I am not qualified to discuss the mapping of disease as such, but I do have information that 1s pertinent to the production of maps in general and, more specifically, the maps already existing in large numbers or in production that can be used as base maps for overlays on transparent base showing distribution of disease. Let me first speak of some general aspects of production of maps principles that are as important in mapping disease as in mapping popuiation, land usage, weather, etc. Representation of the spherical earth on a flat sheet of paper can be accomplished in a number of ways, but all are covered by the general term map projection. There are numerous prOjections each of which has certain properties and characteristics making it suitable or unsuitable for a given job. An overall best projection does not exist. Fbr example, a projection suitable for mapping the Soviet Union, which spreads over 5000 miles east to west, would scarecely hold good for a country like Chile that stretches more than 2600 miles north to south, but averages only 150 m11es east to west. Thus 1t is not reasonable to say that one projection 1s better than another without speCifying conditions. Projections are usually classified according to the principles of their construction. Thus cylindrical, conical and azimuthal projections are based, respectively, on the geometrical projection of the earth'S grid upon a cylinder, a cone and a plane. Equivalence in a projection means that any region, large or small, occupies the same area on a map as on a globe of corresponding scale. It is desirable that maps showing distributional data should have this characteristic, otherwise a false impression will be created and their usefulness will be undermined •
.'
Chief Cartographic DeSigner, Food and Agriculture Organization of the United Nations, Rome.
1
- 102 -
Annex 7 All maps are based on a "survey" of one sort or another. For topographical mapping, the surveryor "spies out the land" with precise instruments and records the relevant information for the cartographer. But a map showing population distribution must begin with a different kind of survey, a statistical survey of the numbers and whereabouts of the people in the area concerned. The professionals use their own terminology, and this is not easily understood by outsiders, so I will try to explain the most important terms. Each map is normally designed on a specific scale, a ratio of distance measured on a map to the corresponding distance on the ground, e.g., 1:100000 or 1:50 000 or 1:25000. Practically, the smaller the number, the larger the scale. Equally important to the map reader is a clear understanding of the ratio shown on the map as compared to the ground; ~ on the map at scale 1: 100 000 means 100 metres on the ground - 1 mm on the map at scale 1:1 000 000 means 100 metres on the ground. This consideration becomes important to any map maker when he must choose the best scale according to the denSity of information to be shown on the map. For detailed working maps the scales would run from 1:10 000 to 1:50 000 and for reconnaissance the scales would run from 1: 100 000 to 1: 1 000 000 and smaller. The grid refers to the network of lines on a plane surface that serve .s a~is for the coordinates by reference to which the map features are situated. Compilation means the assembly of source material such as aerial photographs, photograrrmetry, surveys and data from existing maps. Colour separation is a compilation of images (composites of detailed map features) that are selectively scribed in order to obtain the individual images that are to be printed in the aolour the feature .represepts. The need for appropriate infrastructure information cannot be overemnhasized. This is particularly true for resource maps, which are usually overlays or overprints on basic topographical mapping. The underlying information is obtained from various sources, including photogrammetry for the hydrography, topography, planimetry and co-ordinates. We then combine the four basic types of data into one composed map, and the final representation is printed in grey so as not to overload the map or to interfere with the first three thematic representations. Lastly, I wish to consider practical proposals for the use of already printed maps with computerized map data. In order to get the utmost advantage offered by both techniques, but particularly the past production of up-to-date data by the computer, the use of transparent overlays on a stable (opaque) base seems the best procedure. In this context I must mention a very important factor. If already existing base maps are to be used, it is necessary that the overlay maps be prepared according to the same projection and scale.
,.
- 103 -
-'
ANNEX 8
Morbidity rates of diphtheria in 1958 and 1968 (per 100 000 population)
1958 100 50
1968
#
•
10
Malaysia Macao Taiwan filli i8ines
~Blapo~1 a n Viet-Nam Korea
1
~k~:land ~~~tral1a ~iji
Laos
0.1
Tonga
..
-"
Note:
Plotted only in countries with consistent trends.
, •
•
- 104 Annex 8
•
Cases of diphtheria reported in countries of Western Pacific Region in 1969
o Australia Taiwan
100
500
1000
1500
Fiji F. Polynesia Hong Kong Japan r'lacao
·w.
Malayslll
Sara\'lak
New Zea]and Phili ppi nes Rep. of Singapore Rep. of Viet-Nam W. Samoa
,.
Western Samca 1968 French ?01ynesia 1968
'$
• ~
\ ...
,If
'.
\ •
.. REPORTED CASES ON DIPHTHERIA IN THE WESTERN P ACmC REGION
.
,..
\0;0
"
1937 - 1970 ~-
COUNTRIts AND TERRITORIES AusuaUa Britllh Solomon llIands PlOtectoJale Brunel Cbtn& (Taiwan) Cook lIlal1.
1957 237
1958 103 8 1938
1959 100
196b 28
1961 46
1962 M
1913 225
19M 94
1965 28 (41)
1966 10
11167 88
1988 18
1969
1970 88
110
2 2186 2040
37 953
11
511
418
559
5_
817
842 10 4
Ft.
. 8 13 1 1555 15 Ml 2 10 258 1558 14 50 1 18 20 2213 751 104 7 9 6 1 1334 9790 132 57 75 1883 55 128 1 5 46
921/855 (683)
827
413
111
4
French Polynesla Guam
3
1
1
3 1239 15423 2 38
1 11 113
4
Rolli KOIII Japao Khmer RepubUc
LaOi MAcao Malaysla: Malaya Sallah Sa.wall New Caledonla New Hebddea New Zealand Papua Phlllpplna Republlc of Korea
148 1.UB 12 33
2087 17938 148 38 337 1891 18 105
1460 14921 127 38 434
1017 7514 M 2 71
8118 . fl88 2774 39 11 4 54 39 50
71.
572(581) 307 2159 1520 8 7 22 27 45
228 1207 24 34
807 10 12 20'
62 816 1 11
48 588
28
1439 1933 33
688/988
31 1099
18 9
~
I-'
841
609
1_
1128
1130 99
4 31 69 1M7 857 188
a 18 12 2373 1000 114
66 4 1 30
5 11 21
4(7)
50 1
.
3i
107 2 11 1828 225 587 2 490
12 1589 888 80 400
1 20
2110 789 111 1
1421 914
1M' 434
1.' 81i7 48 206
I
Ryukyu llIal1.
.
Singapore TlmorDW To. . Republic of Viet-Nam Western Samoa
81 606
28 353
I
I
1 8 2062 (1350) 1879
a 29 1271
8 1
(739) . 58 (42) 230
14 1685 (133') 1283 (1281) 28
1253 445/534
1011 5 220 0 605 11
218 1 SOB
3 80 0 435
\()
~
66 0
52 0
2 IS9
289
539
--
576 2
449
801 18
3 36S
515/580
MORBIDITY RATES DIPHTHERIA IN THE WESTERN PACIFIC REGION 1957 - 1969 Rates per 100 000 popu1at1on COUNTRIES AND TERRITORIES Australia British Solomon Islands Prot. Brunei China (Taiwan) Cook Islands Fiji French Polynesia Guam
1957 2.5 23.0 1.6
1958 1.0 10.5 19.7 3.5
1959 1.0 20.0 1.8
1960 0.3 68.0 9·2 2.3
1961 0.4 1.6 12.4 4.8 1.5 1.5 42.0 10.4 2.4 3.0 44.1 24.2 11.7 16.5 1.,
1962 0.6 3.8 1.0 30.7 7.8 1.1 0.1 41.5 18.7
1963 2.0 4.9 0.7 24.7 5.1 0.6 0.2 22.5 15.4
1964 0.8 4.9 0.2 19·9 2.9 0.3 2.8 28.7 15.1
1965 0.36 6.53
19~1~~~"~~~-T~;;~·· t---.~.
r;! -I o f-'
0
0·09
0.54 7.01
0.23 4.66
0.38 3.01 0.77 1.55 0.60 0.03 6·92 6.77 1.1
6.60 52.63 0.22 0.84
O.
s
Hong Kong Japan Khmer Republio Laos Macau Malaysia: Malaya Sabah Sarawak New Caledonia New Hebrides New Zealand Papua Philippines Republic of Korea Ryukyu Islands Singapore Timor Dill Tonga Republic of Vi~t-Nam
\
1.5 45.3 54.5 70.3 47.7 16.9 17.0 19.3 16.0 004 0.04 2.8 2.9 0.6 2.3 2.0 2.0 , 84.4 149.1 197.1 256.8 22.6 2.9 4.8 23.9 3.3 7.0 1.4 0.7 8.8 3.2 12.3 58.1 2.1 1
0.20 3.07 11.00 2·96 0.80 0.15 0.42 7·69 9.59
5.9 1,4 6.6 3.8 22.7 69.1 3.4 1.3
28.2 3.6 14.4 4.1 0.8 8.9 4.1 13.2 67.0 '.9
Western Samoa
1.06 7.7 0.04 0.2 0.4 0.04 0.04 0.41 0.11 0.5 4.2 3.7 1.05 2.40 4.85 7.1 5.0 5.6 4.8 4.88 3.68 5.2 4.2 3.2 3.6 1.7 2.6 3.1 2,60 4.41 3.60 12.7 9.1 3.1 6.5 5.1 4.51 2.23 0.42 76.4 36.75 20.39 20.53 11.32 12.33 11.29 11.25 0.2 4.00 1.30 0 4.1 ,.1 5.4 2.26 '.07 3.56 1.8 13.6 8.21
28.5 1.3 8.9 5.2
15.49 8.23 5·92 2.20 1.54 1.21 0.13 0.11 0.37 0.84 1.00 1.23 16.07 10.07 10.82 17.90 11.66 12.87
0' 17 0.1 1
..
4
g
f-'
2.04 0·29 0.16 24.52 3.49 4.4 1.75 0.72 0·31 3.02 3.27 0 2.50 0
I.e c 2.~ '/
2.88
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