Epidemiology of the leishmaniases: general considerations

Bull. Org. mond. Sante 11971, 44, 529-534Bull. Wid Hith Org. Epidemiology of the Leishmaniases: General Considerations 9. D. MOSKOVSKIJ 1 & N. N. DUHANINA 2 Recent information from various countries shows that the distribution of the leishma- niases is rapidly changing, as are our concepts of the diverse noso-geographical forms of infection. Concerted efforts should be made to improve our knowledge in these fields to enable the preparation of charts forecasting the spread of the disease. The basic considerations, objectives, and methods of epidemiological investigations carried out in the USSR in natural foci, as well as the classifications usedfor typing foci, are discussed. The need to use clear-cut epidemiological concepts is particularly stressed. THE DISTRIBUTION OF THE LEISHMANIASES Our ideas of the distribution of the leishmaniases and the relative importance of the various forms of infection in different countries have changed for a number of reasons. Our knowledge of the forms of leishmaniasis prevalent in many countries is clearly inadequate: new information, about both known and new forms of illness, may lead to substantial changes in distribution patterns. Considerable modifications have already been observed in the distribution of the leishmaniases throughout the world (Krjukova & Latysev, 1948; Rodjakin, 1962; Kolonickij, 1963). In a number of countries the cultivation of new land is leading to the disappearance of natural foci of leishmaniasis, and the wide use of insecticides causes the gradual elimination of old foci of the disease in human populations, as has happened, for example, in Italy (Corradetti et al., 1966) and in the Central Asian foci of the zoonotic type of tegumentary leishmaniasis in the USSR (Bobrov, 1955; Isaev, 1959; Isaev et al., 1966). The foci of anthroponotic leishmaniases disappear first, as has been the case with cutaneous leishmaniasis of the urban type in Azerbaidzhan (Nadzafov, 1966) and in Turkmenia in the USSR, as a result of the detection and treat- ment of patients and the planned use of DDT: kala azar is disappearing i n India as a result of the 1 Scientific Consultant, Marcinovskij Institute of Medical Parasitology and Tropical Medicine, Moscow, USSR. ' Head, Department of Medical Protozoology, Marcinov- skij Institute of Medical Parasitology and Tropical Medicine, Moscow, USSR. introduction of modem diagnostic methods and the development of chemotherapy. These successes are having favourable demographic and economic con- sequences (Bobrov, 1955). With respect to India, Professor P.C. Sen Gupta has stated that the previous decimation of populations in districts of Assam by epidemics of kala azar has now passed into history. These epidemics previously resulted in large tracts of agricultural land lying fallow, in migration of populations, and in consequent econo- mic loss. Professor Sen Gupta has said that leish- maniasis does not now pose a serious menace to the economic development of India. However, as man penetrates into formerly un- touched natural foci, new mass epidemics of both known and new forms of leishmaniasis occur (Coelho & Falcao, 1966). This has occurred in a number of developing countries of Central and South America, East Africa, and the Sudan, where, during the last few years, there have been extensive epidemics of kala azar and, in particular, various forms of cutan- eous and mucocutaneous leishmaniasis (Hoogstraal & Heyneman, 1969; Furtado et al., 1966). In view of the exploitation of desert areas, as in the Central Asian republics of the USSR, and of the development of forest industries, as in Latin America and in a number of other countries, forecasting the spread of leishmaniasis and the compilation of forecasting charts are assuming great importance. It is essential that within the next few years more precise information should be obtained regarding the distribution of leishmaniasis, so that a world forecast chart can be drawn up. 2665 -529 S. D. MOSKOVSKIJ & N. N. DUHANINA The world distribution of the leishmaniases has not yet been fully determined and factors governing their geographical distribution have not been adequately studied. Reconfirmation of the presence of leishmaniases is necessary for a number of locali- ties, especially in places where the transmission of leishmaniasis formerly occurred over a wide area but where it has now been stopped by agricultural development, by insecticide treatment (possibly for other insect pests, as in anti-malaria campaigns), by chemotherapy, or by social changes, such as urbanization. TYPES OF LEISHMANIASIS FOCI Speciation in agents of infectious disease, as in any other living organisms, and the differentiation of strains occurs by selection resulting from interaction of the agent with the host in the given geographical (environmental) conditions. Therefore the diversity of the species, subspecies, and strains is greater with zoonoses than with anthroponoses. The more variable the physico-geographical (environmental) conditions and the species composition of the inver- tebrate and vertebrate hosts in different geographical regions (Dubrovskij et al., 1968), the greater the diversification of the agent and of the clinical and epidemiological pattern of the disease. Accordingly, the zoonotic forms of human leishmaniasis greatly outnumber the anthroponotic forms. In respect of naturally endemic diseases, the occurrence and spread of which depend entirely on specific environmental conditions, the following ecological types may be distinguished: (1) anthroponoses, in which the only source of infection is man (urban type of cutaneous leish- maniasis in Middle Asia); (2) zoonoses, in which vertebrate animals are the only or main source of infection for man; these include: (a) naturally nidalic diseases, the causative agent of which is harboured by wild animals (e.g., the rural type of cutaneous leishmaniasis in Middle Asia); (b) anademic diseases, in which the sources of infection are synanthropic animals (domestic animals or vertebrates inhabiting human dwel- lings, cattle sheds, etc.); (3) anthropozoonoses, when man acts as the main source of infection for other vertebrates. A further distinction may be made between: (1) paraxenoses, in which man and animal occupy a parallel position in the transmission cycle; and (2) metaxenoses, in which man and animal are infected in sequence, mostly harbouring different developmental stages of the causative agents. The species intermediate between man and man is called " xenorganism" (Moskovskij, 1950). Natural nidality represents a special form of natural endemicity. Naturally endemic diseases are those whose transmission depends on some specific abiotic or biotic agent or factor belonging to the natural environment. Both the urban and rural types of tegumentary leishmaniasis represent natur- ally endemic diseases (as transmitted by sandflies belonging to the natural fauna), but only the rural type is naturally nidalic. The anthroponotic forms of malaria are naturally endemic, but the simian species of malaria transmissible to man are naturally nidalic. A proper survey of leishmanial foci requires there- fore a study of the biology and ecology of the vectors and, in the case of zoonotic forms, a study of the related fauna and the biology and ecology of the vertebrate hosts as well. Studies of natural leishmaniasis foci in the USSR include: (1) the study of geomorphological, climatological, and general landscape characteristics of the area concerned, along with related zoological and eco- nomic research (Eliseev, 1963; Tupikova, 1969); (2) epizootiological investigation, i.e. a study of the way the infection circulates in the animal popula- tion, and of laws that govern this circulation (Saf'- janova et al., 1965); (3) epidemiological studies, i.e., investigation of the factors controlling the spread of the infection in the human population (see Mamedov, 1969). To work out systems of leishmaniasis control that will be effective for the broad gamut of conditions in different parts of the globe requires thorough research on the epidemiological features of various forms of the disease in all parts of the world. To carry out epidemiological investigations it is necessary to have a programme based on precise measurements and observations and to work out a set of suitable methods. It is essential to devise methods of reconnaissance for all uninvestigated areas, to be able to detect present and past leish- maniasis cases, and to work out methods of dif- ferential diagnosis applicable to each focal region. 530 EPIDEMIOLOGY OF THE LEISHMANIASES At present, the Montenegro reaction is widely used to detect present and past cases of visceral, cutaneous and mucocutaneous leishmaniasis, though in some areas and circumstances its usefulness is limited. Any locality should be considered potentially dangerous in terms of zoonotic leishmaniases if it falls within the natural distribution of animal reservoirs and the effective sandfly vectors. However, the degree of endemicity and risk of infection for non-immune groups may differ sharply in different types of focus. Study of the leishmaniases in many areas shows that the disease is frequently contracted in natural foci far from centres of population and from the patients' homes. The epidemiological pattern differs sharply in different forms of leish- maniasis. Thus, visceral leishmaniasis is mainly sporadic in distribution and transmission occurs at a low level. Yet, in some countries, and at certain periods, there are local severe outbreaks or even full-scale epidemics (as formerly in India, Kenya, and the Sudan). In cutaneous leishmaniasis the intensity of trans- mission in the centre of its area of distribution is very high every year, but periodic fluctuations in mor- bidity occur. Thus, according to observations car- ried out in Bukhara Oblast, increased morbidity is related to increased humidity and to the mass breed- ing of sandflies thus stimulated. Along the edges of the distribution zone of zoonotic cutaneous leish- maniasis, periodic rises and falls in the numbers of infections are characteristic. METHODS AND AIMS OF EPIDEMIOLOGICAL INVESTIGA- TIONS OF ZOONOTIC CUTANEOUS LEISHMANIASIS Epidemiological investigations are important for working out an effective system of leishmaniasis con- trol measures in view of the diversity of foci of cutaneous leishmaniasis. The basic method of epidemiological study in a focus is to examine the population for sores and the characteristic scars that result from the illness. Other data collected in surveys are used for retrospective analysis of the course of morbidity, for forecasting morbidity, and for describing the features of the focus that are needed to assess the effectiveness of measures taken. In the USSR, population surveys for the detection of specific leishmaniasis scars in foci of cutaneous leishmaniasis of both types have been widely under- taken and are continuing. Similar surveys have also been carried out in a number of countries in the Near and Middle East and in other parts of Asia. In Venezuela, the staff who examine the population for leprosy and mycotic infections also look for leish- maniasis scars. In some countries, however, such as the United Arab Republic and Turkey, it has not been possible to carry out such surveys, since many people bear scars from other diseases. Other people may show an immune response without scars, as was found by several workers in the USSR, and by Pifano (1941) in Venezuela, who believes that sub- clinical infection frequently occurs. In those coun- tries where scar analysis is not reliable, preference is given to the use of the Montenegro skin test (Alkan et al., 1969; van Peenen & Dietlein, 1963; Pons, 1968; Cahill, 1970). The findings from population surveys in the Soviet Union are being used as a basis for conclusions regarding the immunological structure (stratifica- tion) of the population and the risk of infection for non-immune groups. Foci are classified by type according to the extent of their activity. To forecast morbidity from cutaneous leishmaniasis it is essential to determine both the actual intensity of transmis- sion (the loimopotential), and the risk of infection (see below). These can be calculated on the basis of incidence, prevalence, and age-distribution of past and present infection. Non-immune groups-young children or groups of persons who have come from outside the area-are of special concern and provide data of particular importance. The objectives of these epidemiological investiga- tions are: (1) to analyse the geographical distribution of human infection; (2) to recognize foci of natural transmission of cutaneous leishmaniasis; (3) to develop methods of forecasting the risk of infection in these regions; and (4) to assess the risk to new- comers settling in these areas. These objectives require painstaking and detailed investigations of the epidemiology and epizootiology of transmission in each focus of infection. Such investigations should include detailed studies of the population at risk, of the disease landscapes or ecological complexes (ecosystems), of the distribution of epizootics among the rodents, and of the species composition and natural infection levels of the local sandflies. Scar analysis based on house-to-house visits have estab- lished that evidence of past infection is higher among older groups exposed in a region of active transmis- sion (Gozodova et al., 1965; Barkov et al., 1966; Lysenko et al., 1969). The accuracy of the method of counting scars on exposed areas of the body in determining the intensity of past infection has been repeatedly demonstrated in the USSR. 5 531 5. D. MO,KOVSKIJ & N. N. DUHANINA Field epidemiological surveys therefore allow us to map the endemic foci and to type them according to the pattern of infection in the population. The clas- sification of Lysenko, Gozodova & Barkov (1965) established three epidemiological types of natural focus: (1) Active and stable-40-50% of persons up to 50 years of age show scars; new cases appear each year, chiefly among children and non-immune persons. (2) Active and unstable-less than 40-50%, usually below 20-25 %, show scars; all ages contract the disease; some new cases occur each year. (3) Inactive (extinguished)-incidence in children absent for at least five years; number of persons with scars variable, depending upon intensity of trans- mission in the original focus. Curves then can be employed to show the increase in number of non-immune persons, to identify the type of focus, to estimate the probability of risk to new settlers, and to determine the particular type of control measures that would be most effective. ROLE OF ENVIRONMENTAL CHANGES In relation to the effect of changes in the natural environment on the distribution of the leishmaniases, Heyneman has distinguished four types of leish- maniasis distribution among human populations: (1) clusters of cases that occur when groups of human beings penetrate into natural foci; (2) the conversion of a natural focus into an anthroponotic focus, when natural conditions are changed as a result of the development of agriculture or other forms of exploitation of natural resources. This conversion may have led, over a period of many years, to the gradual adaptation of the vector and the parasite to man. However, this is unlikely to occur in the few years immediately following the beginning of economic exploitation of an area. In the case of urban cutaneous leishmaniasis, the disease appears to have come from very ancient human settlements; (3) the achievement of a balance between the roles of man and of mammals in the transmission of infection, when both man and an animal closely associated with him serve as sources of infection. An example of this is the relationship between man and domestic dogs in the transmission of Mediter- ranean kala azar (an amphixenosis, or what Balta- zard called an anademic infection); (4) the occurrence of outbreaks as a result of man-made conditions that make possible the differential survival and mass breeding of the vector or the reservoir host (man-made foci). Human activity, such as the use of insecticides for malaria control, may, on the other hand, lead to a sharp reduction or even cessation of spread of leishmaniasis as a result of destruction of the vector. Agricultural practices can similarly cause local extirpation of reservoir hosts, such as the destruction of gerbil vil- lages in the Uzbekistan SSR. Planned changes in the environment, if knowledge of the original vector-pathogen-host relationship is properly employed, can lead to elimination of leishmaniasis, as has occurred in foci of cutaneous leishmaniasis in the USSR. EPIDEMIOLOGICAL FEATURES OF DRY AND WET CUTANEOUS LEISHMANIASIS IN THE UZBEK SSR Dr V. P. Ipatov has reported marked fluctuations in the incidence of the zoonotic form in the Uzbek SSR. The epidemiology of the urban anthroponotic form caused by L. tropica tropica (L. t. minor) requires firstly a certain level of population density to ensure the presence of a sufficient number of susceptible persons, and secondly conditions enab- ling an effective vector to breed. The protracted, chronic course of this disease in man links one trans- mission season with another, without the interven- tion of a vertebrate host. The improvement of urban amenities and the use of insecticides have led to rapid disappearance of this form. Foci of the rural (zoonotic) form (Leishmaniasis tropica major) exist independently of man. When settlements are established in the immediate vicinity of rodent burrows, the vector that breeds on farm- lands, Phlebotomus papatasi, may enter the rodent burrows and ensure the extensive spread of the infection among the inhabitants of large centres of population. Foci of rural cutaneous leishmaniasis occur in four areas of Uzbekistan. DISCUSSION Several interesting points have been raised con- cerning the epidemiology of the leishmaniases. Pro- fessor 0. Theodor has pointed out that in some areas the former incorrect idea that visceral leish- maniasis predominated among adults (e.g., in China) 532 EPIDEMIOLOGY OF THE LEISHMANIASES arose from the fact that only hospital data were recorded and that in some countries children were rarely taken to hospital. He has also expressed doubts regarding the correctness of the assertion that in some places in the Mediterranean area visceral leishmaniasis occurs in the absence of infected dogs. Professor E. K. Unat has stated that there is no cutaneous leishmaniasis in the southern part of Turkey. Dr D. Heyneman has pointed out the difficulty in interpreting statements on the presence of post-kala azar leishmanoid (as in the Sudan) as interpretation of the condition varies so widely. With respect to the possibility of drawing con- clusions regarding the immunity of populations on the basis of the presence or absence of scars, Dr N. H. Kent, while acknowledging the practical importance of such population surveys, has said that a particular degree of immunity should not be inferred from such survey findings alone. This point of view is supported by Professor Theodor. According to the findings of Soviet investigators, the disease actually recurs in 10-15% of persons with scars. Nevertheless, in view of the stability of immunity following cutaneous leishmaniasis, Soviet research workers are convinced that the immunological structure of the population can be assessed on the basis of scars. It has been suggested that surveys should be carried out using the skin test. In areas where mucocutaneous leishmaniasis is found, neither healed scars nor a positive skin test can be relied upon to indicate a state of immunity. Cases frequently relapse or flare up again in severe mucocutaneous manifestations, often after 5-10 years of quiescence following a supposed cure of a cutan- eous lesion. Maruagvili has stated that he accepts only two basic forms of visceral leishmaniasis-the Indian and Mediterranean forms (Brahmachari, 1926). Both are represented by a number of geographical variants, however, whose definitions depend on special geo- graphical features of the area in which the disease occurs. Clear-cut epidemiological concepts are needed in the analysis of leishmaniasis epidemiology as they are for any other infectious disease (Moskovskij, 1961), and a distinction should be made in particular between incidence, prevalence, and " pervadedness " or cumulative prevalence (the latter term indicates the proportion of persons who have had the infection in either a frank or latent form before or at the moment of the survey). It is essential to establish values for these indicators (" epidemetrons") by various methods. A distinction must also be made between the intensity of transmission (" loimopoten- tial ") and the risk of infection (which corresponds to the overall infection rate) that arises for a popula- tion at the given level of the loimopotential. Dr B. A. Southgate and Dr D. M. Minter have correctly pointed out that it is necessary, in the epidemiology of the leishmaniases, to consider the family or the microfocus formed by groups of family dwellings used as the unit of study. Professor P. A. Petrisceva and Dr V. M. Saf'janova have noted that the study of foci and the forecasting of morbidity require a synthesis of data on morbidity and past and present prevalence with carefully analysed data covering the landscape, zoology, and economics, and with information on occupations and other pertinent factors among the population at risk. RtSUMt EPIDEMIOLOGIE DES LEISHMANIOSES: GENERALITES On a recemment observe de considerables modifica- tions dans la distribution mondiale des leishmanioses. De tres anciens foyers ont ete progressivement elimines de plusieurs pays. En URSS, grace au depistage et au traite- ment systematiques des malades et a l'utilisation ration- nelle du DDT, la leishmaniose du type urbain a disparu de l'Azerbaidjan et du Turkmenistan. Le type zoonotique de cette maladie a recule dans les foyers d'Asie centrale a la suite de la mise en culture de nouvelles terres et d'une large utilisation des insecticides. La faible incidence du kala-azar en Inde est attribuee a l'introduction de me- thodes de diagnostic modernes et it l'extension de la chimiotherapie. Cependant, d'importantes epidemies de formes connues et inconnues de la maladie sont survenues en Amerique centrale, en Amerique du Sud, en Afrique orientale et au Soudan. Afin d'etre en mesure de prevoir quelles seront les zones les plus exposees i la propagation de la maladie, il est indispensable d'acquerir, d'ici quelques annees, des connaissances plus precises sur la distribution mondiale des leishmanioses et sur les facteurs qui la regissent. Ler rassemblement de cartes de prevision exigera des efforts 533 534 S. D. MO§KOVSKIJ & N. N. DUHANINA concertes; son importance est considerable car 1'exploi- tation de vastes regions desertiques ou forestieres, qui constituent des foyers naturels oii l'on n'est pas encore intervenu, ne cesse de croitre. Le present article expose ensuite en detail les conside- rations fondamentales, les objectifs et les methodes des investigations epidemiologiques poursuivies en URSS dans des foyers naturels; elles indiquent ensuite par le menu les classifications employees par les travailleurs sovietiques pour caracteriser les foyers. Parmi les autres sujets speciaux examines figurent: le role des modifica- tions du milieu; l'epidemiologie du kala-azar en URSS, les caracteristiques de la leishmaniose cutanee, seche et humide, en Uzbekistan; la possibilite d'evaluer la struc- ture immunologique d'une population d'apres les cica- trices et, enfin, la necessitd de s'appuyer sur des notions epidemiologiques precises pour analyser les epidemies de leishmaniose. REFERENCES Alkan, M. Gunders, A. E., Naggan, L. & Danon, Y. (1969) Harefuah, 77, 96 Barkov, V. N., Gozodova, G. E. & Fonareva, K. S. (1966) Med. Parazit. (Mosk.), 35, 676 Bobrov, S. I. (1955) Trudy turkmenskogo naueno-issledo- vatel'skogo koztno-venerologiceskogo Instituta, Askabad, 4, 126 Brahmachari, U. N. (1926) Treatise on kala-azar, London, Butterworth and Co. Cahill, K. M. (1970) Trans. roy. Soc. trop. Med. Hyg. 64, 107 Coelho, M. de V. & Falcao, A. R. (1966) J. bras. Med., 10, 259 Corradetti, A., Mantovani, A., Adames, A. J. & Della Bruna, C. 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