Leishmaniasis control

Bull. Org. mond. Sante 1971, 44, 561-566 Bull. Wld Hlth Org. Leishmaniasis Control V. M. SAF'JANOVA1 The article sets forth the basic principles for the control of the leishmaniases, which are for the most part diseases occurring in naturalfoci. The needfor specially planned measures for leishmaniasis control is emphasized. Different measures are required in different regions according to the type of epidemic focus and the nature of the disease cycle. In view of the specificity of the biological interrelationships between leishmaniae and their invertebrate hosts, sandfly control is of paramount importance in the prophylaxis of the leishmaniases. In the USSR, it has been possible to clear completely foci of anthroponotic cutaneous leishmaniasis by the implementation of a series of special measures including measures to eradicate the causal agent (treatment ofpatients) and the vector of the infection. The principles and methods of leishmaniasis con- trol are dictated by the need to consider the three links in the parasite system (the causative agent- the leishmania, its invertebrate host-the sanciily, and its vertebrate host-a mammal or man) that are characteristic of any form of leishmaniasis, as it is an obligately vector-borne disease. However, leishmaniasis control varies in different countries as the different forms of leishmaniasis differ sub- stantially from each other in their epidemiology and in particular in the part played by wild and domestic animals in the epidemic process. The economic activities of mankind are of great importance in determining the epidemiological situation in leishmaniasis foci as human activities often bring about substantial changes in the natural biocoenoses that correspond to these foci. Thus, agriculture and the cultivation of new land lead to a certain standardization of the environmental conditions of organisms and certain animal and plant species usually become dominant while other species are eliminated. Among such dominant species may be found the sandflies, which are the vectors of leishmaniae, and the animal reservoirs of leishmaniae, thus giving rise to an increase in the epidemiological risk. In other cases, as we know from the work of Kozevnikov, Dobrotvorskaja & Latysev (1947) and Petrisceva (1964), the rational planning of the culti- vation of virgin land, in which some of the factors 1 Doctor of Biological Sciences, Gamaleja Institute of Epidemiology and Microbiology, Moscow. that might activate natural foci of infection are controlled, leads to healthier conditions in the area and a reduction in the risk of infection with leish- maniasis. According to Heyneman, man's interaction with foci of leishmaniasis may take different forms: (1) People come into contact with a natural focus without affecting the existing conditions therein to any substantial degree. Such interrelation- ships may occur in desert foci of zoonotic cutaneous leishmaniasis or in foci of chiclero ulcer. The disease takes the form of an anthropozoonosis and man is an accidental host of the parasite. (2) A change in the environment brought about by man (e.g., through agriculture or building) leads to the elimination of some components in the initial animal-sandfly complex. The leishmaniae and the remaining species of sandfly gradually adapt themselves to man and a new (anthroponotic) form of chronic infection arises, such as Indian kala azar or Turkestan urban cutaneous leish- maniasis. (3) The cultivation of virgin land leads to a stable balance between man and the vertebrate hosts of leishmaniae. The disease then takes the form of an amphixenosis (Mediterranean kala azar, South American kala azar, etc.). (4) A sudden acute outbreak of disease develops in connexion with human activities and leads to the swift multiplication of vectors and animal reservoirs of the infection (e.g., the outbreak of 2668 -561- V. M. SAF'JANOVA Sudanese kala azar in the Gezira area on the Blue Nile). There are reasons to believe that, as a result of environmental changes and changes in the con- ditions under which interaction occurs between man, the causative agent, the vectors, and the reservoir of infection, the nature of the disease may evolve, developing from an anthropozoonosis into a zooanthroponosis, then into an amphixenosis, and finally into a pure anthroponosis. The migrations of non-immune populations and of sick persons harbouring leishmaniae are of great importance in the establishment of new epidemic outbreaks and of stable foci of leishmaniasis. Dr J. W. Torrealba has reported a recent out- break of espundia in Venezuela that resulted from the establishment of settlers (among whom had been sick people) in a formerly unaffected area of the country. He said there had been 200 cases and that the disease had apparently developed as an anthroponosis. In the USSR a serious problem arises in regard to the protection of non-immune persons moving to formerly unsettled areas of Central Asia, in which zoonotic cutaneous leishmaniasis is endemic. Zoonotic cutaneous leishmaniasis is a typical example of a disease occurring in natural foci. The theory of diseases with natural focality was first presented in the USSR by Pavlovskij and his school. It provides a solid theoretical basis for the control of those diseases. It should be noted, however, that the question of the natural focality of many forms of leishmaniasis has so far not been sufficiently studied. The direct or indirect effects of environmental factors that change as a result of man's activities, but in many cases act outside his control, alter the epidemiological situation in leishmaniasis foci. Sometimes such changes may be favourable and sometimes unfavourable. One thing is certain: the careful recording and analysis of these factors as they develop is absolutely essential for leishmaniasis control. An example of a favour- able and purposeful change in the environment leading to a sharp reduction in leishmaniasis morbi- dity is that of control measures against other vector- borne diseases in leishmaniasis foci. The WHO malaria eradication programme carried out in many countries has led almost everywhere to a reduction in the numbers of sandflies and in leishmaniasis morbidity. Thus, Professor P. C. Sen Gupta has reported that in India a sharp reduction in the numbers of Phlebotomus argentipes in several places resulted from the use of organo- chlorine insecticides against malaria mosquitos and was followed by a decrease in morbidity from kala azar. The reduction in the number of cases of kala azar was accompanied by a reduc- tion in parasitaemia in the peripheral blood of patients, and this reduced the possibility of addi- tional sandfly infection. The malaria-control cam- paign led to a reduction in leishmaniasis morbidity in Italy, Greece, and the Middle East. Professor 0. Theodor has pointed out the exceptionally low numbers (and in places the complete absence) of sandflies in Israel as a result of insecticide appli- cation against other harmful arthropods. Another example quoted by Petrisceva and by Saf'janova is that of the eradication of morbidity from urban cutaneous leishmaniasis in Ashkabad as a result of a successful campaign against sandfly fever. Conversely, there are instances in which the cessation of malaria-control measures leads to a resurgence of leishmaniasis morbidity. Professor P. C. San Gupta has reported that in East Pakistan after the cessation of control measures against malaria mosquitos, an increase was recorded in morbidity from kala azar as a result of the increase in numbers of the sandfly vectors. Unfortunately the use of insecticides against malaria mosquitos and other parasites does not always exert an effect on foci of leishmaniasis. For example, Professor D. Heyneman has reported that in Portugal morbidity from visceral leish- maniasis was not reduced despite malaria control operations, and this is not the only example. Evidently the " incidental " suppression of leish- maniasis foci resulting from malaria-control measures is possible only in special cases. It undoubtedly takes place in foci of anthroponotic forms of leish- maniasis, in which endophilic species of sandfly are the vectors and are therefore killed when houses are sprayed with insecticides against malaria mosquitos. Malaria control, however, has almost no effect on morbidity from zoonotic forms of leishmaniasis, whose main vectors are sandfly species that have little or nothing to do with human dwellings. Thus, there is no doubt that the leishmaniasis problem, which is so acute today in many countries of the Old and New World, cannot be solved " incidentally" through the control of other infec- tions but requires specially planned control measures. Considerable experience has accumulated in the control of some forms of leishmaniasis in different 562 LEISHMANIASIS CONTROL types of landscape and under various geographical conditions, and there are several methods of control against the causal agents, the specific vectors, and the reservoirs of leishmaniae. All this experience shows that combined measures are necessary if the control operations are to be successful. As a rule, leishmaniasis foci can be finally cleared only if a combination of prophylactic measures (specific and nonspecific) is applied simul- taneously against all the links in the epidemic chain. To determine the best strategy and tactics to be employed in clearing leishmaniasis foci it is neces- sary to study the cycle of the causal agents in the foci and possible ways of breaking that cycle, and to study the nature of territorial distribution, biology, and ecology of the animal reservoirs of leishmaniae and of the specific sandfly vectors. The selection of a particular means of control, and the time and manner of applying it, depends to a great extent on the conditions under which human beings come into contact with the local strains of leish- maniae and on whether it is economically rational to carry out a particular type of measure. In Indian foci of kala azar, where the disease is a pure anthroponosis, control tactics are based on the detection and treatment of sick persons combined with simultaneous eradication of the spe- cific vector, Phlebotomus argentipes. In addition to the malaria-control measures mentioned above, which in India reduced the numbers of kala azar vectors, Professor P. C. Sen Gupta has reported that special work has been done on the tea plantations in the state of Assam to control sandflies. In foci of visceral leishmaniasis where dogs are the source of infection and the disease is therefore an amphixenosis, good results are obtained by detection and destruction of all infected dogs to- gether with the treatment of sick persons and the application of measures to control sandflies. Dr M. de V. Coelho has reported that such measures have been carried out in some states in Brazil. Infected dogs were detected by means of the comple- ment-fixation test with a culture of tubercle bacilli as antigen and the sandflies were destroyed by spraying living quarters, stables, and other farm buildings with DDT. According to Dr R. B. Dzavadov, the same com- bination of measures was used successfully to clear a focus in Geokcaj Rayon in Azerbaidzhan in a campaign against kala azar of the Mediterranean type. In many foci visceral leishmaniasis has been difficult to control, because the question of its natural focality has been insufficiently studied. For instance, Dr D. M. Minter has reported that there are apparently two types of kala azar focus in Kenya. In the east of the country, in thickly populated areas, the disease is transmitted as an anthroponosis from man to man through sandfly bites. The arid part of Kenya in the north, with its sparse population, is characterized by natural foci of kala azar, with some wild animals (so far inadequately studied) as the animal reservoir. Naturally, in this area the tactics of the control campaign must be quite different from those used in the eastern areas of Kenya. The Soviet health services have had experience of successful purpose-planned campaigns for the control of cutaneous leishmaniasis of the urban type (anthroponotic cutaneous leishmaniasis). According to Dr A. Ju. Nadlafov, measures to control this disease have been carried out in the two largest endemic foci in Azerbaidzhan, the towns of Kirovobad and Barda. In Kirovobad the detec- tion and treatment of cutaneous leishmaniasis cases led to a 2.7-fold reduction in morbidity; this was not maintained, however, because no measures of sandfly control were taken. The use of a combi- nation of clearance measures was more successful, however, in Barda. These measures included the detection and treatment of human cases and the control of the sandfly vectors by insecticide spraying of their breeding-places and day resting-places. As a result the endemic focus of cutaneous leishmaniasis was completely eliminated. Similar work was carried out in large towns in the Turkmenian SSR-Ashkabad and Mary-which have long had a high rate of morbidity from anthro- ponotic cutaneous leishmaniasis. As a result of combined measures (detection and treatment of cases and sandfly control) there are no cases of this type of cutaneous leishmaniasis in those towns at present. Thus, the work in the USSR has shown in practice the possibility of completely eliminating foci of anthroponotic cutaneous leishmaniasis through a combination of measures designed to eradicate the causal agent and the specific vector, among which the most important are measures of sandfly control. A more difficult task is the control of zoonotic cutaneous leishmaniasis (or cutaneous leishmaniasis of the rural type), which has now spread fairly widely in some parts of Asia, including Turkmenia 7 563 564 V. M. SAF'JANOVA and Uzbekistan in the USSR, and which represents a serious public health problem. The difficulties are due to the natural focality of zoonotic cutaneous leishmaniasis and the fact that the main reservoir of infection is not man but wild desert rodents, particularly the great gerbil (Rhombomys opimus Lichtenstein). Foci of this disease are characterized by their high degree of stability and their capacity for swift recovery (i.e., a return to the initial epizootic situation) after eradication of the gerbils and sandflies. The first success in campaigns against zoonotic cutaneous leishmaniasis was gained by Latysev & Krjukova (1941) round the Taskepri reservoir in the Murghab Valley of Turkmenia, when they succeeded in reducing human morbidity from 707% to 0.4% by baiting the burrows of the large gerbil with chloropicrin. However, further experiments by Soviet research workers (Eliseev, 1958; Cugunov et al., 1962; Dubrovskij et al., 1962; Saf'janova et al., 1962; Fajzulin, 1967; etc.) indicate that a thorough know- ledge of the animal reservoirs and vectors of zoo- notic cutaneous leishmaniasis is necessary for the control of that disease. Detailed zoological and parasitological investi- gations carried out in the USSR (Eliseev et al., 1962; Dubrovskij & Svidenko, 1963; Saf'janova et al., 1965; Saf'janova & V'jukov, 1967) have revealed the structure of various types of focus of zoonotic cutaneous leishmaniasis and have led to an understanding of the territorial distribution of the causal agent, the animal reservoirs, and the specific vectors of the infection, and have determined those landscape characteristics that make possible an assessment of the epidemiological risk in a given area. All these data have provided a basis for working out tactics for prophylactic measures. Dr L. N. Eliseev has drawn attention to the fact that mea- sures to control zoonotic cutaneous leishmaniasis should be preceded by a period of detailed study of the structure of the focus, using the method of large-scale mapping. When the maps are drawn up, a record should be made of the spatial dis- tribution and numbers of the large gerbil and sandflies and also the extent of their infection with the causal agent of the disease. In the process, light is shed on the connexion between links in the epi- zootic chain and particular types of landscape or smaller natural features within a landscape. In view of the uneven distribution of gerbils and sand- flies infected with leishmaniae throughout the area, mapping shows up the sectors where the epizootic process is most intense or that present the greatest epidemiological risk.1 Attention should be con- centrated mainly on these sectors when eradication measures are undertaken. At the present time a large-scale campaign is being conducted in the USSR to suppress foci of zoonotic cutaneous leishmaniasis. One example is the campaign against the disease in new centres of population in the Golodnaya Steppes in Uzbekistan. The combined measures include the mechanical destruction of the burrows of the great gerbil when the land is being worked for crops and irrigation networks are being established, rodent control by spreading poisoned baits (zinc phosphide), destruc- tion of sandflies by means of insecticides in centres of population and in rodent burrows in the adjoining sectors of the steppe, organized case detection and treatment, and finally inoculations against leish- maniasis. These measures have led to a sharp reduc- tion in morbidity from zoonotic cutaneous leish- maniasis in the Golodnaya Steppe area. Non-specific prophylaxis against the leishmaniases Sandfly control measures can be divided into two basically different groups. Some ensure the protection ofhuman beings from sandfly bites without changing the numbers of sandflies in the natural populations. This group includes mechanical pro- tection measures such as the use of small-mesh nets around rooms and beds and also repellents. Among modern repellents, the most effective against sand- flies are N,N-diethyl-m-toluamide and hexamethyl- enebenzamide, one application of which, under Turkmenian conditions, affords protection from sandflies during a whole activity period (7-8 hours). For defence against sandfly bites it is convenient to use a fish-net with a mesh not exceeding 18 mm x 18 mm, impregnated with repellent (Saf'janova, 1963a, 1963b). Another group of measures designed to eradicate sandflies in their natural resting places consists of the control of the pre-imaginal phases (general measures of sanitation, mechanical destruction of breeding places, the use of larvicides such as the chlorinated hydrocarbons, and control of the adults mainly through the use of synthetic contact insecticides, such as DDT, HCH, dieldrin, and trichlorfon, to which sandflies are highly susceptible. Obser- vations carried out in various countries indicate 1 These two characteristics are not synonymous: the epidemiological risk in an area does not always correspond to the intensity of the epizootic process taking place therein. LEISHMANIASIS CONTROL that so far there has been practically no problem of insecticide resistance in sandflies. The experience of the Soviet health services has shown that health education work to encourage the active participation of the public in eradication measures is of exceptional importance in the control of sandflies in urban areas. With the help of the public, the breeding of sandflies can be prevented within the town concerned and this is a major step in the clearance of a leishmaniasis focus (Petrisceva, 1961). The control of zoonotic cutaneous leishmaniasis depends mainly on a combination of rodent- control and disinfection measures, i.e., the simul- taneous destruction of gerbils and the sandflies that live in their burrows. Chloropicrin is an effective means of destroying gerbils and sandflies at the same time (Latysev & Krjukova, 1941). Another method used in Turk- menian foci of zoonotic cutaneous leishmaniasis is based on the introduction into the rodent burrows of a mixture of motor exhaust gases and insecticide dust (DDT or HCH) by means of a special appa- ratus fitted on the exhaust of a motor vehicle (Cugunov et al., 1962). To eradicate gerbils and other rodents, wide use is made of poisoned grain baits-wheat with zinc phosphide (at the rate of 12% of the weight of the grain) with vegetable oil as an applicator (Eliseev, 1958; Fajzulin, 1967). This method can be combined with the eradication of sandflies in the gerbil burrows by treating them with sprays, dusts, or aerosols of synthetic insecti- cides. The methods available for the control of leishmaniasis of the zoonotic type are still far from adequate and further work is required. In conclusion, it should be emphasized that the selection of agents and methods to be used in a leishmaniasis control campaign always depend on local conditions and on the circulation of the causative agent in the particular focus concerned. In view of this, the effectiveness of the measures depends on the degree to which the structure of the focus and the features of the epizootic and epidemic processes have been studied. ;UME LA LUTTE CONTRE LA LEISHMANIOSE Les principes et les methodes de lutte contre les leish- manioses obeissent a la ndcessite d'agir sur le systeme a trois maillons (I'agent causal - Leishmania -, son h6te invertbr6 - le phlebotome et son h6te vertebre - mammifere ou homme) qui est caracteristique de toutes les formes de cette maladie. De nombreuses formes de leishmaniose sont des affec- tions typiques survenant dans des foyers naturels. 11 faut tenir compte de ce fait lorsqu'on met au point une stra- tegie et une tactique de lutte. On effectuera notamment une analyse approfondie des facteurs du milieu qui ont un effet direct ou indirect sur la situation epizootiologique et dpidemiologique dans les foyers naturels de leishmaniose. Ces facteurs peuvent etre modifies par les activites ecc- nomiques de l'homme. Dans certains cas, l'intervention humaine est b6n6fique, dans d'autres elle a une influence defavorable sur la situation epidemiologique. L'etude de ces changements constitue un element important dans la planification des mesures de lutte contre les leishmanioses. Le programme OMS d'eradication du paludisme a entrain6 dans certains pays (Inde, Italie, Greee, pays de la Mediterranee orientale, etc.) une reduction du nombre des phlebotomes et, en consequence, de la morbidite par leishmaniose. Toutefois, les programmes d'dradication du paludisme n'ont pas toujours eu partout de tels effets. Ainsi, au Pakistan oriental on a observe, une fois sus- pendues les mesures de lutte contre les moustiques, une recrudescence de la morbidite par kala-azar a la suite d'une augmentation de la population vectrice. Au Por- tugal, la morbidite par leishmaniose viscrale n'a pas diminue en depit de l'application de mesures de lutte antipaludique. II est evident que le probleme de la leish- maniose ne peut etre resolu indirectement, c'est-a-dire en combattant d'autres affections. Il faut mener une action specialement dirigee contre la maladie. La meilleure maniere d'elaborer une strategie et une tactique en vue d'eliminer les foyers de leishmaniose est d'etudier en detail l'ecologie des agents causals existant dans les foyers, de determiner quels sont les maillons essentiels de la chaine epidemique qu'il faut briser, de preciser la repartition geographique, la biologie et l'6co- logie des animaux reservoirs de la leishmaniose et des phlebotomes qui en sont les vecteurs specifiques. La lutte contre les phlebotomes est d'une importance capitale dans la prevention des leishmanioses, etant donne la specificite des rapports biologiques entre Leish- mania et ses h6tes. On dispose a l'heure actuelle de toute une serie de moyens efficaces pour combattre les phlebo- tomes (mesures generales d'assainissement destinees a empecher les phlebotomes de se reproduire, emploi d'insecticides synthetiques de contact et egalement de repulsifs pour se proteger des attaques du vecteur). Du 565 566 V. M. SAF'JANOVA fait du faible degre de resistance des phlebotomes aux insecticides, on obtient facilement de bons r6sultats. Les travaux effectues en URSS ont pratiquement demontre qu'il etait possible d'eliminer completement les foyers de leishmaniose cutan&e seche en recourant a toute une gamme de mesures d'6radication de I'agent causal et de son vecteur specifique, celles qui sont dirigees contre les phl6botomes 6tant les plus importantes. REFERENCES Cugunov, Ju. D. et al. (1962) Med. 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