- Email: [email protected]
Cutaneous leishmaniasis: strategies for prevention
Cutaneous Leishmaniasis: Strategies for Prevention RICHARD W. ASHFORD, PhD, DSc
G
eneral guidelines on the prevention of parasitic disease are given by Molyneux,1 who emphasizes the importance of stratification of epidemiological patterns in order to assess priorities and to design focused control measures. The epidemiology and control of leishmaniasis have been reviewed recently by Ashford and Ashford and Bates, in which articles most primary references can be found.2– 4 The first thing to emphasize about the control of cutaneous leishmaniasis (CL) is that this has rarely been successfully achieved, so there is no general set of instructions to follow. The most successful campaigns were in the old Soviet Union, against Leishmania tropica in Azerbaijan and L. major in Turkmenistan and Uzbekistan, many years ago. Descriptions of these interventions are not readily accessible and some of the methods used would not be acceptable today.5 Control strategies cannot, therefore, be proposed in more than theoretical outline. Now that the classification of the parasites is well understood, however, and the structure of many reservoir systems has been established, it is possible to suggest relevant investigations leading to stratification, and interventions leading to control. CL due to infection with either L. major or L. tropica may be either endemic or epidemic. Endemic areas can be identified by case reporting, but areas of potential epidemicity cannot. Although we do not fully understand the reasons, the distribution of these parasites correlates closely with environmental characteristics, notably bioclimatic and vegetation zones. The principles of landscape epidemiology or eco-epidemiology are therefore very important in assessing epidemiological risk. Some excellent examples have been published, allowing the construction of a preliminary stratification of Old World cutaneous leishmaniasis (Table 1), but much exciting study on these lines remains to be carried out. It is frequently the case that transmission cannot reasonably be reduced and infection cannot be avoided. The main action then is to minimize the effects of infection by assuring prompt diagnosis and appropriate From the Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Address correspondence to Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. E-mail: [email protected] © 1999 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
treatment. It is important to recognize that it is sometimes most appropriate not to treat cases at all; the best intervention in such cases is cleaning of the lesions and reassurance of the patient.
General Considerations National Committee Cutaneous leishmaniasis is vector-borne and frequently zoonotic so it requires specialized knowledge in various areas to assess and understand its public health importance and potential control measures, and to make relevant recommendations to the Minister of Health. WHO6 recommend that in any country where CL is perceived as an actual or potential problem, a National Committee should be established, bringing together the relevant expertise, and advising the Minister of Health on appropriate action. The requirements of the National Committee are not only medical, but must include biological, entomological, mammalogical, environmental, sociological, and logistical expertise. In many countries some of this expertise is to be found in malaria control departments, and it is frequently assumed that this department can simply take over the function of leishmaniasis control. This has not usually been successful, partly because malariologists have very specific training and knowledge, so are uncomfortable to explore unfamiliar ground, and partly because the commitment of malaria departments to malaria control leads them to underestimate the importance of leishmaniasis. The National Committee should include representatives from academic institutions as well as operational experts. This is because there will inevitably be a need for investigation at the scientific as well as operational level. Though we have much information, each focus of CL will be different and will require separate assessment.
Intersectorial Collaboration Intersectorial collaboration is particularly important, and has frequently been neglected. CL is frequently a disease of development projects and, with a minimum of health impact assessment, can be predicted and avoided. Close coordination is called for between the National Committee and the agencies responsible for development projects, public or private. 0738-081X/99/$–see front matter PII S0738-081X(99)00051-6
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Table 1. Summary of Main Epidemiological Features Relating to Stratification of Old World Cutaneous Leishmaniasis Stratum, or Nosodemiological Unit
Source of Infection
L. tropica in West and Central Asia
Anthroponotic in dense housing
L. tropica s.1. in West Mediterranean Basin
Focal structure incompletely known
L. tropica in East Africa
Zoonotic; maintenance hosts probably hyraxes Zoonotic; reservoir host Rhombomys opimus Zoonotic; reservoir host Psammomys obesus Zoonotic; reservoir host Meriones spp Zoonotic; reservoir hosts rodents Zoonotic; reservoir host domestic dog
L. major in Central Asia
L. major in North Africa, West Asia L. major in Pakistan, India L. major in sub-Saharan Africa L. infantum in Mediterranean Basin L. aethiopica in East Africa
CL Endemicity
Transmission
Special Features
Endemic in independent foci; becoming epidemic in dependent foci Poorly known; occasional epidemics
Peridomestic in dense cities; also sporadic in villages Peridomestic in villages (Morocco) or sylvatic (Tunisia) Sylvatic in rocky places
Epidemics may be in new housing settlements or ancient buildings
Limited distribution; poorly known Endemic in local people, epidemic in visitors
Sylvatic, in loess landscapes
Epidemics in visitors spread to local people Poorly known; occasional epidemics Rare sporadic cases, with occasional epidemics Rare manifestation of normally visceralising parasite
Sylvatic, in salt-pan basins Sylvatic
Zoonotic; reservoir hosts hyraxes
In many endemic countries the military are greatly affected by CL, as they exercise or operate in zoonotic foci. Sometimes simple operational changes can reduce exposure to infection, but this requires that the military are involved in the intersectorial coordination. The role of the National Committee is to advise the Minister, and to ensure that interested agencies are informed. This need not be an onerous task, and annual meetings may be sufficient to guide and support relevant investigations and operations, and to assess the results.
Caution in Control Measures One vital feature of the epidemiology of CL, which may considerably affect prevention strategy stems from the fact that the disease leads to lifelong immunity. This means that, in a holoendemic area, most of the people have been infected when very young and are immune; intervention to reduce transmission in such an area would, over the long term, lead to a build-up of nonimmune youngsters, who would be liable to infection at an older age, when the stigma of infection is much greater. Reduction of transmission could, therefore lead to an increase in the public health problem. The above problem certainly applies to zoonotic CL, where the force of infection among humans is independent of the number of human cases. With anthroponotic infection (ACL), reduction of transmission will similarly increase the age at which people become infected, but may also more easily eliminate the disease. Precise
Major problem in development projects
Sylvatic, in sahel Peridomestic in villages
Dermotropic strains visceralise with AIDS
Sylvatic, both in rocky and wooded areas
DCL is a rare but important variant
models of ACL epidemiology are required to assess this. Reduction of transmission in holoendemic areas should only therefore be considered with careful forethought. It may be that detection and treatment of the serious cases, and protection of visitors are the preferable options.
Origins of Epidemics One of the most striking features of CL is the tendency of disease in humans to be aggregated in both space and time. That is, cases tend to occur in localized foci, and in outbreaks or epidemics. In principle, epidemics of CL may have one of three origins. L. tropica epidemics seem to be the result of the introduction of the parasite into susceptible populations. Here, the parasite will be spread rapidly for a few years and many people of all ages will be affected. As the proportion of people susceptible decreases, the epidemic will die out or move to another locality; occasionally it may become endemic, with a low incidence of infection, confined to young people and immigrants. L. major in Khartoum in the late 1980s behaved in this way, leading to the belief that this unusual epidemic was anthropogenic in its origin and maintenance. More usually L. major becomes epidemic when large numbers of people move into zoonotic areas. These are frequently military personnel, or people involved with development projects. The semi-desert low lying habitats of L. major are potentially
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valuable for irrigated agriculture, and agricultural development projects have been seriously disrupted. The third source of epidemics, which may be combined with the second, depends on the tendency of desert rodent populations to fluctuate in numbers. These fluctuations are not understood, and are not even well recorded, but it is frequently observed that at the time of an epidemic of human CL in settled people, rodents are very abundant, and that in subsequent years they are much less so. These irruptions in rodent numbers may affect several rodent species simultaneously over wide areas. It is the second and third type of epidemic which are the most unpredictable, both in time and space. Prediction of type two epidemics depends on a thorough knowledge of the structure of the zoonotic focus of infection and the geographical distribution of suitable conditions. Type three epidemics require, in addition, some understanding of rodent population fluctuations and prediction of these.
Public Health Priority Although cutaneous leishmaniasis is usually painless, self-curing, and without serious consequences, it is an infection of great public health importance; people who are not culturally adapted to the infection are greatly upset by it and, in places with growing health expectations, the health service is pressured to take action. Unfortunately, what action to take is not always readily apparent: by the time an epidemic is detected, transmission has ceased, and preventive intervention is impossible.
Imported Cases In countries where cutaneous leishmaniasis is only imported, or rare, the main action is to educate the medical practitioners to recognize the lesion or, at least, to send the patient to a tropical institute. Misdiagnosis has led to some horrific events of mistreatment.
Risk of Introduction There is little risk of introduction of cutaneous leishmaniasis into new areas. This question arose when numerous Fijian soldiers in the Multinational Force of Observers in Sinai became infected with L. major, as sandflies were known to be abundant in Fiji. However, these are ceratopogonid midges which are incapable of transmitting the infection. Possibly more relevant was when Gurkha troops from Nepal on jungle training exercises with the British army in Belize became infected with L. braziliensis and L. panamensis. There was a possibility of introducing the infection to Nepal, where various phlebotomine sandflies are found. The numerous temporary workers from south-east Asia who become infected in Saudi Arabia are unlikely to introduce
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the infection to their home countries on their return, as the distribution of this parasite depends on a precise combination of vector and reservoir host. While the risk of long-distance introduction is minimal, there is little doubt that anthroponotic forms which can be maintained temporarily in “dependent foci” are frequently reintroduced from nearby “independent foci.” L. tropica in Kabul, Afghanistan, appears to depend on repeated reintroduction from endemic foci at lower altitude,7 and the outbreak of L. major-CL in Khartoum in Sudan in the late 1980s is best explained by the introduction of the parasite by displaced people from the west of the country.
Cutaneous Leishmaniasis due to L. major Infection L. major is characterized by endemicity in sparsely inhabited semi-arid habitats, with outbreaks caused either when groups of people enter these areas or when increase in numbers of reservoir hosts leads to a population explosion, or irruption, bringing the rodent and therefore the parasite, to new areas. Where the parasite is endemic it mainly affects young children and usually passes unnoticed and only the relatively few severe cases are reported. Where it affects immigrants, these are usually adult males; they are unaccustomed to the disease and may suffer multiple sores, and may be psychologically as well as physically affected. Worse, they may be accused by their hosts of importing a dreadful disease, and deported. Sometimes, as in the outbreak at Mowakkar in Jordan, it is settlers in a new housing project who are affected. Outbreaks apparently caused by irruption of reservoir host populations have been described in Libya, Tunisia, and Algeria. These affect people of all ages, in their homes, so are notoriously unpopular and can have great public health significance. Some degree of personal protection against L. major is available, by means of leishmanisation. In this process, live, virulent promastigotes from cultures are inoculated into a part of the body where the resulting lesion and scar will not be disfiguring. Following healing of the lesion, the individual is immune to further infection. This method has been used on a large scale by Soviet and Israeli armies, but was discontinued because of the unacceptable number of severe, intractable lesions caused. More recently it was used on an even larger scale in Iranian soldiers who were exposed to infection in the Iran-Iraq war. New information on the precise identity of parasite strains and on the nature of different forms of promastigote, combined with the possibility of culture on defined media may allow refinement of leishmanisation to eliminate the undesirable side effects. The vector of L. major is Phlebotomus papatasi, or
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closely related species. P. papatasi is an important peridomestic nuisance in many towns, and is frequently subjected to crepuscular fogging. Unfortunately, peridomestic populations rarely include infected flies, so this intervention is ineffective in the control of CL. In central Asia where deep ploughing was used to control the reservoir host, Rhombomys opimus, P. papatasi populations were incidentally reduced. As vector populations usually live away from humans, where they are not accessible for intervention, vector control is not usually a useful option for L. major. Reservoir host control may sometimes be the best option for L. major. This has been carried out successfully in central Asia, in development projects whose success was threatened by the risk of CL. Rhombomys opimus was eliminated by a succession of actions. First, the area to be developed was surveyed from the air to locate habitats suitable for the rodent, then ground survey located individual colonies. Colonies were then exterminated either by deep ploughing, or by zinc phosphide poisoning, sometimes combined with anticoagulant treatment. These methods were effective in protecting workers on the development projects, but the extent of the environmental degradation involved could only be justified in places which were scheduled for destruction as part of the project. In the Mediterranean basin where the main reservoir host is Psammomys obesus, areas within one kilometre of habitations have been cleared of all halophytic vegetation and trees planted to inhibit regrowth. The Sidi Bouzid area of Tunisia where this was done is only subject to epidemic CL and the intervention coincided with the end of the epidemic so both the intervention and control sites had a similar reduction in the number of cases. This method of control therefore still requires to be evaluated, and the environmental cost is too great for the method to be applicable over wide areas. Our own (unpublished) detailed studies on the ecology of P. obesus in Tunisia have shown that the rodent breeds in winter, but that transmission is in the summer. This means that the infection depends on being passed from very old animals to their offspring or grand-offspring, when the latter are already adult. Juvenile animals are rarely infected, and the parasites become very rare in the early spring, being maintained mainly by the oldest animals. The tenuous nature of the cycle in this area indicates that if epidemics resulting from rodent population irruptions can be predicted, they could probably be prevented relatively cheaply with minimal environmental damage. One of our studies in Tunisia has developed methods of assessing the population density of reservoir hosts Psammomys obesus by simple transects. If found to be applicable in other countries, this method will give valuable notice of increasing rodent numbers and prediction of outbreaks.
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The above descriptions illustrate the potential value of detailed biological, ecological, and environmental information in each focus of CL. The role of the medical mammalogist is nowhere better illustrated than with ZCL.
Cutaneous Leishmaniasis due to L. tropica Infection Much has been learned recently about the distribution of L. tropica. On one hand, the sporadic cases of cutaneous leishmaniasis in the more humid parts of the Mediterranean basin, once thought to be due to L. tropica are now recognized as being caused by L. infantum. On the other hand, L. tropica, or very closely related parasites are now known to be maintained zoonotically in Namibia, Kenya, and Tunisia, with hyraxes Procavia capensis (Mammalia: Hyracoidea) and, possibly gundis Ctenodactylus gundi (Mammalia: Rodentia) as reservoir hosts. Anthroponotic foci in the great cities of West and Central Asia remain, however, the stronghold of this parasite. L. tropica infection was eliminated in the cities of Azerbaijan in the 1950s by a combination of: (1) detailed epidemiological study to distinguish dependent and independent foci; (2) comprehensive case detection and treatment, combined with complete coverage of independent foci by house-spray with insecticide; (3) continuing active case detection and treatment, combined with focal house-spray; and (4) mop-up operations, with compulsory treatment or deportation of cases of recidivans leishmaniasis. Clearly the degree of coercion involved in these actions would not be acceptable today, but the comprehensive coverage is probably needed in order to ensure effectiveness. Less rigorous use of insecticides to spray houses in the hope of reducing sandfly numbers and thus, transmission, in Kabul failed completely.7 Zoonotic CL due to infection with L. tropica or the closely related L. killicki is poorly known. As mentioned above, foci have been described in Kenya and Namibia, where rock hyraxes appear to be the main reservoir hosts, and in Tunisia, where the gundi may be the reservoir host. Other zoonotic foci may occur in Yemen and Jordan, but these remain to be analyzed fully. In the absence of detailed ecological information, no preventive measures other than avoidance of known foci, and accurate diagnosis and treatment, are available.
Cutaneous Leishmaniasis due to L. aethiopica Infection L. aethiopica infection is restricted to the East African highlands, where it depends on rock hyraxes as reservoir hosts. Sporadic, sometimes aberrant cases of CL
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have been reliably reported further south, in Tanzania, Zambia, and Malawi but nothing is known of the identity of the causative parasite, or of the origin of the infections. Epidemics of L. aethiopica are unknown, though, as the disease lasts much longer than other CL, prevalence may reach high levels. The vector sandflies do not reach serious nuisance numbers. The risk to visitors in these remote areas is minimal. In principle, a single villager armed with a shotgun could keep a village free of rock hyraxes sufficiently to prevent human infection, but this has not been tested. Perhaps more important is the question of accurate diagnosis and appropriate treatment. In many of the affected areas much of the medical provision comes from foreign organizations with rapid staff turnover. Unless new staff are given thorough orientation, they are liable to mistake L. aethiopica infection for skin cancer or leprosy, and to treat it inappropriately.
Cutaneous Leishmaniasis due to L. infantum Infection L. infantum normally causes infantile visceral leishmaniasis but certain variant strains cause cutaneous leishmaniasis in people of all ages. These dermotropic variants may cause visceral leishmaniasis in people whose cellular immune response is impaired. The dermotropic strains are sometimes concentrated in areas where the normal visceralizing strains do not exist, or are rare, such as the Pyrene´es Orientales in France, the Abbruzzo in Italy, and parts of Lebanon, so L. infantum-CL was initially mistaken for L. tropica infection. The domestic dog is the only known reservoir host for L. infantum of any strain, though the red fox Vulpes vulpes and other wild canids as well as the common rat Rattus rattus have been found infected. However, it has been found, in Spain and Morocco for example, that the diversity of parasite strains in vectors is much greater than that in dogs, so there must be an unknown reservoir of these unusual strains. From the practical point of view, it is unlikely that L. infantum-CL will be the subject of specific control measures. It is notoriously difficult to control the behavior of people toward their domestic dogs, and other canine zoonoses such as rabies, visceral leishmaniasis, toxocariasis, echinococcosis, and even dirofilariasis repens provide ample reason for the elimination of strays and careful management of domestic dogs. As with other sporadically occurring CL, the most important action is to ensure correct diagnosis and appropriate treatment. In order to achieve this it is vital to produce good maps of the distribution of the disease and to educate medical personnel in the relevant areas.
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Conclusions: Current Investigations and Future Prospects Ideas are being developed for the control of sandflies, incorporating new information on pheromones, on preferred sugar meals, and on the effects of different host blood on infection, all of which may lead to effective measures. The most important gap in our knowledge of sandflies, however, relates to their breeding sites. We know that larvae require humid conditions without free water, and with rich organic content, but we have no knowledge of where suitable conditions are to be found in the semi-desert habitat in which many sandflies occur. Larvae are quite easily reared in the laboratory and it is common for a single rearing container to hold more larvae than have ever been found in nature! There must be no other group of medically important insects whose breeding habits are so poorly known. Much effort has been expended on the development of vaccines against CL, but so far without applicable result. More important is the development of effective topical treatment. The use of fine-mesh insecticide-impregnated bed-nets needs to be developed, though some preliminary trials have been less than fully successful. For zoonotic CL, much more needs to be known about the ecology of most reservoir host species and the quantitative structure of reservoir systems. This requires the employment of biological scientists trained in ecology and mammalogy. The advent of geographical information systems combined with detailed maps of environmental parameters and cheap, readily available, remote-sensed information provide important new tools for determining the factors limiting and defining the various strata of CL. Preliminary results have been published on CL in the Arabian Peninsula8 and similar studies on the distribution of Phlebotomus orientalis (the vector of visceral leishmaniasis) in Sudan provide models of what can be done, but also illustrate of the pitfalls associated with these tools.9
References 1. Molyneux DH. Control of parasites, parasitic infections and parasitic diseases. In: Cox FEG, Kreier JP, Wakelin D, editors. Topley & Wilson’s microbiology and microbial infections, Ninth edition, Parasitology. London: Arnold; 1998;5:85–112. 2. Ashford RW. Leishmaniasis: Reservoirs and their significance in control. Clin Derm 1996;14:523–32. 3. Ashford RW. The leishmaniases. In: Palmer SR, Lord Soulsby, Simpson DIH, editors. Zoonoses. Oxford: Oxford University Press, 1998:527– 44. 4. Ashford RW, Bates PA. Leishmaniasis. In: Cox FEG, Kreier JP, Wakelin D, editors Topley & Wilson’s microbiology and microbial infections, Ninth edition, Parasitology. London: Arnold; 1998;5:215– 40. 5. World Health Organisation. Report of a training seminar
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on epidemiological methods for the leishmaniases. (Document TDR/LEISH-SEM/80.3) 1986. 6. World Health Organisation. Control of the leishmaniases Technical Report Series 793. Geneva: World Health Organisation, 1990. 7. Ashford RW, Kohestany KA, Karimzad MA. Cutaneous leishmaniasis in Kabul, Afghanistan: Observations on a “prolonged epidemic.” Anns Trop Med Parasit 1992:86;361–71.
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8. Cross ER, Newcomb WW, Tucker CJ. Use of weather data and remote sensing to predict the geographic and seasonal distribution of Phlebotomus papatasi in southwest Asia. Am J Trop Med Hyg 1996:54;530 – 6. 9. ElNaiem D, Connor SJ, Thomson MC, et al. Environmental determinants of the distribution of Phlebotomus orientalis in Sudan: The ecology of the collecting sites. Anns Trop Med Parasitol. 92;877– 87.
G
eneral guidelines on the prevention of parasitic disease are given by Molyneux,1 who emphasizes the importance of stratification of epidemiological patterns in order to assess priorities and to design focused control measures. The epidemiology and control of leishmaniasis have been reviewed recently by Ashford and Ashford and Bates, in which articles most primary references can be found.2– 4 The first thing to emphasize about the control of cutaneous leishmaniasis (CL) is that this has rarely been successfully achieved, so there is no general set of instructions to follow. The most successful campaigns were in the old Soviet Union, against Leishmania tropica in Azerbaijan and L. major in Turkmenistan and Uzbekistan, many years ago. Descriptions of these interventions are not readily accessible and some of the methods used would not be acceptable today.5 Control strategies cannot, therefore, be proposed in more than theoretical outline. Now that the classification of the parasites is well understood, however, and the structure of many reservoir systems has been established, it is possible to suggest relevant investigations leading to stratification, and interventions leading to control. CL due to infection with either L. major or L. tropica may be either endemic or epidemic. Endemic areas can be identified by case reporting, but areas of potential epidemicity cannot. Although we do not fully understand the reasons, the distribution of these parasites correlates closely with environmental characteristics, notably bioclimatic and vegetation zones. The principles of landscape epidemiology or eco-epidemiology are therefore very important in assessing epidemiological risk. Some excellent examples have been published, allowing the construction of a preliminary stratification of Old World cutaneous leishmaniasis (Table 1), but much exciting study on these lines remains to be carried out. It is frequently the case that transmission cannot reasonably be reduced and infection cannot be avoided. The main action then is to minimize the effects of infection by assuring prompt diagnosis and appropriate From the Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Address correspondence to Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. E-mail: [email protected] © 1999 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
treatment. It is important to recognize that it is sometimes most appropriate not to treat cases at all; the best intervention in such cases is cleaning of the lesions and reassurance of the patient.
General Considerations National Committee Cutaneous leishmaniasis is vector-borne and frequently zoonotic so it requires specialized knowledge in various areas to assess and understand its public health importance and potential control measures, and to make relevant recommendations to the Minister of Health. WHO6 recommend that in any country where CL is perceived as an actual or potential problem, a National Committee should be established, bringing together the relevant expertise, and advising the Minister of Health on appropriate action. The requirements of the National Committee are not only medical, but must include biological, entomological, mammalogical, environmental, sociological, and logistical expertise. In many countries some of this expertise is to be found in malaria control departments, and it is frequently assumed that this department can simply take over the function of leishmaniasis control. This has not usually been successful, partly because malariologists have very specific training and knowledge, so are uncomfortable to explore unfamiliar ground, and partly because the commitment of malaria departments to malaria control leads them to underestimate the importance of leishmaniasis. The National Committee should include representatives from academic institutions as well as operational experts. This is because there will inevitably be a need for investigation at the scientific as well as operational level. Though we have much information, each focus of CL will be different and will require separate assessment.
Intersectorial Collaboration Intersectorial collaboration is particularly important, and has frequently been neglected. CL is frequently a disease of development projects and, with a minimum of health impact assessment, can be predicted and avoided. Close coordination is called for between the National Committee and the agencies responsible for development projects, public or private. 0738-081X/99/$–see front matter PII S0738-081X(99)00051-6
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Table 1. Summary of Main Epidemiological Features Relating to Stratification of Old World Cutaneous Leishmaniasis Stratum, or Nosodemiological Unit
Source of Infection
L. tropica in West and Central Asia
Anthroponotic in dense housing
L. tropica s.1. in West Mediterranean Basin
Focal structure incompletely known
L. tropica in East Africa
Zoonotic; maintenance hosts probably hyraxes Zoonotic; reservoir host Rhombomys opimus Zoonotic; reservoir host Psammomys obesus Zoonotic; reservoir host Meriones spp Zoonotic; reservoir hosts rodents Zoonotic; reservoir host domestic dog
L. major in Central Asia
L. major in North Africa, West Asia L. major in Pakistan, India L. major in sub-Saharan Africa L. infantum in Mediterranean Basin L. aethiopica in East Africa
CL Endemicity
Transmission
Special Features
Endemic in independent foci; becoming epidemic in dependent foci Poorly known; occasional epidemics
Peridomestic in dense cities; also sporadic in villages Peridomestic in villages (Morocco) or sylvatic (Tunisia) Sylvatic in rocky places
Epidemics may be in new housing settlements or ancient buildings
Limited distribution; poorly known Endemic in local people, epidemic in visitors
Sylvatic, in loess landscapes
Epidemics in visitors spread to local people Poorly known; occasional epidemics Rare sporadic cases, with occasional epidemics Rare manifestation of normally visceralising parasite
Sylvatic, in salt-pan basins Sylvatic
Zoonotic; reservoir hosts hyraxes
In many endemic countries the military are greatly affected by CL, as they exercise or operate in zoonotic foci. Sometimes simple operational changes can reduce exposure to infection, but this requires that the military are involved in the intersectorial coordination. The role of the National Committee is to advise the Minister, and to ensure that interested agencies are informed. This need not be an onerous task, and annual meetings may be sufficient to guide and support relevant investigations and operations, and to assess the results.
Caution in Control Measures One vital feature of the epidemiology of CL, which may considerably affect prevention strategy stems from the fact that the disease leads to lifelong immunity. This means that, in a holoendemic area, most of the people have been infected when very young and are immune; intervention to reduce transmission in such an area would, over the long term, lead to a build-up of nonimmune youngsters, who would be liable to infection at an older age, when the stigma of infection is much greater. Reduction of transmission could, therefore lead to an increase in the public health problem. The above problem certainly applies to zoonotic CL, where the force of infection among humans is independent of the number of human cases. With anthroponotic infection (ACL), reduction of transmission will similarly increase the age at which people become infected, but may also more easily eliminate the disease. Precise
Major problem in development projects
Sylvatic, in sahel Peridomestic in villages
Dermotropic strains visceralise with AIDS
Sylvatic, both in rocky and wooded areas
DCL is a rare but important variant
models of ACL epidemiology are required to assess this. Reduction of transmission in holoendemic areas should only therefore be considered with careful forethought. It may be that detection and treatment of the serious cases, and protection of visitors are the preferable options.
Origins of Epidemics One of the most striking features of CL is the tendency of disease in humans to be aggregated in both space and time. That is, cases tend to occur in localized foci, and in outbreaks or epidemics. In principle, epidemics of CL may have one of three origins. L. tropica epidemics seem to be the result of the introduction of the parasite into susceptible populations. Here, the parasite will be spread rapidly for a few years and many people of all ages will be affected. As the proportion of people susceptible decreases, the epidemic will die out or move to another locality; occasionally it may become endemic, with a low incidence of infection, confined to young people and immigrants. L. major in Khartoum in the late 1980s behaved in this way, leading to the belief that this unusual epidemic was anthropogenic in its origin and maintenance. More usually L. major becomes epidemic when large numbers of people move into zoonotic areas. These are frequently military personnel, or people involved with development projects. The semi-desert low lying habitats of L. major are potentially
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1999;17:327–332
valuable for irrigated agriculture, and agricultural development projects have been seriously disrupted. The third source of epidemics, which may be combined with the second, depends on the tendency of desert rodent populations to fluctuate in numbers. These fluctuations are not understood, and are not even well recorded, but it is frequently observed that at the time of an epidemic of human CL in settled people, rodents are very abundant, and that in subsequent years they are much less so. These irruptions in rodent numbers may affect several rodent species simultaneously over wide areas. It is the second and third type of epidemic which are the most unpredictable, both in time and space. Prediction of type two epidemics depends on a thorough knowledge of the structure of the zoonotic focus of infection and the geographical distribution of suitable conditions. Type three epidemics require, in addition, some understanding of rodent population fluctuations and prediction of these.
Public Health Priority Although cutaneous leishmaniasis is usually painless, self-curing, and without serious consequences, it is an infection of great public health importance; people who are not culturally adapted to the infection are greatly upset by it and, in places with growing health expectations, the health service is pressured to take action. Unfortunately, what action to take is not always readily apparent: by the time an epidemic is detected, transmission has ceased, and preventive intervention is impossible.
Imported Cases In countries where cutaneous leishmaniasis is only imported, or rare, the main action is to educate the medical practitioners to recognize the lesion or, at least, to send the patient to a tropical institute. Misdiagnosis has led to some horrific events of mistreatment.
Risk of Introduction There is little risk of introduction of cutaneous leishmaniasis into new areas. This question arose when numerous Fijian soldiers in the Multinational Force of Observers in Sinai became infected with L. major, as sandflies were known to be abundant in Fiji. However, these are ceratopogonid midges which are incapable of transmitting the infection. Possibly more relevant was when Gurkha troops from Nepal on jungle training exercises with the British army in Belize became infected with L. braziliensis and L. panamensis. There was a possibility of introducing the infection to Nepal, where various phlebotomine sandflies are found. The numerous temporary workers from south-east Asia who become infected in Saudi Arabia are unlikely to introduce
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the infection to their home countries on their return, as the distribution of this parasite depends on a precise combination of vector and reservoir host. While the risk of long-distance introduction is minimal, there is little doubt that anthroponotic forms which can be maintained temporarily in “dependent foci” are frequently reintroduced from nearby “independent foci.” L. tropica in Kabul, Afghanistan, appears to depend on repeated reintroduction from endemic foci at lower altitude,7 and the outbreak of L. major-CL in Khartoum in Sudan in the late 1980s is best explained by the introduction of the parasite by displaced people from the west of the country.
Cutaneous Leishmaniasis due to L. major Infection L. major is characterized by endemicity in sparsely inhabited semi-arid habitats, with outbreaks caused either when groups of people enter these areas or when increase in numbers of reservoir hosts leads to a population explosion, or irruption, bringing the rodent and therefore the parasite, to new areas. Where the parasite is endemic it mainly affects young children and usually passes unnoticed and only the relatively few severe cases are reported. Where it affects immigrants, these are usually adult males; they are unaccustomed to the disease and may suffer multiple sores, and may be psychologically as well as physically affected. Worse, they may be accused by their hosts of importing a dreadful disease, and deported. Sometimes, as in the outbreak at Mowakkar in Jordan, it is settlers in a new housing project who are affected. Outbreaks apparently caused by irruption of reservoir host populations have been described in Libya, Tunisia, and Algeria. These affect people of all ages, in their homes, so are notoriously unpopular and can have great public health significance. Some degree of personal protection against L. major is available, by means of leishmanisation. In this process, live, virulent promastigotes from cultures are inoculated into a part of the body where the resulting lesion and scar will not be disfiguring. Following healing of the lesion, the individual is immune to further infection. This method has been used on a large scale by Soviet and Israeli armies, but was discontinued because of the unacceptable number of severe, intractable lesions caused. More recently it was used on an even larger scale in Iranian soldiers who were exposed to infection in the Iran-Iraq war. New information on the precise identity of parasite strains and on the nature of different forms of promastigote, combined with the possibility of culture on defined media may allow refinement of leishmanisation to eliminate the undesirable side effects. The vector of L. major is Phlebotomus papatasi, or
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closely related species. P. papatasi is an important peridomestic nuisance in many towns, and is frequently subjected to crepuscular fogging. Unfortunately, peridomestic populations rarely include infected flies, so this intervention is ineffective in the control of CL. In central Asia where deep ploughing was used to control the reservoir host, Rhombomys opimus, P. papatasi populations were incidentally reduced. As vector populations usually live away from humans, where they are not accessible for intervention, vector control is not usually a useful option for L. major. Reservoir host control may sometimes be the best option for L. major. This has been carried out successfully in central Asia, in development projects whose success was threatened by the risk of CL. Rhombomys opimus was eliminated by a succession of actions. First, the area to be developed was surveyed from the air to locate habitats suitable for the rodent, then ground survey located individual colonies. Colonies were then exterminated either by deep ploughing, or by zinc phosphide poisoning, sometimes combined with anticoagulant treatment. These methods were effective in protecting workers on the development projects, but the extent of the environmental degradation involved could only be justified in places which were scheduled for destruction as part of the project. In the Mediterranean basin where the main reservoir host is Psammomys obesus, areas within one kilometre of habitations have been cleared of all halophytic vegetation and trees planted to inhibit regrowth. The Sidi Bouzid area of Tunisia where this was done is only subject to epidemic CL and the intervention coincided with the end of the epidemic so both the intervention and control sites had a similar reduction in the number of cases. This method of control therefore still requires to be evaluated, and the environmental cost is too great for the method to be applicable over wide areas. Our own (unpublished) detailed studies on the ecology of P. obesus in Tunisia have shown that the rodent breeds in winter, but that transmission is in the summer. This means that the infection depends on being passed from very old animals to their offspring or grand-offspring, when the latter are already adult. Juvenile animals are rarely infected, and the parasites become very rare in the early spring, being maintained mainly by the oldest animals. The tenuous nature of the cycle in this area indicates that if epidemics resulting from rodent population irruptions can be predicted, they could probably be prevented relatively cheaply with minimal environmental damage. One of our studies in Tunisia has developed methods of assessing the population density of reservoir hosts Psammomys obesus by simple transects. If found to be applicable in other countries, this method will give valuable notice of increasing rodent numbers and prediction of outbreaks.
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The above descriptions illustrate the potential value of detailed biological, ecological, and environmental information in each focus of CL. The role of the medical mammalogist is nowhere better illustrated than with ZCL.
Cutaneous Leishmaniasis due to L. tropica Infection Much has been learned recently about the distribution of L. tropica. On one hand, the sporadic cases of cutaneous leishmaniasis in the more humid parts of the Mediterranean basin, once thought to be due to L. tropica are now recognized as being caused by L. infantum. On the other hand, L. tropica, or very closely related parasites are now known to be maintained zoonotically in Namibia, Kenya, and Tunisia, with hyraxes Procavia capensis (Mammalia: Hyracoidea) and, possibly gundis Ctenodactylus gundi (Mammalia: Rodentia) as reservoir hosts. Anthroponotic foci in the great cities of West and Central Asia remain, however, the stronghold of this parasite. L. tropica infection was eliminated in the cities of Azerbaijan in the 1950s by a combination of: (1) detailed epidemiological study to distinguish dependent and independent foci; (2) comprehensive case detection and treatment, combined with complete coverage of independent foci by house-spray with insecticide; (3) continuing active case detection and treatment, combined with focal house-spray; and (4) mop-up operations, with compulsory treatment or deportation of cases of recidivans leishmaniasis. Clearly the degree of coercion involved in these actions would not be acceptable today, but the comprehensive coverage is probably needed in order to ensure effectiveness. Less rigorous use of insecticides to spray houses in the hope of reducing sandfly numbers and thus, transmission, in Kabul failed completely.7 Zoonotic CL due to infection with L. tropica or the closely related L. killicki is poorly known. As mentioned above, foci have been described in Kenya and Namibia, where rock hyraxes appear to be the main reservoir hosts, and in Tunisia, where the gundi may be the reservoir host. Other zoonotic foci may occur in Yemen and Jordan, but these remain to be analyzed fully. In the absence of detailed ecological information, no preventive measures other than avoidance of known foci, and accurate diagnosis and treatment, are available.
Cutaneous Leishmaniasis due to L. aethiopica Infection L. aethiopica infection is restricted to the East African highlands, where it depends on rock hyraxes as reservoir hosts. Sporadic, sometimes aberrant cases of CL
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have been reliably reported further south, in Tanzania, Zambia, and Malawi but nothing is known of the identity of the causative parasite, or of the origin of the infections. Epidemics of L. aethiopica are unknown, though, as the disease lasts much longer than other CL, prevalence may reach high levels. The vector sandflies do not reach serious nuisance numbers. The risk to visitors in these remote areas is minimal. In principle, a single villager armed with a shotgun could keep a village free of rock hyraxes sufficiently to prevent human infection, but this has not been tested. Perhaps more important is the question of accurate diagnosis and appropriate treatment. In many of the affected areas much of the medical provision comes from foreign organizations with rapid staff turnover. Unless new staff are given thorough orientation, they are liable to mistake L. aethiopica infection for skin cancer or leprosy, and to treat it inappropriately.
Cutaneous Leishmaniasis due to L. infantum Infection L. infantum normally causes infantile visceral leishmaniasis but certain variant strains cause cutaneous leishmaniasis in people of all ages. These dermotropic variants may cause visceral leishmaniasis in people whose cellular immune response is impaired. The dermotropic strains are sometimes concentrated in areas where the normal visceralizing strains do not exist, or are rare, such as the Pyrene´es Orientales in France, the Abbruzzo in Italy, and parts of Lebanon, so L. infantum-CL was initially mistaken for L. tropica infection. The domestic dog is the only known reservoir host for L. infantum of any strain, though the red fox Vulpes vulpes and other wild canids as well as the common rat Rattus rattus have been found infected. However, it has been found, in Spain and Morocco for example, that the diversity of parasite strains in vectors is much greater than that in dogs, so there must be an unknown reservoir of these unusual strains. From the practical point of view, it is unlikely that L. infantum-CL will be the subject of specific control measures. It is notoriously difficult to control the behavior of people toward their domestic dogs, and other canine zoonoses such as rabies, visceral leishmaniasis, toxocariasis, echinococcosis, and even dirofilariasis repens provide ample reason for the elimination of strays and careful management of domestic dogs. As with other sporadically occurring CL, the most important action is to ensure correct diagnosis and appropriate treatment. In order to achieve this it is vital to produce good maps of the distribution of the disease and to educate medical personnel in the relevant areas.
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Conclusions: Current Investigations and Future Prospects Ideas are being developed for the control of sandflies, incorporating new information on pheromones, on preferred sugar meals, and on the effects of different host blood on infection, all of which may lead to effective measures. The most important gap in our knowledge of sandflies, however, relates to their breeding sites. We know that larvae require humid conditions without free water, and with rich organic content, but we have no knowledge of where suitable conditions are to be found in the semi-desert habitat in which many sandflies occur. Larvae are quite easily reared in the laboratory and it is common for a single rearing container to hold more larvae than have ever been found in nature! There must be no other group of medically important insects whose breeding habits are so poorly known. Much effort has been expended on the development of vaccines against CL, but so far without applicable result. More important is the development of effective topical treatment. The use of fine-mesh insecticide-impregnated bed-nets needs to be developed, though some preliminary trials have been less than fully successful. For zoonotic CL, much more needs to be known about the ecology of most reservoir host species and the quantitative structure of reservoir systems. This requires the employment of biological scientists trained in ecology and mammalogy. The advent of geographical information systems combined with detailed maps of environmental parameters and cheap, readily available, remote-sensed information provide important new tools for determining the factors limiting and defining the various strata of CL. Preliminary results have been published on CL in the Arabian Peninsula8 and similar studies on the distribution of Phlebotomus orientalis (the vector of visceral leishmaniasis) in Sudan provide models of what can be done, but also illustrate of the pitfalls associated with these tools.9
References 1. Molyneux DH. Control of parasites, parasitic infections and parasitic diseases. In: Cox FEG, Kreier JP, Wakelin D, editors. Topley & Wilson’s microbiology and microbial infections, Ninth edition, Parasitology. London: Arnold; 1998;5:85–112. 2. Ashford RW. Leishmaniasis: Reservoirs and their significance in control. Clin Derm 1996;14:523–32. 3. Ashford RW. The leishmaniases. In: Palmer SR, Lord Soulsby, Simpson DIH, editors. Zoonoses. Oxford: Oxford University Press, 1998:527– 44. 4. Ashford RW, Bates PA. Leishmaniasis. In: Cox FEG, Kreier JP, Wakelin D, editors Topley & Wilson’s microbiology and microbial infections, Ninth edition, Parasitology. London: Arnold; 1998;5:215– 40. 5. World Health Organisation. Report of a training seminar
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on epidemiological methods for the leishmaniases. (Document TDR/LEISH-SEM/80.3) 1986. 6. World Health Organisation. Control of the leishmaniases Technical Report Series 793. Geneva: World Health Organisation, 1990. 7. Ashford RW, Kohestany KA, Karimzad MA. Cutaneous leishmaniasis in Kabul, Afghanistan: Observations on a “prolonged epidemic.” Anns Trop Med Parasit 1992:86;361–71.
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8. Cross ER, Newcomb WW, Tucker CJ. Use of weather data and remote sensing to predict the geographic and seasonal distribution of Phlebotomus papatasi in southwest Asia. Am J Trop Med Hyg 1996:54;530 – 6. 9. ElNaiem D, Connor SJ, Thomson MC, et al. Environmental determinants of the distribution of Phlebotomus orientalis in Sudan: The ecology of the collecting sites. Anns Trop Med Parasitol. 92;877– 87.