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Local therapy is another option, provided that the infecting Leishmania sp. is not associated with the potential for mucosal leishmaniasis. Intralesional injections of stibogluconate sodium have been reported to be effective in approximately three-quarters of persons with localized L. (L.) tropica infection, but each lesion must be injected intermittently over a period of approximately 1 month. Topical administration of 15%
paromomycin and 12% methylbenzethonium chloride in soft white paraffin twice daily for 10 days has been used successfully in the treatment of L. (L.) major (el-On et al., 1992). It is associated with local burning, pruritis and vesicle formation in some persons. The local application of heat to the lesions of American cutaneous leishmaniasis can result in cure, but treatment is prolonged and technically difficult (Navin et al., 1990). Immunotherapy with a crude pro-mastigote antigen and BCG has also been reported to be effective (Convit et al., 1987), but the response is slow.
Treatment of Mucosal Leishmaniasis
Mucosal leishmaniasis due to L. (V.) braziliensis is usually treated with a pentavalent antimony-containing drug, but primary failures and relapses are relatively common. Alternatives include amphotericin B deoxycholate and pentamidine isetionate. Liposome-encapsulated and lipid-associated amphotericin B have not been studied. Preliminary data suggest that the combination of pentavalent antimony and IFNy is more effective, but IFNy is available only in research settings. When necessary, plastic surgery should be delayed for 6-12 months after apparent cure of mucosal disease because relapses are common and associated with a poor cosmetic outcome.
The development of leishmaniasis depends on a competent sand fly vector, an appropriate mammalian reservoir(s) and a susceptible human host. A dramatic reduction in the incidence of visceral leishmaniasis occurred in India and other areas following the introduction of residual DDT spraying for malaria control after World War II. Unfortunately, epidemics of visceral leishmaniasis occurred when spraying was discontinued. Although residual insecticides are still useful on a limited scale where peridomestic transmission occurs, their application is impractical in rural areas where leishmaniasis is a zoonosis. It is further limited by cost, the development of
resistance among arthropods and environmental concerns. Permethrin-impregnated clothing and DEET-containing insect repellents applied to exposed skin provide partial protection for short-term visitors and military personnel visiting or working in endemic areas (Schreck et al., 1982; Soto et al., 1995).
Reservoir control programs have been implemented in several areas. In north-eastern Brazil, large numbers of farm dogs in endemic areas have been tested for anti-leishmanial antibodies and killed if positive. The effectiveness of the program is controversial. In north-eastern Brazil the killing of infected dogs has correlated with a decrease in the incidence of human disease in some areas, but outbreaks of visceral leishmaniasis are sporadic there and resolve spontaneously, even in the absence of control programs. Reservoir control programs are obviously impossible in many rural regions where leishmaniasis is a zoonosis involving wild animals.
Given the natural history of leishmanial infections, there is every reason to anticipate that an effective form of immunoprophylaxis will be developed. The resolution of human infection, whether spontaneous or after anti-leishmanial chemotherapy, is typically associated with protection against reinfection with the offending Leishmania sp. For centuries, mothers in the Middle East exposed the bottoms of their infants to sand flies to facilitate the development of cutaneous leishmaniasis at a site that was not of cosmetic importance. The children were protected against later infection on the face or extremities. Immunity has also been achieved by injecting viable, cultured L. (L.) major pro-mastigotes into the buttocks of military personnel in Israel and Russia (Greenblatt, 1980). Although this resulted in protection, the practice was discontinued in Israel because some of the lesions were large and slow to heal, and there was concern that viable amastigotes could persist even after the lesions healed.
A vaccine composed of killed promastigotes from several Leishmania spp. was administered to Brazilian troops (Antunes et al., 1986). It elicited T cell-mediated immune responses, but its efficacy in protecting against cutaneous leishmaniasis was not documented. An attractive alternative is the development of a defined
vaccine, using recombinant leishmanial antigens administered with the proper cytokine or adjuvant to elicit protective Th1 responses. Another alternative is the development of a live, genetically engineered, avirulent leishmanial vaccine. Experience with humans and in animal models suggests that it is only a matter of time until an effective vaccine(s) of some form becomes available.