Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

The nature of the host cellular immune response largely determines the expression of disease following infection with the intracellular protozoans Leishmania spp. In experimental animals control and resolution of infection are mediated by gamma interferon and tumor necrosis factor alpha (TNF-a), whereas disease progression is associated with the production of interleukin 4 (II-4), IL-5, IL-10, and transforming growth factor beta (TGF-13). We have analyzed the profile of cytokine gene expression directly in the lesions of 13 patients with localized cutaneous leishmaniasis due to Leishmania mexicana. All but one patient had a single lesion, and the time of evolution ranged from 8 days to 18 months. Cytokine gene expression was quantitated by reverse transcriptase PCR and interpolation from a standard curve. Gamma interferon, TNF-a, IL-la, IL-6, IL-10, and TGF-1 gene expression was present in all samples. IL-3 and IL-4 gene expression was barely detectable in 1 and 3 of 13 samples, respectively. IL2 and IL-5 mRNAs were not found. A significant increase in the expression of IL-lot, TNF-a, IL-10, and TGF-j8 was observed in late lesions (.4 months) compared with that in early lesions (c2 months). Because of their inhibitory effects on macrophage function, the expression of IL-10 and TGF-j8 may play a role in the immunopathogenesis of chronic cutaneous leishmaniasis.

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Localized cutaneous leishmaniasis (LCL), known as "chiclero´s ulcer" in southeast Mexico

Vectors of cutaneous leishmaniasis in the State of Campeche were studied in relation to the transmission cycle of Leishmania (Le.) mexicana. To determine how transmission of leishmaniasis occurs, we collected phlebotomine sand flies for two years. In the first year (October 1990 to November 1991

Leishmania mexicana is the parasite causing most cases of human cutaneous leishmaniasis in southern Mexico, where Lutzomyia olmeca olmeca and Lu. cruciata are the most probable vectors. In the present study, sandflies were collected during one transmission season (November 2001-March 2002) in the village of La Guadalupe and the nearby village of Dos Naciones, in the southern Mexican county of Calakmul. Using Shannon traps, Disney traps and CDC light traps, 5983 sandflies (Brumptomyia and Lutzomyia) were caught. In Dos Naciones the numbers of Lu. panamensis caught in Shannon or CDC traps outnumbered those of the other sandfly species. In La Guadalupe, in contrast, the most abundant species in the collections made with Shannon or CDC traps was Lu. cruciata , followed by Lu. olmeca olmeca and Lu. deleoni. In both locations, the numbers of sandflies attracted to Shannon traps peaked between 18.00 and 22.00 hours. Given the abundance of Lu. olmeca olmeca in the collections made with Shannon and Disney traps (it was the only species caught in the latter), this species is probably the primary vector of Le. mexicana in Calakmul county.

The genus Leishmania

sUMMaRyIn the Yucatan Peninsula of Mexico, 95% of the human cases of Cutaneous Leishmaniasis are caused by Leishmania (Leishmania) mexicana with an incidence rate of 5.08 per 100,000 inhabitants. Transmission is limited to the winter months (November to March). One study on wild rodents has incriminated Ototylomys phyllotis and Peromyscus yucatanicus as primary reservoirs of L. (L.) mexicana in the focus of La Libertad, Campeche. In the present study, the prevalence of both infection and disease caused by L. (L.) mexicana in small terrestrial mammals were documented during five transmission seasons (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004) in five foci of Leishmaniasis in the state of Campeche. Foci separated by only 100 km, with similar relative abundances of small mammals, were found to differ significantly in their prevalence of both symptoms and infection. Transmission rates and reservoir species seemed to change in space as well as in time which limited the implementation of effective control measures of the disease even in a small endemic area such as the south of the Yucatan Peninsula.