In regions where leishmaniasis is endemic, clinical disease is usually reported more frequently among males than females. This difference could be due to disparate risks of exposure of males and females, but genderrelated differences in the host response to infection may also play a role. Experimental studies of the influence of gender on Leishmania infection have not included parasites of the subgenus Viannia, which is the most common cause of cutaneous leishmaniasis in the Americas. Mice are not readily susceptible to infection by Leishmania (Viannia) spp., but cutaneous infection of hamsters with L. (V.) panamensis or L. (V.) guyanensis resulted in chronic lesions typical of the human disease caused by these parasites. Strikingly, infection of male hamsters resulted in significantly greater lesion size and severity, an increased rate of dissemination to distant cutaneous sites, and a greater parasite burden in the draining lymph node than infection in female animals. Two lines of evidence indicated this gender-related difference in disease evolution was determined at least in part by the sex hormone status of the animal. First, prepubertal male animals had smaller and/or less severe cutaneous lesions than adult male animals. Second, infection of testosterone-treated female animals resulted in significantly larger lesions than in untreated female animals. The increased severity of disease in male compared to female animals was associated with significantly greater intralesional expression of interleukin-4 (IL-4) (P ‫؍‬ 0.04), IL-10 (P ‫؍‬ 0.04), and transforming growth factor ␤ (TGF-␤) (P < 0.001), cytokines known to promote disease in experimental leishmaniasis. There was a direct correlation between the expression of TGF-␤ mRNA and lesion size (Spearman's correlation coefficient ‫؍‬ 0.873; P < 0.001). These findings demonstrate an inherent risk of increased disease severity in male animals, which is associated with a more permissive immune response.The outcome of Leishmania infection depends on several biological traits of both the host and the infecting parasite strain. A number of epidemiological studies indicate that leishmaniasis occurs more frequently among adult males than females (3,13,38). It is unclear whether this difference is due merely to dissimilar risks of exposure because of the distinct activities of males and females or whether gender-related differences in the host immune response play a role in resistance and susceptibility to infection.Epidemiological data for children Ͻ15 years of age, where both genders would seem to have similar risks of infection, indicate that boys are threefold more likely to develop visceral leishmaniasis than girls (35). Similarly, the disease rate for cutaneous leishmaniasis in an area of Brazil where the disease is endemic was shown to be 50% higher in males than females in all age groups, including children, who are expected to have comparable risks of exposure for both sexes (13). In studies of several different endemic foci in both the New and Old Worlds, re...

Progressive disease in the hamster model of visceral leishmaniasis, caused by Leishmania donovani, in contrast to infection in mice, mimics the progressive disease observed in untreated humans. During progressive infection in hamsters, there was a vigorous type 1 cellular immune response, which is typically associated with control of infection, suggesting that there was ineffective IFN-γ-mediated macrophage activation. Indeed, at the site of infection, hamsters did not express NO synthase 2 (NOS2), which is the primary mechanism for control of infection in mice. Furthermore, in striking contrast to mouse macrophages, IFN-γ-activated hamster macrophages did not did not express NOS2 nor generate NO, and were unable to restrict the replication of intracellular L. donovani. The absent hamster NOS2 expression was not the result of NOS2 gene deletion and the NOS2 cDNA had an intact open reading frame. Furthermore, the impaired transcription of NOS2 mRNA was selective and not due to global impairment of IFN-γ signaling (members of the IFN-γ-signaling pathway were expressed and functional and IFN-γ up-regulated several primary and secondary response genes). Strikingly, the proximal hamster NOS2 promoter, like the human ortholog, had &gt;20-fold less basal and IFN-γ/LPS-inducible activity than the corresponding mouse promoter. Thus, reduced basal and IFN-γ-induced activity of the hamster NOS2 transcriptional unit, which is unique to this small animal and similar to the human counterpart, accompanies the inability of the animal to control an intracellular pathogen.

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The role of Proechimys semispinosus as reservoir of Leishmania (Viannia) Key words: spiny rats -Leishmania -reservoir -experimental infection Spiny rats (Proechimys spp.) are parasitized by a variety of Leishmania species, including L. aristidesi and recognized pathogenic species such as L. guyanensis, L. amazonensis, and L. mexicana s.l. Although these rodents have been incriminated as natural hosts for pathogenic species in several endemic foci in South America, encompassing Brazil, French Guiana, Venezuela and Trinidad (Lainson et al. 1979, WHO 1990, their reservoir role still needs to be established.In Colombia, information on spiny rats and their relationships with both cutaneous and visceral leishmaniasis is fragmentary. P. semispinosus is the most abundant small mammal inhabiting tropical wet forests of the Colombian Pacific coast where cutaneous leishmaniasis is endemic (Weigle et al. 1986, Gonzalez & Alberico 1993. In the Northern region of the country, another species of spiny rat, P. canicollis, is infected with L. chagasi in tropical dry forests and areas of subsistence agriculture where the original forest has been extensively degraded .Incriminating wild animals as Leishmania reservoirs is based on several biological parameters, among which natural infection, population dynamics, and interactions with and infectivity to vectors are of capital importance. In the present study, using an experimental approach, we evaluated the potential role of P. semispinosus as a reservoir of cutaneous leishmaniasis caused by L. (V.) panamensis. Also, we determined the susceptibility of this species to L. (L.) chagasi to evaluate the utility of this rodent as a model of reservoir host that could be utilized in the laboratory. MATERIALS AND METHODSCollection of spiny rats and quarantine -Spiny rats from the Pacific lowlands of Colombia (Tumaco, Nariño; 1°48'N,78°46'W) were captured with National-type traps, after the appropriate permission from the departmental agency for the protection of wild fauna (Corponariño) was obtained. Approximately 100 trapping stations were established in areas of secondary forest, where banana, plantain and cocoa are grown. The traps were baited with plantain, set before dusk, and inspected at dawn. To avoid excessive stress and self-inflicted wounds, the animals were transferred immediately to transport cages of aluminum walls, where access to food and water was provided. Specimens were transported by air to the central laboratory in Cali and quarantined for 8 weeks in the vivarium. An individual coprological analysis was conducted, and an anti-parasitic treatment [ivermectin (Virbamec®), and propoxur (Bolfo®)] was implemented. A blood sample (0.5 ml), drawn by intracardial puncture, was cultured in NNN and Senekjie's media to detect natural infections with Leishmania or Trypanosoma. Serum was collected for detecting antibodies against the same parasites by means of ELISA. Total IgG antibodies were determined in serum (diluted 1:100) using a soluble T. cruzi or L. panamensis