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In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B Leishmania (Viannia) braziliensis is the most common species in the Americas and the most important causative agent of cutaneous and mucocutaneous leishmaniasis in Brazil, while Leishmania (Leishmania) amazonensis is the primary etiologic agent of the diffuse cutaneous form of the disease (Lainson & Shaw 1998).The therapeutic arsenal routinely employed to treat patients with leishmaniasis is limited and unsatisfactory. Successful leishmaniasis treatment depends on several aspects such as the immune status of the host, clinical manifestations of the disease and the sensitivity of the causative Leishmania. Widespread resistance to pentavalent antimonials has been identified for Leishmania (L.) donovani in some regions of India and Nepal (Sundar et al. 2000;Rijal et al. 2003). However, only a few studies correlated clinical response with in vitro antimony Tropical Medicine and International Health

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Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.

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Diffuse cutaneous leishmaniasis (DCL) is characterized by disseminated lesions and the absence of a specific cellular immune response. Here, the immunochemotherapy outcome of a patient with DCL from Amazonian Brazil infected with Leishmania (Leishmania) amazonensis is presented. After several unsuccessful chemotherapy treatment regimens and many relapses, a monthly immunotherapy scheme of L. amazonensis PH8 plus L. (Viannia) braziliensis M2903 monovalent vaccines associated with Bacillus Calmette-Guerin (BCG) was established, one round of which also included an M2903 vaccine associated with intermittent antimonial treatment. Temporary healing of all lesions was achieved, although Leishmania skin tests were negative and interferon gamma was not detected in mononuclear cell cultures stimulated with Leishmania antigens. The frequencies of CD16 (+)CD56(+) NK cells (approximately 2x) and CD14 (+)CD16(+) proinflammatory monocytes (approximately 8x) increased in peripheral blood, and CD56 (+) lymphocytes were found infiltrating the lesions. An association between the increase of the frequency of innate immune system cells and the healing of lesions is shown, suggesting that this protocol of immunotherapy reduced the parasite load and activated NK cells and monocytes.

We evaluated whether four recombinant antigens previously used for vaccination against experimental infection with Leishmania (Leishmania) major could also induce protective immunity against a challenge with Leishmania ( The protozoan parasite Leishmania (Viannia) braziliensis commonly causes localized cutaneous leishmaniasis (CL); however, a chronic mucosal leishmaniasis (ML) may develop in some infected individuals, with severe and progressive manifestations (reviewed in reference 11). At present, this species accounts for more than 90% of the 28,712 annual cases of CL and ML recorded in Brazil in 2004 (7). Although chemotherapies for CL and ML do exist, there are several limitations: (i) drug treatment is rarely affordable by those who need them, (ii) drug treatment requires daily injections of the drug for weeks, (iii) drug treatment can be associated with side effects, and (iv) drug resistance is becoming an increasing problem (13, 24; reviewed in references 3 and 32). To make matters worse, control of CL and ML is problematic due to the sylvatic nature of both vectors and reservoirs, making insecticide spraying and the elimination of reservoirs particularly difficult (26). Due to these difficulties, in the long run, the development of an effective vaccine may help both the prevention and the treatment of CL and ML caused by L. (V.) braziliensis.Most studies conducted thus far in vaccination against CL used genes and/or antigens isolated and characterized from Leishmania (Leishmania) major or L. (L.) amazonensis (8, 31; reviewed in references 9 and 21). Among the leading candidates to the development of a vaccine against CL, there are homologues of the receptor for activated C kinase protein (LACK or p36), Leishmania elongation and initiation factor (LeIF), L. (L.) major stress inducible protein 1 (LmSTI1), and thiol-specific antioxidant (TSA) from L. (L.) major (5, 6, 10, 14, 15, 28, and 30).Based on these promising prospects, the present study was designed to test whether four recombinant antigens previously used for vaccination against experimental infection with L. (L.) major (LACK, LmSTI1, LeIF, and TSA) could also generate protective immunity against an intradermal (i.d.) challenge with L. (V.) braziliensis. We considered this question very important because, as mentioned above, this species is responsible for most cases of CL and ML in Brazil and in the New World.