Immunodominant Antigens of Leishmania chagasi Associated with Protection against Human Visceral Leishmaniasis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Isolation of fungi from nature in the region of Botucatu, state of São Paulo, Brazil, an endemic area of paracoccidioidomycosis

In an attempt to isolate Paracoccidioides brasiliensis from nature 887 samples of soil from Botucatu, SP, Brazil, were collected cultured in brain heart infusion agar supplemented with dextrose, in potato dextrose agar and in yeast extract starch dextrose agar, all with antibiotics, at 25º and 37ºC. Five thermo-dependent dimorphic fungi morphologically resembling P. brasiliensis were isolated; two from armadillo holes; further studies of the biology, antigenicity and genetic features of the five dimorphic fungi are necessary to clarify their taxonomy and their possible relation to P. brasiliensis. In addition, 98 dematiaceous fungi and 581 different species of Aspergillus spp. were also isolated. Our findings emphasize that armadillos and their environment are associated with thermo-dimorphic fungi and confirm the ubiquity of pathogenic dematiaceous fungi and Aspergillus spp.

Experimental visceral leishmaniasis in high and low antibody - producer mice (selection IV-A)

A leishmaniose é uma infecção parasitária cuja imunidade protetora envolve a ativação de macrófagos. Neste trabalho avaliamos a susceptibilidade de camundongos H e L (bons e maus produtores de anticorpos, respectivamente) da seleção IV-A, à infecção com o protozoário L. donovani. Camundongos H infectados com 10(7) amastigotas por via intravenosa foram mais suscetíveis, apresentando maior carga parasitária tanto no fígado quanto no baço. Após 60 dias de infecção ambas as linhagens apresentaram um aumento no índice esplênico. Esta esplenomegalia foi conseqüência, pelo menos parcialmente, de um aumento no número de células esplênicas. Os resultados indicam que a seleção IV-A é susceptível à infecção com L. donovani e que dentro desta seleção a linhagem H apresenta maior suscetibilidade do que a linhagem L.

Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications

Background. Visceral leishmaniasis (VL) is almost always lethal if not treated, but most infections with the causative agents are clinically silent. Mannan-binding lectin (MBL), an opsonin, is a candidate molecule for modifying progression to VL because it may enhance infection with intracellular pathogens. Mutations in the MBL2 gene decrease levels of MBL and may protect against development of VL. This case-control study examines genotypes of MBL2 and levels of MBL in individuals presenting with different outcomes of infection with Leishmania chagasi.Methods. Genotypes for MBL2 and levels of serum MBL were determined in uninfected control subjects (n=76) and in individuals presenting with asymptomatic infection (n=90) or VL (n=69).Results. Genotypes resulting in high levels of MBL were more frequent (odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.3-5.0]; P=.006) among individuals with VL than among those with asymptomatic infections and were even more frequent (OR, 3.97 [95% CI, 1.10-14.38];P=.043) among cases of VL presenting with clinical complications than among those with uneventful courses. Serum levels of MBL were higher (P=.011) in individuals with VL than in asymptomatic infections.Conclusions. Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi.

Immunotherapy against murine experimental visceral leishmaniasis with the FML-vaccine

The fucose mannose ligand (Leishmania donovani FML)-saponin vaccine has earlier shown its immunoprophylactic potential against visceral leishmaniasis in the CB hamster (87.7% of parasite load reduction), Balb/c (84.4%) and Swiss albino mouse (85-93%) models. In this investigation its specific immunotherapeutic efficacy against L. donovani infection in Balb/c mice was studied. The effects of vaccine treatment on the Immoral response, delayed type of hypersensitivity to promastigote lysate (DTH), cytokine levels in sera and reduction of the liver parasitic load of L. donovani infected mice, were examined. The types and subtypes of anti-FML antibodies increased significantly in the vaccinees over the saline and saponin controls. As expected for a saponin vaccine, the highest ratios were found in relation to IgG1, IgG2a and IgG2b (4.4, 5 and 2.5, respectively). The DTH response and the in vitro ganglion cell proliferative response against FML antigen were also significantly higher than controls (P < 0.005). Concomitantly, an impressive and specific decrease of liver parasitic burden was detected only in vaccine-treated animals (94.7%). Our results indicate that the therapeutic FML-vaccine has a potent effect on modulation of the murine infection leading to the reduction of parasitic load and signs of disease, being a new potential tool in the therapy and control of visceral leishmaniasis. (C) 2003 Elsevier Ltd. All rights reserved.

Levels of matrix metalloproteinase-2 and metalloproteinase-9 in the cerebrospinal fluid of dogs with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)