Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania) major vaccines in a rhesus monkey (Macaca mulatta) model of the human disease

We have compared the efficacy of two Leishmania (Leishmania) major vaccines, one genetically attenuated (DHFR-TS deficient organisms), the other inactivated [autoclaved promastigotes (ALM) with bacillus Calmete-Guérin (BCG)], in protecting rhesus macaques (Macaca mulatta) against infection with virulent L. (L.) major. Positive antigen-specific recall proliferative response was observed in vaccinees (79 percent in attenuated parasite-vaccinated monkeys, versus 75 percent in ALM-plus-BCG-vaccinated animals), although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g) production or positive delayed-type hypersensitivity (DTH) response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05) between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application

Leishmania (Leishmania) major-infected rhesus macaques (Macaca mulatta) develop varying levels of resistance against homologous re-infections

Seven rhesus macaques were infected intradermally with 10(7) promastigotes of Leishmania (Leishmania) major. All monkeys developed a localized, ulcerative, self-healing nodular skin lesion at the site of inoculation of the parasite. Non-specific chronic inflammation and/or tuberculoid-type granulomatous reaction were the main histopathological manifestations of the disease. Serum Leishmania-specific antibodies (IgG and IgG1) were detected by ELISA in all infected animals; immunoblot analyses indicated that numerous antigens were recognized. A very high degree of variability was observed in the parasite-specific cell-mediated immune responses [as detected by measuring delayed-type hypersensitivity (DTH) reaction, in vitro lymphocyte proliferation, and gamma interferon (IFN-gamma) production] for individuals over time post challenge. From all the recovered monkeys (which showed resolution of the lesions after 11 weeks of infection), 57.2 percent (4/7) and 28.6 percent (2/7) animals remained susceptible to secondary and tertiary infections, respectively, but the disease severity was altered (i.e. lesion size was smaller and healed faster than in the primary infection). The remaining monkeys exhibited complete resistance (i.e. no lesion) to each rechallenge. Despite the inability to consistently detect correlates of cell-mediated immunity to Leishmania or correlation between resistance to challenge and DTH, lymphocyte transformation or IFN-gamma production, partial or complete acquired resistance was conferred by experimental infection. This primate model should be useful for measuring vaccine effectiveness against the human disease

High and low doses of antimony (Sbv) in American cutaneous leishmaniasis. A five years follow-up study of 15 patients

Seventeen patients proceeding from the municipality of Rio de Janeiro, Brazil presenting with the cutaneous ulcerative form of American leishmaniasis were treated with one ampoule of pentavalent antimony daily for 30 days. With this regimen the individuals doses varies greatly: from 3.8 mg/kg of body weight to 22.3 mg/kg. After five years, patients receiving either a smaller dose or a bigger one, showed the same therapeutic result: cutaneous scars and no mucosal lesions.

The possible role of circulating immune complexes in the deficiency of cell-mediated immunity in paracoccidioidomycosis

1. The nature and extent of immune abnormalities was studied in 28 untreated patients with a chronic moderate form of paracoccidioidomycosis (PCM). 2. The patients presented hyporeactivity to skin tests, diminished lymphocyte transformation by mitogens such as phytohamgglutinin-P and concanavalin A and by Paracoccidioides brasiliensis protein antigen. They also presented peripheral blood leukocytosis but normal absolute numbers of T-cell and T-cell subsets. 3. The patients had increased serum levels of C3d, as well as high levels of circulating immune complexes (CIC) detected by C1q-binding and protein A-binding assays. 4. There was a significant negarive correlation between lymphocyte transformation by mitogens and CIC levels which suggested that CIC may be involved in the genesis of the depressed cell-mediated immunity in PCM patients

Active cutaneous leishmaniasis in Brazil, induced by Leishmania donovani chagasi

Em lesöes cutâneas, de um caso humano e de um cäo, procedente de área endêmica de leishmaniose tegumentar no Rio de Janeiro, foi isolada L.d. chagasi. Ambas as culturas foram identificadas por caracterizaçäo molecular e immunológica do parasito utilizando três diferentes métodos: mobilidade eletroforética de isoenzimas, análise do kDNA e anticorpos monoclonais. Este parece ser o primeiro caso humano bem documentado, no Novo Mundo, de uma Leishmania "viscerotrópica" induzindo lesöes cutâneas e demonstra que o diagnóstico do agente etiológico baseado somente na observaçäo clínica e dados epidemiológicos pode levar a conclusöes errôneas