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

Cell populations in lesions of cutaneous leishmaniasis of Leishmania (L. ) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 +/- 13.1 of the infiltrate in active lesions (versus CD2+ = 40.3 +/- 5.7 in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 +/- 7.1) was significantly higher (P < 0.005) from the healing lesions (42.7 +/- 12.7). Moreover, the expression of the activation molecules CD25 (@ 16), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.

Doença de Chagas em virgem da Lapa, Minas Gerais, Brasil. IV. Aspectos clínicos e epidemiológicos do aneurisma ventricular esquerdo / Chagas disease in Virgem da Lapa, Minas Gerais, Brazil. IV. Clinical and epidemiological aspects of left ventricular aneurism

The study aimed at the evaluation of the clinical and epidemiological characteristics of the aneurysm found in the left ventricle in chronic Chagas' disease patients. Three hundred, eighty eight people (298 chagasic patients and 90 randomly selected healthy individuals) were submitted to echocardiography. The ventricular function was assessed in the M mode by calculating the fraction of ejection, and in the bidimensional mode by analyzing he global systolic function. Segmental contractility was evaluated according to the method described by American Society of Echocardiography. Aneurysm of the left ventricle was diagnosed in 58 (18.8%) patients, all from the chagasic population. From these, 38 (12.7%) were found in the apical segment; 10 (3.4%) in the interventricular septum; and 2 (0.7%) each in the posterior wall; the inferior wall; apico-septal; and inferior-posterior. We could not observe any significant difference for the aneurysm frequencies in relation to age group, gender and race, and no association between aneurysm and arterial hypertension could be made. Of the 56 individuals presenting aneurysm, 55 (98.2%) were symptomatic with predominant palpitations; 53 (94.6%) showed an aberrant ECG with predominant ventricular extra-systoles followed by changes in conduction; and 34 (60.%) showed an impairment of the ventricular function, regardless of the affected segment. In view of these results we consider the apical aneurysm of the left ventricle as a marker of Chagas' disease and as an indicator of high morbidity of the human T. cruzi infection in Virgem da Lapa.

Com o objetivo de avaliar as características clínicas e epidemiológicas do aneurisma ventricular esquerdo na doença de Chagas crônica, 388 indivíduos não selecionados: 298 chagásicos e 90 não-chagásicos, foram submetidos ao exame ecocardiográfico. A função ventricular foi avaliada ao modo M através do cálculo da fração de ejeção e ao bidimensional através da análise subjetiva da função sistólica global e a contratilidade regional foi avaliada pelo modelo da Sociedade Americana de Ecocardiografia. Foram diagnosticados 56 (18,8%) aneurismas do ventrículo esquerdo, todos entre os chagásicos, sendo 38 (12,7%) no segmento apical, 10 (3,4%) no septo interventricular, 2 (0,7%) ápico-septal, 2 (0,7%) na parede posterior, 2 (0,7%) na parede inferior e 2 (0,7%) no segmento ínfero-posterior. Não houve diferença significativa nas freqüências dos aneurismas em relação à faixa etária, ao sexo e à etnia. Não houve associação entre aneurismas e hipertensão arterial. Dos 56 indivíduos com aneurismas, 55 (98,2%) eram sintomáticos com predominância de palpitações, 53 (94,6,%) apresentaram ECG anormais, com predominância de extra-sístoles ventriculares, seguidas de alterações da condução e 34 (60,7%) apresentaram comprometimento da função ventricular, sem diferença quanto ao segmento acometido. Diante destes resultados podemos considerar o aneurisma ventricular esquerdo, principalmente apical, como um marcador de doença de Chagas e um indicador da alta morbidade da infecção humana pelo T. cruzi em Virgem da Lapa.

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.

Aspergillus fumigatus fungus ball in hospitalized patients with chronic pulmonary disease: usefulness of double immunodiffusion test as a screening procedure

Trezentos e cinquenta pacientes sintomáticos respiratórios admitidos no Hospial Raphael de Paula Souza, sem diagnóstico etiológico definitivo, foram triados pela técnica de imunodifusäo dupla (IDD) para aspergilose. Quando a IDD foi positiva, informaçöes adicionais como histórico e exames radiológicos foram requisitados e, quando possível, espécimes clínicos foram processados para exames micológicos e histopatológicos. Linhas de precipitaçäo específicas para o antígeno de A. fumigatus foram encontradas em 29(8,3%) dos 350 soros de pacientes testados. Dezenove (65,5% dos 29 pacientes cm sorologia positiva foram reconhecidos como tendo boa fúngica pelos achados radiológicos em dois ou por ambos em oito pacientes. Este estudo prospectivo de dois anos mostrou que aspergilose pulmonar é um problema considerável entre pacientes admitidos em um hospital para sintomáticos respiratórios, especialmente aqueles com cavidades pulmonares ou bronquiectasias

Carcinoma gastrico com estroma linfoide. / Gastric carcinoma with lymphoid stroma

Os autores relatam um caso de carcinoma gastrico com estroma linfoide, ressaltando a sinonimia, a incidencia, os criterios diagnosticos (macro e microscopicos), os diagnosticos diferenciais e o prognostico.Concordam que este tipo especial de neoplasia possui certas peculiaridades e por isto devera ser classificado separadamente