Leishmaniose tegumentar na Região Metropolitana de Belo Horizonte: aspectos clínicos, laboratoriais, terapêuticos e evolutivos (1989-1995) / Cutaneous leishmaniasis in the Metropolitan Region of Belo Horizonte: clinical, laboratorial, therapeutic and prognosis features (1989-1995)

This study investigated clinical, laboratorial, therapeutic and prognostic aspects of American cutaneous leishmaniasis in Belo Horizonte in 358 patients with cutaneous leishmaniasis (CL) and 25 with mucocutaneous leishmaniasis (MCL). Compared to CL patients, the MCL patients reported longer duration of disease and higher frequency of other diseases, suggesting that debilitation caused by leishmaniasis or other conditions might contribute to activation and/or mucous dissemination of the parasite. The sensitivity of skin test, indirect immunofluorescence reactions and direct detection of parasites was 78.4, 79.3 and 68.3%, respectively. The treatment with meglumine antimoniate presented 100% efficacy, but 59% patients had side-effects. During two years of follow-up, there were 32/318 relapses after successful treatment. Most relapses (31/32) were of CL patients treated with 15 mg Sb5+/kg/day. The negative response to skin test was the only factor associated with a significant threefold increased risk of relapse. Higher dose or longer duration of treatment might improve the prognosis in these patients.

Foram investigados aspectos clínicos, laboratoriais, terapêuticos e evolutivos da leishmaniose tegumentar americana em Belo Horizonte. O estudo incluiu 358 pacientes com leishmaniose cutânea (LC) e 25 com leishmaniose mucosa (LM). Comparados aos pacientes com LC, aqueles com LM apresentaram maior tempo de doença e relato de outras doenças concomitantes, sugerindo que a debilitação pela leishmaniose e/ou outras doenças podem contribuir para a ativação e/ou disseminação mucosa do parasito. As sensibilidades das reações intradérmica, de imunofluorescência indireta e da pesquisa direta do parasito foram de 78,4, 79,3 e 68,3%, respectivamente. O tratamento com antimoniato de meglumina foi 100% eficaz, com 59% de efeitos colaterais ao longo do tratamento. A recidiva após tratamento ocorreu em 32 (10,1%) dos 318 casos seguidos por até dois anos. A maioria das recidivas (31 dos 32 casos) ocorreu em pacientes com LC tratados com 15mg Sb5+/kg/dia. Na investigação de critérios de cura, a reação intradérmica negativa foi o único fator associado a um risco três vezes maior de recidiva. Um aumento da dose ou do tempo de tratamento talvez melhore o prognóstico nestes pacientes.

A method for screening drugs against the liver stages of malaria using Plasmodium gallinaceum and Aedes mosquitos

The radical cure of human malaria caused by Plasmodium vivax requires two drugs, i.e., a blood schizontocide such as chloroquine to clear the circulating parasites, and primaquine aimed at the liver stages (hypnozoites) responsible for the late relapses of this parasite. Primaquine is unique as a radical curative drug but is highly toxic. The only useful model currently available

Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture

1. Ninety-five crude extrat obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts wee obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0g/Kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active aginst the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forthy-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40ng/ml) as compared to chloroquine (30ng/ml) and quinine (50ng/ml). The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing

The effect of reinoculation with trypomastigotes on the level of protective antibodies in mice chronically infected with T. cruzi

1. The levels of specific antibodies were determined in sera from mice chronically infected with T. cruzi using indirect immunofluorescence, complement-mediated lysis, and neutralization of bloodstream trypomastigote (Try) infectivity upon their incubation with the test sera in vitro and passive transfer of immune sera. 2. The sera were obtained at different times after T. cruzi inoculation performed one to five times using live Y or CL bloodstream Try, two polar strains of T. cruzi. 3. Hight levels of protective and nonprotective antibodies were detected form week 4, the first interval studied, onward, regardless of number of inoculations and time of infection. 4. Sera from CL-infected mice had lower antibody titers at week 4 and the ability of whole sera or semipurified IgG to neutralize the infectivity of bloodstream Try was lower at this time. 5. All other sera obtained during the chronic phase were strongly effective in decreasing parasite infectivity as measured by lower parasitemia and mortality of mice inoculated with the serum-treated Y strain bloodstream Try

Hemocultures from chronic chagasic patients using EDTA or heparin as anticoagulants

Hemoculture tests, a method for the detection of Trypanosoma cruzi, wre used to investigate the effects of the anticoagulants heparin or EDTA on the parasite growth in culture medium (liver infusion tryptose, LIT). Hemocultures from 13 patients with positive serology for chronic Chagas' disease performed in parallel with both anticoagulants resulted in a total of seven (54%) positive hemocultures, three positive with blood samples collected with EDTA (23%), two with heparin (15%) and two with both anticoagulants (15%). There was no significant difference between the number of positive tubes in blood samples collected with either heparin (11%) or with EDTA (13%), an indication that heparin does not block the growth of T. cruzi. However, the simultaneous use of both anticoagulants may improve the positivity index of the hemocultures

In vitro activity of natural and synthetic naphathoquinones against erythrocytic stages of Plasmodium falciparum

In an attempt to identify new antimalarial compounds we studied the blood schizonticide effect of chemically defined natural products which were isolated from plants (Bignoniaceae) or synthesized. Different concentrations of there drugs (up to 20 micronM) were incubated in vitro with blood forms of Plasmodium falciparum for 72 h. A total of 12 drugs of the naphtoquinones group were tested. Eight of them were isolated from plants (NP) and 4 synthesized (S). Three of the drugs (2 NP and one S) were very active and completely inhibited parasite growth at the higher concentrations used (20 micronM); 5 drugs were partially active (3S and 2NP) and 3 (NP) were totally inactive. Lapachol was among the drugs tested. Although it has been considered a potential antimalarial agent, it exhibited very low activity (20% inhibition of schizogony). The antimalarial activity of our naphthoquinones against drug-resistant strains was superior to that of chloroquine and quinine which were as controls. Two of the P. falciparum strains used for the tests were strongly chloroquine resistant. If these naphthoquinones prove to be active in vivo and are of low toxicity, they will be promising candidates for treatment of human malaria particularly since they are easily synthesized

Anticorpos liticos detectados em liquido pericardico de chagasicos cronicos. / Lytic antibodies detected in pericardial fluid of chronic Chagas' patients

A pesquisa de anticorpos liticos (AL) atraves do teste de lise mediada por complemento (LMCo) foi positiva em 11 liquidos pericardicos obtidos de pacientes chagasicos falecidos subitamente ou por causas nao relacionadas a doenca de Chagas e que estao incluidos em um estudo da forma indeterminada dessa doenca. Em todos esses pacientes a sorologia convencional para doenca de Chagas apresentou resultados positivos e o quadro anatomo-patologico mostrou lesoes caracteristicas ou compativeis com a cardite chagasica cronica. Em 12 liquidos pericardicos de individuos que faleceram por diferentes causas e nos quais sorologia para doenca de Chagas foi negativa, a LMCo tambem foi negativa. A presenca de AL no liquido pericardico constitui forte evidencia da presenca de infeccao ativa por T. cruzi nos chagasicos necropsiados e abre perspectivas para o estudo e o melhor conhecimento da patologia da doenca de Chagas

EVI antibodies in patients with Chagas' disease: relationship with anti-Trypanosoma cruzi immunoglobulins and effects of specific treatment.

Anticorpos contra estruturas vasculares do coracao e intersticio de musculatura estriada (anticorpos EVI) persistem em pacientes com doencas de Chagas curados por tratamento especifico e que apresentam negativos o xenodiagnostico, sorologia convencional (SC) e o teste de lise mediada por complemento (LMCo). Alem disso, o anticorpo EVI pode estar presente ou nao em pacientes tratados que apresentam SC positiva mas LMCo negativa. Como a LMCo detecta anticorpos associados a resistencia, os anticorpos EVI provavelmente nao participam do controle de infeccao pelo T. cruzi (embora sejam induzidos por antigenos comuns a estruturas cardiacas e ao parasita) Os anticorpos EVI nao sao tambem necessariamente relacionados aos anticorpos responsaveis pela SC. Experiencias de absorcao com T. cruzi e tecido cardiaco confirmam a sugestao de que esses anticorpos sao induzidos por varios determinantes antigenicos, a maioria dos quais de tecido cardiaco mas com menor participacao de antigenos do T. cruzi