[Leishmaniasis urbanization and low diagnosis capacity in the Metropolitan Region of Belo Horizonte]. / A urbanização das leishmanioses e a baixa resolutividade diagnóstica em municípios da Região Metropolitana de Belo Horizonte.

During the period from 1994 to 1999 cutaneous leishmaniasis was reported in 32 (89%) out of 36 municipalities in the Metropolitan Region of Belo Horizonte, Brazil, of which one (2,8%) municipality was classified as a very high risk area, 16 (44,5%) as high risk, seven (19,4%) as moderate risk areas and 12 (33,3%) as low risk. From 1994 to 1995, visceral leishmaniasis was reported in six (16%) municipalities whereas in 1998 - 1999 this number increased to 15 (42%). Annual numbers of cases during 1994 to 1999 were 30, 53, 64, 53 and 84, respectively. In 19 (61.3%) municipalities no reference center for the diagnosis of the infection was available, so that most of the patients (80%) were referred to Belo Horizonte. Twelve (39%) municipalities have a center for leishmaniasis evaluation, however in only eight (67%) of these basic specific diagnostic tests were available. Rapid and extensive increase of leishmaniasis associated with low diagnosis capacity has been observed in the metropolitan area of Belo Horizonte.

A urbanização das leishmanioses e a baixa resolutividade diagnóstica em municípios da Região Metropolitana de Belo Horizonte / Leishmaniasis urbanization and low diagnosis capacity in the Metropolitan Region of Belo Horizonte

During the period from 1994 to 1999 cutaneous leishmaniasis was reported in 32 (89%) out of 36 municipalities in the Metropolitan Region of Belo Horizonte, Brazil, of which one (2,8%) municipality was classified as a very high risk area, 16 (44,5%) as high risk, seven (19,4%) as moderate risk areas and 12 (33,3%) as low risk. From 1994 to 1995, visceral leishmaniasis was reported in six (16%) municipalities whereas in 1998 - 1999 this number increased to 15 (42%). Annual numbers of cases during 1994 to 1999 were 30, 53, 64, 53 and 84, respectively. In 19 (61.3%) municipalities no reference center for the diagnosis of the infection was available, so that most of the patients (80%) were referred to Belo Horizonte. Twelve (39%) municipalities have a center for leishmaniasis evaluation, however in only eight (67%) of these basic specific diagnostic tests were available. Rapid and extensive increase of leishmaniasis associated with low diagnosis capacity has been observed in the metropolitan area of Belo Horizonte.

No período de 1994 a 1999, foram notificados casos de leishmaniose tegumentar em 32 (89%) dos 36 municípios da Região Metropolitana de Belo Horizonte. Em um (2,8%) município o risco de adquirir a doença foi considerado muito alto, em 16 (44.5%), médio em sete (19,4%) e baixo em 12 (33.3%). Leishmaniose visceral foi notificada em seis (17%) dos 36 municípios, nos anos 94 e 95, elevando-se para 15 (42%) no biênio 98/99. O total de casos de leishmaniose visceral notificados anualmente no período 94 a 99 foi 30, 53, 64, 60, 53, 84, respectivamente. Não há serviços referenciados para atendimento da doença em 19 (61,3%) de 31 municípios, sendo 80% dos pacientes encaminhados para Belo Horizonte. Em 12 (39%) municípios com serviços referenciados, somente oito (67%) dispõem de testes diagnósticos específicos para leishmaniose. Verificou-se rápida e extensa expansão das leishmanioses na região metropolitana de Belo Horizonte e baixa capacidade de resolução diagnóstica pelos seus municípios.

Immunological and clinical evaluation of chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years ago.

We recently evaluated the in vitro proliferative response and interferon (IFN)-gamma production of peripheral blood mononuclear cells from a group of 25 people who were treated for Chagas' disease during the acute phase of Trypanosoma cruzi infection and followed up for a period of 14-30 years. On the basis of the parasitological and serological tests, the individuals were classified as cured (C), dissociated, or not cured (NC). Members of group C (the group without cardiac alterations) presented significantly stronger proliferative response against the parasite antigens, with secretion of high levels of IFN-gamma in comparison with the NC group, raising a question about the role of this cytokine in the curing of human T. cruzi infection. Severe cardiac alterations were observed only in 1 of 25 patients, which suggests that treatment benefited the patients.

IFN-gamma in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-gamma in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-gamma were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-gamma were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-gamma in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-gamma production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-gamma production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease.

IFN-gamma in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-gamma in human Chagas'disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with bendnidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-gamma were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-gamma were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-gamma in human Chagas'disease is discussed in terms of the possibility of a temporal difference in IFN-gamma production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-gamma production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease.

Influence of parasite presence on the immunologic profile of peripheral blood mononuclear cells from chagasic patients after specific drug therapy.

The aim of this study is to evaluate the effects of parasite clearance on the immunological profile of peripheral blood mononuclear cells (PBMC) from chagasic patients submitted to specific drug therapy. PBMC were examined by flow cytometry and proliferative responsiveness to Trypanosoma cruzi-related stimuli. Three groups of patients were studied: not treated (NT), treated not cured (TNC) and cured (C). All data were compared to values from uninfected individuals (NI). NT displayed a lower percentage of CD3+ cells as compared to NI, while TNC and C had mean values that were between those from NI and NT. Infected patients had double the percent of CD3+ HLA-DR+ cells, independent of the efficacy of the treatment. Thus, absence of circulating parasites did not reduce T cell activation in Chagas' disease. NT displayed a higher percentage of CD5+ B cells as compared to NI, while TNC and C had mean values between those from NI and NT. In contrast to the phenotypic data, the in vitro mean proliferative responses to parasite-related stimuli of PBMC from C were reduced to the low mean levels observed in NI. These striking differences were statistically different from the high responses seen in NT and TNC. Our data suggest that proliferative responses of PBMC from C reflect immunological changes due elimination of parasite. However, successful treatment did not alter the levels of peripheral T cell activation.

[Hemoculture: sensitive technique in the detection of Trypanosoma cruzi in chagasic patients in the chronic phase of Chagas disease]. / Hemocultura: técnica sensível na detecção do Trypanosoma cruzi em pacientes chagásicos na fase crônica da doença de chagas.

The sensitivity of hemocultures, performed once or three times, was investigated in 52 patients in the chronic phase of Chagas disease. Modifications were introduced in the technique such as, processing the blood more rapidly, gently homogenizing the cultures and examining them after 120 days of culture. Our results show a high percent age of positivity i.e. 79% and 94% of patients submitted, respectively, to one or three tests. No significant differences related to the patients age were detected, which varied from 14 to 82 years old. Our results demonstrate that hemoculture is a sensitive method for the parasitological diagnosis of Chagas disease and is ideal for monitoring cure in treated patients.

An experimental and clinical assay with ketoconazole in the treatment of Chagas disease.

Ketoconazole, an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanosoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the suppressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.