Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.

Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Co-infection Trypanosoma cruzi/HIV: systematic review (1980 - 2010) / Coinfecção Trypanosoma cruzi/HIV: revisão sistemática (1980 - 2010)

INTRODUCTION: The co-infection Trypanosoma cruzi/HIV has been described as a clinical event of great relevance. The objective of this study wasto describe clinical and epidemiological aspects published in literature. METHODS: It is a systematic review of a descriptive nature from the databases Medline, Lilacs, SciELO, Scopus, from 1980 to 2010. RESULTS: There were 83 articles (2.8 articles/year) with a total of 291 cases. The co-infection was described in 1980 and this situation has become the defining AIDS clinical event in Brazil. This is the country with the highest number of publication (51.8 percent) followed by Argentina (27.7 percent). The majority of cases are amongst adult men (65.3 percent) native or from endemic regions with serological diagnosis in the chronic stage (97.9 percent) and indeterminate form (50.8 percent). Both diseases follow the normal course, but in 41 percent the reactivation of the Chagas disease occurs. The most severe form is the meningoencephalitis, with 100 percent of mortality without specific and early treatment of the T. cruzi. The medication of choice was the benznidazole on doses and duration normally used for the acute phase. The high parasitemia detected by direct or indirect quantitative methods indicated reactivation and its elevation is the most important predictive factor. The lower survival rate was related to the reactivation of the Chagas disease and the natural complications of both diseases. The role of the antiretroviral treatment on the co-infection cannot yet be defined by the knowledge currently existent. CONCLUSIONS: Despite the relevance of this clinical event there are still gaps to be filled.

INTRODUÇÃO: A coinfecção Trypanosoma cruzi/HIV vem sendo sistematicamente descrita como um evento clínico de grande relevância. O objetivo deste estudo foi descrever aspectos clínicos e epidemiológicos publicados na literatura científica. MÉTODOS: Trata-se de revisão sistemática, de natureza descritiva, a partir da busca nas bases Medline, Lilacs, SciELO, Scopus, de 1980 a 2010. RESULTADOS: Identificou-se 83 artigos (2,8 artigos/ano), com um total de 291 casos registrados. A coinfecção foi descrita em 1980 e, no Brasil, tornou-se evento clínico definidor de AIDS. Este é o país com maior número de publicações (51,8 por cento), seguido pela Argentina (27,7 por cento). A maioria dos casos é de homens adultos (65,3 por cento), naturais ou procedentes de regiões endêmicas, com diagnóstico sorológico, na fase crônica (97,9 por cento) e na forma indeterminada (50,8 por cento). As duas doenças evoluem naturalmente, mas em 41 por cento dos casos ocorreu reativação da doença de Chagas. A forma mais grave é a meningoencefalite, com 100 por cento de letalidade nos casos sem tratamento específico e precoce do T. cruzi. O medicamento indicado foi benznidazole, nas doses e duração utilizadas na fase aguda em imunocompetentes. O diagnóstico da reativação foi comprovado por alta parasitemia, detectada por métodos diretos ou indiretos quantitativos, sendo a sua elevação considerada fator preditivo para reativação. A menor sobrevida nacoinfecção esteve relacionada à reativação da doença de Chagas e às complicações naturais de ambas as doenças. O papel do tratamento antirretroviral sobre a evolução da coinfecção ainda não pode ser definido pelo conhecimento existente. CONCLUSÕES: Apesar da relevância deste evento clínico, ainda persistem lacunas a serem preenchidas.