Recommendations from a Satellite Meeting (International Symposium to Commemorate the 90th Anniversary of the Discovery of Chagas Disease, April 11-16 1999, Rio de Janeiro, Brazil)

During this symposium the standardization of the nomenclature of Trypanosoma cruzi strains was discussed, in a parallel session, with a view to facilitating the use and understanding of a common nomenclature that would serve not only taxonomists but the general community of researchers working with T. cruzi. The diversity in the behavior and morphology of T. cruzi isolates was soon recognized after the discovery of Chagas disease. Since then a variety of biochemical and molecular techniques have revealed the great genetic diversity present in strains of this parasite. Different investigators have described this diversity by using various terms. Correlation between this diversity and the complex epidemiological and clinical manifestations of the disease has however been hindered by the lack of a common nomenclature. Recent studies have indicated a convergence among investigators regarding the clustering of strains of T. cruzi, into two principal groups. This consensus, together with the report of a meeting on the standardization of methods for T. cruzi classification held in Panama (unpublished document TDR/EPICHA-TCC/85.3 Geneva, World Health Organization, 1985), form the basis of the recommendations outlined in this document

A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents

A method is described which permits to determine in vivo an in a short period of time (4-6 hours) the sensitivity of T. cruzo strains to known active chemotherapeutic agents. By using resistant- and sensitive T. cruzi stains a fairly good correlation was observed between the results obtained with this rapid method (which detects activity against the circulating blood forms) and those obtained with long-term schedules which involve drug adminstration for at least 20 consecutive days and a prolonged period of assessment. This method may be used to characterize susceptibility to active drugs used clinically, provide infomation on the specific action against circulating trypomastigotes and screen active compounds. Differences in the natural susceptibility of Trypanosoma cruzi strains to active drugs have been already reported using different criteria, mostly demanding long-term study of the animal (Hauschka, 1949; Bock, Gonnert & Haberkorn, 1969; Brener, Costa & Chiari, 1976; Andrade & Figueira, 1977; Schlemper, 1982). In this paper we report a method which detects in 4-6 hours the effect of drugs on bloodstream forms in mice with established T. cruzi infections. The results obtained with this method show a fairly good correlation with those obtained by prolonged treatment schedules used to assess the action of drugs in experimental Chagas' disease and may be used to study the sensitivity of T. cruzi strains to active drugs.<br>No presente trabalho descreve-se um metodo que permite determinar in vivo e em curto espaço de tempo (4-6 horas) a sensibilidade de cepas de T. cruzi a agentes terapeuticos ativos na doença de Chagas. Usando-se cepas sensíveis e resistentes aos medicamentos foi possível observar uma boa correlação entre os resultados obtidos com o método rápido (que detecta atividade contra as formas circulantes do parasita) e aqueles obtidos com esquema de acao prolongada que envolve a administração da droga por 20 dias e posterior avaliação. Esse metodo pode ser usado para caracterizar a sensibilidade de cepas a drogas ativas usadas clinicamente, fornecer informações específicas sobre a ação medicamentosa em tripomastigotas sanguíneos e, eventualmente, para triagem de novos compostos

Estudo parasitológico e anátomo-patológico da fase aguda da doença de Chagas em cães inoculados com duas diferentes cepas do Trypanosoma cruzi

Cães jovens foram infectados com as cepas Y e CL do T. cruzi usando-se como inóculos 107 formas sangüíneas inoculadaspor via intraperitoneal e 2 x 10³ tripomastigotas metacíclicos obtidos do inseto vetor e inoculadospor via conjuntival. As cepas Ye CL induziram nos cães curvas deparasitemia totalmente distintas, confirmando dados parasitológicos obtidos em camundongos e coelhos. Com a cepa CL a parasitemia, com ambos os inóculos, foi gradualmente ascencional ao passo que com Y a parasitemia foi extremamente baixa, irregular e, com freqüência, subpatente. Com ambas as cepas o parasitismo e as lesões predominaram no miocárdio. Entretanto, com a cepa Y a miocardite foi sempre intensa desde as fases mais precoces da infecção, ao passo que com a cepa CL o processo inflamatório tomou-se acentuado somente a partir do 20.° dia. Freqüentemente a intensidade da miocardite observada em alguns animais não guardava relação com a parasitemia; em alguns cães com parasitemia subpatente, nos quais a infecção só foi diagnosticada pelo xenodiagnóstico, a intensidade da miocardite foi comparável àquela observada nos animais com parasitemia patente. Idêntica correlação também não foi assinalada em relação ao parasitismo tissular. Esses achados sugerem a participação de mecanismo imunológicos na gênese das lesões, ainda na fase aguda da infecção.<br>Young dogs were inoculated with T. cruzi Y and CL strains either by intraperitoneal route with 107 blood forms or by ocular route with 2 x 10³ vector-derived trypomastigotes. With both inocula the patterns of parasitemia were significantly different, confirming data previously obtained in experimentally infected mice and rabbits. CL strain induced a gradual ascencional parasitemia whereas with Y the parasitemia was either subpatent or the number of parasites was very low, rapidly declining. Although myocarditis was present in most animals regardless of the strain used, the inflammatory process was established earlier with the Ystrain. The severity of the myocarditis was not related to parasitemia and in some animals in which parasites could only be detected by xenodiagnosis the lesions were comparable to those detected in animals with high number of blood forms. In a similar way, no correlation was established between tissue parasitism and myocardium inflammatory lesions. Thus, the heart tissue damage in the acute phase was not apparently influenced by the differences inthe course of infection, suggesting a participation of immunological mechanisms even at this early stage of infection

Effect of the host specific treatment in the phagocytosis of Trypanosoma cruzi blood forms by mouse peritoneal macrophages

Single doses of drugs active aginst Trypanosoma cruzi (megazol, nifurtimox and benznidazole) induce a rapid clearence of the blood parasites in experimentally infected mice. Furthermore, the in vitro phagocytosis and intracellular destruction by mouse peritoneal macrophage of blood forms collected from the treatment animals is strongly enhanced as compared with parasites from untreated controls. The uptake of the blood forms by macrophages is significantly higher with megazol than with benznidazole and nifurtimox, a finding that concurs with data showing that megazol is also the most active compound in the living host. The possibility that macrophages participate in a synergic effect between the host immune response and chemotherapeutic effect is discussed