Pathogenic factors for the development of chronic Chagas disease in Latin America

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To investigate the pathogenesis of chronic Chagas disease in Latin America, we have analyzed genetic structure of the field isolates of Trypanosoma cruzi and of the individuals who developed typical chronic Chagas disease in Mexico, Guatemala, Peru, Bolivia and Paraguay.In Mexico, we have collaborated with researchers of National Institute of Cardiac Diseases in Mexico City. We performed a large scale field study in two endemic areas, Pueblo and Chiapaz. Seropositivity of the areas was around 10%, though Chiapaz was a little higher. When we calculated the percentage of the electrocardiogram abnormality positives in the seropositives, both areas showed the same though the endemicity was different. This indicated the prognosis after the infection may be determined by mainly host genetics.In Guatemala, we have collected many isolates from both humans and from triatomine vectors in the endemic areas by the collaborative study with researchers at San Carlos University. Using those isolates, … More Higo found the existence of evidences that genetic exchange occurred between different isolates from the same field. Sone developed a novel method to analyze the genetic distance between individual isolates by the comparison of the two dimensional electrophoresis patterns of the cultured epimastigote protein solutions extracted by strong detergent. According to his analysis, at least 4 major trunks were identified in the evolution tree.In Bolivia, we have initiated a large scaled and a strictly clinically defined chronic Chagas Disease study with local researchers and doctors at Center for Tropical diseases (CENETROP), and Hospital Japones. The research protocol has already approved by the ethical committee at the local and Japanese institutions. We have collected 30% of the planned number of samples from three clinical groups, asymptomatic (indeterminate), cardiac without digestive changes, and digestive form (mega colon). We are planning to search for the susceptible genes by conventional targeted gene analysis and by the genome wide scanning.In Paraguay, Chagas disease is so much endemic in the western reserved areas where original Amerindians are living. Collaborative researcher at Universidad Asuncion have surveyed the seroprevalence in those areas and found around 70-90% were seropositive. We noticed several inhabitants showed unique sero-reactivity to the trypanosome antigens that they reacted with only trans-sialidase. We have planned to do a linkage study using many families related to such special trait. One cardiologist who worked together found such persons have tendency to become cardiac Chagas by ECG study in the same villages. Less