Navegando por Autor "Tibayrenc, Michel"
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Item Chemotherapy with Benznidazole and Itraconazole for mice infected with different Trypanosoma cruzi clonal genotypes.(2003) Toledo, Max Jean de Ornelas; Bahia, Maria Terezinha; Carneiro, Cláudia Martins; Martins Filho, Olindo Assis; Tibayrenc, Michel; Barnabé, Christian; Tafuri, Washington Luiz; Lana, Marta deThe benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.Item Compared vectorial transmissibility of pure and mixed clonal genotypes of Trypanosoma cruzi in Triatoma infestans.(1998) Pinto, Artur da Silveira; Lana, Marta de; Bastrenta, Brigitte; Barnabé, Christian; Quesney, Virginie; Noel, Sébastien; Tibayrenc, MichelA total of 15 mixtures involving 9 di erent stocks attributed to the 19/20, 32 and 39 major clonal genotypes of Trypanosoma cruzi were used to infect third-instar nymphs of Triatoma infestans via an arti®- cial feeding device. Three biological parameters were considered: (1) the percentage of infected insects (%II), (2) the number of ¯agellates per insect (NFI), and (3) the percentage of trypomastigotes per insect (%DIF). Ge- netic characterization by both multilocus enzyme elec- trophoresis (MLEE) and random ampli®cation of polymorphic DNA (RAPD) indicated that in almost all cases (87%), mixtures remained present after completion of the whole cycle in the insect vector. Two lines of comparison were performed: (1) pure clonal genotypes versus corresponding mixed clonal genotypes and (2) the actual behavior of mixed clonal genotypes versus the expected behavior of the theoretical mixture (i.e. the arithmetic mean of the results observed for each of the two clonal genotypes taken separately). Statistical analyses of the variables were made di cult because of the presence of large standard deviations. Nevertheless, in several cases, mixtures di ered signi®cantly from pure clonal genotypes, and in one case the actual mixture di ered signi®cantly from the theoretical mixture. In some cases, interaction (either potentialization or re- ciprocal inhibition) could be suspected.Item Experimental Trypanosoma cruzi biclonal infection in Triatoma infestans : detection of distinct clonal genotypes using kinetoplast DNA probes.(2000) Pinto, Artur da Silveira; Lana, Marta de; Britto, Constança; Bastrenta, Brigitte; Tibayrenc, MichelMonitored biclonal densities of parasites were offered to third-stage larvae of Triatoma infestans via an arti®cial feeding device and 30 days later, the gut contents of the insects were processed for microscopic examination and polymerase chain reaction (PCR) detection of Trypanosoma cruzi kinetoplast DNA [kDNA]). A total of 15 mixtures involving nine different stocks attributed to the 19/20, 32 and 39 major clonal genotypes of Trypanosoma cruzi were used. The presence of each T. cruzi clonal genotype after completion of the cycle through the insects was investigated by hybridising the PCR ampli®cation products with genotype-speci®c minicircle kDNA probes. Sixty-®ve out of 90 examined insects (72.2%) were positive for parasites by microscopic examination and 85 (94.4%) were positive by PCR. The results show that almost half of the biclonal infections are not detectable after completion of the cycle, and that there are important differences in detection of such biclonal infections according to the clonal genotypes considered. Moreover, elimination of a clonal genotype by another is a frequent, but not constant, pattern in biclonal infections of T. infestans. The use of PCR and kDNA probes makes it possible to avoid the culture phase, which makes detection of mixed infections much easier in epidemiological surveys. Moreover, the fact that T. infestansdoes not transmit different T. cruzi clonal genotypes with the same ef®ciency has strong implications for the reliability of xenogiagnosis. q 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.Item Impact of Trypanosoma cruzi clonal evolution on its biological properties in mice.(2002) Toledo, Max Jean de Ornelas; Lana, Marta de; Carneiro, Cláudia Martins; Bahia, Maria Terezinha; Coelho, George Luiz Lins Machado; Veloso, Vanja Maria; Barnabé, Christian; Tibayrenc, MichelTwenty Trypanosoma cruzi stocks attributed to the 19, 20, 39, and 32 clonal genotypes were comparatively studied in BALB/c mice during the acute and chronic phases of the infection to test the working hypothesis that T. cruzi clonal structure has a major impact on its biological properties. Fourteen parameters were assayed: (1) infectivity; (2) prepatent period; (3) patent period; (4) maximum of parasitemia; (5) day of maximum of parasitemia; (6) parasitemia; (7) mortality, (8) percentage of positive hemoculture, (9) tissue parasitism; (10) inflammatory process during the acute phase of the infection; (11) mortality, (12) percentage of positive hemoculture; (13) tissue parasitism; and (14) inflammatory process during the chronic phase of the infection. Statistical comparison showed that the results are overall consistent with the working hypothesis that biological differences are proportional to the evolutionary divergence among the genotypes. Thus, closely related genotypes (19 vs 20 and 32 vs 39) show in general fewer differences than distantly related groups (19 or 20 vs 32 or 39) except for the comparison between 19 and 32. The working hypothesis is even more strongly supported by the result of the nonparametric Mantel test, which showed a highly significant correlation (P ¼ 2:3 _ 10_3) between biological differences and genetic distances among all pairs of stocks. These data taken together emphasize that it is crucial to take into account the phylogenetic diversity of T. cruzi natural clones in all applied studies dealing with diagnosis, drug and vaccine design, epidemiological surveys, and clinical diversity of Chagas’ disease.Item Trypanosoma cruzi : compared vectorial transmissibility of three major clonal genotypes by Triatoma infestans.(1998) Lana, Marta de; Pinto, Artur da Silveira; Barnabé, Christian; Quesney, Virginie; Noel, Sébastien; Tibayrenc, MichelItem Trypanosoma cruzi : infectivity of clonal genotype infections in acute and chronic phases in mice.(2000) Lana, Marta de; Pinto, Artur da Silveira; Bastrenta, Brigitte; Barnabé, Christian; Noel, Sébastien; Tibayrenc, Michel