Caracterização da suscetibilidade in vitro e in vivo de cepas de Toxoplasma gondii obtidas de casos humanos de toxoplasmose congênita no Estado de Minas Gerais frente aos fármacos de segunda escolha no tratamento da toxoplasmose

Abstract

In Brazil, toxoplasmosis has a seroprevalence that varies from 40 to 80% in adults. Currently, the gold standard treatment for toxoplasmosis is the combination of SDZ and PYR and alternative drugs such as SMT, TMP, CLN and ATV can also be used. There are reports of adverse effects and treatment failures due to the resistance of the parasite, mainly in Brazil. Studies with isolates in South America showed that the strains circulating in this region differ considerably from those circulating in Europe and North America, characterizing them as atypical. Thus, the great diversity of strains may be associated with the wide geographic distribution, fauna and sexual recombination of clonal strains, and the genetic diversity among the strains of South America may be the reason for the differences in the pattern of susceptibility to treatment. Previous studies have reported four atypical strains of T. gondii with decreased susceptibility to SDZ and PYR. Therefore, the aim of this study was to study the in vivo and in vitro susceptibility of these atypical strains (TgCTBr4, TgCTBr11, TgCTBr17 and TgCTBr23) to alternative drugs used in the treatment of toxoplasmosis. In vivo assays were performed using female Swiss mice infected i.p. with 10,000 tachyzoites. Mice divided into groups were treated for 10 days with different dosages and associations of SDZ, PYR, SMT, TMP, CLN and ATV. For in vitro assays, tests were performed to evaluate the antiproliferative effect of drugs against T. gondii and invasion and proliferation tests. The in vivo treatment using the association of SDZ and PYR was effective only in the TgCTBr11 strain, as well as the treatment with CLN was positive only in the TgCTBr11 and TgCTBr23 strains. Surviving animals in the groups treated with PYR 6.26 + SDZ 20 and SMT 200 + TMP 200 mg/kg/day of the TgCTBr11 strain did not show the presence of cysts in the brain and positive IgG for T. gondii. In in vitro antiproliferative assays as well as in vivo assays, the TgCTBr4 strain did not respond well to treatment using SDZ and PYR, however, the association of SMT and TMP may be used as they help to reduce parasite proliferation. The use of ATV at a higher concentration helped to reduce the proliferation of parasites in the in vitro assays of both strains, with the exception of TgCTBr4. In addition, the TgCTBr11, TgCTBr17 and TgCTBr23 strains are susceptible to the use of SDZ and PYR, and these drugs can be used to treat toxoplasmosis in these cases.