Trypanosoma cruzi: chemotherapy with benznidazole in mice inoculated with strains from Paraná State and from different endemic areas of Brazil

Abstract

Strains of Trypanosoma cruzi from different geographical areas have shown different levels of susceptibility to trypanosomicidal drugs. The susceptibility in vivo to benznidazole was investigated in eighteen strains of T. cruzi. Twelve were isolated from chronic chagasic patients from different Chagas' disease endemic areas. The other six strains were isolated from the northwestern region of Paraná state; two of them from patients, three from triatomines (Triatoma sordida) and one from wild reservoir (Didelphis sp.). To test drug the infected mice were divided into two groups of twenty. One group was treated with benznidazole for twenty consecutive days and the other group was used as untreated control. The treatment began after detection of the infection by direct blood examination or haemoculture. The control of cure was done through haemoculture and indirect immunofluorescence test. The drug eliminated the inflammatory lesions of the skeletal muscle of mice considered cured and from the heart of most of them. Moreover, the inflammatory lesions were reduced in treated but not cured animals. The T. cruzi strains studied showed a gradient of drug susceptibility that varied from 0% to 100%. Ten strains were considered sensitive to the treatment (61 to 100% of cure), one strain was partially sensitive (50% of cure) and seven strains were considered resistant to the treatment (0 to 40% of cure). This variation was observed both in strains of T. cruzi isolated from domestic and sylvatic cycles.

Impact of Benznidazole on Infection Course in Mice Experimentally Infected with Trypanosoma cruzi I, II, and IV

“…Animals infected with PR1219 were also the only to present with moderate acute-phase TP, suggesting the greater pathogenicity of TcII for mice, which is consistent with other studies (Meza and others, unpublished data). 34 In this study, as shown by the H/E technique, there was no direct association between tissue tropism and parasite DTU. The TcI strains showed tropism for skeletal muscle, heart and liver, whereas TcII strains showed tropism for the heart (++), skeletal muscle and central nervous tissue, and TcIV strains for skeletal muscle.…”

“…38 The pathological changes observed with TcII confirm the results of previous studies that used TcII strains of different origins 8,[39][40][41] and from chronic patients in Paraná (Meza SKL and others, unpublished data). 34 The TcII parasites invade heart cell cultures in lower numbers than TcI parasites; however, intracellular multiplication of TcII parasites was more efficient than that of TcI parasites, strongly suggesting that intracellular development is important to determine parasite tissue tropism. 42 These parasites showed tropism for the heart muscles, a greater amount of tissue amastigote nests, and higher pathogenicity for mice.…”

Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains

“…Several authors have extensively investigated the correlation between T. cruzi genetic background and the different clinical forms of Chagas disease, as well as biological characteristics, such as virulence, pathogenicity and susceptibility to drugs (Revollo et al 1998, Andrade 1999. Filardi and Brener (1987) and Toledo et al (1997) been suggested as an important factor in explaining the low rates of cure detected in treated patients (Murta & Romanha 1998). Several authors have shown that resistance of T. cruzi strains to benznidazole and nifurtimox increased when parasites were isolated from mice previously treated with these same drugs (Marretto & Andrade 1994, Murta & Romanha 1998.…”

Diversidade genética de populações naturais do <em>Trypanosoma</em> cruzi no Paraná, Sul do Brasil

“…In the North and Northwest of this state, T. cruzi strains were isolated from chronic chagasic patients (Gomes et al, 1992), from sylvatic reservoirs and from triatomines captured in the peridomestic environment (Toledo et al, 1997;Guilherme et al, 2001). Strains isolated from chronic chagasic patients showed a homogeneous biological behavior in mice (Araújo et al, 1999), a drug susceptibility gradient that varied from 0 to 100% (Toledo et al, 1997) and a well-correlated genetic group (Gomes et al, 1998). Also, T. cruzi strains isolated from triatomines captured in the same region displayed low virulence in mice (Cardoso et al, 2000).…”