ALTERAÇÃO NATURAL DO PADRÃO DE SUSCEPTIBILIDADE AO BENZNIDAZOL EM POPULAÇÕES DE Trypanosoma cruzi MANTIDAS NA FASE AGUDA OU CRÔNICA DA INFECÇÃO EM DIFERENTES MODELOS EXPERIMENTAIS

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

It was evaluated the influence of the Trypanosoma cruzi maintenance in different vertebrate hosts during the acute or chronic phase of the infection on the biological characteristics. To do so, Swiss mice were infected with five (Be-62A and B, and Be-78C, D and E) T. cruzi isolates obtained from different chronic Chagasic dogs infected with Be-62 and Be-78 T. cruzi strains, both 100% sensitive to benznidazole (Bz). After the determination of Bz susceptibility in the first blood passage in mice (BPM) T. cruzi populations were maintained in successive BPMs (in the absence of specific treatment). The objective was to investigate the occurrence of new alterations in Bz resistance level, and in other biological parameters: pre-patent and patent periods, parasitaemia levels, parasitaemia curve, and mortality rate. The experiments were performed to each five or 10 BPMs and groups of 16 mice were used (10 animals for the treated group, and six for the control group). The parasitological cure was determined by fresh blood examination, hemoculture, serological test, PCR and reactivation of the parasitaemia by cyclophosphamide immunosuppressive therapy. The induction of Bz natural resistance was showed in all evaluated T. cruzi populations. The Be-62A and Be-62B isolates showed 50% and 60% of resistance to Bz after a first BPM, respectively. The Bz resistance of Be-78C, Be- 78D, and Be-78E isolates were, respectively, 90%, 70% and 90% in the same conditions. On the other hand, new alterations in the drug susceptibility phenotype were observed during successive BPMs (during acute phase) maintenance. Two tendencies were observed: (1) stability in Bz resistance level in Be-62A (50 to 40% in 60 BPMs), Be-62B (60 to 80% in 60 BPMs) and Be-78C (90 to 90% in 60 BPMs) populations; and (2) reduction in Bz resistance level in the Be-78 D (70 to 20% in 60 BPMs) and Be-78E (90 to 10% in 60 BPMs) populations. The long-term T. cruzi infection has led to alterations in the other biological parameters in mice. In general, the isolates showed less virulence than the parental strains after the dog chronic infection. However, they showed a tendency of increasing the virulence when maintained in BPMs. These results are in agreement with the hypothesis that T. cruzi maintenance form (long-term chronic infections, or in successive blood passages during the acute phase), can influence the susceptibility phenotype of Bz, as well as the virulence of a parasite population.

ASSUNTO(S)

imunologia trypanosoma cruzi,camundongos swiss ,chagásicos crônicos ,cepas parentais ,

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