Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes.
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2008
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Objectives: To assess different methodologies to better define an early post-therapeutic cure criterion
after benznidazole treatment in BALB/c mice following mixed infection with dual Trypanosoma cruzi
genotypes.
Methods: According to the classical cure criteria, animals were classified as treated not cured (TNC 5
76.4%), treated cured (TC 5 12.5%) and dissociated (DIS 5 11.1%) using parasitological [fresh blood
examination (FBE), blood culture (BC) and blood PCR] and serological methods [conventional serology
(CS-ELISA) and non-conventional serology (NCS-FC-ALTA)]. Tissues were also evaluated by PCR.
Results: FBE was able to detect patent parasitaemia in only 18.1% of TNC and therapeutic failure was
detected in 79.1% and 97.2% of TNC by BC and blood PCR, respectively. CS-ELISA should not be used
before 3 months after treatment since it may lead to false-negative results. At 3 months after treatment
with benznidazole, NCS-FC-ALTA was more efficient for categorizing the groups of treated mice. In the
TNC group, although a decreased frequency of PCR-positive tissue was observed in several host
tissues, increased positivity was also observed, despite the T. cruzi genotype combination. All TC
animals presented at least two positive tissue-PCR results.
Conclusions: Our results confirm that NSC-FC-ALTA and blood PCR are the most suitable methods to
early detect therapeutic failure in acute murine T. cruzi infection. Additionally, our data show that BC
positivity is highly dependent upon the T. cruzi genotype combination. Moreover, our findings demonstrated
that PCR tests performed on tissues from animals considered cured after benznidazole treatment
still detected T. cruzi DNA, most probably indicating residual infection.
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Mixed infection, Genetic diversity, Cure control, Murine model
Citação
MARTINS, H. R. et al. Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes. Journal Of Antimicrobial Chemotherapy, v. 61, p.1319-1327, 2008. Disponível em: <http://jac.oxfordjournals.org/content/61/6/1319.long>. Acesso em: 10 jan. 2017.