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.

Martins, Helen Rodrigues; Moreira, Lílian Figueiredo; Silva, Jaquelline Carla Valamiel de Oliveira e; Carneiro, Claudia Martins; Coelho, George Luiz Lins Machado; Avelar, Danielle Marchetti Vitelli; Bahia, Maria Terezinha; Martins Filho, Olindo Assis; Macedo, Andréa Mara; Lana, Marta de

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.

Date

2008

Authors

Martins, Helen Rodrigues

Moreira, Lílian Figueiredo

Silva, Jaquelline Carla Valamiel de Oliveira e

Carneiro, Claudia Martins

Coelho, George Luiz Lins Machado

Avelar, Danielle Marchetti Vitelli

Bahia, Maria Terezinha

Martins Filho, Olindo Assis

Macedo, Andréa Mara

Lana, Marta de

Abstract

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.

Keywords

Mixed infection, Genetic diversity, Cure control, Murine model

Citation

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.