Posttherapeutic Cure Criteria in Chagas' Disease: Conventional Serology followed by Supplementary Serological, Parasitological, and Molecular Tests

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>We performed a critical study of conventional serology, followed by supplementary serological, parasitological, and molecular tests, to assess the response to etiologic treatment of Chagas' disease. A group of 94 Chagas' disease patients treated with benznidazole at least 10 years earlier were evaluated from the laboratory and clinical points of view. When conventional serology (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IIF], and indirect hemagglutination [IHA]) and classic criteria (consistent results with any two of the three tests) or more rigorous criteria (consistent results from the three tests) were used, 10.6% and 8.5% of patients were considered treated and cured (TC) by classic and rigorous criteria, respectively. Patients were then evaluated using supplementary (recombinant ELISA and<jats:named-content content-type="genus-species">Trypanosoma cruzi</jats:named-content>excreted-secreted antigen blotting [TESA-blot]), parasitological (hemoculture), and molecular (PCR) tests. The results of recombinant ELISA were similar to those with the rigorous criterion (three consistent test results). The TESA-blot group showed a higher percentage (21.3%) of negative results than the groups defined by either cure criterion. Hemoculture and PCR gave negative results for all treated and cured (TC) patients, regardless of the criterion used. Recombinant ELISA and TESA-blot tests showed negative results for 70% and 87.5% of the patients categorized as TC by the classic and three-test criteria, respectively. For patients with discordant conventional serology, the supplementary serological and molecular tests were the decisive factor in determining therapeutic failure. Clinical evaluation showed that 62.5% of TC patients presented with the indeterminate form of the disease. Additionally, treated patients with negative TESA-blot results should be reevaluated later with all methodologies used here to verify whether TESA-blot is a reliable way to determine early parasitological cure of Chagas' disease.</jats:p>

Evaluation of Nifurtimox Treatment of Chronic Chagas Disease by Means of Several Parasitological Methods

“…In addition, these techniques were applied to detect the parasite in T. infestans fed by XD. As a result, it was possible to agree with other authors who point out that monitoring of these patients should be done in a longitudinal manner over the long term in order to detect occasional bloodstream parasites elicited from tissues of the treated and noncured patients (6). The clinical manifestations and variations in the immune response observed during chagasic infection are not well understood but are believed to be associated with the host or parasite genetic variability.…”

“…To date, only two drugs have been effectively used in Chagas disease chemotherapy: Nifurtimox (NF) and Benznidazole (BZ), which presents several limitations due to secondary effects (5). The best chemotherapy results have been achieved in acute or early chronic infections in contrast to those observed in late chronic infections (6). Even in children, who are known to better tolerate treatment with these nitroheterocyclic compounds than adults, the cure rate is up to 62% at 2 years of follow-up, and it may vary according to population and geographical location (7).…”

Chagas Disease Diagnostic Applications

“…Most importantly, this concept of 'non-conventional' serological responses set the basis for multiple screenings looking for parasite molecules that could be the target of antibody responses showing different qualitative, quantitative and/or kinetic properties. Several potential biomarkers have been thereby identified and evaluated for their post-therapeutic application (Andrade et al, 2004; Fernandez-Villegas et al, 2011; Gazzinelli et al, 1993; Laucella et al, 2009; Machado-de-Assis et al, 2012; Sanchez Negrette et al, 2008; Silva et al, 2002). They included different parasite fractions (i.e.…”

Antiparasitic Treatment Induces an Improved CD8+ T Cell Response in Chronic Chagasic Patients

“…During the acute phase, treatment can induce a parasitological cure in ∼60-85% of patients, but it is rare that patients are diagnosed at this stage (1). The efficacy for treatment of CCPs is controversial, but several studies in murine models and humans suggested that antiparasitic treatment during the early chronic phase of the disease prevents the development of a severe chronic cardiomyopathy (10)(11)(12)(13). For instance, chronically infected mice treated with BZL had less parasitism and myocarditis than did untreated infected mice, as well as lower serum levels of Abs against T. cruzi Ags (11).…”