How is the indeterminate-phase of Chagas disease (American trypanosomiasis) treated?

Updated: Apr 26, 2019
  • Author: Louis V Kirchhoff, MD, MPH; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Answer

The current evidence‑based consensus concerning treatment of chronic T cruzi infection is that chronically infected children and adolescents aged 18 years or younger should be treated with either benznidazole or nifurtimox. Convincing data from trials in Argentina and Brazil indicate that a major proportion of these patients will be cured parasitologically. [38, 142, 148]

In contrast, the probability of parasitologic cure with a full course of either drug in adults with long-standing T cruzi infection, including persons in the indeterminate phase, as well as those with manifest chagasic symptoms, most of whom presumably were infected while quite young, is less than 10%. [149, 150, 151, 152, 153, 154, 155] Moreover, determining which treated patients are cured is challenging, since treatment suppresses parasitemias, as reflected in reduced rates of positivity in posttreatment PCR assays, as well as in xenodiagnosis and hemoculture, and levels of anti–T cruzi antibodies can remain positive for years. [134, 156]

Until recently, data from properly structured randomized clinical trials (RCTs) that assess the effect of specific treatment outcomes in chronically infected adults have been lacking. A segment of this void was recently filled by the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. [143, 157] In this blinded, placebo‑controlled trial of benznidazole versus placebo performed in Brazil, Argentina, and Colombia, a total of 2,854 T cruzi–infected patients with mild cardiac disease were followed for a mean of 5.4 years. As expected, parasite detection as shown on PCR assay was suppressed; however, benznidazole did not significantly reduce cardiac clinical deterioration. In view of these results, specific treatment of adults with longstanding T cruzi infection and demonstrable cardiac disease cannot be recommended.

Importantly, no patients in the indeterminate phase of chronic T cruzi infection were included in the BENEFIT trial, so data from proper comparative trials that address the question of the usefulness of treating persons in this group are still lacking. [144] A detailed discussion of this issue took place in 2006 at a two-day meeting convened by the CDC of an expert panel from several endemic countries and the United States, in which the author of this article was a participant. In the publication that resulted from that meeting, [142] the panel recommended that treatment be offered to chronically infected adults (the BENEFIT data were not available then) and that, after discussion of the risks and possible benefits, treatment decisions be shared by patients and caregivers. This recommendation was driven by data from several nonrandomized controlled trials that had suggested that treatment of chronically infected persons might be useful and by the assumption that the suppression of parasitemias was a marker for better clinical outcomes. The BENEFIT results clearly indicate that the latter is not the case, since such suppression was clearly documented in the patients in the benznidazole arm but no clinical benefit was observed. Thus, the assumption regarding suppression of parasitemias can no longer be held out as a reason to treat chronically infected persons.


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