Abstract
BackgroundThe National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas.Methods and findingsWe conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects.To evaluate each individual’s treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive).Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months’ time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment.ConclusionsPlasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation.
Highlights
An estimated seven million people are infected with Trypanosoma cruzi, a parasite that causes Chagas disease worldwide, mostly in Latin America
Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation
103 children without any IL-17A, a possible biomarker for treatment response in T. cruzi infected children acute symptoms, clinical laboratory abnormalities nor typical ECG alteration were confirmed positive by the three serology assays, and 23 were seronegative (Fig 1)
Summary
An estimated seven million people are infected with Trypanosoma cruzi, a parasite that causes Chagas disease worldwide, mostly in Latin America. Two drugs are currently available for Chagas treatment, nifurtimox, and benznidazole (BNZ), which are effective as anti-parasitic for T. cruzi, their prolonged regimens and undesirable side effects are the main drawbacks in their employment [4,5,6,7,8,9]. In a placebo-controlled trial in a rural area of Brazil on school children with endemic Chagas disease, 55.8% of treatment efficacy was observed by a negative seroconversion after a three-year follow-up [13]. Other studies have reported around 60–80% response in children under 15 years old with chronic infection treated with BNZ and assessed by the conventional serology in a long-term follow-up [14,15,16,17]. A treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas
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