IL-17A, a possible biomarker for the evaluation of treatment response in Trypanosoma cruzi infected children: A 12-months follow-up study in Bolivia

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.

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

“…Another important point is that in functionally normal patients, their EVs also led to a decrease in IL-17. A follow-up study in school-aged children with Chagas disease found that higher IL-17A levels were associated with the persistence of infection after treatment with benznidazole, suggesting this cytokine could be a possible biomarker for nonresponse to treatment and the persistence of infection [ 54 ]. However, when we analyzed our data under this hypothesis, in contrast to what was previously described, EVs from chronic patients with no cardiac function loss induced a lower production of IL-17, suggesting that in patients who did not receive benznidazole treatment, this cytokine might have another role, even a protective one.…”