Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), School of Tropical Medicine and Global Health, Nagasaki University, Sakamoto, Nagasaki, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
PLoS Negl Trop Dis. 2019 Sep 25;13(9):e0007715. doi: 10.1371/journal.pntd.0007715. eCollection 2019 Sep.
The 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.
We 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.
Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation.
2006 年，玻利维亚启动了恰加斯病国家计划，通过病媒控制大大减少了感染人数。随后，在经认证的病媒控制区居住的血清阳性学龄儿童中开始了苯硝唑（BNZ）治疗方案。
我们进行了为期 12 个月的随访研究，在治疗期间和治疗后共采集了 7 份血样。进行了血清学、常规诊断 PCR（cPCR）和定量实时 PCR（qPCR）检测。还测定了血浆 Th1/Th2/Th17 细胞因子水平。大约 103 名血清阳性儿童中有 73 名接受了 BNZ 治疗，其中 3 名因副作用而中断。为了评估每个人的治疗效果，观察了随访最后 6 个月的 cPCR 和 qPCR 值。在完成随访的 57 名儿童中，有 6 名（11%）表现为 cPCR（+）和 qPCR（+）（无反应），24 名（42%）cPCR（-）但 qPCR（+）（不确定）和 27 名（47%）cPCR（-）和 qPCR（-）（反应）。在 14 种 Th1/Th2/Th17 细胞因子中，IL-17A 在治疗前的血清阳性儿童中明显高于年龄匹配的血清阴性儿童，一年后明显降至正常水平。此外，在整个随访研究过程中，IL-17A 水平与 qPCR 检测到的寄生虫计数呈正相关。在 12 个月时，无反应者的 IL-17A 水平明显高于反应者或不确定者，这表明 IL-17A 可能有助于确定对 BNZ 治疗的反应性。
血浆中 IL-17A 水平可能是检测 T. cruzi 持续性感染及其慢性炎症的生物标志物。
