Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
PLoS Negl Trop Dis. 2021 Apr 16;15(4):e0009328. doi: 10.1371/journal.pntd.0009328. eCollection 2021 Apr.
In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.
在血吸虫病流行地区，胎儿接触血吸虫抗原可在潜在的自然感染前对后代进行致敏。已证明孕妇用吡喹酮（PZQ）治疗日本血吸虫感染既安全又有效。我们的目的是评估母体 PZQ 治疗是否改变了胎儿对血吸虫抗原的致敏过程，从而潜在地影响了以后的感染风险，以及对日本血吸虫的免疫反应。我们在菲律宾莱特招募了 295 名 6 岁儿童，他们的母亲在妊娠 12-16 周时参加了吡喹酮与安慰剂治疗日本血吸虫感染的随机对照试验。在入组时，我们评估并治疗了当前的日本血吸虫感染，并测量了血清细胞因子。在四周后的随访中，我们评估了外周血单核细胞（PBMC）对可溶性虫体抗原制剂（SWAP）或可溶性卵抗原（SEA）的细胞因子产生情况。使用多元线性回归分析确定母体治疗组与儿童日本血吸虫感染状况和免疫反应之间的关联。妊娠期间使用 PZQ 治疗并未影响 6 岁儿童的自然日本血吸虫感染的患病率（P = 0.12）或感染强度（P = 0.59）。在入组时患有感染的儿童中（12.5%），母体治疗组之间血清细胞因子浓度无显著差异。在入组时患有感染的儿童中，SEA 刺激的 PBMC 产生的 IL-1 更高（P = 0.03），与安慰剂相比，PZQ 组的 IL-1 更高。在未感染的儿童中，与安慰剂相比，SEA 刺激的 PBMC 产生更多的 IL-12（P = 0.03），SWAP 刺激的 PBMC 产生更少的 IL-4（P = 0.01）。PBMC 对 SWAP 和 SEA 的反应产生的几种细胞因子在有日本血吸虫感染的儿童中均显著升高，而与母体治疗无关：IL-4、IL-5、IL-10 和 IL-13。我们报告说，母体 PZQ 治疗日本血吸虫病使 PBMC 免疫反应向更具炎症特征转变，但对其后代的感染可能性或 6 岁时的血清细胞因子没有影响，进一步支持在孕妇中安全使用 PZQ。试验注册：ClinicalTrials.gov NCT00486863。
