Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis

BackgroundSince 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity.Methodology/Principal findingsThis review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome.Conclusion/SignificanceWhile there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.背景 自1984年起，世界卫生组织（WHO）便推荐采用药物疗法以降低血吸虫（Schistosoma）感染及其引发的发病情况。横断面研究显示，治疗前感染强度与血吸虫相关病理的发病风险存在关联。但现有证据同时表明，治疗后感染强度的降低未必能逆转发病情况，这是因为部分病症在各感染水平下均会出现，且部分病症反映了永久性组织损伤。本研究的目的在于系统回顾基于药物控制血吸虫病的相关证据，并定量评估治疗后感染强度降低对感染相关发病患病率的影响。 方法与主要研究结果 本综述于启动阶段在PROSPERO（CRD42015026080）完成注册。通过在线检索与私人档案检索，筛选出评估治疗前后发病情况的相关研究。针对每一项结局指标，计算治疗后的比值比或标准化均差，并通过元回归分析将这些指标与治疗相关虫卵计数减少率（egg count reduction ratios, ERRs）进行关联分析。虫卵计数减少率越高，大多数病症的发病比值比降低幅度越大。采用随机效应元分析得出汇总估计值：针对曼氏血吸虫（S. mansoni）与日本血吸虫（S. japonicum）感染的治疗后，左侧肝肿大缓解54%，右侧肝肿大缓解47%，脾肿大缓解37%，门管周围纤维化缓解52%，腹泻缓解53%，粪便潜血缓解75%；针对埃及血吸虫（S. haematobium）感染，血尿缓解92%，蛋白尿缓解90%，膀胱病变缓解86%，上尿路病变缓解72%。门静脉扩张或血红蛋白水平则未出现一致性变化。亚组分析显示，年龄、感染状态、研究区域、寄生虫种类以及随访间隔均与结局存在具有临床意义的差异相关。 结论与意义 尽管血吸虫病的治疗实施存在诸多挑战，且吡喹酮（praziquantel）疗法并非完全治愈性疗法，但虫卵产出量的降低与发病情况的减少显著相关，在考虑采用更积极的策略以降低感染强度时，可通过该关联预测疾病负担的减轻程度。