Mesh : Africa South of the Sahara / epidemiology Analysis of Variance Antimalarials / therapeutic use Artemisinins / therapeutic use Data Interpretation, Statistical Drug Resistance / genetics Guideline Adherence / statistics & numerical data Guidelines as Topic Humans Kaplan-Meier Estimate Malaria, Falciparum / drug therapy epidemiology mortality parasitology Plasmodium falciparum / drug effects genetics growth & development pathogenicity Recurrence Treatment Outcome

来  源:   DOI:10.4269/ajtmh.20-1481   PDF(Pubmed)

Abstract:
Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in sub-Saharan Africa. Performing and reporting antimalarial efficacy studies in a transparent and standardized fashion permit comparison of efficacy outcomes across countries and time periods. This systematic review summarizes study compliance with WHO laboratory and reporting guidance pertaining to antimalarial therapeutic efficacy studies and evaluates how well studies from sub-Saharan Africa adhered to these guidelines. We included all published studies (January 2020 or before) performed in sub-Saharan Africa where ACT efficacy for treatment of uncomplicated Plasmodium falciparum infection was reported. The primary outcome was a composite indicator for study methodology consistent with WHO guidelines for statistical analysis of corrected efficacy, defined as an article presenting a Kaplan-Meier survival analysis of corrected efficacy or reporting a per-protocol analysis where new infections were excluded from the numerator and denominator. Of 581 articles screened, we identified 279 for the review. Molecular correction was used in 83% (232/279) to distinguish new infections from recrudescences in subjects experiencing recurrent parasitemia. Only 45% (99/221) of articles with therapeutic efficacy as a primary outcome and performing molecular correction reported corrected efficacy outcomes calculated in a way consistent with WHO recommendations. These results indicate a widespread lack of compliance with WHO-recommended methods of analysis, which may result in biases in how antimalarial effectiveness is being measured and reported from sub-Saharan Africa.
摘要:
抗疟药,特别是基于青蒿素的联合疗法(ACTs),是减轻全球疟疾负担的重要工具,集中在撒哈拉以南非洲。以透明和标准化的方式进行和报告抗疟疗效研究,可以比较不同国家和时间段的疗效结果。本系统评价总结了与世卫组织实验室和报告指南有关的抗疟治疗效果研究的研究合规性,并评估了撒哈拉以南非洲的研究遵守这些指南的程度。我们纳入了在撒哈拉以南非洲进行的所有已发表的研究(2020年1月或之前),据报道,ACT对治疗无并发症的恶性疟原虫感染的疗效。主要结果是与WHO校正疗效统计分析指南一致的研究方法的复合指标。定义为一篇文章介绍了校正疗效的Kaplan-Meier生存分析或报告了分子和分母中排除新感染的符合方案分析.在581篇筛选的文章中,我们确定了279项进行审查.83%(232/279)的患者使用分子校正来区分新感染与复发性寄生虫血症的复发。只有45%(99/221)以治疗疗效为主要结果并进行分子校正的文章报告了以与WHO建议一致的方式计算的校正疗效结果。这些结果表明普遍不符合世卫组织推荐的分析方法,这可能会导致撒哈拉以南非洲地区在衡量和报告抗疟效果方面存在偏差。
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