Variation in Calculating and Reporting Antimalarial Efficacy against Plasmodium falciparum in Sub-Saharan Africa: A Systematic Review of Published Reports

• Published in: The American journal of tropical medicine and hygiene Vol. 104; no. 5; pp. 1820 - 1829
• Main Authors: Plucinski, Mateusz M, Hastings, Ian M, Moriarty, Leah F, Venkatesan, Meera, Felger, Ingrid, Halsey, Eric S
• Format: Journal Article
• Language: English
• Published: United States Institute of Tropical Medicine 15.03.2021; The American Society of Tropical Medicine and Hygiene
• Subjects: 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; Malaria, Falciparum - epidemiology; Malaria, Falciparum - mortality; Malaria, Falciparum - parasitology; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Plasmodium falciparum - pathogenicity; Recurrence; Survival analysis; Systematic review; Treatment Outcome; Africa South of the Sahara; Africa
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.20-1481

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.