Comparing Multiple Mass Drug Administration Prophylaxis Strategies to Reduce Malaria Incidence in Endemic Areas: A Network Meta-Analysis of Randomized Trials
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Abstract
Introduction: Malaria remains a major global health burden, with 263 million cases and 597,000 deaths reported worldwide in 2023. Mass drug administration may reduce community transmission, yet the relative performance of prophylactic regimens in endemic settings remains uncertain. This study compared multiple mass drug administration strategies to identify the most promising approach for reducing malaria incidence in endemic areas.
Method: A systematic review and network meta-analysis of randomised and cluster-randomised trials was conducted in line with PRISMA 2020. Scopus, PubMed, CENTRAL, EBSCO, and Epistemonikos were searched. Eligible studies evaluated mass drug administration prophylaxis in endemic or high-risk areas and reported end-study malaria incidence. Risk of bias was assessed with RoB 2.0. Random-effects network meta-analysis was performed in R, with effects expressed as risk ratios and 95% credible intervals.
Results: Included studies were six trials involving 53,381 participants from Africa and Asia were included, comparing five prophylactic strategies against control. Mass drug administration with ivermectin plus dihydroartemisinin-piperaquine (DHP) showed the most favourable trend versus control (RR = 0.74, 95% credible interval 0.18 to 2.19), followed by mass drug administration with DHP alone (RR = 0.88, 0.44 to 1.69). Seasonal malaria chemoprevention ranked worst (RR = 2.46, 0.41 to 8.33). Ranking probabilities suggested the hierarchy ivermectin plus DHP, DHP alone, dihydroartemisinin-piperaquine, focal mass drug administration with DHP, control, and seasonal malaria chemoprevention. No comparison reached statistical significance. Overall risk of bias was mainly some concerns, with one high-risk study.
Conclusion: The network consistently favoured mass drug administration with ivermectin plus DHP as the leading regimen for lowering malaria incidence in endemic areas. These findings support larger head-to-head trials to confirm comparative benefit and guide implementation.
Keywords: Chemoprevention; Endemic Areas; Malaria; Mass Drug Administration; Network Meta-Analysis
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