Background Malaria remains a major burden in sub-Saharan Africa (SSA). While an association between poverty and malaria has been demonstrated, a clearer understanding of explicit mechanisms through which socioeconomic position (SEP) influences malaria risk is needed to guide the design of more comprehensive interventions for malaria risk mitigation. This systematic review provides an overview of the current evidence on the mediators of socioeconomic disparities in malaria in SSA. Methods We searched PubMed and Web of Science for randomised controlled trials, cohort, case-control and cross-sectional studies published in English between January 1, 2000 to May 31, 2022. Further studies were identified following reviews of reference lists of the studies included. We included studies that either (1) conducted a formal mediation analysis of risk factors on the causal pathway between SEP and malaria infections or (2) adjusted for these potential mediators as confounders on the association between SEP and malaria using standard regression models. At least two independent reviewers appraised the studies, conducted data extraction, and assessed risk of bias. A systematic overview is presented for the included studies. Results We identified 41 articles from 20 countries in SSA for inclusion in the final review. Of these, 30 studies used cross-sectional design, and 26 found socioeconomic inequalities in malaria risk. Three formal mediation analyses showed limited evidence of mediation of food security, housing quality, and previous antimalarial use. Housing, education, insecticide-treated nets, and nutrition were highlighted in the remaining studies as being protective against malaria independent of SEP, suggesting potential for mediation. However, methodological limitations included the use of cross-sectional data, insufficient confounder adjustment, heterogeneity in measuring both SEP and malaria, and generally low or moderate-quality studies. No studies considered exposure mediator interactions or considered identifiability assumptions. Conclusions Few studies have conducted formal mediation analyses to elucidate pathways between SEP and malaria. Findings indicate that food security and housing could be more feasible (structural) intervention targets. Further research using well-designed longitudinal studies and improved analysis would illuminate the current sparse evidence into the pathways between SEP and malaria and adduce evidence for more potential targets for effective intervention. Graphical Abstract

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