Associations of childhood exposure to malaria with cognition and behavior outcomes: a systematic review protocol

BACKGROUND: Malaria is one of the major contributing risk factors for poor development of children living in low- and middle-income countries (LMICs). However, little is known about the specific domains of cognition and behavior that are impacted by malaria, the extent of these deficits, and the different types of the malaria spectrum that are associated with these deficits. The objective of this systematic review is to determine the association of the different types of malaria infection on cognition and behavioral outcomes among children living in LMICs. METHODS AND ANALYSIS: We will systematically search online bibliographic databases including MEDLINE (via PubMed), CINAHL (via EBSCO), PsycINFO (via EBSCO), Embase, and The Cochrane Central Register of Controlled Trials (CENTRAL) as well as Google Scholar and bibliographies of pertinent articles. We will include studies with a comparison group (e.g., clinical trials, cohort, observational, cross-sectional case–control, and controlled before and after or interrupted–time–series studies) involving children under 18 years of age living in LMICs, as determined by the World Bank criteria, with either an active malaria infection or history of malaria. Included articles must also measure cognitive and/or behavior outcomes determined by standardized psychological assessments (questionnaire-based scales and or neurocognitive assessments). Studies will be excluded if they are not in English, lack a control group, take place in a high-income country, or if a standardized instrument was not used. Two reviewers will independently review all articles to determine if they meet eligibility criteria. Any conflicts will be resolved after discussion with a third reviewer. When a list of included articles is finalized, two reviewers will extract data to populate and then cross check within an electronic table. Risk of bias and the strength of evidence and recommendations will be assessed independently using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and a final score will be given upon consensus. For sufficiently homogeneous data on measured outcomes in multiple studies, we will investigate the possibility of pooling data to perform a meta-analysis. DISCUSSION: This systematic review will evaluate the evidence of the association of malaria on the cognitive and behavioral outcomes. Findings from this planned review will generate insight on the domains affected by the different forms of malaria infection and may inform subsequent malaria interventions and future research in pediatric care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020154777