False-positive malaria rapid diagnostic tests are prevalent among children under 5 years of age in Uganda

Background Malaria rapid diagnostic tests (mRDTs) are a cornerstone of malaria testing and treatment efforts globally. However, positive mRDT results can occur after treatment due to antigen persistence, even in the absence of malaria parasites. False-negative mRDTs are well-described, but less is known about the prevalence and consequences of such false-positive results. Methods We estimated the prevalence of false-positive mRDTs, defined as mRDT(+)/microscopy(-), using data from the 2018-19 Uganda Malaria Indicator Survey. Children aged <5 years (under-5s) with paired mRDT and microscopy results were included. We estimated the prevalence of false-positive mRDTs among microscopy(-) children using survey weights. We fit bivariate generalized linear models to estimate the prevalence difference (PD) of false-positive mRDTs for pre-specified covariates. We constructed cross-validated weighted lasso regression models to determine which variables best predict false-positive mRDTs among children with recent fever. Results The prevalence of false-positive mRDTs was 10.7% (849/6786) and was strongly correlated with region-level transmission intensity. Prevalence was higher among children with recent fever (PD: 17.2%; 95% CI: 13.7%, 20.6%), recent antimalarial use (14.7%; 7.1%, 22.3%), and comorbid anemia (8.1%; 5.9%, 10.3%). Prevalence was lower among those with recent antibiotic use (-17.6%; -22.5%, -12.7%). A model with clinical, environmental, and household variables better predicted false-positive mRDTs (weighted AUC = 0.79) than individual models. Conclusions False-positive mRDTs are prevalent among under-5s in the 2018-19 Uganda MIS and lead to overestimates of community-level malaria prevalence. These results suggest that false-positive mRDTs may also contribute to misdiagnosis and unnecessary antimalarial use in clinical settings.