False-positive Malaria Rapid Diagnostic Tests are Prevalent Among Children Under 5 Years of Age in Uganda

Journal article

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 2018–2019 Uganda Malaria Indicator Survey (MIS). 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.

Authors: Cassidy, CA; Shook-Sa, BE; Boyce, RM; Ciccone, EJ; Gower, EW

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: The Journal of Infectious Diseases
• Volume: 233
• Issue: 3
• Pages: e782-e790
• Publication date: 2025-11-28
• Acceptance date: 2025-11-25
• DOI: 10.1093/infdis/jiaf604
• EISSN: 1537-6613
• ISSN: 0022-1899
• Language: English
• Keywords: false-positive; Malaria; antimicrobial resistance; rapid diagnostic tests; children under 5