False-Positive And False-Negative Malaria Rapid Diagnostic Test Results: Evidence From A Nationally Representative Survey Of Children In Ghana

Abstract

Background Malaria remains a leading cause of morbidity and mortality among children under five in Ghana, where Plasmodium falciparum predominates. Rapid diagnostic tests (RDTs) are widely used for malaria case manage ment and population surveillance; however, concerns about false‑positive and false‑negative results may compro mise case detection and prevalence estimates. Objective This study aimed to (i) estimate malaria prevalence using microscopy and RDTs, (ii) evaluate the surveil lance performance of RDTs relative to microscopy, and (iii) identify socio‑demographic and household‑level predictors of false‑positive and false‑negative RDT results among Ghanaian children under 5 years. Methods We analyzed data from 4,417 children who participated in the 2022 Ghana Demographic and Health Survey (DHS). Capillary blood samples were tested using HRP2‑based RDTs and light microscopy. Weighted analyses accounted for the DHS sampling design. Malaria prevalence was estimated for both diagnostic methods, and sensi tivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for RDTs using microscopy as the reference. Logistic regression models were used to identify predictors of false‑positive and false negative results, reporting adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Malaria prevalence was 20.3% by RDT and 9.9% by microscopy. Compared to microscopy, RDTs demon strated high sensitivity (89.7%, 95% CI: 86.5–92.2) and specificity (87.4%, 95% CI: 86.3–88.4), with a PPV of 43.9% and NPV of 98.7%. False‑positive results were uncommon (1.0%) and not significantly associated with child or house hold characteristics. False‑negative results were more likely among children living in dwellings sprayed with insec ticide (aOR = 1.56, 95% CI: 1.05–2.30) and in rural areas (aOR = 0.54 for urban residence, 95% CI: 0.43–0.67), with sig nificant regional variation higher odds in Upper East (aOR = 1.93, 95% CI: 1.16–3.21) and lower odds in Greater Accra (aOR = 0.21, 95% CI: 0.07–0.63). Conclusion HRP2‑based RDTs are highly sensitive and reliable for ruling out malaria in children under five in Ghana. However, their lower PPV may lead to overestimation of malaria prevalence, particularly in high‑transmission rural areas and IRS‑targeted districts. Programmatic use of RDT‑based prevalence data should account for this limitation, and confirmatory microscopy or molecular data should be incorporated where feasible. Continued surveillance of pfhrp2/3 deletions and post‑treatment HRP2 persistence is warranted to sustain diagnostic accuracy.