Diagnostic predictive value of suspected false-negative HRP2-based RDT results for detecting pfhrp2/pfhrp3 gene deletions across diverse transmission settings: evidence from Kebbi State, Nigeria

Abstract

The persistence of malaria burden in Nigeria despite widespread use of histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) calls for investigations into Plasmodium falciparum parasites with pfhrp2 and pfhrp3 gene deletions that can cause false-negative test results. This study assessed the diagnostic predictive value of suspected false-negative HRP2-based RDT results for detecting pfhrp2/pfhrp3 gene deletions across varying transmission settings in Kebbi State, Nigeria. A cross-sectional study involving 3,000 febrile patients was conducted in selected health facilities between June and October 2024. HRP2-based RDTs were performed alongside PCR genotyping for P. falciparum confirmation and pfhrp2/pfhrp3 deletion detection. Of the 900 PCR-positive samples, 45 (5.0%) were HRP2-RDT negative and PCR positive, of which 20 (44.4%) were confirmed to have pfhrp2/pfhrp3 deletions. The sensitivity and specificity of false-negative RDTs for predicting deletions were 66.7% and 99.2%, respectively. The findings suggest that HRP2-based RDT false-negatives can serve as a strong early warning indicator for pfhrp2/pfhrp3 gene deletions in Nigeria’s malaria surveillance programs.