Prevalence of Plasmodium falciparum parasites with pfhrp2 exon 2 gene deletion in symptomatic malaria patients across Ghana in 2021

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BACKGROUND: Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (PfHRP2-based RDTs) are the most widely used malaria RDTs across Africa. The emergence and spread of pfhrp2 gene-deleted parasites have prompted nationwide surveillance to monitor trends and potential hotspots for P. falciparum with pfhrp2 gene deletions. This study evaluated the prevalence and distribution of P. falciparum with pfhrp2 gene deletions in Ghana in 2021. METHODS: HRP2 RDT (First Response RDT) and the CareStart™ HRP2/panLDH Combo RDT (Combo kit) to screen individuals with suspected malaria seeking care in 160 public healthcare facilities across the 16 regions of Ghana between June and August 2021. Whole blood was collected from each study participant and used to prepare filter paper blood spots. Genomic DNA (gDNA) was extracted from the dried blood spots. Polymerase chain reaction (PCR) was used to amplify and confirm the presence of P. falciparum and, subsequently, the pfhrp2 gene in each sample . RESULTS: The overall malaria positivity for the two RDTs was similar: 72.3% (95% CI: 71.4-73.2) for the First Response RDT and 71.5% (95% CI: 70.6-72.4) for the HRP2/panLDH Combo kit (p = 0.215). There were no pfhrp2 exon 2 gene deletions resulting from a false negative RDT, however, deletions were identified in 0.3% (19/5,611) of samples that tested positive for both the First Response RDT and the panLDH band of the Combo kit, and 9.1% (2/22) of the missed infections, leading to an overall pfhrp2 exon 2 gene deletion of 0.4% (21/5,633) in the population. CONCLUSION: No false negative sample was identified in this study, and less than 1% of parasites with pfhrp2 gene deletions (mainly from RDT positive samples) were found in the population . This finding offers assurance for the continued reliance on HRP2-based RDTs for malaria screening in public health clinics in Ghana. Nonetheless, continued surveillance is needed to determine the expansion of P. falciparum with these gene deletions.

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