Pfhrp2 and pfhrp3 Gene Deletions That Affect Malaria Rapid Diagnostic Tests for Plasmodium falciparum: Analysis of Archived Blood Samples From 3 African Countries

Rebecca Thomson,Jane Cunningham,Khalid B Beshir,Sarah G Staedke,Katia J Bruxvoort,Heidi Hopkins,Jameel Bharmal,Catherine Maiteki-Sebuguzi,Seth Owusu-Agyei,Frank Baiden

doi:10.1093/infdis/jiz335

Abstract

BackgroundMalaria rapid diagnostic tests (mRDTs) that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis. Parasites with pfhrp2/3 gene deletions threaten the use of these mRDTs and have been reported in Africa, Asia, and South America. We studied blood samples from 3 African countries to determine if these gene deletions were present.MethodsWe analyzed 911 dried blood spots from Ghana (n = 165), Tanzania (n = 176), and Uganda (n = 570). Plasmodium falciparum infection was confirmed by 18S rDNA polymerase chain reaction (PCR), and pfhrp2/3 genes were genotyped. True pfhrp2/3 gene deletions were confirmed if samples were (1) microscopy positive; (2) 18S rDNA PCR positive; (3) positive for merozoite surface protein genes by PCR or positive by loop-mediated isothermal amplification; or (4) quantitative PCR positive with >5 parasites/µL.ResultsNo pfhrp2/3 deletions were detected in samples from Ghana, but deletions were identified in Tanzania (3 pfhrp2; 2 pfhrp3) and Uganda (7 pfhrp2; 2 pfhrp3). Of the 10 samples with pfhrp2 deletions, 9 tested negative by HRP2-based mRDT.ConclusionsThe presence of pfhrp2/3 deletions in Tanzania and Uganda, along with reports of pfhrp2/3-deleted parasites in neighboring countries, reinforces the need for systematic surveillance to monitor the reliability of mRDTs in malaria-endemic countries.

Highlights

Malaria rapid diagnostic tests that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis
This report presents an analysis of pfhrp2/3 in archived human blood samples from three African countries, alongside microscopy and Malaria rapid diagnostic tests (mRDT) results obtained in the primary studies from which the samples were drawn
Molecular analysis identified low levels of pfhrp2 and pfhrp3 gene deletions in samples from Tanzania and Uganda (2014-15), while no evidence of deletions was found t in samples from Ghana (2009-10). ip Of the ten pfhrp2-negative samples identified in this study, nine were recorded as negative by HRP2r based mRDT, seven by the mRDT used in Uganda and two by the mRDT in Tanzania

Summary

Background

Malaria rapid diagnostic tests (mRDT) that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis. Of the 10 samples with d pfhrp deletions, nine tested negative by HRP2-based mRDT. R The majority of mRDTs currently on the market detect histidine-rich protein 2 (HRP2), a parasite c antigen produced throughout the life cycle of Plasmodium falciparum, in a blood sample [3]. In Africa, the Ahighest reported prevalence of pfhrp deletions was in Eritrea, where 62% of samples that tested positive by microscopy were found to lack the pfhrp gene [5]. While fewer studies have confirmed pfhrp deletions among West African countries, a 2015 study in Ghana showed that 29% of samples lacked the pfhrp gene [15]. While awaiting the s implementation of prospective surveillance, this paper reports on stored P. falciparum samples from Accepted Manu three countries, Ghana, Tanzania, and Uganda

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Results

Discussion

28. PubMed PMID