Abstract

BackgroundAccurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.MethodsThe pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs.ResultsSequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified.ConclusionsThe results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

Highlights

  • Accurate diagnosis is essential for prompt and appropriate treatment of malaria

  • To investigate whether a correlation existed between amino acid length of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and P. falciparum histidine-rich protein 3 (PfHRP3), we examined the relationship of total amino acid length for both genes

  • PfHRP2 and PfHRP3 amino acid length correlation To examine whether a correlation existed between amino acid length of PfHRP2 and PfHRP3, we examined the relationship of total amino acid length for both genes

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Summary

Introduction

While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. Rapid diagnostic tests (RDTs) for malaria have the potential to improve case management and thereby reduce morbidity and mortality, especially in remote areas, facilitating the timely delivery of appropriate treatment. The protein is found circulating in the peripheral blood of infected individuals [19] These features make PfHRP2 a good target for diagnosis of P. falciparum infection

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