Plasmodium falciparum histidine-rich protein (PfHRP2 and 3) diversity in Western and Coastal Kenya

David Nderu,Francis Kimani,Edwin Too,Eva Nambati,William Chege,Kelvin Thiong’O,Evaline Karanja,Christian G Meyer,Thirumalaisamy P Velavan,Maureen Akinyi

doi:10.1038/s41598-018-38175-1

Abstract

Plasmodium falciparum histidine-rich proteins 2 (PfHRP2) based RDTs are advocated in falciparum malaria-endemic regions, particularly when quality microscopy is not available. However, diversity and any deletion in the pfhrp2 and pfhrp3 genes can affect the performance of PfHRP2-based RDTs. A total of 400 samples collected from uncomplicated malaria cases from Kenya were investigated for the amino acid repeat profiles in exon 2 of pfhrp2 and pfhrp3 genes. In addition, PfHRP2 levels were measured in 96 individuals with uncomplicated malaria. We observed a unique distribution pattern of amino acid repeats both in the PfHRP2 and PfHRP3. 228 PfHRP2 and 124 PfHRP3 different amino acid sequences were identified. Of this, 214 (94%) PfHRP2 and 81 (65%) PfHRP3 amino acid sequences occurred only once. Thirty-nine new PfHRP2 and 20 new PfHRP3 amino acid repeat types were identified. PfHRP2 levels were not correlated with parasitemia or the number of PfHRP2 repeat types. This study shows the variability of PfHRP2, PfHRP3 and PfHRP2 concentration among uncomplicated malaria cases. These findings will be useful to understand the performance of PfHRP2-based RDTs in Kenya.

Highlights

Microscopic examination of stained blood smears continues to serve as the gold standard for malaria diagnosis[3]
244 pfhrp[2] and 267 pfhrp[3] PCR products were successfully sequenced and their amino acid sequences deduced for an assessment of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and PFHRP3 diversity, respectively
PfHRP2 and PfHRP3 amino acid sequence diversity among Kenyan P. falciparum isolates was characterised by differences in the frequency, occurrence and structural organisation of different amino acid repeat types

Summary

Introduction

Microscopic examination of stained blood smears continues to serve as the gold standard for malaria diagnosis[3]. It is not readily available in resource-limited areas due to the scarcity of skilled personnel, reliable electricity supply, good quality reagents and infrastructure[3]. The WHO and national malaria control programmes (NMCPs) have put in place strategies to circumvent this pitfall One of these strategies is compulsory malaria testing by appropriate test systems, including rapid diagnostic tests (RDTs) prior to the prescription of antimalarial drugs. For regions where P. falciparum is predominant such as sub-Saharan Africa, the WHO recommends the use of PfHRP2-based RDTs. Eighty-three percent of RDTs procured in 2016, globally, were supplied to African countries[2].

Methods

Results

Conclusion