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Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests
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Journal Article
Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests
2014
Overview
Background
The Senegalese National Malaria Control Programme has recommended use of rapid diagnostic tests (RDTs) that target the histidine-rich protein 2 (HRP2), specific to
Plasmodium falciparum,
to diagnose malaria cases. The target antigen has been shown to be polymorphic, which may explain the variability in HRP2-based RDT results reported in field studies. The genetic diversity of the
pfhrp2
gene has not been investigated in depth in many African countries. The goal of this study is to determine the extent of polymorphism in
pfhrp2
among Senegal, Mali and Uganda parasite populations, and discuss the implications of these findings on the utility of RDTs that are based on HRP2 detection.
Methods
Sequencing data from the
pfhrp2
locus were used to analyze the genetic diversity of this gene among three populations, with different transmission dynamics and malaria parasite ecologies. Nucleotide diversity (π) and non-synonymous nucleotide diversity (π
NS
) were studied in the
pfhrp2
gene from isolates obtained in Senegal. Amino acid repeat length polymorphisms in the PfHRP2 antigen were characterized and parameters of genetic diversity, such as frequency and correlation between repeats in these populations, were assessed.
Results
The diversity survey of the
pfhrp2
gene identified 29 SNPs as well as insertion and deletion polymorphisms within a 918 bp region. The Senegal
pfhrp2
exhibited a substantial level of diversity [π = 0.00559 and π
NS
= 0.014111 (π
S
= 0.0291627)], similar to several polymorphic genes, such as
msp1
, involved in immune responses, and the gene encoding the SURFIN polymorphic antigen, which are surface exposed parasite proteins. Extensive repeat length polymorphisms in PfHRP2, as well as similar patterns in the number, organization and the type of predicted amino acid repeats were observed among the three populations, characterized by an occurrence of Type 2, Type 4 and Type 7 repeats.
Conclusions
These results warrant deeper monitoring of the RDT target antigen diversity and emphasize that development of other essential genes as a target for diagnostic tools is critical.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Analysis
/ Antigens
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - genetics
/ Antigens, Protozoan - metabolism
/ Biomedical and Life Sciences
/ Genes
/ Genomics
/ Malaria
/ Malaria, Falciparum - diagnosis
/ Malaria, Falciparum - parasitology
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Repetitive Sequences, Amino Acid
/ Senegal
/ Single nucleotide polymorphisms
/ Studies
