Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests.
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 (πNS) 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 πNS = 0.014111 (πS = 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.
Awa B
AB
Deme
Daniel J
DJ
Park
Amy K
AK
Bei
Ousmane
O
Sarr
Aida Sadikh
AS
Badiane
Papa El Hadji Omar
Pel H
Gueye
Ambroise
A
Ahouidi
Omar
O
Ndir
Souleymane
S
Mboup
Dyann F
DF
Wirth
Daouda
D
Ndiaye
Broad Institute: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. svolkman@hsph.harvard.edu.
Sarah K
SK
Volkman
D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012675:Senegal
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins