Country-wide assessment of the genetic polymorphism in Plasmodium falciparum and Plasmodium vivax antigens detected with rapid diagnostic tests for malaria

Mariette, N.; Barnadas, Céline; Bouchier, Christiane; Tichit, Magali; Ménard, Didier

doi:10.1186/1475-2875-7-219

Cited by 62 publications

(110 citation statements)

References 20 publications

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“…The PCR products of the exon 2 were cloned in the T-vector (Takara Biotechnology, Dalian, China) for sequencing. For amplification of pfhrp3 , primers targeting exon 2 (+77 nt – +180 nt) were used (Baker et al, 2005; Mariette et al, 2008; Trouvay et al, 2013). Samples were considered pfhrp2 -negtive or pfhrp3 -negtive if amplifications were not successful after two attempts.…”

Section: Methodsmentioning

confidence: 99%

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

Li¹,

Hua

Zhao³

et al. 2015

Acta Tropica

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Deletion of the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene may affect the performance of PfHRP2-based rapid diagnostic tests (RDTs). Here we investigated the genetic diversity of the pfhrp2 gene in clinical parasite isolates collected in recent years from the China-Myanmar border area. Deletion of pfhrp2 has been identified in 4 out of 97 parasite isolates. Sequencing of the pfhrp2 exon 2 from 67 isolates revealed a high level of genetic diversity in pfhrp2, which is reflected in the presence of many repeat types and their variants, as well as variable copy numbers and different arrangements of these repeats in parasite isolates. In addition, we observed pfhrp3 deletion in three of the four parasites harboring pfhrp2 deletion, suggesting of double deletions of both genes in these three isolates. Analysis of two cases, which were P. falciparum-positive by microscopy and PCR but failed by two PfHRP2-based RDTs, did not find pfhrp2 deletion. Further correlational studies of pfhrp2 polymorphisms with detection sensitivity are needed to identify factors influencing the performance of RDTs in malaria-endemic areas.

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Section: Methodsmentioning

confidence: 99%

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

Li¹,

Hua

Zhao³

et al. 2015

Acta Tropica

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“…Many studies of the genetic diversity of this antigen show extensive variation within isolates of the same country and between isolates of different countries [10,11,15]. In Senegal, the genetic diversity of the gene target by the RDT has not yet been investigated in depth.…”

Section: Introductionmentioning

confidence: 99%

Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests

Déme

Park

Bei

et al. 2014

Malar J

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BackgroundThe 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.MethodsSequencing 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.ResultsThe 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.ConclusionsThese 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.

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“…One can observe mixed infections with more than one species of Plasmodium in one single individual; coexistence of diverse Plasmodium species infecting populations living in the same area is also frequently encountered. All this pinpoints the need for quick, reliable, sensitive techniques for diagnostic of malaria-causative species (ideally also applicable in remote and poor areas [73]). Lastly, if a drug targeting DARC was designed, it should be carefully checked that it does not interfere with the normal functions of DARC which presently are not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

Smolarek

Hattab

Hassanzadeh-Ghassabeh

et al. 2010

Cell. Mol. Life Sci.

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Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

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Country-wide assessment of the genetic polymorphism in Plasmodium falciparum and Plasmodium vivax antigens detected with rapid diagnostic tests for malaria

Cited by 62 publications

References 20 publications

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China–Myanmar border area

Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

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