Journal Article

Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

Membi, Christopher, Ariey, Frederic, Djalle, Djibrine, Oyibo, Wellington, Pelecanos, Anita, Nhem, Sina, Wang, Shan Qing, Cunningham, Jane, Chen, Nanhua, Luchavez, Jennifer, Abdullah, Salim, Cheng, Qin, Echeverry, Diego F, Ogutu, Bernhards, Menard, Didier, Hii, Jeffery, Albertini, Audrey, Kyaw, Myat Phone, McCarthy, James, Murillo, Claribel, Gamboa, Dionicia, Onyor, Pamela, Baker, Joanne, Barnwell, John, Bell, David, Ho, Mei-Fong, Gatton, Michelle

2010

Overview

Background Accurate 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. Methods The 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. Results Sequence 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. Conclusions The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amino acids / Animals / Antigens / Antigens, Protozoan / Antigens, Protozoan - genetics / Antigens, Protozoan - immunology / Biomedical and Life Sciences / Biomedicine / Case management / Causes of / Deoxyribonucleic acid / Detection / Diagnosis / Diagnostic tests / DNA / DNA, Protozoan / DNA, Protozoan - genetics / Entomology / Ethics / Genes / Genetic aspects / Genetic Variation / Health aspects / Histidine / Human diseases / Humans / Immunoassay / Immunoassay - methods / Immunoassay - standards / Infectious Diseases / Investigations / Laboratories / Life Sciences / Malaria / Malaria, Falciparum / Malaria, Falciparum - diagnosis / Malaria, Falciparum - genetics / Malaria, Falciparum - parasitology / Medical tests / Microbiology / Mortality / Nucleotide sequence / Other / Parasites / Parasitology / Plasmodium falciparum / Plasmodium falciparum - genetics / Plasmodium falciparum - immunology / Plasmodium falciparum - isolation & purification / Polymerase Chain Reaction / Product testing / Proteins / Protozoan Proteins / Protozoan Proteins - genetics / Protozoan Proteins - immunology / Public Health / Quality control / Reagent Kits, Diagnostic / Sensitivity and Specificity / Sequence analysis / Sequence Analysis, DNA / Sequencing / Statistical analysis / Statistical methods / Tropical Medicine / Variation / Vector-borne diseases