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

Baker, Joanne, Ho, Mei-Fong, Pelecanos, Anita M., Gatton, Michelle L., Chen, Nanhua, Abdullah, Salim, Albertini, Audrey, Ariey, Frederic, Barnwell, John, Bell, David, Cunningham, Jane, Djalle, Djibrine, Echeverry, Diego F., Gamboa, Dionicia, Hii, Jeffery, Kyaw, Myat Phone, Luchavez, Jennifer, Membi, Christopher, Menard, Didier, Murillo, Claribel, Nhem, Sina, Ogutu, Bernhards, Onyor, Pamela, Oyibo, Wellington, Wang, Shan Qing, McCarthy, James, & Cheng, Qin (2010) Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests. Malaria Journal, 9(129).

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Abstract

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.

Impact and interest:

48 citations in Scopus
43 citations in Web of Science®
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ID Code: 75117
Item Type: Journal Article
Refereed: Yes
Keywords: Plasmodium falciparum, histidine-rich protein, HPR2, malaria, diagnostics, sequence analysis, rapid diagnostic tests
DOI: 10.1186/1475-2875-9-129
ISSN: 1475-2875
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800) > Medical Parasitology (110803)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Public Health and Health Services not elsewhere classified (111799)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2010 Baker et al; licensee BioMed Central Ltd.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 25 Aug 2014 03:49
Last Modified: 27 Aug 2014 00:06

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