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

Joanne Baker 1, 2 Mei-Fong Ho 1, 3 Anita Pelecanos 3, 4 Michelle Gatton 3, 4 Nanhua Chen 1 Salim Abdullah 5 Audrey Albertini 6 Frederic Ariey 7 John Barnwell 8 David Bell 6, 9 Jane Cunningham 10 Djibrine Djalle 11, * Diego F Echeverry 12 Dionicia Gamboa 13, 14 Jeffery Hii 15 Myat Phone Kyaw 16 Jennifer Luchavez 17 Christopher Membi 5 Didier Menard 18 Claribel Murillo 12 Sina Nhem 7 Bernhards Ogutu 19 Pamela Onyor Wellington Oyibo 20 Shan Qing Wang 21 James Mccarthy 3 Qin Cheng 1, 4
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.
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Submitted on : Friday, November 26, 2010 - 5:29:02 PM
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Joanne Baker, Mei-Fong Ho, Anita Pelecanos, Michelle Gatton, Nanhua Chen, et al.. 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, BioMed Central, 2010, 9, pp.129. ⟨10.1186/1475-2875-9-129⟩. ⟨pasteur-00540480⟩

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