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

Research

Christopher Membi¹  Salim Abdullah¹  Pamela Onyor²  Bernhards Ogutu²  John Barnwell³  Claribel Murillo⁴  Diego F Echeverry⁴  James McCarthy⁵  Anita Pelecanos⁶  Michelle Gatton⁶  Wellington Oyibo⁷  Nanhua Chen⁸  Mei-Fong Ho⁹  Qin Cheng^1,10  Joanne Baker^1,11  Myat Phone Kyaw^1,12  Audrey Albertini^1,13  David Bell^1,14  Shan Qing Wang^1,15  Djibrine Djalle^1,16  Didier Menard^1,17  Dionicia Gamboa^1,18  Frederic Ariey^1,19  Sina Nhem^1,19  Jennifer Luchavez^2,20  Jane Cunningham^2,21  Jeffery Hii^2,22 

[1] Bagamoyo/Ifakara Health Research and Development Centre, Ifakara, United Republic of Tanzania;Centre for Clinical Research, Kenya Medical Research Institute, Kisumu, Kenya;Centre for Disease Control and Prevention, Atlanta, USA;Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali, Colombia;Clinical Tropical Medicine Laboratory, Queensland Institute of Medical Research, University of Queensland, Herston, Australia;Clinical Tropical Medicine Laboratory, Queensland Institute of Medical Research, University of Queensland, Herston, Australia;Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Herston, Australia;College of Medicine, University of Lagos, Odoaraba, Lagos, Nigeria;Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;Clinical Tropical Medicine Laboratory, Queensland Institute of Medical Research, University of Queensland, Herston, Australia;Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Herston, Australia;Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;School of Population Health, University of Queensland, Herston, Queensland, Australia;Department of Medical Research (Lower Myanmar), Yangon, Myanmar;Foundation for Innovative and New Diagnostics, Geneva, Switzerland;Foundation for Innovative and New Diagnostics, Geneva, Switzerland;Global Malaria Programme, World Health Organization, Geneva, Switzerland;Hainan Provincial Centre for Disease Control and Prevention, Haikou, Hainan, China;Institut Pasteur de Bangui, Bangui, Central African Republic;Institut Pasteur de Madagascar, Madagascar;Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Peru;Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Peru;Pasteur Institute of Cambodia, Phnom Penh, Cambodia;Research Institute for Tropical Medicine, Alabang, The Philippines;UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland;Western Pacific Regional Office of the World Health Organization, Solomon Islands;

关键词: Malaria;    Rapid Diagnostic Test;    Parasite Density;    Subtelomeric Region;    Repeat Type;   

DOI  :  10.1186/1475-2875-9-129

 received in 2010-03-08, accepted in 2010-05-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAccurate 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.MethodsThe 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.ResultsSequence 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.ConclusionsThe results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

【 授权许可】

Unknown   
© Baker et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. 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.