Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria

Malaria Journal

Research

Thiranut Ramutton¹  Kamoltip Promnares²  Ermelinda Gomes³  Kathryn Maitland⁴  Marie A Onyamboko⁵  Antoinette K Tshefu⁵  Hugh Reyburn⁶  Rasaq Olaosebikan⁷  Kamolrat Silamut⁸  Kesinee Chotivanich⁸  Charles J Woodrow⁹  Caterina I Fanello⁹  Nicholas J White⁹  Ilse CE Hendriksen⁹  Arjen M Dondorp⁹  Nicholas PJ Day⁹  Mallika Imwong^1,10  Corine Karema^1,11  Juliet Mwanga-Amumpaire^1,12  Lorenz von Seidlein^1,13  George Mtove^1,14  Samwel Gesase^1,15 

[1] Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Department of Molecular Biotechnology and Bioinformatics, Faculty of Science, Prince of Songkla University, 90112, Hat Yai, Songkhla, Thailand;Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, 90112, Hat Yai, Songkhla, Thailand;Hospital Central da Beira, Beira, Mozambique;Kenya Medical Research Institute (KEMRI)–Wellcome Trust Research Programme, Kilifi, Kenya;Kinshasa School of Public Health, Kingasani Research Centre, Kinshasa, DRC;London School of Tropical Medicine and Hygiene, London, UK;MRC laboratories, Banjul, The Gambia;Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK;Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Malaria Control Program, Ministry of Health, Kigali, Rwanda;Mbarara University of Science and Technology and Epicentre Research Base, Mbarara, Uganda;Menzies School of Health Research, Casuarina, NT, Australia;National Institute for Medical Research, Amani Centre, Tanga, Tanzania;National Institute for Medical Research, Korogwe Research Laboratory, Tanga, Tanzania;

关键词: Malaria;    Falciparum;    Severe;    Africa;    Histidine-rich protein;    Tandem repeat;   

DOI  :  10.1186/1475-2875-11-276

 received in 2012-05-23, accepted in 2012-08-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPlasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements.MethodsStudies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania.ResultsThere was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration.ConclusionsThese findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection.

【 授权许可】

Unknown   
© Ramutton et al.; licensee BioMed Central Ltd. 2012. 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.