Open Access Research

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

Thiranut Ramutton1, Ilse CE Hendriksen23, Juliet Mwanga-Amumpaire4, George Mtove5, Rasaq Olaosebikan6, Antoinette K Tshefu7, Marie A Onyamboko7, Corine Karema8, Kathryn Maitland9, Ermelinda Gomes10, Samwel Gesase11, Hugh Reyburn12, Kamolrat Silamut2, Kesinee Chotivanich2, Kamoltip Promnares1314, Caterina I Fanello23, Lorenz von Seidlein15, Nicholas PJ Day23, Nicholas J White23, Arjen M Dondorp23, Mallika Imwong162* and Charles J Woodrow23*

Author Affiliations

1 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

2 Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

3 Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, UK

4 Mbarara University of Science and Technology and Epicentre Research Base, Mbarara, Uganda

5 National Institute for Medical Research, Amani Centre, Tanga, Tanzania

6 MRC laboratories, Banjul, The Gambia

7 Kinshasa School of Public Health, Kingasani Research Centre, Kinshasa, DRC

8 Malaria Control Program, Ministry of Health, Kigali, Rwanda

9 Kenya Medical Research Institute (KEMRI)–Wellcome Trust Research Programme, Kilifi, Kenya

10 Hospital Central da Beira, Beira, Mozambique

11 National Institute for Medical Research, Korogwe Research Laboratory, Tanga, Tanzania

12 London School of Tropical Medicine and Hygiene, London, UK

13 Department of Molecular Biotechnology and Bioinformatics, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

14 Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

15 Menzies School of Health Research, Casuarina, NT, Australia

16 Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

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Malaria Journal 2012, 11:276  doi:10.1186/1475-2875-11-276

Published: 16 August 2012

Abstract

Background

Plasmodium 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.

Methods

Studies 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.

Results

There 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.

Conclusions

These 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.

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