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Title: Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria
Authors: Thiranut Ramutton
Hendriksen, Ilse CE
Mwanga-Amumpaire, Juliet
Mtove, George
Olaosebikan, Rasaq
Tshefu, Antoinette K.
Onyamboko, Marie A.
Karema, Corine
Maitland, Kathryn
Gomes, Ermelinda
Gesase, Samwel
Reyburn, Hugh
Kamolrat Silamut
Kesinee Chotivanich
เกศินี โชติวานิช
Kamoltip Promnares
Fanello, Caterina I.
Seidlein, Lorenz von
Day, Nicholas P.J.
White, Nicholas J.
Dondorp, Arjen M.
Mallika Imwong
มัลลิกา อิ่มวงศ์
Woodrow, Charles J.
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.
Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.
Woodrow, Charles J.
Keywords: Histidine-rich protein;Malaria;Severe;Tandem repeat;Falciparum;Open Access article
Issue Date: 16-Aug-2012
Citation: Ramutton T, Hendriksen IC, Mwanga-Amumpaire J, Mtove G, Olaosebikan R, Tshefu AK, et al. Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. Malar J. 2012 Aug 16;11:276.
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.
ISSN: 1475-2875 (electronic)
Appears in Collections:TM-Article

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