Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria
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 iss...
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th-mahidol.142862018-06-11T12:06:30Z Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria Thiranut Ramutton Ilse Ce Hendriksen Juliet Mwanga-Amumpaire George Mtove Rasaq Olaosebikan Antoinette K. Tshefu Marie A. Onyamboko Corine Karema Kathryn Maitland Ermelinda Gomes Samwel Gesase Hugh Reyburn Kamolrat Silamut Kesinee Chotivanich Kamoltip Promnares Caterina I. Fanello Lorenz Von Seidlein Nicholas Pj Day Nicholas J. White Arjen M. Dondorp Mallika Imwong Charles J. Woodrow Mahidol University University of Oxford Mbarara University of Science and Technology National Institute for Medical Research Tanga Medical Research Council Laboratories Gambia Kingasani Research Centre Ministry of Health Wellcome Trust Research Laboratories Nairobi Hospital Central da Beira London School of Hygiene & Tropical Medicine Prince of Songkla University Menzies School of Health Research Immunology and Microbiology Medicine 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. © 2012 Ramutton et al. 2018-06-11T04:52:23Z 2018-06-11T04:52:23Z 2012-08-20 Article Malaria Journal. Vol.11, (2012) 10.1186/1475-2875-11-276 14752875 2-s2.0-84864948627 https://repository.li.mahidol.ac.th/handle/123456789/14286 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84864948627&origin=inward |
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Immunology and Microbiology Medicine Thiranut Ramutton Ilse Ce Hendriksen Juliet Mwanga-Amumpaire George Mtove Rasaq Olaosebikan Antoinette K. Tshefu Marie A. Onyamboko Corine Karema Kathryn Maitland Ermelinda Gomes Samwel Gesase Hugh Reyburn Kamolrat Silamut Kesinee Chotivanich Kamoltip Promnares Caterina I. Fanello Lorenz Von Seidlein Nicholas Pj Day Nicholas J. White Arjen M. Dondorp Mallika Imwong Charles J. Woodrow Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
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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. © 2012 Ramutton et al. |
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Mahidol University |
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Mahidol University Thiranut Ramutton Ilse Ce Hendriksen Juliet Mwanga-Amumpaire George Mtove Rasaq Olaosebikan Antoinette K. Tshefu Marie A. Onyamboko Corine Karema Kathryn Maitland Ermelinda Gomes Samwel Gesase Hugh Reyburn Kamolrat Silamut Kesinee Chotivanich Kamoltip Promnares Caterina I. Fanello Lorenz Von Seidlein Nicholas Pj Day Nicholas J. White Arjen M. Dondorp Mallika Imwong Charles J. Woodrow |
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Article |
author |
Thiranut Ramutton Ilse Ce Hendriksen Juliet Mwanga-Amumpaire George Mtove Rasaq Olaosebikan Antoinette K. Tshefu Marie A. Onyamboko Corine Karema Kathryn Maitland Ermelinda Gomes Samwel Gesase Hugh Reyburn Kamolrat Silamut Kesinee Chotivanich Kamoltip Promnares Caterina I. Fanello Lorenz Von Seidlein Nicholas Pj Day Nicholas J. White Arjen M. Dondorp Mallika Imwong Charles J. Woodrow |
author_sort |
Thiranut Ramutton |
title |
Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
title_short |
Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
title_full |
Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
title_fullStr |
Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
title_full_unstemmed |
Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
title_sort |
sequence variation does not confound the measurement of plasma pfhrp2 concentration in african children presenting with severe malaria |
publishDate |
2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/14286 |
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1763493979275395072 |