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...
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th-mahidol.6812023-03-31T05:25:33Z Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria 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. 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. Histidine-rich protein Malaria Severe Tandem repeat Falciparum Open Access article 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. 2013-02-27T07:55:26Z 2016-09-21T07:35:42Z 2013-02-27T07:55:26Z 2016-09-21T07:35:42Z 2012 2013-02-27 2012-08-16 Research Article 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. 10.1186/1475-2875-11-276 1475-2875 (electronic) https://repository.li.mahidol.ac.th/handle/123456789/681 eng Mahidol University BioMed Central application/pdf |
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Histidine-rich protein Malaria Severe Tandem repeat Falciparum Open Access article |
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Histidine-rich protein Malaria Severe Tandem repeat Falciparum Open Access article 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. Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria |
description |
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. |
author2 |
Woodrow, Charles J. |
author_facet |
Woodrow, Charles J. 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. |
format |
Article |
author |
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. |
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 |
2013 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/681 |
_version_ |
1763488697449185280 |