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

Ramutton, Thiranut, Hendriksen, Ilse C. E., Mwanga-Amumpaire, Juliet, Mtove, George, Olaosebikan, Rasaq, Tshefu, Antoinette K., Onyamboko, Marie A., Karema, Corine, Maitland, Kathryn, Gomes, Ermelinda, Gesase, Samwel, Reyburn, Hugh, Silamut, Kamolrat, Chotivanich, Kesinee, Promnares, Kamoltip, Fanello, Caterina I., von Seidlein, Lorenz, Day, Nicholas P. J., Dondorp, Arjen M., White, Nicholas J. and et al. (2012). Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. Malaria Journal,11(276):1-7.

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Title Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria
Author Ramutton, Thiranut
Hendriksen, Ilse C. E.
Mwanga-Amumpaire, Juliet
Mtove, George
Olaosebikan, Rasaq
Tshefu, Antoinette K.
Onyamboko, Marie A.
Karema, Corine
Maitland, Kathryn
Gomes, Ermelinda
Gesase, Samwel
Reyburn, Hugh
Silamut, Kamolrat
Chotivanich, Kesinee
Promnares, Kamoltip
Fanello, Caterina I.
von Seidlein, Lorenz
Day, Nicholas P. J.
Dondorp, Arjen M.
White, Nicholas J.
et al.
Journal Name Malaria Journal
Publication Date 2012
Volume Number 11
Issue Number 276
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84864948627
Start Page 1
End Page 7
Total Pages 7
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
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
DOI http://dx.doi.org/10.1186/1475-2875-11-276   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes 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.


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