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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-276) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

TR and KP carried out the molecular biology. IH, JM-A, GM, RO, AT, MO, CK, KM, EG, SG, LvS and HR were responsible for clinical data. KS and KC were responsible for parasitological data. TR, IH, CIF, NW, ND, AD, MI and CW participated in the design of the study. TR, KP, MI and CW were responsible for data analysis and management. TR, MI and CW drafted the manuscript. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Literatur
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