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. 2012 Aug 16:11:276.
doi: 10.1186/1475-2875-11-276.

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

Thiranut Ramutton  1 , Ilse C E 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 P J Day, Nicholas J White, Arjen M Dondorp, Mallika Imwong, Charles J Woodrow
Affiliations

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

Thiranut Ramutton et al. Malar J. .

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.

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Figures

Figure 1
Figure 1
PfHRP2 levels and parasitaemias for samples examined. A: samples subjected to PCR for Pfhrp2 and Pfhrp3 across all relevant AQUAMAT centres; B: samples sequenced from Mozambique and Tanzania (Teule site)
Figure 2
Figure 2
Pfhrp2 exon 2 length and repeat numbers according to country.A: frequency of each exon size (bin width of 20 bp); B: numbers of type 2 and 7 repeats in each sample
Figure 3
Figure 3
Relationship between Pfhrp2 exon 2 length and plasma level.A: individual samples; B: categorized by PFHRP2 level
See this image and copyright information in PMC

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