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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.

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