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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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
2013
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Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/681 |
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Institution: | Mahidol University |
Language: | English |
Summary: | 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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