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 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.
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Thiranut
T
Ramutton
Ilse C E
IC
Hendriksen
Juliet
J
Mwanga-Amumpaire
George
G
Mtove
Rasaq
R
Olaosebikan
Antoinette K
AK
Tshefu
Marie A
MA
Onyamboko
Corine
C
Karema
Kathryn
K
Maitland
Ermelinda
E
Gomes
Samwel
S
Gesase
Hugh
H
Reyburn
Kamolrat
K
Silamut
Kesinee
K
Chotivanich
Kamoltip
K
Promnares
Caterina I
CI
Fanello
Lorenz
L
von Seidlein
Nicholas P J
NP
Day
Nicholas J
NJ
White
Arjen M
AM
Dondorp
Mallika
M
Imwong
Charles J
CJ
Woodrow
D000953:Antigens, Protozoan / Q000097:blood* / Q000235:genetics*; D002648:Child; D019411:Clinical Laboratory Techniques / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis*; D009073:Mozambique; D018512:Parasitemia / Q000175:diagnosis*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000097:blood* / Q000235:genetics*; D012680:Sensitivity and Specificity; D017384:Sequence Deletion; D013636:Tanzania
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins