TY - JOUR
T1 - Sequence variation in Plasmodium falciparum merozoite surface protein-2 is associated with virulence causing severe and cerebral malaria
AU - Chaorattanakawee, Suwanna
AU - Nuchnoi, Pornlada
AU - Hananantachai, Hathairad
AU - Tumkosit, Uranan
AU - Saunders, David
AU - Naka, Izumi
AU - Ohashi, Jun
AU - Patarapotikul, Jintana
N1 - Funding Information:
This study was supported by the Thammasat university research grant and the Thailand Research Fund through the Royal Golden Jubilee PhD programme. The study was partially supported for publication by the China Medical Board (CMB), Faculty of Public Health, Mahidol University, Bangkok, Thailand. We sincerely thank the malaria patients who participated in this study. We are appreciative of Information Technology staffs at Faculty of Public Heath, Mahidol University for assistance with preparation of illustrations and figures.
Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2018/1
Y1 - 2018/1
N2 - Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.
AB - Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.
UR - http://www.scopus.com/inward/record.url?scp=85040717148&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0190418
DO - 10.1371/journal.pone.0190418
M3 - Article
C2 - 29342212
AN - SCOPUS:85040717148
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0190418
ER -