BACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.
BACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparummalaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.
Authors: B Fenton; J T Clark; C M Khan; J V Robinson; D Walliker; R Ridley; J G Scaife; J S McBride Journal: Mol Cell Biol Date: 1991-02 Impact factor: 4.272
Authors: S Viriyakosol; N Siripoon; C Petcharapirat; P Petcharapirat; W Jarra; S Thaithong; K N Brown; G Snounou Journal: Bull World Health Organ Date: 1995 Impact factor: 9.408
Authors: Lauren Gong; Catherine Maiteki-Sebuguzi; Philip J Rosenthal; Alan E Hubbard; Chris J Drakeley; Grant Dorsey; Bryan Greenhouse Journal: Blood Date: 2012-02-10 Impact factor: 22.113
Authors: Godfree Mlambo; David Sullivan; Susan L Mutambu; White Soko; Joel Mbedzi; James Chivenga; Thomas Jaenisch; Armin Gemperli; Nirbhay Kumar Journal: Acta Trop Date: 2007-05-22 Impact factor: 3.112
Authors: Fousseyni S Touré; Odile Ouwe-Missi-Oukem-Boyer; Jérôme Mezui-Me-Ndong; Guy Roger Ndong-Atome; Ulrick Bisvigou; Dominique Mazier; Sylvie Bisser Journal: Clin Med Res Date: 2007-06
Authors: Gavin Band; Ellen M Leffler; Muminatou Jallow; Fatoumatta Sisay-Joof; Carolyne M Ndila; Alexander W Macharia; Christina Hubbart; Anna E Jeffreys; Kate Rowlands; Thuy Nguyen; Sónia Gonçalves; Cristina V Ariani; Jim Stalker; Richard D Pearson; Roberto Amato; Eleanor Drury; Giorgio Sirugo; Umberto d'Alessandro; Kalifa A Bojang; Kevin Marsh; Norbert Peshu; Joseph W Saelens; Mahamadou Diakité; Steve M Taylor; David J Conway; Thomas N Williams; Kirk A Rockett; Dominic P Kwiatkowski Journal: Nature Date: 2021-12-09 Impact factor: 49.962