Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa

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Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control.</p> <p>Methods</p> <p>In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined.</p> <p>Results</p> <p>The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent.</p> <p>Discussion</p> <p>The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible</p> <p>Conclusions</p> <p>The GM allotypes have significant influence on susceptibility to uncomplicated <it>P. falciparum </it>malaria and antigen-dependent influence on total IgG and IgG subclasses.</p

Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa

Raised plasma insulin level and homeostasis model assessment (HOMA) score in cerebral malaria: evidence for insulin resistance and marker of virulence

Objective: To study the glycaemic profile of patients with severe malaria (SM). Methods: For this purpose, 110 SM patients were recruited. Pre-treatment random blood glucose and plasma insulin were measured in a subset of donors. An ex-vivo experiment was developed for estimation of glucose consumption by parasitized erythrocytes. Results: Hyperglycaemia was frequent in SM but more commonly associated with cerebral malaria (CM), while hyperinsulinaemia was recognized in severe-malarial-hypotension (median, 25 %-75 %, 188.2, 93.8-336.8 pmol/L). The plasma insulin level was positively correlated with age (CC = 0.457, p < 0.001) and negatively with parasitaemia (CC = -0.368, p = 0.045). Importantly, fatal-CM was associated with hyperglycaemia (12.22, 6.5-14.6 mmol/L), hyperinsulinaemia (141.0, 54.0-186.8 pmol/L) and elevated homeostasis model assessment (HOMA) values. However, there was a trend of higher glucose consumption by parasites in CM compared with that in uncomplicated malaria (UM). Conclusion: Hyperglycaemia, hyperinsulinaemia and elevated HOMA are evidence for insulin resistance and possibly pancreatic B-cell dysfunction in fatal-CM

FcγRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan

Abstract Background A SNP at position 131, in the FcγRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcγRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria. Methods Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcγRIIa-131 polymorphism. For comparison, 101 non-Fulani donors – (Masaleit, Hausa and Four) – living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses) to four malaria antigens (AMA-1, MSP 2 – 3D7 & FC27, Pf332-C231) were measured using indirect enzyme-linked immunosorbent assays. Results The FcγRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61–5.97, P value Conclusion The FcγRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.</p

The implication of <it>dihydrofolate reductase </it>and <it>dihydropteroate synthetase </it>gene mutations in modification of <it>Plasmodium falciparum </it>characteristics

Abstract Background The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. Objective To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. Method Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. Results & conclusion Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus.</p