Prevalence of malaria parasite infection in pregnant women in three towns of the South West Region of Cameroon

The study was designed to investigate the prevalence and density of Plasmodium infection in 206 pregnant Cameroonian women and to assess their anaemic status. Blood samples were collected from the women during three consecutive antenatal clinical visits and examined for the detection and quantification of malaria parasites and determination of packed cell volume. The results revealed that the prevalence of malaria parasitaemia was 43.2% on the first antenatal visit, 25.2% on the second visit and 6.8% on the third visit. Significantly more primigravidae (54.5%) than multigravidae (32.7%), and more single women (55.3%) than married women (31.1%) were positive for malaria parasitaemia on the first visit (P<0.001). The infection rates varied significantly (P<0.02) with the location of the clinics, the highest prevalence being recorded in Muea. The prevalence decreased progressively during subsequent antenatal visits, irrespective of gravidity status, marital status or clinic of attendance. Significantly more younger women (= or < 20years) were positive for malaria parasitaemia than older women (> 20years) on the first andsecond visits (P<0.001). Geometric mean parasite density was higher in primigravidae and single women than in multigravidae and married women, but the difference was significant only between single and married women (P<0.02). The prevalence of anaemia (PVC<31%) was 53.4% on the first antenatal visit, 50.0% on the second and 28.2% on the third antenatal visit. The prevalence was higher among primigravidae, single women and women less than or equal to 20years of age than in multigravidae, married women and women above 20years of age. Plasmodium falciparum was the only species observed in this studyKey words: Plasmodium, parasitaemia, anaemia, packed cell volume, antenatal, primigravidae, multigravidaeLe présent projet a pour objet d'étude la prévalence, la densité de l'infection au Plasmodium chez 206 femmes camerounaises en gestation, et l'évaluation de leur degré d'anémie. Des échantillons de sang ont été prélevés chez les sujets lors de trois visites prénatales consécutives et analysés en vue de la détection et de la quantification des parasites vecteurs du paludisme ainsi que l’évaluation de la valeur hématocrite. Les résultats obtenus ont révélé une prévalence de parasites vecteurs du paludisme de 43,2% lors de la première visite prénatale, de 25,2% lors de la deuxième et de 6,8% lors de la troisième. Les primipares (54, 5%) et les femmes célibataires (55,3%) se sont revelées beaucoup plus infectées lors de la première visite anténatale (P<0,001) que les multipares ( 32,7%) et les femmes mariées (31.1%). Le taux d'infection variait beaucoup (P<0,02) d'un Centre de Santé à l'autre; le taux de prévalencele plus important fut enregistré à Muea. Pendant les visites subséquentes à la première, le taux de prévalence diminuait progressivement, indépendamment de l'état de la grossesse, du statut ou de la clinique visitée. Les examens de laboratoire faits lors de la première et de la deuxième visites prénatales ont montré que les très jeunes femmes (20 ans ou moins) sont plus victimes de la parasitémie du paludisme que celles qui sont plus agées. La quantité de parasites était plus importante chez les primipares célibataires que chez les multipares mariées. Toutefois, la plus grande différence fut détectée lorsque l'on passait des femmes célibataires aux femmes mariées (P<0,02). La prévalence de l'anémie (PVC<31%) quant à elle, était de 53% lors de la première visite prénatale, de 50% lors de la deuxième visite, et de 28,2% lors de la troisième. Au sein de cette population exposée, il s'est avéré que lesprimipares, les célibataires et les agées de 20 ans ou moins preséntent les taux de prévalence les plus élevés comparativement à leurs congénères respectivement multipares, mariées ou plus agées. Le Plasmodium falcipanum fut la seule espèce découverte lors de cette investigation.Mots clés: Plasmodium, parasitémie, anémie, valeur hématocrite, prénatal, primipare, multipar

Plasmodium falciparum population dynamics in a cohort of pregnant women in Senegal

<p>Abstract</p> <p>Background</p> <p>Pregnant women acquire protective antibodies that cross-react with geographically diverse placental <it>Plasmodium falciparum </it>isolates, suggesting that surface molecules expressed on infected erythrocytes by pregnancy-associated malaria (PAM) parasites have conserved epitopes and, that designing a PAM vaccine may be envisaged. VAR2CSA is the main candidate for a pregnancy malaria vaccine, but vaccine development may be complicated by its sequence polymorphism.</p> <p>Methods</p> <p>The dynamics of <it>P. falciparum </it>genotypes during pregnancy in 32 women in relation to VAR2CSA polymorphism and immunity was determined. The polymorphism of the <it>msp2 </it>gene and five microsatellites was analysed in consecutive parasite isolates, and the <it>DBL5ε + Interdomain 5 </it>(<it>Id5</it>) part of the <it>var2csa </it>gene of the corresponding samples was cloned and sequenced to measure variation.</p> <p>Results</p> <p>In primigravidae, the multiplicity of infection in the placenta was associated with occurrence of low birth weight babies. Some parasite genotypes were able to persist over several weeks and, still be present in the placenta at delivery particularly when the host anti-VAR2CSA antibody level was low. Comparison of diversity among genotyping markers confirmed that some PAM parasites may harbour more than one <it>var2csa </it>gene copy in their genome.</p> <p>Conclusions</p> <p>Host immunity to VAR2CSA influences the parasite dynamics during pregnancy, suggesting that the acquisition of protective immunity requires pre-exposure to a limited number of parasite variants. Presence of highly conserved residues in surface-exposed areas of the VAR2CSA immunodominant DBL5ε domain, suggest its potential in inducing antibodies with broad reactivity.</p

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations

Resistance to malaria through structural variation of red blood cell invasion receptors

Plasmodium falciparum invades erythrocytes via interactions with proteins on the host cell surface. By analyzing genome sequence data from human populations, including 1269 African individuals, we identify a diverse array of large copy number variants affecting the erythrocyte invasion receptor genes GYPA and GYPB. We find that a nearby association with severe malaria is explained by a complex structural rearrangement that involves the loss of GYPB and gain of two hybrid genes, each with a GYPB extracellular domain and GYPA intracellular domain. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya. We show that the structural variant encodes the Dantu blood group antigen, a serologically distinct red cell phenotype. Thus structural variation of erythrocyte invasion receptors is associated with natural resistance to severe malaria

A novel locus of resistance to severe malaria in a region of ancient balancing selection

Malaria Genomic Epidemiology Network The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio= 0.67, 95% confidence interval= 0.60-0.76, P value= 9.5× 10-11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host-parasite interactions that are critical in determining the outcome of malaria infection

Reappraisal of known malaria resistance loci in a large multicenter study

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed