Plasmodium falciparum:Sickle-Cell Trait Is Associated with Higher Prevalence of Multiple Infections in Gabonese Children with Asymptomatic Infections

Ntoumi, Francine; Mercereau‐Puijalon, Odile; Ossari, Simon; Luty, Adrian J. F.; Reltien, Jérôme; Georges, A. J.; Millet, Pascal

doi:10.1006/expr.1997.4173

Cited by 53 publications

(59 citation statements)

References 32 publications

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“…These findings corroborate with those from Dakar, Senegal [20] and Mlimba, Tanzania [21], which reported 3D7 alleles to be more prevalent than FC27 in those infected with single, double and triple infections. Nevertheless, different proportions of the two allelic families in Ulanga observed in this study corroborate with the findings obtained in Dielmo, Senegal [22,23] and Sao Tome [24]. This difference of the two allelic families has been proposed to arise due to the presence of considerable heterogeneity in parasite populations [23].…”

Section: Discussionsupporting

confidence: 91%

Genetic Diversity of Plasmodium falciparum Strains in Children under Five Years of Age in Southeastern Tanzania~!2009-10-12~!2010-01-12~!2010-05-05~!

Sumari¹,

Hosea²,

Mugasa³

et al. 2010

TOTMJ

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Strain diversity may play a role in delaying development of protective immunity in endemic areas. We evaluated genetic diversity of Plasmodium falciparum infected children before being treated with Sulphadoxine Pyrimethamine (SP) and Coartem™ in Southeastern Tanzania. Allelic diversity of P. falciparum strains were determined in order to further assist in correct estimation of recrudescent and new infections.P. falciparum isolated from 300 children aged 1-59 months was used in the study, where nested PCR followed by Restriction Fragment Length Polymorphism (RFLP) of highly polymorphic Merozoite surface protein 2 (msp2) was employed to understand the genetic diversity of the parasites population. Frequency of msp2 gene alleles was calculated and further associated with multiplicity of infection of children under five years of age.A total of 71 and 83 different msp2 alleles were found in Rufiji and Ulanga districts respectively. Children infected with either FC27 or 3D7 allelic type in Rufiji were 42% single, 55.3% double and 2.7% triple, while in Ulanga, 36.7% single, 62% double and 1.3% triple infections. Mean numbers of multiplicity of infections (MOI) in Rufiji and Ulanga were 1.6 and 1.3, respectively. These findings show a high genetic diversity of P. falciparum strains in study areas and low MOI could reflect production of susceptible parasites that immune response can accommodate or can be cleared by the drugs. Furthermore, 3D7 allelic type of msp2 gene was more prevalent than FC27 in Ulanga district, indicating association between msp2 allelic type and disease severity, hence predict possible vaccine candidate in the future.

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Section: Discussionsupporting

confidence: 91%

Genetic Diversity of Plasmodium falciparum Strains in Children under Five Years of Age in Southeastern Tanzania~!2009-10-12~!2010-01-12~!2010-05-05~!

Sumari¹,

Hosea²,

Mugasa³

et al. 2010

TOTMJ

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“…We have to take into account that interactions between host and parasite polymorphisms contribute to add a further layer of complexity in the associations described here. Namely, a previous work performed on genetic polymorphisms of P. falciparum among asymptomatic children from the same Gabonese cohort, demonstrated that sickle-cell trait carriers harbored more multiple P. falciparum parasite genotypes, 45 which allelic distribution, based on the analysis of MSP-1 gene polymorphism, was different as compared with HbAA children. 46 These particular associations might be able to affect disease susceptibility.…”

Section: Discussionmentioning

confidence: 95%

Human genetic factors related to susceptibility to mild malaria in Gabon

Migot-Nabias¹,

Mombo²,

Luty³

et al. 2000

Genes Immun

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Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-␣ and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sicklecell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-␣ promoter mutations (at positions −238: 0.17 and −308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position −238 of the gene coding for the promoter region of TNF-␣ was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum. Genes and Immunity (2000) 1, 435-441.

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“…24 The possibility that other genetic characteristics influence the risk of coinfection was not studied here. In addition, although our method permits EBA-175 genotyping of all samples that are positive by direct examination, the possibility that a minor allele was not detected in some cases of coinfection cannot be ruled out.…”

Section: P Falciparum Genotyping Can Help To Unravel Host-parasite Imentioning

confidence: 99%

Imbalanced Distribution of Plasmodium falciparum EBA-175 Genotypes Related to Clinical Status in Children from Bakoumba, Gabon

Touré¹,

Bisseyé²,

Mavoungou³

2006

Clinical Medicine & Research

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Objective: The erythrocyte binding antigen 175 kDa (EBA-175) of Plasmodium falciparum is one of the major ligands for red blood cell invasion by merozoites. EBA-175 is a dimorphic antigen but the role that dimorphism plays in host parasite interaction is not fully understood. In this study, we sought to determine the distribution of EBA-175 genotypes and its pathogenetic influence. Methods:The nested polymerase chain reaction was used to determine the genotypes of P. falciparum isolates from asymptomatic and symptomatic Gabonese children.Results: CAMP strains (C-segment) and FCR-3 strains (F-segment) were found in 13/50 (26%) and 19/50 (38%) symptomatic children, respectively and in 16/66 (24%) and 46/66 (70%) asymptomatic children, respectively. The prevalence of mixed C-/F-infection was 18/50 (36%) and 4/66 (6%) in symptomatic and asymptomatic children, respectively. Conclusions:These results show that mixed C-/F-infection is associated with clinical malaria (χ 2 , P <0.01) and may have important therapeutic implications. The antigenic diversity of Plasmodium falciparum is the main obstacle to antimalarial vaccine development. Erythrocyte-binding antigen 175 kDa (EBA-175), expressed on the merozoite surface, is involved in P. falciparum binding to erythrocytes. [1][2][3][4][5] In animal models, immunization with synthetic EBA-175 peptides encompassing amino acids 1062 to 1103 elicits antibodies that inhibit merozoite invasion by 80% in vitro. These antibodies appear to act by preventing EBA-175 binding to erythrocytes. 6 In addition, a significant reduction in parasitemia was recently reported in monkeys immunized with EBA-175 is composed of 7 regions (region I-VII) and possesses 2 cysteine-rich segments (F1 and F2) located at the N-terminus in region II (figure 1). These cysteine-rich segments, F1 and F2, are responsible for glycophorin A binding to the erythrocyte membrane 4 and contain a very small number of polymorphic regions. EBA-175 region III is located in the central part of the gene, and genomic studies of two P. falciparum strains revealed two highly dimorphic segments in region III,8,9 Dimorphism is referred to as the F-fragment in the FCR-3 strain and the C-fragment in the CAMP strain. The two segments are inserted at different positions of region III and differ in length by 27 amino acids. These two alleles are both conserved, and Plasmodium merozoites, which are haploid, can possess one or the other, but not both.The role of EBA-175 antigen dimorphism in host-parasite interactions is not fully understood. Preliminary evidence suggests that the initial molecular interaction involves binding of the conserved domain (region II of EBA-175) to glycophorin A sialic acid residues, followed by proteolytic cleavage of EBA-175 and binding of the dimorphic C-and F-segments to the glycophorin A backbone. 8,9 Likewise, the role of this dimorphism in acquired protective immunity to field strains is not known. It was recently shown that EBA-175 is able to use

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Plasmodium falciparum:Sickle-Cell Trait Is Associated with Higher Prevalence of Multiple Infections in Gabonese Children with Asymptomatic Infections

Cited by 53 publications

References 32 publications

Genetic Diversity of Plasmodium falciparum Strains in Children under Five Years of Age in Southeastern Tanzania~!2009-10-12~!2010-01-12~!2010-05-05~!

Genetic Diversity of Plasmodium falciparum Strains in Children under Five Years of Age in Southeastern Tanzania~!2009-10-12~!2010-01-12~!2010-05-05~!

Human genetic factors related to susceptibility to mild malaria in Gabon

Imbalanced Distribution of Plasmodium falciparum EBA-175 Genotypes Related to Clinical Status in Children from Bakoumba, Gabon

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