Variable Adhesion Abilities and Overlapping Antigenic Properties in Placental<i>Plasmodium falciparum</i>Isolates

Ndam, Nicaise Tuikue; Fiévet, Nadine; Bertin, Gwladys; Cottrell, Gilles; Gaye, Alioune; Deloron, Philippe

doi:10.1086/425521

Cited by 65 publications

(53 citation statements)

References 39 publications

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“…1b). Using the analysis of Taylor et al (39), these degenerate primers showed a low bias towards amplification of the most frequently detected sequence of Ͻ2% (since 1.02 40 is Ͼ1.5), which is consistent with those of other "universal" DBL domain degenerate primers (8,24,38). Nevertheless, the bias may prevent the amplification of some DBL␥ sequences.…”

Section: Resultssupporting

confidence: 73%

“…Consequently, with increasing parity, women acquire antibodies that bind to parasites isolated from their own and other placentas (1,16). These antibodies are associated with protection (11,16,36), and some are capable of blocking IE adhesion to CSA (2,16,39). It has therefore been postulated that parasite sequestration in the placenta is caused by a conserved, placenta-specific subset of VSAs.…”

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confidence: 99%

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Transcribed var Genes Associated with Placental Malaria in MalawianWomen

et al. 2006

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Determining the diversity of PfEMP1 sequences expressed by Plasmodium falciparum-infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBL␥ and var2csa DBL3x domains of PfEMP1 molecules are believed to mediate placental sequestration of infected erythrocytes, so the sequences encoding these domains were amplified from the cDNAs of placental parasites by using degenerate oligonucleotides. The levels of specific var cDNAs were then determined by quantitative reverse transcription-PCR. Homologues of var2csa DBL3x were the predominant sequences amplified from the cDNAs of most placental but not most children's parasites. There was 56% identity between all placental var2csa sequences. Many different DBL␥ domains were amplified from the cDNAs of placental and children's isolates. var2csa transcripts were the most abundant var transcripts of those tested in 11 of 12 placental isolates and 1 of 6 children's isolates. Gravidity did not affect the levels of var2csa transcripts. We concluded that placental malaria is frequently associated with transcription of var2csa but that other var genes are also expressed, and parasites expressing high levels of var2csa are not restricted to pregnant women. The diversity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy.

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Section: Resultssupporting

confidence: 73%

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confidence: 99%

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

et al. 2006

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“…Overall, these data strengthen the hypothesis that parasite populations in the peripheral, placental, and cord blood mostly derive from a single population. Moreover, parasites from peripheral and placental compartments share similar phenotypes of adherence to chondroitin sulfate A, the placental receptor of cytoadherence (23). The adhesion of infected erythrocytes to syncytiotrophoblasts in placenta is associated with the expression of distinct variant surface antigens on the membrane of infected erythrocytes.…”

Section: Figmentioning

confidence: 99%

Demonstration of a High Level of Parasite Population Homology by Quantification of Plasmodium falciparum Alleles in Matched Peripheral, Placental, and Umbilical Cord Blood Samples

et al. 2005

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Plasmodium falciparum msp-1 and msp-2 genes were quantified by fragment analysis in matched placental, peripheral, and cord blood samples. In the three compartments, the multiplicity of infection values were similar, and parasite populations only partially overlapped, as reported. However, identical alleles represented 80 to 95% of the overall parasite populations of each compartment, demonstrating much more homogenous parasite populations than previously thought.In areas where malaria is endemic, it is a major cause of morbidity and mortality. During pregnancy, especially the first pregnancy, women are more susceptible and more frequently infected with high levels of placental parasitemia, causing complications for both mothers and newborn babies (5). The mature forms of Plasmodium falciparum sequester in deep microvessels in cerebral malaria and in placental intervillous spaces in pregnant women, while ring stages circulate in the peripheral blood. This phenomenon distorts the analysis of parasites in peripheral blood, revealing only parasites circulating at sampling time. With respect to pregnancy, few studies have investigated the homology of parasite populations from placental, peripheral (21), and cord (12, 13) blood from women at delivery. These studies mostly agree in showing parasite populations partially overlapping and marked differences in the various compartments from most women. While these studies (based on PCR genotyping of polymorphic markers) allow the identification of alleles, they don't permit their quantification. Alternatively, in this work, an attempt was made to obtain quantitative data on allele distribution. We quantified the differences in Plasmodium falciparum msp-1 and msp-2 polymorphisms in matched peripheral and placental samples and matched placental and cord blood samples by using a fragment analysis method.This study was carried out in Thiadiaye, southeast of Dakar. A total of 281 pregnant women were sequentially enrolled and followed until delivery. Placental, peripheral, and cord blood samples were obtained after delivery from all women. Genomic DNA was extracted from the placenta blood samples, and a P. falciparum species-specific PCR (22) identified 60 positive samples. A similar PCR assay performed on the corresponding 60 peripheral and 60 cord blood samples identified 39 positive placental/peripheral blood pairs and 11 positive placental/cord blood pairs. The study was approved by the ethical committee, Ministry of Health, Senegal, and informed consent was obtained from all patients.A fluorescent PCR analyzed block 3 and block 2 of the msp-2 and of msp-1 domains, as described (11). Primers were msp-1 f-5Ј-CACATGAAAGTTATCAAGAACTTGTC-3Ј (sense, fluorescein labeled) and 5Ј-GTACGTCTAATTCCAT TTGCACG-3Ј (antisense) and msp-2 f-5Ј-GAAGGTAATTA AAACATTGTC-3Ј (sense, fluorescein labeled) and 5Ј-GAG GGATGTTGCTGCTCCACA-3Ј (antisense) (Genset SA Europe) (19). Amplification products were processed in an ABI Prism 310 genetic analyzer (Perkin Elmer Applied Biosystems) and analyzed using...

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“…The fact that acquired protection from this syndrome is mediated by an immune response directed against a target that is pregnancy-specific and highly immunogenic is suggested by the strong negative association between gravidity and susceptibility to malaria in pregnancy. Variant surface antigens found in PAM meet these requirements, and initial data implicated this type of antigen in protection from malaria in pregnant women O'Neil-Dunne et al, 2001;Ofori et al, 2003;Ricke et al, 2000;Staalsoe et al, 2001;Tuikue Ndam et al, 2004). This evidence has since been strengthened, since levels of antibodies inhibiting adhesion to CSA correlated inversely with susceptibility to preterm delivery and low birthweight (Duffy & Fried, 2003).…”

Section: Malaria Vaccine Approachmentioning

confidence: 96%

“…the parasite to sequester in the placenta by binding to chondroitin sulfate A (CSA) receptors on syncytiotrophoblast (Beeson et al, 1999;Fried & Duffy, 1996;Ricke et al, 2000;Tuikue Ndam et al, 2004). This placental sequestration is thought to affect the overall organ architecture and function leading to placental insufficiency and impaired intra-uterine growth.…”

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confidence: 99%

Towards a vaccine against pregnancy-associated malaria

Ndam

Deloron

2008

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Summary :The consequences of pregnancy-associated malaria on pregnant women (anaemia), their babies (birth weight reduction), and infants (increased morbidity and mortality) are well documented. Field observations during the last decade have underlined the key role of the interactions between P. falciparum variable surface antigens expressed on infected erythrocytes and a novel receptor: chondroitin sulfate A (CSA) for the placental sequestration of infected erythrocytes. Identification of a distinct P. falciparum erythrocyte membrane protein 1 (PfEMP1) variant, VAR2CSA, as the dominant variant surface antigen and as a clinically important target for protective immune response to pregnancy-associated malaria has raised hope for developing a new preventive strategy based on inducing these immune responses by vaccination. However, despite particular structure and interclonal conservation of VAR2CSA among other PfEMP1, significant challenges still exist concerning the development of a VAR2CSA-based vaccine with profound efficacy.

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Variable Adhesion Abilities and Overlapping Antigenic Properties in PlacentalPlasmodium falciparumIsolates

Cited by 65 publications

References 39 publications

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Demonstration of a High Level of Parasite Population Homology by Quantification of Plasmodium falciparum Alleles in Matched Peripheral, Placental, and Umbilical Cord Blood Samples

Towards a vaccine against pregnancy-associated malaria

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