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      Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes

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          Abstract

          Background

          Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated.

          Methods

          Pregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30–32, and delivery. Antibody levels to VAR2CSA domains were measured using a multiplex bead-based assay.

          Results

          Antibody levels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibody levels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodies levels sharply declined after an infection. A relationship between any VAR2CSA antibody specificity and protection from adverse pregnancy outcomes was not detected.

          Conclusions

          During malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibody reactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.

          Electronic supplementary material

          The online version of this article (10.1186/s12936-018-2258-9) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta.

          Women are particularly susceptible to malaria during first and second pregnancies, even though they may have developed immunity over years of residence in endemic areas. Plasmodium falciparum-infected red blood cells (IRBCs) were obtained from human placentas. These IRBCs bound to purified chondroitin sulfate A (CSA) but not to other extracellular matrix proteins or to other known IRBC receptors. IRBCs from nonpregnant donors did not bind to CSA. Placental IRBCs adhered to sections of fresh-frozen human placenta with an anatomic distribution similar to that of naturally infected placentas, and this adhesion was competitively inhibited by purified CSA. Thus, adhesion to CSA appears to select for a subpopulation of parasites that causes maternal malaria.
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            Applying Cox regression to competing risks.

            Two methods are given for the joint estimation of parameters in models for competing risks in survival analysis. In both cases Cox's proportional hazards regression model is fitted using a data duplication method. In principle either method can be used for any number of different failure types, assuming independent risks. Advantages of the augmented data approach are that it limits over-parametrisation and it runs immediately on existing software. The methods are used to reanalyse data from two well-known published studies, providing new insights.
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              High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction

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                Author and article information

                Contributors
                240 747 7880 , michal.fried@nih.gov
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                9 March 2018
                9 March 2018
                2018
                : 17
                : 106
                Affiliations
                [1 ]ISNI 0000 0001 2164 9667, GRID grid.419681.3, Laboratory of Malaria Immunology and Vaccinology, , National Institute of Allergy and Infectious Diseases, NIH, ; Rockville, MD USA
                [2 ]ISNI 0000 0004 1936 9094, GRID grid.40263.33, Center for International Health Research, Rhode Island Hospital, , Brown University Medical School, ; Providence, RI USA
                [3 ]ISNI 0000 0001 2164 9667, GRID grid.419681.3, Biostatistics Research Branch, , National Institute of Allergy and Infectious Diseases, NIH, ; Rockville, MD USA
                [4 ]Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, P.O Box 1805, Bamako, Mali
                Article
                2258
                10.1186/s12936-018-2258-9
                5845157
                29523137
                0abd6aba-c2eb-42b2-93d8-7cd690639715
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 January 2018
                : 5 March 2018
                Funding
                Funded by: Intramural Research Program of the NIAID-NIH
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                placental malaria,var2csa,birth weight,pregnancy loss,preterm delivery,anaemia

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