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Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade

Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on cl...

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Autores principales: Patel, Jaymin C., Hathaway, Nicholas J., Parobek, Christian M., Thwai, Kyaw L., Madanitsa, Mwayiwawo, Khairallah, Carole, Kalilani-Phiri, Linda, Mwapasa, Victor, Massougbodji, Achille, Fievet, Nadine, Bailey, Jeffery A., ter Kuile, Feiko O., Deloron, Philippe, Engel, Stephanie M., Taylor, Steve M., Juliano, Jonathan J., Tuikue Ndam, Nicaise, Meshnick, Steven R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554196/
https://www.ncbi.nlm.nih.gov/pubmed/28801627
http://dx.doi.org/10.1038/s41598-017-04737-y
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author Patel, Jaymin C.
Hathaway, Nicholas J.
Parobek, Christian M.
Thwai, Kyaw L.
Madanitsa, Mwayiwawo
Khairallah, Carole
Kalilani-Phiri, Linda
Mwapasa, Victor
Massougbodji, Achille
Fievet, Nadine
Bailey, Jeffery A.
ter Kuile, Feiko O.
Deloron, Philippe
Engel, Stephanie M.
Taylor, Steve M.
Juliano, Jonathan J.
Tuikue Ndam, Nicaise
Meshnick, Steven R.
author_facet Patel, Jaymin C.
Hathaway, Nicholas J.
Parobek, Christian M.
Thwai, Kyaw L.
Madanitsa, Mwayiwawo
Khairallah, Carole
Kalilani-Phiri, Linda
Mwapasa, Victor
Massougbodji, Achille
Fievet, Nadine
Bailey, Jeffery A.
ter Kuile, Feiko O.
Deloron, Philippe
Engel, Stephanie M.
Taylor, Steve M.
Juliano, Jonathan J.
Tuikue Ndam, Nicaise
Meshnick, Steven R.
author_sort Patel, Jaymin C.
collection PubMed
description Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA’s ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. Overall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3D7 or FCR3. Across both cohorts, compared to women infected with only FCR3-like variants, women infected with only 3D7-like variants delivered infants with lower birthweight (difference: −267.99 g; 95% Confidence Interval [CI]: −466.43 g,−69.55 g) and higher odds of low birthweight (<2500 g) (Odds Ratio [OR] 5.41; 95% CI:0.99,29.52) and small-for-gestational-age (OR: 3.65; 95% CI: 1.01,13.38). In two distinct malaria-endemic African settings, parasites harboring 3D7-like variants of VAR2CSA were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. The immense diversity coupled with differential clinical effects of this diversity suggest that an effective VAR2CSA-based vaccine may require multivalent activity.
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spelling pubmed-55541962017-08-15 Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade Patel, Jaymin C. Hathaway, Nicholas J. Parobek, Christian M. Thwai, Kyaw L. Madanitsa, Mwayiwawo Khairallah, Carole Kalilani-Phiri, Linda Mwapasa, Victor Massougbodji, Achille Fievet, Nadine Bailey, Jeffery A. ter Kuile, Feiko O. Deloron, Philippe Engel, Stephanie M. Taylor, Steve M. Juliano, Jonathan J. Tuikue Ndam, Nicaise Meshnick, Steven R. Sci Rep Article Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA’s ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. Overall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3D7 or FCR3. Across both cohorts, compared to women infected with only FCR3-like variants, women infected with only 3D7-like variants delivered infants with lower birthweight (difference: −267.99 g; 95% Confidence Interval [CI]: −466.43 g,−69.55 g) and higher odds of low birthweight (<2500 g) (Odds Ratio [OR] 5.41; 95% CI:0.99,29.52) and small-for-gestational-age (OR: 3.65; 95% CI: 1.01,13.38). In two distinct malaria-endemic African settings, parasites harboring 3D7-like variants of VAR2CSA were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. The immense diversity coupled with differential clinical effects of this diversity suggest that an effective VAR2CSA-based vaccine may require multivalent activity. Nature Publishing Group UK 2017-08-11 /pmc/articles/PMC5554196/ /pubmed/28801627 http://dx.doi.org/10.1038/s41598-017-04737-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Patel, Jaymin C.
Hathaway, Nicholas J.
Parobek, Christian M.
Thwai, Kyaw L.
Madanitsa, Mwayiwawo
Khairallah, Carole
Kalilani-Phiri, Linda
Mwapasa, Victor
Massougbodji, Achille
Fievet, Nadine
Bailey, Jeffery A.
ter Kuile, Feiko O.
Deloron, Philippe
Engel, Stephanie M.
Taylor, Steve M.
Juliano, Jonathan J.
Tuikue Ndam, Nicaise
Meshnick, Steven R.
Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title_full Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title_fullStr Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title_full_unstemmed Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title_short Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
title_sort increased risk of low birth weight in women with placental malaria associated with p. falciparum var2csa clade
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554196/
https://www.ncbi.nlm.nih.gov/pubmed/28801627
http://dx.doi.org/10.1038/s41598-017-04737-y
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