Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade
Abstract 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 imp...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-04737-y |
| _version_ | 1818751918339522560 |
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| author | Jaymin C. Patel Nicholas J. Hathaway Christian M. Parobek Kyaw L. Thwai Mwayiwawo Madanitsa Carole Khairallah Linda Kalilani-Phiri Victor Mwapasa Achille Massougbodji Nadine Fievet Jeffery A. Bailey Feiko O. ter Kuile Philippe Deloron Stephanie M. Engel Steve M. Taylor Jonathan J. Juliano Nicaise Tuikue Ndam Steven R. Meshnick |
| author_facet | Jaymin C. Patel Nicholas J. Hathaway Christian M. Parobek Kyaw L. Thwai Mwayiwawo Madanitsa Carole Khairallah Linda Kalilani-Phiri Victor Mwapasa Achille Massougbodji Nadine Fievet Jeffery A. Bailey Feiko O. ter Kuile Philippe Deloron Stephanie M. Engel Steve M. Taylor Jonathan J. Juliano Nicaise Tuikue Ndam Steven R. Meshnick |
| author_sort | Jaymin C. Patel |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-18T04:43:12Z |
| format | Article |
| id | doaj.art-d84acaaa30ce4d708b9c6b83ca45eebc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:43:12Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-d84acaaa30ce4d708b9c6b83ca45eebc2022-12-21T21:20:40ZengNature PortfolioScientific Reports2045-23222017-08-017111210.1038/s41598-017-04737-yIncreased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA cladeJaymin C. Patel0Nicholas J. Hathaway1Christian M. Parobek2Kyaw L. Thwai3Mwayiwawo Madanitsa4Carole Khairallah5Linda Kalilani-Phiri6Victor Mwapasa7Achille Massougbodji8Nadine Fievet9Jeffery A. Bailey10Feiko O. ter Kuile11Philippe Deloron12Stephanie M. Engel13Steve M. Taylor14Jonathan J. Juliano15Nicaise Tuikue Ndam16Steven R. Meshnick17Department of Epidemiology, Gillings School of Global Public Health, University of North CarolinaProgram in Bioinformatics and Integrative Biology, University of MassachusettsCurriculum in Genetics and Molecular Biology, University of North CarolinaDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaCollege of Medicine, University of MalawiDepartment of Clinical Sciences, Liverpool School of Tropical MedicineCollege of Medicine, University of MalawiCollege of Medicine, University of MalawiCentre d’Etude et de Recherche sur le paludisme associé à la Grossesse et à l’Enfance, Université d’Abomey-CalaviCOMUE Sorbonne Paris Cité, Université Paris DescartesProgram in Bioinformatics and Integrative Biology, University of MassachusettsDepartment of Clinical Sciences, Liverpool School of Tropical MedicineCOMUE Sorbonne Paris Cité, Université Paris DescartesDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaCOMUE Sorbonne Paris Cité, Université Paris DescartesDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaAbstract 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.https://doi.org/10.1038/s41598-017-04737-y |
| spellingShingle | Jaymin C. Patel Nicholas J. Hathaway Christian M. Parobek Kyaw L. Thwai Mwayiwawo Madanitsa Carole Khairallah Linda Kalilani-Phiri Victor Mwapasa Achille Massougbodji Nadine Fievet Jeffery A. Bailey Feiko O. ter Kuile Philippe Deloron Stephanie M. Engel Steve M. Taylor Jonathan J. Juliano Nicaise Tuikue Ndam Steven R. Meshnick Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-017-04737-y |
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