Patel J. C. auteur aut IRD Hathaway N. J. auteur aut IRD Parobek C. M. auteur aut IRD Thwai K. L. auteur aut IRD Madanitsa M. auteur aut IRD Khairallah C. auteur aut IRD Kalilani-Phiri L. auteur aut IRD Mwapasa V. auteur aut IRD Massougbodji A. auteur aut IRD Fievet Nadine auteur aut IRD Bailey J. A. auteur aut IRD ter Kuile F. O. auteur aut IRD Deloron Philippe auteur aut IRD Engel S. M. auteur aut IRD Taylor S. M. auteur aut IRD Juliano J. J. auteur aut IRD Tuikue Ndam Nicaise auteur aut IRD Meshnick S. R. auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized 052 050 7 art. 7768 [12 p.] 2017 2045-2322 https://www.documentation.ird.fr/hor/fdi:010070885 10.1038/s41598-017-04737-y 2045-2322 [F B010070885] https://www.documentation.ird.fr/hor/fdi:010070885 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers17-09/010070885.pdf IRD - Base Horizon / Pleins textes 2017-10-03 2017-10-03 fdi:010070885 fre