@article{fdi:010070885, title = {{I}ncreased risk of low birth weight in women with placental malaria associated with {P}. falciparum {VAR}2{CSA} clade}, author = {{P}atel, {J}. {C}. and {H}athaway, {N}. {J}. and {P}arobek, {C}. {M}. and {T}hwai, {K}. {L}. and {M}adanitsa, {M}. and {K}hairallah, {C}. and {K}alilani-{P}hiri, {L}. and {M}wapasa, {V}. and {M}assougbodji, {A}. and {F}ievet, {N}adine and {B}ailey, {J}. {A}. and ter {K}uile, {F}. {O}. and {D}eloron, {P}hilippe and {E}ngel, {S}. {M}. and {T}aylor, {S}. {M}. and {J}uliano, {J}. {J}. and {T}uikue {N}dam, {N}icaise and {M}eshnick, {S}. {R}.}, editor = {}, language = {{ENG}}, abstract = {{P}regnancy associated malaria ({PAM}) causes adverse pregnancy and birth outcomes owing to {P}lasmodium falciparum accumulation in the placenta. {P}lacental accumulation is mediated by {P}. falciparum protein {VAR}2{CSA}, a leading {PAM}-specific vaccine target. {T}he extent of its antigen diversity and impact on clinical outcomes remain poorly understood. {T}hrough amplicon deep-sequencing placental malaria samples from women in {M}alawi and {B}enin, we assessed sequence diversity of {VAR}2{CSA}'s {ID}1-{DBL}2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. {O}verall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3{D}7 or {FCR}3. {A}cross both cohorts, compared to women infected with only {FCR}3-like variants, women infected with only 3{D}7-like variants delivered infants with lower birthweight (difference: -267.99 g; 95% {C}onfidence {I}nterval [{CI}]: -466.43 g, -69.55 g) and higher odds of low birthweight (< 2500 g) ({O}dds {R}atio [{OR}] 5.41; 95% {CI}: 0.99,29.52) and small-for-gestational-age ({OR}: 3.65; 95% {CI}: 1.01,13.38). {I}n two distinct malaria-endemic {A}frican settings, parasites harboring 3{D}7-like variants of {VAR}2{CSA} were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. {T}he immense diversity coupled with differential clinical effects of this diversity suggest that an effective {VAR}2{CSA}-based vaccine may require multivalent activity.}, keywords = {}, booktitle = {}, journal = {{S}cientific {R}eports -{N}ature}, volume = {7}, numero = {}, pages = {art. 7768 [12 p.]}, ISSN = {2045-2322}, year = {2017}, DOI = {10.1038/s41598-017-04737-y}, URL = {https://www.documentation.ird.fr/hor/fdi:010070885}, }