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.
Highlights
Pregnant women are at increased risk of Plasmodium falciparum malaria infection and its adverse outcomes
This accumulation of infected erythrocytes (IE) in the placenta is facilitated by VAR2CSA, a specific variant of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)
Several domains mediate the binding of IE to the chondroitin sulfate A (CSA) or elicit a host immune response[15, 17, 21,22,23,24,25,26,27,28,29], and vaccine development efforts against Pregnancy associated malaria (PAM) have been undermined in part because of the difficulty of producing a vaccine targeting such a large and diverse protein
Summary
Pregnant women are at increased risk of Plasmodium falciparum malaria infection and its adverse outcomes. An estimated 125 million pregnant women are at risk of malaria with 56 million of them living in regions with stable malaria transmission[1,2,3] In these areas, pregnancy associated malaria (PAM) poses a significant risk to the mother and to the newborn and is a common cause of adverse pregnancy and birth outcomes, including maternal anemia, stillbirth, preterm birth, and low birth weight (LBW). The adverse effects of malaria during pregnancy are in part the result of the ability of infected erythrocytes (IE) to accumulate in the placenta[10, 11] This accumulation of IE in the placenta is facilitated by VAR2CSA, a specific variant of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Infection with parasites from different clades was associated with different risk of adverse infant outcomes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
