High titres of immunoglobulin g class 1 antibodies to duffy binding-like (DBL) 5 during the third trimester of pregnancy are associated with past placental malaria at delivery in an area of high seasonal transmission in Burkina Faso

Objective: In malaria endemic area, women acquire throughout successive pregnancies, increasing protection against Plasmodium falciparum malaria infections by having increased levels of antibodies to the Variant 2 Cell Surface antigen- Chondroitin Sulphate A. Primigravidae are more susceptible to placental malaria due to the lack of these specific antibodies to placental malaria-antigens. However, it is currently difficult to diagnose placental malaria by a noninvasive method prior to delivery. The objective of this study was to assess whether VAR2CSA specific antibody levels from peripheral blood obtained during the third trimester of pregnancy, could predict placental infection at delivery. Methods: A total of 263 pregnant women participating to the COSMIC study (NCT01941264) were included in this study. Peripheral blood samples were collected at the third antenatal care visit performed during the third trimester of pregnancy. Placental infec-tions were determined by histology. Antibody levels (total IgG, IgG1 and IgG3) to VAR2CSA subdomains DBL5 and ID1-ID2a in serum samples were quantified using En-zyme Linked ImmunoSorbent Assay. Results: Placental malaria was estimated at 54.9% among pregnant women enrolled in the study. More than half of the study population had a past placental infection. Among factors investigated, in univariate analyses ITN use, gravidity, season of delivery, number of IPTp-SP doses, gestational age and peripheral malaria status at the 3rd ANC visit significantly affected DBL5 and ID1ID2a specific antibody titres. In multivariate analyses, ITN use (OR=5.17, 95% CI: (1.36 - 19.61), p = 0.016) was associated with the risk of placental malaria at delivery, while older women were at lower risk (OR = 0.45, 95% CI: (0.23-0.88), p=0.021). Importantly, higher levels of IgG1 anti-DBL5 at the 3rd trimester (OR=11.96, 95% CI: (3.69-38.77), p