P. falciparum infection and maternofetal antibody transfer in malaria-endemic settings of varying transmission

Abstract

IntroductionDuring pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear.MethodsMother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG.ResultsMaternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG compared to TMBA (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of -0.20 log2 units). Placental P. falciparum infections were associated with substantially lower maternofetal antibody transfer efficiency in PNG primigravid women (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not multigravid women. The lower antibody transfer efficiency amongst primigravid women with placental infection was only partially mediated by gestational age at delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation effects of maternal total serum IgG were observed.DiscussionPrimigravid women may be at risk of impaired maternofetal antibody transport with placental P. falciparum infection. Direct effects of P. falciparum on the placenta, rather than earlier gestational age and elevated serum IgG, are likely responsible for the majority of the reduction in maternofetal antibody transfer efficiency with placental infection.

Malaria in pregnancy shapes the development of foetal and infant immunity

“…Similarly, Moro et al found that maternal malaria at delivery (peripheral or placental) was associated with reduced cord‐to‐maternal ratios of blood stage‐specific P. falciparum antibodies, but no association between these reduced cord‐to‐maternal ratios and the subsequent risk of malaria in the infant during the first year of life. A similar effect was found for PM, but not peripheral malaria, among primigravid, but not multigravida, women from Papua New Guinea, after controlling for both gestational age and maternal total serum IgG level, suggesting a direct effect of P. falciparum ‐induced placental pathology . A study from the Thai‐Myanmar border (a low transmission setting) demonstrated the transfer of a broad range of P. falciparum and P. vivax‐specific IgG, but found that the detection of P. falciparum (but not P. vivax )‐specific antibodies in cord blood was specifically associated with recent maternal infection .…”

“…A limited number of studies have addressed the effect of maternal peripheral malaria infection during the pregnancy on antibody transfer. One study found no association of peripheral infection on the transfer of measles‐specific antibodies, while an additional study demonstrated an effect on the transfer of EBV‐specific antibodies and a third demonstrated an effect on S. pneumoniae ‐specific antibodies, although importantly neither of the positive studies explicitly addressed the placental infection status of the women.…”

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

“…The timing of antibody and parasitaemia determination is indicated. Estimate for McLean et al [63] represents IgG3 responders only as total IgG was not available. DBL5 estimates were only combined when study design was the same.…”

“…We included estimates from nine studies that investigated the association between antibodies (Abs) to pregnancy-specific pRBC or VAR2CSA domains measured at delivery, and placental infection ( Fig. 2a) [35,42,52,53,56,[59][60][61]63]. In all studies, placental infection was confirmed by slide microscopy of placental blood or placental histology.…”

“…Peripheral P. falciparum infection Seven studies provided cross-sectional estimates for the association between antibody responses to pregnancyspecific antigens, measured at various time points, and peripheral P. falciparum infection, yielding heterogeneous results ( Fig. 3a and Additional file 7: Figures S6A and S7A) [42,43,51,55,58,61,63]. For many of the antigens examined, antibody responders had increased odds of peripheral infection compared to nonresponders, but these associations were rarely significant.…”