Kirsty Le Doare

Background: Novel rapid diagnostic tests for congenital syphilis (CS) are needed. Because maternal IgM does not cross the placenta, neonatal treponemal IgM may be leveraged for CS diagnosis. We sought to evaluate the performance of a single-use multiplex rapid immunoassay which differentially detects IgG and IgM antibodies to both Treponema pallidum (TP) and non-treponemal (NT) lipoidal antigens in blood samples from syphilis-exposed maternal-neonatal dyads.Methods: Paired mother-infant hematologic samples (n=148) collected from treponemal (TP) antibody positive mothers from Baltimore, U.S. (n=29), Houston, U.S. (n=20), and maternal-infant umbilical artery blood samples from Kampala, Uganda (n=99). All samples were tested at reference laboratories for TP antibodies and rapid plasma reagin (RPR).Findings: From Baltimore and Uganda, 69% (20/29) and 80.2% (77/96) of mothers were also RPR positive, of whom 75% (15/20) and 62% (61/98) had infants who were IgM-TP positive, respectively. Among Ugandan cord bloods, 41% (40/98) RPR positive, 11.2% (11/98) were IgM-NT positive. One baby with a four-fold higher RPR titer than its mother had the highest IgM-TP and IgM-NT values, was extremely low-birthweight, and died. All Houston infants with confirmed, highly probable, and possible CS (n=7) had positive IgM-TP results compared to 8/13 less likely infants.Interpretation: In neonates exposed to maternal syphilis, RPR-positive newborns produced higher IgM-TP antibody responses than RPR-negative infants; IgM-TP reflectance values correlated with maternal RPR titers. In neonates who were clinically adjudicated, the presence of IgM-TP antibodies showed potential for determining CS status.

Background/Objectives: New vaccines designed to combat infections such as Group B Streptococcus and respiratory syncytial virus will soon be accessible in Africa. While outbreak response vaccines are given to pregnant women, safety data for maternal vaccines in low- and middle-income countries (LMICs) are limited. This study explored Ugandan pregnant women’s knowledge, attitudes, and engagement in adverse event reporting and vaccine decision-making. Methods: This nested qualitative study was part of a national gap analysis of pharmacovigilance systems for maternal vaccines. Five Focus Group Discussions (FGDs), each involving eight participants, were held with pregnant and or breastfeeding women at four healthcare facilities and one research center. The data collected from these discussions were analyzed thematically using a manifest content analysis, conducted in Atlas.ti software version 9 for qualitative data analysis. Results: Women valued maternal vaccines, particularly tetanus, but reported confusion about schedules and hesitancy when informed of potential side effects. Many adverse events were normalized, therefore not reported, and most participants were unaware of national reporting mechanisms beyond informing healthcare providers. Barriers included inadequate information, dismissive or rushed provider interactions and reliance on family, peers, and informal care networks to manage side effects. Women expressed a strong desire to be informed and actively involved in decisions about pregnancy vaccines, including the introduction of new vaccines. Conclusions: Strengthening maternal vaccine safety monitoring requires clearer, balanced communication; simplified and well-publicized reporting tools; supportive provider–patient interactions; and integration of community and informal networks. Pregnant women should be engaged as active partners in pharmacovigilance and maternal vaccine introduction to build trust, improve adverse event reporting, and support vaccine uptake.

Introduction: Vaccination is a key strategy to safeguard the health of pregnant women and newborns. Although vaccine acceptance is often higher in low- and middle-income countries, the COVID-19 pandemic has highlighted increasing vaccine hesitancy. Vaccine hesitancy, specifically in pregnant women, must be understood to increase uptake. We used data from a Ugandan pregnancy registry study to examine sociodemographic factors linked to uptake of vaccines (tetanus toxoid and later COVID-19) in pregnancy. Methods: Pregnant women were recruited in Kampala, Uganda, as part of the PREPARE (Prevention of invasive Group B Streptococcus disease in young infants: a pathway for the evaluation & licensure of an investigational maternal GBS vaccine) study from September 1, 2020 until February 24, 2022. Demographic, socioeconomic and obstetric data were collected alongside COVID-19 and tetanus vaccination. Results: One thousand five hundred sixty-eight participants were included: 151 (10%) were unvaccinated, 11 (1%) received COVID-19 vaccine only, 1230 (78%) received a tetanus vaccine only and 176 (11%) received both. Lower vaccination rates were seen in participants attending fewer than 4 antenatal care episodes ( P < 0.001), and those with higher parity ( P = 0.036). Higher vaccination rates were seen with a managerial or professional occupation or higher maternal education level, but paternal occupation was not significantly associated with maternal vaccination. Parish vaccination rates varied from 0% to 100%, with 49 (29%) of parishes showing a vaccination rate <90%. Conclusions: This study highlights antenatal care as a key route for health promotion, and the stark difference in uptake between new and established antenatal vaccines. Further qualitative studies should investigate effective interventions to establish the safety and benefit of newer maternal vaccines across all demographic groups.

Background: Despite the effectiveness of maternal vaccines, low- and middle-income countries grapple with inadequate safety monitoring systems. Robust safety surveillance is crucial to increasing vaccine confidence and timely identifying any potential safety signal that could put pregnant women and children at risk following vaccination. This study assessed the pharmacovigilance (PV) systems for vaccines used in pregnancy in Uganda. Methods: A qualitative study involves 13 key informant interviews and 8 focus group discussions among key stakeholders. Purposive sampling was used to select study participants. Data analysis was done using Miles and Huberman’s matrices approach and conducted in Atlas.ti software. Findings: A passive system involving multistakeholders at various levels of the healthcare structure existed but was inadequate for monitoring adverse events following maternal immunization. The existence of parallel reporting systems for vaccines was noted. Heavy workload, lack of feedback, inadequate knowledge to recognize and report adverse events following maternal immunizations and logistical challenges impeding reporting and follow-up were among the barriers to reporting. Electronic medical records, though underutilized for safety surveillance, offer promising potential. Conclusions: To address the specific needs of maternal vaccination, the PV system in Uganda needs improvement. A multipronged approach, including policy coherence, embracing active surveillance and leveraging existing birth outcome surveillance and electronic medical records, is essential. Harnessing healthcare provider knowledge and advisory committee capacity in causality assessment is also necessary. The study findings can inform priority interventions to enhance PV for existing and new maternal vaccines.

Although the World Health Organization recommends 2 tetanus vaccine-containing injections in pregnancy, in Uganda, only 59.2% of pregnant women received a 2nd dose in 2022. We set out to (1) create awareness of maternal vaccine-preventable diseases, maternal immunization benefits and vaccination safety through the use of media; (2) determine the effectiveness of maternal immunization campaigns and (3) assess stakeholder’s acceptability of project interventions’ delivery methods.

Background: Significant disparities in group B Streptococcus (GBS) colonization and neonatal disease rates have been documented across different geographic regions. For example, Bangladesh reports notably lower rates as compared with the United Kingdom and Malawi. This study investigates whether this epidemiologic variability correlates with the immune response to GBS in these regions. Methods: Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharide and the Alp protein family were conducted in serum samples from women of childbearing age in the United Kingdom, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonization or protecting newborns from GBS infection was assessed with humanized mouse models. Results: Bangladeshi women displayed the highest diversity in serotype distribution, with elevated IgG levels in the serum against GBS capsular polysaccharides Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing, and neonatal Fc receptor binding while tested against capsular polysaccharide Ib. In a humanized neonatal Fc receptor mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonization. Additionally, offspring from dams passively immunized with Bangladeshi sera demonstrated notably increased survival rates. Conclusions: This study demonstrates significant variability in the immune response to GBS across different geographic regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly affect vaccine efficacy in these regions.