Background: We investigated pregnant women, community leaders, healthcare workers (HCWs) and programme managers’ perceptions of maternal vaccination in Kampala, Uganda. Methods: We conducted focus group discussions, key informant interviews and in-depth discussions with HCWs (3), community leaders (3), pregnant women (8) and programme managers (10) between November 2019 and October 2020. Data were analysed thematically. Results: Pregnant women, community leaders and some HCWs had limited maternal immunisation knowledge. There was confusion over what constitutes a vaccine. Pregnant women may not receive vaccines because of mistrust of government; use of expired vaccines; reliance on traditional medicine; religious beliefs; fear of side effects; HCWs attitudes; and logistical issues. The key facilitators of maternal vaccination were a desire to prevent diseases, positive influences from HCWs and information about vaccine side effects. Community leaders and some pregnant women highlighted that pregnant women do not make decisions about maternal vaccination independently and are influenced by different individuals, including other pregnant women, older people, partners, relatives (parents), community leaders, HCWs and the government. Conclusions: Our results indicate that public health messaging should target all community members, including partners and parents of pregnant women as well as HCWs, to improve knowledge of and confidence in maternal vaccines.

Background: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure.Objectives: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design.Design: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018).Setting: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales.Participants: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria.Interventions: No interventions were performed.Main outcome measures: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus.Results: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V).Limitations: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants.Conclusions: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study.Future work: A large case–control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended.Trial registration: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147.Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information.

Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21-35 days), two (49-63 days), or three months of age (77-91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5-32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60-0.80]). Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease.

Background: Globally there are an estimated 24.1 million cases and 160,700 deaths from pertussis annually in children under five years. The disease burden is higher in low- and middle-income countries, especially the African region, which contributes the largest proportions of cases and deaths. Immunization against pertussis in pregnancy is a recommended strategy for the prevention of infant pertussis in many high-income countries. However, vaccine immunogenicity and effectiveness may be different in immunocompromised individuals such as women living with HIV. There is a need to generate data on the impact of HIV infection in pregnancy on maternal and infant immunity to vaccines against pertussis. Methods: This is a phase II, randomized controlled observer blind clinical trial of 100 women living with HIV and 100 uninfected women randomized to either standard vaccines (tetanus diphtheria vaccine, Td) or a tetanus diphtheria-pertussis vaccine (Tdap). Participants aged 18-40 years carrying a low-risk singleton pregnancy with a gestational age between 16 and 26 weeks confirmed on ultrasound scan, with no history of receipt of tetanus or pertussis vaccines in the current pregnancy will be recruited. Women will receive either two doses of Td or a first dose of Td and second dose of Tdap vaccine. Participants will complete 14-day diary cards to monitor reactogenicity. Mother-infant dyads will be followed up until the infant is one year old. The outcomes include: safety for the pregnant woman and infant; anti-pertussis toxin (PT) and anti-filamentous haemagglutinin (FHA) IgG concentrations in maternal, cord and infant blood and breastmilk, compared by maternal HIV status. Discussion: This study will investigate whether vaccines given to women living with HIV have similar immunogenicity and reactogenicity to vaccines given to pregnant women without HIV and monitor the effect of Tdap in pregnancy on infant immune responses. clinicalTrials.gov registration: NCT04589312 (19/10/2020)

Background: We investigated awareness of neonatal infections among a population of pregnant women and other community members in Kampala, Uganda. We explored perceived causes of neonatal infections and perceptions of appropriate treatments. Methods: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with 97 participants: 25 community leaders who took part in 3 FGDs, 12 pregnant women who took part in IDIs, and 60 pregnant women who took part in 8 FGDs, between November 2019 and October 2020. Data were analyzed thematically. This work formed part of the PROGRESS study, an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021. Results: Beliefs about causes, signs, symptoms, and treatment of infants with suspected infections impacted health-seeking behavior. Some illnesses were perceived to be caused by environmental factors while others were believed to have social or behavioral causes, such as the promiscuity of the male partner causing infections or the mother being bewitched. Local herbs and traditional remedies were the most preferred method of treatment and were commonly relied on to address various health issues rather than conventional medicines. Notably, no participant mentioned vaccines as a way of preventing infections. Conclusions: Pregnant women and community members’ understanding of the causes and treatment of neonatal illnesses were diverse, including environmental, social–behavioral, and supernatural causes, while both conventional and traditional remedies were perceived as appropriate treatments and sought accordingly. Understanding community perceptions and practices around neonatal infections is key to improving neonatal health interventions and outcomes.