Implementation of the vaccination program in Guinea-Bissau: Coverage and missed opportunities for BCG at birth.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is recommended at birth in Guinea-Bissau but often given with delay. Delays are not evident in routine coverage estimates since coverage is measured by 12 months of age. Studies show that BCG protects against other infections than tuberculosis and lowers neonatal mortality. Hence, the timing of BCG is important since the children should benefit from these non-specific effects as early as possible. METHODS: Using data from a nationally representative health and demographic surveillance system in Guinea-Bissau, we assessed BCG coverage at birth (within the first 3 days of life), 1 month, and 12 months for children born in 2013-19. We measured the proportion of children who had a documented health system contact within the first 3 days of life, thus an opportunity for BCG at birth, and whether the opportunities were utilized. In binomial regression models, we investigated factors associated with missed opportunities for vaccination. RESULTS: Among the 22,178 children only 19 % were vaccinated at birth. By 1 month and 12 months, BCG coverages were 64 % and 93 %. The timeliness of BCG improved over time, with coverage at birth increasing from 16 % in 2013 to 25 % in 2019 and 1-month coverage from 63 % in 2013 to 75 % in 2019. If all vaccination opportunities had been utilized, the BCG coverage at birth could have reached 45 % (in the 1-month cohort) instead of the actual coverage of 19 %, as only 40 % of the vaccination opportunities were utilized. Region of residence was associated with having a missed opportunity for vaccination. CONCLUSION: The high coverage estimates at 12 months falsely imply that the vaccine is being administered according to the recommended schedule. Our findings suggest that early coverage could be markedly improved by ensuring that children are vaccinated at their first contact with the health system.

Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau.

OBJECTIVE: To assess the effect of providing BCG and oral polio vaccine (OPV) at an early home visit after delivery. DESIGN: Cluster-randomised trial, randomising 92 geographically defined clusters 1:1 to intervention/control arms. SETTING: Bandim Health Project Health and Demographic Surveillance System, Guinea-Bissau. PARTICIPANTS: 2226 newborns enrolled between July 2016 and August 2019. INTERVENTIONS: In both arms, newborns received a home visit within 72 hours after birth. In intervention clusters (n=46), BCG and OPV were provided at the home visit. MAIN OUTCOME MEASURE: Rates of non-accidental mortality were compared in Cox proportional hazards models from (last of) day 1 or enrolment, until (first of) day 60 or registration of non-trial vaccines. RESULTS: A total of 35 deaths (intervention: 7, control: 28) were registered during the trial. Providing BCG and OPV reduced non-accidental early infant mortality by 59% (8-82%). The intervention also reduced non-accidental hospital admissions. The intervention had little impact on growth and BCG scarring and tended to increase the risk of consultations. CONCLUSIONS: The trial was stopped early due to lower-than-expected enrolment and event rates when 33% of the planned number of newborns had been enrolled. Despite the small size of the trial, the results support that early BCG and OPV vaccinations are beneficial and reduce early child mortality and morbidity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02504203).

Can BCG vaccination at first health-facility contact reduce early infant mortality? Study protocol for a cluster-randomised trial (CS-BCG).

INTRODUCTION: Increasing evidence suggests that the BCG vaccine has non-specific effects, altering the susceptibility to non-tuberculous infections. Thus, early BCG vaccination may reduce mortality. BCG is recommended at birth but is often delayed. Vaccination opportunities are missed due to multidose vials not being opened for a few children. We will assess the effect of making BCG available at the first health-facility contact on early infant mortality and morbidity in a rural setting in Guinea-Bissau. METHODS AND ANALYSIS: In a cluster-randomised crossover trial, we randomise 23 health centres to two different treatment groups. In half of the health centres, BCG is provided as per current practice; in the remaining health centres, we make BCG available everyday to allow opening a vial of BCG if there is just one eligible child present. The randomisation of centres will be crossed over after 12 months and enrolment will continue for another 12 months.We will use logistic regression models with adjustment for village to assess the effect of making BCG available at the first health-facility contact. The main outcome is non-accidental mortality between day 1 and day 42 after birth. We will adjust for sex, health centre, period (before/after crossover) and level of surveillance (level 1 or level 2). Further analyses include assessment of the effect on hospital admission and a cost-effectiveness evaluation. ETHICS AND DISSEMINATION: If BCG vaccination reduces early infant mortality, missed opportunities and delays of vaccinations expose infants in several low-income countries to unnecessary excess mortality risk. The present trial will provide information on the effect of implementing a feasible intervention, where all children receive BCG at their first health-facility contact. Consent is obtained from all pregnant women registered as part of the trial. The results of the study will be published and communicated to the National Institute of Public Health in Guinea-Bissau. TRIAL REGISTRATION NUMBER: NCT04658680; Clinicaltrials.gov.