Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an observational cohort study.
ABSTRACT: The WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when this study was conducted. The WHO assesses coverage by 12 months of age. The sequence of vaccines may have an effect on child mortality, but is not considered in official statistics or assessments of programme performance. We assessed vaccination coverage and frequency of out-of-sequence vaccinations by 12 and 24 months of age.Observational cohort study.The Bandim Health Project's (BHP) rural Health and Demographic Surveillance site covers 258 randomly selected villages in all regions of Guinea-Bissau. Villages are visited biannually and vaccination cards inspected to ascertain vaccination status. Between 2003 and 2009 vaccination status by 12 months of age was assessed for 5806 children aged 12-23 months; vaccination status by 24 months of age was assessed for 3792 children aged 24-35 months.Coverage of EPI vaccinations and frequency of out-of-sequence vaccinations.Half of 12-month-old children and 65% of 24-month-old children had completed all EPI vaccinations. Many children received vaccines out of sequence: by 12 months of age 54% of BCG-vaccinated children had received DTP with or before BCG and 28% of measles-vaccinated children had received DTP with or after MV. By 24 months of age the proportion of out-of-sequence vaccinations was 58% and 35%, respectively, for BCG and MV.In rural Guinea-Bissau vaccination coverage by 12 months of age was low, but continued to increase beyond 12 months of age. More than half of all children received vaccinations out of sequence. This highlights the need to improve vaccination services.
Project description:OBJECTIVES:To assess whether the sequence of diphtheria-tetanus-pertussis vaccine (DTP) and measles vaccine (MV) was associated with child survival in a dataset previously used to assess non-specific effects of vaccines with no consideration of vaccination sequence. DESIGN:Prospective cohort study analysed using the landmark approach. SETTING:Bandim Health Project's Health and Demographic Surveillance System covering 100 village clusters in rural Guinea-Bissau. The recommended vaccination schedule was BCG and oral polio vaccine (OPV) at birth, DTP and OPV at 6, 10 and 14 weeks, MV at 9 months and booster DTP and OPV at 18 months of age. PARTICIPANTS:Children aged 9-17 months (main analysis) and 18-35 months (secondary analysis: age of booster DTP) with vaccination status assessed between April 1991 and April 1996. METHODS:Survival during the 6 months after assessing vaccination status was compared by vaccination sequence in Cox-proportional hazards models with age as underlying time. Analyses were stratified by sex and village cluster. MAIN OUTCOME MEASURE:Mortality rate ratio (MRR) for out-of-sequence vaccinations compared with in-sequence vaccinations. RESULTS:Among children aged 9-17 months, 60% of observations (3574/5937) were from children who had received both MV and DTP. Among these, 1590 observations were classified as in-sequence vaccinations (last DTP before MV), and 1984 observations were out-of-sequence vaccinations (1491: MV with DTP and 493: MV before DTP). Out-of-sequence vaccinations were associated with higher mortality than in-sequence vaccinations (MRR 2.10, 95% CI 1.07 to 4.11); the MRR was 2.30 (95% CI 1.15 to 4.58) for MV with DTP and 1.45 (95% CI 0.50 to 4.22) for DTP after MV. Associations were similar for boys and girls (p=0.77). Between 18 and 35 months the mortality rate increased among children vaccinated in-sequence and the differential effect of out-of-sequence vaccinations disappeared. CONCLUSION:Out-of-sequence vaccinations may increase child mortality. Hence, sequence of vaccinations should be considered when planning vaccination programmes or introducing new vaccines into the current vaccination schedule.
Project description:To determine whether BCG revaccination at 19 months of age reduces overall child mortality.Randomised trial, with follow-up to age 5.A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants.2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrollment.BCG vaccination or no vaccination (control).Hazard ratios for mortality.77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrollment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrollment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrollment (1.78, 1.04 to 3.04).There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions. Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.
Project description:Background:Whole-cell diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) were introduced to children in Guinea-Bissau in 1981. We previously reported that DTP in the target age group from 3 to 5?months of age was associated with higher overall mortality. DTP and OPV were also given to older children and in this study we tested the effect on mortality in children aged 6-35?months. Methods:In the 1980s, the suburb Bandim in the capital of Guinea-Bissau was followed with demographic surveillance and tri-monthly weighing sessions for children under 3?years of age. From June 1981, routine vaccinations were offered at the weighing sessions. We calculated mortality hazard ratio (HR) for DTP-vaccinated and DTP-unvaccinated children aged 6-35?months using Cox proportional hazard models. Including this study, the introduction of DTP vaccine and child mortality has been studied in three studies; we made a meta-estimate of these studies. Results:At the first weighing session after the introduction of vaccines, 6-35-month-old children who received DTP vaccination had better weight-for-age z-scores (WAZ) than children who did not receive DTP; one unit increase in WAZ was associated with an odds ratio of 1.32 (95% CI?=?1.13-1.55) for receiving DTP vaccination. Though lower mortality compared with not being DTP-vaccinated was, therefore, expected, DTP vaccination was associated with a non-significant trend in the opposite direction, the HR being 2.22 (0.82-6.04) adjusted for WAZ. In a sensitivity analysis, including all children weighed at least once before the vaccination program started, DTP (±OPV) as the most recent vaccination compared with live vaccines or no vaccine was associated with a HR of 1.89 (1.00-3.55). In the three studies of the introduction of DTP in rural and urban Guinea-Bissau, DTP-vaccinated children had an HR of 2.14 (1.42-3.23) compared to DTP-unvaccinated children; this effect was separately significant for girls [HR?=?2.60 (1.57-4.32)], but not for boys [HR?=?1.71 (0.99-2.93)] (test for interaction p?=?0.27). Conclusion:Although having better nutritional status and being protected against three infections, 6-35?months old DTP-vaccinated children tended to have higher mortality than DTP-unvaccinated children. All studies of the introduction of DTP have found increased overall mortality.
Project description:Immunization programs currently measure coverage by assessing the proportion of children 12-24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited.To estimate the time to Bacillus Calmette-Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants <6 months of age in a district in southern Nepal where traditional coverage metrics are high.Infants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan-Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine.The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months.A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health.
Project description:WHO recommends BCG at birth and diphtheria-tetanus-pertussis (DTP)-containing vaccine at 6, 10 and 14weeks of age. However, BCG and DTP are often co-administered in low-income countries. The health implications have not been examined.We reanalysed data from Matlab, Bangladesh, to examine the influence of co-administration on mortality; 37,894 children born 1986-1999 were followed with registration of vaccinations and survival.Using Cox models, survival was analysed from 6weeks to 9months of age when measles vaccine is given; 712 children died in this age group. We calculated mortality rate ratios (MRR) for children starting the vaccination schedule with BCG-first, BCG+DTP1-first or DTP1-first.Only 17% followed the WHO-schedule with BCG-first. Mortality was 16/1000 person-years for children who initiated the vaccination schedule with BCG+DTP1 but 32/1000 and 20/1000 for children who received BCG-first or DTP-first, respectively. Compared with BCG+DTP1-first and adjusting for background factors, the BCG-first-schedule was associated with 2-fold higher mortality (MRR=1.94 (1.42-2.63)). DTP1 administered after BCG-first was associated with higher mortality than receiving DTP1 with BCG (MRR=1.78 (1.03-3.03)).Co-administration of BCG and DTP may further reduce mortality. Since all observational studies support this trend, co-administration of BCG and DTP should be tested in randomised trials.
Project description:Vitamin A supplementation (VAS) may amplify the effect of vaccines. We therefore investigated if neonatal VAS given with and without Bacille Calmette-Guérin (BCG) vaccine to low-birth-weight (LBW) neonates had an effect on growth in the first year of life. We hypothesised that VAS would be particularly beneficial when provided with BCG.We conducted a randomised two-by-two factorial trial in Guinea-Bissau; 1,717 LBW neonates were randomly allocated to VAS or placebo at birth as well as early or the usual postponed BCG vaccination. Anthropometric measurements were obtained at 2, 6, and 12 months after inclusion.Overall there was no effect of neonatal VAS on growth in the first year of life. By 2 months, VAS tended to have a beneficial effect on weight and head circumference when given with BCG but not when given without BCG (interaction: weight-for-age p?=?0.07 and head circumference-for-age: p?=?0.06). By 6 months, there was a beneficial effect of VAS on head circumference and weight among children who had not received DTP vaccine 2 months after inclusion (weight: 0.18 (0.00; 0.36) and head circumference 0.27 (0.06; 0.48)), but no beneficial effect among those who had received DTP.The results support other trials indicating that neonatal VAS does not have consistent effects on childhood growth and if anything the effects seem to be temporary. They also show that the effect may differ by vaccination status, being beneficial when given with BCG at birth and when DTP is delayed.www.ClinicalTrials.gov (NCT00168610).
Project description:<h4>Background</h4>Child survival is dependent on several factors including high vaccination coverage. Timely receipt of vaccines ensures optimal immune response to the vaccines. Yet timeliness is not usually emphasized in estimating population immunity. In addition to examining timeliness of the recommended Expanded Programme for Immunisation (EPI) vaccines, this paper identifies predictors of untimely vaccination among children aged 10 to 23 months in Kampala.<h4>Methods</h4>In addition to the household survey interview questions, additional data sources for variables included data collection of child's weight and length. Vaccination dates were obtained from child health cards. Timeliness of vaccinations were assessed with Kaplan-Meier time-to-event analysis for each vaccine based on the following time ranges (lowest-highest target age): BCG (birth-8 weeks), polio 0 (birth-4 weeks), three polio and three pentavalent vaccines (4 weeks-2 months; 8 weeks-4 months; 12 weeks-6 months) and measles vaccine (38 weeks-12 months). Cox regression analysis was used to identify factors associated with vaccination timeliness.<h4>Results</h4>About half of 821 children received all vaccines within the recommended time ranges (45.6%; 95% CI 39.8-51.2). Timely receipt of vaccinations was lowest for measles (67.5%; 95% CI 60.5-73.8) and highest for BCG vaccine (92.7%: 95% CI 88.1-95.6). For measles, 10.7% (95% CI 6.8-16.4) of the vaccinations were administered earlier than the recommended time. Vaccinations that were not received within the recommended age ranges were associated with increasing number of children per woman (adjusted hazard ratio (AHR); 1.84, 95% CI 1.29-2.64), non-delivery at health facilities (AHR 1.58, 95% CI 1.02-2.46), being unmarried (AHR 1.49, 95% CI 1.15-1.94) or being in the lowest wealth quintile (AHR 1.38, 95% CI 1.11-1.72).<h4>Conclusions</h4>Strategies to improve vaccination practices among the poorest, single, multiparous women and among mothers who do not deliver at health facilities are necessary to improve timeliness of vaccinations.
Project description:BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination ("restricted vial-opening policy"). BCG coverage is usually reported as 12-month coverage, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau.Bandim Health Project (BHP) runs a health and demographic surveillance system covering women and their children in 182 randomly selected village clusters in rural Guinea-Bissau. BCG coverage was assessed for children born in 2010, when the restricted vial-opening policy was universally implemented, and in 2012-2013, where BHP provided BCG to all children at monthly visits in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios.Among 3951 children born in 2010, vaccination status was assessed for 84%. BCG coverage by 1 week of age was 11%, 38% by 1 month, and 92% by 12 months. If BCG had been given at first contact with the health system, 1-week coverage would have been 35% and 1-month coverage 54%. When monthly visits were introduced in intervention regions, 1-month coverage was higher in intervention regions (88%) than in control regions (51%), the prevalence ratio being 1.74 (1.53-2.00). Several factors, including socioeconomic factors, were associated with delayed BCG vaccination in the 2010-birth cohort. When BCG was available at monthly visits these factors were no longer associated with delayed BCG vaccination, only region of residence was associated with delayed BCG vaccination.BCG coverage during the first months of life is low in Guinea-Bissau. Providing BCG at monthly vaccination visits removes the risk factors associated with delayed BCG vaccination.
Project description:Bacillus Calmette-Guérin (BCG) vaccination possesses effects on health beyond its target disease, the so called "non-specific effects". We evaluate these effects, as well as the effect of timing of BCG and other vaccinations, on stunting in Sub-Saharan African (SSA) children under five.We use a Big Data design, including cross-sectional data for 368,450 children from 33 SSA countries. Logistic regression analysis is used with control factors at child, mother, household and context level.Overall, BCG vaccination did not affect stunting in SSA children (OR 1.00 [0.98-1.03]). Timing of BCG vaccination was of importance (?time=0.067 [0.061-0.073]): compared to unvaccinated children, BCG was associated with lower odds on stunting for children vaccinated early in life (OR 0.92 [0.89-0.94]) and higher odds for children vaccinated later in infancy (OR 1.64 [1.53-1.76]). Similar findings were done for diphtheria-tetanus-pertussis (DTP)1 and measles vaccination, and when hemoglobin concentration was used as outcome variable.We found a general time-dependent pattern of non-specific effects of vaccination, with positive associations for vaccinations given early in life and negative associations for vaccinations given later in infancy. If confirmed in further research, our findings may provide a new perspective on the non-specific effects of vaccination.
Project description:We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s.The child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV were offered from 3months of age at these sessions. Due to the 3-monthly intervals between sessions, the children were allocated by birthday in a 'natural experiment' to receive vaccinations early or late between 3 and 5months of age. We included children who were <6months of age when vaccinations started and children born until the end of December 1983. We compared mortality between 3 and 5months of age of DTP-vaccinated and not-yet-DTP-vaccinated children in Cox proportional hazard models.Among 3-5-month-old children, having received DTP (±OPV) was associated with a mortality hazard ratio (HR) of 5.00 (95% CI 1.53-16.3) compared with not-yet-DTP-vaccinated children. Differences in background factors did not explain the effect. The negative effect was particularly strong for children who had received DTP-only and no OPV (HR=10.0 (2.61-38.6)). All-cause infant mortality after 3months of age increased after the introduction of these vaccines (HR=2.12 (1.07-4.19)).DTP was associated with increased mortality; OPV may modify the effect of DTP.