Analysis of risk factors for infant mortality in the 1992-3 and 2002-3 birth cohorts in rural Guinea-Bissau.
ABSTRACT: INTRODUCTION:Though still high, the infant mortality rate in Guinea-Bissau has declined. We aimed to identify risk factors including vaccination coverage, for infant mortality in the rural population of Guinea-Bissau and assess whether these risk factors changed from 1992-3 to 2002-3. METHODS:The Bandim Health Project (BHP) continuously surveys children in rural Guinea-Bissau. We investigated the association between maternal and infant factors (especially DTP and measles coverage) and infant mortality. Hazard ratios (HR) were calculated using Cox regression. We tested for interactions with sex, age groups (defined by current vaccination schedule) and cohort to assess whether the risk factors were the same for boys and girls, in different age groups in 1992-3 and in 2002-3. RESULTS:The infant mortality rate declined from 148/1000 person years (PYRS) in 1992-3 to 124/1000 PYRS in 2002-3 (HR = 0.88;95%CI:0.77-0.99); this decline was significant for girls (0.77;0.64-0.94) but not for boys (0.97;0.82-1.15) (p = 0.10 for interaction). Risk factors did not differ significantly by cohort in either distribution or effect. Mortality decline was most marked among girls aged 9-11 months (0.56;0.37-0.83). There was no significant mortality decline for girls 1.5-8 months of age (0.93;0.68-1.28) (p = 0.05 for interaction). DTP and measles coverage increased from 1992-3 to 2002-3. CONCLUSIONS:Risk factors did not change with the decline in mortality. Due to beneficial non-specific effects for girls, the increased coverage of measles vaccination may have contributed to the disproportional decline in mortality by sex and age group.
Project description:Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32-.86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of 0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558.
Project description:<h4>Background</h4>A variety of studies have considered the affects of India's son preference on gender differences in child mortality, sex ratio at birth, and access to health services. Less research has focused on the affects of son preference on gender inequities in immunization coverage and how this may have varied with time, and across regions and with sibling compositions. We present a systematic examination of trends in immunization coverage in India, with a focus on inequities in coverage by gender, birth order, year of birth, and state.<h4>Methods</h4>We analyzed data from three consecutive rounds of the Indian National Family Health Survey undertaken between 1992 and 2006. All children below five years of age with complete immunization histories were included in the analysis. Age-appropriate immunization coverage was determined for the following antigens: bacille Calmette-Guérin (BCG), oral polio (OPV), diphtheria, pertussis (whooping cough) and tetanus (DPT), and measles.<h4>Results</h4>Immunization coverage in India has increased since the early 1990s, but complete, age-appropriate coverage is still under 50% nationally. Girls were found to have significantly lower immunization coverage (p<0.001) than boys for BCG, DPT, and measles across all three surveys. By contrast, improved coverage of OPV suggests a narrowing of the gender differences in recent years. Girls with a surviving older sister were less likely to be immunized compared to boys, and a large proportion of all children were found to be immunized considerably later than recommended.<h4>Conclusions</h4>Gender inequities in immunization coverage are prevalent in India. The low immunization coverage, the late immunization trends and the gender differences in coverage identified in our study suggest that risks of child mortality, especially for girls at higher birth orders, need to be addressed both socially and programmatically. ABSTRACT IN HINDI : See the full article online for a translation of this abstract in Hindi.
Project description:Providing an early, additional measles vaccine (MV) at 4.5 months of age has been shown to reduce child mortality in low-income countries. We studied the effects on growth at 9 and 24 months of age.A randomized controlled trial was conducted in Guinea-Bissau from 2003-2007 including 6,648 children. Children were randomized 1:1:1 to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months (group C) Data on anthropometrics were obtained at enrolment at 4.5 months of age and again at 9 and 24 months of age. Analyses were stratified by sex, season of enrolment, and neonatal vitamin A supplementation (NVAS) status, as all these factors have been shown to modify the effect of early MV on mortality.Overall there was no effect of early MV on anthropometry at 9 months. At 24 months children who had received early MV had a significantly larger mid-upper-arm-circumference (MUAC/in cm) (Difference?=?0.08; 95% CI (0.02;0.14)) compared with children in the control group; this effect was most pronounced among girls (0.12 (0.03;0.20)). The effect of early MV on MUAC remained significant in the dry season and in girls who received placebo rather than NVAS.Early MV was associated with a larger MUAC particularly in girls. These results indicate that a two-dose measles vaccination schedule might not only reduce child mortality but also improve growth.ClinicalTrials.gov NCT00168558 . Registered September 9, 2005, retrospectively registered.
Project description: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:Objective Vitamin A supplementation (VAS) is estimated to reduce all-cause mortality by 24%. Previous studies indicate that the effect of VAS may vary with vaccination status. The authors evaluated the effect of VAS provided in campaigns on child survival overall and by sex and vaccination status at the time of supplementation. Design Observational cohort study. Setting and participants The study was conducted in the urban study area of the Bandim Health Project in Guinea-Bissau. The authors documented participation or non-participation in two national vitamin A campaigns in December 2007 and July 2008 for children between 6 and 35 months of age. Vaccination status was ascertained by inspection of vaccination cards. All children were followed prospectively. Outcome measures Mortality rates for supplemented and non-supplemented children were compared in Cox models providing mortality rate ratios (MRRs). Results The authors obtained information from 93% of 5567 children in 2007 and 90% of 5799 children in 2008. The VAS coverage was 58% in 2007 and 68% in 2008. Mortality in the supplemented group was 1.5% (44 deaths/2873 person-years) and 1.6% (20 deaths/1260 person-years) in the non-supplemented group (adjusted MRR=0.78 (0.46; 1.34)). The effect was similar in boys and girls. Vaccination cards were seen for 86% in 2007 and 84% in 2008. The effect of VAS in children who had measles vaccine as their last vaccine (2814 children, adjusted MRR=0.34 (0.14; 0.85)) differed from the effect in children who had diphtheria-tetanus-pertussis vaccine as their last vaccine (3680 children, adjusted MRR=1.29 (0.52; 3.22), p=0.04 for interaction). Conclusion The effect of VAS differed by most recent vaccination, being beneficial after measles vaccine but not after diphtheria-tetanus-pertussis vaccine.
Project description:Background:This study examines associations between sex composition of older siblings and infant mortality by sex, to guide efforts to address excess female infant mortality in India. Methods:We conducted a retrospective cross-sectional study of infant mortality in India using four waves of data from the nationally-representative National Family Health Survey, collected between 1992 and 2016 (unweighted N?=?338,504 for children aged 1-5). We used sex-stratified multivariable logistic regression models to assess the associations between sex composition of older siblings and risk of infant mortality. Findings:Male infants with two living older sisters and no living older brothers had lower odds of infant mortality relative to those with one living older brother (e.g., 2015-16 AOR 0.62, 95% CI 0.50-0.76); this effect was significant for boys across all waves of data but was not seen for girls in any wave. Exploratory models focused on third order births found that boys were less likely than girls to die in infancy if born subsequent to two older sisters (2015-16 AOR 0.48, 95% CI 0.31-0.74); analysis of crude prevalence data indicated that this converts into a 64% greater risk for infant mortality for girls relative to boys in this third-order group. Interpretation:Higher birth order males with older sisters have greater protection against infant mortality, a finding that has persisted for over 25?years. To address ongoing gender inequities in infant survival in India, greater focus is needed to support higher birth order girls and social norm movements against son preference.
Project description:BACKGROUND:Measles and oral polio vaccinations may reduce child mortality to an extent that cannot be explained by prevention of measles and polio infections; these vaccines seem to have beneficial non-specific effects. In the last decades, billions of children worldwide have received measles vaccine (MV) and oral polio vaccine (OPV) through campaigns. Meanwhile the under-five child mortality has declined. Past MV and OPV campaigns may have contributed to this decline, even in the absence of measles and polio infections. However, cessation of these campaigns, once their targeted infections are eradicated, may reverse the decline in the under-five child mortality. No randomized trial has assessed the real-life effect of either campaign on child mortality and morbidity. We present the research protocol of two concurrent trials: RECAMP-MV and RECAMP-OPV. METHODS:Both trials are cluster-randomized trials among children registered in Bandim Health Project's rural health and demographic surveillance system throughout Guinea-Bissau. RECAMP-MV is conducted among children aged 9-59?months and RECAMP-OPV is conducted among children aged 0-8?months. We randomized 222 geographical clusters to intervention or control clusters. In intervention clusters, children are offered MV or OPV (according to age at enrolment) and a health check-up. In control clusters, children are offered only a health check-up. Enrolments began in November 2016 (RECAMP-MV) and March 2017 (RECAMP-OPV). We plan 18,000 enrolments for RECAMP-MV with an average follow-up period of 18?months and 10,000 enrolments for RECAMP-OPV with an average follow-up period of 10?months. Data collection is ongoing. The primary outcome in both trials is non-accidental death or non-accidental first non-fatal hospitalization with overnight stay (composite outcome). Secondary outcomes are: non-accidental death, repeated non-fatal hospitalizations with overnight stay, cause-specific primary outcome, outpatient visit, and illness. We obtained ethical approval from Guinea-Bissau and consultative approval from Denmark. DISCUSSION:Cluster randomization and minimum risk of loss to follow-up are strengths, and no placebo a limitation. Our trials challenge the understanding that MV and OPV only prevent measles and polio, and that once both infections are eradicated, campaigns with MV and OPV can be phased out without negative implications on child health and survival. TRIAL REGISTRATION:NCT03460002.
Project description:To examine in a randomised trial whether a 25% difference in mortality exists between 4.5 months and 3 years of age for children given two standard doses of Edmonston-Zagreb measles vaccines at 4.5 and 9 months of age compared with those given one dose of measles vaccine at 9 months of age (current policy).Randomised controlled trial.The Bandim Health Project, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area.6648 children aged 4.5 months of age who had received three doses of diphtheria-tetanus-pertussis vaccine at least four weeks before enrolment. A large proportion of the children (80%) had previously taken part in randomised trials of neonatal vitamin A supplementation.Children were randomised to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months of age (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months of age (group C). Main outcome measure Mortality rate ratio between 4.5 and 36 months of age for group A compared with groups B and C. Secondary outcomes tested the hypothesis that the beneficial effect was stronger in the 4.5 to 9 months age group, in girls, and in the dry season, but the study was not powered to test whether effects differed significantly between subgroups.In the intention to treat analysis of mortality between 4.5 and 36 months of age the mortality rate ratio of children who received two doses of Edmonston-Zagreb vaccine at 4.5 and 9 months of age compared with those who received a single dose of Edmonston-Zagreb vaccine or Schwarz vaccine at 9 months of age was 0.78 (95% confidence interval 0.59 to 1.05). In the analyses of secondary outcomes, the intention to treat mortality rate ratio was 0.67 (0.38 to 1.19) between 4.5 and 9 months and 0.83 (0.83 to 1.16) between 9 and 36 months of age. The effect on mortality between 4.5 and 36 months of age was significant for girls (intention to treat mortality rate ratio 0.64 (0.42 to 0.98)), although this was not significantly different from the effect in boys (0.95 (0.64 to 1.42)) (interaction test, P=0.18). The effect did not differ between the dry season and the rainy season. As neonatal vitamin A supplementation is not WHO policy, the analyses were done separately for the 3402 children who did not receive neonatal vitamin A. In these children, the two dose Edmonston-Zagreb measles vaccine schedule was associated with a significantly lower mortality between 4.5 and 36 months of age (intention to treat mortality rate ratio 0.59 (0.39 to 0.89)). The effect was again significant for girls but not statistically significant from the effect in boys. When measles cases were censored, the intention to treat mortality rate ratio was 0.65 (0.43 to 0.99).Although the overall effect did not reach statistical significance, the results may indicate that a two dose schedule with Edmonston-Zagreb measles vaccine given at 4.5 and 9 months of age has beneficial non-specific effects on children's survival, particularly for girls and for children who have not received neonatal vitamin A. This should be tested in future studies in different locations.Clinical trials NCT00168558.
Project description:Background:A recent WHO review concluded that live BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs) reducing mortality from non-targeted diseases. NSEs of oral polio vaccine (OPV) were not examined. If OPV vaccination campaigns reduce the mortality rate, it would suggest beneficial NSEs. Setting:Between 2002 and 2014, Guinea-Bissau had 15 general OPV campaigns and other campaigns with OPV plus vitamin A supplementation (VAS), VAS-only, MV, and H1N1 vaccine. In this period, we conducted seven randomized controlled trials (RCTs) with mortality as main outcome. Methods:Within these RCTs, we assessed whether the mortality rate was lower after-campaign than before-campaign. We used Cox models with age as underlying time and further adjusted for low birth-weight, season and time trend in mortality. We calculated the adjusted mortality rate ratio (MRR) for after-campaign vs before-campaign. Results:The mortality rate was lower after OPV-only campaigns than before, the MRR being 0.81 (95% CI?=?0.68-0.95). With each additional dose of campaign-OPV the mortality rate declined further (MRR?=?0.87 (95% CI: 0.79-0.96) per dose) (test for trend, p?=?0.005). No other type of campaign had similar beneficial effects. Depending on initial age and with follow-up to 3?years of age, the number needed to treat with campaign-OPV-only to save one life was between 68 and 230 children. Conclusion:Bissau had no case of polio infection so the results suggest that campaign-OPV has beneficial NSEs. Discontinuation of OPV-campaigns in low-income countries may affect general child mortality levels negatively.
Project description:Background:Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana. Methods:This was a follow-up study involving annual cohort of children aged 9-23?months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12?months from interview date and until 5?years of age using Cox proportional hazards models. Results:In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15-1.66) in the first 12?months after assessment of vaccination status and 1.22 (1.05-1.41) with follow-up to 5?years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12?months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23-2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97-1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33-2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79-1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9?months to 3?years by 24%. Conclusion:Though an observational study, our findings suggest that measles vaccination, administered in the recommended sequence, is associated with improved child survival and may have contributed importantly to the mortality decline toward the achievement of Millennium Development Goal 4.