Discovering Subgroups of Children With High Mortality in Urban Guinea-Bissau: Exploratory and Validation Cohort Study.

BACKGROUND: The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions. OBJECTIVE: This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy. METHODS: We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling. RESULTS: We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths. CONCLUSIONS: The study's results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

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).

Do Pentavalent (DTwP-Hib-HBV) vaccines have sex-differential nonspecific effects? An observational study.

Vaccines may alter the ability to combat infections unrelated to the target disease, i.e. have "nonspecific effects." The non-live Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for females. In 2008, the DTP-containing Pentavalent vaccine replaced DTP vaccine in Guinea-Bissau. We investigate female relative to male mortality after Penta vaccination. In Guinea-Bissau, Bandim Health Project (BHP) registered children's vaccination and vital status at biannual village visits and provided vaccines. Among children Penta-vaccinated by BHP, we compared mortality of males and females in Cox proportional hazards models. Children aged 6 weeks to 8 months entered the analysis at the date of vaccination and were followed for up to 6 months. Between September 2008 and December 2017, 33,989 children aged 6 weeks to 8 months were under surveillance. Of these 12,753 (females: 6,363; males: 6,390) received Penta by the BHP and entered the study contributing with 19,667 observations. The mortality rate following Penta vaccination was 25.2 per 1,000 person years for females and 26.6 for males, resulting in an adjusted Female/Male mortality rate ratio of (F/M aMRR) 1.01 (0.82-1.25). The association between sex and mortality differed by timeliness of vaccination, F/M aMRR: 0.62 (0.41-0.93) for children vaccinated below median age, and F/M aMRR: 1.38 (0.90-2.13) for children vaccinated above median age. We did not find higher overall mortality in females than males after Penta vaccination. Our findings suggest that mortality differences between males and females following Penta vaccination may depend on timeliness of Penta vaccination.

Stillbirth and early neonatal mortality rates may be underestimated using recall information: A comparison of demographic surveillance methodologies.

OBJECTIVE: Child mortality and stillbirth rates (SBR) remain high in low-income countries but may be underestimated due to incomplete reporting of child deaths in retrospective pregnancy/birth histories. The aim of this study is to compare stillbirth and mortality estimates derived using two different methods: the method assuming full information and the prospective method. METHODS: Bandim Health Project's Health and Demographic Surveillance Systems (HDSS) follows women of reproductive age and children under five through routine home visits every 1, 2 or 6 months. Between 2012 and 2020, we estimated and compared early neonatal (ENMR, <7 days), neonatal (NMR, <28 days), and infant mortality (IMR, <1 year) per 1000 live births and SBR per 1000 births. Risk time for children born to registered women was calculated from birth (the method assuming full information) versus date of first observation in the HDSS (the prospective method), either at birth (for pregnancy registration) or registration. Rates were calculated using the Kaplan-Meier estimator and compared in generalised linear models allowing for within-child correlation obtaining relative risks (RR). RESULTS: We registered and followed 29,413 infants (1380 deaths; 1459 stillbirths) prospectively. An additional 164 infant deaths and 129 stillbirths were registered retrospectively and included in the method assuming full information. The ENMR was 24.5 (95%CI: 22.6-26.4) for the method assuming full information and 25.8 (23.7-27.8) for the prospective method, RR = 0.96 (0.93-0.99). Differences were smaller for the NMRs and IMRs. For SBRs, the estimates were 53.5 (50.9-56.0) and 58.6 (55.7-61.5); RR = 0.91 (0.90-0.93). The difference between methods became more pronounced when the analysis was limited to areas visited every 6 months: RR for ENMR: 0.91 (0.86-0.96) and RR for SBR: 0.85 (0.83-0.87). CONCLUSIONS: Assuming full information underestimates SBR and ENMR. Accounting for omissions of stillbirths and early neonatal deaths may lead to more accurate estimates and improved ability to monitor mortality.

Predictors of serum- per- and polyfluoroalkyl substance (PFAS) concentrations among infants in Guinea-Bissau, West Africa.

BACKGROUND: Knowledge about PFAS exposure in Africa is limited. We have previously detected six types of PFAS in the serum of infants from Guinea-Bissau, West Africa. The aim of this study was to identify predictors of the infant serum-PFAS concentrations. METHODS: This cross-sectional study was based on a subset of data from a randomized controlled trial of early measles vaccination performed in 2012-2015 in three rural regions of Guinea-Bissau. Blood samples were obtained from 237 children aged 4-to-7 months, and six types of PFAS were quantified in serum. Location of residence was recorded, and information about predictors related to socioeconomic status as well as maternal and child characteristics were obtained through structured interviews with the mothers through routine surveillance. Associations between potential predictors and infant serum-PFAS concentrations were examined in linear regression models while adjusting for potential confounding and mediating factors as identified in a directed acyclic graph. RESULTS: Infants from the Cacheu region had the lowest concentrations of perfluorooctanoic acid (PFOA), while infants from the Oio region had the lowest concentrations of all other PFAS. Compared to infants from Oio, infant serum-perfluorooctane sulfonic acid (PFOS) concentrations were 94.1% (95% CI: 52.4, 147.1%) and 81.9% (95% CI: 45.7, 127.1%) higher in Cacheu and Biombo, respectively. Higher maternal age and lower parity were associated with slightly higher child-serum perfluorohexane sulfonic acid (PFHxS) concentrations, while infants with higher socioeconomic status and infants breastfed without supplementary solid foods at inclusion had higher average concentrations of most PFAS, although the confidence intervals were wide and overlapped zero. DISCUSSION: Location of residence was the most important determinant of serum-PFAS concentrations among Guinea-Bissau infants, indicating a potential role of diet as affected by the global spread of PFAS, but future studies should explore reasons for the regional differences in PFAS exposure.

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.

Oral polio revaccination is associated with changes in gut and upper respiratory microbiomes of infants.

After the eradication of polio infection, the plan is to phase-out the live-attenuated oral polio vaccine (OPV). Considering the protective non-specific effects (NSE) of OPV on unrelated pathogens, the withdrawal may impact child health negatively. Within a cluster-randomized trial, we carried out 16S rRNA deep sequencing analysis of fecal and nasopharyngeal microbial content of Bissau-Guinean infants aged 4-8 months, before and after 2 months of OPV revaccination (revaccinated infants = 47) vs. no OPV revaccination (control infants = 47). The aim was to address changes in the gut and upper respiratory bacterial microbiotas due to revaccination. Alpha-diversity for both microbiotas increased similarly over time in OPV-revaccinated infants and controls, whereas greater changes over time in the bacterial composition of gut (p adjusted < 0.001) and upper respiratory microbiotas (p adjusted = 0.018) were observed in the former. Taxonomic analysis of gut bacterial microbiota revealed a decrease over time in the median proportion of Bifidobacterium longum for all infants (25-14.3%, p = 0.0006 in OPV-revaccinated infants and 25.3-11.6%, p = 0.01 in controls), compatible with the reported weaning. Also, it showed a restricted increase in the median proportion of Prevotella_9 genus in controls (1.4-7.1%, p = 0.02), whereas in OPV revaccinated infants an increase over time in Prevotellaceae family (7.2-17.4%, p = 0.005) together with a reduction in median proportion of potentially pathogenic/opportunistic genera such as Escherichia/Shigella (5.8-3.4%, p = 0.01) were observed. Taxonomic analysis of upper respiratory bacterial microbiota revealed an increase over time in median proportions of potentially pathogenic/opportunistic genera in controls, such as Streptococcus (2.9-11.8%, p = 0.001 and Hemophilus (11.3-20.5%, p = 0.03), not observed in OPV revaccinated infants. In conclusion, OPV revaccination was associated with a healthier microbiome composition 2 months after revaccination, based on a more abundant and diversified bacterial community of Prevotellaceae and fewer pathogenic/opportunistic organisms. Further information on species-level differentiation and functional analysis of microbiome content are warranted to elucidate the impact of OPV-associated changes in bacterial microbiota on child health.

Understanding the child mortality decline in Guinea-Bissau: the role of population-level nutritional status measured by mid-upper arm circumference.

BACKGROUND: Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children's MUAC. METHODS: This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003-05) and a late period (2014-16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education. RESULTS: A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality. CONCLUSIONS: From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow's interventions.

Does Influenza Vaccination during Pregnancy Have Effects on Non-Influenza Infectious Morbidity? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from available randomised controlled trials (RCTs) of IIV to pregnant women, to assess whether IIV may have NSEs. Four RCTs, all conducted in low- and middle-income settings, were identified. We extracted information on all-cause and infectious mortality and adverse events in women and their infants. We conducted meta-analyses providing risk ratios (RR). The meta-analysis for maternal all-cause mortality provided a RR of 1.48 (95% CI = 0.52-4.16). The estimates for miscarriage/stillbirth and infant all-cause mortality up to 6 months of age were 1.06 (0.78-1.44) and 1.11 (0.87-1.41), respectively. IIV was associated with a higher risk of non-influenza infectious adverse events, with meta-estimates of 2.01 (1.15-3.50) in women and 1.36 (1.12-1.67) in infants up to 6 months of age. Thus, following a pattern seen for other non-live vaccines, IIV was associated with a higher risk of non-influenza infectious adverse events. To ensure that scarce resources are used well, and no harm is inflicted, further RCTs are warranted.

Disregarding the restrictive vial-opening policy for BCG vaccine in Guinea-Bissau: impact and cost-effectiveness for tuberculosis mortality and all-cause mortality in children aged 0-4 years.

OBJECTIVE: BCG vaccination is frequently delayed in low-income countries. Restrictive vial-opening policies, where a vial of BCG vaccine is not opened for few children, are a major reason for delay. During delays, children are unprotected against tuberculosis (TB) and deprived of non-specific effects of BCG. We assessed the potential effect and cost-effectiveness of disregarding the restrictive vial-opening policy, on TB and all-cause mortality, in children aged 0-4 years in Guinea-Bissau. METHODS: Using static mathematical models, we estimated the absolute and percentage change in TB and all-cause deaths, in children aged 0-4 years, between the current BCG vaccine restrictive-opening policy scenario, and a non-restrictive policy scenario where all children were vaccinated in the first health-facility contact. Incremental cost-effectiveness was estimated by integration of vaccine and treatment costs. FINDINGS: Disregarding the restrictive BCG vial-opening policy was estimated to reduce TB deaths by 11.0% (95% uncertainty range (UR):0.5%-28.8%), corresponding to 4 (UR:0-15) TB deaths averted per birth cohort in Guinea-Bissau, resulting in incremental cost-effectiveness of US$ 911 per discounted life-year gained (LYG) (UR:145-9142). For all-cause deaths, the estimated reduction was 8.1% (UR: 3.3%-12.7%) corresponding to 392 (UR:158-624) fewer all-cause deaths and an incremental cost-effectiveness of US$ 9 (UR:5-23) per discounted LYG. CONCLUSIONS: Disregarding the restrictive BCG vial-opening policy was associated with reductions in TB deaths and all-cause deaths and low cost-effectiveness ratios. Our results suggest that it would be cost-effective to disregard the restrictive vial-opening policy. Other settings with similar practice are also likely to gain from disregarding this policy.

Factors associated with birthweight and adverse pregnancy outcomes among children in rural Guinea-Bissau - a prospective observational study.

BACKGROUND: Low birthweight (LBW) is associated with higher mortality and morbidity, but there is limited data on the prevalence of LBW in rural Africa, where many births occur at home. The Bacillus Calmette-Guérin (BCG) vaccine has non-specific effects. Studies suggest that maternal BCG-vaccination may affect the health of the child. METHODS: The present study is nested within a randomised trial in rural Guinea-Bissau: Pregnancies were registered at two-monthly village visits, where information on BCG scar status and other background factors were obtained. Children were enrolled in the trial and weighed at home within 72 h after birth. In this prospective observational study, we assessed factors associated with adverse pregnancy outcomes and birthweight in binomial and linear regression models. RESULTS: Among 1320 women who had their BCG scar status assessed, 848 (64%) had a scar, 472 (36%) had no scar. The risk of adverse pregnancy outcomes (miscarriages, stillbirths, early neonatal deaths) tended to be higher among BCG scar-negative women (13%) than among women with a BCG scar (10%), adjusted prevalence ratio = 1.29 (0.99-1.68). Birthweight was assessed for 628 (50%) of the 1232 live born children. The mean birthweight was 2.89 kg (SD 0.43) and the proportion of LBW children was 17% (104/628). Sex, twinning, region of birth, maternal age, maternal mid-upper arm circumference (MUAC), antenatal consultations, parity and possession of a mobile phone were associated with birthweight, while maternal BCG scar status was not. CONCLUSIONS: This study provides the first birthweight data for home-born children in rural Guinea-Bissau, with a mean birthweight of 2.89 kg (SD 0.43) and a LBW prevalence of 17%. We found a tendency for higher risk of adverse pregnancy outcomes among BCG scar-negative women. Birthweight was similar in children of mothers with and without BCG scar.

The mortality effects of disregarding the strategy to save doses of measles vaccine: a cluster-randomised trial in Guinea-Bissau.

INTRODUCTION: Measles vaccine (MV) may improve health beyond measles protection. To avoid wastage from multi-dose vials, children in Guinea-Bissau are only measles vaccinated when aged 9-11 months and when six or more children are present. We assessed health impacts of providing MV to all measles-unvaccinated children 9-35 months. METHODS: We cluster-randomised 182 village clusters under demographic surveillance in rural Guinea-Bissau to an 'MV-for-all-policy' arm where we offered MV regardless of age and number of children present at our bi-annual village visits, or a 'Restrictive-MV-policy' arm where we followed national policy. Measles-unvaccinated children aged 9-35 months were eligible for enrolment and followed to 5 years of age. In intention-to-treat analyses, we compared mortality using Cox regression analyses with age as underlying timescale. The primary analysis was for children aged 12-35 months at eligibility assessment. Interactions with several background factors were explored. RESULTS: Between 2011 and 2016, we followed 2778 children in the primary analysis. MV coverage by 3 years was 97% among children eligible for enrolment under the MV-for-all-policy, and 48% under the Restrictive-MV-policy. Mortality was 59% lower than anticipated and did not differ by trial arm (MV-for-all-policy: 45/1405: Restrictive-MV-policy: 44/1373; HR: 0.95 (95% CI 0.64 to 1.43)). The effect of MV-for-all changed over time: The HR was 0.53 (95% CI 0.27 to 1.07) during the first 1½ years of enrolment but 1.47 (95% CI 0.87 to 2.50) later (p=0.02, test of interaction). Explorative analyses indicated that the temporal change may be related to interactions with other childhood interventions. CONCLUSION: The MV-for-all-policy increased MV coverage but had no overall effect on overall mortality. TRIAL REGISTRATION NUMBER: NCT01306006.

Birthweight data completeness and quality in population-based surveys: EN-INDEPTH study.

BACKGROUND: Low birthweight (< 2500 g) is an important marker of maternal health and is associated with neonatal mortality, long-term development and chronic diseases. Household surveys remain an important source of population-based birthweight information, notably Demographic and Health Surveys (DHS) and UNICEF's Multiple Indicator Cluster Surveys (MICS); however, data quality concerns remain. Few studies have addressed how to close these gaps in surveys. METHODS: The EN-INDEPTH population-based survey of 69,176 women was undertaken in five Health and Demographic Surveillance System sites (Matlab-Bangladesh, Dabat-Ethiopia, Kintampo-Ghana, Bandim-Guinea-Bissau, IgangaMayuge-Uganda). Responses to existing DHS/MICS birthweight questions on 14,411 livebirths were analysed and estimated adjusted odds ratios (aORs) associated with reporting weighing, birthweight and heaping reported. Twenty-eight focus group discussions with women and interviewers explored barriers and enablers to reporting birthweight. RESULTS: Almost all women provided responses to birthweight survey questions, taking on average 0.2 min to answer. Of all babies, 62.4% were weighed at birth, 53.8% reported birthweight and 21.1% provided health cards with recorded birthweight. High levels of heterogeneity were observed between sites. Home births and neonatal deaths were less likely to be weighed at birth (home births aOR 0.03(95%CI 0.02-0.03), neonatal deaths (aOR 0.19(95%CI 0.16-0.24)), and when weighed, actual birthweight was less likely to be known (aOR 0.44(95%CI 0.33-0.58), aOR 0.30(95%CI 0.22-0.41)) compared to facility births and post-neonatal survivors. Increased levels of maternal education were associated with increases in reporting weighing and knowing birthweight. Half of recorded birthweights were heaped on multiples of 500 g. Heaping was more common in IgangaMayuge (aOR 14.91(95%CI 11.37-19.55) and Dabat (aOR 14.25(95%CI 10.13-20.3) compared to Bandim. Recalled birthweights were more heaped than those recorded by card (aOR 2.59(95%CI 2.11-3.19)). A gap analysis showed large missed opportunity between facility birth and known birthweight, especially for neonatal deaths. Qualitative data suggested that knowing their baby's weight was perceived as valuable by women in all sites, but lack of measurement and poor communication, alongside social perceptions and spiritual beliefs surrounding birthweight, impacted women's ability to report birthweight. CONCLUSIONS: Substantial data gaps remain for birthweight data in household surveys, even amongst facility births. Improving the accuracy and recording of birthweights, and better communication with women, for example using health cards, could improve survey birthweight data availability and quality.

Birth, stillbirth and death registration data completeness, quality and utility in population-based surveys: EN-INDEPTH study.

BACKGROUND: Birth registration is a child's first right. Registration of live births, stillbirths and deaths is foundational for national planning. Completeness of birth registration for live births in low- and middle-income countries is measured through population-based surveys which do not currently include completeness of stillbirth or death registration. METHODS: The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). In four African sites, we included new/modified questions regarding registration for 1177 stillbirths and 11,881 livebirths (1333 neonatal deaths and 10,548 surviving the neonatal period). Questions were evaluated for completeness of responses, data quality, time to administer and estimates of registration completeness using descriptive statistics. Timing of birth registration, factors associated with non-registration and reported barriers were assessed using descriptive statistics and logistic regression. RESULTS: Almost all women, irrespective of their baby's survival, responded to registration questions, taking an average of < 1 min. Reported completeness of birth registration was 30.7% (6.1-53.5%) for babies surviving the neonatal period, compared to 1.7% for neonatal deaths (0.4-5.7%). Women were able to report age at birth registration for 93.6% of babies. Non-registration of babies surviving the neonatal period was significantly higher for home-born children (aOR 1.43 (95% CI 1.27-1.60)) and in Dabat (Ethiopia) (aOR 4.11 (95% CI 3.37-5.01)). Other socio-demographic factors associated with non-registration included younger age of mother, more prior births, little or no education, and lower socio-economic status. Neonatal death registration questions were feasible (100% women responded; only 1% did not know), revealing extremely low completeness with only 1.2% of neonatal deaths reported as registered. Despite > 70% of stillbirths occurring in facilities, only 2.5% were reported as registered. CONCLUSIONS: Questions on birth, stillbirth and death registration were feasible in a household survey. Completeness of birth registration is low in all four sites, but stillbirth and neonatal death registration was very low. Closing the registration gap amongst facility births could increase registration of both livebirths and facility deaths, including stillbirths, but will require co-ordination between civil registration systems and the often over-stretched health sector. Investment and innovation is required to capture birth and especially deaths in both facility and community systems.

Life expectancy of HIV-infected patients followed at the largest hospital in Guinea-Bissau is one-fourth of life expectancy of the background population.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population. RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed. CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

National Immunization Campaigns With Oral Polio Vaccine May Reduce All-cause Mortality: An Analysis of 13 Years of Demographic Surveillance Data From an Urban African Area.

BACKGROUND: Between 2002 and 2014, Guinea-Bissau had 17 national campaigns with oral polio vaccine (OPV) as well as campaigns with vitamin A supplementation (VAS), measles vaccine (MV), and H1N1 influenza vaccine. We examined the impact of these campaigns on child survival. METHODS: We examined the mortality rate between 1 day and 3 years of age of all children in the study area. We used Cox models with age as underlying time to calculate adjusted mortality rate ratios (MRRs) between "after-campaign" mortality and "before-campaign" mortality, adjusted for temporal change in mortality and stratified for season at risk. RESULTS: Mortality was lower after OPV-only campaigns than before, with an MRR for after-campaign vs before-campaign being 0.75 (95% confidence interval [CI], .67-.85). Other campaigns did not have similar effects, the MRR being 1.22 (95% CI, 1.04-1.44) for OPV + VAS campaigns, 1.39 (95% CI, 1.20-1.61) for VAS-only campaigns, 1.32 (95% CI, 1.09-1.60) for MV + VAS campaigns, and 1.13 (95% CI, .86-1.49) for the H1N1 campaign. Thus, all other campaigns differed significantly from the effect of OPV-only campaigns. Effects did not differ for trivalent, bivalent, or monovalent strains of OPV. With each additional campaign of OPV only, the mortality rate declined further (MRR, 0.86 [95% CI, .81-.92] per campaign). With follow-up to 3 years of age, the number needed to treat to save 1 life with the OPV-only campaign was 50 neonates. CONCLUSIONS: OPV campaigns can have a much larger effect on child survival than otherwise assumed. Stopping OPV campaigns in low-income countries as part of the endgame for polio infection may increase child mortality.

Diphtheria-Tetanus-Pertussis (DTP) Vaccine Is Associated With Increased female-Male Mortality. Studies of DTP administered before and after measles vaccine.

BACKGROUND: The third dose of diphtheria-tetanus-pertussis vaccine (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality. METHODS: We updated previous literature searches for DTP studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV. RESULTS: Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (95% confidence interval [CI], .88-1.57) after DTP1 and increased to 1.66 (95% CI, 1.32-2.09) after DTP3. Following receipt of MV, the F/M MRR declined to 0.63 (95% CI, .42-.96). In 11 studies the F/M MRR increased to 1.73 (95% CI, 1.33-2.27) when DTP-containing vaccine was administered after MV. CONCLUSIONS: F/M MRR increased with increasing doses of DTP. After MV, girls had lower mortality than boys. With DTP after MV, mortality increased again for girls relative to boys. No bias can explain these changes in F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality.

Reduction in Short-term Outpatient Consultations After a Campaign With Measles Vaccine in Children Aged 9-59 Months: Substudy Within a Cluster-Randomized Trial.

BACKGROUND: We assessed a measles vaccination campaign's potential short-term adverse events. METHODS: In a cluster-randomized trial assessing a measles vaccination campaign's effect on all-cause mortality and hospital admission among children aged 9-59 months in Guinea-Bissau, children received a measles vaccination (intervention) or a health check-up (control). One month to 2 months later, we visited a subgroup of children to ask mothers/guardians about outpatient consultations since enrollment. In log-binomial models, we estimated the relative risk (RR) of nonaccidental outpatient consultations. RESULTS: Among 8319 children (4437 intervention/3882 control), 652 nonaccidental outpatient consultations occurred (322 intervention/330 control). The measles vaccination campaign tended to reduce nonaccidental outpatient consultations by 16% (RR, 0.84 [95% confidence interval {CI}, .65-1.11]), especially if caused by respiratory symptoms (RR, 0.68 [95% CI, .42-1.11]). The reduction tended to be larger in children who prior to trial enrollment had a pentavalent vaccination (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b) as the most recent vaccination (RR, 0.61 [95% CI, .42-.89]) than in children who prior to trial enrollment had a routine measles vaccination as the most recent vaccination (RR, 0.93 [95% CI, .68-1.26]) (P = .04 for interaction). CONCLUSIONS: In the short term, a measles vaccination campaign seems not to increase nonaccidental outpatient consultations but may reduce them. CLINICAL TRIALS REGISTRATION: NCT03460002.