Pregnancy-related mortality up to 1 year postpartum in sub-Saharan Africa: an analysis of verbal autopsy data from six countries.

OBJECTIVE: To compare the causes of death for women who died during pregnancy and within the first 42 days postpartum with those of women who died between >42 days and within 1 year postpartum. DESIGN: Open population cohort (Health and Demographic Surveillance Systems). SETTING: Ten Health and Demographic Surveillance Systems (HDSS) in The Gambia, Kenya, Malawi, Tanzania, Ethiopia and South Africa. POPULATION: 2114 deaths which occurred within 1 year of the end of pregnancy where a verbal autopsy interview was conducted from 2000 to 2019. METHODS: InterVA5 and InSilicoVA verbal autopsy algorithms were used to attribute the most likely underlying cause of death, which were grouped according to adapted International Classification of Diseases-Maternal Mortality categories. Multinomial regression was used to compare differences in causes of deaths within 42 days versus 43-365 days postpartum adjusting for HDSS and time period (2000-2009 and 2010-2019). MAIN OUTCOME MEASURES: Cause of death and the verbal autopsy Circumstances of Mortality Categories (COMCATs). RESULTS: Of 2114 deaths, 1212 deaths occurred within 42 days postpartum and 902 between 43 and 365 days postpartum. Compared with deaths within 42 days, deaths from HIV and TB, other infectious diseases, and non-communicable diseases constituted a significantly larger proportion of late pregnancy-related deaths beyond 42 days postpartum, and health system failures were important in the circumstances of those deaths. The contribution of HIV and TB to deaths beyond 42 days postpartum was greatest in Southern Africa. The causes of pregnancy-related mortality within and beyond 42 days postpartum did not change significantly between 2000-2009 and 2010-2019. CONCLUSIONS: Cause of death data from the extended postpartum period are critical to inform prevention. The dominance of HIV and TB, other infectious and non-communicable diseases to (late) pregnancy-related mortality highlights the need for better integration of non-obstetric care with ante-, intra- and postpartum care in high-burden settings.

Drivers of Decline in Diarrhea Mortality Between GEMS and VIDA Studies.

BACKGROUND: Statistical modeling suggests that decreasing diarrhea-associated mortality rates in recent decades are largely attributed to improved case management, rotavirus vaccine, and economic development. METHODS: We examined data collected in 2 multisite population-based diarrhea case-control studies, both conducted in The Gambia, Kenya, and Mali: the Global Enteric Multicenter Study (GEMS; 2008-2011) and Vaccine Impact on Diarrhea in Africa (VIDA; 2015-2018). Population-level diarrhea mortality and risk factor prevalence, estimated using these study data, were used to calculate the attribution of risk factors and interventions for diarrhea mortality using a counterfactual framework. We performed a decomposition of the effects of the changes in exposure to each risk factor between GEMS and VIDA on diarrhea mortality for each site. RESULTS: Diarrhea mortality among children under 5 in our African sites decreased by 65.3% (95% confidence interval [CI]: -80.0%, -45.0%) from GEMS to VIDA. Kenya and Mali had large relative declines in diarrhea mortality between the 2 periods with 85.9% (95% CI: -95.1%, -71.5%) and 78.0% (95% CI: -96.0%, 36.3%) reductions, respectively. Among the risk factors considered, the largest declines in diarrhea mortality between the 2 study periods were attributed to reduction in childhood wasting (27.2%; 95% CI: -39.3%, -16.8%) and an increased rotavirus vaccine coverage (23.1%; 95% CI: -28.4%, -19.4%), zinc for diarrhea treatment (12.1%; 95% CI: -16.0%, -8.9%), and oral rehydration salts (ORS) for diarrhea treatment (10.2%). CONCLUSIONS: The VIDA study sites demonstrated exceptional reduction in diarrhea mortality over the last decade. Site-specific differences highlight an opportunity for implementation science in collaboration with policymakers to improve the equitable coverage of these interventions globally.

Quantifying excess mortality during the COVID-19 pandemic in 2020 in The Gambia: a time-series analysis of three health and demographic surveillance systems.

OBJECTIVES: Estimates for COVID-19-related excess mortality for African populations using local data are needed to design and implement effective control policies. METHODS: We applied time-series analysis using data from three health and demographic surveillance systems in The Gambia (Basse, Farafenni, and Keneba) to examine pandemic-related excess mortality during 2020, when the first SARS-CoV-2 wave was observed, compared to the pre-pandemic period (2016-2019). RESULTS: Across the three sites, average mortality during the pre-pandemic period and the total deaths during 2020 were 1512 and 1634, respectively (Basse: 1099 vs 1179, Farafenni: 316 vs 351, Keneba: 98 vs 104). The overall annual crude mortality rates per 100,000 (95% CI) were 589 (559, 619) and 599 (571, 629) for the pre-pandemic and 2020 periods, respectively. The adjusted excess mortality rate was 8.8 (-34.3, 67.6) per 100,000 person-month with the adjusted rate ratio (aRR) = 1.01 (0.94,1.11). The age-stratified analysis showed excess mortality in Basse for infants (aRR = 1.22 [1.04, 1.46]) and in Farafenni for the 65+ years age group (aRR = 1.19 [1, 1.44]). CONCLUSION: We did not find significant excess overall mortality in 2020 in The Gambia. However, some age groups may have been at risk of excess death. Public health response in countries with weak health systems needs to consider vulnerable age groups and the potential for collateral damage.

Women's risk of death beyond 42 days post partum: a pooled analysis of longitudinal Health and Demographic Surveillance System data in sub-Saharan Africa.

BACKGROUND: WHO's standard definitions of pregnancy-related and maternal deaths only include deaths that occur within 42 days of delivery, termination, or abortion, with major implications for post-partum care and maternal mortality surveillance. We therefore estimated post-partum survival from childbirth up to 1 year post partum to evaluate the empirical justification for the 42-day post-partum threshold. METHODS: We used prospective, longitudinal Health and Demographic Surveillance System (HDSS) data from 30 sites across 12 sub-Saharan African countries to estimate women's risk of death from childbirth until 1 year post partum from all causes. Observations were included if the childbirth occurred from 1991 onwards in the HDSS site and maternal age was 10-54 years. We calculated person-years as the time between childbirth and next birth, outmigration, death, or the end of the first year post partum, whichever occurred first. For six post-partum risk intervals (0-1 days, 2-6 days, 7-13 days, 14-41 days, 42-122 days, and 4-11 months), we calculated the adjusted rate ratios of death relative to a baseline risk of 12-17 months post partum. FINDINGS: Between Jan 1, 1991, and Feb 24, 2020, 647 104 births occurred in the HDSS sites, contributing to 602 170 person-years of exposure time and 1967 deaths within 1 year of delivery. After adjustment for confounding, mortality was 38·82 (95% CI 33·21-45·29) times higher than baseline on days 0-1 after childbirth, 4·97 (3·94-6·21) times higher for days 2-6, 3·35 (2·64-4·20) times higher for days 7-13, and 2·06 (1·74-2·44) times higher for days 14-41. From 42 days to 4 months post partum, mortality was still 1·20 (1·03-1·39) times higher (ie, a 20% higher risk), but deaths in this interval would be excluded from measurement of pregnancy-related mortality. Extending the WHO 42-day post-partum threshold up to 4 months would increase the post-partum pregnancy-related mortality ratio by 40%. INTERPRETATION: This multicountry study has implications for measurement and clinical practice. It makes the case for WHO to extend the 42-day post-partum threshold to capture the full duration of risk of pregnancy-related deaths. There is a need for a new indicator to track late pregnancy-related deaths that occur beyond 42 days, which are otherwise excluded from global maternal health surveillance efforts. Our results also emphasise the need for international agencies to disaggregate estimates by antepartum, intrapartum, postpartum, and extended post-partum periods. Additionally, the schedule and content of postnatal care packages should reflect the extended duration of post-partum risk. FUNDING: The UK Economic and Social Research Council.

Assessment of the consistency of health and demographic surveillance and household survey data: A demonstration at two HDSS sites in The Gambia.

OBJECTIVE: To assess whether an adapted Demographic and Health Survey (DHS) like cross-sectional household survey with full pregnancy histories can demonstrate the validity of health and demographic surveillance (HDSS) data by producing similar population structural characteristics and childhood mortality indicators at two HDSS sites in The Gambia-Farafenni and Basse. METHODS: A DHS-type survey was conducted of 2,580 households in the Farafenni HDSS, and 2,907 in the Basse HDSS. Household members were listed and pregnancy histories obtained for all women aged 15-49. HDSS datasets were extracted for the same households including residency episodes for all current and former members and compared with the survey data. Neonatal (0-28 days), infant (<1 year), child (1-4 years) and under-5 (< 5 years) mortality rates were derived from each source by site and five-year periods from 2001-2015 and by calendar year between 2011 and 2015 using Kaplan-Meier failure probabilities. Survey-HDSS rate ratios were determined using the Mantel-Haenszel method. RESULTS: The selected households in Farafenni comprised a total population of 27,646 in the HDSS, compared to 26,109 captured in the household survey, implying higher coverage of 94.4% (95% CI: 94.1-94.7; p<0.0001) against a hypothesised proportion of 90% in the HDSS. All population subgroups were equally covered by the HDSS except for the Wollof ethnic group. In Basse, the total HDSS population was 49,287, compared to 43,538 enumerated in the survey, representing an undercount of the HDSS by the survey with a coverage of 88.3% (95% CI: 88.0-88.6; p = 1). All sub-population groups were also under-represented by the survey. Except for the neonatal mortality rate for Farafenni, the childhood mortality indicators derived from pregnancy histories and HDSS data compare reasonably well by 5-year periods from 2001-2015. Annual estimates from the two data sources for the most recent quinquennium, 2011-2015, were similar in both sites, except for an excessively high neonatal mortality rate for Farafenni in 2015. CONCLUSION: Overall, the adapted DHS-type survey has reasonably represented the Farafenni HDSS database using population size and structure; and both databases using childhood mortality indicators. If the hypothetical proportion is lowered to 85%, the survey would adequately validate both HDSS databases in all considered aspects. The adapted DHS-type sample household survey therefore has potential for validation of HDSS data.

Healthcare Seeking and Access to Care for Pneumonia, Sepsis, Meningitis, and Malaria in Rural Gambia.

Children with acute infectious diseases may not present to health facilities, particularly in low-income countries. We investigated healthcare seeking using a cross-sectional community survey, health facility-based exit interviews, and interviews with customers of private pharmacies in 2014 in Upper River Region (URR) The Gambia, within the Basse Health & Demographic Surveillance System. We estimated access to care using surveillance data from 2008 to 2017 calculating disease incidence versus distance to the nearest health facility. In the facility-based survey, children and adult patients sought care initially at a pharmacy (27.9% and 16.7% respectively), from a relative (23.1% and 28.6%), at a local shop or market (13.5% and 16.7%), and on less than 5% of occasions with a community-based health worker, private clinic, or traditional healer. In the community survey, recent symptoms of pneumonia or sepsis (15% and 1.5%) or malaria (10% and 4.6%) were common in children and adults. Rates of reported healthcare-seeking were high with families of children favoring health facilities and adults favoring pharmacies. In the pharmacy survey, 47.2% of children and 30.4% of adults had sought care from health facilities before visiting the pharmacy. Incidence of childhood disease declined with increasing distance of the household from the nearest health facility with access to care ratios of 0.75 for outpatient pneumonia, 0.82 for hospitalized pneumonia, 0.87 for bacterial sepsis, and 0.92 for bacterial meningitis. In rural Gambia, patients frequently seek initial care at pharmacies and informal drug-sellers rather than community-based health workers. Surveillance underestimates disease incidence by 8-25%.

Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance.

BACKGROUND: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. METHODS: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. FINDINGS: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49). INTERPRETATION: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. FUNDING: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

Health and demographic surveillance systems in low- and middle-income countries: history, state of the art and future prospects.

Health and Demographic Surveillance Systems (HDSS) have been developed in several low- and middle-income countries (LMICs) in Africa and Asia. This paper reviews their history, state of the art and future potential and highlights substantial areas of contribution by the late Professor Peter Byass.Historically, HDSS appeared in the second half of the twentieth century, responding to a dearth of accurate population data in poorly resourced settings to contextualise the study of interventions to improve health and well-being. The progress of the development of this network is described starting with Pholela, and progressing through Gwembe, Balabgarh, Niakhar, Matlab, Navrongo, Agincourt, Farafenni, and Butajira, and the emergence of the INDEPTH Network in the early 1990'sThe paper describes the HDSS methodology, data, strengths, and limitations. The strengths are particularly their temporal coverage, detail, dense linkage, and the fact that they exist in chronically under-documented populations in LMICs where HDSS sites operate. The main limitations are generalisability to a national population and a potential Hawthorne effect, whereby the project itself may have changed characteristics of the population.The future will include advances in HDSS data harmonisation, accessibility, and protection. Key applications of the data are to validate and assess bias in other datasets. A strong collaboration between a national HDSS network and the national statistics office is modelled in South Africa and Sierra Leone, and it is possible that other low- to middle-income countries will see the benefit and take this approach.

Under-five mortality in The Gambia: Comparison of the results of the first demographic and health survey with those from existing inquiries.

BACKGROUND: In The Gambia, national estimates of under-five mortality (U5M) were from censuses and multiple indicator cluster surveys (MICS). The country's first demographic and health survey (DHS) conducted in 2013 provided empirical disaggregated national estimates of neonatal, post-neonatal and child mortality trends. OBJECTIVE: To assess the consistency and accuracy of the estimates of U5M from the existing data sources and its age-specific components in rural Gambia and produce reliable up-to-date estimates. METHODS: Available national data on under-five mortality from 2000 onwards were extracted. Additionally, data from two DHS regions were compared to those from two health and demographic surveillance systems (HDSS) located within them. Indirect and direct estimates from the data were compared and flexible parametric survival methods used to predict mortality rates for all empirical data points up to 2015. FINDINGS: Internal consistency checks on data quality for indirect estimation of U5M suggest that the data were plausible at national level once information from women aged 15-19 years was excluded. The DHS and HDSS data used to make direct U5M estimates were plausible, however HDSS data were of better quality. For 2009-2013, the DHS estimates agreed well with the 2013 census and 2010 MICS reports of U5M but was less accurate about the early births of older women. The most recent estimates from the 2013 DHS, which refer to 2011-12, are an U5M rate of 54/1000 livebirths (95% CI: 43-64) and a neonatal mortality rate of 21/1000 livebirths (95% CI: 15-27), contributing almost 40% of U5M in The Gambia. The DHS showed that for the decade prior to the survey, child mortality dropped by 55% and neonatal mortality by 31%. This indicates the importance of neonatal mortality in The Gambia, and the need to focus on neonatal survival, while maintaining currently successful strategies to further reduce U5M.

Design of vaccine efficacy trials during public health emergencies.

Public health emergencies, such as an Ebola disease outbreak, provide a complex and challenging environment for the evaluation of candidate vaccines. Here, we outline the need for flexible and responsive vaccine trial designs to be used in public health emergencies, and we summarize recommendations for their use in this setting.

Cryptosporidium infection in rural Gambian children: Epidemiology and risk factors.

BACKGROUND: Cryptosporidium is a major pathogen associated with diarrheal disease in young children. We studied Cryptosporidium diarrhea in children enrolled in the Global Enteric Multicenter Study (GEMS) in rural Gambia. METHODS: We recruited children <5 years of age with moderate-to-severe diarrhea (MSD) for 3 years (2008-2010), and children with either MSD or less severe diarrhea (LSD) for one year (November 2011-November 2012) at sentinel health centers. One or more randomly selected controls were matched to each case. Stool samples were tested to identify Cryptosporidium by immunoassay. A subset of randomly selected case-controls pairs were tested for Cryptosporidium species. We investigated the epidemiology of, and evaluated possible risk factors for, Cryptosporidium-positive diarrhea. RESULTS: We enrolled 1938 cases (1381 MSD, 557 LSD) and 2969 matched controls; 231/1929 (12.0%) of diarrhea cases and 141/2962 (4.8%) of controls were positive for Cryptosporidium. Most Cryptosporidium diarrhea cases (85.7%, 198/231) were aged 6-23 months, and most (81.4%, 188/231) occurred during the rainy season. Cryptosporidium hominis (C. hominis) was the predominant (82.6%) species. We found associations between increased risk of Cryptosporidium-positive MSD or LSD, or both, with consumption of stored drinking water and certain animals living in the compound-cow, cat (MSD only) and rodents (LSD only). Larger households, fowl living in the compound, and the presence of Giardia infection were associated with decreased risk of Cryptosporidium MSD and LSD. CONCLUSION: Cryptosporidium-positive diarrhea is prevalent in this setting, especially at 6-23 months of age. The preponderance of Cryptosporidium infection in the rainy season and increased risk of Cryptosporidium-positive diarrhea with consumption of stored drinking water suggest water-borne transmission. Further investigation is needed to clarify the role of animals and contamination of stored drinking water in Cryptosporidium transmission.

Staphylococcus aureus Bacteremia in Children of Rural Areas of The Gambia, 2008-2015.

Staphylococcus aureus bacteremia is a substantial cause of childhood disease and death, but few studies have described its epidemiology in developing countries. Using a population-based surveillance system for pneumonia, sepsis, and meningitis, we estimated S. aureus bacteremia incidence and the case-fatality ratio in children <5 years of age in 2 regions in the eastern part of The Gambia during 2008-2015. Among 33,060 children with suspected pneumonia, sepsis, or meningitis, we performed blood culture for 27,851; of 1,130 patients with bacteremia, 198 (17.5%) were positive for S. aureus. S. aureus bacteremia incidence was 78 (95% CI 67-91) cases/100,000 person-years in children <5 years of age and 2,080 (95% CI 1,621-2,627) cases/100,000 person-years in neonates. Incidence did not change after introduction of the pneumococcal conjugate vaccine. The case-fatality ratio was 14.1% (95% CI 9.6%-19.8%). Interventions are needed to reduce the S. aureus bacteremia burden in The Gambia, particularly among neonates.

The role of leadership in people-centred health systems: a sub-national study in The Gambia.

Recently, increasing attention has been given to behavioural and relational aspects of the people who both define and shape health systems, placing them at the core. A growing refrain includes the assertion that important decisions determining health system performance, including agenda setting, policy formulation and policy implementation, are made by people. Within this actor-oriented approach, good leadership has been identified as a key contributing factor in health systems strengthening. However, leadership remains ill-defined and under-researched, especially in resource-limited settings, and understanding the links between leadership and health outcomes remains a challenge. We explore the concept and practice of healthcare leadership at sub-national level in a low-income country setting, using a people-centric research methodology. In June and July 2013, 15 in-depth interviews were conducted with key informants in formal healthcare leadership roles across urban, peri-urban and rural settings of The Gambia, West Africa. Participants included the entire spectrum of Regional Health Team (RHT) Directors and Chief Executive Officers of all government hospitals, as well as one clinical officer-in-charge in a secondary-level major health centre. We found reference to several important aspects of, and approaches to, leadership, including (i) setting a clear vision; (ii) engendering shared leadership; and (iii) paying attention to human relations in management. Participants described attending to constituencies in government, international development agencies and civil society, as well as to the populations they serve. By illuminating the multi-polar networks within which these leaders are embedded, and through which they operate, we provide insight into the complex 'organizational ecology' of the Gambian health system. There is a need to further research and develop healthcare leadership across all levels, within various political, socio-economic and cultural contexts, in order to better work with a range of health actors and to engage them in identifying and acting upon opportunities for health systems strengthening.

Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. METHODS: We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2-59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. FINDINGS: We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2-11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7-36) in 2014-15. In the 12-23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12-42). In children aged 2-4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1-39). Incidence of all clinical pneumonia increased by 4% (-1 to 8), but hospitalised cases declined by 8% (3-13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22-77) in children aged 2-11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47-88) in children aged 12-23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42-67) in children aged 2-11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58-82) in children aged 12-23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30-1·08) in children aged 3-11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls. INTERPRETATION: The introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia. FUNDING: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council.

Effect of maternal death on child survival in rural West Africa: 25 years of prospective surveillance data in The Gambia.

BACKGROUND: The death of a mother is a tragedy in itself but it can also have devastating effects for the survival of her children. We aim to explore the impact of a mother's death on child survival in rural Gambia, West Africa. METHODS: We used 25 years of prospective surveillance data from the Farafenni Health and Demographic surveillance system (FHDSS). Mortality rates per 1,000 child-years up to ten years of age were estimated and Kaplan-Meier survival curves plotted by maternal vital status. Cox proportional hazard models were used to examine factors associated with child survival. FINDINGS: Between 1st April 1989 and 31st December 2014, a total of 2, 221 (7.8%) deaths occurred during 152,906 child-years of follow up. Overall mortality rate was 14.53 per 1,000 child-years (95% CI: 13.93-15.14). Amongst those whose mother died, the rate was 25.89 (95% CI: 17.99-37.25) compared to 14.44 (95% CI: 13.84-15.06) per 1,000 child-years for those whose mother did not die. Children were 4.66 (95% CI: 3.15-6.89) times more likely to die if their mother died compared to those with a surviving mother. Infants whose mothers died during delivery or shortly after were up to 7 times more likely to die within the first month of life compared to those whose mothers survived. Maternal vital status was significantly associated with the risk of dying within the first 2 years of life (p-value <0.05), while this was no longer observed for children over 2 years of age (P = 0.872). Other factors associated with an increased risk of dying were living in more rural areas, and birth spacing and year of birth. CONCLUSIONS: Mother's survival is strongly associated with child survival. Our findings highlight the importance of the continuum of care for both the mother and child not only throughout pregnancy, and childbirth but beyond 6 weeks post-partum.

Barriers to timely administration of birth dose vaccines in The Gambia, West Africa.

OBJECTIVE: Although vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6-12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia. METHODS: We used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0-1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014. RESULTS: Most of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR)=6.13, 95%CI: 3.20-11.75, east rural: AOR=6.72, 95%CI: 3.66-12.33) and maternal education (senior-educations: AOR=2.43, 95%CI: 1.17-5.06); and inversely associated with distance to vaccination delivery points (≧2km: AOR=0.41, 95%CI: 0.24-0.70), and Fula ethnicity (AOR=0.60, 95%CI: 0.40-0.91). CONCLUSION: Vaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed.

The large contribution of twins to neonatal and post-neonatal mortality in The Gambia, a 5-year prospective study.

BACKGROUND: A high twinning rate and an increased risk of mortality among twins contribute to the high burden of infant mortality in Africa. This study examined the contribution of twins to neonatal and post-neonatal mortality in The Gambia, and evaluated factors that contribute to the excess mortality among twins. METHODS: We analysed data from the Basse Health and Demographic Surveillance System (BHDSS) collected from January 2009 to December 2013. Demographic and epidemiological variables were assessed for their association with mortality in different age groups. RESULTS: We included 32,436 singletons and 1083 twins in the analysis (twining rate 16.7/1000 deliveries). Twins represented 11.8 % of all neonatal deaths and 7.8 % of post-neonatal deaths. Mortality among twins was higher than in singletons [adjusted odds ratio (AOR) 4.33 (95 % CI: 3.09, 6.06) in the neonatal period and 2.61 (95 % CI: 1.85, 3.68) in the post-neonatal period]. Post-neonatal mortality among twins increased in girls (P for interaction = 0.064), being born during the dry season (P for interaction = 0.030) and lacking access to clean water (P for interaction = 0.042). CONCLUSION: Mortality among twins makes a significant contribution to the high burden of neonatal and post-neonatal mortality in The Gambia and preventive interventions targeting twins should be prioritized.

Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study.

BACKGROUND: Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. METHODS: We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008-May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013-Dec 31, 2014), adjusting for changes in case ascertainment over time. FINDINGS: We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30-71) in the 2-23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64-91) reduction in serotypes covered by the PCV13 vaccine. In the 2-4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25-75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39-83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2-59 months increased by 47% (-21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time. INTERPRETATION: The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2-59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2-4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. FUNDING: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.

Child Mortality after Discharge from a Health Facility following Suspected Pneumonia, Meningitis or Septicaemia in Rural Gambia: A Cohort Study.

OBJECTIVE: To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. METHODS: We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2-59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors. FINDINGS: One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2-11 and 12-59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5-13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5-11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality. CONCLUSION: Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.

Health & Demographic Surveillance System Profile: Farafenni Health and Demographic Surveillance System in The Gambia.

The Farafenni Health and Demographic Surveillance System (Farafenni HDSS) is located 170 km from the coast in a rural area of The Gambia, north of the River Gambia. It was set up in 1981 by the UK Medical Research Council Laboratories to generate demographic and health information required for the evaluation of a village-based, primary health care programme in 40 villages. Regular updates of demographic events and residency status have subsequently been conducted every 4 months. The surveillance area was extended in 2002 to include Farafenni Town and surrounding villages to support randomized, controlled trials. With over three decades of prospective surveillance, and through specific scientific investigations, the platform (population ≈ 50,000) has generated data on: morbidity and mortality due to malaria in children and during pregnancy; non-communicable disease among adults; reproductive health; and levels and trends in childhood and maternal mortality. Other information routinely collected includes causes of death through verbal autopsy, and household socioeconomic indicators. The current portfolio of the platform includes tracking Millennium Development Goal 4 (MDG4) attainments in rural Gambia and cause-of-death determination.