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.

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 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.

Spatial analysis of under-5 mortality and potential risk factors in the Basse Health and Demographic Surveillance System, the Gambia.

OBJECTIVES: To describe the spatial pattern in under-5 mortality rates in the Basse Health and Demographic Surveillance System (BHDSS) and to test for associations between under-5 deaths and biodemographic and socio-economic risk factors. METHODS: Using data on child survival from 2007 to 2011 in the BHDSS, we mapped under-5 mortality by km(2) . We tested for spatial clustering of high or low death rates using Kulldorff's spatial scan statistic. Associations between child death and a variety of biodemographic and socio-economic factors were assessed with Cox proportional hazards models, and deviance residuals from the best-fitting model were tested for spatial clustering. RESULTS: The overall death rate among children under 5 was 0.0195 deaths per child-year. We found two spatial clusters of high death rates and one spatial cluster of low death rates; children in the two high clusters died at a rate of 0.0264 and 0.0292 deaths per child-year, while in the low cluster, the rate was 0.0144 deaths per child-year. We also found that children born to Fula mothers experienced, on average, a higher hazard of death, whereas children born in the households in the upper two quintiles of asset ownership experienced, on average, a lower hazard of death. After accounting for the spatial distribution of biodemographic and socio-economic characteristics, we found no residual spatial pattern in child mortality risk. CONCLUSION: This study demonstrates that significant inequality in under-5 death rates can occur within a relatively small area (1100 km(2) ). Risks of under-5 mortality were associated with mother's ethnicity and household wealth. If high mortality clusters persist, then equity concerns may require additional public health efforts in those areas.

Serogroup W135 meningococcal disease, The Gambia, 2012.

In 2012, an outbreak of Neisseria meningitidis serogroup W135 occurred in The Gambia. The attack rate was highest among young children. The associated risk factors were male sex, contact with meningitis patients, and difficult breathing. Enhanced surveillance facilitates early epidemic detection, and multiserogroup conjugate vaccine could reduce meningococcal epidemics in The Gambia.

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.

Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

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.

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.

Two strategies for the delivery of IPTc in an area of seasonal malaria transmission in the Gambia: a randomised controlled trial.

BACKGROUND: The Expanded Programme on Immunisation (EPI) provides an effective way of delivering intermittent preventive treatment for malaria (IPT) to infants. However, it is uncertain how IPT can be delivered most effectively to older children. Therefore, we have compared two approaches to the delivery of IPT to Gambian children: distribution by village health workers (VHWs) or through reproductive and child health (RCH) trekking teams. In rural areas, RCH trekking teams provide most of the health care to children under the age of 5 years in the Infant Welfare Clinic, and provide antenatal care for pregnant women. METHODS AND FINDINGS: During the 2006 malaria transmission season, the catchment populations of 26 RCH trekking clinics in The Gambia, each with 400-500 children 6 years of age and under, were randomly allocated to receive IPT from an RCH trekking team or from a VHW. Treatment with a single dose of sulfadoxine pyrimethamine (SP) plus three doses of amodiaquine (AQ) were given at monthly intervals during the malaria transmission season. Morbidity from malaria was monitored passively throughout the malaria transmission season in all children, and a random sample of study children from each cluster was examined at the end of the malaria transmission season. The primary study endpoint was the incidence of malaria. Secondary endpoints included coverage of IPTc, mean haemoglobin (Hb) concentration, and the prevalence of asexual malaria parasitaemia at the end of malaria transmission period. Financial and economic costs associated with the two delivery strategies were collected and incremental cost and effects were compared. A nested case-control study was used to estimate efficacy of IPT treatment courses. Treatment with SP plus AQ was safe and well tolerated. There were 49 cases of malaria with parasitaemia above 5,000/µl in the areas where IPT was delivered through RCH clinics and 21 cases in the areas where IPT was delivered by VHWs, (incidence rates 2.8 and 1.2 per 1,000 child months, respectively, rate difference 1.6 [95% confidence interval (CI) -0.24 to 3.5]). Delivery through VHWs achieved a substantially higher coverage level of three courses of IPT than delivery by RCH trekking teams (74% versus 48%, a difference of 27% [95% CI 16%-38%]). For both methods of delivery, coverage was unrelated to indices of wealth, with similar coverage being achieved in the poorest and wealthiest groups. The prevalence of anaemia was low in both arms of the trial at the end of the transmission season. Efficacy of IPTc against malaria during the month after each treatment course was 87% (95% CI 54%-96%). Delivery of IPTc by VHWs was less costly in both economic and financial terms than delivery through RCH trekking teams, resulting in incremental savings of US$872 and US$1,244 respectively. The annual economic cost of delivering at least the first dose of each course of IPTc was US$3.47 and US$1.63 per child using trekking team and VHWs respectively. CONCLUSIONS: In this setting in The Gambia, delivery of IPTc to children 6 years of age and under by VHWs is more effective and less costly than delivery through RCH trekking clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00376155. Please see later in the article for the Editors' Summary.

Reaching millennium development goal 4 - the Gambia.

UNLABELLED: To describe how, through a DSS in a rural area of The Gambia, it has been possible to measure substantial reductions in child mortality rates and how we investigated whether the decline paralleled the registered fall in malaria incidence in the country. METHODS: Demographic surveillance data spanning 19.5 years (1 April 1989-30 September 2008) from 42 villages around the town of Farafenni, The Gambia, were used to estimate childhood mortality rates for neonatal, infant, child (1-4 years) and under-5 age groups. Data were presented in five a priori defined time periods, and annual rates per 1000 live births were derived from Kaplan-Meier survival probabilities. RESULTS: From 1989-1992 to 2004-2008, under-5 mortality declined by 56% (95% CI: 48-63%), from 165 (95% CI: 151-181) per 1000 live births to 74 (95% CI: 65-84) per 1000 live births. In 1- to 4-year-olds, mortality during the period 2004-2008 was 69% (95% CI: 60-76%) less than in 1989-1992. The corresponding mortality decline in infants was 39% (95% CI: 23-52%); in neonates, it was 38% (95% CI: 13-66%). The derived annual under-5 mortality rates declined from 159 per 1000 live births in 1990 to 45 per 1000 live births in 2008, thus implying an attainment of MDG4 seven years in advance of the target year of 2015. CONCLUSION: Achieving MDG4 is possible in poor, rural areas of Africa through widespread deployment of relatively simple measures that improve child survival, such as immunisation and effective malaria control.

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%.

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.

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.

Access to health care and mortality of children under 5 years of age in the Gambia: a case-control study.

OBJECTIVE: To assess whether traditional measures of access to health care (distance and travel time to a facility) and non-traditional measures (social and financial support indicators) are associated with mortality among children under 5 years of age in the Gambia. METHODS: We conducted a case-control study in a population under demographic surveillance. Cases (n = 140) were children under 5 years of age who died between 31 December 2003 and 30 April 2006. Each case was matched in age and sex to five controls (n = 700). Information was gathered by interviewing primary caregivers. The data were analysed using conditional logistic regression. FINDINGS: Of traditional measures of access, only rural versus urban/periurban residence was important: children from rural areas were more likely to die (OR: 4.9; 95% confidence interval, CI: 1.2-20.2). For non-traditional measures, children were more likely to die if their primary caregivers lacked help with meal preparation (OR: 2.3; 95% CI: 1.2-4.1), had no one to relax with (OR: 1.8; 95% CI: 1.1-2.9), had no one who could offer good advice (OR: 23.1; 95% CI: 4.3-123.4), had little say over how earned money was spent (OR: 12.7; 95% CI: 1.3-127.6), were unable to cut spending for health care (OR: 2.5; 95% CI: 1.5-4.2) or had to carry out odd jobs to pay for the care (OR: 3.4; 95% CI: 2.1-5.5). A protective effect was observed when the caregiver had other children to care for (OR: 0.2; 95% CI: 0.1-0.5). CONCLUSION: Improving access to health-care for children in the Gambia and similar settings is not simply a matter of reducing travel time and distance to a health facility, but requires improvements in caregivers' support networks and their access to the financial resources they need.

Preventive measures in infancy to reduce under-five mortality: a case-control study in The Gambia.

OBJECTIVE: To investigate the relationship between child mortality and common preventive interventions: vaccination, trained birthing attendants, tetanus toxoid during pregnancy, breastfeeding and vitamin A supplementation. METHODS: Case-control study in a population under demographic surveillance. Cases (n = 141) were children under five who died. Each was age and sex-matched to five controls (n = 705). Information was gathered by interviewing primary caregivers. RESULTS: All but one of the interventions - whether the mother had received tetanus toxoid during pregnancy - were protective against child mortality after multivariate analysis. Having a trained person assisting at child birth (OR 0.2 95% CI 0.1-0.4), receiving all vaccinations by 9 months of age (OR 0.1; 95% CI 0.01-0.3), being breastfed for more than 12 months (Children breastfed between 13 and 24 months OR 0.1 95% CI 0.03-0.3, more than 25 months OR 0.1 95% CI 0.01-0.5) and receiving vitamin A supplementation at or after 6 months of age (OR 0.05; 95% CI 0.01-0.2) were protective against child death. CONCLUSIONS: This study confirms the value of at least four available interventions in the prevention of under-five death in The Gambia. It is now important to identify those who are not receiving them and why, and to intervene to improve coverage across the population.

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.

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.

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.