Age Patterns of Mortality within Childhood in Sub-Saharan Africa

The age pattern of mortality in sub-Saharan Africa and how it varies across the continent remain poorly understood. The region lacks accurate registration statistics and assumptions about mortality patterns are needed to produce and smooth mortality estimates. These have had to be taken from model life table systems based on non-African data. Birth histories collected in national Demographic and Health Surveys are used to investigate age patterns of mortality in childhood in the sub-national regions of 26 countries of continental Sub-Saharan Africa. The majority of populations display a pattern of higher child relative to infant mortality than in any existing model system, including the Princeton "North" models. This reflects the existence of a "hump" of excess mortality in the late post-neonatal period and second year of life in more than three-quarters of sub-national populations. Age patterns of mortality vary markedly within and between countries, though adjacent parts of neighbouring countries sometimes have similar patterns. Particularly extreme relationships between infant and child mortality are most common in the Sahel, while a coastal belt exists adjoining the Indian Ocean with age patterns of mortality within the range of those in the Princeton models. A three-parameter model, which incorporates this "hump", is fitted to the data using Poisson regression and fitted national life tables are produced. Except for the southwest of Africa, no extensive areas exist with homogenous parameter values for the underlying downward slope of mortality with age in childhood and the size of the "hump" respectively. Thus, the scope for construction of "regional" childhood mortality models is limited. Nevertheless, age patterns of mortality in African populations tend to share features that differ from those of historical Western populations. Thus, using the national and regional average life tables in the indirect estimation of under-5 mortality yields more consistent series of estimates than are obtained using existing models

Risk factors for house-entry by malaria vectors in a rural town and satellite villages in The Gambia.

Background: In the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors, a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry. Methods: Mosquitoes were sampled using CDC light traps in 976 houses, each on one night, in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia. Catches from individual houses were both (a) left unadjusted and (b) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period, to allow for night-to-night variation. Houses were characterized by location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound. Results: 106,536 mosquitoes were caught, of which 55% were Anopheles gambiae sensu lato, the major malaria vectors in the region. There were seven fold higher numbers of An. gambiae s.l. in the villages (geometric mean per trap night = 43.7, 95% confidence intervals, CIs = 39.5–48.4) than in Farafenni town (6.3, 5.7–7.2) and significant variation between residential blocks (p < 0.001). A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data. Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town (odds ratio, OR = 0.11, 95% CIs = 0.09–0.13), the eaves were closed (OR = 0.71, 0.60–0.85), a horse was tethered near the house (OR = 0.77, 0.73–0.82), and churai, a local incense, was burned in the room at night (OR = 0.56, 0.47–0.66). Mosquito numbers increased per additional person in the house (OR = 1.04, 1.02–1.06) or trapping room (OR = 1.19, 1.13–1.25) and when the walls were made of mud blocks compared with concrete (OR = 1.44, 1.10–1.87). Conclusion: This study demonstrates that the risk of malaria transmission is greatest in rural areas, where large numbers of people sleep in houses made of mud blocks, where the eaves are open, horses are not tethered nearby and where churai is not burnt at night. These factors need to be considered in the design and analysis of intervention studies designed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa

Achieving comprehensive childhood immunization: an analysis of obstacles and opportunities in The Gambia

INTRODUCTION: Immunization is a vital component in the drive to decrease global childhood mortality, yet challenges remain in ensuring wide coverage of immunization and full immunization, particularly in low- and middle-income countries. This study assessed immunization coverage and the determinants of immunization in a semi-rural area in The Gambia. METHODS: Data were drawn from the Farafenni Health and Demographic Surveillance System. Children born within the surveillance area between January 2000 and December 2010 were included. Main outcomes assessed included measles, BCG and DTP vaccination status and full immunization by 12 months of age as reported on child healthcards. Predictor variables were evaluated based on a literature review and included gender, ethnicity, area of residence, household wealth and mother's age. RESULTS: Of the 7363 children included in the study, immunization coverage was 73% (CI 72-74) for measles, 86% (CI 86-87) for BCG, 79% (CI 78-80) for three doses of DTP and 52% (CI 51-53) for full immunization. Coverage was significantly associated with area of residence and ethnicity, with children in urban areas and of Mandinka ethnicity being least likely to be fully immunized. CONCLUSIONS: Despite high levels of coverage of many individual vaccines, delivery of vaccinations later in the schedule and achieving high coverage of full immunization remain challenges, even in a country with a committed childhood immunization programme, such as The Gambia. Our data indicate areas for targeted interventions by the national Expanded Programme of Immunization

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

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

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

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Design of vaccine efficacy trials during public health emergencies

Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures,were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseasesmay be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible,and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs

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