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

Beyond good intentions: lessons on equipment donation from an African hospital.

OBJECTIVE: In 2000, a referral hospital in the Gambia accepted a donation of oxygen concentrators to help maintain oxygen supplies. The concentrators broke down and were put into storage. A case study was done to find the reasons for the problem and to draw lessons to help improve both oxygen supplies and the success of future equipment donations. METHODS: A technical assessment of the concentrators was carried out by a biomedical engineer with relevant expertise. Semi-structured interviews were undertaken with key informants, and content analysis and inductive approaches were applied to construct the history of the episode and the reasons for the failure. FINDINGS: Interviews confirmed the importance of technical problems with the equipment. They also revealed that the donation process was flawed, and that the hospital did not have the expertise to assess or maintain the equipment. Technical assessment showed that all units had the wrong voltage and frequency, leading to overheating and breakdown. Subsequently a hospital donations committee was established to oversee the donations process. On-site biomedical engineering expertise was arranged with a nongovernmental organization (NGO) partner. CONCLUSION: Appropriate donations of medical equipment, including oxygen concentrators, can be of benefit to hospitals in resource-poor settings, but recipients and donors need to actively manage donations to ensure that the donations are beneficial. Success requires planning, technical expertise and local participation. Partners with relevant skills and resources may also be needed. In 2002, WHO produced guidelines for medical equipment donations, which address problems that might be encountered. These guidelines should be publicized and used

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

Disease-specific mortality burdens in a rural Gambian population using verbal autopsy, 1998-2007.

OBJECTIVE: To estimate and evaluate the cause-of-death structure and disease-specific mortality rates in a rural area of The Gambia as determined using the InterVA-4 model. DESIGN: Deaths and person-years of observation were determined by age group for the population of the Farafenni Health and Demographic Surveillance area from January 1998 to December 2007. Causes of death were determined by verbal autopsy (VA) using the InterVA-4 model and ICD-10 disease classification. Assigned causes of death were classified into six broad groups: infectious and parasitic diseases; cancers; other non-communicable diseases; neonatal; maternal; and external causes. Poisson regression was used to estimate age and disease-specific mortality rates, and likelihood ratio tests were used to determine statistical significance. RESULTS: A total of 3,203 deaths were recorded and VA administered for 2,275 (71%). All-age mortality declined from 15 per 1,000 person-years in 1998-2001 to 8 per 1,000 person-years in 2005-2007. Children aged 1-4 years registered the most marked (74%) decline from 27 to 7 per 1,000 person-years. Communicable diseases accounted for half (49.9%) of the deaths in all age groups, dominated by acute respiratory infections (ARI) (13.7%), malaria (12.9%) and pulmonary tuberculosis (10.2%). The leading causes of death among infants were ARI (5.59 per 1,000 person-years [95% CI: 4.38-7.15]) and malaria (4.11 per 1,000 person-years [95% CI: 3.09-5.47]). Mortality rates in children aged 1-4 years were 3.06 per 1,000 person-years (95% CI: 2.58-3.63) for malaria, and 1.05 per 1,000 person-years (95% CI: 0.79-1.41) for ARI. The HIV-related mortality rate in this age group was 1.17 per 1,000 person-years (95% CI: 0.89-1.54). Pulmonary tuberculosis and communicable diseases other than malaria, HIV/AIDS and ARI were the main killers of adults aged 15 years and over. Stroke-related mortality increased to become the leading cause of death among the elderly aged 60 years or more in 2005-2007. CONCLUSIONS: Mortality in the Farafenni HDSS area was dominated by communicable diseases. Malaria and ARI were the leading causes of death in the general population. In addition to these, diarrhoeal disease was a particularly important cause of death among children under 5 years of age, as was pulmonary tuberculosis among adults aged 15 years and above

Health Diplomacy the Adaptation of Global Health Interventions to Local Needs in sub-Saharan Africa and Thailand: Evaluating Findings from Project Accept (HPTN 043).

Study-based global health interventions, especially those that are conducted on an international or multi-site basis, frequently require site-specific adaptations in order to (1) respond to socio-cultural differences in risk determinants, (2) to make interventions more relevant to target population needs, and (3) in recognition of 'global health diplomacy' issues. We report on the adaptations development, approval and implementation process from the Project Accept voluntary counseling and testing, community mobilization and post-test support services intervention. We reviewed all relevant documentation collected during the study intervention period (e.g. monthly progress reports; bi-annual steering committee presentations) and conducted a series of semi-structured interviews with project directors and between 12 and 23 field staff at each study site in South Africa, Zimbabwe, Thailand and Tanzania during 2009. Respondents were asked to describe (1) the adaptations development and approval process and (2) the most successful site-specific adaptations from the perspective of facilitating intervention implementation. Across sites, proposed adaptations were identified by field staff and submitted to project directors for review on a formally planned basis. The cross-site intervention sub-committee then ensured fidelity to the study protocol before approval. Successfully-implemented adaptations included: intervention delivery adaptations (e.g. development of tailored counseling messages for immigrant labour groups in South Africa) political, environmental and infrastructural adaptations (e.g. use of local community centers as VCT venues in Zimbabwe); religious adaptations (e.g. dividing clients by gender in Muslim areas of Tanzania); economic adaptations (e.g. co-provision of income generating skills classes in Zimbabwe); epidemiological adaptations (e.g. provision of 'youth-friendly' services in South Africa, Zimbabwe and Tanzania), and social adaptations (e.g. modification of terminology to local dialects in Thailand: and adjustment of service delivery schedules to suit seasonal and daily work schedules across sites). Adaptation selection, development and approval during multi-site global health research studies should be a planned process that maintains fidelity to the study protocol. The successful implementation of appropriate site-specific adaptations may have important implications for intervention implementation, from both a service uptake and a global health diplomacy perspective

Bino Dark Matter and Big Bang Nucleosynthesis in the Constrained E6SSM with Massless Inert Singlinos

We discuss a new variant of the E6 inspired supersymmetric standard model (E6SSM) in which the two inert singlinos are exactly massless and the dark matter candidate has a dominant bino component. A successful relic density is achieved via a novel mechanism in which the bino scatters inelastically into heavier inert Higgsinos during the time of thermal freeze-out. The two massless inert singlinos contribute to the effective number of neutrino species at the time of Big Bang Nucleosynthesis, where the precise contribution depends on the mass of the Z' which keeps them in equilibrium. For example for mZ' > 1300 GeV we find Neff \approx 3.2, where the smallness of the additional contribution is due to entropy dilution. We study a few benchmark points in the constrained E6SSM with massless inert singlinos to illustrate this new scenario.Comment: 24 pages, revised for publication in JHE

Light States in Chern-Simons Theory Coupled to Fundamental Matter

Motivated by developments in vectorlike holography, we study SU(N) Chern-Simons theory coupled to matter fields in the fundamental representation on various spatial manifolds. On the spatial torus T^2, we find light states at small `t Hooft coupling \lambda=N/k, where k is the Chern-Simons level, taken to be large. In the free scalar theory the gaps are of order \sqrt {\lambda}/N and in the critical scalar theory and the free fermion theory they are of order \lambda/N. The entropy of these states grows like N Log(k). We briefly consider spatial surfaces of higher genus. Based on results from pure Chern-Simons theory, it appears that there are light states with entropy that grows even faster, like N^2 Log(k). This is consistent with the log of the partition function on the three sphere S^3, which also behaves like N^2 Log(k). These light states require bulk dynamics beyond standard Vasiliev higher spin gravity to explain them.Comment: 58 pages, LaTeX, no figures, Minor error corrected, references added, The main results of the paper have not change

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae