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

Development and feasibility testing of an education program to improve knowledge and self-care among Aboriginal and Torres Strait Islander patients with heart failure

INTRODUCTION: There is a 70% higher age-adjusted incidence of heart failure (HF) among Aboriginal and Torres Strait Islander people, three times more hospitalisations and twice as many deaths as among non-Aboriginal people. There is a need to develop holistic yet individualised approaches in accord with the values of Aboriginal community health care to support patient education and self-care. The aim of this study was to re-design an existing HF educational resource (Fluid Watchers-Pacific Rim) to be culturally safe for Aboriginal and Torres Strait Islander peoples, working in collaboration with the local community, and to conduct feasibility testing.  METHODS: This study was conducted in two phases and utilised a mixed-methods approach (qualitative and quantitative). Phase 1 used action research methods to develop a culturally safe electronic resource to be provided to Aboriginal HF patients via a tablet computer. An HF expert panel adapted the existing resource to ensure it was evidence-based and contained appropriate language and images that reflects Aboriginal culture. A stakeholder group (which included Aboriginal workers and HF patients, as well as researchers and clinicians) then reviewed the resources, and changes were made accordingly. In Phase 2, the new resource was tested on a sample of Aboriginal HF patients to assess feasibility and acceptability. Patient knowledge, satisfaction and self-care behaviours were measured using a before and after design with validated questionnaires. As this was a pilot test to determine feasibility, no statistical comparisons were made.  RESULTS: Phase 1: Throughout the process of resource development, two main themes emerged from the stakeholder consultation. These were the importance of identity, meaning that it was important to ensure that the resource accurately reflected the local community, with the appropriate clothing, skin tone and voice. The resource was adapted to reflect this, and members of the local community voiced the recordings for the resource. The other theme was comprehension; images were important and all text was converted to the first person and used plain language. Phase 2: Five Aboriginal participants, mean age 61.6±10.0 years, with NYHA Class III and IV heart failure were enrolled. Participants reported a high level of satisfaction with the resource (83.0%). HF knowledge (percentage of correct responses) increased from 48.0±6.7% to 58.0±9.7%, a 20.8% increase, and results of the self-care index indicated that the biggest change was in patient confidence for self-care, with a 95% increase in confidence score (46.7±16.0 to 91.1±11.5). Changes in management and maintenance scores varied between patients.  CONCLUSIONS: By working in collaboration with HF experts, Aboriginal researchers and patients, a culturally safe HF resource has been developed for Aboriginal and Torres Strait Islander patients. Engaging Aboriginal researchers, capacity-building, and being responsive to local systems and structures enabled this pilot study to be successfully completed with the Aboriginal community and positive participant feedback demonstrated that the methodology used in this study was appropriate and acceptable; participants were able to engage with willingness and confidence

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

Nasopharyngeal carriage of pneumococci four years after community-wide vaccination with PCV-7 in The Gambia: long-term evaluation of a cluster randomized trial.

BACKGROUND: A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination. METHODS: PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started. RESULTS: Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found. CONCLUSIONS: The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN51695599

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

A combined long-range phasing and long haplotype imputation method to impute phase for SNP genotypes

<p>Abstract</p> <p>Background</p> <p>Knowing the phase of marker genotype data can be useful in genome-wide association studies, because it makes it possible to use analysis frameworks that account for identity by descent or parent of origin of alleles and it can lead to a large increase in data quantities via genotype or sequence imputation. Long-range phasing and haplotype library imputation constitute a fast and accurate method to impute phase for SNP data.</p> <p>Methods</p> <p>A long-range phasing and haplotype library imputation algorithm was developed. It combines information from surrogate parents and long haplotypes to resolve phase in a manner that is not dependent on the family structure of a dataset or on the presence of pedigree information.</p> <p>Results</p> <p>The algorithm performed well in both simulated and real livestock and human datasets in terms of both phasing accuracy and computation efficiency. The percentage of alleles that could be phased in both simulated and real datasets of varying size generally exceeded 98% while the percentage of alleles incorrectly phased in simulated data was generally less than 0.5%. The accuracy of phasing was affected by dataset size, with lower accuracy for dataset sizes less than 1000, but was not affected by effective population size, family data structure, presence or absence of pedigree information, and SNP density. The method was computationally fast. In comparison to a commonly used statistical method (fastPHASE), the current method made about 8% less phasing mistakes and ran about 26 times faster for a small dataset. For larger datasets, the differences in computational time are expected to be even greater. A computer program implementing these methods has been made available.</p> <p>Conclusions</p> <p>The algorithm and software developed in this study make feasible the routine phasing of high-density SNP chips in large datasets.</p