Seeing, thinking and acting against Malaria: a new approach to health worker training for community empowerment in rural Gambia.

CONTEXT: In the Gambia, West Africa, Malaria is a major cause of death among children in rural areas. It has been estimated that in one division in the country malaria accounts for 40% of all deaths in children aged between one and 4 years. Most malaria cases are managed at home assisted by primary healthcare workers. The strategic plan of Gambia's National Malaria Control Programme includes improved training and supervision of all health care providers, at all levels, and increased community awareness in order to reduce the malaria burden by 50% before 2007. ISSUE: A malaria in-service training program for Community Health Nurses (CHNs) working at village level was piloted in 2004. The program includes a computer-based training (CBT) package, the first of its kind for health professionals in Gambia. The education program is part of a larger initiative funded by the Gates Malaria Partnership, that aims to increase community involvement in malaria control. The objective of the course is to enable CHNs to facilitate the change process. The curriculum was informed by a reference group and stakeholder input. Interviews and evaluation forms were used to gather information about learner experience and learning preferences. ANALYSIS: The CBT package was well received. Learners reported wanting more computer instruction, but felt they had gained confidence. There was resistance from other health professionals regarding the development of information technology skills in CHNs. This related to the perceived role and status of CHNs, as well as confidence in their ability. Some modifications of the CBT package were necessary, including the reworking of some activities and language. LESSONS LEARNED: There are issues related to sustainability and resource implications that need to be addressed. Opportunities exist to expand e-learning in the Gambia for pre-service CHNs and other professionals. An investigation into the viability of reproducing this module as a generic planning tool for allied health workers and other extension workers at community level will be undertaken

A global reference for human genetic variation

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.We thank the many people who were generous with contributing their samples to the project: the African Caribbean in Barbados; Bengali in Bangladesh; British in England and Scotland; Chinese Dai in Xishuangbanna, China; Colombians in Medellin, Colombia; Esan in Nigeria; Finnish in Finland; Gambian in Western Division – Mandinka; Gujarati Indians in Houston, Texas, USA; Han Chinese in Beijing, China; Iberian populations in Spain; Indian Telugu in the UK; Japanese in Tokyo, Japan; Kinh in Ho Chi Minh City, Vietnam; Luhya in Webuye, Kenya; Mende in Sierra Leone; people with African ancestry in the southwest USA; people with Mexican ancestry in Los Angeles, California, USA; Peruvians in Lima, Peru; Puerto Ricans in Puerto Rico; Punjabi in Lahore, Pakistan; southern Han Chinese; Sri Lankan Tamil in the UK; Toscani in Italia; Utah residents (CEPH) with northern and western European ancestry; and Yoruba in Ibadan, Nigeria. Many thanks to the people who contributed to this project: P. Maul, T. Maul, and C. Foster; Z. Chong, X. Fan, W. Zhou, and T. Chen; N. Sengamalay, S. Ott, L. Sadzewicz, J. Liu, and L. Tallon; L. Merson; O. Folarin, D. Asogun, O. Ikpwonmosa, E. Philomena, G. Akpede, S. Okhobgenin, and O. Omoniwa; the staff of the Institute of Lassa Fever Research and Control (ILFRC), Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; A. Schlattl and T. Zichner; S. Lewis, E. Appelbaum, and L. Fulton; A. Yurovsky and I. Padioleau; N. Kaelin and F. Laplace; E. Drury and H. Arbery; A. Naranjo, M. Victoria Parra, and C. Duque; S. Däkel, B. Lenz, and S. Schrinner; S. Bumpstead; and C. Fletcher-Hoppe. Funding for this work was from the Wellcome Trust Core Award 090532/Z/09/Z and Senior Investigator Award 095552/Z/11/Z (P.D.), and grants WT098051 (R.D.), WT095908 and WT109497 (P.F.), WT086084/Z/08/Z and WT100956/Z/13/Z (G.M.), WT097307 (W.K.), WT0855322/Z/08/Z (R.L.), WT090770/Z/09/Z (D.K.), the Wellcome Trust Major Overseas program in Vietnam grant 089276/Z.09/Z (S.D.), the Medical Research Council UK grant G0801823 (J.L.M.), the UK Biotechnology and Biological Sciences Research Council grants BB/I02593X/1 (G.M.) and BB/I021213/1 (A.R.L.), the British Heart Foundation (C.A.A.), the Monument Trust (J.H.), the European Molecular Biology Laboratory (P.F.), the European Research Council grant 617306 (J.L.M.), the Chinese 863 Program 2012AA02A201, the National Basic Research program of China 973 program no. 2011CB809201, 2011CB809202 and 2011CB809203, Natural Science Foundation of China 31161130357, the Shenzhen Municipal Government of China grant ZYC201105170397A (J.W.), the Canadian Institutes of Health Research Operating grant 136855 and Canada Research Chair (S.G.), Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (M.K.D.), a Le Fonds de Recherche duQuébec-Santé (FRQS) research fellowship (A.H.), Genome Quebec (P.A.), the Ontario Ministry of Research and Innovation – Ontario Institute for Cancer Research Investigator Award (P.A., J.S.), the Quebec Ministry of Economic Development, Innovation, and Exports grant PSR-SIIRI-195 (P.A.), the German Federal Ministry of Education and Research (BMBF) grants 0315428A and 01GS08201 (R.H.), the Max Planck Society (H.L., G.M., R.S.), BMBF-EPITREAT grant 0316190A (R.H., M.L.), the German Research Foundation (Deutsche Forschungsgemeinschaft) Emmy Noether Grant KO4037/1-1 (J.O.K.), the Beatriu de Pinos Program grants 2006 BP-A 10144 and 2009 BP-B 00274 (M.V.), the Spanish National Institute for Health Research grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER (A.O.), Ewha Womans University (C.L.), the Japan Society for the Promotion of Science Fellowship number PE13075 (N.P.), the Louis Jeantet Foundation (E.T.D.), the Marie Curie Actions Career Integration grant 303772 (C.A.), the Swiss National Science Foundation 31003A_130342 and NCCR “Frontiers in Genetics” (E.T.D.), the University of Geneva (E.T.D., T.L., G.M.), the US National Institutes of Health National Center for Biotechnology Information (S.S.) and grants U54HG3067 (E.S.L.), U54HG3273 and U01HG5211 (R.A.G.), U54HG3079 (R.K.W., E.R.M.), R01HG2898 (S.E.D.), R01HG2385 (E.E.E.), RC2HG5552 and U01HG6513 (G.T.M., G.R.A.), U01HG5214 (A.C.), U01HG5715 (C.D.B.), U01HG5718 (M.G.), U01HG5728 (Y.X.F.), U41HG7635 (R.K.W., E.E.E., P.H.S.), U41HG7497 (C.L., M.A.B., K.C., L.D., E.E.E., M.G., J.O.K., G.T.M., S.A.M., R.E.M., J.L.S., K.Y.), R01HG4960 and R01HG5701 (B.L.B.), R01HG5214 (G.A.), R01HG6855 (S.M.), R01HG7068 (R.E.M.), R01HG7644 (R.D.H.), DP2OD6514 (P.S.), DP5OD9154 (J.K.), R01CA166661 (S.E.D.), R01CA172652 (K.C.), P01GM99568 (S.R.B.), R01GM59290 (L.B.J., M.A.B.), R01GM104390 (L.B.J., M.Y.Y.), T32GM7790 (C.D.B., A.R.M.), P01GM99568 (S.R.B.), R01HL87699 and R01HL104608 (K.C.B.), T32HL94284 (J.L.R.F.), and contracts HHSN268201100040C (A.M.R.) and HHSN272201000025C (P.S.), Harvard Medical School Eleanor and Miles Shore Fellowship (K.L.), Lundbeck Foundation Grant R170-2014-1039 (K.L.), NIJ Grant 2014-DN-BX-K089 (Y.E.), the Mary Beryl Patch Turnbull Scholar Program (K.C.B.), NSF Graduate Research Fellowship DGE-1147470 (G.D.P.), the Simons Foundation SFARI award SF51 (M.W.), and a Sloan Foundation Fellowship (R.D.H.). E.E.E. is an investigator of the Howard Hughes Medical Institute

Proteomic profiling of the plasma of Gambian children with cerebral malaria

BackgroundCerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection. A number of pathological findings have been correlated with pediatric CM including sequestration, platelet accumulation, petechial haemorrhage and retinopathy. However, the molecular mechanisms leading to death in CM are not yet fully understood. MethodsA shotgun plasma proteomic study was conducted using samples form 52 Gambian children with CM admitted to hospital. Based on clinical outcome, children were assigned to two groups: reversible and fatal CM. Label-free liquid chromatography–tandem mass spectrometry was used to identify and compare plasma proteins that were differentially regulated in children who recovered from CM and those who died. Candidate biomarkers were validated using enzyme immunoassays. ResultsThe plasma proteomic signature of children with CM identified 266 proteins differentially regulated in children with fatal CM. Proteins from the coagulation cascade were consistently decreased in fatal CM, whereas the plasma proteomic signature associated with fatal CM underscored the importance of endothelial activation, tissue damage, inflammation, haemolysis and glucose metabolism. The concentration of circulating proteasomes or PSMB9 in plasma was not significantly different in fatal CM when compared with survivors. Plasma PSMB9 concentration was higher in patients who presented with seizures and was significantly correlated with the number of seizures observed in patients with CM during admission. ConclusionsThe results indicate that increased tissue damage and hypercoagulability may play an important role in fatal CM. The diagnostic value of this molecular signature to identify children at high risk of dying to optimize patient referral practices should be validated prospectively.</p

How caregivers of people with dementia search for dementia-specific information on the internet: Survey study

Background: During the last decade, more research has focused on web-based interventions delivered to support caregivers of people with dementia. However, little information is available in relation to internet use among caregivers in general, especially those caring for people with dementia. Objective: The aim of this study was to evaluate the dementia-related internet use and factors that may be associated with its use among caregivers of people with dementia in Greece. Methods: Secondary data from the Greek Dementia Survey of the Athens Association of Alzheimer's Disease and Related Disorders were collected from April to June 2017. A total of 580 caregivers of people with dementia participated in the study. Results: The majority of the caregivers reported that they had used the internet in the previous 3 months (84.1%, 488/580). Nearly half of the caregivers (47.5%, 276/580) reported that they had received dementia services online. Bivariate analysis showed that a dementia-specific search of information was associated with age, education, kinship, and years of care. Age (odds ratio [OR] 2.362, 95% CI 1.05-5.33) and education (OR 2.228, 95% CI 1.01-4.94) were confirmed as predictors, with younger caregivers and those with higher educational attainment being more likely to search for dementia-specific information. Use of the internet to search for dementia information was only related to hours of care. The internet use by caregivers within the previous 3 months was associated with variables such as age, education, occupation, kinship, years of care, and self-reported impact on physical and social health. Conclusions: Caregivers of people with dementia in Greece, as in the other southern European countries, are essential agents of the national health system. The existing short- and long-term respite care services are limited or nonexistent. Currently, caregivers receive mostly support and education from memory clinics and municipality consultation centers, which are mainly based in central cities in Greece. Despite the dementia awareness movement in Greece, there is still space to integrate the role of technology in the support and education of caregivers. Development of training programs for enhancing electronic health literacy skills as well as web-based services provision could support Greek caregivers in their everyday caring tasks

Genetic variation at the TNF locus and the risk of severe sequelae of ocular Chlamydia trachomatis infection in Gambians.

Tumor necrosis factor (TNF) is thought to be a key mediator of the inflammatory and fibrotic response to Chlamydia trachomatis (Ct) infection. A large matched-pair case-control study investigated putative functional single nucleotide polymorphisms (SNPs) across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of kappa light polypeptide gene enhancer in B cells (IkappaBL), inhibitor like 1 and lymphotoxin alpha (LTA) in relation to the risk of scarring sequelae of ocular Ct infection. Haplotype and linkage disequilibrium analysis demonstrated two haplotypes, differing at position TNF-308, conferring an increased risk of trichiasis. The TNF-308A allele, and its bearing haplotype, correlated with increased TNF production in lymphocyte cultures stimulated with chlamydial elementary body antigen. Thus TNF-308A may determine directly, or be a marker of a high TNF producer phenotype associated with increased risk of sequelae of chlamydial infection. Multivariate analysis provided evidence for the presence of additional risk-associated variants near the TNF locus