Browsing by Author "Helen Fletcher"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    PublicationMetadata only
    Investments in tuberculosis research - what are the gaps?
    (2016-08-25) Mishal S. Khan; Helen Fletcher; Richard Coker; London School of Hygiene & Tropical Medicine; National University of Singapore; Mahidol University
    © 2016 The Author(s). Through decades of research, numerous studies have generated robust evidence about effective interventions for tuberculosis control. Yet, the global annual decline in incidence of approximately 1% is evidence that current approaches and investment strategies are not sufficient. In this article, we assess recent tuberculosis research funding and discuss two critical gaps in funding and in scientific evidence from topics that have been left off the research priority agenda. We first examine research and development funding goals in the 2011-2015 Global Plan to Stop Tuberculosis and analyze disbursements to different research areas by funders worldwide in 2014. We then summarize, through a compilation of published literature and consultation with 35 researchers across multiple disciplines in the London School of Hygiene and Tropical Medicine TB Centre, priorities identified by the tuberculosis research community. Finally, we compare researchers' priority areas to the global funding agendas and activities. Our analysis shows that, among the five key research areas defined in the 2011-2015 Global Plan - namely drugs, basic science, vaccines, diagnostics and operational research - drug discovery and basic science on Mycobacterium tuberculosis accounted for 60% of the $2 billion annual funding target. None of the research areas received the recommended level of funding. Operational research, which had the lowest target, received 66% of its target funding, whereas new diagnostics received only 19%. Although many of the priority research questions identified by researchers fell within the Global Plan categories, our analysis highlights important areas that are not explicitly mentioned in the current plan. These priority research areas included improved understanding of tuberculosis transmission dynamics, the role of social protection and social determinants, and health systems and policy research. While research priorities are increasingly important in light of the limited funding for tuberculosis, there is a risk that we neglect important research areas and encourage the formation of research silos. To ensure that funding priorities, researchers' agendas and national tuberculosis control policies are better coordinated, there should be more, and wider, dialogue between stakeholders in high tuberculosis burden countries, researchers, international policymakers and funders.
  • No Thumbnail Available
    PublicationMetadata only
    Single nucleotide polymorphisms in the toll-like receptor 3 and CD44 genes are associated with persistence of vaccine-induced immunity to the serogroup C meningococcal conjugate vaccine
    (2012-03-01) Catrin E. Moore; Branwen J. Hennig; Kirsten P. Perrett; J. Claire Hoe; Sue J. Lee; Helen Fletcher; Denise Brocklebank; Daniel O'Connor; Matthew D. Snape; Andrew J. Hall; Shelley Segal; Adrian V.S. Hill; Andrew J. Pollarda; University of Oxford; Mahidol University; London School of Hygiene & Tropical Medicine; Wellcome Trust Centre for Human Genetics; University of Melbourne; Angkor Hospital for Children
    The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P = 0.004 [unadjusted]) and CD44 (rs12419062) (P = 0.01 [unadjusted] ) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination. Copyright © 2012, American Society for Microbiology. All Rights Reserved.