Keith P. W. J. McAdam

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BACKGROUND Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age(More)
BACKGROUND Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. In mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in(More)
SETTING Rural and urban health centres in The Gambia, West Africa. OBJECTIVES To estimate the time delay between onset of symptoms and initiation of treatment and identify the risk factors influencing the delay in patients with tuberculosis (TB). DESIGN Structured interviews with newly diagnosed TB patients aged over 15 years presenting to TB control(More)
BACKGROUND RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS 306 men aged 18-45 years were(More)
BACKGROUND Very little longitudinal information is available regarding the performance of T cell-based tests for Mycobacterium tuberculosis infection. To address this deficiency, we conducted a longitudinal assessment of the enzyme-linked immunosorbent spot test (ELISPOT) test in comparison to the standard tuberculin skin test (TST). METHODS AND FINDINGS(More)
SETTING A study of tuberculosis cases and healthy blood donor controls from the Western Region of The Gambia, West Africa. OBJECTIVE To investigate the potential role of candidate gene polymorphisms in host susceptibility to tuberculosis. DESIGN Single base change polymorphisms in interleukin 1 beta (IL1 beta), interleukin 10 (IL10) and(More)
RATIONALE Interferon-gamma (IFN-gamma) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-gamma signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear. METHODS A total(More)
Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by(More)
The active metabolite of vitamin D, 1,25 dihydroxyvitamin D3, is an important immunoregulatory hormone [1]. Its effects are exerted by interaction with the vitamin D receptor, which is present on human monocytes and activated T and B lymphocytes. Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three(More)
Adenosine triphosphate (ATP) ligation of P2X(7) receptors expressed on human macrophages that are infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. Marked heterogeneity observed in cell donor ATP responsiveness suggests that this antimycobacterial mechanism may be genetically regulated. Five(More)