Increasing incidence of invasive pneumococcal disease and pneumonia despite improved vaccination uptake: surveillance in Hull and East Yorkshire, UK, 2002-2009.

Introduction of pneumococcal polysaccharide (PPV23) and conjugate vaccine (PCV7) programmes were expected to change the epidemiology of invasive pneumococcal disease (IPD) and pneumonia in the UK. We describe the epidemiology of IPD and hospitalization with pneumonia using high-quality surveillance data over an 8-year period, 2002-2009. Although PPV23 uptake increased from 49% to 70% and PCV7 uptake reached 98% by 2009, the overall incidence of IPD increased from 11.8/100 000 to 16.4/100 000 (P=0.13), and the incidence of hospitalization with pneumonia increased from 143/100 000 to 207/100 000 (P<0.001). Although a reduction in the proportion of IPD caused by PCV7 serotypes was observed, concurrent increases in PPV23 and non-vaccine serotype IPD contributed to an increased IPD burden overall. Marked inequalities in the geographical distribution of disease were observed. Existing vaccination programmes have, so far, not been sufficient to address an increasing burden of pneumococcal disease in our locality.

Assessing the effect of foreign travel and protection by BCG vaccination on the spread of tuberculosis in a low incidence country, United Kingdom, October 2008 to December 2009.

The contribution of travel to high incidence countries and the impact of the discontinuation of universal Bacillus Calmette­Guérin (BCG) vaccination to there cent rise in tuberculosis (TB) in the United Kingdom remain unclear. An outbreak in a college presented an opportunity to assess these. A cohort of students answered a questionnaire assessing risk factors for TB.Participants were screened with an interferon gamma release assay (IGRA). Unadjusted and adjusted odds ratios (OR) were calculated using logistic regression.Among 2,284 students, 400 (17.5%) were diagnosed with TB infection. A higher risk was noted for travel to a high incidence area in the past two years (OR: 1.39;95% confidence interval (CI): 1.04­1.89) and among those with the greatest exposure to the index case(OR: 3.94; 95% CI: 2.60­5.97). There was no association between BCG and risk of infection (OR: 1.05; 95%CI: 0.80­1.39). The lack of a protective effect by BCG on TB infection supports the discontinuation of universal vaccination. The association with foreign travel suggests the need to assess the cost-effectiveness of serial IGRA testing and treatment of positive persons among returning travellers.

5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro.

1. 5-Hydroxytryptamine (5-HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5-HT(2B) receptors in human colon, and to establish their possible role in the aetiology of IBS. 2. The distribution of 5-HT(2B) receptor mRNA and protein were investigated by quantitative RT - PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5-HT(2B) receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5-HT(2B) receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers. 3. Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally-mediated contractile responses, that were significantly potentiated by application of 5-HT (up to 10(-7) M), with a pEC(50) of 8.2 +/- 0.1 (n=49 donors). The response to 5-HT was inhibited by a number of selective 5-HT(2B) receptor antagonists. 4. This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5-HT in human colon are mediated by 5-HT(2B) receptors. It is proposed that these receptors contribute to the putative 5-HT-induced colonic smooth muscle hypersensitivity associated with IBS.

The relationship between the acetylator and the sparteine hydroxylation polymorphisms.

Thirty-eight healthy white British Caucasian subjects were hydroxylator phenotyped with sparteine and acetylator phenotyped with sulphadimidine. The results showed that there was no significant difference in the mean sparteine metabolic ratio between eight rapid acetylator extensive hydroxylators and 27 slow acetylator extensive hydroxylators.

The genetic control of sparteine and debrisoquine metabolism in man with new methods of analysing bimodal distributions.

Debrisoquine and sparteine tests were carried out in 215 random white British subjects. There is a high degree of correlation between the urinary 'metabolic ratios' of the two drugs. New mathematical techniques have been developed (1) to define phenotypes and (2) to identify the genotypes within the dominant phenotype. The members of 15 families were tested with both debrisoquine and sparteine. The results indicate that persons who are 'poor metabolisers' of sparteine are also 'poor metabolisers' of debrisoquine and are autosomal Mendelian recessives.