201 research outputs found
Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users
No full textThe immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples.Vaccinations were well-tolerated. The rate of responders was higher (P500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor
A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci
No full textThe bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function
The impact and effectiveness of pneumococcal vaccination in Scotland for those aged 65 and over during winter 2003/2004
No full textBackground: For winter 2003/2004 in Scotland, it was recommended that all those aged 65 and over be eligible to receive 23-valent polysaccharide pneumococcal vaccine (23vPPV), which has been shown to be effective in reducing the risk of invasive pneumococcal disease (IPD). We assessed the success of the vaccination programme by examining the age specific incidence rates of IPD compared to four previous winter seasons and estimating vaccination effectiveness.Methods: Winter season incidence rates of IPD for vaccine targeted (65 years and over) and non-targeted (0–4, 5–34, 35–49,50–64) age bands were examined for the Scottish population in a retrospective cohort design for winter 2003/2004. Details of all IPD cases were obtained from the central reference laboratory and population vaccine uptake information was estimated from a GP sentinel practice network. Based on the preceding four winter seasons, standardised incidence ratios (SIR) for invasivepneumococcal disease were determined by age-band and sex during winter 2003/2004. Vaccination effectiveness (VE) wasestimated using both screening and indirect cohort methods. Numbers needed to vaccinate were derived from VE results using equivalent annual incidence estimates for winter 2003/2004.Results: Overall vaccination effectiveness using the screening method (adjusted for age and sex) in those aged 65 and over was 61.7% (95%CI: 45.1, 73.2) which corresponded to a number needed to vaccinate of 5206 (95%CI: 4388, 7122) per IPD case prevented. Estimated effectiveness for the same age group using the indirect cohort method was not significant at 51% (95%CI:-278, 94). Reductions in the winter season incidence rate of IPD were highly significant for all those aged 75+: males SIR = 58.8(95%CI: 41.6, 80.8); females SIR = 70.0 (95%CI: 55.1, 87.8). In the 65–74 years age-group, the reduction for females was significant: SIR = 60.3 (95%CI: 39.3, 88.4), but not for males: SIR = 74.8 (95%CI: 50.8, 106.3). There was no significant protective effect on mortality.Conclusion: The introduction of 23vPPV for those aged 65 and over in Scotland during winter 2003/2004, was accompaniedwith a reduction of around one third in the incidence of IPD in this age group. Vaccination effectiveness estimates were comparable with those from other developed countries
Infections Caused by Streptococcus pneumoniae: Clinical Spectrum, Pathogenesis, Immunity, and Treatment
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