Vaccines for preventing pneumococcal infection in adults.

BACKGROUND: Diseases caused by Streptococcus pneumoniae(S. pneumoniae) continue to cause substantial morbidity and mortality throughout the world. Whilst pneumococcal polysaccharide vaccines (PPV) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain. OBJECTIVES: To assess the effectiveness of PPV in preventing disease or death in adults. Adverse events were not assessed. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2); MEDLINE (January 1966 to June 2007); and EMBASE (1974 to June 2007). SELECTION CRITERIA: A) Randomised controlled trials (RCTs) comparing PPV with placebo, control vaccines, or no intervention.B) Non-RCTs assessing PPV effectiveness against invasive pneumococcal disease (IPD). DATA COLLECTION AND ANALYSIS: A) RCTs: trial quality assessment was conducted by two review authors and data extracted by three authors; odds ratios (OR) and 95% confidence intervals (CI) were estimated using a random-effects model.B) Non-RCTs: study quality, including measures to control for confounding, was assessed and data extracted by two review authors; OR and 95% CI were calculated using a random-effects model following the conversion of each study outcome to a log OR and standard error. MAIN RESULTS: Twenty-two studies met our inclusion criteria (15 RCTs involving 48,656 participants and 7 non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.15 to 0.46; random-effects model, I-squared (I(2)) = 0%). Efficacy against all cause pneumonia was inconclusive with substantial statistical heterogeneity (OR 0.71, 95% CI 0.52 to 0.97; random-effects model, I(2) = 87.3%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.87, 95% CI 0.69 to 1.10; random-effects model, I(2) = 75.3%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness but the difference was not statistically significant. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) = 31.4%). AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide compelling evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

Vaccines for preventing pneumococcal infection in adults.

BACKGROUND: Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality throughout the world. Polysaccharide pneumococcal vaccines have been developed for over 50 years and may have the potential to prevent disease and death. OBJECTIVES: To assess the effectiveness of polysaccharide pneumococcal vaccination in preventing disease or death in adults. SEARCH STRATEGY: Trials were identified by electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) issue 2, 2003 (which includes the Cochrane ARI Group's specialised register); MEDLINE (January 1966 to June 2003); and EMBASE (1974 to June 2003). We searched existing literature. The bibliographies of all newly revealed studies were read in order to identify further studies. The vaccine manufacturers, the lead authors of newly identified studies not included in existing meta-analyses were contacted. SELECTION CRITERIA: A) Prospective, randomised or quasi-randomised studies comparing pneumococcal vaccines with placebo, control vaccines or no intervention.B) Case-control studies (including indirect cohort studies) assessing pneumococcal vaccine effectiveness against invasive pneumococcal disease. Cohort studies are excluded. DATA COLLECTION AND ANALYSIS: A) Randomised studies. Trial quality assessment was conducted by two reviewers (JH and DT). Data extraction was done by three reviewers (JH, DT, KD). There were many instances of unclear or incomplete data in the trial reports, and the final dataset was arrived at after much deliberation and discussion, including comparison with the data used in two previous reviews of this question. Due to the age of the trials (dating back to 1954 in one case) it was not generally possible to obtain clarification from the authors, though a partial clarification was achieved in one case.B) Non-randomised studies. Study quality was assessed by two reviewers (RA and KD). MAIN RESULTS: The combined results from the randomised studies fail to show that the polysaccharide pneumococcal vaccine is effective in preventing either pneumonia (outcome 6: odds ratio = 0.77, confidence interval 0.58, 1.02, number = 14) or death (outcome 8: odds ratio 0.90, confidence interval 0.76, 1.07, number = 11). Despite encouraging data from some very early trials, pooling trials published from 1977 on suggests there is no effect (outcome 6; odds ratio = 0.96, confidence interval 0.80, 1.15, number = 12; outcome 9: odds ratio = 0.98, confidence interval 0.88, 1.09, number = 10). The available data cannot distinguish whether this heterogeneity in results is due to improvements in trial methodology and reporting, to differences in trial setting or to real loss of efficacy over time. This is because the early, poorly reported trials were conducted in high-risk healthy populations where the expected benefit is greatest. The case-control studies show significant efficacy in preventing invasive pneumococcal disease: OR 0.47 (CI 0.37, 0.59) corresponding to an efficacy of 53%. REVIEWER'S CONCLUSIONS: While polysaccharide pneumococcal vaccines do not appear to reduce the incidence of pneumonia or death in adults with or without chronic illness, or in the elderly (55 years and above), the evidence from non-randomised studies suggests that the vaccines are effective in the reducing the incidence of the more specific outcome, invasive pneumococcal disease, among adults and the immunocompetent elderly (55 years and above). Surveillance data suggest that infection rates vary widely between and also within countries, but a typical figure in developed countries is 0.01%, or 10 per 100,000 per year. Efficacy of 50% then corresponds to a number-needed-to-treat (NNT) of 20,000 vaccinations per infection avoided, and perhaps 50,000 per death avoided.

Theoretical descriptors for the correlation of aquatic toxicity of environmental pollutants by quantitative structure-toxicity relationships.

Quantitative structure-toxicity relationships were developed for the prediction of aqueous toxicities for Poecilia reticulata (guppy) using the CODESSA treatment. A two-parameter correlation was found for class 1 toxins with R(2) = 0.96, and a five-parameter correlation was found for class 2 toxins with R(2) = 0.92. A five-parameter correlation for class 3 toxins had R(2) = 0.85. The correlations for class 4 toxins were less satisfactory. All the descriptors utilized are calculated solely from the structures of the molecules, which makes it possible to predict unavailable or unknown toxins.

Interpretation of quantitative structure-property and -activity relationships.

The potential utility of data reduction methods (e.g. principal component analysis) for the analysis of matrices assembled from the related properties of large sets of compounds is discussed by reference to results obtained from solvent polarity scales, ongoing work on solubilities and sweetness properties, and proposed general treatments of toxicities and gas chromatographic retention indices.

Correlation of the solubilities of gases and vapors in methanol and ethanol with their molecular structures.

Two four-parameter quantitative structure-property relations, with R2 = 0.95 and R2 = 0.97, respectively, gave good correlations for the solubilities of 87 gases and vapors in methanol and 61 in ethanol. All the descriptors used are derived solely from the structures of the molecules, making it possible to predict solubilities for unavailable or unknown compounds.

Hepatitis B vaccination for occupational risk: an audit in general practice.

Surveys of hepatitis B vaccine coverage among patients at risk of infection in an urban practice in north west England in 1992 and 1998 showed that the proportion of patients ascertained to be at risk had increased from 4% (194) to 5% (258) and coverage (with a full course of hepatitis B vaccine, with or without confirmed immunity) from 46% to 78%. The contribution from occupational health departments was poorly documented, identifying a need for increased communication.

The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids.

The Yersinia pestis pH 6 antigen was expressed by, and purified from, Escherichia coli containing cloned psa genes. By an enzyme-linked immunosorbence-based assay, purified pH 6 antigen bound to gangliotetraosylceramide (GM1A), gangliotriaosylceramide (GM2A), and lactosylceramide (LC) (designations follow the nomenclature of L. Svennerholm [J. Neurochem. 10:613-623, 1963]). Binding to GM1A, GM2A, and LC was saturable, with 50% maximal binding occurring at 498 +/- 4, 390, and 196 +/- 3 nM, respectively. Thin-layer chromatography (TLC) overlay binding confirmed that purified pH 6 antigen bound to GM1A, GM2A, and LC and also revealed binding to hydroxylated galactosylceramide. Intact E. coli cells which expressed the pH 6 antigen had a specificity similar to that of purified pH 6 in the TLC overlay assay except that nonhydroxylated galactosylceramide was also bound. The binding patterns observed indicate that the presence of beta1-linked galactosyl residues in glycosphingolipids is the minimum determinant required for binding of the pH 6 antigen.