Vaccines for preventing hepatitis B in health-care workers.
Jefferson T., Demicheli V., Deeks J., MacMillan A., Sassi F., Pratt M.
BACKGROUND: Hepatitis B causes acute and chronic liver disease and may be prevented by vaccination. OBJECTIVES: To assess the effectiveness and safety of plasma-derived vaccines against acute and chronic hepatitis B in health-care workers in protecting them from hepatitis B infection and its consequences. SEARCH STRATEGY: MEDLINE and Excerpta Medica Database (EMBASE) search using standard Cochrane strategy, Cochrane Library, full text searching of the journal "Vaccine", bibliography of retrieved studies and correspondence with authors, researchers and manufacturers. SELECTION CRITERIA: All original prospective randomised comparisons of yeast-derived vaccines and plasma-derived vaccines against no intervention, placebo, or vaccines against other disease (control vaccines). Assessment of trial quality was made according to: 1. generation of allocation schedule 2. measure(s) taken to conceal treatment allocation 3. drop-out of allocated health-care worker participants from the analysis of trial results 4. measures taken to implement double blinding Trial reports were blinded by removal of authors and their affiliation, journal reference, introduction, results, and discussion. DATA COLLECTION AND ANALYSIS: To assess efficacy the incidence rates of acute hepatitis B were observed in the surveillance of the vaccinated and control groups of the trials included in the review. Safety was assessed from side-effect rates, classified as systemic (malaise, nausea, fever, arthralgias, rash, headache) or local (induration and soreness at the site of the inoculation). MAIN RESULTS: Four trials fulfilling the criteria were identified and the data synthesised. All trials compared plasma-derived vaccines versus placebo. Differences in the settings (and level of incidence) between three of the trial settings and Dienstag's led us to stratify our comparison grouping the three trials performed in dialysis units together. After our stratification, the Desmyter, Smuzness and Crosnier group appears to be homogeneous (Chi-square = 0.11, degrees of freedom = 2). Our estimates of effectiveness and safety in the high risk group favour treatment, the OR for cases of HB being 0.34; 95% CI (0.21, 0.55). The analysis also revealed a non-significant trend towards benefit in the lower risk health-care workers (Dienstag trial, OR 0.26 (0.05, 1.30). Overall the evidence strongly favours vaccination (OR=0.33; 95% CI (0.21, 0.53)). There was no difference in the incidence and severity of side-effects between the two arms of the trials. We calculated that it was necessary to vaccinate between 145 (assuming a baseline rate of 10 cases/1000/year) and 7 (for a baseline rate of 200/1000/year) health-care workers with plasma-derived vaccines to avoid one case of hepatitis B. Completeness of trial reporting was not good with all four trials failing to report titre results on antibodies against hepatitis B surface antigen and hepatitis B core antigen in the placebo arms (correspondence with two of the four authors failed to shed light on the reasons for such an omission). All four trials achieved low scores in the four quality dimensions assessed (generation of allocation schedule, measure(s) taken to conceal treatment allocation, exclusion of allocated participants from the analysis of the trial and measures taken to implement and protect double blinding). Mean length of follow-up was 14.5 months. REVIEWER'S CONCLUSIONS: Plasma-derived vaccines appear to be efficacious and safe for use in high risk health-care workers, such as staff of renal dialysis and transplant units. There is some uncertainty concerning the effectiveness of the vaccine in lower risk health-care workers, although the trend is towards benefit. We found no evidence of a long-term protective effect due to the short follow-up time of the four trials included in this review. We found relatively poor standard of trial reporting, possibly related to the age of the trials.