Title:
Post-exposure passive immunisation for preventing measles.

Abstract:
Measles outbreaks continue to occur in countries with high vaccination coverage. Passive immunisation is generally considered to prevent measles in someone who is not immune and has been exposed to infection. Estimates of effectiveness have varied and no minimum effective dose has been determined.
To assess the effectiveness and safety of intramuscular injection or intravenous infusion of immunoglobulins (passive immunisation) for preventing measles when administered to exposed susceptible people before the onset of symptoms.
We searched CENTRAL (2013, Issue 7), MEDLINE (1946 to July week 5, 2013), CINAHL (1981 to August 2013) and EMBASE (1974 to August 2013).
We included randomised controlled trials (RCTs), quasi-RCTs and prospective, controlled (cohort) studies if: participants were susceptible and exposed to measles, polyclonal immunoglobulins derived from human sera or plasma were administered intramuscularly or intravenously as the only intervention in at least one group and the number of subsequent measles cases was measured. We excluded studies of other sources of immunoglobulins.
Two authors independently extracted data and critically appraised the included studies. We attempted to contact study authors for missing information. We described the results of studies not included in meta-analyses.
We included one RCT, two quasi-RCTs and 10 cohort studies (3925 participants). No studies were rated as low risk of bias for all criteria. Critical appraisal was constrained by a lack of information in most studies. The overall quality of the evidence was moderate.Seven studies (1432 participants) assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity was explained by subgrouping according to the blood product used as an approximation of dose of immunoglobulin. When given within seven days of exposure, immunoglobulins were effective at preventing measles: gamma globulin (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of different blood products were supported by studies not included in the meta-analysis and by two studies (702 participants) that found gamma globulin more effective than serum (RR 0.56, 95% CI 0.46 to 0.69).Based on three studies (893 participants) immunoglobulin was effective at preventing death due to measles compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44).Two studies included measles vaccine alone among the intervention groups. Meta-analysis could not be undertaken. Both studies suggested the vaccine was more effective than gamma globulin.No serious adverse events were observed in any of the included studies, although reporting of adverse events was poor overall. Non-serious adverse events included transient fever, rash, muscle stiffness, local redness and induration.
Passive immunisation within seven days of exposure is effective at preventing measles, with the risk for non-immune people up to 83% less than if no treatment is given. Given an attack rate of 45 per 1000 (per the control group of the most recent included study), gamma globulin compared to no treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the attack rate of the other included study assessing gamma globulin), the ARR of gamma globulin compared to no treatment is 629 and the NNTB is two.It seems the dose of immunoglobulin administered impacts on effectiveness. A minimum effective dose of measles-specific antibodies could not be identified.Passive immunisation is effective at preventing deaths from measles, reducing the risk by 76% compared to no treatment. Whether the benefits of passive immunisation vary among subgroups of non-immune exposed people could not be determined.Due to a paucity of evidence comparing vaccine to passive immunisation, no firm conclusions can be drawn regarding relative effectiveness.The included studies were not specifically designed to detect adverse events.Future research should consider the effectiveness of passive immunisation for preventing measles in high-risk populations such as pregnant women, immunocompromised people and infants. Further efforts should be made to determine the minimum effective dose of measles-specific antibodies for post-exposure prophylaxis and the relative effectiveness of vaccine compared to immunoglobulin.