We reviewed clinically reported mumps cases in England from January 1, 2004, through March 31, 2005, that were confirmed by oral fluid mumps-specific immunoglobulin M testing within 6 weeks of symptom onset (20). Only case-patients eligible to have received 2 doses of MMR vaccine through the routine program (i.e., those born after 1992) were included. Case-patients 3–5 years of age were excluded because children receive the second dose of MMR between these ages and, therefore, reliable population coverage data are not available for comparison. Possible vaccine-associated cases (i.e., symptom onset within 6 weeks after vaccination) were also excluded. Vaccination histories were obtained from physician records or child health computerized recordkeeping systems.

Quarterly population vaccine coverage data for children 2 and 5 years of age were obtained from the Cover of Vaccination Evaluated Rapidly program (21,22). Because of changes in health service boundaries and child health computerized recordkeeping systems, data for a small number of areas were missing for some quarterly periods. In addition, 5-year coverage data have been shown to underestimate the true coverage in some areas (23). To compensate for this, coverage data were adjusted. Missing values were estimated using linear interpolation from the values submitted in previous and subsequent quarters. When coverage of first-dose MMR for the same birth cohort was lower at 5 than at 2 years of age, the coverage at 5 years of age was assumed to be 3% higher than the value at 2 years of age (based on data from a sentinel surveillance scheme) (22). The adjusted data were used to approximate population coverage for school-year cohorts (born from October 1 through September 30 of the following year) to allow for similar levels of exposure within school years. Coverage data at 5 years of age for children born in 2000 were not yet available, so values were estimated from the previous cohort and data from the first 2 quarters. Coverage data were divided into 2 categories, within and outside London, because coverage estimates are lower in London but fairly similar in the rest of the country (24).

Our estimate of 87.8% effectiveness for 1-dose mumps vaccine is lower than efficacy estimates from clinical trials (8,9) but higher than those from most published field evaluations (10–14). Lower estimates in field studies could result from problems with vaccine storage or administration, errors in case definition (i.e., clinical instead of laboratory-confirmed cases) or ascertainment, inaccurate determination of vaccination status, and bias from conducting studies during outbreaks (10,28,29). Because clinical trials have relatively short follow-up periods, waning immunity may also produce lower observed effectiveness in field evaluations. We observed a decline in protection with increasing age, which suggests that waning immunity may occur. After 2 doses, the magnitude of this decline is small, and effectiveness remains above 85% even 6–7 years after the second vaccination.

Research on whether protection from mumps vaccine declines with time since vaccination is contradictory. In 2 US outbreaks, children vaccinated >5 (12) or >3 (19) years before each outbreak were at higher risk for mumps. In 2 other US outbreaks, no evidence was found for increased infection rate with time since vaccination (11,16). A study from Belgium found increasing risk for disease with time since vaccination (13). In the presence of natural boosting, neutralizing antibodies have been demonstrated up to 12 years after vaccination (30). However, duration of antibody persistence in a high-coverage setting where mumps circulation has declined is not known. In Finland, a decline in mumps antibody titers was demonstrated in vaccinated children (31), and the proportion of children seropositive for mumps antibodies some years after MMR vaccination was lower than expected in Sweden and the United Kingdom (32,33).

Our estimates may be affected by several biases. Unvaccinated children may mix with other unvaccinated children and exposure may be more common than in vaccinated children, which would lead to an overestimation of vaccine effectiveness. Because most cases occurred in age groups not eligible for vaccination, however, it is likely that exposure to mumps was fairly uniform.

In addition, those who do not access healthcare for vaccination may be less likely to seek care for mumps disease. Consequently, these cases may be less likely to be reported, which would lead to an underestimation of vaccine effectiveness. The availability of free universal primary care, however, means that persons with mumps should not have difficulty accessing medical care in the United Kingdom. Studies during local outbreaks may also underestimate vaccine effectiveness, as a chance cluster of cases is more likely to be reported (29). The 2004–2005 outbreak of mumps was a national outbreak affecting all regions of the United Kingdom and is therefore unlikely to be subject to this bias (6).

The screening method relies on accurate estimates of population vaccine coverage (25). Estimates of vaccine effectiveness were similar using raw and adjusted coverage values, which suggests that our adjustments had not introduced any major bias. Sensitivity analyses that explore the effects of underestimation of vaccine coverage demonstrate that overall effectiveness could be as high as 90% for 1 dose, but this would require true coverage to be >5% higher than recorded.

If mumps cases had occurred before the period of our investigation, a false impression of waning immunity could have resulted because these cases would have affected proportionately more unvaccinated than vaccinated children (34). Immunity develops in children who have had mumps, so unvaccinated children would be preferentially removed from the population at risk. Therefore, with increasing age, the proportion of mumps cases diagnosed in vaccinated children would increase. From 1990 through 2003, however, UK mumps incidence was extremely low, so past infection is unlikely to be responsible for the observed decline in vaccine effectiveness with increasing age.

The possible effect of migration to and from the United Kingdom on these estimates is difficult to assess. Of immigrants to the United Kingdom, ≈80% arrive from commonwealth countries or the European Union each year, and ≈40,000 are children <15 years of age (35). Some of these countries do not use routine mumps vaccine; therefore, our estimates of vaccine coverage in older children may be too high. This would lead to an apparent increase in effectiveness with age, rather than the effect observed.

The use of vaccine coverage at the fifth birthday assumes that no further mumps vaccines are given after this age. If coverage gradually increased after this age, effectiveness would be underestimated for older age groups. Children 5–12 years of age, however, have generally not been targeted by MMR catch-up campaigns, and the target payment incentive in primary care does not apply after 6 years of age (36). From the South Thames data, most MMR given after the fifth birthday is given to children 5–6 years of age, and the numbers vaccinated are too low to produce the observed decline in effectiveness. We therefore conclude that an increase in coverage after 5 years of age is unlikely to fully explain the decline.

No evidence has shown that vaccine quality and handling changed over time. All cohorts >6 years of age were only eligible for MMR-II (Sanofi Pasteur MSD, Berkshire, UK) for the first dose, so a change in product cannot be responsible for the decline in first-dose effectiveness after this age. Priorix (GlaxoSmithKline, Uxbridge, UK) became available in 1998, but as population coverage by vaccine manufacturer is not available, we are unable to show any differences between vaccines.

According to this study, <80% of children 11–12 years of age are protected against mumps, less than the suggested threshold of 90%–92% to interrupt transmission (37). The true proportion of those with immunity may now be higher than this because many unvaccinated persons will have acquired natural infection and vaccinated persons may have been boosted by exposure during the outbreak.

Our estimates of vaccine effectiveness suggest that the mumps component of MMR provides excellent protection through routine administration in the United Kingdom. The observation of waning immunity is, however, a cause for concern because the proportion of susceptible adolescents may increase, which could lead to future outbreaks in this age group. Because most recent cases have occurred in persons too old to have been vaccinated, the contribution of waning immunity to the current UK outbreak is small (6). To minimize the risk of future outbreaks, MMR vaccine coverage with both doses must be improved and maintained.