Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus–Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak

Summary of Key Findings

Public Health Burden of Mumps. Parotitis occurs in >85% of mumps cases; however, severe manifestations with complications such as orchitis (12%–66%), aseptic meningitis (0.2%–10%), or encephalitis (0.02%–0.3%) were recognized during the prevaccine era (3) and also can occur in vaccinated persons (3%–11%, <1%, and <0.3%, respectively) (6,8). Since 2012, the number of mumps cases, incidence, number of outbreaks, proportion of outbreak-associated cases, and number of jurisdictions reporting mumps outbreaks have all increased (8). The number of cases reported in 2016 (6,369) and 2017 (5,629, preliminary as of December 31) are the highest reported in a decade. Furthermore, from January 1, 2016 through June 30, 2017, state health departments reported 150 mumps outbreaks (the occurrence of three or more cases linked by place and time) (9), accounting for 9,200 cases; 39 (76%) of 51 of state health departments reported at least one outbreak (2,8). Seventy-five (50%) outbreaks occurred in universities and 16 (11%) in close-knit communities (i.e., communities or groups that are strongly connected by social, cultural, or family ties; participate in communal activities; or have a common living space). A median of 10 cases occurred per outbreak (interquartile range [IQR] = 4–26); 20 (13%) outbreaks had ≥50 cases, and these accounted for 83% of all outbreak-associated cases. Most cases occurred in young adults (median age of outbreak-associated patients = 21 years [IQR = 19–22]). Among 7,187 (78%) of 9,200 patients with known vaccination status, 5,015 (70%) had received 2 doses of MMR vaccine before developing mumps. The overall proportion of outbreak-associated mumps patients with complications was <3% (270 of 9,200); orchitis accounted for 75% (203 of 270) of reported complications. Other investigations also reported significantly lower prevalences of complications among mumps patients who had received 2 vaccine doses than among unvaccinated patients (10,11).

Two-Dose Mumps Vaccine Effectiveness and Immune Response. The median effectiveness of 2 doses of MMR vaccine in preventing mumps is 88%, with estimates ranging from 31% to 95% (3,1216). The studies reporting these findings were conducted during 2005–2016, and most included persons who received the second MMR dose <10 years before the study. Several studies found decreasing effectiveness with increasing time after receipt of the second dose (12,17) or reported increased risk for mumps with increasing time after receipt of the second dose (12,15,18). Limited laboratory data on immune response to mumps virus indicate both lower antibody titers and poorer antibody quality (e.g., lower avidity antibodies, failure to generate strong memory B cell responses) after either natural mumps infection or mumps vaccination compared with the responses to infection with or vaccination against measles and rubella (19,20). Both neutralizing and non-neutralizing mean mumps antibody titers decline over time in persons who have received 2 doses of MMR vaccine (19,2123).

Since 2006, the predominant circulating mumps virus genotype in the United States has been genotype G. Mumps virus–containing vaccines available in the United States are manufactured using the genotype A Jeryl-Lynn mumps virus strain (3). When studied 4–6 weeks and 10 years after receipt of the second MMR dose at age 4–6 years, all recipients had neutralizing antibody against genotype G mumps strain; however, the geometric mean titers of antibodies were lower than those against the vaccine strain (21,24).

Third Dose of MMR Vaccine. Three epidemiologic studies provided evidence regarding use of a third dose of MMR vaccine for prevention of mumps, all conducted in outbreak settings among populations with high coverage with 2 doses of MMR vaccine (schools and a university) (12,25,26). All studies reported lower attack rates among persons who received the third dose during the outbreak compared with persons who had received 2 doses before the outbreak, but only one study (12) found a statistically significant risk ratio (6.7 versus 14.5 per 1,000 person-years; p<0.001). Incremental vaccine effectiveness of the third versus the second MMR dose in these studies ranged from 61% to 88%, with one estimate being statistically significant (78.1%, 95% confidence interval = 60.9%–87.8%) (12). This study also found that students who had received 2 doses of MMR vaccine ≥13 years before the outbreak had nine or more times the risk for contracting mumps than did those who had received the second dose within the 2 years preceding the outbreak.

Two studies evaluated the geometric mean titers of mumps virus–specific antibodies after the third dose of MMR vaccine and demonstrated a significant increase (p<0.0001) 1 month after vaccination; however, antibody titers declined to near baseline by 1 year after vaccination (27,28). In the absence of a correlate of protection that would define the level of antibodies needed to protect a person from mumps disease, the clinical significance of these laboratory findings is unclear.

Five studies evaluated the safety of the third dose of MMR vaccine among children and young adults (aged 9–28 years) using passive and active surveillance for adverse events (J. Routh, CDC, personal communication, 2017) (25,2931). No serious adverse events were reported among 14,368 persons who received a third MMR vaccine dose. Nonserious adverse events were mild and reported at low rates. Among children, 6%–7% reported at least one nonserious adverse event within 2 weeks after receiving the third dose. Among young adults who received a third dose, the prevalences of four symptoms were significantly elevated during the 4-week postvaccination period compared with the prevaccination period. These symptoms and estimated proportions of subjects with episodes attributable to receipt of the third dose were lymphadenopathy (12%), diarrhea (9%), headache (7%), and joint pain (6%) (32). The median duration of these episodes was short (1–3 days).

Stakeholders’ Values, Acceptability, and Implementation Considerations. During July–September 2017, CDC conducted surveys of stakeholders, including students and parents, universities and colleges, and health departments to assess values, acceptability, and considerations for implementation of a third MMR vaccine dose during mumps outbreaks. Because the response rates for the student and parent surveys were very low (<0.5% in one university that agreed to participate), thereby limiting reliability of the results, the values regarding the benefits and harms of using a third dose to prevent mumps from the perspective of these stakeholders was based on expert opinion. Experts concluded that students and parents place high value on preventing mumps and its complications as well as preventing the harms associated with loss of productivity that can occur with mumps disease. Experts also concluded students and parents do not have concerns about safety of a third dose of MMR vaccine.

The survey of colleges and universities was distributed through the American College Health Association. Among 980 member university student health service administrators, 251 (26%) responded, representing colleges and universities from 47 states (33). Among these, 79 (31%) reported having mumps cases on campus since 2014. On a scale ranging from strongly negative (0), to neutral (5), to strongly positive (10), most university administrators felt student and parent attitudes were positive (80% and 83%, respectively, gave a score higher than 5 toward use of a third dose of MMR vaccine to protect students during a mumps outbreak (median = 7 for student attitudes, IQR = 6–9; median = 7 for parent attitudes, IQR = 6–8). With regard to disruption of activities, almost all administrator respondents indicated outbreaks resulted in some degree of disruption on campus. Using a scale from not disruptive (0), to somewhat disruptive (5), to extremely disruptive (10), 57% indicated that mumps outbreaks were more than somewhat disruptive (score >5) to student life (median = 6, IQR = 4–7), and 67% indicated outbreaks were more than somewhat disruptive to staff activities (median = 6, IQR = 5–8). Ranking of disruption to student life and staff activities did not differ significantly by the size of the outbreak experienced by the university (p = 0.20 and p = 0.57, respectively).

The survey of health departments was distributed through the Council of State and Territorial Epidemiologists to 81 health department jurisdictions, including 58 (72%) state and territorial health departments and 23 (28%) city or large urban health departments. Among the 61 (75%) responding health departments, 46 (75%) reported having one or more mumps outbreaks in their jurisdiction since January 1, 2016 (33). Nearly half (47%, 20 of 43) of health departments that reported outbreaks indicated recommending an outbreak dose or third dose of MMR vaccine** during one or more of these outbreaks. Compared with other mumps outbreak control measures, on a scale from not effective (0), to somewhat effective (5), to most effective (10), 42% (8 of 19) of health departments rated the intervention with an effectiveness score >5 (more than somewhat effective) (median = 5, IQR = 3–7). On a scale from least cost beneficial (0), to somewhat cost beneficial (5), to most cost beneficial (10), 53% (8 of 15) of health departments rated the intervention with a cost benefit score >5 (more than somewhat cost beneficial) (median = 7, IQR = 4–7).

GRADE Quality of Evidence Summary. The GRADE evidence type†† for critical outcomes was determined to be 4 for benefits (effectiveness for prevention of mumps) and 2 for harms (serious adverse events) (https://www.cdc.gov/vaccines/acip/recs/grade/mumps.html).

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