A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 ( 1 , 2 ). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus–containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination ( 3 ). In 1977, ACIP recommended 1 dose of mumps vaccine for all children aged ≥12 months ( 4 ). In response to multiple measles outbreaks in the late 1980s, in 1989 ACIP recommended routine administration of 2 doses of MMR vaccine for children, with the first dose administered at ages 12 through 15 months and the second at ages 4 through 6 years ( 5 ). In addition to improved measles control, this policy led to substantial reduction in the number of mumps cases in the United States during the 1990s, which was sustained through 2005 ( 3 ). However, in 2006, mumps outbreaks primarily affecting populations with high coverage with 2 doses of MMR vaccine in midwestern states and colleges resulted in 6,584 reported mumps cases that year ( 6 ). These outbreaks prompted ACIP to formally recommend a routine 2-dose mumps vaccination policy for school-aged children (i.e., kindergarten–grade 12) and adults at high risk (i.e., students at post-high school educational institutions, health care personnel, and international travelers) in 2006 ( 7 ). In addition, ACIP recommended that a second dose of mumps vaccine should be considered in outbreak settings for children aged 1–4 years and adults who have received 1 dose of vaccine, depending on the epidemiology of the outbreak (e.g., the age groups affected or institutions involved). Despite this recommendation, mumps outbreaks continued to be reported throughout the United States, particularly in settings where persons have close, prolonged contact (e.g., universities and close-knit communities). To assist state and local health departments in responding to mumps outbreaks, CDC issued guidance on use of a third dose of MMR vaccine in the 2012 Manual for the Surveillance of Vaccine-Preventable Diseases. † The guidance was based on limited data and provided criteria for health departments regarding when to consider use of a third dose in specifically identified target populations. Additional evidence on effectiveness and safety of the third dose of MMR vaccine recently became available and was presented to ACIP during 2017. This report summarizes the evidence considered by ACIP regarding use of a third dose of a mumps virus–containing vaccine during outbreaks and provides the recommendation for its use among persons who are at increased risk for acquiring mumps because of an outbreak. Methods During March–October 2017, the ACIP Mumps Work Group held biweekly conference calls to review and discuss relevant scientific evidence. Topics addressed included the epidemiology of mumps in the United States since introduction of a routine second dose of MMR vaccine; effectiveness, duration of protection, immunogenicity, and risk factors for 2-dose vaccine failure; and effectiveness, immunogenicity, and safety of a third dose of MMR vaccine. Also assessed were stakeholders’ values attributed to the perceived benefits and harms of a third dose of MMR vaccine, acceptability, and implementation considerations regarding use of a third dose of MMR vaccine. Where scientific data were lacking, the summary of evidence incorporated the opinions of the Mumps Work Group member experts. Quality of evidence related to the benefits and harms of a third dose of mumps virus–containing vaccine was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework (https://www.cdc.gov/vaccines/acip/recs/grade/about-grade.html). Methods and GRADE tables for the evidence for third dose of mumps virus–containing vaccine can be found at https://www.cdc.gov/vaccines/acip/recs/grade/mumps.html. Summaries of the evidence reviewed were presented to ACIP at the February 2017, June 2017, and October 2017 meetings. At the October 2017 ACIP meeting, the proposed recommendation for a third dose of a mumps virus–containing vaccine (i.e., MMR or measles, mumps, rubella, and varicella [MMRV]) during mumps outbreaks was presented, and after a period for public comment, was approved unanimously by the voting ACIP members. § 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%, 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). Summary of Rationale for Recommendation for a Third Dose of Mumps Virus–Containing Vaccine in Persons at Increased Risk for Acquiring Mumps During an Outbreak Mumps outbreaks have occurred primarily in populations in institutional settings with close contact or in close-knit communities. The current routine recommendation for 2 doses of MMR vaccine appears to be sufficient for mumps control in the general population, but insufficient for preventing mumps outbreaks in prolonged, close-contact settings, even where coverage with 2 doses of MMR vaccine is high. Waning of vaccine-induced immunity with time after receipt of the second vaccine dose in high intensity exposure settings typical of outbreaks contributes to this higher risk for mumps disease in these settings. Protection against severe disease, however, is maintained. Considering the evidence regarding the public health burden of disease and the known risk factors, persons who are at increased risk for acquiring mumps because of an outbreak were identified as a public health priority for receiving a third dose of mumps virus–containing vaccine. A third dose of MMR vaccine has at least a short-term benefit for persons in outbreak settings. No serious adverse events were reported, and rates of nonserious adverse events were low. Because mumps is prevented in persons who receive a third dose, complications will also be prevented. Together, the benefit of added protection through administration of a third dose of MMR vaccine outweighs the low risk for vaccine-associated adverse events. Universities and health departments value the prevention of mumps disease and mumps complications and recognize that there is a potential loss of productivity because of mumps disease. A third dose of MMR vaccine was considered acceptable to students, parents, universities/schools, and health departments. Regarding implementation, an ACIP recommendation would allow health departments to make more rapid decisions regarding use of a third dose of MMR vaccine and increase access to vaccine for persons identified by public health authorities as being at increased risk for mumps because of an outbreak. MMRV vaccine, which is the other vaccine licensed in the United States for the prevention of mumps ( 34 ), §§ may also be used when a third dose mumps vaccination is indicated among children aged ≤12 years. Available evidence indicates that a third dose of MMR vaccine improves protection for persons at increased risk for mumps because of an outbreak. Because of the complexity of mumps outbreaks, including the setting, the group or population affected, and risk factors for transmission, public health authorities are uniquely positioned to advise parents, students, clinicians, and universities regarding when and for which groups a third dose of MMR vaccine is appropriate. At this time, evidence is limited and is not sufficient to fully characterize the effect of a third dose of MMR vaccine on reducing the size or duration of an outbreak, nor are any data available to demonstrate the duration of additional protection conferred by a third dose. In addition, limited immunologic evidence suggests antibody titers decline within 1 year after the third dose. As more data on duration of protection after receipt of the third dose become available, evidence for use of a routine third dose will be considered. No evidence is available regarding the benefit of an additional dose of a mumps virus–containing vaccine to persons with documentation of receipt of 3 previous doses; therefore, no additional dose is recommended for persons in outbreak settings who have already received ≥3 doses of a mumps virus–containing vaccine. Recommendation Persons previously vaccinated with 2 doses of a mumps virus–containing vaccine who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak should receive a third dose of a mumps virus–containing vaccine to improve protection against mumps disease and related complications. Implementation Considerations and Future Research In the setting of an identified mumps outbreak, public health authorities should define target groups at increased risk for mumps during the outbreak, determine whether vaccination of at-risk persons is indicated, and provide recommendations for vaccination to health care providers. Persons at increased risk for acquiring mumps are those who are more likely to have prolonged or intense exposure to droplets or saliva from a person infected with mumps, such as through close contact or sharing of drinks or utensils. During an outbreak, persons identified as being at increased risk and who have received ≤2 doses of mumps virus–containing vaccine or have unknown vaccination status should receive 1 dose. Additional guidance can be found in the Manual for the Surveillance of Vaccine-Preventable Diseases ( 9 ). Contraindications and precautions for administration of a third dose of a mumps virus–containing vaccine are the same as those for routine use of the vaccine (1 or 2 doses) ( 3 ). CDC will monitor the burden of mumps among persons who have received 2 and 3 doses of mumps virus–containing vaccine and the duration of protection conferred by the third dose, as well as adverse events after the receipt of a third dose of a mumps virus–containing vaccine. Adverse events occurring after administration of any vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS; https://vaers.hhs.gov/). In addition, CDC will continue to collect data to assess the impact of receipt of a third dose of mumps virus–containing vaccine on mumps outbreaks.
