Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
							Search
		×
			Vaccines site
			Vaccines site
				All CDC
				Submit
			For a full list of topics:A-Z Index
			Advanced Search
		Advanced Search


Advisory Committee on Immunization Practices (ACIP)


Facebook
        Twitter
        LinkedIn
        Syndicate





Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps Disease During an Outbreak																									Related Pages
												On This Page
			IntroductionMethodsResultsSummaryTablesReferences
		
Printer friendly version of this page Cdc-pdf[9 pages, HTML]
Introduction
In 1977, the Advisory Committee on Immunization Practices (ACIP) recommended one dose of mumps vaccine for all children aged ≥12 months (1).  In 1989, in response to multiple measles outbreaks in the late 1980s, ACIP recommended routine administration of two doses of measles, mumps, rubella (MMR) [M-M-R II, Merck & Co., Inc] vaccine for children, with the first dose administered at ages 12 through 15 months and the second at ages 4 through 6 years (2). 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, mumps outbreaks, primarily affecting populations with high coverage with two doses of MMR vaccine in midwestern states and colleges, occurred in 2006, prompting 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 (4). Despite this recommendation, mumps outbreaks continued to be reported throughout the United States. 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 2012 in specifically identified target populations.
As more evidence has accumulated after 2012, in October 2017 the Advisory Committee on Immunization Practices (ACIP) reviewed the evidence on vaccination with a third dose of mumps virus-containing vaccine. The policy question was “Should a third dose of mumps virus-containing vaccine be administered to persons at increased risk for mumps because of an outbreak?” Evidence of benefits and harms was evaluated in accordance with Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methods (5).**Top of Page
Methods
The ACIP Mumps Work Group proposed beneficial and harmful outcomes of vaccination to consider, as well as the importance of these outcomes (critical vs. important).
A systematic review of Medline, Embase, Cochrane Library, CINAHL, Scopus and ClinicalTrials.gov, was conducted for studies in any language published from January 2000 to August 2017. The start date of January 2000 was selected because a large outbreak among persons with two doses of MMR vaccine was first reported in 2006 by the United States (6) and use of a third dose of mumps virus-containing vaccine was not considered before this and other large mumps outbreaks that occurred around the same time. We added five years as an additional capture period. Search terms are described in Table 1. Articles were included if they presented data on a third dose of mumps virus-containing vaccine and 1) reported primary data; 2) included data relevant to the outcome(s) being assessed; and 3) were not animal studies. The work group also pursued available unpublished data.
After review of the titles and abstracts (n=478), 50 studies were identified for further review. Of these, 34 studies did not report data on a third dose, 5 did not report on outcomes of interest, 1 study on a third dose was conducted only in immunocompromised children and 3 studies had results not yet reported or not found. We identified an additional 3 studies that were unpublished at the time of the work group assessment. A total of 10 studies reporting on critical and important outcomes were considered in the GRADE analysis. In this document, we summarize evidence from 7 studies that reported on critical outcomes (7–13).  Studies included in the evaluation of important outcomes are provided in Supplementary Table 1 (7, 11–16). In all studies, MMR vaccine was used as the third dose of mumps virus-containing vaccine.
**Top of Page
Results
The benefits outcomes considered critical were preventing mumps disease and preventing complications of mumps disease and the harms outcome considered critical was occurrence of serious adverse events (SAEs) after vaccination (Table 2). Important outcomes included duration of protection, immune response, and reactogenicity.
Benefits outcomes
Three cohort studies reported on the outcome of preventing mumps disease. Characteristics and results of these studies are presented in Table 3. All studies were conducted in outbreak settings among populations with high two-dose coverage (i.e. >95%) and reported a lower attack rate in three dose MMR vaccine recipients compared with two dose recipients. Incremental vaccine effectiveness (VE) at 21 to 28 days post-vaccination ranged from 61% to 88% but only one estimate (78%, 95% CI 61%–88%) was significant (p<0.001). The GRADE evidence type for preventing mumps disease was 4 (Table 4).
For the outcome of preventing mumps complications, no studies reported on VE against mumps complications and the evidence type was not determined for this outcome (Table 4). However, it was considered that complications from mumps disease also are prevented when mumps disease is prevented by a third dose of MMR vaccine.
Harms outcome
One pre- and post- study and 4 case series studies reported on serious adverse events (SAE) of a third dose of MMR vaccine. Characteristics and results of these studies are presented in Table 3. SAE is defined as death, life-threatening illness, hospitalization or prolongation of existing hospitalization, or permanent disability. No SAEs were reported in 14,368 children and young adults vaccinated with a third dose. Two studies were based on passive reporting and 3 studies actively surveyed vaccine recipients. In addition, no healthcare visits for vaccination-related symptoms were reported in any of the studies. The GRADE evidence type for serious adverse events was 3 for the pre- and post- study and 2 for the cases series studies, and therefore the overall evidence type for this outcome was 2 (Table 4).
**Top of Page
Summary
The evidence types supporting critical outcomes for use of third dose of mumps virus-containing vaccine in persons at increased risk for mumps disease because of an outbreak was determined to be 4 for preventing mumps, not determined for preventing mumps complications, and 2 for serious adverse events (Table 5). A third dose of MMR vaccine is effective in preventing mumps and no serious adverse events were reported in more than 14,000 third dose recipients. Together, the benefit of added protection of a third dose of mumps virus-containing vaccine outweighs the low risk for vaccine adverse events. After reviewing the results of the GRADE analysis and other data related to burden of disease, values attributed to benefits and harms from a third dose of MMR vaccine, acceptability, and implementation, the ACIP recommended that persons previously vaccinated with two 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. Although studies evaluated for the GRADE analysis only assessed MMR vaccine, mumps virus-containing vaccine was used in the recommendation to include the measles, mumps, rubella, and varicella (MMRV) vaccine [ProQuad, Merck & Co., Inc] as an option for children aged 12 years or younger when a third dose mumps vaccination is indicated. The full recommendations for the use of mumps virus-containing vaccine in persons at increased risk for mumps because of an outbreak have been published in MMWR.
**Top of Page
Tables
Table 1. Use of a Third Dose of Mumps Virus-Containing Vaccine During Outbreaks: Literature Search Terms by Database
Literature Search Terms by Database
Database
StrategyMedline
(OVID)
1946-
[Mumps OR parotitis] AND [Vaccin* OR immuni?ation* OR MMR*] AND
[(third ADJ5 (Dose* OR dosage)) OR (three ADJ5 (Dose* OR dosage)) OR (outbreak* ADJ5 (dose* OR dosage)) OR (additional ADJ5 (dose* OR dosage)) OR (booster* AND (outbreak* OR epidemic*)) OR (booster ADJ5 (dose* OR dosage)) OR military]Embase
(OVID)
1947-
[Mumps OR parotitis] AND [Vaccin* OR immuni?ation* OR MMR*] AND
[(third ADJ5 (Dose* OR dosage))  OR (three ADJ5 (Dose* OR dosage)) OR (outbreak* ADJ5 (dose* OR dosage)) OR (additional ADJ5 (dose* OR dosage)) OR (booster* AND (outbreak* OR epidemic*)) OR (booster ADJ5 (dose* OR dosage)) OR military]Cochrane Library
[Mumps OR parotitis] AND [Vaccin* OR immuni?ation* OR MMR*] AND
[(third N5 (Dose* OR dosage))  OR (three N5 (Dose* OR dosage)) OR (outbreak* N5 (dose* OR dosage)) OR (additional N5 (dose* OR dosage)) OR (booster* AND (outbreak* OR epidemic*)) OR (booster N5 (dose* OR dosage)) OR military]Clinical Trials.gov
[mh mumps] OR (Mumps OR parotitis):ti,ab AND (Vaccin* OR immuni?ation* OR MMR*) AND (third NEAR/5 (Dose* OR dosage))  OR (three NEAR/5 (Dose* OR dosage)) OR (outbreak* NEAR/5 (dose* OR dosage)) OR (additional NEAR/5 (dose* OR dosage)) OR (booster* AND (outbreak* OR epidemic*)) OR (booster NEAR/5 (dose* OR dosage)) OR militaryScopus
1960-
TITLE-ABS-KEY(Mumps OR parotitis) AND TITLE-ABS-KEY(Vaccin* OR immuni?ation* OR MMR*) AND TITLE-ABS-KEY((third W/5 Dose*) OR (third W/5 dosage) OR (three W/5 Dose*) OR (three W/5 dosage) OR (outbreak* W/5 dose*) OR (outbreak* W/5 dosage) OR (additional W/5 Dose*) OR (additional W/5 dosage) OR (booster* AND (outbreak* OR epidemic*)) OR (booster W/5 dose*) OR (booster W/5 dosage) OR military) AND NOT INDEX(medline) AND NOT INDEX(embase)Clinicaltrials.gov
(Mumps OR parotitis)**Top of Page
Table 2. Use of a Third Dose of Mumps Virus-Containing Vaccine During Mumps Outbreaks: Outcomes, Importance, and Data Availability
Outcomes, Importance, and Data Availablity
Outcome
Importance
Data availableBenefitsPrevent mumps disease
Critical
YesPrevent mumps disease complications
Critical
NoDuration of protection
Important
NoImmune response
Important
YesHarmsSerious adverse events
Critical
YesReactogenicity
Important
Yes**Top of Page
Table 3. Use of a Third Dose of MMR Vaccine During Mumps Outbreaks: Characteristics and Results of Included Studies for Critical Outcomes
Literature Search Terms by Database
Author, year
Study design
Study population; setting
Comparison group
Benefit outcome (results)
Harm outcome (results)Cardemil, 2017
Cohort
University students; outbreak
Two MMR dose vaccinated
Prevention of mumps disease (incremental VE=60%, 95% CI: 38%–74%)
NoneNelson, 2013*
Cohort
School children aged 9–14 yrs; outbreak
One or two MMR dose vaccinated
Prevention of mumps disease (incremental VE=61%, 95% CI: -243–95%)
Serious adverse events (0/533 doses administered)Ogbuanu, 2012*†
Cohort
School children aged 11–17 yrs; outbreak
Two MMR dose vaccinated
Prevention of mumps disease (incremental VE=88%, 95% CI: -32–99%)
Serious adverse events(0/1,597 doses administered)Albertson, 2016
Case series
University students and staff; outbreak
None
None
Serious adverse events (0/11,500 doses administered)Aasheim, 2014
Case series
School children aged 12–19 years; outbreak
None
None
Serious adverse events(0/76 doses administered)Abedi, 2012†
Case series
School children aged 11–17 years; outbreak
None
None
Serious adverse events (0/1,597 doses administered)Routh, unpublished
Pre- and post-intervention
Young adults; non-outbreak
Pre-third MMR dose symptoms
None
Serious adverse events (0/662 doses administered)VE=vaccine effectiveness; CI=confidence interval
*Considered case series studies for the outcome serious adverse events because the outcome was reported only for persons that received a third dose and not the comparison group
†Studies reported survey data from the same study for the outcomes serious adverse events and are considered in the analysis as one study for this outcome
Top of Page
Table 4. Use of a Third Dose of MMR Vaccine During Mumps Outbreaks: Evidence Table for Critical Outcomes
Evidence Table for Critical Outcomes
Outcome
Design (# studies)
Initial Evidence
Risk of Bias
Inconsistency
Indirectness
Imprecision
Other considerations
Final Evidence type
Overall Evidence TypeBenefitsPrevent mumps disease
Cohort (3)
3
Serious* (-1)
No serious
No serious
Serious† (-1)
None
4
4Prevent complications of mumps disease
No studies
ND
ND
ND
ND
ND
ND
ND
NDHarmsSerious adverse events
Pre- and post- (1)
3
No serious
No serious
No serious
Unable to assess
None
3
2Case series (4)
3
No serious
No serious
No serious
Unable to assess
Yes‡
2ND=Not determined
*Selection bias; downgraded by 1
†The CI around the effect estimate are large or include both effect and non-effect; downgraded by 1
‡Strong strength of association. No reported serious adverse events in over 13,000 vaccinated persons; upgraded by 1
**Top of Page
Table 5. Considerations for Use of a Third Dose of Mumps Virus-Containing Vaccine During Mumps Outbreaks
Considerations for Use of a Third Dose of Mumps Virus-Containing Vaccine During Mumps Outbreaks
Key factors
CommentsBalance between benefits and harms
A third dose of MMR vaccine is effective in preventing mumps. No evidence available but complications of mumps disease are prevented when mumps disease is prevented. There are no concerns for serious adverse events after vaccination with a third dose of MMR vaccine.
ACIP considered that this evidence also would pertain to MMRV vaccine.Evidence type for benefits and harms
**Benefits:**
Prevent mumps disease: evidence type 4
Prevent complications of mumps disease: evidence type not determined**Harms:**
Serious adverse events: evidence type 2**Top of Page
Supplementary Table 1. Use of a Third Dose of MMR Vaccine During Mumps Outbreaks: Characteristics of Included Studies for Important Outcomes
Characteristics of Included Studies for Important Outcomes
Author, year
Study design
Study population; setting
Comparison group
Benefit outcome
Harm outcomeRouth, unpublished
Pre- and post-intervention
Young adults; non-outbreak
Pre-third MMR dose symptoms
None
ReactogenicityLatner, in press*
Repeated measures
Young adults; non-outbreak
Pre-third MMR dose titers
Immune response (IgG against whole virus, hemagglutinin-neuraminidase (HN) and nucleoprotein)
NoneFiebelkorn, 2014*
Repeated measures
Young adults; non-outbreak
Pre-third MMR dose titers
Immune response (plaque reduction neutralization (PRN) neutralizing antibody titers)
NoneNelson, 2013†
Cohort
School children aged 9–14 yrs; outbreak
One or two MMR dose vaccinated
None
ReactogenicityAbedi, 2012‡
Case series
School children aged 11–17 years; outbreak
None
None
ReactogenicityOgbuanu, 2012†‡
Cohort
School children aged 11–17 yrs; outbreak
Two MMR dose vaccinated
None
ReactogenicityDate, 2008
Repeated measures
University students seronegative for mumps; post-outbreak
Pre-third MMR dose titers
Immune response (IgG against whole virus)
None*Studies used serum samples from same cohort but different antibody detection methods
†Considered case series studies for the outcome reactogenicity because the outcome was reported only for persons that received a third dose and not the comparison group
‡Studies reported survey data from the same study for the outcome reactogenicity and are considered in the analysis as one study for this outcome
**Top of Page
References
Centers for Disease Control and Prevention. Mumps vaccine. MMWR 1977;26(48):393–4.
Centers for Disease Control and Prevention. Measles prevention. MMWR 1989;38:1–18.
Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2013;62:1–34.
Centers for Disease Control and Prevention. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP) for the control and elimination of mumps. MMWR Morb Mortal Wkly Rep 2006;22:629–30.
Ahmed F, Temte J, Campos-Outcalt D, Schunemann H, ACIP Evidence Based Recommendations Work Group. Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC). Vaccine 2011;29:9171–6.
Centers for Disease Control and Prevention. Mumps epidemic—Iowa, 2006. MMWR 2006;55:366–8.
Routh J. MMR3 Adverse Events. ACIP Workgroup presentation, May 25, 2017. Unpublished data.
Cardemil C, Dahl RM, James L, Wannemuehler K, Gary HE, Shah M, Marin M, Riley J, Feikin DR, Patel M, Quinlisk P. Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control. N Engl J Med, 2017;377:947–956.
Albertson JP, Clegg WJ, Reid HD, Arbise BS, Pryde J, Vaid A, Thompson-Brown R, Echols F. Mumps Outbreak at a University and Recommendation for a Third Dose of Measles-Mumps-Rubella Vaccine – Illinois, 2015-2016. MMWR, 2016;65(29):731–734.
Aasheim ET, Inns T, Trindall A, Emmett L, Brown KE, Williams CJ, Reacher M. Outbreak of mumps in a school setting, United Kingdom, 2013. Hum Vaccin Immunother, 2014;10(8): 2446–2449.
Nelson GE, Aguon A, Valencia E, Oliva R, Guerrero ML, Reyes R, Lizama A, Diras D, Mathew A, Camacho EJ, Monforte MN, Chen TH, Mahamud A, Kutty PK, Hickman C, Bellini WJ, Seward JF, Gallagher K, Fiebelkorn AP. Epidemiology of a mumps outbreak in a highly vaccinated island population and use of a third dose of measles-mumps-rubella vaccine for outbreak control–Guam 2009 to 2010. Pediatr Infect Dis J, 2013. 32(4):374–80.
Abedi GR, Mutuca JD, Lawlerd J, Leroyb ZC, Hudsond JM, Bloge DS, Schultee CR, Rausch-Phunge E, Ogbuanuc IU, Gallaghera K, Kuttya PK. Adverse events following a third dose of measles, mumps, and rubella vaccine in a mumps outbreak. Vaccine, 2012. 30(49):7052–
Ogbuanu IU, Kutty PK, Hudson JM, Blog D, Abedi GR, Goodell S, Lawler J, McLean HQ, Pollock J, Rausch-Phung E, Schulte C, Valure B, Armstrong GL, Gallagher K. Impact of a third dose of measles-mumps-rubella vaccine on a mumps outbreak. Pediatrics, 2012. 130(6):e1567–74.
Latner DR, Fiebelkorn AP, McGrew M, Williams NJ, Coleman LA, McLean HQ, Rubin S, Hickman CJ. Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella (MMR) Vaccine. Open Forum Infectious Diseases, in press.
Fiebelkorn AP, Coleman LA, Belongia EA, Freeman SK, York D, Bi D, Zhang C, Ngo L, Rubin S. Mumps antibody response in young adults after a third dose of measles-mumps-rubella vaccine. Open Forum Infectious Diseases, 2014. 1(3); 1–9.
Date AA, Kyaw MH, Rue AM, Klahn J, Obrecht L, Krohn T, Rowland J, Rubin S, Safranek TJ, Bellini WJ, Dayan GH. Long-term persistence of mumps antibody after receipt of 2 measles-mumps-rubella (MMR) vaccinations and antibody response after a third MMR vaccination among a university population. J Infect Dis, 2008. 197(12):1662–8.**Top of Page

			View Page In:Cdc-pdf PDF [111K]
							
								Page last reviewed:  January 10, 2018						Content source:  	National Center for Immunization and Respiratory Diseases homeACIP Home
Meeting Information
Committee Informationplus icon
Role of the ACIP in CDC’s Vaccine Recommendations
Charter
Economics Studies
Committee Membersplus icon
ACIP Membership Roster
Apply for ACIP Membership
Work Groupsplus icon
VaST Reportsplus icon
June 28, 2021
May 24, 2021
May 17, 2021
March 29, 2021
Recommendationsplus icon
Shared Clinical Decision-Making Recommendations
Evidence Based Recommendationsplus icon
About GRADE
Grade Evidence Tables
Evidence to Recommendations Frameworks Vaccines & ImmunizationsImmunization SchedulesVFC ResolutionsVaccine Information Statements (VISs)
  1600 Clifton Road, N.E., Mailstop A27
Atlanta, GA 30329-4027acip@cdc.gov


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov





Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue