The recent mumps outbreak in adults in Los Angeles County serves as a reminder that sporadic mumps outbreaks continue to occur and that clinicians should keep mumps in their differential when evaluating patients. Because the mumps vaccine is so effective, many clinicians have never seen a patient with mumps and the diagnosis of mumps can be elusive. As the current mumps outbreak reminds us, this viral illness can have a significant impact on individuals and their community.  

The LA County mumps outbreak, which started in January 2017, is winding down. To date, there are 54 confirmed cases, of whom only 2 had documented proof of mumps vaccination. Thirty-five cases did report a history of vaccination but lacked corroborating documentation. As with many less common illnesses, cases were initially misdiagnosed, most frequently as salivary duct stones or lymphadenopathy. Several cases were initially missed due to clinician misunderstanding that mumps can occur in vaccinated individuals and that a negative IgM can be seen with clinical disease.

The goals of this article are to raise awareness of mumps in the vaccine era and to increase providers’ confidence in their ability to diagnose and manage a patient in whom mumps is suspected.

Epidemiology in the Era of Vaccination

In the United States (U.S.) since the introduction of the mumps vaccine, there has been more than a 99% decrease in mumps cases.¹ The incidence dropped dramatically from 50-251 per 100,000 in the pre-vaccine era to 0.1 per 100,000 in 1999.² The vaccine responsible for this dramatic reduction was first licensed in the U.S. in 1967.² A single dose of mumps vaccine was recommended by the Advisory Committee on Immunization Practices (ACIP) in 1977 and two doses of measles, mumps, and rubella (MMR) vaccine were recommended in 1989.

Transmission and Outbreaks

The mumps virus replicates in the upper respiratory tract and spreads through contact with respiratory secretions, saliva, and fomites.³ Transmission is facilitated by being in a crowded environment, living in a dormitory, playing on the same sports team, exchanging saliva through kissing, and sharing utensils, lipstick, or cigarettes.¹ Outbreaks can occur any time of the year and historically have predominantly affected people 18-24 years of age.² There have been several mumps outbreaks nationally since 2006 despite good vaccine coverage with two doses (Figure 1).^1,4 High vaccination coverage limits the size, duration, and spread of mumps outbreaks.

Figure 1.

Source: Centers for Disease Control and Prevention: National Notifiable Disease Surveillance System (passive surveillance); 2016 data is preliminary (May 31, 2017) and subject to change.

Clinical Presentation

The average incubation period is 16 -18 days (range 12-25 days).² Mumps often begins with non-specific symptoms such as fever, fatigue, myalgia, anorexia, headache, and non-specific respiratory symptoms.³ The classic unilateral or bilateral painful swelling of the parotid gland occurs about 48 hours after symptom onset (Figure 2). Swelling peaks in 1-3 days, pushing the ear upwards and outwards and obscuring the angle of the jawbone. Swelling may last for longer than 10 days. The other salivary glands (submandibular and sublingual) are affected in approximately 10% of cases (Figure 3). It is important to note that one-third of cases do not have any apparent salivary gland swelling.² Other causes of parotitis are listed in Box 1.

Complications

Adults with mumps infection tend to have a more severe illness and greater likelihood of complications compared to children.⁵ The most common complication in adult males is orchitis (3-10%) which may present without parotitis.³ In the majority of the cases, a single testis is involved (60-83%). Up to 13% have impaired fertility, though sterility is rare.^6,7 Among adolescent and adult females, mastitis and oophoritis occur at a rate of ≤1%.⁵ Other reported complications are pancreatitis, deafness, meningitis, and encephalitis (all <1%).  During outbreaks, male suspect cases and contacts should be asked specifically about testicular pain.⁸ No mumps-related deaths have been reported in recent outbreaks in the U.S.

Diagnosis

The recommended laboratory tests are a reverse-transcriptase polymerase chain reaction (RT-PCR) for virus isolation and IgM and IgG serological testing.^8,9 Specimens positive on RT-PCR testing can be further sequenced to determine viral genotype.⁸ For suspect cases in LA County, providers are encouraged to immediately contact the LA County Department of Public Health (DPH) for guidance on specimen collection, test selection, and facilitation of testing (Box 2).

Specimen collection

• RT-PCR: The preferred sample is a buccal swab with parotid gland secretions (see Box 2).¹⁰
• Serology (serum): Blood is the preferred sample and should be collected in a red top or serum-separator tube (SST). Serological assays can be performed at reference labs and are also commercially available.

Timing of specimen collection

It is recommended that serology and RT-PCR specimens be collected as soon as mumps disease is suspected.^9,10 Test sensitivity and result interpretation depend on the timing of specimen collection.  

• The percent positivity with RT-PCR testing decreases over the first five days of symptom-onset, as seen in Figure 4.¹¹ The optimal time for testing with RT-PCR is within three days of symptom onset, though specimens may be collected up for to nine days.
• For IgM tests, percent positivity increases with time, as per Figure 4. Although it is recommended that serum be collected upon initial presentation, repeat serologic testing may be needed.

Figure 4. Percentage of Mumps Specimens Determined Positive by CDC IgM Capture EIA or rRT (N target gene) as a Function of Time Post Parotitis Onset¹¹

Source: Centers for Disease Control and Prevention: Questions and Answers about Lab Testing https://www.cdc.gov/mumps/lab/qa-lab-test-infect.html

The percentage of positive results obtained from testing 296 confirmed mumps cases from New York City by day of sample collection after onset of symptoms. The serum samples were tested for presence of IgM using the CDC capture IgM EIA. The buccal swab samples were tested by rRT-PCR using the mumps nucleoprotein (N) gene as the target.
Done in collaboration with New York City Department of Health and Mental Hygiene Public Health Laboratory, New York, NY
Mumps virus was isolated from 209 (71%) of the 296 buccal swabs tested.

Interpretation of results

• RT-PCR: A positive PCR result indicates the presence of mumps virus RNA in the sample and confirms a mumps infection (if patient has not been vaccinated within the preceding 45 days).  A negative test, however, does not effectively rule out the infection. As demonstrated in Figure 4, sensitivity drops significantly after 3 days. Overall sensitivity of RT-PCR for mumps has been shown to be as high as 79%.^7,10,12
• Serology: The rate of seropositivity in mumps cases depends on the vaccination-status and prior disease history (see Table 1 adapted from the CDC).¹³ A positive IgM test in the setting of high clinical suspicion and no vaccination within three months suggests acute infection.¹³ In unvaccinated individuals with no disease history, a four-fold rise in IgG titers between acute- and convalescent-phase serum specimens confirms the diagnosis.² Diagnosis is challenging in vaccinated individuals since the IgM test may remain negative and  fourfold rise in IgG titers is rarely seen.

Table 1. Seropositivity in Mumps Cases Based on Prior Immunity

Treatment

Treatment is largely supportive. Pain control with analgesics and warm/cold packs can be considered. Neither immunoglobulin nor vaccination have a role in the treatment of an infected person.

Infection Prevention and Control: General Recommendations

Vaccine recommendations

The mumps vaccine is available in two combination vaccines: the MMR and the pediatric measles-mumps-rubella-varicella (MMRV) vaccine. The mumps vaccine is very effective: 88% with two doses (range 66-95%) and 78% with one dose (range 49-92%).³ Vaccination with two doses has been recommended by the ACIP since 1989.² Ensuring a high rate of childhood vaccination is the most effective strategy to prevent disease in the population.

The ACIP recommends that all adults without proof of immunity to mumps be vaccinated unless they have a medical contraindication like pregnancy or severe immunodeficiency.¹⁴

• A single dose of MMR is recommended for most adults.
• Two vaccine doses are recommended for the following individuals:
  1. HIV infected (CD4+ T-lymphocyte count ≥200 cells/µl for at least 6 months)
  2. Health care personnel
  3. Students in postsecondary educational institutions
  4. Those who plan to travel internationally
  5. Those who received inactivated (killed) measles vaccine or measles vaccine of unknown type during years 1963–1967
  6. Those who were vaccinated before 1979 with either inactivated mumps vaccine or mumps vaccine of unknown type who are at high risk for mumps infection, e.g., health care workers.

In adults, proof of immunity includes birth before 1957, documentation of MMR receipt, or laboratory evidence of immunity or disease.¹⁴ Proof of immunity among health care workers differs slightly from the general population⁵ and includes any one of the following:

1. Written documentation of vaccination with two doses of live mumps or MMR vaccine administered after 12 months of age and at least 28 days apart
2. Laboratory evidence of immunity: equivocal results should be considered negative
3. Laboratory confirmation of disease
4. Birth before 1957 which presumes natural immunity. A caveat here is if there is laboratory evidence of lack of immunity or disease in a person born before 1957, vaccination with two doses is required in an outbreak setting and is encouraged in a routine setting. 

Infection control and reporting

Suspect mumps patients should remain home and away from public spaces such as school and work for five days after parotitis onset or, in its absence, until the resolution of constitutional symptoms.³

In the health care setting, droplet precautions (mask with eye protection) in addition to standard precautions (hand hygiene and appropriate environmental cleaning) are recommended until five days after onset of parotid swelling.^5,15,16 Health care workers without evidence of immunity should be excluded from the 12th day after the first unprotected exposure to mumps through the 25th day after the last unprotected exposure.⁵ Those with partial vaccination may continue working following an unprotected exposure but should immediately receive a second dose of vaccine. Workers with immunity do not need to be removed from work.

Suspected mumps cases should be promptly reported to the local health department without waiting for laboratory confirmation (Box 3). In LA County, once reported, DPH will assist in the management of all suspect cases and their contacts.

Infection Prevention and Control: Outbreak Setting

A mumps outbreak is defined as three or more cases linked by time and place.⁵ In this setting, the mumps vaccine should be administered to all at-risk contacts without evidence of immunity, provided the vaccine is not contraindicated. Control of infection maybe challenging in a school or college setting, particularly if students have no immunity and do not get vaccinated. Unvaccinated/non-immune students should be excluded from schools and colleges through the 25^th day after the onset of parotitis in the last person with mumps. Immune globulin is not indicated for mumps post-exposure prophylaxis.

In recent outbreaks in New York and Guam, a third dose of vaccine was administered as post-exposure prophylaxis.⁴ The antibody response was higher and the rate of infection was lower in those vaccinated with a third dose. However, limitations include lack of qualitative data regarding the antibody response, incremental decrease in rates of infection, and inability to tease out the effects of interventions other than the receipt of a third vaccine dose. As data regarding the effectiveness and safety of a third vaccine dose is growing, the ACIP is reviewing results to determine the appropriateness of making this a routine recommendation. In the interim, the CDC has issued criteria for public health departments to consider when deciding whether to recommend a third dose for mumps outbreak control.

Conclusions

Sporadic mumps outbreaks continue to occur in the U.S. despite an effective vaccine. Clinicians should remain vigilant for mumps infection. A summary of key action steps is below.

References

1. Centers for Disease Control and Prevention. Mumps Cases and Outbreaks. https://www.cdc.gov/mumps/outbreaks.html. Updated August 23, 2017. Accessed September 6, 2017.
2. American Academy of Pediatrics. Mumps. In:Kimberlin D, et al.,editors. Red Book: 2015 Report of the Committee on Infectious Diseases.  30th ed. Elk Grove Village, Illinois:,2015.
3. Centers for Disease Control and Prevention. Mumps: For Healthcare Providers. https://www.cdc.gov/mumps/hcp.html.  October 24, 2016. Accessed June 15, 2017.
4. Marin M. Update on Mumps Epidemiology in the United States, 2017 and Review of Studies of 3rd Dose of MMR Vaccine 2017. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-06/mumps-02-marin.pdf. Accessed June 15, 2017.
5. Fiebelkorn AP, et al. Chapter 9: Mumps. Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt09-mumps.html. Updated April 1, 2014. Accessed June 15, 2017.
6. Werner CA. Mumps Orchitis and Testicular Atrophy. II. A Factor in Male Sterility. Ann Intern Med. 1950;32(6):1075-1086.
7. Hatchette T, et al. Laboratory diagnosis of mumps in a partially immunized population: The Nova Scotia experience. Can J Infect Dis Med Microbiol. 2009; 20: e157–e162.
8. Los Angeles County Department of Public Health. LAC DPH Health Alert: Mumps Outbreak in Adults in LA County, June 1, 2017. http://publichealth.lacounty.gov/eprp/Health%20Alerts/LAC%20DPH%20Alert%20Mumps%20060117.pdf Accessed September 1, 2017.
9. California Department of Public Health Viral and Rickettsial Disease Laboratory. Mumps Laboratory Testing Guidance, March 2017. https://archive.cdph.ca.gov/programs/vrdl/Documents/Mumps_Testing_VRDL_Quicksheet.pdf. Updated February 24, 2017. Accessed August 17, 2017.
10. Centers for Disease Control and Prevention. Mumps: Specimen Collection, Storage,and Shipment. https://www.cdc.gov/mumps/lab/specimen-collect.html. Updated November 17, 2016. Accessed August 17, 2017.
11. Centers for Disease Control and Prevention. Mumps: Questions and Answers about Lab Testing. www.cdc.gov/mumps/lab/qa-lab-test-infect.html. Updated February 14, 2017. Accessed August 17, 2017.
12. Rota JS, et al. Comparison of the sensitivity of laboratory diagnostic methods from a well-characterized outbreak of mumps in New York city in 2009. Clin Vaccine Immunol  2013; 20: 391–396.
13. Centers for Disease Control and Prevention. Mumps: Laboratory Confirmation by IgM Serology. https://www.cdc.gov/mumps/lab/overview-serology.html. Updated January 17, 2017. Accessed August 17, 2017.
14. Centers for Disease Control and Prevention. Adult Immunization Schedule by Vaccine and Age Group. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html. Updated February 6, 2017. Accessed July 27, 2017.
15. Centers for Disease Control and Prevention. Transmission-Based Precautions | Basics. https://www.cdc.gov/infectioncontrol/basics/transmission-based-precautions.html. Updated February 28, 2017. Accessed August 11, 2017.
16. Centers for Disease Control and Prevention. Standard Precautions for All Patient Care. https://www.cdc.gov/infectioncontrol/basics/standard-precautions.html. Updated January 16, 2017.Accessed August 11, 2017.