Mumps in Vaccinated Children and Adolescents: 2007–2019

Mumps is a nationally notifiable disease: US health department jurisdictions report all confirmed and probable mumps cases to the Centers for Disease Control and Prevention through the National Notifiable Diseases Surveillance System (NNDSS). Cases are classified by health departments according to the Council of State and Territorial Epidemiologists (CSTE) mumps case definitions; mumps CSTE case definitions were updated in 2008, 2010, and 2012 (Supplemental Table 3).^13–15  We defined pediatric mumps cases as those that occurred among children and adolescents aged <18 years. We included in the analysis cases reported by the 50 US state and the District of Columbia health departments.

To assess characteristics over time, we analyzed confirmed and probable mumps cases reported to NNDSS from January 1, 2007, through December 31, 2019. Variables analyzed included age, state of residence, vaccination status, and whether the case was outbreak-associated. Annual age-specific incidence rates (per 1 000 000 population) were calculated by using the National Center for Health Statistics’ vintage bridge-race postcensal population estimates.^16,17  Because annual incidence and other case characteristics varied widely each year, we report the median (eg, median annual incidence) and range across years to provide an overall estimate during the study period.

To describe current epidemiology and characteristics of pediatric mumps cases during the most recent resurgence, we analyzed cases reported to NNDSS from January 1, 2015, through December 31, 2019. Variables analyzed included sex, age, race and ethnicity, state of residence, import status, outbreak-associated, vaccination status, parotitis, complications, hospitalization, and death. Complications captured in NNDSS include orchitis, deafness, meningitis, and encephalitis. Data on other mumps complications, such as pancreatitis, oophoritis, and mastitis, were not available. We defined geographic regions according to US Census classifications.¹⁸  Patients were considered vaccinated if they had at least 1 dose of MMR. “Up to date” vaccination status was assigned on the basis of the recommended number of MMR doses for the respective age group: patients 1 to 4 years old were up to date if they had 1 dose of MMR and patients 5 to 17 years old were up to date if they had 2 doses of MMR.

Results for the same analyses on adult cases are provided for comparison in the Supplemental Information. Analyses were performed by using SAS version 9.4 (SAS Institute, Inc, Cary, NC).

During 2007–2019, US health departments reported 28 306 mumps cases, of which 9172 (32%) were pediatric cases (median age = 11 years; range: 0–17). All 50 states and the District of Columbia reported mumps cases during this period, with a median of 212 cases (range: 4–5040) per state, and a median of 48 pediatric cases (range: 3–2263) per state.

Overall, the median number of mumps cases per year was 1328 (range: 229–6369), of which the median number of pediatric mumps cases reported each year was 349 (range: 92–2329) representing a median of 32% of mumps cases each year (range: 13%–59%). There were 2 peaks in pediatric cases in 2009–2010 (2627 cases) and 2016–2017 (4093 cases), coinciding with peaks in all cases (Supplemental Fig 6).

Overall mumps median annual incidence was 4.1 per 1 000 000 population (range: 0.7–19.7). Median annual pediatric incidence was 4.7 per 1 000 000 population (range: 1.3–31.6) (Fig 1). The pediatric age groups with the highest median annual incidence were 5- to 10-year-olds (5.8 per 1 000 000; range: 1.5–34.4) followed by 1- to 4-year-olds (5.8 per 1 000 000; range: 1.9–16.2); however, incidence for each age group varied widely by year (Fig 2). In peak years, among pediatric cases, mumps incidence increased with increasing age of the age group (ie, incidence was higher in older age groups). In nonpeak years, incidence was generally similar across all age groups. Pediatric mumps incidence was lowest in <1-year-olds for all years except 2012. Of all age groups, including adult age groups, median annual incidence was highest among 18- to 22-year-olds (16.1 per 1 000 000; range: 0.7–88.7) (Supplemental Fig 7).

Among all pediatric patients during the study period who had information on whether they were vaccinated (79% of patients), 89% had ≥1 MMR dose (median = 87% of patients, range: 81%–94% per year) (Fig 3).

Among cases with information available on whether they were associated with an outbreak (78% of cases), 64% were outbreak-associated. In most years, the largest proportion of pediatric cases were not outbreak-associated (ie, sporadic cases) (median outbreak-associated: 39%, range: 2%–93% per year), except for 2016 and 2017, when 93% and 85% of cases were outbreak-associated, respectively (Fig 4).

During 2015–2019, 5461 mumps cases were reported among children and adolescents, representing 27% of all reported US cases. Since 2016, pediatric mumps cases have been reported in most US states each year (range: 38–45 states).

Among pediatric cases, 55% occurred among males (Table 1). By age group, cases occurred most frequently among children and adolescents aged 11 to 17 years (54%), followed by children aged 5 to 10 years (33%), 1 to 4 years (13%), and <1 year (1%). Non-Hispanic Asian and/or Pacific Islander was the most frequently reported ethnicity and race (38%), followed by non-Hispanic White (22%). More than half of all pediatric cases during 2015–2019 were in the South US Region. Among those with information on import status (74%), only 2% of all pediatric mumps cases were associated with international travel and assessed to likely have acquired mumps while outside the United States (ie, import cases). Sex, ethnicity and race, region, and import status proportions were similar across age groups. Among those with information on outbreak association (92%), cases in patients aged 5 to 10 years (78%) and 11 to 17 years (86%) were more frequently outbreak-associated than those in children aged 1 to 4 years (39%) and <1 year (45%) (Table 1).

Of pediatric mumps patients ≥1 year of age, 75% were vaccinated with at least 1 dose of MMR, 8% were unvaccinated, and 17% had unknown vaccination status. Among patients ≥1 year of age with known vaccination status and number of doses received (72%), most (84%) were up to date on MMR doses; 74% of 1- to 4-year-olds had received at least 1 dose of MMR and 86% of 5- to 17-year-olds had received at least 2 doses of MMR (Fig 5).

Of 4771 (87%) patients with information on parotitis, 97% experienced parotitis. Seventy-five (1%) patients experienced at least 1 complication. Orchitis was the most frequently reported complication and was reported in 2% of males (median age = 14 years, range: 0–17): 46 (3%) postpubertal males (>10 years) and 16 (1%) prepubertal males (≤10 years), including 1 case in an infant <1 year old. Of male patients ≥1 year of age with orchitis and known vaccination status (66%), 31 (66%) were up to date on MMR vaccination. Deafness was reported in 10 (<1%) patients with a median age of 14 years (range: 7–17). Vaccination status was known for 4 of the patients, and of those, 1 patient was up to date on MMR vaccination. There were 3 (<1%) cases of meningitis, in a 10-year-old, a 13-year-old, and a 17-year-old, all female. The 10- and 13-year-olds were fully vaccinated with 2 doses of MMR, and the 17-year-old was vaccinated but the number of MMR doses was unknown. There were 2 (<1%) cases of encephalitis, in a 1-year-old male and a 17-year-old female, both of whom were up to date on MMR vaccination (Table 2).

Of 4374 (80%) patients with information on hospitalization, 110 (3%) were hospitalized, with a median hospital stay of 2 days (range: 1–10) (Table 2). The median age of hospitalized patients was 7 years (range: 0–17). Of hospitalized patients who were ≥1 year of age and had known vaccination status and number of doses received (78%), 69% were up to date on MMR vaccination for their age group. No deaths were reported.

Since 2007, pediatric mumps cases have represented an important burden of mumps in the United States, accounting for approximately one-third of all reported mumps cases; since 2016, pediatric mumps cases have been reported in most states each year. The majority of pediatric patients with mumps were up to date with their recommended MMR vaccination. Although the age group with the highest incidence was college-aged young adults, consistent with the largest outbreaks during this time occurring on university campuses,¹⁹  median annual incidence was still higher among children and adolescents versus adults.

Experts have suggested 2 main reasons for occurrence of mumps in vaccinated persons: waning of vaccine-induced immunity and antigenic mismatch between the vaccine strain and the circulating wild-type mumps strains.²⁰  Increasing incidence with increasing age, correlating with likely increasing time since vaccination, supports the hypothesis of potential waning immunity against mumps infection after vaccination. Researchers in some epidemiological or modeling studies have suggested that vaccine-derived immune protection against mumps wanes by early adulthood.^21,22  However, the results presented in this study reveal vaccinated individuals can become susceptible sooner than young adulthood. The plateau in cases at ∼10 years of age, or ∼5 years after the second MMR dose, is consistent with immunologic studies that reveal mumps antibodies start to decrease within the first year after vaccination with the second dose²³  and decline to near baseline levels (ie, return to antibody levels before vaccination with a second dose of MMR) 10 years after vaccination for children vaccinated with the second dose at age 4 to 6 years (against both vaccine and wild-type genotype G strains).²⁴  Second, several studies have revealed that, although vaccine-induced antibodies neutralize wild-type virus, the vaccine-induced immune response is notably lower against the circulating wild-type strains (predominately genotype G in the United States) than against the vaccine strain (genotype A).^24–26  One study among children revealed neutralizing antibody titers to genotype G mumps strain were approximately one-half those of the vaccine strain,²⁴  and researchers in another study among young adults found genotype G–neutralizing antibody titers were sixfold lower.²⁶ 

We report that the majority of pediatric mumps cases were sporadic, except during 2016–2017. During peak years, mumps epidemiology is primarily influenced by large outbreaks that occur in close contact settings. A large outbreak in a close-knit Marshallese community in Arkansas in 2016–2017¹¹  resulted in non-Hispanic Asian and/or Pacific Islander being the most frequently reported ethnicity and race during 2015–2019. On college campuses, outbreaks are often associated with groups of students who participate in large gatherings or social groups (eg, Greek life, sports teams). For this reason, findings of studies on mumps waning immunity that use epidemiological data without accounting for outbreak setting or contact rate should be interpreted with caution, because young adults are more likely to be at an increased risk for exposure than children and adolescents through notably more close contacts during large events and intense close contact behaviors that facilitate transmission of mumps. The sudden increase in cases among 18-year-olds (shown in Fig 4, for comparison) can skew the data toward the appearance that young adults are more susceptible to disease versus at higher risk for exposure.

Although mumps was a leading cause of acquired unilateral sensorineural hearing loss and aseptic meningitis among children in the prevaccine era,^27,28  these complications, as well as other mumps complications, are now relatively rare among pediatric patients in the United States. The low frequency of complications is likely due to a high rate of vaccination among pediatric mumps patients in the United States in the vaccine era.²⁹  However, as shown here, complications still occurred in vaccinated children. The most commonly reported complication was orchitis, mostly in postpubertal males, although orchitis still occurred in prepubescent males as well, including an infant. The rate of 3% of orchitis among mostly vaccinated postpubertal males in this study is consistent with an average rate of 5% orchitis among vaccinated postpubertal males, compared with ∼30% of unvaccinated postpubertal males.^6,8,29–31 

During 1998–2017, >90% of children in the United States had received at least 1 dose of MMR by age 35 months³² ; among adolescents 13 to 17 years of age in 2019, >90% had received ≥2 doses.³³  Despite this high coverage, cases have been consistently reported in most states since 2016, mostly among people who were vaccinated. Furthermore, only 1 in 50 pediatric mumps cases with known import status were associated with international travel. This suggests that mumps is endemic in the United States. Mumps is therefore different from the other 2 diseases prevented by the MMR vaccine, measles and rubella, both of which are eliminated in the United States. Most measles cases or outbreaks result from disease acquired while traveling abroad and then spread in communities with low vaccination coverage.³⁴ 

In 2020, geographically widespread mumps transmission has continued across the United States despite coronavirus disease 2019 (COVID-19) lockdowns and other COVID-19 prevention measures, with 32 US states reporting 142 cases during April 1 through December 31, 2020.³⁵  With continued transmission and decreases and delays in MMR vaccination among children during the COVID-19 pandemic,³⁶  there is a risk that mumps cases and outbreaks among children and adolescents will increase, along with a potential increase in mumps complications, once regular activities and in-person learning resume.

There are several limitations to this study. Although mumps is a nationally notifiable disease, cases and complications may have been underreported. Clinicians may lack suspicion of mumps when a patient is fully vaccinated, even if presenting with parotitis,¹²  or may not suspect mumps in cases with mumps complications in the absence of parotitis. A study of medical records at Children’s Healthcare of Atlanta revealed that among children and adolescents presenting to the emergency department with parotitis during 2007–2017, <5% were tested for mumps, and of these, 19% were positive for mumps.³⁷  Obtaining a positive laboratory test for diagnosis may be challenging in vaccinated patients and also lead to underreporting. Failure to detect mumps RNA through reverse transcription polymerase chain reaction (RT-PCR) in buccal swabs or immunoglobulin M (IgM) through serological tests in vaccinated patients is likely, because viral loads are lower and the IgM response is often undetectable, transient, or delayed in these individuals.³⁸  Given this, clinicians should not rule out mumps because of a negative laboratory result. Another limitation was the completeness of data in NNDSS. Missing or unknown data for some key variables, including vaccination status, number of doses received, outbreak-associated, import status, or hospitalization ranged from 8% to 26%. Additionally, NNDSS does not provide information on outbreaks or which outbreak a case is associated with, so further details regarding outbreaks or how large outbreaks influenced the epidemiology could not be studied.

Mumps has largely been controlled in the general US population for several decades; most clinicians have never seen patients with mumps and may be unaware that most mumps cases in the United States currently occur among fully vaccinated persons. Since 2007, one-third of reported US mumps cases occurred in children and adolescents, the majority of whom were vaccinated. Mumps vaccination remains the best tool to protect children and adolescents against mumps and mumps complications. However, the occurrence of pediatric mumps cases among vaccinated patients in most states highlights the need for clinicians to suspect mumps in pediatric patients with parotitis or mumps complications, regardless of age, vaccination status, or travel history. Appropriate timing and collection technique of specimens is needed for accurate results. The parotid gland should be massaged for 30 seconds before buccal swab collection. A buccal swab specimen should be collected for RT-PCR if it has been ≤3 days since parotitis onset. A buccal swab specimen and a serum specimen for IgM detection should be collected if it has been >3 days since parotitis onset.³⁹  Suspect mumps cases should be reported to the local health department to further investigate potential links to other mumps cases and outbreaks to help identify cases and prevent outbreaks.

COVID-19

coronavirus disease 2019

CSTE

Council of State and Territorial Epidemiologists

IgM

immunoglobulin M

MMR

measles, mumps, and rubella

NNDSS

National Notifiable Diseases Surveillance System

RT-PCR

reverse transcription polymerase chain reaction