Mumps is a vaccine-preventable disease that primarily presents as parotitis (inflammation or enlargement of the parotoid glands located on the side of the face), or other salivary gland swelling. Prodromal symptoms include low-grade fever, myalgia, anorexia, malaise, and headache. Clinical complications include orchitis, oophoritis, aseptic meningitis, encephalitis, hearing loss, mastitis, and pancreatitis [1]. Mumps can also be asymptomatic; among unvaccinated persons, approximately 20% of cases are asymptomatic, while the prevalence of asymptomatic disease among vaccinated persons is unknown [1].

Mumps was a notable public health burden in the United States (U. S.) before the introduction of the mumps vaccine in 1967, causing approximately 10% of aseptic meningitis cases and 36% of all reported encephalitis cases [2,3]. The introduction of the mumps vaccine in the U.S. has decreased mumps incidence by more than 99% [4,5]. However, since 2006, there have been a number of mumps outbreaks across the U. S. [6]. From 2006–2015, three large outbreaks arose in geographically localized settings such as 6 Midwestern states [7,8], New York [9], and the Territory of Guam [10]; outbreaks continued from 2016–2019 and ranged in size, setting, and geography [11,12]. For the last two decades, a majority of cases and outbreaks have occurred in vaccinated individuals [8,13].

Due to the increasing number of mumps outbreaks among fully vaccinated young adults, the Advisory Committee on Immunization Practices (ACIP) recommended a third dose of measles-mumps-rubella (MMR) vaccine for groups at increased risk for mumps during an outbreak [14]. The intent of the third dose is to provide short-term protection against mumps and its complications, with the public health authority in charge of identifying group(s) or population(s) with increased risk for mumps and providing recommendations for 3rd dose vaccination. At this time, there is no recommendation for routine third dose MMR vaccine as the duration of immunity is unknown and immunologic studies suggest the additional benefits may last for less than one year [15].

Non-pharmaceutical interventions (i.e., mask-wearing, social distancing, stay-at-home orders) enacted to protect against COVID-19 disrupted disease transmission for many pathogens [16]. We leveraged both the National Notifiable Disease Surveillance System (NNDSS) and the Epidemiology-Laboratory Cooperative Agreement (ELC) data [17] to investigate changes in mumps epidemiology before and after the start of the COVID-19 pandemic [16]. We evaluate the incidence of reported mumps and explore trends in vaccination status, sociodemographic characteristics, and laboratory testing among reported mumps patients.

Mumps is a nationally notifiable disease in the U.S.; jurisdictions report confirmed and probable mumps cases to the Centers for Disease Control and Prevention through NNDSS. Case classification occurs according to the Council of State and Territorial Epidemiologists (CSTE) mumps case definition [18]. During the study period, the 2011 CSTE mumps case definition was used to classify cases: A confirmed case was defined as a case with laboratory confirmation by reverse-transcriptase polymerase chain reaction (RT-PCR) or culture in a patient with acute mumps illness (parotitis or other salivary gland swelling lasting ≥ 2 days or mumps-related complications); a probable case was defined as a patient with acute mumps illness and a positive IgM or epi-linkage to another case or outbreak. The CSTE mumps case definition was updated effective January 2024, after the cases in this analysis were reported [18]. Eight cases reported through NNDSS from 2018–2023 with ‘Unknown’ case status were removed from the analysis. The analysis includes data from U.S. states and the District of Columbia.

We descriptively assessed epidemiologic trends of confirmed and probable mumps cases reported to NNDSS from January 1, 2018–December 31, 2023, with data pulled on February 14, 2024. We assessed patient age, sex, and vaccination status, as well as outbreak-association of cases, clinical complications, and hospitalization. Due to heterogeneity in the number of mumps cases reported per year, we report medians and inter-quartile range (IQR) for continuous variables. The pre-pandemic period was defined as January 1, 2018–April 4, 2020 (end of MMWR epidemiologic week 14) and the pandemic period was defined as April 5, 2020–December 31, 2023 [19]. To assess age-specific incidence rates per 100,000 persons, we used the National Center for Health Statistics’ vintage 2022 median age and age by sex tables (National Population by Characteristics: 2020–2023 (census.gov)) and vintage 2019 median age and age by sex tables (National Population by Characteristics: 2010–2019 (census.gov)).

We also explored quarterly ELC data from the 24 jurisdictions consistently reporting supplemental mumps data from 2018–2023: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Georgia, Indiana, Iowa, Kansas, Louisiana, Maryland, Massachusetts, Minnesota, Nebraska, New York City, New York State, North Dakota, Ohio, Pennsylvania, Philadelphia, Tennessee, Texas, and Washington. ELC Mumps data are collected as part of the optional tier 2 activity through Project O: Enhanced Surveillance for Vaccine-Preventable and Respiratory Diseases of the ELC cooperative agreement. Variables collected include all NNDSS variables as well as key variables related to laboratory testing sites, modality, and results, outbreaks and travel, and vaccination records. More complete information was available for clinical, outbreak-associated, and laboratory testing data in ELC data; thus, characteristics of mumps cases and age group classification of mumps cases were analyzed using NNDSS data, while clinical, outbreak, and laboratory variables were analyzed using ELC data. All analyses were repeated using both datasets, and those not shown in the main text are shown in the Supplement. Data from all jurisdictions who reported mumps virus genotypes from 2018–2023 were included due to sparsity of genotypic data available.

Analyses were performed using SAS version 9.4 (SAS Institute, Inc, Cary, NC) and R version 4.4.0 (R Foundation for Statistical Computing, Vienna, Austria). The activity was deemed non research by CDC and was conducted in accordance with applicable federal law and CDC policy (45 CFR 46, 21 CFR 56; 42 USC 241d; 5 USC 552a; 44 USC 3501 et seq).

Infectious disease surveillance for vaccine-preventable pathogens remains essential to evaluate the changing epidemiology of mumps and document the effect of the COVID-19 pandemic. NNDSS provides essential national-level surveillance data for reportable diseases, and the supplemental data provided by ELC permits a more detailed evaluation of clinical, outbreak-related, and laboratory variables to complete the epidemiologic picture of mumps virus in the U.S. Despite the onset of the COVID-19 pandemic, mumps cases continued to occur across the U.S. However, beginning in 2021, mumps cases and incidence dramatically declined, and from 2021–2023, there were only 9 outbreak-associated cases of mumps reported. Mumps incidence has remained lower in the pandemic period as compared to the pre-pandemic period for all age groups. Additionally, most cases of mumps were sporadic, non-outbreak-associated, and only 3% were internationally imported, underscoring that mumps continues to be endemic in the U.S.

The COVID-19 pandemic also marked a change in the epidemiology of reported mumps cases. From 2009–2019, a large fraction of mumps cases occurred in young adults [13,20,21], often associated with outbreaks in university settings. This trend was not unique to the U.S. and had also been observed in Canada [22], Denmark [23], Belgium [24], Korea [25], and other countries using a mumps-containing vaccine. The decline of mumps cases among college-aged adults from 2021–2023, leading to a growing proportion of cases occurring in those under age 10 years, is notable, though incidence in younger children remains lower in 2021–2023 than 2018–2019. Amid declining vaccination rates for routine immunizations [26,27], it is essential to understand how epidemiologic risk may be changing for mumps virus. Additionally, it is possible that COVID-19 prevention protocols, including masking, hand hygiene, increase in remote classes, and perhaps reduction in sharing of personal items, reduced the risk of mumps transmission and the number of cases in congregate settings such as universities. While vaccination status among reported mumps cases is incomplete, 15% of patients with mumps were unvaccinated; most of the burden of mumps is among those with prior MMR vaccination.

This surveillance analysis enabled an assessment of clinical characteristics and complications of mumps, which generally matched the reported literature [1]. Orchitis was the most commonly reported complication among males, occurring twice as frequently in unvaccinated vs. vaccinated patients. Our findings support that mumps among vaccinated persons generally results in milder presentation with fewer complications [1]. The proportion of patients with mumps presenting with parotitis and orchitis were similar among those vaccinated with 1 or 2 doses. Other complications of mumps, such as oophoritis, mastitis, hearing loss, encephalitis, and meningitis were exceedingly rare, and we did not see apparent differences by vaccination status or vaccine-dose. Overall, 6% of mumps patients were hospitalized, with nearly equal proportions among those vaccinated and unvaccinated, in contrast to prior studies that have found an inverse association between number of vaccine doses received and risk of hospitalization [28,29]. Among those hospitalized for mumps, individuals spent a median of 3 days in the hospital, highlighting the potential burden of mumps infection for those with complications. However, the primary cause of hospitalization was not available; less than a quarter of hospitalized cases were lab-confirmed and likely may not have been hospitalized exclusively due to mumps complications.

Characterizing the epidemiology of mumps from 2018–2020 was driven by the occurrence of large outbreaks. The years from 2021–2023 represent a period with nearly no mumps outbreaks, and thus provide insight into the background epidemiology of endemic mumps in the U.S., though behavioral changes due to the COVID-19 pandemic may be suppressing transmission. For the cases in 2018–2020 that were outbreak associated, nearly half occurred in a correctional/detention facility [30] and a quarter occurred in a college setting. It is important to note that the nature of mumps outbreaks has varied over time, is highly dependent upon the setting in which those outbreaks occur, with large, localized outbreaks driving peaks in 2006, 2009–2010, while 2016–2017 experienced >150 outbreaks and >9,000 cases reported in more than half of US states in a range of settings [7,12].

Another notable trend was the decreasing proportion of mumps cases classified as confirmed – ranging from a high of 53.6% in 2019 to a low of 5.8% in 2022. The substantial decline in confirmation of cases is concerning – especially amid the rise of COVID-19, which has been sporadically reported to cause parotitis [31,32]. Since 2018, the relative proportion of laboratory tests done on mumps cases has shifted to pre-dominantly IgM testing, rather than PCR. However, IgM is not a confirmatory test for mumps, and it may lead to both false negative and false positive results, and can cross-react with other viruses, including parainfluenza viruses, Epstein-Barr virus, adenovirus, and human herpesvirus-6 [33], and is often undetectable, transient, or delayed in vaccinated individuals.

The 2024 mumps CSTE case definition [18] seeks to improve both the sensitivity and specificity of the mumps case definition; removing the 2-day duration of parotitis for epidemiologically linked cases, ensuring that all cases with confirmatory laboratory criteria are considered cases, regardless of clinical presentation, and establishing IgM testing as supportive laboratory evidence only. Laboratory confirmation will be critical for capturing the true burden of mumps [6]. It is important to continue to monitor the epidemiology of mumps, and to evaluate whether the new case definition leads to increased laboratory confirmation and molecular characterization of circulating mumps virus.

The increase in mumps observed among fully vaccinated young adults since 2006 may be due to waning immunity, antigenic mismatch between vaccine strain mumps virus and circulating wild type virus, or the combination of the two [34]. Immunologic studies have shown that mumps antibodies wane over time [35,36]. Additionally, vaccine-induced neutralizing antibody titers have been found to be significantly lower to circulating wild-type mumps virus (predominately Genotype G) than to vaccine strain (Genotype A) [37]. While the vaccines in the U.S. include the Jeryl-Lynn and RIT-4385 strains of mumps virus (Genotype A) [38], the majority of outbreak-related mumps cases in the U.S. since 2006 have been Genotype G, and Genotype G is considered endemic in the U.S. [22,39–41]. The detection of other genotypes since 2018 suggests imported cases from other countries. It is important to better understand genomic epidemiology of circulating mumps virus to aid interpretation of these two leading theories of mumps resurgence [34].

There are several limitations to this study. Mumps is a nationally notifiable disease, but there may be underreporting, as mumps has become generally uncommon. Additionally, 2022–2023 data are provisional and subject to change. Clinicians may lack suspicion of mumps, especially among fully vaccinated patients, and may be unaware of the correct laboratory test to order to confirm mumps cases. Additionally, data were incomplete for some variables that are critical for mumps surveillance and completeness decreased during the pandemic era: vaccination status was missing for 48% cases in NNDSS, data on the number of doses was limited, and information on clinical symptoms such as parotitis, complications, outbreak-related variables and laboratory testing were also limited or not available in NNDSS. Data from ELC were valuable for supplementing key variables, though data were not available from all states. Further, electronic data submission may present challenges for data transmission and reception due to the lack of inter-operability of different surveillance systems at the local, state, and federal levels [42].

Mumps cases have declined substantially since the onset of the COVID-19 pandemic, though sporadic cases of mumps have continued to occur, primarily in children under 10 years of age. Mumps remains endemic in the United States, and it is important to increase RT-PCR and molecular characterization of circulating mumps virus, both to improve diagnoses of mumps and to quickly implement appropriate control measures, and to understand the genotypic diversity of mumps virus in the U.S. Since 2018, 15% of mumps cases have occurred in unvaccinated persons, and it is essential to maintain high MMR vaccination coverage to prevent future vaccine-preventable outbreaks and minimize severe complications from infection.