mumps

INTRODUCTION  —

 The mumps virus causes an acute, self-limited, viral syndrome. Prior to the widespread use of an effective vaccine, mumps primarily occurred in young children attending primary grade school; mumps was also a leading cause of viral meningitis and the most common cause of unilateral acquired sensorineural deafness in children . Sporadic outbreaks have occurred in the United States and Europe; some of these patients have required hospitalizations due to complications of infection.

VIROLOGY

  — Mumps virus is a single-stranded RNA virus and is a member of the Paramyxovirus genus, which also includes human parainfluenza virus. Humans serve as the only natural host for mumps virus. 

The mumps virion possesses a helical core containing the genomic nucleocapsid portion, which is surrounded by an external glycoprotein envelope . The major surface glycoproteins provide two discrete functions: hemagglutination-neuraminidase activity and cell fusion activity . Only one mumps serotype has been identified. Primary viral isolation culture techniques use a number of cell types, including monkey kidney cell lines; mumps may be isolated from saliva, cerebrospinal fluid, and urine .

EPIDEMIOLOGY  

— Mumps epidemics have occurred worldwide with school-aged children generally serving as the vector for horizontal spread to household family members. Data from the National Health and Nutrition Examination Study (NHANES) from 1999 to 2004 demonstrated that the seroprevalence of antibody to mumps virus is 90 percent, which is at the low end of the estimated seroprevalence rates needed for herd immunity (ie, 92 percent) [ 7 ]. Mumps seroprevalence was significantly lower in the 1967 to 1976 birth cohort (86 percent), suggesting that these individuals may be at increased risk of mumps infection upon exposure.

Prior to the introduction of vaccination in the United States, the peak incidence of mumps was typically in the late winter to early spring, although sporadic outbreaks have occurred throughout the year.

United States  

— Cases of mumps in the United States declined 99 percent from 1968 to 1993 (152,209 versus 1,692 reported cases) following the approval and introduction of a live, attenuated mumps vaccine in 1967 .

However, extensive outbreaks of mumps were reported between 1986 and 1987 in persons born between 1967 and 1977 who did not routinely receive mandatory mumps vaccine for school entry; these outbreaks led to a change in peak incidence of cases from five to nine years to 10 to 19 years of age [ 8 ]. Adults also remained susceptible to mumps with more than 10 percent of cases in 1987 reported in individuals >20 years of age. This led to a revision of the ACIP guidelines to recommend that the first dose of MMR be routinely administered at 12 to 15 months of age with a second dose at four to six years . The ACIP also recommended two doses of MMR for college students. 

Outbreaks

  — Following the decline in United States mumps incidence since 1967 (coincident with an effective vaccine strategy), there have been a number of sporadic mumps outbreaks reported in cohorts of susceptible (unexposed) individuals from military posts, high schools, colleges , and summer camps . There have also been hospital-based  and workplace outbreaks . These outbreaks have frequently involved older individuals who are at risk for more serious morbidity and for complications requiring hospital admission .

• A mumps outbreak occurred in 2011 on a California university campus that did not require proof of MMR vaccination of students prior to enrollment . The presumed source patient was an unvaccinated student who had recently returned from Western Europe, where mumps virus had been circulating. Among 29 cases of mumps, 76 percent occurred among individuals previously vaccinated with two doses of MMR vaccine.
• A mumps outbreak that began in the New York area in June 2009 was traced to a boy aged 11 years who returned from the United Kingdom, where a mumps outbreak had been occurring. He then attended a summer camp for orthodox Jewish boys where he became symptomatic. Between June 28, 2009 and June 27, 2010, 3502 cases of mumps were reported . The outbreak was largely confined to males aged 7 to 18 years within this religious community. Resulting complications included orchitis, pancreatitis, aseptic meningitis, transient deafness, Bell's palsy and oophoritis. Approximately 89 percent of patients had received two doses of mumps-containing vaccine before the outbreak. Thus, this outbreak occurred in a highly vaccinated population, and most cases developed in previously immunized individuals.
• In 2006, 45 states reported a total of 5783 confirmed or probable cases of mumps . Parotitis was reported in 66 percent of patients for whom clinical data were available. Complications included orchitis, meningitis, encephalitis, and deafness. The identified mumps strain was genotype G, the same genotype that caused an outbreak in the UK involving more than 70,000 individuals between 2004 and 2006 . Among the 1192 patients who were evaluated for their immunization status in Iowa, where the largest number of cases occurred, 6 percent were unvaccinated, 12 percent had received one dose of MMR vaccine, 51 percent had received two doses of MMR, and 31 percent did not have vaccination records.

Worldwide

Immunization practices

  — Based on a 1998 update from the World Health Organization (WHO), mumps vaccine is routinely utilized by national immunization programs in 82 countries/areas: 23 (92 percent) of 25 developed countries, 19 (86 percent) of 22 countries with economies in transition (Newly Independent States of the former Soviet Union), and 40 (24 percent) of 168 developing countries . The impact of mumps-associated complications and fatal outcomes in susceptible individuals in developing countries remains an area of public health concern and warrants ongoing surveillance and intensive large scale MMR vaccination programs.

Outbreaks 

 — During 2004, the number of confirmed cases of mumps increased dramatically in all regions across England and Wales (8104 compared to 3907 cases in the previous five years) . Mumps occurred in older teenagers and young adults born before 1987. Some of these patients may have received only one dose of MMR as part of a "catch up" immunization program after the availability of vaccine in 1988. In contrast, only 2.4 percent of confirmed cases occurred in children born between 1993 and 1999, when two doses of mumps vaccine were offered routinely.

The health service, investigating an outbreak of confirmed mumps cases which occurred primarily in adolescents and young adults in Scotland during 2003 and 2004, determined that transmission was greatly facilitated in enclosed settings, such as high schools and universities in which social interactions were frequent.

TRANSMISSION

  — Mumps is highly infectious and spreads rapidly among susceptible people living in close quarters. Mumps virus is typically transmitted by respiratory droplets, direct contact, or fomites . Infants less than one year rarely acquire mumps due to passage of maternal antibodies.

The incubation period is usually 14 to 18 days from exposure to onset of symptoms. Viral shedding in respiratory secretions precedes the onset of symptomatic illness and the period of peak contagion is just before the onset of parotitis (approximately three days).

A committee composed of members from the CDC, the American Academy of Pediatrics, and the Healthcare Infection Control Practices Advisory Committee reviewed data on viral isolation and shedding during infection to determine the optimal number of days of required isolation . During the 2006 Iowa outbreak, viral shedding generally decreased rapidly after the onset of symptoms; only 4 percent of patients still shed virus on day nine . Vaccination status had no appreciable impact on duration of shedding. Another study found that mumps viral load decreased substantially during the first four days of illness . Based on these data, the guideline committee recommended that the isolation duration be shortened from nine days to five days since the risk of transmission after this time is low .

CLINICAL FEATURES

  — Mumps infection is frequently accompanied by a nonspecific prodrome consisting of low-grade fever, malaise, headache, myalgias, and anorexia . These symptoms are generally followed within 48 hours by the development of parotitis, a classic feature of mumps infection. Symptomatic infection in adults is usually more severe than in children.

Parotitis 

 — Parotid swelling is present in 95 percent of symptomatic cases of mumps. Parotitis is due to direct infection of ductal epithelium and local inflammation.

Local parotid tenderness and occasionally earache precedes the onset of parotid swelling. Enlargement of the contralateral parotid gland occurs in 90 percent of patients, but may be delayed by several days . On physical examination, parotid swelling may obscure the angle of the mandible and the orifice of Stensen's duct is erythematous and enlarged .

Parotid swelling can last up to 10 days. Increased serum amylase supports the clinical diagnosis.

Inapparent infection 

 — In contrast to these classic manifestations, asymptomatic infection occurs in 15 to 20 percent of cases, and only nonspecific or predominantly respiratory symptoms are seen in up to 50 percent of cases in whom the diagnosis of mumps is not usually made . Inapparent or subclinical infections are more frequent in adults, while parotitis is most common in children between the ages of two and nine years .

COMPLICATIONS

  — The more serious complications of mumps, such as meningitis, encephalitis, and orchitis, may occur in the absence of parotitis , which can delay accurate diagnosis of the clinical syndrome.

Orchitis

  — Epididymoorchitis, the most common complication of mumps infection in the adult male, may develop in up to 38 percent of infected postpubertal males . Symptoms are characterized by the abrupt onset of fever from 39 to 41ºC and severe testicular pain, accompanied by swelling and erythema of the scrotum. The following case series illustrates the range of findings:

• In a descriptive series of 67 male patients with orchitis that occurred during a mumps outbreak in the Gran Canaria Island from 2000 to 2001, nearly all patients had onset of fever and parotitis that preceded orchitis by approximately five days . Orchitis was unilateral in approximately 90 percent and bilateral in 10 percent of cases. Fifty-six patients required hospitalization; nine patients also had mumps meningitis. During the follow-up period, a high incidence of sperm abnormalities was observed.
• In one Swiss outbreak of mumps orchitis documented in 11 men (mean age 32 years, range 17 to 55), all required hospitalization for management of testicular pain, fever (>38.5ºC), and swelling. Nine of these patients (82 percent) had mumps parotitis prior to the development of orchitis; the interval between parotitis and the onset of orchitis was 10 days. Patients were hospitalized for an average of six days and were treated with bed rest, nonsteroidal antiinflammatory agents, and local cooling measures. Ten of the 11 patients had never received mumps vaccination; vaccination status of the remaining patient was unknown.

While testicular atrophy has been documented in as many as 30 to 50 percent of patients following mumps orchitis and impaired fertility in approximately 13 percent, sterility is estimated to be rare . The risk of sterility is higher in men who have bilateral orchitis .

A possible association between mumps orchitis and the subsequent development of testicular cancer has been evaluated in several retrospective case series ; to date, no causal link has been definitively established. In a Danish review of 494 cases of testicular cancer in men born between 1941 and 1957, no patient had documented mumps orchitis prior to the diagnosis of testicular cancer. 

Oophoritis

  — Oophoritis occurs in approximately 7 percent of post-pubertal girls.

Aseptic meningitis  

— Aseptic meningitis is the most frequent extrasalivary complication of mumps virus infection . Asymptomatic CSF pleocytosis was documented in more than 50 percent of patients with clinical mumps, in one series , while clinical aseptic meningitis due to mumps ranged from 4 to 6 percent in larger clinical series of mumps outbreaks . Cases of mumps aseptic meningitis occur three times more often in males than in females .

The onset of meningitis is variable and can occur before, during, or after an episode of mumps parotitis; aseptic meningitis has been reported in 1 to 10 percent of patients with mumps parotitis . In some series, up to 50 percent of patients present with mumps meningitis in the absence of parotitis . The most frequent manifestations are headache, low grade fever, and mild nuchal rigidity.

The CSF profile may have 10 to 2000 white blood cells (WBC)/microL . The predominating cells are usually lymphocytes, but an early polymorphonuclear predominance can occasionally be seen . The CSF total protein is generally normal or mildly elevated. CSF glucose levels can be mildly depressed, but values below 30 to 40 mg/dL (1.7 to 2.2 mmol/L) have been reported .

Mumps aseptic meningitis generally has a benign course with full neurologic recovery and no permanent deficits.

Other neurologic complications  

— Encephalitis, deafness, Guillain-Barré syndrome, transverse myelitis, and facial palsy are other, less frequent, neurologic complications of mumps .

Encephalitis  — In the pre-vaccine era, the incidence of mumps encephalitis was estimated to be approximately 1 in 6000 cases ; through the 1960s, mumps was the most frequent cause of confirmed viral encephalitis cases in the United States. However, since the implementation of the MMR vaccination program, this incidence has dramatically decreased. In 1981, mumps accounted for only 0.5 percent of cases of viral encephalitis in the United States . Similar findings were noted in a review from Finland . After widespread use of MMR vaccine in 1982, mumps encephalitis virtually disappeared.

Patients with mumps encephalitis typically present with fever, altered level of consciousness, seizures, paresis and/or paralysis. As many as one-third of patients present without parotitis; as a result, the absence of parotitis does not exclude the diagnosis of mumps . The CSF profile is similar to that seen with mumps aseptic meningitis which, as noted above, can occasionally mimic those with bacterial meningitis rather than viral infection .

Most patients with mumps encephalitis make a complete recovery. Cerebellitis and cerebellar ataxia are usually self-limited . Hydrocephalus has been rarely been reported.

Deafness  

— In the pre-vaccine era, mumps infection was a prominent cause of sensorineural hearing loss in children .

 The onset of deafness was often abrupt but occasionally exhibited a more gradual clinical course; bilateral involvement has been reported. Permanent deafness attributable to mumps infection has been documented .

Some patients with sensorineural hearing loss during mumps infection have concurrently developed prominent vestibular symptoms. Labyrinthitis and endolymphatic hydrops (Meniere syndrome) also developed subsequently in a patient with prior acute deafness due to mumps infection . In a 22-year-old man with a recent mumps infection and the onset of sudden deafness and vertigo, enhanced magnetic resonance imaging (MRI) confirmed labyrinthian and cranial nerve VIII nerve bundle involvement [ 70 ].

Other neurologic syndromes  

— Several other neurologic syndromes that have been reported less frequently in patients with mumps infection include Guillain-Barré syndrome /ascending polyradiculitis, transverse myelitis  and facial palsy.

Less frequent complications  — Other end organ syndromes occasionally linked to mumps infection include thyroiditis , myocardial involvement, pancreatitis, interstitial nephritis, and arthritis .

Arthritis  

— Mumps-associated arthropathy is a relatively infrequent complication but affects males more often than females; monoarticular large joint (knee, hip) involvement has been reported in addition to a polyarticular syndrome .

Pancreatitis 

 — Acute pancreatitis has occasionally been reported in both children and adults with mumps infection . The clinical course is typically benign, with the majority of cases resolving with conservative management; rarely, pseudocyst formation requiring surgical drainage has occurred .

In a retrospective review of 49 children who were diagnosed with acute pancreatitis, the most common causes were mumps (39 percent) and trauma (14 percent) . The diagnosis is supported by an elevated serum lipase level.

Myocardial involvement  

— Electrocardiographic changes including depressed ST segments can be seen transiently in up to 15 percent of patients with mumps. Although rarely encountered, cases of rapidly progressive and fulminant fatal myocarditis with dilated cardiomyopathy attributed to acute infection with mumps have been reported . Most of these myocarditis patients with fatal outcomes developed refractory arrhythmias and congestive heart failure. Coronary artery involvement has also been documented in a case of mumps myocarditis .

Mumps in pregnancy  

— Mumps in pregnancy has not been associated with congenital malformations, although the risk of miscarriage with mumps infection is increased during the first trimester .

DIAGNOSIS 

 — When the patient has parotitis, the diagnosis of mumps is based upon the characteristic clinical features. Leukopenia, with a relative lymphocytosis, and an elevated serum amylase may be noted on routine blood testing.

Specific assays for the diagnosis of mumps are more often used in the setting of prominent extrasalivary gland involvement or during a mumps outbreak, when laboratory criteria are necessary to establish accurate incidence figures.

Laboratory evidence supportive of a mumps diagnosis include :

• A positive IgM mumps antibody
• Significant rise in IgG titers between acute and convalescent specimens
• Isolation of mumps virus or nucleic acid from a clinical specimen

In patients with classic symptoms of mumps, laboratory confirmation is not required. In patients with more atypical presentations (eg, mumps meningitis) polymerase chain reaction testing of the appropriate fluids enables a rapid diagnosis. Targeted serologic testing may be recommended by the public health department in the setting of a localized outbreak.

Serology  

— Serum IgM antibody testing should be obtained as soon as mumps infection is suspected . A second convalescent phase serum sample obtained about two to three weeks after the first sample should be collected. A fourfold or greater increase in IgG titer is considered a positive diagnostic result for mumps. In vaccinated persons with breakthrough disease, IgG titers may rise rapidly and precipitously, which can impair the ability to capture a fourfold rise in serum antibodies. Thus, it is important to obtain the first serum sample soon after clinical presentation.

Serum IgM antibody to mumps typically remains positive for up to four weeks but may be negative in up to 50 to 60 percent of specimens from individuals with acute disease who were previously immunized . A negative mumps IgM titer in vaccinated individuals, therefore, does not rule out mumps.

A positive mumps IgG serology is expected among previously immunized persons; however, the level of neutralizing antibody that is needed for protection against mumps is not known . Serologic tests cannot differentiate between prior exposure to mumps virus or mumps vaccine.

Viral culture 

 — In patients with aseptic meningitis due to mumps, the virus can frequently be isolated from the CSF during the first three days of clinical symptoms . Virus is present in saliva for approximately one week, starting two to three days before the onset of parotitis. Virus is also excreted in urine for the first two weeks of illness . However, the selective viral isolation culture techniques are time consuming and may require days to yield a positive identification of mumps virus, thus delaying the diagnosis.

Polymerase chain reaction assays  

— The use of an IgM antibody capture immunoassay or a nested polymerase chain reaction (PCR) assay enables more rapid confirmation of mumps in the CSF . A nested mumps reverse transcriptase (RT) PCR assay using a specific 122 bp fragment proved capable of detecting 0.001 plaque forming units (PFU)/mL of mumps virus in one study . Mumps virus RNA was detected in all 18 CSF samples confirmed by viral isolation techniques. Overall, PCR confirmed mumps virus RNA in the CSF of 96 percent of patients compared to 39 percent for CSF culture alone.

The RT-PCR assay has enhanced characterization of genomically discrete mumps strains associated with sporadic outbreaks and serves as a particularly useful tool when applied to epidemiologic surveillance. Use of mumps RT-PCR assay in various clinical specimens (ie, saliva, urine, CSF) provides an efficient method to differentiate distinct mumps strains circulating during a given outbreak and also facilitates distinguishing wild-type stains from vaccine-derived mumps strains.

DIFFERENTIAL DIAGNOSIS 

 — In the presence of bilateral parotitis, the clinical diagnosis is usually straightforward. Other causes of unilateral or bilateral parotitis include other viral infections (parainfluenza, coxsackievirus, influenza A, Epstein-Barr virus, adenovirus, HIV, cytomegalovirus) and bacterial infections, particularly Staphylococcus aureus . Noninfectious etiologies include salivary calculi, tumors, sarcoid, Sjögren’s syndrome, and thiazide diuretics.

TREATMENT  

— Therapy for mumps parotitis is symptomatic and includes analgesics or antipyretics, such as aspirin or acetaminophen . Topical application of warm or cold packs to the parotid may also be soothing.

Patients who have meningitis or pancreatitis with nausea and vomiting may require hospitalization for intravenous fluids.

Patients with orchitis are also treated symptomatically with bed rest, nonsteroidal antiinflammatory agents, support of the inflamed testis, and ice packs.

PREVENTION  

— Prevention of transmission of mumps to others is dependent on early diagnosis, isolation of the infected patient, and immunization of susceptible exposed individuals. Since the introduction of vaccine, mumps cases have declined by 96 percent in the United States .

Isolation of infectious patients 

 — Recommendations for the management of mumps include isolation until the parotid swelling has resolved to prevent the spread of infection to susceptible persons. Patients with mumps should stay home from school or work for five days after onset of clinical symptoms, as recommended by the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) . The CDC, AAP, and HICPAC recommend use of droplet precautions . However, it is important to note that the virus is present in saliva days before clinical parotitis occurs and viral shedding can occur in asymptomatic persons, often making control measures quite difficult.

Factors that contribute to local outbreaks of mumps include closed environments (eg, college dormitories)  and a delay in recognition of mumps by health care providers . Only 25 states require two doses of MMR vaccine on entrance to college. Furthermore, two doses of vaccine are not 100 percent effective in preventing disease; thus, increasing numbers of susceptible individuals who were not effectively immunized may be sufficient to sustain transmission in outbreak situations.

Immunization of susceptible patients 

 — The first inactivated mumps vaccine was introduced in the 1940s; this formulation was eventually replaced by the attenuated vaccine (ie, Jeryl Lynn strain) in 1967 .

Active immunization with attenuated mumps virus vaccine is recommended for those who have not been vaccinated in the past, or in those who only received one dose of vaccine. Immunization after exposure has not been demonstrated to be protective, although it is recommended by the CDC; the rationale for vaccination is to decrease the risk of disease with possible future exposures. Recently immunized persons should be educated about the symptoms and signs of illness and be instructed to contact their medical provider should they become sick.

Evidence of immunity  

— The ACIP issued new guidelines for mumps vaccination after reviewing data on the 2006 outbreak and previous data on mumps vaccine effectiveness . Acceptable presumptive evidence of adequate vaccination now requires two doses of vaccine (instead of one) in:

• School-aged children (K-12)
• Adults considered at high risk (eg, persons who work in healthcare facilities, international travelers, and students at post-high school education institutions)

In outbreak situations a second dose of vaccine should be considered in exposed children (ages 1-4) and adults. Two doses of vaccine should also be recommended in healthcare workers born before 1957 who do not have evidence of immunity.

A third MMR dose may also be a useful option in an outbreak setting. Following the New York outbreak in 2009-2010, a third dose of MMR vaccine was offered to 2265 eligible students in grades 6 to 12; 81 percent chose to receive a third dose [ 118 ]. Mumps attack rates declined from 4.9 percent (three weeks before vaccination) to 0.13 percent (three weeks after vaccination). This report suggests, though does not prove, that a third dose may reduce infections during an outbreak.

The persistence of cellular and humoral immunity to mumps virus was evaluated in 50 individuals who had been vaccinated twice with MMR vaccine during early childhood and who had follow-up for more than 21 years after immunization [ 119 ]. Compared to a control group who had a history of naturally-acquired immunity to mumps, levels of detectable anti-mumps virus IgG antibodies were lower in the vaccinated group. However, mumps antigen-specific lymphoproliferative responses were detected in 98 percent of all patients, consistent with long persistence of cellular immunity.

Contradictions to vaccine  

— Vaccine should not be administered to pregnant women, immunosuppressed patients, or persons with advanced malignancies. A full discussion of the vaccine's efficacy, risks and benefits, and complications is presented elsewhere.