Mumps Virus

Medical Experts

Contributor

Jackson

Adjunct Professor of Pathology and Biomedical Informatics, University of Utah

Medical Director, Business Development, ARUP Laboratories

Mumps is an acute, contagious disease generally characterized by swelling of the parotid gland. The most common complications from mumps infection include orchitis, oophoritis, mastitis, pancreatitis, hearing loss, meningitis, and encephalitis. In the United States, mumps is relatively rare due to successful vaccination programs. Although the prevalence is relatively low, the CDC has noted a substantial increase in mumps cases since late 2015. Breakthrough infections in vaccinated individuals are possible, although they are less common than infections in unvaccinated (or incompletely vaccinated) individuals. Breakthrough infections are generally milder than infections in unvaccinated individuals. A probable diagnosis may be made based on clinical findings alone; however, laboratory tests should be performed for a definitive diagnosis. Confirming the diagnosis provides important epidemiological information and can help rule out other diseases that present similarly to mumps. Laboratory confirmation of mumps can be more challenging in vaccinated patients due to low viral load and/or low, absent, or delayed immunoglobulin M (IgM) response causing false-negative results. Reverse transcription polymerase chain reaction (RT-PCR) or viral culture testing may be used to confirm a diagnosis. Serology may be helpful to provide supportive evidence to aid in diagnosis (ie, presence of IgM antibodies) or provide presumptive evidence of past infection or vaccination (ie, presence of IgG antibodies).

Quick Answers for Clinicians

When should tests be ordered to optimize test accuracy for mumps diagnosis?

Timing is very important when considering the proper laboratory tests to order for mumps diagnosis. For diagnostic tests like reverse transcription polymerase chain reaction (RT-PCR) and viral culture, testing should be performed when the patient’s viral load is at its peak (≤3 days from the onset of symptoms) to minimize the risk of a false-negative result. If more than 3 days have elapsed since the onset of symptoms, immunoglobulin M (IgM) serology should be performed in addition to RT-PCR testing to provide supportive evidence of mumps infection. In vaccinated individuals, viral load and IgM are often low, which causes a higher rate of false-negative results, so timing is particularly important to minimize this risk. Detailed information about test selection can be found in the Laboratory Testing section.

How does vaccination status impact laboratory testing for mumps diagnosis?

Diagnosis of a breakthrough case of mumps in a vaccinated individual can be challenging. Viral load is generally low, and infection is cleared quickly in patients who are vaccinated. This means that diagnostic tests like reverse transcription polymerase chain reaction (RT-PCR) are more likely to produce false-negative results, even if specimens are taken early in the disease course. Additionally, vaccinated patients may have a very low or absent immunoglobulin M (IgM) immune response, resulting in false-negative IgM serology results. Finally, vaccinated individuals already have mumps IgG antibodies, so collecting acute and convalescent samples is not informative.

What are the recommendations for mumps virus vaccination?

Detailed vaccination recommendations are provided by the CDC. In brief, it is recommended that all children receive two doses of the measles, mumps, and rubella (MMR) vaccine. If teens and adults are not up to date on their MMR vaccine, they should be vaccinated as soon as possible. In some situations (eg, during outbreaks), a third dose of a mumps-containing vaccine may be recommended to individuals at an increased risk. Laboratory testing for mumps immunoglobulin G (IgG) antibodies can provide presumptive evidence of previous vaccination or infection. Detailed information about vaccination recommendations can be found in the ARUP Consult Immunization Status topic.

Indications for Testing

If mumps is suspected based on clinical presentation or recent exposure, laboratory testing should be performed. Mumps may be suspected in patients with parotitis, acute salivary gland swelling, orchitis, or oophoritis that cannot be explained by another, more likely diagnosis. Refer to the CDC’s Mumps Case Definition for detailed information about case classification and diagnosis.

Laboratory Testing

The sensitivity of RT-PCR, culture, and serologic testing is heavily impacted by the duration of time since symptom onset. Therefore, the selection of appropriate laboratory testing strategies is time-dependent. The table below describes the optimal timing for RT-PCR, culture, and serologic testing and details the appropriate specimen types for various clinical situations.

Days Since Symptom Onset	Recommended Test	Potentially Useful Additional Tests
≤3	RT-PCR or viral culture (buccal/parotid swab)	RT-PCR (urine)^a IgG serology (acute phase)^b
>3	RT-PCR or viral culture (buccal/parotid swab) IgM serology	RT-PCR (urine)^a IgG serology (convalescent phase)^b
^aUrine should be added as an additional specimen type in patients without parotitis who present with orchitis, oophoritis, mastitis, pancreatitis, hearing loss, meningitis, or encephalitis. ^bObservation of seroconversion and/or a fourfold increase in titer from paired acute and convalescent sera can confirm past mumps infection in unvaccinated patients. Sources: CDC, 2022

Days Since Symptom Onset

Recommended Test

Potentially Useful Additional Tests

≤3

RT-PCR or viral culture (buccal/parotid swab)

RT-PCR (urine)^a

IgG serology (acute phase)^b

RT-PCR or viral culture (buccal/parotid swab)

IgM serology

RT-PCR (urine)^a

IgG serology (convalescent phase)^b

^aUrine should be added as an additional specimen type in patients without parotitis who present with orchitis, oophoritis, mastitis, pancreatitis, hearing loss, meningitis, or encephalitis.

^bObservation of seroconversion and/or a fourfold increase in titer from paired acute and convalescent sera can confirm past mumps infection in unvaccinated patients.

Sources: CDC, 2022

RT-PCR and Viral Culture

RT-PCR or viral culture can be used to confirm an acute mumps infection. While viral culture was traditionally considered the gold standard test for mumps diagnosis, it has a longer turnaround time than RT-PCR testing. For both testing methods, samples should be collected 0-3 days after the onset of parotitis when the viral load is at its peak to minimize the likelihood of a false-negative result. This timing is particularly important among vaccinated individuals for whom viral load is generally low. If it has been more than 3 days since symptom onset, IgM serology should be included.

A buccal/parotid swab is the preferred sample type; however, when patients without parotitis present with orchitis, oophoritis, mastitis, pancreatitis, hearing loss, meningitis, or encephalitis, collecting a urine specimen in addition to the buccal/parotid swab is recommended.

Serology

IgM

The detection of mumps IgM antibodies is suggestive of an active mumps infection, but RT-PCR or culture tests are required for a definitive diagnosis, particularly in vaccinated patients. Ideally, a specimen for IgM testing should be collected >3 days after the onset of parotitis. False-negative results can occur if a specimen is taken too early in the disease course, particularly in vaccinated individuals. Viruses such as human parainfluenza viruses (HPIVs) and Epstein-Barr virus (EBV) may cause false-positive mumps IgM results.

IgG

IgG antibodies may confirm a mumps diagnosis if paired acute and convalescent sera show a fourfold rise in IgG titer. However, this method is not recommended for vaccinated individuals because IgG is likely to already be elevated in the acute-phase sample.

Detection of IgG antibodies against mumps provides presumptive evidence of previous infection or vaccination. However, the presence of mumps-specific IgG antibodies does not necessarily prove protection from mumps infection. Generally, if patients do not know whether they have been vaccinated against mumps, the CDC recommends revaccination without serology testing. Detailed information may be found in the ARUP Consult Immunization Status topic.