Guidance for Optimizing Mumps Testing

Since late 2015, a substantial rise in mumps cases and outbreaks has occurred in the United States. This has resulted in an increased burden on local, state, and federal public health response resources, including laboratory testing for mumps case classification and outbreak confirmation. Many local and state labs have been overwhelmed by the surge in volume of specimens sent, causing an increase in testing at the federal level.

In 2013, CDC, in collaboration with the Association of Public Health Laboratories (APHL) and the Council of State and Territorial Epidemiologists (CSTE), established four Vaccine Preventable Disease Reference Centers (VPD-RCs) to provide state and local jurisdictions with enhanced surveillance testing capacity for seven VPDs, including mumps, measles, rubella, varicella zoster virus, Bordetella pertussis, Haemophilus influenzae, and Neisseria meningitidis. These VPDs are typically detected by laboratory testing such as quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay of clinical specimens. The VPD-RCs provide state and local health departments with surge capacity for large outbreaks, testing for jurisdictions without RT-qPCR capabilities, and genotyping. Since their establishment, VPD-RCs have received and tested 65% of the mumps clinical specimens sent to the federal level. Currently, they are receiving an unsustainable number of specimens for mumps RT-qPCR testing. The disproportionate amount of resources used for mumps testing resulted in re-allocation of funds from other VPDs, and specimens being routed to the CDC mumps laboratory for testing. To help local and state health departments conserve public health resources while concurrently improving molecular surveillance at the local and national levels, particularly during mumps outbreaks, CDC, in collaboration with CSTE and APHL, developed guidance to optimize mumps testing practices aimed to reduce the number of specimens unnecessarily or improperly collected and tested.

This guide for health departments includes the following:

  1. Recommendations to ensure effective and efficient testing during mumps outbreaks, including implementation of the CSTE probable case definition and education of healthcare providers
  2. Introduction of the CDC Outbreak Mumps Consultation Service for local and state health departments that request additional technical and laboratory assistance
  3. Information about priority patients and settings for which we recommend sequencing to determine the genotype for adequate molecular surveillance

1. Ensuring effective and efficient mumps testing during outbreaks

1a. Using the CSTE probable case definition during established outbreaks

At the onset of a suspected mumps outbreak, patients suspected to have mumps should be tested by RT-qPCR to confirm mumps and rule out other possible etiologies. However, once a mumps outbreak is confirmed, jurisdictions should consider alternate strategies to ensure more efficient use of testing resources.

One strategy is to consider limiting testing of patients who meet the probable mumps case definition when resources are constrained or testing volume is unusually high. The CSTE case definition for mumps defines a probable case as a clinically compatible mumps case with “epidemiologic linkage to another probable or confirmed case or linkage to a group/community defined by public health during an outbreak of mumps.” Consider limiting testing of probable cases when resources are constrained or testing volume is unusually high.

During an outbreak, jurisdictions’ communication with providers should define the specific groups or communities that are considered epidemiologically linked to the outbreak and which therefore may not require testing in a public health laboratory. Jurisdictions can use the Provider Job-Aid as a tool to communicate this information to providers.

In certain situations, even epidemiologically linked cases warrant testing. These include:

  • Patients with complications such as oophoritis, orchitis, aseptic meningitis, encephalitis, hearing loss, mastitis, or pancreatitis
  • Patients who received ≥3 doses of measles, mumps, and rubella vaccine (MMR) more than 28 days before symptom onset
  • Patients with recurrent parotitis (test samples from both occurrences when possible)
  • Patients who traveled during their incubation period (12–25 days prior to onset), especially those with international travel

1b. Communication with healthcare providers
Improved mumps testing practices among providers can increase the sensitivity and specificity of case classification and reduce unnecessary initial or repeat testing. Communication with providers regarding appropriate testing procedures, including information on specimen type, timing of specimen collection, and specimen collection techniques is critical to ensure best practices before and during an outbreak. Jurisdictions can use the Provider Job-Aid as a tool for communicating best testing practices to providers. The Job-Aid includes an algorithm to help providers determine if testing is necessary and which specimens to collect based on symptoms. This Job-Aid is a template and can be modified by each jurisdiction based on resources, outbreak epidemiology, and other local factors. It also includes a call-out box where jurisdictions can communicate to providers about situations in which testing is not indicated and encourage them to notify the local health department about increased mumps activity.

It is important to note that laboratorians may be the first to recognize increased testing activity and unusual patterns of testing requests by specific providers (e.g., only serum being sent, no buccal swabs sent for RT-qPCR). Frequent communication between epidemiologists and laboratorians during an outbreak can help create efficient testing strategies and protocols and identify needs for provider-specific education. Additionally, jurisdictions and providers should identify and address logistical and institutional barriers for sending appropriate specimens to the local or public health laboratory.

2. CDC Mumps Outbreak Consultation Service

The CDC Mumps Outbreak Consultation Service is available to all jurisdictions that request technical assistance from CDC or the VPD-RCs at the onset of increased activity or during a mumps outbreak. The consultation (by teleconference) should include CDC epidemiology and laboratory subject matter experts (SMEs), the VPD-RC point of contact, and the jurisdiction’s response team, including the epidemiologist, laboratorian, VPD coordinator, and immunization coordinator. During the consultation, the CDC Mumps Outbreak Consultation Service team will:

  • Review the epidemiology and current response to the increased mumps activity or outbreak (Appendix 1)
  • Troubleshoot potential case/outbreak investigation and testing challenges
  • Develop a plan for testing suspected mumps cases to optimize resource use, and anticipate and mitigate laboratory workload
  • Provide additional outbreak response materials (e.g., the Provider Job-Aid, education and communication materials)

2a. Implementing the mumps laboratory testing threshold
The increased burden in mumps testing has resulted in substantial resource challenges for many public health laboratories, including the VPD-RCs. To address this, CDC, in collaboration with APHL and CSTE, established a mumps testing threshold. A jurisdiction may submit up to 10 specimens per week to CDC or the VPD-RCs for RT-qPCR testing. This process will ensure resources are adequately maintained and appropriately distributed to support jurisdictions during mumps surge activities, to monitor mumps nationally, and to manage outbreak response across all seven VPD-RCs for jurisdictions requesting assistance.

Submissions of more than 10 specimens per week will initiate the CDC Mumps Outbreak Consultation Service to contact the jurisdiction in an effort to identify the reason for the increase in testing needs and implement appropriate surveillance and laboratory testing guidance. The threshold was determined based on historical submissions to CDC and VPD-RCs and does not change the mumps outbreak case definition (≥3 mumps cases linked by space and time). Since most jurisdictions submit fewer than 10 clinical specimens per week for RT-qPCR testing, an increase in submissions to >10 specimens for RT-qPCR testing per week may indicate increased mumps activity or an outbreak within the jurisdiction. The jurisdiction and CDC consultation team will develop a tailored plan to support the jurisdiction’s response needs while ensuring optimal use of VPD-RC and CDC resources.

3. Sequencing at CDC and the VPD-RCs to determine the mumps genotype

Sequencing is an important public health tool that can inform the molecular epidemiology of mumps outbreaks as well as support national surveillance. CDC and the VPD-RCs can perform mumps genotyping on RT-qPCR–positive specimens. To ascertain the mumps genotype, the entire nucleotide sequence of the short hydrophobic (SH) gene is determined and then compared to the SH gene sequences of World Health Organization (WHO) reference strains. Currently, WHO recognizes 12 genotypes of mumps. Although multiple mumps genotypes have been detected in the United States since 2006 when molecular surveillance became routine, more than 95% of specimens submitted for sequencing have been genotype G.

Analysis of SH sequences, even those within the same genotype, may reveal differences that could help identify unique cases within an outbreak (e.g., travel importation) or distinguish between different outbreaks within a jurisdiction. Additionally, the analysis may show similarities to sequences from outbreaks in other jurisdictions that were not previously linked epidemiologically. Sequence analysis is conducted at CDC and can be requested during the Mumps Outbreak Consultation Service.

Sequencing of the SH gene enhances public health response and surveillance activities, both at the local and national level. Examples of these public health uses include:
Jurisdictions

  • Detecting new outbreaks
  • Distinguishing sporadic cases or new outbreaks from ongoing outbreaks
  • Identifying imported cases
  • Determining when an outbreak in a specified group(s) or population is over
  • Differentiating infection due to vaccine-type versus wild-type strains

National mumps surveillance

  • Detecting and linking multistate outbreaks
  • Characterizing baseline strain prevalence and monitoring for changes over time
  • Assessing risk factors or other clinical outcomes associated with strains
  • Informing vaccine and diagnostics development

Epidemiologists and laboratory scientists should communicate frequently to make strategic decisions about which clinical specimens should be genotyped. CDC recommends that jurisdictions submit specimens for sequencing from all sporadic cases, cases from new outbreaks (<1 incubation period), and patients with specific characteristics (Table 1) that could help inform local responses and national surveillance. To monitor ongoing established outbreaks, a maximum of 5 specimens per week from these outbreaks should be sent to a VPD-RC or CDC for sequencing. Jurisdictions that perform mumps RT-qPCR testing at their state or local public health laboratories should also send RT-qPCR–positive specimens to monitor new or ongoing outbreaks as well as specimens from patients described in Table 1 to a VPD-RC or CDC for sequencing. CDC or the VPD-RCs may sequence other regions of the mumps genome in addition to the SH gene to provide increased resolution for tracking transmission pathways.

Jurisdictions should be sure to include complete case IDs, specimen IDs, and patient demographics with the specimen to ensure patient data can be linked to laboratory data by CDC and the VPD-RC.

Priority patients for sequencing
Table: Priority patients for sequencing
Patients with parotitis, salivary gland swelling, oophoritis, or orchitis who are not epidemiologically linked to a confirmed or probable mumps case-patient (sporadic cases)
Patients with aseptic meningitis, encephalitis, hearing loss, mastitis, or pancreatitis in the absence of parotitis, salivary gland swelling, oophoritis, or orchitis (severe mumps complications)
Patients who traveled internationally during their likely incubation period (12–25 days prior to onset)
Patients with recurrent parotitis (submit samples from both occurrences when possible)
Patient who received ≥3 doses of MMR more than 28 days before symptom onset
Cases from outbreaks that spread to new settings (e.g., cases that spread from a university to the surrounding community)

This guidance is intended to help jurisdictions provide clear messages to providers and save testing resources at the local, state, and federal levels. To learn more about the VPD-RCs, to see if your jurisdiction is enrolled, or to learn how to enroll, visit the APHL websiteExternal.

Appendix 1: Consultation Questionnaire

On the consultation phone call, please be prepared to discuss or provide the following:

  1. Describe your current mumps situation.
    1. Send epi-curve (if possible).
    2. What is your current case definition?
      1. Are there specific groups or populations involved?
      2. Is there a specific geographic area involved?
      3. What is the timeframe?
    3. When do you consider a case epi-linked?
    4. How many confirmed cases?
    5. How many probable cases?
      1. How have those been determined: serology or epi-linked?
    6. How many suspect cases?
      1. Why are they considered suspect and not probable?
    7. Are you considering recommending a third dose of measles, mumps, and rubella (MMR) vaccine for those at increased risk?
    8. Is your laboratory able to test for mumps?
      1. If quantitative reverse transcription polymerase chain reaction (RT-qPCR), what is factors are used when deciding to test in-house versus using a Vaccine Preventable Disease Reference Center (VPD-RC)?
      2. What tests have been validated in your laboratory, for what type of specimens?
      3. Does the state or local laboratory perform mumps genotyping or are RT-qPCR positive samples forwarded to CDC or the VPD-RCs?
    9. Do you perform testing on all specimens received from providers?
      1. If not, how do you decide who should be tested?

How do the epidemiologists and laboratorians communicate about testing and share results?