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Febrile #102 – Rubeola Response

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Summary

Step into the role of a hospital epidemiologist managing a measles outbreak response with Drs. Palak Patel, Emily Landon, and David Zhang from the University of Chicago!

Table of Contents

Credits

Hosts: Palak Patel, Sara Dong

Guests: Emily Landon, David Zhang

Writing: Palak Patel

Editing, Cover Art: Sara Dong

Produced by Sara Dong with support from the Infectious Diseases Society of America (IDSA)

Our Guests

Palak Patel, DO

Palak Patel is a first year ID fellow at the University of Chicago. She completed her medical school training at Midwestern University and internal medicine residency at John H. Stroger Hospital of Cook County. She is passionate about infection control and prevention, with specific research interest in the use of artificial intelligence in infection control.

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Emily Landon, MD

Emily Landon, MD is Associate Professor of Medicine at the University of Chicago in the Section of Infectious Diseases & Global Health where she also serves as the Hospital Epidemiologist and Executive Medical Director of the Infection Prevention & Control Program. After medical school at Loyola University Chicago Stritch School of Medicine, she completed her medical residency, chief residency, and fellowship in infectious diseases at the University of Chicago Medicine. She also completed a fellowship in Clinical Medical Ethics at the MacLean Center for Clinical Medical Ethics at the University of Chicago and is an assistant director of the MacLean Center. Dr. Landon’s work includes studying ethical implications of infection control interventions and finding novel and innovative ways to address common and uncommon infection control problems but her main research interest is in hand hygiene and behavior change. Her work in using automated monitoring systems to improve hand hygiene compliance has made her a goto expert in this field. As the leader of the University of Chicago’s Infection Prevention & Control Program, Dr. Landon manages a team of outstanding practitioners in infection surveillance, outbreak investigation, performance improvement, and regulatory compliance activities and serves as the medical director for the High Consequence Pathogen Preparedness Program for the University of Chicago.

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David Zhang, MD

David Zhang is an Assistant Professor of Pediatrics in the Section of Infectious Diseases at the University of Chicago Medicine Comer Children’s Hospital. He completed his pediatrics residency at Loyola University Medical Center and his fellowship training in pediatric infectious disease at University of Chicago Medicine. He currently serves as Associate Medical Director of Infection Prevention & Control. His research interests include the intersection of infection control and hospital sustainability.

Culture

Palak: Laapataa Ladies, a movie available on Netflix

David: playing the drums and conjuring rhythms.  If he ever gets the chance to be in a band with like-minded ID-centric individuals, the band name would be the “Fluoroquino-tones”!

Emily: growing seedlings, preparing her new dress for Chicago’s Frocktails

Consult Notes

Case Summary

Multiple children with measles infection

Key Points

Some general measles resources:

What is measles? A quick intro and notes on epidemiology

  • Measles is also known as rubeola
  • This is an acute febrile illness caused by a single-stranded, enveloped RNA virus with 1 serotype
  • The virus is classified as a member of the genus Morbillivirus in the Paramyxoviridae family
  • Transmitted by direct contact with infectious droplets or airborne route
  • Measles is highly contagious
      • 90% of susceptible household contacts will develop illness
      • R0 (the number of people who are infected by a single case) is estimated to be 12-16 in an unvaccinated population
      • Emily mentioned that in the example outbreak that the R0 was 25-35
  • Measles is a nationally notifiable illness and cases should be reported immediately to the appropriate health department

Clinical presentation of measles (aka rubeola)

  • The measles clinical case definition (according to CSTE – Council of State and Territorial Epidemiologists / CDC):
      • An acute illness characterized by:
          • Fever (≥101°F or 38.3°C)
          • AND
          • Generalized, maculopapular rash
          • AND
          • At least 1 of the “3 C’s”: cough, coryza (runny nose), conjunctivitis
      • As discussed in the episode, these surveillance case definitions provide a set of uniform criteria to define a disease for public health surveillance. Cases can then be classified as “probably” or “confirmed”. There are additional epidemiologic classifications too (such as US acquired vs international imported)
  • Measles rash typical presentation (see COCA call for some images):
      • Starts on face, at hairline, or behind the ears
      • Spreads downwards to neck, trunk, extremities
      • Maculopapular (small raised or flat red bumps → which may coalesce as rash spread)
      • Not usually itchy
  • Koplik spots may be present on buccal mucosa
  • Typical measles timeline
      • Incubation period 10-14d (asymptomatic)
      • Prodrome with fever about day -4 to -2 (fever and 3Cs)
      • Day 0 = appearance of rash
      • Infectious period is 4 days before rash to 4 days after rash – so you can see how the challenge is that people are infectious before the rash and the prodrome is nonspecific
  • Measles complications
      • Thrombocytopenia and leukopenia may be observed
      • Diarrhea is the most common complication, seen in ~8% of cases
      • Otitis media seen in 5-10% of cases
      • Respiratory tract complications such as pneumonia or neurologic complications such as encephalitis are the cause of most deaths. Two additional neurologic complications of measles to note include:
          • Subacute sclerosing panencephalitis (SSPE)
            • Fatal, progressive degenerative disease of the central nervous system. Pathogenesis not well understood but may be related to persistent infection with genetic variant of measles virus in CNS
            • Usually occurs 7-10 years after natural measles infection
          • Acute disseminated encephalomyelitis (ADEM):
            • Demyelinating disease, likely a postinfectious autoimmune response
            • Occurs in ~1 per 1000 cases
            • Manifests as fever, headache, neck stiffness, seizures, mental status changes typically within 2 wks of the exanthem
            • Significant mortality, associated with 10-20% mortality and higher than mortality from ADEM due to other causes. Residual neurologic abnormalities are common
      • Secondary infection and coinfections with other viruses or bacteria are possible and important risk of measles-related morbidity and mortality as well
      • Hospitalization 1 in 4 cases
      • Encephalitis 1 in 1000 cases
      • Death 1-3 per 1000 cases
  • Remember that measles infection among immunized individuals may be atypical, such as higher and more prolonged fever, different rash characteristics, etc

What are other common causes of maculopapular febrile rash?  What else might be on the differential for measles?

  • Parvovirus B-19 (Fifth disease): “slapped cheek” rash which can spread to trunk and extremities; more common in school aged children than infants
  • Human herpesvirus 6 (Roseola, Sixth disease): common cause of fever and rash in children; fever often resolves, and rash appears the next day starting on trunk and spreading outwards
  • Enteroviruses: rash can be maculopapular or urticarial, often on hands/feet (hand foot mouth)
  • Antibiotic sensitivity reactions or allergies

How do we diagnose measles?

  • Clinical, epidemiologic, and lab data should all be considered when diagnosing measles infection
  • All suspected cases should have a serum IgM and nasopharyngeal / oropharyngeal swabs sent for PCR
  • Using serology (IgM) alone to test patients with low pre-test probability of having measles will result primarily in false positive results
  • Both serum and NP/OP swabs should be collected for all suspect cases
  • Measles serology
  • Measles PCR
      • rRT-PCR testing can be performed on nasopharyngeal and throat swabs as well as urine
        • Specimens are ideally collected within 3 days of rash onset, but can be positive up to 10 days after rash onset
          • It is best to collect specimens for rRT-PCR as soon as possible after rash onset
        • Proper specimen collection, storage, and processing is critical to maintain the stability of viral nucleic acids. Most rRT-PCR assays include a control for specimen integrity (reference gene)
        • rRT-PCR has much higher sensitivity and specificity than serology
          • False positive results can occur but are MUCH less common
        • CDC and state public health labs can perform rRT-PCR
      • Commercial PCR testing
        • Some large commercial laboratories offer measles rRT-PCR testing and others are in the process of onboarding tests
        • Some issues that arise with commercial testing:
          • Loss of integration with public health departments
          • Specimens are not maintained appropriately or for long enough to allow for genotyping or additional testing if necessary
  • Additional testing is available
      • Serology
        • Paired (acute and convalescent) IgG testing: can provide additional evidence of measles infection if other data are inconclusive
        • Avidity testing (IgG): can provide information about breakthrough measles cases among previously vaccinated people
      • Genotyping
        • Assist with outbreak detection and tracking and should be performed ideally on all rRT-PCR positive specimens
        • Important to document sustained elimination of measles in the US
        • Performed at CDC and vaccine-preventable disease reference centers (CA, MN, NY, WI)
      • MeVA
        • A specialized rRT-PCR assay which can determine if detected measles virus is vaccine-derived or from community transmission
        • Among people recently exposed but also recently vaccinated, can differentiate a vaccine reaction from a measles case
        • Performed at CDC and vaccine-preventable disease reference centers (CA, MN, NY, WI)
  • Key diagnosis points
      • Measles serology is a useful piece of diagnostic testing but is limited by:
        • Cross-reactivity with other causes of febrile rash
        • High dependence on disease prevalence
      • Diagnostic evaluation of measles should include
        • Both molecular testing (rRT-PCR) and serology
        • Consideration of the clinical and epidemiologic context (e.g., travel history, vaccination status)
      • Additional testing is available at CDC and VPD reference centers, in coordination with state or local public health labs
      • What testing is recommended for measles diagnosis? Both serology and NP/OP swab for rRT-PCR

Management of measles infection

Measles vaccination

  • Measles vaccine was licensed in the U.S. in 1963, and combination MMR vaccine was licensed in 1971
  • MMR is an attenuated (weakened) live virus vaccine
      • The vaccine cannot cause measles, mumps, or rubella and cannot be transmitted from person to person
      • However, transient side effects can occur which can mimic these diseases
  • The vaccine is highly effective
      • 1 dose ~93% protection
      • 2 doses ~97% protection
  • MMR vaccination has an excellent safety record
  • MMR vaccine routine recommendations
      • Pediatric vaccination schedule:
          • First dose at 12-15 months
          • Second dose at 4-6 years of age
          • A dose between 6-11 months of age can be given for travel or outbreak response (a “zero” dose)
            • If given between 6-11 months of age, two more doses should be given on the usual schedule
      • Adult vaccination:
          • Adults who have presumptive evidence of immunity include:
            • Birth before 1957
            • Laboratory evidence of immunity (positive IgG)
            • Prior lab confirmed measles diagnosis
          • Adults without evidence of immunity generally should get one dose of MMR
            • Two doses are required/recommended for high-risk adults (healthcare personnel, international travelers, postsecondary school students)
          • 2013 ACIP recommendations: http://www.cdc.gov/mmwr/pdf/rr/rr6204.pdf
          • 2019 Adult Immunization schedule: http://www.cdc.gov/vaccines/schedules/hcp/adult.html
      • MMR recommendations for international travelers
          • CDC recommends that all U.S. residents older than age 6 months who will travel internationally receive MMR vaccine prior to departure if they are without evidence of immunity:
            • Infants 6–11 months of age: 1 dose of MMR vaccine
              • Followed by two more doses on the typical pediatric schedule
            • Children 12 months of age or older: 2 doses of MMR vaccine, separated by at least 28 days
            • Teenagers or adults without evidence of immunity: 2 doses of MMR vaccine separated by at least 28 days
            • CDC Guidance on Measles during the summer travel season (Jun 21 2023) https://emergency.cdc.gov/han/2023/han00493.asp
  • MMR vaccine contraindications
      • Severe immunocompromising conditions (e.g., hematologic malignancy, receipt of chemotherapy, long-term immunosuppressive therapy)
        • HIV if CD4 % < 15% or absolute CD4 <200
      • Family history suggestive of a congenital immunocompromising condition, unless assessed to be immunocompetent by a clinician or laboratory testing
      • History of severe allergic reaction to MMR or to an MMR vaccine component (e.g., gelatin)
      • Pregnancy
      • https://www.cdc.gov/vaccines/vpd/mmr/public/index.html
  • MMR vaccine adverse events
      • MMR vaccine is generally very well tolerated
      • Common side effects include: fever (<15%), brief rash (5%), lymphadenopathy (5% of children; 20% of adults)
      • Rare serious adverse events include:
        • Anaphylaxis (2-14 events per million doses)
        • Febrile seizures (1 event per 3-4000 doses)
        • Low platelet count (1 event per 40,000 doses; may be higher risk if known ITP)
      • MMR can cause a short-lived febrile rash syndrome that is not contagious to others
        • Differentiating measles from an MMR reaction in the setting of an outbreak can be challenging, especially if MMR was given to prevent measles after an exposure
        • Serology cannot differentiate measles infection from measles vaccination
        • Molecular testing (MeVA) can differentiate measles from an MMR reaction
      • Rash or URI panels may detect vaccine reactions
        • Some commercial labs nationally have begun offering measles rRT-PCR as part of a viral exanthem or upper respiratory infection panel
        • Positive results for measles have so far only detected vaccine reactions
        • Clinicians should be aware that measles PCR can detect vaccine-derived measles virus 14+ days after MMR vaccination

Measles outbreak response

  • Below are some notes and resources on outbreak response for measles. For another episode on outbreak investigation and response, check out Febrile episode #71 entitled Outbreak Investigation
  • Identify cases and establish the diagnosis
      • Clinical case definition
      • Vaccination history
      • Travel or exposure history in prior 21 days
      • Public health departments can help advice on the need for testing and on the appropriate routing for specimens → early involvement of public health departments can help prevent measles outbreaks
  • Perform case and contact investigations
      • Obtain accurate and complete immunization and travel histories
      • Identify and prioritize contacts without presumptive evidence of immunity
          • Susceptible contacts without presumptive evidence of immunity are at high risk to develop measles
          • Exposed persons who are at high risk for serious disease include infants <1 year old, pregnant people, people with immunocompromising conditions or medications
  • Implement control measures
      • Community vaccination
          • Providers can ensure patients are up to date with MMR vaccine requirements
          • If preschool-aged children are at risk due to outbreak location and transmission settings: A 2nd dose early between age 1 and 4 years could be considered
            • Any MMR dose should be given at least 28 days after a prior dose. 2 MMR doses is considered fully protective, but some states or territories may require an additional dose between ages 4–6 years in accordance with the usual schedule
          • If infants <12 months of age are at risk:
            • A “zero-dose” between age 6-11 months could be considered
            • Repeat vaccination should be pursued according to the routine schedule
      • Consider PEP for susceptible contacts
          • PEP within the target window may provide measles protection or modify the clinical course of disease among susceptible people
          • MMR
            • Should be given within 72 hrs (3 days) of initial measles exposure
            • Vaccination can be given after this window, but would only be expected to protect from future exposures and not considered “adequate PEP”
          • Immunoglobulin
            • Needs to be given within 6 days of initial exposure
            • Can be given intramuscularly (IMIG) or intravenously (IVIG)
              • IVIG should be prioritized for adults at high risk of severe disease
      • Isolation of cases and exclusion of susceptible contacts
          • Case-patients should be isolated for four days after rash onset
            • People with immunocompromising conditions with measles may require more prolonged isolation
          • Susceptible contacts without evidence of immunity should be offered PEP or otherwise excluded from congregate settings
      • Implement specific precautions in health settings
          • Encourage patients to contact health care facility before arrival, if known (e.g., if they contact health department prior to seeking care)
          • Provide facemask to patient and promptly isolate the patient in a room with the door closed
          • Use standard and airborne precautions including patient placement in an airborne infection isolation room (AIIR) (if unavailable, a single room with closed door may be used pending transfer to an AIIR)
  • Measles outbreak toolkit for healthcare providers from CDC

Episode Art & Infographics

Infographics

Find all the Febrile infographics here!

Goal

Listeners will be able to diagnose measles infection and consider outbreak response measures

Learning Objectives

After listening to this episode, listeners will be able to:

  • Identify the clinical presentation of measles
  • Diagnose measles with appropriate laboratory diagnostics
  • Discuss measles prevention and public health control strategies in the setting of an outbreak

Disclosures

Our guests (Palak Patel, Emily Landon, David Zhang) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Patel, P., Landon, E., Zhang, D., Dong, S. “#102: Rubeola Response”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/2b246fd7-1d2b-4898-aeaf-92d94f501c15/

Transcript

https://docs.google.com/document/d/1W_5_tdtcFq7alvRd4rzt9_CC89hcqhGlqtkLsX3UAO0/edit?usp=sharing

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