Measles Virus - Rubeola

Measles is a highly contagious disease caused by the rubeola virus, a single-stranded RNA virus that is the only member of genus Morbillivirus in the Paramyxoviridae family. Humans are the only natural reservoirs for the rubeola virus. Laboratory testing options include serum testing for antibodies, viral culture, and PCR.

Diagnosis

Indications for Testing

  • Suspicious rash with clinical syndrome
  • Known exposure to measles by an unvaccinated person
  • Confirmation of immunity to measles after vaccination

Criteria for Diagnosis

  • Acute febrile rash with ≥1 of the following (CDC, 2013)
    • Isolation of measles virus from clinical specimen
    • Detection of nucleic acid specific to the measles virus using polymerase chain reaction (PCR)
    • Significant rise in measles IgG antibody or IgG seroconversion
    • Positive test for measles IgM antibody
    • Established epidemiologic link to a confirmed case

Laboratory Testing

  • Measles testing recommendations (CDC)
  • Serum testing for antibodies
    • Confirm acute infection with measles using IgM and IgG serial testing – IgM is very sensitive if performed 2-3 days after onset of rash
    • Confirm seroconversion after vaccination using IgG testing
  • Viral culture
    • Nasopharyngeal and blood cultures are most sensitive if collected during prodrome up to 1-2 days after onset of rash
    • Virus can be isolated from urine culture up to 1 week or more after onset of rash
    • Difficult to isolate from cerebrospinal fluid (CSF) and brain tissue
  • Reverse transcription PCR (RT-PCR) – not widely available but more specific and may be preferred over serologic testing

Other Testing

  • Subacute sclerosis panencephalitis (SSPE) – rare complication of measles
    • Electroencephalogram (EEG) – periodic complexes
    • Magnetic resonance imaging (MRI)
      • Early – asymmetrical hyperintense lesions
      • Later – atrophy, new lesions
    • CSF IgM, IgG analysis
      • Cellular pleocytosis
      • Normal glucose
      • Normal to elevated protein
      • Elevated IgG titers
      • PCR positive

Differential Diagnosis

Background

Epidemiology

  • Prevalence – minimal number of cases yearly in U.S. due to high rate of vaccination
    • >750,000 deaths worldwide
    • Occasional small outbreaks from imported cases of measles primarily infecting unvaccinated individuals
  • Transmission
    • Respiratory droplets
    • Highly contagious – >90% transmission among nonimmune individuals

Clinical Presentation

  • Highly contagious, acute, exanthematous respiratory disease
    • Incubation
      • 7-21 days (Kumar, 2016)
      • Most cases become apparent 10-12 days after exposure
    • Pathognomonic Koplik spots (bluish-gray specks on an erythematous base) on buccal mucosa
    • Maculopapular rash starts at face and neck and spreads to entire body
    • High fever, malaise, anorexia, coryza, cough, conjunctivitis
  • Diagnosis based on clinical exam may be difficult, especially in atypical cases
    • Can occur in persons vaccinated from 1963-1967 if exposed to wild measles – symptoms believed to be hypersensitivity reactions to vaccine
    • Atypical rash begins peripherally and moves centrally
    • High fever and edema
    • May occur in patients who received killed vaccines and later came in contact with wild virus strain
  • Complications – most often <5 years or >20 years, pregnant women, and immunosuppressed individuals
    • Pulmonary – primary giant cell pneumonia (Hecht pneumonia)
      • Severe, often fatal pneumonia can occur in patients with deficient cell-mediated immunity
    • Neurological – coma, seizures, encephalitis
      • Acute disseminated encephalomyelitis
      • Measles inclusion body encephalitis in immunocompromised patients
      • Subacute sclerosing panencephalitis (SSPE) – rare, progressive encephalitis that may result in dementia and death
        • Chronic encephalitis appears on average 7-10 years after measles
        • More prevalent in areas where measles vaccination rate is low
        • Disease affects neurons – can survive in latent form for years
        • Virus exposure at earlier age increases likelihood of SSPE infection due to immune system immaturity
    • Other respiratory complications – otitis media (most common complication), laryngotracheobronchitis, mastoiditis, pneumothorax, and mediastinal emphysema
    • Gastrointestinal – disease mimicking appendicitis, hepatitis, ileocolitis
    • Cardiovascular – myocarditis, pericarditis
    • Ocular – corneal ulceration and scarring
    • Gestational – increased incidence of pneumonia in pregnant women, spontaneous abortion, premature delivery, and low-birth-weight babies

ARUP Lab Tests

Aid in diagnosis of measles infection

May not be helpful in patients who have recently received an MMR vaccination

Low IgM antibody levels occasionally persist >12 months after infection or immunization

Culture test for detecting measles virus in specimens other than cerebrospinal fluid (CSF)

Not recommended as a stand-alone test unless testing for evidence of antibody production from vaccination

For cerebrospinal fluid, order measles antibody, IgG, CSF

Aid in diagnosis of measles encephalitis

False-positive results will occur due to low incidence of measles in the U.S.

Rubeola CSF antibody detection may indicate central nervous system infection; however, consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier

Not a recommended test

False-positive results will occur due to low incidence of measles in the U.S.

Rubeola CSF antibody detection may indicate central nervous system infection; however, consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier

Related Tests

Aid in diagnosis of acute measles infection

Consider ordering panel which contains both IgG and IgM antibodies

Molecular testing is preferred for patients presenting with meningitis/encephalitis; refer to meningitis/encephalitis panel by PCR

Panel includes measles (Rubeola) antibody, IgG, CSF; measles (Rubeola) antibody, IgM, CSF; mumps virus antibody IgG, CSF; mumps virus antibody IgM, CSF; varicella-zoster virus antibody, IgG, CSF; varicella-zoster virus antibody, IgM by ELISA (CSF); herpes simplex virus type 1 and/or 2 antibodies, IgM by ELISA, CSF; herpes simplex virus type 1 and/or 2 antibodies, IgG, CSF; herpes simplex virus type 1 glycoprotein G-specific antibody, IgG by ELISA, CSF; herpes simplex virus type 2 glycoprotein G-specific antibody, IgG by ELISA, CSF; West Nile virus antibody, IgG by ELISA, CSF; West Nile virus antibody, IgM by ELISA, CSF

Reflex pattern: if HSV 1 and/or 2 IgG, CSF is 1.10 IV or greater, then HSV 1 G-Specific IgG, CSF and HSV 2 G-Specific IgG, CSF will be added

Not a preferred test; refer to relevant test for specific pathogen suspected

Panel includes measles (Rubeola) antibody, IgG; measles (Rubeola) antibody, IgM; mumps virus antibody, IgG; mumps virus antibody, IgM; varicella-zoster virus antibody, IgG; varicella-zoster virus antibody, IgM; herpes simplex virus type 1 and/or 2 antibodies, IgM by ELISA; herpes simplex virus type 1 glycoprotein G-specific antibody, IgG by CIA; herpes simplex virus type 2 glycoprotein G-specific antibody, IgG by CIA; herpes simplex virus type 1 and/or 2 antibodies, IgG; West Nile virus antibody, IgG by ELISA, serum; West Nile virus antibody, IgM by ELISA, serum

Reflex pattern: if HSV 1 and/or 2 IgG is 1.10 IV or greater, then HSV 1 G-Specific IgG and HSV 2 G-Specific IgG will be added

Use to diagnose and manage diabetes mellitus and other carbohydrate metabolism disorders

Detect common respiratory viruses; molecular methods may offer improved sensitivity

Respiratory viruses rapid culture offers faster turnaround time

Viruses that can be isolated: adenovirus; cytomegalovirus (CMV); enterovirus; herpes simplex virus (HSV); influenza A and B; parainfluenza types 1,2, and 3; respiratory syncytial virus (RSV); and varicella-zoster virus (VZV)

Virus-specific tests are recommended

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®