Measles Virus - Rubeola

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

  • Diagnostic criteria for subacute sclerosis panencephalitis (SSPE)

Clinical Stages of SSPE

Stage

Clinical manifestations

IPersonality changes, failure in school, strange behavior
IIMassive, repetitive, and frequent myoclonic jerks, seizures, and dementia
IIIRigidity, extrapyramidal symptoms, and progressive unresponsiveness
IVComa, vegetative state, autonomic failure, and akinetic mutism

Laboratory Testing

  • CDC - testing recommendations
  • 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 cerebral spinal fluid (CSF) and brain tissue
  • RT-PCR – not widely available but useful for testing CSF

Other Testing

  • SSPE
    • EEG – periodic complexes
    • 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

Clinical Background

Measles is a highly contagious disease caused by the rubeola virus.

Epidemiology

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

Organism

  • Single-stranded RNA virus – the only member of genus Morbillivirus (Paramyxoviridae family)
  • Humans are the only natural reservoirs

Clinical Presentation

  • Highly contagious, acute, exanthematous respiratory disease with pathognomonic Koplik spots (bluish gray specks on an erythematous base) on the buccal mucosa
    • Incubation – 10-12 days
    • Cutaneous rash starts centrally and spreads to the periphery
  • 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 the 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
    • Pulmonary – primary giant cell pneumonia (Hecht pneumonia)
      • Severe, often fatal pneumonia can occur in patients with deficient cell-mediated immunity
    • Neurological – coma, seizures, encephalitis
      • Subacute sclerosing panencephalitis (SSPE) – rare, progressive encephalitis that may result in dementia and death
        • Chronic encephalitis appears on average 7 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
      • Acute disseminated encephalomyelitis
      • Measles inclusion body encephalitis in immunocompromised patients
    • Gastrointestinal – disease mimicking appendicitis, hepatitis, ileocolitis
    • Cardiovascular – myocarditis, pericarditis
    • Ocular – corneal ulceration and scaring
    • Gestational – increased incidence of pneumonia in pregnant women, spontaneous abortion, premature delivery, and low-birth-weight babies

Prevention

  • Prevention includes measles, mumps and rubella (MMR) vaccine administered to 12-15-month-old children, with revaccination between 4-12 years
    • Mass U.S. immunization has greatly reduced measles infections
      • Some individuals may be susceptible to measles due to vaccine failure or nonimmunization
  • Because vaccine is live, attenuated virus, do not use in pregnant patients or those with significant immunosuppression

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Measles (Rubeola) Antibodies, IgG and IgM 0050375
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Diagnose measles

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

Residual IgM response may be distinguished from early IgM response by testing patient sera 2-3 weeks later for changes in specific IgM antibody levels
Measles (Rubeola) Virus Culture 0065055
Method: Cell Culture/Immunofluorescence

Gold standard test – recommended for detecting measles virus in specimens other than CSF

   
Measles (Rubeola) Antibody, IgG 0050380
Method: Semi-Quantitative Chemiluminescent Immunoassay

Screen for vaccination response

   
Measles (Rubeola) Antibody, IgM, CSF 0054441
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Diagnose rare but fatal subacute sclerosing panencephalitis (SSPE) in CSF samples 

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

 
Measles (Rubeola) Antibody, IgG, CSF 0054440
Method: Semi-Quantitative Chemiluminescent Immunoassay

Diagnose rare but fatal SSPE in CSF samples 

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

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Measles (Rubeola) Antibody, IgM 0099597
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008916
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay
Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, Serum 2008915
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008917
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, Serum 2008918
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic
Viral Culture, Respiratory 2006499
Method: Cell Culture

Viruses that can be isolated – adenovirus; CMV; enterovirus; HSV; influenza A and B; parainfluenza types 1,2, and 3; RSV; and VZV

Virus-specific tests are recommended