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

• 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

• Rash with prodrome – erythema multiforme
• Infectious
  • Viral
    • Rubella
    • Enterovirus
    • Parvovirus B19
    • Arboviruses
    • Dengue fever
    • HIV
    • HHV6/HHV7
  • Bacterial 
    • Streptococcal disease, Group A (scarlet fever)
    • Treponema pallidum (secondary syphilis)
  • Vasculitis
    • Kawasaki disease
    • Drug eruptions
    • Stevens-Johnson Syndrome
•  Late-onset central nervous system (CNS) disease
  • Meningitis
  • Encephalitis
  • Dementia
  • Multiple sclerosis
  • Seizure disorder
  • Metabolic white matter disease
  • Bovine spongiform encephalomyelitis (mad cow disease)

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