Measles Virus - Rubeola

Dx
Background
Lab Tests

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
I	Personality changes, failure in school, strange behavior
II	Massive, repetitive, and frequent myoclonic jerks, seizures, and dementia
III	Rigidity, extrapyramidal symptoms, and progressive unresponsiveness
IV	Coma, 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

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 CNS disease
- Meningitis
- Encephalitis
- Dementia
- Multiple sclerosis
- Seizure disorder
- Metabolic white matter disease
- Bovine spongiform encephalomyelitis (mad cow disease)

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; requires nasopharyngeal aspirate/washing, throat swab, lung tissue, CSF or urine samples
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 Number	Comments
Measles (Rubeola) Antibody, IgM 0099597 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Encephalitis Panel, CSF with Reflex to HSV Type 1 and 2 Glycoprotein G-Specific Ab, IgG 2001741 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody Semi-Quantitative Chemiluminescent Immunoassay
Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001742 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001765 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001764 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