Measles Virus - Rubeola

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

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 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)

Background

Measles is a highly contagious disease caused by the measles (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

Treatment

Treatment of measles is largely symptomatic
Vitamin A shown to be effective (American Academy of Pediatrics)
Treat any secondary infections

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 non-immunization
Because vaccine is live, attenuated virus, do not use in pregnant patients or those with significant immunosuppression

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Measles (Rubeola) Antibodies, IgG & IgM

ARUP #: 0050375

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Diagnose measles

Limitations:

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

Follow-up: 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

Test name: Measles (Rubeola) Virus Culture

ARUP #: 0065055

Methodology: Cell Culture/Immunofluorescence

Use:

Gold standard test; requires nasopharyngeal aspirate/washing, throat swab, lung tissue, CSF or urine samples

Test name: Measles (Rubeola) Antibody, IgG

ARUP #: 0050380

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Screen for vaccination response

Test name: Measles (Rubeola) Antibody, IgM, CSF

ARUP #: 0054441

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

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

Limitations:

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

Test name: Measles (Rubeola) Antibody, IgG, CSF

ARUP #: 0054440

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Diagnose rare but fatal SSPE in CSF samples

Limitations:

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

Test name: Measles (Rubeola) Antibody, IgM

ARUP #: 0099597

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Encephalitis Panel, CSF with Reflex to HSV Type 1 & 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001741

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001742

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001765

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001764

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Chemiluminescent Immunoassay

Comments:

Test name: Glucose, Plasma or Serum

ARUP #: 0020024

Methodology: Quantitative Enzymatic

Comments:

References

Guidelines

General

American Academy of Pediatrics. Measles. In Pickering LK, ed. Red Book: 2006 Report of the Committee on Infectious Diseases, 26 ed. Elk Grove Village, IL: American Academy of Pediatrics, 2006. pp. 441-452.
Booy R, Sengupta N, Bedford H, Elliman D. Measles, mumps, and rubella: prevention. Clin Evid. 2006; (15) :448-468.PubMed
Dietz V, Rota J, Izurieta H, Carrasco P, Bellini W. The laboratory confirmation of suspected measles cases in settings of low measles transmission: conclusions from the experience in the Americas. Bull World Health Organ. 2004; 82 (11) :852-857.PubMed
Duke T, Mgone CS. Measles: not just another viral exanthem. Lancet. 2003; 361 (9359) :763-773.PubMed
Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol. 2010; 52 (10) :901-907.PubMed
Ota MO, Moss WJ, Griffin DE. Emerging diseases: measles. J Neurovirol. 2005; 11 (5) :447-454.PubMed
Oxman MN. Measles Virus. In Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology, 2nd ed. Washington, DC: ASM Press, 2002. pp. 791-828.
Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. 2004; 189 Suppl 1 :S4-16.PubMed
Rima BK, Duprex WP. Morbilliviruses and human disease. J Pathol. 2006; 208 (2) :199-214.PubMed
Sabella C. Measles: not just a childhood rash. Cleve Clin J Med. 2010; 77 (3) :207-213.PubMed

Medical Reviewers

Comprehensive Review: August 2011
Last Update: August 2011