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
- 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
- Viral
- 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
- Incubation
- 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
- Pulmonary – primary giant cell pneumonia (Hecht pneumonia)
ARUP Laboratory 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
Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay
Culture test for detecting measles virus in specimens other than cerebrospinal fluid (CSF)
Cell Culture/Immunofluorescence
Not recommended as a stand-alone test unless testing for evidence of antibody production from vaccination
For cerebrospinal fluid, order measles antibody, IgG, CSF
Semi-Quantitative Chemiluminescent Immunoassay
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
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
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
Semi-Quantitative Chemiluminescent Immunoassay
Aid in diagnosis of acute measles infection
Consider ordering panel which contains both IgG and IgM antibodies
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Molecular testing is preferred for patients presenting with meningitis/encephalitis; refer to meningitis/encephalitis panel by PCR
Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)/Semi-Quantitative Chemiluminescent Immunoassay (CLIA)
Not a preferred test; refer to relevant test for specific pathogen suspected
Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)/Semi-Quantitative Chemiluminescent Immunoassay (CLIA)
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
Quantitative Enzymatic Assay
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
Cell Culture
References
Red Book 2012: 2012 Report of the Committee on Infectious Diseases - American Academy of Pediatrics. Measles
American Academy of Pediatrics. Measles. In: Pickering LK, ed. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. American Academy of Pediatrics; 2012.
CDC - Manual for the Surveillance of Vaccine-Preventable Diseases - Chapters
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. [Updated: Jun 2020; Accessed: Mar 2021]
CDC - Measles / Rubeola 2013 Case Definition
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. NNDSS: measles/rubeola 2013 case definition. [Last reviewed: Apr 2021; Accessed: Mar 2023]
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Centers for Disease Control and Prevention (CDC). Recommendations from an ad hoc Meeting of the WHO Measles and Rubella Laboratory Network (LabNet) on use of alternative diagnostic samples for measles and rubella surveillance. MMWR Morb Mortal Wkly Rep. 2008;57(24):657-660.
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Gutiérrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol. 2010;52(10):901-907.
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Kumar D, Sabella C. Measles: Back again. Cleve Clin J Med. 2016;83(5):340-344.
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Rima BK, Duprex P. Morbilliviruses and human disease. J Pathol. 2006;208(2):199-214.
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Sabella C. Measles: not just a childhood rash. Cleve Clin J Med. 2010;77(3):207-213.
CDC - Adult Immunization Schedule
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended adult immunization schedule for ages 19 years or older, United States, 2020. [Last reviewed: Feb 2022; Accessed: Jun 2022]
CDC - Recommended Immunization Schedules for Children and Adolescents Aged 18 Years or Younger
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for children and adolescents aged 18 years or younger – United States, 2019. [Last reviewed: Feb 2019; Accessed: Jun 2022]
Medical Experts
Couturier

Schlaberg

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