Laboratory Tests to Rule Out Measles
Order measles-specific IgM serology and collect specimens for measles virus PCR (throat/nasopharyngeal swab and urine) at the first clinical encounter with any suspected measles case. 1
Primary Diagnostic Tests
Serologic Testing (IgM Antibody)
- Draw blood immediately during the first clinical encounter with suspected measles
- Use a sensitive and specific assay (direct-capture IgM EIA method preferred) 1
- Critical timing considerations:
- IgM may not be detectable in the first 72 hours after rash onset with less sensitive assays
- If initial specimen is collected <72 hours post-rash and is negative, repeat testing ≥72 hours after rash onset 1
- IgM peaks ~10 days after rash onset
- IgM remains detectable for 30-60 days (at least 1 month) after rash onset 1
Molecular Testing (PCR)
- Collect specimens as close to rash onset as possible - delays reduce isolation success 1
- Specimen types:
- Throat/nasopharyngeal swab
- Urine sample
- PCR sensitivity within 0-3 days post-rash: 94.39% 2
- PCR enables genotyping for epidemiologic tracking and distinguishing wild-type from vaccine strains 1, 3
Alternative/Confirmatory Testing
Acute and Convalescent Serology
- Acute specimen: Within 1-3 days after rash onset
- Convalescent specimen: 2-4 weeks later
- Demonstrates significant rise in measles antibody titer
- This method has been largely supplanted by single-specimen IgM testing 1
Important Caveats and Pitfalls
False Positives
- Parvovirus infection (fifth disease) can cause false-positive IgM results with some commercial ELISA assays 1
- Consider confirmatory testing with direct-capture IgM EIA when:
- No identified source of infection
- No epidemiologic linkage to confirmed case
- Low measles prevalence settings increase false-positive likelihood 1
False Negatives
- Specimens collected <72 hours post-rash may be negative with less sensitive assays 1
- Vaccinated individuals show lower sensitivity for both IgM and PCR 2
- Commercial IgM kits show variable performance: sensitivity ranges 50-83%, specificity 86.9-98% compared to CDC reference assay 4
Special Populations
- Vaccinated cases/breakthrough infections: May have negative IgM but positive PCR 5
- Adults ≥15 years: Often lack written immunization records; unknown vaccination history lowers PCR sensitivity 2
- Combination of IgM and PCR testing is essential for vaccinated individuals 5, 2
Additional Testing to Consider
- Test for rubella if measles serology is negative in patients with febrile rash illness 1
- Contact local/state health department immediately for guidance on specimen collection, shipping, and additional testing requirements 1
Laboratory Confirmation Criteria
A case is laboratory-confirmed by any of the following 1, 6:
- Positive measles IgM antibody
- Significant rise in measles antibody level between acute and convalescent specimens
- Isolation of measles virus from clinical specimen (by PCR or culture)
Do not delay reporting, investigation, or control measures while awaiting laboratory results 1