Measles Immunity Testing
Use enzyme immunoassay (EIA/ELISA) to measure measles-specific IgG antibodies as the primary test for determining measles immunity, as this has supplanted older hemagglutination inhibition (HI) testing and is the most commonly used commercial assay available today. 1
Recommended Testing Approach
First-Line Test: Measles IgG by EIA/ELISA
- Any licensed EIA showing antibody levels above the standard positive cutoff value is considered evidence of immunity 1
- EIAs have equal or greater sensitivity compared to the older HI test and are now the most commonly used commercial assays 1
- The test requires only a single serum sample and provides straightforward positive/negative results 1
Alternative Acceptable Methods
Other commercially available assays that can detect measles immunity include: 1
- Latex agglutination
- Immunofluorescence assay (IFA)
- Passive hemagglutination
- Hemolysis-in-gel
- Virus neutralization tests (plaque reduction neutralization/PRN test)
Critical Interpretation Considerations
Understanding Test Sensitivity Differences
- When adults who appeared antibody-negative by older HI testing were retested with more sensitive assays like EIA, almost all (>95%) had detectable antibodies 1
- Children who "lost" detectable HI antibodies over 16 years of follow-up almost all retained antibodies detectable by more sensitive tests 1
- This confirms that modern EIA testing is superior for detecting vaccine-induced immunity 1
Important Caveats for EIA Testing
Be aware that current commercial EIAs have limitations in detecting vaccine-induced immunity: 2
- Approximately 10% of healthcare workers with documented vaccination history and protective neutralizing antibody levels (PRN >120 mIU/mL) tested falsely negative on commercial EIAs 2
- This false-negative rate increased to 19% among persons born 1975-1985, representing the early measles vaccination period 2
- When 154 healthcare workers were tested, 99.4% had protective antibody levels by neutralizing test, but commercial EIAs missed approximately 10% 2
When Neutralizing Antibody Testing May Be Preferred
Consider plaque reduction neutralization (PRN) testing as the gold standard when: 2
- Assessing vaccine-induced immunity in healthcare workers or other high-risk populations
- EIA results are equivocal or negative despite documented vaccination history
- Determining true protective immunity rather than just antibody presence
- PRN >120 mIU/mL is considered protective 2
Clinical Algorithm for Equivocal Results
If a person with documented measles vaccination history has borderline or negative IgG by ELISA: 1
- Administer one dose of MMR vaccine
- Do not retest for serologic evidence of immunity
- This approach is more practical than pursuing additional serologic testing 1
Confirming Immunity After Revaccination
- In persons with initially undetectable antibodies who receive revaccination, immunity can be confirmed by documenting a booster response (absence of IgM with rapid rise in IgG) 1
Practical Recommendations by EIA Titer Ranges
Based on correlation studies between EIA-IgG and protective antibody levels: 3
- EIA-IgG ≥12.0: Person is protected against measles
- EIA-IgG 8.0-12.0: May benefit from booster vaccination
- EIA-IgG 4.0-8.0: Insufficiently protected, requires booster dose
Key Pitfalls to Avoid
False-Positive IgM Results
- As measles becomes rare, false-positive IgM results increase significantly in low-prevalence settings 4
- IgM testing is NOT appropriate for routine immunity screening—only use IgG 1
- If IgM is detected without epidemiologic linkage to confirmed measles, perform confirmatory testing with direct-capture IgM EIA method 4
Test Selection Based on Clinical Context
- Do not use hemagglutination inhibition (HI) testing, as it has been supplanted by more sensitive assays 1
- Commercial EIAs are adequate for most clinical purposes but may miss some vaccine-induced immunity 2
- Reserve neutralizing antibody testing (PRN) for research purposes or when precise determination of protective immunity is critical 2