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Laboratory Diagnosis of Measles

Laboratory confirmation is essential for all outbreaks and all sporadic measles cases. Detection of measles-specific IgM antibody and measles RNA by real-time reverse transcription polymerase chain reaction (RT-PCR) are the most common laboratory tests used to diagnose measles. Efforts should be made to obtain a serum sample and throat swab (or nasopharyngeal swab) from suspected cases at first contact. Urine samples may also contain virus and when feasible to do so, collection of both respiratory and urine samples can increase the likelihood of detecting virus.

Because measles is a rare disease in the United States, even with the excellent laboratory tests available, false positive results for measles IgM will occur. To minimize the problem of false positive laboratory results, it is important to restrict case investigation and laboratory tests to patients most likely to have measles.  Most likely to have measles are those who meet the clinical case definition, especially if they have risk factors for measles such as:

-Being unvaccinated

-Recent history of travel abroad

-No alternative explanation for symptoms but have fever and generalized maculopapular rash with a strong suspicion of measles

 

Virus isolation in cell culture and measles RNA detection (RT-PCR)

Clinical specimens for real-time polymerase chain reaction (RT-PCR) and virus isolation should be collected at the same time as samples taken for serologic testing. The preferred specimens for virus isolation or RT-PCR are throat or nasopharyngeal swabs, but urine may also contain virus. Virus isolation and RNA detection are more likely to be successful when the specimens are collected early (ideally within three days of rash onset, but up to ten days post rash may be successful). Isolation of measles virus in culture or detection of measles RNA by RT-PCR in clinical specimens confirms the diagnosis of measles.

Successful isolation of measles virus in culture or direct detection of measles RNA by RT-PCR in the clinical sample is particularly helpful for case confirmation when serology results are inconclusive. The Vero/hSLAM cell line, a recombinant cell line with a receptor for measles virus, has greatly improved the ability to isolate measles virus in cell culture.

 

Use of IgM for confirmation of measles:

Unvaccinated persons

Following measles virus infection in an unvaccinated individual, measles IgM antibodies appear within the first few days (1-4 days) of rash onset, peak within the first week post rash onset and are rarely detected after 6-8 weeks. Measles IgG antibodies are generally produced and detectable a few days after the IgM response.

The serologic response following vaccination is slower; measles IgM may not be detectable until 8-14 days after vaccination and measles IgG may not be detectable for up to three weeks post vaccination.

Vaccinated persons

Individuals who have been previously exposed to measles antigen may have a modified disease presentation. These cases are usually detected during an outbreak or after a known exposure to a confirmed measles case. In rare instances, such cases can occur without a known exposure or other risk factor.

Often there is a blunted and/or transient production of IgM and therefore a negative IgM test in vaccinated persons suspected of having measles. This should not be used to rule out the case; RT-PCR testing may be the best method to confirm such cases. If viral testing results are noncontributory, additional testing can be performed for highly suspicious cases.

 

Plaque reduction neutralization assay (PRN)

The gold standard test for serologic evidence of recent measles infection is a four-fold rise in titer as measured in a measles virus plaque reduction neutralization test (PRN or PRNT) between acute and convalescent serum samples. Unlike the IgG enzyme immunoassays (EIA), this test measures measles functional (neutralizing) antibodies, requires specialized reagents, and is labor and time intensive. Only in rare situations would such testing be deemed necessary.

 

 

Source:

https://www.cdc.gov/vaccines/pubs/surv-manual/chpt07-measles.html