Implications of Measles Inclusion by Commercial Syndromic Polymerase Chain Reaction Panels — United States, May 2022–April 2023

Discussion

These measles virus detections by syndromic PCR panels were attributed to previous MMR vaccination because nearly all occurred in persons without risk factors for measles and shortly after receipt of MMR vaccine. Detection of the strain of measles virus used in MMR vaccine typically occurs within 21 days of vaccination, but detection >100 days later has been reported (7), a period that aligns with findings described here. Children frequently experience symptoms of rash and fever from many causes, including other viral illnesses and typical vaccine side effects. This investigation identified an alternative viral etiology for rash for one half of the patients with measles virus detections.

Measles is a highly contagious airborne infection that can infect 90% of susceptible contacts (1). Preventing measles is essential for population and personal health. Prodromal signs and symptoms include high fever (up to 105°F [40.6°C]) and either cough, coryza, or conjunctivitis. The prodrome is followed by a maculopapular rash that spreads from head to trunk to lower extremities (8). Severe complications include pneumonia, encephalitis, and death. Viral transmission can occur from 4 days before to 4 days after rash onset. A single MMR vaccine dose is 93% effective in preventing measles, and receipt of 2 doses is 97% effective (4). In the United States, 90% of children receive MMR vaccines by age 24 months (1). Although measles is not endemic in the United States, cases and outbreaks occur sporadically when cases are imported from parts of the world where measles remains endemic (8). Preventing further measles transmission after detection of a case requires a rapid and robust public health response that can include isolating ill persons, verifying immunity of exposed persons, offering postexposure prophylaxis with measles vaccine or immunoglobulin, and implementation of quarantine measures if necessary (8). Notifying public health agencies immediately is imperative to determine which response measures are needed when measles is detected or clinically suspected.

As demonstrated by this analysis, inclusion of measles virus in syndromic PCR panels can result in incidental detection of measles vaccine virus. Some clinicians who received reports of measles detection by syndromic PCR panels anecdotally shared with health departments that they had neither suspected measles infection in the patient nor realized that the test panel included measles. These clinicians had diagnosed common childhood illnesses, such as roseola or impetigo before receiving test results. When choosing diagnostic tests to evaluate skin rash illnesses, clinicians should consider likely etiologies and determine whether laboratory findings will guide treatment recommendations. Syndromic PCR panels provide the opportunity to rapidly test for multiple pathogens, including those unlikely to cause the illness in question. Inability of these testing panels to differentiate between measles virus causing illness and incidental detection of measles vaccine virus RNA can have significant public health reporting and response ramifications, potentially leading to misdiagnosis of measles virus infection. Any detection of measles virus by syndromic PCR testing, even if suspected to be incidental detection of vaccine strain, should be reported to public health agencies immediately so that appropriate investigation and additional testing can proceed if indicated.

In collaboration with CDC, the state health departments that conducted this analysis developed a process to assist public health agencies in determining response measures that consider risk factors and pretest probability of measles infection when measles virus is detected by syndromic PCR panels (Box). Investigators should determine MMR vaccination status and date of receipt and assess whether the person has epidemiologic risk factors for measles. Because signs and symptoms of vaccine reactions can be similar to those associated with measles infection (9), clinical presentations consistent with the measles case definition should be interpreted within the context of identified risk factors for measles. If a person was not recently vaccinated, public health response measures to prevent measles virus transmission are necessary and should include specimen referral for genotyping. However, if the person who received the positive test result was vaccinated during the preceding 21 days and has no epidemiologic risk factors (e.g., travel to a region with endemic measles or a known exposure to a person with measles), further public health response is likely unnecessary, because the positive test result likely represents detection of the attenuated vaccine strain measles virus. For persons who were vaccinated within the preceding 21 days and have a risk factor for measles, public health measures to prevent measles transmission should continue while testing for measles vaccine virus by MeVA or genotype. Genetic confirmation of vaccine reaction might also be considered if a person was vaccinated >21 days earlier and has no epidemiologic risk factors.

Limitations

The findings in this report are subject to at least three limitations. First, 12 persons with measles detected by syndromic PCR panels were not reported to public health agencies, and descriptions of their clinical signs, symptoms, and risk factors are limited to clinician recall and documentation, increasing susceptibility for recall bias. Second, the small number of syndromic PCR panels and measles detections in only a subset of states limits generalizability. Finally, because of delayed reporting to public health officials, only two specimens underwent confirmatory molecular testing.

Implications for Public Health Practice

During the first year of measles inclusion in commercial syndromic multiplex PCR panels, approximately 1% of tests reported a positive measles test result after recent routine childhood MMR vaccination. These positive test results most likely represented detection of measles vaccine virus in patients with rashes from a vaccine reaction or other cause, rather than measles infection. To facilitate appropriate public health response, clinicians should notify their local public health agency immediately if they are concerned about possible measles infection or patients receive positive measles test results. Commercial laboratories should critically evaluate use of measles in syndromic PCR panels and rapidly notify public health officials of any measles-positive specimens. When measles infection is not clinically suspected but detected by syndromic PCR testing, public health agencies should consider the likelihood of incidental measles vaccine virus detection by assessing measles vaccination history and risk factors. Because 1 dose of MMR vaccine is 93% effective in preventing measles (4), if a person recently received MMR vaccine and has no risk factors for acquiring measles, additional public health response is likely unnecessary. However, if a person has not recently received MMR vaccine, subsequent public health response should include necessary measures to prevent measles transmission. For a person who recently received MMR vaccine and has a risk factor for acquiring measles, additional testing for measles vaccine virus is needed to determine subsequent response measures.