As ongoing outbreaks threaten the US's measles elimination status, laboratories face increasing pressure to rapidly identify cases and inform the public health response. Benjamin Bradley, Vice Chair of the College of American Pathologists Microbiology Committee, explains why outbreak response is overdue for improvement.
Why is measles becoming a growing concern in the United States, and why is there a risk of losing the country's measles elimination status?
Over the past 20 years, national vaccination coverage has gradually declined, with the trend accelerating in recent years because of several factors, including disruptions during the COVID-19 pandemic, growing skepticism about vaccine safety, and increasing anti-science rhetoric. As a result, some communities in the US now have measles-mumps-rubella (MMR) vaccination coverage below 50 percent. These under-vaccinated communities, particularly in Texas, South Carolina, and Utah, have become hotspots for outbreaks. To prevent sustained measles transmission, approximately 95 percent of a population must be vaccinated. Because the MMR vaccine is a live-attenuated vaccine, some patients – including those who are immunosuppressed or pregnant – cannot receive it and therefore rely on herd immunity for protection.
From a clinical perspective, the risks associated with measles extend well beyond the flu-like illness and rash that many people associate with the disease. Acute complications include pneumonia and encephalitis, but measles can also have serious long-term consequences. One is a phenomenon known as immune amnesia, in which measles infection reduces preexisting immunity to other pathogens, increasing susceptibility to secondary infections. Another is subacute sclerosing panencephalitis (SSPE), a rare but progressive and fatal neurologic disease that can develop years after the initial infection has resolved.
A country is considered to have eliminated measles when there is no sustained endemic transmission for more than 12 months. The US has reported measles cases almost continuously since January 2025. However, the Pan American Health Organization (PAHO), which determines whether countries maintain their measles elimination status, has not yet reevaluated the US. That review, originally scheduled for earlier this year, has been postponed until November. In making its determination, PAHO considers both epidemiologic evidence and viral genetic sequencing data.
What are the biggest challenges laboratories face in diagnosing measles, and why is molecular testing so important?
Currently, there are no US FDA-cleared or approved assays for measles, so testing relies on laboratory-developed tests (LDTs). Developing and validating these assays can be beyond the capacity of many clinical laboratories.
Historically, diagnosis of acute measles has relied on immunoglobulin M (IgM) serology. However, IgM results may be falsely negative for up to three days after rash onset. Polymerase chain reaction (PCR) testing can detect infection earlier, including before the characteristic rash develops. This is particularly important because patients can transmit the virus before the rash appears.
Molecular testing also offers another important advantage. Up to 5 percent of people who receive the MMR vaccine develop a mild measles-like rash, but these patients are not infectious. Specialized PCR assays can distinguish wild-type measles virus from the attenuated vaccine strain, helping clinicians determine whether a rash is caused by natural infection or recent vaccination.
This distinction is especially valuable during an outbreak. For example, an unvaccinated person who is exposed to measles may choose to receive the MMR vaccine. If that individual subsequently develops a measles-like rash, molecular testing can determine whether the rash is due to infection with wild-type virus or the noninfectious vaccine strain.
What can pathologists and laboratory professionals do to ensure accurate testing and prepare their laboratories for potential outbreaks?
I think the most important step is to have a testing plan. Whether or not your laboratory performs measles testing in-house, it's essential to know how suspected cases will be managed. That includes contacting your state or local public health laboratory to understand its testing capacity, as some may be able to handle all testing while others may have limited resources. Many reference laboratories also now offer measles testing, so it's important to ensure the correct specimen is collected and transported appropriately.
Because many physicians may be unfamiliar with the availability of measles PCR testing, laboratories should work with their infection prevention teams and infectious disease physicians to develop a standardized measles testing order set that includes PCR.
For laboratories performing clinical measles testing, ongoing quality assurance is equally important. Assays should be monitored with appropriate quality controls to ensure consistent performance. As a member of the College of American Pathologists' Microbiology Committee, I've helped develop a new proficiency testing survey that includes several vaccine-preventable viruses, including measles, mumps, rubella, and varicella-zoster virus. The survey includes both vaccine and wild-type measles strains to help laboratories verify that their assays accurately distinguish between them.
Once a measles case is confirmed, what role do laboratories play in monitoring disease spread and supporting public health efforts?
Public health laboratories rely on clinical laboratories for timely access to specimens and the patient information needed to support outbreak investigations. For that reason, laboratories should have established processes for sharing specimens and relevant clinical information with their state or local public health laboratory.
Because outbreak situations evolve rapidly, clear communication between clinical and public health laboratories is essential. Laboratories should be prepared to receive updated guidance and adapt their workflows as circumstances change. For example, early in an outbreak, it may be appropriate to submit all positive specimens to the public health laboratory for sequencing. As the outbreak grows and transmission patterns become better understood, sequencing every specimen may become unnecessary or impractical. Laboratories should be prepared to adjust their submission practices accordingly to avoid placing unnecessary strain on laboratory resources.
Are there any advances in measles diagnostics that could improve detection or outbreak response in the future?
It may sound surprising, but PCR testing is actually a relatively recent advance in measles diagnostics. Until around 2020, measles PCR testing was largely limited to public health laboratories. That was partly because measles cases were so uncommon in the US and partly because, when measles was widespread in the 1960s and 1970s, PCR technology didn't yet exist.
Since then, clinical microbiology has undergone a molecular revolution. Modern platforms have automated many steps in the testing process, including nucleic acid extraction, amplification, and result reporting, allowing laboratories to deliver results much more quickly. During an outbreak, rapid turnaround times are critical because they enable hospitals to implement infection control measures, such as airborne isolation, while allowing public health officials to begin contact tracing and provide postexposure prophylaxis, including vaccination or intravenous immunoglobulin (IVIG), when appropriate.
We also now have much more robust whole-genome sequencing capabilities. These data help us track how the virus is spreading, distinguish between circulating strains, and monitor for genetic changes that could affect the performance of diagnostic assays.
What is the most important message you would like pathologists and laboratory professionals to take away about measles testing and preparedness?
We are now seeing the return of diseases that once seemed close to elimination, such as measles and pertussis, at levels not observed in decades. As a result, testing that was once largely confined to public health laboratories – low-volume testing for relatively uncommon pathogens – is becoming increasingly relevant for clinical laboratories. Laboratories should evaluate how they can support timely diagnosis for their patients. That doesn't necessarily mean developing in-house testing, but it does mean having a clear plan for accessing and performing appropriate testing when cases arise.
What makes measles outbreaks particularly challenging is the virus's extraordinary transmissibility. A single case introduced into an under-vaccinated community can quickly lead to hundreds more. That rapid growth can create testing surges, delays, and reagent shortages – many of the same challenges laboratories experienced during the COVID-19 pandemic. We should use the lessons learned from both past and current outbreaks to build a more resilient laboratory infrastructure, and that effort will require active participation from laboratories of all sizes.
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