Measles Outbreaks Still Occur: How the APHL/CDC VPD Reference Centers Are Working to Identify Them

1981 poster promoting measles vaccination that says, "Make Measles a Memory." Photo source: CDC

By Donna Campisano, specialist, Communications, APHL

A vaccine to prevent measles has been available since 1963. And yet this highly contagious disease, characterized by fever, respiratory symptoms and a telltale body rash, is still with us.

While measles is thought of as a childhood illness, its outcomes can be far from benign.

According to the Centers for Disease Control and Prevention (CDC), 1 in 5 unvaccinated people who contract the virus will be hospitalized. One in every 20 children with the disease will develop pneumonia. And up to 3 of every 1,000 children infected will die from the neurological and respiratory complications measles cause.

Disease Outbreaks and the Role of Vaccine Preventable Disease Reference Centers

Thanks to a robust vaccination program, measles practically disappeared from this country and was declared eliminated in the US by the World Health Organization (WHO) in 2000. But increased vaccine hesitancy and a return to global travel (most cases of measles in this country are imported from elsewhere) following the pandemic have officials concerned.

As of the first week in March, 45 measles cases from 17 jurisdictions have been reported to the CDC in 2024. Compare that to 58 total cases from 20 jurisdictions reported in all of 2023. Florida accounts for 10 of those cases, nine in one county alone. While the vast majority are children and teens, one is an adult. All 10 cases were reported in February, demonstrating how quickly cases can spread. And more cases are popping up every day. The CDC recently sent a team to Chicago to help with a measles outbreak clustered mostly in a migrant shelter. Eight cases have been confirmed in about as many days.

While the number of cases reported thus far in this country isn’t staggering, the same can’t be said for other parts of the world where vaccination rates are particularly dismal. According to WHO, measles cases increased 18% globally from 2021 to 2022 and deaths jumped by 43%.

In 2013, APHL, in partnership with CDC, established four Vaccine Preventable Diseases (VPD) Reference Centers to help reduce the diagnostic load of state laboratories and assist with the pathogen typing that’s necessary to detect the origin and spread of disease outbreaks.

These four centers—located in California, New York, Wisconsin and Minnesota—perform molecular testing for the viruses that cause measles, mumps, rubella (German measles), chickenpox, enterovirus (which can cause diseases like polio and hepatitis A) and MERS-CoV (Middle East respiratory syndrome-related coronavirus). The Wisconsin and Minnesota centers also perform bacterial pathogen testing.

Testing, both diagnostic and characterization, is performed using standardized methods developed by CDC and is available to public health departments free of charge. Submitting sites are assigned to one or two VPD Reference Centers depending on what services they need. Test results are reported to the submitting site and to CDC.

Detecting Outbreaks in Real Time

How do VPD Reference Centers help curb outbreaks?

To reduce vaccine-preventable diseases like measles and the burden they cause, officials—from clinicians to public health professionals to lab scientists—need details about what diseases are circulating where. And the more immediate the information, the more immediate a response.

To that end, APHL will be launching a VPD dashboard in the next few months. The VPD Reference Centers will submit monthly or bimonthly data reports to APHL detailing the number of specimens submitted to them for testing, how many tests were performed per pathogen and the number of positive specimens detected. That information will be fed into the publicly available dashboard.

The dashboard, along with the rapid detection of disease provided by member labs and the outreach conducted by public health officials, will play a pivotal role in responding to disease outbreaks. APHL and CDC will continue to work together to provide training and improve knowledge in identifying and curtailing disease outbreaks, whatever form they take, wherever they erupt.

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Public health labs at center of 2017 mumps outbreaks: ‘This really could be a new normal for mumps’

Public health labs at center of 2017 mumps outbreaks: ‘This really could be a new normal for mumps’ | www.APHLblog.org

by Kim Krisberg

As of December 2, more than 4,900 cases of mumps had been reported to the Centers for Disease Control and Prevention in 2017. That’s less than the previous year’s case count of more than 6,000, but it’s still thousands more than any year in over a decade. Peter Shult, who works in one of the nation’s four Vaccine Preventable Disease Reference Centers, believes the last two years may be the new normal.

“This is happening in well-immunized populations,” said Shult, PhD, director of the Communicable Disease Division at the Wisconsin State Laboratory of Hygiene. “So (unlike measles outbreaks), it’s not an issue that people are unvaccinated — it’s probably more that we have a less-than-perfect vaccine. And with no new mumps vaccine coming down the pipeline anytime soon, this really could be a new normal for mumps.”

In early January, the Wisconsin Department of Health Services reported 62 confirmed mumps cases since November 2016, mostly clustered on college campuses. Many fellow Midwestern states — Illinois, Indiana, Iowa, Michigan, Minnesota, Missouri and Kansas — reported mumps cases as well this year, some outbreaks numbering in the hundreds. In Wisconsin, 65% of those diagnosed with mumps had received two doses of vaccine, 6% had received one dose and 29% had an unknown immunization history. Wisconsin’s state public health lab conducts all the mumps testing for the state, but as a Vaccine Preventable Disease Reference Center, it also provides mumps testing for state public health labs that drew down such testing capacity as vaccine-preventable outbreaks became less common in the U.S.

Since summer 2016, according to Shult, the Wisconsin lab has received about 1,300 specimens for mumps testing — that’s a significantly higher number than in recent years, he added. Hundreds of those samples came in from other states, most notably from Alabama and Missouri, both of which experienced recent mumps outbreaks on university campuses. Of those 1,300 samples, about 220 tested positive for mumps, said Tim Davis, senior microbiologist in the Wisconsin lab.

Responding to a surge in mumps testing demands, especially during the typically busy flu season, means a “pretty substantial uptick” in the lab’s overall workload, said Shult, who also serves as the lab’s associate director. Fortunately, as one of the country’s four reference labs, the Wisconsin lab has built up the capacity to handle such surges. Lab technicians processed up to 20 mumps specimens a day, with a goal of delivering results the same day they’re received for both in-state and out-of-state samples. That speed is essential for the epidemiologists working to get ahead of a spreading outbreak and stop transmission. If a specimen comes back positive for mumps, it undergoes genotyping to determine if it’s linked to a larger outbreak.

Commercial labs in Wisconsin can do diagnostic testing for mumps, Shult said, but not as quickly and not as accurately as the state public health lab.

“It’s really the public health lab,” he said, “that’s on the front line.”

To the west in Washington state, the mumps case count from October 2016 to September 2017 was at 891 — that’s at least 700 more cases than any year since 2005. As of the end of August, the Washington State Department of Health Public Health Laboratories had received just more than 2,600 specimens for mumps testing, according to Ailyn Perez-Osorio, PhD, supervisor for molecular PFGE and virology. She said lab staff worked with epidemiologists to triage the daily flow of mumps specimens, using criteria such as date of illness onset and the risk of disease transmission to prioritize samples for testing. The lab also gathered results from commercial labs and shipped specimens for testing to the Minnesota Public Health Laboratory Division, which serves as a Vaccine Preventable Disease Reference Center.

One goal of the triage system, Perez-Osorio said, was making sure the lab’s rapid mumps testing capacity directly supported outbreak containment efforts, instead of only providing diagnostic results.

“We took a lot of consideration with our testing decisions to make sure we weren’t using up all of our resources,” Perez-Osorio said. “We had to preserve our capacity to prioritize testing for the public health response over diagnostic testing.”

The lab’s mumps screening is “highly complex,” she said, requiring RNA extraction and real-time polymerase chain reaction (RT-PCR) testing. Testing specimens in batches of about 30, it takes about five hours to get a result. Perez-Osorio said while additional staff were trained in mumps testing, the outbreak was simply too big to handle all the specimens without triaging the need and depending on outside help.

“People often stayed late, the majority were having to work extra hours — it was very taxing because of how long the outbreak went on for,” she said.

As of September, Perez-Osorio said mumps testing in the Washington lab had slowed to every other day, instead of every day, and the outbreak was tapering down. Thankfully, she said, the bulk of the outbreak didn’t happen during the summer when the same staff responsible for mumps testing is busy responding to peak rabies testing season.

On the issue of mumps spreading among vaccinated populations, Perez-Osorio said “it leaves a lot of questions.” On the flip side, she said her main concern is with pockets of anti-vaccine sentiment.

“It’s definitely hard to see people going in that direction because vaccines have brought so much safety to our communities,” she said. “It seems people have forgotten how horrible mumps and measles were back in the day.”

Emerging research is pointing to waning mumps immunity as a contributor to recent outbreaks. For example, a study published earlier this year in Frontiers in Physiology that studied mumps outbreaks in Scotland found that “waning immunity is the main factor in a repeated pattern of outbreaks.” In another study published in September in the New England Journal of Medicine, researchers studied the impact of a third dose of the measles-mumps-rubella vaccine in stemming an outbreak on an Iowa college campus. They found the third dose did improve mumps control and that waning immunity likely contributed to the outbreak’s spread. In late October, CDC’s Advisory Committee on Immunization Practices recommended a third dose of mumps vaccine as part of public health’s outbreak response.

Shult, at the Wisconsin State Laboratory of Hygiene, said just a handful of years ago, he wouldn’t have argued that all public health labs needed the complex testing capacity to deal with mumps outbreaks. As vaccine-preventable disease outbreaks became less common in the U.S., it just wasn’t practical for every state public health lab to sustain state-of-the-art testing technologies for the diseases. And, in fact, current funding levels wouldn’t even support all 50 states in building and maintaining that kind of lab capacity, which makes the country’s four Vaccine Preventable Disease Reference Centers all the more important.

Today, however, Shult said it’s “reasonable” to expect annual mumps outbreaks into the foreseeable future. And if that’s the case, he said it might be time to consider strengthening mumps testing across state public health labs.

“Moving forward, we should be asking ourselves if this is a capability that more states need or maybe we need to expand this part of the reference lab,” he said. “One could argue that states will be inundating reference labs (with mumps testing) in the future, and so we have to at least ask those questions.”

For more on recent mumps outbreaks, visit www.cdc.gov/mumps/outbreaks.html.

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Public health labs aren’t just on the frontlines of vaccine-preventable outbreaks. They’re often the only line.

Public health labs aren’t just on the frontlines of vaccine-preventable outbreaks. They’re often the only line. | www.APHLblog.org

by Kim Krisberg

In the U.S., rates of vaccine-preventable diseases are so low that many commercial labs don’t even have the ability to test for them anymore. The shift reflects the hard work of decades-long immunization efforts. But it also means that when there is a vaccine-preventable outbreak, just about all of our rapid diagnostic capacity resides in one place: the public health lab.

The latest example of this is in Minnesota, where a measles outbreak hit 78 confirmed cases as of June 16. The state is typically home to less than a handful of measles cases each year — most years, the case count is between zero and two. At the Minnesota Department of Health’s Public Health Laboratory, which is the only lab in the state that can do real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing for measles, staff have received more than 800 specimens for measles testing since April, with a goal of fully processing each one the same day it’s received. To stop an outbreak, both speed and accuracy are critical.

Fortunately, Minnesota lab workers are trained and ready to provide both. But sustaining that kind of surge capacity over the long run and in the face of new and emerging disease threats is always challenging — even in the best funding environments.

“We’ve spent a lot of time increasing our capacity over the last 10 years and we’re seeing that capacity being put to work,” said Sara Vetter, PhD, manager for infectious diseases at the Minnesota Public Health Laboratory. Vetter noted that Minnesota last experienced a measles outbreak in 2011 — “and that one seemed huge and it was just 26 cases of measles.”

This year’s measles outbreak is almost entirely concentrated in a Somali community in Minnesota’s Hennepin County, home to more than 1 million residents. The outbreak officially began on April 10, the same day the lab confirmed the first positive case. Nearly all the cases are among unvaccinated children younger than 4 years old. No deaths have occurred, though about a quarter of infections have led to hospitalization.

Inside the public health lab’s Virology/Immunology Unit, technicians track the measles outbreak using a rRT-PCR test, which allows them to detect the highly contagious virus much quicker than private labs that can perform serological testing for measles antibodies. That quickness is key, said Anna Strain, PhD, supervisor of the Virology/Immunology Unit, because it means the health agency’s epidemiology team can then quickly locate people who may have been infected and get ahead of the outbreak before it spreads.

The rRT-PCR test may be quicker than serological testing — it detects measles RNA, as opposed to measles antibodies, and is less confounding than serology — but it’s not completely definitive, Strain said. After conducting rRT-PCR testing on each of the more than 800 specimens that come into the lab, any positive specimens undergo genotyping to determine if the patient is infected with a wild-type measles strain or if the rRT-PCR is simply picking up on the live attenuated virus that’s contained in the measles-mumps-rubella vaccine. Genotyping can also determine if the case is related to the larger outbreak. (On a side note: In addition to its regular testing responsibilities, the Minnesota Public Health Lab is partnering with the Centers for Disease Control and Prevention and Canadian public health officials to develop a PCR test that’s specific to the vaccine strain of measles. Such an test would be particularly helpful in an outbreak, Strain said, because technicians could then forgo the extra step of genotyping.)

“It’s actually meant quite a lot of maneuvering,” Strain said, referring to the logistics of responding to the surge in measles testing. “In some ways, we were lucky that it happened in April when flu season was dying down — otherwise a number of testing staff trained for measles testing would have also been doing flu testing. If the (measles outbreak) had happened any sooner, it would have been really hard to keep up.”

From start to finish, the measles test takes about five hours, Strain said. Lab staff can process 10 measles specimens at a time and up to 30 specimens in day — though that’s a stretch, she noted. In comparison, the lab can process up to 150 flu samples in day and often does.

“As hard as it’s been in the lab, it’s been even harder for our epidemiologists — they’ve had more than 7,000 contacts to trace and to follow up on,” said Joanne Bartkus, PhD, director of the Minnesota Public Health Laboratory. “It’s been daunting for all of us.”

Vetter said that most of the lab’s current surge and response capacity is thanks to federal public health preparedness funding as well as funding from CDC’s Epidemiology and Laboratory Capacity for Infectious Diseases (ELC) Program, both of which currently sit on the budgetary chopping block. On preparedness, President Trump’s fiscal year 2018 budget proposal calls for cutting CDC’s emergency preparedness budget by $136 million — that’s on top of years of preparedness cuts public health agencies have already absorbed. (In total, Trump’s budget calls for cutting CDC’s budget by $1.2 billion, or a whopping 17 percent.) The ELC, on the other hand, is wholly entwined with the Affordable Care Act’s Prevention and Public Health Fund, which allocates $40 million in annual ELC funds to state and local health departments in every state. Under current ACA repeal-and-replace bills in Congress, the Prevention and Public Health Fund would disappear.

And while ELC and preparedness monies don’t categorically support the Minnesota lab’s vaccine-preventable disease work, Vetter said the funds have been essential in ensuring the lab can quickly scale up its response, regardless of whether the emergency is vaccine-preventable or not. In other words, the Minnesota lab has spent years building an all-hazards response system that readies it to face any health threat that lands at its doorstep. Being able to sustain that nimbleness, however, would be at risk if funding declined.

“Without that funding, we’d probably have to choose what we respond to because we’d run out of people and out of machines — we just couldn’t keep up,” Vetter said. “If our funding gets cut, we can’t maintain our machines, we can’t replace machines, we can’t train more people … what we do is very complex.”

At the same time the Minnesota Virology/Immunology Unit has been responding to the measles outbreak, it’s also been responding to a mumps outbreak on the University of Minnesota-Twin Cities campus, providing surge testing for a mumps outbreak in Washington state that recently hit nearly 900 cases, and taking in and testing about 20 specimens a week for Zika virus. All of that is in addition to its more regular duties, like rabies and West Nile monitoring.

In the wake of the measles outbreak, Minnesota Health Commissioner Edward Ehlinger, MD, MSPH, called on state policymakers to create and support a public health response contingency fund. Such a bill was introduced into the Minnesota House of Representatives for consideration in May.

“Our commissioner always says that data are the coins of public health,” Bartkus said. “And it’s the public health lab that creates that data.”

As of late May, Strain said the Minnesota measles outbreak — which exceeded total U.S. cases for all of 2016 — seemed to be entering a “tapering phase.” As she said that, however, she paused — and quickly added “we all just knocked on wood.”

 

For more on the Minnesota measles outbreak, visit www.health.state.mn.us/divs/idepc/diseases/measles.

 

 

 

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