Why the huge surge in EEE cases? Federal rules requiring quick sample disposal mean we may never know

A massive surge in human cases of Eastern equine encephalitis this autumn has raised urgent questions about whether the dangerous virus has changed. But federal regulations that are leading most states to quickly destroy any positive EEE samples they find will stymie future efforts to come up with any answers, worried arbovirus experts warned.

The World Reference Center for Emerging Viruses and Arboviruses has been trying to amass specimens from this year’s EEE outbreak to place in its repository, the world’s largest and a resource from which researchers worldwide draw. But because EEE has been deemed a select agent — those are pathogens that pose a bioterror threat — most state laboratories that find the virus in specimens from mosquitoes, birds, or mammals (including humans) must destroy the material within seven days. Only labs that are certified to handle select agents can retain samples past that time.

If uncertified state laboratories can arrange to ship specimens to the reference center — housed at the University of Texas Medical Branch in Galveston — within the seven-day limit, they are allowed to do so. But transferring a select agent is expensive and involves a mountain of paperwork.

Even though the reference center — funded by the National Institutes of Health — will cover the shipping costs, most labs in states dealing with EEE this fall have been unwilling or unable to take on the extra work, said Scott Weaver, director of the repository and a virologist who specializes in arboviruses, which are spread by mosquitoes, ticks, or other arthropods.

“During the past month or two we’ve reached out to all the major state health labs where these cases are being detected. And only one of those has been willing to send us any samples. It was New Jersey,” Weaver told STAT.

“It’s a huge hassle for them. In the middle of this emergency situation, the last thing you want to do is worry about spending half your day to ship a sample out,” he said. “They understand the value of these samples but … if they had some additional support to do this, if the time window would be extended a little bit under these kinds of conditions, I think it would be more likely that they’d be able to help us.”

There is actually a provision in the select agent rules that allows uncertified state laboratories to ask for an exemption to hold on to samples for a little longer. Weaver was unaware of that provision and said a number of state officials he raised it with likewise didn’t know it existed.

The division of select agents and toxins at the Centers for Disease Control and Prevention — which oversees the federal Select Agent Program in conjunction with the Department of Agriculture — said in an email that requests for extensions are dealt with on a case-by-case basis, with one-week extensions having been granted in the past to allow time to make necessary shipping arrangements. The World Reference Center helped New Jersey secure a short extension — a couple of days — to arrange to ship its sample, officials of the center said.

Eastern equine encephalitis, which is found in the eastern half of the U.S. and some parts of southeastern Canada, causes mild flu-like illness in most people who contract the virus from an infected mosquito. But about 20% of people develop more serious illness and in about half of them the virus moves into the brain, causing encephalitis. Roughly one-third of people who develop encephalitis die from the disease, and survivors are often left with long-term cognitive damage.

This year nine states have reported a total of 37 human cases — an off-the-charts total for a virus that most years is seen to cause fewer than 10 cases nationwide. (Typically only the severe cases come to medical attention.)

More than 20 states have found EEE this year in at least one species — in pools of mosquitoes, birds, people, horses, deer, alpaca, and even a wolf cub in a Michigan zoo. The virus has been found in dozens of counties in eastern and central states, as far west as Minnesota in the north and eastern Texas to the south.

Despite all that activity, the reference center so far has received only the New Jersey sample — brain tissue from an infected deer from which virus could be extracted. Weaver said Connecticut, which has recorded four human cases — three of them fatal — has indicated it will share samples eventually. Its public health laboratory is certified to work with select agents, so does not have to follow the seven-day rule.

The reality is that at this point, many of this season’s samples have already been destroyed — a scientific tragedy, said Shannan Rossi, an associate professor of infectious diseases virology at the University of Texas Medical Branch.

“Within a couple of years we’re going to look back and wonder why we didn’t have the samples to try to figure out what was going on at the time. And once they’re gone, they’re gone,” she said.

Some state labs with select agent certification may still hold some samples, with plans to do their own research. That may be the case in Massachusetts, which recorded 12 human cases this year, the most of any state. At least three of those infected people died.

“While the federal Select Agent Program does indeed place significant restrictions on the storage, transport, and provision of public information about EEE virus and other select agents, the Massachusetts Department of Public Health is working internally, and in collaboration with other public health partners, to perform the genetic analyses that are necessary to help understand the observed epidemiology,” state epidemiologist Dr. Catherine Brown said via email. She declined to be interviewed.

Brown’s comment does not make clear if Massachusetts still has the types of material — brain tissue from fatal cases, or pools of mosquitoes that tested positive — from which actual viruses could be extracted. Most laboratories diagnose EEE using polymerase chain reaction — PCR — a test that looks for and amplifies genetic material that can be used to generate a sequence of the virus.

Comparing viral sequences can answer some questions. But having the actual virus to work with broadens the scope of the science that can be done, Weaver said. “We need virus isolates to allow scientists to do experimental work on pathogenesis, virulence, mosquito transmission, etc. It is unlikely that sequences will give us a complete answer regarding the magnitude of the outbreak this year.”

Weaver said if state labs are concerned about sharing samples before they have an opportunity to conduct their own studies, restrictions can be written into the transfer agreement that limit how the samples are used so that other labs couldn’t beat them to publication.

Correction: An earlier version of the article misstated the number of extensions granted this year. There has been one.