If you live in Massachusetts or Michigan, you are probably hearing a lot these days about something called EEE. If not, that combination of vowels may cause you to draw a blank.

But 2019 is turning out to be a big year for Eastern equine encephalitis, generally called EEE — “triple E” — for short. In fact, it’s been more than a half-century since there have been this many reported EEE cases in people, the Centers for Disease Control and Prevention has confirmed.

If EEE is just hitting your radar, you probably have questions. We’ve put together some answers.

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What is EEE?

Eastern equine encephalitis is one of several New World encephalitis viruses. It is also what is known as an arbovirus — viruses that are spread by a mosquito or other arthropod. West Nile is another kind of arbovirus.

The virus is found in the northeast of the country as well as along the Great Lakes and the Gulf Coast. It is also occasionally found in Canada; there has been at least one human case reported in Ontario, in 2016.

What kind of illness does it cause?

In a word: severe.

Actually, some people have mild, flu-like illness when they become infected, said Marc Fischer, a medical epidemiologist with the Center for Disease Control and Prevention’s arboviral disease branch, located at Fort Collins, Colo.

But about 20% of the people infected develop clinical illness and about half of them develop neuroinvasive disease — in which the virus moves into and inflames the brain, triggering encephalitis.

It can start with the sudden onset of a headache, high fever, chills, and vomiting, and lead to disorientation and seizures.

The death rate is high: About a third of EEE patients who develop encephalitis die. And survivors of severe EEE often have lasting side effects, including mild to severe brain damage.

“It is the highest case fatality of all of the arboviruses that occur in the United States,” Fischer said.

“It’s a devastating disease,” said Scott Weaver, an arbovirus expert at the University of Texas Medical Branch in Galveston.

How common is EEE?

That’s the good news. It is not common at all.

“It is a severe disease … but the numbers are small, and much smaller than for West Nile virus,” Fischer said.

From 2009 to 2018, 21 states recorded 72 human EEE cases, the CDC reports. Most had only single cases during that decade; Florida (13), Massachusetts (10), New York (8), Michigan and North Carolina (7), and Georgia (6) are the only states to have recorded more than a handful of human cases over that period.

The CDC says the United States sees an average of seven cases a year, with the typical range varying between three and 15 cases a year.

That is far less common than West Nile virus cases, of which there are generally hundreds each year. To date this year, there have been 468 cases of West Nile virus reported to the CDC, including 21 deaths — and this is not a particularly bad year for West Nile.

But it seems to be shaping up to be a bad year for EEE, isn’t it? Why?

Seven states have reported 28 cases of EEE so far this year, with Massachusetts — a historic hot spot for the virus — recording 10 cases and Michigan reporting eight. New Jersey and Rhode Island have each reported three, Connecticut has reported two, and North Carolina and Tennessee have recorded one each.

Nine of the infected people have died to date.

This case count is the highest number of human cases in decades — there hasn’t been a year this bad since sometime prior to 1964. (EEE only became a notifiable disease — cases must be reported to the CDC — in the early 1960s.)

The previous peak over that timeframe came in 2005, when there were 21 cases.

Hyacinth Empinado/STAT

“I guess what’s a little bit concerning is that we’re already at the upper limit of the normal range and it’s still only mid-September,” said Weaver, who heads the microbiology and immunology department at UTMB. “In Massachusetts and other areas of the northeast and mid-Atlantic, we may have another month or even more of active transmission and more cases to come.”

Some years are more active than others when it comes to these kinds of viruses, explained Fischer.

“Every few years you get a higher number of cases. And they can be in different places. Massachusetts is one of the states that has historically had a higher number of cases. But there are other states. Florida typically has the most cases overall,” Fischer said. “So it moves around, it occurs in different places in different years. And you have high and low years.”

The reasons for that aren’t entirely clear, but it’s definitely influenced by EEE’s complicated life cycle.

What is the virus’ life cycle?

If you know anything about West Nile virus, this is going to sound familiar. The virus infects mosquitoes, which feed on birds, infecting them in the process. It’s what’s known as an amplification cycle: Uninfected mosquitoes that feed on infected birds become infected themselves, building up more and more virus in a particular area.

With EEE, the mosquitoes involved in this cycle are called Culiseta melanura, which live in freshwater swamps and feed on songbirds. It’s thought these mosquitoes feed almost exclusively on birds.

At a point — generally from July onward — there’s enough of the virus in the mosquitoes and birds in a location that it spills over into other populations. Different types of mosquitoes — some Culex mosquitoes that can transmit West Nile virus, for instance — feed on infected birds and pick up the virus. These different mosquitoes, known as bridging vectors, can then draw other species such as humans into EEE’s web.

Once an area has had a hard frost, mosquito activity drops off, and the virus effectively goes dormant until the next spring. Weaver said along the Gulf Coast, where hard frosts are uncommon, human cases can occur at pretty much any time of the year.

Why more spillovers happen some years than others is not certain.

Climatic conditions likely play a role; a mild winter, for instance, may allow the amplification cycle to start quicker, producing more virus in the environment, Weaver said.

Many of the studies looking at the virus’ life cycle are decades old, and may not fully reflect the current circumstances.

“A lot of our understanding of the basic enzootic transmission cycle comes from work done more than 60 years ago,” Weaver said. “And there have been very few especially field oriented projects on this avian cycle done for many decades.”

When EEE spills out of its mosquito-songbird cycle, which species does it infect?

The second E of EEE is a clue. The first known outbreaks of eastern equine encephalitis actually occurred in the 1800s in horses — long before what was causing the disease was discovered in 1930s.

Deer also contract the virus, as on occasion do dogs. But these other animals, like humans, are considered dead-end hosts in the EEE transmission cycle. We don’t contribute to its onward spread.

The virus is very dangerous for horses and they can and should be vaccinated against it in places where EEE is known to spread.

If horses can be vaccinated against EEE, can people?

Not unless you are a researcher studying EEE. Weaver and some other scientists who study the dangerous virus have been vaccinated with an unlicensed vaccine developed by U.S. military laboratories, but it’s not available to the general public.

Multiple experimental EEE vaccines for people have gone through the preliminary stages of development, but because cases are so uncommon, there isn’t a human market for EEE vaccine. Given the very high cost of developing, testing and licensing a vaccine — north of $1 billion — without a market there’s no chance one will get made.

Darci Smith, an arbovirus expert and chief of the immunodiagnostics department at the Naval Medical Research Center at Fort Detrick, Md., brought up West Nile virus to make that point.

When West Nile was first found in North America in 1999, there was deep concern. And in a number of the years since, there have been cases in the thousands. Like EEE, West Nile can cause severe illness and death. In fact, it is believed to have killed more than 2,000 Americans between 1999 and 2016.

Sanofi (SNY) Pasteur began to develop a West Nile vaccine, but eventually shelved the project after concluding there weren’t enough cases or enough public concern to guarantee sales. Pharmaceutical companies don’t make what they can’t sell.

“And there’s still no licensed [West Nile] vaccine,’’ said Smith.

If there are no commercial prospects for a vaccine, why does EEE vaccine work continue?

The Department of Defense sees EEE as a potential biological weapons threat, because of the severity of disease it causes and its high case fatality.

But for the Pentagon’s interest, there would be little EEE research, Weaver and others said.

This story has been updated to reflect increases in the number of states that have reported cases in 2019 as well as the case count and death toll.

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  • Thanks for this information. I think the takeaway for citizens is that the “amplification” of the virus starts sooner and runs longer because of warmer longer summer weather. The virus is spread among birds by mosquitoes species that feed only on birds, and then another species, which bites mammals and birds, spreads it to humans. Longer, hotter, more humid summers mean more time to spread. The solution is not a vaccine (which must be pretty gnarly)–it’s two things. Better surveillance of the virus among mosquito populations, which means more trapping in the field, more lab tests and more money, will give humans advance warning. And then we need better laws regulating greenhouse gasses. Your elected officials are shirking their responsibility to protect the people and the planet. Burning fossil fuels causes the planet to heat up and this extends the hot season, which means this dangerous virus spreads. Get them to do their jobs!

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