I if you live in Massachusetts or Michigan, you probably hear a lot about these days called EEE. If not, that combination of vowels can make you draw a blank subject.
But 2019 is proving to be a big year for Eastern Equine Encephalitis, commonly called the EEE – "triple E" – in short. And if it hasn't hit your radar yet, it probably will.
We think you have questions. We have compiled some answers.
What is EEE?
Eastern encephalitis in horse is one of several encephalitic viruses in the New World. It is also what is called 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 sometimes found in Canada; at least one human case has been reported in Ontario 2016.
What type of illness does it cause?
In one word: difficult.
In fact, some people have mild, flu-like illness when infected, said Marc Fischer, a medical epidemiologist with the Center for Disease Control and Prevention's Arboviral Nuclear Branch, located at Fort Collins, Colo.
But about 20% of those infected develop clinical disease and about half of them develop neuroinvasive disease – where the virus moves into and inflates the brain, triggering encephalitis.
It can start with a sudden onset of headache, high fever, chills and vomiting and lead to disorientation and cramps.  The death rate is high: About one 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 death rate in all arboviruses that occur in the United States," Fischer said.
How common is EEE?
That's the good news. It is not common at all.
"It's a serious disease … but the number is small and much smaller than for West Nile virus," Fischer said.
From 2009 to 2018, 21 states registered 72 human EEE cases, the CDC reports. Most had only a few cases during that decade; Florida (13), Massachusetts (10), New York (8), Michigan and North Carolina (7) and Georgia (6) are the only states that have registered more than a handful of human cases during that period.
The CDC states that the United States sees an average of seven cases per year, with the typical range varying between three and 15 cases per year.
It is much less common than West Nile virus cases, of which there are generally hundreds every year. . So far this year, 468 cases of West Nile virus have been 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, right? Why?
Six states have reported 20 cases of EEE so far this year, with Massachusetts – a historically hot spot for the virus – registering nine cases and Michigan reporting seven. Other states that have seen cases in 2019 are New Jersey, North Carolina, Rhode Island and Connecticut.
Six of the infected have so far died.
There were 21 cases in 2005, so this is not completely off the charts – but 2019 is shaping up to be a very active EEE year, says Scott Weaver, an expert on arbovirus at the University of Texas Medical Branch in Galveston.
"I guess what's a little concerning is that we're already at the upper limit of the normal range and it's still only in mid-September," says Weaver, who is head of the Department of Microbiology and Immunology at UTMB. and other areas in the northeast and mid-Atlantic we may have another month or even more active transmission and more cases to come. "
Some years are more active than others in this type of virus.," Fischer explained.  "Every few years you get a larger 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 usually has the most cases overall "So it's moving, it's happening in different places for different years. And you have high and low years."
The reasons for that are not entirely clear, but it is definitely influenced by EEE's complicity life cycle.
What is the life cycle of the virus?  If you know anything about the West Nile virus it will sound familiar. The virus infects mosquitoes, which feed on birds, and infects them in the process. This is what is known as a reinforcement cycle: Uninfected mosquitoes that feed on infected birds are themselves infected and build up more and more viruses in a particular area.
With the EEE, the mosquitoes involved in this cycle are called Culiseta melanura, which lives in freshwater soups and feeds on songbirds. It is believed that these mosquitoes feed almost exclusively on birds.
At one point – usually from July onwards – there is enough virus in the mosquitoes and birds in a place that it infects other populations. Different types of mosquitoes – some Culex mosquitoes that can, for example, transmit West Nile virus – feed on infected birds and pick up the virus. These various mosquitoes, known as bridging vectors, can then drag other species, such as humans, into the EEE's web page.
When an area has had a severe frost, mosquito activity drops and the virus goes to sleep until next spring. Weaver said along the Gulf Coast, where harsh frosts are unusual, human cases can occur at any time of the year.
Why more spills over hands some years than others is not certain.
Climate conditions are likely to play a role; A mild winter can, for example, allow the reinforcement cycle to start faster and produce more virus in the environment, Weaver said.
Many of the studies looking at the life cycle of the virus are decades old and may not fully reflect current circumstances.
"Much 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 special field-oriented projects on this bird cycle that have been done for many decades."
When EEE is released from its mosquito songbird cycle, what species does it infect?
EEE's second E is a clue. The first known outbreaks of eastern encephalitis actually occurred in horses in the 19th century – long before what caused the disease was discovered in the 1930s.
Deer are also affected by the virus, which sometimes makes dogs. However, these other animals, like humans, are considered final hosts in the EEE transmission cycle. We do not contribute to its further 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 humans?
Not if you are a scientist studying EEE. Weaver and some other researchers studying the dangerous virus have been vaccinated with an unlicensed vaccine developed by US military laboratories, but it is not available to the public.
Several experimental EEE vaccines for humans have gone through the preliminary stages of development, but as cases are so uncommon, there is no human market for EEE vaccines. Given the very high cost of developing, testing and licensing a vaccine – north of a billion dollars – without a market, there is no chance that anyone will be made.
Darci Smith, an expert on arboviruses and head of the Department of Immunosuppression at the Naval Medical Research Center in Fort Detrick, Md., Picked up the West Nile virus to do this.
When West Nile was first found in North America in 1999, there was deep concern. And for a number of years, there have been cases in the thousands. Like the EEE, West Nile can cause serious illness and death. In fact, it is believed to have killed more than 2,000 Americans between 1999 and 2016.
Sanofi (SNY) Pasteur began developing a West Nile vaccine, but finally protected the project after concluding that there were not enough cases or enough public concern to guarantee sales. Pharmaceutical companies do not do what they cannot sell.
"And there is still no licensed vaccine [West Nile]," Smith said.
If there are no commercial prospects for a vaccine, why does the EEE vaccine work continue?
The Department of Defense sees the EEE as a potential biological weapons threat because of the severity of the disease it causes and its mortality in high cases.
But for Pentagon's interest, there would be some EEE research, Weaver and others said.