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Largest Outbreak of EEE Since 1959 Linked to 13 Deaths
Neurologists Urged to be Vigilant

Article In Brief

Longer-lasting warm weather has led to an outbreak of eastern equine encephalitis this year. Neuroinfectious disease experts offer guidance on what neurologists should look for and how to treat it.


The Culiseta melanura mosquito is the primary vector for EEE.

More cases of eastern equine encephalitis (EEE) virus disease have been reported in the United States this year—34, including 13 deaths, than in any year since 1959, according to the Centers for Disease Control and Prevention (CDC) and local news reports.

By comparison, in the decade prior to 2019, the average annual number of neuroinvasive cases was 7.2 and the average number of deaths was three, according to the CDC.

The already high number of cases as of mid-October could go higher, with forecasts calling for continued warm weather in the Northeast through at least the end of the month. Not until a hard frost kills the mosquitoes that transmit the EEE virus to humans will the risk end for additional cases to occur, at least in northerly regions.

In the meanwhile, neurologists should consider the possibility of EEE in any patients in the Atlantic, Gulf Coast, and Great Lakes regions who present with the classic signs and symptoms of encephalitis: high fever, cognitive confusion, and elevated white cell count in cerebrospinal fluid.

Following positive test results from a state health department, some neuroinfection specialists recommend intravenous immunoglobulin (IVIg) as empiric therapy.

While no randomized trial has demonstrated the efficacy of IVIg against EEE, two recent case reports described the rare, near-total recovery of patients who received it early.

Specialists tracking the outbreak said that warm and rainy weather in Massachusetts, where 12 of the 34 cases have been diagnosed, could be behind the unusually high numbers. But they declined to speculate on the current or future role of global warming.

“We don't really have a good explanation for these high numbers,” said Marc Fischer, MD, MPH, chief of surveillance and epidemiology activity in the arboviral disease branch at the CDC. “It's typical for most mosquito-borne diseases, including EEE, to have ups and downs in their numbers. Weather does play a role in the number of mosquitoes there are, the number of birds, and the presence of standing water. But whether there will be any longer-term trend, we can't say.”

Background on the Virus

The EEE virus cycles between mosquitoes and birds that live in freshwater hardwood swamps and bogs, said Daniel Pastula, MD, MHS, associate professor of neurology, infectious diseases and epidemiology at the University of Colorado School of Medicine and Colorado School of Public Health.

“It only cycles in these freshwater hardwood swamps,” Dr. Pastula said. “Think of places with maple trees or oak trees in the eastern half of the United States.”

The disease has been recognized at least since the 1800s, although the modern name was not coined until years later, Dr. Fischer said. A paper published in the New England Journal of Medicine in 1938 was the first to identify the virus as the same one that causes a similar disease in horses.

“There was a large outbreak in the late 1930s in Massachusetts and in the late 1950s in New Jersey,” Dr. Fischer said. “Case numbers were only reported for each state but were similar to the case numbers seen this year for the whole US.”


Shown is a mosquito salivary gland infected with EEE.


Transmission electron micrograph of tissue from a human central nervous system (CNS), showing infection by eastern equine encephalitis virus particles (virions, brown).

An Associated Press report published in The New York Times on October 7, 1959, stated that “the disease is believed to have taken nineteen lives and caused ten persons to be ill” in southern New Jersey.

Dr. Fischer noted, however, that the CDC has kept national statistics only since 1964. “Changes in available diagnostic testing, national surveillance case definitions, and reporting systems make it difficult to compare annual case numbers prior to 2003,” he said.

Even so, Shibani S. Mukerji, MD, associate director of the neuro-infectious disease unit at Massachusetts General Hospital in Boston, called the 1959 outbreak a “benchmark.” And as of mid-October, the season there wasn't over.

“We haven't had a hard frost yet in Massachusetts,” she said. “It's still pretty warm. The number of cases here is already by far the most I've ever seen in a single season.”

This year, Dr. Fischer said, the CDC has received reports of 12 cases in Massachusetts, 10 in Michigan, four in Connecticut, three in New Jersey, three in Rhode Island, and one each in North Carolina and Tennessee. Authorities in northern Indiana have also reported one additional case resulting in death. That report, however, had not been received by the CDC as of October 16, Dr. Fischer said.

Two horses (but no humans) have also tested positive for the virus in New Hampshire, according to local news reports, resulting in public health threat warnings there. The high number of cases in Massachusetts also led public health officials there to have warnings placed on electronic signs on highways.

During the 10 years prior to 2019, the biggest national outbreak was in 2012, when 15 cases occurred, according to the CDC. The next-largest outbreak was in 2010, when 10 cases were confirmed. Last year just six cases were reported.

During that same decade, cases were reported in Alabama, Arkansas, Connecticut, Florida, Georgia, Louisiana, Maine, Massachusetts, Maryland, Michigan, Missouri, Montana, New Hampshire, New Jersey, New York, North Carolina, Pennsylvania, Rhode Island, Vermont, Virginia and Wisconsin. The state with the most cases during those ten years was Florida, with 13, followed by Massachusetts (10), New York (8), North Carolina (7) and Georgia (6). No other state had more than three.

A paper coauthored by Dr. Fischer describing all cases of EEE in the United States between 2003 and 2016 noted that among the 118 cases that occurred during that period, 98 percent of patients were hospitalized and 41 percent died.

Treatment and Prevention

The management of EEE, Dr. Fischer said, is the same as for any cause of encephalitis: symptomatic treatment of seizures, fluid status, elevated intracranial pressure, and maintenance of an open airway.

“It's unfortunate that we don't have a specific treatment for this disease,” he said. “But it's rare despite the numbers we're seeing this year. As a result, it's unlikely that there will be a specific treatment in the foreseeable future.”


“There is certainly some scientific rationale for why IVIg might be effective against EEE or West Nile Virus.” “Unfortunately we really dont have any rigorous data to support its use. Its hard to draw conclusions from individual case reports. And for every positive report, there are probably many more of ineffectiveness.”—DR. FELICIA CHOW


“With EEE specifically, a cardinal sign is that people become markedly confused. They may walk into the ED just not feeling well, with a high fever, but there comes a point when people with neuroinvasive disease become quickly confused. Right at that point, you cant delay a lumbar puncture. The cognitive confusion is key and striking.”—DR. SHABANI S. MUKERJI

Regarding more general treatments aimed at reducing inflammation in the brain, he said, “There are clinical case reports or series using IVIg or other medications, primarily for West Nile virus or other arboviral diseases, but there are no controlled clinical trials.”

Two of those case reports were coauthored by Dr. Mukerji. As described in a 2016 paper in Neurohospitalist, a 68-year-old man presented to a hospital emergency department in early September of 2012, a peak period for cases. The man's symptoms included “four days of fever, headache, fatigue, generalized weakness, nausea, vomiting, neck discomfort, and one day of inattention and difficulty putting on his clothes after camping in a Massachusetts state park six days earlier.” With a temperature of 104.8°F and confirmation by his family that he had been bitten by mosquitoes during his camping trip, the neurologist on call decided to perform a spinal tap, which revealed 330 nucleated cells per mm3 (11 percent neutrophils, 68 percent lymphocytes, and 21percent monocytes).

“The median white cell count for EEE is about 370,” Dr. Mukerji said. “Normal is zero to five.”

As it happened, that neurologist was Michael R. Wilson, MD, FAAN, who now specializes in infectious and autoimmune syndromes of the central nervous system at the University of California, San Francisco. With a strong suspicion of EEE, he transferred the patient to Mass General with a recommendation that IVIg should be started immediately. After just one day on treatment, the paper reported, “he opened his eyes to voice and protruded his tongue to command.... One month later, he returned home with improvement in communication and memory skills, scoring 28 of 30 on the Montreal Cognitive Assessment.... Nine months after his acute illness, he returned to driving, cooking meals for a group of 50 veterans, and singing Irish ballads to his family.”

Dr. Mukerji said she believes that the unusually quick treatment with IVIg, beginning “almost on admission” at Mass General, may have played a role in his recovery, but that only a well powered clinical trial will be adequate to determine whether IVIg is effective in EEE. That will be difficult, she added, given the low number of cases.

“With EEE specifically, a cardinal sign is that people become markedly confused,” she said. “They may walk into the ED just not feeling well, with a high fever, but there comes a point when people with neuroinvasive disease become quickly confused. Right at that point, you can't delay a lumbar puncture. The cognitive confusion is key and striking.”

Felicia Chow, MD, MAS, director of the UCSF Neuro-Infectious Diseases Clinic at the Parnassus campus, has never treated EEE, but has treated many cases of West Nile Virus. Her experience with IVIg, she said, is mixed at best.

“There is certainly some scientific rationale for why IVIg might be effective against EEE or West Nile virus,” she said. “Unfortunately we really don't have any rigorous data to support its use. It's hard to draw conclusions from individual case reports. And for every positive report, there are probably many more of ineffectiveness.”

Even so, Dr. Chow said, “If anything is going to work, it needs to be given early on—the sooner, the better.”

Researchers are also exploring the protective effect of other anti-inflammatory agents, such as the IL-1 receptor antagonist anakinra, in animal models of West Nile virus encephalitis, Dr. Chow said. No study, however, has yet reported its use in animal studies of EEE.

For now, the best approach for neurologists to take is to recommend preventive measures among their patients in endemic areas from spring to early fall, Dr. Pastula said.

“The best way to prevent EEE is to avoid being bitten by mosquitoes,” he said. “That means wearing long sleeves and pants when possible, avoiding the outdoors from dusk till dawn, using mosquito repellant on exposed skin and consider treating clothing with permethrin.”


None of the sources quoted in this story had disclosures.

Link Up for More Information

• Wendell LC, Potter NS, Roth JL, et al. Successful management of severe neuroinvasive eastern equine encephalitis Neurocrit Care 2013;19:111–115.
• Mukerji SS, Lam AD, Wilson MR. Eastern equine encephalitis treated with intravenous immunoglobulins Neurohospitalist 2016;6:29–31.
• Solomon IH, Ciarlini PDSC, Santagata S, et al. Fatal eastern equine encephalitis in a patient on maintenance rituximab: A case report Open Forum Infect Dis 2017;4(1):ofx021.
• Fothergill LD, Dingle JH, Farber S, et al. Human encephalitis caused by the virus of the eastern variety of equine encephalomyelitis N Engl J Med 1938;219–411.
    • Lindsey NP, Staples JE, Fischer M. Eastern equine encephalitis virus in the United States, 2003-2016 Am J Trop Med Hyg 2018;98(5):1472–1477.