For the first time since 2013, Massachusetts has reported human cases of Eastern Equine Encephalitis (EEE), a rare and potentially fatal mosquito-borne disease. So far in 2019, Massachusetts has reported 4 cases, including 1 death. Additionally, Michigan and New Jersey have recently reported cases of the disease. The US typically sees an average of only 7 cases a year, so this year’s cases in Massachusetts and elsewhere raise questions about the factors influencing the elevated incidence of this and potentially other vector-borne diseases and what can be expected in the coming years. This week, Outbreak Thursday will take a look at the health impacts of EEE and explore possible explanations for its reemergence in Massachusetts.
What is Eastern Equine Encephalitis (EEE)?
EEE is caused by the Eastern Equine Encephalitis virus (EEEV), a single-stranded RNA Alphavirus in the Togaviridae family. The primary animal reservoir for EEEV is wild birds, with transmission to mammals via various species of mosquito. The principal vectors of EEV are the Culiseta melanura mosquito, which transmits the disease between wild birds, and various species of Aedes, Culex, and Coquillettidia mosquitoes, which can transmit EEEV to mammals such as horses and humans. Similar to humans, horses are “dead-end” hosts of EEEV, which means that they are not typically able to infect mosquitoes and further spread the disease.
EEEV is widely distributed throughout the Americas and the Caribean, based on surveillance of mosquito populations in these areas. In the US, cases of human EEEV infections are sporadic, occurring mainly in the summer, with the highest transmission in August. EEEV circulates more in avian species than in mammalian hosts, but there is no clear explanation regarding why there is such a low reported incidence of EEE in humans. One possibly explanation is that humans generally do not often visit the freshwater hardwood swamp areas where transmission between C. melanura and avian hosts most often occurs, which reduces the opportunity for transmission to humans and other mammals via Aedes, Culex, and Coquillettidia mosquitoes. Another potential explanation is that surveillance for EEE is based on infected persons showing symptoms. Only 4-5% of humans infected with EEEV develop symptoms, so this method of surveillance likely underestimates the prevalence of EEEV infection in humans.
On average, approximately 7 cases of EEE are reported in the US each year, with Florida, Massachusetts, New York, and North Carolina accounting for the largest proportion of cases between 2009 and 2018. The incubation period is 4-10 days, and EEE presents symptomatically in one of 2 ways: systemic or encephalitic. Systemic EEE presents with arthralgia, chills, fever, malaise, and myalgia, and symptoms can last 1-2 weeks. Encephalitic EEE can present abruptly in infants and following the onset of systematic EEE symptoms in adults and older children. Encephalitic EEE can cause fever, headache, irritability, restlessness, drowsiness, anorexia, vomiting, diarrhea, cyanosis, convulsions, and coma. Death occurs in approximately one-third of EEE cases, typically within 2-10 days of showing symptoms. Those who experience neurological symptoms and survive can be left with permanent and severe neurological impairments including seizures, paralysis, and intellectual impairment. Severe long-term sequelae can also lead to death within a few years of infection. Those without neurological involvement typically recover fully without long-term effects. Due to the small number of reported cases, it is unclear exactly what proportion of present as encephalitic EEE; however, adults over 50 years of age and children under the age of 15 appear to be at the highest risk.
As a member of the encephalitic Alphavirus family, EEEV has been explored for its potential use as a biological weapon. The US has designated it as a Tier II Select Agent and a Category B agent due to its moderate risk for deliberate use.
Far and away, the most effective intervention for reducing the risk of EEE is preventing mosquito bites in the first place. Mosquitoes transmitting EEEV bite during both day and night, and wearing clothes that cover exposed skin and using insect repellent while outdoors can prevent biting. In addition, eliminating mosquito breeding locations, especially those around the home (eg, flower pots and buckets), can limit mosquito populations. Insecticides can also be used to reduce mosquito populations over larger areas. In addition to EEE, these practices can also prevent or reduce transmission of other mosquito-borne diseases such as West Nile, Zika, and Dengue.
While there is a licensed EEE vaccine for horses, there is unfortunately, no vaccine currently licensed for use in humans. There is an investigational human EEE vaccine, but does not elicit a sufficient immune response in many recipients. The vaccine is also largely limited to those individuals who work directly with the virus in laboratories. There is no specialized therapeutic available for EEE beyond supportive care.
EEE in Massachusetts
This summer, Massachusetts has seen historically high numbers of mosquitoes carrying EEEV, with 333 mosquitoes testing positive, and the state reported the first human cases of EEE in Massachusetts since 2013. Massachusetts has reported 4 total human cases of EEE so far in 2019, including 1 death. The state has also reported cases in other mammals, including a young goat. In an effort to reduce transmission risk, Massachusetts is spraying high-risk with insecticide in an effort to reduce mosquito populations. Massachusetts reported 10 cases of EEE reported between 2009 and 2018, 7 of which were reported in 2012. There is currently no consensus on the driver of Massachusetts’ surge in EEE; however, there are a number of potential contributing factors.
As mentioned previously, transmission of EEEV is concentrated in freshwater hardwood swamps. Humans continue to expand deeper into forested and swamp areas (eg, to live, for recreation), which can place them at elevated risk for mosquito bites, which can transmit EEE and a myriad of other diseases. Additionally, climate change and rising global temperatures have been central to discussions of increased vector-borne disease incidence. Mosquitoes can survive the winter in egg or larva form, if they can remain in water and the temperature does not drop low enough to kill them. In Massachusetts, swamps usually dry out in autumn and winter, which can kill mosquito eggs and larvae and result in decreased numbers of mosquitoes in the following year. Similarly, during cold winters, as are historically typical in New England, the temperature is cold enough to kill mosquito eggs and larvae. Last year, however, warmer and wetter conditions resulted in many of the hardwood swamps never completely drying out. More mosquitoes survived the winter, so mosquito populations were elevated in 2019. Similar conditions occurred in the 2011-12 winter (the 4th warmest winter on record nationally and 3rd warmest in Massachusetts), which preceded 7 reported EEE cases in 2012. As areas become warmer, and more mosquitoes survive the winter, the geographic ranges of some mosquitoes can expand. While some species (eg, Coquillettidia) traditionally cover most of the US, others, including many Aedes and Culex species, are expanding further north and west in the US, placing larger portions of the country at elevated risk.
EEE remains a relatively rare disease but serious neuroinvasive disease in the US, but the elevated incidence in Massachusetts, illustrates the potential risks associated with changing climate conditions and vector expansion. Individuals at higher risk of infection should take steps to limit their exposure to mosquitoes, and public health and healthcare professionals should continue to consider EEE in patients presenting with relevant symptoms. EEE surveillance largely relies on patients seeking care for symptoms, so providers must remain vigilant. Accurate diagnosis and timely reporting can not only support necessary public health messaging and interventions (eg, spraying insecticide), it can also provide valuable clinical and epidemiological data to help us better understand disease and transmission dynamics, including evolving transmission risk.
Photo: Transmission electron microscope (TEM) image of mosquito salivary glands infected with Eastern Equine Encephalitis (EEE); virus particles colored red. Courtesy of CDC/Fred Murphy & Sylvia Whitfield.
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