Important points to consider in patient history are outdoor exposures, recent travels, social history, insect bite history, work/home in high-risk areas, exposure to areas with high prevalence of mosquitoes and work related to marshes or horses.

The presentation is similar to typical viral diseases starting from headaches, vague fevers and tremendous body aches. A short prodrome of 5 to 10 days might be present with symptoms like abdominal pain, fever, diarrhea and headache.

There is rapid progress to CNS involvement, severe fatigue and weakness and high grade fever along with myalgia. Frequent headaches are felt by the patient due to meningeal irritation. Photophobia and neck stiffness are another important feature. Nausea and vomiting are present during the prodromal stage and may persist in the later stages as well. Somnolence, confusion, cranial nerve palsy, abdominal pain and diarrhea, and autonomic disturbances like sialorrhoea are common.

Lastly, patients have seizures and fall into unconsciousness. Seizures are noted in almost 50% patients; mostly generalized tonic clonic. All this eventually leads to death. Hence, this disease though rare, is very fatal.

Tachycardia and tachypnoea might be appreciable with cyanosis, generalized edema and possibly depressed/exaggerated reflexes. Complications are mostly those pertaining to CNS impairment like paralysis, permanent focal deficits and mental retardation.

• Fever

  Symptoms in horses occur 1-3 weeks after infection, and begins with a fever that may reach as high as 106°F (41°C). The fever usually lasts for 24–48 hours. [en.wikipedia.org]

  The presentation is similar to typical viral diseases starting from headaches, vague fevers and tremendous body aches. A short prodrome of 5 to 10 days might be present with symptoms like abdominal pain, fever, diarrhea and headache. [symptoma.com]

  Nervous signs appear during the fever that include sensitivity to sound, periods of excitement, and restlessness. [omicsonline.org]

  However, those who do develop symptoms may have fever and joint or muscle pain. [witn.com]

• Chills

  Symptoms of illness begin with the sudden onset of high fever, chills, headache, nausea, and vomiting. Severe illness includes encephalitis, seizures, and coma. Arboviral diseases home Last Revised: July 27, 2018 [dhs.wisconsin.gov]

  According to the Centers for Disease Control and Prevention, those with a severe form of the disease will have “sudden onset of headache, high fever, chills, and vomiting. The illness may then progress into disorientation, seizures, and coma.” [witn.com]

  Severe cases of EEE (involving encephalitis, an inflammation of the brain) begin with the sudden onset of headache, high fever, chills and vomiting. [epi.publichealth.nc.gov]

  Systemic infection has an abrupt onset and is characterized by chills, fever, malaise, arthralgia, and myalgia. The illness lasts 1 to 2 weeks, and recovery is complete when there is no central nervous system involvement. [health.ri.gov]

• High Fever

  Symptoms of illness begin with the sudden onset of high fever, chills, headache, nausea, and vomiting. Severe illness includes encephalitis, seizures, and coma. Arboviral diseases home Last Revised: July 27, 2018 [dhs.wisconsin.gov]

  The Illness The virus can cause disease in humans, horses and birds.Most infections in humans cause no symptoms and severe brain infection is rare; (on average 6 cases each year in the US) 4-10 days after infection, a high fever develops followed followed [fitfortravel.nhs.uk]

  According to the Centers for Disease Control and Prevention, those with a severe form of the disease will have “sudden onset of headache, high fever, chills, and vomiting. The illness may then progress into disorientation, seizures, and coma.” [witn.com]

  fever, spinal pleocytosis Prognosis 30-70% mortality; severe neurologic sequelae. [medical-dictionary.thefreedictionary.com]

  Severe cases of EEE (involving encephalitis, an inflammation of the brain) begin with the sudden onset of headache, high fever, chills and vomiting. [epi.publichealth.nc.gov]

• Malaise

  Systemic infection has an abrupt onset and is characterized by chills, fever, malaise, arthralgia, and myalgia. The illness lasts 1 to 2 weeks, and recovery is complete when there is no central nervous system involvement. [health.ri.gov]

• Fatigue

  The symptoms manifesting are headache, high grade fever, joint pains, myalgia, nausea and vomiting, neck stiffness, photophobia, seizures, fatigue and severe weakness and lastly, death. [symptoma.com]

  Other symptoms include high fever, fatigue, muscle aches, neck stiffness, tremors, or confusion. Severe cases include inflammation of the brain (encephalitis) which can lead to coma, convulsions, and death. [ct.gov]

  Symptoms may include fever, headache, vomiting, muscle aches, joint pain, and fatigue. There is no specific treatment for West Nile virus. Patients are treated with supportive therapy as needed. [riverheadlocal.com]

  Most people with this type of EEE disease recover completely, but fatigue and weakness can last for weeks or months. Severe symptoms in a few people. [michigan.gov]

• Vomiting

  A 21-year-old man initially presented with headache, fever, and vomiting and was found to have a neutrophilic pleocytosis in his cerebrospinal fluid. [ncbi.nlm.nih.gov]

  Symptoms of illness begin with the sudden onset of high fever, chills, headache, nausea, and vomiting. Severe illness includes encephalitis, seizures, and coma. Arboviral diseases home Last Revised: July 27, 2018 [dhs.wisconsin.gov]

  According to the Centers for Disease Control and Prevention, those with a severe form of the disease will have “sudden onset of headache, high fever, chills, and vomiting. The illness may then progress into disorientation, seizures, and coma.” [witn.com]

  Severe cases of EEE (involving encephalitis, an inflammation of the brain) begin with the sudden onset of headache, high fever, chills and vomiting. [epi.publichealth.nc.gov]

  Signs and symptoms in encephalitic patients are fever, headache, irritability, restlessness, drowsiness, anorexia, vomiting, diarrhea, cyanosis, convulsions, and coma. [health.ri.gov]

• Nausea

  Symptoms of illness begin with the sudden onset of high fever, chills, headache, nausea, and vomiting. Severe illness includes encephalitis, seizures, and coma. Arboviral diseases home Last Revised: July 27, 2018 [dhs.wisconsin.gov]

  The symptoms manifesting are headache, high grade fever, joint pains, myalgia, nausea and vomiting, neck stiffness, photophobia, seizures, fatigue and severe weakness and lastly, death. [symptoma.com]

  Most patients have non-specific viral prodromal symptoms for approximately one week, including fevers, headache, nausea and vomiting, and malaise 1. [radiopaedia.org]

  These symptoms usually last for 24 to 72 hours and may be followed by a cough, sore throat, nausea, vomiting and diarrhea. The disease usually lasts 1 to 2 weeks. [nj.gov]

• Hypertension

  His course in the NeuroIntensive Care Unit was complicated by cerebral edema and intracranial hypertension, requiring osmotherapy, pentobarbital and placement of an external ventricular device, and subclinical seizures, necessitating multiple anti-epileptic [ncbi.nlm.nih.gov]

  People with certain medical conditions, such as cancer, diabetes, hypertension, kidney disease, and people who have received organ transplants, are also at greater risk for serious illness. [michigan.gov]

• Tachycardia

  Tachycardia and tachypnoea might be appreciable with cyanosis, generalized edema and possibly depressed/exaggerated reflexes. [symptoma.com]

  List of Symptoms/Signs Top of page Sign Life Stages Type Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Pigs:Piglet Diagnosis Digestive Signs / Diarrhoea [cabi.org]

• Myalgia

  The symptoms manifesting are headache, high grade fever, joint pains, myalgia, nausea and vomiting, neck stiffness, photophobia, seizures, fatigue and severe weakness and lastly, death. [symptoma.com]

  Systemic infection has an abrupt onset and is characterized by chills, fever, malaise, arthralgia, and myalgia. The illness lasts 1 to 2 weeks, and recovery is complete when there is no central nervous system involvement. [health.ri.gov]

• Photophobia

  Photophobia and neck stiffness are another important feature. Nausea and vomiting are present during the prodromal stage and may persist in the later stages as well. [symptoma.com]

  Eastern equine encephalitis Specialty Infectious disease Symptoms high fever, muscle pain, altered mental status, headache, meningeal irritation, photophobia, and seizures Causes Eastern equine encephalitis virus Eastern equine encephalitis ( EEE ), commonly [en.wikipedia.org]

  The clinical signs may include fever, generalized malaise, severe headache, photophobia and myalgia, particularly in the legs and lumbosacral region. [nj.gov]

• Insect Bite

  The permethrin wont help repel the mosquitoes but reduces biting and kills the insect after a bite preventing further spread of disease. Full sleeved clothes and full pants should be opted for whenever the weather permits. [symptoma.com]

• Headache

  The presentation is similar to typical viral diseases starting from headaches, vague fevers and tremendous body aches. A short prodrome of 5 to 10 days might be present with symptoms like abdominal pain, fever, diarrhea and headache. [symptoma.com]

  The most common clinical and laboratory features were fever, headache, seizures, peripheral leukocytosis, and cerebrospinal fluid neutrophilic pleocytosis. Radiographic lesions were found in the basal ganglia, thalami, and cerebral cortex. [ncbi.nlm.nih.gov]

  Symptoms of illness begin with the sudden onset of high fever, chills, headache, nausea, and vomiting. Severe illness includes encephalitis, seizures, and coma. Arboviral diseases home Last Revised: July 27, 2018 [dhs.wisconsin.gov]

  The first symptoms are fever (103-106ºF), stiff neck, and headache starting 2-10 days after infection. Swelling of the brain (encephalitis) is the most feared feature. [medicinenet.com]

• Seizure

  Lastly, patients have seizures and fall into unconsciousness. Seizures are noted in almost 50% patients; mostly generalized tonic clonic. All this eventually leads to death. Hence, this disease though rare, is very fatal. [symptoma.com]

  […] drugs A multifaceted approach including aggressive management of cerebral edema and ICP as well as treatment with immunomodulating agents and cessation of seizures may prevent brain herniation, secondary neurologic injury and death in patients with EEE [ncbi.nlm.nih.gov]

  RESULTS: A 78 year-old healthy male from Maine presented in late summer with six days of fever, headache, and confusion that progressed rapidly to seizure and coma. [neurology.org]

• Irritability

  Signs and symptoms in encephalitic patients are fever, headache, irritability, restlessness, drowsiness, anorexia, vomiting, diarrhea, cyanosis, convulsions, and coma. [health.ri.gov]

  Onset of fever, headache, irritability, restlessness, drowsiness, anorexia, vomiting, diarrhea, cyanosis, convulsions and coma. In infants- abrupt onset. In older children and adults- manifested after a few days of systemic illness. [hnhu.org]

  Do not apply insect repellent to a child’s hands, eyes, mouth, cuts, or irritated skin. Adults: Spray insect repellent onto your hands and then apply to a child’s face. Tips for Everyone Always follow the product label instructions. [cdc.gov]

• Confusion

  RESULTS: A 78 year-old healthy male from Maine presented in late summer with six days of fever, headache, and confusion that progressed rapidly to seizure and coma. [neurology.org]

  Eastern equine encephalitis virus (EEE) commonly called Triple E or, sleeping sickness (not to be confused with Trypanosomiasis) is a zoonotic alphavirus and arbovirus present in North, Central and South America and the Caribbean. [omicsonline.org]

  This is followed by the emergence of neurological features, such as confusion, focal neurological signs, generalized or focal seizures, meningism, and somnolence 1. [radiopaedia.org]

  The typical course includes increasing drowsiness, neck rigidity, confusion, paralysis, convulsions and coma. EEE is fatal in more than 20% of cases which develop encephalitis. [web.stanford.edu]

  Eastern equine encephalitis (EEE), commonly called Triple E or, sleeping sickness (not to be confused with trypanosomiasis) is a zoonotic alphavirus and arbovirus present in North, Central, and South America and the Caribbean. [en.wikipedia.org]

• Stupor

  Massachusetts; infection of horses and humans is an accidental 'dead-end', occurring when the virus is transmitted to other mosquitoes–eg, Aedes vexans, Aedes sollicitans, Coquillitidia perturbans ; ± 5 human cases/yr in the US–Clinical Meningismus, lethargy, stupor [medical-dictionary.thefreedictionary.com]

  These neurological features rapidly progress and the patient's condition typically deteriorates within days to become stuporous or comatose 1. EEE is caused by the eastern equine encephalitis virus (EEEV), a single-stranded RNA alphavirus 1,2. [radiopaedia.org]

  Four were stuporous or comatose when first evaluated; 21 others (for a total of 69 percent) became stuporous within two days after admission. In all, 32 of the 36 patients (89 percent) eventually became stuporous or comatose. [doi.org]

  This prodrome is often followed by neurologic signs; the symptoms may include confusion, focal neurologic deficits, somnolence, neck stiffness, stupor, disorientation, coma, tremors, seizures and paralysis. [nj.gov]

Laboratory tests

The diagnosis of eastern equine encephalitis is difficult as its presentation is very similar to meningitis or epilepsy. Certain laboratory reports like the complete blood count show leucocytosis.

VecTest antigen test and Vero cell plaque test assay have been shown to be effective in diagnosing humans as well as in arthropod surveillance projects [3].

The CSF examination will show an increased protein concentration. There will also be increased red blood cells and white blood cells in the CSF. The virus can be isolated from the CSF and it is an excellent technique for confirming the diagnosis. Enzyme linked immunosorbent assay or ELISA technique is useful in detecting immunoglobulin M (IgM) antibodies during the convalescent stage and antiarboviral IgG antibodies [4].

Imaging

CT scan of the brain reveals areas of injury in the cerebral matter but the MRI test is more precise in diagnosing the Eastern Equine Encephalitis. MRI differentiates the disease from herpes simplex encephalitis. MRI is more sensitive to the early changes produced by the virus especially when using a T2- weighted imaging for optimal image outcomes. The basal ganglion is most commonly affected in Eastern Equine Encephalitis.

EEG i.e. electro encephalography reveals that there is generalized disorganization of the impulses travelling across the cerebrum. The results of the tests should be correlated very carefully as the Eastern Equine Encephalitis closely mimics encephalitis, meningitis and herpes simplex virus meningitis.

A reverse transcriptase duplex real time polymerase chain reaction or PCR assay has been developed by scientists to detect the virus with a 10 fold greater sensitivity that the current gold standard of viral isolation for diagnosis [5].

• Periodic Lateralized Epileptiform Discharges

  Epileptiform discharges were noted in six patients, including four who had periodic lateralizing epileptiform discharges. No correlations could be drawn between specific clinical events and electroencephalographic patterns. [doi.org]

• Hyponatremia

  The presence of large radiographic lesions did not predict a poor outcome, but either high cerebrospinal fluid white-cell counts or severe hyponatremia did. Eastern equine encephalitis produces focal radiographic signs. [ncbi.nlm.nih.gov]

  Leukocytosis and hyponatremia were common ( Table 1 ). [doi.org]

There is no specific treatment for this disease neither do we have any vaccinations for prevention, just like all other diseases caused by the alphaviruses [6]. The only form of treatment includes medications like steroids to control inflammation and anti pyretics to control fever.

A case managed by Wendell et al used high doses of methyprednisolone and immunoglobulins given intravenously with use of anti-epileptic drugs for seizure control.The patient recovered dramatically and ultimately survived [7].

To control the seizures anti-epileptic drugs like Phenobarbital, phenytoin and benzodiazepines are useful. Only supportive treatment is available for this extremely fatal disease. Analgesics are used to control muscle pain and body aches.

Experiments have attempted the use of pyrimidine derivatives, inosine derivative Isoprinosine for treatment of the lethal virus, but results on in-vivo studies were poor [8].

Prognosis of the patient is poor as the patient will invariably have seizures and fever. The morbidity rate of patients is more than 90%. Around 70% of the patients die due to the massive involvement of the central nervous system.

The patients who survive the disease need critical and long term rehabilitation. Depending upon the areas of involvement and the deficits caused one must undergo physiotherapy, occupational therapy or speech therapy as per need.

The Eastern equine encephalitis virus flourishes in the blood of the birds and gets transmitted to mosquitoes as they feed on these infected birds. It is a zoonotic disease.

The mosquitoes which act as carriers of this virus are Culiseta melanura and Culiseta morsitans. Once the blood meal is taken, the infected mosquitoes infect mammals like horses, humans and other animals by biting them. The mosquitoes which infect humans are Aedes vensxa and Coquilleditia pertubans.

The virus is carried in the vector’s proboscis and is injected into the mammal while having a blood meal. The infected mammals cannot transmit the viru; it’s a zoonotic cycle which involves the mosquitoes, birds and mammals.

The disease is seen to affect 12 to 17 people annually in the United States of America. The infection is commonest east to the Mississippi River [1].

The episodes are seen when the presence of mosquitoes increases in the months of July to September. All the cases are fatal. It can be seen in people of all the age groups.

Eastern Equine Encephalitis has chief involvement of the central nervous system. Groups of immunologically active cells are seen proliferating in the brain tissue along with neuronal destruction and vascular inflammation. On gross inspection, there is oedema, vascular congestion, hemorrhage and cerebral atrophy.

The mosquito injects the Eastern Equine Encephalitis virus into the subcutaneous or cutaneous tissue of skin. The virus may cross the placenta and affect the fetus also; otherwise it cannot be transferred from one human to another human. The virus binds to particular tissue receptors only, undergoes a process of endocytosis and commences a synthesis of protein and RNA which is RNA-dependent [2].

The viral symptoms of headache and fever along with myalgia are seen due to viral replication in the non neuronal tissue. The meningitis and the seizures are seen due to infection of the central nervous tissue. On coming in contact with the central nervous tissue, the virus undergoes endocytosis and its toxicity increases.

Prevention and control are one of the most important aspects of Eastern equine encephalitis. Individuals planning to undertake trips to endemic or high-risk regions must be warned to take all the necessary prescribed precautions [9].

Preventing bites from mosquitoes is the mainstay of prevention. It is advisable to always apply a coat of mosquito repellant permethrin 5% cream while going outdoors especially when in forest areas. The permethrin wont help repel the mosquitoes but reduces biting and kills the insect after a bite preventing further spread of disease [10].

Full sleeved clothes and full pants should be opted for whenever the weather permits. Stagnant water bodies should be emptied as flower pots and marshy places are potential breeding sites for mosquitoes. Window mosquito screens should be used to cover windows and doors.

Eastern Equine Encephalitis is a rare but fatal disease caused by the Eastern Equine Encephalitis virus which infects the mosquitoes and then these mosquitoes have the potential to affect humans, birds and horses. It is also referred to as the EEE viral disease.

Eastern Equine Encephalitis is a viral disease also called as EEE disease. It is caused by the Eastern equine encephalitis virus. This virus survives in the birds and the mosquitoes but causes infection in horses, mammals and humans.

Human to human transfer of virus is not possible except when the mother is infected and the virus crosses the placenta to affect the fetus. The mosquitoes participating in the bird-mosquito cycle are Culiseta melanura and Culiseta morsitans while the ones infecting humans are Aedes vensxa, Coquilleditia pertubans etc.

The mosquito while feeding on a blood meal infects the human and transmits the virus subcutaneously into the skin. The virus significantly affects both the non-neuronal tissue and the neuronal tissue.

The symptoms manifesting are headache, high grade fever, joint pains, myalgia, nausea and vomiting, neck stiffness, photophobia, seizures, fatigue and severe weakness and lastly, death.

The disease is very rare but extremely fatal and around 70% of the patients die. The ones which remain have to undergo extensive rehabilitation by following up with physiotherapist, occupational therapist and speech therapist if the speech is also affected.

The diagnostic tests consist of blood tests, Cerebrospinal fluid tests, CT scan, MRI scan and an EEG scan. Isolating the virus is extremely important as prognosis of this disease is very poor while the spread is easy.

Once the diagnosis is confirmed, palliation of the patient’s symptoms with antipyretics for fever, anticonvulsants for seizures and analgesics for joint pains and muscle pains is essential.

Despite significant medical advances in recent years, there is no vaccine available for this fatal disease. Prevention becomes the main stay of the treatment as there is no cure and no vaccinations either.

One must avoid travelling to places where there is a high density of mosquitoes or where mosquito borne diseases are endemic. One must apply insect-repellant creams while going outside. Full length clothes should be worn and potential breeding sites of the mosquitoes should be destroyed. All this will help prevent the Eastern Equine Encephalitis disease from fatally infecting people.

1. Vander Kelen PT, Downs JA, Stark LM, Loraamm RW, Anderson JH, Unnasch TR. Spatial epidemiology of eastern equine encephalitis in Florida. Int J Health Geogr. Nov 5 2012;11:47.
2. Jose J, Snyder JE, Kuhn RJ. A structural and functional perspective of alphavirus replication and assembly. Future Microbiol. Sep 2009;4(7):837-56
3. Nasci RS, Gottfried KL, Burkhalter KL, Ryan JR, Emmerich E, Davé K. Sensitivity of the VecTest antigen assay for eastern equine encephalitis and western equine encephalitis viruses. J Am Mosq Control Assoc. Dec 2003;19(4):440-4
4. Johnson AJ, Martin DA, Karabatsos N, Roehrig JT. Detection of anti-arboviral immunoglobulin G by using a monoclonal antibody-based capture enzyme-linked immunosorbent assay. J Clin Microbiol. May 2000;38(5):1827-31
5. Kang X et al. A duplex real-time reverese transcriptase polymerase chain reaction assay for detecting western equine and eastern equine encephalitis viruses. Virol J. 2010 Oct 26;7:284.
6. Davis LE, Beckham JD, Tyler KL. North American encephalitic arboviruses. Neurol Clin. Aug 2008;26(3):727-57, ix.
7. Wendell LC et al. Successful management of severe neuroinvasive eastern equine encephalitis. Neurocrit Care. 2013 Aug;19(1):111-5.
8. Chang TW, Weinstein L. Antiviral activity of isoprinosine in vitro and in vivo. Am J Med Sci. Feb 1973;265(2):143-6.
9. Chiodini J. Mosquito-borne viral infections and the traveller. Nurs Stand. May 7-13 2008;22(35):50-7; quiz 58
10. Elgart ML. Medical pearl: permethrin can prevent arthropod bites and stings. J Am Acad Dermatol. Aug 2004;51(2):289.