Deadly Neuroinvasive Mosquito-Borne Virus: A Case of Eastern Equine Encephalitis



 

Natalie Millet, DO1; Saif Faiek, MD1; Daniel Gurrieri, DO1; Karanvir Kals, DO2; William Adams, DO1,3; Edward Hamaty, DO1,3; Manish Trivedi, MD1,4; David Zeidwerg, DO1,5

Perm J 2021;25:20.288

https://doi.org/10.7812/TPP/20.288
E-pub: 03/01/2021

Eastern equine encephalitis (EEE) is a rare and potentially fatal neuroinvasive disease with a high mortality rate of > 30%. It is an uncommon vector-borne illness, with an average of 8 cases reported in the United States annually. Alarmingly, in 2019 alone, the Centers for Disease Control and Prevention (CDC) confirmed 38 cases of EEE virus in the United States, reported from 10 states.

In this report, we describe a 42-year-old man who worked primarily in wooded areas and presented to a hospital in southern New Jersey with an intractable headache and global facial paraesthesia. He reported multiple tick bites in the weeks prior to his presentation. Based on high clinical suspicion, cerebrospinal samples were sent to the CDC, which confirmed the diagnosis of EEE. The patient was treated with supportive care, and, after spending 9 days on mechanical ventilation in the intensive care unit, he was extubated and subsequently had some improvement of his symptoms with the implementation of an extensive physical therapy program.

We hope this report will contribute to increasing awareness among the public health and medical communities regarding the increasing number of EEE cases and the importance of following prevention measures, especially in areas with high prevalence and early recognition of the disease for treatment.

CASE PRESENTATION

Presenting Concerns

On August 28, 2019, at 10:30 am, a 42-year-old male with no significant past medical history who worked primarily in wooded areas in southern New Jersey presented to our hospital’s emergency department complaining of an intractable headache described as the “worst headache of his life.” His headache began the morning of his presentation and was associated with global facial paresthesia, nausea, and generalized malaise. The patient reported multiple tick bites in the weeks preceding his presentation. He was started on intravenous doxycycline on admission for presumed tick-borne illness. Despite reporting improvement in his symptoms with supportive care on day 1 of admission, on day 2 of admission, his headaches recurred and worsened in severity in the afternoon. He also became febrile, with body temperature as high as 102°F. At 3:28 am on day 3 of admission, a rapid response was called because the patient was actively seizing. He received a total of 8 mg intravenous lorazepam with a termination of his seizure. He also started on 1 g of levetiracetam every 12 hours. After the seizure episode, he was noted to have an altered level of consciousness along with right upper and lower extremity weakness; these symptoms were initially thought to be a result of his postictal state. Intravenous cancomycin, ceftriaxone, acyclovir, and dexamethasone were initiated, given our high index of suspicion for encephalitis versus meningitis. A lumbar puncture was performed with a mildly elevated opening pressure of 24 cm of water; cerebrospinal fluid (CSF) analysis revealed an elevated CSF polymorphonuclear cells of 11 and normal CSF lymphocytes, and monocytes were 47 and 42. The patient had a normal glucose level of 74 mg/dL (reference range: 40-70 mg/dL), an elevated protein level of 104.7 mg/dL (reference range: 15-45 mg/dL), and an elevated serum sodium of 150 (reference range: 135-145 mEq/L). Magnetic resonance imaging of the brain with and without gadolinium contrast demonstrated an area of edema involving the medial aspect of the left temporal lobe with diffuse abnormal T2 signal within the basal ganglia extending into the midbrain concerning for encephalitis (Figure 1).

tpj20288pdf1

Figure 1. T2 FLAIR MRI of the brain. T1 MI of the brain.

Table 1. Timeline table

Relevant past medical history and interventions
A 42-year-old male with no significant past medical history who worked primarily in wooded areas in southern New Jersey presented to our hospital’s emergency department complaining of an intractable headache associated with global facial paresthesia, nausea, and generalized malaise. The patient reported multiple tick bites in the weeks preceding his presentation.
Date Summaries from initial and follow-up visits Diagnostic testing (including dates) Interventions
August 28, 2019 Patient presented with the above-mentioned complaints and symptoms. No relevant testing He was Started on intravenous doxycycline on admission for presumed tickborne illness.
August 29, 2019 His headaches reoccurred and worsened in severity with, high temperature 102°F. No relevant testing He received antipyretics.
August 30, 2019 A rapid response was called because the patient was actively seizing. No relevant testing He received a total of 8 mg intravenous lorazepam with a termination of his seizure. He was also started on 1 g of levetiracetam every 12 h.
August 30, 2019 After the seizure episode, he was noted to have an altered level of consciousness along with right upper and lower extremity weakness; these symptoms were initially thought to be a result of his postictal state. A lumbar puncture was performed with a mildly elevated opening pressure of 24 cm of water; CSF analysis revealed a normal glucose level of 74 mg/dL (reference rage: 40-70 mg/dL) and an elevated protein level of 104.7 mg/dL (reference range: 15-45 mg/dL). Magnetic resonance imaging of the brain with and without gadolinium contrast demonstrated an area of edema involving the medial aspect of the left temporal lobe with diffuse abnormal T2 signal within the basal ganglia extending into the midbrain concerning for encephalitis. Intravenous vancomycin, ceftriaxone, acyclovir, and dexamethasone were initiated, given our high index of suspicion for encephalitis versus meningitis.
August 30, 2019 The patient remained febrile with temperatures ranging from 102 to 105°F despite antipyretics and passive cooling techniques. At approximately 10:00 pm on day 3 of admission, targeted temperature management to achieve normothermia was initiated. CSF samples obtained from the EVD were sent to the CDC, which later returned positive for IgM and IgG EEEV antibodies confirming the EEEV diagnosis. Blood and CSF cultures demonstrated no growth. The decision was made to insert a prophylactic EVD given the increased opening pressure during lumbar puncture, cerebral edema on imaging, and deterioration of the patient’s mental status. Prior to the EVD procedure, the patient’s respiratory condition worsened with paradoxical breathing, accessory muscle use, and a respiratory rate in the fifties. He was subsequently intubated at 11:30 pm on day 3 of admission.
September 9, 2019 The patient was treated with supportive care and was successfully extubated after 9 days of mechanical ventilation.    
Follow-up Postextubation, he exhibited significant neurological deficits, including moderate aphasia, dysphagia, and global weakness. He was transferred to a long-term rehabilitation center where he underwent aggressive physical and occupational therapy with progressive improvement in his neurologic and clinical status.    

CDC = Centers for Disease Control and Prevention; CSF = cerebral spinal fluid; EEEV = eastern equine encephalitis virus; EVD = external ventricular drain.

Therapeutic Intervention and Treatment

Over the next 16 hours, the patient remained febrile, with temperatures ranging from 102 to 105°F despite antipyretics and passive cooling techniques. At approximately 10:00 pm on day 3 of admission, targeted temperature management to achieve normothermia was initiated. The decision was made to insert a prophylactic external ventricular drain (EVD) given the increased opening pressure during lumbar puncture, cerebral edema on imaging, and deterioration of the patient’s mental status. Prior to the EVD procedure, the patient’s respiratory condition worsened with paradoxical breathing, accessory muscle use, and a respiratory rate in the fifties. He was intubated at 11:30 pm on day 3 of admission. CSF samples obtained from the EVD were sent to the Centers for Disease Control and Prevention (CDC), which returned positive for IgM and IgG EEE virus (EEEV) antibodies, confirming the EEEV diagnosis. Blood and CSF cultures demonstrated no growth. The patient was treated with supportive care and was successfully extubated after 9 days of mechanical ventilation.

Follow-Up and Outcomes

Postextubation, he exhibited significant neurological deficits, including moderate aphasia, dysphagia, and global weakness. He was transferred to a long-term rehabilitation center where he underwent aggressive physical and occupational therapy with some improvement in his neurologic and clinical status. The patient followed up with the outpatient neurology clinic. He had an improvement in his weakness and dysphagia but continued to have a moderate expressive aphasia as a sequelae of the disease.

DISCUSSION

EEEV is a mosquito-borne arbovirus that is considered one of the most severe and potentially fatal arboviral encephalitides in North America. It consists of 2 subtypes: 1) EEEV subtype I, which is found in North America and the Caribbean, and 2) Madariaga virus (EEEV subtype II-IV), which is found in South and Central America. It is transmitted to humans primarily from Aedes or Coquillettidia mosquitoes. EEEV is maintained in a transmission cycle between mosquitoes and birds in freshwater swamps.1 Aedes, Coquillettidia, and Culex species are responsible for transmission to humans to create a bridge between virus-infected birds (primary host) and humans (incidental host). The Culiseta melanura is the vector that maintains the EEEV primary transmission cycle in birds. Cross transmission from its usual reservoirs to other hosts such as humans, horses, swine, and exotic birds occurs at unpredictable intervals. Factors that increase the risk of these transmissions are thought to include complex interaction among human behaviors, weather, habitat destruction, bird migration, and other variables.2 Affected humans and horses are considered dead-end hosts because they do not develop sufficient viremia levels to infect other susceptible hosts.1 Although infections can occur throughout the year, the peak incidence is in August and September (as happened in the case report), mostly along the Atlantic and Gulf coasts.

EEE-infected patients usually present with nonspecific signs and symptoms, including fever, malaise, severe headache, muscle aches, nausea, and vomiting after a 7-10-day incubation period.2 When neurological symptoms related to encephalitis develop, the clinical condition usually worsens rapidly, with 90% of patients progressing to comatose or stuporous. One-half of the patients develop seizures or focal neurologic signs. EEE neuroinvasive disease is estimated to have a case-fatality rate of 30% or higher, with approximately 50% of survivors left with debilitating neurological sequelae.3 In the absence of a human vaccine against EEEV and no available antiviral therapies, treatment is primarily supportive.4,5 Between 2003 and 2018, an average of 8 EEE cases were reported annually in the United States, with a range of 4-21 cases per year.3 However, as of December 17, 2019, CDC has received reports of 38 cases of EEE disease in 2019 alone. Cases were reported from 10 states, including Alabama, Connecticut, Georgia, Indiana, Massachusetts, Michigan, New Jersey, North Carolina (1), Rhode Island, and Tennessee.6

Healthcare providers should consider EEE infection in the differential diagnosis of cases concerning for meningitis and encephalitis, especially in swamp areas where EEEV mosquito vectors are found. Suspicion for EEE should prompt an urgent workup with the collection of CSF specimens and appropriate imaging. Polymerase chain reaction analysis from blood and spinal fluid and testing for EEEV-specific IgM are usually used to confirm the diagnosis. Imaging can support the diagnosis while definitive testing is pending. Magnetic resonance imaging typically demonstrates the involvement of the basal ganglia and thalami, similar to our patient.2

CONCLUSION

Providers are encouraged to report suspected EEE infections to their state or local health department to facilitate diagnosis. Prevention of EEE depends on the community to reduce mosquito populations and protective measures to decrease exposure to mosquitoes. Increased public awareness and implementation of vector control to mitigate the risk for further transmission will be essential in reducing the risk of new EEEV outbreaks.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Acknowledgments

Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

Author Affiliations

1Department of Medicine, AtlantiCare Regional Medical Center, Atlantic City, NJ

2Rowan University School of Osteopathic Medicine, Stanford, NJ

3Department of Critical Care, AtlantiCare Regional Medical Center, Atlantic City, NJ

4Division of Infectious Disease, AtlantiCare Regional Medical Center, Atlantic City, NJ

5Division of Neurology Medicine, AtlantiCare Regional Medical Center, Atlantic City, NJ

Corresponding Author

Saif Faiek, MD ()

Author Contributions

All of the authors participated in evaluating the patient and writing the case report.

Funding Statement

The author(s) have no funding source to disclose.

References

1. Lindsey NP, Staples JE, Fischer M. Eastern equine encephalitis virus in the United States, 2003-2016. Am J Trop Med Hyg 2018 May;98(5):1472-7. DOI: https://doi.org/10.4269/ajtmh.17-0927

2. Morens DM, Folkers GK, Fauci AS. Eastern equine encephalitis virus - another emergent arbovirus in the United States. N Engl J Med 2019 Nov;381(21):1989-92. DOI: https://doi.org/10.1056/NEJMp1914328

3. Garlick J, Lee TJ, Shepherd P, et al. Locally acquired eastern equine encephalitis virus disease, Arkansas, USA. Emerg Infect Dis 2016 Dec;22(12):2216–7. DOI: https://doi.org/10.3201/eid2212.160844

4. Lindsey NP, Martin SW, Staples JE, Fischer M. Notes from the field: Multistate outbreak of eastern equine encephalitis virus - United States, 2019. MMWR Morb Mortal Wkly Rep 2020 Jan;69(2):50–1. DOI: https://doi.org/10.15585/mmwr.mm6902a4

5. Jonsson CB, Cao X, Lee J, et al. Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses. Antivir Res 2019 Jul;167:25–34. DOI: https://doi.org/10.1016/j.antiviral.2019.04.004

6. CDC. Eastern equine encephalitis virus: US Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/easternequineencephalitis/index.html

Keywords: arbovirus, eastern equine encephalitis, mosquito-borne virus, Centers for Disease Control and Prevention, CSF, cerebrospinal fluid, EEE, eastern equine encephalitis, EEEV, eastern equine encephalitis virus, EVD, external ventricular drain

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