Eastern Equine Encephalitis: An Emerging Arboviral Disease Threat,Maine,2009

Introduction

E astern equine encephalitis (EEE) is one of the most severe arboviral encephalitides in North America. EEE virus (EEEV), a mosquito-borne alphavirus, is maintained in an enzootic cycle primarily between Culiseta melanura mosquitoes and wild birds. Spread of EEEV to mammals, who are dead end hosts, requires bridging mosquitoes that feed on both birds and mammals (Morris 1988). An estimated 4% of persons infected with EEEV will develop meningitis or encephalitis, with a 30% case fatality rate and neurologic sequelae in >50% of survivors (Feemster 1938, Ayres and Feemster 1949, Goldfield et al. 1968). A median of four human EEE cases were reported to the U.S. Centers for Disease Control and Prevention (CDC) annually from 1964–2008 (range: 0–21 cases/year) (CDC 2009).

Maine is a large, predominantly rural state with ecosystems that could sustain EEEV transmission. To date, no human EEE cases have been reported in a Maine resident, although in 2008, a visitor to Maine died from EEE. From 2001 to 2008, 3 EEE equine cases, 13 EEEV-infected birds, and 2 EEEV-positive mosquito pools were reported in Maine; all occurred in York and Cumberland Counties. We summarize the increased and expanded EEEV activity that occurred in Maine in 2009, describe current testing practices for possible human EEE cases, and make recommendations for identifying future EEE cases.

We identified all EEE activity reported to Maine CDC in 2009, and conducted active surveillance for human disease. Human arboviral encephalitis is a nationally notifiable condition and is reportable in Maine. Reporting of nonhuman EEEV activity is passive and voluntary. Suspected animal cases are reported to the state veterinarian and are tested for rabies before being tested for EEEV. Routine mosquito-based surveillance occurs in York and Cumberland counties from June to September.

A possible human EEE case was defined as a patient hospitalized in Maine from July–September 2009 with unexplained acute meningitis or encephalitis (i.e., acute onset of fever with meningismus, mental status changes, seizures, or cerebrospinal fluid [CSF] white blood cells ≥6 cells/mm³). We identified possible cases by searching international classification of diseases (ICD)-9 discharge codes ^* at Maine's four largest hospitals and CSF specimens submitted to five laboratories for diagnostic testing for herpes simplex virus, enterovirus, West Nile virus, or EEEV. The study hospitals have a statewide catchment area. Patients <1 month of age were excluded. We reviewed medical records to confirm the clinical syndrome and excluded patients with defined etiologies. Negative test results for anti-EEEV immunoglobulin M (IgM) antibodies were considered adequate to exclude EEEV infection if the sample was collected >7 days after illness onset. This investigation was determined to be a public health response activity and did not require review by the state or CDC institutional review boards.

From August–October 2009, fatal cases of EEE were identified among 15 horses, 1 llama, and 3 pheasant flocks in Maine. Five counties were affected, extending into central Maine (Fig. 1). In addition, EEEV was detected in two pools of Cs. melanura collected in York County. None of the horses had completed the recommended vaccination course (Wilson et al. 1995).

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FIG. 1.

Eastern equine encephalitis cases in horses, Maine, 2009. In 2009, eastern equine encephalitis virus infection also was detected in three pheasant flocks, one llama, and two mosquito pools, all in York County.

No human cases of EEE were reported in Maine in 2009. We identified 30 possible EEE cases admitted to four Maine hospitals from July 1 to September 30; 26 (87%) were identified through laboratory records, 1 (3%) by ICD-9 code search, and 3 (10%) by both methods. Anti-EEEV IgM testing was performed on 7 (23%) possible EEE cases, and only 3 (10%) had specimens that were adequate to exclude EEEV infection. All EEEV tests were negative.

Of the 27 patients for whom EEE could not be ruled out, 14 (52%) were women and the median age was 37 years (range: 1 month–80 years). Seventeen (63%) patients resided in a county that reported nonhuman EEEV activity in 2009. The median hospital stay was 4 days (range: 1–35 days). Five (19%) were admitted to the intensive care unit; one (4%) patient died. Only 5 (19%) of the 27 patients were tested for West Nile virus; all specimens were collected ≤7 days after symptom onset and all tested negative.

Increased and more widespread EEEV activity was reported in Maine in 2009, possibly indicating expansion of the range of this virus. Human EEE cases have been reported in the neighboring states of New Hampshire and Massachusetts. EEEV activity also has been detected in eastern Canada, suggesting that the EEEV enzootic cycle can likely be sustained throughout Maine (Calisher 1994).

While no human EEE cases were identified, nonhuman EEEV activity indicates potential risk to humans. In addition to the high case fatality rate, the neurologic sequelae associated with EEE disease has been estimated to cost $3 million per patient (Villari et al. 1995). Therefore, even a small number of EEE cases could have a substantial economic and public health impact.

Our investigation identified that diagnostic testing practices were inadequate to exclude EEEV infection in 90% of possible EEE cases either because testing was not requested or it was conducted too early in the illness. EEE disease should be considered in all patients hospitalized with unexplained meningitis or encephalitis in an endemic area during the arboviral season. EEEV is rarely isolated from blood or CSF, and anti-EEEV IgM may not be detectable during the first week of illness (Feemster 1938, Morse et al. 1992). Submission of a convalescent serum specimen for EEEV testing should be considered if the initial sample was collected ≤7 days after illness onset and the diagnosis remains uncertain.

Our investigation was subject to several limitations. We did not survey all hospitals and laboratories in Maine or investigate unexplained deaths; therefore, we likely missed some possible EEE cases. In addition, patients with alternate clinical diagnoses made after hospital discharge may have been misclassified as possible EEE. Compared to published descriptions of confirmed EEE cases, the 27 possible cases identified in Maine had shorter hospital admissions and a lower case fatality rate (Feemster 1938, Ayres and Feemster 1949, Deresiewicz et al. 1997), suggesting that most of these patients likely did not have EEE. However, convalescent serum specimens, which could have been tested to determine if any of the possible cases had EEE, were not obtained.

Activities to further define the geographic range and extent of EEEV activity in Maine could include expanded surveillance of mosquitoes or sentinel animals. To prevent equine cases, horses in Maine should receive EEE vaccine (Wilson et al. 1995). When EEEV activity is identified, active surveillance for human cases should be considered, including appropriate collection and testing of convalescent samples. Finally, efforts should be made to improve testing practices among healthcare providers and increase public awareness regarding EEE.