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

None: 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.

Five Emerging Neuroinvasive Arboviral Diseases: Cache Valley, Eastern Equine Encephalitis, Jamestown Canyon, Powassan, and Usutu.

There are many arthropod-borne viruses (arboviruses) capable of neuroinvasion, with West Nile virus being one of the most well known. In this review, we highlight five rarer emerging or reemerging arboviruses capable of neuroinvasion: Cache Valley, eastern equine encephalitis, Jamestown Canyon, Powassan, and Usutu viruses. Cache Valley and Jamestown Canyon viruses likely circulate throughout most of North America, while eastern equine encephalitis and Powassan viruses typically circulate in the eastern half. Usutu virus is not currently circulating in North America, but has the potential to be introduced in the future given similar climate, vectors, and host species to Europe (where it has been circulating). Health care providers should contact their state or local health departments with any questions regarding arboviral disease surveillance, diagnosis, treatment, or prevention. To prevent neuroinvasive arboviral diseases, use of insect repellent and other mosquito and tick bite prevention strategies are key.

Eastern equine encephalomyelitis virus infection in six captive southern cassowaries (Casuarius casuarius).

CASE DESCRIPTION Within a 2-week period, 4 southern cassowaries (Casuarius casuarius) at an exhibit at a Virginia zoo died acutely subsequent to eastern equine encephalitis virus (EEEV) infection. This prompted a search for other EEEV outbreaks in cassowaries, which resulted in the identification of 2 additional cassowaries that died of EEEV infection at a conservation center in Florida. CLINICAL FINDINGS Both juvenile and adult birds were affected. Three of the 6 birds died acutely with no premonitory signs. Clinical disease in the other 3 birds was characterized by lethargy and ataxia. Clinicopathologic findings typically included leukocytosis, hyperuricemia, abnormally high liver enzyme activities, and hyper-ß globulinemia, which was indicative of acute inflammation. TREATMENT AND OUTCOME The 3 birds with clinical disease died despite supportive treatment. Gross abnormalities commonly observed during necropsy included coelomitis and evidence of diarrhea. Frequently observed histologic abnormalities were encephalitis, vasculitis, hepatitis, nephritis, and splenitis. The diagnosis of EEEV infection was confirmed by detection of serum anti-EEEV antibodies or detection of viral RNA in brain tissue by use of a reverse-transcriptase PCR assay. CLINICAL RELEVANCE Findings suggested that EEEV can cause high morbidity and mortality rates in southern cassowaries. Clinical disease might be reduced or prevented by vaccination, isolation of ill birds, and mosquito control strategies.

Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure.

MRI findings in eastern equine encephalitis: the "parenthesis" sign.

Two patients with eastern equine encephalitis (EEE) presented to a tertiary referral center. Both subjects' brain magnetic resonance imaging showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities including linear areas of hyperintensity in the external and internal capsules with sparing of the lentiform nuclei. Single case reports of imaging findings in EEE exist with nonspecific patterns of abnormality. We propose that this "( ) parentheses sign" on T2 or FLAIR imaging may distinguish EEE from other processes.

Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis.

Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed.

Eastern equine encephalitis: a classical case.

We present the case of a 40-year-old man with rapidly deteriorating acute meningoencephalitis, finally diagnosed as eastern equine encephalitis (EEE). The course and timing in this patient are quite characteristic. EEE is an arthropod borneviral illness in which the mosquito serves as the vector. It is amongst the most severe of the arbovirus encephalitides and has a high mortality and morbidity. In nonfatal cases, residual neurological deficits are often severe and permanent. North American lineage of EEE is mainly found in the northeast especially along the coastal areas. EEE is primarily found in horses and other domestic mammals that remain outdoors nocturnally. In humans, symptoms range from nonspecific constitutional features to catastrophic neurological sequelae including death. Hyponatremia and increased cerebrospinal fluid (CSF) white blood cell count are independent predictors of poor outcomes. Diagnosis is suggestive by demonstrating IgM antibody in blood or CSF samples and can be confirmed by other serologic assay including immunohistochemistry and polymerase chain reaction (PCR). Measures recommended by the Center for Disease Control (CDC) for prevention include using repellents, protective clothing, screens, and eradication of mosquito breeding areas. EEE remains without cure and prevention is the best medicine.

Surto de encefalomielite equina Leste na Ilha de Marajó, Pará / Eastern equine encephalitis on Marajó Island, Pará state, Brazil

Nove casos de encefalomielite equina foram estudados na Ilha de Marajó, estado do Pará, Brasil. Os equinos apresentavam dificuldade em se manter em estação, andavam em círculo, tinham acentuada depressão, pálpebras cerradas, paralisia da língua, tremores musculares, bruxismo, anorexia e desidratação. Alguns apresentavam diminuição dos reflexos auricular, palpebral, de ameaça, diminuição do tônus da língua e taquicardia. Posição de auto-auscultação foi observada com frequência. Os animais muitas vezes eram encontrados apoiados em troncos e cercas para se manterem em estação. À necropsia verificou-se hemorragia das leptomeninges e da medula, alguns apresentaram ainda aderência das leptomeninges. À histopatologia verificou-se encefalite difusa que afetava principalmente a substância cinzenta, com meningite e coroidite. Foi observada perivasculite mononuclear. Em dois equinos identificou-se o vírus da encefalomielite equina Leste pela reação de Semi-Nested transcrição reversa de polimerase em cadeia (Semi-Nested RT-PCR).

Nine cases of equine encephalomyelitis on Marajó Island, state of Pará, Brazil, were studied. The affected horses had difficulty to stand, walked in circles, with marked depression, closed eyelids, tongue paralysis, muscle tremors, bruxism, anorexia and dehydration. Some had their ear and eyelid reflexes diminished, decreased tongue tone and tachycardia; laid down frequently they kept their head on the chest. Often they were seen resting their head on tree trunks or fences. At necropsy, hemorrhages of the meninges and spinal cord, and in some animals also adhesion of the meninges were found. Histologically there was diffuse encephalitis affecting mainly the gray matter, with meningitis and choroiditis. Presence of perivascular cuffs consisting of mononuclear inflammatory cells was observed. From two horses the Eastern equine encephalitis virus was identified by semi-nested reverse transcription polymerase chain reaction (semi-nested RT-PCR).

Outbreaks of Eastern equine encephalitis in northeastern Brazil.

Outbreaks of eastern equine encephalitis observed from May 2008 to August 2009 in the Brazilian states of Pernambuco, Ceará, and Paraíba are reported. The disease occurred in 93 farms affecting 229 equids with a case fatality rate of 72.92%. Main clinical signs were circling, depression or hyperexcitability, ataxia, and progressive paralysis with a clinical manifestation period of 3-15 days. Main histologic lesions were a diffuse lymphocytic encephalomyelitis with neuronal death, satellitosis, neuronophagia, and hemorrhages being more severe in the cerebral gray matter of the telencephalon, diencephalon, and mesencephalon. Some animals also had areas of malacia in the telencephalon, thalamus, and basal nuclei. From 1 case, the virus was isolated by mice inoculation, and in other 13 cases was identified as Eastern equine encephalitis virus by semi-nested reverse transcription polymerase chain reaction. After DNA sequencing, all samples were identified as eastern equine encephalitis through the BLASTn analysis, but samples from the Ceará and Paraíba states corresponded to the same cluster, while the sample from the state of Pernambuco corresponded to a different cluster.

Eastern equine encephalitis: an emerging arboviral disease threat, Maine, 2009.

BACKGROUND: Eastern equine encephalitis (EEE) is one of the most severe arboviral encephalitides in North America. Before 2009, limited nonhuman EEE virus activity had been reported in Maine, all from the southernmost area of the state. No human case has been reported in a Maine resident. METHODS: We review all EEE virus activity reported to Maine Centers for Disease Control in 2009 and describe current testing practices for possible human EEE cases. RESULTS: In 2009, fatal cases of EEE were identified in 15 horses, 1 llama, and 3 flocks of pheasants in Maine, with activity extending into the central part of the state. Although no human EEE cases were identified, diagnostic testing practices of most meningitis and encephalitis cases were inadequate to exclude EEE. CONCLUSIONS: Work to better define the expanding range of EEE virus in Maine is warranted, along with education of healthcare providers regarding appropriate testing for this serious disease.

Eastern equine encephalitis virus infection and hemophagocytic lymphohistiocytosis in a 5-month-old infant.

Eastern equine encephalitis virus infection is a rare sporadic central nervous system infection transmitted by a mosquito vector. Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease associated with the inability of an overactive immune system to effectively respond to infections. Many viruses are known to trigger primary, as well as secondary, HLH. We report a pediatric case of eastern equine encephalitis virus-associated HLH which caused severe neurologic injury and death.

Case report: Eastern equine encephalitis virus imported to the UK.

Eastern equine encephalitis (EEE) is rare, but the most severe of the mosquito-borne encephalitides in the United States with a high case fatality rate of 30%. Here, we present a patient with EEE. EEE virus causes sporadic human disease in the Eastern parts of the United States, but the case we describe was a Scottish tourist who acquired the disease from mosquito bites while in holiday in the United States. This is a first report of an imported case to Europe.

Eastern equine encephalitis in a captive harbor seal (Phoca vitulina).

A 31-yr-old male, captive harbor seal (Phoca vitulina) was evaluated for a 48-hr period of anorexia followed by the onset of seizures. A prolonged seizure failed to respond to anticonvulsant therapy and the animal was euthanized. At necropsy, no significant gross lesions were identified. Reverse transcriptase-polymerase chain reaction testing of brain samples was positive for eastern equine encephalitis virus (EEEV) RNA, and serum was positive for anti-EEEV antibodies by plaque reduction neutralization. Histopathologic evaluation revealed severe and multifocal encephalitis with leptomeningitis, characterized by neutrophilic infiltrates in neuropil, neuronal necrosis, satellitosis, neuronophagia, and perivascular cuffs of lymphocytes, macrophages, and neutrophils. Additionally there was moderate, multifocal, adrenal cortical necrosis. Immunohistochemical staining for EEEV demonstrated viral antigen within necrotic neurons and glial cells. Virus was isolated from frozen brain tissue, sequenced for comparison to other strains, and determined to be a typical North American strain. EEEV should be included as a possible cause of neurologic disease in harbor seals with compatible signs located in geographic regions where vector transmission of EEEV is encountered.

Eastern equine encephalitis in 9 South American camelids.

BACKGROUND: Eastern equine encephalitis (EEE) virus is a mosquito-borne togavirus (alphavirus) that causes severe (often fatal) encephalitis in many mammalian species, but it has not been reported previously in South American camelids. HYPOTHESIS: South American camelids can become naturally infected with EEE virus and show encephalitic signs similar to those observed in other affected species. ANIMALS: Nine cases (8 alpacas and 1 llama, aged 3.5 weeks to 12 years) were identified; 4 of 9 were 510 weeks old. All cases were from the East Coast of the United States and presented in late summer and fall. METHODS: A retrospective study was performed to include confirmed cases of EEE in camelids in North America before 2006. RESULTS: Eight of nine (89%) camelids died or were euthanized in extremis, with the mean time to death of 2 days. Clinical signs were consistent with encephalitis and included fever, lethargy, ataxia, seizures, recumbency, torticollis, opisthotonus, and vestibular signs. No consistent hematologic abnormalities were identified, and cerebrospinal fluid contained an increased protein concentration in the single camelid analyzed. No successful therapy was identified. EEE was confirmed by alphavirus detection by using immunohistochemistry (IHC) and polymerase chain reaction (PCR) in the central nervous system (CNS) and by serology. Findings included polioencephalitis with lymphocytic perivascular cuffing; neutrophil infiltration; gliosis; neuron satellitosis; necrosis; and edema, with intracytoplasmic alphavirus within neurons and glial cells. No virus was detected in extraneural tissues. CONCLUSIONS AND CLINICAL IMPORTANCE: In endemic areas, EEE should be considered a differential diagnosis for young and adult camelids with CNS disease. Brain histopathology with indirect IHC or PCR is diagnostic.