Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients.

BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.

Surveys for Antibodies Against Mosquitoborne Encephalitis Viruses in California Birds, 1996-2013.

From 1996 through 2013, 54,546 individual birds comprising 152 species and 7 orders were banded, bled, and released at four study areas within California, from which 28,388 additional serum samples were collected at one or more recapture encounters. Of these, 142, 99, and 1929 birds from 41 species were positive for neutralizing antibodies against western equine encephalomyelitis virus (WEEV), St. Louis encephalitis virus (SLEV), or West Nile virus (WNV) at initial capture or recapture, respectively. Overall, 83% of the positive serum samples were collected from five species: House Finch, House Sparrow, Mourning Dove, California Quail, and Western Scrub-Jay. Temporal data supported concurrent arbovirus surveillance and documented the disappearance of birds positive for WEEV in 2008 and SLEV in 2003 and the appearance of birds positive for WNV after its invasion in 2003. Results of these serosurveys agreed well with the host selection patterns of the Culex vectors as described from bloodmeal sequencing data and indicated that transmission of WNV seemed most effective within urban areas where avian and mosquito host diversity was limited to relatively few competent species.

Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence.

The Alphavirus genus of the family Togaviridae contains mosquito-vectored viruses that primarily cause either arthritogenic disease or acute encephalitis. North American eastern equine encephalitis virus (NA-EEEV) is uniquely neurovirulent among encephalitic alphaviruses, causing mortality in a majority of symptomatic cases and neurological sequelae in many survivors. Unlike many alphaviruses, NA-EEEV infection of mice yields limited signs of febrile illness typically associated with lymphoid tissue replication. Rather, signs of brain infection, including seizures, are prominent. Use of heparan sulfate (HS) as an attachment receptor increases the neurovirulence of cell culture-adapted strains of Sindbis virus, an arthritogenic alphavirus. However, this receptor is not known to be used by naturally circulating alphaviruses. We demonstrate that wild-type NA-EEEV strain FL91-4679 uses HS as an attachment receptor and that the amino acid sequence of its E2 attachment protein is identical to those of natural isolates sequenced by RT-PCR amplification of field samples. This finding unequivocally confirms the use of HS receptors by naturally circulating NA-EEEV strains. Inactivation of the major HS binding domain in NA-EEEV E2 demonstrated that the HS binding increased brain replication and neurologic disease but reduced lymphoid tissue replication, febrile illness signs, and cytokine/chemokine induction in mice. We propose that HS binding by natural NA-EEEV strains alters tropism in vivo to antagonize/evade immune responses, and the extreme neurovirulence of wild-type NA-EEEV may be a consequence. Therefore, reinvestigation of HS binding by this and other arboviruses is warranted.

Identificaçäo do vírus causador da encefalomielite eqüina, Paraná, Brasil / Identification of the encephalitis equine virus, Brazil

Objetivo: No período de 1996 a 1999, um agente viral causador de encefalomielite afetou as populaçöes de eqüinos em diferentes regiöes do Estado do Paraná, Brasil. Objetivou-se realizar pesquisa sorológica na tentativa de isolar o vírus causador da doença. Métodos: Em quatro municípios do Estado do Paraná, Brasil, foram coletados culicídeos com armadilha Shannon e isca humana, identificados e processados para isolamento de vírus. Em dois municípios estudados foram colhidas amostras de sangue de eqüinos para isolamento de vírus e para pesquisa sorológica. Os soros foram analisados pelo teste de inibiçäo da hemaglutinaçäo frente a diferentes antígenos de Alphavirus e Flavivirus. Aqueles que revelaram reaçöes positivas-cruzadas foram analisados pelo teste de neutralizaçäo. Resultados: Foram coletados culicídeos dos gêneros: Culex, Aedes, Mansonia, Coquillettidia, Psorophora, Sabethes, Wyeomyia e Limatus. Embora näo sendo isolado o agente viral, foram detectados anticorpos hemaglutinantes para o vírus Encefalomielite eqüina do Leste, Mucambo, Pixuna, Maguari e St. Luis. Em doze amostras de soros foram detectados anticorpos neutralizantes para o vírus Encefalomielite eqüina do Leste. Conclusöes: Foram coletadas espécies de culicídeos, considerados na bibliografia como vetores de vírus causadores de encefalomielite buniavírus e outras arboviroses de importância epidemiológica. Pela presença de sintomas de encefalomielite e de anticorpos para o vírus Encefalomielite eqüina do Leste nos soros de cavalos, supöe-se ser esse o vírus causador da doença nos eqüinos das regiöes estudadas

Vigilancia de las encefalitis de San Luis, equina del este y equina del oeste en la provincia Ciego de Avila / Surveillance of St. Louis, Eastern equine, and Wester equine encephalitis in the province of Ciego de Avila

Se realizaron estudios serologicos utilizando las tecnicas de inhibicion de la hemaglutinacion y neutralizacion con el objetivo de conocer la dinamica de circulacion de algunos Arbovirus, con el empleo de los antigenos de encefalitis equina del este, equina del oeste y San Luis en sueros humanos de personas sanas y sintomaticas, asi como de aves centinelas, en el periodo de 1987 a 1991 y durante el ano 1994. El 1,7 por ciento de las personas asintomaticas testadas presentaron anticuerpos neutralizantes a equina del este y un 4,8 por ciento a encefalitis de San Luis. Se detectaron 16 pacientes con seroconversion por inhibicion de la hemaglutinacion al virus de San Luis. La vigilancia con aves centinelas demostro que durante los anos 1988, 1989 y 1994 circulo San Luis en los municipios de Moron, Bolivia y Chambas, mientra que en este ultimo municipio en los anos 1988 y 1989 circulo la encefalitis equina del este. Se detectaron en personas sanas anticuerpos heterologos, ya que no hubo presencia de anticuerpos neutralizantes contra este virus

Clinical and pathological features of Nigerian equine encephalitis.

Thirteen cases of a disease with a low morbidity and very high mortality in horses in Nigeria are described; the disease is characterised by fever (rectal temperature > or = 40 degrees C), generalised muscle spasms, ataxia, increased respiratory and heart rates and terminal lateral recumbency. The illness generally lasts three to five days but durations of 12 to 30 hours have been observed. Laboratory investigations, including histopathology and serology suggest a viral aetiology, possibly an alphavirus of the equine encephalitis group.

Agents of equine viral encephalomyelitis: correlation of serum and cerebrospinal fluid antibodies.

A survey was conducted by testing 115 paired equine serum and cerebrospinal fluid samples by hemagglutination-inhibition for antibodies to Powassan and snowshoe hare viruses, and by virus neutralization for antibodies to equine herpesvirus type 1. Twenty-five samples were from horses with spontaneous neurological disease and the remainder from horses euthanized because of various nonneurological disorders. All sera and cerebrospinal fluids were negative for antibodies to Powassan virus. Fifty-one sera (44.3%) and 15 cerebrospinal fluids (13.0%) had antibodies to snowshoe hare virus. Ninety-eight sera (85.2%) and four cerebrospinal fluids (3.5%) were positive for antibodies to equine herpesvirus type 1. Powassan virus was inoculated intracerebrally into one, and intravenously into four ponies. Neurological signs associated with a nonsuppurative encephalomyelitis occurred in three ponies. Antibodies to Powassan virus were detected in sera of all animals but in cerebrospinal fluids of only two. Powassan virus was isolated from brain and spinal cord of only the intracerebrally inoculated animal.

Changes in serum and striatal free amino acids after Venezuelan equine encephalomyelitis virus infection.

The infection with the Venezuelan equine encephalomyelitis virus produced a significant increase in the concentration of alanine, arginine, asparagine, glutamine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine in the striatum of rats. On the contrary, the concentrations of aspartate, GABA, glutamate, and taurine were reduced. Arginine, aspartate, glycine, methionine, phenylalanine, taurine, and tyrosine concentrations were increased in the serum of infected rats. However, the modifications in the content of free amino acids in the striatum and serum of rats that survived the infection were qualitatively and quantitatively different from those detected during the acute phase of the infection.

Serum epidemiology of eastern, western and Venezuelan equine encephalitides in Mexico.

The presence of HI antibodies for the Eastern, Western and Venezuelan equine encephalitis was investigated in 16,405 human sera collected in 47 communities in the Mexican Republic. It was found that there is a high percentage of individuals who have antibodies against Venezuelan equine encephalitis. In turn, it was discovered that persons with Western equine encephalitis virus antibodies live in the northwestern states of the country. Very few cases with Eastern equine encephalitis antibodies were detected.

Studies of glucose metabolism in rhesus monkeys after Venezuelan equine encephalitis virus infection.

Previous studies have demonstrated a diabetogenic effect of Venezuelan equine encephalitis (VEE) virus in hamsters. A preliminary study was conducted in which five 2- to 3-year-old rhesus monkeys were infected with the virulent Trinidad donkey strain of VEE virus and their carbohydrate metabolism was studied over 10 months. All animals developed mild clinical illness (rhinorrhea, cough, fever), were viremic, and developed antibodies. As compared with the results of preinoculation intravenous glucose tolerance tests (IVGTT), the monkeys had abnormally high glucose values by 2 months postinoculation (PI), progressively diminished insulin responses between 8 days and 5 months PI, and significantly lower glucagon curves 2, 5, and 10 months PI. Pancreatic histology and insulin content were normal. A second, controlled study was conducted of glucose and insulin metabolism in somewhat older (3- to 8-year-old) rhesus monkey after they were infected with both the Trinidad donkey strain of VEE virus and the attenuated VEE vaccine (TC-83). Groups of six monkeys received the virulent virus and the TC-83 vaccine, and five animals were sham-inoculated with saline. Monkeys inoculated with virulent virus became viremic, and 50% became febrile without overt signs of illness, whereas those given TC-83 virus remained afebrile and did not become viremic, but five of six developed antibodies. Intravenous glucose tolerance tests were performed and serum immunoreactive insulin responses to glucose administration measured before infection and 2 and 5 months later. No significant and consistent alterations of glucose or insulin responses were detected in the infected or control groups. Although several animals had preinoculation anti-islet cell antibodies, none developed new antibodies during the study.

Early protection in hamsters immunized with attenuated Venezuelan equine encephalomyelitis vaccine.

The rapid onset and persistence of homologous and heterologous protection induced by attenuated Venezuelan equine encephalomyelitis (VEE) vaccine (TC-83) were studied in the hamster, by using challenge response as the index of protection. At 8 hr postvaccination with 10(3) median immunizing doses of TC-83 vaccine, 15 to 20% of animals were protected against challenge with VEE virus as well as Eastern and Western equine encephalomyelitis viruses. The percentage of protection increased with time postvaccination until 80 to 90% homologous and heterologous protection was achieved by 18 hr postvaccination. Temporal studies indicated that early protection (days 1 to 6) correlated with vaccine viremia, and that the percentage of protection against heterologous challenge decreased with the cessation of viremia. Data are presented to indicate that the early protection phenomenon is one of interference, since little or no replication of a challenge virus occurred when it was administered during the vaccine viremia stage.

Field studies of an attenuated Venezuelan equine encephalomyelitis vaccine (strain TC-83).

A series of field studies using strain TC-83 attenuated Venezuelan equine encephalomyelitis vaccine in horses was made to determine the rate of seroconversions, the postvaccination viremia, and the possibility of adverse reactions to the vaccine. The rate of seroconversions varied from 50% in one study to 91 and 100% in two others. The highest level of viremia measured was 7 x 10(3) to 8 x 10(3) plaqueforming units per ml. No adverse reactions to the vaccine were observed in any horses, including 42 pregnant mares and their resulting foals.