Viral Equine Encephalitis, a Growing Threat to the Horse Population in Europe?

Neurological disorders represent an important sanitary and economic threat for the equine industry worldwide. Among nervous diseases, viral encephalitis is of growing concern, due to the emergence of arboviruses and to the high contagiosity of herpesvirus-infected horses. The nature, severity and duration of the clinical signs could be different depending on the etiological agent and its virulence. However, definite diagnosis generally requires the implementation of combinations of direct and/or indirect screening assays in specialized laboratories. The equine practitioner, involved in a mission of prevention and surveillance, plays an important role in the clinical diagnosis of viral encephalitis. The general management of the horse is essentially supportive, focused on controlling pain and inflammation within the central nervous system, preventing injuries and providing supportive care. Despite its high medical relevance and economic impact in the equine industry, vaccines are not always available and there is no specific antiviral therapy. In this review, the major virological, clinical and epidemiological features of the main neuropathogenic viruses inducing encephalitis in equids in Europe, including rabies virus (Rhabdoviridae), Equid herpesviruses (Herpesviridae), Borna disease virus (Bornaviridae) and West Nile virus (Flaviviridae), as well as exotic viruses, will be presented.

Egg production drops in breeder turkeys associated with western equine encephalitis virus infection.

Egg production drops associated with western equine encephalitis (WEE) virus infection occurred in three turkey breeder flocks in California during summer 1993 and again in one flock the following year. Egg production losses totaled 8.76%, 9.57%, 9.71%, and 10.12% and were accompanied by an increase in small white-shelled and shell-less eggs. The outbreaks coincided with peak WEE virus activity in the state on the basis of statistics compiled by the California Department of Health Services on seroconversion rates in sentinel chicken flocks. Paired serum samples taken 2-3 wk apart showed increased titers to WEE between acute and convalescent sera in turkeys from three affected flocks. Convalescent sera were not available for testing from the fourth flock. WEE virus was isolated from one breeder hen submitted to the diagnostic laboratory during the early stages of the outbreak.

The economic burden imposed by a residual case of eastern encephalitis.

To estimate the economic burden imposed by eastern encephalitis (EE), we identified a series of residents of eastern Massachusetts who had survived EE infection and enumerated any costs that could be attributed to their experience. The records of three people who suffered only a transient episode of disease were analyzed as well as those of three who suffered severe residual sequelae. Transiently affected subjects mainly required assistance for direct medical services; the average total cost per case was $21,000. Those who suffered persistent sequelae remained at home and seemed likely to live a normal span of years, but without gainful employment. Early in the course of their chronic illness, costs ranged as high as $0.4 million per year, but plateaued at about $0.1 million after three years. Hospital costs, which dominated early in the disease experience, approached $0.3 million per patient. Educational costs tended to replace hospital costs after two years as the dominant economic burden and totaled about $0.3 million per patient during the first six years. Total costs then averaged almost $0.8 million. By the time that these subjects will have reached 22 years of age, disease-related costs will have totaled about $1.5 million. Institutionalization will impose an additional lifetime cost of $1.0 million. Insecticidal interventions designed to avert outbreaks of human EE infection cost between $0.7 million and $1.4 million, depending on the extent of the treated region. The direct costs of an intervention are less than the $3 million imposed on one person suffering residual sequelae of EE.

Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent epidemiologic trends, and the association of rainfall with EEE occurrence.

An Eastern equine encephalitis (EEE) outbreak in 1989 led to nine human and 196 equine cases, chiefly in coastal Atlantic and Gulf Coast counties. In the past two decades, EEE age-specific incidence and mortality rates have declined compared with earlier years. Analysis of rainfall patterns in areas where human EEE cases occurred between 1983 and 1989 revealed an association between occurrence of human cases and excess rainfall. The association was stronger with data from local weather stations than from statewide rainfall averages and the predictive models were best when applied to northern states. The sensitivity and specificity of these measures varied, depending on the model used, but the positive predictive value was no better than 50%, regardless of the rainfall model applied.

Eastern equine encephalitis in Massachusetts: a report of 16 cases, 1970-1984.

We studied the case records of 16 patients with eastern equine encephalitis (EEE) in Massachusetts from 1970 to 1984 and compared their presentations, courses, and outcomes with the data available from previous epidemics. In recent years, there has been a greater frequency of EEE in adults, whereas in the past it was considered a disease of children. Also, prognosis for a good functional recovery seems to be correlated with age over 40 years, a long prodromal course (5 to 7 days) of constitutional symptoms, and the absence of coma. Previous reports did not mention these significant correlations. We also stress the positive and negative diagnostic correlations, in order to distinguish between EEE and herpes simplex encephalitis.

Sleep apnea and nocturnal hypoventilation after western equine encephalitis.

That viral encephalitis can produce daytime hypoventilation is well appreciated, but an association of this infection with the development of a prolonged disturbance of breathing during sleep once the ventilatory disorder during wakefulness has resolved, has not been reported. We describe a young male who required assisted mechanical ventilation in association with western equine encephalitis. Normal waking ventilation returned over 3 to 4 wk, but frequent apneas and severe hypoventilation persisted during sleep with a near absence of waking ventilatory response to chemical stimuli. Over 3 months there was considerable improvement in breathing during sleep associated with an increase in both hypoxic and hypercapnic ventilatory responsiveness.

Human Venezuelan equine encephalitis virus infection and diabetes in Zulia State, Venezuela.

Venezuelan equine encephalitis (VEE) virus has been implicated as producing alterations in glucose metabolism in animals. We performed oral glucose tolerance tests and measured serum immunoreactive insulin responses in 13 patients who were infected by VEE virus during an epidemic in 1969, in Zulia State, Venezuela. No significant alterations in the glucose tolerance test were found. Sera of 86 diabetic outpatients and 98 control individuals with normal glycemia at a local hospital were tested for antibodies to VEE virus by hemagglutination inhibition. No statistically significant difference was found between the two groups; 10.4% of the diabetic patients had detectable antibodies against VEE virus, compared to 7.1% of controls. Seventy-three percent of the diabetics with antibodies were individuals over 40 yr old, whose diabetes could be catalogued as insulin independent. The results of these studies indicate no relationship of VEE virus infection to subsequent diabetes.

Teratological effects of western equine encephalitis virus on the fetal nervous system of Macaca mulatta.

Fetal rhesus monkeys were inoculated intracerebrally with an attenuated strain of western equine encephalitis virus. All animals developed microcephaly. Twelve of sixteen monkeys developed ex vacuo hydrocephalus. All virus inoculated fetuses developed WEE virus antibody. Virus could not be recovered at the time of delivery. Monkeys with the highest WEE antibody titers showed the greatest degree of hydrocephalus.

Effects of influenza, mumps, and western equine encephalitis viruses on fetal rhesus monkeys (Macaca mulatta).

Pregnant Rhesus monkeys were infected via instillation of influenza, mumps and western equine encephalomyelitis viruses respectively into the amniotic sacs at approximately 90 days gestation to determine if fetal infections would occur. Virus was recovered from fetal tissues after seven days in 100% of the exposed animals. Thus, the viruses are capable of causing fetal infection. Rhesus monkey fetuses were inoculated with influenza, mumps and WEE viruses by the direct intracerebral route at approximately 90 days gestation to determine possible teratogenicity of the viruses. influenza virus caused no malformations or measurable fetal effects. Mumps virus resulted in significant fetal mortality. WEE virus resulted in a 100% incidence of encephalitis and hydrocephalus. Thus, mumps and WEE viruses are teratogens in primates and are potential teratogens of man.

Fetal mortality and malformations associated with experimental infections of western equine encephalomyelitis vaccine virus in rhesus monkeys (Macaca mulatta).

Pregnant Rhesus monkeys were infected via installation of Western Equine Encephalomyelitis (WEE) vaccine virus into the amniotic sacs at 50 and 80 days gestation to determine if the resulting infections would produce fetal mortality or fetal malformations, particularly within the central nervous system. Of those receiving virus at 50 days gestation, 13 of 18 fetuses were aborted or dead in utero at time of Caesarean section; 2 of 18 were malformed (hydrocephalus and polyarthrosis); and 3 of 18 were anatomically normal. Of those receiving virus at 80 days gestation four of eight fetuses were aborted or dead in utero at time of Caesarean section, one of eight was malformed (hydrocephalus) and three of eight were anatomically normal. Three of three controls receiving neutralized virus at each gestational age were anatomically normal. Fetal WEE vaccine virus infection significantly increased fetal mortality and resulted in a significant incidence of fetal malformations.

Congenital cerebral and ocular malformations induced in rhesus monkeys by Venezuelan equine encephalitis virus.

Rhesus monkey fetuses were inoculated with Venezuelan Equine Encephalitis (VEE) vaccine virus by the direct intracerebral route at approximately 100 days gestation to determine possible teratogenicity of the virus. Congenital micrencephaly, hydrocephalus and cataracts were found in all animals and porencephaly in 67 percent of the cases. The virus replicated in the brain and other organs of the fetus. VEE vaccine virus is teratogenic for non-human primates and must be considered a potential teratogen of man.

Western equine encephalitis with rapid onset of parkinsonism.

A patient with confirmed western equine encephalitis had the rapid onset of postencephalitic parkinsonian sequelae. This observation corroborates similar previous but rare reports. Response to therapy with levodopa, dopa decarboxylase inhibitor, and trihexyphenidyl was dramatic. However, remission maintained for 12 months without medication suggests that the parkinsonism would have remitted spontaneously. In either case, this has not previously been reported with the western equine togavirus.

Virus-induced pancreatic disease by Venezuelan encephalitis virus. Alterations in glucose tolerance and insulin release.

Viral infections have been implicated in the induction of diabetes mellitus in man and laboratory animals. Since virus-specific immunofluorescence (FA) is detectable in hamster pancreas during the acute phase of Venezuelan encephalitis (VE), experiments were designed to correlate pathologic and virologic events with metabolic studies in VE-infected hamsters. Golden Syrian hamsters were inoculated s.c. in groups of four to 12 with 100,000 plaque-forming units (PFU) of the vaccine strain (TC-83) of VE or 1,000 PFU of the virulent Trinidad strain of VE. Ultrastructurally, during Trinidad infection, mature virions were associated with the cell surfaces and within pancreatic beta cells in contrast to absence of virus-related changes in TC-83-infected hamsters. Virus-specific-FA was noted in islet cells and acinar cells of Trinidad-infected hamsters. VE growth curves demonstrated viral replication in pancreas with both strains. Although ultrastructural and FA changes were much more prominent in Trinidad-infected hamsters in contrast to TC-83-infected hamsters during the first few days of illness, the rapid lethality of the Trinidad-infected group necessitated performing all metabolic studies in TC-83-strain-infected hamsters. Accordingly, for the metabolic studies, glucose tolerance tests (GTT) using 2 mg. or 5 gm./kg. glucose i.p. were performed in groups of hamsters acutely infected two days earlier with the TC-83 vaccine strain and in 24-day and 90-day convalescent hamsters after TC-83 vaccine strain. Samples were obtained for glucose and immunoreactive insulin (IRI) determinations. Glucose intolerance occurred in hamsters in each of the infected groups given 5 gm./kg. glucose except for the 90-day convalescent TC-83 group. Severely decreased IRI responses occurred in the 24-day and 90-day convalescent TC-83 hamsters following both 2- and 5-gm./kg. glucose. Pancreatic IRI content in 24-day convalescent TC-83 hamsters was within normal limits, suggesting a defect in IRI release from the beta cells at this stage of convalescence.

Sequelae of Venezuelan equine encephalitis in humans: a four year follow-up.

The purpose of this study was the identification of possible sequelae of the infection of human individuals with Virus of Venezuelan Equine Encephalitis (VEE). Special emphasis was laid on exploring neurological, psychological and behavioural aspects and particularly on the search for a possible association of the disease with epileptic phenomena, brain damage and/or mental deficiency. A four-year period of observation was conducted on a sample of children from El Carmelo (Colombia) where an epidemic of VEE took place in 1967. A group of seven children who presented the encephalitic type of the illness and were hospitalized with symptoms of CNS involvement and a confirmed diagnosis of VEE constituted the index group. This group was compared with four control groups of children with matched demographic characteristics but separated according to whether they were ill at the time of the epidemic and whether they presented serological evidence of having been infected with VEE Virus. Evaluations were conducted at three points in time during the follow-up period and they included the following procedures: (1) Survey on personal background and behaviour (through a standard questionnaire dealing with all areas of functioning); (2) Complete paediatric examination, including a careful neurological check-up; (3) Psychological examination using intelligence tests; (4) Electro-encephalographic examination according to standard techniques, with the patient awake, asleep and under photic stimulation; (5) Bi-weekly home visits to keep a record on intercurrent illness throughout the observation period. Statistical analysis of results shows significant differences between the groups in regard to the distribution of abnormalities.

Virus-initiated septic shock. Acute death of Venezuelan encephalitis virus-infected hamsters.

Hamster hematopoietic and lymphatic organs were studied sequentially by light and electron microscopy following Venezuelan encephalitis virus inoculation. In addition to extensive marrow and splenic necrosis nearly transmural necrosis of the ileum in Peyer's patch areas, with concomitant bacterial overgrowth, was noted. Viruses were observed ultrastructurally in reticular cells of Peyer's patches. In addition, bacterial blood cultures, consistent with an enteric origin, were generally positive in late stages of the infection. Reticuloendothelial function, measured by clearance of colloidal carbon, was significantly depressed in Venezuelan encephalitis virus-infected hamsters. It is proposed that the acute death of hamsters infected with Venezuelan encephalitis virus may be determined by the development of an endotoxic shock syndrome mediated by the extensive ileal lesions, coupled with impaired reticuloendothelial detoxifying function.