SEQUELAE OF ENCEPHALITIS—Report of a Study After the California Epidemic

In a study of almost 500 patients to determine residual effects, the sequelae of both St. Louis and Western equine encephalitis were more prominent in the younger age group. Infants under three months with Western equine encephalitis had the greatest central nervous system damage. Forty-four per cent of this entire group had sequelae.In patients between one and four years of age, the incidence of sequelae was less. The Western equine infection was associated with the more disabling residual damage. Postencephalitic convulsions were fairly common in the younger patients with Western equine disease, but not in the St. Louis group. After the age of five the sequelae rate dropped. In all age groups the Western equine residual changes were more severe than the damage of St. Louis infection.Some infants, children and adults showed remarkable improvement from sequelae even as much as two years after the abnormalities occurred.With the longer period of follow-up, some late sequelae were noted in children and adults, primarily among those who had Western equine infection.     

The 1952 outbreak of encephalitis in California; epidemiologic aspects

For the most part, epidemiologic phenomena observed in the outbreak of encephalitis in 1952 accorded with patterns that had been apparent in previous years. Ninety-seven per cent of the 414 laboratory-confirmed cases of western equine and St. Louis encephalitis in humans occurred in the 20 Central Valley counties. The cases of western equine encephalomyelitis in horses were generally scattered over the state. In the Central Valley most of the cases in horses were in animals less than two years of age; elsewhere the incidence was higher in older horses.There were no laboratory-confirmed cases of western equine or St. Louis encephalitis in humans earlier than June or later than October. In 1952 there were far more cases of western equine than of St. Louis encephalitis-a departure from the pattern in the previous seven years when there were about as many of one as of the other. No known satisfactory index is available for the prediction of the extent or type of outbreaks in humans. Approximately one-third of the cases of western equine encephalitis were in patients less than one year of age, whereas there were no cases of the St. Louis disease in patients that young.The incidence of western equine encephalitis in persons under 5 years of age was about the same for girls as for boys. In higher age brackets, males with western equine encephalitis outnumbered females 2 to 1. The corresponding ratio for St. Louis encephalitis was only 1.2 to 1.     

The 1952 Outbreak of Encephalitis in California (A Symposium): EPIDEMIOLOGIC ASPECTS

For the most part, epidemiologic phenomena observed in the outbreak of encephalitis in 1952 accorded with patterns that had been apparent in previous years. Ninety-seven per cent of the 414 laboratory-confirmed cases of western equine and St. Louis encephalitis in humans occurred in the 20 Central Valley counties. The cases of western equine encephalomyelitis in horses were generally scattered over the state. In the Central Valley most of the cases in horses were in animals less than two years of age; elsewhere the incidence was higher in older horses.There were no laboratory-confirmed cases of western equine or St. Louis encephalitis in humans earlier than June or later than October.In 1952 there were far more cases of western equine than of St. Louis encephalitis—a departure from the pattern in the previous seven years when there were about as many of one as of the other. No known satisfactory index is available for the prediction of the extent or type of outbreaks in humans.Approximately one-third of the cases of western equine encephalitis were in patients less than one year of age, whereas there were no cases of the St. Louis disease in patients that young.The incidence of western equine encephalitis in persons under 5 years of age was about the same for girls as for boys. In higher age brackets, males with western equine encephalitis outnumbered females 2 to 1. The corresponding ratio for St. Louis encephalitis was only 1.2 to 1.     

Western equine encephalitis in infants; a report on three cases with sequelae

Approximately one-third of the laboratory-confirmed cases of Western equine encephalitis occur in children under the age of 10. The present paper describes three instances of Western equine encephalomyelitis virus infection in infants under one year of age, together with the resultant sequelae. The difficulties associated with diagnosis of central nervous system disturbances in very young children are discussed, and it is pointed out that in view of the frequent occurrence of clinical infections with the arthropod-borne encephalitis viruses these agents should be given serious consideration as a cause of acute central nervous system infection in childhood and as the possible etiology for obscure, severe neurological disturbances in the pediatric age groups.     

WESTERN EQUINE ENCEPHALITIS IN INFANTS—A Report on Three Cases with Sequelae

Approximately one-third of the laboratory-confirmed cases of Western equine encephalitis occur in children under the age of 10. The present paper describes three instances of Western equine encephalomyelitis virus infection in infants under one year of age, together with the resultant sequelae. The difficulties associated with diagnosis of central nervous system disturbances in very young children are discussed, and it is pointed out that in view of the frequent occurrence of clinical infections with the arthropod-borne encephalitis viruses these agents should be given serious consideration as a cause of acute central nervous system infection in childhood and as the possible etiology for obscure, severe neurological disturbances in the pediatric age groups.     

Prevalence of selected zoonotic diseases in vertebrates from Haiti, 1972.

Vertebrate animals collected in Haiti in 1972 were tested for selected zoonotic diseases. No rabies virus or neutralizing (N) antibody was detected in bats (Artibeus jamaicensis). However, N antibody against St. Louis encephalitis, Western equine encephalitis (WEE), and Eastern equine encephalitis were detected in resident species of birds and WEE antibody in bats. No N antibody against Venezuelan equine encephalitis was found. The possible introduction by migratory birds and local transmission of these arboviruses is discussed.     

The 1952 Outbreak of Encephalitis in California (A Symposium): DIFFERENTIAL DIAGNOSIS

Clinical data adequate for analysis were available in 386 laboratory-confirmed cases of arthropod-borne encephalitis — 38 St. Louis and 348 western equine. Consistently observed symptoms varied with the age of the patient. Symptoms that occurred in a high proportion of patients in each age group were:Less than one year of age: Fever and convulsions. (None had the St. Louis disease.)One through four years: Fever, headache, vomiting, drowsiness, irritability, restlessness, nuchal rigidity, tremor, and sometimes convulsions.Five through fourteen years: Headache, fever, and drowsiness. Sometimes the disease progressed no further, but if it did, nausea, vomiting, muscular pain, photophobia and limitation of neck and back flexion often were noted; and sometimes convulsions and intention tremors.Fifteen years and older: Drowsiness, lethargy, malaise, fever, stiffness at the back of the neck and, almost always, severe intractable occipital headache associated with nausea, disturbance of vision, photophobia and vertigo.The extreme difficulty of differential diagnosis on the basis of clinical observation was indicated by the wide range of diagnoses made in these cases before the invading organism was identified by laboratory studies.     

Arbovirus infections in man in British Columbia

During the summer of 1971, the first laboratory-proved cases of acute encephalitis in man due to any of the known arboviruses occurred in the south-central region of British Columbia. Five human cases of encephalitis with two deaths were diagnosed; three of these patients, including one of the fatalities, were proven in the laboratory to have contracted western equine encephalitis.During 1968 and 1969, a human serum survey undertaken in approximately 2000 life-long residents of the province discovered low levels of hemagglutinin-inhibiting and/or complement-fixing as well as neutralizing antibodies for western equine encephalitis, St. Louis encephalitis, Powassan encephalitis, California encephalitis and Colorado tick fever. Evidence of recent sub-clinical infection was detected in some cases.     

Experimental inoculation of three arboviruses in black-bellied whistling ducks (Dendrocygna autumnalis).

Wild-caught, immature black-bellied whistling ducks (Dendrocygna autumnalis) were inoculated with eastern equine encephalitis (EEE), St. Louis encephalitis (SLE), or western equine encephalitis (WEE) virus. Susceptibility, duration and titer of viremia, and antibody response to these arboviruses were determined. Birds from all inoculated groups became viremic. Higher virus titers occurred in the EEE group but overall mean titers were not significantly different among experimental groups. All birds inoculated with EEE and SLE viruses developed antibodies, and six of seven ducks receiving WEE virus were seropositive. All seropositive ducks had antibodies for at least 59 days, when the study was terminated. The EEE group had significantly more seropositive ducks during more days than the WEE and SLE groups. Geometric mean antibody titers were significantly smaller in the WEE group when compared to the EEE and SLE groups. Control ducks did not develop viremia or antibodies. Gross and histopathologic lesions compatible with viral encephalitis were absent in all of nine ducks necropsied. Black-bellied whistling ducks can develop low and short-term levels of viremia sufficient to infect mosquitoes, but probably cannot contribute significantly to the transmission of EEE and SLE. They may serve as good indicators of virus activity.     

The 1952 outbreak of encephalitis in California; differential diagnosis

Clinical data adequate for analysis were available in 386 laboratory-confirmed cases of arthropod-borne encephalitis - 38 St. Louis and 348 western equine. Consistently observed symptoms varied with the age of the patient. Symptoms that occurred in a high proportion of patients in each age group were:LESS THAN ONE YEAR OF AGE: Fever and convulsions. (None had the St. Louis disease.)ONE THROUGH FOUR YEARS: Fever, headache, vomiting, drowsiness, irritability, restlessness, nuchal rigidity, tremor, and sometimes convulsions. FIVE THROUGH FOURTEEN YEARS: Headache, fever, and drowsiness. Sometimes the disease progressed no further, but if it did, nausea, vomiting, muscular pain, photophobia and limitation of neck and back flexion often were noted; and sometimes convulsions and intention tremors. FIFTEEN YEARS AND OLDER: Drowsiness, lethargy, malaise, fever, stiffness at the back of the neck and, almost always, severe intractable occipital headache associated with nausea, disturbance of vision, photophobia and vertigo. The extreme difficulty of differential diagnosis on the basis of clinical observation was indicated by the wide range of diagnoses made in these cases before the invading organism was identified by laboratory studies.     

Labile Serum Factor and Its Effect on Arbovirus Neutralization

Enhancement of neutralization of Sindbis, Venezuelan equine encephalitis, Eastern equine encephalitis, Western equine encephalitis, and St. Louis encephalitis viruses by labile serum factor (LSF) in human serum and plasma was demonstrated. Human serum and plasma could be diluted 1:8 and 1:16 and still retain some LSF activity. Satisfactory storage temperatures for retention of LSF activity were −20 or −56 C. Repeated freeze-thaw cycles of serum did not alter LSF activity, but the activity was completely eliminated by heating at 56 C for 5 min. LSF of human serum equally enhanced neutralization by Sindbis immune mouse and rabbit sera; these results suggest a lack of species specificity. Rehydrated lyophilized gunea pig complement did not restore LSF activity to heated human plasma. Serum components responsible for LSF activity were not dialyzable. Discovery of fresh serum without LSF activity established the need to pretest all sera used as LSF sources.     

California encephalitis virus,a newly described agent

In three cases of encephalitis in humans that occurred in the area where the newly described California virus was isolated from mosquitoes, serological evidence seemed to indict the California virus as the etiological agent. In the case of an infant with very severe disease, the serological evidence was convincing; the evidence was almost as strong in the case of a seven-year-old boy; the results in an adult were equivocal. Inapparent infection in man is quite common as indicated by neutralization tests on the sera of nearly 600 residents of California, but encephalitic manifestations of infection are extremely rare. In Kern County, California, where the virus was discovered, approximately 11 per cent of the population has been infected. Infection rates are higher in adults than in very young children. Absence of neutralizing antibodies from 64 specimens of blood from persons in Japan, Washington, and other states supports the specificity of the neutralization test in man and suggests that this virus is absent or is not being similarly transmitted in some areas. Serological evidence from serial bleedings of two sick horses suggested, but did not definitely establish, that this virus leads to a naturally acquired encephalomyelitis in horses. Serological tests with the viruses of western equine and St. Louis encephalitis did not lead to any other etiological diagnosis in the sick animals studied. Results of neutralization tests on the sera of eight horses and three cows in Kern County suggested extremely high infection rates, and an immunity rate of 18 per cent was noted in rabbits and ground squirrels. In the natural biological cycle rabbits and ground squirrels are suspected as the possible counterpart of birds in the St. Louis and western equine virus cycles. There is no evidence from field or laboratory to indicate that birds become infected with the California virus. Sera from 33 mammals other than man were collected from Northern California and Washington. All were free from neutralizing antibodies, again supporting the specificity of positive findings from Kern County.     

CALIFORNIA ENCEPHALITIS VIRUS—A Newly Described Agent

In three cases of encephalitis in humans that occurred in the area where the newly described California virus was isolated from mosquitoes, serological evidence seemed to indict the California virus as the etiological agent. In the case of an infant with very severe disease, the serological evidence was convincing; the evidence was almost as strong in the case of a seven-year-old boy; the results in an adult were equivocal.Inapparent infection in man is quite common as indicated by neutralization tests on the sera of nearly 600 residents of California, but encephalitic manifestations of infection are extremely rare. In Kern County, California, where the virus was discovered, approximately 11 per cent of the population has been infected. Infection rates are higher in adults than in very young children.Absence of neutralizing antibodies from 64 specimens of blood from persons in Japan, Washington, and other states supports the specificity of the neutralization test in man and suggests that this virus is absent or is not being similarly transmitted in some areas.Serological evidence from serial bleedings of two sick horses suggested, but did not definitely establish, that this virus leads to a naturally acquired encephalomyelitis in horses. Serological tests with the viruses of western equine and St. Louis encephalitis did not lead to any other etiological diagnosis in the sick animals studied.Results of neutralization tests on the sera of eight horses and three cows in Kern County suggested extremely high infection rates, and an immunity rate of 18 per cent was noted in rabbits and ground squirrels. In the natural biological cycle rabbits and ground squirrels are suspected as the possible counterpart of birds in the St. Louis and western equine virus cycles. There is no evidence from field or laboratory to indicate that birds become infected with the California virus.Sera from 33 mammals other than man were collected from Northern California and Washington. All were free from neutralizing antibodies, again supporting the specificity of positive findings from Kern County.     

Arbovirus-related encephalitis.

Arthropod-borne virus encephalitis in the U.S.A. includes LaCrosse, St Louis, western equine, eastern equine, Venezuelan equine, and Powassan in that order of frequency. Diagnosis can be aided by the history of seasonal occurrence, climate, geographic location, exposure to vectors, and age of the patient. The definitive diagnosis is usually made by serological tests such as neutralization, complement-fixation, hemagglutination-inhibition, and immunofluorescence, the radioimmune assay and the enzyme-linked immunosorbent assay show promise of future utility. These diseases are prevented by vector control. It is unlikely that vaccines or anti-viral agents will have application in the near future.     

Serologic survey for selected arboviruses and other potential pathogens in wildlife from Mexico.

During 1988 and 1989, a serologic survey of wildlife was conducted in northeastern Mexico to determine the presence, prevalence, and distribution of arboviruses and other selected disease agents. Eighty mammal specimens were tested. Antibodies to vesicular stomatitis-Indiana, Venezuelan equine encephalitis-Mena II, Rio Grande virus, and vesicular stomatitis-New Jersey were detected predominantly in small mammals. Deer and mouflon (Ovis musimon) had antibodies to bluetongue and epizootic hemorrhagic disease. Two species had serologic evidence of recent exposure to Francisella tularensis. A white-tailed deer (Odocoileus virginianus) had antibodies to Anaplasma marginale. All specimens tested for antibodies against Yersinia pestis and Brucella abortus were negative. Sera from 315 birds were tested for antibody against five equine encephalitis viruses and six avian pathogens. During 1988, antibodies to Venezuelan equine encephalitis-Mena II, Venezuelan equine encephalitis-TC83, St. Louis encephalitis, eastern equine encephalitis, and western equine encephalitis were detected in birds of several species. Antibodies to Pasteurella multocida and Newcastle disease virus were also detected. Birds from five species presented antibodies to Mycoplasma meleagridis. Specimens tested for M. gallisepticum, M. synoviae, and Chlamydia psittaci were negative. To the best of our knowledge, this survey represents the first serologic evidence of bluetongue, Cache Valley virus, epizootic hemorrhagic disease, Jamestown Canyon virus, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey, Rio Grande virus, and tularemia reported among wildlife in Mexico.     

Viral parkinsonism

Parkinson's disease is a debilitating neurological disorder that affects 1-2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses.     

Comparison of immune responses of brown-headed cowbird and related blackbirds to west Nile and other mosquito-borne encephalitis viruses

The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses. Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.     

The 1952 outbreak of encephalitis in California; long term neurologic and psychiatric studies of sequelae

For fuller understanding of the nature of infectious encephalitis, continuing study must be made of patients with regard to possible neurological sequelae or aberrations in behavior. The large outbreak of encephalitis in California in 1952 having offered opportunity for follow-up observation of a large series of patients, many of them children who had convulsions during the acute phase of the disease, pilot studies already have been started and funds are being sought for extending the scope of the investigation over a period of years. In early observations of patients included in the pilot study, changes in emotional and behavior patterns were noted in some instances. Thus far, with the exception of two infants who had recurrence of convulsions, patients who recovered apparently free of residual effects have remained so. Further neurological and psychiatric investigation should be carried out.     

Western equine and St. Louis encephalomyelitis

In a clinical review of 50 cases of western equine and 16 cases of St. Louis encephalomyelitis in humans it was noted that fever, headache, lethargy, drowsiness, tremor and stiffness of the neck were the most frequent signs or symptoms initiating the illness. The great majority of patients recovered without residual effect. These two diseases of the central nervous system can only be differentiated on an immunological basis but may be suspected during seasonal periods in geographical areas where these virus infections are known to exist. Neuropathological studies were done in four cases of human western equine and two cases of St. Louis encephalomyelitis. The primary point of attack by the virus is the cell body, the lesions being concentrated in the striate body, diencephalon, the brain stem and cerebellum. All histo-anatomical findings (nerve cell destruction, microglial nests, small isolated and confluent areas of necrosis and perivascular round cell infiltration) are secondary to the injury of the nerve cell body caused by the neurotropic virus.     

The 1952 Outbreak of Encephalitis in California (A Symposium): LONG TERM NEUROLOGIC AND PSYCHIATRIC STUDIES OF SEQUELAE

For fuller understanding of the nature of infectious encephalitis, continuing study must be made of patients with regard to possible neurological sequelae or aberrations in behavior.The large outbreak of encephalitis in California in 1952 having offered opportunity for follow-up observation of a large series of patients, many of them children who had convulsions during the acute phase of the disease, pilot studies already have been started and funds are being sought for extending the scope of the investigation over a period of years.In early observations of patients included in the pilot study, changes in emotional and behavior patterns were noted in some instances. Thus far, with the exception of two infants who had recurrence of convulsions, patients who recovered apparently free of residual effects have remained so.Further neurological and psychiatric investigation should be carried out.