Eastern equine encephalitis (EEE) virus was first isolated in 1933 by Ten Broeck and Merrill from brains of horses that died in an extensive epizootic in Delaware, Maryland, New Jersey, and Virginia. The first isolations from man were obtained by Fothergill and Webster from brain tissue of fatal cases in the 1938 epidemic in Massachusetts. Subsequently, most isolations of EEE virus have been from Culiseta melanura, a swamp mosquito of the eastern United States. .This species most commonly feeds on birds. The noteworthy rarity of its feeding on man is emphasized by the existence of only one published report. It has been observed feeding on horses. This may be a significant feature of the vector when a profusion of C. melanura mosquitoes cannot find avian hosts and consequently turn to horses and man for an infectious blood meal.
The first evidence that an equine encephalitis virus could be transmitted by a mosquito was that of Merrill in 1934, who showed multiplication of EEE virus in Aedes sollicitans. The implications of such behavior of a salt marsh mosquito were noted in 1959 when A. sollicitans was found in abundance in the area where epidemic EEE occurred along the New Jersey coast. In 1965, Gold- field reported isolation of EEE virus from Aedes sollicitans collected from the premises of laboratory-diagnosed cases of EEE in New Jersey. The virus has also been isolated in Connecticut from Aedes uexans. another prevalent man-biting mosquito.
Many antigenically identical strains of EEE virus have been recovered from the blood of many species of resident and migratory wild birds collected in sylvan habitats. In an epizootic situation immunity rates for EEE up to 100 per cent have been found in some avian species.
Such isolations of EEE virus from widely distributed birds provide one of several reasonable explanations of how EEE virus is moved, even southward into such Caribbean island epizootic- epidemics as occurred in the Dominican Republic in 1948-1949 and in Jamaica in November- December 1962.
The relative frequency of EEE virus isolations annually from sylvan mosquitoes and birds, compared to the rarity of such isolations from sporadic human cases and from extremely rare human epidemics, indicates that EEE virus parasitism is successfully maintained in a geographically extensive wild cycle,” and only accidentally tangentially produces disease in equines and man residing or working in rural or suburban areas.
Casals has determined that there are at least two distinct antigenic types of EEE virus, one characteristic of North America and another of South America. The agent responsible for the Jamaican epidemic of 1962 was the .North American type.
It was formerly thought that human epidemics were caused by excursions of virus activity into the human domain from distant natural foci. The U.S. Public Health Service Communicable Disease- Center monitored :he appearance of EEE virus in mosquitoes sod wild birds between May and October 1965 in every state along the eastern seaboard from Florida to Massachusetts. where only a few scattered human cases occurred Reports re recovery of EEE virus during winter months frorr. Xe Jersey rodents indicate another possible manifestation of the natural maintenance of EEE virus, aloof from the immediate environs of man.
At the rise of the recognized geographic area of EEE virus activity, which extends from southern Texas and Florida northward east of the Appalachian crest to Massachusetts and Ontario in Canada, there is little evidence of inapparent human infection. However, in serologic surveys of rural populations more closely associated with the swamp epizootic ecology or tropical island epidemics, significant numbers of immunes have been found who have no history of overt CNS disease. There are other rural residents, possessing specific neutralizing antibody for EEE, who have post-acute CNS disease sequelae.
On the basis of accumulating data, the former impression that overt CNS disease occurred in almost all who were infected with EEE virus has shifted to an opinion that it is observed only in a majority of those infected. In up to two thirds of those who develop signs of CNS disease it either terminates fatally or the patients sustain permanent neurologic or mental and emotional sequelae. Although the epidemics reported in Massachusetts (1938, 1955) and New Jersey (1959) afflicted children chiefly, with no significant sex difference in attack rates, disease occurs in adults sporadically or as constituents of epidemic clusters.
The epizootic appearance in equines, about two weeks before the first occurrence in human beings, has been observed repeatedly. Eastern equine encephalomyelitis in equines is also severe, up to 90 per cent of the affected animals dying within the first day or so after onset. Such an explosive fatal epizootic is an important differential to epizootic WEE, in which many of the animals survive.
In contrast to the usual inapparent or nonfatal infection of indigenous wild birds, EEE virus produces severe epizootics in exotic gallinaceous birds, such as pheasants and chukar partridges, and in pekin ducks. Such outbreaks in flocks of domestically reared game birds on East Coast game farms have often been the first indication of appearance of EEE virus transmission in the area. The selective occurrence of an epizootic in one pen and freedom from disease in others indicates that there is an alternative bird-to-bird mechanism of virus transmission not involving mosquitoes.
Laboratory infections have occurred in workers manipulating EEE virus experimentally. This emphasizes that the decision to use such a virus in the laboratory requires caution and special facilities for safe handling.
Although there have been reports of EEE virus isolations from as widely separated localities as the Philippines and Thailand in southeast Asia and Czechoslovakia and Poland in central Europe, EEE is considered to be a disease of the Western Hemisphere, where serologic or virologic evidence of its presence has been obtained from eastern Canada and the United States, south into Mexico; in the Caribbean islands of Cuba, the Dominican Republic, Jamaica, and Trinidad; and in South America in Panama, Guiana, Brazil, and Argentina.
Clinical Characteristics of Eastern Equine Encephalitis.
The incubation period is not accurately known, but it is assumed to be seven to ten days. Onset may be sudden, particularly in adults, with high fever, headache, conjunctivitis, nausea and vomiting, and rapid progression from drowsiness to delirium and coma.Neurologic signs are manifested by stiff neck, positive Kernig’s sign, absent to hyperactive reflexes, irritability, photophobia, and intermittently spastic muscles in the extremities, sometimes more marked on one side than on the other Patients can be momentarily aroused by painful stimuli and strong pressure on the muscles.The course terminates fatally, or the shifting signs of deep CNS involvement may persist for several weeks, the patient gradually returning to consciousness. Frequent and careful neurologic examination, particularly of muscle power and co-ordination, may indicate which centers and nerve supplies have been permanently damaged.
Mild to severe polymorphonuclear leukocytes, from 11,000 to more than 50,000 cells per cubic millimeter, is characteristic. In the first few days the CSF, usually under significant pressure, also shows a polymorphonuclear response up to 1000 cells per cubic millimeter and an increase in protein. Later there is a shift to mononuclear cell predominance in the CSF.A biphasic course may be initiated after a shorter incubation period. This is more characteristic of the disease in young children. The prodromal onset is marked by fever, headache, nausea, and vomiting that persist for a day or so followed by apparent recovery.
Then a fulminating CNS involvement occurs, with a high fever, severe gastrointestinal disturbances with vomiting, somnolence, delirium, convulsions, and coma. The stiff neck and positive Kernig’s sign often advance to intermittent or persistent opisthotonos, generalized rigidity, localized paralyses, bulging fonta- nelles in infants, and cyanosis resulting from circulatory stasis and mechanical obstruction of the airways.
Acute neurologic involvement lasts a week and is often prolonged for several weeks, followed by slow convalescence, during v/hich the neurologic residual becomes apparent. This ranges from severe paralyses involving cranial nerves to paralysis of the extremity muscles. The brain damage is frequently severe enough to cause mental deterioration, with loss of intelligence requiring permanent institutional care. Less evident at this time but of equal need for subsequent .care is emotional instability, which is permanent and prevents resumption of normal family and social life.
Diagnosis of Eastern Equine Encephalitis.
Clinical appearance and history with clinical laboratory findings of a leukocytosis and pleocytosis and protein in the CSF lead to suspicion of viral origin. Although isolation of EEE virus from acute blood has proved fruitless in the past, isolation of virus post mortem from brains of patients who succumb within the first week after onset has been repeatedly successful. In those who survive, the specific diagnosis is established by the serologic response.An acute serum specimen should be obtained immediately on suspicion of a diagnosis of EEE. Serial sera should be collected every rew days subsequently. Neutralizing and hemagglutination-inhibiting antibodies appear soon after onset, and a presumptive diagnosis can be obtained by the HI test if such antibodies are present, even in low titer. Rise in titer and appearance of specific complement-fixing antibodies in.subsequent sera confirm the diagnosis.
Because of the infrequency of specific EEE antibody in the general population, and the persistence of neutralizing and HI antibodies, possibly for life, establishment of a presumptive diagnosis in postencephalitic institutional or neurologic cases may be obtained by serologic examination many months after the acute illness.
Eastern Equine Encephalitis Treatment
Frequent examination for critical neurologic changes and continuous nursing care are important during the first few days of acute illness. Temperature control by sponge baths, maintenance of hydration, induction of artificial airway when respiratory difficulties occur, and prevention of bedsores and other complications are necessary components of good patient care. As convalescence proceeds, physiotherapy will minimize paralytic contractures, and special attention may lessen consequences of mental and emotional changes.
No regimen of chemotherapy has been demonstrated to be of any use, and there is no evidence that convalescent serum or other immune substance modifies the course of disease in any way after onset of the first symptoms.
Although effective formalinized vaccines have been developed for protection of equines, no practical immunization procedure is available for the general population. Diluted vaccine for equines has been used for protection of laboratory workers, but even this is no longer available.Transfusion of blood from donors possessing specific serum-neutralizing antibody to EEE has been used for prophylaxis immediately following accidental laboratory inoculation or other exposure. However, it is unlikely that even this is of much value more than 24 hours after exposure. Lots of gamma globulin from convalescent sera are presently under preparation and evaluation for specific prophylaxis in laboratory accidents.
Therefore, the only practical protection in areas where EEE virus is active is prevention of mosquito bites. This is accomplished by appropriate protective clothing, mosquito repellents, and proper screening of houses. In situations in which infected mosquitoes have been detected, control measures against the specific implicated vector may be effective in lowering the transmission potential to equines and man.