NAME OF DISEASE:     Encephalitis
                                        Encephalitides
                                        Sleeping Sickness

ETIOLOGICAL AGENTS:     Mumpsvirus
                                                Human Herpesvirus 1 (Herpes Simplex 1 Virus)
                                                Any of 350 different arboviruses
                                                Poxvirus
                                                Enteroviruses (polio, Coxsackie, ECHO)
                                                Adenovirus
                                                Human Immunodeficiency Virus

THE DISEASE:

    A viral infection of the brain which is usually transmitted to man as an incidental terminal host. The arbovirus encephalitides are zoonoses, with the virus surviving in infection cycles involving biting arthropods and various vertebrates, especially birds and rodents. Some of the common encephalitides:

    1.     Eastern Equine Encephalitis (mosquito borne)

    2.     Western Equine Encephalitis (mosquito borne)

    3.     Venezuelan Equine Encephalitis (mosquito borne)

    4.     St. Louis Encephalitis (mosquito borne)

    5.     Japanese B Encephalitis (mosquito borne)

    6.     Murray Valley Encephalitis (mosquito borne)

    7.     California Encephalitis (mosquito borne)

    8.     Tick-Borne Encephalitis

    9.     Herpesvirus Encephalitis (person to person contact)

PATHOGENESIS AND PATHOLOGY:

    In infections with arboviruses, an initial viremia is followed by localization in the central nervous system. In fatal cases, there is little histopathologic change outside the nervous system, possibly excepting renal involvement in St. Louis encephalitis. On gross examination, there are varying degrees of meningitis, cerebral edema, congestion, and hemorrhage in the brain. Microscopic examination confirms a leptomeningitis with round-cell infiltration, small hemorrhages with perivascular cuffing, and nodules of leukocytes or microglial cells. Neuronal damage is seen as chromatolysis and neuronophagia. Areas of necrosis may be extensive especially in Eastern equine encephalitis, Japanese B encephalitis, and the Far Eastern form of tick-borne encephalitis. In patients who survive the initial illness, there are varying degrees of repair, which may include calcification. The pattern of distribution of lesions in the brain is rarely sufficiently specific to enable the identification of the infecting virus. However, the lesions in Eastern equine encephalitis are concentrated in the cortex, in Western equine encephalitis in the basal nuclei, and in St. Louis encephalitis in substantia nigra, thalamus, pons, cerebellum, cortex, bulb, and anterior horn cells. European forms of tickborne encephalitis, including louping ill, commonly show a polioencephalomyelitis, with extensive involvement of the anterior horn cells mimicking poliomyelitis pathologically and clinically.

    Herpesvirus encephalitis in infants may be part of a general infection that produces focal necrotic lesions with typical intranuclear inclusions in many organs. In the adult and in some children, lesions are confined to the brain. Necrotic foci may be macroscopically evident as softening. Inclusion bodies are readily found in the margins of areas of necrosis; focal perivascular infiltration and neuronal damage is evident. The temporal cortex and pons are commonly involved, but the lesions may be widespread.

DIAGNOSIS:

    Infection with arboviruses is usually subclinical. Clinically evident infection varies in severity from a mild, aseptic meningitis to a rapidly fatal, necrotizing encephalitis. Typically, arbovirus encephalitides begin with the acute onset of fever, headache, and vomiting; progress to signs of meningeal involvement (stiff neck and back); and go on to show evidence of neuronal damage (drowsiness, coma, paralysis, convulsions, ataxia, organic psychoses).

    Cerebrospinal fluid (CSF) pleocytosis is usual, with up to 1000 leukocytes/mm³. Mononuclear cells usually predominate, although early in fulminant encephalitis, polymorphonuclear leukocytes predominate, glucose and chloride concentrations in the CSF are normal, and the protein is increased. The peripheral blood commonly shows a moderate polymorphonuclear leukocytosis.

    Individual arbovirus encephalitides have some characteristic clinical features, although, as with histopathology, it is rarely possible to make a specific diagnosis on clinical evidence alone.

    During epidemics, viral encephalitis is readily diagnosed on clinical grounds. However, sporadic cases are often difficult to distinguish from other febrile illnesses (e.g., a child with gastroenteritis, dehydration, and convulsions) or from intoxications. Other infectious processes that must be considered include meningitis and meningoencephalitis caused by enteroviruses, mumps, Leptospira spp., Naegleria spp., bacteria, fungi, and the postinfectious encephalitides that follow measles, varicella, rubella, or vaccination.

    The specific laboratory tests available give only a retrospective diagnosis in most cases. The serologic tests depend on the occurrence of a rise in antibody titer. However, the early detection of specific IgM antibody may assist early diagnosis.

PROGNOSIS:

    Secondary bacterial infections of the respiratory and urinary tracts are major complications of acute encephalitis. They vary in severity directly with the severity of the encephalitis and generally decline in importance as the acute illness passes.

    With recovery from acute viral encephalitis, evidence of neuronal injury and death becomes apparent as residual neurologic defects, impairment of intelligence, and psychiatric disturbances. The severity of these sequelae apparently varies according to the causative virus. Thus, after western equine encephalitis, sequelae are uncommon in adults, but frequent in children - recurring convulsions with motor or behavioral changes afflict more than half the children infected before they are 1 month old. With Eastern equine encephalitis, most adults over the age of 40 who survive, do so unscathed; children under 5 years in age have crippling sequelae consisting of mental retardation, convulsions, and paralysis. Permanent sequelae after St. Louis encephalitis are uncommon.

    Sequelae are reported in only 3-10% of cases of Japanese B encephalitis in Japan. Yet, 25-30% of young adult males of the armed forces of the United States in World War II had sequelae (including neuroses) 6 months after infection. In addition, 10 of 25 cases of Japanese B encephalitis on Guam, seen in 1948, had neurologic or intellect defects 10 years later.

THERAPY:

    There is no specific treatment for the arbovirus encephalitides. Accordingly, supportive care is of paramount importance, requiring devoted attention to the airway, bladder function, fluid and electrolyte balance, nutrition, prevention of bed sores, secondary pulmonary infection, and hyperpyrexia.

PREVENTION:

    Killed virus vaccines have been produced experimentally for several arboviruses. There has been wide use of only one such vaccine, a Japanese B virus preparation made from formalinized mouse brain; users of this vaccine in Japan claim it gives a high degree of protection. Limited use (e.g., in exposed laboratory workers) has been made of Venezuelan equine encephalitis and tick-borne encephalitis virus vaccines. Passive immunization of laboratory workers exposed to a known virus in a laboratory accident has been accomplished with immune (human) serum or gamma globulin.

    Control of the mosquito vector has been used with apparent good effect on several recent epidemics.