74 Japanese B Encephalitis
Japanese B encephalitis is a relatively uncommon disease, even in areas where the infection is endemic. The disease is one of several caused by arthropod-borne viruses (arboviruses); carried by mosquitoes of the genus Culex, this one is a member of the family Togaviridae and genus Flavivirus and thus is an RNA virus.
The species of Culex that is the most common insect vector for Japanese B encephalitis is Culex Iritaeniorhyncus.The disease was first recognized and described in 1871, and the virus was first isolated in 1935. The infection may appear in epidemic or in sporadic outbreaks, and is carried particularly in swine, but also has been isolated from a variety of birds and from equine animals. The virus is distributed principally in East and Southeast Asia.
Epidemiology
Epidemic outbreaks of Japanese B encephalitis, like those of arboviruses in general, tend to occur in regions that are usually dry and arid and, therefore, relatively free of viral activity; such areas may accumulate a large number of individuals who, because of lack of previous exposure, are relatively susceptible. Then with rain and the appearance of conditions favorable to the proliferation of the insect vector, epidemic outbreaks may occur, particularly where there are relatively high population densities of the human host and of the amplifying hosts such as equine or porcine animal species. In addition, there is evidence that for some arboviruses a change occurs in the relative virulence of the infecting strain, which may also account for an epidemic outbreak. Why, given the presence of Japanese B encephalitis virus in birds with wide-ranging migratory patterns, the disease remains localized to certain geographic areas is not entirely clear, but presumably has to do with the specificity of the insect vector in carrying the infectious agent. The mosquito vector, C.
tritaeniorhyncus, is found in rice fields and feeds on pigs and birds, as well as human and other hosts. However, the Japanese custom of raising pigs in the fall, after the flooding of rice paddies is over, and of taking the pigs to market early the following year, may also help to account for the general lack of large outbreaks as well as for the usual pattern of sporadic cases. As might be expected with such a pattern, the few large outbreaks tend to occur in more rural areas, street antibody to the virus is relatively common, and clinical cases account for about 2 percent of all of the infections, as judged by antibody surveys.Pathology
Most of the information on the early stages of the disease has been gained from studies in the mouse. Pathological features of fatal human cases have generally been consistent with the experimental findings. Early in the disease, focal hemorrhages, congestion, and edema are found in the brain. Microscopically widespread damage to Purkinje cells of the cerebellum is noted, with pervascular inflammation and multiple foci of degeneration and necrosis. Extraneural evidence of spread of the virus is found in the form of hyperplasia of the germinal centers of the lymph nodes and of the spleen; multiple foci of round-cell infiltration in many organs, including the heart, kidneys, and lungs; and, in pregnancy, infiltration of the placenta with corresponding abortion and stillbirth. Multiple lesions in the offspring indicate cross- placental passage of the virus.
Clinical Manifestations
The clinical disease consists of the usual signs and symptoms of encephalitis, and no syndrome has been elicited that is specific for Japanese B encephalitis. Within a few days to several weeks (mean of 10 days) after a bite by a mosquito carrying the virus, susceptible patients manifest fever and evidence of damage to the central nervous system, which may include meningism, delirium, drowsiness, confusion, stupor, paralyses especially of the facial muscles, and, in the most severe cases, coma and death within a few days after onset.
The cerebrospinal fluid shows the presence of a nonpyogenic infection, with increased numbers of mononuclear cells, rarely over 1,000 per cubic millimeter, and elevated protein; sugar is therefore not generally decreased and may be elevated in the spinal fluid.
Diagnosis
The definitive diagnosis is made only from studies of the antibody status of the affected individual, with evidence of the absence of specific antibody at the time of onset of the disease followed by a 4-fold or greater rise in titer of the antibody during the following days or weeks. Complement-fixing antibody is the first to appear in most patients, but hemagglutinating and neutralizing antibodies are usually demonstrable shortly thereafter. More recently, antibody tests using fluorescein- or enzyme-labeled antibody, or the various modifications of these, showing specific rise in titer, are sufficient to establish the diagnosis. Antigenic variation is common among viral isolates, and at least two immunotypes have been delineated; thus the Serodiagnosis must be performed in laboratories that have on hand the several subtypes that may be needed for a full serologic analysis of a given case or outbreak.
The disease is one of the most fatal among arboviruses, with case fatality rates of 50 to 70 percent having been recorded in outbreaks. Recovery may be complete, or there may be residual damage to the central nervous system; Japanese B encephalitis, in contrast to other arboviral encephalitides, is accompanied by relatively high rates of complete recovery despite the high case fatality rates.
There is no specific treatment, and supportive care is the major intervention that can be offered. The protective effect of antibody suggests that convalescent serum or other sources of antibody might have some therapeutic value, but this has not been systematically investigated on a suitable scale.
Prevention and Control
Vaccines have been available for many years for immunization of humans and of livestock.
Live attenuated vaccines have been available in Japan since 1972, and in China more recently, and their effectiveness is shown by seroconversion rates of up to 96 percent. Vaccines are prepared by purification of viral suspensions from mouse brains, or from hamster kidney cultures, but several newer technologies are presently under active investigation. Widespread immunization campaigns have been successful in Japan, Taiwan, and China. At present, the vaccines are composed principally of the prototype Nakayama strain, and reasonable control of the disease has taken place. It is therefore unclear how necessary or desirable the addition of the newer isolates, with slightly different antigenic specificities, would be.Currently used vaccines require primary immunization with two injections at 7- to 14-day intervals, a booster within 1 year, and further boosters at 3- to 4year intervals. Fortunately, the vaccine produces relatively few side reactions, and postvaccinal encephalitis must be exceedingly rare because few if any reliable reports of this complication following administration of the vaccine are in evidence.
Vector control has been investigated in some detail. Larvicides and adulticides aimed at the chief mosquito vector have reduced attack rates in areas where these have been tested, and programs of control of insect vectors, coupled with elimination of aquatic vegetation in irrigation channels and with spraying of insecticides in livestock pens, have had some success in China. Under epidemic conditions, spraying with appropriate insecticides has sometimes been necessary.
Edward H. Kass
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