The results of this inquiry indicated that illnesses reported as encephalitis to health departments in the Central Valley of California covered a broad spectrum of syndromes ranging from frank severe encephalitis to mild meningitic illness with no definite signs of cerebral involvement. Of 153 illnesses observed during three consecutive summers and recorded as cases of encephalitis in official morbidity records, unequivocal encephalitic manifestations were noted in approximately 30%, and borderline encephalitic signs in an additional 22%. In the entire group of reported encephalitis cases, group B Coxsackie virus and WEE virus infections were encountered with equal frequency, although each virus was associated with only 14% of the cases. Mumps, ECHO, SLE, and herpes simplex viruses, in declining order of frequency, were each associated with a lesser number of illnesses, but in 40% of the cases no viral infection was established. When only the illnesses classified unequivocally as encephalitis were considered, however, the proportion attributed to WEE virus increased to 35%; Coxsackie virus infection was associated with 13%, and other virus infections were encountered in less than 10% of the cases. In the cases of doubtful encephalitis, the mumps virus was implicated most frequently (25%) followed by Coxsackie B virus (11%), WEE virus (8%), and SLE virus (3%). In illnesses classified as aseptic meningitis with no signs of encephalitic involvement, group B Coxsackie and polioviruses were the agents most frequently encountered (each in 16%) followed by ECHO (10%), mumps (7%) and WEE (4%). In each clinical category, no viral infection was established in 35 to 45% of the cases. There was appreciable variation in these proportions from year to year, but in each year the arthropod-borne viruses, WEE and SLE together, were implicated most often in cases classified as frank encephalitis, and Coxsackie group B viruses equaled or exceeded the mumps virus in such illnesses. Of the other enteroviruses, an ECHO virus (type undetermined) was associated in only one instance, and poliovirus not at all, with frank encephalitis. Inasmuch as the role of group B Coxsackie viruses as causal agents of aseptic meningitis is well established,7,9 the association of these viruses with 12 to 19% of such illnesses each year is believed to be a reasonable approximation of their relative etiologic importance in the endemic occurrence of this syndrome in the particular localities and seasons represented in this study.
While the frank encephalitic illness observed in association with group B Coxsackie viruses in this study could reflect the occurrence of coincidental infections in persons whose illness was due to other unrecognized causes, the probability of an etiologic association may be supported on several grounds: (1) the frequency of association of group B Coxsackie viruses with encephalitic illness equaled or exceeded that of other commonly recognized encephalitogenic viruses including mumps and herpes simplex, and was exceeded only by WEE virus; (2) the consistency of such association over three consecutive summer periods; (3) the lack of a similar association of poliovirus or ECHO viruses with encephalitis, although both of the latter were associated with other illnesses in the areas under study and could have been present in coincidental alimentary infections; (4) the occurrence of rises in titer of neutralising antibody to Coxsackie virus, indicating a temporal relationship of the infection to the encephalitic illness; and (5) the concentration in infants and young children of encephalitic illness associated with Coxsackie viruses.
It appears reasonable to conclude that perhaps 10 to 15% or more of the incidence of summer illnesses reported as encephalitis from the California Central Valley in recent years may have been attributable to Coxsackie group B viruses. Although the majority of the reported cases of encephalitis found to be associated with a Coxsackie virus infection could more appropriately be classified as an aseptic meningitis syndrome, group B Coxsackie viruses may also have accounted for possibly 10 to 15% of the frank encephalitic illnesses. Poliovirus and ECHO viruses were also implicated in about 15% of the cases reported as encephalitis, but on review these cases were almost uniformly classified clinically as aseptic meningitis or doubtful encephalitis. Despite the implication of enteroviruses in over one-fourth of the cases of reported encephalitis, there still remained roughly one-fourth of the cases in which both virus isolation attempts and serologic tests failed to establish a possible viral etiology.