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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
two of those 15 patients, exposure to measles virus was probable, but clinical measles was not recorded (Landrigan and Witte, 1973; Parker et al., 1970). The latency between vaccination against measles and the onset of SSPE symptoms ranged from 3 weeks (Landrigan and Witte, 1973; Schneck, 1968) to 5 years (Cho et al., 1973).
The absence of prevaccination serology and the inability to characterize the cause of SSPE as wild-type or vaccine-strain measles virus in all cases preclude, as discussed below, a determination that the SSPE was caused by administration of the live attenuated measles vaccine. A negative history of natural measles disease in unimmunized persons is always suspect because measles infection can occur subclinically without rash. No case reports of SSPE definitively show that the cause of SSPE in a specific patient was the vaccine-strain virus and not the wild-type virus.
In 1978 the question about SSPE and measles vaccine surfaced again in response to a report concerning a boy who at age 7 years showed signs of SSPE, including deterioration in school performance, incontinence, and forgetfulness (Dodson et al., 1978). Within a few weeks of receiving live attenuated measles vaccine at age 8 years, the patient's symptoms progressed. At 2.5 to 3 months after vaccination, the patient died. SSPE was diagnosed by high measles virus titers in serum and CSF and a high ratio of immunoglobulin G/albumin in serum and CSF. At age 13 months he had suffered a mild illness considered by history to be measles. The authors hypothesized that the measles vaccine accelerated an already evolving SSPE.
The National Registry for Subacute Sclerosing Panencephalitis was founded in 1969, in response to an interest in the effects of measles vaccine on the incidence of SSPE (Schacher, 1968). Originally housed at the University of Tennessee Center for Health Sciences, it now resides at the University of South Alabama. The registry now includes data on more than 575 patients (Paul R. Dyken, University of South Alabama, Mobile, personal communication, 1993). The number of new cases of SSPE documented in the registry decreased from 46 in 1967 to 33 in 1972 to 13 in 1974 (Modlin et al., 1977). The average number of new reports of SSPE per year from 1982 to 1986 was 4.2 (Dyken et al., 1989) and is now about 1, although underreporting is suspected (Paul R. Dyken, University of South Alabama, Mobile, personal communication, 1993).
Analysis of 375 confirmed cases of SSPE that occurred in the United States from 1960 to 1974 (Modlin et al., 1977) demonstrated a decreasing incidence of SSPE beginning in the early 1970's. From 1967 to 1970 the proportion of new cases of SSPE associated with measles vaccine was less than 13 percent, but it increased to 20.6 percent in 1973 and 38.5 percent in 1974. This prompted the authors to note:
Although far from conclusive, the data presented here suggest that live,