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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
most important environmental triggers of pancreatic beta cell destruction in individuals with a genetic predisposition for IDDM (Banatvala et al., 1987; Maclaren, 1992). Genetic susceptibility has been associated with certain histocompatibility locus antigens (HLAs) on chromosome 6 (Gutierrez-Lopez et al., 1992; Maclaren, 1992).
Evidence favoring a role for environmental factors such as viral infections in the development of IDDM includes the finding that only about one of every two or three pairs of identical twins who develop IDDM are concordant for the disease, and individuals at highest genetic risk for IDDM, as well as rodents genetically homogeneous for spontaneously developing IDDM, do not always acquire the disease (Gutierrez-Lopez et al., 1992; Lipton et al., 1992; Maclaren, 1992).
Several different mechanisms appear to be involved in the pathogenesis of virus-induced IDDM. These have been summarized by Yoon and colleagues and consist of four main categories: (1) direct destruction of pancreatic beta cells by cytolytic viruses without the stimulation of an autoimmune reaction, (2) viral triggering of an autoimmune response, either by molecular mimicry or by altering the immunologic appearance of beta cell antigens, (3) cumulative insults to beta cells by environmental factors such as viral infections and toxins (Dahlquist, 1991; Tishon and Oldstone, 1987; Yoon et al., 1987b), and (4) persistent vital infection resulting in an altered ability to produce insulin with or without progressive beta cell destruction over a period of time (Oldstone, 1989; Tishon and Oldstone, 1987; Yoon et al., 1987a; Yoon and Ray, 1985).
There is no notable history of a suspected association between monovalent measles vaccine and IDDM. Suspicion of an association between mumps vaccine and IDDM is based on the ability of the wild-type mumps virus to cause pancreatitis (Association for the Study of Infectious Disease, 1974; Craighead, 1975; Prince et al., 1978), individual cases of IDDM with onset shortly following acute clinical mumps infections (Gamble et al., 1980; Harris, 1899; Hinden, 1962; Kremer, 1947; McCrae, 1963; Messaritakis, 1971; Otten et al., 1984; Patrick, 1924; Peig et al., 1981), clusters of IDDM after mumps epidemics (Dacou-Voutetakis et al., 1974), and large epidemiologic studies demonstrating parallel curves between outbreaks of mumps disease and new cases of IDDM (Gunderson, 1927; Sultz et al., 1975). Some cases of IDDM with clinical onset temporally related to immunization with mumps vaccine have been reported in the literature and VAERS (submitted between November 1990 and July 1992) (Blom et al., 1991; Helmke et al., 1986; Otten et al., 1984; Pawlowski and Gries, 1991; Quast et al., 1979; Sinaniotis et al., 1975; Taranger and Wiholm, 1987).