subsequent IDDM has been provided by a report by Jenson and colleagues who found evidence of insulitis and beta cell damage in pancreatic sections from four of seven neonates who died of coxsackievirus B infection, although this finding does not prove that the infants would have developed IDDM if they had lived (Jenson et al., 1980).

Evidence that persistent viral infection may cause IDDM comes from studies of patients with the congenital rubella syndrome and experimental evidence that rubella infection in rabbit and hamster models causes pancreatic beta cell damage (Menser, 1978; Rayfield et al., 1986). Rubella virus has been isolated from the pancreases of several patients with congenital infections (De Prins et al., 1978; Monif, 1974), and inflammation of the pancreas has been reported in other children with congenital rubella (Bunnell and Monif, 1972; Patterson et al., 1981). Epidemiologic studies have shown that the prevalence of IDDM among children with congenital rubella infection is high in some countries, but not in others, suggesting that only patients with congenital rubella plus a genetic predisposition for developing IDDM are affected (Menset et al., 1978; Rubinstein et al., 1982). Indeed, it has been demonstrated that the frequencies of the HLAs DR2 and DR3 are significantly lower and higher, respectively, in patients with IDDM and congenital rubella than in those without IDDM (Rubinstein et al, 1982).

Experiments in animals have demonstrated that viruses such as coxsackievirus, encephalomyocarditis virus, mengovirus, reovirus, and lymphocytic choriomeningitis virus are capable of inducing IDDM, but most studies have shown that both the strain of the virus and the genetic susceptibility of the animal are important in the development of IDDM (Menser et al., 1978; Rayfield et al., 1986; Tishon and Oldstone, 1987; Yoon and Ray, 1985; Yoon et al., 1978, 1979, 1987a,b). This is illustrated particularly well by the ability of certain strains of lymphocytic choriomeningitis virus to stimulate the onset of IDDM and of others to prevent it (Dyrberg et al., 1988; Oldstone, 1988; Oldstone et al., 1990a,b; Tishon and Oldstone, 1987).

Infection with live (but not inactivated) mumps and rubella viruses, and coxsackievirus B4 has been found to lead to increased expression of HLA class I molecules and minor decreases in insulin secretion in cultured human beta cells (Parkkonen et al., 1992). Several common viruses including mumps virus, coxsackievirus B, and reovirus type 3 can infect human pancreatic beta cells in vitro and destroy them (Parkkonen et al., 1992; Prince et al., 1978; Yoon and Ray, 1985).

Case Reports, Case Series, and Uncontrolled Observational Studies

The case reports implicating measles vaccine as a potential cause of IDDM involve administration of the mumps vaccine at the same time.

There have been several cases of IDDM reported following MMR, measles-

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