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Evidence from Studies in Humans
Acute Arthropathy and Arthritis

Case Series and Controlled Epidemiologic Studies There is a substantial body of evidence, both from controlled and noncontrolled studies in humans, relating rubella vaccine to acute arthropathy and arthritis. The earliest evidence derives from noncontrolled retrospective and prospective studies conducted in the late 1960s and early 1970s, the former generally designed to test the efficacy of various rubella vaccine strains, rather than their side effects, and the latter as part of the routine administration of the vaccine in population-based immunization campaigns (e.g., Austin et al., 1972; Balfour et al., 1976, 1980; Barnes et al., 1972; Cooper et al., 1969; Dudgeon et al., 1969; Fox et al., 1976; Freestone et al., 1971; Grand et al., 1972; Kilroy et al., 1970; Lerman et al., 1971; Monto et al., 1970; Rowlands and Freestone, 1971; Spruance and Smith, 1971; Swartz et al., 1971; Wallace et al., 1972; Weibel et al., 1972, 1980). The vaccines examined in these studies were the HPV-77 strain (no longer in use), developed in simian tissue culture and then grown for production in dog kidney (DK) culture or in duck embryo (DEV) culture; the Cendehill strain (in limited use now), developed in rabbit kidney tissue culture; and the RA 27/3 strain (most commonly used now), developed in human diploid cells (WI38).

These and more recent studies (e.g., Peltola and Heinonen, 1986; Polk et al., 1982; Valensin et al., 1987) provide generally consistent findings with respect to the acute arthropathy and arthritis observed following rubella immunization. These include the observation that arthropathy and, less commonly, arthritis occur rarely in children but occur in 10 to 40 percent of susceptible (seronegative for rubella at the time of immunization) postpubertal women. Occurrence of these reactions increases with age, and they are less frequent in men and prepubescent children. Rates of acute arthropathy and arthritis following rubella immunization differ by vaccine strain, with the HPV-77 (DK) variant producing the most joint manifestations in all age groups (Barnes et al., 1972; Spruance and Smith, 1971; Wallace et al., 1972).  The HPV-77 (DEV) and RA 27/3 strains have also been observed to produce joint symptoms, but the symptoms are more akin to the reaction following natural disease, and the arthropathy is more likely to occur in adults than in children (Polk et al., 1982; Swartz et al., 1971; Weibel et al., 1972).

In one of the few double-masked controlled studies of joint reactions to rubella vaccine conducted to date,  Polk and colleagues (1982) compared reactions in 112 adult, seronegative female employees of a Boston hospital receiving either the HPV-77 (DEV) or the RA 27/3 strain in response to a rubella outbreak. Allocation to the vaccines was haphazard, because the

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