RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY ON ADVERSE-EFFECTS OF RUBELLA IMMUNIZATION IN SERONEGATIVE WOMEN

Background The objective of our study was to investigate the associati on of adverse clinical musculoskeletal and neurological events in heal thy postpartum women with live attenuated (RA27/3 strain) rubella-viru s vaccine, and to assess the frequency of acute and recurrent arthralg ia and arthritis and associations with acute and recurrent muscle pain (myalgia) and neurological manifestations (paraesthesias). Methods We used a randomised placebo-controlled, double-blind design in a commun ity setting. 636 women were enrolled and, after 90 women dropped out, 546 healthy women aged 18-41 years, who were rubella seronegative on r outine screening were immunised parenterally with either monovalent li ve attenuated (RA27/3 strain) rubella vaccine (n=270) or saline placeb o (n=276) in the postpartum period. Outcome measures were the occurren ce of acute and persistent or recurrent joint manifestations (arthralg ia or arthritis) at 1, 3, 6, 9, and 12 months after immunisation. Occu rrence of muscle pain (myalgia), and neurological symptoms (paraesthes ia) was also assessed at the same times. Findings 543 women completed 1-month follow-up, 456 women completed the 12-month assessment. There were no differences at the time of immunisation between rubella vaccin e and placebo groups in distribution of age, ethnic origin, parity, ti me between delivery and immunisation, breastfeeding history, or histor ies of earlier rubella vaccination or joint complaints. Results indica ted a significantly higher incidence (p=0.006; odds ratio=1.73 [95% CI =1.17-2.57]) of acute joint manifestations in rubella-vaccine recipien ts (30%) than in placebo recipients (20%). Frequency of chronic (recur rent) arthralgia or arthritis was only marginally significant (p=0.042 ; 1.58 [1.01-2.45]). Interpretation RA27/3 rubella vaccine given to se ronegative women during the postpartum period was significantly associ ated with development of acute arthralgia or arthritis. Although the n umbers of women assessed and length of follow-up revealed only margina lly significant differences in persistent or recurrent joint manifesta tions between rubella vaccine and placebo recipients, it is possible t hat susceptible women who are given rubella vaccination may experience this outcome.