The optimal dose of disease-specific antibodies for post-exposure prophylaxis of measles and rubella in Australia: new guidelines recommended

Abstract

Background: It is unclear whether recommended doses of intramuscular polyvalent immune globulin are optimal for both effectiveness and efficiency of disease prevention when administered post-exposure to measles and rubella.

Methods: The peak concentration and decay of disease-specific antibodies after intramuscular dosing of polyvalent immune globulin in adults were modeled using published pharmacokinetic parameters and product disease-specific antibody concentrations. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of disease-specific immunoglobulins for post-exposure prophylaxis of nonimmune individuals against measles and rubella. Optimal dosing assumed a target serum concentration of disease-specific antibodies of the correlate of protection plus a 10% margin of error at an incubation period.

Results: Current Australian guidelines appeared to underdose a measles-naïve subpopulation. The optimal dose of measles-specific antibodies was 17.5 IU/kg assuming 75% bioavailability and 25.5 IU/kg assuming 50% bioavailability. Current Australian guidelines recommend 520 IU/kg rubella antibodies for an 80-kg individual. This model suggests that 13 IU/kg is more than sufficient.

Conclusions: The recommended dose of intramuscular polyvalent immune globulin should be increased following measles exposure and decreased following rubella exposure for recommended subgroups. These models may be adapted for use internationally.