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.

KEYWORDS:

• Immunoglobulin
• measles
• passive immunization
• pharmacokinetics
• post-exposure prophylaxis
• rubella

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.