Post-exposure prophylaxis during pandemic outbreaks.

Area of Science:

• Epidemiology
• Virology
• Pharmacology

Background:

• The second wave of the novel influenza A (H1N1) virus necessitates re-evaluation of pandemic plans, especially antiviral drug strategies.
• Emergence of oseltamivir-resistant H1N1 strains raises concerns for treatment and post-exposure prophylaxis.
• Prudent use of neuraminidase inhibitors is critical during influenza pandemics.

Purpose of the Study:

• To evaluate the combined effects of antiviral treatment and post-exposure prophylaxis on pandemic influenza.
• To assess strategies for minimizing morbidity and mortality in the context of transmissible drug resistance.
• To determine optimal antiviral drug use policies during an influenza pandemic.

Main Methods:

• An established population dynamical model of pandemic influenza was extended to include post-exposure prophylaxis.
• Simulations were performed using published parameter estimates to analyze treatment and prophylaxis effects.
• Sensitivity analysis was conducted to test the model's robustness across various parameters.

Main Results:

• Post-exposure prophylaxis can accelerate the spread of drug-resistant strains, particularly with aggressive treatment.
• An optimal prophylaxis coverage exists to minimize total infections, decreasing as treatment levels rise.
• Intermediate treatment levels combined with limited prophylaxis offer an optimal strategy to reduce pandemic size and deaths.

Conclusions:

• Prioritizing treatment of infected individuals over prophylaxis for exposed contacts is most effective in reducing pandemic morbidity and mortality.
• The impact of prophylaxis is critically dependent on treatment levels and the transmissibility of resistant strains.
• Enhanced surveillance for drug-resistant influenza mutants is essential for comprehensive antiviral drug use plans.