Post-exposure prophylaxis during pandemic outbreaks.
BACKGROUND
With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.


METHODS
We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.


RESULTS
We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.


CONCLUSIONS
Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.
Moghadas
Seyed M
SM
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba, Canada. seyed.moghadas@nrc-cnrc.gc.ca
Bowman
Christopher S
CS
Röst
Gergely
G
Fisman
David N
DN
Wu
Jianhong
J
D000998:Antiviral Agents / Q000627:therapeutic use; D004196:Disease Outbreaks / Q000517:prevention & control*; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission*; D008962:Models, Theoretical; D053139:Oseltamivir / Q000627:therapeutic use; D056990:Post-Exposure Prophylaxis
D000998:Antiviral Agents; D053139:Oseltamivir