title: Age-prioritized use of antivirals during an influenza pandemic.
abstract: BACKGROUND
  The WHO suggested that governments stockpile, as part of preparations for the next influenza pandemic, sufficient influenza antiviral drugs to treat approximately 25% of their populations. Our aim is two-fold: first, since in many countries the antiviral stockpile is well below this level, we search for suboptimal strategies based on treatment provided only to an age-dependent fraction of cases. Second, since in some countries the stockpile exceeds the suggested minimum level, we search for optimal strategies for post-exposure prophylactic treatment of close contacts of cases.
  
  
  METHODS
  We used a stochastic, spatially structured individual-based model, considering explicit transmission in households, schools and workplaces, to simulate the spatiotemporal spread of an influenza pandemic in Italy and to evaluate the efficacy of interventions based on age-prioritized use of antivirals.
  
  
  RESULTS
  Our results show that the antiviral stockpile required for treatment of cases ranges from 10% to 35% of the population for R0 in 1.4 - 3. No suboptimal strategies, based on treatment provided to an age-dependent fraction of cases, were found able to remarkably reduce both clinical attack rate and antiviral drugs needs, though they can contribute to largely reduce the excess mortality. Treatment of all cases coupled with prophylaxis provided to younger individuals is the only intervention resulting in a significant reduction of the clinical attack rate and requiring a relatively small stockpile of antivirals.
  
  
  CONCLUSIONS
  Our results strongly suggest that governments stockpile sufficient influenza antiviral drugs to treat approximately 25% of their populations, under the assumption that R0 is not much larger than 2. In countries where the number of antiviral stockpiled exceeds the suggested minimum level, providing prophylaxis to younger individuals is an option that could be taken into account in preparedness plans. In countries where the number of antivirals stockpiled is well below 25% of the population, priority should be decided based on age-specific case fatality rates. However, late detection of cases (administration of antivirals 48 hours after the clinical onset of symptoms) dramatically affects the efficacy of both treatment and prophylaxis.
authors.affiliation: Predictive Models for Biomedicine and Environment, Fondazione Bruno Kessler, Trento, Italy. merler@fbk.eu
authors.forename: Stefano
authors.initials: S
authors.lastname: Merler
authors.forename: Marco
authors.initials: M
authors.lastname: Ajelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Rizzo
mesh_terms: D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000600:supply & distribution*; D003140:Communicable Disease Control / Q000379:methods; D003198:Computer Simulation; D004196:Disease Outbreaks; D015276:Health Care Rationing; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy / Q000453:epidemiology*; D007558:Italy; D008954:Models, Biological
chemical_list: D000998:Antiviral Agents