title: Reducing disease burden in an influenza pandemic by targeted delivery of neuraminidase inhibitors: mathematical models in the Australian context.
abstract: BACKGROUND
  Many nations maintain stockpiles of neuraminidase inhibitor (NAI) antiviral agents for use in influenza pandemics to reduce transmission and mitigate the course of clinical infection. Pandemic preparedness plans include the use of these stockpiles to deliver proportionate responses, informed by emerging evidence of clinical impact. Recent uncertainty about the effectiveness of NAIs has prompted these nations to reconsider the role of NAIs in pandemic response, with implications for pandemic planning and for NAI stockpile size.
  
  
  METHODS
  We combined a dynamic model of influenza epidemiology with a model of the clinical care pathways in the Australian health care system to identify effective NAI strategies for reducing morbidity and mortality in pandemic events, and the stockpile requirements for these strategies. The models were informed by a 2015 assessment of NAI effectiveness against susceptibility, pathogenicity, and transmission of influenza.
  
  
  RESULTS
  Liberal distribution of NAIs for early treatment in outpatient settings yielded the greatest benefits in all of the considered scenarios. Restriction of community-based treatment to risk groups was effective in those groups, but failed to prevent the large proportion of cases arising from lower risk individuals who comprise the majority of the population.
  
  
  CONCLUSIONS
  These targeted strategies are only effective if they can be deployed within the constraints of existing health care infrastructure. This finding highlights the critical importance of identifying optimal models of care delivery for effective emergency health care response.
authors.affiliation: Modelling and Simulation Unit Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health, The University of Melbourne, Level 3, 207 Bouverie St, Melbourne, 3010, Victoria, Australia. rgmoss@unimelb.edu.au.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-4568-2012
authors.initials: R
authors.lastname: Moss
authors.affiliation: Modelling and Simulation Unit Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health, The University of Melbourne, Level 3, 207 Bouverie St, Melbourne, 3010, Victoria, Australia.|School of Mathematics and Statistics, The University of Melbourne, Melbourne, Australia.|Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: McCaw
authors.affiliation: Infectious Disease Epidemiology Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.|Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Australia.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Australia.
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
authors.affiliation: Modelling and Simulation Unit Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health, The University of Melbourne, Level 3, 207 Bouverie St, Melbourne, 3010, Victoria, Australia.|Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D017281:Cost of Illness; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008962:Models, Theoretical; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D058873:Pandemics / Q000517:prevention & control*; D018570:Risk Assessment
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase
keywords: Emergency response; Influenza; Neuraminidase inhibitor; Pandemic preparedness