title: Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.
abstract: BACKGROUND
  Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact.
  
  
  RESULTS
  We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis.
  
  
  CONCLUSIONS
  We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for contact identification and prophylaxis delivery, utilising a range of existing services and infrastructure in a "whole of society" response.
authors.affiliation: Vaccine and Immunisation Research Group, Murdoch Childrens Research Institute and Melbourne School of Population Health, The University of Melbourne, Parkville, Australia. rgmoss@unimelb.edu.au
authors.forename: Robert
authors.initials: R
authors.lastname: Moss
authors.forename: James M
authors.initials: JM
authors.lastname: McCaw
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
mesh_terms: D000998:Antiviral Agents / Q000600:supply & distribution / Q000627:therapeutic use*; D058872:Epidemics / Q000517:prevention & control*; D006801:Humans; D007251:Influenza, Human / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D058873:Pandemics / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D015980:Public Health Practice; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000998:Antiviral Agents