title: Design of non-pharmaceutical intervention strategies for pandemic influenza outbreaks.
abstract: BACKGROUND
  As seen during past pandemic influenza outbreaks, pharmaceutical interventions (PHIs) with vaccines and antivirals are the most effective methods of mitigation. However, availability of PHIs is unlikely to be adequate during the early stages of a pandemic. Hence, for early mitigation and possible containment, non-pharmaceutical interventions (NPIs) offer a viable alternative. Also, NPIs may be the only available interventions for most underdeveloped countries. In this paper we present a comprehensive methodology for design of effective NPI strategies.
  
  
  METHODS
  We develop a statistical ANOVA-based design approach that uses a detailed agent-based simulation as an underlying model. The design approach obtains the marginal effect of the characteristic parameters of NPIs, social behavior, and their interactions on various pandemic outcome measures including total number of contacts, infections, and deaths. We use the marginal effects to establish regression equations for the outcome measures, which are optimized to obtain NPI strategies. Efficacy of the NPI strategies designed using our methodology is demonstrated using simulated pandemic influenza outbreaks with different levels of virus transmissibility.
  
  
  RESULTS
  Our methodology was able to design effective NPI strategies, which were able to contain outbreaks by reducing infection attack rates (IAR) to below 10% in low and medium virus transmissibility scenarios with 33% and 50% IAR, respectively. The level of reduction in the high transmissibility scenario (with 65% IAR) was also significant. As noted in the published literature, we also found school closure to be the single most effective intervention among all NPIs.
  
  
  CONCLUSIONS
  If harnessed effectively, NPIs offer a significant potential for mitigation of pandemic influenza outbreaks. The methodology presented here fills a gap in the literature, which, though replete with models on NPI strategy evaluation, lacks a treatise on optimal strategy design.
authors.affiliation: Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA, USA, 02115. d.martinez@neu.edu.
authors.forename: Dayna L
authors.initials: DL
authors.lastname: Martinez
authors.affiliation: Industrial and Management Systems Engineering, University of South Florida, 4202 East Fowler Avenue, ENB 118, Tampa, FL, USA, 33620. das@usf.edu.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Das
mesh_terms: D003140:Communicable Disease Control / Q000379:methods*; D015438:Health Behavior; D006801:Humans; D007251:Influenza, Human / Q000453:epidemiology* / Q000517:prevention & control / Q000635:transmission; D008962:Models, Theoretical; D058873:Pandemics / Q000517:prevention & control*; D014481:United States / Q000453:epidemiology