Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.
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We thank the National Institute of General Medical Sciences MIDAS Program (N.M.F., D.A.T.C. and D.S.B.), the Medical Research Council (N.M.F.), the Royal Society (N.M.F. and C.F.), the Howard Hughes Medical Institute (N.M.F.), the Research Fund for the Control of Infectious Diseases of the Hong Kong SAR government (S.R.) and INSERM (S.C.) for research funding. We thank F. Carrat for providing household data used in this study, and N. Cox, F. Hayden, B. Schwartz, K. Stohr and members of the MIDAS consortium for useful discussions. We thank the MIDAS informatics group for computational resources. Author Contributions N.M.F. designed, implemented and ran the model, integrated the demographic and disease datasets used, and drafted and revised the text. All other authors edited or commented on the text. D.A.T.C. identified, collated and processed the Thai demographic and travel datasets used and provided input on model assumptions. S.C. analysed the French household dataset used to estimate key epidemiological parameters. C.F. performed analytical modelling of household transmission, which aided the verification of the simulation and gave suggestions on control strategies to be modelled. S.R. contributed to the design of some algorithms within the simulation model. A.M. assisted with collating data on Thai schools and administrative boundaries. S.I. provided feedback on the realism of model assumptions and the likely feasibility of different control options. D.S.B. provided input into model design and assumptions, advised on the presentation of results, assisted with data collection and organized meetings with stakeholders.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
Provides details of model structure, parameter estimation and sensitivity analyses undertaken. (PDF 557 kb)
Example of baseline simulated pandemic emergence in Thailand (R0=1.5). Greyscale represents population density of susceptibles (on logarithmic scale), red represents areas with infected individuals, and green represents areas which have recovered from infection. The video shows 300 days of spread. (MOV 3144 kb)
Example of successful containment of emergent pandemic influenza. Simulation shown assumes R0=1.8 and implementation of a social+5km radial prophylaxis policy combined with 5km area quarantine (see main text). Colours as for Supplementary Video 1, except blue represents areas in which treatment is occurring. The video shows 100 days of spread. (MOV 706 kb)
Example of containment failure due to single-country policy implementation. Simulation shown assumes R0=1.7 and implementation in Thailand only of a social+5km radial prophylaxis policy combined with 5km radial closure of 90% of schools and 50% of workplaces (see main text). Colours as for Supplementary Video 2. The video shows 300 days of spread. (MOV 3136 kb)
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Ferguson, N., Cummings, D., Cauchemez, S. et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature 437, 209–214 (2005). https://doi.org/10.1038/nature04017
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