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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 977-990
© 2003 The British Society for Antimicrobial Chemotherapy

A population-dynamic model for evaluating the potential spread of drug-resistant influenza virus infections during community-based use of antivirals

Neil M. Ferguson1,*, Susan Mallett2, Helen Jackson3, Noel Roberts4 and Penelope Ward3

1 Department of Infectious Disease Epidemiology, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG; 2 The UK Cochrane Centre, NHS R & D Programme, Oxford; 3 Roche Global Development, Welwyn Garden City; 4 Roche Discovery Welwyn, Welwyn Garden City, UK

Received 18 February 2002; returned 23 September 2002; revised 6 December 2002; accepted 2 January 2003

A mathematical model of influenza transmission dynamics is used to simulate the impact of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains. The model incorporates population age structure, seasonal transmission, immunity and inclusion of elderly nursing home residents or non-residents. Key parameter values are estimated from epidemiological, clinical and experimental data. The analysis examines the factors determining the population spread of antiviral resistance, and predicts no significant transmission of neuraminidase inhibitor resistant virus. This conclusion is robust even at high therapy levels and under conservative assumptions regarding the likely frequency of transmission of resistant virus. The predicted incidence of resistance following protracted usage reflects primary drug resistance, currently estimated as ~2% for neuraminidase inhibitor therapy. It is also shown that until high levels of therapy are attained, early treatment of symptomatic cases is more efficient (per unit of drug) at preventing infections than prophylactic therapy.

* Corresponding author. Fax: +44-20-7262-3495; E-mail: neil.ferguson{at}imperial.ac.uk


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