{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T17:17:48Z","timestamp":1771867068494,"version":"3.50.1"},"reference-count":31,"publisher":"The Royal Society","issue":"1619","license":[{"start":{"date-parts":[[2007,5,16]],"date-time":"2007-05-16T00:00:00Z","timestamp":1179273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proc. R. Soc. B."],"published-print":{"date-parts":[[2007,7,22]]},"abstract":"<jats:p>\n            Given the danger of an unprecedented spread of the highly pathogenic avian influenza strain H5N1 in humans, and great challenges to the development of an effective influenza vaccine, antiviral drugs will probably play a pivotal role in combating a novel pandemic strain. A critical limitation to the use of these drugs is the evolution of highly transmissible drug-resistant viral mutants. Here, we develop a mathematical model to evaluate the potential impact of an antiviral treatment strategy on the emergence of drug resistance and containment of a pandemic. The results show that elimination of the wild-type strain depends crucially on both the early onset of treatment in indexed cases and population-level treatment. Given the probable delay of 0.5\u20131 day in seeking healthcare and therefore initiating therapy, the findings indicate that a single strategy of antiviral treatment will be unsuccessful at controlling the spread of disease if the reproduction number of the wild-type strain\n            <jats:inline-formula>\n              <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"1675equ19.gif\"\/>\n            <\/jats:inline-formula>\n            exceeds 1.4. We demonstrate the possible occurrence of a self-sustaining epidemic of resistant strain, in terms of its transmission fitness relative to the wild-type, and the reproduction number\n            <jats:inline-formula>\n              <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"1675equ20.gif\"\/>\n            <\/jats:inline-formula>\n            . Considering reproduction numbers estimated for the past three pandemics, the findings suggest that an uncontrollable pandemic is likely to occur if resistant viruses with relative transmission fitness above 0.4 emerge. While an antiviral strategy is crucial for containing a pandemic, its effectiveness depends critically on timely and strategic use of drugs.\n          <\/jats:p>","DOI":"10.1098\/rspb.2007.0422","type":"journal-article","created":{"date-parts":[[2007,5,18]],"date-time":"2007-05-18T00:36:12Z","timestamp":1179448572000},"page":"1675-1684","source":"Crossref","is-referenced-by-count":68,"title":["Emergence of drug resistance: implications for antiviral control of pandemic influenza"],"prefix":"10.1098","volume":"274","author":[{"given":"Murray E","family":"Alexander","sequence":"first","affiliation":[{"name":"Institute for Biodiagnostics, National Research Council CanadaWinnipeg, Manitoba, Canada R3B 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher S","family":"Bowman","sequence":"additional","affiliation":[{"name":"Institute for Biodiagnostics, National Research Council CanadaWinnipeg, Manitoba, Canada R3B 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Purdue University150 N University Street, West Lafayette, IN 47907-2067, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gardam","sequence":"additional","affiliation":[{"name":"Toronto General Hospital, Eaton South WingThird Floor Room 428, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed M","family":"Moghadas","sequence":"additional","affiliation":[{"name":"Institute for Biodiagnostics, National Research Council CanadaWinnipeg, Manitoba, Canada R3B 1Y6"},{"name":"Department of Mathematics and Statistics, The University of WinnipegWinnipeg, Manitoba, Canada R3B 2E9"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely","family":"R\u00f6st","sequence":"additional","affiliation":[{"name":"Analysis and Stochastics Research Group, Hungarian Academy of Sciences, Bolyai Institute, University of SzegedAradi v\u00e9rtan\u00fak tere 1, 6720 Szeged, Hungary"},{"name":"Department of Mathematics and Statistics, York University4700 Keele Street, Toronto, Ontario, Canada M3J 1P3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, York University4700 Keele Street, Toronto, Ontario, Canada M3J 1P3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yan","sequence":"additional","affiliation":[{"name":"Modelling &amp; Projection Section, Centre for Infectious Disease Prevention and Control, Public Health Agency of CanadaOttawa, Ontario, Canada K1A 0K9"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2007,5,16]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2006.0112"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01623-05"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67338-2"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040013"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054512"},{"key":"e_1_3_2_7_1","unstructured":"Diekmann O& Heesterbeek J.A.P Mathematical epidemiology of infectious diseases. 2000 Chichester UK:Wiley."},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg136"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04017"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04795"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1209.041344"},{"key":"e_1_3_2_12_1","unstructured":"Gardam M. Liang D. Moghadas S. M. Wu J. Zeng Q. & Zhu H. 2007 The impact of prophylaxis of healthcare workers on influenza pandemic burden. J. R. Soc. Interface . 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