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Here, we use a mathematical model of influenza transmission embedded within a Bayesian synthesis inferential framework to jointly analyze syndromic, virological, and serological surveillance data collected in England in 2009\u20132011 and thereby assess epidemiological mechanisms which might have generated the third wave. We find that substantially increased transmissibility of the H1N1pdm09 virus is required to reproduce the third wave, suggesting that the virus evolved and increased fitness in the human host by the end of 2010, or that the very cold weather experienced in the United Kingdom at that time enhanced transmission rates. We also find some evidence that the preexisting heterologous immunity which reduced attack rates in adults during 2009 had substantially decayed by the winter of 2010, thus increasing the susceptibility of the adult population to infection. Finally, our analysis suggests that a pandemic vaccination campaign targeting adults and school-age children could have mitigated or prevented the third wave even at moderate levels of coverage.<\/jats:p>","DOI":"10.1073\/pnas.1303117110","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T13:32:58Z","timestamp":1374672778000},"page":"13422-13427","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Increased transmissibility explains the third wave of infection by the 2009 H1N1 pandemic virus in England"],"prefix":"10.1073","volume":"110","author":[{"given":"Ilaria","family":"Dorigatti","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Cauchemez","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil M.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,7,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3310\/hta14550-03"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2807\/ese.17.14.20139-en"},{"key":"e_1_3_3_3_2","first-page":"19760","article-title":"Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010\/11","volume":"16","author":"Ellis J","year":"2011","unstructured":"J Ellis, et al., Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010\/11. 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Pandemic H1N1 (swine) influenza vaccine uptake amongst patients groups in primary care in England. Available at http:\/\/www.dh.gov.uk\/prod_consum_dh\/groups\/dh_digitalassets\/@dh\/@en\/@ps\/documents\/digitalasset\/dh_121014.pdf. Accessed January 28 2012."},{"key":"e_1_3_3_11_2","unstructured":"Health Protection Agency. Seasonal influenza vaccine uptake amongst GP patient groups in England. Winter season 2010-11. Available at http:\/\/www.dh.gov.uk\/prod_consum_dh\/groups\/dh_digitalassets\/documents\/digitalasset\/dh_129856.pdf. Accessed January 28 2012."},{"key":"e_1_3_3_12_2","unstructured":"World Health Organization (WHO). WHO recommendations on the composition of influenza virus vaccines. Available at http:\/\/www.who.int\/influenza\/vaccines\/virus\/recommendations\/en\/. 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