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Fisman)] TJ ET 0.271 0.267 0.267 rg BT 165.500 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 170.921 663.247 Td /F1 9.8 Tf [(Jeffrey C. Kwong)] TJ ET 0.271 0.267 0.267 rg BT 245.157 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 250.578 663.247 Td /F1 9.8 Tf [(Amy Greer)] TJ ET 0.271 0.267 0.267 rg BT 26.250 651.342 Td /F1 9.8 Tf [(Tuite A, Fisman DN, Kwong JC, Greer A. Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian )] TJ ET BT 26.250 639.438 Td /F1 9.8 Tf [(Population. PLOS Currents Influenza. 2010 Jan 7 . Edition 1. doi: 10.1371/currents.RRN1144.)] TJ ET q 15.000 23.815 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 610.335 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 590.381 Td /F1 9.8 Tf [(Background: The world is currently confronting the first influenza pandemic of the 21st century. Influenza vaccination is an )] TJ ET BT 26.250 578.476 Td /F1 9.8 Tf [(effective preventive measure, but the unique epidemiological features of swine-origin influenza A \(H1N1\) \(pH1N1\) introduce )] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(mortality.)] TJ ET BT 26.250 523.357 Td /F1 9.8 Tf [(Methodology/Principal Findings: We developed a deterministic, age-structured compartmental model of influenza transmission, )] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(mortality. In all scenarios, prioritization of high-risk groups \(individuals with underlying chronic conditions and pregnant women\) )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(markedly decreased the frequency of severe outcomes. Preferential vaccination of age groups at increased risk of severe )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(outcomes following infection resulted in decreased mortality compared to targeting vaccine to age groups with higher )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(epidemic peak.)] TJ ET BT 26.250 408.714 Td /F1 9.8 Tf [(Conclusions/Significance: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of )] TJ ET BT 26.250 396.810 Td /F1 9.8 Tf [(age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable )] TJ ET BT 26.250 384.905 Td /F1 9.8 Tf [(morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake.)] TJ ET BT 26.250 348.302 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 328.348 Td /F1 9.8 Tf [(AT receives support from the Mathematics of Information Technology and Complex Systems \(MITACS\) Accelerate Program )] TJ ET BT 26.250 316.443 Td /F1 9.8 Tf [(through both MITACS funding and a matching contribution from the Ontario Agency for Health Protection and Promotion. DF is )] TJ ET BT 26.250 304.539 Td /F1 9.8 Tf [(supported by an Early Researcher Award from the Ontario Ministry of Research and Innovation and is supported by the )] TJ ET BT 26.250 292.634 Td /F1 9.8 Tf [(Canadian Consortium for Pandemic Preparedness Modelling, MITACS and the CIHR. JK was supported by an Ontario Ministry )] TJ ET BT 26.250 280.729 Td /F1 9.8 Tf [(of Health and Long-Term Care \(MOHLTC\) Career Scientist Award, a University of Toronto Department of Family and )] TJ ET BT 26.250 268.824 Td /F1 9.8 Tf [(Community Medicine Research Scholar Award, and the Institute for Clinical Evaluative Sciences \(ICES\).)] TJ ET BT 26.250 239.722 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 219.768 Td /F1 9.8 Tf [(The rapid global spread of a novel swine-origin influenza A \(H1N1\) \(pH1N1\) virus led the World Health Organization to declare )] TJ ET BT 26.250 207.863 Td /F1 9.8 Tf [(an influenza pandemic on June 11, 2009 )] TJ ET 0.267 0.267 0.267 rg BT 204.568 207.863 Td /F1 9.8 Tf [([1])] TJ ET 0.271 0.267 0.267 rg BT 215.410 207.863 Td /F1 9.8 Tf [(. When there is a good match between circulating and vaccine strains, influenza )] TJ ET BT 26.250 195.958 Td /F1 9.8 Tf [(immunization is the most effective preventive measure for reducing influenza-related morbidity and mortality )] TJ ET 0.267 0.267 0.267 rg BT 493.334 195.958 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 504.175 195.958 Td /F1 9.8 Tf [(. Development of )] TJ ET BT 26.250 184.053 Td /F1 9.8 Tf [(a vaccine against pH1N1 began in the early phases of the epidemic, leading to questions about prioritization of vaccine )] TJ ET BT 26.250 172.149 Td /F1 9.8 Tf [(allocation within populations, given that not all vaccine will be distributed at once \(due to production and logistical constraints\).)] TJ ET BT 26.250 152.744 Td /F1 9.8 Tf [(Seasonal influenza immunization campaigns typically target the elderly and those of any age with one or more underlying )] TJ ET BT 26.250 140.839 Td /F1 9.8 Tf [(medical conditions, under the assumption that it is best to protect those most likely to have complications from influenza. )] TJ ET BT 26.250 128.934 Td /F1 9.8 Tf [(Recently, there has been debate over whether this is the best approach )] TJ ET 0.267 0.267 0.267 rg BT 337.334 128.934 Td /F1 9.8 Tf [([3])] TJ ET BT 348.175 128.934 Td /F1 9.8 Tf [([4])] TJ ET 0.271 0.267 0.267 rg BT 359.017 128.934 Td /F1 9.8 Tf [(. The degree of protection conferred by the )] TJ ET BT 26.250 117.030 Td /F1 9.8 Tf [(influenza vaccine appears to be lower in the elderly than in the general population )] TJ ET 0.267 0.267 0.267 rg BT 381.228 117.030 Td /F1 9.8 Tf [([5])] TJ ET 0.271 0.267 0.267 rg BT 392.070 117.030 Td /F1 9.8 Tf [( and it has been suggested that an )] TJ ET BT 26.250 105.125 Td /F1 9.8 Tf [(immunization strategy based on reducing transmission would have a greater impact on reducing overall disease burden than )] TJ ET BT 26.250 93.220 Td /F1 9.8 Tf [(the current practice of focusing vaccination efforts on at-risk groups )] TJ ET 0.267 0.267 0.267 rg BT 318.877 93.220 Td /F1 9.8 Tf [([6])] TJ ET 0.271 0.267 0.267 rg BT 329.719 93.220 Td /F1 9.8 Tf [(. In particular, the potential benefit of preferentially )] TJ ET BT 26.250 81.315 Td /F1 9.8 Tf [(vaccinating school-aged children has been discussed, since this age group is disproportionately responsible for influenza )] TJ ET BT 26.250 69.411 Td /F1 9.8 Tf [(transmission)] TJ ET 0.267 0.267 0.267 rg BT 80.967 69.411 Td /F1 9.8 Tf [([7])] TJ ET BT 91.809 69.411 Td /F1 9.8 Tf [([8])] TJ ET BT 102.651 69.411 Td /F1 9.8 Tf [([9])] TJ ET 0.271 0.267 0.267 rg BT 113.493 69.411 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 50.006 Td /F1 9.8 Tf [(As with earlier pandemics, pH1N1 is characterized by age distributions that are distinct from those observed in seasonal )] TJ ET BT 26.250 38.101 Td /F1 9.8 Tf [(influenza epidemics, with higher attack rates and increased proportionate mortality, in younger individuals )] TJ ET 0.267 0.267 0.267 rg BT 483.067 38.101 Td /F1 9.8 Tf [([10])] TJ ET BT 499.330 38.101 Td /F1 9.8 Tf [([11])] TJ ET BT 515.593 38.101 Td /F1 9.8 Tf [([12])] TJ ET 0.271 0.267 0.267 rg BT 531.856 38.101 Td /F1 9.8 Tf [(. This )] TJ ET Q q 15.000 684.354 577.500 53.646 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Optimal Pandemic Influenza Vaccine Allocation Strategies for )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(the Canadian Population)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(January 7, 2010)] TJ ET BT 83.513 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 88.388 675.088 Td /F3 9.8 Tf [(Influenza)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Ashleigh Tuite)] TJ ET 0.271 0.267 0.267 rg BT 88.026 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 93.447 663.247 Td /F1 9.8 Tf [(David N. Fisman)] TJ ET 0.271 0.267 0.267 rg BT 165.500 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 170.921 663.247 Td /F1 9.8 Tf [(Jeffrey C. Kwong)] TJ ET 0.271 0.267 0.267 rg BT 245.157 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 250.578 663.247 Td /F1 9.8 Tf [(Amy Greer)] TJ ET 0.271 0.267 0.267 rg BT 26.250 651.342 Td /F1 9.8 Tf [(Tuite A, Fisman DN, Kwong JC, Greer A. Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian )] TJ ET BT 26.250 639.438 Td /F1 9.8 Tf [(Population. PLOS Currents Influenza. 2010 Jan 7 . Edition 1. doi: 10.1371/currents.RRN1144.)] TJ ET q 15.000 23.815 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 610.335 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 590.381 Td /F1 9.8 Tf [(Background: The world is currently confronting the first influenza pandemic of the 21st century. Influenza vaccination is an )] TJ ET BT 26.250 578.476 Td /F1 9.8 Tf [(effective preventive measure, but the unique epidemiological features of swine-origin influenza A \(H1N1\) \(pH1N1\) introduce )] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(mortality.)] TJ ET BT 26.250 523.357 Td /F1 9.8 Tf [(Methodology/Principal Findings: We developed a deterministic, age-structured compartmental model of influenza transmission, )] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(mortality. In all scenarios, prioritization of high-risk groups \(individuals with underlying chronic conditions and pregnant women\) )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(markedly decreased the frequency of severe outcomes. Preferential vaccination of age groups at increased risk of severe )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(outcomes following infection resulted in decreased mortality compared to targeting vaccine to age groups with higher )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(epidemic peak.)] TJ ET BT 26.250 408.714 Td /F1 9.8 Tf [(Conclusions/Significance: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of )] TJ ET BT 26.250 396.810 Td /F1 9.8 Tf [(age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable )] TJ ET BT 26.250 384.905 Td /F1 9.8 Tf [(morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake.)] TJ ET BT 26.250 348.302 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 328.348 Td /F1 9.8 Tf [(AT receives support from the Mathematics of Information Technology and Complex Systems \(MITACS\) Accelerate Program )] TJ ET BT 26.250 316.443 Td /F1 9.8 Tf [(through both MITACS funding and a matching contribution from the Ontario Agency for Health Protection and Promotion. DF is )] TJ ET BT 26.250 304.539 Td /F1 9.8 Tf [(supported by an Early Researcher Award from the Ontario Ministry of Research and Innovation and is supported by the )] TJ ET BT 26.250 292.634 Td /F1 9.8 Tf [(Canadian Consortium for Pandemic Preparedness Modelling, MITACS and the CIHR. JK was supported by an Ontario Ministry )] TJ ET BT 26.250 280.729 Td /F1 9.8 Tf [(of Health and Long-Term Care \(MOHLTC\) Career Scientist Award, a University of Toronto Department of Family and )] TJ ET BT 26.250 268.824 Td /F1 9.8 Tf [(Community Medicine Research Scholar Award, and the Institute for Clinical Evaluative Sciences \(ICES\).)] TJ ET BT 26.250 239.722 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 219.768 Td /F1 9.8 Tf [(The rapid global spread of a novel swine-origin influenza A \(H1N1\) \(pH1N1\) virus led the World Health Organization to declare )] TJ ET BT 26.250 207.863 Td /F1 9.8 Tf [(an influenza pandemic on June 11, 2009 )] TJ ET 0.267 0.267 0.267 rg BT 204.568 207.863 Td /F1 9.8 Tf [([1])] TJ ET 0.271 0.267 0.267 rg BT 215.410 207.863 Td /F1 9.8 Tf [(. When there is a good match between circulating and vaccine strains, influenza )] TJ ET BT 26.250 195.958 Td /F1 9.8 Tf [(immunization is the most effective preventive measure for reducing influenza-related morbidity and mortality )] TJ ET 0.267 0.267 0.267 rg BT 493.334 195.958 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 504.175 195.958 Td /F1 9.8 Tf [(. Development of )] TJ ET BT 26.250 184.053 Td /F1 9.8 Tf [(a vaccine against pH1N1 began in the early phases of the epidemic, leading to questions about prioritization of vaccine )] TJ ET BT 26.250 172.149 Td /F1 9.8 Tf [(allocation within populations, given that not all vaccine will be distributed at once \(due to production and logistical constraints\).)] TJ ET BT 26.250 152.744 Td /F1 9.8 Tf [(Seasonal influenza immunization campaigns typically target the elderly and those of any age with one or more underlying )] TJ ET BT 26.250 140.839 Td /F1 9.8 Tf [(medical conditions, under the assumption that it is best to protect those most likely to have complications from influenza. )] TJ ET BT 26.250 128.934 Td /F1 9.8 Tf [(Recently, there has been debate over whether this is the best approach )] TJ ET 0.267 0.267 0.267 rg BT 337.334 128.934 Td /F1 9.8 Tf [([3])] TJ ET BT 348.175 128.934 Td /F1 9.8 Tf [([4])] TJ ET 0.271 0.267 0.267 rg BT 359.017 128.934 Td /F1 9.8 Tf [(. The degree of protection conferred by the )] TJ ET BT 26.250 117.030 Td /F1 9.8 Tf [(influenza vaccine appears to be lower in the elderly than in the general population )] TJ ET 0.267 0.267 0.267 rg BT 381.228 117.030 Td /F1 9.8 Tf [([5])] TJ ET 0.271 0.267 0.267 rg BT 392.070 117.030 Td /F1 9.8 Tf [( and it has been suggested that an )] TJ ET BT 26.250 105.125 Td /F1 9.8 Tf [(immunization strategy based on reducing transmission would have a greater impact on reducing overall disease burden than )] TJ ET BT 26.250 93.220 Td /F1 9.8 Tf [(the current practice of focusing vaccination efforts on at-risk groups )] TJ ET 0.267 0.267 0.267 rg BT 318.877 93.220 Td /F1 9.8 Tf [([6])] TJ ET 0.271 0.267 0.267 rg BT 329.719 93.220 Td /F1 9.8 Tf [(. In particular, the potential benefit of preferentially )] TJ ET BT 26.250 81.315 Td /F1 9.8 Tf [(vaccinating school-aged children has been discussed, since this age group is disproportionately responsible for influenza )] TJ ET BT 26.250 69.411 Td /F1 9.8 Tf [(transmission)] TJ ET 0.267 0.267 0.267 rg BT 80.967 69.411 Td /F1 9.8 Tf [([7])] TJ ET BT 91.809 69.411 Td /F1 9.8 Tf [([8])] TJ ET BT 102.651 69.411 Td /F1 9.8 Tf [([9])] TJ ET 0.271 0.267 0.267 rg BT 113.493 69.411 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 50.006 Td /F1 9.8 Tf [(As with earlier pandemics, pH1N1 is characterized by age distributions that are distinct from those observed in seasonal )] TJ ET BT 26.250 38.101 Td /F1 9.8 Tf [(influenza epidemics, with higher attack rates and increased proportionate mortality, in younger individuals )] TJ ET 0.267 0.267 0.267 rg BT 483.067 38.101 Td /F1 9.8 Tf [([10])] TJ ET BT 499.330 38.101 Td /F1 9.8 Tf [([11])] TJ ET BT 515.593 38.101 Td /F1 9.8 Tf [([12])] TJ ET 0.271 0.267 0.267 rg BT 531.856 38.101 Td /F1 9.8 Tf [(. This )] TJ ET Q q 15.000 684.354 577.500 53.646 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Optimal Pandemic Influenza Vaccine Allocation Strategies for )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(the Canadian Population)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(January 7, 2010)] TJ ET BT 83.513 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 88.388 675.088 Td /F3 9.8 Tf [(Influenza)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Ashleigh Tuite)] TJ ET 0.271 0.267 0.267 rg BT 88.026 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 93.447 663.247 Td /F1 9.8 Tf [(David N. Fisman)] TJ ET 0.271 0.267 0.267 rg BT 165.500 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 170.921 663.247 Td /F1 9.8 Tf [(Jeffrey C. Kwong)] TJ ET 0.271 0.267 0.267 rg BT 245.157 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 250.578 663.247 Td /F1 9.8 Tf [(Amy Greer)] TJ ET 0.271 0.267 0.267 rg BT 26.250 651.342 Td /F1 9.8 Tf [(Tuite A, Fisman DN, Kwong JC, Greer A. Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian )] TJ ET BT 26.250 639.438 Td /F1 9.8 Tf [(Population. PLOS Currents Influenza. 2010 Jan 7 . Edition 1. doi: 10.1371/currents.RRN1144.)] TJ ET q 15.000 23.815 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 610.335 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 590.381 Td /F1 9.8 Tf [(Background: The world is currently confronting the first influenza pandemic of the 21st century. Influenza vaccination is an )] TJ ET BT 26.250 578.476 Td /F1 9.8 Tf [(effective preventive measure, but the unique epidemiological features of swine-origin influenza A \(H1N1\) \(pH1N1\) introduce )] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(mortality.)] TJ ET BT 26.250 523.357 Td /F1 9.8 Tf [(Methodology/Principal Findings: We developed a deterministic, age-structured compartmental model of influenza transmission, )] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(mortality. In all scenarios, prioritization of high-risk groups \(individuals with underlying chronic conditions and pregnant women\) )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(markedly decreased the frequency of severe outcomes. Preferential vaccination of age groups at increased risk of severe )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(outcomes following infection resulted in decreased mortality compared to targeting vaccine to age groups with higher )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(epidemic peak.)] TJ ET BT 26.250 408.714 Td /F1 9.8 Tf [(Conclusions/Significance: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of )] TJ ET BT 26.250 396.810 Td /F1 9.8 Tf [(age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable )] TJ ET BT 26.250 384.905 Td /F1 9.8 Tf [(morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake.)] TJ ET BT 26.250 348.302 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 328.348 Td /F1 9.8 Tf [(AT receives support from the Mathematics of Information Technology and Complex Systems \(MITACS\) Accelerate Program )] TJ ET BT 26.250 316.443 Td /F1 9.8 Tf [(through both MITACS funding and a matching contribution from the Ontario Agency for Health Protection and Promotion. DF is )] TJ ET BT 26.250 304.539 Td /F1 9.8 Tf [(supported by an Early Researcher Award from the Ontario Ministry of Research and Innovation and is supported by the )] TJ ET BT 26.250 292.634 Td /F1 9.8 Tf [(Canadian Consortium for Pandemic Preparedness Modelling, MITACS and the CIHR. JK was supported by an Ontario Ministry )] TJ ET BT 26.250 280.729 Td /F1 9.8 Tf [(of Health and Long-Term Care \(MOHLTC\) Career Scientist Award, a University of Toronto Department of Family and )] TJ ET BT 26.250 268.824 Td /F1 9.8 Tf [(Community Medicine Research Scholar Award, and the Institute for Clinical Evaluative Sciences \(ICES\).)] TJ ET BT 26.250 239.722 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 219.768 Td /F1 9.8 Tf [(The rapid global spread of a novel swine-origin influenza A \(H1N1\) \(pH1N1\) virus led the World Health Organization to declare )] TJ ET BT 26.250 207.863 Td /F1 9.8 Tf [(an influenza pandemic on June 11, 2009 )] TJ ET 0.267 0.267 0.267 rg BT 204.568 207.863 Td /F1 9.8 Tf [([1])] TJ ET 0.271 0.267 0.267 rg BT 215.410 207.863 Td /F1 9.8 Tf [(. When there is a good match between circulating and vaccine strains, influenza )] TJ ET BT 26.250 195.958 Td /F1 9.8 Tf [(immunization is the most effective preventive measure for reducing influenza-related morbidity and mortality )] TJ ET 0.267 0.267 0.267 rg BT 493.334 195.958 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 504.175 195.958 Td /F1 9.8 Tf [(. Development of )] TJ ET BT 26.250 184.053 Td /F1 9.8 Tf [(a vaccine against pH1N1 began in the early phases of the epidemic, leading to questions about prioritization of vaccine )] TJ ET BT 26.250 172.149 Td /F1 9.8 Tf [(allocation within populations, given that not all vaccine will be distributed at once \(due to production and logistical constraints\).)] TJ ET BT 26.250 152.744 Td /F1 9.8 Tf [(Seasonal influenza immunization campaigns typically target the elderly and those of any age with one or more underlying )] TJ ET BT 26.250 140.839 Td /F1 9.8 Tf [(medical conditions, under the assumption that it is best to protect those most likely to have complications from influenza. )] TJ ET BT 26.250 128.934 Td /F1 9.8 Tf [(Recently, there has been debate over whether this is the best approach )] TJ ET 0.267 0.267 0.267 rg BT 337.334 128.934 Td /F1 9.8 Tf [([3])] TJ ET BT 348.175 128.934 Td /F1 9.8 Tf [([4])] TJ ET 0.271 0.267 0.267 rg BT 359.017 128.934 Td /F1 9.8 Tf [(. The degree of protection conferred by the )] TJ ET BT 26.250 117.030 Td /F1 9.8 Tf [(influenza vaccine appears to be lower in the elderly than in the general population )] TJ ET 0.267 0.267 0.267 rg BT 381.228 117.030 Td /F1 9.8 Tf [([5])] TJ ET 0.271 0.267 0.267 rg BT 392.070 117.030 Td /F1 9.8 Tf [( and it has been suggested that an )] TJ ET BT 26.250 105.125 Td /F1 9.8 Tf [(immunization strategy based on reducing transmission would have a greater impact on reducing overall disease burden than )] TJ ET BT 26.250 93.220 Td /F1 9.8 Tf [(the current practice of focusing vaccination efforts on at-risk groups )] TJ ET 0.267 0.267 0.267 rg BT 318.877 93.220 Td /F1 9.8 Tf [([6])] TJ ET 0.271 0.267 0.267 rg BT 329.719 93.220 Td /F1 9.8 Tf [(. 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important implications for the choice of optimal vaccination strategies )] TJ ET 0.267 0.267 0.267 rg BT 549.708 767.476 Td /F1 9.8 Tf [([13])] TJ ET 0.271 0.267 0.267 rg BT 565.971 767.476 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Given the uncertainty surrounding optimal vaccine allocation strategies and the unique epidemiological characteristics of )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(pH1N1, we sought to determine optimal prioritization of vaccine distribution among different age groups in order to minimize )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(influenza-attributable morbidity and mortality in the Canadian population. To address this question we developed an age-)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(structured mathematical model to describe expected pH1N1 transmission during the 2009-2010 influenza season. We used this )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(model to evaluate the optimal sequencing of vaccination allocation strategies. Each strategy was tested using different )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(assumptions relating to pre-existing immunity, vaccination coverage, and the timing of the epidemic peak. The outcomes of )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(interest were influenza-attributable morbidity and mortality under different vaccination strategies.)] TJ ET BT 26.250 640.040 Td /F4 12.0 Tf [(Methods)] TJ ET BT 26.250 620.086 Td /F5 9.8 Tf [(Model Structure)] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(We developed a deterministic, age-structured compartmental model of influenza transmission in the Canadian population \(see )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(Figure 1 for overall structure\).)] TJ ET q 450.000 0 0 337.500 26.250 241.396 cm /I3 Do Q BT 26.250 224.372 Td /F4 9.8 Tf [(Fig 1:)] TJ ET BT 52.253 224.372 Td /F1 9.8 Tf [( Outline of model structure, showing population flows between compartments. Each compartment is further stratified by )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(age category \(and by healthy and chronic condition states, where required\).)] TJ ET BT 26.250 193.062 Td /F1 9.8 Tf [(The model ran from mid-April, 2009 \(the date of the first identified cases of pH1N1 in Ontario, Canada\) to June 30, 2010, )] TJ ET BT 26.250 181.158 Td /F1 9.8 Tf [(representing a single influenza season. As a result, we did not consider waning immunity following infection or vaccination, )] TJ ET BT 26.250 169.253 Td /F1 9.8 Tf [(migration into or out of the population, or population aging.)] TJ ET BT 26.250 149.848 Td /F1 9.8 Tf [(The population was divided into four compartments representing different disease states: susceptible \(S\), exposed \(E; i.e., )] TJ ET BT 26.250 137.943 Td /F1 9.8 Tf [(infected but not infectious\), infectious \(I\), and recovered \(R\). Transmission of infection occurred through contact between )] TJ ET BT 26.250 126.039 Td /F1 9.8 Tf [(susceptible and infectious individuals. We assumed that 40% of infections were asymptomatic )] TJ ET 0.267 0.267 0.267 rg BT 433.751 126.039 Td /F1 9.8 Tf [([14])] TJ ET 0.271 0.267 0.267 rg BT 450.014 126.039 Td /F1 9.8 Tf [(, but did not consider )] TJ ET BT 26.250 114.134 Td /F1 9.8 Tf [(differential transmission in symptomatic versus asymptomatic cases.)] TJ ET BT 26.250 94.729 Td /F5 9.8 Tf [(Age Structure and mixing patterns)] TJ ET BT 26.250 75.324 Td /F1 9.8 Tf [(To explore how vaccination of different age groups would impact overall influenza morbidity and mortality and to enable the )] TJ ET BT 26.250 63.420 Td /F1 9.8 Tf [(representation of more realistic contact patterns within and between age groups, we included age stratification. The population )] TJ ET BT 26.250 51.515 Td /F1 9.8 Tf [(was divided into seven age classes with the following cutoffs: 0-4, 5-13, 14-17, 18-22, 23-52, 53-64 and ?65. Demographic )] TJ ET BT 26.250 39.610 Td /F1 9.8 Tf [(information was obtained from 2006 Canadian census data )] TJ ET 0.267 0.267 0.267 rg BT 283.670 39.610 Td /F1 9.8 Tf [([15])] TJ ET 0.271 0.267 0.267 rg BT 299.933 39.610 Td /F1 9.8 Tf [(. We included the 53-64 year old age category to model the )] TJ ET Q q 15.000 25.324 577.500 751.676 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(differential vulnerability to infection by age will have important implications for the choice of optimal vaccination strategies )] TJ ET 0.267 0.267 0.267 rg BT 549.708 767.476 Td /F1 9.8 Tf [([13])] TJ ET 0.271 0.267 0.267 rg BT 565.971 767.476 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Given the uncertainty surrounding optimal vaccine allocation strategies and the unique epidemiological characteristics of )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(pH1N1, we sought to determine optimal prioritization of vaccine distribution among different age groups in order to minimize )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(influenza-attributable morbidity and mortality in the Canadian population. To address this question we developed an age-)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(structured mathematical model to describe expected pH1N1 transmission during the 2009-2010 influenza season. We used this )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(model to evaluate the optimal sequencing of vaccination allocation strategies. Each strategy was tested using different )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(assumptions relating to pre-existing immunity, vaccination coverage, and the timing of the epidemic peak. The outcomes of )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(interest were influenza-attributable morbidity and mortality under different vaccination strategies.)] TJ ET BT 26.250 640.040 Td /F4 12.0 Tf [(Methods)] TJ ET BT 26.250 620.086 Td /F5 9.8 Tf [(Model Structure)] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(We developed a deterministic, age-structured compartmental model of influenza transmission in the Canadian population \(see )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(Figure 1 for overall structure\).)] TJ ET q 450.000 0 0 337.500 26.250 241.396 cm /I3 Do Q BT 26.250 224.372 Td /F4 9.8 Tf [(Fig 1:)] TJ ET BT 52.253 224.372 Td /F1 9.8 Tf [( Outline of model structure, showing population flows between compartments. Each compartment is further stratified by )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(age category \(and by healthy and chronic condition states, where required\).)] TJ ET BT 26.250 193.062 Td /F1 9.8 Tf [(The model ran from mid-April, 2009 \(the date of the first identified cases of pH1N1 in Ontario, Canada\) to June 30, 2010, )] TJ ET BT 26.250 181.158 Td /F1 9.8 Tf [(representing a single influenza season. As a result, we did not consider waning immunity following infection or vaccination, )] TJ ET BT 26.250 169.253 Td /F1 9.8 Tf [(migration into or out of the population, or population aging.)] TJ ET BT 26.250 149.848 Td /F1 9.8 Tf [(The population was divided into four compartments representing different disease states: susceptible \(S\), exposed \(E; i.e., )] TJ ET BT 26.250 137.943 Td /F1 9.8 Tf [(infected but not infectious\), infectious \(I\), and recovered \(R\). Transmission of infection occurred through contact between )] TJ ET BT 26.250 126.039 Td /F1 9.8 Tf [(susceptible and infectious individuals. We assumed that 40% of infections were asymptomatic )] TJ ET 0.267 0.267 0.267 rg BT 433.751 126.039 Td /F1 9.8 Tf [([14])] TJ ET 0.271 0.267 0.267 rg BT 450.014 126.039 Td /F1 9.8 Tf [(, but did not consider )] TJ ET BT 26.250 114.134 Td /F1 9.8 Tf [(differential transmission in symptomatic versus asymptomatic cases.)] TJ ET BT 26.250 94.729 Td /F5 9.8 Tf [(Age Structure and mixing patterns)] TJ ET BT 26.250 75.324 Td /F1 9.8 Tf [(To explore how vaccination of different age groups would impact overall influenza morbidity and mortality and to enable the )] TJ ET BT 26.250 63.420 Td /F1 9.8 Tf [(representation of more realistic contact patterns within and between age groups, we included age stratification. The population )] TJ ET BT 26.250 51.515 Td /F1 9.8 Tf [(was divided into seven age classes with the following cutoffs: 0-4, 5-13, 14-17, 18-22, 23-52, 53-64 and ?65. Demographic )] TJ ET BT 26.250 39.610 Td /F1 9.8 Tf [(information was obtained from 2006 Canadian census data )] TJ ET 0.267 0.267 0.267 rg BT 283.670 39.610 Td /F1 9.8 Tf [([15])] TJ ET 0.271 0.267 0.267 rg BT 299.933 39.610 Td /F1 9.8 Tf [(. We included the 53-64 year old age category to model the )] TJ ET Q q 15.000 25.324 577.500 751.676 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(differential vulnerability to infection by age will have important implications for the choice of optimal vaccination strategies )] TJ ET 0.267 0.267 0.267 rg BT 549.708 767.476 Td /F1 9.8 Tf [([13])] TJ ET 0.271 0.267 0.267 rg BT 565.971 767.476 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Given the uncertainty surrounding optimal vaccine allocation strategies and the unique epidemiological characteristics of )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(pH1N1, we sought to determine optimal prioritization of vaccine distribution among different age groups in order to minimize )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(influenza-attributable morbidity and mortality in the Canadian population. To address this question we developed an age-)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(structured mathematical model to describe expected pH1N1 transmission during the 2009-2010 influenza season. We used this )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(model to evaluate the optimal sequencing of vaccination allocation strategies. Each strategy was tested using different )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(assumptions relating to pre-existing immunity, vaccination coverage, and the timing of the epidemic peak. The outcomes of )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(interest were influenza-attributable morbidity and mortality under different vaccination strategies.)] TJ ET BT 26.250 640.040 Td /F4 12.0 Tf [(Methods)] TJ ET BT 26.250 620.086 Td /F5 9.8 Tf [(Model Structure)] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(We developed a deterministic, age-structured compartmental model of influenza transmission in the Canadian population \(see )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(Figure 1 for overall structure\).)] TJ ET q 450.000 0 0 337.500 26.250 241.396 cm /I3 Do Q BT 26.250 224.372 Td /F4 9.8 Tf [(Fig 1:)] TJ ET BT 52.253 224.372 Td /F1 9.8 Tf [( Outline of model structure, showing population flows between compartments. Each compartment is further stratified by )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(age category \(and by healthy and chronic condition states, where required\).)] TJ ET BT 26.250 193.062 Td /F1 9.8 Tf [(The model ran from mid-April, 2009 \(the date of the first identified cases of pH1N1 in Ontario, Canada\) to June 30, 2010, )] TJ ET BT 26.250 181.158 Td /F1 9.8 Tf [(representing a single influenza season. As a result, we did not consider waning immunity following infection or vaccination, )] TJ ET BT 26.250 169.253 Td /F1 9.8 Tf [(migration into or out of the population, or population aging.)] TJ ET BT 26.250 149.848 Td /F1 9.8 Tf [(The population was divided into four compartments representing different disease states: susceptible \(S\), exposed \(E; i.e., )] TJ ET BT 26.250 137.943 Td /F1 9.8 Tf [(infected but not infectious\), infectious \(I\), and recovered \(R\). Transmission of infection occurred through contact between )] TJ ET BT 26.250 126.039 Td /F1 9.8 Tf [(susceptible and infectious individuals. We assumed that 40% of infections were asymptomatic )] TJ ET 0.267 0.267 0.267 rg BT 433.751 126.039 Td /F1 9.8 Tf [([14])] TJ ET 0.271 0.267 0.267 rg BT 450.014 126.039 Td /F1 9.8 Tf [(, but did not consider )] TJ ET BT 26.250 114.134 Td /F1 9.8 Tf [(differential transmission in symptomatic versus asymptomatic cases.)] TJ ET BT 26.250 94.729 Td /F5 9.8 Tf [(Age Structure and mixing patterns)] TJ ET BT 26.250 75.324 Td /F1 9.8 Tf [(To explore how vaccination of different age groups would impact overall influenza morbidity and mortality and to enable the )] TJ ET BT 26.250 63.420 Td /F1 9.8 Tf [(representation of more realistic contact patterns within and between age groups, we included age stratification. The population )] TJ ET BT 26.250 51.515 Td /F1 9.8 Tf [(was divided into seven age classes with the following cutoffs: 0-4, 5-13, 14-17, 18-22, 23-52, 53-64 and ?65. Demographic )] TJ ET BT 26.250 39.610 Td /F1 9.8 Tf [(information was obtained from 2006 Canadian census data )] TJ ET 0.267 0.267 0.267 rg BT 283.670 39.610 Td /F1 9.8 Tf [([15])] TJ ET 0.271 0.267 0.267 rg BT 299.933 39.610 Td /F1 9.8 Tf [(. 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(h((Š(((h? ? (h((Š(((h? ? (h((Š(((h(){Ew4RR~4~~~4~4~~~4PEPEPEPEP^![]7Eׯ][CE7mS#G<(|֊UWFѾR@>^_> .kS69Fjh?c/+FǍ_x+"H;ig,hT7HѺ 0i+_0q$^ۺ~ۛ߿e-G7 xPRvEKl#f2V|FJ0>ωlxcHhm[{VxYDLhq8@?ּQQ =kQiUh~ٖ[OoqMrRdK=QMK$Y qۃOp*Q+Zj'[yay-펩dlBfFvds@;8~R}ӼTo|%g:ڎs$9p>{_/||D1EIyh֗9h֗9hiyN=hiyN=hiyOƎ=iyOƎ=iyOƏƗ9֏Ɨ9֏Ɨ9h֗9h֗9hiyN=h)(h)i)}hJ;QP߭wG@ E~QEQEQQ@~P~)CӮhC爾m1qG[bh`o9P1`u~~~4'GGG@0@?7)dt'_ |zq𿌬W2[ȓFIGWd5_/*=@τuk}6K]oe#oxpcYv?xֶw1t]X!&TEQ$̀9%q|oU?_Ujz=~_Et UAc232%D!sx~̿'-e'U΢ڶZbHL;y0k_Ujzw?Z^x;I^ ;kTvW",VW @ǹiӮöM;KfEw#h$Wø Ϸ?/*=@y#UMKC6ܷEE~?}s]qn4@lUk߳OGp4Ӭ_C41شhb4oO! w`+OG--SW腮v7q?] p}1^>?_'«Pø Ϸ?z(_l:9g:̧a,nˊk: - ٴl%"N 95_/*=G;x CP뿲O [jNu_fI6H ԯ ]u$T,^Vfjƀ=(җhҎ=(iN=(ҏƗҎ=(hhҎ=)Oƀ=(җhҎ=(iN=(ҏƗҎ=(hhҎ=)Oƀ=(җhҎ=(iN=(ҏƗҊ?(h)(JO^ii=hh€ ?(((hƊ? ()OJ8 = oI?iv{~>VU4R.ot˔\[# XÌRV"(9y4QV W(д*ǹWtǀ6!XOG7zGXg>g΃myqE ?GKO(O~^? (+ÌRV"(9y4QiU]cr8@`lB= o_zyGHAH66qn~~?GK_B|P| ®@Ҋw8xcGX^,B7qL0xÂ5+b>mn㎕z<_ cc|1t M00~^j͇&Q%ge R2H2€4A/IG~'G~'G@GG~4'G~4'GG~'G~'G@GG~4'G~4'GG~'G~'G@GG~4'G~4'GG~'G~'G@Ez@ Gz)(ғ֗ғրJ;QGj(Z(i)h(JZ(9O€i? ? ^hO€9((yO€i? ? ^hO€9((yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ9Ҏ=(yN=(Ҁ)8 _Ɗ? J_ZJZ=)=xN(ҏNhր((hhh(Š?(? (hƊ?OƗi? ? OƗhi ? ?OƗi ? OƗi? ? OƏƗi ? OƗ) OƗ) OƏƏ€i O€i O€Ɨ) OƗ) OƏƏ€i O€i O€Ɨ) OƗ) OƏƏ€i O€i O€Ɨ) OƗ) OƊ? 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Vaccination began in mid-November )] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(\(November 15)] TJ ET BT 88.016 519.579 Td /F1 8.7 Tf [(th)] TJ ET BT 95.244 515.691 Td /F1 9.8 Tf [(\), with a delay of 21 days between administration of the first and second doses. The fraction of the vaccinated )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(population that acquired immunity was based on vaccine effectiveness estimates of 70 percent; for a given age group, with a )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(vaccine effectiveness \()] TJ ET BT 124.871 491.881 Td /F6 9.8 Tf [(VE)] TJ ET BT 137.878 491.881 Td /F1 9.8 Tf [(\) and coverage \()] TJ ET BT 208.868 491.881 Td /F6 9.8 Tf [(C)] TJ ET BT 215.907 491.881 Td /F1 9.8 Tf [(\), the proportion removed from the susceptible to the resistant compartment was )] TJ ET BT 26.250 479.976 Td /F6 9.8 Tf [(VE*C)] TJ ET BT 50.089 479.976 Td /F1 9.8 Tf [(. We assumed that this group was fully protected against infection, with the remaining fraction )] TJ ET BT 455.435 479.976 Td /F6 9.8 Tf [(VE *)] TJ ET BT 474.945 479.976 Td /F1 9.8 Tf [(\()] TJ ET BT 478.192 479.976 Td /F6 9.8 Tf [(1- C)] TJ ET BT 496.610 479.976 Td /F1 9.8 Tf [( \) receiving no )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(protection. Although this does not reflect the true situation, where most vaccinated individuals will experience some degree of )] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(protection, this approach has been used previously and has been demonstrated to provide a reasonable model of partial )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(efficacy )] TJ ET 0.267 0.267 0.267 rg BT 62.013 444.262 Td /F1 9.8 Tf [([21])] TJ ET 0.271 0.267 0.267 rg BT 78.276 444.262 Td /F1 9.8 Tf [(. We did not consider the effect of partial protection following the first dose. We assumed that it took four weeks to )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(administer the first dose of vaccine to all age groups and vaccine allocation within each targeted sub-group \(described below\) )] TJ ET BT 26.250 420.453 Td /F1 9.8 Tf [(occurred simultaneously at the beginning of each week.)] TJ ET BT 26.250 401.048 Td /F5 9.8 Tf [(Disease natural history and model parameterization)] TJ ET BT 26.250 381.643 Td /F1 9.8 Tf [(Model parameters for pH1N1 were based on the currently available case data from the province of Ontario \()] TJ ET BT 490.652 381.643 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 524.251 381.643 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 530.208 381.643 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 546.471 381.643 Td /F1 9.8 Tf [(. A )] TJ ET BT 26.250 369.738 Td /F1 9.8 Tf [(range of estimates of the proportion of the population aged ?53 with pre-existing immunity to pH1N1 influenza was derived from )] TJ ET BT 26.250 357.834 Td /F1 9.8 Tf [(reported serological data )] TJ ET 0.267 0.267 0.267 rg BT 136.259 357.834 Td /F1 9.8 Tf [([23])] TJ ET 0.271 0.267 0.267 rg BT 152.522 357.834 Td /F1 9.8 Tf [(, the relative risk of infection by age observed in Ontario )] TJ ET 0.267 0.267 0.267 rg BT 395.843 357.834 Td /F1 9.8 Tf [([12])] TJ ET 0.271 0.267 0.267 rg BT 412.106 357.834 Td /F1 9.8 Tf [(and model calibration to the Ontario )] TJ ET BT 26.250 345.929 Td /F1 9.8 Tf [(epidemic curve.)] TJ ET BT 26.250 326.524 Td /F4 9.8 Tf [(Table 1:)] TJ ET BT 63.095 326.524 Td /F1 9.8 Tf [( Model Parameter Values.)] TJ ET Q q 15.000 -20.857 577.500 797.857 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(decreased susceptibility observed in persons born prior to the 1957 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 363.863 767.476 Td /F1 9.8 Tf [([12][16][17])] TJ ET 0.271 0.267 0.267 rg BT 412.652 767.476 Td /F1 9.8 Tf [( and divided the younger ages )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(according to school groupings to allow for the modeling of school-based vaccination programs. Mixing within and between age )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(strata was based on a population-based prospective study of contact patterns in eight European countries )] TJ ET 0.267 0.267 0.267 rg BT 484.744 743.667 Td /F1 9.8 Tf [([18])] TJ ET 0.271 0.267 0.267 rg BT 501.007 743.667 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(For a subset of model scenarios, each age class was further subdivided into two states: healthy or underlying chronic medical )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(condition for which seasonal influenza immunization is recommended. Transitions between model compartments were identical )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(for individuals in the healthy or chronic condition states, but probabilities of experiencing severe clinical outcomes were different. )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(We included a separate pregnancy state, representing women in the second or third trimester of pregnancy, with the number of )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(women expected to be in this state at any given point in time derived using annual estimates of pregnancies and live births in )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(Canada )] TJ ET 0.267 0.267 0.267 rg BT 63.105 664.738 Td /F1 9.8 Tf [([19][20])] TJ ET 0.271 0.267 0.267 rg BT 95.631 664.738 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 645.333 Td /F5 9.8 Tf [(Pre-existing immunity)] TJ ET BT 26.250 625.929 Td /F1 9.8 Tf [(To reflect the presence of immunity due to previous exposure to related influenza strains among individuals aged 53 and over, )] TJ ET BT 26.250 614.024 Td /F1 9.8 Tf [(resistance to pH1N1 was modeled by moving some individuals from the susceptible to the resistant compartment at time zero. )] TJ ET BT 26.250 602.119 Td /F1 9.8 Tf [(Since it is currently clinically impractical to distinguish individuals with pre-existing exposure to the circulating strains, we )] TJ ET BT 26.250 590.214 Td /F1 9.8 Tf [(assumed that they received the same vaccination coverage as the susceptible population \(i.e. there was no way to preferentially )] TJ ET BT 26.250 578.310 Td /F1 9.8 Tf [(immunize the truly susceptible population\).)] TJ ET BT 26.250 558.905 Td /F5 9.8 Tf [(Vaccination)] TJ ET BT 26.250 539.500 Td /F1 9.8 Tf [(Vaccination with two doses of H1N1 vaccine was modeled by removing a select number of individuals from the susceptible )] TJ ET BT 26.250 527.595 Td /F1 9.8 Tf [(compartment immediately following administration of the second dose of vaccine. Vaccination began in mid-November )] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(\(November 15)] TJ ET BT 88.016 519.579 Td /F1 8.7 Tf [(th)] TJ ET BT 95.244 515.691 Td /F1 9.8 Tf [(\), with a delay of 21 days between administration of the first and second doses. The fraction of the vaccinated )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(population that acquired immunity was based on vaccine effectiveness estimates of 70 percent; for a given age group, with a )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(vaccine effectiveness \()] TJ ET BT 124.871 491.881 Td /F6 9.8 Tf [(VE)] TJ ET BT 137.878 491.881 Td /F1 9.8 Tf [(\) and coverage \()] TJ ET BT 208.868 491.881 Td /F6 9.8 Tf [(C)] TJ ET BT 215.907 491.881 Td /F1 9.8 Tf [(\), the proportion removed from the susceptible to the resistant compartment was )] TJ ET BT 26.250 479.976 Td /F6 9.8 Tf [(VE*C)] TJ ET BT 50.089 479.976 Td /F1 9.8 Tf [(. We assumed that this group was fully protected against infection, with the remaining fraction )] TJ ET BT 455.435 479.976 Td /F6 9.8 Tf [(VE *)] TJ ET BT 474.945 479.976 Td /F1 9.8 Tf [(\()] TJ ET BT 478.192 479.976 Td /F6 9.8 Tf [(1- C)] TJ ET BT 496.610 479.976 Td /F1 9.8 Tf [( \) receiving no )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(protection. Although this does not reflect the true situation, where most vaccinated individuals will experience some degree of )] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(protection, this approach has been used previously and has been demonstrated to provide a reasonable model of partial )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(efficacy )] TJ ET 0.267 0.267 0.267 rg BT 62.013 444.262 Td /F1 9.8 Tf [([21])] TJ ET 0.271 0.267 0.267 rg BT 78.276 444.262 Td /F1 9.8 Tf [(. We did not consider the effect of partial protection following the first dose. We assumed that it took four weeks to )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(administer the first dose of vaccine to all age groups and vaccine allocation within each targeted sub-group \(described below\) )] TJ ET BT 26.250 420.453 Td /F1 9.8 Tf [(occurred simultaneously at the beginning of each week.)] TJ ET BT 26.250 401.048 Td /F5 9.8 Tf [(Disease natural history and model parameterization)] TJ ET BT 26.250 381.643 Td /F1 9.8 Tf [(Model parameters for pH1N1 were based on the currently available case data from the province of Ontario \()] TJ ET BT 490.652 381.643 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 524.251 381.643 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 530.208 381.643 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 546.471 381.643 Td /F1 9.8 Tf [(. A )] TJ ET BT 26.250 369.738 Td /F1 9.8 Tf [(range of estimates of the proportion of the population aged ?53 with pre-existing immunity to pH1N1 influenza was derived from )] TJ ET BT 26.250 357.834 Td /F1 9.8 Tf [(reported serological data )] TJ ET 0.267 0.267 0.267 rg BT 136.259 357.834 Td /F1 9.8 Tf [([23])] TJ ET 0.271 0.267 0.267 rg BT 152.522 357.834 Td /F1 9.8 Tf [(, the relative risk of infection by age observed in Ontario )] TJ ET 0.267 0.267 0.267 rg BT 395.843 357.834 Td /F1 9.8 Tf [([12])] TJ ET 0.271 0.267 0.267 rg BT 412.106 357.834 Td /F1 9.8 Tf [(and model calibration to the Ontario )] TJ ET BT 26.250 345.929 Td /F1 9.8 Tf [(epidemic curve.)] TJ ET BT 26.250 326.524 Td /F4 9.8 Tf [(Table 1:)] TJ ET BT 63.095 326.524 Td /F1 9.8 Tf [( Model Parameter Values.)] TJ ET Q q 15.000 -20.857 577.500 797.857 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(decreased susceptibility observed in persons born prior to the 1957 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 363.863 767.476 Td /F1 9.8 Tf [([12][16][17])] TJ ET 0.271 0.267 0.267 rg BT 412.652 767.476 Td /F1 9.8 Tf [( and divided the younger ages )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(according to school groupings to allow for the modeling of school-based vaccination programs. Mixing within and between age )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(strata was based on a population-based prospective study of contact patterns in eight European countries )] TJ ET 0.267 0.267 0.267 rg BT 484.744 743.667 Td /F1 9.8 Tf [([18])] TJ ET 0.271 0.267 0.267 rg BT 501.007 743.667 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(For a subset of model scenarios, each age class was further subdivided into two states: healthy or underlying chronic medical )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(condition for which seasonal influenza immunization is recommended. Transitions between model compartments were identical )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(for individuals in the healthy or chronic condition states, but probabilities of experiencing severe clinical outcomes were different. )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(We included a separate pregnancy state, representing women in the second or third trimester of pregnancy, with the number of )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(women expected to be in this state at any given point in time derived using annual estimates of pregnancies and live births in )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(Canada )] TJ ET 0.267 0.267 0.267 rg BT 63.105 664.738 Td /F1 9.8 Tf [([19][20])] TJ ET 0.271 0.267 0.267 rg BT 95.631 664.738 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 645.333 Td /F5 9.8 Tf [(Pre-existing immunity)] TJ ET BT 26.250 625.929 Td /F1 9.8 Tf [(To reflect the presence of immunity due to previous exposure to related influenza strains among individuals aged 53 and over, )] TJ ET BT 26.250 614.024 Td /F1 9.8 Tf [(resistance to pH1N1 was modeled by moving some individuals from the susceptible to the resistant compartment at time zero. )] TJ ET BT 26.250 602.119 Td /F1 9.8 Tf [(Since it is currently clinically impractical to distinguish individuals with pre-existing exposure to the circulating strains, we )] TJ ET BT 26.250 590.214 Td /F1 9.8 Tf [(assumed that they received the same vaccination coverage as the susceptible population \(i.e. there was no way to preferentially )] TJ ET BT 26.250 578.310 Td /F1 9.8 Tf [(immunize the truly susceptible population\).)] TJ ET BT 26.250 558.905 Td /F5 9.8 Tf [(Vaccination)] TJ ET BT 26.250 539.500 Td /F1 9.8 Tf [(Vaccination with two doses of H1N1 vaccine was modeled by removing a select number of individuals from the susceptible )] TJ ET BT 26.250 527.595 Td /F1 9.8 Tf [(compartment immediately following administration of the second dose of vaccine. Vaccination began in mid-November )] TJ ET BT 26.250 515.691 Td /F1 9.8 Tf [(\(November 15)] TJ ET BT 88.016 519.579 Td /F1 8.7 Tf [(th)] TJ ET BT 95.244 515.691 Td /F1 9.8 Tf [(\), with a delay of 21 days between administration of the first and second doses. The fraction of the vaccinated )] TJ ET BT 26.250 503.786 Td /F1 9.8 Tf [(population that acquired immunity was based on vaccine effectiveness estimates of 70 percent; for a given age group, with a )] TJ ET BT 26.250 491.881 Td /F1 9.8 Tf [(vaccine effectiveness \()] TJ ET BT 124.871 491.881 Td /F6 9.8 Tf [(VE)] TJ ET BT 137.878 491.881 Td /F1 9.8 Tf [(\) and coverage \()] TJ ET BT 208.868 491.881 Td /F6 9.8 Tf [(C)] TJ ET BT 215.907 491.881 Td /F1 9.8 Tf [(\), the proportion removed from the susceptible to the resistant compartment was )] TJ ET BT 26.250 479.976 Td /F6 9.8 Tf [(VE*C)] TJ ET BT 50.089 479.976 Td /F1 9.8 Tf [(. We assumed that this group was fully protected against infection, with the remaining fraction )] TJ ET BT 455.435 479.976 Td /F6 9.8 Tf [(VE *)] TJ ET BT 474.945 479.976 Td /F1 9.8 Tf [(\()] TJ ET BT 478.192 479.976 Td /F6 9.8 Tf [(1- C)] TJ ET BT 496.610 479.976 Td /F1 9.8 Tf [( \) receiving no )] TJ ET BT 26.250 468.072 Td /F1 9.8 Tf [(protection. Although this does not reflect the true situation, where most vaccinated individuals will experience some degree of )] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(protection, this approach has been used previously and has been demonstrated to provide a reasonable model of partial )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(efficacy )] TJ ET 0.267 0.267 0.267 rg BT 62.013 444.262 Td /F1 9.8 Tf [([21])] TJ ET 0.271 0.267 0.267 rg BT 78.276 444.262 Td /F1 9.8 Tf [(. We did not consider the effect of partial protection following the first dose. We assumed that it took four weeks to )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(administer the first dose of vaccine to all age groups and vaccine allocation within each targeted sub-group \(described below\) )] TJ ET BT 26.250 420.453 Td /F1 9.8 Tf [(occurred simultaneously at the beginning of each week.)] TJ ET BT 26.250 401.048 Td /F5 9.8 Tf [(Disease natural history and model parameterization)] TJ ET BT 26.250 381.643 Td /F1 9.8 Tf [(Model parameters for pH1N1 were based on the currently available case data from the province of Ontario \()] TJ ET BT 490.652 381.643 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 524.251 381.643 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 530.208 381.643 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 546.471 381.643 Td /F1 9.8 Tf [(. A )] TJ ET BT 26.250 369.738 Td /F1 9.8 Tf [(range of estimates of the proportion of the population aged ?53 with pre-existing immunity to pH1N1 influenza was derived from )] TJ ET BT 26.250 357.834 Td /F1 9.8 Tf [(reported serological data )] TJ ET 0.267 0.267 0.267 rg BT 136.259 357.834 Td /F1 9.8 Tf [([23])] TJ ET 0.271 0.267 0.267 rg BT 152.522 357.834 Td /F1 9.8 Tf [(, the relative risk of infection by age observed in Ontario )] TJ ET 0.267 0.267 0.267 rg BT 395.843 357.834 Td /F1 9.8 Tf [([12])] TJ ET 0.271 0.267 0.267 rg BT 412.106 357.834 Td /F1 9.8 Tf [(and model calibration to the Ontario )] TJ ET BT 26.250 345.929 Td /F1 9.8 Tf [(epidemic curve.)] TJ ET BT 26.250 326.524 Td /F4 9.8 Tf [(Table 1:)] TJ ET BT 63.095 326.524 Td /F1 9.8 Tf [( Model Parameter Values.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(3)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 152 0 obj << /Type /Font /Subtype /Type1 /Name /F6 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Integrated Public )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(Health Information System \(iPHIS\), which collected information on all laboratory-confirmed cases of pH1N1 in the province )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(reported between April 13 and June 21, 2009 \()] TJ ET BT 227.324 398.667 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 260.923 398.667 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 266.880 398.667 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 283.143 398.667 Td /F1 9.8 Tf [(. To account for expected under-ascertainment of less severe )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(cases, we multiplied the denominator \(total cases\) by a factor of ten when calculating hospitalization and case-fatality rates )] TJ ET 0.267 0.267 0.267 rg BT 557.859 386.762 Td /F1 9.8 Tf [([24])] TJ ET 0.271 0.267 0.267 rg BT 574.122 386.762 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 367.357 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 59.849 367.357 Td /F1 9.8 Tf [(: Estimated Rates of Hospitalization, ICU Admission, and Mortality by Age and Risk Group for pH1N1 in Ontario, April to )] TJ ET BT 26.250 355.452 Td /F1 9.8 Tf [(June 2009.)] TJ ET Q q 15.000 8.072 577.500 768.928 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I4 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(Age-specific hospitalization, ICU admission, and mortality rates were calculated using data from Ontarios Integrated Public )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(Health Information System \(iPHIS\), which collected information on all laboratory-confirmed cases of pH1N1 in the province )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(reported between April 13 and June 21, 2009 \()] TJ ET BT 227.324 398.667 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 260.923 398.667 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 266.880 398.667 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 283.143 398.667 Td /F1 9.8 Tf [(. To account for expected under-ascertainment of less severe )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(cases, we multiplied the denominator \(total cases\) by a factor of ten when calculating hospitalization and case-fatality rates )] TJ ET 0.267 0.267 0.267 rg BT 557.859 386.762 Td /F1 9.8 Tf [([24])] TJ ET 0.271 0.267 0.267 rg BT 574.122 386.762 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 367.357 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 59.849 367.357 Td /F1 9.8 Tf [(: Estimated Rates of Hospitalization, ICU Admission, and Mortality by Age and Risk Group for pH1N1 in Ontario, April to )] TJ ET BT 26.250 355.452 Td /F1 9.8 Tf [(June 2009.)] TJ ET Q q 15.000 8.072 577.500 768.928 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I4 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(Age-specific hospitalization, ICU admission, and mortality rates were calculated using data from Ontarios Integrated Public )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(Health Information System \(iPHIS\), which collected information on all laboratory-confirmed cases of pH1N1 in the province )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(reported between April 13 and June 21, 2009 \()] TJ ET BT 227.324 398.667 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 260.923 398.667 Td /F1 9.8 Tf [(\) )] TJ ET 0.267 0.267 0.267 rg BT 266.880 398.667 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 283.143 398.667 Td /F1 9.8 Tf [(. To account for expected under-ascertainment of less severe )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(cases, we multiplied the denominator \(total cases\) by a factor of ten when calculating hospitalization and case-fatality rates )] TJ ET 0.267 0.267 0.267 rg BT 557.859 386.762 Td /F1 9.8 Tf [([24])] TJ ET 0.271 0.267 0.267 rg BT 574.122 386.762 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 367.357 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 59.849 367.357 Td /F1 9.8 Tf [(: Estimated Rates of Hospitalization, ICU Admission, and Mortality by Age and Risk Group for pH1N1 in Ontario, April to )] TJ ET BT 26.250 355.452 Td /F1 9.8 Tf [(June 2009.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(4)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 197 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 50131>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih)+_+ uh-ԉ:Vɒ7v3k'ß/o.;^(+ß/o.]mik ß/o.;j1\W.??_6]tъw99 ֊w99 W ͷG.??_6]v]m?w99=(+ï/o.]~mh=+ ï/o.;Z?Jw:9 ֊w:9 ]~m?w:9=(+ï/o.]~mh=+ ï/o.;Z?Jw:9 ֊w:9 ]~m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9]m?w:9=ŶOwբRxՀd$g{֧4QEQE~R Z(B3F)i(1K(b(4,p%rs`玵7/|m| c]x?uޛj7D0φ'?;k-$:][Y1}*Vcv7 ,v #s@~G&HYc;cV` cӾ#uΫ6i >{aSoi& t|(.=S׊|QTQѴY!6$I iq+4F |ǭm^A]OUũoBJƯ-06@>ϯ>!OuoڗmYWQ$0@X.&(ǽ/>s@ < Ώ;yj_[4-MCZݔncpJ̱1#@4=cjvwUHOBX=瞡)~'xnL!hWmi0-c(xV'mX2-cW=3]ԒJ ɦNpe9Tuk-b RY i-Yd: uyyo#Ӽa?B@_w6ߕ<#v DҨې72|:FV?IkiqGXѶL;C>o|O7m//|WZhS[My]i5C}nK8c.%RRHw`N1)|k(l|]5u -kQ\VSFd `~"CI#Aff8Nm5 {ol#YaI*GZ+~0jߵ]neJL{k4[-܆$nWWi`X]WUM4E>5 i$GqcQKb_Əƀb%hhIhBCJA'S:5X!Ӽ?yᛍsJed@!%"2;cn_%gi,~%u!iL荡5 w<מV2J ?|1٠qE|+TͩxBO?^!/%^P6Aeo%#fU8+[~t {6z=1i=xyo-@r7Q_%O#Yssh} #k :b&F܇;}h(/G@ F)?LQKKQQGE-Q@(J;][Sy#$V$Htx/ 'G`_G`8] &] &oŠ_-h|?`&z_Z?sx+4Wk'7`|gPMvWhmEq?<A?tx+5 _G?o|?] _֊tx+4Ah!:S{l+lӎR떲E * PFEw=$^sWxR qI\.a3w6't75Q@y|Lw 6}?S5 [kHJ]_@W.~&] MvP _G?o|?]Whkڊtx+47Mvz _0[/W 5ڀ8\ MS>'*|?t{ Z5x!d$QUP0+Gztx+4Wkր8] M<Ah@W.~&] Mv+G?o|G.~&_Z( __׵-h?`ҏZGo~&\ kq?A_] Mv+G?o|G.~&_Z( __׵ __ҏZ=֕v66 z(Z(h;RJZc|r|5T=&MR^\mkkivƹ$=1߳~#Q׵oկ-li;[ +"!99c@8Ε]*ϊ(gѮ-Yhᶫb@OwC@֥>6x~N Aa ᶑW*@a;HK!f[O5sraEY@أ&[T[ Iz(1Hb <|S<9Z3\[ 5K:Mogk$+od$ 6*S <]&ZJ\c:kXߓ"RrT!*@bAW_asMڄ^ѭt6Y^;&ރ ?r,7z-k\G$rݤ=Wq!A9 'NlRm3Z]Tv0jęV'm$1MF|HӴ-MO1 L3bxcH2iZαjz^5'il, 6aY t_Fc_Ūy%g 1p}kZ%WZ,hZU`3G!`?g Ui4cskyjz&ZOD2f%jR͸gp Um'2>ba|Ek=mu&Ғ"6V/1<߈?f 벥w摪ǩ_QjU3zQ[QFho's{=~J.m+hZf,rAa2GY|wl& MB}zL:6)VdV%ÒB7*F0YII,xxzCKH[{{#Mζ X$'%+R{]k uMIl.5k/ibd%wFFW^-M ^E$r4%gl ^fY[x`>\f|é$+- bB~W(U!#G9:K+8PދYLr'8 )k"m bA[]FH4{F.⸒O.d;+eIa" l%񕟉 ZO 9/ ~]BE$˖ zQGQڊ;PޏJ;@y < xL8ӮUBV`BY$f 䁴#нk|h:ˢ6XgWhxdR m8w9 ?\758Z['Hk5֥*}AS-.yi?l]JMXеmwGt%0bH&Sqvd67W\|Я|Mu=ɸ1UT@L%Nh<%euwewg<˱Kq@e"eU@ ( O귶z!k+ YXä,pHeĄ=g\|?]{)[ҔCLѼHRp*ޙgöz?,/R}hmnL!XX#PhRIY-E,u]WTԧnL.\YHJS1lo""9`q',kjVGi٭waK}F <`Z~SlSax1 T@ Yٷ̍?ѤtVPMv/s&ĉ%*.d>L.Oا׆|AEƢ\\^j`2l`Kѵ6kk_nE"A9u_j|YwkMTNnU {bv.uGhtvV)ɐ+ɵՍ[&7Z/c\Aaj}=Ī,1 c,)䲮^^+~ ouoMΡR\~lPVE0At#1shO>ֵ+ŷui6[eVrgdU[fl*o1ƫg5I HSal9A]mu #Z^IZg4IĬN^9 x9 `T?"lеYlΘoe cw`q@Om844}+oI423o10QK|\?cTMQK -u*9a2M,S(I rM4x?zRT ݝA,6axy_ sx8w/ٛK}cZ'УѮ4>koy]'@' 烂2hj|71 nn#:45DXDp!TBF-Sj4OÞ-zIuI(%3.ɛj홆 N00[g xw4լΩ$ij2|C[[}VƷ<}X EG%VU+jIymJV:Y \[otpTBscy/G|!B çKײInf&dBʠ8\SxgG4 h^ Z+hb̦]FXlFP㛿?lEVү6#Z\m3( ٪3x~"E_&ȶ6 0F+Hn|&o[[Mw{slYIc@Q@QQEQEQQEQEPTMtm2ycX\'M{U!ky6:ӴM",4:;KKXQ"D9җJ9N=)xh=)8hғJ^k~$|i<^KI|?iWrvvl۴z`׳qp~49kjwOvs1 [ B025E[<`x_'4}WMK6Ac$?Y4r#|njj=2ᇉu Ayy+OkZpba`^7*d p0&|.k ݍLK[%k-d2PwV &7;SM#Nү}}mvK|ɑ+2Ɖx3X ] Ǧ5gg/<c=޳msEM]Ո,"Y̑@ $Q 7nfR IV͒J*IPKsZ|#ۻ9CBΓm}i*{rc90+eɠ5MAwBCY [Ra9-ik3a$b}@'p  s|_Ej |?j-l֚bD8K2Qj?OuI$j͎AwQoJJ6 PB -e?GUX5[>/6W?^[FF.a ~7~+M+I.4l.BfFUaVE` *pӈ&tmBG|EsuBm[ t2̡&3rKJL0+MwY]zᣟڴ,ڭo+]\OTj1}e.T,IR* p@'h ۑ,7wvL[Ũ\[GqHY]Xʬ]٫? ho|Y"l5M<$zcj1Dmb4'zPqK4sG4qIǥ/4sGzPEsE((((J  Z@sEPQE-%PQPGGG@GGG@E~4~~~4~4~~~4QQPQP4~4~~~4~4~~~4~4zG@GGG@GGG~4~4~~~4~4~~~4~4zG@GGG@GGG~4~4~~~4~4~~~4~4zG@GGG@GGG~4~4~~~4~4~~~4QPhP_.G/ 7%տo>k0z]>+[O*Cnq9v p)rޯ[am׍Ku.|ou4֤5Y/P YBB723|+a7V0k/O#;k_DžZω=~$my-s `+Bn< [lj+Qο>lڤmlмWf*A# }ϵOZ7ıa42ۋEee` +hMoG7n<9_ G}v"d$%U'VIȬIʁ"Eѓ7 ERuvjwVVjkyDlkV >)YR2HBZoXI";i6rS=Mbf+ I[ij:5]cK(<lڥ bUxZhQ! yxR; xC]S_r`Q=>Ɔ}nm<=Qi}ymW}igxQJS$DL|VU$O]/PGjƙu;u C$rG7RŊ3$& TzG^#OKΐeqs<1[QLZ$`WPT1@)Y~ڞ<fXᜲZWQع2̑&F&ٻ |%uZe/Ow%bu)|8<^}mY,"zC?u5c%15=:']H0%,ÖڋNj⯃A~Mf u oݺYGTmRoI @vʕROQvy:v^.mbIm.DkR Âz O |!i.$:5M/%sIK,DYcpӫxNG⧚&ե]dž]?H -2,Nchb}`0J5 |9o}{OfZAܭ«-b߈6dbQ~4PE/c/G@n^#^(SMr+Qf6zXwo()9lv3 ]~hZ\ DۼNuvHVPJN#? 4~4SK=2N` FUǥ'zQqK4~4~4qIǥ/G@zR4~4qr~)W_jZ֒/d.Axx46FNzƏƀ89~xK.."lĂ(cGܓk:|7ZkXl6Es4^e F4сֵA^.fCF2}Ѳ15q;|=5)N땑A&&,KqHhh>x?F-u =ɸ1P͞ 5x;ƾ+ D΍tn!8 弒@9ݘUEoPxB?|AdsE(HEE׿fj^񎓧xvwtXUo$s=EnWׁogm3JDzё"˟C=΋]_j>_WZ-u"]pp^ƪ"oHܩePx?w6_״kDӵm#«oڳZ&z›e"V\`\1v߁la}|#G;hu5O:U`Cls A5g6|,=KGoP%vhxF9= 5H|%桤Y4kO62E3\+v˯o|W.}T{Hp#; K &WJh|K(ckee 56titK l`,QL$`=r(tOSPR𕽍x~[}JH1drŃV-UV.4ٴwZU棣h[m]V-yhvݜr"YQEP+˝A\-&y9oSaZk"sO ݭj![dT=foy. 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Telephone survey data on willingness to accept H1N1 vaccine in the province of Ontario )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(obtained using the provinces Rapid Risk Factor Surveillance System \(RRFSS\) )] TJ ET 0.267 0.267 0.267 rg BT 368.690 386.762 Td /F1 9.8 Tf [([27])] TJ ET 0.271 0.267 0.267 rg BT 384.952 386.762 Td /F1 9.8 Tf [( was used as an upper bound of vaccine )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(uptake in the Canadian population \(Ruth Sanderson, Ontario Agency for Health Protection and Promotion, personal )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(communication\). Age-specific data on underlying chronic conditions were obtained from the 2007 cycle of the Canadian )] TJ ET BT 26.250 351.048 Td /F1 9.8 Tf [(Community Health Survey )] TJ ET 0.267 0.267 0.267 rg BT 142.197 351.048 Td /F1 9.8 Tf [([25])] TJ ET 0.271 0.267 0.267 rg BT 158.460 351.048 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 331.643 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 59.849 331.643 Td /F1 9.8 Tf [(: Influenza Vaccination Coverage Levels.)] TJ ET Q q 15.000 -15.738 577.500 792.738 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I5 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(We used vaccination coverage data for the province of Ontario )] TJ ET 0.267 0.267 0.267 rg BT 298.841 422.476 Td /F1 9.8 Tf [([25][26])] TJ ET 0.271 0.267 0.267 rg BT 331.367 422.476 Td /F1 9.8 Tf [(, which operates a universal influenza immunization )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(program that provides influenza vaccine free of charge to the entire population aged six months or older, as a base case for )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(H1N1 vaccine uptake \()] TJ ET BT 124.871 398.667 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 158.470 398.667 Td /F1 9.8 Tf [(\). Telephone survey data on willingness to accept H1N1 vaccine in the province of Ontario )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(obtained using the provinces Rapid Risk Factor Surveillance System \(RRFSS\) )] TJ ET 0.267 0.267 0.267 rg BT 368.690 386.762 Td /F1 9.8 Tf [([27])] TJ ET 0.271 0.267 0.267 rg BT 384.952 386.762 Td /F1 9.8 Tf [( was used as an upper bound of vaccine )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(uptake in the Canadian population \(Ruth Sanderson, Ontario Agency for Health Protection and Promotion, personal )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(communication\). Age-specific data on underlying chronic conditions were obtained from the 2007 cycle of the Canadian )] TJ ET BT 26.250 351.048 Td /F1 9.8 Tf [(Community Health Survey )] TJ ET 0.267 0.267 0.267 rg BT 142.197 351.048 Td /F1 9.8 Tf [([25])] TJ ET 0.271 0.267 0.267 rg BT 158.460 351.048 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 331.643 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 59.849 331.643 Td /F1 9.8 Tf [(: Influenza Vaccination Coverage Levels.)] TJ ET Q q 15.000 -15.738 577.500 792.738 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I5 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(We used vaccination coverage data for the province of Ontario )] TJ ET 0.267 0.267 0.267 rg BT 298.841 422.476 Td /F1 9.8 Tf [([25][26])] TJ ET 0.271 0.267 0.267 rg BT 331.367 422.476 Td /F1 9.8 Tf [(, which operates a universal influenza immunization )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(program that provides influenza vaccine free of charge to the entire population aged six months or older, as a base case for )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(H1N1 vaccine uptake \()] TJ ET BT 124.871 398.667 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 158.470 398.667 Td /F1 9.8 Tf [(\). Telephone survey data on willingness to accept H1N1 vaccine in the province of Ontario )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(obtained using the provinces Rapid Risk Factor Surveillance System \(RRFSS\) )] TJ ET 0.267 0.267 0.267 rg BT 368.690 386.762 Td /F1 9.8 Tf [([27])] TJ ET 0.271 0.267 0.267 rg BT 384.952 386.762 Td /F1 9.8 Tf [( was used as an upper bound of vaccine )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(uptake in the Canadian population \(Ruth Sanderson, Ontario Agency for Health Protection and Promotion, personal )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(communication\). Age-specific data on underlying chronic conditions were obtained from the 2007 cycle of the Canadian )] TJ ET BT 26.250 351.048 Td /F1 9.8 Tf [(Community Health Survey )] TJ ET 0.267 0.267 0.267 rg BT 142.197 351.048 Td /F1 9.8 Tf [([25])] TJ ET 0.271 0.267 0.267 rg BT 158.460 351.048 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 331.643 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 59.849 331.643 Td /F1 9.8 Tf [(: Influenza Vaccination Coverage Levels.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(5)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 212 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 45464>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((RE2IS=7f?ؠ ~}(Z*/=k{}\?Q?ؠ FjA=l{}4fd?Q?ؠ FjA=l{}4fd?Q?ؠ FjA=l{}8}(^(d/Q?_ؠ xxG b%*/A=l{}8}(^(d/Q?_ؠ xxG b%*/A=l{}8}(^(d/Q?_ؠ h\?Q?ؠ xpxGb%⊋pxGb%*/=k{}8}-KG ?R-KTF-l{}*/=x@G ??Q?ؠ xpxGb%pxGb%*/=k{}*/=k{}8}(^(\?Q?ؠ h\?Q?ؠ xpxR+@ ~4PE~-XZ,eeN38cœ'  k4P s'h/;O?ƊN4/ EcQ@w)Н_M| Bv5cĝ ᎋM:󭭭77sv 19( 8qk<7vnW>XɒB r9P< Bv?N50񕏄Z{xKm=gF1x^_{&bpHbPG9;O? w'h/IZCڝ3PGyݵ6Oh lR䋖Ancx /S;C|_M< Bv A8S;C|_M| Bv}h;?N_G)Н/& ZN"h;O?' ' h;O?5Z߁,$Z< =M ,eHBB9vQ,[bM w'hG)Н_Mky/ZӤnDq ⭝jt#}n4o̫w?N/&S;D|_MkBc{MkOKv7~B81RyRUt[pE) n~V$$P)Н_M| Bv5s%kV$inB2X dz֊Ht` Er_| Bv4' E_Gj?N4' E_Er| Bv4' E_HN(;O??N?_P`;^H|Okg 10`Q'BM"CNj0ϩY^1ƪ imrC`WHGԦԴWI2Sѯ岺e%IcPzt#4~ڶ< t7ðxTm(fI"]"#b#8{ @'=cOƍYi6$s\<7$xۀ>Rj\k}sj~Ѵ븮|0Io pVGTV V9x;Ij6:6l_H[)>S(8n(=ɾx_ ,/V7|/gچj^G턖4>iOpPFG5~IgWmAm{;[vyMŒ|;ݸ`K_ֳxǒx/C"n4[H\J {/;9}#~$& -2HYI {GoF}MxU K 7ᕦxO5橢[]Kt%6L@koA RrW־5|-sxg<,%M?RFgJ6s})*3V<7caǓ붠r.3$\I#ҹ;[%1ojuǪͫjq$p1!%Xu {s@>qsMd}imy;< 7(8 OS;C|_Mj'6^6K46mln3HR瓴` x_'t#RnTKLb1ĥPde>#Ћk)4_U,+s,ţi<2NHj~5?hxS&QXdm/ ϔ 70yȠN"h;O?$uiޛᤷ}Qֱ\# Fi&*M-e߈M\6ũMFkCzH %;Φ>;O? w'h_'>B6iۛ}0jwy,Ȓ,ڗ ېW|soxKCNO[XIyOXL%m2IX~|9ѧ}p-` 2fBaOr@8Y)exRWWz}ŕR$(,&@} f(Nt$ iwGdמ>OǤi>( LZ\Rx.gPHbs@P#D"j߅In<%o 4JE$C~*]h~լ4c[C4 ~Yu—63DIȬl[ ]9sx@Դ*z5'nu5m0ychI.X9-WHKoCotj{;{ =>)c2 mwz̿i/ _\C%j4P L6ˮO85oQ>|4𾙦]I,l[FW.Zm)I|s\~xÏg܍?MҼWiIᶻK(D"FG(mw ;H/5ۉ-i.͸ひ6kt|)'h_~rYhR-I41H|@jAx?Q_Jϟ e |O_N}I2g <'h1< x!uơkEc'P{{Rc%5c@ǐŗxW>?iQ}cFF íCD}USZfJ3}=Yefr) 3׼GyzGJxq|MZj ӭsigmo*6 %8e$TP'4E<hu6 qtz-~4QE%-PQE [_&wc~=g\WPouPf_̰u%|b, z(7/_ |Ux?]4$"ᵑر Or!L&+,Jۍ_T!MӞMTBsͫ<9e@$| Qeq/ ].M^K44DIf&sO#4ckvǪgY߈|6O:ͭg9Bn|2 @lH݂>WUo ͪ VE(۸l˞1Sxh>Pm.',FU/VRA AcEIG4=SWjZj\YbI`ۉkyj_Y_߇B_Y1G|Η2y'I; ~lDÿ K{IZuXDd@0ۘ$@=3'adn9Mxg>-æhm@rv>=(Z(Gz;QހԸҏZy uOj&4l$iJ* A7Jkz$QjFk5Ԧ*('#,@xQZ [Ya<r( ɝoNxό$rh$##ﷆ[yDRLDNTFrS>x]וa0 zq$ *’x倫W?>Yj L75E@pfU+>5|HGP_g\=ϕ[uH;J#Poo|=  :iHY2~!2#ڇi Yk{_Km-4}YͻāmV/ſ |=kueiz|W:d սq,0Glp 3\^(6ֵnJhti# BV$<ǟi}_ |D. 4%dWX`d  z{^ ӼY_ j\X&/9!OD`;>5ߴ;_ڲGm ҹa +@@ $¶4+ZPÞ!յi BYk|yh'gaj߱|vO%jM%X]IpɕLp{zx?icr䮞f×P3-^~ag>]ƥ]n]v{F܁A 2 Eyd X|@b:YlD;Uc ߎ7ci]7?t][Nwb{kK{3ig Ll^2BLq@ڌqEG֊=h(ľ íz7XdL 8:mJ[-+:?_3GW(-Ȝ'mҽ-i~%#;9<24{H_%2bEx.4MMuY(ӵK;Sz0_>tl9LuyN<=n)]_ͪg\\ .c_* w .݁+xBVVo__5 CƩcnι 8$ ;Iu >^ZJ͵"YE'-^5%ҭ|soχdoxcHU#I>o,@ŕ2fxooPصuMFMMnxp#.XF.0@=MfOZس-ڍnTna#R'8橿#ѥ[͵^ 4?ts\fK-8h~_ iZ4Iݴ4 ,B:'| j:hӦ[T[p {RPn!zIOtόĞk=d5bEPyhcx0Uw4U߉u]>iv «+y;JrsQy7c={Ě? *Pl|KOY m<8Y,5G X܎z}?V­>ͮgcn촻$Hyy ON@'$zN/Tծo]JUG(䨋 + A Ε&F]69&daYA _`A9y<]]=ߋ"ԭMbvk"i* T7߱e߅| ;-+TṂ͏ 0.гc4-⸃Ǿ% T(b(boJ;P o1I o1]z=(oyCϊ?>(b_Z=(oyCNJ?oyCϊ?׵oyCNJ?oyCϊ?ҏZ[m)?[m+q_?yG?xGwҀ8V<?[m+Ҁ8V(b(boJ;P o1I o1]z=(oyCϊ?>(b_Z=(oyCNJ?oyCϊ?׵oyCNJ?oyCϊ?ҏZ[m)?[m+q_?yGiV/Als4K]2I@V@z@ E+̾#|V/įM;źl]l{i{-x" ,1c<{ה|Ww? ^7<87vZ}I;G$Nf)d >2|\|g^ЬAy. ԯ EyHHU]$@.ia^%޻yu~ Q D.̂:/~w~5L/m+ou51a/okx}Ѻb4 WpِA5cZqM'A[xrݢkMIt3+:aDn7@:|qDö^%֯c4RͧM$Wx AcWd+#HjOKQKZO3%vn|tHN&xh>-vWol&Kҥxc1wvX35k9/].R.?o,kgnDy J*Ĩ4迶'?SP ea}ma,_s%)βTշ'y|MW1xjEV-ZTdӬ,Q$17٭0]9j~~~!K}GEMAopJ?"eh IX]H5{oӟICM@M:>6mWֵbc4PHbRp2Tw@Q@Q@Q@QQEQEQ,WŷTuwhU6ʱZǏ,XD@l=H+ɼ[>x%Ŧ^sOʲ[2˼l0kd ^s |3_52]K,fe$Ҁ0+|haxSNNT]լTZ%L<m z2g}▭}iZj2o}rx)fTRr8a^PGW=Я5uQk$q"Y;218<ם|tc^$t.gi.4c Nx'Zǿt:[8/{md|c2FrUb`֏/ڟΥiV_G"o,wFv ,23㿅]7Oӵ]vH涹LxHeYG)v8a֡lt{FkI{{euߨ}N2"eHX^&cmu#{eqm7S$3J)kU* P/׈i|:D+l,[e7. ħvSq8t9JN=(y8=(i8Ҁh擏J^99JN=(ylKǥ!@ww]~(ht ;=VI'?},-nĘ$j [m5bq,; DYA(0G>%Q[SO2A0 92nj g>|E]biiu91ݼJo9I 0F\K5~q@4sIǥ/ǥ'zRq@ qPh~4w ( ( ( )()i(ZJ(Ə€ƏƏ€Ƽtˏ nMFus/'[Y myeASf l9$<5ՃIn%ܐG$F6T2(wAլ;WO"Go.<)e`p@Ҹ##KoxSQ} 4fKO۲m_#BNAq얖Xmm p[‹qDQ p+|BҢO*+t yrFN94Mk~+ռ/iĈL#&0cUWHܪ;I(Mbx;'>/j/o+HR? 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(RzRzGj=(@z(ŠJZ? )(h? ))h()yN(▎h8^h8N(◚9)yN(▎h8^h8N(◚9h֗9hiyN=hiyN=hiyOƎ=iyOƎ=iyOƏƗ9֏Ɨ9֏Ɨ9h֗9h֗9hiyN=hiyN=hiyOƎ=iyOƎ=iyOƏƗ9֊^h_ƀրJOZ_JO^(QۥG~~QG@QPEPEQGE'GK~4~~~4'GGK~~~4~4~~'@GK~4~~~4'GGK~~~4~4~~'@qGKqG~4'qGG@qK~4qG'@qGKqG~4'qGG@qK~4qG'@qGKqG~4'qGG@qK~4qG'@qGKqG~4'Q@ GIEzRzKI@4vGhhE-~QG@Q@E~4QQ@GIP~Q/GIP~Q/GIP~Q/GIP~Q/GIP~Q/Iǭ/IQQǭ/IQǭ/IQǭ/Iǭ/IQQǭ/IQǭ/IQǭ/Iǭ/IQQǭ/IQǭ/IQǭ/Iǭ/IQGP:REEzSh ( (IE/zNŠ(}hNƗPvQ@ EPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEP endstream endobj 213 0 obj << /Type /Annot /Subtype /Link /A 214 0 R /Border [0 0 0] /H /I /Rect [ 298.8405 421.5743 331.3665 431.4950 ] >> endobj 214 0 obj << /Type /Action >> endobj 215 0 obj << /Type /Annot /Subtype /Link /A 216 0 R /Border [0 0 0] /H /I /Rect [ 368.6895 385.8601 384.9525 395.7807 ] >> endobj 216 0 obj << /Type /Action >> endobj 217 0 obj << /Type /Annot /Subtype /Link /A 218 0 R /Border [0 0 0] /H /I /Rect [ 142.1970 350.1458 158.4600 360.0665 ] >> endobj 218 0 obj << /Type /Action >> endobj 219 0 obj << /Type /Annot /Subtype /Link /A 220 0 R /Border [0 0 0] /H /I /Rect [ 298.8405 421.5743 331.3665 431.4950 ] >> endobj 220 0 obj << /Type /Action >> endobj 221 0 obj << /Type /Annot /Subtype /Link /A 222 0 R /Border [0 0 0] /H /I /Rect [ 368.6895 385.8601 384.9525 395.7807 ] >> endobj 222 0 obj << /Type /Action >> endobj 223 0 obj << /Type /Annot /Subtype /Link /A 224 0 R /Border [0 0 0] /H /I /Rect [ 142.1970 350.1458 158.4600 360.0665 ] >> endobj 224 0 obj << /Type /Action >> endobj 225 0 obj << /Type /Annot /Subtype /Link /A 226 0 R /Border [0 0 0] /H /I /Rect [ 298.8405 421.5743 331.3665 431.4950 ] >> endobj 226 0 obj << /Type /Action >> endobj 227 0 obj << /Type /Annot /Subtype /Link /A 228 0 R /Border [0 0 0] /H /I /Rect [ 368.6895 385.8601 384.9525 395.7807 ] >> endobj 228 0 obj << /Type /Action >> endobj 229 0 obj << /Type /Annot /Subtype /Link /A 230 0 R /Border [0 0 0] /H /I /Rect [ 142.1970 350.1458 158.4600 360.0665 ] >> endobj 230 0 obj << /Type /Action >> endobj 231 0 obj << /Type /Page /Parent 3 0 R /Annots [ 234 0 R 236 0 R 238 0 R 240 0 R 242 0 R 244 0 R ] /Contents 232 0 R >> endobj 232 0 obj << /Length 13657 >> stream 0.271 0.267 0.267 rg q 15.000 23.012 577.500 753.988 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I6 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(To model the impact of assumptions about the dynamics of H1N1 transmission over the course of the summer, where typical )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(influenza seasonality and changes in contact patterns may reduce the basic reproductive number \(R0\), we modified R0 to )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(generate differential timing of the peak of the epidemic curve. We considered the effect of different vaccination strategies when )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(the epidemic peak occurred in October \(no change in R0 over the summer\), November \(R0 decreases but remains above )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(endemic levels from July to September\), December \(R0 = 1 from July to September\), or January \(R0 = 1 from July to October\). )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(We also adjusted R0 to account for different levels of pre-existing immunity to pH1N1 in the population \(i.e., to give the same )] TJ ET BT 26.250 351.048 Td /F6 9.8 Tf [(effective)] TJ ET BT 62.559 351.048 Td /F1 9.8 Tf [( reproductive number under different immunity assumptions\).)] TJ ET BT 26.250 331.643 Td /F5 9.8 Tf [(Vaccination scenarios)] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(We considered four vaccination strategies. For all scenarios, the total number of vaccine doses was not a limiting factor; )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(adequate supply of vaccine was available for all individuals requiring immunization )] TJ ET 0.267 0.267 0.267 rg BT 383.890 300.333 Td /F1 9.8 Tf [([28])] TJ ET 0.271 0.267 0.267 rg BT 400.153 300.333 Td /F1 9.8 Tf [(.)] TJ ET BT 32.206 280.946 Td /F1 9.8 Tf [(1.)] TJ ET BT 45.750 280.929 Td /F1 9.8 Tf [(Attack rate-based strategy \(AR\): Vaccine distributed first to age groups with the highest model-predicted attack rates \(order )] TJ ET BT 45.750 269.024 Td /F1 9.8 Tf [(of vaccine allocation by age group: 5-17, 18-52, 0-4, ?53\).)] TJ ET BT 32.206 253.387 Td /F1 9.8 Tf [(2.)] TJ ET BT 45.750 253.369 Td /F1 9.8 Tf [(Outcome-based strategy \(Outcome\): Vaccine distributed first to age groups at the highest risk of a severe outcome, defined )] TJ ET BT 45.750 241.464 Td /F1 9.8 Tf [(as hospitalization, ICU admission, or death, following infection with pH1N1 \(order of vaccine allocation by age group: ?53, )] TJ ET BT 45.750 229.560 Td /F1 9.8 Tf [(18-52, 0-4, 5-17\).)] TJ ET BT 32.206 213.922 Td /F1 9.8 Tf [(3.)] TJ ET BT 45.750 213.905 Td /F1 9.8 Tf [(and 4. Risk-based strategy \(High risk/AR or High risk/Outcome\) : Vaccine preferentially distributed to individuals of any age )] TJ ET BT 45.750 202.000 Td /F1 9.8 Tf [(with an underlying risk condition \(based on seasonal influenza recommendations )] TJ ET 0.267 0.267 0.267 rg BT 396.360 202.000 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 407.202 202.000 Td /F1 9.8 Tf [(\) and pregnant women \(in the second )] TJ ET BT 45.750 190.095 Td /F1 9.8 Tf [(or third trimester\), followed by an attack rate- or outcome-based strategy described above \(delayed by one week to allow )] TJ ET BT 45.750 178.191 Td /F1 9.8 Tf [(for immunization of high-risk groups first\).)] TJ ET BT 26.250 155.036 Td /F5 9.8 Tf [(Model calibration)] TJ ET BT 26.250 135.631 Td /F1 9.8 Tf [(The model was calibrated to fit the initial epidemic curve observed in Ontario. Data for laboratory-confirmed cases with a )] TJ ET BT 26.250 123.726 Td /F1 9.8 Tf [(reported exposure date between April 13 and June 1, 2009 were obtained from iPHIS. Travel history data, including illness on )] TJ ET BT 26.250 111.822 Td /F1 9.8 Tf [(return to Mexico, were used to model the observed multiple introductions of pH1N1 into the Ontario population early on in the )] TJ ET BT 26.250 99.917 Td /F1 9.8 Tf [(pandemic.)] TJ ET BT 26.250 80.512 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 61.107 Td /F1 9.8 Tf [(We tested the robustness of model projections to baseline assumptions and parameter values by performing sensitivity )] TJ ET BT 26.250 49.203 Td /F1 9.8 Tf [(analyses, with model inputs varied over plausible ranges, and incorporating alternate assumptions regarding vaccine program )] TJ ET BT 26.250 37.298 Td /F1 9.8 Tf [(attributes. We evaluated the effect on model outputs of changing the time period for delivery of the first dose of vaccine to the )] TJ ET Q q 15.000 23.012 577.500 753.988 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I6 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(To model the impact of assumptions about the dynamics of H1N1 transmission over the course of the summer, where typical )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(influenza seasonality and changes in contact patterns may reduce the basic reproductive number \(R0\), we modified R0 to )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(generate differential timing of the peak of the epidemic curve. We considered the effect of different vaccination strategies when )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(the epidemic peak occurred in October \(no change in R0 over the summer\), November \(R0 decreases but remains above )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(endemic levels from July to September\), December \(R0 = 1 from July to September\), or January \(R0 = 1 from July to October\). )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(We also adjusted R0 to account for different levels of pre-existing immunity to pH1N1 in the population \(i.e., to give the same )] TJ ET BT 26.250 351.048 Td /F6 9.8 Tf [(effective)] TJ ET BT 62.559 351.048 Td /F1 9.8 Tf [( reproductive number under different immunity assumptions\).)] TJ ET BT 26.250 331.643 Td /F5 9.8 Tf [(Vaccination scenarios)] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(We considered four vaccination strategies. For all scenarios, the total number of vaccine doses was not a limiting factor; )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(adequate supply of vaccine was available for all individuals requiring immunization )] TJ ET 0.267 0.267 0.267 rg BT 383.890 300.333 Td /F1 9.8 Tf [([28])] TJ ET 0.271 0.267 0.267 rg BT 400.153 300.333 Td /F1 9.8 Tf [(.)] TJ ET BT 32.206 280.946 Td /F1 9.8 Tf [(1.)] TJ ET BT 45.750 280.929 Td /F1 9.8 Tf [(Attack rate-based strategy \(AR\): Vaccine distributed first to age groups with the highest model-predicted attack rates \(order )] TJ ET BT 45.750 269.024 Td /F1 9.8 Tf [(of vaccine allocation by age group: 5-17, 18-52, 0-4, ?53\).)] TJ ET BT 32.206 253.387 Td /F1 9.8 Tf [(2.)] TJ ET BT 45.750 253.369 Td /F1 9.8 Tf [(Outcome-based strategy \(Outcome\): Vaccine distributed first to age groups at the highest risk of a severe outcome, defined )] TJ ET BT 45.750 241.464 Td /F1 9.8 Tf [(as hospitalization, ICU admission, or death, following infection with pH1N1 \(order of vaccine allocation by age group: ?53, )] TJ ET BT 45.750 229.560 Td /F1 9.8 Tf [(18-52, 0-4, 5-17\).)] TJ ET BT 32.206 213.922 Td /F1 9.8 Tf [(3.)] TJ ET BT 45.750 213.905 Td /F1 9.8 Tf [(and 4. Risk-based strategy \(High risk/AR or High risk/Outcome\) : Vaccine preferentially distributed to individuals of any age )] TJ ET BT 45.750 202.000 Td /F1 9.8 Tf [(with an underlying risk condition \(based on seasonal influenza recommendations )] TJ ET 0.267 0.267 0.267 rg BT 396.360 202.000 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 407.202 202.000 Td /F1 9.8 Tf [(\) and pregnant women \(in the second )] TJ ET BT 45.750 190.095 Td /F1 9.8 Tf [(or third trimester\), followed by an attack rate- or outcome-based strategy described above \(delayed by one week to allow )] TJ ET BT 45.750 178.191 Td /F1 9.8 Tf [(for immunization of high-risk groups first\).)] TJ ET BT 26.250 155.036 Td /F5 9.8 Tf [(Model calibration)] TJ ET BT 26.250 135.631 Td /F1 9.8 Tf [(The model was calibrated to fit the initial epidemic curve observed in Ontario. Data for laboratory-confirmed cases with a )] TJ ET BT 26.250 123.726 Td /F1 9.8 Tf [(reported exposure date between April 13 and June 1, 2009 were obtained from iPHIS. Travel history data, including illness on )] TJ ET BT 26.250 111.822 Td /F1 9.8 Tf [(return to Mexico, were used to model the observed multiple introductions of pH1N1 into the Ontario population early on in the )] TJ ET BT 26.250 99.917 Td /F1 9.8 Tf [(pandemic.)] TJ ET BT 26.250 80.512 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 61.107 Td /F1 9.8 Tf [(We tested the robustness of model projections to baseline assumptions and parameter values by performing sensitivity )] TJ ET BT 26.250 49.203 Td /F1 9.8 Tf [(analyses, with model inputs varied over plausible ranges, and incorporating alternate assumptions regarding vaccine program )] TJ ET BT 26.250 37.298 Td /F1 9.8 Tf [(attributes. We evaluated the effect on model outputs of changing the time period for delivery of the first dose of vaccine to the )] TJ ET Q q 15.000 23.012 577.500 753.988 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I6 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F1 9.8 Tf [(To model the impact of assumptions about the dynamics of H1N1 transmission over the course of the summer, where typical )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(influenza seasonality and changes in contact patterns may reduce the basic reproductive number \(R0\), we modified R0 to )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(generate differential timing of the peak of the epidemic curve. We considered the effect of different vaccination strategies when )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(the epidemic peak occurred in October \(no change in R0 over the summer\), November \(R0 decreases but remains above )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(endemic levels from July to September\), December \(R0 = 1 from July to September\), or January \(R0 = 1 from July to October\). )] TJ ET BT 26.250 362.952 Td /F1 9.8 Tf [(We also adjusted R0 to account for different levels of pre-existing immunity to pH1N1 in the population \(i.e., to give the same )] TJ ET BT 26.250 351.048 Td /F6 9.8 Tf [(effective)] TJ ET BT 62.559 351.048 Td /F1 9.8 Tf [( reproductive number under different immunity assumptions\).)] TJ ET BT 26.250 331.643 Td /F5 9.8 Tf [(Vaccination scenarios)] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(We considered four vaccination strategies. For all scenarios, the total number of vaccine doses was not a limiting factor; )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(adequate supply of vaccine was available for all individuals requiring immunization )] TJ ET 0.267 0.267 0.267 rg BT 383.890 300.333 Td /F1 9.8 Tf [([28])] TJ ET 0.271 0.267 0.267 rg BT 400.153 300.333 Td /F1 9.8 Tf [(.)] TJ ET BT 32.206 280.946 Td /F1 9.8 Tf [(1.)] TJ ET BT 45.750 280.929 Td /F1 9.8 Tf [(Attack rate-based strategy \(AR\): Vaccine distributed first to age groups with the highest model-predicted attack rates \(order )] TJ ET BT 45.750 269.024 Td /F1 9.8 Tf [(of vaccine allocation by age group: 5-17, 18-52, 0-4, ?53\).)] TJ ET BT 32.206 253.387 Td /F1 9.8 Tf [(2.)] TJ ET BT 45.750 253.369 Td /F1 9.8 Tf [(Outcome-based strategy \(Outcome\): Vaccine distributed first to age groups at the highest risk of a severe outcome, defined )] TJ ET BT 45.750 241.464 Td /F1 9.8 Tf [(as hospitalization, ICU admission, or death, following infection with pH1N1 \(order of vaccine allocation by age group: ?53, )] TJ ET BT 45.750 229.560 Td /F1 9.8 Tf [(18-52, 0-4, 5-17\).)] TJ ET BT 32.206 213.922 Td /F1 9.8 Tf [(3.)] TJ ET BT 45.750 213.905 Td /F1 9.8 Tf [(and 4. Risk-based strategy \(High risk/AR or High risk/Outcome\) : Vaccine preferentially distributed to individuals of any age )] TJ ET BT 45.750 202.000 Td /F1 9.8 Tf [(with an underlying risk condition \(based on seasonal influenza recommendations )] TJ ET 0.267 0.267 0.267 rg BT 396.360 202.000 Td /F1 9.8 Tf [([2])] TJ ET 0.271 0.267 0.267 rg BT 407.202 202.000 Td /F1 9.8 Tf [(\) and pregnant women \(in the second )] TJ ET BT 45.750 190.095 Td /F1 9.8 Tf [(or third trimester\), followed by an attack rate- or outcome-based strategy described above \(delayed by one week to allow )] TJ ET BT 45.750 178.191 Td /F1 9.8 Tf [(for immunization of high-risk groups first\).)] TJ ET BT 26.250 155.036 Td /F5 9.8 Tf [(Model calibration)] TJ ET BT 26.250 135.631 Td /F1 9.8 Tf [(The model was calibrated to fit the initial epidemic curve observed in Ontario. Data for laboratory-confirmed cases with a )] TJ ET BT 26.250 123.726 Td /F1 9.8 Tf [(reported exposure date between April 13 and June 1, 2009 were obtained from iPHIS. Travel history data, including illness on )] TJ ET BT 26.250 111.822 Td /F1 9.8 Tf [(return to Mexico, were used to model the observed multiple introductions of pH1N1 into the Ontario population early on in the )] TJ ET BT 26.250 99.917 Td /F1 9.8 Tf [(pandemic.)] TJ ET BT 26.250 80.512 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 61.107 Td /F1 9.8 Tf [(We tested the robustness of model projections to baseline assumptions and parameter values by performing sensitivity )] TJ ET BT 26.250 49.203 Td /F1 9.8 Tf [(analyses, with model inputs varied over plausible ranges, and incorporating alternate assumptions regarding vaccine program )] TJ ET BT 26.250 37.298 Td /F1 9.8 Tf [(attributes. We evaluated the effect on model outputs of changing the time period for delivery of the first dose of vaccine to the )] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(6)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 233 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 38266>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((REPEQEQ@ 3E%.h4Q@h%-4Q/4s@ RG>Q/4s@ RG4Q/>s@ RG>Q/4s@ RG4Q/>s@ RG4qGG@qGG@QQQG~4~4qG~4~4qEQQqGG@qGG@QQQG~4~4qG~4~4qEQEPh(ŠJ( )i(֊J((/IQE/IE/Iڊ? ? ()? (@ R~Q@KRz@KRvŠ=h((֊? ? ;QހJ=h((֊? ? ;QހJ=h((֊? ? ;QހJ=h((Z(h;RJZ?((? ? ??? ? 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N(—hր—hh((֏ƀ(֏ƀ(hր—hր—hh((֏ƀ(֏ƀ(hր—hր—hh((֏ƀ(֏ƀ(hր—hր—hh(Z()hh=)Q@Q@Q@h'aEzQE'cKފ(; _Z((((((((((((((((((((((((((((( endstream endobj 234 0 obj << /Type /Annot /Subtype /Link /A 235 0 R /Border [0 0 0] /H /I /Rect [ 383.8897 299.4316 400.1527 309.3522 ] >> endobj 235 0 obj << /Type /Action >> endobj 236 0 obj << /Type /Annot /Subtype /Link /A 237 0 R /Border [0 0 0] /H /I /Rect [ 396.3600 201.0983 407.2020 211.0189 ] >> endobj 237 0 obj << /Type /Action >> endobj 238 0 obj << /Type /Annot /Subtype /Link /A 239 0 R /Border [0 0 0] /H /I /Rect [ 383.8897 299.4316 400.1527 309.3522 ] >> endobj 239 0 obj << /Type /Action >> endobj 240 0 obj << /Type /Annot /Subtype /Link /A 241 0 R /Border [0 0 0] /H /I /Rect [ 396.3600 201.0983 407.2020 211.0189 ] >> endobj 241 0 obj << /Type /Action >> endobj 242 0 obj << /Type /Annot /Subtype /Link /A 243 0 R /Border [0 0 0] /H /I /Rect [ 383.8897 299.4316 400.1527 309.3522 ] >> endobj 243 0 obj << /Type /Action >> endobj 244 0 obj << /Type /Annot /Subtype /Link /A 245 0 R /Border [0 0 0] /H /I /Rect [ 396.3600 201.0983 407.2020 211.0189 ] >> endobj 245 0 obj << /Type /Action >> endobj 246 0 obj << /Type /Page /Parent 3 0 R /Contents 247 0 R >> endobj 247 0 obj << /Length 7747 >> stream 0.271 0.267 0.267 rg q 15.000 -158.723 577.500 935.723 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(entire population to two or six weeks, switching to a single vaccine dose, reducing vaccine effectiveness in the ?65 age group )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(\(across a range of effectiveness of 30-60 percent\), and varying the proportion of asymptomatic cases.)] TJ ET BT 26.250 718.969 Td /F4 12.0 Tf [(Results)] TJ ET BT 26.250 699.015 Td /F5 9.8 Tf [(Initial epidemic dynamics and model calibration)] TJ ET BT 26.250 679.610 Td /F1 9.8 Tf [(The model appeared well-calibrated to epidemic curves for pH1N1 influenza and matched the initial transmission dynamics )] TJ ET BT 26.250 667.705 Td /F1 9.8 Tf [(observed in Ontario \()] TJ ET BT 117.286 667.705 Td /F4 9.8 Tf [(Figure 2)] TJ ET BT 155.213 667.705 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 320.324 cm /I7 Do Q BT 26.250 303.300 Td /F4 9.8 Tf [(Fig. 2:)] TJ ET BT 54.964 303.300 Td /F4 9.8 Tf [( Confirmed cases of locally-acquired pH1N1 in Ontario by symptom onset date, April 16 June 1, 2009.)] TJ ET BT 531.788 303.300 Td /F1 9.8 Tf [( Cases )] TJ ET BT 26.250 291.396 Td /F1 9.8 Tf [(that reported a history of travel to Mexico prior to illness onset are not included. Model-predicted cases assuming 50 percent pre-)] TJ ET BT 26.250 279.491 Td /F1 9.8 Tf [(existing immunity in the ?53 age group, R0 of 1.3, latent period of 3.5 days, and duration of infectiousness of 2.5 days are )] TJ ET BT 26.250 267.586 Td /F1 9.8 Tf [(shown \(line\).)] TJ ET BT 26.250 248.181 Td /F4 9.8 Tf [(Figure 3)] TJ ET BT 64.178 248.181 Td /F1 9.8 Tf [( illustrates the pH1N1 infection dynamics generated by the model; epidemic curves peaked in different months, )] TJ ET BT 26.250 236.277 Td /F1 9.8 Tf [(depending on assumptions made about influenza transmission behaviour during the summer months, but overall attack rates )] TJ ET BT 26.250 224.372 Td /F1 9.8 Tf [(were consistent across model runs for a given estimate of pre-existing immunity in the pre-1957 cohort. In the absence of )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(vaccination, the average infection attack rate across the entire Canadian population was 35.1% \(range 33.2 36.8%\). Age-)] TJ ET BT 26.250 200.562 Td /F1 9.8 Tf [(specific patterns of influenza transmission reflected typical mixing patterns within a population, with epidemic curves peaking )] TJ ET BT 26.250 188.658 Td /F1 9.8 Tf [(first in younger age groups, followed by the elderly.)] TJ ET Q q 15.000 -158.723 577.500 935.723 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(entire population to two or six weeks, switching to a single vaccine dose, reducing vaccine effectiveness in the ?65 age group )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(\(across a range of effectiveness of 30-60 percent\), and varying the proportion of asymptomatic cases.)] TJ ET BT 26.250 718.969 Td /F4 12.0 Tf [(Results)] TJ ET BT 26.250 699.015 Td /F5 9.8 Tf [(Initial epidemic dynamics and model calibration)] TJ ET BT 26.250 679.610 Td /F1 9.8 Tf [(The model appeared well-calibrated to epidemic curves for pH1N1 influenza and matched the initial transmission dynamics )] TJ ET BT 26.250 667.705 Td /F1 9.8 Tf [(observed in Ontario \()] TJ ET BT 117.286 667.705 Td /F4 9.8 Tf [(Figure 2)] TJ ET BT 155.213 667.705 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 320.324 cm /I7 Do Q BT 26.250 303.300 Td /F4 9.8 Tf [(Fig. 2:)] TJ ET BT 54.964 303.300 Td /F4 9.8 Tf [( Confirmed cases of locally-acquired pH1N1 in Ontario by symptom onset date, April 16 June 1, 2009.)] TJ ET BT 531.788 303.300 Td /F1 9.8 Tf [( Cases )] TJ ET BT 26.250 291.396 Td /F1 9.8 Tf [(that reported a history of travel to Mexico prior to illness onset are not included. Model-predicted cases assuming 50 percent pre-)] TJ ET BT 26.250 279.491 Td /F1 9.8 Tf [(existing immunity in the ?53 age group, R0 of 1.3, latent period of 3.5 days, and duration of infectiousness of 2.5 days are )] TJ ET BT 26.250 267.586 Td /F1 9.8 Tf [(shown \(line\).)] TJ ET BT 26.250 248.181 Td /F4 9.8 Tf [(Figure 3)] TJ ET BT 64.178 248.181 Td /F1 9.8 Tf [( illustrates the pH1N1 infection dynamics generated by the model; epidemic curves peaked in different months, )] TJ ET BT 26.250 236.277 Td /F1 9.8 Tf [(depending on assumptions made about influenza transmission behaviour during the summer months, but overall attack rates )] TJ ET BT 26.250 224.372 Td /F1 9.8 Tf [(were consistent across model runs for a given estimate of pre-existing immunity in the pre-1957 cohort. In the absence of )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(vaccination, the average infection attack rate across the entire Canadian population was 35.1% \(range 33.2 36.8%\). Age-)] TJ ET BT 26.250 200.562 Td /F1 9.8 Tf [(specific patterns of influenza transmission reflected typical mixing patterns within a population, with epidemic curves peaking )] TJ ET BT 26.250 188.658 Td /F1 9.8 Tf [(first in younger age groups, followed by the elderly.)] TJ ET Q q 15.000 -158.723 577.500 935.723 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(entire population to two or six weeks, switching to a single vaccine dose, reducing vaccine effectiveness in the ?65 age group )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(\(across a range of effectiveness of 30-60 percent\), and varying the proportion of asymptomatic cases.)] TJ ET BT 26.250 718.969 Td /F4 12.0 Tf [(Results)] TJ ET BT 26.250 699.015 Td /F5 9.8 Tf [(Initial epidemic dynamics and model calibration)] TJ ET BT 26.250 679.610 Td /F1 9.8 Tf [(The model appeared well-calibrated to epidemic curves for pH1N1 influenza and matched the initial transmission dynamics )] TJ ET BT 26.250 667.705 Td /F1 9.8 Tf [(observed in Ontario \()] TJ ET BT 117.286 667.705 Td /F4 9.8 Tf [(Figure 2)] TJ ET BT 155.213 667.705 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 320.324 cm /I7 Do Q BT 26.250 303.300 Td /F4 9.8 Tf [(Fig. 2:)] TJ ET BT 54.964 303.300 Td /F4 9.8 Tf [( Confirmed cases of locally-acquired pH1N1 in Ontario by symptom onset date, April 16 June 1, 2009.)] TJ ET BT 531.788 303.300 Td /F1 9.8 Tf [( Cases )] TJ ET BT 26.250 291.396 Td /F1 9.8 Tf [(that reported a history of travel to Mexico prior to illness onset are not included. Model-predicted cases assuming 50 percent pre-)] TJ ET BT 26.250 279.491 Td /F1 9.8 Tf [(existing immunity in the ?53 age group, R0 of 1.3, latent period of 3.5 days, and duration of infectiousness of 2.5 days are )] TJ ET BT 26.250 267.586 Td /F1 9.8 Tf [(shown \(line\).)] TJ ET BT 26.250 248.181 Td /F4 9.8 Tf [(Figure 3)] TJ ET BT 64.178 248.181 Td /F1 9.8 Tf [( illustrates the pH1N1 infection dynamics generated by the model; epidemic curves peaked in different months, )] TJ ET BT 26.250 236.277 Td /F1 9.8 Tf [(depending on assumptions made about influenza transmission behaviour during the summer months, but overall attack rates )] TJ ET BT 26.250 224.372 Td /F1 9.8 Tf [(were consistent across model runs for a given estimate of pre-existing immunity in the pre-1957 cohort. In the absence of )] TJ ET BT 26.250 212.467 Td /F1 9.8 Tf [(vaccination, the average infection attack rate across the entire Canadian population was 35.1% \(range 33.2 36.8%\). Age-)] TJ ET BT 26.250 200.562 Td /F1 9.8 Tf [(specific patterns of influenza transmission reflected typical mixing patterns within a population, with epidemic curves peaking )] TJ ET BT 26.250 188.658 Td /F1 9.8 Tf [(first in younger age groups, followed by the elderly.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(7)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 248 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 44166>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((RE_ k?Xb>3O毩k76޳ncuXb!!H{u%y6Sޜ_&ͻȗn fz'!//PGjZ~tmFK E.(ډD&LȸBC DgފO|[ծ4>KHQԭDЃFܤFpp,H&%晥~MNTwӦL C2_ ,{}kļ^t;vUt)3,( |2qW|Y@ gu&љӵ . 3iX?J4̦6(H@VVdKEmkPEPE@Q@Qڀ (EQEQڎQEQڊ;PޏJ;@z@j;ڎzQGQڊ;PޏJ;@z@j;ڎzQGQڊ;PޏJ;@z@j;ڳ'/Ǿ1W𮫡%"x?.;>}HV,QH84̿} DmkM|Q:W&o,~!!]'.oOz_K5/5*}'yOǷJh֧ZI[{P trl@gTZu]G[ve;-7'ך(ndAPO-Dr+s 󊬚 maC3F#g-3ֽ"

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(ŠO—h((iOƗ((hh()Oƀ41DKVG PGz߅l<? {F%iOos&c fTd2`&aX]I'W-XiVo5&kxr2 939'Q̚]gwOG5qkm* );GQ4p%o >^цyElt;5}…V!FKWT0jnDfƜ"FrG@1~4b/@) 4^+/h#R.`@F ryҬ4t;m1Q[/qf'I9Z?rW¯h:O^O ]M8|`.oVU!@J5O^ Q|xuk6 \T32DRp3+i?Dž$Jx57 q.Ì*އ ZƏiMƧ?oHZ_)P7G&?_ƀ9f[ uIΛ yG2mYC09u>xJKԲnhImtip )tF z_ƀ8=IN_sƱiNUb~@ .0yÏJ??8J_ƓJ8i?8J?_ƀJ8h8J??8J_ƓJ8i?8J?_ƀJ8h8J??8J_ƓJ8i?8J?_ƀJ8h8ƊZ? J(ғךZOZ=9Z=(@GGz(hhƊ? (?((Š? ? N(( ? N(( ? N(( ? N(( ? N(() OƎ=h) OƏƀŽ=hh OŽ=hh OƎ=h) OƎ=h) OƏƀŽ=hh OŽ=hh OƎ=h) OƎ=h) OƏƀŽ=hh OŽ=hh OƎ=h) OƎ=h) OƏƀŠ8Җ(?֏Z(қEQEQEJNƊ({vQ@ GPv4袀Z( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (? endstream endobj 249 0 obj << /Type /Page /Parent 3 0 R /Contents 250 0 R >> endobj 250 0 obj << /Length 4831 >> stream 0.271 0.267 0.267 rg q 15.000 -35.143 577.500 812.143 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I8 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 3: \(a\) Simulated age-stratified daily pH1N1 infection incidence per 100,000 population and \(b\) age-specific attack )] TJ ET BT 26.250 410.571 Td /F4 9.8 Tf [(rates between April 2009 and June 2010, in the absence of vaccination or other interventions.)] TJ ET BT 458.107 410.571 Td /F1 9.8 Tf [( Both symptomatic and )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(asymptomatic cases are shown. The curves are based on an assumption of fifty percent pre-existing immunity in the ?53 age )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(group and a decrease in R0 from 1.3 to 1.15 between July and September.)] TJ ET BT 26.250 367.357 Td /F5 9.8 Tf [(Effect of timing of epidemic peak in relation to vaccine availability on outcomes)] TJ ET BT 26.250 347.952 Td /F1 9.8 Tf [(Given the uncertainty around pH1N1 dynamics over the coming months and timelines for vaccine delivery, we investigated the )] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(impact of the timing of the epidemic peak on whether an attack rate- or outcome-based vaccination strategy was preferred \()] TJ ET BT 26.250 324.143 Td /F4 9.8 Tf [(Figure 4)] TJ ET BT 64.178 324.143 Td /F1 9.8 Tf [(\). For an October peak, neither approach is likely to significantly alter outcomes. For each month that the epidemic is )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(delayed, there is enhanced effectiveness of all vaccination strategies.)] TJ ET Q q 15.000 -35.143 577.500 812.143 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I8 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 3: \(a\) Simulated age-stratified daily pH1N1 infection incidence per 100,000 population and \(b\) age-specific attack )] TJ ET BT 26.250 410.571 Td /F4 9.8 Tf [(rates between April 2009 and June 2010, in the absence of vaccination or other interventions.)] TJ ET BT 458.107 410.571 Td /F1 9.8 Tf [( Both symptomatic and )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(asymptomatic cases are shown. The curves are based on an assumption of fifty percent pre-existing immunity in the ?53 age )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(group and a decrease in R0 from 1.3 to 1.15 between July and September.)] TJ ET BT 26.250 367.357 Td /F5 9.8 Tf [(Effect of timing of epidemic peak in relation to vaccine availability on outcomes)] TJ ET BT 26.250 347.952 Td /F1 9.8 Tf [(Given the uncertainty around pH1N1 dynamics over the coming months and timelines for vaccine delivery, we investigated the )] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(impact of the timing of the epidemic peak on whether an attack rate- or outcome-based vaccination strategy was preferred \()] TJ ET BT 26.250 324.143 Td /F4 9.8 Tf [(Figure 4)] TJ ET BT 64.178 324.143 Td /F1 9.8 Tf [(\). For an October peak, neither approach is likely to significantly alter outcomes. For each month that the epidemic is )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(delayed, there is enhanced effectiveness of all vaccination strategies.)] TJ ET Q q 15.000 -35.143 577.500 812.143 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I8 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 3: \(a\) Simulated age-stratified daily pH1N1 infection incidence per 100,000 population and \(b\) age-specific attack )] TJ ET BT 26.250 410.571 Td /F4 9.8 Tf [(rates between April 2009 and June 2010, in the absence of vaccination or other interventions.)] TJ ET BT 458.107 410.571 Td /F1 9.8 Tf [( Both symptomatic and )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(asymptomatic cases are shown. The curves are based on an assumption of fifty percent pre-existing immunity in the ?53 age )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(group and a decrease in R0 from 1.3 to 1.15 between July and September.)] TJ ET BT 26.250 367.357 Td /F5 9.8 Tf [(Effect of timing of epidemic peak in relation to vaccine availability on outcomes)] TJ ET BT 26.250 347.952 Td /F1 9.8 Tf [(Given the uncertainty around pH1N1 dynamics over the coming months and timelines for vaccine delivery, we investigated the )] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(impact of the timing of the epidemic peak on whether an attack rate- or outcome-based vaccination strategy was preferred \()] TJ ET BT 26.250 324.143 Td /F4 9.8 Tf [(Figure 4)] TJ ET BT 64.178 324.143 Td /F1 9.8 Tf [(\). For an October peak, neither approach is likely to significantly alter outcomes. For each month that the epidemic is )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(delayed, there is enhanced effectiveness of all vaccination strategies.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(8)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 251 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 26949>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(.̞X!wFI>qu -,1.20UdzQE(=(s¨]Y3\0CSQzRdc.~QzQEQ?*?J(QFh4QzQEQ?*?J(QE(Q(@fEf (-Q@sEQEQG4QEQEQG4PEPEs@Q@Q@E ()((i(4fJ\њ)(=x55]@9;K;o㧍>$|P)=G)+ܒeb68)wN5vwEHFlRAey '3;2rO;+y"?]@qGG@qGG@QQ~4~4qG~4~4qG~4~4QQQGE-Q@(()h()}h(ZJ()h js@.-'UY,nI&x.P Yt`| kr-i7 n4r ʧHzgj|Yotϕ֓Zl;OP\;L gʠMKݢ׽ҥf{t`Ef[FdwTu4AcS._ErAٗDF?0_|LVz~p]Y5QI6 {WK/?Iu۸ s>_'^7m`2\\2M*^vpAcʆUPwp}(֓ JFnD[":4dY!\WG?jݗTm6nTT1ag!rhxwA_֠ ?Š=h OŠ;PPRPW+;2xGW6v%u K8.˜9Oj] o煴4KfM͒CErGS q@jƓLIZԚriZ[VDvZ;,!#1 Elև#`7WҔ[V+,i.3CmpJΈWе{o=դm-ͨem 0rtv~~z@GGj;QQGv\?ʟޣy??ʀ0ȅ?WCW=D/ׄŽwҏZ? ? 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KjF[-g'dX̙rG\5{iDRȌr2#sϭM]ESW/4hZr,U 5+0I'dOm?TNxn6' 2 J~q/ A-G^i޳g"S&6P[b(,$Wŝ'e-4ا{F%FݲENlbӌ0$sϥHuRrp8_G_|igZ>*2fOöEN.Jm9R6$*@(`ܶdg@P|;@?IG}yx< ῵I46{Ԛ~/ӬY5Ӽzm˹e'R0I. z4ry<];Lw+liQݓkV8EJp: Ci>q*_1F?fc#|_  .2`6Kr(Pz֋mBԦRxkI bHF PG \CKiFy`S'JUI)4{$v> endobj 253 0 obj << /Length 13036 >> stream 0.271 0.267 0.267 rg q 15.000 -228.714 577.500 1005.714 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I9 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 4: )] TJ ET BT 57.674 422.476 Td /F4 9.8 Tf [(Effect of timing of epidemic peak on preferred vaccination strategy. )] TJ ET BT 373.009 422.476 Td /F1 9.8 Tf [(Total model-predicted attack rates and deaths )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(by month of the pandemic peak are shown, when implementing attack rate \(AR\)- or outcome-based vaccination strategies. For )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(each month of the epidemic peak, outcomes are presented for three values of pre-existing immunity among individuals aged )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(?53 \(30%, 50%, and 70%\) and two vaccination coverage levels \(base case and upper bound\). For all scenarios, vaccination )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(campaigns are initiated on November 15, 2009.)] TJ ET BT 26.250 355.452 Td /F5 9.8 Tf [(Attack rate-based versus outcome-based vaccination strategies)] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(We evaluated the percent reduction in predicted attack rates, number of hospitalizations, ICU admissions, and deaths under )] TJ ET BT 26.250 324.143 Td /F1 9.8 Tf [(these two strategies, relative to the no intervention scenario. The attack rate-based strategy was most effective at reducing the )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(total number of infections and minimizing hospitalizations when the epidemic peaked in December or January, with minimal )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(difference in the impact of competing strategies on overall attack rates when the epidemic peaked earlier. When there was 30 )] TJ ET BT 26.250 288.429 Td /F1 9.8 Tf [(percent pre-existing immunity in the individuals born prior to 1957 group, there was no preferred strategy for minimizing )] TJ ET BT 26.250 276.524 Td /F1 9.8 Tf [(hospitalizations. Using ICU admissions as the outcome of interest, the outcome-based strategy was preferred when there were )] TJ ET BT 26.250 264.619 Td /F1 9.8 Tf [(low levels of pre-existing immunity, but there was no advantage to using one strategy over the other when immunity in the older )] TJ ET BT 26.250 252.714 Td /F1 9.8 Tf [(age groups was )] TJ ET BT 97.786 252.714 Td /F1 9.8 Tf [(>)] TJ ET BT 103.480 252.714 Td /F1 9.8 Tf [(50 percent. By contrast, when mortality was assessed as the endpoint of interest, an outcome-based strategy )] TJ ET BT 26.250 240.810 Td /F1 9.8 Tf [(was preferred to an attack rate-based strategy for any combination of values for pre-existing immunity and vaccine coverage, )] TJ ET BT 26.250 228.905 Td /F1 9.8 Tf [(with the exception of the assumption of 70 percent immunity to pH1N1 in individuals aged )] TJ ET BT 414.807 228.905 Td /F1 9.8 Tf [(>)] TJ ET BT 420.501 228.905 Td /F1 9.8 Tf [(53 combined with a January peak. )] TJ ET BT 26.250 217.000 Td /F1 9.8 Tf [(Under this latter scenario, there was no difference between strategies.)] TJ ET BT 26.250 197.595 Td /F5 9.8 Tf [(Prioritization of vaccine delivery to individuals with underlying high-risk conditions \(risk-based strategy\))] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(We assessed the effect of preferentially immunizing individuals of any age with an underlying medical condition, prior to )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(implementing an attack rate- or outcome-based strategy. Despite the resulting delay in vaccine allocation to the remaining )] TJ ET BT 26.250 154.381 Td /F1 9.8 Tf [(population, for all scenarios, hospitalizations and ICU admissions were reduced compared to vaccination strategies that did not )] TJ ET BT 26.250 142.476 Td /F1 9.8 Tf [(target high-risk groups \()] TJ ET BT 129.200 142.476 Td /F4 9.8 Tf [(Figure 5)] TJ ET BT 167.128 142.476 Td /F1 9.8 Tf [(\). When the epidemic peak occurred in December or January, this approach had a less marked )] TJ ET BT 26.250 130.572 Td /F1 9.8 Tf [(effect in reducing mortality and resulted in higher cumulative attack rates than strategies that did not prioritize high-risk groups, )] TJ ET BT 26.250 118.667 Td /F1 9.8 Tf [(whereas for an October or November epidemic peak, this approach had a larger effect in reducing mortality.)] TJ ET Q q 15.000 -228.714 577.500 1005.714 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I9 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 4: )] TJ ET BT 57.674 422.476 Td /F4 9.8 Tf [(Effect of timing of epidemic peak on preferred vaccination strategy. )] TJ ET BT 373.009 422.476 Td /F1 9.8 Tf [(Total model-predicted attack rates and deaths )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(by month of the pandemic peak are shown, when implementing attack rate \(AR\)- or outcome-based vaccination strategies. For )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(each month of the epidemic peak, outcomes are presented for three values of pre-existing immunity among individuals aged )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(?53 \(30%, 50%, and 70%\) and two vaccination coverage levels \(base case and upper bound\). For all scenarios, vaccination )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(campaigns are initiated on November 15, 2009.)] TJ ET BT 26.250 355.452 Td /F5 9.8 Tf [(Attack rate-based versus outcome-based vaccination strategies)] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(We evaluated the percent reduction in predicted attack rates, number of hospitalizations, ICU admissions, and deaths under )] TJ ET BT 26.250 324.143 Td /F1 9.8 Tf [(these two strategies, relative to the no intervention scenario. The attack rate-based strategy was most effective at reducing the )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(total number of infections and minimizing hospitalizations when the epidemic peaked in December or January, with minimal )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(difference in the impact of competing strategies on overall attack rates when the epidemic peaked earlier. When there was 30 )] TJ ET BT 26.250 288.429 Td /F1 9.8 Tf [(percent pre-existing immunity in the individuals born prior to 1957 group, there was no preferred strategy for minimizing )] TJ ET BT 26.250 276.524 Td /F1 9.8 Tf [(hospitalizations. Using ICU admissions as the outcome of interest, the outcome-based strategy was preferred when there were )] TJ ET BT 26.250 264.619 Td /F1 9.8 Tf [(low levels of pre-existing immunity, but there was no advantage to using one strategy over the other when immunity in the older )] TJ ET BT 26.250 252.714 Td /F1 9.8 Tf [(age groups was )] TJ ET BT 97.786 252.714 Td /F1 9.8 Tf [(>)] TJ ET BT 103.480 252.714 Td /F1 9.8 Tf [(50 percent. By contrast, when mortality was assessed as the endpoint of interest, an outcome-based strategy )] TJ ET BT 26.250 240.810 Td /F1 9.8 Tf [(was preferred to an attack rate-based strategy for any combination of values for pre-existing immunity and vaccine coverage, )] TJ ET BT 26.250 228.905 Td /F1 9.8 Tf [(with the exception of the assumption of 70 percent immunity to pH1N1 in individuals aged )] TJ ET BT 414.807 228.905 Td /F1 9.8 Tf [(>)] TJ ET BT 420.501 228.905 Td /F1 9.8 Tf [(53 combined with a January peak. )] TJ ET BT 26.250 217.000 Td /F1 9.8 Tf [(Under this latter scenario, there was no difference between strategies.)] TJ ET BT 26.250 197.595 Td /F5 9.8 Tf [(Prioritization of vaccine delivery to individuals with underlying high-risk conditions \(risk-based strategy\))] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(We assessed the effect of preferentially immunizing individuals of any age with an underlying medical condition, prior to )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(implementing an attack rate- or outcome-based strategy. Despite the resulting delay in vaccine allocation to the remaining )] TJ ET BT 26.250 154.381 Td /F1 9.8 Tf [(population, for all scenarios, hospitalizations and ICU admissions were reduced compared to vaccination strategies that did not )] TJ ET BT 26.250 142.476 Td /F1 9.8 Tf [(target high-risk groups \()] TJ ET BT 129.200 142.476 Td /F4 9.8 Tf [(Figure 5)] TJ ET BT 167.128 142.476 Td /F1 9.8 Tf [(\). When the epidemic peak occurred in December or January, this approach had a less marked )] TJ ET BT 26.250 130.572 Td /F1 9.8 Tf [(effect in reducing mortality and resulted in higher cumulative attack rates than strategies that did not prioritize high-risk groups, )] TJ ET BT 26.250 118.667 Td /F1 9.8 Tf [(whereas for an October or November epidemic peak, this approach had a larger effect in reducing mortality.)] TJ ET Q q 15.000 -228.714 577.500 1005.714 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I9 Do Q 0.271 0.267 0.267 rg BT 26.250 422.476 Td /F4 9.8 Tf [(Fig. 4: )] TJ ET BT 57.674 422.476 Td /F4 9.8 Tf [(Effect of timing of epidemic peak on preferred vaccination strategy. )] TJ ET BT 373.009 422.476 Td /F1 9.8 Tf [(Total model-predicted attack rates and deaths )] TJ ET BT 26.250 410.571 Td /F1 9.8 Tf [(by month of the pandemic peak are shown, when implementing attack rate \(AR\)- or outcome-based vaccination strategies. For )] TJ ET BT 26.250 398.667 Td /F1 9.8 Tf [(each month of the epidemic peak, outcomes are presented for three values of pre-existing immunity among individuals aged )] TJ ET BT 26.250 386.762 Td /F1 9.8 Tf [(?53 \(30%, 50%, and 70%\) and two vaccination coverage levels \(base case and upper bound\). For all scenarios, vaccination )] TJ ET BT 26.250 374.857 Td /F1 9.8 Tf [(campaigns are initiated on November 15, 2009.)] TJ ET BT 26.250 355.452 Td /F5 9.8 Tf [(Attack rate-based versus outcome-based vaccination strategies)] TJ ET BT 26.250 336.048 Td /F1 9.8 Tf [(We evaluated the percent reduction in predicted attack rates, number of hospitalizations, ICU admissions, and deaths under )] TJ ET BT 26.250 324.143 Td /F1 9.8 Tf [(these two strategies, relative to the no intervention scenario. The attack rate-based strategy was most effective at reducing the )] TJ ET BT 26.250 312.238 Td /F1 9.8 Tf [(total number of infections and minimizing hospitalizations when the epidemic peaked in December or January, with minimal )] TJ ET BT 26.250 300.333 Td /F1 9.8 Tf [(difference in the impact of competing strategies on overall attack rates when the epidemic peaked earlier. When there was 30 )] TJ ET BT 26.250 288.429 Td /F1 9.8 Tf [(percent pre-existing immunity in the individuals born prior to 1957 group, there was no preferred strategy for minimizing )] TJ ET BT 26.250 276.524 Td /F1 9.8 Tf [(hospitalizations. Using ICU admissions as the outcome of interest, the outcome-based strategy was preferred when there were )] TJ ET BT 26.250 264.619 Td /F1 9.8 Tf [(low levels of pre-existing immunity, but there was no advantage to using one strategy over the other when immunity in the older )] TJ ET BT 26.250 252.714 Td /F1 9.8 Tf [(age groups was )] TJ ET BT 97.786 252.714 Td /F1 9.8 Tf [(>)] TJ ET BT 103.480 252.714 Td /F1 9.8 Tf [(50 percent. By contrast, when mortality was assessed as the endpoint of interest, an outcome-based strategy )] TJ ET BT 26.250 240.810 Td /F1 9.8 Tf [(was preferred to an attack rate-based strategy for any combination of values for pre-existing immunity and vaccine coverage, )] TJ ET BT 26.250 228.905 Td /F1 9.8 Tf [(with the exception of the assumption of 70 percent immunity to pH1N1 in individuals aged )] TJ ET BT 414.807 228.905 Td /F1 9.8 Tf [(>)] TJ ET BT 420.501 228.905 Td /F1 9.8 Tf [(53 combined with a January peak. )] TJ ET BT 26.250 217.000 Td /F1 9.8 Tf [(Under this latter scenario, there was no difference between strategies.)] TJ ET BT 26.250 197.595 Td /F5 9.8 Tf [(Prioritization of vaccine delivery to individuals with underlying high-risk conditions \(risk-based strategy\))] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(We assessed the effect of preferentially immunizing individuals of any age with an underlying medical condition, prior to )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(implementing an attack rate- or outcome-based strategy. Despite the resulting delay in vaccine allocation to the remaining )] TJ ET BT 26.250 154.381 Td /F1 9.8 Tf [(population, for all scenarios, hospitalizations and ICU admissions were reduced compared to vaccination strategies that did not )] TJ ET BT 26.250 142.476 Td /F1 9.8 Tf [(target high-risk groups \()] TJ ET BT 129.200 142.476 Td /F4 9.8 Tf [(Figure 5)] TJ ET BT 167.128 142.476 Td /F1 9.8 Tf [(\). When the epidemic peak occurred in December or January, this approach had a less marked )] TJ ET BT 26.250 130.572 Td /F1 9.8 Tf [(effect in reducing mortality and resulted in higher cumulative attack rates than strategies that did not prioritize high-risk groups, )] TJ ET BT 26.250 118.667 Td /F1 9.8 Tf [(whereas for an October or November epidemic peak, this approach had a larger effect in reducing mortality.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(9)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 254 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 31110>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((REPEQEQ@ 3E%.h4Q@h%-4Q/4s@ RG>Q/4s@ RG4Q/>s@ RG>Q/4s@ RG4Q/>s@ RG4qGG@qGG@QQQG~4~4qG~4~4qEQQqGG@qGG@QQQG~4~4qG~4~4qEQEPh(ŠJ( )i(֊J((/IQE/IE/Iڊ? ? 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N(—hր—hh((֏ƀ(֏ƀ(hր—hր—hh((֏ƀ(֏ƀ(hր—hր—hh((֏ƀ(֏ƀ(hր—hր—hh(Z()hh=)Q@Q@Q@h'aEzQE'cKފ(; _Z((((((((((((((((((((((((((((( endstream endobj 255 0 obj << /Type /Page /Parent 3 0 R /Contents 256 0 R >> endobj 256 0 obj << /Length 2906 >> stream 0.271 0.267 0.267 rg q 15.000 27.476 577.500 749.524 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I10 Do Q q 450.000 0 0 337.500 26.250 94.500 cm /I11 Do Q 0.271 0.267 0.267 rg BT 26.250 77.476 Td /F4 9.8 Tf [(Fig. 5:)] TJ ET BT 54.964 77.476 Td /F4 9.8 Tf [( Percent reduction in attack rate, hospitalizations, ICU admissions, and total deaths, relative to no vaccination, )] TJ ET BT 26.250 65.571 Td /F4 9.8 Tf [(under different vaccination strategies. )] TJ ET BT 205.591 65.571 Td /F1 9.8 Tf [(The effectiveness of different strategies was evaluated assuming an epidemic peak in )] TJ ET BT 26.250 53.667 Td /F1 9.8 Tf [(\(a\) November, 2009 or \(b\) January, 2010, with vaccination campaigns initiated on November 15, 2009. Results for October, )] TJ ET BT 26.250 41.762 Td /F1 9.8 Tf [(2009 and December, 2009 were similar to November, 2009 and January, 2010, respectively, and are not shown. The impact of )] TJ ET Q q 15.000 27.476 577.500 749.524 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I10 Do Q q 450.000 0 0 337.500 26.250 94.500 cm /I11 Do Q 0.271 0.267 0.267 rg BT 26.250 77.476 Td /F4 9.8 Tf [(Fig. 5:)] TJ ET BT 54.964 77.476 Td /F4 9.8 Tf [( Percent reduction in attack rate, hospitalizations, ICU admissions, and total deaths, relative to no vaccination, )] TJ ET BT 26.250 65.571 Td /F4 9.8 Tf [(under different vaccination strategies. )] TJ ET BT 205.591 65.571 Td /F1 9.8 Tf [(The effectiveness of different strategies was evaluated assuming an epidemic peak in )] TJ ET BT 26.250 53.667 Td /F1 9.8 Tf [(\(a\) November, 2009 or \(b\) January, 2010, with vaccination campaigns initiated on November 15, 2009. Results for October, )] TJ ET BT 26.250 41.762 Td /F1 9.8 Tf [(2009 and December, 2009 were similar to November, 2009 and January, 2010, respectively, and are not shown. The impact of )] TJ ET Q q 15.000 27.476 577.500 749.524 re W n q 450.000 0 0 337.500 26.250 439.500 cm /I10 Do Q q 450.000 0 0 337.500 26.250 94.500 cm /I11 Do Q 0.271 0.267 0.267 rg BT 26.250 77.476 Td /F4 9.8 Tf [(Fig. 5:)] TJ ET BT 54.964 77.476 Td /F4 9.8 Tf [( Percent reduction in attack rate, hospitalizations, ICU admissions, and total deaths, relative to no vaccination, )] TJ ET BT 26.250 65.571 Td /F4 9.8 Tf [(under different vaccination strategies. )] TJ ET BT 205.591 65.571 Td /F1 9.8 Tf [(The effectiveness of different strategies was evaluated assuming an epidemic peak in )] TJ ET BT 26.250 53.667 Td /F1 9.8 Tf [(\(a\) November, 2009 or \(b\) January, 2010, with vaccination campaigns initiated on November 15, 2009. Results for October, )] TJ ET BT 26.250 41.762 Td /F1 9.8 Tf [(2009 and December, 2009 were similar to November, 2009 and January, 2010, respectively, and are not shown. The impact of )] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(10)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 257 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 39606>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((ߌ8o_ ):sMۈbX+IFv#HIXe#H"2F2A=@kw]ZGY-@NqX7C]][㶶 4@$/q\#kYk3xDGq& 1!mO&ofY+"u#\[rs gᎴVL>/Юu-kNV͹K3ŸxG#1T%4ˍF_qi$S]7u[8MG~/CY=[7 <1Fjh]ϯ6ɭ,^sitGwm(W8{'qKϭqG%QQ|I`kGΑ&'~Γ$-"񎙬|wg|o֭}&vUmbxX kfC3^;xgglu"+kM&3woL Z6hѨ4ψ^즼ӼM_C:=RF3X+/RH5=yiC }i8*?)<4W+'t汹e !pؐ8M7?|-׏EѴ}oJՓBTȎ$;C1W3Ҁ:(]gwfJrח Wk`g(ttn2-M;4lFBI (|R|+Xn[E7:-]ȋ?r޵"߇Σkɮi-EyvKebx 4W%|[f_wR [8L. d&?4okc}H\[[EɳaBh`>bJ nȠ+]WHV>yI!/x@ (69֞# ԴBTfAe]IG]+)<[˭]hZ'[3w*B3%5f$rZ_E*'RrV;G<8 (-KǾѭPc\&(nXf?wOuTLִ}Fg-,We cB1h[8 >, ?vs'ԎF #S$(tA4vuj D-a|rr03ހ:.(al:A^OهC==6K rmb7rvu N95;GEx.|CH$յ :|vOo(OaE^3|#~j=YN%Kx"UU X#gCj?v'υ _~}rXP\{Le1L]D8 f_ OmWQ.mݠG[pU^5;GEy_ٯľ>/5X:쵛mV-[U0yʲy[|͛BBMX|  Szw'a]*Wt;NVUrkh_j?v<5V[xkB>ivoni(${F28_7^~McI> :gZE-Ԑ\~|k*. ǡ5~O? 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(h“8()8_“8 SKwݒi]1%Yc8 99b 択zRhs[k$gt%ZG Pvgm JDQ 1b'5/IPdcqG|@oW֗(yj(7120/-x[~zٖmhcl;*ʂz9 znj>kK ?T$D`G7 6H\HoyUkٻj7ң+Y1cb\]K)6I5 A zS`e݋oi~moG|-ikZY(˻UY+K/GHHq@KR~4q@KR~4~4~~qG@ R~qG@ R~~4q@KR~4q@KR~4~4~~qG@ R~qG@ V;xKI'GN[Ie.$1Xxǭp<aͦqa.q$yLc>m+LtM>6gg*,ēIV8)??T;Y1K$B0U 5Kvqq V6as4ۭ[xxWG@Wg-|,lN)C$53[їb#=xuj-!dC2v* cqxZ? 4_ [X+E(G&'gf,Fq  D?g#LNo Xc b[[M:KdY2y W~4q@BMúxb_1Y9bO~zRqE-褠֒JOZ_JOZ=(Gh JZ(()h(i? ? Z9((yO€)? ? ^hi? ? f2~%xH/ I;GI/>ۈ4 l Vp\7fៅ|uLmŪy-ؒcZr=&%{)hWRA:IAe΃̌?UN>|[x¾[?}NVynSL EA+ש!B]ƙ5|1-,w2is$FE{Gdk}HE`#* w]4O.m'Lm 2)~wPĞxwGu/+5;џGJ-a.0I-Q_m~[xOxMyp^=:Ki^H7xl 55tCRo@'ұu_ٯᖷh gQv6VV[W9F |ߎjEt;ɬ o(A3ljLh7Wmm3icv8xڛ??<+a5ɒ(+S W+>bixo⮏xҷubv}y;K~7Lgao d]qҸi8J^h擏J8i8J^h擏J8i8J^h擏J8i8J^h擏J8i8J^h擏J8i8J^h擏J8i8J^hҊ)(()}i)hғך=8J=9Z;ƀ ? (h((Š?(i?_€h((?_Ə€((i?_€Ɠ((?_Ə€h((??_€Ɠ((?_Ɠ(?_Ɠ(??? ? _Ɠ)? _Ɠ)? ?_Ɠ(?_Ɠ(??? ? _Ɠ)? _Ɠ)? ?_Ɠ(?_Ɠ(??? ? _Ɠ)? _Ɠ)? ?_Ɠ(?_Ɠ(?((Z;RRIKI@袊Z? )(h(((𢒖8h8Z9)yN(◚(8^h8h8Z9)yN(◚(8^hZ^hh8h8h?8h?8h??^hZ?^hZ?^hZ^hZ^hh8h8h?8h?8h??^hZ)y J)JZJ_Z=)=i})=xҎzqGnwEQPEQG@Q@~PE/IQQ4/@ QQQR4/IQQ4/@ QQQR4zQǥ/@ ǥzQ4zQǥzQǥ/IǥzR4zQǥ/@ ǥzQ4zQǥzQǥ/IǥzR4zQǥ/@ ǥzQ4zQǥzQǥ/IǥzR4zQǥ/@ ǥzQ4zQGE-%RRI-'ۭv~4QPGEQE~PGE'q@ QRqG'q@ QRqG'q@ QRqG'q@ QRqG'q@ QRqG~'G~'G@GG~4'G~4'GG~'G~'G@GG~4'G~4'GG~'G~'G@GG~4'G~4'GG~'G~'G@Ez@KEGPM((w'cE; (Ҋ(;^Q@ RE-Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@ endstream endobj 259 0 obj << /Type /Page /Parent 3 0 R /Annots [ 262 0 R 264 0 R 266 0 R ] /Contents 260 0 R >> endobj 260 0 obj << /Length 13718 >> stream 0.271 0.267 0.267 rg q 15.000 20.920 577.500 756.080 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(vaccination coverage is also shown, with base case rates representing the lower bound of vaccine uptake in the Canadian )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population, compared to likely upper limits of vaccine uptake. The midpoint of the boxes represents the median percent )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reduction in the outcome of interest, with the upper and lower bounds representing the maximum and minimum reductions, )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(respectively, under varying assumptions of pre-existing immunity in individuals aged ?53 \(i.e., 30%, 50%, or 70%\). Details of the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(different vaccination strategies \(AR, Outcome, High risk/AR, High risk/Outcome\) are outlined in the Methods.)] TJ ET BT 26.250 700.452 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Increasing the length of time to administer the first vaccine dose in all age groups from two to six weeks decreased the )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(effectiveness of vaccination programs when the epidemic peak was in December or January, but did not have an effect when )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(the peak occurred earlier \()] TJ ET BT 140.042 657.238 Td /F4 9.8 Tf [(Figure 6)] TJ ET BT 177.970 657.238 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 309.857 cm /I12 Do Q BT 26.250 292.833 Td /F4 9.8 Tf [(Fig. 6:)] TJ ET BT 54.964 292.833 Td /F4 9.8 Tf [(Percent reduction in attack rate, hospitalizations, ICU admission, and total deaths, relative to no vaccination with )] TJ ET BT 26.250 280.929 Td /F4 9.8 Tf [(different program roll-out lengths. )] TJ ET BT 186.599 280.929 Td /F1 9.8 Tf [(Outcomes were assessed assuming that time to administration of a single dose of vaccine )] TJ ET BT 26.250 269.024 Td /F1 9.8 Tf [(to all age groups was 2, 4, or 6 weeks, with vaccination campaigns commencing on November 15, 2009. Estimates are pooled )] TJ ET BT 26.250 257.119 Td /F1 9.8 Tf [(across vaccination strategy used \(attack rate- and outcome-based\), vaccination coverage \(base case and upper bound\), and )] TJ ET BT 26.250 245.214 Td /F1 9.8 Tf [(levels of pre-existing immunity in individuals aged ?53 \(30%, 50%, and 70%\) and are shown by month of epidemic peak.)] TJ ET BT 26.250 225.810 Td /F1 9.8 Tf [(Reducing vaccine effectiveness in individuals aged ?65 did not have a marked effect on the ranking of vaccination strategies )] TJ ET BT 26.250 213.905 Td /F1 9.8 Tf [(when levels of pre-existing immunity in the pre-1957 group were 30 or 50 percent. With 70 percent pre-existing immunity and )] TJ ET BT 26.250 202.000 Td /F1 9.8 Tf [(lower bound vaccination coverage, reducing vaccine effectiveness to 60 percent or lower resulted in the attack rate-based )] TJ ET BT 26.250 190.095 Td /F1 9.8 Tf [(strategy becoming favoured over outcome-based, when evaluating total deaths as the outcome of interest. Lowering vaccine )] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(effectiveness did not alter the ranking of the strategies when other outcomes \(ICU admissions, hospitalizations, or attack rate\) )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(were the endpoints of interest.)] TJ ET BT 26.250 146.881 Td /F1 9.8 Tf [(Emerging data suggest that a single dose of vaccine may be sufficient to confer protective immunity against infection with )] TJ ET BT 26.250 134.976 Td /F1 9.8 Tf [(pH1N1 )] TJ ET 0.267 0.267 0.267 rg BT 59.303 134.976 Td /F1 9.8 Tf [([29][30])] TJ ET 0.271 0.267 0.267 rg BT 91.829 134.976 Td /F1 9.8 Tf [(. When we tested the impact of a single dose on outcomes, we found no qualitative differences in the rank-order )] TJ ET BT 26.250 123.072 Td /F1 9.8 Tf [(of vaccination strategies under different conditions for the majority of scenarios. However, for a January epidemic peak with high )] TJ ET BT 26.250 111.167 Td /F1 9.8 Tf [(vaccination coverage, the attack rate-based strategy was more attractive than the outcome-based strategy, regardless of which )] TJ ET BT 26.250 99.262 Td /F1 9.8 Tf [(endpoint was evaluated.)] TJ ET BT 26.250 79.857 Td /F1 9.8 Tf [(Increasing the proportion of infectious individuals with asymptomatic influenza reduced the absolute number of cases )] TJ ET BT 26.250 67.953 Td /F1 9.8 Tf [(experiencing severe outcomes, but did not change the relative rankings of the different strategies.)] TJ ET Q q 15.000 20.920 577.500 756.080 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(vaccination coverage is also shown, with base case rates representing the lower bound of vaccine uptake in the Canadian )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population, compared to likely upper limits of vaccine uptake. The midpoint of the boxes represents the median percent )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reduction in the outcome of interest, with the upper and lower bounds representing the maximum and minimum reductions, )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(respectively, under varying assumptions of pre-existing immunity in individuals aged ?53 \(i.e., 30%, 50%, or 70%\). Details of the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(different vaccination strategies \(AR, Outcome, High risk/AR, High risk/Outcome\) are outlined in the Methods.)] TJ ET BT 26.250 700.452 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Increasing the length of time to administer the first vaccine dose in all age groups from two to six weeks decreased the )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(effectiveness of vaccination programs when the epidemic peak was in December or January, but did not have an effect when )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(the peak occurred earlier \()] TJ ET BT 140.042 657.238 Td /F4 9.8 Tf [(Figure 6)] TJ ET BT 177.970 657.238 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 309.857 cm /I12 Do Q BT 26.250 292.833 Td /F4 9.8 Tf [(Fig. 6:)] TJ ET BT 54.964 292.833 Td /F4 9.8 Tf [(Percent reduction in attack rate, hospitalizations, ICU admission, and total deaths, relative to no vaccination with )] TJ ET BT 26.250 280.929 Td /F4 9.8 Tf [(different program roll-out lengths. )] TJ ET BT 186.599 280.929 Td /F1 9.8 Tf [(Outcomes were assessed assuming that time to administration of a single dose of vaccine )] TJ ET BT 26.250 269.024 Td /F1 9.8 Tf [(to all age groups was 2, 4, or 6 weeks, with vaccination campaigns commencing on November 15, 2009. Estimates are pooled )] TJ ET BT 26.250 257.119 Td /F1 9.8 Tf [(across vaccination strategy used \(attack rate- and outcome-based\), vaccination coverage \(base case and upper bound\), and )] TJ ET BT 26.250 245.214 Td /F1 9.8 Tf [(levels of pre-existing immunity in individuals aged ?53 \(30%, 50%, and 70%\) and are shown by month of epidemic peak.)] TJ ET BT 26.250 225.810 Td /F1 9.8 Tf [(Reducing vaccine effectiveness in individuals aged ?65 did not have a marked effect on the ranking of vaccination strategies )] TJ ET BT 26.250 213.905 Td /F1 9.8 Tf [(when levels of pre-existing immunity in the pre-1957 group were 30 or 50 percent. With 70 percent pre-existing immunity and )] TJ ET BT 26.250 202.000 Td /F1 9.8 Tf [(lower bound vaccination coverage, reducing vaccine effectiveness to 60 percent or lower resulted in the attack rate-based )] TJ ET BT 26.250 190.095 Td /F1 9.8 Tf [(strategy becoming favoured over outcome-based, when evaluating total deaths as the outcome of interest. Lowering vaccine )] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(effectiveness did not alter the ranking of the strategies when other outcomes \(ICU admissions, hospitalizations, or attack rate\) )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(were the endpoints of interest.)] TJ ET BT 26.250 146.881 Td /F1 9.8 Tf [(Emerging data suggest that a single dose of vaccine may be sufficient to confer protective immunity against infection with )] TJ ET BT 26.250 134.976 Td /F1 9.8 Tf [(pH1N1 )] TJ ET 0.267 0.267 0.267 rg BT 59.303 134.976 Td /F1 9.8 Tf [([29][30])] TJ ET 0.271 0.267 0.267 rg BT 91.829 134.976 Td /F1 9.8 Tf [(. When we tested the impact of a single dose on outcomes, we found no qualitative differences in the rank-order )] TJ ET BT 26.250 123.072 Td /F1 9.8 Tf [(of vaccination strategies under different conditions for the majority of scenarios. However, for a January epidemic peak with high )] TJ ET BT 26.250 111.167 Td /F1 9.8 Tf [(vaccination coverage, the attack rate-based strategy was more attractive than the outcome-based strategy, regardless of which )] TJ ET BT 26.250 99.262 Td /F1 9.8 Tf [(endpoint was evaluated.)] TJ ET BT 26.250 79.857 Td /F1 9.8 Tf [(Increasing the proportion of infectious individuals with asymptomatic influenza reduced the absolute number of cases )] TJ ET BT 26.250 67.953 Td /F1 9.8 Tf [(experiencing severe outcomes, but did not change the relative rankings of the different strategies.)] TJ ET Q q 15.000 20.920 577.500 756.080 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(vaccination coverage is also shown, with base case rates representing the lower bound of vaccine uptake in the Canadian )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population, compared to likely upper limits of vaccine uptake. The midpoint of the boxes represents the median percent )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reduction in the outcome of interest, with the upper and lower bounds representing the maximum and minimum reductions, )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(respectively, under varying assumptions of pre-existing immunity in individuals aged ?53 \(i.e., 30%, 50%, or 70%\). Details of the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(different vaccination strategies \(AR, Outcome, High risk/AR, High risk/Outcome\) are outlined in the Methods.)] TJ ET BT 26.250 700.452 Td /F5 9.8 Tf [(Sensitivity analyses)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(Increasing the length of time to administer the first vaccine dose in all age groups from two to six weeks decreased the )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(effectiveness of vaccination programs when the epidemic peak was in December or January, but did not have an effect when )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(the peak occurred earlier \()] TJ ET BT 140.042 657.238 Td /F4 9.8 Tf [(Figure 6)] TJ ET BT 177.970 657.238 Td /F1 9.8 Tf [(\).)] TJ ET q 450.000 0 0 337.500 26.250 309.857 cm /I12 Do Q BT 26.250 292.833 Td /F4 9.8 Tf [(Fig. 6:)] TJ ET BT 54.964 292.833 Td /F4 9.8 Tf [(Percent reduction in attack rate, hospitalizations, ICU admission, and total deaths, relative to no vaccination with )] TJ ET BT 26.250 280.929 Td /F4 9.8 Tf [(different program roll-out lengths. )] TJ ET BT 186.599 280.929 Td /F1 9.8 Tf [(Outcomes were assessed assuming that time to administration of a single dose of vaccine )] TJ ET BT 26.250 269.024 Td /F1 9.8 Tf [(to all age groups was 2, 4, or 6 weeks, with vaccination campaigns commencing on November 15, 2009. Estimates are pooled )] TJ ET BT 26.250 257.119 Td /F1 9.8 Tf [(across vaccination strategy used \(attack rate- and outcome-based\), vaccination coverage \(base case and upper bound\), and )] TJ ET BT 26.250 245.214 Td /F1 9.8 Tf [(levels of pre-existing immunity in individuals aged ?53 \(30%, 50%, and 70%\) and are shown by month of epidemic peak.)] TJ ET BT 26.250 225.810 Td /F1 9.8 Tf [(Reducing vaccine effectiveness in individuals aged ?65 did not have a marked effect on the ranking of vaccination strategies )] TJ ET BT 26.250 213.905 Td /F1 9.8 Tf [(when levels of pre-existing immunity in the pre-1957 group were 30 or 50 percent. With 70 percent pre-existing immunity and )] TJ ET BT 26.250 202.000 Td /F1 9.8 Tf [(lower bound vaccination coverage, reducing vaccine effectiveness to 60 percent or lower resulted in the attack rate-based )] TJ ET BT 26.250 190.095 Td /F1 9.8 Tf [(strategy becoming favoured over outcome-based, when evaluating total deaths as the outcome of interest. Lowering vaccine )] TJ ET BT 26.250 178.191 Td /F1 9.8 Tf [(effectiveness did not alter the ranking of the strategies when other outcomes \(ICU admissions, hospitalizations, or attack rate\) )] TJ ET BT 26.250 166.286 Td /F1 9.8 Tf [(were the endpoints of interest.)] TJ ET BT 26.250 146.881 Td /F1 9.8 Tf [(Emerging data suggest that a single dose of vaccine may be sufficient to confer protective immunity against infection with )] TJ ET BT 26.250 134.976 Td /F1 9.8 Tf [(pH1N1 )] TJ ET 0.267 0.267 0.267 rg BT 59.303 134.976 Td /F1 9.8 Tf [([29][30])] TJ ET 0.271 0.267 0.267 rg BT 91.829 134.976 Td /F1 9.8 Tf [(. When we tested the impact of a single dose on outcomes, we found no qualitative differences in the rank-order )] TJ ET BT 26.250 123.072 Td /F1 9.8 Tf [(of vaccination strategies under different conditions for the majority of scenarios. However, for a January epidemic peak with high )] TJ ET BT 26.250 111.167 Td /F1 9.8 Tf [(vaccination coverage, the attack rate-based strategy was more attractive than the outcome-based strategy, regardless of which )] TJ ET BT 26.250 99.262 Td /F1 9.8 Tf [(endpoint was evaluated.)] TJ ET BT 26.250 79.857 Td /F1 9.8 Tf [(Increasing the proportion of infectious individuals with asymptomatic influenza reduced the absolute number of cases )] TJ ET BT 26.250 67.953 Td /F1 9.8 Tf [(experiencing severe outcomes, but did not change the relative rankings of the different strategies.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(11)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 261 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 450 /ColorSpace /DeviceRGB /Filter /DCTDecode /BitsPerComponent 8 /Length 40557>> stream JFIF;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90 C     C   X" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?Q(}ih))h((Q@(1EP(Ҋ(Ҋ((?J(Ҋ(Ҋ((?J( ((((((9((9 ( ((((((9((REPEQEQ@ 3E%.h4Q@h%-4Q/4s@ RG>Q/4s@ RG4Q/>s@ RG>Q/4s@ RG4Q/>s@ RG4qGG@qGG@QQQG~4~4qG~4~4qEQQqGG@qGG@QQQG~4~4qG~4~4qEQEPh(ŠJ( )i(֊J(OJykf49on%cE,7? 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O€>pӿb I;>"..t;쁧0_\ElaD$@eFPpW׫xcO*mJ\~өS]< "F"4—'5#xg[ ,GU60p0VRrr0 ~̿|:N`=|?gp2>-'w;.cW(|?9x;z>ǩoP?{OCo)9HaBA:xVgQuig5}nmB]E >s/€.>sG}xX:^Z DNvG$“i?_“i? _€i? _€i?_“i?_“i? _€i? _€Š(%-%/zQڏJ;Pފ(𢒀ŠJZ(ŠJZ? ))h8^h8N(◚9)y8h8^h8N(◚9)y8h?8h??^hZ?^hZ?^hZ^hZ^hh8h8h?8h?8h??^hZ?^hZ?^hZ^hZ^hh8(ғ֗ғ׊=(Gv@~Qߥ-QPE~QEQGEQQ@ QR4/@ QQ4/IQR4/@ QQ4/IǥzQ4zQǥ/@ ǥzQǥzR4zQǥ/IǥzQ4zQǥ/@ ǥzQǥzR4zQǥ/IǥzQ4zQǥ/@ ǥzQǥzR4zQǥ/IǥzQ4zQǥ/@ ǥ~4PRQ@-%-zGj??;@ GE~4QPEPGE~PQRqG'q@ QRqG'q@ QRqG'q@ QRqG'q@ QRqG'q@KR~4q@KR~4~4~~qG@ R~qG@ R~~4q@KR~4q@KR~4~4~~qG@ R~qG@ R~~4q@KR~4q@KR~4~4~~qG@ R~qG@ R~~4q@KR~4q@KR~4~4~QǭQ@zE(((zRv4Q@ ޓ_Z=(E/PEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQEQE endstream endobj 262 0 obj << /Type /Annot /Subtype /Link /A 263 0 R /Border [0 0 0] /H /I /Rect [ 59.3025 134.0746 91.8285 143.9952 ] >> endobj 263 0 obj << /Type /Action >> endobj 264 0 obj << /Type /Annot /Subtype /Link /A 265 0 R /Border [0 0 0] /H /I /Rect [ 59.3025 134.0746 91.8285 143.9952 ] >> endobj 265 0 obj << /Type /Action >> endobj 266 0 obj << /Type /Annot /Subtype /Link /A 267 0 R /Border [0 0 0] /H /I /Rect [ 59.3025 134.0746 91.8285 143.9952 ] >> endobj 267 0 obj << /Type /Action >> endobj 268 0 obj << /Type /Page /Parent 3 0 R /Annots [ 270 0 R 272 0 R 274 0 R 276 0 R 278 0 R 280 0 R 282 0 R 284 0 R 286 0 R 288 0 R 290 0 R 292 0 R 294 0 R 296 0 R 298 0 R 300 0 R 302 0 R 304 0 R 306 0 R 308 0 R 310 0 R 312 0 R 314 0 R 316 0 R 318 0 R 320 0 R 322 0 R 324 0 R 326 0 R 328 0 R 330 0 R 332 0 R 334 0 R 336 0 R 338 0 R 340 0 R 342 0 R 344 0 R 346 0 R ] /Contents 269 0 R >> endobj 269 0 obj << /Length 28151 >> stream 0.271 0.267 0.267 rg q 15.000 17.806 577.500 759.194 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 730.324 Td /F1 9.8 Tf [(We used a mathematical model to evaluate optimal pH1N1 vaccination strategies, focusing our analysis on the Canadian )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(population and considering the effect of targeting different age groups for prioritization of vaccine allocation on projected )] TJ ET BT 26.250 706.515 Td /F1 9.8 Tf [(hospitalizations and mortality. Depending on the outcome assessed and the assumptions used, both attack rate- and outcome-)] TJ ET BT 26.250 694.610 Td /F1 9.8 Tf [(based strategies were effective in reducing morbidity and mortality, but in most scenarios, delaying vaccine distribution by one )] TJ ET BT 26.250 682.705 Td /F1 9.8 Tf [(week to preferentially immunize individuals with underlying high-risk conditions was the optimal strategy. We observed that the )] TJ ET BT 26.250 670.800 Td /F1 9.8 Tf [(dynamics of pH1N1 transmission is a critical area of uncertainty, with all vaccination strategies having limited impact if the )] TJ ET BT 26.250 658.896 Td /F1 9.8 Tf [(epidemic peak occurs prior to or concomitantly with vaccine availability \(projected for mid-November\).)] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(Our analysis focused on the occurrence of severe outcomes and did not directly consider the effect of vaccination on reducing )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(disease transmission and the resultant downstream effects, such as reduced societal disruption and economic costs \(such as )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(those associated with time lost from work or school\). Additionally, when assessing severe outcomes, there is a need to consider )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(how these outcomes may interact; for instance, a strategy that focuses on reducing mortality at the expense of higher attack )] TJ ET BT 26.250 591.872 Td /F1 9.8 Tf [(rates could lead to the saturation of ICU capacity, resulting in higher mortality in younger age groups than has been observed to )] TJ ET BT 26.250 579.967 Td /F1 9.8 Tf [(date.)] TJ ET BT 26.250 560.562 Td /F1 9.8 Tf [(The epidemiology of pH1N1 appears distinct from that of seasonal influenza \(but similar to that of prior pandemics )] TJ ET 0.267 0.267 0.267 rg BT 519.376 560.562 Td /F1 9.8 Tf [([11])] TJ ET BT 535.639 560.562 Td /F1 9.8 Tf [([31])] TJ ET 0.271 0.267 0.267 rg BT 551.902 560.562 Td /F1 9.8 Tf [(\) in )] TJ ET BT 26.250 548.658 Td /F1 9.8 Tf [(that younger age is associated with the highest attack rates, a phenomenon that has resulted in a higher absolute burden of )] TJ ET BT 26.250 536.753 Td /F1 9.8 Tf [(morbidity and mortality in this age group than is typically observed with seasonal influenza, even though per-case risks of poor )] TJ ET BT 26.250 524.848 Td /F1 9.8 Tf [(outcome may not differ from those seen with seasonal influenza. However, although older age groups are less likely to be )] TJ ET BT 26.250 512.943 Td /F1 9.8 Tf [(infected with the pandemic strain than younger individuals, infections in individuals aged >50 years documented in Ontario have )] TJ ET BT 26.250 501.039 Td /F1 9.8 Tf [(been associated with increased ICU admissions and death )] TJ ET 0.267 0.267 0.267 rg BT 282.031 501.039 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 298.294 501.039 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(Our model assumes that two doses of pH1N1 vaccine will be required to elicit a protective response, but emerging data have )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(demonstrated that a single dose may be sufficiently immunogenic in healthy adults )] TJ ET 0.267 0.267 0.267 rg BT 384.455 469.729 Td /F1 9.8 Tf [([29])] TJ ET BT 400.718 469.729 Td /F1 9.8 Tf [([30])] TJ ET 0.271 0.267 0.267 rg BT 416.981 469.729 Td /F1 9.8 Tf [(. Whether these results extend to )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(children, the elderly, or individuals with underlying medical conditions remains to be seen. The implications of a single dose )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(vaccine are similar to shifting the epidemic peak to later in the winter, resulting in enhanced effectiveness for any vaccination )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(strategy adopted, relative to a two-dose schedule. The preference for an attack rate-based strategy using a single vaccine dose )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(when vaccination coverage is high agrees with a recent study suggesting that targeting age groups at the highest risk of )] TJ ET BT 26.250 410.205 Td /F1 9.8 Tf [(infection may be the optimal solution )] TJ ET 0.267 0.267 0.267 rg BT 186.657 410.205 Td /F1 9.8 Tf [([32])] TJ ET 0.271 0.267 0.267 rg BT 202.920 410.205 Td /F1 9.8 Tf [(, but in our model, this is only the case when vaccine is available well before the )] TJ ET BT 26.250 398.301 Td /F1 9.8 Tf [(epidemic peak. Finally, we evaluated the impact of poor vaccine effectiveness in older individuals on preferred strategies, as )] TJ ET BT 26.250 386.396 Td /F1 9.8 Tf [(this has been a concern with seasonal vaccine )] TJ ET 0.267 0.267 0.267 rg BT 230.015 386.396 Td /F1 9.8 Tf [([33])] TJ ET 0.271 0.267 0.267 rg BT 246.278 386.396 Td /F1 9.8 Tf [(; we found limited impact of decreased effectiveness on the rank-ordering of )] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(preferred strategies except when older individuals were highly likely \(70%\) to be immune to infection in the absence of )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(vaccination, and were effectively pre-vacccinated by early life influenza exposures.)] TJ ET BT 26.250 343.182 Td /F1 9.8 Tf [(Our analysis is subject to several important limitations. As with all mathematic models, this model includes simplifying )] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(assumptions and incorporates parameter values that are subject to some uncertainty. Model calibration to existing data was )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(used to derive estimates of key epidemiologic parameters and these values are in agreement with estimates from other settings )] TJ ET 0.267 0.267 0.267 rg BT 26.250 307.467 Td /F1 9.8 Tf [([34])] TJ ET BT 42.513 307.467 Td /F1 9.8 Tf [([35])] TJ ET 0.271 0.267 0.267 rg BT 58.776 307.467 Td /F1 9.8 Tf [(. We incorporated non-homogeneous mixing patterns between age groups, but did not consider the effect of spatial )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(heterogeneity. However, other studies have demonstrated that estimates of R0 appear to be consistent across locations and )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(spatial scales )] TJ ET 0.267 0.267 0.267 rg BT 87.480 283.658 Td /F1 9.8 Tf [([36])] TJ ET BT 103.743 283.658 Td /F1 9.8 Tf [([37])] TJ ET 0.271 0.267 0.267 rg BT 120.006 283.658 Td /F1 9.8 Tf [(. Some other simplifying assumptions included non-differential transmissibility of influenza by symptomatic )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(and asymptomatic cases and non-incorporation of other concurrent mitigation strategies on influenza transmission, including )] TJ ET BT 26.250 259.848 Td /F1 9.8 Tf [(antivirals and social distancing measures, on influenza transmission. We also did not consider the impact of co-circulating )] TJ ET BT 26.250 247.944 Td /F1 9.8 Tf [(seasonal influenza strains, although recent data suggest that reduced circulation of seasonal strains may be observed in the )] TJ ET BT 26.250 236.039 Td /F1 9.8 Tf [(upcoming influenza season )] TJ ET 0.267 0.267 0.267 rg BT 147.101 236.039 Td /F1 9.8 Tf [([38])] TJ ET BT 163.364 236.039 Td /F1 9.8 Tf [([39])] TJ ET 0.271 0.267 0.267 rg BT 179.627 236.039 Td /F1 9.8 Tf [(. To address the uncertainty in our estimates of mortality and hospitalization rates, due to )] TJ ET BT 26.250 224.134 Td /F1 9.8 Tf [(both the low frequency of occurrence of these outcomes and reporting biases and other limitations inherent in surveillance data, )] TJ ET BT 26.250 212.229 Td /F1 9.8 Tf [(we have focused our analysis on qualitative results.)] TJ ET BT 26.250 192.825 Td /F1 9.8 Tf [(In summary, we have developed an age-structured mathematical model to evaluate optimal vaccination strategies for pH1N1. )] TJ ET BT 26.250 180.920 Td /F1 9.8 Tf [(This model demonstrates the importance of the interaction between pH1N1 transmission dynamics and the demographic )] TJ ET BT 26.250 169.015 Td /F1 9.8 Tf [(characteristics of population at risk of pH1N1 infection on the potential effectiveness of vaccination strategies. It also highlights )] TJ ET BT 26.250 157.110 Td /F1 9.8 Tf [(the value of moving away from strictly age-based vaccination prioritization schemes toward strategies that target high-risk )] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(groups, regardless of age.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 88.649 Td /F1 9.8 Tf [(DF received matching funds from Sanofi-Pasteur for an Ontario Early Researcher Award on pertussis epidemiology. Sanofi-)] TJ ET BT 26.250 76.744 Td /F1 9.8 Tf [(Pasteur manufactures a pandemic influenza vaccine not distributed in Canada. No competing interests declared by the other )] TJ ET BT 26.250 64.839 Td /F1 9.8 Tf [(authors.)] TJ ET Q q 15.000 17.806 577.500 759.194 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 730.324 Td /F1 9.8 Tf [(We used a mathematical model to evaluate optimal pH1N1 vaccination strategies, focusing our analysis on the Canadian )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(population and considering the effect of targeting different age groups for prioritization of vaccine allocation on projected )] TJ ET BT 26.250 706.515 Td /F1 9.8 Tf [(hospitalizations and mortality. Depending on the outcome assessed and the assumptions used, both attack rate- and outcome-)] TJ ET BT 26.250 694.610 Td /F1 9.8 Tf [(based strategies were effective in reducing morbidity and mortality, but in most scenarios, delaying vaccine distribution by one )] TJ ET BT 26.250 682.705 Td /F1 9.8 Tf [(week to preferentially immunize individuals with underlying high-risk conditions was the optimal strategy. We observed that the )] TJ ET BT 26.250 670.800 Td /F1 9.8 Tf [(dynamics of pH1N1 transmission is a critical area of uncertainty, with all vaccination strategies having limited impact if the )] TJ ET BT 26.250 658.896 Td /F1 9.8 Tf [(epidemic peak occurs prior to or concomitantly with vaccine availability \(projected for mid-November\).)] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(Our analysis focused on the occurrence of severe outcomes and did not directly consider the effect of vaccination on reducing )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(disease transmission and the resultant downstream effects, such as reduced societal disruption and economic costs \(such as )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(those associated with time lost from work or school\). Additionally, when assessing severe outcomes, there is a need to consider )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(how these outcomes may interact; for instance, a strategy that focuses on reducing mortality at the expense of higher attack )] TJ ET BT 26.250 591.872 Td /F1 9.8 Tf [(rates could lead to the saturation of ICU capacity, resulting in higher mortality in younger age groups than has been observed to )] TJ ET BT 26.250 579.967 Td /F1 9.8 Tf [(date.)] TJ ET BT 26.250 560.562 Td /F1 9.8 Tf [(The epidemiology of pH1N1 appears distinct from that of seasonal influenza \(but similar to that of prior pandemics )] TJ ET 0.267 0.267 0.267 rg BT 519.376 560.562 Td /F1 9.8 Tf [([11])] TJ ET BT 535.639 560.562 Td /F1 9.8 Tf [([31])] TJ ET 0.271 0.267 0.267 rg BT 551.902 560.562 Td /F1 9.8 Tf [(\) in )] TJ ET BT 26.250 548.658 Td /F1 9.8 Tf [(that younger age is associated with the highest attack rates, a phenomenon that has resulted in a higher absolute burden of )] TJ ET BT 26.250 536.753 Td /F1 9.8 Tf [(morbidity and mortality in this age group than is typically observed with seasonal influenza, even though per-case risks of poor )] TJ ET BT 26.250 524.848 Td /F1 9.8 Tf [(outcome may not differ from those seen with seasonal influenza. However, although older age groups are less likely to be )] TJ ET BT 26.250 512.943 Td /F1 9.8 Tf [(infected with the pandemic strain than younger individuals, infections in individuals aged >50 years documented in Ontario have )] TJ ET BT 26.250 501.039 Td /F1 9.8 Tf [(been associated with increased ICU admissions and death )] TJ ET 0.267 0.267 0.267 rg BT 282.031 501.039 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 298.294 501.039 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(Our model assumes that two doses of pH1N1 vaccine will be required to elicit a protective response, but emerging data have )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(demonstrated that a single dose may be sufficiently immunogenic in healthy adults )] TJ ET 0.267 0.267 0.267 rg BT 384.455 469.729 Td /F1 9.8 Tf [([29])] TJ ET BT 400.718 469.729 Td /F1 9.8 Tf [([30])] TJ ET 0.271 0.267 0.267 rg BT 416.981 469.729 Td /F1 9.8 Tf [(. Whether these results extend to )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(children, the elderly, or individuals with underlying medical conditions remains to be seen. The implications of a single dose )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(vaccine are similar to shifting the epidemic peak to later in the winter, resulting in enhanced effectiveness for any vaccination )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(strategy adopted, relative to a two-dose schedule. The preference for an attack rate-based strategy using a single vaccine dose )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(when vaccination coverage is high agrees with a recent study suggesting that targeting age groups at the highest risk of )] TJ ET BT 26.250 410.205 Td /F1 9.8 Tf [(infection may be the optimal solution )] TJ ET 0.267 0.267 0.267 rg BT 186.657 410.205 Td /F1 9.8 Tf [([32])] TJ ET 0.271 0.267 0.267 rg BT 202.920 410.205 Td /F1 9.8 Tf [(, but in our model, this is only the case when vaccine is available well before the )] TJ ET BT 26.250 398.301 Td /F1 9.8 Tf [(epidemic peak. Finally, we evaluated the impact of poor vaccine effectiveness in older individuals on preferred strategies, as )] TJ ET BT 26.250 386.396 Td /F1 9.8 Tf [(this has been a concern with seasonal vaccine )] TJ ET 0.267 0.267 0.267 rg BT 230.015 386.396 Td /F1 9.8 Tf [([33])] TJ ET 0.271 0.267 0.267 rg BT 246.278 386.396 Td /F1 9.8 Tf [(; we found limited impact of decreased effectiveness on the rank-ordering of )] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(preferred strategies except when older individuals were highly likely \(70%\) to be immune to infection in the absence of )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(vaccination, and were effectively pre-vacccinated by early life influenza exposures.)] TJ ET BT 26.250 343.182 Td /F1 9.8 Tf [(Our analysis is subject to several important limitations. As with all mathematic models, this model includes simplifying )] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(assumptions and incorporates parameter values that are subject to some uncertainty. Model calibration to existing data was )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(used to derive estimates of key epidemiologic parameters and these values are in agreement with estimates from other settings )] TJ ET 0.267 0.267 0.267 rg BT 26.250 307.467 Td /F1 9.8 Tf [([34])] TJ ET BT 42.513 307.467 Td /F1 9.8 Tf [([35])] TJ ET 0.271 0.267 0.267 rg BT 58.776 307.467 Td /F1 9.8 Tf [(. We incorporated non-homogeneous mixing patterns between age groups, but did not consider the effect of spatial )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(heterogeneity. However, other studies have demonstrated that estimates of R0 appear to be consistent across locations and )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(spatial scales )] TJ ET 0.267 0.267 0.267 rg BT 87.480 283.658 Td /F1 9.8 Tf [([36])] TJ ET BT 103.743 283.658 Td /F1 9.8 Tf [([37])] TJ ET 0.271 0.267 0.267 rg BT 120.006 283.658 Td /F1 9.8 Tf [(. Some other simplifying assumptions included non-differential transmissibility of influenza by symptomatic )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(and asymptomatic cases and non-incorporation of other concurrent mitigation strategies on influenza transmission, including )] TJ ET BT 26.250 259.848 Td /F1 9.8 Tf [(antivirals and social distancing measures, on influenza transmission. We also did not consider the impact of co-circulating )] TJ ET BT 26.250 247.944 Td /F1 9.8 Tf [(seasonal influenza strains, although recent data suggest that reduced circulation of seasonal strains may be observed in the )] TJ ET BT 26.250 236.039 Td /F1 9.8 Tf [(upcoming influenza season )] TJ ET 0.267 0.267 0.267 rg BT 147.101 236.039 Td /F1 9.8 Tf [([38])] TJ ET BT 163.364 236.039 Td /F1 9.8 Tf [([39])] TJ ET 0.271 0.267 0.267 rg BT 179.627 236.039 Td /F1 9.8 Tf [(. To address the uncertainty in our estimates of mortality and hospitalization rates, due to )] TJ ET BT 26.250 224.134 Td /F1 9.8 Tf [(both the low frequency of occurrence of these outcomes and reporting biases and other limitations inherent in surveillance data, )] TJ ET BT 26.250 212.229 Td /F1 9.8 Tf [(we have focused our analysis on qualitative results.)] TJ ET BT 26.250 192.825 Td /F1 9.8 Tf [(In summary, we have developed an age-structured mathematical model to evaluate optimal vaccination strategies for pH1N1. )] TJ ET BT 26.250 180.920 Td /F1 9.8 Tf [(This model demonstrates the importance of the interaction between pH1N1 transmission dynamics and the demographic )] TJ ET BT 26.250 169.015 Td /F1 9.8 Tf [(characteristics of population at risk of pH1N1 infection on the potential effectiveness of vaccination strategies. It also highlights )] TJ ET BT 26.250 157.110 Td /F1 9.8 Tf [(the value of moving away from strictly age-based vaccination prioritization schemes toward strategies that target high-risk )] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(groups, regardless of age.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 88.649 Td /F1 9.8 Tf [(DF received matching funds from Sanofi-Pasteur for an Ontario Early Researcher Award on pertussis epidemiology. Sanofi-)] TJ ET BT 26.250 76.744 Td /F1 9.8 Tf [(Pasteur manufactures a pandemic influenza vaccine not distributed in Canada. No competing interests declared by the other )] TJ ET BT 26.250 64.839 Td /F1 9.8 Tf [(authors.)] TJ ET Q q 15.000 17.806 577.500 759.194 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 730.324 Td /F1 9.8 Tf [(We used a mathematical model to evaluate optimal pH1N1 vaccination strategies, focusing our analysis on the Canadian )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(population and considering the effect of targeting different age groups for prioritization of vaccine allocation on projected )] TJ ET BT 26.250 706.515 Td /F1 9.8 Tf [(hospitalizations and mortality. Depending on the outcome assessed and the assumptions used, both attack rate- and outcome-)] TJ ET BT 26.250 694.610 Td /F1 9.8 Tf [(based strategies were effective in reducing morbidity and mortality, but in most scenarios, delaying vaccine distribution by one )] TJ ET BT 26.250 682.705 Td /F1 9.8 Tf [(week to preferentially immunize individuals with underlying high-risk conditions was the optimal strategy. We observed that the )] TJ ET BT 26.250 670.800 Td /F1 9.8 Tf [(dynamics of pH1N1 transmission is a critical area of uncertainty, with all vaccination strategies having limited impact if the )] TJ ET BT 26.250 658.896 Td /F1 9.8 Tf [(epidemic peak occurs prior to or concomitantly with vaccine availability \(projected for mid-November\).)] TJ ET BT 26.250 639.491 Td /F1 9.8 Tf [(Our analysis focused on the occurrence of severe outcomes and did not directly consider the effect of vaccination on reducing )] TJ ET BT 26.250 627.586 Td /F1 9.8 Tf [(disease transmission and the resultant downstream effects, such as reduced societal disruption and economic costs \(such as )] TJ ET BT 26.250 615.681 Td /F1 9.8 Tf [(those associated with time lost from work or school\). Additionally, when assessing severe outcomes, there is a need to consider )] TJ ET BT 26.250 603.777 Td /F1 9.8 Tf [(how these outcomes may interact; for instance, a strategy that focuses on reducing mortality at the expense of higher attack )] TJ ET BT 26.250 591.872 Td /F1 9.8 Tf [(rates could lead to the saturation of ICU capacity, resulting in higher mortality in younger age groups than has been observed to )] TJ ET BT 26.250 579.967 Td /F1 9.8 Tf [(date.)] TJ ET BT 26.250 560.562 Td /F1 9.8 Tf [(The epidemiology of pH1N1 appears distinct from that of seasonal influenza \(but similar to that of prior pandemics )] TJ ET 0.267 0.267 0.267 rg BT 519.376 560.562 Td /F1 9.8 Tf [([11])] TJ ET BT 535.639 560.562 Td /F1 9.8 Tf [([31])] TJ ET 0.271 0.267 0.267 rg BT 551.902 560.562 Td /F1 9.8 Tf [(\) in )] TJ ET BT 26.250 548.658 Td /F1 9.8 Tf [(that younger age is associated with the highest attack rates, a phenomenon that has resulted in a higher absolute burden of )] TJ ET BT 26.250 536.753 Td /F1 9.8 Tf [(morbidity and mortality in this age group than is typically observed with seasonal influenza, even though per-case risks of poor )] TJ ET BT 26.250 524.848 Td /F1 9.8 Tf [(outcome may not differ from those seen with seasonal influenza. However, although older age groups are less likely to be )] TJ ET BT 26.250 512.943 Td /F1 9.8 Tf [(infected with the pandemic strain than younger individuals, infections in individuals aged >50 years documented in Ontario have )] TJ ET BT 26.250 501.039 Td /F1 9.8 Tf [(been associated with increased ICU admissions and death )] TJ ET 0.267 0.267 0.267 rg BT 282.031 501.039 Td /F1 9.8 Tf [([22])] TJ ET 0.271 0.267 0.267 rg BT 298.294 501.039 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 481.634 Td /F1 9.8 Tf [(Our model assumes that two doses of pH1N1 vaccine will be required to elicit a protective response, but emerging data have )] TJ ET BT 26.250 469.729 Td /F1 9.8 Tf [(demonstrated that a single dose may be sufficiently immunogenic in healthy adults )] TJ ET 0.267 0.267 0.267 rg BT 384.455 469.729 Td /F1 9.8 Tf [([29])] TJ ET BT 400.718 469.729 Td /F1 9.8 Tf [([30])] TJ ET 0.271 0.267 0.267 rg BT 416.981 469.729 Td /F1 9.8 Tf [(. Whether these results extend to )] TJ ET BT 26.250 457.824 Td /F1 9.8 Tf [(children, the elderly, or individuals with underlying medical conditions remains to be seen. The implications of a single dose )] TJ ET BT 26.250 445.920 Td /F1 9.8 Tf [(vaccine are similar to shifting the epidemic peak to later in the winter, resulting in enhanced effectiveness for any vaccination )] TJ ET BT 26.250 434.015 Td /F1 9.8 Tf [(strategy adopted, relative to a two-dose schedule. The preference for an attack rate-based strategy using a single vaccine dose )] TJ ET BT 26.250 422.110 Td /F1 9.8 Tf [(when vaccination coverage is high agrees with a recent study suggesting that targeting age groups at the highest risk of )] TJ ET BT 26.250 410.205 Td /F1 9.8 Tf [(infection may be the optimal solution )] TJ ET 0.267 0.267 0.267 rg BT 186.657 410.205 Td /F1 9.8 Tf [([32])] TJ ET 0.271 0.267 0.267 rg BT 202.920 410.205 Td /F1 9.8 Tf [(, but in our model, this is only the case when vaccine is available well before the )] TJ ET BT 26.250 398.301 Td /F1 9.8 Tf [(epidemic peak. Finally, we evaluated the impact of poor vaccine effectiveness in older individuals on preferred strategies, as )] TJ ET BT 26.250 386.396 Td /F1 9.8 Tf [(this has been a concern with seasonal vaccine )] TJ ET 0.267 0.267 0.267 rg BT 230.015 386.396 Td /F1 9.8 Tf [([33])] TJ ET 0.271 0.267 0.267 rg BT 246.278 386.396 Td /F1 9.8 Tf [(; we found limited impact of decreased effectiveness on the rank-ordering of )] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(preferred strategies except when older individuals were highly likely \(70%\) to be immune to infection in the absence of )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(vaccination, and were effectively pre-vacccinated by early life influenza exposures.)] TJ ET BT 26.250 343.182 Td /F1 9.8 Tf [(Our analysis is subject to several important limitations. As with all mathematic models, this model includes simplifying )] TJ ET BT 26.250 331.277 Td /F1 9.8 Tf [(assumptions and incorporates parameter values that are subject to some uncertainty. Model calibration to existing data was )] TJ ET BT 26.250 319.372 Td /F1 9.8 Tf [(used to derive estimates of key epidemiologic parameters and these values are in agreement with estimates from other settings )] TJ ET 0.267 0.267 0.267 rg BT 26.250 307.467 Td /F1 9.8 Tf [([34])] TJ ET BT 42.513 307.467 Td /F1 9.8 Tf [([35])] TJ ET 0.271 0.267 0.267 rg BT 58.776 307.467 Td /F1 9.8 Tf [(. We incorporated non-homogeneous mixing patterns between age groups, but did not consider the effect of spatial )] TJ ET BT 26.250 295.563 Td /F1 9.8 Tf [(heterogeneity. However, other studies have demonstrated that estimates of R0 appear to be consistent across locations and )] TJ ET BT 26.250 283.658 Td /F1 9.8 Tf [(spatial scales )] TJ ET 0.267 0.267 0.267 rg BT 87.480 283.658 Td /F1 9.8 Tf [([36])] TJ ET BT 103.743 283.658 Td /F1 9.8 Tf [([37])] TJ ET 0.271 0.267 0.267 rg BT 120.006 283.658 Td /F1 9.8 Tf [(. Some other simplifying assumptions included non-differential transmissibility of influenza by symptomatic )] TJ ET BT 26.250 271.753 Td /F1 9.8 Tf [(and asymptomatic cases and non-incorporation of other concurrent mitigation strategies on influenza transmission, including )] TJ ET BT 26.250 259.848 Td /F1 9.8 Tf [(antivirals and social distancing measures, on influenza transmission. We also did not consider the impact of co-circulating )] TJ ET BT 26.250 247.944 Td /F1 9.8 Tf [(seasonal influenza strains, although recent data suggest that reduced circulation of seasonal strains may be observed in the )] TJ ET BT 26.250 236.039 Td /F1 9.8 Tf [(upcoming influenza season )] TJ ET 0.267 0.267 0.267 rg BT 147.101 236.039 Td /F1 9.8 Tf [([38])] TJ ET BT 163.364 236.039 Td /F1 9.8 Tf [([39])] TJ ET 0.271 0.267 0.267 rg BT 179.627 236.039 Td /F1 9.8 Tf [(. To address the uncertainty in our estimates of mortality and hospitalization rates, due to )] TJ ET BT 26.250 224.134 Td /F1 9.8 Tf [(both the low frequency of occurrence of these outcomes and reporting biases and other limitations inherent in surveillance data, )] TJ ET BT 26.250 212.229 Td /F1 9.8 Tf [(we have focused our analysis on qualitative results.)] TJ ET BT 26.250 192.825 Td /F1 9.8 Tf [(In summary, we have developed an age-structured mathematical model to evaluate optimal vaccination strategies for pH1N1. )] TJ ET BT 26.250 180.920 Td /F1 9.8 Tf [(This model demonstrates the importance of the interaction between pH1N1 transmission dynamics and the demographic )] TJ ET BT 26.250 169.015 Td /F1 9.8 Tf [(characteristics of population at risk of pH1N1 infection on the potential effectiveness of vaccination strategies. It also highlights )] TJ ET BT 26.250 157.110 Td /F1 9.8 Tf [(the value of moving away from strictly age-based vaccination prioritization schemes toward strategies that target high-risk )] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(groups, regardless of age.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(Competing Interests)] TJ ET BT 26.250 88.649 Td /F1 9.8 Tf [(DF received matching funds from Sanofi-Pasteur for an Ontario Early Researcher Award on pertussis epidemiology. Sanofi-)] TJ ET BT 26.250 76.744 Td /F1 9.8 Tf [(Pasteur manufactures a pandemic influenza vaccine not distributed in Canada. No competing interests declared by the other )] TJ ET BT 26.250 64.839 Td /F1 9.8 Tf [(authors.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(12)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 270 0 obj << /Type /Annot /Subtype /Link /A 271 0 R /Border [0 0 0] /H /I /Rect [ 519.3757 559.6606 535.6387 569.5812 ] >> endobj 271 0 obj << /Type /Action >> endobj 272 0 obj << /Type /Annot /Subtype /Link /A 273 0 R /Border [0 0 0] /H /I /Rect [ 535.6387 559.6606 551.9017 569.5812 ] >> endobj 273 0 obj << /Type /Action >> endobj 274 0 obj << /Type /Annot /Subtype /Link /A 275 0 R /Border [0 0 0] /H /I /Rect [ 282.0315 500.1368 298.2945 510.0575 ] >> endobj 275 0 obj << /Type /Action >> endobj 276 0 obj << /Type /Annot /Subtype /Link /A 277 0 R /Border [0 0 0] /H /I /Rect [ 384.4552 468.8273 400.7182 478.7479 ] >> endobj 277 0 obj << /Type /Action >> endobj 278 0 obj << /Type /Annot /Subtype /Link /A 279 0 R /Border [0 0 0] /H 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ET BT 26.250 730.324 Td /F1 9.8 Tf [(We thank Michael Campitelli and Ruth Sanderson for providing data, and Barbara Law and Susan Tamblyn for helpful )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(discussions related to plausible vaccination strategies. The opinions, results and conclusions reported in this paper are those of )] TJ ET BT 26.250 706.515 Td /F1 9.8 Tf [(the authors and are independent from the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or )] TJ ET BT 26.250 694.610 Td /F1 9.8 Tf [(the Ontario Ministry of Health and Long-Term Care is intended or should be inferred.)] TJ ET BT 26.250 665.507 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 638.053 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 638.053 Td /F1 9.8 Tf [(Chan M World now at the start of 2009 influenza pandemic \(June 11, 2009\). Retrieved 26 Jul 2009, from )] TJ ET BT 26.250 626.148 Td /F1 9.8 Tf [(http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/.)] TJ ET BT 26.250 606.744 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 606.744 Td /F1 9.8 Tf [(National Advisory Committee on Immunization \(2008\) Statement on influenza vaccination for the 2008-2009 season. An )] TJ ET BT 26.250 594.839 Td /F1 9.8 Tf [(Advisory Committee Statement \(ACS\). Can Commun Dis Rep 34: 1-46.)] TJ ET BT 26.250 575.434 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 575.434 Td /F1 9.8 Tf [(Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E \(2007\) Effectiveness of influenza vaccine in the community-dwelling )] TJ ET BT 26.250 563.529 Td /F1 9.8 Tf [(elderly. N Engl J Med 357: 1373-1381.)] TJ ET BT 26.250 544.125 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 544.125 Td /F1 9.8 Tf [(Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA \(2007\) Mortality benefits of influenza vaccination in elderly people: )] TJ ET BT 26.250 532.220 Td /F1 9.8 Tf [(an ongoing controversy. Lancet Infect Dis 7: 658-666.)] TJ ET BT 26.250 512.815 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 512.815 Td /F1 9.8 Tf [(Goodwin K, Viboud C, Simonsen L \(2006\) Antibody response to influenza vaccination in the elderly: a quantitative review. )] TJ ET BT 26.250 500.910 Td /F1 9.8 Tf [(Vaccine 24: 1159-1169.)] TJ ET BT 26.250 481.506 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 481.506 Td /F1 9.8 Tf [(Galvani AP, Reluga TC, Chapman GB \(2007\) Long-standing influenza vaccination policy is in accord with individual self-)] TJ ET BT 26.250 469.601 Td /F1 9.8 Tf [(interest but not with the utilitarian optimum. Proc Natl Acad Sci U S A 104: 5692-5697.)] TJ ET BT 26.250 450.196 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 450.196 Td /F1 9.8 Tf [(Negri E, Colombo C, Giordano L, Groth N, Apolone G, et al. \(2005\) Influenza vaccine in healthy children: a meta-analysis. )] TJ ET BT 26.250 438.291 Td /F1 9.8 Tf [(Vaccine 23: 2851-2861.)] TJ ET BT 26.250 418.887 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 418.887 Td /F1 9.8 Tf [(Smith S, Demicheli V, Di Pietrantonj C, Harnden AR, Jefferson T, et al. \(2006\) Vaccines for preventing influenza in healthy )] TJ ET BT 26.250 406.982 Td /F1 9.8 Tf [(children. Cochrane Db Syst Rev \(Online\) 1: CD004879.)] TJ ET BT 26.250 387.577 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 387.577 Td /F1 9.8 Tf [(Manzoli L, Schioppa F, Boccia A, Villari P \(2007\) The efficacy of influenza vaccine for healthy children: a meta-analysis )] TJ ET BT 26.250 375.672 Td /F1 9.8 Tf [(evaluating potential sources of variation in efficacy estimates including study quality. Pediatr Infect Dis J 26: 97-106.)] TJ ET BT 26.250 356.268 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 356.268 Td /F1 9.8 Tf [(Ahmed R, Oldstone MB, Palese P \(2007\) Protective immunity and susceptibility to infectious diseases: lessons from the )] TJ ET BT 26.250 344.363 Td /F1 9.8 Tf [(1918 influenza pandemic. Nat Immunol 8: 1188-1193.)] TJ ET BT 26.250 324.958 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 324.958 Td /F1 9.8 Tf [(Miller MA, Viboud C, Balinska M, Simonsen L \(2009\) The signature features of influenza pandemics -- implications for )] TJ ET BT 26.250 313.053 Td /F1 9.8 Tf [(policy. N Engl J Med.)] TJ ET BT 26.250 293.649 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 293.649 Td /F1 9.8 Tf [(Fisman DN, Savage R, Gubbay J, Achonu C, Akwar H, et al. \(2009\) Older age and a reduced likelihood of 2009 H1N1 virus )] TJ ET BT 26.250 281.744 Td /F1 9.8 Tf [(infection. N Engl J Med 361: 2000-2001.)] TJ ET BT 26.250 262.339 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 262.339 Td /F1 9.8 Tf [(Miller MA, Viboud C, Olson DR, Grais RF, Rabaa MA, et al. \(2008\) Prioritization of influenza pandemic vaccination to )] TJ ET BT 26.250 250.434 Td /F1 9.8 Tf [(minimize years of life lost. J Infect Dis 198: 305-311.)] TJ ET BT 26.250 231.030 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 231.030 Td /F1 9.8 Tf [(Fraser C, Riley S, Anderson RM, Ferguson NM \(2004\) Factors that make an infectious disease outbreak controllable. Proc )] TJ ET BT 26.250 219.125 Td /F1 9.8 Tf [(Natl Acad Sci U S A 101: 6146-6151.)] TJ ET BT 26.250 199.720 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 199.720 Td /F1 9.8 Tf [(Statistics Canada. Age and sex highlight tables, 2006 Census, catalogue number 97-551-XWE2006002, released 17 Jul )] TJ ET BT 26.250 187.815 Td /F1 9.8 Tf [(2007.)] TJ ET BT 26.250 168.411 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 168.411 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, et al. \(2009\) Severe respiratory disease )] TJ ET BT 26.250 156.506 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med 361: 674-679.)] TJ ET BT 26.250 137.101 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 137.101 Td /F1 9.8 Tf [(Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. \(2009\) Emergence of a novel swine-origin influenza A \(H1N1\) )] TJ ET BT 26.250 125.196 Td /F1 9.8 Tf [(virus in humans. N Engl J Med 360: 2605-2615.)] TJ ET BT 26.250 105.792 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 105.792 Td /F1 9.8 Tf [(Mossong J, Hens N, Jit M, Beutels P, Auranen K, et al. \(2008\) Social contacts and mixing patterns relevant to the spread of )] TJ ET BT 26.250 93.887 Td /F1 9.8 Tf [(infectious diseases. PLoS Med 5: e74.)] TJ ET BT 26.250 74.482 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 74.482 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(live births\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 62.577 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65b-eng.htm.)] TJ ET Q q 15.000 52.696 577.500 724.304 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 730.324 Td /F1 9.8 Tf [(We thank Michael Campitelli and Ruth Sanderson for providing data, and Barbara Law and Susan Tamblyn for helpful )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(discussions related to plausible vaccination strategies. The opinions, results and conclusions reported in this paper are those of )] TJ ET BT 26.250 706.515 Td /F1 9.8 Tf [(the authors and are independent from the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or )] TJ ET BT 26.250 694.610 Td /F1 9.8 Tf [(the Ontario Ministry of Health and Long-Term Care is intended or should be inferred.)] TJ ET BT 26.250 665.507 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 638.053 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 638.053 Td /F1 9.8 Tf [(Chan M World now at the start of 2009 influenza pandemic \(June 11, 2009\). Retrieved 26 Jul 2009, from )] TJ ET BT 26.250 626.148 Td /F1 9.8 Tf [(http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/.)] TJ ET BT 26.250 606.744 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 606.744 Td /F1 9.8 Tf [(National Advisory Committee on Immunization \(2008\) Statement on influenza vaccination for the 2008-2009 season. An )] TJ ET BT 26.250 594.839 Td /F1 9.8 Tf [(Advisory Committee Statement \(ACS\). Can Commun Dis Rep 34: 1-46.)] TJ ET BT 26.250 575.434 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 575.434 Td /F1 9.8 Tf [(Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E \(2007\) Effectiveness of influenza vaccine in the community-dwelling )] TJ ET BT 26.250 563.529 Td /F1 9.8 Tf [(elderly. N Engl J Med 357: 1373-1381.)] TJ ET BT 26.250 544.125 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 544.125 Td /F1 9.8 Tf [(Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA \(2007\) Mortality benefits of influenza vaccination in elderly people: )] TJ ET BT 26.250 532.220 Td /F1 9.8 Tf [(an ongoing controversy. Lancet Infect Dis 7: 658-666.)] TJ ET BT 26.250 512.815 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 512.815 Td /F1 9.8 Tf [(Goodwin K, Viboud C, Simonsen L \(2006\) Antibody response to influenza vaccination in the elderly: a quantitative review. )] TJ ET BT 26.250 500.910 Td /F1 9.8 Tf [(Vaccine 24: 1159-1169.)] TJ ET BT 26.250 481.506 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 481.506 Td /F1 9.8 Tf [(Galvani AP, Reluga TC, Chapman GB \(2007\) Long-standing influenza vaccination policy is in accord with individual self-)] TJ ET BT 26.250 469.601 Td /F1 9.8 Tf [(interest but not with the utilitarian optimum. Proc Natl Acad Sci U S A 104: 5692-5697.)] TJ ET BT 26.250 450.196 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 450.196 Td /F1 9.8 Tf [(Negri E, Colombo C, Giordano L, Groth N, Apolone G, et al. \(2005\) Influenza vaccine in healthy children: a meta-analysis. )] TJ ET BT 26.250 438.291 Td /F1 9.8 Tf [(Vaccine 23: 2851-2861.)] TJ ET BT 26.250 418.887 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 418.887 Td /F1 9.8 Tf [(Smith S, Demicheli V, Di Pietrantonj C, Harnden AR, Jefferson T, et al. \(2006\) Vaccines for preventing influenza in healthy )] TJ ET BT 26.250 406.982 Td /F1 9.8 Tf [(children. Cochrane Db Syst Rev \(Online\) 1: CD004879.)] TJ ET BT 26.250 387.577 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 387.577 Td /F1 9.8 Tf [(Manzoli L, Schioppa F, Boccia A, Villari P \(2007\) The efficacy of influenza vaccine for healthy children: a meta-analysis )] TJ ET BT 26.250 375.672 Td /F1 9.8 Tf [(evaluating potential sources of variation in efficacy estimates including study quality. Pediatr Infect Dis J 26: 97-106.)] TJ ET BT 26.250 356.268 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 356.268 Td /F1 9.8 Tf [(Ahmed R, Oldstone MB, Palese P \(2007\) Protective immunity and susceptibility to infectious diseases: lessons from the )] TJ ET BT 26.250 344.363 Td /F1 9.8 Tf [(1918 influenza pandemic. Nat Immunol 8: 1188-1193.)] TJ ET BT 26.250 324.958 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 324.958 Td /F1 9.8 Tf [(Miller MA, Viboud C, Balinska M, Simonsen L \(2009\) The signature features of influenza pandemics -- implications for )] TJ ET BT 26.250 313.053 Td /F1 9.8 Tf [(policy. N Engl J Med.)] TJ ET BT 26.250 293.649 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 293.649 Td /F1 9.8 Tf [(Fisman DN, Savage R, Gubbay J, Achonu C, Akwar H, et al. \(2009\) Older age and a reduced likelihood of 2009 H1N1 virus )] TJ ET BT 26.250 281.744 Td /F1 9.8 Tf [(infection. N Engl J Med 361: 2000-2001.)] TJ ET BT 26.250 262.339 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 262.339 Td /F1 9.8 Tf [(Miller MA, Viboud C, Olson DR, Grais RF, Rabaa MA, et al. \(2008\) Prioritization of influenza pandemic vaccination to )] TJ ET BT 26.250 250.434 Td /F1 9.8 Tf [(minimize years of life lost. J Infect Dis 198: 305-311.)] TJ ET BT 26.250 231.030 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 231.030 Td /F1 9.8 Tf [(Fraser C, Riley S, Anderson RM, Ferguson NM \(2004\) Factors that make an infectious disease outbreak controllable. Proc )] TJ ET BT 26.250 219.125 Td /F1 9.8 Tf [(Natl Acad Sci U S A 101: 6146-6151.)] TJ ET BT 26.250 199.720 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 199.720 Td /F1 9.8 Tf [(Statistics Canada. Age and sex highlight tables, 2006 Census, catalogue number 97-551-XWE2006002, released 17 Jul )] TJ ET BT 26.250 187.815 Td /F1 9.8 Tf [(2007.)] TJ ET BT 26.250 168.411 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 168.411 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, et al. \(2009\) Severe respiratory disease )] TJ ET BT 26.250 156.506 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med 361: 674-679.)] TJ ET BT 26.250 137.101 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 137.101 Td /F1 9.8 Tf [(Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. \(2009\) Emergence of a novel swine-origin influenza A \(H1N1\) )] TJ ET BT 26.250 125.196 Td /F1 9.8 Tf [(virus in humans. N Engl J Med 360: 2605-2615.)] TJ ET BT 26.250 105.792 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 105.792 Td /F1 9.8 Tf [(Mossong J, Hens N, Jit M, Beutels P, Auranen K, et al. \(2008\) Social contacts and mixing patterns relevant to the spread of )] TJ ET BT 26.250 93.887 Td /F1 9.8 Tf [(infectious diseases. PLoS Med 5: e74.)] TJ ET BT 26.250 74.482 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 74.482 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(live births\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 62.577 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65b-eng.htm.)] TJ ET Q q 15.000 52.696 577.500 724.304 re W n 0.271 0.267 0.267 rg BT 26.250 750.278 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 730.324 Td /F1 9.8 Tf [(We thank Michael Campitelli and Ruth Sanderson for providing data, and Barbara Law and Susan Tamblyn for helpful )] TJ ET BT 26.250 718.419 Td /F1 9.8 Tf [(discussions related to plausible vaccination strategies. 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Age and sex highlight tables, 2006 Census, catalogue number 97-551-XWE2006002, released 17 Jul )] TJ ET BT 26.250 187.815 Td /F1 9.8 Tf [(2007.)] TJ ET BT 26.250 168.411 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 168.411 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, et al. \(2009\) Severe respiratory disease )] TJ ET BT 26.250 156.506 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med 361: 674-679.)] TJ ET BT 26.250 137.101 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 137.101 Td /F1 9.8 Tf [(Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. \(2009\) Emergence of a novel swine-origin influenza A \(H1N1\) )] TJ ET BT 26.250 125.196 Td /F1 9.8 Tf [(virus in humans. N Engl J Med 360: 2605-2615.)] TJ ET BT 26.250 105.792 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 105.792 Td /F1 9.8 Tf [(Mossong J, Hens N, Jit M, Beutels P, Auranen K, et al. \(2008\) Social contacts and mixing patterns relevant to the spread of )] TJ ET BT 26.250 93.887 Td /F1 9.8 Tf [(infectious diseases. PLoS Med 5: e74.)] TJ ET BT 26.250 74.482 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 74.482 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(live births\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 62.577 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65b-eng.htm.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(13)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 350 0 obj << /Type /Page /Parent 3 0 R /Contents 351 0 R >> endobj 351 0 obj << /Length 17282 >> stream 0.271 0.267 0.267 rg q 15.000 195.334 577.500 581.666 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(total pregnancies\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65a-eng.htm.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Meyers LA \(2006\) A comparative analysis of influenza vaccination programs. 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Retrieved 3 Nov 2009, from http://www.phac-)] TJ ET BT 26.250 533.310 Td /F1 9.8 Tf [(aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php.)] TJ ET BT 26.250 513.905 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 513.905 Td /F1 9.8 Tf [(Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, et al. \(2009\) Trial of influenza A \(H1N1\) 2009 monovalent MF59-)] TJ ET BT 26.250 502.000 Td /F1 9.8 Tf [(adjuvanted vaccine -- preliminary report. N Engl J Med.)] TJ ET BT 26.250 482.595 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 482.595 Td /F1 9.8 Tf [(Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, et al. \(2009\) Response after one dose of a monovalent )] TJ ET BT 26.250 470.691 Td /F1 9.8 Tf [(influenza A \(H1N1\) 2009 vaccine -- preliminary report. 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Euro Surveill 14.)] TJ ET Q q 15.000 195.334 577.500 581.666 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(total pregnancies\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65a-eng.htm.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Meyers LA \(2006\) A comparative analysis of influenza vaccination programs. PLoS Med 3: e387.)] TJ ET BT 26.250 709.262 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 709.262 Td /F1 9.8 Tf [(Tuite AR, Greer AL, Whelan M, Winter AL, Lee B, et al. \(2009\) Estimated epidemiologic parameters and morbidity )] TJ ET BT 26.250 697.357 Td /F1 9.8 Tf [(associated with pandemic H1N1 influenza. CMAJ.)] TJ ET BT 26.250 677.952 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 677.952 Td /F1 9.8 Tf [(\(2009\) Serum cross-reactive antibody response to a novel influenza A \(H1N1\) virus after vaccination with seasonal )] TJ ET BT 26.250 666.048 Td /F1 9.8 Tf [(influenza vaccine. MMWR Morb Mortal Wkly Rep 58: 521-524.)] TJ ET BT 26.250 646.643 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 646.643 Td /F1 9.8 Tf [(Wilson N, Baker MG \(2009\) The emerging influenza pandemic: estimating the case fatality ratio. Euro Surveill 14.)] TJ ET BT 26.250 627.238 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 627.238 Td /F1 9.8 Tf [(Beland Y \(2002\) Canadian community health survey--methodological overview. Health Rep 13: 9-14.)] TJ ET BT 26.250 607.833 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 607.833 Td /F1 9.8 Tf [(Kwong JC, Stukel TA, Lim J, McGeer AJ, Upshur RE, et al. \(2008\) The effect of universal influenza immunization on )] TJ ET BT 26.250 595.929 Td /F1 9.8 Tf [(mortality and health care use. PLoS Med 5: e211.)] TJ ET BT 26.250 576.524 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 576.524 Td /F1 9.8 Tf [(Bingle CL, Holowaty PH, Koren IE, Picard L, Stewart PJ, et al. \(2005\) An evaluation of the Ontario Rapid Risk Factor )] TJ ET BT 26.250 564.619 Td /F1 9.8 Tf [(Surveillance System. Can J Public Health 96: 145-150.)] TJ ET BT 26.250 545.214 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 545.214 Td /F1 9.8 Tf [(Public Health Agency of Canada Guidance on H1N1 flu vaccine sequencing. Retrieved 3 Nov 2009, from http://www.phac-)] TJ ET BT 26.250 533.310 Td /F1 9.8 Tf [(aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php.)] TJ ET BT 26.250 513.905 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 513.905 Td /F1 9.8 Tf [(Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, et al. \(2009\) Trial of influenza A \(H1N1\) 2009 monovalent MF59-)] TJ ET BT 26.250 502.000 Td /F1 9.8 Tf [(adjuvanted vaccine -- preliminary report. N Engl J Med.)] TJ ET BT 26.250 482.595 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 482.595 Td /F1 9.8 Tf [(Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, et al. \(2009\) Response after one dose of a monovalent )] TJ ET BT 26.250 470.691 Td /F1 9.8 Tf [(influenza A \(H1N1\) 2009 vaccine -- preliminary report. N Engl J Med.)] TJ ET BT 26.250 451.286 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 451.286 Td /F1 9.8 Tf [(Henderson DA, Courtney B, Inglesby TV, Toner E, Nuzzo JB \(2009\) Public health and medical responses to the 1957-58 )] TJ ET BT 26.250 439.381 Td /F1 9.8 Tf [(influenza pandemic. Biosecur Bioterror.)] TJ ET BT 26.250 419.976 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 419.976 Td /F1 9.8 Tf [(Medlock J, Galvani AP \(2009\) Optimizing influenza vaccine distribution. Science 325: 1705-1708.)] TJ ET BT 26.250 400.572 Td /F1 9.8 Tf [(33.)] TJ ET BT 43.553 400.572 Td /F1 9.8 Tf [(Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, et al. \(2005\) Impact of influenza vaccination on seasonal )] TJ ET BT 26.250 388.667 Td /F1 9.8 Tf [(mortality in the US elderly population. Arch Intern Med 165: 265-272.)] TJ ET BT 26.250 369.262 Td /F1 9.8 Tf [(34.)] TJ ET BT 43.553 369.262 Td /F1 9.8 Tf [(Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, et al. \(2009\) Pandemic potential of a strain of )] TJ ET BT 26.250 357.357 Td /F1 9.8 Tf [(influenza A \(H1N1\): early findings. Science 324: 1557-1561.)] TJ ET BT 26.250 337.953 Td /F1 9.8 Tf [(35.)] TJ ET BT 43.553 337.953 Td /F1 9.8 Tf [(Pourbohloul B, Ahued A, Davoudi B, Meza R, Meyers LA, et al. \(2009\) Initial human transmission dynamics of the pandemic )] TJ ET BT 26.250 326.048 Td /F1 9.8 Tf [(\(H1N1\) 2009 virus in North America. Influenza Other Respi Viruses 3: 215-222.)] TJ ET BT 26.250 306.643 Td /F1 9.8 Tf [(36.)] TJ ET BT 43.553 306.643 Td /F1 9.8 Tf [(Mills CE, Robins JM, Lipsitch M \(2004\) Transmissibility of 1918 pandemic influenza. Nature 432: 904-906.)] TJ ET BT 26.250 287.238 Td /F1 9.8 Tf [(37.)] TJ ET BT 43.553 287.238 Td /F1 9.8 Tf [(Viboud C, Bjornstad ON, Smith DL, Simonsen L, Miller MA, et al. \(2006\) Synchrony, waves, and spatial hierarchies in the )] TJ ET BT 26.250 275.334 Td /F1 9.8 Tf [(spread of influenza. Science 312: 447-451.)] TJ ET BT 26.250 255.929 Td /F1 9.8 Tf [(38.)] TJ ET BT 43.553 255.929 Td /F1 9.8 Tf [(Uphoff H, Geis S, Gruber A, Hauri A \(2009\) What will the next influenza season bring about: seasonal influenza or the new )] TJ ET BT 26.250 244.024 Td /F1 9.8 Tf [(A\(H1N1\)v? An analysis of German influenza surveillance data. Euro Surveill 14.)] TJ ET BT 26.250 224.619 Td /F1 9.8 Tf [(39.)] TJ ET BT 43.553 224.619 Td /F1 9.8 Tf [(Kelly H, Grant K \(2009\) Interim analysis of pandemic influenza \(H1N1\) 2009 in Australia: surveillance trends, age of )] TJ ET BT 26.250 212.715 Td /F1 9.8 Tf [(infection and effectiveness of seasonal vaccination. Euro Surveill 14.)] TJ ET Q q 15.000 195.334 577.500 581.666 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Statistics Canada. Pregnancy outcomes by age group \(total pregnancies\). Retrieved 21 Aug 2009, from )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(http://www40.statcan.gc.ca/l01/cst01/hlth65a-eng.htm.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Meyers LA \(2006\) A comparative analysis of influenza vaccination programs. PLoS Med 3: e387.)] TJ ET BT 26.250 709.262 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 709.262 Td /F1 9.8 Tf [(Tuite AR, Greer AL, Whelan M, Winter AL, Lee B, et al. \(2009\) Estimated epidemiologic parameters and morbidity )] TJ ET BT 26.250 697.357 Td /F1 9.8 Tf [(associated with pandemic H1N1 influenza. CMAJ.)] TJ ET BT 26.250 677.952 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 677.952 Td /F1 9.8 Tf [(\(2009\) Serum cross-reactive antibody response to a novel influenza A \(H1N1\) virus after vaccination with seasonal )] TJ ET BT 26.250 666.048 Td /F1 9.8 Tf [(influenza vaccine. MMWR Morb Mortal Wkly Rep 58: 521-524.)] TJ ET BT 26.250 646.643 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 646.643 Td /F1 9.8 Tf [(Wilson N, Baker MG \(2009\) The emerging influenza pandemic: estimating the case fatality ratio. Euro Surveill 14.)] TJ ET BT 26.250 627.238 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 627.238 Td /F1 9.8 Tf [(Beland Y \(2002\) Canadian community health survey--methodological overview. Health Rep 13: 9-14.)] TJ ET BT 26.250 607.833 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 607.833 Td /F1 9.8 Tf [(Kwong JC, Stukel TA, Lim J, McGeer AJ, Upshur RE, et al. \(2008\) The effect of universal influenza immunization on )] TJ ET BT 26.250 595.929 Td /F1 9.8 Tf [(mortality and health care use. PLoS Med 5: e211.)] TJ ET BT 26.250 576.524 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 576.524 Td /F1 9.8 Tf [(Bingle CL, Holowaty PH, Koren IE, Picard L, Stewart PJ, et al. \(2005\) An evaluation of the Ontario Rapid Risk Factor )] TJ ET BT 26.250 564.619 Td /F1 9.8 Tf [(Surveillance System. Can J Public Health 96: 145-150.)] TJ ET BT 26.250 545.214 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 545.214 Td /F1 9.8 Tf [(Public Health Agency of Canada Guidance on H1N1 flu vaccine sequencing. Retrieved 3 Nov 2009, from http://www.phac-)] TJ ET BT 26.250 533.310 Td /F1 9.8 Tf [(aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php.)] TJ ET BT 26.250 513.905 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 513.905 Td /F1 9.8 Tf [(Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, et al. \(2009\) Trial of influenza A \(H1N1\) 2009 monovalent MF59-)] TJ ET BT 26.250 502.000 Td /F1 9.8 Tf [(adjuvanted vaccine -- preliminary report. N Engl J Med.)] TJ ET BT 26.250 482.595 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 482.595 Td /F1 9.8 Tf [(Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, et al. \(2009\) Response after one dose of a monovalent )] TJ ET BT 26.250 470.691 Td /F1 9.8 Tf [(influenza A \(H1N1\) 2009 vaccine -- preliminary report. N Engl J Med.)] TJ ET BT 26.250 451.286 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 451.286 Td /F1 9.8 Tf [(Henderson DA, Courtney B, Inglesby TV, Toner E, Nuzzo JB \(2009\) Public health and medical responses to the 1957-58 )] TJ ET BT 26.250 439.381 Td /F1 9.8 Tf [(influenza pandemic. Biosecur Bioterror.)] TJ ET BT 26.250 419.976 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 419.976 Td /F1 9.8 Tf [(Medlock J, Galvani AP \(2009\) Optimizing influenza vaccine distribution. Science 325: 1705-1708.)] TJ ET BT 26.250 400.572 Td /F1 9.8 Tf [(33.)] TJ ET BT 43.553 400.572 Td /F1 9.8 Tf [(Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, et al. \(2005\) Impact of influenza vaccination on seasonal )] TJ ET BT 26.250 388.667 Td /F1 9.8 Tf [(mortality in the US elderly population. Arch Intern Med 165: 265-272.)] TJ ET BT 26.250 369.262 Td /F1 9.8 Tf [(34.)] TJ ET BT 43.553 369.262 Td /F1 9.8 Tf [(Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, et al. \(2009\) Pandemic potential of a strain of )] TJ ET BT 26.250 357.357 Td /F1 9.8 Tf [(influenza A \(H1N1\): early findings. Science 324: 1557-1561.)] TJ ET BT 26.250 337.953 Td /F1 9.8 Tf [(35.)] TJ ET BT 43.553 337.953 Td /F1 9.8 Tf [(Pourbohloul B, Ahued A, Davoudi B, Meza R, Meyers LA, et al. \(2009\) Initial human transmission dynamics of the pandemic )] TJ ET BT 26.250 326.048 Td /F1 9.8 Tf [(\(H1N1\) 2009 virus in North America. Influenza Other Respi Viruses 3: 215-222.)] TJ ET BT 26.250 306.643 Td /F1 9.8 Tf [(36.)] TJ ET BT 43.553 306.643 Td /F1 9.8 Tf [(Mills CE, Robins JM, Lipsitch M \(2004\) Transmissibility of 1918 pandemic influenza. Nature 432: 904-906.)] TJ ET BT 26.250 287.238 Td /F1 9.8 Tf [(37.)] TJ ET BT 43.553 287.238 Td /F1 9.8 Tf [(Viboud C, Bjornstad ON, Smith DL, Simonsen L, Miller MA, et al. \(2006\) Synchrony, waves, and spatial hierarchies in the )] TJ ET BT 26.250 275.334 Td /F1 9.8 Tf [(spread of influenza. Science 312: 447-451.)] TJ ET BT 26.250 255.929 Td /F1 9.8 Tf [(38.)] TJ ET BT 43.553 255.929 Td /F1 9.8 Tf [(Uphoff H, Geis S, Gruber A, Hauri A \(2009\) What will the next influenza season bring about: seasonal influenza or the new )] TJ ET BT 26.250 244.024 Td /F1 9.8 Tf [(A\(H1N1\)v? An analysis of German influenza surveillance data. Euro Surveill 14.)] TJ ET BT 26.250 224.619 Td /F1 9.8 Tf [(39.)] TJ ET BT 43.553 224.619 Td /F1 9.8 Tf [(Kelly H, Grant K \(2009\) Interim analysis of pandemic influenza \(H1N1\) 2009 in Australia: surveillance trends, age of )] TJ ET BT 26.250 212.715 Td /F1 9.8 Tf [(infection and effectiveness of seasonal vaccination. 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