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0 R >> endobj 7 0 obj << /Length 25340 >> stream q 375.000 0 0 39.000 222.000 738.000 cm /I2 Do 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 [(The severity of pandemic H1N1 influenza in the United States, )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(April July 2009)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(September 25, 2009)] TJ ET BT 97.592 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 102.467 675.088 Td /F3 9.8 Tf [(Epidemiology)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Anne M Presanis)] TJ ET 0.271 0.267 0.267 rg BT 100.487 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 105.908 663.247 Td /F1 9.8 Tf [(Marc Lipsitch)] TJ ET 0.271 0.267 0.267 rg BT 163.335 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 168.756 663.247 Td /F1 9.8 Tf [(Daniela De Angelis)] TJ ET 0.271 0.267 0.267 rg BT 251.660 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 257.081 663.247 Td /F1 9.8 Tf [(Swine Flu Investigation Team, New York City Department of Health and )] TJ ET BT 26.250 651.342 Td /F1 9.8 Tf [(Mental Hygiene)] TJ ET 0.271 0.267 0.267 rg BT 93.983 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 99.404 651.342 Td /F1 9.8 Tf [(Angie Hagy)] TJ ET 0.271 0.267 0.267 rg BT 149.802 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 155.223 651.342 Td /F1 9.8 Tf [(Carrie Reed)] TJ ET 0.271 0.267 0.267 rg BT 207.776 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 213.197 651.342 Td /F1 9.8 Tf [(Steven Riley)] TJ ET 0.271 0.267 0.267 rg BT 267.923 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 273.344 651.342 Td /F1 9.8 Tf [(Ben Cooper)] TJ ET 0.271 0.267 0.267 rg BT 325.370 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 330.791 651.342 Td /F1 9.8 Tf [(Paul Biedrzycki)] TJ ET 0.271 0.267 0.267 rg BT 397.433 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 402.853 651.342 Td /F1 9.8 Tf [(Lyn Finelli)] TJ ET 0.271 0.267 0.267 rg BT 446.738 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 452.159 651.342 Td /F1 9.8 Tf [(Jade B)] TJ ET 0.271 0.267 0.267 rg BT 26.250 639.438 Td /F1 9.8 Tf [(Presanis AM, Lipsitch M, De Angelis D, New York City Department of Health and Mental Hygiene SFIT, Hagy A, Reed C, Riley )] TJ ET BT 26.250 627.533 Td /F1 9.8 Tf [(S, Cooper B, Biedrzycki P, Finelli L, B J. The severity of pandemic H1N1 influenza in the United States, April July 2009. PLOS )] TJ ET BT 26.250 615.628 Td /F1 9.8 Tf [(Currents Influenza. 2009 Sep 25 . Edition 1. doi: 10.1371/currents.RRN1042.)] TJ ET q 15.000 29.878 577.500 583.370 re W n 0.271 0.267 0.267 rg BT 26.250 586.526 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(Background: Accurate measures of the severity of pandemic influenza A/H1N1 \(pH1N1\) are needed to assess the likely impact )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with )] TJ ET BT 26.250 530.857 Td /F1 9.8 Tf [(confidence. Also, detection of severe cases may be more likely.)] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(attended infection whether or not they required hospitalization, while New York City focused on the identification of )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(hospitalizations, intensive care admission or mechanical ventilation \(hereafter, ICU\), and deaths. New York data were used to )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(\(symptomatic case-fatality ratio, sCFR\), required ICU \(sCIR\), and required hospitalization \(sCHR\), overall and by age category. )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using )] TJ ET BT 26.250 416.214 Td /F1 9.8 Tf [(medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of )] TJ ET BT 26.250 404.310 Td /F1 9.8 Tf [(0.048% \(95% credible interval, CI 0.026%-0.096%\), sCIR of 0.239% \(0.134%-0.458%\), and sCHR of 1.44% \(0.83%-2.64%\). )] TJ ET BT 26.250 392.405 Td /F1 9.8 Tf [(Using self-reported ILI, we obtained estimates approximately 7-9x lower. sCFR and sCIR appear to be highest in persons 18 )] TJ ET BT 26.250 380.500 Td /F1 9.8 Tf [(and older, and lowest in children 5-17. sCHR appears to be lowest in persons 5-17; our data were too sparse to allow us to )] TJ ET BT 26.250 368.595 Td /F1 9.8 Tf [(determine the group in which it was the highest.)] TJ ET BT 26.250 349.191 Td /F1 9.8 Tf [(Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case )] TJ ET BT 26.250 337.286 Td /F1 9.8 Tf [(could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, )] TJ ET BT 26.250 325.381 Td /F1 9.8 Tf [(but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total )] TJ ET BT 26.250 313.476 Td /F1 9.8 Tf [(incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral )] TJ ET BT 26.250 301.572 Td /F1 9.8 Tf [(virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the )] TJ ET BT 26.250 289.667 Td /F1 9.8 Tf [(proportion infected or symptomatic were lower.)] TJ ET BT 26.250 253.064 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 233.110 Td /F1 9.8 Tf [(AP and DDeA were funded by the UK Medical Research Council. DDeA was funded also by the UK Health Protection Agency. )] TJ ET BT 26.250 221.205 Td /F1 9.8 Tf [(ML and SR were supported by Cooperative Agreements 1U54GM088558 and 5U01GM076497 of the Models of Infectious )] TJ ET BT 26.250 209.301 Td /F1 9.8 Tf [(Disease Agent Study program of the US National Institutes of Health \(US NIH\). SR also received funding from grant )] TJ ET BT 26.250 197.396 Td /F1 9.8 Tf [(3R01TW008246-01S1 from the US NIH from the RAPIDD program of the Fogarty International Center of the US NIH and the )] TJ ET BT 26.250 185.491 Td /F1 9.8 Tf [(Science and Technology Directorate of the US Department of Homeland Security. The funders had no role in study design, data )] TJ ET BT 26.250 173.586 Td /F1 9.8 Tf [(collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 144.484 Td /F4 12.0 Tf [(Article Updated)] TJ ET BT 26.250 124.530 Td /F4 9.8 Tf [(This article has been updated:)] TJ ET BT 166.582 124.530 Td /F1 9.8 Tf [( )] TJ ET 0.267 0.267 0.267 rg BT 172.539 124.530 Td /F1 9.8 Tf [(The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A )] TJ ET BT 26.250 112.625 Td /F1 9.8 Tf [(Bayesian Analysis)] TJ ET 0.271 0.267 0.267 rg BT 105.362 112.625 Td /F1 9.8 Tf [( in )] TJ ET BT 121.615 112.625 Td /F5 9.8 Tf [(PLOS Medicine)] TJ ET BT 189.348 112.625 Td /F1 9.8 Tf [(, doi: 10.1371/journal.pmed.1000207. This update is in line with PLOS policy at the time of )] TJ ET BT 26.250 100.720 Td /F1 9.8 Tf [(publication, see )] TJ ET 0.267 0.267 0.267 rg BT 96.704 100.720 Td /F1 9.8 Tf [(here)] TJ ET 0.271 0.267 0.267 rg BT 116.213 100.720 Td /F1 9.8 Tf [( for further details.)] TJ ET BT 26.250 64.118 Td /F4 12.0 Tf [(INTRODUCTION)] TJ ET BT 26.250 44.163 Td /F1 9.8 Tf [(The present pandemic of pandemic influenza A/H1N1 \(pH1N1\) has resulted in over 209,000 laboratory-confirmed cases and )] 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 [(The severity of pandemic H1N1 influenza in the United States, )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(April July 2009)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(September 25, 2009)] TJ ET BT 97.592 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 102.467 675.088 Td /F3 9.8 Tf [(Epidemiology)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Anne M Presanis)] TJ ET 0.271 0.267 0.267 rg BT 100.487 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 105.908 663.247 Td /F1 9.8 Tf [(Marc Lipsitch)] TJ ET 0.271 0.267 0.267 rg BT 163.335 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 168.756 663.247 Td /F1 9.8 Tf [(Daniela De Angelis)] TJ ET 0.271 0.267 0.267 rg BT 251.660 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 257.081 663.247 Td /F1 9.8 Tf [(Swine Flu Investigation Team, New York City Department of Health and )] TJ ET BT 26.250 651.342 Td /F1 9.8 Tf [(Mental Hygiene)] TJ ET 0.271 0.267 0.267 rg BT 93.983 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 99.404 651.342 Td /F1 9.8 Tf [(Angie Hagy)] TJ ET 0.271 0.267 0.267 rg BT 149.802 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 155.223 651.342 Td /F1 9.8 Tf [(Carrie Reed)] TJ ET 0.271 0.267 0.267 rg BT 207.776 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 213.197 651.342 Td /F1 9.8 Tf [(Steven Riley)] TJ ET 0.271 0.267 0.267 rg BT 267.923 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 273.344 651.342 Td /F1 9.8 Tf [(Ben Cooper)] TJ ET 0.271 0.267 0.267 rg BT 325.370 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 330.791 651.342 Td /F1 9.8 Tf [(Paul Biedrzycki)] TJ ET 0.271 0.267 0.267 rg BT 397.433 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 402.853 651.342 Td /F1 9.8 Tf [(Lyn Finelli)] TJ ET 0.271 0.267 0.267 rg BT 446.738 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 452.159 651.342 Td /F1 9.8 Tf [(Jade B)] TJ ET 0.271 0.267 0.267 rg BT 26.250 639.438 Td /F1 9.8 Tf [(Presanis AM, Lipsitch M, De Angelis D, New York City Department of Health and Mental Hygiene SFIT, Hagy A, Reed C, Riley )] TJ ET BT 26.250 627.533 Td /F1 9.8 Tf [(S, Cooper B, Biedrzycki P, Finelli L, B J. The severity of pandemic H1N1 influenza in the United States, April July 2009. PLOS )] TJ ET BT 26.250 615.628 Td /F1 9.8 Tf [(Currents Influenza. 2009 Sep 25 . Edition 1. doi: 10.1371/currents.RRN1042.)] TJ ET q 15.000 29.878 577.500 583.370 re W n 0.271 0.267 0.267 rg BT 26.250 586.526 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(Background: Accurate measures of the severity of pandemic influenza A/H1N1 \(pH1N1\) are needed to assess the likely impact )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with )] TJ ET BT 26.250 530.857 Td /F1 9.8 Tf [(confidence. Also, detection of severe cases may be more likely.)] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(attended infection whether or not they required hospitalization, while New York City focused on the identification of )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(hospitalizations, intensive care admission or mechanical ventilation \(hereafter, ICU\), and deaths. New York data were used to )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(\(symptomatic case-fatality ratio, sCFR\), required ICU \(sCIR\), and required hospitalization \(sCHR\), overall and by age category. )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using )] TJ ET BT 26.250 416.214 Td /F1 9.8 Tf [(medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of )] TJ ET BT 26.250 404.310 Td /F1 9.8 Tf [(0.048% \(95% credible interval, CI 0.026%-0.096%\), sCIR of 0.239% \(0.134%-0.458%\), and sCHR of 1.44% \(0.83%-2.64%\). )] TJ ET BT 26.250 392.405 Td /F1 9.8 Tf [(Using self-reported ILI, we obtained estimates approximately 7-9x lower. sCFR and sCIR appear to be highest in persons 18 )] TJ ET BT 26.250 380.500 Td /F1 9.8 Tf [(and older, and lowest in children 5-17. sCHR appears to be lowest in persons 5-17; our data were too sparse to allow us to )] TJ ET BT 26.250 368.595 Td /F1 9.8 Tf [(determine the group in which it was the highest.)] TJ ET BT 26.250 349.191 Td /F1 9.8 Tf [(Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case )] TJ ET BT 26.250 337.286 Td /F1 9.8 Tf [(could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, )] TJ ET BT 26.250 325.381 Td /F1 9.8 Tf [(but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total )] TJ ET BT 26.250 313.476 Td /F1 9.8 Tf [(incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral )] TJ ET BT 26.250 301.572 Td /F1 9.8 Tf [(virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the )] TJ ET BT 26.250 289.667 Td /F1 9.8 Tf [(proportion infected or symptomatic were lower.)] TJ ET BT 26.250 253.064 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 233.110 Td /F1 9.8 Tf [(AP and DDeA were funded by the UK Medical Research Council. DDeA was funded also by the UK Health Protection Agency. )] TJ ET BT 26.250 221.205 Td /F1 9.8 Tf [(ML and SR were supported by Cooperative Agreements 1U54GM088558 and 5U01GM076497 of the Models of Infectious )] TJ ET BT 26.250 209.301 Td /F1 9.8 Tf [(Disease Agent Study program of the US National Institutes of Health \(US NIH\). SR also received funding from grant )] TJ ET BT 26.250 197.396 Td /F1 9.8 Tf [(3R01TW008246-01S1 from the US NIH from the RAPIDD program of the Fogarty International Center of the US NIH and the )] TJ ET BT 26.250 185.491 Td /F1 9.8 Tf [(Science and Technology Directorate of the US Department of Homeland Security. The funders had no role in study design, data )] TJ ET BT 26.250 173.586 Td /F1 9.8 Tf [(collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 144.484 Td /F4 12.0 Tf [(Article Updated)] TJ ET BT 26.250 124.530 Td /F4 9.8 Tf [(This article has been updated:)] TJ ET BT 166.582 124.530 Td /F1 9.8 Tf [( )] TJ ET 0.267 0.267 0.267 rg BT 172.539 124.530 Td /F1 9.8 Tf [(The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A )] TJ ET BT 26.250 112.625 Td /F1 9.8 Tf [(Bayesian Analysis)] TJ ET 0.271 0.267 0.267 rg BT 105.362 112.625 Td /F1 9.8 Tf [( in )] TJ ET BT 121.615 112.625 Td /F5 9.8 Tf [(PLOS Medicine)] TJ ET BT 189.348 112.625 Td /F1 9.8 Tf [(, doi: 10.1371/journal.pmed.1000207. This update is in line with PLOS policy at the time of )] TJ ET BT 26.250 100.720 Td /F1 9.8 Tf [(publication, see )] TJ ET 0.267 0.267 0.267 rg BT 96.704 100.720 Td /F1 9.8 Tf [(here)] TJ ET 0.271 0.267 0.267 rg BT 116.213 100.720 Td /F1 9.8 Tf [( for further details.)] TJ ET BT 26.250 64.118 Td /F4 12.0 Tf [(INTRODUCTION)] TJ ET BT 26.250 44.163 Td /F1 9.8 Tf [(The present pandemic of pandemic influenza A/H1N1 \(pH1N1\) has resulted in over 209,000 laboratory-confirmed cases and )] 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 [(The severity of pandemic H1N1 influenza in the United States, )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(April July 2009)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(September 25, 2009)] TJ ET BT 97.592 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 102.467 675.088 Td /F3 9.8 Tf [(Epidemiology)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Anne M Presanis)] TJ ET 0.271 0.267 0.267 rg BT 100.487 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 105.908 663.247 Td /F1 9.8 Tf [(Marc Lipsitch)] TJ ET 0.271 0.267 0.267 rg BT 163.335 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 168.756 663.247 Td /F1 9.8 Tf [(Daniela De Angelis)] TJ ET 0.271 0.267 0.267 rg BT 251.660 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 257.081 663.247 Td /F1 9.8 Tf [(Swine Flu Investigation Team, New York City Department of Health and )] TJ ET BT 26.250 651.342 Td /F1 9.8 Tf [(Mental Hygiene)] TJ ET 0.271 0.267 0.267 rg BT 93.983 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 99.404 651.342 Td /F1 9.8 Tf [(Angie Hagy)] TJ ET 0.271 0.267 0.267 rg BT 149.802 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 155.223 651.342 Td /F1 9.8 Tf [(Carrie Reed)] TJ ET 0.271 0.267 0.267 rg BT 207.776 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 213.197 651.342 Td /F1 9.8 Tf [(Steven Riley)] TJ ET 0.271 0.267 0.267 rg BT 267.923 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 273.344 651.342 Td /F1 9.8 Tf [(Ben Cooper)] TJ ET 0.271 0.267 0.267 rg BT 325.370 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 330.791 651.342 Td /F1 9.8 Tf [(Paul Biedrzycki)] TJ ET 0.271 0.267 0.267 rg BT 397.433 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 402.853 651.342 Td /F1 9.8 Tf [(Lyn Finelli)] TJ ET 0.271 0.267 0.267 rg BT 446.738 651.342 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 452.159 651.342 Td /F1 9.8 Tf [(Jade B)] TJ ET 0.271 0.267 0.267 rg BT 26.250 639.438 Td /F1 9.8 Tf [(Presanis AM, Lipsitch M, De Angelis D, New York City Department of Health and Mental Hygiene SFIT, Hagy A, Reed C, Riley )] TJ ET BT 26.250 627.533 Td /F1 9.8 Tf [(S, Cooper B, Biedrzycki P, Finelli L, B J. The severity of pandemic H1N1 influenza in the United States, April July 2009. PLOS )] TJ ET BT 26.250 615.628 Td /F1 9.8 Tf [(Currents Influenza. 2009 Sep 25 . Edition 1. doi: 10.1371/currents.RRN1042.)] TJ ET q 15.000 29.878 577.500 583.370 re W n 0.271 0.267 0.267 rg BT 26.250 586.526 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 566.571 Td /F1 9.8 Tf [(Background: Accurate measures of the severity of pandemic influenza A/H1N1 \(pH1N1\) are needed to assess the likely impact )] TJ ET BT 26.250 554.667 Td /F1 9.8 Tf [(of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because )] TJ ET BT 26.250 542.762 Td /F1 9.8 Tf [(jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with )] TJ ET BT 26.250 530.857 Td /F1 9.8 Tf [(confidence. Also, detection of severe cases may be more likely.)] TJ ET BT 26.250 511.452 Td /F1 9.8 Tf [(Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically )] TJ ET BT 26.250 499.548 Td /F1 9.8 Tf [(attended infection whether or not they required hospitalization, while New York City focused on the identification of )] TJ ET BT 26.250 487.643 Td /F1 9.8 Tf [(hospitalizations, intensive care admission or mechanical ventilation \(hereafter, ICU\), and deaths. New York data were used to )] TJ ET BT 26.250 475.738 Td /F1 9.8 Tf [(estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported )] TJ ET BT 26.250 463.833 Td /F1 9.8 Tf [(influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data )] TJ ET BT 26.250 451.929 Td /F1 9.8 Tf [(with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died )] TJ ET BT 26.250 440.024 Td /F1 9.8 Tf [(\(symptomatic case-fatality ratio, sCFR\), required ICU \(sCIR\), and required hospitalization \(sCHR\), overall and by age category. )] TJ ET BT 26.250 428.119 Td /F1 9.8 Tf [(Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using )] TJ ET BT 26.250 416.214 Td /F1 9.8 Tf [(medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of )] TJ ET BT 26.250 404.310 Td /F1 9.8 Tf [(0.048% \(95% credible interval, CI 0.026%-0.096%\), sCIR of 0.239% \(0.134%-0.458%\), and sCHR of 1.44% \(0.83%-2.64%\). )] TJ ET BT 26.250 392.405 Td /F1 9.8 Tf [(Using self-reported ILI, we obtained estimates approximately 7-9x lower. sCFR and sCIR appear to be highest in persons 18 )] TJ ET BT 26.250 380.500 Td /F1 9.8 Tf [(and older, and lowest in children 5-17. sCHR appears to be lowest in persons 5-17; our data were too sparse to allow us to )] TJ ET BT 26.250 368.595 Td /F1 9.8 Tf [(determine the group in which it was the highest.)] TJ ET BT 26.250 349.191 Td /F1 9.8 Tf [(Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case )] TJ ET BT 26.250 337.286 Td /F1 9.8 Tf [(could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, )] TJ ET BT 26.250 325.381 Td /F1 9.8 Tf [(but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total )] TJ ET BT 26.250 313.476 Td /F1 9.8 Tf [(incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral )] TJ ET BT 26.250 301.572 Td /F1 9.8 Tf [(virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the )] TJ ET BT 26.250 289.667 Td /F1 9.8 Tf [(proportion infected or symptomatic were lower.)] TJ ET BT 26.250 253.064 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 233.110 Td /F1 9.8 Tf [(AP and DDeA were funded by the UK Medical Research Council. DDeA was funded also by the UK Health Protection Agency. )] TJ ET BT 26.250 221.205 Td /F1 9.8 Tf [(ML and SR were supported by Cooperative Agreements 1U54GM088558 and 5U01GM076497 of the Models of Infectious )] TJ ET BT 26.250 209.301 Td /F1 9.8 Tf [(Disease Agent Study program of the US National Institutes of Health \(US NIH\). SR also received funding from grant )] TJ ET BT 26.250 197.396 Td /F1 9.8 Tf [(3R01TW008246-01S1 from the US NIH from the RAPIDD program of the Fogarty International Center of the US NIH and the )] TJ ET BT 26.250 185.491 Td /F1 9.8 Tf [(Science and Technology Directorate of the US Department of Homeland Security. The funders had no role in study design, data )] TJ ET BT 26.250 173.586 Td /F1 9.8 Tf [(collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 144.484 Td /F4 12.0 Tf [(Article Updated)] TJ ET BT 26.250 124.530 Td /F4 9.8 Tf [(This article has been updated:)] TJ ET BT 166.582 124.530 Td /F1 9.8 Tf [( )] TJ ET 0.267 0.267 0.267 rg BT 172.539 124.530 Td /F1 9.8 Tf [(The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A )] TJ ET BT 26.250 112.625 Td /F1 9.8 Tf [(Bayesian Analysis)] TJ ET 0.271 0.267 0.267 rg BT 105.362 112.625 Td /F1 9.8 Tf [( in )] TJ ET BT 121.615 112.625 Td /F5 9.8 Tf [(PLOS Medicine)] TJ ET BT 189.348 112.625 Td /F1 9.8 Tf [(, doi: 10.1371/journal.pmed.1000207. 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stream 0.271 0.267 0.267 rg q 15.000 23.777 577.500 753.223 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(over 3205 deaths worldwide as of September 11 \()] TJ ET 0.267 0.267 0.267 rg BT 241.393 767.476 Td /F1 9.8 Tf [(http://www.who.int/csr/don/2009_09_11/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 472.800 767.476 Td /F1 9.8 Tf [(, accessed September )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(14, 2009\), but national and international authorities have acknowledged that these counts are substantial underestimates, )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reflecting an inability to identify, test, confirm and report many cases, especially mild cases. Severity of infection may be )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(measured in many ways, the simplest of which is the case-fatality ratio \(CFR\), the probability that an infection causes death. )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(Other measures of severity, which are most relevant to the burden a pandemic exerts on a health care system, are the case-)] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(hospitalization and case-intensive care ratios \(CHR and CIR respectively\), the probabilities that an infection leads to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(hospitalization or intensive care unit \(ICU\) admission. In the absence of a widely available and validated serologic test for )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(infection, it is impossible to estimate these quantities directly, and in this report we instead focus on the probabilities of fatality, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(hospitalization and ICU admission per )] TJ ET BT 192.605 672.238 Td /F5 9.8 Tf [(symptomatic)] TJ ET BT 247.322 672.238 Td /F1 9.8 Tf [( case; we denote these ratios sCFR, sCHR, and sCIR respectively.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(Although it is difficult to estimate these quantities, estimates of their values and associated uncertainty are important for decision )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(making, planning and response during the progression of this pandemic. Initially, some national and international pandemic )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(response plans were tied partly to estimates of the CFR, but such plans had to be modified in the early weeks of this pandemic, )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(as it became clear that the CFR could not at that time be reliably estimated [1]. Costly measures to mitigate the pandemic, such )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(as the purchase of medical countermeasures and the use of disruptive social distancing strategies may be acceptable to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(combat a more severe pandemic but not to slow a milder one. While past experience [2] and mathematical models [3][4][5] )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(suggest that between 40% and 60% of the population will be infected in a pandemic with a reproduction number similar to those )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seen in previous pandemics, the number of deaths and the burden on the health care system also depend on the age-specific )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(severity of infection, which varies by orders of magnitude between pandemics [6] and even between different waves in the same )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(pandemic [7]. Reports from the Southern Hemisphere suggest that a relatively low fraction of the population experienced )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(symptomatic pH1N1 infection \(7.5% in New Zealand, for example [8]\), though these numbers are considered highly uncertain )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [([8]. On the other hand, primary care utilization for influenza-like illness has been considerably higher than in recent years [8], )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(and anecdotal reports in the Southern Hemisphere have indicated that some intensive care units have been overwhelmed and )] TJ ET BT 26.250 498.072 Td /F1 9.8 Tf [(surgery postponed due to a heavy burden of pH1N1 cases [9][10].)] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(The problem of estimating severity of pH1N1 infection is also the problem of estimating how many of the infected individuals in a )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(given population and time period subsequently develop symptoms, are medically attended, hospitalized, admitted to ICU, and )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(die due to the virus. No large jurisdiction in the world has been able to maintain an accurate count of total pH1N1 cases once )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(the epidemic has grown beyond hundreds of cases, because the effort required to confirm and count such cases grows in )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(proportion to the size of the exponentially-growing epidemic [11], making it impossible to estimate reliably the frequency of an )] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(event \(death\) that occurs on the order of 1 in 1000 patients or fewer. As a result, simple comparisons of the number of deaths to )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(the number of cases suffer from underascertainment of cases \(making the estimated ratio too large\), and underascertainment of )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(deaths due to inability to identify deaths caused by the illness and due to delays from symptom onset to death \(making the )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(estimated ratio too small\) [1]. Imperfect ascertainment of both numerator and denominator will lead to biased estimates of the )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(case-fatality ratio. Estimating the number of persons at these varying levels of severity therefore depends on estimating the )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(proportion of true cases that are recognized and reported by existing surveillance systems. Similar problems affect estimates of )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(key parameters for other diseases, such as HIV. In HIV, a solution to this problem which now forms the basis for the UKs )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(annual HIV prevalence estimates published by the Health Protection Agency [12][13] has been to synthesize evidence from a )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(variety of sources that together provide a clearer picture of incidence, prevalence, and diagnosis probabilities. This synthesis is )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(performed within a Bayesian framework that allows each piece of evidence, with associated uncertainties, to be combined into )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(an estimate of the numbers of greatest interest [14][15].)] TJ ET BT 26.250 280.691 Td /F1 9.8 Tf [(Here we use a similar framework to synthesize evidence from two cities in the United States New York and Milwaukee )] TJ ET BT 26.250 268.786 Td /F1 9.8 Tf [(together with estimates of important detection probabilities from epidemiologic investigations carried out by the Centers for )] TJ ET BT 26.250 256.881 Td /F1 9.8 Tf [(Disease Control and Prevention \(CDC\) and other data from CDC. We estimate the severity of pH1N1 infection from data from )] TJ ET BT 26.250 244.977 Td /F1 9.8 Tf [(spring-summer, 2009 wave of infections in the United States. The New York City and Milwaukee health departments pursued )] TJ ET BT 26.250 233.072 Td /F1 9.8 Tf [(differing surveillance strategies that provided high-quality data on complementary aspects of pH1N1 severity, with Milwaukee )] TJ ET BT 26.250 221.167 Td /F1 9.8 Tf [(documenting medically attended cases and hospitalizations, and New York documenting hospitalizations, ICU/ventilation use, )] TJ ET BT 26.250 209.262 Td /F1 9.8 Tf [(and fatalities. These are the numerators of the ratios of interest.)] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(The denominator for these ratios is the number of symptomatic pH1N1 cases in a population, which cannot be assessed )] TJ ET BT 26.250 177.953 Td /F1 9.8 Tf [(directly. We use two different approaches to estimate this quantity. In the first, we use self-reported rates of seeking medical )] TJ ET BT 26.250 166.048 Td /F1 9.8 Tf [(attention for influenza-like illness from several CDC investigations to estimate the number of symptomatic cases from the )] TJ ET BT 26.250 154.143 Td /F1 9.8 Tf [(number of medically attended cases, which are estimated from data from Milwaukee. In the second, we use self-reported )] TJ ET BT 26.250 142.239 Td /F1 9.8 Tf [(incidence of influenza-like illness \(ILI\) in New York City, and making the assumption that these ILI cases represent the true )] TJ ET BT 26.250 130.334 Td /F1 9.8 Tf [(denominator of symptomatic cases, we directly estimate the ratio between hospitalizations, ICU admissions/mechanical )] TJ ET BT 26.250 118.429 Td /F1 9.8 Tf [(ventilation, and deaths \(adjusting for ascertainment\) in New York. Each of these two methods provides estimates for the general )] TJ ET BT 26.250 106.524 Td /F1 9.8 Tf [(population, and also for broad age categories 0-4, 5-17, 18-64, and 65+ years. The result of each approach is a tiered severity )] TJ ET BT 26.250 94.620 Td /F1 9.8 Tf [(estimate of the pandemic.)] TJ ET BT 26.250 58.017 Td /F4 12.0 Tf [(METHODS)] TJ ET BT 26.250 38.063 Td /F5 9.8 Tf [(Methods Overview:)] TJ ET BT 109.691 38.063 Td /F1 9.8 Tf [( The overall goal of this study was to estimate, for each symptomatic pH1N1 case, what was the probability )] TJ ET Q q 15.000 23.777 577.500 753.223 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(over 3205 deaths worldwide as of September 11 \()] TJ ET 0.267 0.267 0.267 rg BT 241.393 767.476 Td /F1 9.8 Tf [(http://www.who.int/csr/don/2009_09_11/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 472.800 767.476 Td /F1 9.8 Tf [(, accessed September )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(14, 2009\), but national and international authorities have acknowledged that these counts are substantial underestimates, )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reflecting an inability to identify, test, confirm and report many cases, especially mild cases. Severity of infection may be )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(measured in many ways, the simplest of which is the case-fatality ratio \(CFR\), the probability that an infection causes death. )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(Other measures of severity, which are most relevant to the burden a pandemic exerts on a health care system, are the case-)] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(hospitalization and case-intensive care ratios \(CHR and CIR respectively\), the probabilities that an infection leads to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(hospitalization or intensive care unit \(ICU\) admission. In the absence of a widely available and validated serologic test for )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(infection, it is impossible to estimate these quantities directly, and in this report we instead focus on the probabilities of fatality, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(hospitalization and ICU admission per )] TJ ET BT 192.605 672.238 Td /F5 9.8 Tf [(symptomatic)] TJ ET BT 247.322 672.238 Td /F1 9.8 Tf [( case; we denote these ratios sCFR, sCHR, and sCIR respectively.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(Although it is difficult to estimate these quantities, estimates of their values and associated uncertainty are important for decision )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(making, planning and response during the progression of this pandemic. Initially, some national and international pandemic )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(response plans were tied partly to estimates of the CFR, but such plans had to be modified in the early weeks of this pandemic, )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(as it became clear that the CFR could not at that time be reliably estimated [1]. Costly measures to mitigate the pandemic, such )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(as the purchase of medical countermeasures and the use of disruptive social distancing strategies may be acceptable to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(combat a more severe pandemic but not to slow a milder one. While past experience [2] and mathematical models [3][4][5] )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(suggest that between 40% and 60% of the population will be infected in a pandemic with a reproduction number similar to those )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seen in previous pandemics, the number of deaths and the burden on the health care system also depend on the age-specific )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(severity of infection, which varies by orders of magnitude between pandemics [6] and even between different waves in the same )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(pandemic [7]. Reports from the Southern Hemisphere suggest that a relatively low fraction of the population experienced )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(symptomatic pH1N1 infection \(7.5% in New Zealand, for example [8]\), though these numbers are considered highly uncertain )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [([8]. On the other hand, primary care utilization for influenza-like illness has been considerably higher than in recent years [8], )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(and anecdotal reports in the Southern Hemisphere have indicated that some intensive care units have been overwhelmed and )] TJ ET BT 26.250 498.072 Td /F1 9.8 Tf [(surgery postponed due to a heavy burden of pH1N1 cases [9][10].)] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(The problem of estimating severity of pH1N1 infection is also the problem of estimating how many of the infected individuals in a )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(given population and time period subsequently develop symptoms, are medically attended, hospitalized, admitted to ICU, and )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(die due to the virus. No large jurisdiction in the world has been able to maintain an accurate count of total pH1N1 cases once )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(the epidemic has grown beyond hundreds of cases, because the effort required to confirm and count such cases grows in )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(proportion to the size of the exponentially-growing epidemic [11], making it impossible to estimate reliably the frequency of an )] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(event \(death\) that occurs on the order of 1 in 1000 patients or fewer. As a result, simple comparisons of the number of deaths to )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(the number of cases suffer from underascertainment of cases \(making the estimated ratio too large\), and underascertainment of )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(deaths due to inability to identify deaths caused by the illness and due to delays from symptom onset to death \(making the )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(estimated ratio too small\) [1]. Imperfect ascertainment of both numerator and denominator will lead to biased estimates of the )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(case-fatality ratio. Estimating the number of persons at these varying levels of severity therefore depends on estimating the )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(proportion of true cases that are recognized and reported by existing surveillance systems. Similar problems affect estimates of )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(key parameters for other diseases, such as HIV. In HIV, a solution to this problem which now forms the basis for the UKs )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(annual HIV prevalence estimates published by the Health Protection Agency [12][13] has been to synthesize evidence from a )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(variety of sources that together provide a clearer picture of incidence, prevalence, and diagnosis probabilities. This synthesis is )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(performed within a Bayesian framework that allows each piece of evidence, with associated uncertainties, to be combined into )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(an estimate of the numbers of greatest interest [14][15].)] TJ ET BT 26.250 280.691 Td /F1 9.8 Tf [(Here we use a similar framework to synthesize evidence from two cities in the United States New York and Milwaukee )] TJ ET BT 26.250 268.786 Td /F1 9.8 Tf [(together with estimates of important detection probabilities from epidemiologic investigations carried out by the Centers for )] TJ ET BT 26.250 256.881 Td /F1 9.8 Tf [(Disease Control and Prevention \(CDC\) and other data from CDC. We estimate the severity of pH1N1 infection from data from )] TJ ET BT 26.250 244.977 Td /F1 9.8 Tf [(spring-summer, 2009 wave of infections in the United States. The New York City and Milwaukee health departments pursued )] TJ ET BT 26.250 233.072 Td /F1 9.8 Tf [(differing surveillance strategies that provided high-quality data on complementary aspects of pH1N1 severity, with Milwaukee )] TJ ET BT 26.250 221.167 Td /F1 9.8 Tf [(documenting medically attended cases and hospitalizations, and New York documenting hospitalizations, ICU/ventilation use, )] TJ ET BT 26.250 209.262 Td /F1 9.8 Tf [(and fatalities. These are the numerators of the ratios of interest.)] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(The denominator for these ratios is the number of symptomatic pH1N1 cases in a population, which cannot be assessed )] TJ ET BT 26.250 177.953 Td /F1 9.8 Tf [(directly. We use two different approaches to estimate this quantity. In the first, we use self-reported rates of seeking medical )] TJ ET BT 26.250 166.048 Td /F1 9.8 Tf [(attention for influenza-like illness from several CDC investigations to estimate the number of symptomatic cases from the )] TJ ET BT 26.250 154.143 Td /F1 9.8 Tf [(number of medically attended cases, which are estimated from data from Milwaukee. In the second, we use self-reported )] TJ ET BT 26.250 142.239 Td /F1 9.8 Tf [(incidence of influenza-like illness \(ILI\) in New York City, and making the assumption that these ILI cases represent the true )] TJ ET BT 26.250 130.334 Td /F1 9.8 Tf [(denominator of symptomatic cases, we directly estimate the ratio between hospitalizations, ICU admissions/mechanical )] TJ ET BT 26.250 118.429 Td /F1 9.8 Tf [(ventilation, and deaths \(adjusting for ascertainment\) in New York. Each of these two methods provides estimates for the general )] TJ ET BT 26.250 106.524 Td /F1 9.8 Tf [(population, and also for broad age categories 0-4, 5-17, 18-64, and 65+ years. The result of each approach is a tiered severity )] TJ ET BT 26.250 94.620 Td /F1 9.8 Tf [(estimate of the pandemic.)] TJ ET BT 26.250 58.017 Td /F4 12.0 Tf [(METHODS)] TJ ET BT 26.250 38.063 Td /F5 9.8 Tf [(Methods Overview:)] TJ ET BT 109.691 38.063 Td /F1 9.8 Tf [( The overall goal of this study was to estimate, for each symptomatic pH1N1 case, what was the probability )] TJ ET Q q 15.000 23.777 577.500 753.223 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(over 3205 deaths worldwide as of September 11 \()] TJ ET 0.267 0.267 0.267 rg BT 241.393 767.476 Td /F1 9.8 Tf [(http://www.who.int/csr/don/2009_09_11/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 472.800 767.476 Td /F1 9.8 Tf [(, accessed September )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(14, 2009\), but national and international authorities have acknowledged that these counts are substantial underestimates, )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(reflecting an inability to identify, test, confirm and report many cases, especially mild cases. Severity of infection may be )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(measured in many ways, the simplest of which is the case-fatality ratio \(CFR\), the probability that an infection causes death. )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(Other measures of severity, which are most relevant to the burden a pandemic exerts on a health care system, are the case-)] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(hospitalization and case-intensive care ratios \(CHR and CIR respectively\), the probabilities that an infection leads to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(hospitalization or intensive care unit \(ICU\) admission. In the absence of a widely available and validated serologic test for )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(infection, it is impossible to estimate these quantities directly, and in this report we instead focus on the probabilities of fatality, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(hospitalization and ICU admission per )] TJ ET BT 192.605 672.238 Td /F5 9.8 Tf [(symptomatic)] TJ ET BT 247.322 672.238 Td /F1 9.8 Tf [( case; we denote these ratios sCFR, sCHR, and sCIR respectively.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(Although it is difficult to estimate these quantities, estimates of their values and associated uncertainty are important for decision )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(making, planning and response during the progression of this pandemic. Initially, some national and international pandemic )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(response plans were tied partly to estimates of the CFR, but such plans had to be modified in the early weeks of this pandemic, )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(as it became clear that the CFR could not at that time be reliably estimated [1]. Costly measures to mitigate the pandemic, such )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(as the purchase of medical countermeasures and the use of disruptive social distancing strategies may be acceptable to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(combat a more severe pandemic but not to slow a milder one. While past experience [2] and mathematical models [3][4][5] )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(suggest that between 40% and 60% of the population will be infected in a pandemic with a reproduction number similar to those )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seen in previous pandemics, the number of deaths and the burden on the health care system also depend on the age-specific )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(severity of infection, which varies by orders of magnitude between pandemics [6] and even between different waves in the same )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(pandemic [7]. Reports from the Southern Hemisphere suggest that a relatively low fraction of the population experienced )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(symptomatic pH1N1 infection \(7.5% in New Zealand, for example [8]\), though these numbers are considered highly uncertain )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [([8]. On the other hand, primary care utilization for influenza-like illness has been considerably higher than in recent years [8], )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(and anecdotal reports in the Southern Hemisphere have indicated that some intensive care units have been overwhelmed and )] TJ ET BT 26.250 498.072 Td /F1 9.8 Tf [(surgery postponed due to a heavy burden of pH1N1 cases [9][10].)] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(The problem of estimating severity of pH1N1 infection is also the problem of estimating how many of the infected individuals in a )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(given population and time period subsequently develop symptoms, are medically attended, hospitalized, admitted to ICU, and )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(die due to the virus. No large jurisdiction in the world has been able to maintain an accurate count of total pH1N1 cases once )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(the epidemic has grown beyond hundreds of cases, because the effort required to confirm and count such cases grows in )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(proportion to the size of the exponentially-growing epidemic [11], making it impossible to estimate reliably the frequency of an )] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(event \(death\) that occurs on the order of 1 in 1000 patients or fewer. As a result, simple comparisons of the number of deaths to )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(the number of cases suffer from underascertainment of cases \(making the estimated ratio too large\), and underascertainment of )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(deaths due to inability to identify deaths caused by the illness and due to delays from symptom onset to death \(making the )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(estimated ratio too small\) [1]. Imperfect ascertainment of both numerator and denominator will lead to biased estimates of the )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(case-fatality ratio. Estimating the number of persons at these varying levels of severity therefore depends on estimating the )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(proportion of true cases that are recognized and reported by existing surveillance systems. Similar problems affect estimates of )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(key parameters for other diseases, such as HIV. In HIV, a solution to this problem which now forms the basis for the UKs )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(annual HIV prevalence estimates published by the Health Protection Agency [12][13] has been to synthesize evidence from a )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(variety of sources that together provide a clearer picture of incidence, prevalence, and diagnosis probabilities. This synthesis is )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(performed within a Bayesian framework that allows each piece of evidence, with associated uncertainties, to be combined into )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(an estimate of the numbers of greatest interest [14][15].)] TJ ET BT 26.250 280.691 Td /F1 9.8 Tf [(Here we use a similar framework to synthesize evidence from two cities in the United States New York and Milwaukee )] TJ ET BT 26.250 268.786 Td /F1 9.8 Tf [(together with estimates of important detection probabilities from epidemiologic investigations carried out by the Centers for )] TJ ET BT 26.250 256.881 Td /F1 9.8 Tf [(Disease Control and Prevention \(CDC\) and other data from CDC. We estimate the severity of pH1N1 infection from data from )] TJ ET BT 26.250 244.977 Td /F1 9.8 Tf [(spring-summer, 2009 wave of infections in the United States. The New York City and Milwaukee health departments pursued )] TJ ET BT 26.250 233.072 Td /F1 9.8 Tf [(differing surveillance strategies that provided high-quality data on complementary aspects of pH1N1 severity, with Milwaukee )] TJ ET BT 26.250 221.167 Td /F1 9.8 Tf [(documenting medically attended cases and hospitalizations, and New York documenting hospitalizations, ICU/ventilation use, )] TJ ET BT 26.250 209.262 Td /F1 9.8 Tf [(and fatalities. These are the numerators of the ratios of interest.)] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(The denominator for these ratios is the number of symptomatic pH1N1 cases in a population, which cannot be assessed )] TJ ET BT 26.250 177.953 Td /F1 9.8 Tf [(directly. We use two different approaches to estimate this quantity. In the first, we use self-reported rates of seeking medical )] TJ ET BT 26.250 166.048 Td /F1 9.8 Tf [(attention for influenza-like illness from several CDC investigations to estimate the number of symptomatic cases from the )] TJ ET BT 26.250 154.143 Td /F1 9.8 Tf [(number of medically attended cases, which are estimated from data from Milwaukee. In the second, we use self-reported )] TJ ET BT 26.250 142.239 Td /F1 9.8 Tf [(incidence of influenza-like illness \(ILI\) in New York City, and making the assumption that these ILI cases represent the true )] TJ ET BT 26.250 130.334 Td /F1 9.8 Tf [(denominator of symptomatic cases, we directly estimate the ratio between hospitalizations, ICU admissions/mechanical )] TJ ET BT 26.250 118.429 Td /F1 9.8 Tf [(ventilation, and deaths \(adjusting for ascertainment\) in New York. Each of these two methods provides estimates for the general )] TJ ET BT 26.250 106.524 Td /F1 9.8 Tf [(population, and also for broad age categories 0-4, 5-17, 18-64, and 65+ years. The result of each approach is a tiered severity )] TJ ET BT 26.250 94.620 Td /F1 9.8 Tf [(estimate of the pandemic.)] TJ ET BT 26.250 58.017 Td /F4 12.0 Tf [(METHODS)] TJ ET BT 26.250 38.063 Td /F5 9.8 Tf [(Methods Overview:)] TJ ET BT 109.691 38.063 Td /F1 9.8 Tf [( The overall goal of this study was to estimate, for each symptomatic pH1N1 case, what was the probability )] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(2)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Influenza)] TJ ET Q endstream endobj 125 0 obj << /Type /Annot /Subtype /Link /A 126 0 R /Border [0 0 0] /H /I /Rect [ 241.3935 766.5743 472.8000 776.4950 ] >> endobj 126 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/don/2009_09_11/en/index.html) >> endobj 127 0 obj << /Type /Annot /Subtype /Link /A 128 0 R /Border [0 0 0] /H /I /Rect [ 241.3935 766.5743 472.8000 776.4950 ] >> endobj 128 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/don/2009_09_11/en/index.html) >> endobj 129 0 obj << /Type /Annot /Subtype /Link /A 130 0 R /Border [0 0 0] /H /I /Rect [ 241.3935 766.5743 472.8000 776.4950 ] >> endobj 130 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/don/2009_09_11/en/index.html) >> endobj 131 0 obj << /Type /Page /Parent 3 0 R /Annots [ 133 0 R 135 0 R 137 0 R ] /Contents 132 0 R >> endobj 132 0 obj << /Length 29830 >> stream 0.271 0.267 0.267 rg q 15.000 22.120 577.500 754.880 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(of hospitalization, ICU admission or mechanical ventilation, or death, overall and by age group. The challenge is that in any )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population large enough to have significant numbers of the severe outcomes, there was no reliable measure of the number of )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic pH1N1 cases. The problem was approached in two ways. Approach 1 was to view the severity of infection as a )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(pyramid [16], with each successive level representing greater severity; to estimate the ratio of the top level to the base )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(\(symptomatic cases\), we estimated the ratios of each successive level to the one below it \(Fig. 1, left side\). Thus we broke )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(down \(for example\) the sCFR \(Fig. 1, black\), i.e. the probability of death per symptomatic case, into components for which data )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were available the probability of coming to medical attention given symptomatic infection \(CDC survey data\); the probability of )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(being hospitalized given medical attention \(Milwaukee data\); and the probability of dying given hospitalization \(New York data, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(including a correction for those who died of pH1N1 but were not hospitalized\). A second approach was to use the self-reported )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(incidence of influenza-like illness from a telephone survey in New York as the estimate of total pH1N1 symptomatic disease, )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(and the total number of confirmed deaths in New York City as the estimate of the deaths \(after accounting for possibly imperfect )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(viral testing sensitivity\). In each case, prior distributions were used to quantify information on the probability that individuals at )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(each level of severity were detected; these prior distributions reflected the limited data available on detection probabilities and )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(associated uncertainty.)] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(All of these estimates were combined within a Bayesian evidence synthesis framework. This framework permits the estimation )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(of probabilities for the quantities of interest \(the sCFR, sCIR and sCHR\) and associated uncertainty \(expressed as credible )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(intervals\). These credible intervals appropriately reflect the combined uncertainties associated with each of the inputs to the )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(estimate mainly, the true numbers of cases at each level of severity, after accounting for imperfect detection as well as the )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(uncertainties due to sampling error \(chance\).)] TJ ET BT 26.250 526.286 Td /F5 9.8 Tf [(Study populations:)] TJ ET BT 106.463 526.286 Td /F1 9.8 Tf [( Data were obtained from enhanced pandemic surveillance efforts by the City of Milwaukee Health )] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(Department and the New York City Department of Health and Mental Hygiene. Details of testing policies, data acquisition, and )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(analysis are given in )] TJ ET 0.267 0.267 0.267 rg BT 117.286 502.476 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 157.933 502.476 Td /F1 9.8 Tf [(. All data were analyzed first in aggregate and then by age category.)] TJ ET BT 26.250 483.072 Td /F5 9.8 Tf [(Milwaukee data:)] TJ ET BT 96.694 483.072 Td /F1 9.8 Tf [( Between April 6 and July 16, 2009, Milwaukee had recorded 3278 confirmed cases and 4 deaths due to )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(pH1N1, reflecting sustained efforts to test cases of influenza-like illness and their household contacts from the start of the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(epidemic in April until mid-July. On April 27, Milwaukee initiated protocols including recommendations for testing persons with )] TJ ET BT 26.250 447.357 Td /F1 9.8 Tf [(influenza symptoms and travel history to a novel H1N1 area, using a reverse-transcriptase polymerase chain reaction \(RT-PCR\) )] TJ ET BT 26.250 435.453 Td /F1 9.8 Tf [(test specific for pH1N1. By May 7, Milwaukee issued testing guidance updated to recommend testing persons with moderate to )] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(severe symptoms, except health care workers, for whom testing persons with mild symptoms continued to be recommended. )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(We used a line list dated July 21, and in a preliminary analysis examined the frequency of hospitalization among cases by )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(episode date \(the earliest date in their case report\). The proportion of confirmed cases hospitalized was stable around 3% up )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(to May 20, after which it increased markedly to 6-8% in the following weeks. We judged that this change reflected reduced )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(testing of mild cases and limited our analysis \(used to inform the ratio of hospitalizations to medically attended cases\) to the 763 )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(cases with an episode date up to or including May 20. While Milwaukee data were not the main source of estimates of ICU )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(admission or death probabilities, we did employ hospitalized cases up to an episode date of June 14 to contribute to estimates )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(of the ratio of deaths or ICU admissions to hospitalizations, since these should not be affected by failure to test mild cases.)] TJ ET BT 26.250 320.810 Td /F5 9.8 Tf [(New York case data:)] TJ ET BT 116.204 320.810 Td /F1 9.8 Tf [( New York City maintained a policy from April 26 to July 7, 2009 of testing hospitalized patients with )] TJ ET BT 26.250 308.905 Td /F1 9.8 Tf [(influenza-like illness \(ILI\) according to various criteria. These criteria changed up to May 12, from which point they remained as )] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(follows: all hospitalized ILI patients received a rapid influenza antigen test. Those patients who tested positive on rapid test )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(\(which is known to have low sensitivity for seasonal influenza [17] and for pH1N1 [18]\), and any patient in the ICU or on a )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(ventilator, regardless of rapid test result, received RT-PCR tests for pH1N1. We obtained a line list of confirmed or probable )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(hospitalized cases dated July 7, and found in preliminary analysis that all patients in this line list had a date \(onset or admission\) )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(in their record no later than June 30, 7 days prior to the date of the line list. Given that >90% of hospitalizations were reported in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(New York within 7 days, we used this entire line list without accounting for delays in reporting of hospitalizations. Also, given )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(that 98% of admissions occurred after May 12, we did not attempt to account for changes in testing practices prior to May 12. )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(This line list included a field indicating whether the patient had been admitted to the ICU or ventilated; patients were not followed )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(up after admission to determine if this status changed. However, a chart review of 99 hospitalized cases indicated that none had )] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(been admitted to the ICU after admission, so no effort was made to account for this limitation.)] TJ ET BT 26.250 170.453 Td /F1 9.8 Tf [(Separately, we obtained a list of 53 deaths attributed to pH1N1, of whom 44 \(83%\) had been hospitalized before dying. All )] TJ ET BT 26.250 158.548 Td /F1 9.8 Tf [(patients with known influenza or unexplained febrile respiratory illness at the time of death had post-mortem samples and/or )] TJ ET BT 26.250 146.643 Td /F1 9.8 Tf [(samples from before they died sent for PCR testing.)] TJ ET BT 26.250 127.239 Td /F5 9.8 Tf [(New York telephone survey data:)] TJ ET BT 169.858 127.239 Td /F1 9.8 Tf [( To estimate levels of ILI in New York City, DOHMH conducted 1,006 surveys between May 20 )] TJ ET BT 26.250 115.334 Td /F1 9.8 Tf [(and May 27, 2009, and 1,010 between June 15 and June 19. Interviews lasted 5 minutes and were conducted with households )] TJ ET BT 26.250 103.429 Td /F1 9.8 Tf [(in both English and Spanish. The survey used a random-digit dialing \(RDD\) telephone sampling methodology to obtain data )] TJ ET BT 26.250 91.524 Td /F1 9.8 Tf [(from a random sample of residential households in New York City. A non-random individual from each selected household was )] TJ ET BT 26.250 79.620 Td /F1 9.8 Tf [(interviewed and provided information about all household members. Sampled numbers were dialed between 5 and 15 times to )] TJ ET BT 26.250 67.715 Td /F1 9.8 Tf [(contact and interview a household, or until the sampled number was determined to be non-working.)] TJ ET BT 26.250 48.310 Td /F1 9.8 Tf [(To account for this design, the data were weighted to the 2007 American Community Survey \(ACS\); respondents were weighted )] TJ ET BT 26.250 36.405 Td /F1 9.8 Tf [(to householders by borough, age, gender, and race/ethnicity, and the population was weighted by age to the borough of )] TJ ET Q q 15.000 22.120 577.500 754.880 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(of hospitalization, ICU admission or mechanical ventilation, or death, overall and by age group. The challenge is that in any )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population large enough to have significant numbers of the severe outcomes, there was no reliable measure of the number of )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic pH1N1 cases. The problem was approached in two ways. Approach 1 was to view the severity of infection as a )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(pyramid [16], with each successive level representing greater severity; to estimate the ratio of the top level to the base )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(\(symptomatic cases\), we estimated the ratios of each successive level to the one below it \(Fig. 1, left side\). Thus we broke )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(down \(for example\) the sCFR \(Fig. 1, black\), i.e. the probability of death per symptomatic case, into components for which data )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were available the probability of coming to medical attention given symptomatic infection \(CDC survey data\); the probability of )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(being hospitalized given medical attention \(Milwaukee data\); and the probability of dying given hospitalization \(New York data, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(including a correction for those who died of pH1N1 but were not hospitalized\). A second approach was to use the self-reported )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(incidence of influenza-like illness from a telephone survey in New York as the estimate of total pH1N1 symptomatic disease, )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(and the total number of confirmed deaths in New York City as the estimate of the deaths \(after accounting for possibly imperfect )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(viral testing sensitivity\). In each case, prior distributions were used to quantify information on the probability that individuals at )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(each level of severity were detected; these prior distributions reflected the limited data available on detection probabilities and )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(associated uncertainty.)] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(All of these estimates were combined within a Bayesian evidence synthesis framework. This framework permits the estimation )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(of probabilities for the quantities of interest \(the sCFR, sCIR and sCHR\) and associated uncertainty \(expressed as credible )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(intervals\). These credible intervals appropriately reflect the combined uncertainties associated with each of the inputs to the )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(estimate mainly, the true numbers of cases at each level of severity, after accounting for imperfect detection as well as the )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(uncertainties due to sampling error \(chance\).)] TJ ET BT 26.250 526.286 Td /F5 9.8 Tf [(Study populations:)] TJ ET BT 106.463 526.286 Td /F1 9.8 Tf [( Data were obtained from enhanced pandemic surveillance efforts by the City of Milwaukee Health )] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(Department and the New York City Department of Health and Mental Hygiene. Details of testing policies, data acquisition, and )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(analysis are given in )] TJ ET 0.267 0.267 0.267 rg BT 117.286 502.476 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 157.933 502.476 Td /F1 9.8 Tf [(. All data were analyzed first in aggregate and then by age category.)] TJ ET BT 26.250 483.072 Td /F5 9.8 Tf [(Milwaukee data:)] TJ ET BT 96.694 483.072 Td /F1 9.8 Tf [( Between April 6 and July 16, 2009, Milwaukee had recorded 3278 confirmed cases and 4 deaths due to )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(pH1N1, reflecting sustained efforts to test cases of influenza-like illness and their household contacts from the start of the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(epidemic in April until mid-July. On April 27, Milwaukee initiated protocols including recommendations for testing persons with )] TJ ET BT 26.250 447.357 Td /F1 9.8 Tf [(influenza symptoms and travel history to a novel H1N1 area, using a reverse-transcriptase polymerase chain reaction \(RT-PCR\) )] TJ ET BT 26.250 435.453 Td /F1 9.8 Tf [(test specific for pH1N1. By May 7, Milwaukee issued testing guidance updated to recommend testing persons with moderate to )] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(severe symptoms, except health care workers, for whom testing persons with mild symptoms continued to be recommended. )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(We used a line list dated July 21, and in a preliminary analysis examined the frequency of hospitalization among cases by )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(episode date \(the earliest date in their case report\). The proportion of confirmed cases hospitalized was stable around 3% up )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(to May 20, after which it increased markedly to 6-8% in the following weeks. We judged that this change reflected reduced )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(testing of mild cases and limited our analysis \(used to inform the ratio of hospitalizations to medically attended cases\) to the 763 )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(cases with an episode date up to or including May 20. While Milwaukee data were not the main source of estimates of ICU )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(admission or death probabilities, we did employ hospitalized cases up to an episode date of June 14 to contribute to estimates )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(of the ratio of deaths or ICU admissions to hospitalizations, since these should not be affected by failure to test mild cases.)] TJ ET BT 26.250 320.810 Td /F5 9.8 Tf [(New York case data:)] TJ ET BT 116.204 320.810 Td /F1 9.8 Tf [( New York City maintained a policy from April 26 to July 7, 2009 of testing hospitalized patients with )] TJ ET BT 26.250 308.905 Td /F1 9.8 Tf [(influenza-like illness \(ILI\) according to various criteria. These criteria changed up to May 12, from which point they remained as )] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(follows: all hospitalized ILI patients received a rapid influenza antigen test. Those patients who tested positive on rapid test )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(\(which is known to have low sensitivity for seasonal influenza [17] and for pH1N1 [18]\), and any patient in the ICU or on a )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(ventilator, regardless of rapid test result, received RT-PCR tests for pH1N1. We obtained a line list of confirmed or probable )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(hospitalized cases dated July 7, and found in preliminary analysis that all patients in this line list had a date \(onset or admission\) )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(in their record no later than June 30, 7 days prior to the date of the line list. Given that >90% of hospitalizations were reported in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(New York within 7 days, we used this entire line list without accounting for delays in reporting of hospitalizations. Also, given )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(that 98% of admissions occurred after May 12, we did not attempt to account for changes in testing practices prior to May 12. )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(This line list included a field indicating whether the patient had been admitted to the ICU or ventilated; patients were not followed )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(up after admission to determine if this status changed. However, a chart review of 99 hospitalized cases indicated that none had )] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(been admitted to the ICU after admission, so no effort was made to account for this limitation.)] TJ ET BT 26.250 170.453 Td /F1 9.8 Tf [(Separately, we obtained a list of 53 deaths attributed to pH1N1, of whom 44 \(83%\) had been hospitalized before dying. All )] TJ ET BT 26.250 158.548 Td /F1 9.8 Tf [(patients with known influenza or unexplained febrile respiratory illness at the time of death had post-mortem samples and/or )] TJ ET BT 26.250 146.643 Td /F1 9.8 Tf [(samples from before they died sent for PCR testing.)] TJ ET BT 26.250 127.239 Td /F5 9.8 Tf [(New York telephone survey data:)] TJ ET BT 169.858 127.239 Td /F1 9.8 Tf [( To estimate levels of ILI in New York City, DOHMH conducted 1,006 surveys between May 20 )] TJ ET BT 26.250 115.334 Td /F1 9.8 Tf [(and May 27, 2009, and 1,010 between June 15 and June 19. Interviews lasted 5 minutes and were conducted with households )] TJ ET BT 26.250 103.429 Td /F1 9.8 Tf [(in both English and Spanish. The survey used a random-digit dialing \(RDD\) telephone sampling methodology to obtain data )] TJ ET BT 26.250 91.524 Td /F1 9.8 Tf [(from a random sample of residential households in New York City. A non-random individual from each selected household was )] TJ ET BT 26.250 79.620 Td /F1 9.8 Tf [(interviewed and provided information about all household members. Sampled numbers were dialed between 5 and 15 times to )] TJ ET BT 26.250 67.715 Td /F1 9.8 Tf [(contact and interview a household, or until the sampled number was determined to be non-working.)] TJ ET BT 26.250 48.310 Td /F1 9.8 Tf [(To account for this design, the data were weighted to the 2007 American Community Survey \(ACS\); respondents were weighted )] TJ ET BT 26.250 36.405 Td /F1 9.8 Tf [(to householders by borough, age, gender, and race/ethnicity, and the population was weighted by age to the borough of )] TJ ET Q q 15.000 22.120 577.500 754.880 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(of hospitalization, ICU admission or mechanical ventilation, or death, overall and by age group. The challenge is that in any )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(population large enough to have significant numbers of the severe outcomes, there was no reliable measure of the number of )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic pH1N1 cases. The problem was approached in two ways. Approach 1 was to view the severity of infection as a )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(pyramid [16], with each successive level representing greater severity; to estimate the ratio of the top level to the base )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(\(symptomatic cases\), we estimated the ratios of each successive level to the one below it \(Fig. 1, left side\). Thus we broke )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(down \(for example\) the sCFR \(Fig. 1, black\), i.e. the probability of death per symptomatic case, into components for which data )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were available the probability of coming to medical attention given symptomatic infection \(CDC survey data\); the probability of )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(being hospitalized given medical attention \(Milwaukee data\); and the probability of dying given hospitalization \(New York data, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(including a correction for those who died of pH1N1 but were not hospitalized\). A second approach was to use the self-reported )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(incidence of influenza-like illness from a telephone survey in New York as the estimate of total pH1N1 symptomatic disease, )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(and the total number of confirmed deaths in New York City as the estimate of the deaths \(after accounting for possibly imperfect )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(viral testing sensitivity\). In each case, prior distributions were used to quantify information on the probability that individuals at )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(each level of severity were detected; these prior distributions reflected the limited data available on detection probabilities and )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(associated uncertainty.)] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(All of these estimates were combined within a Bayesian evidence synthesis framework. This framework permits the estimation )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(of probabilities for the quantities of interest \(the sCFR, sCIR and sCHR\) and associated uncertainty \(expressed as credible )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(intervals\). These credible intervals appropriately reflect the combined uncertainties associated with each of the inputs to the )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(estimate mainly, the true numbers of cases at each level of severity, after accounting for imperfect detection as well as the )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(uncertainties due to sampling error \(chance\).)] TJ ET BT 26.250 526.286 Td /F5 9.8 Tf [(Study populations:)] TJ ET BT 106.463 526.286 Td /F1 9.8 Tf [( Data were obtained from enhanced pandemic surveillance efforts by the City of Milwaukee Health )] TJ ET BT 26.250 514.381 Td /F1 9.8 Tf [(Department and the New York City Department of Health and Mental Hygiene. Details of testing policies, data acquisition, and )] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(analysis are given in )] TJ ET 0.267 0.267 0.267 rg BT 117.286 502.476 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 157.933 502.476 Td /F1 9.8 Tf [(. All data were analyzed first in aggregate and then by age category.)] TJ ET BT 26.250 483.072 Td /F5 9.8 Tf [(Milwaukee data:)] TJ ET BT 96.694 483.072 Td /F1 9.8 Tf [( Between April 6 and July 16, 2009, Milwaukee had recorded 3278 confirmed cases and 4 deaths due to )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(pH1N1, reflecting sustained efforts to test cases of influenza-like illness and their household contacts from the start of the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(epidemic in April until mid-July. On April 27, Milwaukee initiated protocols including recommendations for testing persons with )] TJ ET BT 26.250 447.357 Td /F1 9.8 Tf [(influenza symptoms and travel history to a novel H1N1 area, using a reverse-transcriptase polymerase chain reaction \(RT-PCR\) )] TJ ET BT 26.250 435.453 Td /F1 9.8 Tf [(test specific for pH1N1. By May 7, Milwaukee issued testing guidance updated to recommend testing persons with moderate to )] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(severe symptoms, except health care workers, for whom testing persons with mild symptoms continued to be recommended. )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(We used a line list dated July 21, and in a preliminary analysis examined the frequency of hospitalization among cases by )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(episode date \(the earliest date in their case report\). The proportion of confirmed cases hospitalized was stable around 3% up )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(to May 20, after which it increased markedly to 6-8% in the following weeks. We judged that this change reflected reduced )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(testing of mild cases and limited our analysis \(used to inform the ratio of hospitalizations to medically attended cases\) to the 763 )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(cases with an episode date up to or including May 20. While Milwaukee data were not the main source of estimates of ICU )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(admission or death probabilities, we did employ hospitalized cases up to an episode date of June 14 to contribute to estimates )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(of the ratio of deaths or ICU admissions to hospitalizations, since these should not be affected by failure to test mild cases.)] TJ ET BT 26.250 320.810 Td /F5 9.8 Tf [(New York case data:)] TJ ET BT 116.204 320.810 Td /F1 9.8 Tf [( New York City maintained a policy from April 26 to July 7, 2009 of testing hospitalized patients with )] TJ ET BT 26.250 308.905 Td /F1 9.8 Tf [(influenza-like illness \(ILI\) according to various criteria. These criteria changed up to May 12, from which point they remained as )] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(follows: all hospitalized ILI patients received a rapid influenza antigen test. Those patients who tested positive on rapid test )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(\(which is known to have low sensitivity for seasonal influenza [17] and for pH1N1 [18]\), and any patient in the ICU or on a )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(ventilator, regardless of rapid test result, received RT-PCR tests for pH1N1. We obtained a line list of confirmed or probable )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(hospitalized cases dated July 7, and found in preliminary analysis that all patients in this line list had a date \(onset or admission\) )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(in their record no later than June 30, 7 days prior to the date of the line list. Given that >90% of hospitalizations were reported in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(New York within 7 days, we used this entire line list without accounting for delays in reporting of hospitalizations. Also, given )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(that 98% of admissions occurred after May 12, we did not attempt to account for changes in testing practices prior to May 12. )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(This line list included a field indicating whether the patient had been admitted to the ICU or ventilated; patients were not followed )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(up after admission to determine if this status changed. However, a chart review of 99 hospitalized cases indicated that none had )] TJ ET BT 26.250 189.858 Td /F1 9.8 Tf [(been admitted to the ICU after admission, so no effort was made to account for this limitation.)] TJ ET BT 26.250 170.453 Td /F1 9.8 Tf [(Separately, we obtained a list of 53 deaths attributed to pH1N1, of whom 44 \(83%\) had been hospitalized before dying. All )] TJ ET BT 26.250 158.548 Td /F1 9.8 Tf [(patients with known influenza or unexplained febrile respiratory illness at the time of death had post-mortem samples and/or )] TJ ET BT 26.250 146.643 Td /F1 9.8 Tf [(samples from before they died sent for PCR testing.)] TJ ET BT 26.250 127.239 Td /F5 9.8 Tf [(New York telephone survey data:)] TJ ET BT 169.858 127.239 Td /F1 9.8 Tf [( To estimate levels of ILI in New York City, DOHMH conducted 1,006 surveys between May 20 )] TJ ET BT 26.250 115.334 Td /F1 9.8 Tf [(and May 27, 2009, and 1,010 between June 15 and June 19. Interviews lasted 5 minutes and were conducted with households )] TJ ET BT 26.250 103.429 Td /F1 9.8 Tf [(in both English and Spanish. The survey used a random-digit dialing \(RDD\) telephone sampling methodology to obtain data )] TJ ET BT 26.250 91.524 Td /F1 9.8 Tf [(from a random sample of residential households in New York City. A non-random individual from each selected household was )] TJ ET BT 26.250 79.620 Td /F1 9.8 Tf [(interviewed and provided information about all household members. Sampled numbers were dialed between 5 and 15 times to )] TJ ET BT 26.250 67.715 Td /F1 9.8 Tf [(contact and interview a household, or until the sampled number was determined to be non-working.)] TJ ET BT 26.250 48.310 Td /F1 9.8 Tf [(To account for this design, the data were weighted to the 2007 American Community Survey \(ACS\); respondents were weighted )] TJ ET BT 26.250 36.405 Td /F1 9.8 Tf [(to householders by borough, age, gender, and race/ethnicity, and the population was weighted by age to the borough of )] 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 133 0 obj << /Type /Annot /Subtype /Link /A 134 0 R /Border [0 0 0] /H /I /Rect [ 117.2857 501.5746 157.9335 511.4952 ] >> endobj 134 0 obj << /Type /Action /S /URI /URI (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784967/#pmed.1000207.s001) >> endobj 135 0 obj << /Type /Annot /Subtype /Link /A 136 0 R /Border [0 0 0] /H /I /Rect [ 117.2857 501.5746 157.9335 511.4952 ] >> endobj 136 0 obj << /Type /Action /S /URI /URI (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784967/#pmed.1000207.s001) >> endobj 137 0 obj << /Type /Annot /Subtype /Link /A 138 0 R /Border [0 0 0] /H /I /Rect [ 117.2857 501.5746 157.9335 511.4952 ] >> endobj 138 0 obj << /Type /Action /S /URI /URI (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784967/#pmed.1000207.s001) >> endobj 139 0 obj << /Type /Page /Parent 3 0 R /Annots [ 141 0 R 145 0 R 148 0 R 156 0 R 158 0 R 162 0 R 164 0 R 172 0 R 174 0 R 178 0 R 180 0 R 188 0 R ] /Contents 140 0 R >> endobj 140 0 obj << /Length 18435 >> stream 0.271 0.267 0.267 rg q 15.000 32.273 577.500 744.727 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(residence.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(The surveys RDD sampling methodology gave a useful overview of ILI in the community, but it has limitations. The design does )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(not include individual living in households only reachable by cellular telephone but not by a landline telephone number, and also )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(omitted those living in group or institutional housing. Although households were randomly selected, for the sake of efficiency, )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(the interviewed adult was not. Instead, an available adult in the household provided information about all household members )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(and themselves, which may have introduced bias. The results of the survey are being compiled for publication elsewhere. Here, )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(we use summaries of these results by age group \(see )] TJ ET 0.267 0.267 0.267 rg BT 260.347 688.548 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 300.995 688.548 Td /F1 9.8 Tf [(\) as one means to provide denominators of symptomatic cases.)] TJ ET BT 26.250 669.143 Td /F5 9.8 Tf [(Data on detection probabilities from CDC investigations: )] TJ ET BT 270.634 669.143 Td /F1 9.8 Tf [( Sources of data include two community surveys on influenza-like )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(illness \(ILI\) and health seeking behavior, and two field investigations conducted during early outbreaks of pH1N1 in the United )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(States. These sources are described in further detail elsewhere [19], but are summarized here briefly. In 2007, the Behavioral )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(Risk Factor Surveillance Survey \(BRFSS\), a random-digit dialed telephone survey, included a module on ILI in 9 states. This )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(module included questions to assess the incidence of ILI, health-seeking behavior, physician diagnosis of influenza, and )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(treatment of influenza with antiviral medications during the annual 2006-2007 influenza season. In May 2009, following the )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(emergence of pH1N1, a random-digit dialed telephone survey sampled similarly to the BRFSS was conducted in the same 9 )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(states using only the ILI module from the 2007 BRFSS and limited demographic questions. In addition, some data was available )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(from field investigations conducted during large outbreaks of pH1N1 in one community in Chicago and a university campus in )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(Delaware. Investigations of these outbreaks consisted of household interviews in a Chicago neighborhood and an online survey )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(of students and faculty in Delaware. These data were used to inform detection probabilities. In addition, these data were used to )] TJ ET BT 26.250 535.714 Td /F1 9.8 Tf [(inform a prior distribution on the ratio between symptomatic and medically attended cases, )] TJ ET q 35.250 0 0 15.000 418.580 532.714 cm /I4 Do Q BT 453.830 535.714 Td /F1 9.8 Tf [(: these surveys estimated )] TJ ET BT 26.250 523.191 Td /F1 9.8 Tf [(that between 42% and 58% of symptomatic ILI cases sought medical attention [19].)] TJ ET 0.965 0.965 0.965 rg 26.250 90.487 555.000 422.822 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 513.310 m 581.250 513.310 l 581.250 512.560 l 26.250 512.560 l f 26.250 90.487 m 581.250 90.487 l 581.250 91.237 l 26.250 91.237 l f q 450.000 0 0 288.000 35.250 215.560 cm /I5 Do Q q 35.250 101.737 537.000 107.822 re W n 0.271 0.267 0.267 rg BT 35.250 200.036 Td /F4 9.8 Tf [(Fig. 1: Diagram of two approaches to estimating the symptomatic case-fatality ratio \(sCFR\), shown in black.)] TJ ET BT 35.250 180.666 Td /F1 9.8 Tf [(Approach 1 used three data sets to estimate successive steps of the severity pyramid. Approach 2 used self-reported )] TJ ET BT 35.250 166.930 Td /F1 9.8 Tf [(influenza-like illness for the denominator, and confirmed deaths for the numerator, both from New York City. Both )] TJ ET BT 35.250 153.193 Td /F1 9.8 Tf [(approaches used prior distributions, in some cases informed by additional data, to inform the probability of detecting )] TJ ET BT 35.250 139.457 Td /F1 9.8 Tf [(\(confirming and reporting\) cases at each level of severity \(not shown in the diagram; see )] TJ ET 0.267 0.267 0.267 rg BT 418.366 139.457 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 459.014 139.457 Td /F1 9.8 Tf [(\). The Bayesian evidence )] TJ ET BT 35.250 125.721 Td /F1 9.8 Tf [(synthesis framework was used as a formal way to combine information and uncertainty about each level of severity into a )] TJ ET BT 35.250 111.985 Td /F1 9.8 Tf [(single estimate and associated uncertainty that reflected all of the uncertainty in the inputs.)] TJ ET Q BT 26.250 70.987 Td /F5 9.8 Tf [(Analysis:)] TJ ET BT 65.260 70.987 Td /F1 9.8 Tf [( Estimation of the probabilities of primary interest, )] TJ ET q 33.000 0 0 15.000 281.466 67.987 cm /I7 Do Q BT 314.466 70.987 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 319.887 67.987 cm /I9 Do Q BT 347.637 70.987 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 372.031 67.987 cm /I11 Do Q BT 403.531 70.987 Td /F1 9.8 Tf [( , respectively the sCHR, sCIR, and )] TJ ET BT 26.250 58.464 Td /F1 9.8 Tf [(sCFR, was undertaken using a Bayesian evidence synthesis framework [14]. Details are given in the )] TJ ET 0.267 0.267 0.267 rg BT 461.929 58.464 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 502.577 58.464 Td /F1 9.8 Tf [(, and a )] TJ ET BT 26.250 46.559 Td /F1 9.8 Tf [(schematic illustration of the model is given in Figure 2. Briefly, in this framework, prior information about the quantities of interest )] TJ ET Q q 15.000 32.273 577.500 744.727 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(residence.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(The surveys RDD sampling methodology gave a useful overview of ILI in the community, but it has limitations. The design does )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(not include individual living in households only reachable by cellular telephone but not by a landline telephone number, and also )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(omitted those living in group or institutional housing. Although households were randomly selected, for the sake of efficiency, )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(the interviewed adult was not. Instead, an available adult in the household provided information about all household members )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(and themselves, which may have introduced bias. The results of the survey are being compiled for publication elsewhere. Here, )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(we use summaries of these results by age group \(see )] TJ ET 0.267 0.267 0.267 rg BT 260.347 688.548 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 300.995 688.548 Td /F1 9.8 Tf [(\) as one means to provide denominators of symptomatic cases.)] TJ ET BT 26.250 669.143 Td /F5 9.8 Tf [(Data on detection probabilities from CDC investigations: )] TJ ET BT 270.634 669.143 Td /F1 9.8 Tf [( Sources of data include two community surveys on influenza-like )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(illness \(ILI\) and health seeking behavior, and two field investigations conducted during early outbreaks of pH1N1 in the United )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(States. These sources are described in further detail elsewhere [19], but are summarized here briefly. In 2007, the Behavioral )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(Risk Factor Surveillance Survey \(BRFSS\), a random-digit dialed telephone survey, included a module on ILI in 9 states. This )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(module included questions to assess the incidence of ILI, health-seeking behavior, physician diagnosis of influenza, and )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(treatment of influenza with antiviral medications during the annual 2006-2007 influenza season. In May 2009, following the )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(emergence of pH1N1, a random-digit dialed telephone survey sampled similarly to the BRFSS was conducted in the same 9 )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(states using only the ILI module from the 2007 BRFSS and limited demographic questions. In addition, some data was available )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(from field investigations conducted during large outbreaks of pH1N1 in one community in Chicago and a university campus in )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(Delaware. Investigations of these outbreaks consisted of household interviews in a Chicago neighborhood and an online survey )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(of students and faculty in Delaware. These data were used to inform detection probabilities. In addition, these data were used to )] TJ ET BT 26.250 535.714 Td /F1 9.8 Tf [(inform a prior distribution on the ratio between symptomatic and medically attended cases, )] TJ ET q 35.250 0 0 15.000 418.580 532.714 cm /I13 Do Q BT 453.830 535.714 Td /F1 9.8 Tf [(: these surveys estimated )] TJ ET BT 26.250 523.191 Td /F1 9.8 Tf [(that between 42% and 58% of symptomatic ILI cases sought medical attention [19].)] TJ ET 0.965 0.965 0.965 rg 26.250 90.487 555.000 422.822 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 513.310 m 581.250 513.310 l 581.250 512.560 l 26.250 512.560 l f 26.250 90.487 m 581.250 90.487 l 581.250 91.237 l 26.250 91.237 l f q 450.000 0 0 288.000 35.250 215.560 cm /I5 Do Q q 35.250 101.737 537.000 107.822 re W n 0.271 0.267 0.267 rg BT 35.250 200.036 Td /F4 9.8 Tf [(Fig. 1: Diagram of two approaches to estimating the symptomatic case-fatality ratio \(sCFR\), shown in black.)] TJ ET BT 35.250 180.666 Td /F1 9.8 Tf [(Approach 1 used three data sets to estimate successive steps of the severity pyramid. Approach 2 used self-reported )] TJ ET BT 35.250 166.930 Td /F1 9.8 Tf [(influenza-like illness for the denominator, and confirmed deaths for the numerator, both from New York City. Both )] TJ ET BT 35.250 153.193 Td /F1 9.8 Tf [(approaches used prior distributions, in some cases informed by additional data, to inform the probability of detecting )] TJ ET BT 35.250 139.457 Td /F1 9.8 Tf [(\(confirming and reporting\) cases at each level of severity \(not shown in the diagram; see )] TJ ET 0.267 0.267 0.267 rg BT 418.366 139.457 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 459.014 139.457 Td /F1 9.8 Tf [(\). The Bayesian evidence )] TJ ET BT 35.250 125.721 Td /F1 9.8 Tf [(synthesis framework was used as a formal way to combine information and uncertainty about each level of severity into a )] TJ ET BT 35.250 111.985 Td /F1 9.8 Tf [(single estimate and associated uncertainty that reflected all of the uncertainty in the inputs.)] TJ ET Q BT 26.250 70.987 Td /F5 9.8 Tf [(Analysis:)] TJ ET BT 65.260 70.987 Td /F1 9.8 Tf [( Estimation of the probabilities of primary interest, )] TJ ET q 33.000 0 0 15.000 281.466 67.987 cm /I15 Do Q BT 314.466 70.987 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 319.887 67.987 cm /I17 Do Q BT 347.637 70.987 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 372.031 67.987 cm /I19 Do Q BT 403.531 70.987 Td /F1 9.8 Tf [( , respectively the sCHR, sCIR, and )] TJ ET BT 26.250 58.464 Td /F1 9.8 Tf [(sCFR, was undertaken using a Bayesian evidence synthesis framework [14]. Details are given in the )] TJ ET 0.267 0.267 0.267 rg BT 461.929 58.464 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 502.577 58.464 Td /F1 9.8 Tf [(, and a )] TJ ET BT 26.250 46.559 Td /F1 9.8 Tf [(schematic illustration of the model is given in Figure 2. Briefly, in this framework, prior information about the quantities of interest )] TJ ET Q q 15.000 32.273 577.500 744.727 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(residence.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(The surveys RDD sampling methodology gave a useful overview of ILI in the community, but it has limitations. The design does )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(not include individual living in households only reachable by cellular telephone but not by a landline telephone number, and also )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(omitted those living in group or institutional housing. Although households were randomly selected, for the sake of efficiency, )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(the interviewed adult was not. Instead, an available adult in the household provided information about all household members )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(and themselves, which may have introduced bias. The results of the survey are being compiled for publication elsewhere. Here, )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(we use summaries of these results by age group \(see )] TJ ET 0.267 0.267 0.267 rg BT 260.347 688.548 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 300.995 688.548 Td /F1 9.8 Tf [(\) as one means to provide denominators of symptomatic cases.)] TJ ET BT 26.250 669.143 Td /F5 9.8 Tf [(Data on detection probabilities from CDC investigations: )] TJ ET BT 270.634 669.143 Td /F1 9.8 Tf [( Sources of data include two community surveys on influenza-like )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(illness \(ILI\) and health seeking behavior, and two field investigations conducted during early outbreaks of pH1N1 in the United )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(States. These sources are described in further detail elsewhere [19], but are summarized here briefly. In 2007, the Behavioral )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(Risk Factor Surveillance Survey \(BRFSS\), a random-digit dialed telephone survey, included a module on ILI in 9 states. This )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(module included questions to assess the incidence of ILI, health-seeking behavior, physician diagnosis of influenza, and )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(treatment of influenza with antiviral medications during the annual 2006-2007 influenza season. In May 2009, following the )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(emergence of pH1N1, a random-digit dialed telephone survey sampled similarly to the BRFSS was conducted in the same 9 )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(states using only the ILI module from the 2007 BRFSS and limited demographic questions. In addition, some data was available )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(from field investigations conducted during large outbreaks of pH1N1 in one community in Chicago and a university campus in )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(Delaware. Investigations of these outbreaks consisted of household interviews in a Chicago neighborhood and an online survey )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(of students and faculty in Delaware. These data were used to inform detection probabilities. In addition, these data were used to )] TJ ET BT 26.250 535.714 Td /F1 9.8 Tf [(inform a prior distribution on the ratio between symptomatic and medically attended cases, )] TJ ET q 35.250 0 0 15.000 418.580 532.714 cm /I21 Do Q BT 453.830 535.714 Td /F1 9.8 Tf [(: these surveys estimated )] TJ ET BT 26.250 523.191 Td /F1 9.8 Tf [(that between 42% and 58% of symptomatic ILI cases sought medical attention [19].)] TJ ET 0.965 0.965 0.965 rg 26.250 90.487 555.000 422.822 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 513.310 m 581.250 513.310 l 581.250 512.560 l 26.250 512.560 l f 26.250 90.487 m 581.250 90.487 l 581.250 91.237 l 26.250 91.237 l f q 450.000 0 0 288.000 35.250 215.560 cm /I5 Do Q q 35.250 101.737 537.000 107.822 re W n 0.271 0.267 0.267 rg BT 35.250 200.036 Td /F4 9.8 Tf [(Fig. 1: Diagram of two approaches to estimating the symptomatic case-fatality ratio \(sCFR\), shown in black.)] TJ ET BT 35.250 180.666 Td /F1 9.8 Tf [(Approach 1 used three data sets to estimate successive steps of the severity pyramid. Approach 2 used self-reported )] TJ ET BT 35.250 166.930 Td /F1 9.8 Tf [(influenza-like illness for the denominator, and confirmed deaths for the numerator, both from New York City. Both )] TJ ET BT 35.250 153.193 Td /F1 9.8 Tf [(approaches used prior distributions, in some cases informed by additional data, to inform the probability of detecting )] TJ ET BT 35.250 139.457 Td /F1 9.8 Tf [(\(confirming and reporting\) cases at each level of severity \(not shown in the diagram; see )] TJ ET 0.267 0.267 0.267 rg BT 418.366 139.457 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 459.014 139.457 Td /F1 9.8 Tf [(\). The Bayesian evidence )] TJ ET BT 35.250 125.721 Td /F1 9.8 Tf [(synthesis framework was used as a formal way to combine information and uncertainty about each level of severity into a )] TJ ET BT 35.250 111.985 Td /F1 9.8 Tf [(single estimate and associated uncertainty that reflected all of the uncertainty in the inputs.)] TJ ET Q BT 26.250 70.987 Td /F5 9.8 Tf [(Analysis:)] TJ ET BT 65.260 70.987 Td /F1 9.8 Tf [( Estimation of the probabilities of primary interest, )] TJ ET q 33.000 0 0 15.000 281.466 67.987 cm /I23 Do Q BT 314.466 70.987 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 319.887 67.987 cm /I25 Do Q BT 347.637 70.987 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 372.031 67.987 cm /I27 Do Q BT 403.531 70.987 Td /F1 9.8 Tf [( , respectively the sCHR, sCIR, and )] TJ ET BT 26.250 58.464 Td /F1 9.8 Tf [(sCFR, was undertaken using a Bayesian evidence synthesis framework [14]. Details are given in the )] TJ ET 0.267 0.267 0.267 rg BT 461.929 58.464 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 502.577 58.464 Td /F1 9.8 Tf [(, and a )] TJ ET BT 26.250 46.559 Td /F1 9.8 Tf [(schematic illustration of the model is given in Figure 2. 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This posterior distribution fully reflects all )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(information about the quantities of interest that is contained in the prior distribution and the observed data. Specifically, it was )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(assumed that detected cases )] TJ ET q 10.500 0 0 11.250 155.779 730.036 cm /I29 Do Q BT 166.279 731.762 Td /F1 9.8 Tf [( at each level of severity medically attended \()] TJ ET q 14.250 0 0 10.500 368.952 730.786 cm /I31 Do Q BT 383.202 731.762 Td /F1 9.8 Tf [(\), hospitalized \()] TJ ET q 12.000 0 0 10.500 449.307 730.786 cm /I33 Do Q BT 461.307 731.762 Td /F1 9.8 Tf [(\), ICU-admitted \()] TJ ET q 7.500 0 0 10.500 533.360 730.786 cm /I35 Do Q BT 540.860 731.762 Td /F1 9.8 Tf [(\), and )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(fatal \()] TJ ET q 11.250 0 0 10.500 50.635 718.881 cm /I37 Do Q BT 61.885 719.857 Td /F1 9.8 Tf [(\) represented binomially distributed samples from the true number of cases )] TJ ET q 12.000 0 0 10.500 396.222 718.881 cm /I39 Do Q BT 408.222 719.857 Td /F1 9.8 Tf [( at the corresponding level of severity, )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(in the given location \(New York, abbreviated )] TJ ET q 12.000 0 0 10.500 219.709 706.976 cm /I41 Do Q BT 231.709 707.952 Td /F1 9.8 Tf [( or Milwaukee, abbreviated )] TJ ET q 15.000 0 0 11.250 350.923 706.226 cm /I43 Do Q BT 365.923 707.952 Td /F1 9.8 Tf [(\), with probability equal to the probability of )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(detection at each level \()] TJ ET q 7.500 0 0 10.500 129.220 695.072 cm /I45 Do Q BT 136.720 696.048 Td /F1 9.8 Tf [(\). The probability )] TJ ET q 7.500 0 0 10.500 212.038 695.072 cm /I47 Do Q BT 219.538 696.048 Td /F1 9.8 Tf [( for each level was informed by evidence on the probability of testing at each level )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(of severity \(which may have depended on the sensitivity of the rapid test if this was required for PCR testing\) and the sensitivity )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(of the PCR test \(Table 1\). Thus, for example, we defined the probability of detecting a hospitalized case in New York as )] TJ ET q 106.500 0 0 13.500 26.250 656.357 cm /I49 Do Q BT 132.750 659.057 Td /F1 9.8 Tf [(, where )] TJ ET q 31.500 0 0 13.500 167.431 656.357 cm /I51 Do Q BT 198.931 659.057 Td /F1 9.8 Tf [( was the probability of performing an RT-PCR based test and )] TJ ET q 32.250 0 0 13.500 464.998 656.357 cm /I53 Do Q BT 497.248 659.057 Td /F1 9.8 Tf [( was the sensitivity )] TJ ET BT 26.250 645.557 Td /F1 9.8 Tf [(of that test. Hence, the observed number of hospitalized patients in New York, )] TJ ET q 29.250 0 0 13.500 365.501 642.857 cm /I55 Do Q BT 394.751 645.557 Td /F1 9.8 Tf [(, was assumed to be distributed as )] TJ ET q 124.500 0 0 14.250 26.250 628.607 cm /I57 Do Q BT 150.750 631.457 Td /F1 9.8 Tf [(.)] TJ ET 0.965 0.965 0.965 rg 26.250 255.853 555.000 365.255 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 621.107 m 581.250 621.107 l 581.250 620.357 l 26.250 620.357 l f 26.250 255.853 m 581.250 255.853 l 581.250 256.603 l 26.250 256.603 l f q 450.000 0 0 171.000 35.250 440.357 cm /I59 Do Q q 35.250 267.103 537.000 167.255 re W n 0.271 0.267 0.267 rg BT 35.250 424.833 Td /F4 9.8 Tf [(Fig. 2: Schematic illustration of the relationship between the observed data \(rectangles\) and the conditional )] TJ ET BT 35.250 412.929 Td /F4 9.8 Tf [(probabilities \(blue circles\).)] TJ ET BT 35.250 393.559 Td /F1 9.8 Tf [(The key quantities of interest, sCHR, sCIR, and sCFR are products of the relevant conditional probabilities. \(a\) Approach 1, )] TJ ET BT 35.250 378.811 Td /F1 9.8 Tf [(synthesizing data from New York City and Milwaukee. Note that )] TJ ET q 35.250 0 0 15.000 312.686 375.811 cm /I61 Do Q BT 347.936 378.811 Td /F1 9.8 Tf [( \(double circle\) is informed by prior information [19] )] TJ ET BT 35.250 364.822 Td /F1 9.8 Tf [(rather than observed data. \(b\) Approach 2, using data from New York City only, including the telephone survey. )] TJ ET BT 35.250 351.086 Td /F1 9.8 Tf [(Abbreviations: sCFR: symptomatic case-fatality ratio; sCIR: symptomatic case-ICU \(or mechanical ventilation\) ratio; sCHR: )] TJ ET BT 35.250 336.339 Td /F1 9.8 Tf [(symptomatic case-hospitalization ratio. Variables: )] TJ ET q 37.500 0 0 15.000 251.446 333.339 cm /I63 Do Q BT 288.947 336.339 Td /F1 9.8 Tf [( : the ratio of deaths to medically-attended cases; )] TJ ET q 35.250 0 0 15.000 504.100 333.339 cm /I65 Do Q BT 539.350 336.339 Td /F1 9.8 Tf [( : the )] TJ ET BT 35.250 321.339 Td /F1 9.8 Tf [(ratio of deaths to hospitalized cases; )] TJ ET q 35.250 0 0 15.000 195.667 318.339 cm /I67 Do Q BT 230.917 321.339 Td /F1 9.8 Tf [( : the ratio of cases admitted to intensive care or using mechanical ventilation )] TJ ET BT 35.250 306.339 Td /F1 9.8 Tf [(to hospitalized cases; )] TJ ET q 38.250 0 0 15.000 131.171 303.339 cm /I69 Do Q BT 169.421 306.339 Td /F1 9.8 Tf [( : the ratio of hospitalized cases to medically attended cases; )] TJ ET q 35.250 0 0 15.000 434.425 303.339 cm /I71 Do Q BT 469.675 306.339 Td /F1 9.8 Tf [( : the ratio of medically-)] TJ ET BT 35.250 291.339 Td /F1 9.8 Tf [(attended cases to symptomatic cases; )] TJ ET q 31.500 0 0 15.000 203.243 288.339 cm /I73 Do Q BT 234.743 291.339 Td /F1 9.8 Tf [( : the ratio of deaths to symptomatic cases; )] TJ ET q 33.000 0 0 15.000 422.791 288.339 cm /I75 Do Q BT 455.791 291.339 Td /F1 9.8 Tf [( : the ratio of hospitalized )] TJ ET BT 35.250 277.350 Td /F1 9.8 Tf [(cases to symptomatic cases.)] TJ ET Q BT 26.250 236.353 Td /F1 9.8 Tf [(We noted that the ratios )] TJ ET q 33.000 0 0 15.000 132.476 233.353 cm /I77 Do Q BT 165.476 236.353 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 170.897 233.353 cm /I79 Do Q BT 198.647 236.353 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 223.042 233.353 cm /I81 Do Q BT 254.542 236.353 Td /F1 9.8 Tf [( can be built up multiplicatively from simpler components: for instance, the )] TJ ET BT 26.250 221.353 Td /F1 9.8 Tf [(ratio of deaths to symptomatic infections may be expressed as )] TJ ET q 154.500 0 0 15.000 298.285 218.353 cm /I83 Do Q BT 452.785 221.353 Td /F1 9.8 Tf [(, the product of the ratios of )] TJ ET BT 26.250 208.829 Td /F1 9.8 Tf [(deaths:hospitalizations, of hospitalizations:medically attended cases, and of medically attended cases:symptomatic cases. )] TJ ET BT 26.250 196.924 Td /F1 9.8 Tf [(These ratios of increasing severity are similar to conditional probabilities but are not strictly so in all cases, since for example )] TJ ET BT 26.250 185.019 Td /F1 9.8 Tf [(some deaths in New York City occurred in persons who were not hospitalized. For this reason we model deaths separately )] TJ ET BT 26.250 170.638 Td /F1 9.8 Tf [(among hospitalized and non-hospitalized patients, i.e. )] TJ ET q 240.000 0 0 15.000 260.913 167.638 cm /I85 Do Q BT 500.913 170.638 Td /F1 9.8 Tf [(. For each )] TJ ET BT 26.250 158.115 Td /F1 9.8 Tf [(observed level of severity \(medically-attended, hospitalized, ICU, death\), the true number of cases was modeled as a binomial )] TJ ET BT 26.250 146.210 Td /F1 9.8 Tf [(sample from the true number of cases at an appropriate lower level, hence)] TJ ET q 305.250 0 0 18.000 26.250 118.329 cm /I87 Do Q BT 331.500 121.929 Td /F1 9.8 Tf [(,)] TJ ET q 291.750 0 0 18.000 26.250 92.829 cm /I89 Do Q BT 318.000 96.429 Td /F1 9.8 Tf [(,)] TJ ET BT 26.250 75.805 Td /F1 9.8 Tf [(where the first subscript indicates severity and the second indicates the population \(New York, Milwaukee to May 20, Milwaukee )] TJ ET BT 26.250 63.900 Td /F1 9.8 Tf [(to June 14\).)] TJ ET BT 26.250 44.496 Td /F1 9.8 Tf [(In Approach 1 \(New York and Milwaukee data combined\), for the unobserved level of severity \(symptomatic cases\) we used a )] TJ ET Q q 15.000 30.210 577.500 746.790 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(\(including the uncertainty associated with this prior information\) is combined with the information coming from the observed )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(cases at each severity level to derive aposterior distribution on these quantities. This posterior distribution fully reflects all )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(information about the quantities of interest that is contained in the prior distribution and the observed data. Specifically, it was )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(assumed that detected cases )] TJ ET q 10.500 0 0 11.250 155.779 730.036 cm /I91 Do Q BT 166.279 731.762 Td /F1 9.8 Tf [( at each level of severity medically attended \()] TJ ET q 14.250 0 0 10.500 368.952 730.786 cm /I93 Do Q BT 383.202 731.762 Td /F1 9.8 Tf [(\), hospitalized \()] TJ ET q 12.000 0 0 10.500 449.307 730.786 cm /I95 Do Q BT 461.307 731.762 Td /F1 9.8 Tf [(\), ICU-admitted \()] TJ ET q 7.500 0 0 10.500 533.360 730.786 cm /I97 Do Q BT 540.860 731.762 Td /F1 9.8 Tf [(\), and )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(fatal \()] TJ ET q 11.250 0 0 10.500 50.635 718.881 cm /I99 Do Q BT 61.885 719.857 Td /F1 9.8 Tf [(\) represented binomially distributed samples from the true number of cases )] TJ ET q 12.000 0 0 10.500 396.222 718.881 cm /I101 Do Q BT 408.222 719.857 Td /F1 9.8 Tf [( at the corresponding level of severity, )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(in the given location \(New York, abbreviated )] TJ ET q 12.000 0 0 10.500 219.709 706.976 cm /I103 Do Q BT 231.709 707.952 Td /F1 9.8 Tf [( or Milwaukee, abbreviated )] TJ ET q 15.000 0 0 11.250 350.923 706.226 cm /I105 Do Q BT 365.923 707.952 Td /F1 9.8 Tf [(\), with probability equal to the probability of )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(detection at each level \()] TJ ET q 7.500 0 0 10.500 129.220 695.072 cm /I107 Do Q BT 136.720 696.048 Td /F1 9.8 Tf [(\). The probability )] TJ ET q 7.500 0 0 10.500 212.038 695.072 cm /I109 Do Q BT 219.538 696.048 Td /F1 9.8 Tf [( for each level was informed by evidence on the probability of testing at each level )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(of severity \(which may have depended on the sensitivity of the rapid test if this was required for PCR testing\) and the sensitivity )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(of the PCR test \(Table 1\). Thus, for example, we defined the probability of detecting a hospitalized case in New York as )] TJ ET q 106.500 0 0 13.500 26.250 656.357 cm /I111 Do Q BT 132.750 659.057 Td /F1 9.8 Tf [(, where )] TJ ET q 31.500 0 0 13.500 167.431 656.357 cm /I113 Do Q BT 198.931 659.057 Td /F1 9.8 Tf [( was the probability of performing an RT-PCR based test and )] TJ ET q 32.250 0 0 13.500 464.998 656.357 cm /I115 Do Q BT 497.248 659.057 Td /F1 9.8 Tf [( was the sensitivity )] TJ ET BT 26.250 645.557 Td /F1 9.8 Tf [(of that test. Hence, the observed number of hospitalized patients in New York, )] TJ ET q 29.250 0 0 13.500 365.501 642.857 cm /I117 Do Q BT 394.751 645.557 Td /F1 9.8 Tf [(, was assumed to be distributed as )] TJ ET q 124.500 0 0 14.250 26.250 628.607 cm /I119 Do Q BT 150.750 631.457 Td /F1 9.8 Tf [(.)] TJ ET 0.965 0.965 0.965 rg 26.250 255.853 555.000 365.255 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 621.107 m 581.250 621.107 l 581.250 620.357 l 26.250 620.357 l f 26.250 255.853 m 581.250 255.853 l 581.250 256.603 l 26.250 256.603 l f q 450.000 0 0 171.000 35.250 440.357 cm /I121 Do Q q 35.250 267.103 537.000 167.255 re W n 0.271 0.267 0.267 rg BT 35.250 424.833 Td /F4 9.8 Tf [(Fig. 2: Schematic illustration of the relationship between the observed data \(rectangles\) and the conditional )] TJ ET BT 35.250 412.929 Td /F4 9.8 Tf [(probabilities \(blue circles\).)] TJ ET BT 35.250 393.559 Td /F1 9.8 Tf [(The key quantities of interest, sCHR, sCIR, and sCFR are products of the relevant conditional probabilities. \(a\) Approach 1, )] TJ ET BT 35.250 378.811 Td /F1 9.8 Tf [(synthesizing data from New York City and Milwaukee. Note that )] TJ ET q 35.250 0 0 15.000 312.686 375.811 cm /I123 Do Q BT 347.936 378.811 Td /F1 9.8 Tf [( \(double circle\) is informed by prior information [19] )] TJ ET BT 35.250 364.822 Td /F1 9.8 Tf [(rather than observed data. \(b\) Approach 2, using data from New York City only, including the telephone survey. )] TJ ET BT 35.250 351.086 Td /F1 9.8 Tf [(Abbreviations: sCFR: symptomatic case-fatality ratio; sCIR: symptomatic case-ICU \(or mechanical ventilation\) ratio; sCHR: )] TJ ET BT 35.250 336.339 Td /F1 9.8 Tf [(symptomatic case-hospitalization ratio. Variables: )] TJ ET q 37.500 0 0 15.000 251.446 333.339 cm /I125 Do Q BT 288.947 336.339 Td /F1 9.8 Tf [( : the ratio of deaths to medically-attended cases; )] TJ ET q 35.250 0 0 15.000 504.100 333.339 cm /I127 Do Q BT 539.350 336.339 Td /F1 9.8 Tf [( : the )] TJ ET BT 35.250 321.339 Td /F1 9.8 Tf [(ratio of deaths to hospitalized cases; )] TJ ET q 35.250 0 0 15.000 195.667 318.339 cm /I129 Do Q BT 230.917 321.339 Td /F1 9.8 Tf [( : the ratio of cases admitted to intensive care or using mechanical ventilation )] TJ ET BT 35.250 306.339 Td /F1 9.8 Tf [(to hospitalized cases; )] TJ ET q 38.250 0 0 15.000 131.171 303.339 cm /I131 Do Q BT 169.421 306.339 Td /F1 9.8 Tf [( : the ratio of hospitalized cases to medically attended cases; )] TJ ET q 35.250 0 0 15.000 434.425 303.339 cm /I133 Do Q BT 469.675 306.339 Td /F1 9.8 Tf [( : the ratio of medically-)] TJ ET BT 35.250 291.339 Td /F1 9.8 Tf [(attended cases to symptomatic cases; )] TJ ET q 31.500 0 0 15.000 203.243 288.339 cm /I135 Do Q BT 234.743 291.339 Td /F1 9.8 Tf [( : the ratio of deaths to symptomatic cases; )] TJ ET q 33.000 0 0 15.000 422.791 288.339 cm /I137 Do Q BT 455.791 291.339 Td /F1 9.8 Tf [( : the ratio of hospitalized )] TJ ET BT 35.250 277.350 Td /F1 9.8 Tf [(cases to symptomatic cases.)] TJ ET Q BT 26.250 236.353 Td /F1 9.8 Tf [(We noted that the ratios )] TJ ET q 33.000 0 0 15.000 132.476 233.353 cm /I139 Do Q BT 165.476 236.353 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 170.897 233.353 cm /I141 Do Q BT 198.647 236.353 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 223.042 233.353 cm /I143 Do Q BT 254.542 236.353 Td /F1 9.8 Tf [( can be built up multiplicatively from simpler components: for instance, the )] TJ ET BT 26.250 221.353 Td /F1 9.8 Tf [(ratio of deaths to symptomatic infections may be expressed as )] TJ ET q 154.500 0 0 15.000 298.285 218.353 cm /I145 Do Q BT 452.785 221.353 Td /F1 9.8 Tf [(, the product of the ratios of )] TJ ET BT 26.250 208.829 Td /F1 9.8 Tf [(deaths:hospitalizations, of hospitalizations:medically attended cases, and of medically attended cases:symptomatic cases. )] TJ ET BT 26.250 196.924 Td /F1 9.8 Tf [(These ratios of increasing severity are similar to conditional probabilities but are not strictly so in all cases, since for example )] TJ ET BT 26.250 185.019 Td /F1 9.8 Tf [(some deaths in New York City occurred in persons who were not hospitalized. For this reason we model deaths separately )] TJ ET BT 26.250 170.638 Td /F1 9.8 Tf [(among hospitalized and non-hospitalized patients, i.e. )] TJ ET q 240.000 0 0 15.000 260.913 167.638 cm /I147 Do Q BT 500.913 170.638 Td /F1 9.8 Tf [(. For each )] TJ ET BT 26.250 158.115 Td /F1 9.8 Tf [(observed level of severity \(medically-attended, hospitalized, ICU, death\), the true number of cases was modeled as a binomial )] TJ ET BT 26.250 146.210 Td /F1 9.8 Tf [(sample from the true number of cases at an appropriate lower level, hence)] TJ ET q 305.250 0 0 18.000 26.250 118.329 cm /I149 Do Q BT 331.500 121.929 Td /F1 9.8 Tf [(,)] TJ ET q 291.750 0 0 18.000 26.250 92.829 cm /I151 Do Q BT 318.000 96.429 Td /F1 9.8 Tf [(,)] TJ ET BT 26.250 75.805 Td /F1 9.8 Tf [(where the first subscript indicates severity and the second indicates the population \(New York, Milwaukee to May 20, Milwaukee )] TJ ET BT 26.250 63.900 Td /F1 9.8 Tf [(to June 14\).)] TJ ET BT 26.250 44.496 Td /F1 9.8 Tf [(In Approach 1 \(New York and Milwaukee data combined\), for the unobserved level of severity \(symptomatic cases\) we used a )] TJ ET Q q 15.000 30.210 577.500 746.790 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(\(including the uncertainty associated with this prior information\) is combined with the information coming from the observed )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(cases at each severity level to derive aposterior distribution on these quantities. This posterior distribution fully reflects all )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(information about the quantities of interest that is contained in the prior distribution and the observed data. Specifically, it was )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(assumed that detected cases )] TJ ET q 10.500 0 0 11.250 155.779 730.036 cm /I153 Do Q BT 166.279 731.762 Td /F1 9.8 Tf [( at each level of severity medically attended \()] TJ ET q 14.250 0 0 10.500 368.952 730.786 cm /I155 Do Q BT 383.202 731.762 Td /F1 9.8 Tf [(\), hospitalized \()] TJ ET q 12.000 0 0 10.500 449.307 730.786 cm /I157 Do Q BT 461.307 731.762 Td /F1 9.8 Tf [(\), ICU-admitted \()] TJ ET q 7.500 0 0 10.500 533.360 730.786 cm /I159 Do Q BT 540.860 731.762 Td /F1 9.8 Tf [(\), and )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(fatal \()] TJ ET q 11.250 0 0 10.500 50.635 718.881 cm /I161 Do Q BT 61.885 719.857 Td /F1 9.8 Tf [(\) represented binomially distributed samples from the true number of cases )] TJ ET q 12.000 0 0 10.500 396.222 718.881 cm /I163 Do Q BT 408.222 719.857 Td /F1 9.8 Tf [( at the corresponding level of severity, )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(in the given location \(New York, abbreviated )] TJ ET q 12.000 0 0 10.500 219.709 706.976 cm /I165 Do Q BT 231.709 707.952 Td /F1 9.8 Tf [( or Milwaukee, abbreviated )] TJ ET q 15.000 0 0 11.250 350.923 706.226 cm /I167 Do Q BT 365.923 707.952 Td /F1 9.8 Tf [(\), with probability equal to the probability of )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(detection at each level \()] TJ ET q 7.500 0 0 10.500 129.220 695.072 cm /I169 Do Q BT 136.720 696.048 Td /F1 9.8 Tf [(\). The probability )] TJ ET q 7.500 0 0 10.500 212.038 695.072 cm /I171 Do Q BT 219.538 696.048 Td /F1 9.8 Tf [( for each level was informed by evidence on the probability of testing at each level )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(of severity \(which may have depended on the sensitivity of the rapid test if this was required for PCR testing\) and the sensitivity )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(of the PCR test \(Table 1\). Thus, for example, we defined the probability of detecting a hospitalized case in New York as )] TJ ET q 106.500 0 0 13.500 26.250 656.357 cm /I173 Do Q BT 132.750 659.057 Td /F1 9.8 Tf [(, where )] TJ ET q 31.500 0 0 13.500 167.431 656.357 cm /I175 Do Q BT 198.931 659.057 Td /F1 9.8 Tf [( was the probability of performing an RT-PCR based test and )] TJ ET q 32.250 0 0 13.500 464.998 656.357 cm /I177 Do Q BT 497.248 659.057 Td /F1 9.8 Tf [( was the sensitivity )] TJ ET BT 26.250 645.557 Td /F1 9.8 Tf [(of that test. Hence, the observed number of hospitalized patients in New York, )] TJ ET q 29.250 0 0 13.500 365.501 642.857 cm /I179 Do Q BT 394.751 645.557 Td /F1 9.8 Tf [(, was assumed to be distributed as )] TJ ET q 124.500 0 0 14.250 26.250 628.607 cm /I181 Do Q BT 150.750 631.457 Td /F1 9.8 Tf [(.)] TJ ET 0.965 0.965 0.965 rg 26.250 255.853 555.000 365.255 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 621.107 m 581.250 621.107 l 581.250 620.357 l 26.250 620.357 l f 26.250 255.853 m 581.250 255.853 l 581.250 256.603 l 26.250 256.603 l f q 450.000 0 0 171.000 35.250 440.357 cm /I183 Do Q q 35.250 267.103 537.000 167.255 re W n 0.271 0.267 0.267 rg BT 35.250 424.833 Td /F4 9.8 Tf [(Fig. 2: Schematic illustration of the relationship between the observed data \(rectangles\) and the conditional )] TJ ET BT 35.250 412.929 Td /F4 9.8 Tf [(probabilities \(blue circles\).)] TJ ET BT 35.250 393.559 Td /F1 9.8 Tf [(The key quantities of interest, sCHR, sCIR, and sCFR are products of the relevant conditional probabilities. \(a\) Approach 1, )] TJ ET BT 35.250 378.811 Td /F1 9.8 Tf [(synthesizing data from New York City and Milwaukee. Note that )] TJ ET q 35.250 0 0 15.000 312.686 375.811 cm /I185 Do Q BT 347.936 378.811 Td /F1 9.8 Tf [( \(double circle\) is informed by prior information [19] )] TJ ET BT 35.250 364.822 Td /F1 9.8 Tf [(rather than observed data. \(b\) Approach 2, using data from New York City only, including the telephone survey. )] TJ ET BT 35.250 351.086 Td /F1 9.8 Tf [(Abbreviations: sCFR: symptomatic case-fatality ratio; sCIR: symptomatic case-ICU \(or mechanical ventilation\) ratio; sCHR: )] TJ ET BT 35.250 336.339 Td /F1 9.8 Tf [(symptomatic case-hospitalization ratio. Variables: )] TJ ET q 37.500 0 0 15.000 251.446 333.339 cm /I187 Do Q BT 288.947 336.339 Td /F1 9.8 Tf [( : the ratio of deaths to medically-attended cases; )] TJ ET q 35.250 0 0 15.000 504.100 333.339 cm /I189 Do Q BT 539.350 336.339 Td /F1 9.8 Tf [( : the )] TJ ET BT 35.250 321.339 Td /F1 9.8 Tf [(ratio of deaths to hospitalized cases; )] TJ ET q 35.250 0 0 15.000 195.667 318.339 cm /I191 Do Q BT 230.917 321.339 Td /F1 9.8 Tf [( : the ratio of cases admitted to intensive care or using mechanical ventilation )] TJ ET BT 35.250 306.339 Td /F1 9.8 Tf [(to hospitalized cases; )] TJ ET q 38.250 0 0 15.000 131.171 303.339 cm /I193 Do Q BT 169.421 306.339 Td /F1 9.8 Tf [( : the ratio of hospitalized cases to medically attended cases; )] TJ ET q 35.250 0 0 15.000 434.425 303.339 cm /I195 Do Q BT 469.675 306.339 Td /F1 9.8 Tf [( : the ratio of medically-)] TJ ET BT 35.250 291.339 Td /F1 9.8 Tf [(attended cases to symptomatic cases; )] TJ ET q 31.500 0 0 15.000 203.243 288.339 cm /I197 Do Q BT 234.743 291.339 Td /F1 9.8 Tf [( : the ratio of deaths to symptomatic cases; )] TJ ET q 33.000 0 0 15.000 422.791 288.339 cm /I199 Do Q BT 455.791 291.339 Td /F1 9.8 Tf [( : the ratio of hospitalized )] TJ ET BT 35.250 277.350 Td /F1 9.8 Tf [(cases to symptomatic cases.)] TJ ET Q BT 26.250 236.353 Td /F1 9.8 Tf [(We noted that the ratios )] TJ ET q 33.000 0 0 15.000 132.476 233.353 cm /I201 Do Q BT 165.476 236.353 Td /F1 9.8 Tf [(, )] TJ ET q 27.750 0 0 15.000 170.897 233.353 cm /I203 Do Q BT 198.647 236.353 Td /F1 9.8 Tf [(, and )] TJ ET q 31.500 0 0 15.000 223.042 233.353 cm /I205 Do Q BT 254.542 236.353 Td /F1 9.8 Tf [( can be built up multiplicatively from simpler components: for instance, the )] TJ ET BT 26.250 221.353 Td /F1 9.8 Tf [(ratio of deaths to symptomatic infections may be expressed as )] TJ ET q 154.500 0 0 15.000 298.285 218.353 cm /I207 Do Q BT 452.785 221.353 Td /F1 9.8 Tf [(, the product of the ratios of )] TJ ET BT 26.250 208.829 Td /F1 9.8 Tf [(deaths:hospitalizations, of hospitalizations:medically attended cases, and of medically attended cases:symptomatic cases. )] TJ ET BT 26.250 196.924 Td /F1 9.8 Tf [(These ratios of increasing severity are similar to conditional probabilities but are not strictly so in all cases, since for example )] TJ ET BT 26.250 185.019 Td /F1 9.8 Tf [(some deaths in New York City occurred in persons who were not hospitalized. For this reason we model deaths separately )] TJ ET BT 26.250 170.638 Td /F1 9.8 Tf [(among hospitalized and non-hospitalized patients, i.e. )] TJ ET q 240.000 0 0 15.000 260.913 167.638 cm /I209 Do Q BT 500.913 170.638 Td /F1 9.8 Tf [(. For each )] TJ ET BT 26.250 158.115 Td /F1 9.8 Tf [(observed level of severity \(medically-attended, hospitalized, ICU, death\), the true number of cases was modeled as a binomial )] TJ ET BT 26.250 146.210 Td /F1 9.8 Tf [(sample from the true number of cases at an appropriate lower level, hence)] TJ ET q 305.250 0 0 18.000 26.250 118.329 cm /I211 Do Q BT 331.500 121.929 Td /F1 9.8 Tf [(,)] TJ ET q 291.750 0 0 18.000 26.250 92.829 cm /I213 Do Q BT 318.000 96.429 Td /F1 9.8 Tf [(,)] TJ ET BT 26.250 75.805 Td /F1 9.8 Tf [(where the first subscript indicates severity and the second indicates the population \(New York, Milwaukee to May 20, Milwaukee )] TJ ET BT 26.250 63.900 Td /F1 9.8 Tf [(to June 14\).)] TJ ET BT 26.250 44.496 Td /F1 9.8 Tf [(In Approach 1 \(New York and Milwaukee data combined\), for the unobserved level of severity \(symptomatic cases\) we used a )] TJ ET Q q 450.000 0 0 171.000 35.250 440.357 cm /I215 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(5)] 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The main analysis of this first approach was performed using prior information to )] TJ ET BT 26.250 737.571 Td /F1 9.8 Tf [(inform the detection probabilities. An additional nave analysis was performed, in which the detection probabilities )] TJ ET q 7.500 0 0 10.500 523.168 736.595 cm /I219 Do Q BT 530.668 737.571 Td /F1 9.8 Tf [( were set )] TJ ET BT 26.250 725.667 Td /F1 9.8 Tf [(equal to 1 at all levels of severity. Our prior distributions for the number of symptomatic cases in New York \(overall and by age\) )] TJ ET BT 26.250 713.762 Td /F1 9.8 Tf [(were taken as ranging uniformly between zero and the proportion reporting ILI in the telephone survey \(with the upper bound of )] TJ ET BT 26.250 701.857 Td /F1 9.8 Tf [(that distribution having a prior reflecting the confidence bounds of the survey results, details in the )] TJ ET 0.267 0.267 0.267 rg BT 450.043 701.857 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 490.691 701.857 Td /F1 9.8 Tf [(\). For Milwaukee, )] TJ ET BT 26.250 689.952 Td /F1 9.8 Tf [(the prior on symptomatic cases was taken as uniform between 0 and 25% of the population.)] TJ ET BT 26.250 670.548 Td /F1 9.8 Tf [(In Approach 2 \(New York case data and telephone survey data\), we made the assumption that self-reported ILI cases )] TJ ET BT 26.250 658.643 Td /F1 9.8 Tf [(represented symptomatic pH1N1 infection, and used the mean and 95% confidence intervals from that survey to define a prior )] TJ ET BT 26.250 646.738 Td /F1 9.8 Tf [(distribution on the number of symptomatic cases overall and by age group. We then used observed hospitalizations, )] TJ ET BT 26.250 634.833 Td /F1 9.8 Tf [(ICU/ventilator use, and fatalities along with prior distributions on detection probabilities as above to inform estimates of true )] TJ ET BT 26.250 622.929 Td /F1 9.8 Tf [(numbers of hospitalizations, ICU/ventilator use, and fatalities, and these in turn were used to estimate sCHR, sCIR, and sCFR.)] TJ ET BT 26.250 603.524 Td /F1 9.8 Tf [(The evidence was synthesized through a full probability model in a Bayesian framework, implemented in the OpenBUGS )] TJ ET BT 26.250 591.619 Td /F1 9.8 Tf [(software [20], which uses Markov chain Monte Carlo to sample from the posterior distribution.)] TJ ET 0.965 0.965 0.965 rg 26.250 83.502 555.000 498.236 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 581.738 m 581.250 581.738 l 581.250 580.988 l 26.250 580.988 l f 26.250 83.502 m 581.250 83.502 l 581.250 84.252 l 26.250 84.252 l f q 435.000 0 0 450.000 35.250 121.988 cm /I220 Do Q q 35.250 94.752 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 104.999 Td /F4 9.8 Tf [(Table 1: Detection Probabilities)] TJ ET Q BT 26.250 49.280 Td /F4 12.0 Tf [(RESULTS)] TJ ET Q q 15.000 38.850 577.500 738.150 re W n 0.271 0.267 0.267 rg BT 26.250 762.600 Td /F1 9.8 Tf [(prior distribution of )] TJ ET q 121.500 0 0 18.000 109.154 759.000 cm /I222 Do Q BT 230.654 762.600 Td /F1 9.8 Tf [( to represent uncertainty between 42% and 58% ; this distribution has 90% of its )] TJ ET BT 26.250 749.476 Td /F1 9.8 Tf [(mass in this range, with a mean of 0.515. The main analysis of this first approach was performed using prior information to )] TJ ET BT 26.250 737.571 Td /F1 9.8 Tf [(inform the detection probabilities. An additional nave analysis was performed, in which the detection probabilities )] TJ ET q 7.500 0 0 10.500 523.168 736.595 cm /I224 Do Q BT 530.668 737.571 Td /F1 9.8 Tf [( were set )] TJ ET BT 26.250 725.667 Td /F1 9.8 Tf [(equal to 1 at all levels of severity. Our prior distributions for the number of symptomatic cases in New York \(overall and by age\) )] TJ ET BT 26.250 713.762 Td /F1 9.8 Tf [(were taken as ranging uniformly between zero and the proportion reporting ILI in the telephone survey \(with the upper bound of )] TJ ET BT 26.250 701.857 Td /F1 9.8 Tf [(that distribution having a prior reflecting the confidence bounds of the survey results, details in the )] TJ ET 0.267 0.267 0.267 rg BT 450.043 701.857 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 490.691 701.857 Td /F1 9.8 Tf [(\). For Milwaukee, )] TJ ET BT 26.250 689.952 Td /F1 9.8 Tf [(the prior on symptomatic cases was taken as uniform between 0 and 25% of the population.)] TJ ET BT 26.250 670.548 Td /F1 9.8 Tf [(In Approach 2 \(New York case data and telephone survey data\), we made the assumption that self-reported ILI cases )] TJ ET BT 26.250 658.643 Td /F1 9.8 Tf [(represented symptomatic pH1N1 infection, and used the mean and 95% confidence intervals from that survey to define a prior )] TJ ET BT 26.250 646.738 Td /F1 9.8 Tf [(distribution on the number of symptomatic cases overall and by age group. We then used observed hospitalizations, )] TJ ET BT 26.250 634.833 Td /F1 9.8 Tf [(ICU/ventilator use, and fatalities along with prior distributions on detection probabilities as above to inform estimates of true )] TJ ET BT 26.250 622.929 Td /F1 9.8 Tf [(numbers of hospitalizations, ICU/ventilator use, and fatalities, and these in turn were used to estimate sCHR, sCIR, and sCFR.)] TJ ET BT 26.250 603.524 Td /F1 9.8 Tf [(The evidence was synthesized through a full probability model in a Bayesian framework, implemented in the OpenBUGS )] TJ ET BT 26.250 591.619 Td /F1 9.8 Tf [(software [20], which uses Markov chain Monte Carlo to sample from the posterior distribution.)] TJ ET 0.965 0.965 0.965 rg 26.250 83.502 555.000 498.236 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 581.738 m 581.250 581.738 l 581.250 580.988 l 26.250 580.988 l f 26.250 83.502 m 581.250 83.502 l 581.250 84.252 l 26.250 84.252 l f q 435.000 0 0 450.000 35.250 121.988 cm /I220 Do Q q 35.250 94.752 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 104.999 Td /F4 9.8 Tf [(Table 1: Detection Probabilities)] TJ ET Q BT 26.250 49.280 Td /F4 12.0 Tf [(RESULTS)] TJ ET Q q 15.000 38.850 577.500 738.150 re W n 0.271 0.267 0.267 rg BT 26.250 762.600 Td /F1 9.8 Tf [(prior distribution of )] TJ ET q 121.500 0 0 18.000 109.154 759.000 cm /I226 Do Q BT 230.654 762.600 Td /F1 9.8 Tf [( to represent uncertainty between 42% and 58% ; this distribution has 90% of its )] TJ ET BT 26.250 749.476 Td /F1 9.8 Tf [(mass in this range, with a mean of 0.515. The main analysis of this first approach was performed using prior information to )] TJ ET BT 26.250 737.571 Td /F1 9.8 Tf [(inform the detection probabilities. An additional nave analysis was performed, in which the detection probabilities )] TJ ET q 7.500 0 0 10.500 523.168 736.595 cm /I228 Do Q BT 530.668 737.571 Td /F1 9.8 Tf [( were set )] TJ ET BT 26.250 725.667 Td /F1 9.8 Tf [(equal to 1 at all levels of severity. Our prior distributions for the number of symptomatic cases in New York \(overall and by age\) )] TJ ET BT 26.250 713.762 Td /F1 9.8 Tf [(were taken as ranging uniformly between zero and the proportion reporting ILI in the telephone survey \(with the upper bound of )] TJ ET BT 26.250 701.857 Td /F1 9.8 Tf [(that distribution having a prior reflecting the confidence bounds of the survey results, details in the )] TJ ET 0.267 0.267 0.267 rg BT 450.043 701.857 Td /F1 9.8 Tf [(Appendix)] TJ ET 0.271 0.267 0.267 rg BT 490.691 701.857 Td /F1 9.8 Tf [(\). For Milwaukee, )] TJ ET BT 26.250 689.952 Td /F1 9.8 Tf [(the prior on symptomatic cases was taken as uniform between 0 and 25% of the population.)] TJ ET BT 26.250 670.548 Td /F1 9.8 Tf [(In Approach 2 \(New York case data and telephone survey data\), we made the assumption that self-reported ILI cases )] TJ ET BT 26.250 658.643 Td /F1 9.8 Tf [(represented symptomatic pH1N1 infection, and used the mean and 95% confidence intervals from that survey to define a prior )] TJ ET BT 26.250 646.738 Td /F1 9.8 Tf [(distribution on the number of symptomatic cases overall and by age group. We then used observed hospitalizations, )] TJ ET BT 26.250 634.833 Td /F1 9.8 Tf [(ICU/ventilator use, and fatalities along with prior distributions on detection probabilities as above to inform estimates of true )] TJ ET BT 26.250 622.929 Td /F1 9.8 Tf [(numbers of hospitalizations, ICU/ventilator use, and fatalities, and these in turn were used to estimate sCHR, sCIR, and sCFR.)] TJ ET BT 26.250 603.524 Td /F1 9.8 Tf [(The evidence was synthesized through a full probability model in a Bayesian framework, implemented in the OpenBUGS )] TJ ET BT 26.250 591.619 Td /F1 9.8 Tf [(software [20], which uses Markov chain Monte Carlo to sample from the posterior distribution.)] TJ ET 0.965 0.965 0.965 rg 26.250 83.502 555.000 498.236 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 581.738 m 581.250 581.738 l 581.250 580.988 l 26.250 580.988 l f 26.250 83.502 m 581.250 83.502 l 581.250 84.252 l 26.250 84.252 l f q 435.000 0 0 450.000 35.250 121.988 cm /I220 Do Q q 35.250 94.752 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 104.999 Td /F4 9.8 Tf [(Table 1: Detection Probabilities)] TJ ET Q BT 26.250 49.280 Td /F4 12.0 Tf [(RESULTS)] TJ ET Q q 435.000 0 0 450.000 35.250 121.988 cm /I220 Do 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 388 0 obj << /Type /XObject /Subtype /Image /Width 162 /Height 24 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 162 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 1248>> stream HՖgz_WLIdm&-3Iffff2o-II$$+L&I$dr%՟~ιjgx9<9O9'(t{h+AoM\?Nሱ8kr2lU󿴸i-6R 3M@>3` +Ds{\gC}*ڏէEdXY0mFM wDUP@Uw(eX>Zf[~!g&1BڌC4Y '" qvUays2Yqg2rvL^ ga˂5BDPG?͞*mrەn('ҞPDΛ9y@r}a wEisшAa/Ng>%q!iTYfOq60ij LcE{6^y6R?0rO %,qzZ.T17}wC Ygmh#'IB&1#с2*/F$:t ̗ BxO:<ހqlaSA|WZhY؂Yi^P=J]W6! 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the period \(to May 20\) for which we believe medically attended cases were consistently )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(detected, and the period \(to June 14\) for which we consider only hospitalized cases, ICU admissions and deaths.)] TJ ET q 26.250 733.786 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 505.169 555.000 228.617 re f 0.965 0.965 0.965 rg 27.000 720.756 88.280 12.280 re f 0.267 0.267 0.267 rg 26.625 732.661 88.655 0.750 re f 26.625 720.381 0.750 13.030 re f 0.965 0.965 0.965 rg 115.280 720.756 98.458 12.280 re f 0.267 0.267 0.267 rg 115.280 732.661 98.458 0.750 re f 0.271 0.267 0.267 rg BT 119.780 723.512 Td /F4 9.8 Tf [(Severity)] TJ ET 0.965 0.965 0.965 rg 213.738 720.756 64.657 12.280 re f 0.267 0.267 0.267 rg 213.738 732.661 64.657 0.750 re f 0.965 0.965 0.965 rg 278.395 720.756 63.805 12.280 re f 0.267 0.267 0.267 rg 278.395 732.661 63.805 0.750 re f 0.965 0.965 0.965 rg 342.199 720.756 82.621 12.280 re f 0.267 0.267 0.267 rg 342.199 732.661 82.621 0.750 re f 0.965 0.965 0.965 rg 424.820 720.756 155.680 12.280 re f 0.267 0.267 0.267 rg 424.820 732.661 156.055 0.750 re f 580.125 720.381 0.750 13.030 re f 26.625 720.381 89.030 0.750 re f 26.625 704.500 0.750 16.631 re f 114.905 720.381 99.208 0.750 re f 114.905 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 710.526 Td /F1 9.8 Tf [(Medically attended)] TJ ET 0.267 0.267 0.267 rg 213.363 720.381 65.032 0.750 re f 278.395 720.381 64.180 0.750 re f 213.363 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 710.526 Td /F1 9.8 Tf [(Hospitalized)] TJ ET 0.267 0.267 0.267 rg 341.824 720.381 83.371 0.750 re f 341.824 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 710.526 Td /F1 9.8 Tf [(ICU-admitted)] TJ ET 0.267 0.267 0.267 rg 424.445 720.381 156.430 0.750 re f 424.445 704.500 0.750 16.631 re f 580.125 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 710.526 Td /F1 9.8 Tf [(Dead)] TJ ET 0.965 0.965 0.965 rg 27.000 688.994 88.280 15.881 re f 0.267 0.267 0.267 rg 26.625 704.500 89.030 0.750 re f 26.625 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.500 695.351 Td /F4 9.8 Tf [(Milwaukee)] TJ ET 0.267 0.267 0.267 rg 114.905 704.500 99.208 0.750 re f 114.905 688.619 0.750 16.631 re f 213.363 704.500 65.032 0.750 re f 278.395 704.500 64.180 0.750 re f 213.363 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 694.645 Td /F1 9.8 Tf [(to May 20 / to June 14)] TJ ET 0.267 0.267 0.267 rg 341.824 704.500 83.371 0.750 re f 341.824 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 424.445 704.500 156.430 0.750 re f 424.445 688.619 0.750 16.631 re f 580.125 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 26.625 688.619 89.030 0.750 re f 26.625 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 678.764 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 688.619 99.208 0.750 re f 114.905 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 678.764 Td /F1 9.8 Tf [(126 \(16%\))] TJ ET 0.267 0.267 0.267 rg 213.363 688.619 65.407 0.750 re f 213.363 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 678.764 Td /F1 9.8 Tf [(7 \(28%\))] TJ ET 0.267 0.267 0.267 rg 278.020 688.619 64.555 0.750 re f 278.020 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 678.764 Td /F1 9.8 Tf [(27 \(18%\))] TJ ET 0.267 0.267 0.267 rg 341.824 688.619 83.371 0.750 re f 341.824 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 678.764 Td /F1 9.8 Tf [(5 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 688.619 156.430 0.750 re f 424.445 672.737 0.750 16.631 re f 580.125 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 678.764 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 672.737 89.030 0.750 re f 26.625 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 662.882 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 672.737 99.208 0.750 re f 114.905 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 662.882 Td /F1 9.8 Tf [(470 \(60%\))] TJ ET 0.267 0.267 0.267 rg 213.363 672.737 65.407 0.750 re f 213.363 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 662.882 Td /F1 9.8 Tf [(6 \(24%\))] TJ ET 0.267 0.267 0.267 rg 278.020 672.737 64.555 0.750 re f 278.020 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 662.882 Td /F1 9.8 Tf [(29 \(20%\))] TJ ET 0.267 0.267 0.267 rg 341.824 672.737 83.371 0.750 re f 341.824 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 662.882 Td /F1 9.8 Tf [(7 \(26%\))] TJ ET 0.267 0.267 0.267 rg 424.445 672.737 156.430 0.750 re f 424.445 656.856 0.750 16.631 re f 580.125 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 662.882 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 656.856 89.030 0.750 re f 26.625 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 647.001 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 656.856 99.208 0.750 re f 114.905 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 647.001 Td /F1 9.8 Tf [(189 \(24%\))] TJ ET 0.267 0.267 0.267 rg 213.363 656.856 65.407 0.750 re f 213.363 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 647.001 Td /F1 9.8 Tf [(12 \(48%\))] TJ ET 0.267 0.267 0.267 rg 278.020 656.856 64.555 0.750 re f 278.020 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 647.001 Td /F1 9.8 Tf [(87 \(59%\))] TJ ET 0.267 0.267 0.267 rg 341.824 656.856 83.371 0.750 re f 341.824 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 647.001 Td /F1 9.8 Tf [(14 \(52%\))] TJ ET 0.267 0.267 0.267 rg 424.445 656.856 156.430 0.750 re f 424.445 640.975 0.750 16.631 re f 580.125 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 647.001 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 640.975 89.030 0.750 re f 26.625 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 631.120 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 640.975 99.208 0.750 re f 114.905 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 631.120 Td /F1 9.8 Tf [(3 \(0.4%\))] TJ ET 0.267 0.267 0.267 rg 213.363 640.975 65.407 0.750 re f 213.363 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 278.020 640.975 64.555 0.750 re f 278.020 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 631.120 Td /F1 9.8 Tf [(4 \(3%\))] TJ ET 0.267 0.267 0.267 rg 341.824 640.975 83.371 0.750 re f 341.824 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 631.120 Td /F1 9.8 Tf [(1 \(4%\))] TJ ET 0.267 0.267 0.267 rg 424.445 640.975 156.430 0.750 re f 424.445 625.094 0.750 16.631 re f 580.125 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 625.094 89.030 0.750 re f 26.625 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 615.239 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 625.094 99.208 0.750 re f 114.905 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 615.239 Td /F1 9.8 Tf [(788)] TJ ET 0.267 0.267 0.267 rg 213.363 625.094 65.407 0.750 re f 213.363 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 278.020 625.094 64.555 0.750 re f 278.020 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 615.239 Td /F1 9.8 Tf [(147)] TJ ET 0.267 0.267 0.267 rg 341.824 625.094 83.371 0.750 re f 341.824 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 424.445 625.094 156.430 0.750 re f 424.445 609.212 0.750 16.631 re f 580.125 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 615.239 Td /F1 9.8 Tf [(4)] TJ ET 0.267 0.267 0.267 rg 26.625 609.212 89.030 0.750 re f 26.625 608.462 0.750 1.500 re f 114.905 609.212 99.208 0.750 re f 114.905 608.462 0.750 1.500 re f 213.363 609.212 65.407 0.750 re f 213.363 608.462 0.750 1.500 re f 278.020 609.212 64.555 0.750 re f 278.020 608.462 0.750 1.500 re f 341.824 609.212 83.371 0.750 re f 341.824 608.462 0.750 1.500 re f 424.445 609.212 156.430 0.750 re f 424.445 608.462 0.750 1.500 re f 580.125 608.462 0.750 1.500 re f 0.965 0.965 0.965 rg 27.000 585.325 88.280 23.512 re f 0.267 0.267 0.267 rg 26.625 608.462 89.030 0.750 re f 26.625 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.500 599.313 Td /F4 9.8 Tf [(New York)] TJ ET 0.267 0.267 0.267 rg 114.905 608.462 99.208 0.750 re f 114.905 584.950 0.750 24.262 re f 213.363 608.462 65.407 0.750 re f 213.363 584.950 0.750 24.262 re f 278.020 608.462 64.555 0.750 re f 278.020 584.950 0.750 24.262 re f 341.824 608.462 83.371 0.750 re f 341.824 584.950 0.750 24.262 re f 424.445 608.462 156.430 0.750 re f 424.445 584.950 0.750 24.262 re f 580.125 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 429.695 598.607 Td /F1 9.8 Tf [(Dead \(total\) / Dead but not )] TJ ET BT 429.695 590.976 Td /F1 9.8 Tf [(hospitalized)] TJ ET 0.267 0.267 0.267 rg 26.625 584.950 89.030 0.750 re f 26.625 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 575.095 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 584.950 99.208 0.750 re f 114.905 569.069 0.750 16.631 re f 213.363 584.950 65.407 0.750 re f 213.363 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 575.095 Td /F1 9.8 Tf [(225 \(23%\))] TJ ET 0.267 0.267 0.267 rg 278.020 584.950 64.555 0.750 re f 278.020 569.069 0.750 16.631 re f 341.824 584.950 83.371 0.750 re f 341.824 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 575.095 Td /F1 9.8 Tf [(44 \(17%\))] TJ ET 0.267 0.267 0.267 rg 424.445 584.950 156.430 0.750 re f 424.445 569.069 0.750 16.631 re f 580.125 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 575.095 Td /F1 9.8 Tf [(2 \(4%\) / 2)] TJ ET 0.267 0.267 0.267 rg 26.625 569.069 89.030 0.750 re f 26.625 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 559.214 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 569.069 99.208 0.750 re f 114.905 553.187 0.750 16.631 re f 213.363 569.069 65.407 0.750 re f 213.363 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 559.214 Td /F1 9.8 Tf [(197 \(20%\))] TJ ET 0.267 0.267 0.267 rg 278.020 569.069 64.555 0.750 re f 278.020 553.187 0.750 16.631 re f 341.824 569.069 83.371 0.750 re f 341.824 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 559.214 Td /F1 9.8 Tf [(51 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 569.069 156.430 0.750 re f 424.445 553.187 0.750 16.631 re f 580.125 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 559.214 Td /F1 9.8 Tf [(2 \(4%\) / 1)] TJ ET 0.267 0.267 0.267 rg 26.625 553.187 89.030 0.750 re f 26.625 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 543.332 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 553.187 99.208 0.750 re f 114.905 537.306 0.750 16.631 re f 213.363 553.187 65.407 0.750 re f 213.363 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 543.332 Td /F1 9.8 Tf [(518 \(52%\))] TJ ET 0.267 0.267 0.267 rg 278.020 553.187 64.555 0.750 re f 278.020 537.306 0.750 16.631 re f 341.824 553.187 83.371 0.750 re f 341.824 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 543.332 Td /F1 9.8 Tf [(147 \(57%\))] TJ ET 0.267 0.267 0.267 rg 424.445 553.187 156.430 0.750 re f 424.445 537.306 0.750 16.631 re f 580.125 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 543.332 Td /F1 9.8 Tf [(46 \(87%\) / 6)] TJ ET 0.267 0.267 0.267 rg 26.625 537.306 89.030 0.750 re f 26.625 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 527.451 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 537.306 99.208 0.750 re f 114.905 521.425 0.750 16.631 re f 213.363 537.306 65.407 0.750 re f 213.363 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 527.451 Td /F1 9.8 Tf [(56 \(6%\))] TJ ET 0.267 0.267 0.267 rg 278.020 537.306 64.555 0.750 re f 278.020 521.425 0.750 16.631 re f 341.824 537.306 83.371 0.750 re f 341.824 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 527.451 Td /F1 9.8 Tf [(15 \(6%\))] TJ ET 0.267 0.267 0.267 rg 424.445 537.306 156.430 0.750 re f 424.445 521.425 0.750 16.631 re f 580.125 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 527.451 Td /F1 9.8 Tf [(3 \(6%\) / 0)] TJ ET 0.267 0.267 0.267 rg 26.625 521.425 89.030 0.750 re f 26.625 505.544 89.030 0.750 re f 26.625 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 511.570 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 521.425 99.208 0.750 re f 114.905 505.544 99.208 0.750 re f 114.905 505.544 0.750 16.631 re f 213.363 521.425 65.407 0.750 re f 213.363 505.544 65.407 0.750 re f 213.363 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 511.570 Td /F1 9.8 Tf [(996)] TJ ET 0.267 0.267 0.267 rg 278.020 521.425 64.555 0.750 re f 278.020 505.544 64.555 0.750 re f 278.020 505.544 0.750 16.631 re f 341.824 521.425 83.371 0.750 re f 341.824 505.544 83.371 0.750 re f 341.824 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 511.570 Td /F1 9.8 Tf [(257)] TJ ET 0.267 0.267 0.267 rg 424.445 521.425 156.430 0.750 re f 424.445 505.544 156.430 0.750 re f 424.445 505.544 0.750 16.631 re f 580.125 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 511.570 Td /F1 9.8 Tf [(53 / 9)] TJ ET BT 26.250 450.645 Td /F4 9.8 Tf [(Table 2: Cases at each level of severity)] TJ ET BT 26.250 431.240 Td /F5 9.8 Tf [(Approach 1:)] TJ ET BT 78.822 431.240 Td /F1 9.8 Tf [( We considered two alternatives to estimate the ratios of interest from the combined New York and Milwaukee data, )] TJ ET BT 26.250 419.335 Td /F1 9.8 Tf [(using self-reported rates of seeking medical attention to establish the denominator. First, we obtained a naive estimate of the )] TJ ET BT 26.250 407.430 Td /F1 9.8 Tf [(ratios of deaths to hospitalizations, ignoring differences in detection across levels of severity; and second, we obtained an )] TJ ET BT 26.250 395.526 Td /F1 9.8 Tf [(estimate that incorporated evidence and expert opinion on the detection probabilities at each level of severity.)] TJ ET BT 26.250 374.245 Td /F1 9.8 Tf [(The nave estimate would suggest a median \(95% credible interval \(CI\)\) ratio of deaths to hospitalizations \()] TJ ET q 24.750 0 0 14.250 486.313 371.395 cm /I230 Do Q BT 511.063 374.245 Td /F1 9.8 Tf [(\) of 4.3% \(95% )] TJ ET BT 26.250 359.995 Td /F1 9.8 Tf [(CI 3.2%-5.5%\), of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 260.328 357.145 cm /I232 Do Q BT 285.078 359.995 Td /F1 9.8 Tf [(\) of 25% \(95% CI 22%-27%\), and of hospitalizations to medically )] TJ ET BT 26.250 345.745 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 342.895 cm /I234 Do Q BT 128.332 345.745 Td /F1 9.8 Tf [(\) of 3.1% \(95% CI 2.0%-4.4%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 328.645 cm /I236 Do Q BT 55.500 331.495 Td /F1 9.8 Tf [(\) is estimated to be 0.03% \(95% CI 0.01%-0.06%\). Incorporating the prior evidence that 42 to 58% of symptomatic ILI is )] TJ ET BT 26.250 319.121 Td /F1 9.8 Tf [(medically attended, this would imply a nave estimate of the symptomatic case-fatality ratio of 0.081% \(95% CI 0.049%-)] TJ ET BT 26.250 307.216 Td /F1 9.8 Tf [(0.131%\), a corresponding estimate of the symptomatic case-ICU admission ratio of 0.38% \(95% CI 0.24%-0.58%\), and an )] TJ ET BT 26.250 295.311 Td /F1 9.8 Tf [(estimate of the symptomatic case-hospitalization ratio of 1.55% \(95% CI 0.98%-2.32%\). If one assumes that detection )] TJ ET BT 26.250 283.407 Td /F1 9.8 Tf [(probabilities are no worse at higher levels of severity than at lower levels, then these figures would be reasonableupper )] TJ ET BT 26.250 271.502 Td /F1 9.8 Tf [(boundson the symptomatic case-fatality and case-ICU admission ratios.)] TJ ET BT 26.250 252.097 Td /F1 9.8 Tf [(Incorporating prior evidence of the detection probabilities at each level of severity, and thus accommodating structural and )] TJ ET BT 26.250 238.316 Td /F1 9.8 Tf [(statistical uncertainties in these probabilities, we estimated that ratio of deaths to hospitalizations \()] TJ ET q 27.750 0 0 14.250 448.396 235.466 cm /I238 Do Q BT 476.146 238.316 Td /F1 9.8 Tf [(\) of 2.7% \(95% CI )] TJ ET BT 26.250 224.066 Td /F1 9.8 Tf [(1.8%-3.8%\) of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 245.157 221.216 cm /I240 Do Q BT 269.907 224.066 Td /F1 9.8 Tf [(\) of 17% \(95% CI 12%-21%\) and of hospitalizations to medically )] TJ ET BT 26.250 209.816 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 206.966 cm /I242 Do Q BT 128.332 209.816 Td /F1 9.8 Tf [(\) of 2.9% \(95% CI 1.6%-5.0%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 192.716 cm /I244 Do Q BT 55.500 195.566 Td /F1 9.8 Tf [(\) is estimated to be 0.02% \(95% CI 0.01%-0.04%\).)] TJ ET BT 26.250 175.692 Td /F1 9.8 Tf [(Table 3 shows the estimates for the quantities of primary interest, overall and by age group, in the analysis that incorporated )] TJ ET BT 26.250 163.788 Td /F1 9.8 Tf [(prior evidence of detection probabilities. Here, the posterior median estimate for the symptomatic case-fatality ratio is 0.048% )] TJ ET BT 26.250 151.883 Td /F1 9.8 Tf [(\(95% credible interval 0.026%-0.096%\) and for the symptomatic case-ICU admissions ratio is 0.239% \(95% CI 0.134%-)] TJ ET BT 26.250 139.978 Td /F1 9.8 Tf [(0.458%\). The symptomatic case-hospitalization ratio is estimated as 1.44% \(95% CI 0.83%-2.64%\).)] TJ ET Q q 15.000 130.097 577.500 646.903 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Table 2 shows the numbers of medically attended cases, hospitalizations, ICU visits and deaths in the two cities, with the )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(Milwaukee data separated into the period \(to May 20\) for which we believe medically attended cases were consistently )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(detected, and the period \(to June 14\) for which we consider only hospitalized cases, ICU admissions and deaths.)] TJ ET q 26.250 733.786 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 505.169 555.000 228.617 re f 0.965 0.965 0.965 rg 27.000 720.756 88.280 12.280 re f 0.267 0.267 0.267 rg 26.625 732.661 88.655 0.750 re f 26.625 720.381 0.750 13.030 re f 0.965 0.965 0.965 rg 115.280 720.756 98.458 12.280 re f 0.267 0.267 0.267 rg 115.280 732.661 98.458 0.750 re f 0.271 0.267 0.267 rg BT 119.780 723.512 Td /F4 9.8 Tf [(Severity)] TJ ET 0.965 0.965 0.965 rg 213.738 720.756 64.657 12.280 re f 0.267 0.267 0.267 rg 213.738 732.661 64.657 0.750 re f 0.965 0.965 0.965 rg 278.395 720.756 63.805 12.280 re f 0.267 0.267 0.267 rg 278.395 732.661 63.805 0.750 re f 0.965 0.965 0.965 rg 342.199 720.756 82.621 12.280 re f 0.267 0.267 0.267 rg 342.199 732.661 82.621 0.750 re f 0.965 0.965 0.965 rg 424.820 720.756 155.680 12.280 re f 0.267 0.267 0.267 rg 424.820 732.661 156.055 0.750 re f 580.125 720.381 0.750 13.030 re f 26.625 720.381 89.030 0.750 re f 26.625 704.500 0.750 16.631 re f 114.905 720.381 99.208 0.750 re f 114.905 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 710.526 Td /F1 9.8 Tf [(Medically attended)] TJ ET 0.267 0.267 0.267 rg 213.363 720.381 65.032 0.750 re f 278.395 720.381 64.180 0.750 re f 213.363 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 710.526 Td /F1 9.8 Tf [(Hospitalized)] TJ ET 0.267 0.267 0.267 rg 341.824 720.381 83.371 0.750 re f 341.824 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 710.526 Td /F1 9.8 Tf [(ICU-admitted)] TJ ET 0.267 0.267 0.267 rg 424.445 720.381 156.430 0.750 re f 424.445 704.500 0.750 16.631 re f 580.125 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 710.526 Td /F1 9.8 Tf [(Dead)] TJ ET 0.965 0.965 0.965 rg 27.000 688.994 88.280 15.881 re f 0.267 0.267 0.267 rg 26.625 704.500 89.030 0.750 re f 26.625 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.500 695.351 Td /F4 9.8 Tf [(Milwaukee)] TJ ET 0.267 0.267 0.267 rg 114.905 704.500 99.208 0.750 re f 114.905 688.619 0.750 16.631 re f 213.363 704.500 65.032 0.750 re f 278.395 704.500 64.180 0.750 re f 213.363 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 694.645 Td /F1 9.8 Tf [(to May 20 / to June 14)] TJ ET 0.267 0.267 0.267 rg 341.824 704.500 83.371 0.750 re f 341.824 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 424.445 704.500 156.430 0.750 re f 424.445 688.619 0.750 16.631 re f 580.125 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 26.625 688.619 89.030 0.750 re f 26.625 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 678.764 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 688.619 99.208 0.750 re f 114.905 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 678.764 Td /F1 9.8 Tf [(126 \(16%\))] TJ ET 0.267 0.267 0.267 rg 213.363 688.619 65.407 0.750 re f 213.363 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 678.764 Td /F1 9.8 Tf [(7 \(28%\))] TJ ET 0.267 0.267 0.267 rg 278.020 688.619 64.555 0.750 re f 278.020 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 678.764 Td /F1 9.8 Tf [(27 \(18%\))] TJ ET 0.267 0.267 0.267 rg 341.824 688.619 83.371 0.750 re f 341.824 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 678.764 Td /F1 9.8 Tf [(5 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 688.619 156.430 0.750 re f 424.445 672.737 0.750 16.631 re f 580.125 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 678.764 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 672.737 89.030 0.750 re f 26.625 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 662.882 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 672.737 99.208 0.750 re f 114.905 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 662.882 Td /F1 9.8 Tf [(470 \(60%\))] TJ ET 0.267 0.267 0.267 rg 213.363 672.737 65.407 0.750 re f 213.363 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 662.882 Td /F1 9.8 Tf [(6 \(24%\))] TJ ET 0.267 0.267 0.267 rg 278.020 672.737 64.555 0.750 re f 278.020 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 662.882 Td /F1 9.8 Tf [(29 \(20%\))] TJ ET 0.267 0.267 0.267 rg 341.824 672.737 83.371 0.750 re f 341.824 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 662.882 Td /F1 9.8 Tf [(7 \(26%\))] TJ ET 0.267 0.267 0.267 rg 424.445 672.737 156.430 0.750 re f 424.445 656.856 0.750 16.631 re f 580.125 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 662.882 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 656.856 89.030 0.750 re f 26.625 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 647.001 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 656.856 99.208 0.750 re f 114.905 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 647.001 Td /F1 9.8 Tf [(189 \(24%\))] TJ ET 0.267 0.267 0.267 rg 213.363 656.856 65.407 0.750 re f 213.363 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 647.001 Td /F1 9.8 Tf [(12 \(48%\))] TJ ET 0.267 0.267 0.267 rg 278.020 656.856 64.555 0.750 re f 278.020 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 647.001 Td /F1 9.8 Tf [(87 \(59%\))] TJ ET 0.267 0.267 0.267 rg 341.824 656.856 83.371 0.750 re f 341.824 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 647.001 Td /F1 9.8 Tf [(14 \(52%\))] TJ ET 0.267 0.267 0.267 rg 424.445 656.856 156.430 0.750 re f 424.445 640.975 0.750 16.631 re f 580.125 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 647.001 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 640.975 89.030 0.750 re f 26.625 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 631.120 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 640.975 99.208 0.750 re f 114.905 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 631.120 Td /F1 9.8 Tf [(3 \(0.4%\))] TJ ET 0.267 0.267 0.267 rg 213.363 640.975 65.407 0.750 re f 213.363 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 278.020 640.975 64.555 0.750 re f 278.020 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 631.120 Td /F1 9.8 Tf [(4 \(3%\))] TJ ET 0.267 0.267 0.267 rg 341.824 640.975 83.371 0.750 re f 341.824 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 631.120 Td /F1 9.8 Tf [(1 \(4%\))] TJ ET 0.267 0.267 0.267 rg 424.445 640.975 156.430 0.750 re f 424.445 625.094 0.750 16.631 re f 580.125 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 625.094 89.030 0.750 re f 26.625 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 615.239 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 625.094 99.208 0.750 re f 114.905 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 615.239 Td /F1 9.8 Tf [(788)] TJ ET 0.267 0.267 0.267 rg 213.363 625.094 65.407 0.750 re f 213.363 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 278.020 625.094 64.555 0.750 re f 278.020 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 615.239 Td /F1 9.8 Tf [(147)] TJ ET 0.267 0.267 0.267 rg 341.824 625.094 83.371 0.750 re f 341.824 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 424.445 625.094 156.430 0.750 re f 424.445 609.212 0.750 16.631 re f 580.125 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 615.239 Td /F1 9.8 Tf [(4)] TJ ET 0.267 0.267 0.267 rg 26.625 609.212 89.030 0.750 re f 26.625 608.462 0.750 1.500 re f 114.905 609.212 99.208 0.750 re f 114.905 608.462 0.750 1.500 re f 213.363 609.212 65.407 0.750 re f 213.363 608.462 0.750 1.500 re f 278.020 609.212 64.555 0.750 re f 278.020 608.462 0.750 1.500 re f 341.824 609.212 83.371 0.750 re f 341.824 608.462 0.750 1.500 re f 424.445 609.212 156.430 0.750 re f 424.445 608.462 0.750 1.500 re f 580.125 608.462 0.750 1.500 re f 0.965 0.965 0.965 rg 27.000 585.325 88.280 23.512 re f 0.267 0.267 0.267 rg 26.625 608.462 89.030 0.750 re f 26.625 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.500 599.313 Td /F4 9.8 Tf [(New York)] TJ ET 0.267 0.267 0.267 rg 114.905 608.462 99.208 0.750 re f 114.905 584.950 0.750 24.262 re f 213.363 608.462 65.407 0.750 re f 213.363 584.950 0.750 24.262 re f 278.020 608.462 64.555 0.750 re f 278.020 584.950 0.750 24.262 re f 341.824 608.462 83.371 0.750 re f 341.824 584.950 0.750 24.262 re f 424.445 608.462 156.430 0.750 re f 424.445 584.950 0.750 24.262 re f 580.125 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 429.695 598.607 Td /F1 9.8 Tf [(Dead \(total\) / Dead but not )] TJ ET BT 429.695 590.976 Td /F1 9.8 Tf [(hospitalized)] TJ ET 0.267 0.267 0.267 rg 26.625 584.950 89.030 0.750 re f 26.625 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 575.095 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 584.950 99.208 0.750 re f 114.905 569.069 0.750 16.631 re f 213.363 584.950 65.407 0.750 re f 213.363 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 575.095 Td /F1 9.8 Tf [(225 \(23%\))] TJ ET 0.267 0.267 0.267 rg 278.020 584.950 64.555 0.750 re f 278.020 569.069 0.750 16.631 re f 341.824 584.950 83.371 0.750 re f 341.824 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 575.095 Td /F1 9.8 Tf [(44 \(17%\))] TJ ET 0.267 0.267 0.267 rg 424.445 584.950 156.430 0.750 re f 424.445 569.069 0.750 16.631 re f 580.125 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 575.095 Td /F1 9.8 Tf [(2 \(4%\) / 2)] TJ ET 0.267 0.267 0.267 rg 26.625 569.069 89.030 0.750 re f 26.625 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 559.214 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 569.069 99.208 0.750 re f 114.905 553.187 0.750 16.631 re f 213.363 569.069 65.407 0.750 re f 213.363 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 559.214 Td /F1 9.8 Tf [(197 \(20%\))] TJ ET 0.267 0.267 0.267 rg 278.020 569.069 64.555 0.750 re f 278.020 553.187 0.750 16.631 re f 341.824 569.069 83.371 0.750 re f 341.824 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 559.214 Td /F1 9.8 Tf [(51 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 569.069 156.430 0.750 re f 424.445 553.187 0.750 16.631 re f 580.125 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 559.214 Td /F1 9.8 Tf [(2 \(4%\) / 1)] TJ ET 0.267 0.267 0.267 rg 26.625 553.187 89.030 0.750 re f 26.625 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 543.332 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 553.187 99.208 0.750 re f 114.905 537.306 0.750 16.631 re f 213.363 553.187 65.407 0.750 re f 213.363 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 543.332 Td /F1 9.8 Tf [(518 \(52%\))] TJ ET 0.267 0.267 0.267 rg 278.020 553.187 64.555 0.750 re f 278.020 537.306 0.750 16.631 re f 341.824 553.187 83.371 0.750 re f 341.824 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 543.332 Td /F1 9.8 Tf [(147 \(57%\))] TJ ET 0.267 0.267 0.267 rg 424.445 553.187 156.430 0.750 re f 424.445 537.306 0.750 16.631 re f 580.125 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 543.332 Td /F1 9.8 Tf [(46 \(87%\) / 6)] TJ ET 0.267 0.267 0.267 rg 26.625 537.306 89.030 0.750 re f 26.625 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 527.451 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 537.306 99.208 0.750 re f 114.905 521.425 0.750 16.631 re f 213.363 537.306 65.407 0.750 re f 213.363 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 527.451 Td /F1 9.8 Tf [(56 \(6%\))] TJ ET 0.267 0.267 0.267 rg 278.020 537.306 64.555 0.750 re f 278.020 521.425 0.750 16.631 re f 341.824 537.306 83.371 0.750 re f 341.824 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 527.451 Td /F1 9.8 Tf [(15 \(6%\))] TJ ET 0.267 0.267 0.267 rg 424.445 537.306 156.430 0.750 re f 424.445 521.425 0.750 16.631 re f 580.125 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 527.451 Td /F1 9.8 Tf [(3 \(6%\) / 0)] TJ ET 0.267 0.267 0.267 rg 26.625 521.425 89.030 0.750 re f 26.625 505.544 89.030 0.750 re f 26.625 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 511.570 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 521.425 99.208 0.750 re f 114.905 505.544 99.208 0.750 re f 114.905 505.544 0.750 16.631 re f 213.363 521.425 65.407 0.750 re f 213.363 505.544 65.407 0.750 re f 213.363 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 511.570 Td /F1 9.8 Tf [(996)] TJ ET 0.267 0.267 0.267 rg 278.020 521.425 64.555 0.750 re f 278.020 505.544 64.555 0.750 re f 278.020 505.544 0.750 16.631 re f 341.824 521.425 83.371 0.750 re f 341.824 505.544 83.371 0.750 re f 341.824 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 511.570 Td /F1 9.8 Tf [(257)] TJ ET 0.267 0.267 0.267 rg 424.445 521.425 156.430 0.750 re f 424.445 505.544 156.430 0.750 re f 424.445 505.544 0.750 16.631 re f 580.125 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 511.570 Td /F1 9.8 Tf [(53 / 9)] TJ ET BT 26.250 450.645 Td /F4 9.8 Tf [(Table 2: Cases at each level of severity)] TJ ET BT 26.250 431.240 Td /F5 9.8 Tf [(Approach 1:)] TJ ET BT 78.822 431.240 Td /F1 9.8 Tf [( We considered two alternatives to estimate the ratios of interest from the combined New York and Milwaukee data, )] TJ ET BT 26.250 419.335 Td /F1 9.8 Tf [(using self-reported rates of seeking medical attention to establish the denominator. First, we obtained a naive estimate of the )] TJ ET BT 26.250 407.430 Td /F1 9.8 Tf [(ratios of deaths to hospitalizations, ignoring differences in detection across levels of severity; and second, we obtained an )] TJ ET BT 26.250 395.526 Td /F1 9.8 Tf [(estimate that incorporated evidence and expert opinion on the detection probabilities at each level of severity.)] TJ ET BT 26.250 374.245 Td /F1 9.8 Tf [(The nave estimate would suggest a median \(95% credible interval \(CI\)\) ratio of deaths to hospitalizations \()] TJ ET q 24.750 0 0 14.250 486.313 371.395 cm /I246 Do Q BT 511.063 374.245 Td /F1 9.8 Tf [(\) of 4.3% \(95% )] TJ ET BT 26.250 359.995 Td /F1 9.8 Tf [(CI 3.2%-5.5%\), of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 260.328 357.145 cm /I248 Do Q BT 285.078 359.995 Td /F1 9.8 Tf [(\) of 25% \(95% CI 22%-27%\), and of hospitalizations to medically )] TJ ET BT 26.250 345.745 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 342.895 cm /I250 Do Q BT 128.332 345.745 Td /F1 9.8 Tf [(\) of 3.1% \(95% CI 2.0%-4.4%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 328.645 cm /I252 Do Q BT 55.500 331.495 Td /F1 9.8 Tf [(\) is estimated to be 0.03% \(95% CI 0.01%-0.06%\). Incorporating the prior evidence that 42 to 58% of symptomatic ILI is )] TJ ET BT 26.250 319.121 Td /F1 9.8 Tf [(medically attended, this would imply a nave estimate of the symptomatic case-fatality ratio of 0.081% \(95% CI 0.049%-)] TJ ET BT 26.250 307.216 Td /F1 9.8 Tf [(0.131%\), a corresponding estimate of the symptomatic case-ICU admission ratio of 0.38% \(95% CI 0.24%-0.58%\), and an )] TJ ET BT 26.250 295.311 Td /F1 9.8 Tf [(estimate of the symptomatic case-hospitalization ratio of 1.55% \(95% CI 0.98%-2.32%\). If one assumes that detection )] TJ ET BT 26.250 283.407 Td /F1 9.8 Tf [(probabilities are no worse at higher levels of severity than at lower levels, then these figures would be reasonableupper )] TJ ET BT 26.250 271.502 Td /F1 9.8 Tf [(boundson the symptomatic case-fatality and case-ICU admission ratios.)] TJ ET BT 26.250 252.097 Td /F1 9.8 Tf [(Incorporating prior evidence of the detection probabilities at each level of severity, and thus accommodating structural and )] TJ ET BT 26.250 238.316 Td /F1 9.8 Tf [(statistical uncertainties in these probabilities, we estimated that ratio of deaths to hospitalizations \()] TJ ET q 27.750 0 0 14.250 448.396 235.466 cm /I254 Do Q BT 476.146 238.316 Td /F1 9.8 Tf [(\) of 2.7% \(95% CI )] TJ ET BT 26.250 224.066 Td /F1 9.8 Tf [(1.8%-3.8%\) of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 245.157 221.216 cm /I256 Do Q BT 269.907 224.066 Td /F1 9.8 Tf [(\) of 17% \(95% CI 12%-21%\) and of hospitalizations to medically )] TJ ET BT 26.250 209.816 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 206.966 cm /I258 Do Q BT 128.332 209.816 Td /F1 9.8 Tf [(\) of 2.9% \(95% CI 1.6%-5.0%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 192.716 cm /I260 Do Q BT 55.500 195.566 Td /F1 9.8 Tf [(\) is estimated to be 0.02% \(95% CI 0.01%-0.04%\).)] TJ ET BT 26.250 175.692 Td /F1 9.8 Tf [(Table 3 shows the estimates for the quantities of primary interest, overall and by age group, in the analysis that incorporated )] TJ ET BT 26.250 163.788 Td /F1 9.8 Tf [(prior evidence of detection probabilities. Here, the posterior median estimate for the symptomatic case-fatality ratio is 0.048% )] TJ ET BT 26.250 151.883 Td /F1 9.8 Tf [(\(95% credible interval 0.026%-0.096%\) and for the symptomatic case-ICU admissions ratio is 0.239% \(95% CI 0.134%-)] TJ ET BT 26.250 139.978 Td /F1 9.8 Tf [(0.458%\). The symptomatic case-hospitalization ratio is estimated as 1.44% \(95% CI 0.83%-2.64%\).)] TJ ET Q q 15.000 130.097 577.500 646.903 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Table 2 shows the numbers of medically attended cases, hospitalizations, ICU visits and deaths in the two cities, with the )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(Milwaukee data separated into the period \(to May 20\) for which we believe medically attended cases were consistently )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(detected, and the period \(to June 14\) for which we consider only hospitalized cases, ICU admissions and deaths.)] TJ ET q 26.250 733.786 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 505.169 555.000 228.617 re f 0.965 0.965 0.965 rg 27.000 720.756 88.280 12.280 re f 0.267 0.267 0.267 rg 26.625 732.661 88.655 0.750 re f 26.625 720.381 0.750 13.030 re f 0.965 0.965 0.965 rg 115.280 720.756 98.458 12.280 re f 0.267 0.267 0.267 rg 115.280 732.661 98.458 0.750 re f 0.271 0.267 0.267 rg BT 119.780 723.512 Td /F4 9.8 Tf [(Severity)] TJ ET 0.965 0.965 0.965 rg 213.738 720.756 64.657 12.280 re f 0.267 0.267 0.267 rg 213.738 732.661 64.657 0.750 re f 0.965 0.965 0.965 rg 278.395 720.756 63.805 12.280 re f 0.267 0.267 0.267 rg 278.395 732.661 63.805 0.750 re f 0.965 0.965 0.965 rg 342.199 720.756 82.621 12.280 re f 0.267 0.267 0.267 rg 342.199 732.661 82.621 0.750 re f 0.965 0.965 0.965 rg 424.820 720.756 155.680 12.280 re f 0.267 0.267 0.267 rg 424.820 732.661 156.055 0.750 re f 580.125 720.381 0.750 13.030 re f 26.625 720.381 89.030 0.750 re f 26.625 704.500 0.750 16.631 re f 114.905 720.381 99.208 0.750 re f 114.905 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 710.526 Td /F1 9.8 Tf [(Medically attended)] TJ ET 0.267 0.267 0.267 rg 213.363 720.381 65.032 0.750 re f 278.395 720.381 64.180 0.750 re f 213.363 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 710.526 Td /F1 9.8 Tf [(Hospitalized)] TJ ET 0.267 0.267 0.267 rg 341.824 720.381 83.371 0.750 re f 341.824 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 710.526 Td /F1 9.8 Tf [(ICU-admitted)] TJ ET 0.267 0.267 0.267 rg 424.445 720.381 156.430 0.750 re f 424.445 704.500 0.750 16.631 re f 580.125 704.500 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 710.526 Td /F1 9.8 Tf [(Dead)] TJ ET 0.965 0.965 0.965 rg 27.000 688.994 88.280 15.881 re f 0.267 0.267 0.267 rg 26.625 704.500 89.030 0.750 re f 26.625 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.500 695.351 Td /F4 9.8 Tf [(Milwaukee)] TJ ET 0.267 0.267 0.267 rg 114.905 704.500 99.208 0.750 re f 114.905 688.619 0.750 16.631 re f 213.363 704.500 65.032 0.750 re f 278.395 704.500 64.180 0.750 re f 213.363 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 694.645 Td /F1 9.8 Tf [(to May 20 / to June 14)] TJ ET 0.267 0.267 0.267 rg 341.824 704.500 83.371 0.750 re f 341.824 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 424.445 704.500 156.430 0.750 re f 424.445 688.619 0.750 16.631 re f 580.125 688.619 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 694.645 Td /F1 9.8 Tf [(to June 14)] TJ ET 0.267 0.267 0.267 rg 26.625 688.619 89.030 0.750 re f 26.625 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 678.764 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 688.619 99.208 0.750 re f 114.905 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 678.764 Td /F1 9.8 Tf [(126 \(16%\))] TJ ET 0.267 0.267 0.267 rg 213.363 688.619 65.407 0.750 re f 213.363 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 678.764 Td /F1 9.8 Tf [(7 \(28%\))] TJ ET 0.267 0.267 0.267 rg 278.020 688.619 64.555 0.750 re f 278.020 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 678.764 Td /F1 9.8 Tf [(27 \(18%\))] TJ ET 0.267 0.267 0.267 rg 341.824 688.619 83.371 0.750 re f 341.824 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 678.764 Td /F1 9.8 Tf [(5 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 688.619 156.430 0.750 re f 424.445 672.737 0.750 16.631 re f 580.125 672.737 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 678.764 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 672.737 89.030 0.750 re f 26.625 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 662.882 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 672.737 99.208 0.750 re f 114.905 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 662.882 Td /F1 9.8 Tf [(470 \(60%\))] TJ ET 0.267 0.267 0.267 rg 213.363 672.737 65.407 0.750 re f 213.363 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 662.882 Td /F1 9.8 Tf [(6 \(24%\))] TJ ET 0.267 0.267 0.267 rg 278.020 672.737 64.555 0.750 re f 278.020 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 662.882 Td /F1 9.8 Tf [(29 \(20%\))] TJ ET 0.267 0.267 0.267 rg 341.824 672.737 83.371 0.750 re f 341.824 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 662.882 Td /F1 9.8 Tf [(7 \(26%\))] TJ ET 0.267 0.267 0.267 rg 424.445 672.737 156.430 0.750 re f 424.445 656.856 0.750 16.631 re f 580.125 656.856 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 662.882 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 656.856 89.030 0.750 re f 26.625 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 647.001 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 656.856 99.208 0.750 re f 114.905 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 647.001 Td /F1 9.8 Tf [(189 \(24%\))] TJ ET 0.267 0.267 0.267 rg 213.363 656.856 65.407 0.750 re f 213.363 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 647.001 Td /F1 9.8 Tf [(12 \(48%\))] TJ ET 0.267 0.267 0.267 rg 278.020 656.856 64.555 0.750 re f 278.020 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 647.001 Td /F1 9.8 Tf [(87 \(59%\))] TJ ET 0.267 0.267 0.267 rg 341.824 656.856 83.371 0.750 re f 341.824 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 647.001 Td /F1 9.8 Tf [(14 \(52%\))] TJ ET 0.267 0.267 0.267 rg 424.445 656.856 156.430 0.750 re f 424.445 640.975 0.750 16.631 re f 580.125 640.975 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 647.001 Td /F1 9.8 Tf [(2 \(50%\))] TJ ET 0.267 0.267 0.267 rg 26.625 640.975 89.030 0.750 re f 26.625 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 631.120 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 640.975 99.208 0.750 re f 114.905 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 631.120 Td /F1 9.8 Tf [(3 \(0.4%\))] TJ ET 0.267 0.267 0.267 rg 213.363 640.975 65.407 0.750 re f 213.363 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 278.020 640.975 64.555 0.750 re f 278.020 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 631.120 Td /F1 9.8 Tf [(4 \(3%\))] TJ ET 0.267 0.267 0.267 rg 341.824 640.975 83.371 0.750 re f 341.824 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 631.120 Td /F1 9.8 Tf [(1 \(4%\))] TJ ET 0.267 0.267 0.267 rg 424.445 640.975 156.430 0.750 re f 424.445 625.094 0.750 16.631 re f 580.125 625.094 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 631.120 Td /F1 9.8 Tf [(0)] TJ ET 0.267 0.267 0.267 rg 26.625 625.094 89.030 0.750 re f 26.625 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 615.239 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 625.094 99.208 0.750 re f 114.905 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 120.155 615.239 Td /F1 9.8 Tf [(788)] TJ ET 0.267 0.267 0.267 rg 213.363 625.094 65.407 0.750 re f 213.363 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 278.020 625.094 64.555 0.750 re f 278.020 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 283.270 615.239 Td /F1 9.8 Tf [(147)] TJ ET 0.267 0.267 0.267 rg 341.824 625.094 83.371 0.750 re f 341.824 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 615.239 Td /F1 9.8 Tf [(25)] TJ ET 0.267 0.267 0.267 rg 424.445 625.094 156.430 0.750 re f 424.445 609.212 0.750 16.631 re f 580.125 609.212 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 615.239 Td /F1 9.8 Tf [(4)] TJ ET 0.267 0.267 0.267 rg 26.625 609.212 89.030 0.750 re f 26.625 608.462 0.750 1.500 re f 114.905 609.212 99.208 0.750 re f 114.905 608.462 0.750 1.500 re f 213.363 609.212 65.407 0.750 re f 213.363 608.462 0.750 1.500 re f 278.020 609.212 64.555 0.750 re f 278.020 608.462 0.750 1.500 re f 341.824 609.212 83.371 0.750 re f 341.824 608.462 0.750 1.500 re f 424.445 609.212 156.430 0.750 re f 424.445 608.462 0.750 1.500 re f 580.125 608.462 0.750 1.500 re f 0.965 0.965 0.965 rg 27.000 585.325 88.280 23.512 re f 0.267 0.267 0.267 rg 26.625 608.462 89.030 0.750 re f 26.625 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.500 599.313 Td /F4 9.8 Tf [(New York)] TJ ET 0.267 0.267 0.267 rg 114.905 608.462 99.208 0.750 re f 114.905 584.950 0.750 24.262 re f 213.363 608.462 65.407 0.750 re f 213.363 584.950 0.750 24.262 re f 278.020 608.462 64.555 0.750 re f 278.020 584.950 0.750 24.262 re f 341.824 608.462 83.371 0.750 re f 341.824 584.950 0.750 24.262 re f 424.445 608.462 156.430 0.750 re f 424.445 584.950 0.750 24.262 re f 580.125 584.950 0.750 24.262 re f 0.271 0.267 0.267 rg BT 429.695 598.607 Td /F1 9.8 Tf [(Dead \(total\) / Dead but not )] TJ ET BT 429.695 590.976 Td /F1 9.8 Tf [(hospitalized)] TJ ET 0.267 0.267 0.267 rg 26.625 584.950 89.030 0.750 re f 26.625 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 575.095 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 114.905 584.950 99.208 0.750 re f 114.905 569.069 0.750 16.631 re f 213.363 584.950 65.407 0.750 re f 213.363 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 575.095 Td /F1 9.8 Tf [(225 \(23%\))] TJ ET 0.267 0.267 0.267 rg 278.020 584.950 64.555 0.750 re f 278.020 569.069 0.750 16.631 re f 341.824 584.950 83.371 0.750 re f 341.824 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 575.095 Td /F1 9.8 Tf [(44 \(17%\))] TJ ET 0.267 0.267 0.267 rg 424.445 584.950 156.430 0.750 re f 424.445 569.069 0.750 16.631 re f 580.125 569.069 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 575.095 Td /F1 9.8 Tf [(2 \(4%\) / 2)] TJ ET 0.267 0.267 0.267 rg 26.625 569.069 89.030 0.750 re f 26.625 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 559.214 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 114.905 569.069 99.208 0.750 re f 114.905 553.187 0.750 16.631 re f 213.363 569.069 65.407 0.750 re f 213.363 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 559.214 Td /F1 9.8 Tf [(197 \(20%\))] TJ ET 0.267 0.267 0.267 rg 278.020 569.069 64.555 0.750 re f 278.020 553.187 0.750 16.631 re f 341.824 569.069 83.371 0.750 re f 341.824 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 559.214 Td /F1 9.8 Tf [(51 \(20%\))] TJ ET 0.267 0.267 0.267 rg 424.445 569.069 156.430 0.750 re f 424.445 553.187 0.750 16.631 re f 580.125 553.187 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 559.214 Td /F1 9.8 Tf [(2 \(4%\) / 1)] TJ ET 0.267 0.267 0.267 rg 26.625 553.187 89.030 0.750 re f 26.625 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 543.332 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 114.905 553.187 99.208 0.750 re f 114.905 537.306 0.750 16.631 re f 213.363 553.187 65.407 0.750 re f 213.363 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 543.332 Td /F1 9.8 Tf [(518 \(52%\))] TJ ET 0.267 0.267 0.267 rg 278.020 553.187 64.555 0.750 re f 278.020 537.306 0.750 16.631 re f 341.824 553.187 83.371 0.750 re f 341.824 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 543.332 Td /F1 9.8 Tf [(147 \(57%\))] TJ ET 0.267 0.267 0.267 rg 424.445 553.187 156.430 0.750 re f 424.445 537.306 0.750 16.631 re f 580.125 537.306 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 543.332 Td /F1 9.8 Tf [(46 \(87%\) / 6)] TJ ET 0.267 0.267 0.267 rg 26.625 537.306 89.030 0.750 re f 26.625 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 527.451 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 114.905 537.306 99.208 0.750 re f 114.905 521.425 0.750 16.631 re f 213.363 537.306 65.407 0.750 re f 213.363 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 527.451 Td /F1 9.8 Tf [(56 \(6%\))] TJ ET 0.267 0.267 0.267 rg 278.020 537.306 64.555 0.750 re f 278.020 521.425 0.750 16.631 re f 341.824 537.306 83.371 0.750 re f 341.824 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 527.451 Td /F1 9.8 Tf [(15 \(6%\))] TJ ET 0.267 0.267 0.267 rg 424.445 537.306 156.430 0.750 re f 424.445 521.425 0.750 16.631 re f 580.125 521.425 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 527.451 Td /F1 9.8 Tf [(3 \(6%\) / 0)] TJ ET 0.267 0.267 0.267 rg 26.625 521.425 89.030 0.750 re f 26.625 505.544 89.030 0.750 re f 26.625 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 511.570 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 114.905 521.425 99.208 0.750 re f 114.905 505.544 99.208 0.750 re f 114.905 505.544 0.750 16.631 re f 213.363 521.425 65.407 0.750 re f 213.363 505.544 65.407 0.750 re f 213.363 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 218.613 511.570 Td /F1 9.8 Tf [(996)] TJ ET 0.267 0.267 0.267 rg 278.020 521.425 64.555 0.750 re f 278.020 505.544 64.555 0.750 re f 278.020 505.544 0.750 16.631 re f 341.824 521.425 83.371 0.750 re f 341.824 505.544 83.371 0.750 re f 341.824 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 347.074 511.570 Td /F1 9.8 Tf [(257)] TJ ET 0.267 0.267 0.267 rg 424.445 521.425 156.430 0.750 re f 424.445 505.544 156.430 0.750 re f 424.445 505.544 0.750 16.631 re f 580.125 505.544 0.750 16.631 re f 0.271 0.267 0.267 rg BT 429.695 511.570 Td /F1 9.8 Tf [(53 / 9)] TJ ET BT 26.250 450.645 Td /F4 9.8 Tf [(Table 2: Cases at each level of severity)] TJ ET BT 26.250 431.240 Td /F5 9.8 Tf [(Approach 1:)] TJ ET BT 78.822 431.240 Td /F1 9.8 Tf [( We considered two alternatives to estimate the ratios of interest from the combined New York and Milwaukee data, )] TJ ET BT 26.250 419.335 Td /F1 9.8 Tf [(using self-reported rates of seeking medical attention to establish the denominator. First, we obtained a naive estimate of the )] TJ ET BT 26.250 407.430 Td /F1 9.8 Tf [(ratios of deaths to hospitalizations, ignoring differences in detection across levels of severity; and second, we obtained an )] TJ ET BT 26.250 395.526 Td /F1 9.8 Tf [(estimate that incorporated evidence and expert opinion on the detection probabilities at each level of severity.)] TJ ET BT 26.250 374.245 Td /F1 9.8 Tf [(The nave estimate would suggest a median \(95% credible interval \(CI\)\) ratio of deaths to hospitalizations \()] TJ ET q 24.750 0 0 14.250 486.313 371.395 cm /I262 Do Q BT 511.063 374.245 Td /F1 9.8 Tf [(\) of 4.3% \(95% )] TJ ET BT 26.250 359.995 Td /F1 9.8 Tf [(CI 3.2%-5.5%\), of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 260.328 357.145 cm /I264 Do Q BT 285.078 359.995 Td /F1 9.8 Tf [(\) of 25% \(95% CI 22%-27%\), and of hospitalizations to medically )] TJ ET BT 26.250 345.745 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 342.895 cm /I266 Do Q BT 128.332 345.745 Td /F1 9.8 Tf [(\) of 3.1% \(95% CI 2.0%-4.4%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 328.645 cm /I268 Do Q BT 55.500 331.495 Td /F1 9.8 Tf [(\) is estimated to be 0.03% \(95% CI 0.01%-0.06%\). Incorporating the prior evidence that 42 to 58% of symptomatic ILI is )] TJ ET BT 26.250 319.121 Td /F1 9.8 Tf [(medically attended, this would imply a nave estimate of the symptomatic case-fatality ratio of 0.081% \(95% CI 0.049%-)] TJ ET BT 26.250 307.216 Td /F1 9.8 Tf [(0.131%\), a corresponding estimate of the symptomatic case-ICU admission ratio of 0.38% \(95% CI 0.24%-0.58%\), and an )] TJ ET BT 26.250 295.311 Td /F1 9.8 Tf [(estimate of the symptomatic case-hospitalization ratio of 1.55% \(95% CI 0.98%-2.32%\). If one assumes that detection )] TJ ET BT 26.250 283.407 Td /F1 9.8 Tf [(probabilities are no worse at higher levels of severity than at lower levels, then these figures would be reasonableupper )] TJ ET BT 26.250 271.502 Td /F1 9.8 Tf [(boundson the symptomatic case-fatality and case-ICU admission ratios.)] TJ ET BT 26.250 252.097 Td /F1 9.8 Tf [(Incorporating prior evidence of the detection probabilities at each level of severity, and thus accommodating structural and )] TJ ET BT 26.250 238.316 Td /F1 9.8 Tf [(statistical uncertainties in these probabilities, we estimated that ratio of deaths to hospitalizations \()] TJ ET q 27.750 0 0 14.250 448.396 235.466 cm /I270 Do Q BT 476.146 238.316 Td /F1 9.8 Tf [(\) of 2.7% \(95% CI )] TJ ET BT 26.250 224.066 Td /F1 9.8 Tf [(1.8%-3.8%\) of ICU admissions to hospitalizations \()] TJ ET q 24.750 0 0 14.250 245.157 221.216 cm /I272 Do Q BT 269.907 224.066 Td /F1 9.8 Tf [(\) of 17% \(95% CI 12%-21%\) and of hospitalizations to medically )] TJ ET BT 26.250 209.816 Td /F1 9.8 Tf [(attended cases \()] TJ ET q 30.000 0 0 14.250 98.332 206.966 cm /I274 Do Q BT 128.332 209.816 Td /F1 9.8 Tf [(\) of 2.9% \(95% CI 1.6%-5.0%\). The ratio of deaths outside of hospitals to medically attended cases \()] TJ ET q 29.250 0 0 14.250 26.250 192.716 cm /I276 Do Q BT 55.500 195.566 Td /F1 9.8 Tf [(\) is estimated to be 0.02% \(95% CI 0.01%-0.04%\).)] TJ ET BT 26.250 175.692 Td /F1 9.8 Tf [(Table 3 shows the estimates for the quantities of primary interest, overall and by age group, in the analysis that incorporated )] TJ ET BT 26.250 163.788 Td /F1 9.8 Tf [(prior evidence of detection probabilities. Here, the posterior median estimate for the symptomatic case-fatality ratio is 0.048% )] TJ ET BT 26.250 151.883 Td /F1 9.8 Tf [(\(95% credible interval 0.026%-0.096%\) and for the symptomatic case-ICU admissions ratio is 0.239% \(95% CI 0.134%-)] TJ ET BT 26.250 139.978 Td /F1 9.8 Tf [(0.458%\). The symptomatic case-hospitalization ratio is estimated as 1.44% \(95% CI 0.83%-2.64%\).)] 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 415 0 obj << /Type /XObject /Subtype /Image /Width 33 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 33 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 253>> stream (c`o٤| BH0£C^+0 ,CsDZypv݊]LvEKLrs`Z ׉> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 23>> stream 8c``Q0 F-l endstream endobj 417 0 obj << /Type /XObject /Subtype /Image /Width 33 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 33 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 253>> stream (c`o٤| BH0£C^+0 ,CsDZypv݊]LvEKLrs`Z ׉> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 23>> stream 8c``Q0 F-l endstream endobj 419 0 obj << /Type /XObject /Subtype 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obj << /Type /XObject /Subtype /Image /Width 40 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 40 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 317>> stream (c`b߲I=D "w:3^ ym8E ]<8nŮI&i LcG9 ڲDm1cRȐ%H2 R&"9@b$(Xa*[ %bRX931M3 Bztn:1eҤE`V[϶cNSⶇ@Ddp"D}lI !PՁv"č) pQ`'&!/]N1kPӌ9 +fLc`r4gFN "bβ#R!z] endstream endobj 436 0 obj << /Type /XObject /Subtype /Image /Width 40 /Height 19 /SMask 435 0 R /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 40 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 24>> stream H nH@ endstream endobj 437 0 obj << /Type /XObject /Subtype /Image /Width 39 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 39 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 319>> stream (c`"߲I=l`;DP/6V`!qlݳeݤI*y|}zU&1ps "'f@10L"Q&"4:Qgq%i$OdMCŤ , sLJk@8S* a gbLz:P-["CAKa8ǠpN O']b^ ê $]h cۗQgdA<$Pr6ӔYpI`a[u:Oo:.`embbBs̤93&Mj)sf̙ǀ@Ù P V1`o"_Wu endstream endobj 438 0 obj << /Type /XObject /Subtype /Image /Width 39 /Height 19 /SMask 437 0 R /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 39 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 25>> stream Hc``Q0 F(j endstream endobj 439 0 obj << /Type /XObject /Subtype /Image /Width 37 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 37 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 296>> stream (c`o٤BBH0"C^U+0aA86ٲnҤe J> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 25>> stream Hc``Q0 F( P endstream endobj 441 0 obj << /Type /XObject /Subtype /Image /Width 33 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 33 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 253>> stream (c`o٤| BH0£C^+0 ,CsDZypv݊]LvEKLrs`Z ׉> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 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sLJk@8S* a gbLz:P-["CAKa8ǠpN O']b^ ê $]h cۗQgdA<$Pr6ӔYpI`a[u:Oo:.`embbBs̤93&Mj)sf̙ǀ@Ù P V1`o"_Wu endstream endobj 454 0 obj << /Type /XObject /Subtype /Image /Width 39 /Height 19 /SMask 453 0 R /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 39 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 25>> stream Hc``Q0 F(j endstream endobj 455 0 obj << /Type /XObject /Subtype /Image /Width 37 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 37 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 296>> stream (c`o٤BBH0"C^U+0aA86ٲnҤe J> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 25>> stream Hc``Q0 F( P endstream endobj 457 0 obj << /Type /XObject /Subtype /Image /Width 33 /Height 19 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 33 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 253>> stream (c`o٤| BH0£C^+0 ,CsDZypv݊]LvEKLrs`Z ׉> /ColorSpace 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"'f@10L"Q&"4:Qgq%i$OdMCŤ , sLJk@8S* a gbLz:P-["CAKa8ǠpN O']b^ ê $]h cۗQgdA<$Pr6ӔYpI`a[u:Oo:.`embbBs̤93&Mj)sf̙ǀ@Ù P V1`o"_Wu endstream endobj 462 0 obj << /Type /XObject /Subtype /Image /Width 39 /Height 19 /SMask 461 0 R /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 39 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 25>> stream Hc``Q0 F(j endstream endobj 463 0 obj << /Type /Page /Parent 3 0 R /Annots [ 465 0 R 468 0 R 470 0 R ] /Contents 464 0 R >> endobj 464 0 obj << /Length 34788 >> stream 0.271 0.267 0.267 rg q 15.000 65.708 577.500 711.292 re W n q 26.250 777.000 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 613.172 555.000 163.828 re f 0.267 0.267 0.267 rg 26.625 775.875 40.804 0.750 re f 26.625 759.994 0.750 16.631 re f 66.679 775.875 50.894 0.750 re f 66.679 759.994 0.750 16.631 re f 116.823 775.875 66.296 0.750 re f 183.119 775.875 92.646 0.750 re f 116.823 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 766.020 Td /F1 9.8 Tf [(sCFR)] TJ ET 0.267 0.267 0.267 rg 275.015 775.875 66.296 0.750 re f 341.310 775.875 92.646 0.750 re f 275.015 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 766.020 Td /F1 9.8 Tf [(sCIR)] TJ ET 0.267 0.267 0.267 rg 433.206 775.875 57.949 0.750 re f 491.155 775.875 89.720 0.750 re f 433.206 759.994 0.750 16.631 re f 580.125 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 766.020 Td /F1 9.8 Tf [(sCHR)] TJ ET 0.267 0.267 0.267 rg 26.625 759.994 40.804 0.750 re f 26.625 616.819 40.804 0.750 re f 26.625 744.487 0.750 16.256 re f 26.625 728.606 0.750 15.881 re f 26.625 648.956 0.750 79.650 re f 26.625 633.075 0.750 15.881 re f 26.625 616.819 0.750 16.256 re f 26.625 613.547 0.750 4.022 re f 0.271 0.267 0.267 rg BT 31.875 750.139 Td /F1 9.8 Tf [(age)] TJ ET 0.267 0.267 0.267 rg 66.679 759.994 50.894 0.750 re f 66.679 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 750.139 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 116.823 759.994 66.671 0.750 re f 116.823 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 750.139 Td /F1 9.8 Tf [(0.026%)] TJ ET 0.267 0.267 0.267 rg 182.744 759.994 93.021 0.750 re f 182.744 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 750.139 Td /F1 9.8 Tf [(\(0.006%-0.092%\))] TJ ET 0.267 0.267 0.267 rg 275.015 759.994 66.671 0.750 re f 275.015 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 750.139 Td /F1 9.8 Tf [(0.321%)] TJ ET 0.267 0.267 0.267 rg 340.935 759.994 93.021 0.750 re f 340.935 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 750.139 Td /F1 9.8 Tf [(\(0.133%-0.776%\))] TJ ET 0.267 0.267 0.267 rg 433.206 759.994 58.324 0.750 re f 433.206 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 750.139 Td /F1 9.8 Tf [(2.45%)] TJ ET 0.267 0.267 0.267 rg 490.780 759.994 90.095 0.750 re f 490.780 744.112 0.750 16.631 re f 580.125 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 750.139 Td /F1 9.8 Tf [(\(1.10%-5.56%\))] TJ ET 0.267 0.267 0.267 rg 66.679 744.112 50.894 0.750 re f 66.679 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 734.258 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 116.823 744.112 66.671 0.750 re f 116.823 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 734.258 Td /F1 9.8 Tf [(0.010%)] TJ ET 0.267 0.267 0.267 rg 182.744 744.112 93.021 0.750 re f 182.744 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 734.258 Td /F1 9.8 Tf [(\(0.003%-0.031%\))] TJ ET 0.267 0.267 0.267 rg 275.015 744.112 66.671 0.750 re f 275.015 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 734.258 Td /F1 9.8 Tf [(0.106%)] TJ ET 0.267 0.267 0.267 rg 340.935 744.112 93.021 0.750 re f 340.935 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 734.258 Td /F1 9.8 Tf [(\(0.043%-0.244%\))] TJ ET 0.267 0.267 0.267 rg 433.206 744.112 58.324 0.750 re f 433.206 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 734.258 Td /F1 9.8 Tf [(0.61%)] TJ ET 0.267 0.267 0.267 rg 490.780 744.112 90.095 0.750 re f 490.780 728.231 0.750 16.631 re f 580.125 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 734.258 Td /F1 9.8 Tf [(\(0.27%-1.34%\))] TJ ET 0.267 0.267 0.267 rg 66.679 728.231 50.894 0.750 re f 66.679 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 71.929 718.376 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 116.823 728.231 66.671 0.750 re f 116.823 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 122.073 718.376 Td /F1 9.8 Tf [(0.159%)] TJ ET 0.267 0.267 0.267 rg 182.744 728.231 93.021 0.750 re f 182.744 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 187.994 718.376 Td /F1 9.8 Tf [(\(0.066%-0.333%\))] TJ ET 0.267 0.267 0.267 rg 275.015 728.231 66.671 0.750 re f 275.015 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 280.265 718.376 Td /F1 9.8 Tf [(0.542%)] TJ ET 0.267 0.267 0.267 rg 340.935 728.231 93.021 0.750 re f 340.935 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 346.185 718.376 Td /F1 9.8 Tf [(\(0.230%-1.090%\))] TJ ET 0.267 0.267 0.267 rg 433.206 728.231 58.324 0.750 re f 433.206 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 438.456 718.376 Td /F1 9.8 Tf [(3.00%)] TJ ET 0.267 0.267 0.267 rg 490.780 728.231 90.095 0.750 re f 490.780 648.581 0.750 80.400 re f 580.125 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 496.030 718.376 Td /F1 9.8 Tf [(\(1.35%-5.92%\))] TJ ET 0.267 0.267 0.267 rg 66.679 648.581 50.894 0.750 re f 66.679 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 638.726 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 116.823 648.581 66.671 0.750 re f 116.823 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 638.726 Td /F1 9.8 Tf [(0.090%)] TJ ET 0.267 0.267 0.267 rg 182.744 648.581 93.021 0.750 re f 182.744 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 638.726 Td /F1 9.8 Tf [(\(0.008%-1.471%\))] TJ ET 0.267 0.267 0.267 rg 275.015 648.581 66.671 0.750 re f 275.015 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 638.726 Td /F1 9.8 Tf [(0.327%)] TJ ET 0.267 0.267 0.267 rg 340.935 648.581 93.021 0.750 re f 340.935 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 638.726 Td /F1 9.8 Tf [(\(0.035%-4.711%\))] TJ ET 0.267 0.267 0.267 rg 433.206 648.581 58.324 0.750 re f 433.206 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 638.726 Td /F1 9.8 Tf [(1.84%)] TJ ET 0.267 0.267 0.267 rg 490.780 648.581 90.095 0.750 re f 490.780 632.700 0.750 16.631 re f 580.125 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 638.726 Td /F1 9.8 Tf [(\(0.21%-25.38%\))] TJ ET 0.267 0.267 0.267 rg 66.679 632.700 50.894 0.750 re f 66.679 616.819 50.894 0.750 re f 66.679 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 622.845 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 116.823 632.700 66.671 0.750 re f 116.823 616.819 66.671 0.750 re f 116.823 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 622.845 Td /F1 9.8 Tf [(0.048%)] TJ ET 0.267 0.267 0.267 rg 182.744 632.700 93.021 0.750 re f 182.744 616.819 93.021 0.750 re f 182.744 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 622.845 Td /F1 9.8 Tf [(\(0.026%-0.096%\))] TJ ET 0.267 0.267 0.267 rg 275.015 632.700 66.671 0.750 re f 275.015 616.819 66.671 0.750 re f 275.015 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 622.845 Td /F1 9.8 Tf [(0.239%)] TJ ET 0.267 0.267 0.267 rg 340.935 632.700 93.021 0.750 re f 340.935 616.819 93.021 0.750 re f 340.935 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 622.845 Td /F1 9.8 Tf [(\(0.134%-0.458%\))] TJ ET 0.267 0.267 0.267 rg 433.206 632.700 58.324 0.750 re f 433.206 616.819 58.324 0.750 re f 433.206 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 622.845 Td /F1 9.8 Tf [(1.44%)] TJ ET 0.267 0.267 0.267 rg 490.780 632.700 90.095 0.750 re f 490.780 616.819 90.095 0.750 re f 490.780 616.819 0.750 16.631 re f 580.125 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 622.845 Td /F1 9.8 Tf [(\(0.83%-2.64%\))] TJ ET BT 26.250 558.648 Td /F4 9.8 Tf [(Table 3:)] TJ ET BT 63.095 558.648 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 26.250 546.743 Td /F4 9.8 Tf [(hospitalization ratios, by age group, based on a combination of data from New York City and Milwaukee, and survey )] TJ ET BT 26.250 534.839 Td /F4 9.8 Tf [(data on the frequency of medical attendance for symptomatic cases.)] TJ ET BT 26.250 515.434 Td /F1 9.8 Tf [(Estimates of each of these severity measures vary dramatically by age group, with the lowest severity by each measure in the 5-)] TJ ET BT 26.250 503.529 Td /F1 9.8 Tf [(17 year age group. Comparing the two groups for which we have the most data, the relative risk of death for a symptomatic 18-)] TJ ET BT 26.250 491.624 Td /F1 9.8 Tf [(64-year-old compared to a symptomatic 5-17 year old is 15 \(95% CI 5-57\). The corresponding relative risks of ICU admission )] TJ ET BT 26.250 479.720 Td /F1 9.8 Tf [(and hospitalization are 5 \(95% CI 2-13\) and 5 \(95% CI 2-12\) respectively. The Bayesian framework provides a natural way to )] TJ ET BT 26.250 467.815 Td /F1 9.8 Tf [(estimate confidence \(measured as the posterior probability\) that one rate is higher than another. The probability that severity is )] TJ ET BT 26.250 455.910 Td /F1 9.8 Tf [(higher in the 18-64 age group than in the 5-17 age group is >99.9%, for each of fatality, ICU admission, and hospitalization )] TJ ET BT 26.250 444.005 Td /F1 9.8 Tf [(respectively. The data are too sparse to say with confidence whether adults over 65 or under 65 have greater severity. For )] TJ ET BT 26.250 432.101 Td /F1 9.8 Tf [(example, among the four age groups, the symptomatic case-fatality ratio is highest in the 18-64 year old age group with )] TJ ET BT 26.250 420.196 Td /F1 9.8 Tf [(posterior probability 62.%, and in those 65 and over with probability 38%. The symptomatic case-ICU admission ratio is highest )] TJ ET BT 26.250 408.291 Td /F1 9.8 Tf [(in 18-64 year olds with posterior probability 51% and in those over 65 with posterior probability 38%. The symptomatic case-)] TJ ET BT 26.250 396.386 Td /F1 9.8 Tf [(hospitalization ratio is highest in 18-64 year olds with posterior probability 37% and in those over 65 with posterior probability )] TJ ET BT 26.250 384.482 Td /F1 9.8 Tf [(37%.)] TJ ET BT 26.250 365.077 Td /F5 9.8 Tf [(Approach 2:)] TJ ET BT 78.822 365.077 Td /F1 9.8 Tf [( Table 4 shows the estimates for the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios, )] TJ ET BT 26.250 353.172 Td /F1 9.8 Tf [(by age group, when self-reported influenza-like illness is used as the denominator for total symptomatic cases. Overall these )] TJ ET BT 26.250 341.267 Td /F1 9.8 Tf [(are, respectively, sCFR=0.007% \(95% CI 0.005%-0.009%\), sCIR=0.028% \(95%CI 0.022%-0.035%\) and sCHR=0.16% \(95% CI )] TJ ET BT 26.250 329.363 Td /F1 9.8 Tf [(0.12%-0.26%\). Compared to Approach 1, these estimates are nearly an order of magnitude smaller, and the age distribution )] TJ ET BT 26.250 317.458 Td /F1 9.8 Tf [(differs. The relative risks for each severity in the 18-64 year old group compared to the 5-17 year old group are 7 \(95% CI 3-25\) )] TJ ET BT 26.250 305.553 Td /F1 9.8 Tf [(for fatalities, 1.5 \(95% CI 0.9-2.5\) for ICU admissions and 1.4 \(95% CI 0.9-2.1\) for hospitalizations. The case-fatality ratio is )] TJ ET BT 26.250 293.648 Td /F1 9.8 Tf [(highest in the 18-64 group with posterior probability 52%. In contrast to Approach 1, the case-ICU admission ratio is highest )] TJ ET BT 26.250 281.744 Td /F1 9.8 Tf [(among 0-4 year olds, with posterior probability 79%, and the case-hospitalization ratio is highest among 0-4 year olds with )] TJ ET BT 26.250 269.839 Td /F1 9.8 Tf [(posterior probability 99%.)] TJ ET 0.965 0.965 0.965 rg 26.250 65.708 555.000 194.250 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 259.958 m 581.250 259.958 l 581.250 259.208 l 26.250 259.208 l f q 447.000 0 0 178.500 35.250 71.708 cm /I277 Do Q q 35.250 65.708 537.000 0.000 re W n Q Q q 15.000 65.708 577.500 711.292 re W n q 26.250 777.000 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 613.172 555.000 163.828 re f 0.267 0.267 0.267 rg 26.625 775.875 40.804 0.750 re f 26.625 759.994 0.750 16.631 re f 66.679 775.875 50.894 0.750 re f 66.679 759.994 0.750 16.631 re f 116.823 775.875 66.296 0.750 re f 183.119 775.875 92.646 0.750 re f 116.823 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 766.020 Td /F1 9.8 Tf [(sCFR)] TJ ET 0.267 0.267 0.267 rg 275.015 775.875 66.296 0.750 re f 341.310 775.875 92.646 0.750 re f 275.015 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 766.020 Td /F1 9.8 Tf [(sCIR)] TJ ET 0.267 0.267 0.267 rg 433.206 775.875 57.949 0.750 re f 491.155 775.875 89.720 0.750 re f 433.206 759.994 0.750 16.631 re f 580.125 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 766.020 Td /F1 9.8 Tf [(sCHR)] TJ ET 0.267 0.267 0.267 rg 26.625 759.994 40.804 0.750 re f 26.625 616.819 40.804 0.750 re f 26.625 744.487 0.750 16.256 re f 26.625 728.606 0.750 15.881 re f 26.625 648.956 0.750 79.650 re f 26.625 633.075 0.750 15.881 re f 26.625 616.819 0.750 16.256 re f 26.625 613.547 0.750 4.022 re f 0.271 0.267 0.267 rg BT 31.875 750.139 Td /F1 9.8 Tf [(age)] TJ ET 0.267 0.267 0.267 rg 66.679 759.994 50.894 0.750 re f 66.679 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 750.139 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 116.823 759.994 66.671 0.750 re f 116.823 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 750.139 Td /F1 9.8 Tf [(0.026%)] TJ ET 0.267 0.267 0.267 rg 182.744 759.994 93.021 0.750 re f 182.744 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 750.139 Td /F1 9.8 Tf [(\(0.006%-0.092%\))] TJ ET 0.267 0.267 0.267 rg 275.015 759.994 66.671 0.750 re f 275.015 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 750.139 Td /F1 9.8 Tf [(0.321%)] TJ ET 0.267 0.267 0.267 rg 340.935 759.994 93.021 0.750 re f 340.935 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 750.139 Td /F1 9.8 Tf [(\(0.133%-0.776%\))] TJ ET 0.267 0.267 0.267 rg 433.206 759.994 58.324 0.750 re f 433.206 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 750.139 Td /F1 9.8 Tf [(2.45%)] TJ ET 0.267 0.267 0.267 rg 490.780 759.994 90.095 0.750 re f 490.780 744.112 0.750 16.631 re f 580.125 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 750.139 Td /F1 9.8 Tf [(\(1.10%-5.56%\))] TJ ET 0.267 0.267 0.267 rg 66.679 744.112 50.894 0.750 re f 66.679 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 734.258 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 116.823 744.112 66.671 0.750 re f 116.823 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 734.258 Td /F1 9.8 Tf [(0.010%)] TJ ET 0.267 0.267 0.267 rg 182.744 744.112 93.021 0.750 re f 182.744 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 734.258 Td /F1 9.8 Tf [(\(0.003%-0.031%\))] TJ ET 0.267 0.267 0.267 rg 275.015 744.112 66.671 0.750 re f 275.015 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 734.258 Td /F1 9.8 Tf [(0.106%)] TJ ET 0.267 0.267 0.267 rg 340.935 744.112 93.021 0.750 re f 340.935 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 734.258 Td /F1 9.8 Tf [(\(0.043%-0.244%\))] TJ ET 0.267 0.267 0.267 rg 433.206 744.112 58.324 0.750 re f 433.206 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 734.258 Td /F1 9.8 Tf [(0.61%)] TJ ET 0.267 0.267 0.267 rg 490.780 744.112 90.095 0.750 re f 490.780 728.231 0.750 16.631 re f 580.125 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 734.258 Td /F1 9.8 Tf [(\(0.27%-1.34%\))] TJ ET 0.267 0.267 0.267 rg 66.679 728.231 50.894 0.750 re f 66.679 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 71.929 718.376 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 116.823 728.231 66.671 0.750 re f 116.823 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 122.073 718.376 Td /F1 9.8 Tf [(0.159%)] TJ ET 0.267 0.267 0.267 rg 182.744 728.231 93.021 0.750 re f 182.744 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 187.994 718.376 Td /F1 9.8 Tf [(\(0.066%-0.333%\))] TJ ET 0.267 0.267 0.267 rg 275.015 728.231 66.671 0.750 re f 275.015 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 280.265 718.376 Td /F1 9.8 Tf [(0.542%)] TJ ET 0.267 0.267 0.267 rg 340.935 728.231 93.021 0.750 re f 340.935 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 346.185 718.376 Td /F1 9.8 Tf [(\(0.230%-1.090%\))] TJ ET 0.267 0.267 0.267 rg 433.206 728.231 58.324 0.750 re f 433.206 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 438.456 718.376 Td /F1 9.8 Tf [(3.00%)] TJ ET 0.267 0.267 0.267 rg 490.780 728.231 90.095 0.750 re f 490.780 648.581 0.750 80.400 re f 580.125 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 496.030 718.376 Td /F1 9.8 Tf [(\(1.35%-5.92%\))] TJ ET 0.267 0.267 0.267 rg 66.679 648.581 50.894 0.750 re f 66.679 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 638.726 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 116.823 648.581 66.671 0.750 re f 116.823 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 638.726 Td /F1 9.8 Tf [(0.090%)] TJ ET 0.267 0.267 0.267 rg 182.744 648.581 93.021 0.750 re f 182.744 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 638.726 Td /F1 9.8 Tf [(\(0.008%-1.471%\))] TJ ET 0.267 0.267 0.267 rg 275.015 648.581 66.671 0.750 re f 275.015 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 638.726 Td /F1 9.8 Tf [(0.327%)] TJ ET 0.267 0.267 0.267 rg 340.935 648.581 93.021 0.750 re f 340.935 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 638.726 Td /F1 9.8 Tf [(\(0.035%-4.711%\))] TJ ET 0.267 0.267 0.267 rg 433.206 648.581 58.324 0.750 re f 433.206 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 638.726 Td /F1 9.8 Tf [(1.84%)] TJ ET 0.267 0.267 0.267 rg 490.780 648.581 90.095 0.750 re f 490.780 632.700 0.750 16.631 re f 580.125 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 638.726 Td /F1 9.8 Tf [(\(0.21%-25.38%\))] TJ ET 0.267 0.267 0.267 rg 66.679 632.700 50.894 0.750 re f 66.679 616.819 50.894 0.750 re f 66.679 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 622.845 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 116.823 632.700 66.671 0.750 re f 116.823 616.819 66.671 0.750 re f 116.823 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 622.845 Td /F1 9.8 Tf [(0.048%)] TJ ET 0.267 0.267 0.267 rg 182.744 632.700 93.021 0.750 re f 182.744 616.819 93.021 0.750 re f 182.744 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 622.845 Td /F1 9.8 Tf [(\(0.026%-0.096%\))] TJ ET 0.267 0.267 0.267 rg 275.015 632.700 66.671 0.750 re f 275.015 616.819 66.671 0.750 re f 275.015 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 622.845 Td /F1 9.8 Tf [(0.239%)] TJ ET 0.267 0.267 0.267 rg 340.935 632.700 93.021 0.750 re f 340.935 616.819 93.021 0.750 re f 340.935 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 622.845 Td /F1 9.8 Tf [(\(0.134%-0.458%\))] TJ ET 0.267 0.267 0.267 rg 433.206 632.700 58.324 0.750 re f 433.206 616.819 58.324 0.750 re f 433.206 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 622.845 Td /F1 9.8 Tf [(1.44%)] TJ ET 0.267 0.267 0.267 rg 490.780 632.700 90.095 0.750 re f 490.780 616.819 90.095 0.750 re f 490.780 616.819 0.750 16.631 re f 580.125 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 622.845 Td /F1 9.8 Tf [(\(0.83%-2.64%\))] TJ ET BT 26.250 558.648 Td /F4 9.8 Tf [(Table 3:)] TJ ET BT 63.095 558.648 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 26.250 546.743 Td /F4 9.8 Tf [(hospitalization ratios, by age group, based on a combination of data from New York City and Milwaukee, and survey )] TJ ET BT 26.250 534.839 Td /F4 9.8 Tf [(data on the frequency of medical attendance for symptomatic cases.)] TJ ET BT 26.250 515.434 Td /F1 9.8 Tf [(Estimates of each of these severity measures vary dramatically by age group, with the lowest severity by each measure in the 5-)] TJ ET BT 26.250 503.529 Td /F1 9.8 Tf [(17 year age group. Comparing the two groups for which we have the most data, the relative risk of death for a symptomatic 18-)] TJ ET BT 26.250 491.624 Td /F1 9.8 Tf [(64-year-old compared to a symptomatic 5-17 year old is 15 \(95% CI 5-57\). The corresponding relative risks of ICU admission )] TJ ET BT 26.250 479.720 Td /F1 9.8 Tf [(and hospitalization are 5 \(95% CI 2-13\) and 5 \(95% CI 2-12\) respectively. The Bayesian framework provides a natural way to )] TJ ET BT 26.250 467.815 Td /F1 9.8 Tf [(estimate confidence \(measured as the posterior probability\) that one rate is higher than another. The probability that severity is )] TJ ET BT 26.250 455.910 Td /F1 9.8 Tf [(higher in the 18-64 age group than in the 5-17 age group is >99.9%, for each of fatality, ICU admission, and hospitalization )] TJ ET BT 26.250 444.005 Td /F1 9.8 Tf [(respectively. The data are too sparse to say with confidence whether adults over 65 or under 65 have greater severity. For )] TJ ET BT 26.250 432.101 Td /F1 9.8 Tf [(example, among the four age groups, the symptomatic case-fatality ratio is highest in the 18-64 year old age group with )] TJ ET BT 26.250 420.196 Td /F1 9.8 Tf [(posterior probability 62.%, and in those 65 and over with probability 38%. The symptomatic case-ICU admission ratio is highest )] TJ ET BT 26.250 408.291 Td /F1 9.8 Tf [(in 18-64 year olds with posterior probability 51% and in those over 65 with posterior probability 38%. The symptomatic case-)] TJ ET BT 26.250 396.386 Td /F1 9.8 Tf [(hospitalization ratio is highest in 18-64 year olds with posterior probability 37% and in those over 65 with posterior probability )] TJ ET BT 26.250 384.482 Td /F1 9.8 Tf [(37%.)] TJ ET BT 26.250 365.077 Td /F5 9.8 Tf [(Approach 2:)] TJ ET BT 78.822 365.077 Td /F1 9.8 Tf [( Table 4 shows the estimates for the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios, )] TJ ET BT 26.250 353.172 Td /F1 9.8 Tf [(by age group, when self-reported influenza-like illness is used as the denominator for total symptomatic cases. Overall these )] TJ ET BT 26.250 341.267 Td /F1 9.8 Tf [(are, respectively, sCFR=0.007% \(95% CI 0.005%-0.009%\), sCIR=0.028% \(95%CI 0.022%-0.035%\) and sCHR=0.16% \(95% CI )] TJ ET BT 26.250 329.363 Td /F1 9.8 Tf [(0.12%-0.26%\). Compared to Approach 1, these estimates are nearly an order of magnitude smaller, and the age distribution )] TJ ET BT 26.250 317.458 Td /F1 9.8 Tf [(differs. The relative risks for each severity in the 18-64 year old group compared to the 5-17 year old group are 7 \(95% CI 3-25\) )] TJ ET BT 26.250 305.553 Td /F1 9.8 Tf [(for fatalities, 1.5 \(95% CI 0.9-2.5\) for ICU admissions and 1.4 \(95% CI 0.9-2.1\) for hospitalizations. The case-fatality ratio is )] TJ ET BT 26.250 293.648 Td /F1 9.8 Tf [(highest in the 18-64 group with posterior probability 52%. In contrast to Approach 1, the case-ICU admission ratio is highest )] TJ ET BT 26.250 281.744 Td /F1 9.8 Tf [(among 0-4 year olds, with posterior probability 79%, and the case-hospitalization ratio is highest among 0-4 year olds with )] TJ ET BT 26.250 269.839 Td /F1 9.8 Tf [(posterior probability 99%.)] TJ ET 0.965 0.965 0.965 rg 26.250 65.708 555.000 194.250 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 259.958 m 581.250 259.958 l 581.250 259.208 l 26.250 259.208 l f q 447.000 0 0 178.500 35.250 71.708 cm /I277 Do Q q 35.250 65.708 537.000 0.000 re W n Q Q q 15.000 65.708 577.500 711.292 re W n q 26.250 777.000 555.000 0.000 re W n Q 1.000 1.000 1.000 rg 26.250 613.172 555.000 163.828 re f 0.267 0.267 0.267 rg 26.625 775.875 40.804 0.750 re f 26.625 759.994 0.750 16.631 re f 66.679 775.875 50.894 0.750 re f 66.679 759.994 0.750 16.631 re f 116.823 775.875 66.296 0.750 re f 183.119 775.875 92.646 0.750 re f 116.823 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 766.020 Td /F1 9.8 Tf [(sCFR)] TJ ET 0.267 0.267 0.267 rg 275.015 775.875 66.296 0.750 re f 341.310 775.875 92.646 0.750 re f 275.015 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 766.020 Td /F1 9.8 Tf [(sCIR)] TJ ET 0.267 0.267 0.267 rg 433.206 775.875 57.949 0.750 re f 491.155 775.875 89.720 0.750 re f 433.206 759.994 0.750 16.631 re f 580.125 759.994 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 766.020 Td /F1 9.8 Tf [(sCHR)] TJ ET 0.267 0.267 0.267 rg 26.625 759.994 40.804 0.750 re f 26.625 616.819 40.804 0.750 re f 26.625 744.487 0.750 16.256 re f 26.625 728.606 0.750 15.881 re f 26.625 648.956 0.750 79.650 re f 26.625 633.075 0.750 15.881 re f 26.625 616.819 0.750 16.256 re f 26.625 613.547 0.750 4.022 re f 0.271 0.267 0.267 rg BT 31.875 750.139 Td /F1 9.8 Tf [(age)] TJ ET 0.267 0.267 0.267 rg 66.679 759.994 50.894 0.750 re f 66.679 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 750.139 Td /F1 9.8 Tf [(0-4)] TJ ET 0.267 0.267 0.267 rg 116.823 759.994 66.671 0.750 re f 116.823 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 750.139 Td /F1 9.8 Tf [(0.026%)] TJ ET 0.267 0.267 0.267 rg 182.744 759.994 93.021 0.750 re f 182.744 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 750.139 Td /F1 9.8 Tf [(\(0.006%-0.092%\))] TJ ET 0.267 0.267 0.267 rg 275.015 759.994 66.671 0.750 re f 275.015 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 750.139 Td /F1 9.8 Tf [(0.321%)] TJ ET 0.267 0.267 0.267 rg 340.935 759.994 93.021 0.750 re f 340.935 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 750.139 Td /F1 9.8 Tf [(\(0.133%-0.776%\))] TJ ET 0.267 0.267 0.267 rg 433.206 759.994 58.324 0.750 re f 433.206 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 750.139 Td /F1 9.8 Tf [(2.45%)] TJ ET 0.267 0.267 0.267 rg 490.780 759.994 90.095 0.750 re f 490.780 744.112 0.750 16.631 re f 580.125 744.112 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 750.139 Td /F1 9.8 Tf [(\(1.10%-5.56%\))] TJ ET 0.267 0.267 0.267 rg 66.679 744.112 50.894 0.750 re f 66.679 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 734.258 Td /F1 9.8 Tf [(5-17)] TJ ET 0.267 0.267 0.267 rg 116.823 744.112 66.671 0.750 re f 116.823 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 734.258 Td /F1 9.8 Tf [(0.010%)] TJ ET 0.267 0.267 0.267 rg 182.744 744.112 93.021 0.750 re f 182.744 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 734.258 Td /F1 9.8 Tf [(\(0.003%-0.031%\))] TJ ET 0.267 0.267 0.267 rg 275.015 744.112 66.671 0.750 re f 275.015 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 734.258 Td /F1 9.8 Tf [(0.106%)] TJ ET 0.267 0.267 0.267 rg 340.935 744.112 93.021 0.750 re f 340.935 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 734.258 Td /F1 9.8 Tf [(\(0.043%-0.244%\))] TJ ET 0.267 0.267 0.267 rg 433.206 744.112 58.324 0.750 re f 433.206 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 734.258 Td /F1 9.8 Tf [(0.61%)] TJ ET 0.267 0.267 0.267 rg 490.780 744.112 90.095 0.750 re f 490.780 728.231 0.750 16.631 re f 580.125 728.231 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 734.258 Td /F1 9.8 Tf [(\(0.27%-1.34%\))] TJ ET 0.267 0.267 0.267 rg 66.679 728.231 50.894 0.750 re f 66.679 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 71.929 718.376 Td /F1 9.8 Tf [(18-64)] TJ ET 0.267 0.267 0.267 rg 116.823 728.231 66.671 0.750 re f 116.823 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 122.073 718.376 Td /F1 9.8 Tf [(0.159%)] TJ ET 0.267 0.267 0.267 rg 182.744 728.231 93.021 0.750 re f 182.744 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 187.994 718.376 Td /F1 9.8 Tf [(\(0.066%-0.333%\))] TJ ET 0.267 0.267 0.267 rg 275.015 728.231 66.671 0.750 re f 275.015 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 280.265 718.376 Td /F1 9.8 Tf [(0.542%)] TJ ET 0.267 0.267 0.267 rg 340.935 728.231 93.021 0.750 re f 340.935 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 346.185 718.376 Td /F1 9.8 Tf [(\(0.230%-1.090%\))] TJ ET 0.267 0.267 0.267 rg 433.206 728.231 58.324 0.750 re f 433.206 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 438.456 718.376 Td /F1 9.8 Tf [(3.00%)] TJ ET 0.267 0.267 0.267 rg 490.780 728.231 90.095 0.750 re f 490.780 648.581 0.750 80.400 re f 580.125 648.581 0.750 80.400 re f 0.271 0.267 0.267 rg BT 496.030 718.376 Td /F1 9.8 Tf [(\(1.35%-5.92%\))] TJ ET 0.267 0.267 0.267 rg 66.679 648.581 50.894 0.750 re f 66.679 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 638.726 Td /F1 9.8 Tf [(65+)] TJ ET 0.267 0.267 0.267 rg 116.823 648.581 66.671 0.750 re f 116.823 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 638.726 Td /F1 9.8 Tf [(0.090%)] TJ ET 0.267 0.267 0.267 rg 182.744 648.581 93.021 0.750 re f 182.744 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 638.726 Td /F1 9.8 Tf [(\(0.008%-1.471%\))] TJ ET 0.267 0.267 0.267 rg 275.015 648.581 66.671 0.750 re f 275.015 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 638.726 Td /F1 9.8 Tf [(0.327%)] TJ ET 0.267 0.267 0.267 rg 340.935 648.581 93.021 0.750 re f 340.935 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 638.726 Td /F1 9.8 Tf [(\(0.035%-4.711%\))] TJ ET 0.267 0.267 0.267 rg 433.206 648.581 58.324 0.750 re f 433.206 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 638.726 Td /F1 9.8 Tf [(1.84%)] TJ ET 0.267 0.267 0.267 rg 490.780 648.581 90.095 0.750 re f 490.780 632.700 0.750 16.631 re f 580.125 632.700 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 638.726 Td /F1 9.8 Tf [(\(0.21%-25.38%\))] TJ ET 0.267 0.267 0.267 rg 66.679 632.700 50.894 0.750 re f 66.679 616.819 50.894 0.750 re f 66.679 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 71.929 622.845 Td /F1 9.8 Tf [(Total)] TJ ET 0.267 0.267 0.267 rg 116.823 632.700 66.671 0.750 re f 116.823 616.819 66.671 0.750 re f 116.823 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 122.073 622.845 Td /F1 9.8 Tf [(0.048%)] TJ ET 0.267 0.267 0.267 rg 182.744 632.700 93.021 0.750 re f 182.744 616.819 93.021 0.750 re f 182.744 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 187.994 622.845 Td /F1 9.8 Tf [(\(0.026%-0.096%\))] TJ ET 0.267 0.267 0.267 rg 275.015 632.700 66.671 0.750 re f 275.015 616.819 66.671 0.750 re f 275.015 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 280.265 622.845 Td /F1 9.8 Tf [(0.239%)] TJ ET 0.267 0.267 0.267 rg 340.935 632.700 93.021 0.750 re f 340.935 616.819 93.021 0.750 re f 340.935 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 346.185 622.845 Td /F1 9.8 Tf [(\(0.134%-0.458%\))] TJ ET 0.267 0.267 0.267 rg 433.206 632.700 58.324 0.750 re f 433.206 616.819 58.324 0.750 re f 433.206 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 438.456 622.845 Td /F1 9.8 Tf [(1.44%)] TJ ET 0.267 0.267 0.267 rg 490.780 632.700 90.095 0.750 re f 490.780 616.819 90.095 0.750 re f 490.780 616.819 0.750 16.631 re f 580.125 616.819 0.750 16.631 re f 0.271 0.267 0.267 rg BT 496.030 622.845 Td /F1 9.8 Tf [(\(0.83%-2.64%\))] TJ ET BT 26.250 558.648 Td /F4 9.8 Tf [(Table 3:)] TJ ET BT 63.095 558.648 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 26.250 546.743 Td /F4 9.8 Tf [(hospitalization ratios, by age group, based on a combination of data from New York City and Milwaukee, and survey )] TJ ET BT 26.250 534.839 Td /F4 9.8 Tf [(data on the frequency of medical attendance for symptomatic cases.)] TJ ET BT 26.250 515.434 Td /F1 9.8 Tf [(Estimates of each of these severity measures vary dramatically by age group, with the lowest severity by each measure in the 5-)] TJ ET BT 26.250 503.529 Td /F1 9.8 Tf [(17 year age group. Comparing the two groups for which we have the most data, the relative risk of death for a symptomatic 18-)] TJ ET BT 26.250 491.624 Td /F1 9.8 Tf [(64-year-old compared to a symptomatic 5-17 year old is 15 \(95% CI 5-57\). The corresponding relative risks of ICU admission )] TJ ET BT 26.250 479.720 Td /F1 9.8 Tf [(and hospitalization are 5 \(95% CI 2-13\) and 5 \(95% CI 2-12\) respectively. The Bayesian framework provides a natural way to )] TJ ET BT 26.250 467.815 Td /F1 9.8 Tf [(estimate confidence \(measured as the posterior probability\) that one rate is higher than another. The probability that severity is )] TJ ET BT 26.250 455.910 Td /F1 9.8 Tf [(higher in the 18-64 age group than in the 5-17 age group is >99.9%, for each of fatality, ICU admission, and hospitalization )] TJ ET BT 26.250 444.005 Td /F1 9.8 Tf [(respectively. The data are too sparse to say with confidence whether adults over 65 or under 65 have greater severity. For )] TJ ET BT 26.250 432.101 Td /F1 9.8 Tf [(example, among the four age groups, the symptomatic case-fatality ratio is highest in the 18-64 year old age group with )] TJ ET BT 26.250 420.196 Td /F1 9.8 Tf [(posterior probability 62.%, and in those 65 and over with probability 38%. The symptomatic case-ICU admission ratio is highest )] TJ ET BT 26.250 408.291 Td /F1 9.8 Tf [(in 18-64 year olds with posterior probability 51% and in those over 65 with posterior probability 38%. The symptomatic case-)] TJ ET BT 26.250 396.386 Td /F1 9.8 Tf [(hospitalization ratio is highest in 18-64 year olds with posterior probability 37% and in those over 65 with posterior probability )] TJ ET BT 26.250 384.482 Td /F1 9.8 Tf [(37%.)] TJ ET BT 26.250 365.077 Td /F5 9.8 Tf [(Approach 2:)] TJ ET BT 78.822 365.077 Td /F1 9.8 Tf [( Table 4 shows the estimates for the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios, )] TJ ET BT 26.250 353.172 Td /F1 9.8 Tf [(by age group, when self-reported influenza-like illness is used as the denominator for total symptomatic cases. Overall these )] TJ ET BT 26.250 341.267 Td /F1 9.8 Tf [(are, respectively, sCFR=0.007% \(95% CI 0.005%-0.009%\), sCIR=0.028% \(95%CI 0.022%-0.035%\) and sCHR=0.16% \(95% CI )] TJ ET BT 26.250 329.363 Td /F1 9.8 Tf [(0.12%-0.26%\). Compared to Approach 1, these estimates are nearly an order of magnitude smaller, and the age distribution )] TJ ET BT 26.250 317.458 Td /F1 9.8 Tf [(differs. The relative risks for each severity in the 18-64 year old group compared to the 5-17 year old group are 7 \(95% CI 3-25\) )] TJ ET BT 26.250 305.553 Td /F1 9.8 Tf [(for fatalities, 1.5 \(95% CI 0.9-2.5\) for ICU admissions and 1.4 \(95% CI 0.9-2.1\) for hospitalizations. The case-fatality ratio is )] TJ ET BT 26.250 293.648 Td /F1 9.8 Tf [(highest in the 18-64 group with posterior probability 52%. In contrast to Approach 1, the case-ICU admission ratio is highest )] TJ ET BT 26.250 281.744 Td /F1 9.8 Tf [(among 0-4 year olds, with posterior probability 79%, and the case-hospitalization ratio is highest among 0-4 year olds with )] TJ ET BT 26.250 269.839 Td /F1 9.8 Tf [(posterior probability 99%.)] TJ ET 0.965 0.965 0.965 rg 26.250 65.708 555.000 194.250 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 259.958 m 581.250 259.958 l 581.250 259.208 l 26.250 259.208 l f q 447.000 0 0 178.500 35.250 71.708 cm /I277 Do Q q 35.250 65.708 537.000 0.000 re W n Q Q q 447.000 0 0 178.500 35.250 71.708 cm /I277 Do 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 465 0 obj << /Type /Annot /Subtype /Link /A 466 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 71.7079 482.2500 250.2079 ] >> endobj 466 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/influenza/files/2009/09/2015-10-09-14_44_18.png) >> endobj 467 0 obj << /Type /XObject /Subtype /Image /Width 596 /Height 238 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 596 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 118929>> stream x]g|UU_[B 8: 4(PTlc6*<"MP(tBr)+F$H0w9w]^}M(@!("\4RrEQ[UUy(؇ KDa_1zJ) !aTBBQq,˂s@. /'>RA4M(u4M3c4B/3Pk$N)e]^RI>3bd$a۶W.c"t]%߹v8 Di@h9B|?+k( 0 0EQ򒒒hWUUMuݶxJ)R`ԉE ETf(Ҙ>Xsh@y@Ϣ B~e-?Dѿ^M;4۵kl񘓓ʕ+M,N!z왝裏r DѲ~w}׶mÇp8iZcl߾}߲eKjL4M @RUuĈkѢERRke? ])PJ}>8~8ͥGqϫ꺮K,-%폮뚦QJ~?I/KC8QgTҢBYi.\q\8SPdiŷ>_v;(!~NCC!O/qcF[%+Ѹ8sYQ0ߪ(Qj7ʚ)K%]2}b0p>yaE{2ِRQ)v0Cⴍ[ئm?_ʘGaLhZA#%&8窦I!$pZJ\d)eՇRBh݅seJ!롔B0G Y[s|t]B0 s1^c(Ƙ8k{qnta2 aE9!o+paPTՈ-%`L>D J>9.%J>!R)AJ`H>BU(C!RJuc Xv(/]VN3c.kMS4M4-&jUU-jFQt !PCE2󤔦iڊm꺎lPd5 C%2.%k8狑DU%L5MӶm\zL}<R|>u t]<2 ryF3+guyl1UL)@pZ"kh3& Euž? 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Hb]`4)'/6(3X]*KRH$ c^V[@ vO9f&k&{Tr(yN6G87ڰ|ٛD ;תRr\<0 z*DaC5<'A((Q/$@2G3܍,w_@Dy'/ uM*gcW]iX]N=|L}@`FK=AgH׬!I.|а!H2с i^m|/ᖩ&P6s]9|Iclo 3 P %x0QA.im|') "qS8YZ'@cȜ g4M=f=fSݺ&ؓv+x }UO./VDE] g^%7ntnDZPB!TJKÆ$ɯyۏwƘ'Zjb5<%yB>4ukWmx2l"D'9tNwa!mIy~{"kxk,\O~#kN8l5'b:#2%=xlpuIe~R ~˹'sO&s KJG+KV?VXeNXdsUf&+ @ @8wӜ4uZΨ-O뇦Y9wqSVfרceiH< >Ly4_jj0zdhk+u+-Fcof8b8YZLo!7w:C[Zәi--T[Dž[N\:}#|AKD7tJ>Z-ns2"<'өVDv糨Oݞs5hԼ[֠:n6<>+lFsmOĥsǖ3:W\ Ðy`v:%'i>3I'94Kw>ީ|NW2k}"rΎX،.%UOuNM\.87epGuNp#).x/VjS%SrEYeDF֩wWV@a@sT|b$Y<5IYХkVTY9UnI yTy-EUo mysi5tS*sW`V<>|wVptN](BZ<'nf[jv U>[-#}5MEm~Zu:UoaM&s53>a^wMYAX( Y mV&Q1sp)ϮU#שAmO6Btr,I 9LS))~h/i9I7yCtۚ>P(BrG[hZ%c޽{'&&D*;k$*|G5{===`;tA 3?)OLL Waqy:U<,6?nVeU۷o6n{+y|QdMP`:k׮1N5."y)eTb`t!,Z?y#ηVt[cOP(J%cX$Z*?jgEl-oּA);([UsU>RK.$ i`:9< IP]TWNm9iJ ISO-owJdi[w6֝BƘ'AB lt|#mBҷXNU3|}>ߠ&v˪nA'.?'FZrh} H)Sgz[]jY)E:8SV'g]0 endstream endobj 468 0 obj << /Type /Annot /Subtype /Link /A 469 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 71.7079 482.2500 250.2079 ] >> endobj 469 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/influenza/files/2009/09/2015-10-09-14_44_18.png) >> endobj 470 0 obj << /Type /Annot /Subtype /Link /A 471 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 71.7079 482.2500 250.2079 ] >> endobj 471 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/influenza/files/2009/09/2015-10-09-14_44_18.png) >> endobj 472 0 obj << /Type /Page /Parent 3 0 R /Annots [ 474 0 R 476 0 R 478 0 R 480 0 R 482 0 R 484 0 R 486 0 R 488 0 R 490 0 R ] /Contents 473 0 R >> endobj 473 0 obj << /Length 28906 >> stream q 15.000 23.342 577.500 753.658 re W n 0.965 0.965 0.965 rg 26.250 717.041 555.000 59.959 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 717.041 m 581.250 717.041 l 581.250 717.791 l 26.250 717.791 l f q 35.250 728.291 537.000 48.709 re W n 0.271 0.267 0.267 rg BT 35.250 766.011 Td /F4 9.8 Tf [(Table 4:)] TJ ET BT 72.095 766.011 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 35.250 752.275 Td /F4 9.8 Tf [(hospitalization ratios, by age group, using self-reported influenza-like illness as the denominator of symptomatic )] TJ ET BT 35.250 738.538 Td /F4 9.8 Tf [(cases.)] TJ ET Q BT 26.250 682.820 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 662.865 Td /F1 9.8 Tf [(We have estimated, using data from two cities on tiered levels of severity and self-reported rates of seeking medical attention, )] TJ ET BT 26.250 650.961 Td /F1 9.8 Tf [(that approximately 1.44% of symptomatic 2009 pH1N1 patients during the spring in the United States were hospitalized; 0.239% )] TJ ET BT 26.250 639.056 Td /F1 9.8 Tf [(required intensive care or mechanical ventilation; and 0.048% died. Within the assumptions made in our model, these estimates )] TJ ET BT 26.250 627.151 Td /F1 9.8 Tf [(are uncertain up to a factor of about 2 in either direction, as reflected in the 95% credible intervals associated with the )] TJ ET BT 26.250 615.246 Td /F1 9.8 Tf [(estimates. These estimates take into account differences in detection and reporting of cases at different levels of severity, which )] TJ ET BT 26.250 603.342 Td /F1 9.8 Tf [(we believe, based on some evidence, to be more complete at higher levels of severity. Without such corrections for detection )] TJ ET BT 26.250 591.437 Td /F1 9.8 Tf [(and reporting, estimates are approximately two-fold higher for each level of severity. Using a second approach, which uses self-)] TJ ET BT 26.250 579.532 Td /F1 9.8 Tf [(reported rates of influenza-like illness in New York City to estimate symptomatic infections, we have estimated rates )] TJ ET BT 26.250 567.627 Td /F1 9.8 Tf [(approximately an order of magnitude lower, with a symptomatic case-hospitalization ratio \(sCHR\) of 0.16%, a symptomatic case-)] TJ ET BT 26.250 555.723 Td /F1 9.8 Tf [(intensive care ratio of 0.028%, and a symptomatic case-fatality ratio of 0.007%. In both approaches, the sCFR was highest in )] TJ ET BT 26.250 543.818 Td /F1 9.8 Tf [(adults and lowest in school-age children \(5-17\); data on children 0-4 and adults 65 and older were relatively sparse, making )] TJ ET BT 26.250 531.913 Td /F1 9.8 Tf [(statements about their ordering more difficult. Nonetheless, given the large number of cases in nonelderly adults, this )] TJ ET BT 26.250 520.008 Td /F1 9.8 Tf [(represents a substantial shift in the burden of hospitalization and mortality from those over 65, for whom seasonal influenza is )] TJ ET BT 26.250 508.104 Td /F1 9.8 Tf [(most severe [21], to middle-aged adults, consistent with findings from previous pandemics [22].)] TJ ET BT 26.250 488.699 Td /F1 9.8 Tf [(These estimates are valuable for attempting to project, in approximate terms, the possible severity of a fall-winter wave of )] TJ ET BT 26.250 476.794 Td /F1 9.8 Tf [(pH1N1, under the assumption that the virus does not change its characteristics. From the 1957 and 1968 pandemics, it appears )] TJ ET BT 26.250 464.889 Td /F1 9.8 Tf [(that perhaps 40-60% of the population was serologically infected, and that of those, 40-60% were symptomatic [2][23][24][25]. )] TJ ET BT 26.250 452.985 Td /F1 9.8 Tf [(Current estimates of the transmission of 2009 pH1N1 range between about 1.4 and about 2.2, consistent with estimates of the )] TJ ET BT 26.250 441.080 Td /F1 9.8 Tf [(reproduction numbers from prior [26][27][28][29][30]. To convert our estimates into population impacts, one needs to make an )] TJ ET BT 26.250 429.175 Td /F1 9.8 Tf [(assumption about the attack rate and its age distribution. For each 10% of the US population symptomatically infected \(with the )] TJ ET BT 26.250 417.270 Td /F1 9.8 Tf [(same age distribution observed in the spring wave\), our Approach 1 estimates suggest that approximately 7800-29,000 deaths )] TJ ET BT 26.250 405.366 Td /F1 9.8 Tf [(\(3-10 per 100,000 population\), 40,000-140,000 intensive care admissions \(13-46 per 100,000 population\), and 250,000-790,000 )] TJ ET BT 26.250 393.461 Td /F1 9.8 Tf [(hospitalizations \(170-630 per 100,000 population\). These estimates will scale up and down in proportion to the attack rate; for )] TJ ET BT 26.250 381.556 Td /F1 9.8 Tf [(example, they should be doubled if 20% of the population were symptomatic, producing for example 15,000-58,000 deaths, or 6-)] TJ ET BT 26.250 369.651 Td /F1 9.8 Tf [(20 per 100,000 population. Approach 2 suggests much smaller figures \(for each 10% of the population symptomatic\) of 1500-)] TJ ET BT 26.250 357.747 Td /F1 9.8 Tf [(2700 deaths \(0.5-0.9 per 100,000\); 6600-11,000 ICU admissions/uses of mechanical ventilation \(22-35 per 100,000\); and )] TJ ET BT 26.250 345.842 Td /F1 9.8 Tf [(36,000-78,000 hospitalizations \(12-26 per 100,000\). Again, these numbers should be scaled in proportion to the attack rate.)] TJ ET BT 26.250 326.437 Td /F1 9.8 Tf [(To date, symptomatic attack rates seem to be far lower than 25% in both the completed Southern Hemisphere winter epidemic )] TJ ET BT 26.250 314.532 Td /F1 9.8 Tf [(and the autumn epidemic in progress in the United States; severe outcomes seem to be considerably less numerous than those )] TJ ET BT 26.250 302.628 Td /F1 9.8 Tf [(described for Approach 1 with a 25% attack rate. In New Zealand, just under 2% of the population consulted a general )] TJ ET BT 26.250 290.723 Td /F1 9.8 Tf [(practitioner for influenza-like illness during the winter wave of the pandemic there \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 278.818 Td /F1 9.8 Tf [(http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809)] TJ ET 0.271 0.267 0.267 rg BT 368.202 278.818 Td /F1 9.8 Tf [(\), consistent with an attack rate significantly )] TJ ET BT 26.250 266.913 Td /F1 9.8 Tf [(lower than 25%, though somewhat higher than the GP consultation rate observed in severe seasonal flu outbreaks such as )] TJ ET BT 26.250 255.009 Td /F1 9.8 Tf [(those in 2003 and 2004 \()] TJ ET 0.267 0.267 0.267 rg BT 134.114 255.009 Td /F1 9.8 Tf [(http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf)] TJ ET 0.271 0.267 0.267 rg BT 545.915 255.009 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 235.604 Td /F1 9.8 Tf [(Our estimates reflect a level of antiviral treatment and health care capacity that will not be available in all populations. )] TJ ET BT 26.250 223.699 Td /F1 9.8 Tf [(Oseltamivir use was common in Milwaukee \(Milwaukee Department of Health, unpublished data\), and although the health )] TJ ET BT 26.250 211.794 Td /F1 9.8 Tf [(system was stressed in both cities studied, there was no shortage of intensive care or other life-saving medical resources. In a )] TJ ET BT 26.250 199.890 Td /F1 9.8 Tf [(situation of greater stress on the health system, as has been observed in certain locations in the Southern Hemisphere [9][10] )] TJ ET 0.267 0.267 0.267 rg BT 26.250 187.985 Td /F1 9.8 Tf [(http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589)] TJ ET 0.271 0.267 0.267 rg BT 353.606 187.985 Td /F1 9.8 Tf [(, or in areas that lack a high-quality health system, )] TJ ET BT 26.250 176.080 Td /F1 9.8 Tf [(severity might increase in proportion as adequate medical attention is less available. Worryingly, our estimates of the proportion )] TJ ET BT 26.250 164.175 Td /F1 9.8 Tf [(of symptomatic cases requiring mechanical ventilation or ICU care was approximately 4-5x our estimate of the sCFR. It is )] TJ ET BT 26.250 152.271 Td /F1 9.8 Tf [(possible that a substantial proportion of those admitted to ICUs would have died without intensive care. In populations without )] TJ ET BT 26.250 140.366 Td /F1 9.8 Tf [(widespread access to intensive care, our results suggest that the same burden of disease would lead to a death rate 4-5 times )] TJ ET BT 26.250 128.461 Td /F1 9.8 Tf [(higher. Likewise, a change in the virus to become more virulent or resistant to existing antiviral drugs, or the emergence of more )] TJ ET BT 26.250 116.556 Td /F1 9.8 Tf [(frequent bacterial coinfections could increase the severity of infection compared to that observed so far.)] TJ ET BT 26.250 97.152 Td /F1 9.8 Tf [(Estimates of severity for an infection such as influenza are fraught with uncertainties [1]. Our analysis has accounted for many )] TJ ET BT 26.250 85.247 Td /F1 9.8 Tf [(of these uncertainties, including imperfect detection and reporting of cases, bias due to delays between events \(such as the )] TJ ET BT 26.250 73.342 Td /F1 9.8 Tf [(delay from illness onset to death\), and the statistical uncertainties associated with limited numbers of cases, hospitalizations )] TJ ET BT 26.250 61.437 Td /F1 9.8 Tf [(and deaths. Another major source of difficulty is the spatial and temporal variation in reporting effort for mild and severe cases; )] TJ ET BT 26.250 49.533 Td /F1 9.8 Tf [(for example, most jurisdictions in the United States stopped reporting mild cases on or before the second week of May, but this )] TJ ET BT 26.250 37.628 Td /F1 9.8 Tf [(change varied by jurisdiction. We have attempted to avoid this difficulty by focusing on individual jurisdictions New York and )] TJ ET Q q 15.000 23.342 577.500 753.658 re W n 0.965 0.965 0.965 rg 26.250 717.041 555.000 59.959 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 717.041 m 581.250 717.041 l 581.250 717.791 l 26.250 717.791 l f q 35.250 728.291 537.000 48.709 re W n 0.271 0.267 0.267 rg BT 35.250 766.011 Td /F4 9.8 Tf [(Table 4:)] TJ ET BT 72.095 766.011 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 35.250 752.275 Td /F4 9.8 Tf [(hospitalization ratios, by age group, using self-reported influenza-like illness as the denominator of symptomatic )] TJ ET BT 35.250 738.538 Td /F4 9.8 Tf [(cases.)] TJ ET Q BT 26.250 682.820 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 662.865 Td /F1 9.8 Tf [(We have estimated, using data from two cities on tiered levels of severity and self-reported rates of seeking medical attention, )] TJ ET BT 26.250 650.961 Td /F1 9.8 Tf [(that approximately 1.44% of symptomatic 2009 pH1N1 patients during the spring in the United States were hospitalized; 0.239% )] TJ ET BT 26.250 639.056 Td /F1 9.8 Tf [(required intensive care or mechanical ventilation; and 0.048% died. Within the assumptions made in our model, these estimates )] TJ ET BT 26.250 627.151 Td /F1 9.8 Tf [(are uncertain up to a factor of about 2 in either direction, as reflected in the 95% credible intervals associated with the )] TJ ET BT 26.250 615.246 Td /F1 9.8 Tf [(estimates. These estimates take into account differences in detection and reporting of cases at different levels of severity, which )] TJ ET BT 26.250 603.342 Td /F1 9.8 Tf [(we believe, based on some evidence, to be more complete at higher levels of severity. Without such corrections for detection )] TJ ET BT 26.250 591.437 Td /F1 9.8 Tf [(and reporting, estimates are approximately two-fold higher for each level of severity. Using a second approach, which uses self-)] TJ ET BT 26.250 579.532 Td /F1 9.8 Tf [(reported rates of influenza-like illness in New York City to estimate symptomatic infections, we have estimated rates )] TJ ET BT 26.250 567.627 Td /F1 9.8 Tf [(approximately an order of magnitude lower, with a symptomatic case-hospitalization ratio \(sCHR\) of 0.16%, a symptomatic case-)] TJ ET BT 26.250 555.723 Td /F1 9.8 Tf [(intensive care ratio of 0.028%, and a symptomatic case-fatality ratio of 0.007%. In both approaches, the sCFR was highest in )] TJ ET BT 26.250 543.818 Td /F1 9.8 Tf [(adults and lowest in school-age children \(5-17\); data on children 0-4 and adults 65 and older were relatively sparse, making )] TJ ET BT 26.250 531.913 Td /F1 9.8 Tf [(statements about their ordering more difficult. Nonetheless, given the large number of cases in nonelderly adults, this )] TJ ET BT 26.250 520.008 Td /F1 9.8 Tf [(represents a substantial shift in the burden of hospitalization and mortality from those over 65, for whom seasonal influenza is )] TJ ET BT 26.250 508.104 Td /F1 9.8 Tf [(most severe [21], to middle-aged adults, consistent with findings from previous pandemics [22].)] TJ ET BT 26.250 488.699 Td /F1 9.8 Tf [(These estimates are valuable for attempting to project, in approximate terms, the possible severity of a fall-winter wave of )] TJ ET BT 26.250 476.794 Td /F1 9.8 Tf [(pH1N1, under the assumption that the virus does not change its characteristics. From the 1957 and 1968 pandemics, it appears )] TJ ET BT 26.250 464.889 Td /F1 9.8 Tf [(that perhaps 40-60% of the population was serologically infected, and that of those, 40-60% were symptomatic [2][23][24][25]. )] TJ ET BT 26.250 452.985 Td /F1 9.8 Tf [(Current estimates of the transmission of 2009 pH1N1 range between about 1.4 and about 2.2, consistent with estimates of the )] TJ ET BT 26.250 441.080 Td /F1 9.8 Tf [(reproduction numbers from prior [26][27][28][29][30]. To convert our estimates into population impacts, one needs to make an )] TJ ET BT 26.250 429.175 Td /F1 9.8 Tf [(assumption about the attack rate and its age distribution. For each 10% of the US population symptomatically infected \(with the )] TJ ET BT 26.250 417.270 Td /F1 9.8 Tf [(same age distribution observed in the spring wave\), our Approach 1 estimates suggest that approximately 7800-29,000 deaths )] TJ ET BT 26.250 405.366 Td /F1 9.8 Tf [(\(3-10 per 100,000 population\), 40,000-140,000 intensive care admissions \(13-46 per 100,000 population\), and 250,000-790,000 )] TJ ET BT 26.250 393.461 Td /F1 9.8 Tf [(hospitalizations \(170-630 per 100,000 population\). These estimates will scale up and down in proportion to the attack rate; for )] TJ ET BT 26.250 381.556 Td /F1 9.8 Tf [(example, they should be doubled if 20% of the population were symptomatic, producing for example 15,000-58,000 deaths, or 6-)] TJ ET BT 26.250 369.651 Td /F1 9.8 Tf [(20 per 100,000 population. Approach 2 suggests much smaller figures \(for each 10% of the population symptomatic\) of 1500-)] TJ ET BT 26.250 357.747 Td /F1 9.8 Tf [(2700 deaths \(0.5-0.9 per 100,000\); 6600-11,000 ICU admissions/uses of mechanical ventilation \(22-35 per 100,000\); and )] TJ ET BT 26.250 345.842 Td /F1 9.8 Tf [(36,000-78,000 hospitalizations \(12-26 per 100,000\). Again, these numbers should be scaled in proportion to the attack rate.)] TJ ET BT 26.250 326.437 Td /F1 9.8 Tf [(To date, symptomatic attack rates seem to be far lower than 25% in both the completed Southern Hemisphere winter epidemic )] TJ ET BT 26.250 314.532 Td /F1 9.8 Tf [(and the autumn epidemic in progress in the United States; severe outcomes seem to be considerably less numerous than those )] TJ ET BT 26.250 302.628 Td /F1 9.8 Tf [(described for Approach 1 with a 25% attack rate. In New Zealand, just under 2% of the population consulted a general )] TJ ET BT 26.250 290.723 Td /F1 9.8 Tf [(practitioner for influenza-like illness during the winter wave of the pandemic there \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 278.818 Td /F1 9.8 Tf [(http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809)] TJ ET 0.271 0.267 0.267 rg BT 368.202 278.818 Td /F1 9.8 Tf [(\), consistent with an attack rate significantly )] TJ ET BT 26.250 266.913 Td /F1 9.8 Tf [(lower than 25%, though somewhat higher than the GP consultation rate observed in severe seasonal flu outbreaks such as )] TJ ET BT 26.250 255.009 Td /F1 9.8 Tf [(those in 2003 and 2004 \()] TJ ET 0.267 0.267 0.267 rg BT 134.114 255.009 Td /F1 9.8 Tf [(http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf)] TJ ET 0.271 0.267 0.267 rg BT 545.915 255.009 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 235.604 Td /F1 9.8 Tf [(Our estimates reflect a level of antiviral treatment and health care capacity that will not be available in all populations. )] TJ ET BT 26.250 223.699 Td /F1 9.8 Tf [(Oseltamivir use was common in Milwaukee \(Milwaukee Department of Health, unpublished data\), and although the health )] TJ ET BT 26.250 211.794 Td /F1 9.8 Tf [(system was stressed in both cities studied, there was no shortage of intensive care or other life-saving medical resources. In a )] TJ ET BT 26.250 199.890 Td /F1 9.8 Tf [(situation of greater stress on the health system, as has been observed in certain locations in the Southern Hemisphere [9][10] )] TJ ET 0.267 0.267 0.267 rg BT 26.250 187.985 Td /F1 9.8 Tf [(http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589)] TJ ET 0.271 0.267 0.267 rg BT 353.606 187.985 Td /F1 9.8 Tf [(, or in areas that lack a high-quality health system, )] TJ ET BT 26.250 176.080 Td /F1 9.8 Tf [(severity might increase in proportion as adequate medical attention is less available. Worryingly, our estimates of the proportion )] TJ ET BT 26.250 164.175 Td /F1 9.8 Tf [(of symptomatic cases requiring mechanical ventilation or ICU care was approximately 4-5x our estimate of the sCFR. It is )] TJ ET BT 26.250 152.271 Td /F1 9.8 Tf [(possible that a substantial proportion of those admitted to ICUs would have died without intensive care. In populations without )] TJ ET BT 26.250 140.366 Td /F1 9.8 Tf [(widespread access to intensive care, our results suggest that the same burden of disease would lead to a death rate 4-5 times )] TJ ET BT 26.250 128.461 Td /F1 9.8 Tf [(higher. Likewise, a change in the virus to become more virulent or resistant to existing antiviral drugs, or the emergence of more )] TJ ET BT 26.250 116.556 Td /F1 9.8 Tf [(frequent bacterial coinfections could increase the severity of infection compared to that observed so far.)] TJ ET BT 26.250 97.152 Td /F1 9.8 Tf [(Estimates of severity for an infection such as influenza are fraught with uncertainties [1]. Our analysis has accounted for many )] TJ ET BT 26.250 85.247 Td /F1 9.8 Tf [(of these uncertainties, including imperfect detection and reporting of cases, bias due to delays between events \(such as the )] TJ ET BT 26.250 73.342 Td /F1 9.8 Tf [(delay from illness onset to death\), and the statistical uncertainties associated with limited numbers of cases, hospitalizations )] TJ ET BT 26.250 61.437 Td /F1 9.8 Tf [(and deaths. Another major source of difficulty is the spatial and temporal variation in reporting effort for mild and severe cases; )] TJ ET BT 26.250 49.533 Td /F1 9.8 Tf [(for example, most jurisdictions in the United States stopped reporting mild cases on or before the second week of May, but this )] TJ ET BT 26.250 37.628 Td /F1 9.8 Tf [(change varied by jurisdiction. We have attempted to avoid this difficulty by focusing on individual jurisdictions New York and )] TJ ET Q q 15.000 23.342 577.500 753.658 re W n 0.965 0.965 0.965 rg 26.250 717.041 555.000 59.959 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 717.041 m 581.250 717.041 l 581.250 717.791 l 26.250 717.791 l f q 35.250 728.291 537.000 48.709 re W n 0.271 0.267 0.267 rg BT 35.250 766.011 Td /F4 9.8 Tf [(Table 4:)] TJ ET BT 72.095 766.011 Td /F4 9.8 Tf [( Posterior median \(95% credible interval\) estimates of the symptomatic case-fatality, case-ICU and case-)] TJ ET BT 35.250 752.275 Td /F4 9.8 Tf [(hospitalization ratios, by age group, using self-reported influenza-like illness as the denominator of symptomatic )] TJ ET BT 35.250 738.538 Td /F4 9.8 Tf [(cases.)] TJ ET Q BT 26.250 682.820 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 662.865 Td /F1 9.8 Tf [(We have estimated, using data from two cities on tiered levels of severity and self-reported rates of seeking medical attention, )] TJ ET BT 26.250 650.961 Td /F1 9.8 Tf [(that approximately 1.44% of symptomatic 2009 pH1N1 patients during the spring in the United States were hospitalized; 0.239% )] TJ ET BT 26.250 639.056 Td /F1 9.8 Tf [(required intensive care or mechanical ventilation; and 0.048% died. Within the assumptions made in our model, these estimates )] TJ ET BT 26.250 627.151 Td /F1 9.8 Tf [(are uncertain up to a factor of about 2 in either direction, as reflected in the 95% credible intervals associated with the )] TJ ET BT 26.250 615.246 Td /F1 9.8 Tf [(estimates. These estimates take into account differences in detection and reporting of cases at different levels of severity, which )] TJ ET BT 26.250 603.342 Td /F1 9.8 Tf [(we believe, based on some evidence, to be more complete at higher levels of severity. Without such corrections for detection )] TJ ET BT 26.250 591.437 Td /F1 9.8 Tf [(and reporting, estimates are approximately two-fold higher for each level of severity. Using a second approach, which uses self-)] TJ ET BT 26.250 579.532 Td /F1 9.8 Tf [(reported rates of influenza-like illness in New York City to estimate symptomatic infections, we have estimated rates )] TJ ET BT 26.250 567.627 Td /F1 9.8 Tf [(approximately an order of magnitude lower, with a symptomatic case-hospitalization ratio \(sCHR\) of 0.16%, a symptomatic case-)] TJ ET BT 26.250 555.723 Td /F1 9.8 Tf [(intensive care ratio of 0.028%, and a symptomatic case-fatality ratio of 0.007%. In both approaches, the sCFR was highest in )] TJ ET BT 26.250 543.818 Td /F1 9.8 Tf [(adults and lowest in school-age children \(5-17\); data on children 0-4 and adults 65 and older were relatively sparse, making )] TJ ET BT 26.250 531.913 Td /F1 9.8 Tf [(statements about their ordering more difficult. Nonetheless, given the large number of cases in nonelderly adults, this )] TJ ET BT 26.250 520.008 Td /F1 9.8 Tf [(represents a substantial shift in the burden of hospitalization and mortality from those over 65, for whom seasonal influenza is )] TJ ET BT 26.250 508.104 Td /F1 9.8 Tf [(most severe [21], to middle-aged adults, consistent with findings from previous pandemics [22].)] TJ ET BT 26.250 488.699 Td /F1 9.8 Tf [(These estimates are valuable for attempting to project, in approximate terms, the possible severity of a fall-winter wave of )] TJ ET BT 26.250 476.794 Td /F1 9.8 Tf [(pH1N1, under the assumption that the virus does not change its characteristics. From the 1957 and 1968 pandemics, it appears )] TJ ET BT 26.250 464.889 Td /F1 9.8 Tf [(that perhaps 40-60% of the population was serologically infected, and that of those, 40-60% were symptomatic [2][23][24][25]. )] TJ ET BT 26.250 452.985 Td /F1 9.8 Tf [(Current estimates of the transmission of 2009 pH1N1 range between about 1.4 and about 2.2, consistent with estimates of the )] TJ ET BT 26.250 441.080 Td /F1 9.8 Tf [(reproduction numbers from prior [26][27][28][29][30]. To convert our estimates into population impacts, one needs to make an )] TJ ET BT 26.250 429.175 Td /F1 9.8 Tf [(assumption about the attack rate and its age distribution. For each 10% of the US population symptomatically infected \(with the )] TJ ET BT 26.250 417.270 Td /F1 9.8 Tf [(same age distribution observed in the spring wave\), our Approach 1 estimates suggest that approximately 7800-29,000 deaths )] TJ ET BT 26.250 405.366 Td /F1 9.8 Tf [(\(3-10 per 100,000 population\), 40,000-140,000 intensive care admissions \(13-46 per 100,000 population\), and 250,000-790,000 )] TJ ET BT 26.250 393.461 Td /F1 9.8 Tf [(hospitalizations \(170-630 per 100,000 population\). These estimates will scale up and down in proportion to the attack rate; for )] TJ ET BT 26.250 381.556 Td /F1 9.8 Tf [(example, they should be doubled if 20% of the population were symptomatic, producing for example 15,000-58,000 deaths, or 6-)] TJ ET BT 26.250 369.651 Td /F1 9.8 Tf [(20 per 100,000 population. Approach 2 suggests much smaller figures \(for each 10% of the population symptomatic\) of 1500-)] TJ ET BT 26.250 357.747 Td /F1 9.8 Tf [(2700 deaths \(0.5-0.9 per 100,000\); 6600-11,000 ICU admissions/uses of mechanical ventilation \(22-35 per 100,000\); and )] TJ ET BT 26.250 345.842 Td /F1 9.8 Tf [(36,000-78,000 hospitalizations \(12-26 per 100,000\). Again, these numbers should be scaled in proportion to the attack rate.)] TJ ET BT 26.250 326.437 Td /F1 9.8 Tf [(To date, symptomatic attack rates seem to be far lower than 25% in both the completed Southern Hemisphere winter epidemic )] TJ ET BT 26.250 314.532 Td /F1 9.8 Tf [(and the autumn epidemic in progress in the United States; severe outcomes seem to be considerably less numerous than those )] TJ ET BT 26.250 302.628 Td /F1 9.8 Tf [(described for Approach 1 with a 25% attack rate. In New Zealand, just under 2% of the population consulted a general )] TJ ET BT 26.250 290.723 Td /F1 9.8 Tf [(practitioner for influenza-like illness during the winter wave of the pandemic there \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 278.818 Td /F1 9.8 Tf [(http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809)] TJ ET 0.271 0.267 0.267 rg BT 368.202 278.818 Td /F1 9.8 Tf [(\), consistent with an attack rate significantly )] TJ ET BT 26.250 266.913 Td /F1 9.8 Tf [(lower than 25%, though somewhat higher than the GP consultation rate observed in severe seasonal flu outbreaks such as )] TJ ET BT 26.250 255.009 Td /F1 9.8 Tf [(those in 2003 and 2004 \()] TJ ET 0.267 0.267 0.267 rg BT 134.114 255.009 Td /F1 9.8 Tf [(http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf)] TJ ET 0.271 0.267 0.267 rg BT 545.915 255.009 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 235.604 Td /F1 9.8 Tf [(Our estimates reflect a level of antiviral treatment and health care capacity that will not be available in all populations. )] TJ ET BT 26.250 223.699 Td /F1 9.8 Tf [(Oseltamivir use was common in Milwaukee \(Milwaukee Department of Health, unpublished data\), and although the health )] TJ ET BT 26.250 211.794 Td /F1 9.8 Tf [(system was stressed in both cities studied, there was no shortage of intensive care or other life-saving medical resources. In a )] TJ ET BT 26.250 199.890 Td /F1 9.8 Tf [(situation of greater stress on the health system, as has been observed in certain locations in the Southern Hemisphere [9][10] )] TJ ET 0.267 0.267 0.267 rg BT 26.250 187.985 Td /F1 9.8 Tf [(http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589)] TJ ET 0.271 0.267 0.267 rg BT 353.606 187.985 Td /F1 9.8 Tf [(, or in areas that lack a high-quality health system, )] TJ ET BT 26.250 176.080 Td /F1 9.8 Tf [(severity might increase in proportion as adequate medical attention is less available. Worryingly, our estimates of the proportion )] TJ ET BT 26.250 164.175 Td /F1 9.8 Tf [(of symptomatic cases requiring mechanical ventilation or ICU care was approximately 4-5x our estimate of the sCFR. It is )] TJ ET BT 26.250 152.271 Td /F1 9.8 Tf [(possible that a substantial proportion of those admitted to ICUs would have died without intensive care. In populations without )] TJ ET BT 26.250 140.366 Td /F1 9.8 Tf [(widespread access to intensive care, our results suggest that the same burden of disease would lead to a death rate 4-5 times )] TJ ET BT 26.250 128.461 Td /F1 9.8 Tf [(higher. Likewise, a change in the virus to become more virulent or resistant to existing antiviral drugs, or the emergence of more )] TJ ET BT 26.250 116.556 Td /F1 9.8 Tf [(frequent bacterial coinfections could increase the severity of infection compared to that observed so far.)] TJ ET BT 26.250 97.152 Td /F1 9.8 Tf [(Estimates of severity for an infection such as influenza are fraught with uncertainties [1]. Our analysis has accounted for many )] TJ ET BT 26.250 85.247 Td /F1 9.8 Tf [(of these uncertainties, including imperfect detection and reporting of cases, bias due to delays between events \(such as the )] TJ ET BT 26.250 73.342 Td /F1 9.8 Tf [(delay from illness onset to death\), and the statistical uncertainties associated with limited numbers of cases, hospitalizations )] TJ ET BT 26.250 61.437 Td /F1 9.8 Tf [(and deaths. Another major source of difficulty is the spatial and temporal variation in reporting effort for mild and severe cases; )] TJ ET BT 26.250 49.533 Td /F1 9.8 Tf [(for example, most jurisdictions in the United States stopped reporting mild cases on or before the second week of May, but this )] TJ ET BT 26.250 37.628 Td /F1 9.8 Tf [(change varied by jurisdiction. We have attempted to avoid this difficulty by focusing on individual jurisdictions New York and )] 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 474 0 obj << /Type /Annot /Subtype /Link /A 475 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 277.9163 368.2020 287.8369 ] >> endobj 475 0 obj << /Type /Action /S /URI /URI (http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809) >> endobj 476 0 obj << /Type /Annot /Subtype /Link /A 477 0 R /Border [0 0 0] /H /I /Rect [ 134.1142 254.1068 545.9153 264.0274 ] >> endobj 477 0 obj << /Type /Action /S /URI /URI (http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf) >> endobj 478 0 obj << /Type /Annot /Subtype /Link /A 479 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 187.0831 353.6062 197.0037 ] >> endobj 479 0 obj << /Type /Action /S /URI /URI (http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589) >> endobj 480 0 obj << /Type /Annot /Subtype /Link /A 481 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 277.9163 368.2020 287.8369 ] >> endobj 481 0 obj << /Type /Action /S /URI /URI (http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809) >> endobj 482 0 obj << /Type /Annot /Subtype /Link /A 483 0 R /Border [0 0 0] /H /I /Rect [ 134.1142 254.1068 545.9153 264.0274 ] >> endobj 483 0 obj << /Type /Action /S /URI /URI (http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf) >> endobj 484 0 obj << /Type /Annot /Subtype /Link /A 485 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 187.0831 353.6062 197.0037 ] >> endobj 485 0 obj << /Type /Action /S /URI /URI (http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589) >> endobj 486 0 obj << /Type /Annot /Subtype /Link /A 487 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 277.9163 368.2020 287.8369 ] >> endobj 487 0 obj << /Type /Action /S /URI /URI (http://www.moh.govt.nz/moh.nsf/indexmh/influenza-a-h1n1-update-138-180809) >> endobj 488 0 obj << /Type /Annot /Subtype /Link /A 489 0 R /Border [0 0 0] /H /I /Rect [ 134.1142 254.1068 545.9153 264.0274 ] >> endobj 489 0 obj << /Type /Action /S /URI /URI (http://www.surv.esr.cri.nz/PDF_surveillance/Virology/FluWeekRpt/2004/FluWeekRpt200444.pdf) >> endobj 490 0 obj << /Type /Annot /Subtype /Link /A 491 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 187.0831 353.6062 197.0037 ] >> endobj 491 0 obj << /Type /Action /S /URI /URI (http://www.capegateway.gov.za/eng/your_gov/3576/news/2009/aug/185589) >> endobj 492 0 obj << /Type /Page /Parent 3 0 R /Annots [ 494 0 R 498 0 R 502 0 R ] /Contents 493 0 R >> endobj 493 0 obj << /Length 17069 >> stream 0.271 0.267 0.267 rg q 15.000 33.179 577.500 743.821 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Milwaukee for which the approach to reporting was relatively stable over time. One limitation is that Milwaukee changed its )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(guidance during our surveillance period from testing of all symptomatic cases to testing of all symptomatic health care workers )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(but only moderate to severe cases in non-health care workers. We believe that testing policies did not change dramatically )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(during this period, because the proportion of hospitalized case remained fairly constant; however, the sample size prior to this )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(change in guidance was small. Thus, our estimates should be seen as being the risk of severe outcome among persons with )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(symptoms, possibly biased somewhat toward those with more severe symptoms.)] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(Despite our efforts to account for sources of uncertainty, several others remain and have not been accounted for in our analysis. )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(First, we have assumed that for each level of severity \(from medically attended up to fatal\), case reporting was equal across age )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(groups; for example, we assumed that medically attended cases were as likely to be reported for young children as for adults. It )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(is possible that this is not the case, for example that mild cases were more likely to come to medical attention if they occurred in )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(children than if they occurred in adults. If this were true, our conclusion that severity was higher in adults than children could be )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(partly a result of differential reporting.)] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(Second, the overall estimates of severity \(not stratified by age group\) reflect the age composition of cases in the sample we )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(studied, especially the age composition of the lowest level of severity examined, medically attended illness. Among medically )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(attended cases in Milwaukee, 60% were in the 5-17 age group, the one in which severe outcomes were the least likely. A )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(preponderance of cases within this age group may be typical of the early part of influenza epidemics, and while it has been )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(argued that there is a shift from younger to older age groups in seasonal influenza [31] as the epidemic progresses, there is )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(evidence from at least the 1957 pandemic that attack rates remain higher in children than adults throughout the course of the )] TJ ET BT 26.250 538.191 Td /F1 9.8 Tf [(epidemic [2]. Since severity appears to be considerably higher in adults, then a shift in the burden of disease from children to )] TJ ET BT 26.250 526.286 Td /F1 9.8 Tf [(adults as the epidemic progresses would lead to an increase in average severity.)] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(We note that the association between age and severity may also affect observed trends in the characteristics of cases. The )] TJ ET BT 26.250 494.976 Td /F1 9.8 Tf [(World Health Organization has noted worldwide a shift from younger to older mean age among confirmed cases \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 483.072 Td /F1 9.8 Tf [(http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 397.471 483.072 Td /F1 9.8 Tf [(\). If severity is lowest among children, this )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(upward shift in age distribution may partially reflect a shift toward detection of more severe cases, rather than a true shift in the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(ages of those becoming infected.)] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(Third, the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios are dependent upon our estimates of )] TJ ET BT 26.250 427.276 Td /F1 9.8 Tf [(the true number of symptomatic cases, )] TJ ET q 27.750 0 0 12.750 196.943 424.726 cm /I279 Do Q BT 224.693 427.276 Td /F1 9.8 Tf [( and hence are sensitive to the choice of prior for these, as well as to our prior )] TJ ET BT 26.250 415.203 Td /F1 9.8 Tf [(assumptions on the detection probabilities. In particular, if the probability that symptomatic cases seek medical attention and are )] TJ ET BT 26.250 403.298 Td /F1 9.8 Tf [(confirmed is lower than we assume in our prior distributions, then there are more cases than are inferred by our model, and )] TJ ET BT 26.250 391.393 Td /F1 9.8 Tf [(severity is correspondingly lower than our estimates. If the probability of detecting severe outcomes \(hospitalizations, deaths, )] TJ ET BT 26.250 379.488 Td /F1 9.8 Tf [(ICU\) is lower than our priors reflect, then there are more severe outcomes than our model infers, so severity is correspondingly )] TJ ET BT 26.250 367.584 Td /F1 9.8 Tf [(higher.)] TJ ET BT 26.250 348.179 Td /F1 9.8 Tf [(Finally, the small sample sizes in some age groups, the over-65 year olds in particular, lead to large uncertainty about the age-)] TJ ET BT 26.250 336.274 Td /F1 9.8 Tf [(specific estimates. This level of uncertainty is reflected in the wide 95% credible intervals for the estimates.)] TJ ET Q q 15.000 33.179 577.500 743.821 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Milwaukee for which the approach to reporting was relatively stable over time. One limitation is that Milwaukee changed its )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(guidance during our surveillance period from testing of all symptomatic cases to testing of all symptomatic health care workers )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(but only moderate to severe cases in non-health care workers. We believe that testing policies did not change dramatically )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(during this period, because the proportion of hospitalized case remained fairly constant; however, the sample size prior to this )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(change in guidance was small. Thus, our estimates should be seen as being the risk of severe outcome among persons with )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(symptoms, possibly biased somewhat toward those with more severe symptoms.)] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(Despite our efforts to account for sources of uncertainty, several others remain and have not been accounted for in our analysis. )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(First, we have assumed that for each level of severity \(from medically attended up to fatal\), case reporting was equal across age )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(groups; for example, we assumed that medically attended cases were as likely to be reported for young children as for adults. It )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(is possible that this is not the case, for example that mild cases were more likely to come to medical attention if they occurred in )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(children than if they occurred in adults. If this were true, our conclusion that severity was higher in adults than children could be )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(partly a result of differential reporting.)] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(Second, the overall estimates of severity \(not stratified by age group\) reflect the age composition of cases in the sample we )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(studied, especially the age composition of the lowest level of severity examined, medically attended illness. Among medically )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(attended cases in Milwaukee, 60% were in the 5-17 age group, the one in which severe outcomes were the least likely. A )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(preponderance of cases within this age group may be typical of the early part of influenza epidemics, and while it has been )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(argued that there is a shift from younger to older age groups in seasonal influenza [31] as the epidemic progresses, there is )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(evidence from at least the 1957 pandemic that attack rates remain higher in children than adults throughout the course of the )] TJ ET BT 26.250 538.191 Td /F1 9.8 Tf [(epidemic [2]. Since severity appears to be considerably higher in adults, then a shift in the burden of disease from children to )] TJ ET BT 26.250 526.286 Td /F1 9.8 Tf [(adults as the epidemic progresses would lead to an increase in average severity.)] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(We note that the association between age and severity may also affect observed trends in the characteristics of cases. The )] TJ ET BT 26.250 494.976 Td /F1 9.8 Tf [(World Health Organization has noted worldwide a shift from younger to older mean age among confirmed cases \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 483.072 Td /F1 9.8 Tf [(http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 397.471 483.072 Td /F1 9.8 Tf [(\). If severity is lowest among children, this )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(upward shift in age distribution may partially reflect a shift toward detection of more severe cases, rather than a true shift in the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(ages of those becoming infected.)] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(Third, the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios are dependent upon our estimates of )] TJ ET BT 26.250 427.276 Td /F1 9.8 Tf [(the true number of symptomatic cases, )] TJ ET q 27.750 0 0 12.750 196.943 424.726 cm /I281 Do Q BT 224.693 427.276 Td /F1 9.8 Tf [( and hence are sensitive to the choice of prior for these, as well as to our prior )] TJ ET BT 26.250 415.203 Td /F1 9.8 Tf [(assumptions on the detection probabilities. In particular, if the probability that symptomatic cases seek medical attention and are )] TJ ET BT 26.250 403.298 Td /F1 9.8 Tf [(confirmed is lower than we assume in our prior distributions, then there are more cases than are inferred by our model, and )] TJ ET BT 26.250 391.393 Td /F1 9.8 Tf [(severity is correspondingly lower than our estimates. If the probability of detecting severe outcomes \(hospitalizations, deaths, )] TJ ET BT 26.250 379.488 Td /F1 9.8 Tf [(ICU\) is lower than our priors reflect, then there are more severe outcomes than our model infers, so severity is correspondingly )] TJ ET BT 26.250 367.584 Td /F1 9.8 Tf [(higher.)] TJ ET BT 26.250 348.179 Td /F1 9.8 Tf [(Finally, the small sample sizes in some age groups, the over-65 year olds in particular, lead to large uncertainty about the age-)] TJ ET BT 26.250 336.274 Td /F1 9.8 Tf [(specific estimates. This level of uncertainty is reflected in the wide 95% credible intervals for the estimates.)] TJ ET Q q 15.000 33.179 577.500 743.821 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Milwaukee for which the approach to reporting was relatively stable over time. One limitation is that Milwaukee changed its )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(guidance during our surveillance period from testing of all symptomatic cases to testing of all symptomatic health care workers )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(but only moderate to severe cases in non-health care workers. We believe that testing policies did not change dramatically )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(during this period, because the proportion of hospitalized case remained fairly constant; however, the sample size prior to this )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(change in guidance was small. Thus, our estimates should be seen as being the risk of severe outcome among persons with )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(symptoms, possibly biased somewhat toward those with more severe symptoms.)] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(Despite our efforts to account for sources of uncertainty, several others remain and have not been accounted for in our analysis. )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(First, we have assumed that for each level of severity \(from medically attended up to fatal\), case reporting was equal across age )] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(groups; for example, we assumed that medically attended cases were as likely to be reported for young children as for adults. It )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(is possible that this is not the case, for example that mild cases were more likely to come to medical attention if they occurred in )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(children than if they occurred in adults. If this were true, our conclusion that severity was higher in adults than children could be )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(partly a result of differential reporting.)] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(Second, the overall estimates of severity \(not stratified by age group\) reflect the age composition of cases in the sample we )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(studied, especially the age composition of the lowest level of severity examined, medically attended illness. Among medically )] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(attended cases in Milwaukee, 60% were in the 5-17 age group, the one in which severe outcomes were the least likely. A )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(preponderance of cases within this age group may be typical of the early part of influenza epidemics, and while it has been )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(argued that there is a shift from younger to older age groups in seasonal influenza [31] as the epidemic progresses, there is )] TJ ET BT 26.250 550.095 Td /F1 9.8 Tf [(evidence from at least the 1957 pandemic that attack rates remain higher in children than adults throughout the course of the )] TJ ET BT 26.250 538.191 Td /F1 9.8 Tf [(epidemic [2]. Since severity appears to be considerably higher in adults, then a shift in the burden of disease from children to )] TJ ET BT 26.250 526.286 Td /F1 9.8 Tf [(adults as the epidemic progresses would lead to an increase in average severity.)] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(We note that the association between age and severity may also affect observed trends in the characteristics of cases. The )] TJ ET BT 26.250 494.976 Td /F1 9.8 Tf [(World Health Organization has noted worldwide a shift from younger to older mean age among confirmed cases \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 483.072 Td /F1 9.8 Tf [(http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html)] TJ ET 0.271 0.267 0.267 rg BT 397.471 483.072 Td /F1 9.8 Tf [(\). If severity is lowest among children, this )] TJ ET BT 26.250 471.167 Td /F1 9.8 Tf [(upward shift in age distribution may partially reflect a shift toward detection of more severe cases, rather than a true shift in the )] TJ ET BT 26.250 459.262 Td /F1 9.8 Tf [(ages of those becoming infected.)] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(Third, the symptomatic case-fatality, case-ICU admission and case-hospitalization ratios are dependent upon our estimates of )] TJ ET BT 26.250 427.276 Td /F1 9.8 Tf [(the true number of symptomatic cases, )] TJ ET q 27.750 0 0 12.750 196.943 424.726 cm /I283 Do Q BT 224.693 427.276 Td /F1 9.8 Tf [( and hence are sensitive to the choice of prior for these, as well as to our prior )] TJ ET BT 26.250 415.203 Td /F1 9.8 Tf [(assumptions on the detection probabilities. In particular, if the probability that symptomatic cases seek medical attention and are )] TJ ET BT 26.250 403.298 Td /F1 9.8 Tf [(confirmed is lower than we assume in our prior distributions, then there are more cases than are inferred by our model, and )] TJ ET BT 26.250 391.393 Td /F1 9.8 Tf [(severity is correspondingly lower than our estimates. If the probability of detecting severe outcomes \(hospitalizations, deaths, )] TJ ET BT 26.250 379.488 Td /F1 9.8 Tf [(ICU\) is lower than our priors reflect, then there are more severe outcomes than our model infers, so severity is correspondingly )] TJ ET BT 26.250 367.584 Td /F1 9.8 Tf [(higher.)] TJ ET BT 26.250 348.179 Td /F1 9.8 Tf [(Finally, the small sample sizes in some age groups, the over-65 year olds in particular, lead to large uncertainty about the age-)] TJ ET BT 26.250 336.274 Td /F1 9.8 Tf [(specific estimates. This level of uncertainty is reflected in the wide 95% credible intervals for the estimates.)] 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 494 0 obj << /Type /Annot /Subtype /Link /A 495 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 482.1698 397.4715 492.0904 ] >> endobj 495 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html) >> endobj 496 0 obj << /Type /XObject /Subtype /Image /Width 37 /Height 17 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 37 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 349>> stream (c````R l@it.H91%*(.> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 23>> stream 8c``Q0 Fp endstream endobj 498 0 obj << /Type /Annot /Subtype /Link /A 499 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 482.1698 397.4715 492.0904 ] >> endobj 499 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html) >> endobj 500 0 obj << /Type /XObject /Subtype /Image /Width 37 /Height 17 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 37 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 349>> stream (c````R l@it.H91%*(.> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 23>> stream 8c``Q0 Fp endstream endobj 502 0 obj << /Type /Annot /Subtype /Link /A 503 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 482.1698 397.4715 492.0904 ] >> endobj 503 0 obj << /Type /Action /S /URI /URI (http://www.who.int/csr/disease/swineflu/notes/h1n1_situation_20090724/en/index.html) >> endobj 504 0 obj << /Type /XObject /Subtype /Image /Width 37 /Height 17 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 37 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 349>> stream (c````R l@it.H91%*(.> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 23>> stream 8c``Q0 Fp endstream endobj 506 0 obj << /Type /Page /Parent 3 0 R /Annots [ 508 0 R 510 0 R 512 0 R 514 0 R 516 0 R 518 0 R ] /Contents 507 0 R >> endobj 507 0 obj << /Length 23900 >> stream 0.271 0.267 0.267 rg q 15.000 32.715 577.500 744.285 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our two approaches yield estimates that differ by almost an order of magnitude in the severity of the infection, on each of the )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(three measures considered. How should planners evaluate these contrasting estimates? The lower estimates, using the )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(denominator of self-reported influenza-like illness in New York City, may reasonably be considered lower bounds on the true )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(ratios. Influenza-like illness is thought to be relatively rare in May-June, hence true influenza-like illness was probably largely )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(attributable to pH1N1 during this period in New York. However, self-reported ILI is notoriously prone to various biases, most of )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(which suggest that true rates are probably lower than self-reported rates. A previous telephone survey conducted in New York )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(City found that 18.5% of New Yorkers reported influenza-like illness in the 30 days prior to being surveyed in late March, 2003 )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [([32], which represented a period of above-baseline but declining influenza activity nationally and no known influenza outbreaks )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(in New York City [32]. The survey was repeated in October-November, 2003, prior to the appearance of significant influenza )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(activity, and 20.8% reported influenza-like illness in the 30 days prior [32]. If these surveys represent a baseline level of self-)] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(reported ILI in the absence of significant influenza activity, then the approximately 12% self-reported ILI in the telephone survey )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(is substantially lower than this out-of-season baseline, suggesting that it likely overstates the total burden if symptomatic pH1N1 )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(disease. The lower estimates are also broadly consistent with estimates from New Zealand, which has experienced a nearly )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(complete influenza season [8], and from Australia \()] TJ ET 0.267 0.267 0.267 rg BT 245.722 612.714 Td /F1 9.8 Tf [(http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-)] TJ ET BT 26.250 600.810 Td /F1 9.8 Tf [(ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf)] TJ ET 0.271 0.267 0.267 rg BT 214.288 600.810 Td /F1 9.8 Tf [(\). The higher estimates, on the other hand, were obtained using ratios of )] TJ ET BT 26.250 588.905 Td /F1 9.8 Tf [(hospitalizations to confirmed medically attended cases and self-reported rates of seeking medical attention for ILI, which have )] TJ ET BT 26.250 577.000 Td /F1 9.8 Tf [(been consistently measured in the range of about 40-60%. It is possible that the special efforts of the New York City health )] TJ ET BT 26.250 565.095 Td /F1 9.8 Tf [(department to identify pH1N1-related fatalities \(including those not hospitalized\) provides a fuller picture of the total number of )] TJ ET BT 26.250 553.191 Td /F1 9.8 Tf [(deaths from this infection. Interestingly, New York City reports about the same number of hospitalizations for our study period )] TJ ET BT 26.250 541.286 Td /F1 9.8 Tf [(\(996\) as New Zealand reports up to mid-August \(972\), but 3.5x as many deaths \(53 vs. 16\) [8]. If this discrepancy reflects more )] TJ ET BT 26.250 529.381 Td /F1 9.8 Tf [(complete ascertainment of deaths in New York City, it may account for much of the difference between our higher estimates of )] TJ ET BT 26.250 517.476 Td /F1 9.8 Tf [(case-fatality ratios and those from New Zealand. Given the number of uncertainties cataloged above \(which apply also to other )] TJ ET BT 26.250 505.572 Td /F1 9.8 Tf [(jurisdictions within and outside the USA\), we believe that our two approaches probably bracket the reasonable range of severity )] TJ ET BT 26.250 493.667 Td /F1 9.8 Tf [(for the US spring wave.)] TJ ET BT 26.250 474.262 Td /F1 9.8 Tf [(Age-specific severity patterns as estimated here are largely consistent with those one would obtain by simply comparing the )] TJ ET BT 26.250 462.357 Td /F1 9.8 Tf [(incidence of confirmed cases, hospitalizations, and deaths in the United States as a whole for a similar period [19], although the )] TJ ET BT 26.250 450.453 Td /F1 9.8 Tf [(estimates for persons over 65 are highly uncertain, with 95% credible intervals spanning several orders of magnitude, due to the )] TJ ET BT 26.250 438.548 Td /F1 9.8 Tf [(very small number of individuals in our sample from that age group.)] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(The estimates provided here may be compared to those for seasonal influenza. Compared to seasonal influenza, these )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(estimates \(assuming a 25% symptomatic attack rate\) suggest a number of deaths in the United States that could range from )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(about half the number estimated for an average year to nearly twice the number estimated for an average year [33] \(Approach )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(1\), or a range about 10-fold lower than that \(Approach 2\); however, the deaths would be expected to occur in younger age )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(groups, compared to the preponderance of deaths in persons over 65 in seasonal influenza. Such a shift in age distribution is )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(typical for pandemics and the years that follow them [22]. Under Approach 1, and assuming a typical pandemic symptomatic )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(attack rate of 25%, the estimated number of hospitalizations for an autumn-winter pandemic wave is considerably more than the )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(approximately 300,000 estimated for typical seasonal influenza [34], whereas Approach 2 suggests a number between 1/3 and )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(2/3 of that observed in typical seasonal influenza. It should be noted that most hospitalizations, and about 90% of deaths )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(attributed to seasonal influenza are categorized as respiratory and circulatory, not including the more specific diagnoses of )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(pneumonia and influenza; that is, they are due to myocardial infarction, stroke, and other proximate causes, but are nonetheless )] TJ ET BT 26.250 288.191 Td /F1 9.8 Tf [(likely caused initially by influenza infection [35]. The deaths included in this may have reflected more directly influenza-related )] TJ ET BT 26.250 276.286 Td /F1 9.8 Tf [(causes and may not reflect these indirect causes of influenza-related death. Indeed, it is unclear whether the proportion of )] TJ ET BT 26.250 264.381 Td /F1 9.8 Tf [(indirect respiratory and circulatory causes of death and hospitalization will be so high in this pandemic year, given the younger )] TJ ET BT 26.250 252.477 Td /F1 9.8 Tf [(ages involved in most severe cases. Given these differences between the estimates here based on virologically confirmed )] TJ ET BT 26.250 240.572 Td /F1 9.8 Tf [(deaths and the ecological statistical approach to estimating influenza-attributable deaths and hospitalizations for seasonal )] TJ ET BT 26.250 228.667 Td /F1 9.8 Tf [(influenza, it will be difficult to interpret comparisons between the two types of estimates until \(after the pandemic has passed\) )] TJ ET BT 26.250 216.762 Td /F1 9.8 Tf [(comparisons can be made between the ecological and the confirmed-case approach to estimating burden of hospitalization and )] TJ ET BT 26.250 204.858 Td /F1 9.8 Tf [(deaths.)] TJ ET Q q 15.000 32.715 577.500 744.285 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our two approaches yield estimates that differ by almost an order of magnitude in the severity of the infection, on each of the )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(three measures considered. How should planners evaluate these contrasting estimates? The lower estimates, using the )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(denominator of self-reported influenza-like illness in New York City, may reasonably be considered lower bounds on the true )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(ratios. Influenza-like illness is thought to be relatively rare in May-June, hence true influenza-like illness was probably largely )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(attributable to pH1N1 during this period in New York. However, self-reported ILI is notoriously prone to various biases, most of )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(which suggest that true rates are probably lower than self-reported rates. A previous telephone survey conducted in New York )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(City found that 18.5% of New Yorkers reported influenza-like illness in the 30 days prior to being surveyed in late March, 2003 )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [([32], which represented a period of above-baseline but declining influenza activity nationally and no known influenza outbreaks )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(in New York City [32]. The survey was repeated in October-November, 2003, prior to the appearance of significant influenza )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(activity, and 20.8% reported influenza-like illness in the 30 days prior [32]. If these surveys represent a baseline level of self-)] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(reported ILI in the absence of significant influenza activity, then the approximately 12% self-reported ILI in the telephone survey )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(is substantially lower than this out-of-season baseline, suggesting that it likely overstates the total burden if symptomatic pH1N1 )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(disease. The lower estimates are also broadly consistent with estimates from New Zealand, which has experienced a nearly )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(complete influenza season [8], and from Australia \()] TJ ET 0.267 0.267 0.267 rg BT 245.722 612.714 Td /F1 9.8 Tf [(http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-)] TJ ET BT 26.250 600.810 Td /F1 9.8 Tf [(ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf)] TJ ET 0.271 0.267 0.267 rg BT 214.288 600.810 Td /F1 9.8 Tf [(\). The higher estimates, on the other hand, were obtained using ratios of )] TJ ET BT 26.250 588.905 Td /F1 9.8 Tf [(hospitalizations to confirmed medically attended cases and self-reported rates of seeking medical attention for ILI, which have )] TJ ET BT 26.250 577.000 Td /F1 9.8 Tf [(been consistently measured in the range of about 40-60%. It is possible that the special efforts of the New York City health )] TJ ET BT 26.250 565.095 Td /F1 9.8 Tf [(department to identify pH1N1-related fatalities \(including those not hospitalized\) provides a fuller picture of the total number of )] TJ ET BT 26.250 553.191 Td /F1 9.8 Tf [(deaths from this infection. Interestingly, New York City reports about the same number of hospitalizations for our study period )] TJ ET BT 26.250 541.286 Td /F1 9.8 Tf [(\(996\) as New Zealand reports up to mid-August \(972\), but 3.5x as many deaths \(53 vs. 16\) [8]. If this discrepancy reflects more )] TJ ET BT 26.250 529.381 Td /F1 9.8 Tf [(complete ascertainment of deaths in New York City, it may account for much of the difference between our higher estimates of )] TJ ET BT 26.250 517.476 Td /F1 9.8 Tf [(case-fatality ratios and those from New Zealand. Given the number of uncertainties cataloged above \(which apply also to other )] TJ ET BT 26.250 505.572 Td /F1 9.8 Tf [(jurisdictions within and outside the USA\), we believe that our two approaches probably bracket the reasonable range of severity )] TJ ET BT 26.250 493.667 Td /F1 9.8 Tf [(for the US spring wave.)] TJ ET BT 26.250 474.262 Td /F1 9.8 Tf [(Age-specific severity patterns as estimated here are largely consistent with those one would obtain by simply comparing the )] TJ ET BT 26.250 462.357 Td /F1 9.8 Tf [(incidence of confirmed cases, hospitalizations, and deaths in the United States as a whole for a similar period [19], although the )] TJ ET BT 26.250 450.453 Td /F1 9.8 Tf [(estimates for persons over 65 are highly uncertain, with 95% credible intervals spanning several orders of magnitude, due to the )] TJ ET BT 26.250 438.548 Td /F1 9.8 Tf [(very small number of individuals in our sample from that age group.)] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(The estimates provided here may be compared to those for seasonal influenza. Compared to seasonal influenza, these )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(estimates \(assuming a 25% symptomatic attack rate\) suggest a number of deaths in the United States that could range from )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(about half the number estimated for an average year to nearly twice the number estimated for an average year [33] \(Approach )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(1\), or a range about 10-fold lower than that \(Approach 2\); however, the deaths would be expected to occur in younger age )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(groups, compared to the preponderance of deaths in persons over 65 in seasonal influenza. Such a shift in age distribution is )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(typical for pandemics and the years that follow them [22]. Under Approach 1, and assuming a typical pandemic symptomatic )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(attack rate of 25%, the estimated number of hospitalizations for an autumn-winter pandemic wave is considerably more than the )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(approximately 300,000 estimated for typical seasonal influenza [34], whereas Approach 2 suggests a number between 1/3 and )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(2/3 of that observed in typical seasonal influenza. It should be noted that most hospitalizations, and about 90% of deaths )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(attributed to seasonal influenza are categorized as respiratory and circulatory, not including the more specific diagnoses of )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(pneumonia and influenza; that is, they are due to myocardial infarction, stroke, and other proximate causes, but are nonetheless )] TJ ET BT 26.250 288.191 Td /F1 9.8 Tf [(likely caused initially by influenza infection [35]. The deaths included in this may have reflected more directly influenza-related )] TJ ET BT 26.250 276.286 Td /F1 9.8 Tf [(causes and may not reflect these indirect causes of influenza-related death. Indeed, it is unclear whether the proportion of )] TJ ET BT 26.250 264.381 Td /F1 9.8 Tf [(indirect respiratory and circulatory causes of death and hospitalization will be so high in this pandemic year, given the younger )] TJ ET BT 26.250 252.477 Td /F1 9.8 Tf [(ages involved in most severe cases. Given these differences between the estimates here based on virologically confirmed )] TJ ET BT 26.250 240.572 Td /F1 9.8 Tf [(deaths and the ecological statistical approach to estimating influenza-attributable deaths and hospitalizations for seasonal )] TJ ET BT 26.250 228.667 Td /F1 9.8 Tf [(influenza, it will be difficult to interpret comparisons between the two types of estimates until \(after the pandemic has passed\) )] TJ ET BT 26.250 216.762 Td /F1 9.8 Tf [(comparisons can be made between the ecological and the confirmed-case approach to estimating burden of hospitalization and )] TJ ET BT 26.250 204.858 Td /F1 9.8 Tf [(deaths.)] TJ ET Q q 15.000 32.715 577.500 744.285 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our two approaches yield estimates that differ by almost an order of magnitude in the severity of the infection, on each of the )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(three measures considered. How should planners evaluate these contrasting estimates? The lower estimates, using the )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(denominator of self-reported influenza-like illness in New York City, may reasonably be considered lower bounds on the true )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(ratios. Influenza-like illness is thought to be relatively rare in May-June, hence true influenza-like illness was probably largely )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(attributable to pH1N1 during this period in New York. However, self-reported ILI is notoriously prone to various biases, most of )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(which suggest that true rates are probably lower than self-reported rates. A previous telephone survey conducted in New York )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(City found that 18.5% of New Yorkers reported influenza-like illness in the 30 days prior to being surveyed in late March, 2003 )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [([32], which represented a period of above-baseline but declining influenza activity nationally and no known influenza outbreaks )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(in New York City [32]. The survey was repeated in October-November, 2003, prior to the appearance of significant influenza )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(activity, and 20.8% reported influenza-like illness in the 30 days prior [32]. If these surveys represent a baseline level of self-)] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(reported ILI in the absence of significant influenza activity, then the approximately 12% self-reported ILI in the telephone survey )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(is substantially lower than this out-of-season baseline, suggesting that it likely overstates the total burden if symptomatic pH1N1 )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(disease. The lower estimates are also broadly consistent with estimates from New Zealand, which has experienced a nearly )] TJ ET BT 26.250 612.714 Td /F1 9.8 Tf [(complete influenza season [8], and from Australia \()] TJ ET 0.267 0.267 0.267 rg BT 245.722 612.714 Td /F1 9.8 Tf [(http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-)] TJ ET BT 26.250 600.810 Td /F1 9.8 Tf [(ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf)] TJ ET 0.271 0.267 0.267 rg BT 214.288 600.810 Td /F1 9.8 Tf [(\). The higher estimates, on the other hand, were obtained using ratios of )] TJ ET BT 26.250 588.905 Td /F1 9.8 Tf [(hospitalizations to confirmed medically attended cases and self-reported rates of seeking medical attention for ILI, which have )] TJ ET BT 26.250 577.000 Td /F1 9.8 Tf [(been consistently measured in the range of about 40-60%. It is possible that the special efforts of the New York City health )] TJ ET BT 26.250 565.095 Td /F1 9.8 Tf [(department to identify pH1N1-related fatalities \(including those not hospitalized\) provides a fuller picture of the total number of )] TJ ET BT 26.250 553.191 Td /F1 9.8 Tf [(deaths from this infection. Interestingly, New York City reports about the same number of hospitalizations for our study period )] TJ ET BT 26.250 541.286 Td /F1 9.8 Tf [(\(996\) as New Zealand reports up to mid-August \(972\), but 3.5x as many deaths \(53 vs. 16\) [8]. If this discrepancy reflects more )] TJ ET BT 26.250 529.381 Td /F1 9.8 Tf [(complete ascertainment of deaths in New York City, it may account for much of the difference between our higher estimates of )] TJ ET BT 26.250 517.476 Td /F1 9.8 Tf [(case-fatality ratios and those from New Zealand. Given the number of uncertainties cataloged above \(which apply also to other )] TJ ET BT 26.250 505.572 Td /F1 9.8 Tf [(jurisdictions within and outside the USA\), we believe that our two approaches probably bracket the reasonable range of severity )] TJ ET BT 26.250 493.667 Td /F1 9.8 Tf [(for the US spring wave.)] TJ ET BT 26.250 474.262 Td /F1 9.8 Tf [(Age-specific severity patterns as estimated here are largely consistent with those one would obtain by simply comparing the )] TJ ET BT 26.250 462.357 Td /F1 9.8 Tf [(incidence of confirmed cases, hospitalizations, and deaths in the United States as a whole for a similar period [19], although the )] TJ ET BT 26.250 450.453 Td /F1 9.8 Tf [(estimates for persons over 65 are highly uncertain, with 95% credible intervals spanning several orders of magnitude, due to the )] TJ ET BT 26.250 438.548 Td /F1 9.8 Tf [(very small number of individuals in our sample from that age group.)] TJ ET BT 26.250 419.143 Td /F1 9.8 Tf [(The estimates provided here may be compared to those for seasonal influenza. Compared to seasonal influenza, these )] TJ ET BT 26.250 407.238 Td /F1 9.8 Tf [(estimates \(assuming a 25% symptomatic attack rate\) suggest a number of deaths in the United States that could range from )] TJ ET BT 26.250 395.334 Td /F1 9.8 Tf [(about half the number estimated for an average year to nearly twice the number estimated for an average year [33] \(Approach )] TJ ET BT 26.250 383.429 Td /F1 9.8 Tf [(1\), or a range about 10-fold lower than that \(Approach 2\); however, the deaths would be expected to occur in younger age )] TJ ET BT 26.250 371.524 Td /F1 9.8 Tf [(groups, compared to the preponderance of deaths in persons over 65 in seasonal influenza. Such a shift in age distribution is )] TJ ET BT 26.250 359.619 Td /F1 9.8 Tf [(typical for pandemics and the years that follow them [22]. Under Approach 1, and assuming a typical pandemic symptomatic )] TJ ET BT 26.250 347.715 Td /F1 9.8 Tf [(attack rate of 25%, the estimated number of hospitalizations for an autumn-winter pandemic wave is considerably more than the )] TJ ET BT 26.250 335.810 Td /F1 9.8 Tf [(approximately 300,000 estimated for typical seasonal influenza [34], whereas Approach 2 suggests a number between 1/3 and )] TJ ET BT 26.250 323.905 Td /F1 9.8 Tf [(2/3 of that observed in typical seasonal influenza. It should be noted that most hospitalizations, and about 90% of deaths )] TJ ET BT 26.250 312.000 Td /F1 9.8 Tf [(attributed to seasonal influenza are categorized as respiratory and circulatory, not including the more specific diagnoses of )] TJ ET BT 26.250 300.096 Td /F1 9.8 Tf [(pneumonia and influenza; that is, they are due to myocardial infarction, stroke, and other proximate causes, but are nonetheless )] TJ ET BT 26.250 288.191 Td /F1 9.8 Tf [(likely caused initially by influenza infection [35]. The deaths included in this may have reflected more directly influenza-related )] TJ ET BT 26.250 276.286 Td /F1 9.8 Tf [(causes and may not reflect these indirect causes of influenza-related death. Indeed, it is unclear whether the proportion of )] TJ ET BT 26.250 264.381 Td /F1 9.8 Tf [(indirect respiratory and circulatory causes of death and hospitalization will be so high in this pandemic year, given the younger )] TJ ET BT 26.250 252.477 Td /F1 9.8 Tf [(ages involved in most severe cases. Given these differences between the estimates here based on virologically confirmed )] TJ ET BT 26.250 240.572 Td /F1 9.8 Tf [(deaths and the ecological statistical approach to estimating influenza-attributable deaths and hospitalizations for seasonal )] TJ ET BT 26.250 228.667 Td /F1 9.8 Tf [(influenza, it will be difficult to interpret comparisons between the two types of estimates until \(after the pandemic has passed\) )] TJ ET BT 26.250 216.762 Td /F1 9.8 Tf [(comparisons can be made between the ecological and the confirmed-case approach to estimating burden of hospitalization and )] TJ ET BT 26.250 204.858 Td /F1 9.8 Tf [(deaths.)] 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 508 0 obj << /Type /Annot /Subtype /Link /A 509 0 R /Border [0 0 0] /H /I /Rect [ 245.7225 611.8126 563.8162 621.7332 ] >> endobj 509 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 510 0 obj << /Type /Annot /Subtype /Link /A 511 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 599.9078 214.2885 609.8284 ] >> endobj 511 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 512 0 obj << /Type /Annot /Subtype /Link /A 513 0 R /Border [0 0 0] /H /I /Rect [ 245.7225 611.8126 563.8162 621.7332 ] >> endobj 513 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 514 0 obj << /Type /Annot /Subtype /Link /A 515 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 599.9078 214.2885 609.8284 ] >> endobj 515 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 516 0 obj << /Type /Annot /Subtype /Link /A 517 0 R /Border [0 0 0] /H /I /Rect [ 245.7225 611.8126 563.8162 621.7332 ] >> endobj 517 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 518 0 obj << /Type /Annot /Subtype /Link /A 519 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 599.9078 214.2885 609.8284 ] >> endobj 519 0 obj << /Type /Action /S /URI /URI (http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm/$FILE/ozflu-no14-2009.pdf) >> endobj 520 0 obj << /Type /Page /Parent 3 0 R /Annots [ 522 0 R 524 0 R 526 0 R ] /Contents 521 0 R >> endobj 521 0 obj << /Length 22394 >> stream 0.271 0.267 0.267 rg q 15.000 51.735 577.500 725.265 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our estimate of the symptomatic case-fatality ratio is lower than those provided by Garske et al. [16], which ranges from 0.11% )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(to 1.47% overall, and between 0.59% and 0.78% in the US, but which was based on confirmed plus probable \(rather than )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic\) cases. Garske et al. do not account for differences in reporting by level of severity; when we ignore such )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(differences in our nave analysis, we get approximately a 2-fold increase in the estimated sCFR. This suggests that the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(differences in detection of mild and severe cases may have been greater in the data sets used by Garske et al. than in those we )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(have examined. Nishiura et al [36] estimate that between 0.16% and 4.48% of confirmed cases in the United States and Mexico )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were fatal. Wilson and Baker [37], on the other hand, use a denominator of infections \(rather than symptomatic or confirmed )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(cases\) and estimate a range of CFR from 0.0004% up to 0.6%. Our estimates fall in the middle part of this range. More recently, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(Baker et al. [8] used their estimates of the total incidence of symptomatic disease in New Zealand to estimate a sCFR of )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(0.005%, equal to the lower end of the credible interval for our Approach 2 estimate, and considerably below our Approach 1 )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(estimate. The generally downward trend in the estimates of severity reflects early ascertainment of more severe cases \(e.g., )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(mainly hospitalized cases in the early Mexican outbreak\); the issue of ascertainment and its potential biasing effect on severity )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(estimates has been discussed by each of these earlier reports.)] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(While we have been careful to highlight uncertainties in the estimates of severity, our results are sufficiently well-resolved to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(have important implications for ongoing pH1N1 pandemic planning. The estimated severity indicates that a reasonable )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(expectation for the autumn pandemic wave in the United States is a death toll less than or equal to that which is typical for )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seasonal influenza, though possibly with considerably more deaths in younger persons. If attack rates in the autumn match )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(those of prior pandemics and hospitalization rates are comparable to our estimates using Approach 1, the surge of ill individuals )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(and subsequent burden on hospitals and intensive care units could be large. However, using Approach 2, estimates of )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(hospitalizations and intensive care admissions are considerably lower. Either set of estimates places the epidemic within the )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(lowest category of severity considered in pandemic planning conducted prior to the appearance of pH1N1 in the United States, )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(which considered case-fatality ratios up to 0.1% \()] TJ ET 0.267 0.267 0.267 rg BT 238.127 509.976 Td /F1 9.8 Tf [(http://www.flu.gov/professional/community/community_mitigation.pdf)] TJ ET 0.271 0.267 0.267 rg BT 533.435 509.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(Continued close monitoring of severity of pandemic H1N1 disease is needed to assess how patterns of hospitalization, intensive )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(care utilization, and fatality are varying in space and time, and across age groups. Increases in severity might reflect changes in )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(the host population for example, infection of persons with conditions that predispose them to severe outcomes, or increased )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(severity might reflect changes in the age distribution of cases, for example a shift toward adults, in whom infection is more )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(severe. Changes in severity might also reflect changes in the virus or variation in the access and quality of care available to )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(infected persons.)] TJ ET BT 26.250 394.445 Td /F4 12.0 Tf [(Conflict of Interest)] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(ML has received consulting fees from the Avian/Pandemic Flu Registry \(Outcome Sciences\), sponsored in part by Roche. All )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(other authors declare no conflict of interest.)] TJ ET BT 26.250 325.984 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 306.030 Td /F1 9.8 Tf [(We thank Michael G. Baker for helpful discussions and Carolyn Bridges for useful comments on earlier drafts.)] TJ ET BT 26.250 276.927 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 249.473 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 249.473 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 237.568 Td /F1 9.8 Tf [(United States, April-July 2009. Submitted.)] TJ ET BT 26.250 218.163 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 218.163 Td /F1 9.8 Tf [(Jordan WS, Jr., Denny FW, Jr., Badger GF, Curtiss C, Dingle JH, et al. \(1958\) A study of illness in a group of Cleveland )] TJ ET BT 26.250 206.259 Td /F1 9.8 Tf [(families. XVII. The occurrence of Asian influenza. Am J Hyg 68: 190-212.)] TJ ET BT 26.250 186.854 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 186.854 Td /F1 9.8 Tf [(Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, et al. \(2006\) Strategies for mitigating an influenza pandemic. )] TJ ET BT 26.250 174.949 Td /F1 9.8 Tf [(Nature.)] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 155.544 Td /F1 9.8 Tf [(Halloran ME, Ferguson NM, Eubank S, Longini IM, Jr., Cummings DA, et al. \(2008\) Modeling targeted layered containment of )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(an influenza pandemic in the United States. Proc Natl Acad Sci U S A 105: 4639-4644.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Mills CE, Robins JM, Lipsitch M \(2004\) Transmissibility of 1918 pandemic influenza. Nature 432: 904-906.)] TJ ET BT 26.250 104.830 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 104.830 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 92.925 Td /F1 9.8 Tf [(minimize years of life lost. J Infect Dis 198: 305-311.)] TJ ET BT 26.250 73.521 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 73.521 Td /F1 9.8 Tf [(Andreasen V, Viboud C, Simonsen L \(2008\) Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 61.616 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis 197: 270-278.)] TJ ET Q q 15.000 51.735 577.500 725.265 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our estimate of the symptomatic case-fatality ratio is lower than those provided by Garske et al. [16], which ranges from 0.11% )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(to 1.47% overall, and between 0.59% and 0.78% in the US, but which was based on confirmed plus probable \(rather than )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic\) cases. Garske et al. do not account for differences in reporting by level of severity; when we ignore such )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(differences in our nave analysis, we get approximately a 2-fold increase in the estimated sCFR. This suggests that the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(differences in detection of mild and severe cases may have been greater in the data sets used by Garske et al. than in those we )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(have examined. Nishiura et al [36] estimate that between 0.16% and 4.48% of confirmed cases in the United States and Mexico )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were fatal. Wilson and Baker [37], on the other hand, use a denominator of infections \(rather than symptomatic or confirmed )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(cases\) and estimate a range of CFR from 0.0004% up to 0.6%. Our estimates fall in the middle part of this range. More recently, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(Baker et al. [8] used their estimates of the total incidence of symptomatic disease in New Zealand to estimate a sCFR of )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(0.005%, equal to the lower end of the credible interval for our Approach 2 estimate, and considerably below our Approach 1 )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(estimate. The generally downward trend in the estimates of severity reflects early ascertainment of more severe cases \(e.g., )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(mainly hospitalized cases in the early Mexican outbreak\); the issue of ascertainment and its potential biasing effect on severity )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(estimates has been discussed by each of these earlier reports.)] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(While we have been careful to highlight uncertainties in the estimates of severity, our results are sufficiently well-resolved to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(have important implications for ongoing pH1N1 pandemic planning. The estimated severity indicates that a reasonable )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(expectation for the autumn pandemic wave in the United States is a death toll less than or equal to that which is typical for )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seasonal influenza, though possibly with considerably more deaths in younger persons. If attack rates in the autumn match )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(those of prior pandemics and hospitalization rates are comparable to our estimates using Approach 1, the surge of ill individuals )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(and subsequent burden on hospitals and intensive care units could be large. However, using Approach 2, estimates of )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(hospitalizations and intensive care admissions are considerably lower. Either set of estimates places the epidemic within the )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(lowest category of severity considered in pandemic planning conducted prior to the appearance of pH1N1 in the United States, )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(which considered case-fatality ratios up to 0.1% \()] TJ ET 0.267 0.267 0.267 rg BT 238.127 509.976 Td /F1 9.8 Tf [(http://www.flu.gov/professional/community/community_mitigation.pdf)] TJ ET 0.271 0.267 0.267 rg BT 533.435 509.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(Continued close monitoring of severity of pandemic H1N1 disease is needed to assess how patterns of hospitalization, intensive )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(care utilization, and fatality are varying in space and time, and across age groups. Increases in severity might reflect changes in )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(the host population for example, infection of persons with conditions that predispose them to severe outcomes, or increased )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(severity might reflect changes in the age distribution of cases, for example a shift toward adults, in whom infection is more )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(severe. Changes in severity might also reflect changes in the virus or variation in the access and quality of care available to )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(infected persons.)] TJ ET BT 26.250 394.445 Td /F4 12.0 Tf [(Conflict of Interest)] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(ML has received consulting fees from the Avian/Pandemic Flu Registry \(Outcome Sciences\), sponsored in part by Roche. All )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(other authors declare no conflict of interest.)] TJ ET BT 26.250 325.984 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 306.030 Td /F1 9.8 Tf [(We thank Michael G. Baker for helpful discussions and Carolyn Bridges for useful comments on earlier drafts.)] TJ ET BT 26.250 276.927 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 249.473 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 249.473 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 237.568 Td /F1 9.8 Tf [(United States, April-July 2009. Submitted.)] TJ ET BT 26.250 218.163 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 218.163 Td /F1 9.8 Tf [(Jordan WS, Jr., Denny FW, Jr., Badger GF, Curtiss C, Dingle JH, et al. \(1958\) A study of illness in a group of Cleveland )] TJ ET BT 26.250 206.259 Td /F1 9.8 Tf [(families. XVII. The occurrence of Asian influenza. Am J Hyg 68: 190-212.)] TJ ET BT 26.250 186.854 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 186.854 Td /F1 9.8 Tf [(Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, et al. \(2006\) Strategies for mitigating an influenza pandemic. )] TJ ET BT 26.250 174.949 Td /F1 9.8 Tf [(Nature.)] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 155.544 Td /F1 9.8 Tf [(Halloran ME, Ferguson NM, Eubank S, Longini IM, Jr., Cummings DA, et al. \(2008\) Modeling targeted layered containment of )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(an influenza pandemic in the United States. Proc Natl Acad Sci U S A 105: 4639-4644.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Mills CE, Robins JM, Lipsitch M \(2004\) Transmissibility of 1918 pandemic influenza. Nature 432: 904-906.)] TJ ET BT 26.250 104.830 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 104.830 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 92.925 Td /F1 9.8 Tf [(minimize years of life lost. J Infect Dis 198: 305-311.)] TJ ET BT 26.250 73.521 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 73.521 Td /F1 9.8 Tf [(Andreasen V, Viboud C, Simonsen L \(2008\) Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 61.616 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis 197: 270-278.)] TJ ET Q q 15.000 51.735 577.500 725.265 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Our estimate of the symptomatic case-fatality ratio is lower than those provided by Garske et al. [16], which ranges from 0.11% )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(to 1.47% overall, and between 0.59% and 0.78% in the US, but which was based on confirmed plus probable \(rather than )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(symptomatic\) cases. Garske et al. do not account for differences in reporting by level of severity; when we ignore such )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(differences in our nave analysis, we get approximately a 2-fold increase in the estimated sCFR. This suggests that the )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(differences in detection of mild and severe cases may have been greater in the data sets used by Garske et al. than in those we )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(have examined. Nishiura et al [36] estimate that between 0.16% and 4.48% of confirmed cases in the United States and Mexico )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(were fatal. Wilson and Baker [37], on the other hand, use a denominator of infections \(rather than symptomatic or confirmed )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(cases\) and estimate a range of CFR from 0.0004% up to 0.6%. Our estimates fall in the middle part of this range. More recently, )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(Baker et al. [8] used their estimates of the total incidence of symptomatic disease in New Zealand to estimate a sCFR of )] TJ ET BT 26.250 660.333 Td /F1 9.8 Tf [(0.005%, equal to the lower end of the credible interval for our Approach 2 estimate, and considerably below our Approach 1 )] TJ ET BT 26.250 648.429 Td /F1 9.8 Tf [(estimate. The generally downward trend in the estimates of severity reflects early ascertainment of more severe cases \(e.g., )] TJ ET BT 26.250 636.524 Td /F1 9.8 Tf [(mainly hospitalized cases in the early Mexican outbreak\); the issue of ascertainment and its potential biasing effect on severity )] TJ ET BT 26.250 624.619 Td /F1 9.8 Tf [(estimates has been discussed by each of these earlier reports.)] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(While we have been careful to highlight uncertainties in the estimates of severity, our results are sufficiently well-resolved to )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(have important implications for ongoing pH1N1 pandemic planning. The estimated severity indicates that a reasonable )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(expectation for the autumn pandemic wave in the United States is a death toll less than or equal to that which is typical for )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(seasonal influenza, though possibly with considerably more deaths in younger persons. If attack rates in the autumn match )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(those of prior pandemics and hospitalization rates are comparable to our estimates using Approach 1, the surge of ill individuals )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(and subsequent burden on hospitals and intensive care units could be large. However, using Approach 2, estimates of )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(hospitalizations and intensive care admissions are considerably lower. Either set of estimates places the epidemic within the )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(lowest category of severity considered in pandemic planning conducted prior to the appearance of pH1N1 in the United States, )] TJ ET BT 26.250 509.976 Td /F1 9.8 Tf [(which considered case-fatality ratios up to 0.1% \()] TJ ET 0.267 0.267 0.267 rg BT 238.127 509.976 Td /F1 9.8 Tf [(http://www.flu.gov/professional/community/community_mitigation.pdf)] TJ ET 0.271 0.267 0.267 rg BT 533.435 509.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(Continued close monitoring of severity of pandemic H1N1 disease is needed to assess how patterns of hospitalization, intensive )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(care utilization, and fatality are varying in space and time, and across age groups. Increases in severity might reflect changes in )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(the host population for example, infection of persons with conditions that predispose them to severe outcomes, or increased )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(severity might reflect changes in the age distribution of cases, for example a shift toward adults, in whom infection is more )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(severe. Changes in severity might also reflect changes in the virus or variation in the access and quality of care available to )] TJ ET BT 26.250 431.048 Td /F1 9.8 Tf [(infected persons.)] TJ ET BT 26.250 394.445 Td /F4 12.0 Tf [(Conflict of Interest)] TJ ET BT 26.250 374.491 Td /F1 9.8 Tf [(ML has received consulting fees from the Avian/Pandemic Flu Registry \(Outcome Sciences\), sponsored in part by Roche. All )] TJ ET BT 26.250 362.586 Td /F1 9.8 Tf [(other authors declare no conflict of interest.)] TJ ET BT 26.250 325.984 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 306.030 Td /F1 9.8 Tf [(We thank Michael G. Baker for helpful discussions and Carolyn Bridges for useful comments on earlier drafts.)] TJ ET BT 26.250 276.927 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 249.473 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 249.473 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 237.568 Td /F1 9.8 Tf [(United States, April-July 2009. Submitted.)] TJ ET BT 26.250 218.163 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 218.163 Td /F1 9.8 Tf [(Jordan WS, Jr., Denny FW, Jr., Badger GF, Curtiss C, Dingle JH, et al. \(1958\) A study of illness in a group of Cleveland )] TJ ET BT 26.250 206.259 Td /F1 9.8 Tf [(families. XVII. The occurrence of Asian influenza. Am J Hyg 68: 190-212.)] TJ ET BT 26.250 186.854 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 186.854 Td /F1 9.8 Tf [(Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, et al. \(2006\) Strategies for mitigating an influenza pandemic. )] TJ ET BT 26.250 174.949 Td /F1 9.8 Tf [(Nature.)] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 155.544 Td /F1 9.8 Tf [(Halloran ME, Ferguson NM, Eubank S, Longini IM, Jr., Cummings DA, et al. \(2008\) Modeling targeted layered containment of )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(an influenza pandemic in the United States. Proc Natl Acad Sci U S A 105: 4639-4644.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Mills CE, Robins JM, Lipsitch M \(2004\) Transmissibility of 1918 pandemic influenza. Nature 432: 904-906.)] TJ ET BT 26.250 104.830 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 104.830 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 92.925 Td /F1 9.8 Tf [(minimize years of life lost. J Infect Dis 198: 305-311.)] TJ ET BT 26.250 73.521 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 73.521 Td /F1 9.8 Tf [(Andreasen V, Viboud C, Simonsen L \(2008\) Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 61.616 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis 197: 270-278.)] 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 522 0 obj << /Type /Annot /Subtype /Link /A 523 0 R /Border [0 0 0] /H /I /Rect [ 238.1273 509.0746 533.4352 518.9952 ] >> endobj 523 0 obj << /Type /Action /S /URI /URI (http://www.flu.gov/professional/community/community_mitigation.pdf) >> endobj 524 0 obj << /Type /Annot /Subtype /Link /A 525 0 R /Border [0 0 0] /H /I /Rect [ 238.1273 509.0746 533.4352 518.9952 ] >> endobj 525 0 obj << /Type /Action /S /URI /URI (http://www.flu.gov/professional/community/community_mitigation.pdf) >> endobj 526 0 obj << /Type /Annot /Subtype /Link /A 527 0 R /Border [0 0 0] /H /I /Rect [ 238.1273 509.0746 533.4352 518.9952 ] >> endobj 527 0 obj << /Type /Action /S /URI /URI (http://www.flu.gov/professional/community/community_mitigation.pdf) >> endobj 528 0 obj << /Type /Page /Parent 3 0 R /Contents 529 0 R >> endobj 529 0 obj << /Length 21956 >> stream 0.271 0.267 0.267 rg q 15.000 37.477 577.500 739.523 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Baker MG, Wilson N, Huang QS, Paine S, Lopez L, et al. \(2009\) Pandemic influenza A\(H1N1\)v in New Zealand: the )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(experience from April to August 2009. Euro Surveill 14.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 728.667 Td /F1 9.8 Tf [(Bita N \(2009\) No bed for swine flu man on life support. The Australian.)] TJ ET BT 26.250 709.262 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 709.262 Td /F1 9.8 Tf [(Newton K \(2009\) Swine flu puts hold on surgery The Dominion Post Wellington, NZ.)] TJ ET BT 26.250 689.857 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 689.857 Td /F1 9.8 Tf [(Lipsitch M, Hayden FG, Cowling BJ, Leung GM \(2009\) How to maintain surveillance for novel influenza A H1N1 when there )] TJ ET BT 26.250 677.952 Td /F1 9.8 Tf [(are too many cases to count. Lancet 374: 1209-1211.)] TJ ET BT 26.250 658.548 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 658.548 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) HIV in the United Kingdom: 2008 Report. www.hpa.org.uk/hivuk2008.)] TJ ET BT 26.250 639.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 639.143 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) Sexually transmitted infections and men who have sex with men in )] TJ ET BT 26.250 627.238 Td /F1 9.8 Tf [(the United Kingdom: 2008 report. www.hpa.org.uk/hivmsm2008.)] TJ ET BT 26.250 607.833 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 607.833 Td /F1 9.8 Tf [(Goubar A, Ades AE, De Angelis D, McGarrigle CA, Mercer CH, et al. \(2008\) Estimates of human immunodeficiency virus )] TJ ET BT 26.250 595.929 Td /F1 9.8 Tf [(prevalence and proportion diagnosed based on Bayesian multiparameter synthesis of surveillance data. Journal of the Royal )] TJ ET BT 26.250 584.024 Td /F1 9.8 Tf [(Statistical Society, Series A 171: 1-27.)] TJ ET BT 26.250 564.619 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 564.619 Td /F1 9.8 Tf [(Presanis AM, De Angelis D, Spiegelhalter DJ, Seaman S, Goubar A, et al. \(2008\) Conflicting evidence in a Bayesian )] TJ ET BT 26.250 552.714 Td /F1 9.8 Tf [(synthesis of surveillance data to estimate human immunodeficiency virus prevalence. . J R Stat Soc Series A - Stat Soc 171: )] TJ ET BT 26.250 540.810 Td /F1 9.8 Tf [(915-937.)] TJ ET BT 26.250 521.405 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 521.405 Td /F1 9.8 Tf [(Garske T, Legrand J, Donnelly CA, Ward H, Cauchemez S, et al. \(2009\) Assessing the severity of the novel influenza )] TJ ET BT 26.250 509.500 Td /F1 9.8 Tf [(A/H1N1 pandemic. BMJ 339: b2840.)] TJ ET BT 26.250 490.095 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 490.095 Td /F1 9.8 Tf [(Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, et al. \(2009\) Low sensitivity of rapid diagnostic test for influenza. )] TJ ET BT 26.250 478.191 Td /F1 9.8 Tf [(Clin Infect Dis 48: e89-92.)] TJ ET BT 26.250 458.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 458.786 Td /F1 9.8 Tf [(CDC \(2009\) Evaluation of rapid influenza diagnostic tests for detection of novel influenza A \(H1N1\) Virus - United States, )] TJ ET BT 26.250 446.881 Td /F1 9.8 Tf [(2009. MMWR Morb Mortal Wkly Rep 58: 826-829.)] TJ ET BT 26.250 427.476 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 427.476 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 415.572 Td /F1 9.8 Tf [(United States, April-July 2009. Emerg Infect Dis In press.)] TJ ET BT 26.250 396.167 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 396.167 Td /F1 9.8 Tf [(Thomas A, O'Hara B, Ligges U, Sturtz S \(2006\) Making BUGS Open. R News 6: 12-17.)] TJ ET BT 26.250 376.762 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 376.762 Td /F1 9.8 Tf [(Thompson WW, Weintraub E, Dhankhar P, Cheng PY, Brammer L, et al. \(2009\) Estimates of US influenza-associated )] TJ ET BT 26.250 364.857 Td /F1 9.8 Tf [(deaths made using four different methods. Influenza Other Respi Viruses 3: 37-49.)] TJ ET BT 26.250 345.453 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 345.453 Td /F1 9.8 Tf [(Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, et al. \(1998\) Pandemic versus epidemic influenza mortality: a )] TJ ET BT 26.250 333.548 Td /F1 9.8 Tf [(pattern of changing age distribution. J Infect Dis 178: 53-60.)] TJ ET BT 26.250 314.143 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 314.143 Td /F1 9.8 Tf [(Clarke SK, Heath RB, Sutton RN, Stuart-Harris CH \(1958\) Serological studies with Asian strain of influenza A. Lancet 1: )] TJ ET BT 26.250 302.238 Td /F1 9.8 Tf [(814-818.)] TJ ET BT 26.250 282.834 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 282.834 Td /F1 9.8 Tf [(Davis LE, Caldwell GG, Lynch RE, Bailey RE, Chin TD \(1970\) Hong Kong influenza: the epidemiologic features of a high )] TJ ET BT 26.250 270.929 Td /F1 9.8 Tf [(school family study analyzed and compared with a similar study during the 1957 Asian influenza epidemic. Am J Epidemiol 92: )] TJ ET BT 26.250 259.024 Td /F1 9.8 Tf [(240-247.)] TJ ET BT 26.250 239.619 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 239.619 Td /F1 9.8 Tf [(Foy HM, Cooney MK, Allan I \(1976\) Longitudinal studies of types A and B influenza among Seattle schoolchildren and )] TJ ET BT 26.250 227.715 Td /F1 9.8 Tf [(families, 1968-74. J Infect Dis 134: 362-369.)] TJ ET BT 26.250 208.310 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 208.310 Td /F1 9.8 Tf [(Boelle PY, Bernillon P, Desenclos JC \(2009\) A preliminary estimation of the reproduction ratio for new influenza A\(H1N1\) )] TJ ET BT 26.250 196.405 Td /F1 9.8 Tf [(from the outbreak in Mexico, March-April 2009. Euro Surveill 14.)] TJ ET BT 26.250 177.000 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 177.000 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 26.250 165.096 Td /F1 9.8 Tf [(influenza A \(H1N1\): early findings. Science 324: 1557-1561.)] TJ ET BT 26.250 145.691 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 145.691 Td /F1 9.8 Tf [(Nishiura H, Castillo-Chavez C, Safan M, Chowell G \(2009\) Transmission potential of the new influenza A\(H1N1\) virus and )] TJ ET BT 26.250 133.786 Td /F1 9.8 Tf [(its age-specificity in Japan. Euro Surveill 14.)] TJ ET BT 26.250 114.381 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 114.381 Td /F1 9.8 Tf [(White LF, Wallinga J, Finelli L, Reed C, Riley S, et al. \(2009\) Estimation of the reproductive number and the serial interval in )] TJ ET BT 26.250 102.477 Td /F1 9.8 Tf [(the current influenza A/H1N1 outbreak. Influenza and Other Respiratory Viruses Submitted.)] TJ ET BT 26.250 83.072 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 83.072 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 71.167 Td /F1 9.8 Tf [(\(H1N1\) 2009 virus in North America. Influenza Other Respi Viruses 3: 215-222.)] TJ ET BT 26.250 51.762 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 51.762 Td /F1 9.8 Tf [(Brownstein JS, Kleinman KP, Mandl KD \(2005\) Identifying pediatric age groups for influenza vaccination using a real-time )] TJ ET Q q 15.000 37.477 577.500 739.523 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Baker MG, Wilson N, Huang QS, Paine S, Lopez L, et al. \(2009\) Pandemic influenza A\(H1N1\)v in New Zealand: the )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(experience from April to August 2009. Euro Surveill 14.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 728.667 Td /F1 9.8 Tf [(Bita N \(2009\) No bed for swine flu man on life support. The Australian.)] TJ ET BT 26.250 709.262 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 709.262 Td /F1 9.8 Tf [(Newton K \(2009\) Swine flu puts hold on surgery The Dominion Post Wellington, NZ.)] TJ ET BT 26.250 689.857 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 689.857 Td /F1 9.8 Tf [(Lipsitch M, Hayden FG, Cowling BJ, Leung GM \(2009\) How to maintain surveillance for novel influenza A H1N1 when there )] TJ ET BT 26.250 677.952 Td /F1 9.8 Tf [(are too many cases to count. Lancet 374: 1209-1211.)] TJ ET BT 26.250 658.548 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 658.548 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) HIV in the United Kingdom: 2008 Report. www.hpa.org.uk/hivuk2008.)] TJ ET BT 26.250 639.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 639.143 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) Sexually transmitted infections and men who have sex with men in )] TJ ET BT 26.250 627.238 Td /F1 9.8 Tf [(the United Kingdom: 2008 report. www.hpa.org.uk/hivmsm2008.)] TJ ET BT 26.250 607.833 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 607.833 Td /F1 9.8 Tf [(Goubar A, Ades AE, De Angelis D, McGarrigle CA, Mercer CH, et al. \(2008\) Estimates of human immunodeficiency virus )] TJ ET BT 26.250 595.929 Td /F1 9.8 Tf [(prevalence and proportion diagnosed based on Bayesian multiparameter synthesis of surveillance data. Journal of the Royal )] TJ ET BT 26.250 584.024 Td /F1 9.8 Tf [(Statistical Society, Series A 171: 1-27.)] TJ ET BT 26.250 564.619 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 564.619 Td /F1 9.8 Tf [(Presanis AM, De Angelis D, Spiegelhalter DJ, Seaman S, Goubar A, et al. \(2008\) Conflicting evidence in a Bayesian )] TJ ET BT 26.250 552.714 Td /F1 9.8 Tf [(synthesis of surveillance data to estimate human immunodeficiency virus prevalence. . J R Stat Soc Series A - Stat Soc 171: )] TJ ET BT 26.250 540.810 Td /F1 9.8 Tf [(915-937.)] TJ ET BT 26.250 521.405 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 521.405 Td /F1 9.8 Tf [(Garske T, Legrand J, Donnelly CA, Ward H, Cauchemez S, et al. \(2009\) Assessing the severity of the novel influenza )] TJ ET BT 26.250 509.500 Td /F1 9.8 Tf [(A/H1N1 pandemic. BMJ 339: b2840.)] TJ ET BT 26.250 490.095 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 490.095 Td /F1 9.8 Tf [(Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, et al. \(2009\) Low sensitivity of rapid diagnostic test for influenza. )] TJ ET BT 26.250 478.191 Td /F1 9.8 Tf [(Clin Infect Dis 48: e89-92.)] TJ ET BT 26.250 458.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 458.786 Td /F1 9.8 Tf [(CDC \(2009\) Evaluation of rapid influenza diagnostic tests for detection of novel influenza A \(H1N1\) Virus - United States, )] TJ ET BT 26.250 446.881 Td /F1 9.8 Tf [(2009. MMWR Morb Mortal Wkly Rep 58: 826-829.)] TJ ET BT 26.250 427.476 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 427.476 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 415.572 Td /F1 9.8 Tf [(United States, April-July 2009. Emerg Infect Dis In press.)] TJ ET BT 26.250 396.167 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 396.167 Td /F1 9.8 Tf [(Thomas A, O'Hara B, Ligges U, Sturtz S \(2006\) Making BUGS Open. R News 6: 12-17.)] TJ ET BT 26.250 376.762 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 376.762 Td /F1 9.8 Tf [(Thompson WW, Weintraub E, Dhankhar P, Cheng PY, Brammer L, et al. \(2009\) Estimates of US influenza-associated )] TJ ET BT 26.250 364.857 Td /F1 9.8 Tf [(deaths made using four different methods. Influenza Other Respi Viruses 3: 37-49.)] TJ ET BT 26.250 345.453 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 345.453 Td /F1 9.8 Tf [(Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, et al. \(1998\) Pandemic versus epidemic influenza mortality: a )] TJ ET BT 26.250 333.548 Td /F1 9.8 Tf [(pattern of changing age distribution. J Infect Dis 178: 53-60.)] TJ ET BT 26.250 314.143 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 314.143 Td /F1 9.8 Tf [(Clarke SK, Heath RB, Sutton RN, Stuart-Harris CH \(1958\) Serological studies with Asian strain of influenza A. Lancet 1: )] TJ ET BT 26.250 302.238 Td /F1 9.8 Tf [(814-818.)] TJ ET BT 26.250 282.834 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 282.834 Td /F1 9.8 Tf [(Davis LE, Caldwell GG, Lynch RE, Bailey RE, Chin TD \(1970\) Hong Kong influenza: the epidemiologic features of a high )] TJ ET BT 26.250 270.929 Td /F1 9.8 Tf [(school family study analyzed and compared with a similar study during the 1957 Asian influenza epidemic. Am J Epidemiol 92: )] TJ ET BT 26.250 259.024 Td /F1 9.8 Tf [(240-247.)] TJ ET BT 26.250 239.619 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 239.619 Td /F1 9.8 Tf [(Foy HM, Cooney MK, Allan I \(1976\) Longitudinal studies of types A and B influenza among Seattle schoolchildren and )] TJ ET BT 26.250 227.715 Td /F1 9.8 Tf [(families, 1968-74. J Infect Dis 134: 362-369.)] TJ ET BT 26.250 208.310 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 208.310 Td /F1 9.8 Tf [(Boelle PY, Bernillon P, Desenclos JC \(2009\) A preliminary estimation of the reproduction ratio for new influenza A\(H1N1\) )] TJ ET BT 26.250 196.405 Td /F1 9.8 Tf [(from the outbreak in Mexico, March-April 2009. Euro Surveill 14.)] TJ ET BT 26.250 177.000 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 177.000 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 26.250 165.096 Td /F1 9.8 Tf [(influenza A \(H1N1\): early findings. Science 324: 1557-1561.)] TJ ET BT 26.250 145.691 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 145.691 Td /F1 9.8 Tf [(Nishiura H, Castillo-Chavez C, Safan M, Chowell G \(2009\) Transmission potential of the new influenza A\(H1N1\) virus and )] TJ ET BT 26.250 133.786 Td /F1 9.8 Tf [(its age-specificity in Japan. Euro Surveill 14.)] TJ ET BT 26.250 114.381 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 114.381 Td /F1 9.8 Tf [(White LF, Wallinga J, Finelli L, Reed C, Riley S, et al. \(2009\) Estimation of the reproductive number and the serial interval in )] TJ ET BT 26.250 102.477 Td /F1 9.8 Tf [(the current influenza A/H1N1 outbreak. Influenza and Other Respiratory Viruses Submitted.)] TJ ET BT 26.250 83.072 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 83.072 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 71.167 Td /F1 9.8 Tf [(\(H1N1\) 2009 virus in North America. Influenza Other Respi Viruses 3: 215-222.)] TJ ET BT 26.250 51.762 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 51.762 Td /F1 9.8 Tf [(Brownstein JS, Kleinman KP, Mandl KD \(2005\) Identifying pediatric age groups for influenza vaccination using a real-time )] TJ ET Q q 15.000 37.477 577.500 739.523 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Baker MG, Wilson N, Huang QS, Paine S, Lopez L, et al. \(2009\) Pandemic influenza A\(H1N1\)v in New Zealand: the )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(experience from April to August 2009. Euro Surveill 14.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 728.667 Td /F1 9.8 Tf [(Bita N \(2009\) No bed for swine flu man on life support. The Australian.)] TJ ET BT 26.250 709.262 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 709.262 Td /F1 9.8 Tf [(Newton K \(2009\) Swine flu puts hold on surgery The Dominion Post Wellington, NZ.)] TJ ET BT 26.250 689.857 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 689.857 Td /F1 9.8 Tf [(Lipsitch M, Hayden FG, Cowling BJ, Leung GM \(2009\) How to maintain surveillance for novel influenza A H1N1 when there )] TJ ET BT 26.250 677.952 Td /F1 9.8 Tf [(are too many cases to count. Lancet 374: 1209-1211.)] TJ ET BT 26.250 658.548 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 658.548 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) HIV in the United Kingdom: 2008 Report. www.hpa.org.uk/hivuk2008.)] TJ ET BT 26.250 639.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 639.143 Td /F1 9.8 Tf [(Health Protection Agency Centre for Infections \(2009\) Sexually transmitted infections and men who have sex with men in )] TJ ET BT 26.250 627.238 Td /F1 9.8 Tf [(the United Kingdom: 2008 report. www.hpa.org.uk/hivmsm2008.)] TJ ET BT 26.250 607.833 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 607.833 Td /F1 9.8 Tf [(Goubar A, Ades AE, De Angelis D, McGarrigle CA, Mercer CH, et al. \(2008\) Estimates of human immunodeficiency virus )] TJ ET BT 26.250 595.929 Td /F1 9.8 Tf [(prevalence and proportion diagnosed based on Bayesian multiparameter synthesis of surveillance data. Journal of the Royal )] TJ ET BT 26.250 584.024 Td /F1 9.8 Tf [(Statistical Society, Series A 171: 1-27.)] TJ ET BT 26.250 564.619 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 564.619 Td /F1 9.8 Tf [(Presanis AM, De Angelis D, Spiegelhalter DJ, Seaman S, Goubar A, et al. \(2008\) Conflicting evidence in a Bayesian )] TJ ET BT 26.250 552.714 Td /F1 9.8 Tf [(synthesis of surveillance data to estimate human immunodeficiency virus prevalence. . J R Stat Soc Series A - Stat Soc 171: )] TJ ET BT 26.250 540.810 Td /F1 9.8 Tf [(915-937.)] TJ ET BT 26.250 521.405 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 521.405 Td /F1 9.8 Tf [(Garske T, Legrand J, Donnelly CA, Ward H, Cauchemez S, et al. \(2009\) Assessing the severity of the novel influenza )] TJ ET BT 26.250 509.500 Td /F1 9.8 Tf [(A/H1N1 pandemic. BMJ 339: b2840.)] TJ ET BT 26.250 490.095 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 490.095 Td /F1 9.8 Tf [(Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, et al. \(2009\) Low sensitivity of rapid diagnostic test for influenza. )] TJ ET BT 26.250 478.191 Td /F1 9.8 Tf [(Clin Infect Dis 48: e89-92.)] TJ ET BT 26.250 458.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 458.786 Td /F1 9.8 Tf [(CDC \(2009\) Evaluation of rapid influenza diagnostic tests for detection of novel influenza A \(H1N1\) Virus - United States, )] TJ ET BT 26.250 446.881 Td /F1 9.8 Tf [(2009. MMWR Morb Mortal Wkly Rep 58: 826-829.)] TJ ET BT 26.250 427.476 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 427.476 Td /F1 9.8 Tf [(Reed C, Angulo F, Swerdlow D, Lipsitch M, Meltzer M, et al. \(2009\) Estimating the burden of pandemic influenza A/H1N1 -- )] TJ ET BT 26.250 415.572 Td /F1 9.8 Tf [(United States, April-July 2009. Emerg Infect Dis In press.)] TJ ET BT 26.250 396.167 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 396.167 Td /F1 9.8 Tf [(Thomas A, O'Hara B, Ligges U, Sturtz S \(2006\) Making BUGS Open. R News 6: 12-17.)] TJ ET BT 26.250 376.762 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 376.762 Td /F1 9.8 Tf [(Thompson WW, Weintraub E, Dhankhar P, Cheng PY, Brammer L, et al. \(2009\) Estimates of US influenza-associated )] TJ ET BT 26.250 364.857 Td /F1 9.8 Tf [(deaths made using four different methods. Influenza Other Respi Viruses 3: 37-49.)] TJ ET BT 26.250 345.453 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 345.453 Td /F1 9.8 Tf [(Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, et al. \(1998\) Pandemic versus epidemic influenza mortality: a )] TJ ET BT 26.250 333.548 Td /F1 9.8 Tf [(pattern of changing age distribution. J Infect Dis 178: 53-60.)] TJ ET BT 26.250 314.143 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 314.143 Td /F1 9.8 Tf [(Clarke SK, Heath RB, Sutton RN, Stuart-Harris CH \(1958\) Serological studies with Asian strain of influenza A. Lancet 1: )] TJ ET BT 26.250 302.238 Td /F1 9.8 Tf [(814-818.)] TJ ET BT 26.250 282.834 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 282.834 Td /F1 9.8 Tf [(Davis LE, Caldwell GG, Lynch RE, Bailey RE, Chin TD \(1970\) Hong Kong influenza: the epidemiologic features of a high )] TJ ET BT 26.250 270.929 Td /F1 9.8 Tf [(school family study analyzed and compared with a similar study during the 1957 Asian influenza epidemic. Am J Epidemiol 92: )] TJ ET BT 26.250 259.024 Td /F1 9.8 Tf [(240-247.)] TJ ET BT 26.250 239.619 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 239.619 Td /F1 9.8 Tf [(Foy HM, Cooney MK, Allan I \(1976\) Longitudinal studies of types A and B influenza among Seattle schoolchildren and )] TJ ET BT 26.250 227.715 Td /F1 9.8 Tf [(families, 1968-74. J Infect Dis 134: 362-369.)] TJ ET BT 26.250 208.310 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 208.310 Td /F1 9.8 Tf [(Boelle PY, Bernillon P, Desenclos JC \(2009\) A preliminary estimation of the reproduction ratio for new influenza A\(H1N1\) )] TJ ET BT 26.250 196.405 Td /F1 9.8 Tf [(from the outbreak in Mexico, March-April 2009. Euro Surveill 14.)] TJ ET BT 26.250 177.000 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 177.000 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 26.250 165.096 Td /F1 9.8 Tf [(influenza A \(H1N1\): early findings. Science 324: 1557-1561.)] TJ ET BT 26.250 145.691 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 145.691 Td /F1 9.8 Tf [(Nishiura H, Castillo-Chavez C, Safan M, Chowell G \(2009\) Transmission potential of the new influenza A\(H1N1\) virus and )] TJ ET BT 26.250 133.786 Td /F1 9.8 Tf [(its age-specificity in Japan. Euro Surveill 14.)] TJ ET BT 26.250 114.381 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 114.381 Td /F1 9.8 Tf [(White LF, Wallinga J, Finelli L, Reed C, Riley S, et al. \(2009\) Estimation of the reproductive number and the serial interval in )] TJ ET BT 26.250 102.477 Td /F1 9.8 Tf [(the current influenza A/H1N1 outbreak. Influenza and Other Respiratory Viruses Submitted.)] TJ ET BT 26.250 83.072 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 83.072 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 71.167 Td /F1 9.8 Tf [(\(H1N1\) 2009 virus in North America. Influenza Other Respi Viruses 3: 215-222.)] TJ ET BT 26.250 51.762 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 51.762 Td /F1 9.8 Tf [(Brownstein JS, Kleinman KP, Mandl KD \(2005\) Identifying pediatric age groups for influenza vaccination using a real-time )] 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 530 0 obj << /Type /Page /Parent 3 0 R /Contents 531 0 R >> endobj 531 0 obj << /Length 6302 >> stream 0.271 0.267 0.267 rg q 15.000 562.238 577.500 214.762 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(regional surveillance system. Am J Epidemiol 162: 686-693.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 748.071 Td /F1 9.8 Tf [(Metzger KB, Hajat A, Crawford M, Mostashari F \(2004\) How many illnesses does one emergency department visit )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(represent? Using a population-based telephone survey to estimate the syndromic multiplier. MMWR Morb Mortal Wkly Rep 53 )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(Suppl: 106-111.)] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(33.)] TJ ET BT 43.553 704.857 Td /F1 9.8 Tf [(Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, et al. \(2003\) Mortality associated with influenza and respiratory )] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(syncytial virus in the United States. JAMA 289: 179-186.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(34.)] TJ ET BT 43.553 673.548 Td /F1 9.8 Tf [(Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, et al. \(2004\) Influenza-associated hospitalizations in the )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(United States. JAMA 292: 1333-1340.)] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(35.)] TJ ET BT 43.553 642.238 Td /F1 9.8 Tf [(Reichert TA, Simonsen L, Sharma A, Pardo SA, Fedson DS, et al. \(2004\) Influenza and the winter increase in mortality in )] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(the United States, 1959-1999. Am J Epidemiol 160: 492-502.)] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(36.)] TJ ET BT 43.553 610.929 Td /F1 9.8 Tf [(Nishiura H, Klinkenberg D, Roberts M, Heesterbeek JA \(2009\) Early epidemiological assessment of the virulence of )] TJ ET BT 26.250 599.024 Td /F1 9.8 Tf [(emerging infectious diseases: a case study of an influenza pandemic. PLoS One 4: e6852.)] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(37.)] TJ ET BT 43.553 579.619 Td /F1 9.8 Tf [(Wilson N, Baker MG \(2009\) The emerging influenza pandemic: estimating the case fatality ratio. 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PLoS One 4: e6852.)] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(37.)] TJ ET BT 43.553 579.619 Td /F1 9.8 Tf [(Wilson N, Baker MG \(2009\) The emerging influenza pandemic: estimating the case fatality ratio. Euro Surveill 14.)] TJ ET Q q 15.000 562.238 577.500 214.762 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(regional surveillance system. Am J Epidemiol 162: 686-693.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 748.071 Td /F1 9.8 Tf [(Metzger KB, Hajat A, Crawford M, Mostashari F \(2004\) How many illnesses does one emergency department visit )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(represent? Using a population-based telephone survey to estimate the syndromic multiplier. 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Am J Epidemiol 160: 492-502.)] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(36.)] TJ ET BT 43.553 610.929 Td /F1 9.8 Tf [(Nishiura H, Klinkenberg D, Roberts M, Heesterbeek JA \(2009\) Early epidemiological assessment of the virulence of )] TJ ET BT 26.250 599.024 Td /F1 9.8 Tf [(emerging infectious diseases: a case study of an influenza pandemic. PLoS One 4: e6852.)] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(37.)] TJ ET BT 43.553 579.619 Td /F1 9.8 Tf [(Wilson N, Baker MG \(2009\) The emerging influenza pandemic: estimating the case fatality ratio. 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