%PDF-1.3 1 0 obj << /Type /Catalog /Outlines 2 0 R /Pages 3 0 R >> endobj 2 0 obj << /Type /Outlines /Count 0 >> endobj 3 0 obj << /Type /Pages /Kids [6 0 R 104 0 R 214 0 R 244 0 R 260 0 R 360 0 R 416 0 R 418 0 R ] /Count 8 /Resources << /ProcSet 4 0 R /Font << /F1 8 0 R /F2 9 0 R /F3 10 0 R /F4 11 0 R >> /XObject << /I1 12 0 R /I2 13 0 R /I3 218 0 R /I4 219 0 R /I5 222 0 R /I6 223 0 R /I7 226 0 R /I8 227 0 R /I9 230 0 R /I10 231 0 R /I11 234 0 R /I12 235 0 R /I13 238 0 R /I14 239 0 R /I15 240 0 R /I16 241 0 R /I17 242 0 R /I18 243 0 R /I19 248 0 R /I20 249 0 R /I21 252 0 R /I22 253 0 R /I23 256 0 R /I24 257 0 R /I25 258 0 R /I26 259 0 R /I27 264 0 R /I28 265 0 R /I29 296 0 R /I30 297 0 R /I31 328 0 R /I32 329 0 R /I33 358 0 R /I34 359 0 R >> >> /MediaBox [0.000 0.000 612.000 792.000] >> endobj 4 0 obj [/PDF /Text /ImageC ] endobj 5 0 obj << /Creator (DOMPDF) /CreationDate (D:20180721153931+00'00') /ModDate (D:20180721153931+00'00') /Title (Substantial Morbidity and Mortality Associated with Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity PLOS Currents Outbreaks) >> endobj 6 0 obj << /Type /Page /Parent 3 0 R /Annots [ 14 0 R 16 0 R 18 0 R 20 0 R 22 0 R 24 0 R 26 0 R 28 0 R 30 0 R 32 0 R 34 0 R 36 0 R 38 0 R 40 0 R 42 0 R 44 0 R 46 0 R 48 0 R 50 0 R 52 0 R 54 0 R 56 0 R 58 0 R 60 0 R 62 0 R 64 0 R 66 0 R 68 0 R 70 0 R 72 0 R 74 0 R 76 0 R 78 0 R 80 0 R 82 0 R 84 0 R 86 0 R 88 0 R 90 0 R 92 0 R 94 0 R 96 0 R 98 0 R 100 0 R 102 0 R ] /Contents 7 0 R >> endobj 7 0 obj << /Length 25802 >> stream q 375.000 0 0 39.000 222.000 738.000 cm /I2 Do Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Substantial Morbidity and Mortality Associated with Pandemic )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Shift and Severity)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(March 26, 2014)] TJ ET BT 82.431 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 87.306 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(Javier Dvila)] TJ ET 0.271 0.267 0.267 rg BT 82.049 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 87.470 638.299 Td /F1 9.8 Tf [(Gerardo Chowell)] TJ ET 0.271 0.267 0.267 rg BT 160.615 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 166.036 638.299 Td /F1 9.8 Tf [(Vctor H. Borja-Aburto)] TJ ET 0.271 0.267 0.267 rg BT 261.400 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 266.821 638.299 Td /F1 9.8 Tf [(Ccile Viboud)] TJ ET 0.271 0.267 0.267 rg BT 326.969 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 332.390 638.299 Td /F1 9.8 Tf [(Concepcin Grajales Muiz)] TJ ET 0.271 0.267 0.267 rg BT 451.594 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 457.015 638.299 Td /F1 9.8 Tf [(Mark Miller)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Dvila J, Chowell G, Borja-Aburto VH, Viboud C, Grajales Muiz C, Miller M. Substantial Morbidity and Mortality Associated )] TJ ET BT 560.491 626.394 Td /F1 9.8 Tf [(with )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity. PLOS Currents Outbreaks. 2014 )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(Mar 26 . Edition 1. doi: 10.1371/currents.outbreaks.a855a92f19db1d90ca955f5e908d6631.)] TJ ET q 15.000 30.177 577.500 570.027 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F4 9.8 Tf [(BACKGROUND:)] TJ ET BT 103.694 553.528 Td /F1 9.8 Tf [(A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(time.)] TJ ET BT 26.250 474.600 Td /F4 9.8 Tf [(METHODS:)] TJ ET BT 80.957 474.600 Td /F1 9.8 Tf [(We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection \(SARI\), )] TJ ET BT 26.250 462.695 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system )] TJ ET BT 26.250 450.790 Td /F1 9.8 Tf [(maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age )] TJ ET BT 26.250 438.885 Td /F1 9.8 Tf [(and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated )] TJ ET BT 26.250 426.981 Td /F1 9.8 Tf [(the reproduction number \(R\) based on the growth rate of daily case incidence by date of symptoms onset.)] TJ ET BT 26.250 407.576 Td /F4 9.8 Tf [(RESULTS:)] TJ ET BT 75.000 407.576 Td /F1 9.8 Tf [(A total of 7,886 SARI hospitalizations and 529 inpatient-deaths \(3.2%\) were reported between 01-October 2013 and )] TJ ET BT 26.250 395.671 Td /F1 9.8 Tf [(31-January 2014 \(resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed )] TJ ET BT 26.250 383.766 Td /F1 9.8 Tf [(A/H1N1-positive deaths per 100,000\). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during )] TJ ET BT 26.250 371.862 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y \(SD=20.3\) for )] TJ ET BT 26.250 359.957 Td /F1 9.8 Tf [(hospitalizations and 49.2 y \(SD=16.7\) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were )] TJ ET BT 26.250 348.052 Td /F1 9.8 Tf [(significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, )] TJ ET BT 26.250 336.147 Td /F1 9.8 Tf [(compared to the 2011-12 A/H1N1 epidemic \(Chi-square test, P<0.001\). The reproduction number of the winter 2013-14 wave in )] TJ ET BT 26.250 324.243 Td /F1 9.8 Tf [(central Mexico was estimated at 1.3-1.4 which is slightly higher than that reported for the 2011-2012 A/H1N1 epidemic.)] TJ ET BT 26.250 304.838 Td /F4 9.8 Tf [(CONCLUSIONS:)] TJ ET BT 104.250 304.838 Td /F1 9.8 Tf [(We have documented a substantial and ongoing increase in the number of A/H1N1-related hospitalizations )] TJ ET BT 26.250 292.933 Td /F1 9.8 Tf [(and deaths during the period October 2013-January 2014 and a proportionate shift of severe disease to middle aged adults, )] TJ ET BT 26.250 281.028 Td /F1 9.8 Tf [(relative to the preceding A/H1N1 2011-2012 epidemic in Mexico. In the absence of clear antigenic drift in globally circulating )] TJ ET BT 26.250 269.124 Td /F1 9.8 Tf [(A/H1N1 viruses in the post-pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in )] TJ ET BT 26.250 257.219 Td /F1 9.8 Tf [(Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.)] TJ ET BT 26.250 220.616 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 200.662 Td /F1 9.8 Tf [(IMSS was responsible for the influenza surveillance system and data gathering. This report was conducted in the context of the )] TJ ET BT 26.250 188.757 Td /F1 9.8 Tf [(MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international collaborative effort to understand influenza )] TJ ET BT 26.250 176.853 Td /F1 9.8 Tf [(epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health )] TJ ET BT 26.250 164.948 Td /F1 9.8 Tf [(\(http://www.origem.info/misms/index.php\). The MISMS study is funded by the International Influenza Unit, Office of Global )] TJ ET BT 26.250 153.043 Td /F1 9.8 Tf [(Health Affairs, Department of Health and Human Services. LS acknowledges support from the RAPIDD \(Research and Policy )] TJ ET BT 26.250 141.138 Td /F1 9.8 Tf [(for Infectious Disease Dynamics\) program of the Science and Technology Directorate, Department of Homeland Security, and )] TJ ET BT 26.250 129.234 Td /F1 9.8 Tf [(the Fogarty International Center.)] TJ ET BT 26.250 100.131 Td /F4 12.0 Tf [(INTRODUCTION)] TJ ET BT 26.250 80.177 Td /F1 9.8 Tf [(The resurgence of swine-origin pandemic A/H1N1 influenza virus in winter 2013-14 is causing substantial morbidity and )] TJ ET BT 26.250 68.272 Td /F1 9.8 Tf [(mortality in Mexico at the time of writing of this report. Mexico has experienced a series of three A/H1N1 pandemic waves in the )] TJ ET BT 26.250 56.367 Td /F1 9.8 Tf [(spring, summer, and fall of 2009 )] TJ ET 0.267 0.267 0.267 rg BT 168.230 57.875 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 173.048 60.256 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 175.458 57.875 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 180.276 56.367 Td /F1 9.8 Tf [(, and a recrudescent fourth wave in the winter of 2011-2012 )] TJ ET 0.267 0.267 0.267 rg BT 440.416 57.875 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 445.235 56.367 Td /F1 9.8 Tf [(. Mexico experienced )] TJ ET BT 26.250 44.463 Td /F1 9.8 Tf [(particularly high excess mortality associated with pandemic A/H1N1 influenza in 2009, relative to other countries )] TJ ET 0.267 0.267 0.267 rg BT 512.317 45.970 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 517.135 48.351 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 519.545 45.970 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 524.363 44.463 Td /F1 9.8 Tf [(. In contrast, )] TJ ET Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Substantial Morbidity and Mortality Associated with Pandemic )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Shift and Severity)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(March 26, 2014)] TJ ET BT 82.431 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 87.306 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(Javier Dvila)] TJ ET 0.271 0.267 0.267 rg BT 82.049 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 87.470 638.299 Td /F1 9.8 Tf [(Gerardo Chowell)] TJ ET 0.271 0.267 0.267 rg BT 160.615 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 166.036 638.299 Td /F1 9.8 Tf [(Vctor H. Borja-Aburto)] TJ ET 0.271 0.267 0.267 rg BT 261.400 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 266.821 638.299 Td /F1 9.8 Tf [(Ccile Viboud)] TJ ET 0.271 0.267 0.267 rg BT 326.969 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 332.390 638.299 Td /F1 9.8 Tf [(Concepcin Grajales Muiz)] TJ ET 0.271 0.267 0.267 rg BT 451.594 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 457.015 638.299 Td /F1 9.8 Tf [(Mark Miller)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Dvila J, Chowell G, Borja-Aburto VH, Viboud C, Grajales Muiz C, Miller M. Substantial Morbidity and Mortality Associated )] TJ ET BT 560.491 626.394 Td /F1 9.8 Tf [(with )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity. PLOS Currents Outbreaks. 2014 )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(Mar 26 . Edition 1. doi: 10.1371/currents.outbreaks.a855a92f19db1d90ca955f5e908d6631.)] TJ ET q 15.000 30.177 577.500 570.027 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F4 9.8 Tf [(BACKGROUND:)] TJ ET BT 103.694 553.528 Td /F1 9.8 Tf [(A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(time.)] TJ ET BT 26.250 474.600 Td /F4 9.8 Tf [(METHODS:)] TJ ET BT 80.957 474.600 Td /F1 9.8 Tf [(We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection \(SARI\), )] TJ ET BT 26.250 462.695 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system )] TJ ET BT 26.250 450.790 Td /F1 9.8 Tf [(maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age )] TJ ET BT 26.250 438.885 Td /F1 9.8 Tf [(and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated )] TJ ET BT 26.250 426.981 Td /F1 9.8 Tf [(the reproduction number \(R\) based on the growth rate of daily case incidence by date of symptoms onset.)] TJ ET BT 26.250 407.576 Td /F4 9.8 Tf [(RESULTS:)] TJ ET BT 75.000 407.576 Td /F1 9.8 Tf [(A total of 7,886 SARI hospitalizations and 529 inpatient-deaths \(3.2%\) were reported between 01-October 2013 and )] TJ ET BT 26.250 395.671 Td /F1 9.8 Tf [(31-January 2014 \(resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed )] TJ ET BT 26.250 383.766 Td /F1 9.8 Tf [(A/H1N1-positive deaths per 100,000\). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during )] TJ ET BT 26.250 371.862 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y \(SD=20.3\) for )] TJ ET BT 26.250 359.957 Td /F1 9.8 Tf [(hospitalizations and 49.2 y \(SD=16.7\) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were )] TJ ET BT 26.250 348.052 Td /F1 9.8 Tf [(significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, )] TJ ET BT 26.250 336.147 Td /F1 9.8 Tf [(compared to the 2011-12 A/H1N1 epidemic \(Chi-square test, P<0.001\). The reproduction number of the winter 2013-14 wave in )] TJ ET BT 26.250 324.243 Td /F1 9.8 Tf [(central Mexico was estimated at 1.3-1.4 which is slightly higher than that reported for the 2011-2012 A/H1N1 epidemic.)] TJ ET BT 26.250 304.838 Td /F4 9.8 Tf [(CONCLUSIONS:)] TJ ET BT 104.250 304.838 Td /F1 9.8 Tf [(We have documented a substantial and ongoing increase in the number of A/H1N1-related hospitalizations )] TJ ET BT 26.250 292.933 Td /F1 9.8 Tf [(and deaths during the period October 2013-January 2014 and a proportionate shift of severe disease to middle aged adults, )] TJ ET BT 26.250 281.028 Td /F1 9.8 Tf [(relative to the preceding A/H1N1 2011-2012 epidemic in Mexico. In the absence of clear antigenic drift in globally circulating )] TJ ET BT 26.250 269.124 Td /F1 9.8 Tf [(A/H1N1 viruses in the post-pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in )] TJ ET BT 26.250 257.219 Td /F1 9.8 Tf [(Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.)] TJ ET BT 26.250 220.616 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 200.662 Td /F1 9.8 Tf [(IMSS was responsible for the influenza surveillance system and data gathering. This report was conducted in the context of the )] TJ ET BT 26.250 188.757 Td /F1 9.8 Tf [(MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international collaborative effort to understand influenza )] TJ ET BT 26.250 176.853 Td /F1 9.8 Tf [(epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health )] TJ ET BT 26.250 164.948 Td /F1 9.8 Tf [(\(http://www.origem.info/misms/index.php\). The MISMS study is funded by the International Influenza Unit, Office of Global )] TJ ET BT 26.250 153.043 Td /F1 9.8 Tf [(Health Affairs, Department of Health and Human Services. LS acknowledges support from the RAPIDD \(Research and Policy )] TJ ET BT 26.250 141.138 Td /F1 9.8 Tf [(for Infectious Disease Dynamics\) program of the Science and Technology Directorate, Department of Homeland Security, and )] TJ ET BT 26.250 129.234 Td /F1 9.8 Tf [(the Fogarty International Center.)] TJ ET BT 26.250 100.131 Td /F4 12.0 Tf [(INTRODUCTION)] TJ ET BT 26.250 80.177 Td /F1 9.8 Tf [(The resurgence of swine-origin pandemic A/H1N1 influenza virus in winter 2013-14 is causing substantial morbidity and )] TJ ET BT 26.250 68.272 Td /F1 9.8 Tf [(mortality in Mexico at the time of writing of this report. Mexico has experienced a series of three A/H1N1 pandemic waves in the )] TJ ET BT 26.250 56.367 Td /F1 9.8 Tf [(spring, summer, and fall of 2009 )] TJ ET 0.267 0.267 0.267 rg BT 168.230 57.875 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 173.048 60.256 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 175.458 57.875 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 180.276 56.367 Td /F1 9.8 Tf [(, and a recrudescent fourth wave in the winter of 2011-2012 )] TJ ET 0.267 0.267 0.267 rg BT 440.416 57.875 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 445.235 56.367 Td /F1 9.8 Tf [(. Mexico experienced )] TJ ET BT 26.250 44.463 Td /F1 9.8 Tf [(particularly high excess mortality associated with pandemic A/H1N1 influenza in 2009, relative to other countries )] TJ ET 0.267 0.267 0.267 rg BT 512.317 45.970 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 517.135 48.351 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 519.545 45.970 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 524.363 44.463 Td /F1 9.8 Tf [(. In contrast, )] TJ ET Q q 15.000 659.406 577.500 78.594 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(Substantial Morbidity and Mortality Associated with Pandemic )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age )] TJ ET BT 15.000 668.146 Td /F2 21.0 Tf [(Shift and Severity)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 650.140 Td /F3 9.8 Tf [(March 26, 2014)] TJ ET BT 82.431 650.140 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 87.306 650.140 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 638.299 Td /F1 9.8 Tf [(Javier Dvila)] TJ ET 0.271 0.267 0.267 rg BT 82.049 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 87.470 638.299 Td /F1 9.8 Tf [(Gerardo Chowell)] TJ ET 0.271 0.267 0.267 rg BT 160.615 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 166.036 638.299 Td /F1 9.8 Tf [(Vctor H. Borja-Aburto)] TJ ET 0.271 0.267 0.267 rg BT 261.400 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 266.821 638.299 Td /F1 9.8 Tf [(Ccile Viboud)] TJ ET 0.271 0.267 0.267 rg BT 326.969 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 332.390 638.299 Td /F1 9.8 Tf [(Concepcin Grajales Muiz)] TJ ET 0.271 0.267 0.267 rg BT 451.594 638.299 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 457.015 638.299 Td /F1 9.8 Tf [(Mark Miller)] TJ ET 0.271 0.267 0.267 rg BT 26.250 626.394 Td /F1 9.8 Tf [(Dvila J, Chowell G, Borja-Aburto VH, Viboud C, Grajales Muiz C, Miller M. Substantial Morbidity and Mortality Associated )] TJ ET BT 560.491 626.394 Td /F1 9.8 Tf [(with )] TJ ET BT 26.250 614.490 Td /F1 9.8 Tf [(Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity. PLOS Currents Outbreaks. 2014 )] TJ ET BT 26.250 602.585 Td /F1 9.8 Tf [(Mar 26 . Edition 1. doi: 10.1371/currents.outbreaks.a855a92f19db1d90ca955f5e908d6631.)] TJ ET q 15.000 30.177 577.500 570.027 re W n 0.271 0.267 0.267 rg BT 26.250 573.482 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 553.528 Td /F4 9.8 Tf [(BACKGROUND:)] TJ ET BT 103.694 553.528 Td /F1 9.8 Tf [(A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild )] TJ ET BT 26.250 541.623 Td /F1 9.8 Tf [(2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, )] TJ ET BT 26.250 529.719 Td /F1 9.8 Tf [(summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older )] TJ ET BT 26.250 517.814 Td /F1 9.8 Tf [(ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons )] TJ ET BT 26.250 505.909 Td /F1 9.8 Tf [(dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real )] TJ ET BT 26.250 494.004 Td /F1 9.8 Tf [(time.)] TJ ET BT 26.250 474.600 Td /F4 9.8 Tf [(METHODS:)] TJ ET BT 80.957 474.600 Td /F1 9.8 Tf [(We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection \(SARI\), )] TJ ET BT 26.250 462.695 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system )] TJ ET BT 26.250 450.790 Td /F1 9.8 Tf [(maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age )] TJ ET BT 26.250 438.885 Td /F1 9.8 Tf [(and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated )] TJ ET BT 26.250 426.981 Td /F1 9.8 Tf [(the reproduction number \(R\) based on the growth rate of daily case incidence by date of symptoms onset.)] TJ ET BT 26.250 407.576 Td /F4 9.8 Tf [(RESULTS:)] TJ ET BT 75.000 407.576 Td /F1 9.8 Tf [(A total of 7,886 SARI hospitalizations and 529 inpatient-deaths \(3.2%\) were reported between 01-October 2013 and )] TJ ET BT 26.250 395.671 Td /F1 9.8 Tf [(31-January 2014 \(resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed )] TJ ET BT 26.250 383.766 Td /F1 9.8 Tf [(A/H1N1-positive deaths per 100,000\). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during )] TJ ET BT 26.250 371.862 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y \(SD=20.3\) for )] TJ ET BT 26.250 359.957 Td /F1 9.8 Tf [(hospitalizations and 49.2 y \(SD=16.7\) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were )] TJ ET BT 26.250 348.052 Td /F1 9.8 Tf [(significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, )] TJ ET BT 26.250 336.147 Td /F1 9.8 Tf [(compared to the 2011-12 A/H1N1 epidemic \(Chi-square test, P<0.001\). The reproduction number of the winter 2013-14 wave in )] TJ ET BT 26.250 324.243 Td /F1 9.8 Tf [(central Mexico was estimated at 1.3-1.4 which is slightly higher than that reported for the 2011-2012 A/H1N1 epidemic.)] TJ ET BT 26.250 304.838 Td /F4 9.8 Tf [(CONCLUSIONS:)] TJ ET BT 104.250 304.838 Td /F1 9.8 Tf [(We have documented a substantial and ongoing increase in the number of A/H1N1-related hospitalizations )] TJ ET BT 26.250 292.933 Td /F1 9.8 Tf [(and deaths during the period October 2013-January 2014 and a proportionate shift of severe disease to middle aged adults, )] TJ ET BT 26.250 281.028 Td /F1 9.8 Tf [(relative to the preceding A/H1N1 2011-2012 epidemic in Mexico. In the absence of clear antigenic drift in globally circulating )] TJ ET BT 26.250 269.124 Td /F1 9.8 Tf [(A/H1N1 viruses in the post-pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in )] TJ ET BT 26.250 257.219 Td /F1 9.8 Tf [(Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.)] TJ ET BT 26.250 220.616 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 200.662 Td /F1 9.8 Tf [(IMSS was responsible for the influenza surveillance system and data gathering. This report was conducted in the context of the )] TJ ET BT 26.250 188.757 Td /F1 9.8 Tf [(MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international collaborative effort to understand influenza )] TJ ET BT 26.250 176.853 Td /F1 9.8 Tf [(epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health )] TJ ET BT 26.250 164.948 Td /F1 9.8 Tf [(\(http://www.origem.info/misms/index.php\). The MISMS study is funded by the International Influenza Unit, Office of Global )] TJ ET BT 26.250 153.043 Td /F1 9.8 Tf [(Health Affairs, Department of Health and Human Services. LS acknowledges support from the RAPIDD \(Research and Policy )] TJ ET BT 26.250 141.138 Td /F1 9.8 Tf [(for Infectious Disease Dynamics\) program of the Science and Technology Directorate, Department of Homeland Security, and )] TJ ET BT 26.250 129.234 Td /F1 9.8 Tf [(the Fogarty International Center.)] TJ ET BT 26.250 100.131 Td /F4 12.0 Tf [(INTRODUCTION)] TJ ET BT 26.250 80.177 Td /F1 9.8 Tf [(The resurgence of swine-origin pandemic A/H1N1 influenza virus in winter 2013-14 is causing substantial morbidity and )] TJ ET BT 26.250 68.272 Td /F1 9.8 Tf [(mortality in Mexico at the time of writing of this report. Mexico has experienced a series of three A/H1N1 pandemic waves in the )] TJ ET BT 26.250 56.367 Td /F1 9.8 Tf [(spring, summer, and fall of 2009 )] TJ ET 0.267 0.267 0.267 rg BT 168.230 57.875 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 173.048 60.256 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 175.458 57.875 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 180.276 56.367 Td /F1 9.8 Tf [(, and a recrudescent fourth wave in the winter of 2011-2012 )] TJ ET 0.267 0.267 0.267 rg BT 440.416 57.875 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 445.235 56.367 Td /F1 9.8 Tf [(. Mexico experienced )] TJ ET BT 26.250 44.463 Td /F1 9.8 Tf [(particularly high excess mortality associated with pandemic A/H1N1 influenza in 2009, relative to other countries )] TJ ET 0.267 0.267 0.267 rg BT 512.317 45.970 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 517.135 48.351 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 519.545 45.970 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 524.363 44.463 Td /F1 9.8 Tf [(. 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>> endobj 96 0 obj << /Type /Annot /Subtype /Link /A 97 0 R /Border [0 0 0] /H /I /Rect [ 175.4575 57.0729 180.2762 65.8913 ] >> endobj 97 0 obj << /Type /Action >> endobj 98 0 obj << /Type /Annot /Subtype /Link /A 99 0 R /Border [0 0 0] /H /I /Rect [ 440.4159 57.0729 445.2346 65.8913 ] >> endobj 99 0 obj << /Type /Action >> endobj 100 0 obj << /Type /Annot /Subtype /Link /A 101 0 R /Border [0 0 0] /H /I /Rect [ 512.3167 45.1682 517.1354 53.9865 ] >> endobj 101 0 obj << /Type /Action >> endobj 102 0 obj << /Type /Annot /Subtype /Link /A 103 0 R /Border [0 0 0] /H /I /Rect [ 519.5448 45.1682 524.3634 53.9865 ] >> endobj 103 0 obj << /Type /Action >> endobj 104 0 obj << /Type /Page /Parent 3 0 R /Annots [ 106 0 R 108 0 R 110 0 R 112 0 R 114 0 R 116 0 R 118 0 R 120 0 R 122 0 R 124 0 R 126 0 R 128 0 R 130 0 R 132 0 R 134 0 R 136 0 R 138 0 R 140 0 R 142 0 R 144 0 R 146 0 R 148 0 R 150 0 R 152 0 R 154 0 R 156 0 R 158 0 R 160 0 R 162 0 R 164 0 R 166 0 R 168 0 R 170 0 R 172 0 R 174 0 R 176 0 R 178 0 R 180 0 R 182 0 R 184 0 R 186 0 R 188 0 R 190 0 R 192 0 R 194 0 R 196 0 R 198 0 R 200 0 R 202 0 R 204 0 R 206 0 R 208 0 R 210 0 R 212 0 R ] /Contents 105 0 R >> endobj 105 0 obj << /Length 28477 >> stream 0.271 0.267 0.267 rg q 15.000 30.673 577.500 746.327 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(the 2012-13 influenza season was mild and dominated by the A/H3N2 virus.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Here we report preliminary findings on the epidemiology of the on-going A/H1N1 outbreak in Mexico from October 2013 to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(January 2014. Because past influenza pandemics have had substantial morbidity and mortality burden for several seasons after )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(the initial pandemic waves )] TJ ET 0.267 0.267 0.267 rg BT 142.753 725.769 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 147.571 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 149.981 725.769 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 154.799 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 157.209 725.769 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 162.027 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 164.437 725.769 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 169.255 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 171.665 725.769 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 181.302 724.262 Td /F1 9.8 Tf [(, continued vigilance is prudent. We compare the demographic and clinical characteristics of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 hospitalizations and deaths in winter 2013-14 with those reported for the preceding 2011-12 )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(A/H1N1 epidemic. Our data highlight a change in the age distribution of A/H1N1 patients and a slightly higher reproduction )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(number compared to the 2011-12 A/H1N1 outbreak.)] TJ ET BT 26.250 651.945 Td /F4 12.0 Tf [(MATERIALS AND METHODS)] TJ ET BT 26.250 631.991 Td /F4 9.8 Tf [(Epidemiological Data)] TJ ET BT 26.250 612.586 Td /F1 9.8 Tf [(Individual level hospitalization data were available from a prospective influenza surveillance system that was initiated especially )] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(for the 2009 pandemic by the Mexican Institute for Social Security \(IMSS\) )] TJ ET 0.267 0.267 0.267 rg BT 345.426 602.189 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 350.245 604.570 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 352.654 602.189 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 362.291 600.681 Td /F1 9.8 Tf [(. IMSS is a tripartite Mexican health system )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(covering approximately 40% of the Mexican population comprising workers in the private sector and their families, relying on a )] TJ ET BT 26.250 576.872 Td /F1 9.8 Tf [(network of 1,099 primary health-care units and 259 hospitals nationwide. The age and gender distributions of persons affiliated )] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(to the IMSS medical system are representative of the general Mexican population )] TJ ET 0.267 0.267 0.267 rg BT 380.116 566.474 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 384.935 564.967 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 545.562 Td /F1 9.8 Tf [(We analyzed all patients admitted to the hospital for > 24 hrs with a diagnosis of severe acute respiratory infection \(SARI\) )] TJ ET BT 26.250 533.658 Td /F1 9.8 Tf [(during October 2013 to January 2014. SARI was defined as the presence of respiratory difficulty with fever >38C and cough, )] TJ ET BT 26.250 521.753 Td /F1 9.8 Tf [(together with one or more of the following clinical symptoms: confinement to bed, thoracic pain, polypnea, or acute respiratory )] TJ ET BT 26.250 509.848 Td /F1 9.8 Tf [(distress syndrome. Children <5 years with pneumonia or severe pneumonia that required hospitalization were also considered )] TJ ET BT 26.250 497.943 Td /F1 9.8 Tf [(as SARI cases. Respiratory swabs were obtained for about 52% of SARI hospitalizations \(SARI\) in winter 2013-14 and were )] TJ ET BT 26.250 486.039 Td /F1 9.8 Tf [(tested for the influenza virus by RT-PCR)] TJ ET 0.267 0.267 0.267 rg BT 200.726 487.546 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 210.364 486.039 Td /F1 9.8 Tf [(. For reference, the average influenza testing rate was 26% in the IMSS system for )] TJ ET BT 26.250 474.134 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic )] TJ ET 0.267 0.267 0.267 rg BT 170.404 475.641 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 175.222 474.134 Td /F1 9.8 Tf [(, and 33% during the 2009 pandemic period)] TJ ET 0.267 0.267 0.267 rg BT 364.372 475.641 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 369.191 474.134 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 454.729 Td /F1 9.8 Tf [(For all SARI hospitalizations, we retrieved age, gender, influenza laboratory test results \(for patients tested\), discharge status )] TJ ET BT 26.250 442.824 Td /F1 9.8 Tf [(\(alive or deceased\), reporting state \(including 31 states plus the Federal District\), and self-reported onset dates of symptoms. )] TJ ET BT 26.250 430.920 Td /F1 9.8 Tf [(We also obtained population data by state and age group for all persons affiliated with IMSS to calculate incidence rates.)] TJ ET BT 26.250 411.515 Td /F4 9.8 Tf [(Age distribution and severity of A/H1N1 influenza in winter 2013-2014)] TJ ET BT 26.250 392.110 Td /F1 9.8 Tf [(We examined the age distribution of all SARI hospitalizations, laboratory-confirmed influenza A/H1N1 hospitalizations and )] TJ ET BT 26.250 380.205 Td /F1 9.8 Tf [(deaths from October 2013 to January 2014 with those associated with 2011-12 A/H1N1 epidemic from 01-October 2011 to 15-)] TJ ET BT 26.250 368.301 Td /F1 9.8 Tf [(March 2012, using the same IMSS reporting system.)] TJ ET BT 26.250 348.896 Td /F1 9.8 Tf [(We also calculated preliminary estimates of in-hospital case fatality rate for SARI and laboratory-confirmed A/H1N1 influenza. )] TJ ET BT 26.250 336.991 Td /F1 9.8 Tf [(These estimates are preliminary as we likely underestimate the true fatality ratio due to a delay from symptoms onset to death )] TJ ET BT 26.250 325.086 Td /F1 9.8 Tf [(and laboratory confirmation.)] TJ ET BT 26.250 305.682 Td /F4 9.8 Tf [(Spatial distribution of A/H1N1 influenza in winter 2013-14 and)] TJ ET BT 310.151 305.682 Td /F4 9.8 Tf [( reproduction number estimates)] TJ ET BT 26.250 286.277 Td /F1 9.8 Tf [(We analyzed the geographic dissemination of the 2013-2014 A/H1N1 outbreak in Mexico based on state- and age-specific time )] TJ ET BT 26.250 274.372 Td /F1 9.8 Tf [(series of laboratory-confirmed hospitalizations by day of symptom onset.)] TJ ET BT 26.250 254.967 Td /F1 9.8 Tf [(Further, we estimated the reproduction number, R, in Central Mexico where the great majority of A/H1N1 cases have been )] TJ ET BT 26.250 243.063 Td /F1 9.8 Tf [(reported in 2013-14, based on a simple method previously used to characterize the 2009 A/H1N1 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 493.392 244.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 498.211 243.063 Td /F1 9.8 Tf [( and the 2011-12 )] TJ ET BT 26.250 231.158 Td /F1 9.8 Tf [(A/H1N1 epidemic in Mexico )] TJ ET 0.267 0.267 0.267 rg BT 148.700 232.665 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 153.519 231.158 Td /F1 9.8 Tf [(. Specifically we estimated the initial epidemic growth rate by fitting an exponential function to )] TJ ET BT 26.250 219.253 Td /F1 9.8 Tf [(entire ascending phase of daily A/H1N1 hospitalizations by date of symptoms onset )] TJ ET 0.267 0.267 0.267 rg BT 388.794 220.760 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 398.431 219.253 Td /F1 9.8 Tf [(. We assumed a mean generation )] TJ ET BT 26.250 207.348 Td /F1 9.8 Tf [(interval of three and four days, which are within the range of mean estimates for the 2009 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 500.441 208.856 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 510.079 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 512.488 208.856 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 522.125 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 524.535 208.856 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 534.172 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 536.581 208.856 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 546.219 207.348 Td /F1 9.8 Tf [(. As a )] TJ ET BT 26.250 195.444 Td /F1 9.8 Tf [(sensitivity analysis we also assessed small variations in the length of the ascending epidemic phase used to estimate the )] TJ ET BT 26.250 183.539 Td /F1 9.8 Tf [(exponential growth rate.)] TJ ET BT 26.250 164.134 Td /F1 9.8 Tf [(This study did not require approval from a scientific committee; all individual data were kept de-identified.)] TJ ET BT 26.250 144.729 Td /F1 9.8 Tf [(Analyses were performed using SPSS 20.0 and Matlab \(The Mathworks, Inc\).)] TJ ET BT 26.250 108.127 Td /F4 12.0 Tf [(RESULTS)] TJ ET BT 26.250 88.173 Td /F4 9.8 Tf [(Overall epidemiological patterns)] TJ ET BT 26.250 68.768 Td /F1 9.8 Tf [(Bewteen 01-October 2013 and 31-January 2014, 7,886 SARI hospitalizations were reported to the IMSS medical system, of )] TJ ET BT 26.250 56.863 Td /F1 9.8 Tf [(which 1,203 were confirmed for A/H1N1 \(Table 1\). Daily time series for the last 3 consecutive seasons are shown in Figures 1 )] TJ ET BT 26.250 44.958 Td /F1 9.8 Tf [(and 2. The influenza A/H1N1 percent positivity rate picked up around mid-November 2013 and A/H1N1 has remained the )] TJ ET Q q 15.000 30.673 577.500 746.327 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(the 2012-13 influenza season was mild and dominated by the A/H3N2 virus.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Here we report preliminary findings on the epidemiology of the on-going A/H1N1 outbreak in Mexico from October 2013 to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(January 2014. Because past influenza pandemics have had substantial morbidity and mortality burden for several seasons after )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(the initial pandemic waves )] TJ ET 0.267 0.267 0.267 rg BT 142.753 725.769 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 147.571 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 149.981 725.769 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 154.799 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 157.209 725.769 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 162.027 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 164.437 725.769 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 169.255 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 171.665 725.769 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 181.302 724.262 Td /F1 9.8 Tf [(, continued vigilance is prudent. We compare the demographic and clinical characteristics of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 hospitalizations and deaths in winter 2013-14 with those reported for the preceding 2011-12 )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(A/H1N1 epidemic. Our data highlight a change in the age distribution of A/H1N1 patients and a slightly higher reproduction )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(number compared to the 2011-12 A/H1N1 outbreak.)] TJ ET BT 26.250 651.945 Td /F4 12.0 Tf [(MATERIALS AND METHODS)] TJ ET BT 26.250 631.991 Td /F4 9.8 Tf [(Epidemiological Data)] TJ ET BT 26.250 612.586 Td /F1 9.8 Tf [(Individual level hospitalization data were available from a prospective influenza surveillance system that was initiated especially )] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(for the 2009 pandemic by the Mexican Institute for Social Security \(IMSS\) )] TJ ET 0.267 0.267 0.267 rg BT 345.426 602.189 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 350.245 604.570 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 352.654 602.189 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 362.291 600.681 Td /F1 9.8 Tf [(. IMSS is a tripartite Mexican health system )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(covering approximately 40% of the Mexican population comprising workers in the private sector and their families, relying on a )] TJ ET BT 26.250 576.872 Td /F1 9.8 Tf [(network of 1,099 primary health-care units and 259 hospitals nationwide. The age and gender distributions of persons affiliated )] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(to the IMSS medical system are representative of the general Mexican population )] TJ ET 0.267 0.267 0.267 rg BT 380.116 566.474 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 384.935 564.967 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 545.562 Td /F1 9.8 Tf [(We analyzed all patients admitted to the hospital for > 24 hrs with a diagnosis of severe acute respiratory infection \(SARI\) )] TJ ET BT 26.250 533.658 Td /F1 9.8 Tf [(during October 2013 to January 2014. SARI was defined as the presence of respiratory difficulty with fever >38C and cough, )] TJ ET BT 26.250 521.753 Td /F1 9.8 Tf [(together with one or more of the following clinical symptoms: confinement to bed, thoracic pain, polypnea, or acute respiratory )] TJ ET BT 26.250 509.848 Td /F1 9.8 Tf [(distress syndrome. Children <5 years with pneumonia or severe pneumonia that required hospitalization were also considered )] TJ ET BT 26.250 497.943 Td /F1 9.8 Tf [(as SARI cases. Respiratory swabs were obtained for about 52% of SARI hospitalizations \(SARI\) in winter 2013-14 and were )] TJ ET BT 26.250 486.039 Td /F1 9.8 Tf [(tested for the influenza virus by RT-PCR)] TJ ET 0.267 0.267 0.267 rg BT 200.726 487.546 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 210.364 486.039 Td /F1 9.8 Tf [(. For reference, the average influenza testing rate was 26% in the IMSS system for )] TJ ET BT 26.250 474.134 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic )] TJ ET 0.267 0.267 0.267 rg BT 170.404 475.641 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 175.222 474.134 Td /F1 9.8 Tf [(, and 33% during the 2009 pandemic period)] TJ ET 0.267 0.267 0.267 rg BT 364.372 475.641 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 369.191 474.134 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 454.729 Td /F1 9.8 Tf [(For all SARI hospitalizations, we retrieved age, gender, influenza laboratory test results \(for patients tested\), discharge status )] TJ ET BT 26.250 442.824 Td /F1 9.8 Tf [(\(alive or deceased\), reporting state \(including 31 states plus the Federal District\), and self-reported onset dates of symptoms. )] TJ ET BT 26.250 430.920 Td /F1 9.8 Tf [(We also obtained population data by state and age group for all persons affiliated with IMSS to calculate incidence rates.)] TJ ET BT 26.250 411.515 Td /F4 9.8 Tf [(Age distribution and severity of A/H1N1 influenza in winter 2013-2014)] TJ ET BT 26.250 392.110 Td /F1 9.8 Tf [(We examined the age distribution of all SARI hospitalizations, laboratory-confirmed influenza A/H1N1 hospitalizations and )] TJ ET BT 26.250 380.205 Td /F1 9.8 Tf [(deaths from October 2013 to January 2014 with those associated with 2011-12 A/H1N1 epidemic from 01-October 2011 to 15-)] TJ ET BT 26.250 368.301 Td /F1 9.8 Tf [(March 2012, using the same IMSS reporting system.)] TJ ET BT 26.250 348.896 Td /F1 9.8 Tf [(We also calculated preliminary estimates of in-hospital case fatality rate for SARI and laboratory-confirmed A/H1N1 influenza. )] TJ ET BT 26.250 336.991 Td /F1 9.8 Tf [(These estimates are preliminary as we likely underestimate the true fatality ratio due to a delay from symptoms onset to death )] TJ ET BT 26.250 325.086 Td /F1 9.8 Tf [(and laboratory confirmation.)] TJ ET BT 26.250 305.682 Td /F4 9.8 Tf [(Spatial distribution of A/H1N1 influenza in winter 2013-14 and)] TJ ET BT 310.151 305.682 Td /F4 9.8 Tf [( reproduction number estimates)] TJ ET BT 26.250 286.277 Td /F1 9.8 Tf [(We analyzed the geographic dissemination of the 2013-2014 A/H1N1 outbreak in Mexico based on state- and age-specific time )] TJ ET BT 26.250 274.372 Td /F1 9.8 Tf [(series of laboratory-confirmed hospitalizations by day of symptom onset.)] TJ ET BT 26.250 254.967 Td /F1 9.8 Tf [(Further, we estimated the reproduction number, R, in Central Mexico where the great majority of A/H1N1 cases have been )] TJ ET BT 26.250 243.063 Td /F1 9.8 Tf [(reported in 2013-14, based on a simple method previously used to characterize the 2009 A/H1N1 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 493.392 244.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 498.211 243.063 Td /F1 9.8 Tf [( and the 2011-12 )] TJ ET BT 26.250 231.158 Td /F1 9.8 Tf [(A/H1N1 epidemic in Mexico )] TJ ET 0.267 0.267 0.267 rg BT 148.700 232.665 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 153.519 231.158 Td /F1 9.8 Tf [(. Specifically we estimated the initial epidemic growth rate by fitting an exponential function to )] TJ ET BT 26.250 219.253 Td /F1 9.8 Tf [(entire ascending phase of daily A/H1N1 hospitalizations by date of symptoms onset )] TJ ET 0.267 0.267 0.267 rg BT 388.794 220.760 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 398.431 219.253 Td /F1 9.8 Tf [(. We assumed a mean generation )] TJ ET BT 26.250 207.348 Td /F1 9.8 Tf [(interval of three and four days, which are within the range of mean estimates for the 2009 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 500.441 208.856 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 510.079 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 512.488 208.856 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 522.125 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 524.535 208.856 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 534.172 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 536.581 208.856 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 546.219 207.348 Td /F1 9.8 Tf [(. As a )] TJ ET BT 26.250 195.444 Td /F1 9.8 Tf [(sensitivity analysis we also assessed small variations in the length of the ascending epidemic phase used to estimate the )] TJ ET BT 26.250 183.539 Td /F1 9.8 Tf [(exponential growth rate.)] TJ ET BT 26.250 164.134 Td /F1 9.8 Tf [(This study did not require approval from a scientific committee; all individual data were kept de-identified.)] TJ ET BT 26.250 144.729 Td /F1 9.8 Tf [(Analyses were performed using SPSS 20.0 and Matlab \(The Mathworks, Inc\).)] TJ ET BT 26.250 108.127 Td /F4 12.0 Tf [(RESULTS)] TJ ET BT 26.250 88.173 Td /F4 9.8 Tf [(Overall epidemiological patterns)] TJ ET BT 26.250 68.768 Td /F1 9.8 Tf [(Bewteen 01-October 2013 and 31-January 2014, 7,886 SARI hospitalizations were reported to the IMSS medical system, of )] TJ ET BT 26.250 56.863 Td /F1 9.8 Tf [(which 1,203 were confirmed for A/H1N1 \(Table 1\). Daily time series for the last 3 consecutive seasons are shown in Figures 1 )] TJ ET BT 26.250 44.958 Td /F1 9.8 Tf [(and 2. The influenza A/H1N1 percent positivity rate picked up around mid-November 2013 and A/H1N1 has remained the )] TJ ET Q q 15.000 30.673 577.500 746.327 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(the 2012-13 influenza season was mild and dominated by the A/H3N2 virus.)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Here we report preliminary findings on the epidemiology of the on-going A/H1N1 outbreak in Mexico from October 2013 to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(January 2014. Because past influenza pandemics have had substantial morbidity and mortality burden for several seasons after )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(the initial pandemic waves )] TJ ET 0.267 0.267 0.267 rg BT 142.753 725.769 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 147.571 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 149.981 725.769 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 154.799 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 157.209 725.769 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 162.027 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 164.437 725.769 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 169.255 728.150 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 171.665 725.769 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 181.302 724.262 Td /F1 9.8 Tf [(, continued vigilance is prudent. We compare the demographic and clinical characteristics of )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(laboratory-confirmed A/H1N1 hospitalizations and deaths in winter 2013-14 with those reported for the preceding 2011-12 )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(A/H1N1 epidemic. Our data highlight a change in the age distribution of A/H1N1 patients and a slightly higher reproduction )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(number compared to the 2011-12 A/H1N1 outbreak.)] TJ ET BT 26.250 651.945 Td /F4 12.0 Tf [(MATERIALS AND METHODS)] TJ ET BT 26.250 631.991 Td /F4 9.8 Tf [(Epidemiological Data)] TJ ET BT 26.250 612.586 Td /F1 9.8 Tf [(Individual level hospitalization data were available from a prospective influenza surveillance system that was initiated especially )] TJ ET BT 26.250 600.681 Td /F1 9.8 Tf [(for the 2009 pandemic by the Mexican Institute for Social Security \(IMSS\) )] TJ ET 0.267 0.267 0.267 rg BT 345.426 602.189 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 350.245 604.570 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 352.654 602.189 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 362.291 600.681 Td /F1 9.8 Tf [(. IMSS is a tripartite Mexican health system )] TJ ET BT 26.250 588.777 Td /F1 9.8 Tf [(covering approximately 40% of the Mexican population comprising workers in the private sector and their families, relying on a )] TJ ET BT 26.250 576.872 Td /F1 9.8 Tf [(network of 1,099 primary health-care units and 259 hospitals nationwide. The age and gender distributions of persons affiliated )] TJ ET BT 26.250 564.967 Td /F1 9.8 Tf [(to the IMSS medical system are representative of the general Mexican population )] TJ ET 0.267 0.267 0.267 rg BT 380.116 566.474 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 384.935 564.967 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 545.562 Td /F1 9.8 Tf [(We analyzed all patients admitted to the hospital for > 24 hrs with a diagnosis of severe acute respiratory infection \(SARI\) )] TJ ET BT 26.250 533.658 Td /F1 9.8 Tf [(during October 2013 to January 2014. SARI was defined as the presence of respiratory difficulty with fever >38C and cough, )] TJ ET BT 26.250 521.753 Td /F1 9.8 Tf [(together with one or more of the following clinical symptoms: confinement to bed, thoracic pain, polypnea, or acute respiratory )] TJ ET BT 26.250 509.848 Td /F1 9.8 Tf [(distress syndrome. Children <5 years with pneumonia or severe pneumonia that required hospitalization were also considered )] TJ ET BT 26.250 497.943 Td /F1 9.8 Tf [(as SARI cases. Respiratory swabs were obtained for about 52% of SARI hospitalizations \(SARI\) in winter 2013-14 and were )] TJ ET BT 26.250 486.039 Td /F1 9.8 Tf [(tested for the influenza virus by RT-PCR)] TJ ET 0.267 0.267 0.267 rg BT 200.726 487.546 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 210.364 486.039 Td /F1 9.8 Tf [(. For reference, the average influenza testing rate was 26% in the IMSS system for )] TJ ET BT 26.250 474.134 Td /F1 9.8 Tf [(the 2011-2012 A/H1N1 epidemic )] TJ ET 0.267 0.267 0.267 rg BT 170.404 475.641 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 175.222 474.134 Td /F1 9.8 Tf [(, and 33% during the 2009 pandemic period)] TJ ET 0.267 0.267 0.267 rg BT 364.372 475.641 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 369.191 474.134 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 454.729 Td /F1 9.8 Tf [(For all SARI hospitalizations, we retrieved age, gender, influenza laboratory test results \(for patients tested\), discharge status )] TJ ET BT 26.250 442.824 Td /F1 9.8 Tf [(\(alive or deceased\), reporting state \(including 31 states plus the Federal District\), and self-reported onset dates of symptoms. )] TJ ET BT 26.250 430.920 Td /F1 9.8 Tf [(We also obtained population data by state and age group for all persons affiliated with IMSS to calculate incidence rates.)] TJ ET BT 26.250 411.515 Td /F4 9.8 Tf [(Age distribution and severity of A/H1N1 influenza in winter 2013-2014)] TJ ET BT 26.250 392.110 Td /F1 9.8 Tf [(We examined the age distribution of all SARI hospitalizations, laboratory-confirmed influenza A/H1N1 hospitalizations and )] TJ ET BT 26.250 380.205 Td /F1 9.8 Tf [(deaths from October 2013 to January 2014 with those associated with 2011-12 A/H1N1 epidemic from 01-October 2011 to 15-)] TJ ET BT 26.250 368.301 Td /F1 9.8 Tf [(March 2012, using the same IMSS reporting system.)] TJ ET BT 26.250 348.896 Td /F1 9.8 Tf [(We also calculated preliminary estimates of in-hospital case fatality rate for SARI and laboratory-confirmed A/H1N1 influenza. )] TJ ET BT 26.250 336.991 Td /F1 9.8 Tf [(These estimates are preliminary as we likely underestimate the true fatality ratio due to a delay from symptoms onset to death )] TJ ET BT 26.250 325.086 Td /F1 9.8 Tf [(and laboratory confirmation.)] TJ ET BT 26.250 305.682 Td /F4 9.8 Tf [(Spatial distribution of A/H1N1 influenza in winter 2013-14 and)] TJ ET BT 310.151 305.682 Td /F4 9.8 Tf [( reproduction number estimates)] TJ ET BT 26.250 286.277 Td /F1 9.8 Tf [(We analyzed the geographic dissemination of the 2013-2014 A/H1N1 outbreak in Mexico based on state- and age-specific time )] TJ ET BT 26.250 274.372 Td /F1 9.8 Tf [(series of laboratory-confirmed hospitalizations by day of symptom onset.)] TJ ET BT 26.250 254.967 Td /F1 9.8 Tf [(Further, we estimated the reproduction number, R, in Central Mexico where the great majority of A/H1N1 cases have been )] TJ ET BT 26.250 243.063 Td /F1 9.8 Tf [(reported in 2013-14, based on a simple method previously used to characterize the 2009 A/H1N1 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 493.392 244.570 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 498.211 243.063 Td /F1 9.8 Tf [( and the 2011-12 )] TJ ET BT 26.250 231.158 Td /F1 9.8 Tf [(A/H1N1 epidemic in Mexico )] TJ ET 0.267 0.267 0.267 rg BT 148.700 232.665 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 153.519 231.158 Td /F1 9.8 Tf [(. Specifically we estimated the initial epidemic growth rate by fitting an exponential function to )] TJ ET BT 26.250 219.253 Td /F1 9.8 Tf [(entire ascending phase of daily A/H1N1 hospitalizations by date of symptoms onset )] TJ ET 0.267 0.267 0.267 rg BT 388.794 220.760 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 398.431 219.253 Td /F1 9.8 Tf [(. We assumed a mean generation )] TJ ET BT 26.250 207.348 Td /F1 9.8 Tf [(interval of three and four days, which are within the range of mean estimates for the 2009 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 500.441 208.856 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 510.079 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 512.488 208.856 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 522.125 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 524.535 208.856 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 534.172 211.237 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 536.581 208.856 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 546.219 207.348 Td /F1 9.8 Tf [(. As a )] TJ ET BT 26.250 195.444 Td /F1 9.8 Tf [(sensitivity analysis we also assessed small variations in the length of the ascending epidemic phase used to estimate the )] TJ ET BT 26.250 183.539 Td /F1 9.8 Tf [(exponential growth rate.)] TJ ET BT 26.250 164.134 Td /F1 9.8 Tf [(This study did not require approval from a scientific committee; all individual data were kept de-identified.)] TJ ET BT 26.250 144.729 Td /F1 9.8 Tf [(Analyses were performed using SPSS 20.0 and Matlab \(The Mathworks, Inc\).)] TJ ET BT 26.250 108.127 Td /F4 12.0 Tf [(RESULTS)] TJ ET BT 26.250 88.173 Td /F4 9.8 Tf [(Overall epidemiological patterns)] TJ ET BT 26.250 68.768 Td /F1 9.8 Tf [(Bewteen 01-October 2013 and 31-January 2014, 7,886 SARI hospitalizations were reported to the IMSS medical system, of )] TJ ET BT 26.250 56.863 Td /F1 9.8 Tf [(which 1,203 were confirmed for A/H1N1 \(Table 1\). Daily time series for the last 3 consecutive seasons are shown in Figures 1 )] TJ ET BT 26.250 44.958 Td /F1 9.8 Tf [(and 2. 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B: 2%\); transmission is still ongoing at the time of writing )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(of this report \(Figure 2\). Most of the recent A/H1N1 activity has been reported in the Central region of Mexico \(55.0%\), followed )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(by southeastern states \(6.5%\), which was also the case in the 2011-12 outbreak \(Figure 1, Table 1\). Daily and cumulative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(numbers of SARI hospitalizations in winter 2013-14 are exceeding the levels that were observed during the 2011-2012 A/H1N1 )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(influenza pandemic.)] TJ ET q 26.250 682.504 555.000 27.473 re W n 0.271 0.267 0.267 rg BT 26.250 698.987 Td /F1 9.8 Tf [(Table 1. Characteristics of all SARI hospitalizations and laboratory-confirmed A/H1N1 influenza hospitalizations, Mexico, )] TJ ET BT 26.250 685.251 Td /F1 9.8 Tf [(October 2013 through January 2014.)] TJ ET Q 1.000 1.000 1.000 rg 26.250 578.163 555.000 96.841 re f 0.965 0.965 0.965 rg 27.000 650.069 215.905 24.185 re f 0.267 0.267 0.267 rg 26.625 673.879 216.280 0.750 re f 26.625 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 31.500 664.730 Td /F4 9.8 Tf [(Variable)] TJ ET 0.965 0.965 0.965 rg 242.905 650.069 175.317 24.185 re f 0.267 0.267 0.267 rg 242.905 673.879 175.317 0.750 re f 0.271 0.267 0.267 rg BT 247.405 664.730 Td /F4 9.8 Tf [(SARI hospitalizations \(%\))] TJ ET 0.965 0.965 0.965 rg 418.222 650.069 162.278 24.185 re f 0.267 0.267 0.267 rg 418.222 673.879 162.653 0.750 re f 580.125 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 422.722 664.730 Td /F4 9.8 Tf [(A/H1N1 confirmed )] TJ ET BT 422.722 652.825 Td /F4 9.8 Tf [(hospitalizations \(%\))] TJ ET 0.267 0.267 0.267 rg 26.625 649.694 216.655 0.750 re f 26.625 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 639.839 Td /F1 9.8 Tf [(GeographicCentralSouthernOther states)] TJ ET 0.267 0.267 0.267 rg 242.530 649.694 176.067 0.750 re f 242.530 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 639.839 Td /F1 9.8 Tf [(3134 \(39.7\)978 \(12.4\)3774 \(47.9\))] TJ ET 0.267 0.267 0.267 rg 417.847 649.694 163.028 0.750 re f 417.847 633.813 0.750 16.631 re f 580.125 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 639.839 Td /F1 9.8 Tf [(662 \(55.0\)78 \(6.5\)463 \(38.5\))] TJ ET 0.267 0.267 0.267 rg 26.625 633.813 216.655 0.750 re f 26.625 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 623.958 Td /F1 9.8 Tf [(DemographyFemale)] TJ ET 0.267 0.267 0.267 rg 242.530 633.813 176.067 0.750 re f 242.530 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 623.958 Td /F1 9.8 Tf [(3849 \(48.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 633.813 163.028 0.750 re f 417.847 617.932 0.750 16.631 re f 580.125 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 623.958 Td /F1 9.8 Tf [(586 \(48.7\))] TJ ET 0.267 0.267 0.267 rg 26.625 617.932 216.655 0.750 re f 26.625 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.875 608.077 Td /F1 9.8 Tf [(Age \(years\)0-45-1415-2930-4445-59>=60)] TJ ET 0.267 0.267 0.267 rg 242.530 617.932 176.067 0.750 re f 242.530 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 247.780 608.077 Td /F1 9.8 Tf [(1542 \(19.5\)418 \(5.3\)805 \(10.2\)1460 )] TJ ET BT 247.780 600.445 Td /F1 9.8 Tf [(\(18.5\)1551 \(19.7\)2110 \(26.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 617.932 163.028 0.750 re f 417.847 594.419 0.750 24.262 re f 580.125 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 423.097 608.077 Td /F1 9.8 Tf [(94 \(7.8\)68 \(5.6\)142 11.8\)352 )] TJ ET BT 423.097 600.445 Td /F1 9.8 Tf [(\(29.3\)338 \(28.1\)209 \(17.4\))] TJ ET 0.267 0.267 0.267 rg 26.625 594.419 216.655 0.750 re f 26.625 578.538 216.655 0.750 re f 26.625 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 584.564 Td /F1 9.8 Tf [(Inpatient severityDeaths)] TJ ET 0.267 0.267 0.267 rg 242.530 594.419 176.067 0.750 re f 242.530 578.538 176.067 0.750 re f 242.530 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 584.564 Td /F1 9.8 Tf [(529 \(6.7\))] TJ ET 0.267 0.267 0.267 rg 417.847 594.419 163.028 0.750 re f 417.847 578.538 163.028 0.750 re f 417.847 578.538 0.750 16.631 re f 580.125 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 584.564 Td /F1 9.8 Tf [(196 \(16.3\))] TJ ET 0.965 0.965 0.965 rg 26.250 177.103 555.000 356.060 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 533.163 m 581.250 533.163 l 581.250 532.413 l 26.250 532.413 l f 26.250 177.103 m 581.250 177.103 l 581.250 177.853 l 26.250 177.853 l f q 450.000 0 0 299.250 35.250 224.163 cm /I4 Do Q q 35.250 188.353 537.000 29.810 re W n 0.271 0.267 0.267 rg BT 35.250 208.639 Td /F4 9.8 Tf [(Fig. 1: Daily epidemic curves of all SARI hospitalizations \(top\) and deaths \(bottom\) by dates of symptoms onset in )] TJ ET BT 35.250 196.734 Td /F4 9.8 Tf [(northern, central, and southeastern states of Mexico, 01-December 2013 to 25-January 2014.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -119.897 555.000 289.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 169.603 m 581.250 169.603 l 581.250 168.853 l 26.250 168.853 l f q 450.000 0 0 273.750 35.250 -113.897 cm /I6 Do Q q 35.250 -119.897 537.000 0.000 re W n Q Q q 15.000 -119.897 577.500 896.897 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(dominant influenza subtype this season \(A/H1N1: 90.8%, H3N2: 3.7%. B: 2%\); transmission is still ongoing at the time of writing )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(of this report \(Figure 2\). Most of the recent A/H1N1 activity has been reported in the Central region of Mexico \(55.0%\), followed )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(by southeastern states \(6.5%\), which was also the case in the 2011-12 outbreak \(Figure 1, Table 1\). Daily and cumulative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(numbers of SARI hospitalizations in winter 2013-14 are exceeding the levels that were observed during the 2011-2012 A/H1N1 )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(influenza pandemic.)] TJ ET q 26.250 682.504 555.000 27.473 re W n 0.271 0.267 0.267 rg BT 26.250 698.987 Td /F1 9.8 Tf [(Table 1. Characteristics of all SARI hospitalizations and laboratory-confirmed A/H1N1 influenza hospitalizations, Mexico, )] TJ ET BT 26.250 685.251 Td /F1 9.8 Tf [(October 2013 through January 2014.)] TJ ET Q 1.000 1.000 1.000 rg 26.250 578.163 555.000 96.841 re f 0.965 0.965 0.965 rg 27.000 650.069 215.905 24.185 re f 0.267 0.267 0.267 rg 26.625 673.879 216.280 0.750 re f 26.625 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 31.500 664.730 Td /F4 9.8 Tf [(Variable)] TJ ET 0.965 0.965 0.965 rg 242.905 650.069 175.317 24.185 re f 0.267 0.267 0.267 rg 242.905 673.879 175.317 0.750 re f 0.271 0.267 0.267 rg BT 247.405 664.730 Td /F4 9.8 Tf [(SARI hospitalizations \(%\))] TJ ET 0.965 0.965 0.965 rg 418.222 650.069 162.278 24.185 re f 0.267 0.267 0.267 rg 418.222 673.879 162.653 0.750 re f 580.125 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 422.722 664.730 Td /F4 9.8 Tf [(A/H1N1 confirmed )] TJ ET BT 422.722 652.825 Td /F4 9.8 Tf [(hospitalizations \(%\))] TJ ET 0.267 0.267 0.267 rg 26.625 649.694 216.655 0.750 re f 26.625 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 639.839 Td /F1 9.8 Tf [(GeographicCentralSouthernOther states)] TJ ET 0.267 0.267 0.267 rg 242.530 649.694 176.067 0.750 re f 242.530 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 639.839 Td /F1 9.8 Tf [(3134 \(39.7\)978 \(12.4\)3774 \(47.9\))] TJ ET 0.267 0.267 0.267 rg 417.847 649.694 163.028 0.750 re f 417.847 633.813 0.750 16.631 re f 580.125 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 639.839 Td /F1 9.8 Tf [(662 \(55.0\)78 \(6.5\)463 \(38.5\))] TJ ET 0.267 0.267 0.267 rg 26.625 633.813 216.655 0.750 re f 26.625 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 623.958 Td /F1 9.8 Tf [(DemographyFemale)] TJ ET 0.267 0.267 0.267 rg 242.530 633.813 176.067 0.750 re f 242.530 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 623.958 Td /F1 9.8 Tf [(3849 \(48.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 633.813 163.028 0.750 re f 417.847 617.932 0.750 16.631 re f 580.125 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 623.958 Td /F1 9.8 Tf [(586 \(48.7\))] TJ ET 0.267 0.267 0.267 rg 26.625 617.932 216.655 0.750 re f 26.625 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.875 608.077 Td /F1 9.8 Tf [(Age \(years\)0-45-1415-2930-4445-59>=60)] TJ ET 0.267 0.267 0.267 rg 242.530 617.932 176.067 0.750 re f 242.530 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 247.780 608.077 Td /F1 9.8 Tf [(1542 \(19.5\)418 \(5.3\)805 \(10.2\)1460 )] TJ ET BT 247.780 600.445 Td /F1 9.8 Tf [(\(18.5\)1551 \(19.7\)2110 \(26.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 617.932 163.028 0.750 re f 417.847 594.419 0.750 24.262 re f 580.125 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 423.097 608.077 Td /F1 9.8 Tf [(94 \(7.8\)68 \(5.6\)142 11.8\)352 )] TJ ET BT 423.097 600.445 Td /F1 9.8 Tf [(\(29.3\)338 \(28.1\)209 \(17.4\))] TJ ET 0.267 0.267 0.267 rg 26.625 594.419 216.655 0.750 re f 26.625 578.538 216.655 0.750 re f 26.625 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 584.564 Td /F1 9.8 Tf [(Inpatient severityDeaths)] TJ ET 0.267 0.267 0.267 rg 242.530 594.419 176.067 0.750 re f 242.530 578.538 176.067 0.750 re f 242.530 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 584.564 Td /F1 9.8 Tf [(529 \(6.7\))] TJ ET 0.267 0.267 0.267 rg 417.847 594.419 163.028 0.750 re f 417.847 578.538 163.028 0.750 re f 417.847 578.538 0.750 16.631 re f 580.125 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 584.564 Td /F1 9.8 Tf [(196 \(16.3\))] TJ ET 0.965 0.965 0.965 rg 26.250 177.103 555.000 356.060 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 533.163 m 581.250 533.163 l 581.250 532.413 l 26.250 532.413 l f 26.250 177.103 m 581.250 177.103 l 581.250 177.853 l 26.250 177.853 l f q 450.000 0 0 299.250 35.250 224.163 cm /I8 Do Q q 35.250 188.353 537.000 29.810 re W n 0.271 0.267 0.267 rg BT 35.250 208.639 Td /F4 9.8 Tf [(Fig. 1: Daily epidemic curves of all SARI hospitalizations \(top\) and deaths \(bottom\) by dates of symptoms onset in )] TJ ET BT 35.250 196.734 Td /F4 9.8 Tf [(northern, central, and southeastern states of Mexico, 01-December 2013 to 25-January 2014.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -119.897 555.000 289.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 169.603 m 581.250 169.603 l 581.250 168.853 l 26.250 168.853 l f q 450.000 0 0 273.750 35.250 -113.897 cm /I10 Do Q q 35.250 -119.897 537.000 0.000 re W n Q Q q 15.000 -119.897 577.500 896.897 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(dominant influenza subtype this season \(A/H1N1: 90.8%, H3N2: 3.7%. B: 2%\); transmission is still ongoing at the time of writing )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(of this report \(Figure 2\). Most of the recent A/H1N1 activity has been reported in the Central region of Mexico \(55.0%\), followed )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(by southeastern states \(6.5%\), which was also the case in the 2011-12 outbreak \(Figure 1, Table 1\). Daily and cumulative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(numbers of SARI hospitalizations in winter 2013-14 are exceeding the levels that were observed during the 2011-2012 A/H1N1 )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(influenza pandemic.)] TJ ET q 26.250 682.504 555.000 27.473 re W n 0.271 0.267 0.267 rg BT 26.250 698.987 Td /F1 9.8 Tf [(Table 1. Characteristics of all SARI hospitalizations and laboratory-confirmed A/H1N1 influenza hospitalizations, Mexico, )] TJ ET BT 26.250 685.251 Td /F1 9.8 Tf [(October 2013 through January 2014.)] TJ ET Q 1.000 1.000 1.000 rg 26.250 578.163 555.000 96.841 re f 0.965 0.965 0.965 rg 27.000 650.069 215.905 24.185 re f 0.267 0.267 0.267 rg 26.625 673.879 216.280 0.750 re f 26.625 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 31.500 664.730 Td /F4 9.8 Tf [(Variable)] TJ ET 0.965 0.965 0.965 rg 242.905 650.069 175.317 24.185 re f 0.267 0.267 0.267 rg 242.905 673.879 175.317 0.750 re f 0.271 0.267 0.267 rg BT 247.405 664.730 Td /F4 9.8 Tf [(SARI hospitalizations \(%\))] TJ ET 0.965 0.965 0.965 rg 418.222 650.069 162.278 24.185 re f 0.267 0.267 0.267 rg 418.222 673.879 162.653 0.750 re f 580.125 649.694 0.750 24.935 re f 0.271 0.267 0.267 rg BT 422.722 664.730 Td /F4 9.8 Tf [(A/H1N1 confirmed )] TJ ET BT 422.722 652.825 Td /F4 9.8 Tf [(hospitalizations \(%\))] TJ ET 0.267 0.267 0.267 rg 26.625 649.694 216.655 0.750 re f 26.625 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 639.839 Td /F1 9.8 Tf [(GeographicCentralSouthernOther states)] TJ ET 0.267 0.267 0.267 rg 242.530 649.694 176.067 0.750 re f 242.530 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 639.839 Td /F1 9.8 Tf [(3134 \(39.7\)978 \(12.4\)3774 \(47.9\))] TJ ET 0.267 0.267 0.267 rg 417.847 649.694 163.028 0.750 re f 417.847 633.813 0.750 16.631 re f 580.125 633.813 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 639.839 Td /F1 9.8 Tf [(662 \(55.0\)78 \(6.5\)463 \(38.5\))] TJ ET 0.267 0.267 0.267 rg 26.625 633.813 216.655 0.750 re f 26.625 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 623.958 Td /F1 9.8 Tf [(DemographyFemale)] TJ ET 0.267 0.267 0.267 rg 242.530 633.813 176.067 0.750 re f 242.530 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 623.958 Td /F1 9.8 Tf [(3849 \(48.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 633.813 163.028 0.750 re f 417.847 617.932 0.750 16.631 re f 580.125 617.932 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 623.958 Td /F1 9.8 Tf [(586 \(48.7\))] TJ ET 0.267 0.267 0.267 rg 26.625 617.932 216.655 0.750 re f 26.625 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 31.875 608.077 Td /F1 9.8 Tf [(Age \(years\)0-45-1415-2930-4445-59>=60)] TJ ET 0.267 0.267 0.267 rg 242.530 617.932 176.067 0.750 re f 242.530 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 247.780 608.077 Td /F1 9.8 Tf [(1542 \(19.5\)418 \(5.3\)805 \(10.2\)1460 )] TJ ET BT 247.780 600.445 Td /F1 9.8 Tf [(\(18.5\)1551 \(19.7\)2110 \(26.8\))] TJ ET 0.267 0.267 0.267 rg 417.847 617.932 163.028 0.750 re f 417.847 594.419 0.750 24.262 re f 580.125 594.419 0.750 24.262 re f 0.271 0.267 0.267 rg BT 423.097 608.077 Td /F1 9.8 Tf [(94 \(7.8\)68 \(5.6\)142 11.8\)352 )] TJ ET BT 423.097 600.445 Td /F1 9.8 Tf [(\(29.3\)338 \(28.1\)209 \(17.4\))] TJ ET 0.267 0.267 0.267 rg 26.625 594.419 216.655 0.750 re f 26.625 578.538 216.655 0.750 re f 26.625 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 31.875 584.564 Td /F1 9.8 Tf [(Inpatient severityDeaths)] TJ ET 0.267 0.267 0.267 rg 242.530 594.419 176.067 0.750 re f 242.530 578.538 176.067 0.750 re f 242.530 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 247.780 584.564 Td /F1 9.8 Tf [(529 \(6.7\))] TJ ET 0.267 0.267 0.267 rg 417.847 594.419 163.028 0.750 re f 417.847 578.538 163.028 0.750 re f 417.847 578.538 0.750 16.631 re f 580.125 578.538 0.750 16.631 re f 0.271 0.267 0.267 rg BT 423.097 584.564 Td /F1 9.8 Tf [(196 \(16.3\))] TJ ET 0.965 0.965 0.965 rg 26.250 177.103 555.000 356.060 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 533.163 m 581.250 533.163 l 581.250 532.413 l 26.250 532.413 l f 26.250 177.103 m 581.250 177.103 l 581.250 177.853 l 26.250 177.853 l f q 450.000 0 0 299.250 35.250 224.163 cm /I12 Do Q q 35.250 188.353 537.000 29.810 re W n 0.271 0.267 0.267 rg BT 35.250 208.639 Td /F4 9.8 Tf [(Fig. 1: Daily epidemic curves of all SARI hospitalizations \(top\) and deaths \(bottom\) by dates of symptoms onset in )] TJ ET BT 35.250 196.734 Td /F4 9.8 Tf [(northern, central, and southeastern states of Mexico, 01-December 2013 to 25-January 2014.)] TJ ET Q 0.965 0.965 0.965 rg 26.250 -119.897 555.000 289.500 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 169.603 m 581.250 169.603 l 581.250 168.853 l 26.250 168.853 l f q 450.000 0 0 273.750 35.250 -113.897 cm /I14 Do Q q 35.250 -119.897 537.000 0.000 re W n Q Q q 450.000 0 0 299.250 35.250 224.163 cm /I16 Do Q q 450.000 0 0 273.750 35.250 -113.897 cm /I18 Do 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 Outbreaks)] TJ ET Q endstream endobj 216 0 obj << /Type /Annot /Subtype /Link /A 217 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 224.1630 485.2500 523.4130 ] >> endobj 217 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/02/Figure_curvesLab2014.png) >> endobj 218 0 obj << /Type /XObject /Subtype /Image /Width 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B;4fa2C HLOO2mp3%qøEѵdZ,l@)՚BӴLÉ';Ht鯾Yˏ;@]0\A3> endobj 245 0 obj << /Length 16161 >> stream q 15.000 33.143 577.500 743.857 re W n 0.965 0.965 0.965 rg 26.250 724.036 555.000 52.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 724.036 m 581.250 724.036 l 581.250 724.786 l 26.250 724.786 l f q 35.250 735.286 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 2: Daily number of influenza tests among SARI hospitalizations and laboratory-confirmed influenza )] TJ ET BT 35.250 755.571 Td /F4 9.8 Tf [(hospitalizations by dates of symptoms onset spanning 01-December 2011 to 25-January 2014.in the 32 Mexican )] TJ ET BT 35.250 743.667 Td /F4 9.8 Tf [(states according to influenza subtype.)] TJ ET Q BT 26.250 707.012 Td /F4 9.8 Tf [(Severity of disease)] TJ ET BT 26.250 687.607 Td /F1 9.8 Tf [(Between October 2013 and January 2014, 529 inpatient-SARI deaths were reported among 7,886 SARI hospitalizations, with a )] TJ ET BT 26.250 675.702 Td /F1 9.8 Tf [(preliminary case fatality rate of 6.7% \(95% CI: 6.1, 7.3\). The preliminary estimate of hospital CFR for laboratory-confirmed )] TJ ET BT 26.250 663.798 Td /F1 9.8 Tf [(A/H1N1 was 16.3% \(95% CI: 14.2, 18.4\) over the same period \(1203 inpatients and 196 deaths\). The A/H1N1-specific CFR )] TJ ET BT 26.250 651.893 Td /F1 9.8 Tf [(estimate for the 2013-2014 epidemic was similar to that of earlier A/H1N1 seasons in Mexico, including the 2011-12 epidemic )] TJ ET BT 26.250 639.988 Td /F1 9.8 Tf [(\(13.8% \(95% CI: 11.7, 15.9\)\) and the 2009 pandemic \(16.1% \(95% CI: 15.0, 17.2\)\). Hospital CFRs were not significantly )] TJ ET BT 26.250 628.083 Td /F1 9.8 Tf [(different across geographic regions \(Chi-square test, P=0.34\).)] TJ ET BT 26.250 608.679 Td /F4 9.8 Tf [(Age patterns)] TJ ET BT 26.250 589.274 Td /F1 9.8 Tf [(Overall the majority of laboratory-confirmed influenza inpatients during Oct 2013 Jan 2014 were among persons aged 30-59 )] TJ ET BT 26.250 577.369 Td /F1 9.8 Tf [(years \(57.4%\) followed by seniors >=60 years \(17.4%\). Severity increased with older age, with a hospital CFR of 22.5% \(95% )] TJ ET BT 26.250 565.464 Td /F1 9.8 Tf [(CI: 16.7, 28.3\) in seniors. Laboratory testing practices were similar between age groups, with 49% of SARI hospitalizations )] TJ ET BT 26.250 553.560 Td /F1 9.8 Tf [(tested for influenza in persons <30 yrs , 54% among people 30-59 yrs and 48% among older individuals.)] TJ ET BT 26.250 534.155 Td /F1 9.8 Tf [(Comparison of the age-specific A/H1N1 hospitalization and death rates between the 2013-2014 season and previous A/H1N1 )] TJ ET BT 26.250 522.250 Td /F1 9.8 Tf [(epidemic in 2011-2012 reveals an increasing burden among adults \(>=30 yrs\), particularly among middle-aged individuals )] TJ ET BT 26.250 510.345 Td /F1 9.8 Tf [(\(Figure 3\). The shift is seen both in absolute and relative terms. Specifically, we note a significantly higher proportion of )] TJ ET BT 26.250 498.441 Td /F1 9.8 Tf [(individuals aged 30-59 yrs hospitalized with laboratory-confirmed A/H1N1 in 2013-14, relative to the 2011-12 A/H1N1 epidemic, )] TJ ET BT 26.250 486.536 Td /F1 9.8 Tf [(as well as a significant decrease in the proportion hospitalizations among younger persons \(Chi-square test, df=5, P<0.0001\).)] TJ ET BT 26.250 467.131 Td /F1 9.8 Tf [(We found a similar change in the age distribution of A/H1N1 inpatient deaths in 2013-14 compared to the 2011-12 A/H1N1 )] TJ ET BT 26.250 455.226 Td /F1 9.8 Tf [(influenza epidemic. Specifically, 67.4% of deaths occurred among persons 30-59 years of age in the ongoing 2013-14 epidemic )] TJ ET BT 26.250 443.322 Td /F1 9.8 Tf [(period whereas only 50% in the 2011-12 A/H1N1 epidemic. Similarly to the age shift in hospitalization data, the proportion of )] TJ ET BT 26.250 431.417 Td /F1 9.8 Tf [(A/H1N1 inpatient deaths among individuals aged 0-29 declined, relative to the 2011-12 A/H1N1 epidemic \(Chi-square test, )] TJ ET BT 26.250 419.512 Td /F1 9.8 Tf [(df=5, P=0.002\))] TJ ET 0.965 0.965 0.965 rg 26.250 107.667 555.000 301.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 409.631 m 581.250 409.631 l 581.250 408.881 l 26.250 408.881 l f 26.250 107.667 m 581.250 107.667 l 581.250 108.417 l 26.250 108.417 l f q 450.000 0 0 233.250 35.250 166.631 cm /I20 Do Q q 35.250 118.917 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 151.107 Td /F4 9.8 Tf [(Fig. 3: Age-specific A/H1N1 influenza hospitalization rates \(left\) and A/H1N1 inpatient death rates \(right\) for the )] TJ ET BT 35.250 139.203 Td /F4 9.8 Tf [(ongoing A/H1N1 influenza epidemic \(01-Oct 2013 to 31-Jan 2014\) compared to the preceding 2011-12 A/H1N1 )] TJ ET BT 35.250 127.298 Td /F4 9.8 Tf [(epidemic and those of the entire 2009 A/H1N1 pandemic period \(01-Apr 2009 to 31-Mar 2010\).)] TJ ET Q BT 26.250 90.643 Td /F4 9.8 Tf [(Estimates of the reproduction number)] TJ ET BT 26.250 71.238 Td /F1 9.8 Tf [(Assuming a mean generation interval of 3 \(4\) days, the mean R was estimated to be 1.3 \(1.4\) during the monotonically )] TJ ET BT 26.250 59.334 Td /F1 9.8 Tf [(ascending period 04-Dec 2013 to 08-Jan 2014, based on daily laboratory-confirmed A/H1N1 case series in central Mexican )] TJ ET BT 26.250 47.429 Td /F1 9.8 Tf [(states. As a sensitivity analysis we also estimated R using a slightly shorter ascending phase and obtained a similar estimate at )] TJ ET Q q 15.000 33.143 577.500 743.857 re W n 0.965 0.965 0.965 rg 26.250 724.036 555.000 52.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 724.036 m 581.250 724.036 l 581.250 724.786 l 26.250 724.786 l f q 35.250 735.286 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 2: Daily number of influenza tests among SARI hospitalizations and laboratory-confirmed influenza )] TJ ET BT 35.250 755.571 Td /F4 9.8 Tf [(hospitalizations by dates of symptoms onset spanning 01-December 2011 to 25-January 2014.in the 32 Mexican )] TJ ET BT 35.250 743.667 Td /F4 9.8 Tf [(states according to influenza subtype.)] TJ ET Q BT 26.250 707.012 Td /F4 9.8 Tf [(Severity of disease)] TJ ET BT 26.250 687.607 Td /F1 9.8 Tf [(Between October 2013 and January 2014, 529 inpatient-SARI deaths were reported among 7,886 SARI hospitalizations, with a )] TJ ET BT 26.250 675.702 Td /F1 9.8 Tf [(preliminary case fatality rate of 6.7% \(95% CI: 6.1, 7.3\). The preliminary estimate of hospital CFR for laboratory-confirmed )] TJ ET BT 26.250 663.798 Td /F1 9.8 Tf [(A/H1N1 was 16.3% \(95% CI: 14.2, 18.4\) over the same period \(1203 inpatients and 196 deaths\). The A/H1N1-specific CFR )] TJ ET BT 26.250 651.893 Td /F1 9.8 Tf [(estimate for the 2013-2014 epidemic was similar to that of earlier A/H1N1 seasons in Mexico, including the 2011-12 epidemic )] TJ ET BT 26.250 639.988 Td /F1 9.8 Tf [(\(13.8% \(95% CI: 11.7, 15.9\)\) and the 2009 pandemic \(16.1% \(95% CI: 15.0, 17.2\)\). Hospital CFRs were not significantly )] TJ ET BT 26.250 628.083 Td /F1 9.8 Tf [(different across geographic regions \(Chi-square test, P=0.34\).)] TJ ET BT 26.250 608.679 Td /F4 9.8 Tf [(Age patterns)] TJ ET BT 26.250 589.274 Td /F1 9.8 Tf [(Overall the majority of laboratory-confirmed influenza inpatients during Oct 2013 Jan 2014 were among persons aged 30-59 )] TJ ET BT 26.250 577.369 Td /F1 9.8 Tf [(years \(57.4%\) followed by seniors >=60 years \(17.4%\). Severity increased with older age, with a hospital CFR of 22.5% \(95% )] TJ ET BT 26.250 565.464 Td /F1 9.8 Tf [(CI: 16.7, 28.3\) in seniors. Laboratory testing practices were similar between age groups, with 49% of SARI hospitalizations )] TJ ET BT 26.250 553.560 Td /F1 9.8 Tf [(tested for influenza in persons <30 yrs , 54% among people 30-59 yrs and 48% among older individuals.)] TJ ET BT 26.250 534.155 Td /F1 9.8 Tf [(Comparison of the age-specific A/H1N1 hospitalization and death rates between the 2013-2014 season and previous A/H1N1 )] TJ ET BT 26.250 522.250 Td /F1 9.8 Tf [(epidemic in 2011-2012 reveals an increasing burden among adults \(>=30 yrs\), particularly among middle-aged individuals )] TJ ET BT 26.250 510.345 Td /F1 9.8 Tf [(\(Figure 3\). The shift is seen both in absolute and relative terms. Specifically, we note a significantly higher proportion of )] TJ ET BT 26.250 498.441 Td /F1 9.8 Tf [(individuals aged 30-59 yrs hospitalized with laboratory-confirmed A/H1N1 in 2013-14, relative to the 2011-12 A/H1N1 epidemic, )] TJ ET BT 26.250 486.536 Td /F1 9.8 Tf [(as well as a significant decrease in the proportion hospitalizations among younger persons \(Chi-square test, df=5, P<0.0001\).)] TJ ET BT 26.250 467.131 Td /F1 9.8 Tf [(We found a similar change in the age distribution of A/H1N1 inpatient deaths in 2013-14 compared to the 2011-12 A/H1N1 )] TJ ET BT 26.250 455.226 Td /F1 9.8 Tf [(influenza epidemic. Specifically, 67.4% of deaths occurred among persons 30-59 years of age in the ongoing 2013-14 epidemic )] TJ ET BT 26.250 443.322 Td /F1 9.8 Tf [(period whereas only 50% in the 2011-12 A/H1N1 epidemic. Similarly to the age shift in hospitalization data, the proportion of )] TJ ET BT 26.250 431.417 Td /F1 9.8 Tf [(A/H1N1 inpatient deaths among individuals aged 0-29 declined, relative to the 2011-12 A/H1N1 epidemic \(Chi-square test, )] TJ ET BT 26.250 419.512 Td /F1 9.8 Tf [(df=5, P=0.002\))] TJ ET 0.965 0.965 0.965 rg 26.250 107.667 555.000 301.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 409.631 m 581.250 409.631 l 581.250 408.881 l 26.250 408.881 l f 26.250 107.667 m 581.250 107.667 l 581.250 108.417 l 26.250 108.417 l f q 450.000 0 0 233.250 35.250 166.631 cm /I22 Do Q q 35.250 118.917 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 151.107 Td /F4 9.8 Tf [(Fig. 3: Age-specific A/H1N1 influenza hospitalization rates \(left\) and A/H1N1 inpatient death rates \(right\) for the )] TJ ET BT 35.250 139.203 Td /F4 9.8 Tf [(ongoing A/H1N1 influenza epidemic \(01-Oct 2013 to 31-Jan 2014\) compared to the preceding 2011-12 A/H1N1 )] TJ ET BT 35.250 127.298 Td /F4 9.8 Tf [(epidemic and those of the entire 2009 A/H1N1 pandemic period \(01-Apr 2009 to 31-Mar 2010\).)] TJ ET Q BT 26.250 90.643 Td /F4 9.8 Tf [(Estimates of the reproduction number)] TJ ET BT 26.250 71.238 Td /F1 9.8 Tf [(Assuming a mean generation interval of 3 \(4\) days, the mean R was estimated to be 1.3 \(1.4\) during the monotonically )] TJ ET BT 26.250 59.334 Td /F1 9.8 Tf [(ascending period 04-Dec 2013 to 08-Jan 2014, based on daily laboratory-confirmed A/H1N1 case series in central Mexican )] TJ ET BT 26.250 47.429 Td /F1 9.8 Tf [(states. As a sensitivity analysis we also estimated R using a slightly shorter ascending phase and obtained a similar estimate at )] TJ ET Q q 15.000 33.143 577.500 743.857 re W n 0.965 0.965 0.965 rg 26.250 724.036 555.000 52.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 724.036 m 581.250 724.036 l 581.250 724.786 l 26.250 724.786 l f q 35.250 735.286 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 2: Daily number of influenza tests among SARI hospitalizations and laboratory-confirmed influenza )] TJ ET BT 35.250 755.571 Td /F4 9.8 Tf [(hospitalizations by dates of symptoms onset spanning 01-December 2011 to 25-January 2014.in the 32 Mexican )] TJ ET BT 35.250 743.667 Td /F4 9.8 Tf [(states according to influenza subtype.)] TJ ET Q BT 26.250 707.012 Td /F4 9.8 Tf [(Severity of disease)] TJ ET BT 26.250 687.607 Td /F1 9.8 Tf [(Between October 2013 and January 2014, 529 inpatient-SARI deaths were reported among 7,886 SARI hospitalizations, with a )] TJ ET BT 26.250 675.702 Td /F1 9.8 Tf [(preliminary case fatality rate of 6.7% \(95% CI: 6.1, 7.3\). The preliminary estimate of hospital CFR for laboratory-confirmed )] TJ ET BT 26.250 663.798 Td /F1 9.8 Tf [(A/H1N1 was 16.3% \(95% CI: 14.2, 18.4\) over the same period \(1203 inpatients and 196 deaths\). The A/H1N1-specific CFR )] TJ ET BT 26.250 651.893 Td /F1 9.8 Tf [(estimate for the 2013-2014 epidemic was similar to that of earlier A/H1N1 seasons in Mexico, including the 2011-12 epidemic )] TJ ET BT 26.250 639.988 Td /F1 9.8 Tf [(\(13.8% \(95% CI: 11.7, 15.9\)\) and the 2009 pandemic \(16.1% \(95% CI: 15.0, 17.2\)\). Hospital CFRs were not significantly )] TJ ET BT 26.250 628.083 Td /F1 9.8 Tf [(different across geographic regions \(Chi-square test, P=0.34\).)] TJ ET BT 26.250 608.679 Td /F4 9.8 Tf [(Age patterns)] TJ ET BT 26.250 589.274 Td /F1 9.8 Tf [(Overall the majority of laboratory-confirmed influenza inpatients during Oct 2013 Jan 2014 were among persons aged 30-59 )] TJ ET BT 26.250 577.369 Td /F1 9.8 Tf [(years \(57.4%\) followed by seniors >=60 years \(17.4%\). Severity increased with older age, with a hospital CFR of 22.5% \(95% )] TJ ET BT 26.250 565.464 Td /F1 9.8 Tf [(CI: 16.7, 28.3\) in seniors. Laboratory testing practices were similar between age groups, with 49% of SARI hospitalizations )] TJ ET BT 26.250 553.560 Td /F1 9.8 Tf [(tested for influenza in persons <30 yrs , 54% among people 30-59 yrs and 48% among older individuals.)] TJ ET BT 26.250 534.155 Td /F1 9.8 Tf [(Comparison of the age-specific A/H1N1 hospitalization and death rates between the 2013-2014 season and previous A/H1N1 )] TJ ET BT 26.250 522.250 Td /F1 9.8 Tf [(epidemic in 2011-2012 reveals an increasing burden among adults \(>=30 yrs\), particularly among middle-aged individuals )] TJ ET BT 26.250 510.345 Td /F1 9.8 Tf [(\(Figure 3\). The shift is seen both in absolute and relative terms. Specifically, we note a significantly higher proportion of )] TJ ET BT 26.250 498.441 Td /F1 9.8 Tf [(individuals aged 30-59 yrs hospitalized with laboratory-confirmed A/H1N1 in 2013-14, relative to the 2011-12 A/H1N1 epidemic, )] TJ ET BT 26.250 486.536 Td /F1 9.8 Tf [(as well as a significant decrease in the proportion hospitalizations among younger persons \(Chi-square test, df=5, P<0.0001\).)] TJ ET BT 26.250 467.131 Td /F1 9.8 Tf [(We found a similar change in the age distribution of A/H1N1 inpatient deaths in 2013-14 compared to the 2011-12 A/H1N1 )] TJ ET BT 26.250 455.226 Td /F1 9.8 Tf [(influenza epidemic. Specifically, 67.4% of deaths occurred among persons 30-59 years of age in the ongoing 2013-14 epidemic )] TJ ET BT 26.250 443.322 Td /F1 9.8 Tf [(period whereas only 50% in the 2011-12 A/H1N1 epidemic. Similarly to the age shift in hospitalization data, the proportion of )] TJ ET BT 26.250 431.417 Td /F1 9.8 Tf [(A/H1N1 inpatient deaths among individuals aged 0-29 declined, relative to the 2011-12 A/H1N1 epidemic \(Chi-square test, )] TJ ET BT 26.250 419.512 Td /F1 9.8 Tf [(df=5, P=0.002\))] TJ ET 0.965 0.965 0.965 rg 26.250 107.667 555.000 301.964 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 409.631 m 581.250 409.631 l 581.250 408.881 l 26.250 408.881 l f 26.250 107.667 m 581.250 107.667 l 581.250 108.417 l 26.250 108.417 l f q 450.000 0 0 233.250 35.250 166.631 cm /I24 Do Q q 35.250 118.917 537.000 41.714 re W n 0.271 0.267 0.267 rg BT 35.250 151.107 Td /F4 9.8 Tf [(Fig. 3: Age-specific A/H1N1 influenza hospitalization rates \(left\) and A/H1N1 inpatient death rates \(right\) for the )] TJ ET BT 35.250 139.203 Td /F4 9.8 Tf [(ongoing A/H1N1 influenza epidemic \(01-Oct 2013 to 31-Jan 2014\) compared to the preceding 2011-12 A/H1N1 )] TJ ET BT 35.250 127.298 Td /F4 9.8 Tf [(epidemic and those of the entire 2009 A/H1N1 pandemic period \(01-Apr 2009 to 31-Mar 2010\).)] TJ ET Q BT 26.250 90.643 Td /F4 9.8 Tf [(Estimates of the reproduction number)] TJ ET BT 26.250 71.238 Td /F1 9.8 Tf [(Assuming a mean generation interval of 3 \(4\) days, the mean R was estimated to be 1.3 \(1.4\) during the monotonically )] TJ ET BT 26.250 59.334 Td /F1 9.8 Tf [(ascending period 04-Dec 2013 to 08-Jan 2014, based on daily laboratory-confirmed A/H1N1 case series in central Mexican )] TJ ET BT 26.250 47.429 Td /F1 9.8 Tf [(states. As a sensitivity analysis we also estimated R using a slightly shorter ascending phase and obtained a similar estimate at )] TJ ET Q q 450.000 0 0 233.250 35.250 166.631 cm /I26 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(4)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 246 0 obj << /Type /Annot /Subtype /Link /A 247 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 166.6312 485.2500 399.8812 ] >> endobj 247 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/02/Figure_RatesAge2014.png) >> endobj 248 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 311 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 600 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 806>> stream xA 0 =" ʝ<2;EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EX$EbM` endstream endobj 249 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 311 /SMask 248 0 R /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 600 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 72522>> stream x]y|Mdbh(-RC'C T[C5КRZ-)S5UӇD!4Q![}Z{s~p?Z]kO'%>>~˖-YYYޝ:uTJn[]5MO/(.kҤIÆ 6mZ|Rk0V .,L*͌;w 칗)ׯ_k뮭-qs!4Fx@LNN_~תUA5jԸWF;`ѣQQQwVbbfSTTTT^;`ĉu[N*((_| sDx Uڤk~!J$7K'.^0tgee>}sΞqTڲq:l}O>9+U9ܴiӝBڋ\n]6m]vС]>}n;%*aMm]^qNOpunl6JXDȄM:m$ IW :dѨ.nAa`&'Qfi94à@GJ(,Ca$a* *h:RPP"_ԩSׯ f!̙<κ9Ks[E5 o2:6.)U /̇3jjbjmM[R}-ZLѨV,_CF҉ *4! 4F: [(xH@xE*%d'`𷁁(-PTTdpaF (ZGK jcԪU1֣G+@5J*^|xBBŠ+^z饡C޸q/T"ׯoٲŋ<77wSNYYYYYYW\i֬icƌ={ɓ'?䓜~ٳ+VҥKll_z饣G>|77nҥKy&W0QO,Z `fBƘM+)* X [BU^CK1~>}||9p޽{B{>#4׫W2_޼y~i޽G]7lзoߕ+W꺾cǎ޽{1ƍ#GRSS%4M+**:u/j*^l2Cq ڷo]}Q4x://oѯʊ+t]_dI>}nʻoܸԩS~M2)2 (145"@Ԭ1%$sNP@[%M@Io!IDkCa#BR.uػ]+W=<<ƍ7nظq?[`A^^ޱcVZcǎ)SsGEE4k֬]v Zh;v㓗(f RPyI'mP0¯8baX1VcIRJ^5a$%//oٲe ,8sLRRҶmۆ r?55׮]EEE/^ܵk8r۷dUV=#-ZtiBBBrr… ?ov…{pŋϟ]Vu˵pUV}|KK,ٸqcQQт NjLFt]2eʿo?gku*U,Yd۶mLHHXp_~rʱc^~]3f̚5r|D%FǨqJhz5ЮB! 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[;ݶMX q:ի8!&Bڏ~+VG>e˖'f{G=iR/X!F(^4޹sw1eʔSNݹsAޛvA5tIwy_>88xqe,ef!b "UX,iTBQ+eپ-ؚ&Y̬՛eQymmp2722rQG;}נgb:&6Y@[8+ -)J`\9z1 \9kNߙGtϤ/}K|ChSNyޗׂEFzo?3;tjX-<ƾoXbܹwM74w\,I%|s̹[͛7k֬3fo۷??N?!,]r~]v]n{;ޑp.\~N8;묳|v۲e˞zꩧ~G=c8Š+=S<:<<5#N=}P˖-'O/XsqLg*/AGC]Y\q)җpI`,]K/}GRkvX̏gݻ_z|jk֬!oy֭8UV=ccc!{~s[| ;t5gKX.py]vş'wy}m޼y>=B9PVCwqǖ-[\ Ē%KFFF&Onݺ .ٳ{ٳg={{wϘ1#Ƹ:jƍa E!5׳FkQјhH1J !BAN͛򖷌ٳ'?O3|CZzP{ԨKgӄHD1nܸn#k <3G}r}|ܱcۿ3fXr+֭[o>qy9'᷿D~#x'I'/?-L-̐΅Gy͛McܴiScO?={v޽dɒw]~:}722SOٟٱ{ן|D4gΜ}c]w駟~"}fxx]z___ve<>oG}tQQVss>ە{> /ݣ>#lݺuhhַp /R}0HmΜ9W3ϥ[B7o޴i5/2p[n1c矟2gΜO>z)S8hSP]'|O?iӦK/N {g ,H~@)hܹ{$[o߾zs>#gqQ0G}g}vƍ'Rw;v4i?aݻ'@={챛7o1cƹ{\c,Y/_x?χSB ̝;SC= :0'0o޼ӟ??k}I&M4iٲeׯw{'{>hQ=élͅfr4csH 6a8gҀe bM=OLsG?K/?/ /|[Zf͛__>o}[ G;w'pΝ>˗;,UNEZ&9>ϐm9fhTS??Q]Cx@lDsϵ+!Som۶}_\fMRxGoUVz뭓&M:3]ң߿c!۷[l;R@ )Uz`l논q7*մ809xڰ`5Y 7\㭷:}􁁁˗3gavgYFJnziM2c/p׌Y>7Ds t:tO '?VwXMk0Owy7xGw}?gΜy]w=Swޞ={N:'|2 < _՗e"ڸq1;Kte<['p0.oN{Wr('fV_v^)%]z=_~ʔ)_=]y啣/>;}{g}y-Ydxx83gΚ5k\tE7lؐ}Wo_O|Nmn"7Z|QgJup:\KicccW]uՑGB8>豱{nΜ9+Wlܸ//ΡwZ7oޅ^)_`p3̭_#d[xSϕz2eW󪫮g?sϝ{ӧO׾x]tQywW_r%r_{vV#5ѯ^dQ!@c}aSΉ 0uOGGGɓO;??gΜy)lܸ _—²e.H{ ][\ ƕõ;EbasV?r, endstream endobj 260 0 obj << /Type /Page /Parent 3 0 R /Annots [ 262 0 R 266 0 R 268 0 R 270 0 R 272 0 R 274 0 R 276 0 R 278 0 R 280 0 R 282 0 R 284 0 R 286 0 R 288 0 R 290 0 R 292 0 R 294 0 R 298 0 R 300 0 R 302 0 R 304 0 R 306 0 R 308 0 R 310 0 R 312 0 R 314 0 R 316 0 R 318 0 R 320 0 R 322 0 R 324 0 R 326 0 R 330 0 R 332 0 R 334 0 R 336 0 R 338 0 R 340 0 R 342 0 R 344 0 R 346 0 R 348 0 R 350 0 R 352 0 R 354 0 R 356 0 R ] /Contents 261 0 R >> endobj 261 0 obj << /Length 18918 >> stream 0.271 0.267 0.267 rg q 15.000 30.586 577.500 746.414 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(1.2 \(1.3\) \(Figure 4\). Our R estimate was slightly higher than that estimated for the 2011-12 A/H1N1 season, with R at 1.2 \(1.3\).)] TJ ET 0.965 0.965 0.965 rg 26.250 450.476 555.000 307.119 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 757.595 m 581.250 757.595 l 581.250 756.845 l 26.250 756.845 l f 26.250 450.476 m 581.250 450.476 l 581.250 451.226 l 26.250 451.226 l f q 450.000 0 0 226.500 35.250 521.345 cm /I28 Do Q q 35.250 461.726 537.000 53.619 re W n 0.271 0.267 0.267 rg BT 35.250 505.821 Td /F4 9.8 Tf [(Fig. 4: Model fits \(solid line\) obtained after fitting an exponential curve to the growth phase of the initial epidemic )] TJ ET BT 35.250 493.917 Td /F4 9.8 Tf [(phase of the 2013-14 A/H1N1 epidemic to estimate the initial growth rate based on the case series of laboratory-)] TJ ET BT 35.250 482.012 Td /F4 9.8 Tf [(confirmed A/H1N1 SARI A/H1N1 hospitalizations \(left\) and using a slightly shorter ascending phase as a sensitivity )] TJ ET BT 35.250 470.107 Td /F4 9.8 Tf [(analysis \(right\).)] TJ ET Q BT 26.250 416.255 Td /F4 12.0 Tf [(DISCUSSION)] TJ ET BT 26.250 396.300 Td /F1 9.8 Tf [(We have characterized the epidemiology of a recrudescent wave of pandemic A/H1N1 influenza activity in Mexico during )] TJ ET BT 26.250 384.396 Td /F1 9.8 Tf [(October 2013-January 2014, based on individual-level laboratory-confirmed influenza hospitalizations and deaths, and )] TJ ET BT 26.250 372.491 Td /F1 9.8 Tf [(compared with the well-described epidemiology of earlier A/H1N1 seasons )] TJ ET 0.267 0.267 0.267 rg BT 350.281 373.998 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 355.100 376.379 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 357.510 373.998 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 362.328 372.491 Td /F1 9.8 Tf [(. Our data show that the level of hospitalizations )] TJ ET BT 26.250 360.586 Td /F1 9.8 Tf [(in 2013-2014 has exceeded that of the last A/H1N1 epidemic in 2011-12. We have also documented a significant shift in )] TJ ET BT 26.250 348.681 Td /F1 9.8 Tf [(absolute and relative severe disease burden from young individuals \(<30 yrs\) to middle-aged adults 30-59 years, relative to the )] TJ ET BT 26.250 336.777 Td /F1 9.8 Tf [(preceding A/H1N1 epidemic.)] TJ ET BT 26.250 317.372 Td /F1 9.8 Tf [(The observed gradual change in age distribution of hospitalization and deaths in the post 2009 pandemic period is reminiscent )] TJ ET BT 26.250 305.467 Td /F1 9.8 Tf [(of the influenza seasons following the 1918 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 302.107 306.974 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 306.925 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 309.335 306.974 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 318.972 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 321.381 306.974 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 331.019 305.467 Td /F1 9.8 Tf [( and the 1968 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 438.337 306.974 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 447.974 305.467 Td /F1 9.8 Tf [(. A quantitative analysis of )] TJ ET BT 26.250 293.562 Td /F1 9.8 Tf [(excess mortality in the decade following the 1918 influenza pandemic found that the age distribution of influenza-related )] TJ ET BT 26.250 281.658 Td /F1 9.8 Tf [(mortality returned to pre-pandemic mortality levels a few years after the initial pandemic waves as a result of emerging drift )] TJ ET BT 26.250 269.753 Td /F1 9.8 Tf [(variants)] TJ ET 0.267 0.267 0.267 rg BT 60.385 271.260 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 65.203 273.641 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.613 271.260 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.250 269.753 Td /F1 9.8 Tf [(. Hence the age shift seen in the 2011-12 and 2013-14 A/H1N1 epidemics could signal a build up of immunity )] TJ ET BT 26.250 257.848 Td /F1 9.8 Tf [(among younger populations, which has implications for influenza prevention and mitigation strategies.)] TJ ET BT 26.250 238.443 Td /F1 9.8 Tf [(It is now well recognized that during the first year of circulation of the 2009 A/H1N1 influenza pandemic virus, seniors over 60 )] TJ ET BT 26.250 226.539 Td /F1 9.8 Tf [(years enjoyed protection from influenza-related morbidity and mortality. This phenomenon of senior sparing in age cohorts )] TJ ET BT 26.250 214.634 Td /F1 9.8 Tf [(born prior to the 1957 pandemic is consistent with the protective effect of first exposure to antigenically-related A/H1N1 viruses )] TJ ET BT 26.250 202.729 Td /F1 9.8 Tf [(in childhood, which aligns with antigen recycling and original antigenic sin hypotheses)] TJ ET 0.267 0.267 0.267 rg BT 395.288 204.236 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 404.925 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.334 204.236 Td /F4 8.7 Tf [(23)] TJ ET 0.271 0.267 0.267 rg BT 416.972 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 419.381 204.236 Td /F4 8.7 Tf [(24)] TJ ET 0.271 0.267 0.267 rg BT 429.018 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 431.428 204.236 Td /F4 8.7 Tf [(25)] TJ ET 0.271 0.267 0.267 rg BT 441.065 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 443.474 204.236 Td /F4 8.7 Tf [(26)] TJ ET 0.271 0.267 0.267 rg BT 453.112 202.729 Td /F1 9.8 Tf [(. A high fraction of the )] TJ ET BT 26.250 190.824 Td /F1 9.8 Tf [(Mexican population is now presumably protected against the 2009 A/H1N1 influenza virus through natural exposure since 2009 )] TJ ET BT 26.250 178.920 Td /F1 9.8 Tf [(\(children and young adults\), prior immunity \(seniors\) )] TJ ET 0.267 0.267 0.267 rg BT 253.815 180.427 Td /F4 8.7 Tf [(27)] TJ ET 0.271 0.267 0.267 rg BT 263.452 178.920 Td /F1 9.8 Tf [( and by pandemic vaccines. In parallel, waning of immunity is also )] TJ ET BT 26.250 167.015 Td /F1 9.8 Tf [(expected in individuals that are not periodically re-vaccinated. To the best of our knowledge, no serological studies were )] TJ ET BT 26.250 155.110 Td /F1 9.8 Tf [(conducted prior to this epidemic or are currently being carried out in Mexico.)] TJ ET Q q 15.000 30.586 577.500 746.414 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(1.2 \(1.3\) \(Figure 4\). Our R estimate was slightly higher than that estimated for the 2011-12 A/H1N1 season, with R at 1.2 \(1.3\).)] TJ ET 0.965 0.965 0.965 rg 26.250 450.476 555.000 307.119 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 757.595 m 581.250 757.595 l 581.250 756.845 l 26.250 756.845 l f 26.250 450.476 m 581.250 450.476 l 581.250 451.226 l 26.250 451.226 l f q 450.000 0 0 226.500 35.250 521.345 cm /I30 Do Q q 35.250 461.726 537.000 53.619 re W n 0.271 0.267 0.267 rg BT 35.250 505.821 Td /F4 9.8 Tf [(Fig. 4: Model fits \(solid line\) obtained after fitting an exponential curve to the growth phase of the initial epidemic )] TJ ET BT 35.250 493.917 Td /F4 9.8 Tf [(phase of the 2013-14 A/H1N1 epidemic to estimate the initial growth rate based on the case series of laboratory-)] TJ ET BT 35.250 482.012 Td /F4 9.8 Tf [(confirmed A/H1N1 SARI A/H1N1 hospitalizations \(left\) and using a slightly shorter ascending phase as a sensitivity )] TJ ET BT 35.250 470.107 Td /F4 9.8 Tf [(analysis \(right\).)] TJ ET Q BT 26.250 416.255 Td /F4 12.0 Tf [(DISCUSSION)] TJ ET BT 26.250 396.300 Td /F1 9.8 Tf [(We have characterized the epidemiology of a recrudescent wave of pandemic A/H1N1 influenza activity in Mexico during )] TJ ET BT 26.250 384.396 Td /F1 9.8 Tf [(October 2013-January 2014, based on individual-level laboratory-confirmed influenza hospitalizations and deaths, and )] TJ ET BT 26.250 372.491 Td /F1 9.8 Tf [(compared with the well-described epidemiology of earlier A/H1N1 seasons )] TJ ET 0.267 0.267 0.267 rg BT 350.281 373.998 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 355.100 376.379 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 357.510 373.998 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 362.328 372.491 Td /F1 9.8 Tf [(. Our data show that the level of hospitalizations )] TJ ET BT 26.250 360.586 Td /F1 9.8 Tf [(in 2013-2014 has exceeded that of the last A/H1N1 epidemic in 2011-12. We have also documented a significant shift in )] TJ ET BT 26.250 348.681 Td /F1 9.8 Tf [(absolute and relative severe disease burden from young individuals \(<30 yrs\) to middle-aged adults 30-59 years, relative to the )] TJ ET BT 26.250 336.777 Td /F1 9.8 Tf [(preceding A/H1N1 epidemic.)] TJ ET BT 26.250 317.372 Td /F1 9.8 Tf [(The observed gradual change in age distribution of hospitalization and deaths in the post 2009 pandemic period is reminiscent )] TJ ET BT 26.250 305.467 Td /F1 9.8 Tf [(of the influenza seasons following the 1918 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 302.107 306.974 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 306.925 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 309.335 306.974 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 318.972 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 321.381 306.974 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 331.019 305.467 Td /F1 9.8 Tf [( and the 1968 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 438.337 306.974 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 447.974 305.467 Td /F1 9.8 Tf [(. A quantitative analysis of )] TJ ET BT 26.250 293.562 Td /F1 9.8 Tf [(excess mortality in the decade following the 1918 influenza pandemic found that the age distribution of influenza-related )] TJ ET BT 26.250 281.658 Td /F1 9.8 Tf [(mortality returned to pre-pandemic mortality levels a few years after the initial pandemic waves as a result of emerging drift )] TJ ET BT 26.250 269.753 Td /F1 9.8 Tf [(variants)] TJ ET 0.267 0.267 0.267 rg BT 60.385 271.260 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 65.203 273.641 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.613 271.260 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.250 269.753 Td /F1 9.8 Tf [(. Hence the age shift seen in the 2011-12 and 2013-14 A/H1N1 epidemics could signal a build up of immunity )] TJ ET BT 26.250 257.848 Td /F1 9.8 Tf [(among younger populations, which has implications for influenza prevention and mitigation strategies.)] TJ ET BT 26.250 238.443 Td /F1 9.8 Tf [(It is now well recognized that during the first year of circulation of the 2009 A/H1N1 influenza pandemic virus, seniors over 60 )] TJ ET BT 26.250 226.539 Td /F1 9.8 Tf [(years enjoyed protection from influenza-related morbidity and mortality. This phenomenon of senior sparing in age cohorts )] TJ ET BT 26.250 214.634 Td /F1 9.8 Tf [(born prior to the 1957 pandemic is consistent with the protective effect of first exposure to antigenically-related A/H1N1 viruses )] TJ ET BT 26.250 202.729 Td /F1 9.8 Tf [(in childhood, which aligns with antigen recycling and original antigenic sin hypotheses)] TJ ET 0.267 0.267 0.267 rg BT 395.288 204.236 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 404.925 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.334 204.236 Td /F4 8.7 Tf [(23)] TJ ET 0.271 0.267 0.267 rg BT 416.972 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 419.381 204.236 Td /F4 8.7 Tf [(24)] TJ ET 0.271 0.267 0.267 rg BT 429.018 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 431.428 204.236 Td /F4 8.7 Tf [(25)] TJ ET 0.271 0.267 0.267 rg BT 441.065 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 443.474 204.236 Td /F4 8.7 Tf [(26)] TJ ET 0.271 0.267 0.267 rg BT 453.112 202.729 Td /F1 9.8 Tf [(. A high fraction of the )] TJ ET BT 26.250 190.824 Td /F1 9.8 Tf [(Mexican population is now presumably protected against the 2009 A/H1N1 influenza virus through natural exposure since 2009 )] TJ ET BT 26.250 178.920 Td /F1 9.8 Tf [(\(children and young adults\), prior immunity \(seniors\) )] TJ ET 0.267 0.267 0.267 rg BT 253.815 180.427 Td /F4 8.7 Tf [(27)] TJ ET 0.271 0.267 0.267 rg BT 263.452 178.920 Td /F1 9.8 Tf [( and by pandemic vaccines. In parallel, waning of immunity is also )] TJ ET BT 26.250 167.015 Td /F1 9.8 Tf [(expected in individuals that are not periodically re-vaccinated. To the best of our knowledge, no serological studies were )] TJ ET BT 26.250 155.110 Td /F1 9.8 Tf [(conducted prior to this epidemic or are currently being carried out in Mexico.)] TJ ET Q q 15.000 30.586 577.500 746.414 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(1.2 \(1.3\) \(Figure 4\). Our R estimate was slightly higher than that estimated for the 2011-12 A/H1N1 season, with R at 1.2 \(1.3\).)] TJ ET 0.965 0.965 0.965 rg 26.250 450.476 555.000 307.119 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 757.595 m 581.250 757.595 l 581.250 756.845 l 26.250 756.845 l f 26.250 450.476 m 581.250 450.476 l 581.250 451.226 l 26.250 451.226 l f q 450.000 0 0 226.500 35.250 521.345 cm /I32 Do Q q 35.250 461.726 537.000 53.619 re W n 0.271 0.267 0.267 rg BT 35.250 505.821 Td /F4 9.8 Tf [(Fig. 4: Model fits \(solid line\) obtained after fitting an exponential curve to the growth phase of the initial epidemic )] TJ ET BT 35.250 493.917 Td /F4 9.8 Tf [(phase of the 2013-14 A/H1N1 epidemic to estimate the initial growth rate based on the case series of laboratory-)] TJ ET BT 35.250 482.012 Td /F4 9.8 Tf [(confirmed A/H1N1 SARI A/H1N1 hospitalizations \(left\) and using a slightly shorter ascending phase as a sensitivity )] TJ ET BT 35.250 470.107 Td /F4 9.8 Tf [(analysis \(right\).)] TJ ET Q BT 26.250 416.255 Td /F4 12.0 Tf [(DISCUSSION)] TJ ET BT 26.250 396.300 Td /F1 9.8 Tf [(We have characterized the epidemiology of a recrudescent wave of pandemic A/H1N1 influenza activity in Mexico during )] TJ ET BT 26.250 384.396 Td /F1 9.8 Tf [(October 2013-January 2014, based on individual-level laboratory-confirmed influenza hospitalizations and deaths, and )] TJ ET BT 26.250 372.491 Td /F1 9.8 Tf [(compared with the well-described epidemiology of earlier A/H1N1 seasons )] TJ ET 0.267 0.267 0.267 rg BT 350.281 373.998 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 355.100 376.379 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 357.510 373.998 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 362.328 372.491 Td /F1 9.8 Tf [(. Our data show that the level of hospitalizations )] TJ ET BT 26.250 360.586 Td /F1 9.8 Tf [(in 2013-2014 has exceeded that of the last A/H1N1 epidemic in 2011-12. We have also documented a significant shift in )] TJ ET BT 26.250 348.681 Td /F1 9.8 Tf [(absolute and relative severe disease burden from young individuals \(<30 yrs\) to middle-aged adults 30-59 years, relative to the )] TJ ET BT 26.250 336.777 Td /F1 9.8 Tf [(preceding A/H1N1 epidemic.)] TJ ET BT 26.250 317.372 Td /F1 9.8 Tf [(The observed gradual change in age distribution of hospitalization and deaths in the post 2009 pandemic period is reminiscent )] TJ ET BT 26.250 305.467 Td /F1 9.8 Tf [(of the influenza seasons following the 1918 influenza pandemic )] TJ ET 0.267 0.267 0.267 rg BT 302.107 306.974 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 306.925 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 309.335 306.974 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 318.972 309.355 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 321.381 306.974 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 331.019 305.467 Td /F1 9.8 Tf [( and the 1968 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 438.337 306.974 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 447.974 305.467 Td /F1 9.8 Tf [(. A quantitative analysis of )] TJ ET BT 26.250 293.562 Td /F1 9.8 Tf [(excess mortality in the decade following the 1918 influenza pandemic found that the age distribution of influenza-related )] TJ ET BT 26.250 281.658 Td /F1 9.8 Tf [(mortality returned to pre-pandemic mortality levels a few years after the initial pandemic waves as a result of emerging drift )] TJ ET BT 26.250 269.753 Td /F1 9.8 Tf [(variants)] TJ ET 0.267 0.267 0.267 rg BT 60.385 271.260 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 65.203 273.641 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.613 271.260 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.250 269.753 Td /F1 9.8 Tf [(. Hence the age shift seen in the 2011-12 and 2013-14 A/H1N1 epidemics could signal a build up of immunity )] TJ ET BT 26.250 257.848 Td /F1 9.8 Tf [(among younger populations, which has implications for influenza prevention and mitigation strategies.)] TJ ET BT 26.250 238.443 Td /F1 9.8 Tf [(It is now well recognized that during the first year of circulation of the 2009 A/H1N1 influenza pandemic virus, seniors over 60 )] TJ ET BT 26.250 226.539 Td /F1 9.8 Tf [(years enjoyed protection from influenza-related morbidity and mortality. This phenomenon of senior sparing in age cohorts )] TJ ET BT 26.250 214.634 Td /F1 9.8 Tf [(born prior to the 1957 pandemic is consistent with the protective effect of first exposure to antigenically-related A/H1N1 viruses )] TJ ET BT 26.250 202.729 Td /F1 9.8 Tf [(in childhood, which aligns with antigen recycling and original antigenic sin hypotheses)] TJ ET 0.267 0.267 0.267 rg BT 395.288 204.236 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 404.925 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.334 204.236 Td /F4 8.7 Tf [(23)] TJ ET 0.271 0.267 0.267 rg BT 416.972 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 419.381 204.236 Td /F4 8.7 Tf [(24)] TJ ET 0.271 0.267 0.267 rg BT 429.018 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 431.428 204.236 Td /F4 8.7 Tf [(25)] TJ ET 0.271 0.267 0.267 rg BT 441.065 206.617 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 443.474 204.236 Td /F4 8.7 Tf [(26)] TJ ET 0.271 0.267 0.267 rg BT 453.112 202.729 Td /F1 9.8 Tf [(. A high fraction of the )] TJ ET BT 26.250 190.824 Td /F1 9.8 Tf [(Mexican population is now presumably protected against the 2009 A/H1N1 influenza virus through natural exposure since 2009 )] TJ ET BT 26.250 178.920 Td /F1 9.8 Tf [(\(children and young adults\), prior immunity \(seniors\) )] TJ ET 0.267 0.267 0.267 rg BT 253.815 180.427 Td /F4 8.7 Tf [(27)] TJ ET 0.271 0.267 0.267 rg BT 263.452 178.920 Td /F1 9.8 Tf [( and by pandemic vaccines. In parallel, waning of immunity is also )] TJ ET BT 26.250 167.015 Td /F1 9.8 Tf [(expected in individuals that are not periodically re-vaccinated. 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!k׮=uׯ_/\022֭[dnԬXBWW_X&744466R*֭;}4榦7VVV_xMKK;p BhT( }zyy9,h4L&!!!::::::>>>p0OOOH--Hooo!}||`߃fq # #n*!444"""|||Z*MP(C65agj)ToW222BBBh4Zss3!KgΜ9` yd~6Xܘ1c`ڵkǏ hʘ===544ZZZRiXXXNNرca&`cccnn^VV6zhՍ7ƌ H9e03gLKK2w[[X,Ά[o8Å{kkR 4߼ysȑ"7o^^^8rww֮ZZZ޺u+""bhhRSSΝSSSa&1caivv.̃GGGJRfq0>{y<ޓ'Obccܹnaaabbd``PUUd0 |+**455!!dbbrݹsۃ1ׯ_Ϙ1#33ѣGFFFDmCCC46 ""  z{{[47$$$ S)G͐*[&ȶD1rƱ6ne% ?(**\0RBHJJBKW^ࠩfpyyW_}u;'8)G-[ x<#u[gggBB;ɤn۶ 0y?3@#ܰa!1 [K[lD!B(##ܹs`DA){3C$lggVaXfffrr2`=ztpppbb"T\f 5[ZZ֭[Ąso}ԩ ӧOC=#Gk'N<}vSf͚!bٳ{]z͛2a!wZѶh" Dooo:nhhg7RRR,X`aa188xphyl6ի ݻ_}V'Oq|pp͛7III={1")G>f["$ _)DzrwŞEmH$yE^VVFׯ_õFbo߾#]&SBp ]zHyT3x ye| 21[p~#&lȒx TT)s Y[[k``cS@ DVVV1ǏG EDD6Tzz:r'r:$d2Q8???//!P(VZedd$9"Hd23t äR… `Mq6JC r;;;m1(Efj>?kDQQQ b1T`mllz5Q́(0FQ09*ioo/S\WWMܰ 7oW`zdo69 p""GO"SDP(JJJ|}})k0 "A2f JˉR D%6o'#ill"Rtĉ!TQQQff&aCCCK,߇{8C/_l61BQ endstream endobj 360 0 obj << /Type /Page /Parent 3 0 R /Annots [ 362 0 R 364 0 R 366 0 R 368 0 R 370 0 R 372 0 R 374 0 R 376 0 R 378 0 R 380 0 R 382 0 R 384 0 R 386 0 R 388 0 R 390 0 R 392 0 R 394 0 R 396 0 R 398 0 R 400 0 R 402 0 R 404 0 R 406 0 R 408 0 R 410 0 R 412 0 R 414 0 R ] /Contents 361 0 R >> endobj 361 0 obj << /Length 28636 >> stream 0.271 0.267 0.267 rg q 15.000 47.458 577.500 729.542 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(For the first time since the emergence of the 2009 pandemic virus, the absolute risk of hospitalization is greater among )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(individuals >=30 yrs compared to that of individuals <30 yrs in Mexico \(Figure 3\). The declining rates of severe cases in younger )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(age groups is most consistent with the build-up of immunity in these age groups. In contrast, seniors still experience relative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(protection against A/H1N1 hospitalization and death compared to persons aged 30-59 yrs in the current epidemic, indicating )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(residual immunity in this population. Residual protection among seniors is consistent with a lack antigenic drift in A/H1N1 )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(viruses circulating in Mexico or elsewhere in winter 2013-14. Overall the age distribution of A/H1N1 is gradually progressing to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(an older adult age risk profile that characterizes seasonal influenza but is not yet that of a typical inter-pandemic season, with )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(90% of deaths occuring in seniors. In the longer term, we expect the pandemic A/H1N1 virus to drift genetically to escape )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(mounting population immunity perhaps with the result that seniors are less protected )] TJ ET 0.267 0.267 0.267 rg BT 400.709 673.745 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 405.527 672.238 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(We estimated a slightly higher reproduction number for the ongoing A/H1N1 epidemic \(R = 1.3 \(95% CI: 1.2-1.3\) than for the )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(2011-2012 A/H1N1 epidemic \(R ~1.2 95% CI: 1.1-1.2\). We note that even a slight difference in R, similar to that reported here, )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(results in a substantial difference in final epidemic size and in the size of interventions required to stop transmission. The slightly )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(higher R measured for the ongoing epidemic could be explained by differences in population immunity through vaccination or )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(natural exposure. Since transmission of the A/H1N1 influenza virus was sporadic in the previous winter of 2012-2013 in Mexico, )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(population immunity may have slightly waned. Further, the early timing of onset of the on-going 2013-2014 season \(early )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(October 2013, Figure 2\) could have prevented the population from getting immunized and reaching protective antibody levels by )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(the time transmission started. Of note, influenza vaccination coverage among the IMSS population has increased in the last )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(three seasons and mid-December estimates were 8.7% \(2011\), 11% \(2012\) and 14% \(2013\). Influenza vaccination through )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(IMSS is focused primarily on high-risk groups including infants, pregnant women, health care workers and seniors. In particular, )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(among seniors >=60 yrs. the influenza vaccination coverage was ~16% in 2011-12 and 2012-13 and 29% in 2013-2014. Finally, )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(we cannot rule out that reporting or measurement issues could account for the observed differences in estimated Rs.)] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(It is also worth comparing the transmission dynamics of the 2013-2014 season with that of the 2009 pandemic. Our R estimate )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(for the ongoing epidemic is lower to that of the spring \(R~1.8-2.1\) and summer \(R~1.6-1.9\) pandemic waves in 2009 in Mexico, )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(but similar to estimates for the fall \(3rd\) 2009 wave \(R~ 1.2-1.3\) )] TJ ET 0.267 0.267 0.267 rg BT 302.331 480.174 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 307.150 478.667 Td /F1 9.8 Tf [( . These declining trends are consistent with a gradual build up )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(of immunity in the first few months and years of A/H1N1 circulation. Further, the gradual shift of A/H1N1 infection towards )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(adults, who transmit less than children due to behavioral and biological differences, may contribute to the post-pandemic decline )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(in R.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(Most countries have experienced several waves of A/H1N1 pandemic activity by now. The Mexican 2013-14 outbreak coincides )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(with a highly-publicized recrudescence of A/H1N1 activity in North America, associated with an increase in young adults )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(hospitalizations and deaths in Canada and the US )] TJ ET 0.267 0.267 0.267 rg BT 245.206 401.246 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 254.843 399.738 Td /F1 9.8 Tf [(. Although there is no serological information specific to Mexico, Canadian )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(surveys indicate low levels of immune protection in young and middle-aged adults prior to the 2013-14 winter, in contrast to )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(children, potentially explaining the recrudescence of young adult cases observed in 2013-14 in the region )] TJ ET 0.267 0.267 0.267 rg BT 482.024 377.436 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 491.661 375.929 Td /F1 9.8 Tf [(. The epidemiology )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(of the 2013-14 Mexican outbreak also echoes the increased severity and transmissibility of the 3)] TJ ET BT 441.356 367.912 Td /F1 8.7 Tf [(rd)] TJ ET BT 449.061 364.024 Td /F1 9.8 Tf [( pandemic wave in the UK in )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(2011-12 )] TJ ET 0.267 0.267 0.267 rg BT 64.733 353.627 Td /F4 8.7 Tf [(29)] TJ ET 0.271 0.267 0.267 rg BT 74.371 352.119 Td /F1 9.8 Tf [(. Gradual build-up of A/H1N1-specific humoral immunity in various age groups likely explains some of the differences )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(reported between countries and successive pandemic waves. However the increased propensity of young and middle aged )] TJ ET BT 26.250 328.310 Td /F1 9.8 Tf [(adults to be infected in later waves of the pandemic, rather than during the initial outbreak, remains intriguing, and could reflect )] TJ ET BT 26.250 316.405 Td /F1 9.8 Tf [(the dynamics of contact rates )] TJ ET 0.267 0.267 0.267 rg BT 155.769 317.912 Td /F4 8.7 Tf [(30)] TJ ET 0.271 0.267 0.267 rg BT 165.406 316.405 Td /F1 9.8 Tf [( or non-specific T-cell mediated immunity )] TJ ET 0.267 0.267 0.267 rg BT 345.284 317.912 Td /F4 8.7 Tf [(31)] TJ ET 0.271 0.267 0.267 rg BT 354.921 316.405 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(In summary our findings indicate a changing age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(deaths in winter 2013-14, relative to the preceding A/H1N1 seasons in 2011-2012 and 2009-10. The proportion of )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(hospitalizations and deaths is increasing particularly among middle aged adults. In contrast, rates of A/H1N1 hospitalizations )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(and deaths are declining significantly among children, consistent with a gradual build up of immunity. This epidemiological shift )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(is reminiscent of outbreaks in historical post-pandemic periods and consistent with on-going influenza outbreaks elsewhere in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(North America. As this epidemic is still underway, it is too early to determine whether its cumulative mortality impact will be more )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(susbtantial than the previous waves, similarly to the 1889 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 320.505 227.079 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 330.142 229.460 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 332.552 227.079 Td /F4 8.7 Tf [(32)] TJ ET 0.271 0.267 0.267 rg BT 342.189 225.572 Td /F1 9.8 Tf [(. A systematic multinational comparison of the )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(epidemiology of pandemic and post-pandemic waves would be useful to shed light on the transmission dynamics and build up )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(of immunity to pandemic viruses, and inform long-term control strategies.)] TJ ET BT 26.250 165.160 Td /F4 12.0 Tf [(Competing interests)] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(The authors declare no relevant competing interests.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 81.149 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 81.149 Td /F1 9.8 Tf [(Chowell G, Echevarra-Zuno S, Viboud C, Simonsen L, Tamerius J, Miller MA, Borja-Aburto VH. Characterizing the )] TJ ET BT 26.250 69.244 Td /F1 9.8 Tf [(epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico. PLoS Med. 2011 May;8\(5\):e1000436. PubMed )] TJ ET BT 26.250 57.339 Td /F1 9.8 Tf [(PMID:21629683.)] TJ ET Q q 15.000 47.458 577.500 729.542 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(For the first time since the emergence of the 2009 pandemic virus, the absolute risk of hospitalization is greater among )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(individuals >=30 yrs compared to that of individuals <30 yrs in Mexico \(Figure 3\). The declining rates of severe cases in younger )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(age groups is most consistent with the build-up of immunity in these age groups. In contrast, seniors still experience relative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(protection against A/H1N1 hospitalization and death compared to persons aged 30-59 yrs in the current epidemic, indicating )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(residual immunity in this population. Residual protection among seniors is consistent with a lack antigenic drift in A/H1N1 )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(viruses circulating in Mexico or elsewhere in winter 2013-14. Overall the age distribution of A/H1N1 is gradually progressing to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(an older adult age risk profile that characterizes seasonal influenza but is not yet that of a typical inter-pandemic season, with )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(90% of deaths occuring in seniors. In the longer term, we expect the pandemic A/H1N1 virus to drift genetically to escape )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(mounting population immunity perhaps with the result that seniors are less protected )] TJ ET 0.267 0.267 0.267 rg BT 400.709 673.745 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 405.527 672.238 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(We estimated a slightly higher reproduction number for the ongoing A/H1N1 epidemic \(R = 1.3 \(95% CI: 1.2-1.3\) than for the )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(2011-2012 A/H1N1 epidemic \(R ~1.2 95% CI: 1.1-1.2\). We note that even a slight difference in R, similar to that reported here, )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(results in a substantial difference in final epidemic size and in the size of interventions required to stop transmission. The slightly )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(higher R measured for the ongoing epidemic could be explained by differences in population immunity through vaccination or )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(natural exposure. Since transmission of the A/H1N1 influenza virus was sporadic in the previous winter of 2012-2013 in Mexico, )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(population immunity may have slightly waned. Further, the early timing of onset of the on-going 2013-2014 season \(early )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(October 2013, Figure 2\) could have prevented the population from getting immunized and reaching protective antibody levels by )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(the time transmission started. Of note, influenza vaccination coverage among the IMSS population has increased in the last )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(three seasons and mid-December estimates were 8.7% \(2011\), 11% \(2012\) and 14% \(2013\). Influenza vaccination through )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(IMSS is focused primarily on high-risk groups including infants, pregnant women, health care workers and seniors. In particular, )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(among seniors >=60 yrs. the influenza vaccination coverage was ~16% in 2011-12 and 2012-13 and 29% in 2013-2014. Finally, )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(we cannot rule out that reporting or measurement issues could account for the observed differences in estimated Rs.)] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(It is also worth comparing the transmission dynamics of the 2013-2014 season with that of the 2009 pandemic. Our R estimate )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(for the ongoing epidemic is lower to that of the spring \(R~1.8-2.1\) and summer \(R~1.6-1.9\) pandemic waves in 2009 in Mexico, )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(but similar to estimates for the fall \(3rd\) 2009 wave \(R~ 1.2-1.3\) )] TJ ET 0.267 0.267 0.267 rg BT 302.331 480.174 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 307.150 478.667 Td /F1 9.8 Tf [( . These declining trends are consistent with a gradual build up )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(of immunity in the first few months and years of A/H1N1 circulation. Further, the gradual shift of A/H1N1 infection towards )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(adults, who transmit less than children due to behavioral and biological differences, may contribute to the post-pandemic decline )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(in R.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(Most countries have experienced several waves of A/H1N1 pandemic activity by now. The Mexican 2013-14 outbreak coincides )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(with a highly-publicized recrudescence of A/H1N1 activity in North America, associated with an increase in young adults )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(hospitalizations and deaths in Canada and the US )] TJ ET 0.267 0.267 0.267 rg BT 245.206 401.246 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 254.843 399.738 Td /F1 9.8 Tf [(. Although there is no serological information specific to Mexico, Canadian )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(surveys indicate low levels of immune protection in young and middle-aged adults prior to the 2013-14 winter, in contrast to )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(children, potentially explaining the recrudescence of young adult cases observed in 2013-14 in the region )] TJ ET 0.267 0.267 0.267 rg BT 482.024 377.436 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 491.661 375.929 Td /F1 9.8 Tf [(. The epidemiology )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(of the 2013-14 Mexican outbreak also echoes the increased severity and transmissibility of the 3)] TJ ET BT 441.356 367.912 Td /F1 8.7 Tf [(rd)] TJ ET BT 449.061 364.024 Td /F1 9.8 Tf [( pandemic wave in the UK in )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(2011-12 )] TJ ET 0.267 0.267 0.267 rg BT 64.733 353.627 Td /F4 8.7 Tf [(29)] TJ ET 0.271 0.267 0.267 rg BT 74.371 352.119 Td /F1 9.8 Tf [(. Gradual build-up of A/H1N1-specific humoral immunity in various age groups likely explains some of the differences )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(reported between countries and successive pandemic waves. However the increased propensity of young and middle aged )] TJ ET BT 26.250 328.310 Td /F1 9.8 Tf [(adults to be infected in later waves of the pandemic, rather than during the initial outbreak, remains intriguing, and could reflect )] TJ ET BT 26.250 316.405 Td /F1 9.8 Tf [(the dynamics of contact rates )] TJ ET 0.267 0.267 0.267 rg BT 155.769 317.912 Td /F4 8.7 Tf [(30)] TJ ET 0.271 0.267 0.267 rg BT 165.406 316.405 Td /F1 9.8 Tf [( or non-specific T-cell mediated immunity )] TJ ET 0.267 0.267 0.267 rg BT 345.284 317.912 Td /F4 8.7 Tf [(31)] TJ ET 0.271 0.267 0.267 rg BT 354.921 316.405 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(In summary our findings indicate a changing age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(deaths in winter 2013-14, relative to the preceding A/H1N1 seasons in 2011-2012 and 2009-10. The proportion of )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(hospitalizations and deaths is increasing particularly among middle aged adults. In contrast, rates of A/H1N1 hospitalizations )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(and deaths are declining significantly among children, consistent with a gradual build up of immunity. This epidemiological shift )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(is reminiscent of outbreaks in historical post-pandemic periods and consistent with on-going influenza outbreaks elsewhere in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(North America. As this epidemic is still underway, it is too early to determine whether its cumulative mortality impact will be more )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(susbtantial than the previous waves, similarly to the 1889 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 320.505 227.079 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 330.142 229.460 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 332.552 227.079 Td /F4 8.7 Tf [(32)] TJ ET 0.271 0.267 0.267 rg BT 342.189 225.572 Td /F1 9.8 Tf [(. A systematic multinational comparison of the )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(epidemiology of pandemic and post-pandemic waves would be useful to shed light on the transmission dynamics and build up )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(of immunity to pandemic viruses, and inform long-term control strategies.)] TJ ET BT 26.250 165.160 Td /F4 12.0 Tf [(Competing interests)] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(The authors declare no relevant competing interests.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 81.149 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 81.149 Td /F1 9.8 Tf [(Chowell G, Echevarra-Zuno S, Viboud C, Simonsen L, Tamerius J, Miller MA, Borja-Aburto VH. Characterizing the )] TJ ET BT 26.250 69.244 Td /F1 9.8 Tf [(epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico. PLoS Med. 2011 May;8\(5\):e1000436. PubMed )] TJ ET BT 26.250 57.339 Td /F1 9.8 Tf [(PMID:21629683.)] TJ ET Q q 15.000 47.458 577.500 729.542 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(For the first time since the emergence of the 2009 pandemic virus, the absolute risk of hospitalization is greater among )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(individuals >=30 yrs compared to that of individuals <30 yrs in Mexico \(Figure 3\). The declining rates of severe cases in younger )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(age groups is most consistent with the build-up of immunity in these age groups. In contrast, seniors still experience relative )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(protection against A/H1N1 hospitalization and death compared to persons aged 30-59 yrs in the current epidemic, indicating )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(residual immunity in this population. Residual protection among seniors is consistent with a lack antigenic drift in A/H1N1 )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(viruses circulating in Mexico or elsewhere in winter 2013-14. Overall the age distribution of A/H1N1 is gradually progressing to )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(an older adult age risk profile that characterizes seasonal influenza but is not yet that of a typical inter-pandemic season, with )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(90% of deaths occuring in seniors. In the longer term, we expect the pandemic A/H1N1 virus to drift genetically to escape )] TJ ET BT 26.250 672.238 Td /F1 9.8 Tf [(mounting population immunity perhaps with the result that seniors are less protected )] TJ ET 0.267 0.267 0.267 rg BT 400.709 673.745 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 405.527 672.238 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(We estimated a slightly higher reproduction number for the ongoing A/H1N1 epidemic \(R = 1.3 \(95% CI: 1.2-1.3\) than for the )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(2011-2012 A/H1N1 epidemic \(R ~1.2 95% CI: 1.1-1.2\). We note that even a slight difference in R, similar to that reported here, )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(results in a substantial difference in final epidemic size and in the size of interventions required to stop transmission. The slightly )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(higher R measured for the ongoing epidemic could be explained by differences in population immunity through vaccination or )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(natural exposure. Since transmission of the A/H1N1 influenza virus was sporadic in the previous winter of 2012-2013 in Mexico, )] TJ ET BT 26.250 593.310 Td /F1 9.8 Tf [(population immunity may have slightly waned. Further, the early timing of onset of the on-going 2013-2014 season \(early )] TJ ET BT 26.250 581.405 Td /F1 9.8 Tf [(October 2013, Figure 2\) could have prevented the population from getting immunized and reaching protective antibody levels by )] TJ ET BT 26.250 569.500 Td /F1 9.8 Tf [(the time transmission started. Of note, influenza vaccination coverage among the IMSS population has increased in the last )] TJ ET BT 26.250 557.595 Td /F1 9.8 Tf [(three seasons and mid-December estimates were 8.7% \(2011\), 11% \(2012\) and 14% \(2013\). Influenza vaccination through )] TJ ET BT 26.250 545.691 Td /F1 9.8 Tf [(IMSS is focused primarily on high-risk groups including infants, pregnant women, health care workers and seniors. In particular, )] TJ ET BT 26.250 533.786 Td /F1 9.8 Tf [(among seniors >=60 yrs. the influenza vaccination coverage was ~16% in 2011-12 and 2012-13 and 29% in 2013-2014. Finally, )] TJ ET BT 26.250 521.881 Td /F1 9.8 Tf [(we cannot rule out that reporting or measurement issues could account for the observed differences in estimated Rs.)] TJ ET BT 26.250 502.476 Td /F1 9.8 Tf [(It is also worth comparing the transmission dynamics of the 2013-2014 season with that of the 2009 pandemic. Our R estimate )] TJ ET BT 26.250 490.572 Td /F1 9.8 Tf [(for the ongoing epidemic is lower to that of the spring \(R~1.8-2.1\) and summer \(R~1.6-1.9\) pandemic waves in 2009 in Mexico, )] TJ ET BT 26.250 478.667 Td /F1 9.8 Tf [(but similar to estimates for the fall \(3rd\) 2009 wave \(R~ 1.2-1.3\) )] TJ ET 0.267 0.267 0.267 rg BT 302.331 480.174 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 307.150 478.667 Td /F1 9.8 Tf [( . These declining trends are consistent with a gradual build up )] TJ ET BT 26.250 466.762 Td /F1 9.8 Tf [(of immunity in the first few months and years of A/H1N1 circulation. Further, the gradual shift of A/H1N1 infection towards )] TJ ET BT 26.250 454.857 Td /F1 9.8 Tf [(adults, who transmit less than children due to behavioral and biological differences, may contribute to the post-pandemic decline )] TJ ET BT 26.250 442.953 Td /F1 9.8 Tf [(in R.)] TJ ET BT 26.250 423.548 Td /F1 9.8 Tf [(Most countries have experienced several waves of A/H1N1 pandemic activity by now. The Mexican 2013-14 outbreak coincides )] TJ ET BT 26.250 411.643 Td /F1 9.8 Tf [(with a highly-publicized recrudescence of A/H1N1 activity in North America, associated with an increase in young adults )] TJ ET BT 26.250 399.738 Td /F1 9.8 Tf [(hospitalizations and deaths in Canada and the US )] TJ ET 0.267 0.267 0.267 rg BT 245.206 401.246 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 254.843 399.738 Td /F1 9.8 Tf [(. Although there is no serological information specific to Mexico, Canadian )] TJ ET BT 26.250 387.834 Td /F1 9.8 Tf [(surveys indicate low levels of immune protection in young and middle-aged adults prior to the 2013-14 winter, in contrast to )] TJ ET BT 26.250 375.929 Td /F1 9.8 Tf [(children, potentially explaining the recrudescence of young adult cases observed in 2013-14 in the region )] TJ ET 0.267 0.267 0.267 rg BT 482.024 377.436 Td /F4 8.7 Tf [(28)] TJ ET 0.271 0.267 0.267 rg BT 491.661 375.929 Td /F1 9.8 Tf [(. The epidemiology )] TJ ET BT 26.250 364.024 Td /F1 9.8 Tf [(of the 2013-14 Mexican outbreak also echoes the increased severity and transmissibility of the 3)] TJ ET BT 441.356 367.912 Td /F1 8.7 Tf [(rd)] TJ ET BT 449.061 364.024 Td /F1 9.8 Tf [( pandemic wave in the UK in )] TJ ET BT 26.250 352.119 Td /F1 9.8 Tf [(2011-12 )] TJ ET 0.267 0.267 0.267 rg BT 64.733 353.627 Td /F4 8.7 Tf [(29)] TJ ET 0.271 0.267 0.267 rg BT 74.371 352.119 Td /F1 9.8 Tf [(. Gradual build-up of A/H1N1-specific humoral immunity in various age groups likely explains some of the differences )] TJ ET BT 26.250 340.215 Td /F1 9.8 Tf [(reported between countries and successive pandemic waves. However the increased propensity of young and middle aged )] TJ ET BT 26.250 328.310 Td /F1 9.8 Tf [(adults to be infected in later waves of the pandemic, rather than during the initial outbreak, remains intriguing, and could reflect )] TJ ET BT 26.250 316.405 Td /F1 9.8 Tf [(the dynamics of contact rates )] TJ ET 0.267 0.267 0.267 rg BT 155.769 317.912 Td /F4 8.7 Tf [(30)] TJ ET 0.271 0.267 0.267 rg BT 165.406 316.405 Td /F1 9.8 Tf [( or non-specific T-cell mediated immunity )] TJ ET 0.267 0.267 0.267 rg BT 345.284 317.912 Td /F4 8.7 Tf [(31)] TJ ET 0.271 0.267 0.267 rg BT 354.921 316.405 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 297.000 Td /F1 9.8 Tf [(In summary our findings indicate a changing age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and )] TJ ET BT 26.250 285.096 Td /F1 9.8 Tf [(deaths in winter 2013-14, relative to the preceding A/H1N1 seasons in 2011-2012 and 2009-10. The proportion of )] TJ ET BT 26.250 273.191 Td /F1 9.8 Tf [(hospitalizations and deaths is increasing particularly among middle aged adults. In contrast, rates of A/H1N1 hospitalizations )] TJ ET BT 26.250 261.286 Td /F1 9.8 Tf [(and deaths are declining significantly among children, consistent with a gradual build up of immunity. This epidemiological shift )] TJ ET BT 26.250 249.381 Td /F1 9.8 Tf [(is reminiscent of outbreaks in historical post-pandemic periods and consistent with on-going influenza outbreaks elsewhere in )] TJ ET BT 26.250 237.477 Td /F1 9.8 Tf [(North America. As this epidemic is still underway, it is too early to determine whether its cumulative mortality impact will be more )] TJ ET BT 26.250 225.572 Td /F1 9.8 Tf [(susbtantial than the previous waves, similarly to the 1889 pandemic )] TJ ET 0.267 0.267 0.267 rg BT 320.505 227.079 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 330.142 229.460 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 332.552 227.079 Td /F4 8.7 Tf [(32)] TJ ET 0.271 0.267 0.267 rg BT 342.189 225.572 Td /F1 9.8 Tf [(. A systematic multinational comparison of the )] TJ ET BT 26.250 213.667 Td /F1 9.8 Tf [(epidemiology of pandemic and post-pandemic waves would be useful to shed light on the transmission dynamics and build up )] TJ ET BT 26.250 201.762 Td /F1 9.8 Tf [(of immunity to pandemic viruses, and inform long-term control strategies.)] TJ ET BT 26.250 165.160 Td /F4 12.0 Tf [(Competing interests)] TJ ET BT 26.250 145.206 Td /F1 9.8 Tf [(The authors declare no relevant competing interests.)] TJ ET BT 26.250 108.603 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 81.149 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 81.149 Td /F1 9.8 Tf [(Chowell G, Echevarra-Zuno S, Viboud C, Simonsen L, Tamerius J, Miller MA, Borja-Aburto VH. Characterizing the )] TJ ET BT 26.250 69.244 Td /F1 9.8 Tf [(epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico. PLoS Med. 2011 May;8\(5\):e1000436. 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[(Zepeda-Lopez HM, Perea-Araujo L, Miliar-Garca A, Dominguez-Lpez A, Xoconostle-Czarez B, Lara-Padilla E, Ramrez )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hernandez JA, Sevilla-Reyes E, Orozco ME, Ahued-Ortega A, Villaseor-Ruiz I, Garcia-Cavazos RJ, Teran LM. Inside the )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(outbreak of the 2009 influenza A \(H1N1\)v virus in Mexico. PLoS One. 2010 Oct 8;5\(10\):e13256. PubMed PMID:20949040.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Borja-Aburto VH, Chowell G, Viboud C, Simonsen L, Miller MA, Grajales-Muiz C, Gonzlez-Bonilla CR, Diaz-Quionez JA, )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Echevarra-Zuno S. Epidemiological characterization of a fourth wave of pandemic A/H1N1 influenza in Mexico, winter 2011-)] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2012: age shift and severity. Arch Med Res. 2012 Oct;43\(7\):563-70. PubMed PMID:23079035.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Charu V, Chowell G, Palacio Mejia LS, Echevarra-Zuno S, Borja-Aburto VH, Simonsen L, Miller MA, Viboud C. 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Proc Natl Acad Sci U S A. 2010 May 11;107\(19\):8778-81.)] TJ ET BT 26.250 406.762 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 406.762 Td /F1 9.8 Tf [(Echevarria-Zuno S, Mejia-Arangure JM, Mar-Obeso AJ, Grajales-Muniz C, Robles-Perez E, Gonzalez-Leon M, et al. )] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009 Dec 19;374\(9707\):2072-9.)] TJ ET BT 26.250 375.453 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 375.453 Td /F1 9.8 Tf [(Centers for Disease Control and Prevention. Serum cross-reactive antibody response to a novel influenza A \(H1N1\) virus )] TJ ET BT 26.250 363.548 Td /F1 9.8 Tf [(after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009 May 22;58\(19\):521-4.)] TJ ET BT 26.250 344.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 344.143 Td /F1 9.8 Tf [(Wallinga J, Lipsitch M. How generation intervals shape the relationship between growth rates and reproductive numbers. )] TJ ET BT 26.250 332.238 Td /F1 9.8 Tf [(Proc Biol Sci. 2007 Feb 22;274\(1609\):599-604. 14. Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, )] TJ ET BT 26.250 320.334 Td /F1 9.8 Tf [(Hollingsworth TD, et al. Pandemic potential of a strain of influenza A \(H1N1\): early findings. Science. 2009 Jun )] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(19;324\(5934\):1557-61.)] TJ ET BT 26.250 289.024 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 289.024 Td /F1 9.8 Tf [(Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD, et al. Pandemic potential of a )] TJ ET BT 26.250 277.119 Td /F1 9.8 Tf [(strain of influenza A \(H1N1\): early findings. Science. 2009 Jun 19;324\(5934\):1557-61.)] TJ ET BT 26.250 257.715 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 257.715 Td /F1 9.8 Tf [(Yang Y, Sugimoto JD, Halloran ME, Basta NE, Chao DL, Matrajt L, et al. 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Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 57.953 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis. 2008 Jan 15;197\(2\):270-8.)] TJ ET Q q 15.000 48.072 577.500 728.928 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Zepeda-Lopez HM, Perea-Araujo L, Miliar-Garca A, Dominguez-Lpez A, Xoconostle-Czarez B, Lara-Padilla E, Ramrez )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hernandez JA, Sevilla-Reyes E, Orozco ME, Ahued-Ortega A, Villaseor-Ruiz I, Garcia-Cavazos RJ, Teran LM. Inside the )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(outbreak of the 2009 influenza A \(H1N1\)v virus in Mexico. PLoS One. 2010 Oct 8;5\(10\):e13256. PubMed PMID:20949040.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Borja-Aburto VH, Chowell G, Viboud C, Simonsen L, Miller MA, Grajales-Muiz C, Gonzlez-Bonilla CR, Diaz-Quionez JA, )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Echevarra-Zuno S. Epidemiological characterization of a fourth wave of pandemic A/H1N1 influenza in Mexico, winter 2011-)] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2012: age shift and severity. Arch Med Res. 2012 Oct;43\(7\):563-70. PubMed PMID:23079035.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Charu V, Chowell G, Palacio Mejia LS, Echevarra-Zuno S, Borja-Aburto VH, Simonsen L, Miller MA, Viboud C. Mortality )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. Clin Infect Dis. )] TJ ET BT 26.250 649.738 Td /F1 9.8 Tf [(2011 Nov;53\(10\):985-93. PubMed PMID:21976464.)] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 630.333 Td /F1 9.8 Tf [(Simonsen L, Spreeuwenberg P, Lustig R, Taylor RJ, Fleming DM, Kroneman M, Van Kerkhove MD, Mounts AW, Paget WJ. )] TJ ET BT 26.250 618.429 Td /F1 9.8 Tf [(Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study. PLoS Med. 2013 )] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(Nov;10\(11\):e1001558. PubMed PMID:24302890.)] TJ ET BT 26.250 587.119 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 587.119 Td /F1 9.8 Tf [(Saglanmak N, Andreasen V, Simonsen L, Mlbak K, Miller MA, Viboud C. Gradual changes in the age distribution of excess )] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(deaths in the years following the 1918 influenza pandemic in Copenhagen: using epidemiological evidence to detect antigenic )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(drift. Vaccine. 2011 Jul 22;29 Suppl 2:B42-8. PubMed PMID:21757103.)] TJ ET BT 26.250 543.905 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 543.905 Td /F1 9.8 Tf [(Olson DR, Simonsen L, Edelson PJ, Morse SS. Epidemiological evidence of an early wave of the 1918 influenza pandemic in )] TJ ET BT 26.250 532.000 Td /F1 9.8 Tf [(New York City. Proc Natl Acad Sci U S A. 2005 Aug 2;102\(31\):11059-63.)] TJ ET BT 26.250 512.595 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 512.595 Td /F1 9.8 Tf [(Chowell G, Viboud C, Simonsen L, Miller MA, Acuna-Soto R. Mortality patterns associated with the 1918 influenza pandemic )] TJ ET BT 26.250 500.691 Td /F1 9.8 Tf [(in Mexico: evidence for a spring herald wave and lack of preexisting immunity in older populations. J Infect Dis. 2010 Aug )] TJ ET BT 26.250 488.786 Td /F1 9.8 Tf [(15;202\(4\):567-75.)] TJ ET BT 26.250 469.381 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 469.381 Td /F1 9.8 Tf [(Chowell G, Viboud C, Simonsen L, Miller MA, Hurtado J, Soto G, et al. The 1918-1920 influenza pandemic in Peru. Vaccine. )] TJ ET BT 26.250 457.476 Td /F1 9.8 Tf [(2011 Jul 22;29 Suppl 2:B21-6.)] TJ ET BT 26.250 438.072 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 438.072 Td /F1 9.8 Tf [(Valleron AJ, Cori A, Valtat S, Meurisse S, Carrat F, Boelle PY. Transmissibility and geographic spread of the 1889 influenza )] TJ ET BT 26.250 426.167 Td /F1 9.8 Tf [(pandemic. Proc Natl Acad Sci U S A. 2010 May 11;107\(19\):8778-81.)] TJ ET BT 26.250 406.762 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 406.762 Td /F1 9.8 Tf [(Echevarria-Zuno S, Mejia-Arangure JM, Mar-Obeso AJ, Grajales-Muniz C, Robles-Perez E, Gonzalez-Leon M, et al. )] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009 Dec 19;374\(9707\):2072-9.)] TJ ET BT 26.250 375.453 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 375.453 Td /F1 9.8 Tf [(Centers for Disease Control and Prevention. Serum cross-reactive antibody response to a novel influenza A \(H1N1\) virus )] TJ ET BT 26.250 363.548 Td /F1 9.8 Tf [(after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009 May 22;58\(19\):521-4.)] TJ ET BT 26.250 344.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 344.143 Td /F1 9.8 Tf [(Wallinga J, Lipsitch M. How generation intervals shape the relationship between growth rates and reproductive numbers. )] TJ ET BT 26.250 332.238 Td /F1 9.8 Tf [(Proc Biol Sci. 2007 Feb 22;274\(1609\):599-604. 14. Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, )] TJ ET BT 26.250 320.334 Td /F1 9.8 Tf [(Hollingsworth TD, et al. Pandemic potential of a strain of influenza A \(H1N1\): early findings. Science. 2009 Jun )] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(19;324\(5934\):1557-61.)] TJ ET BT 26.250 289.024 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 289.024 Td /F1 9.8 Tf [(Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD, et al. Pandemic potential of a )] TJ ET BT 26.250 277.119 Td /F1 9.8 Tf [(strain of influenza A \(H1N1\): early findings. Science. 2009 Jun 19;324\(5934\):1557-61.)] TJ ET BT 26.250 257.715 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 257.715 Td /F1 9.8 Tf [(Yang Y, Sugimoto JD, Halloran ME, Basta NE, Chao DL, Matrajt L, et al. The transmissibility and control of pandemic )] TJ ET BT 26.250 245.810 Td /F1 9.8 Tf [(influenza A \(H1N1\) virus. Science. 2009 Oct 30;326\(5953\):729-33.)] TJ ET BT 26.250 226.405 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 226.405 Td /F1 9.8 Tf [(Cauchemez S, Donnelly CA, Reed C, Ghani AC, Fraser C, Kent CK, et al. Household transmission of 2009 pandemic )] TJ ET BT 26.250 214.500 Td /F1 9.8 Tf [(influenza A \(H1N1\) virus in the United States. N Engl J Med. 2009 Dec 31;361\(27\):2619-27.)] TJ ET BT 26.250 195.096 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 195.096 Td /F1 9.8 Tf [(Cowling BJ, Chan KH, Fang VJ, Lau LL, So HC, Fung RO, et al. Comparative epidemiology of pandemic and seasonal )] TJ ET BT 26.250 183.191 Td /F1 9.8 Tf [(influenza A in households. N Engl J Med. 2010 Jun 10;362\(23\):2175-84.)] TJ ET BT 26.250 163.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 163.786 Td /F1 9.8 Tf [(Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a )] TJ ET BT 26.250 151.881 Td /F1 9.8 Tf [(pattern of changing age distribution. J Infect Dis. 1998 Jul;178\(1\):53-60.)] TJ ET BT 26.250 132.477 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 132.477 Td /F1 9.8 Tf [(Simonsen L, Reichert TA, Miller M. The Virtues of antigenic sin: consequences of pandemic recycling on influenza-)] TJ ET BT 26.250 120.572 Td /F1 9.8 Tf [(associated mortality: Options for the control of influenza V: International Congress Series; 2004.)] TJ ET BT 26.250 101.167 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 101.167 Td /F1 9.8 Tf [(Viboud C, Grais RF, Lafont BA, Miller MA, Simonsen L. Multinational impact of the 1968 Hong Kong influenza pandemic: )] TJ ET BT 26.250 89.262 Td /F1 9.8 Tf [(evidence for a smoldering pandemic. J Infect Dis. 2005 Jul 15;192\(2\):233-48.)] TJ ET BT 26.250 69.858 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 69.858 Td /F1 9.8 Tf [(Andreasen V, Viboud C, Simonsen L. Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 57.953 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis. 2008 Jan 15;197\(2\):270-8.)] TJ ET Q q 15.000 48.072 577.500 728.928 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Zepeda-Lopez HM, Perea-Araujo L, Miliar-Garca A, Dominguez-Lpez A, Xoconostle-Czarez B, Lara-Padilla E, Ramrez )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hernandez JA, Sevilla-Reyes E, Orozco ME, Ahued-Ortega A, Villaseor-Ruiz I, Garcia-Cavazos RJ, Teran LM. Inside the )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(outbreak of the 2009 influenza A \(H1N1\)v virus in Mexico. PLoS One. 2010 Oct 8;5\(10\):e13256. PubMed PMID:20949040.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Borja-Aburto VH, Chowell G, Viboud C, Simonsen L, Miller MA, Grajales-Muiz C, Gonzlez-Bonilla CR, Diaz-Quionez JA, )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Echevarra-Zuno S. Epidemiological characterization of a fourth wave of pandemic A/H1N1 influenza in Mexico, winter 2011-)] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2012: age shift and severity. Arch Med Res. 2012 Oct;43\(7\):563-70. PubMed PMID:23079035.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Charu V, Chowell G, Palacio Mejia LS, Echevarra-Zuno S, Borja-Aburto VH, Simonsen L, Miller MA, Viboud C. Mortality )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. Clin Infect Dis. )] TJ ET BT 26.250 649.738 Td /F1 9.8 Tf [(2011 Nov;53\(10\):985-93. PubMed PMID:21976464.)] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 630.333 Td /F1 9.8 Tf [(Simonsen L, Spreeuwenberg P, Lustig R, Taylor RJ, Fleming DM, Kroneman M, Van Kerkhove MD, Mounts AW, Paget WJ. )] TJ ET BT 26.250 618.429 Td /F1 9.8 Tf [(Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study. PLoS Med. 2013 )] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(Nov;10\(11\):e1001558. PubMed PMID:24302890.)] TJ ET BT 26.250 587.119 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 587.119 Td /F1 9.8 Tf [(Saglanmak N, Andreasen V, Simonsen L, Mlbak K, Miller MA, Viboud C. Gradual changes in the age distribution of excess )] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(deaths in the years following the 1918 influenza pandemic in Copenhagen: using epidemiological evidence to detect antigenic )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(drift. Vaccine. 2011 Jul 22;29 Suppl 2:B42-8. PubMed PMID:21757103.)] TJ ET BT 26.250 543.905 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 543.905 Td /F1 9.8 Tf [(Olson DR, Simonsen L, Edelson PJ, Morse SS. Epidemiological evidence of an early wave of the 1918 influenza pandemic in )] TJ ET BT 26.250 532.000 Td /F1 9.8 Tf [(New York City. Proc Natl Acad Sci U S A. 2005 Aug 2;102\(31\):11059-63.)] TJ ET BT 26.250 512.595 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 512.595 Td /F1 9.8 Tf [(Chowell G, Viboud C, Simonsen L, Miller MA, Acuna-Soto R. Mortality patterns associated with the 1918 influenza pandemic )] TJ ET BT 26.250 500.691 Td /F1 9.8 Tf [(in Mexico: evidence for a spring herald wave and lack of preexisting immunity in older populations. J Infect Dis. 2010 Aug )] TJ ET BT 26.250 488.786 Td /F1 9.8 Tf [(15;202\(4\):567-75.)] TJ ET BT 26.250 469.381 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 469.381 Td /F1 9.8 Tf [(Chowell G, Viboud C, Simonsen L, Miller MA, Hurtado J, Soto G, et al. The 1918-1920 influenza pandemic in Peru. Vaccine. )] TJ ET BT 26.250 457.476 Td /F1 9.8 Tf [(2011 Jul 22;29 Suppl 2:B21-6.)] TJ ET BT 26.250 438.072 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 438.072 Td /F1 9.8 Tf [(Valleron AJ, Cori A, Valtat S, Meurisse S, Carrat F, Boelle PY. Transmissibility and geographic spread of the 1889 influenza )] TJ ET BT 26.250 426.167 Td /F1 9.8 Tf [(pandemic. Proc Natl Acad Sci U S A. 2010 May 11;107\(19\):8778-81.)] TJ ET BT 26.250 406.762 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 406.762 Td /F1 9.8 Tf [(Echevarria-Zuno S, Mejia-Arangure JM, Mar-Obeso AJ, Grajales-Muniz C, Robles-Perez E, Gonzalez-Leon M, et al. )] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009 Dec 19;374\(9707\):2072-9.)] TJ ET BT 26.250 375.453 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 375.453 Td /F1 9.8 Tf [(Centers for Disease Control and Prevention. Serum cross-reactive antibody response to a novel influenza A \(H1N1\) virus )] TJ ET BT 26.250 363.548 Td /F1 9.8 Tf [(after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009 May 22;58\(19\):521-4.)] TJ ET BT 26.250 344.143 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 344.143 Td /F1 9.8 Tf [(Wallinga J, Lipsitch M. How generation intervals shape the relationship between growth rates and reproductive numbers. )] TJ ET BT 26.250 332.238 Td /F1 9.8 Tf [(Proc Biol Sci. 2007 Feb 22;274\(1609\):599-604. 14. Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, )] TJ ET BT 26.250 320.334 Td /F1 9.8 Tf [(Hollingsworth TD, et al. Pandemic potential of a strain of influenza A \(H1N1\): early findings. Science. 2009 Jun )] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(19;324\(5934\):1557-61.)] TJ ET BT 26.250 289.024 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 289.024 Td /F1 9.8 Tf [(Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD, et al. Pandemic potential of a )] TJ ET BT 26.250 277.119 Td /F1 9.8 Tf [(strain of influenza A \(H1N1\): early findings. Science. 2009 Jun 19;324\(5934\):1557-61.)] TJ ET BT 26.250 257.715 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 257.715 Td /F1 9.8 Tf [(Yang Y, Sugimoto JD, Halloran ME, Basta NE, Chao DL, Matrajt L, et al. The transmissibility and control of pandemic )] TJ ET BT 26.250 245.810 Td /F1 9.8 Tf [(influenza A \(H1N1\) virus. Science. 2009 Oct 30;326\(5953\):729-33.)] TJ ET BT 26.250 226.405 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 226.405 Td /F1 9.8 Tf [(Cauchemez S, Donnelly CA, Reed C, Ghani AC, Fraser C, Kent CK, et al. Household transmission of 2009 pandemic )] TJ ET BT 26.250 214.500 Td /F1 9.8 Tf [(influenza A \(H1N1\) virus in the United States. N Engl J Med. 2009 Dec 31;361\(27\):2619-27.)] TJ ET BT 26.250 195.096 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 195.096 Td /F1 9.8 Tf [(Cowling BJ, Chan KH, Fang VJ, Lau LL, So HC, Fung RO, et al. Comparative epidemiology of pandemic and seasonal )] TJ ET BT 26.250 183.191 Td /F1 9.8 Tf [(influenza A in households. N Engl J Med. 2010 Jun 10;362\(23\):2175-84.)] TJ ET BT 26.250 163.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 163.786 Td /F1 9.8 Tf [(Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a )] TJ ET BT 26.250 151.881 Td /F1 9.8 Tf [(pattern of changing age distribution. J Infect Dis. 1998 Jul;178\(1\):53-60.)] TJ ET BT 26.250 132.477 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 132.477 Td /F1 9.8 Tf [(Simonsen L, Reichert TA, Miller M. The Virtues of antigenic sin: consequences of pandemic recycling on influenza-)] TJ ET BT 26.250 120.572 Td /F1 9.8 Tf [(associated mortality: Options for the control of influenza V: International Congress Series; 2004.)] TJ ET BT 26.250 101.167 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 101.167 Td /F1 9.8 Tf [(Viboud C, Grais RF, Lafont BA, Miller MA, Simonsen L. Multinational impact of the 1968 Hong Kong influenza pandemic: )] TJ ET BT 26.250 89.262 Td /F1 9.8 Tf [(evidence for a smoldering pandemic. J Infect Dis. 2005 Jul 15;192\(2\):233-48.)] TJ ET BT 26.250 69.858 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 69.858 Td /F1 9.8 Tf [(Andreasen V, Viboud C, Simonsen L. Epidemiologic characterization of the 1918 influenza pandemic summer wave in )] TJ ET BT 26.250 57.953 Td /F1 9.8 Tf [(Copenhagen: implications for pandemic control strategies. J Infect Dis. 2008 Jan 15;197\(2\):270-8.)] 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 Outbreaks)] TJ ET Q endstream endobj 418 0 obj << /Type /Page /Parent 3 0 R /Contents 419 0 R >> endobj 419 0 obj << /Length 11491 >> stream 0.271 0.267 0.267 rg q 15.000 393.786 577.500 383.214 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al. Severe respiratory disease )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med. 2009 Aug 13;361\(7\):674-9.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Vaillant L, La Ruche G, Tarantola A, Barboza P. Epidemiology of fatal cases associated with pandemic H1N1 influenza )] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(2009. Euro Surveill. 2009;14\(33\).)] TJ ET BT 26.250 697.357 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 697.357 Td /F1 9.8 Tf [(Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary Estimates of Mortality and Years of Life Lost )] TJ ET BT 26.250 685.452 Td /F1 9.8 Tf [(Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons. PLoS Curr. )] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(2010:RRN1153.)] TJ ET BT 26.250 654.143 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 654.143 Td /F1 9.8 Tf [(Miller MA, Viboud C, Balinska M, Simonsen L. The signature features of influenza pandemics--implications for policy. N )] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(Engl J Med. 2009 Jun 18;360\(25\):2595-8.)] TJ ET BT 26.250 622.833 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 622.833 Td /F1 9.8 Tf [(Reichert T, Chowell G, Nishiura H, Christensen RA, McCullers JA. Does Glycosylation as a modifier of Original Antigenic )] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC Infect Dis. 2010;10:5.)] TJ ET BT 26.250 591.524 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 591.524 Td /F1 9.8 Tf [(Elizondo-Montemayor L, Alvarez MM, Hernandez-Torre M, Ugalde-Casas PA, Lam-Franco L, Bustamante-Careaga H, et al. )] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(Seroprevalence of antibodies to influenza A/H1N1/2009 among transmission risk groups after the second wave in Mexico, by a )] TJ ET BT 26.250 567.714 Td /F1 9.8 Tf [(virus-free ELISA method. Int J Infect Dis. 2011 Aug 18.)] TJ ET BT 26.250 548.310 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 548.310 Td /F1 9.8 Tf [(Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2013/14 )] TJ ET BT 26.250 536.405 Td /F1 9.8 Tf [(vaccine effectiveness against influenza A\(H1N1\)pdm09 from Canadas sentinel surveillance network, January 2014. Euro )] TJ ET BT 26.250 524.500 Td /F1 9.8 Tf [(Surveill 2014;19\(5\).)] TJ ET BT 26.250 505.095 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 505.095 Td /F1 9.8 Tf [(Dorigatti I, Cauchemez S, Ferguson NM. Increased transmissibility explains the third wave of infection by the 2009 H1N1 )] TJ ET BT 26.250 493.191 Td /F1 9.8 Tf [(pandemic virus in England. Proc Natl Acad Sci U S A. 2013 Aug 13;110\(33\):13422-7.)] TJ ET BT 26.250 473.786 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 473.786 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Hupert N, Grenfell B, Meyers LA. The shifting demographic landscape of pandemic influenza. )] TJ ET BT 26.250 461.881 Td /F1 9.8 Tf [(PLoS One. 2010;5\(2\):e9360.)] TJ ET BT 26.250 442.476 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 442.476 Td /F1 9.8 Tf [(Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature. 2003 Mar )] TJ ET BT 26.250 430.572 Td /F1 9.8 Tf [(27;422\(6930\):428-33.)] TJ ET BT 26.250 411.167 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 411.167 Td /F1 9.8 Tf [(Stuart-Harris CH. Pandemic influenza: an unresolved problem in prevention. J Infect Dis. 1970 Jul-Aug;122\(1\):108-15.)] TJ ET Q q 15.000 393.786 577.500 383.214 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al. Severe respiratory disease )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med. 2009 Aug 13;361\(7\):674-9.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Vaillant L, La Ruche G, Tarantola A, Barboza P. Epidemiology of fatal cases associated with pandemic H1N1 influenza )] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(2009. Euro Surveill. 2009;14\(33\).)] TJ ET BT 26.250 697.357 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 697.357 Td /F1 9.8 Tf [(Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary Estimates of Mortality and Years of Life Lost )] TJ ET BT 26.250 685.452 Td /F1 9.8 Tf [(Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons. PLoS Curr. )] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(2010:RRN1153.)] TJ ET BT 26.250 654.143 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 654.143 Td /F1 9.8 Tf [(Miller MA, Viboud C, Balinska M, Simonsen L. The signature features of influenza pandemics--implications for policy. N )] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(Engl J Med. 2009 Jun 18;360\(25\):2595-8.)] TJ ET BT 26.250 622.833 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 622.833 Td /F1 9.8 Tf [(Reichert T, Chowell G, Nishiura H, Christensen RA, McCullers JA. Does Glycosylation as a modifier of Original Antigenic )] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC Infect Dis. 2010;10:5.)] TJ ET BT 26.250 591.524 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 591.524 Td /F1 9.8 Tf [(Elizondo-Montemayor L, Alvarez MM, Hernandez-Torre M, Ugalde-Casas PA, Lam-Franco L, Bustamante-Careaga H, et al. )] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(Seroprevalence of antibodies to influenza A/H1N1/2009 among transmission risk groups after the second wave in Mexico, by a )] TJ ET BT 26.250 567.714 Td /F1 9.8 Tf [(virus-free ELISA method. Int J Infect Dis. 2011 Aug 18.)] TJ ET BT 26.250 548.310 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 548.310 Td /F1 9.8 Tf [(Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2013/14 )] TJ ET BT 26.250 536.405 Td /F1 9.8 Tf [(vaccine effectiveness against influenza A\(H1N1\)pdm09 from Canadas sentinel surveillance network, January 2014. Euro )] TJ ET BT 26.250 524.500 Td /F1 9.8 Tf [(Surveill 2014;19\(5\).)] TJ ET BT 26.250 505.095 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 505.095 Td /F1 9.8 Tf [(Dorigatti I, Cauchemez S, Ferguson NM. Increased transmissibility explains the third wave of infection by the 2009 H1N1 )] TJ ET BT 26.250 493.191 Td /F1 9.8 Tf [(pandemic virus in England. Proc Natl Acad Sci U S A. 2013 Aug 13;110\(33\):13422-7.)] TJ ET BT 26.250 473.786 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 473.786 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Hupert N, Grenfell B, Meyers LA. The shifting demographic landscape of pandemic influenza. )] TJ ET BT 26.250 461.881 Td /F1 9.8 Tf [(PLoS One. 2010;5\(2\):e9360.)] TJ ET BT 26.250 442.476 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 442.476 Td /F1 9.8 Tf [(Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature. 2003 Mar )] TJ ET BT 26.250 430.572 Td /F1 9.8 Tf [(27;422\(6930\):428-33.)] TJ ET BT 26.250 411.167 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 411.167 Td /F1 9.8 Tf [(Stuart-Harris CH. Pandemic influenza: an unresolved problem in prevention. J Infect Dis. 1970 Jul-Aug;122\(1\):108-15.)] TJ ET Q q 15.000 393.786 577.500 383.214 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(22.)] TJ ET BT 43.553 759.976 Td /F1 9.8 Tf [(Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al. Severe respiratory disease )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(concurrent with the circulation of H1N1 influenza. N Engl J Med. 2009 Aug 13;361\(7\):674-9.)] TJ ET BT 26.250 728.667 Td /F1 9.8 Tf [(23.)] TJ ET BT 43.553 728.667 Td /F1 9.8 Tf [(Vaillant L, La Ruche G, Tarantola A, Barboza P. Epidemiology of fatal cases associated with pandemic H1N1 influenza )] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(2009. Euro Surveill. 2009;14\(33\).)] TJ ET BT 26.250 697.357 Td /F1 9.8 Tf [(24.)] TJ ET BT 43.553 697.357 Td /F1 9.8 Tf [(Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary Estimates of Mortality and Years of Life Lost )] TJ ET BT 26.250 685.452 Td /F1 9.8 Tf [(Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons. PLoS Curr. )] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(2010:RRN1153.)] TJ ET BT 26.250 654.143 Td /F1 9.8 Tf [(25.)] TJ ET BT 43.553 654.143 Td /F1 9.8 Tf [(Miller MA, Viboud C, Balinska M, Simonsen L. The signature features of influenza pandemics--implications for policy. N )] TJ ET BT 26.250 642.238 Td /F1 9.8 Tf [(Engl J Med. 2009 Jun 18;360\(25\):2595-8.)] TJ ET BT 26.250 622.833 Td /F1 9.8 Tf [(26.)] TJ ET BT 43.553 622.833 Td /F1 9.8 Tf [(Reichert T, Chowell G, Nishiura H, Christensen RA, McCullers JA. Does Glycosylation as a modifier of Original Antigenic )] TJ ET BT 26.250 610.929 Td /F1 9.8 Tf [(Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC Infect Dis. 2010;10:5.)] TJ ET BT 26.250 591.524 Td /F1 9.8 Tf [(27.)] TJ ET BT 43.553 591.524 Td /F1 9.8 Tf [(Elizondo-Montemayor L, Alvarez MM, Hernandez-Torre M, Ugalde-Casas PA, Lam-Franco L, Bustamante-Careaga H, et al. )] TJ ET BT 26.250 579.619 Td /F1 9.8 Tf [(Seroprevalence of antibodies to influenza A/H1N1/2009 among transmission risk groups after the second wave in Mexico, by a )] TJ ET BT 26.250 567.714 Td /F1 9.8 Tf [(virus-free ELISA method. Int J Infect Dis. 2011 Aug 18.)] TJ ET BT 26.250 548.310 Td /F1 9.8 Tf [(28.)] TJ ET BT 43.553 548.310 Td /F1 9.8 Tf [(Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2013/14 )] TJ ET BT 26.250 536.405 Td /F1 9.8 Tf [(vaccine effectiveness against influenza A\(H1N1\)pdm09 from Canadas sentinel surveillance network, January 2014. Euro )] TJ ET BT 26.250 524.500 Td /F1 9.8 Tf [(Surveill 2014;19\(5\).)] TJ ET BT 26.250 505.095 Td /F1 9.8 Tf [(29.)] TJ ET BT 43.553 505.095 Td /F1 9.8 Tf [(Dorigatti I, Cauchemez S, Ferguson NM. Increased transmissibility explains the third wave of infection by the 2009 H1N1 )] TJ ET BT 26.250 493.191 Td /F1 9.8 Tf [(pandemic virus in England. Proc Natl Acad Sci U S A. 2013 Aug 13;110\(33\):13422-7.)] TJ ET BT 26.250 473.786 Td /F1 9.8 Tf [(30.)] TJ ET BT 43.553 473.786 Td /F1 9.8 Tf [(Bansal S, Pourbohloul B, Hupert N, Grenfell B, Meyers LA. The shifting demographic landscape of pandemic influenza. )] TJ ET BT 26.250 461.881 Td /F1 9.8 Tf [(PLoS One. 2010;5\(2\):e9360.)] TJ ET BT 26.250 442.476 Td /F1 9.8 Tf [(31.)] TJ ET BT 43.553 442.476 Td /F1 9.8 Tf [(Ferguson NM, Galvani AP, Bush RM. Ecological and immunological determinants of influenza evolution. Nature. 2003 Mar )] TJ ET BT 26.250 430.572 Td /F1 9.8 Tf [(27;422\(6930\):428-33.)] TJ ET BT 26.250 411.167 Td /F1 9.8 Tf [(32.)] TJ ET BT 43.553 411.167 Td /F1 9.8 Tf [(Stuart-Harris CH. Pandemic influenza: an unresolved problem in prevention. 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