UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Epidemiology of pandemic H1N1 influenza ('swine influenza')

Author
Anna R Thorner, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH

INTRODUCTION

In late March and early April 2009, an outbreak of H1N1 influenza A virus infection was detected in Mexico, with subsequent cases observed in many other countries including the United States [1,2]. In June 2009, the World Health Organization (WHO) raised its pandemic alert level to the highest level, phase 6, indicating widespread community transmission on at least two continents [3,4]. The pandemic was declared to be over in August 2010 [5].

The epidemiology, transmission, and virology of pandemic H1N1 influenza A virus infection will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of pandemic H1N1 influenza A virus infection are discussed separately. (See "Clinical manifestations and diagnosis of pandemic H1N1 influenza ('swine influenza')" and "Treatment and prevention of pandemic H1N1 influenza ('swine influenza')".)

The epidemiology of seasonal and avian (H5N1) influenza virus infections is discussed separately. (See "Epidemiology of influenza" and "Epidemiology, transmission, and pathogenesis of avian influenza".)

HISTORICAL PERSPECTIVE

The pandemic that began in March 2009 was caused by an H1N1 influenza A virus that represents a quadruple reassortment of two swine strains, one human strain, and one avian strain of influenza; the largest proportion of genes came from swine influenza viruses. (See 'Genetic and antigenic characterization' below.)

Illness with influenza in pigs was first recognized during the influenza pandemic of 1918 to 1919, and a swine influenza virus was first isolated from a human in 1974 [6-8]. In 1976, swine influenza virus caused a respiratory illness with one fatality among 13 soldiers in Fort Dix, New Jersey [9]. No exposure to pigs was found. A subsequent epidemiologic study showed that up to 230 soldiers had been infected with the virus [6,10].

                                   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Dec 02 00:00:00 GMT 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Centers for Disease Control and Prevention (CDC). Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep 2009; 58:467.
  2. World Health Organization. Influenza-like illness in the United States and Mexico, 24 April 2009. http://www.who.int/csr/don/2009_04_24/en/index.html (Accessed on April 27, 2009).
  3. World Health Organization. World now at the start of 2009 influenza pandemic. http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html (Accessed on June 11, 2009).
  4. Fineberg HV. Pandemic preparedness and response--lessons from the H1N1 influenza of 2009. N Engl J Med 2014; 370:1335.
  5. World Health Organization. In focus: H1N1 now in the post-pandemic period. August 10, 2010. http://www.who.int/csr/disease/swineflu/en/index.html (Accessed on September 21, 2010).
  6. Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis 2007; 44:1084.
  7. Smith TF, Burgert EO Jr, Dowdle WR, et al. Isolation of swine influenza virus from autopsy lung tissue of man. N Engl J Med 1976; 294:708.
  8. Zimmer SM, Burke DS. Historical perspective--Emergence of influenza A (H1N1) viruses. N Engl J Med 2009; 361:279.
  9. Gaydos JC, Hodder RA, Top FH Jr, et al. Swine influenza A at Fort Dix, New Jersey (January-February 1976). I. Case finding and clinical study of cases. J Infect Dis 1977; 136 Suppl:S356.
  10. Gaydos JC, Hodder RA, Top FH Jr, et al. Swine influenza A at Fort Dix, New Jersey (January-February 1976). II. Transmission and morbidity in units with cases. J Infect Dis 1977; 136 Suppl:S363.
  11. Dawood FS, Dong L, Liu F, et al. A pre-pandemic outbreak of triple-reassortant swine influenza virus infection among university students, South Dakota, 2008. J Infect Dis 2011; 204:1165.
  12. Khan K, Arino J, Hu W, et al. Spread of a novel influenza A (H1N1) virus via global airline transportation. N Engl J Med 2009; 361:212.
  13. Morens DM, Taubenberger JK, Fauci AS. The 2009 H1N1 pandemic influenza virus: what next? MBio 2010; 1.
  14. World Health Organization. Pandemic (H1N1) 2009 - update 86. http://www.who.int/csr/don/2010_02_5/en/index.html (Accessed on February 09, 2010).
  15. United States Centers for Disease Control and Prevention. 2009-2010 Influenza Season Week 20 ending May 22, 2010. http://www.cdc.gov/flu/weekly/ (Accessed on June 11, 2010).
  16. Jhung MA, Swerdlow D, Olsen SJ, et al. Epidemiology of 2009 pandemic influenza A (H1N1) in the United States. Clin Infect Dis 2011; 52 Suppl 1:S13.
  17. Brammer L, Blanton L, Epperson S, et al. Surveillance for influenza during the 2009 influenza A (H1N1) pandemic-United States, April 2009-March 2010. Clin Infect Dis 2011; 52 Suppl 1:S27.
  18. Chao DL, Halloran ME, Longini IM Jr. School opening dates predict pandemic influenza A(H1N1) outbreaks in the United States. J Infect Dis 2010; 202:877.
  19. World Health Organization. Pandemic (H1N1) 2009 - update 112, 6 August 2010. http://www.who.int/csr/don/2010_08_06/en/index.html (Accessed on October 04, 2010).
  20. Changes in reporting requirements for pandemic (H1N1) 2009 infection http://www.who.int/csr/disease/swineflu/notes/h1n1_surveillance_20090710/en/index.html (Accessed on October 14, 2011).
  21. Reed C, Angulo FJ, Swerdlow DL, et al. Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July 2009. Emerg Infect Dis 2009; 15:2004.
  22. Shrestha SS, Swerdlow DL, Borse RH, et al. Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010). Clin Infect Dis 2011; 52 Suppl 1:S75.
  23. United States Centers for Disease Control and Prevention. CDC estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the United States, April – December 12, 2009 http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm (Accessed on January 19, 2010).
  24. United States Centers for Disease Control and Prevention. 2009 H1N1 early outbreak and disease characteristics http://www.cdc.gov/h1n1flu/surveillanceqa.htm (Accessed on October 13, 2011).
  25. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360:2605.
  26. Belshe RB. Implications of the emergence of a novel H1 influenza virus. N Engl J Med 2009; 360:2667.
  27. Miller E, Hoschler K, Hardelid P, et al. Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet 2010; 375:1100.
  28. Fisman DN, Savage R, Gubbay J, et al. Older age and a reduced likelihood of 2009 H1N1 virus infection. N Engl J Med 2009; 361:2000.
  29. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009; 361:1945.
  30. Skowronski DM, Hottes TS, McElhaney JE, et al. Immuno-epidemiologic correlates of pandemic H1N1 surveillance observations: higher antibody and lower cell-mediated immune responses with advanced age. J Infect Dis 2011; 203:158.
  31. United States Centers for Disease Control and Prevention. Interim guidance on infection control measures for 2009 h1n1 influenza in healthcare settings, including protection of healthcare personnel http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm (Accessed on October 14, 2011).
  32. Yoo SJ, Moon SJ, Kuak EY, et al. Frequent detection of pandemic (H1N1) 2009 virus in stools of hospitalized patients. J Clin Microbiol 2010; 48:2314.
  33. United States Centers for Disease Control and Prevention. Interim CDC guidance for nonpharmaceutical community mitigation in response to human infections with swine influenza (H1N1) virus http://www.cdc.gov/swineflu/mitigation.htm (Accessed on October 14, 2011).
  34. Centers for Disease Control and Prevention (CDC). Update: swine influenza A (H1N1) infections--California and Texas, April 2009. MMWR Morb Mortal Wkly Rep 2009; 58:435.
  35. Libster R, Bugna J, Coviello S, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med 2010; 362:45.
  36. Wise ME, De Perio M, Halpin J, et al. Transmission of pandemic (H1N1) 2009 influenza to healthcare personnel in the United States. Clin Infect Dis 2011; 52 Suppl 1:S198.
  37. Witkop CT, Duffy MR, Macias EA, et al. Novel Influenza A (H1N1) outbreak at the U.S. Air Force Academy: epidemiology and viral shedding duration. Am J Prev Med 2010; 38:121.
  38. Cao B, Li XW, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med 2009; 361:2507.
  39. Ling LM, Chow AL, Lye DC, et al. Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis 2010; 50:963.
  40. Bhattarai A, Villanueva J, Palekar RS, et al. Viral shedding duration of pandemic influenza A H1N1 virus during an elementary school outbreak--Pennsylvania, May-June 2009. Clin Infect Dis 2011; 52 Suppl 1:S102.
  41. To KK, Hung IF, Li IW, et al. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 2010; 50:850.
  42. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza, Bautista E, Chotpitayasunondh T, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010; 362:1708.
  43. Lessler J, Reich NG, Cummings DA, et al. Outbreak of 2009 pandemic influenza A (H1N1) at a New York City school. N Engl J Med 2009; 361:2628.
  44. Yang Y, Sugimoto JD, Halloran ME, et al. The transmissibility and control of pandemic influenza A (H1N1) virus. Science 2009; 326:729.
  45. Cauchemez S, Donnelly CA, Reed C, et al. Household transmission of 2009 pandemic influenza A (H1N1) virus in the United States. N Engl J Med 2009; 361:2619.
  46. Crum-Cianflone NF, Blair PJ, Faix D, et al. Clinical and epidemiologic characteristics of an outbreak of novel H1N1 (swine origin) influenza A virus among United States military beneficiaries. Clin Infect Dis 2009; 49:1801.
  47. Iuliano AD, Reed C, Guh A, et al. Notes from the field: outbreak of 2009 pandemic influenza A (H1N1) virus at a large public university in Delaware, April-May 2009. Clin Infect Dis 2009; 49:1811.
  48. Chen MI, Lee VJ, Lim WY, et al. 2009 influenza A(H1N1) seroconversion rates and risk factors among distinct adult cohorts in Singapore. JAMA 2010; 303:1383.
  49. Fraser C, Donnelly CA, Cauchemez S, et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science 2009; 324:1557.
  50. World Health Organization. Assessing the severity of an influenza pandemic, 11 May 2009 http://www.who.int/csr/disease/swineflu/assess/disease_swineflu_assess_20090511/en/index.html (Accessed on October 14, 2011).
  51. Center for Infectious Disease Research and Policy. CDC: H1N1 spreads about as readily as seasonal flu, May 20, 2009 http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/may2009attack.html (Accessed on October 14, 2011).
  52. Centers for Disease Control and Prevention (CDC). Introduction and transmission of 2009 pandemic influenza A (H1N1) Virus--Kenya, June-July 2009. MMWR Morb Mortal Wkly Rep 2009; 58:1143.
  53. France AM, Jackson M, Schrag S, et al. Household transmission of 2009 influenza A (H1N1) virus after a school-based outbreak in New York City, April-May 2009. J Infect Dis 2010; 201:984.
  54. Cowling BJ, Chan KH, Fang VJ, et al. Comparative epidemiology of pandemic and seasonal influenza A in households. N Engl J Med 2010; 362:2175.
  55. Chowell G, Echevarría-Zuno S, Viboud C, et al. Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico. PLoS Med 2011; 8:e1000436.
  56. Jackson ML, France AM, Hancock K, et al. Serologically confirmed household transmission of 2009 pandemic influenza A (H1N1) virus during the first pandemic wave--New York City, April-May 2009. Clin Infect Dis 2011; 53:455.
  57. Papenburg J, Baz M, Hamelin MÈ, et al. Household transmission of the 2009 pandemic A/H1N1 influenza virus: elevated laboratory‐confirmed secondary attack rates and evidence of asymptomatic infections. Clin Infect Dis 2010; 51:1033.
  58. Donnelly CA, Finelli L, Cauchemez S, et al. Serial intervals and the temporal distribution of secondary infections within households of 2009 pandemic influenza A (H1N1): implications for influenza control recommendations. Clin Infect Dis 2011; 52 Suppl 1:S123.
  59. Iuliano AD, Dawood FS, Silk BJ, et al. Investigating 2009 pandemic influenza A (H1N1) in US schools: what have we learned? Clin Infect Dis 2011; 52 Suppl 1:S161.
  60. Earn DJ, He D, Loeb MB, et al. Effects of school closure on incidence of pandemic influenza in Alberta, Canada. Ann Intern Med 2012; 156:173.
  61. Copeland DL, Basurto-Davila R, Chung W, et al. Effectiveness of a school district closure for pandemic influenza A (H1N1) on acute respiratory illnesses in the community: a natural experiment. Clin Infect Dis 2013; 56:509.
  62. Cauchemez S, Bhattarai A, Marchbanks TL, et al. Role of social networks in shaping disease transmission during a community outbreak of 2009 H1N1 pandemic influenza. Proc Natl Acad Sci U S A 2011; 108:2825.
  63. Marchbanks TL, Bhattarai A, Fagan RP, et al. An outbreak of 2009 pandemic influenza A (H1N1) virus infection in an elementary school in Pennsylvania. Clin Infect Dis 2011; 52 Suppl 1:S154.
  64. Guh A, Reed C, Gould LH, et al. Transmission of 2009 pandemic influenza A (H1N1) at a Public University--Delaware, April-May 2009. Clin Infect Dis 2011; 52 Suppl 1:S131.
  65. Seto WH, Cowling BJ, Lam HS, et al. Clinical and nonclinical health care workers faced a similar risk of acquiring 2009 pandemic H1N1 infection. Clin Infect Dis 2011; 53:280.
  66. Marshall C, Kelso A, McBryde E, et al. Pandemic (H1N1) 2009 risk for frontline health care workers. Emerg Infect Dis 2011; 17:1000.
  67. Simmerman JM, Suntarattiwong P, Levy J, et al. Influenza virus contamination of common household surfaces during the 2009 influenza A (H1N1) pandemic in Bangkok, Thailand: implications for contact transmission. Clin Infect Dis 2010; 51:1053.
  68. De Vleeschauwer A, Van Poucke S, Braeckmans D, et al. Efficient transmission of swine-adapted but not wholly avian influenza viruses among pigs and from pigs to ferrets. J Infect Dis 2009; 200:1884.
  69. Choi MJ, Torremorell M, Bender JB, et al. Live Animal Markets in Minnesota: A Potential Source for Emergence of Novel Influenza A Viruses and Interspecies Transmission. Clin Infect Dis 2015; 61:1355.
  70. Ito T, Couceiro JN, Kelm S, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 1998; 72:7367.
  71. Thacker E, Janke B. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas. J Infect Dis 2008; 197 Suppl 1:S19.
  72. Wang TT, Palese P. Unraveling the mystery of swine influenza virus. Cell 2009; 137:983.
  73. Vijaykrishna D, Smith GJ, Pybus OG, et al. Long-term evolution and transmission dynamics of swine influenza A virus. Nature 2011; 473:519.
  74. Shinde V, Bridges CB, Uyeki TM, et al. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med 2009; 360:2616.
  75. Olsen CW. The emergence of novel swine influenza viruses in North America. Virus Res 2002; 85:199.
  76. Vincent AL, Ma W, Lager KM, et al. Swine influenza viruses a North American perspective. Adv Virus Res 2008; 72:127.
  77. World Health Organization. Influenza A (H1N1) - update 13, 4 May 2009 http://www.who.int/csr/don/2009_05_04/en/index.html (Accessed on October 14, 2011).
  78. Forgie SE, Keenliside J, Wilkinson C, et al. Swine outbreak of pandemic influenza A virus on a Canadian research farm supports human-to-swine transmission. Clin Infect Dis 2011; 52:10.
  79. Gray GC, Baker WS. Editorial commentary: the problem with pigs: it's not about bacon. Clin Infect Dis 2011; 52:19.
  80. Centers for Disease Control and Prevention (CDC). Update: Influenza A (H3N2)v transmission and guidelines - five states, 2011. MMWR Morb Mortal Wkly Rep 2012; 60:1741.
  81. Centers for Disease Control and Prevention (CDC). Notes from the field: Outbreak of influenza A (H3N2) virus among persons and swine at a county fair--Indiana, July 2012. MMWR Morb Mortal Wkly Rep 2012; 61:561.
  82. Centers for Disease Control and Prevention. First H3N2 variant virus infection reported for 2012. http://www.cdc.gov/flu/spotlights/h3n2v-variant-utah.htm (Accessed on August 10, 2012).
  83. Centers for Disease Control and Prevention (CDC). CDC Health Advisory. Variant influenza virus (H3N2v) infections. http://emergency.cdc.gov/HAN/han00351.asp (Accessed on July 17, 2013).
  84. Finelli L, Swerdlow DL. The emergence of influenza A (H3N2)v virus: what we learned from the first wave. Clin Infect Dis 2013; 57 Suppl 1:S1.
  85. Epperson S, Jhung M, Richards S, et al. Human infections with influenza A(H3N2) variant virus in the United States, 2011-2012. Clin Infect Dis 2013; 57 Suppl 1:S4.
  86. Jhung MA, Epperson S, Biggerstaff M, et al. Outbreak of variant influenza A(H3N2) virus in the United States. Clin Infect Dis 2013; 57:1703.
  87. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 2012; 12:687.
  88. Simonsen L, Spreeuwenberg P, Lustig R, et al. Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study. PLoS Med 2013; 10:e1001558.
  89. Viboud C, Miller M, Olson D, et al. Preliminary Estimates of Mortality and Years of Life Lost Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons. PLoS Curr 2010; 2:RRN1153.
  90. Butler D. Portrait of a year-old pandemic. Nature 2010; 464:1112.
  91. World Health Organization. Human infection with new influenza A (H1N1) virus: clinical observations from Mexico and other affected countries, May 2009 http://www.who.int/wer/2009/wer8421.pdf (Accessed on October 13, 2011).
  92. Centers for Disease Control and Prevention (CDC). Hospitalized patients with novel influenza A (H1N1) virus infection - California, April-May, 2009. MMWR Morb Mortal Wkly Rep 2009; 58:536.
  93. Centers for Disease Control and Prevention (CDC). Update: novel influenza A (H1N1) virus infections - worldwide, May 6, 2009. MMWR Morb Mortal Wkly Rep 2009; 58:453.
  94. World Health Organization. Human infection with pandemic A (H1N1) 2009 influenza virus: clinical observations in hospitalized patients, Americas, July 2009 - update. Weekly epidemiological record 2009 http://www.who.int/wer/2009/wer8430/en/index.html (Accessed on October 14, 2011).
  95. Fowlkes AL, Arguin P, Biggerstaff MS, et al. Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States, April-July 2009. Clin Infect Dis 2011; 52 Suppl 1:S60.
  96. Louie JK, Acosta M, Winter K, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 2009; 302:1896.
  97. Charu V, Chowell G, Palacio Mejia LS, et al. Mortality burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. Clin Infect Dis 2011; 53:985.
  98. Lee EH, Wu C, Lee EU, et al. Fatalities associated with the 2009 H1N1 influenza A virus in New York city. Clin Infect Dis 2010; 50:1498.
  99. Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States, 2009-10 season. MMWR Morb Mortal Wkly Rep 2010; 59:901.
  100. Skarbinski J, Jain S, Bramley A, et al. Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009. Clin Infect Dis 2011; 52 Suppl 1:S50.
  101. Armstrong GL, Brammer L, Finelli L. Timely assessment of the severity of the 2009 H1N1 influenza pandemic. Clin Infect Dis 2011; 52 Suppl 1:S83.
  102. Centers for Disease Control and Prevention (CDC). Severe illness from 2009 pandemic influenza A (H1N1)--Utah, 2009-10 influenza season. MMWR Morb Mortal Wkly Rep 2011; 60:1310.
  103. Cox CM, D'Mello T, Perez A, et al. Increase in rates of hospitalization due to laboratory-confirmed influenza among children and adults during the 2009-10 influenza pandemic. J Infect Dis 2012; 206:1350.
  104. Reed C, Chaves SS, Perez A, et al. Complications among adults hospitalized with influenza: a comparison of seasonal influenza and the 2009 H1N1 pandemic. Clin Infect Dis 2014; 59:166.
  105. Randolph AG, Vaughn F, Sullivan R, et al. Critically ill children during the 2009-2010 influenza pandemic in the United States. Pediatrics 2011; 128:e1450.
  106. Cox CM, Blanton L, Dhara R, et al. 2009 Pandemic influenza A (H1N1) deaths among children--United States, 2009-2010. Clin Infect Dis 2011; 52 Suppl 1:S69.
  107. Presanis AM, Pebody RG, Paterson BJ, et al. Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian evidence synthesis. BMJ 2011; 343:d5408.
  108. Sachedina N, Donaldson LJ. Paediatric mortality related to pandemic influenza A H1N1 infection in England: an observational population-based study. Lancet 2010; 376:1846.
  109. Bishop JF, Murnane MP, Owen R. Australia's winter with the 2009 pandemic influenza A (H1N1) virus. N Engl J Med 2009; 361:2591.
  110. Echevarría-Zuno S, Mejía-Aranguré JM, Mar-Obeso AJ, et al. Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet 2009; 374:2072.
  111. Wu JT, Ma ES, Lee CK, et al. The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis 2010; 51:1184.
  112. United States Centers for Disease Control and Prevention. 2009 H1N1 flu: situation update http://www.cdc.gov/h1n1flu/update.htm (Accessed on October 14, 2011).
  113. Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009; 361:1935.
  114. The New York Times. 2 more swine flu deaths http://www.nytimes.com/2009/05/11/health/23webflu.html?emc=tnt&tntemail0=y (Accessed on October 14, 2011).
  115. ANZIC Influenza Investigators, Webb SA, Pettilä V, et al. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 2009; 361:1925.
  116. United States Centers for Disease Control and Prevention. Novel H1N1 flu: facts and figures http://www.cdc.gov/h1n1flu/surveillanceqa.htm (Accessed on October 14, 2011).
  117. Gordon CL, Johnson PD, Permezel M, et al. Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency. Clin Infect Dis 2010; 50:672.
  118. O'Riordan S, Barton M, Yau Y, et al. Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza. CMAJ 2010; 182:39.
  119. Centers for Disease Control and Prevention (CDC). Patients hospitalized with 2009 pandemic influenza A (H1N1) - New York City, May 2009. MMWR Morb Mortal Wkly Rep 2010; 58:1436.
  120. Kloepfer KM, Olenec JP, Lee WM, et al. Increased H1N1 infection rate in children with asthma. Am J Respir Crit Care Med 2012; 185:1275.
  121. Strouse JJ, Reller ME, Bundy DG, et al. Severe pandemic H1N1 and seasonal influenza in children and young adults with sickle cell disease. Blood 2010; 116:3431.
  122. Peters PJ, Skarbinski J, Louie JK, et al. HIV-infected hospitalized patients with 2009 pandemic influenza A (pH1N1)--United States, spring and summer 2009. Clin Infect Dis 2011; 52 Suppl 1:S183.
  123. Perez CM, Dominguez MI, Ceballos ME, et al. Pandemic influenza A (H1N1) in HIV-1-infected patients. AIDS 2010; 24:2867.
  124. Riera M, Payeras A, Marcos MA, et al. Clinical presentation and prognosis of the 2009 H1N1 influenza A infection in HIV-1-infected patients: a Spanish multicenter study. AIDS 2010; 24:2461.
  125. Kumar D, Michaels MG, Morris MI, et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis 2010; 10:521.
  126. Smud A, Nagel CB, Madsen E, et al. Pandemic influenza A/H1N1 virus infection in solid organ transplant recipients: a multicenter study. Transplantation 2010; 90:1458.
  127. Choi SM, Boudreault AA, Xie H, et al. Differences in clinical outcomes after 2009 influenza A/H1N1 and seasonal influenza among hematopoietic cell transplant recipients. Blood 2011; 117:5050.
  128. Espinosa-Aguilar L, Green JS, Forrest GN, et al. Novel H1N1 influenza in hematopoietic stem cell transplantation recipients: two centers' experiences. Biol Blood Marrow Transplant 2011; 17:566.
  129. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; 374:451.
  130. Hewagama S, Walker SP, Stuart RL, et al. 2009 H1N1 influenza A and pregnancy outcomes in Victoria, Australia. Clin Infect Dis 2010; 50:686.
  131. Siston AM, Rasmussen SA, Honein MA, et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010; 303:1517.
  132. Creanga AA, Johnson TF, Graitcer SB, et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstet Gynecol 2010; 115:717.
  133. Miller AC, Safi F, Hussain S, et al. Novel influenza A(H1N1) virus among gravid admissions. Arch Intern Med 2010; 170:868.
  134. Centers for Disease Control and Prevention (CDC). Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1)--United States, April 2009-August 2010. MMWR Morb Mortal Wkly Rep 2011; 60:1193.
  135. Louie JK, Acosta M, Jamieson DJ, et al. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med 2010; 362:27.
  136. United States Centers for Disease Control and Prevention. Pregnant women and novel influenza A (H1N1): Considerations for clinicians http://www.cdc.gov/h1n1flu/clinician_pregnant.htm (Accessed on October 14, 2011).
  137. Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ 2007; 176:463.
  138. United States Centers for Disease Control and Prevention. Weekly 2009 H1N1 Flu Media Briefing, October 1, 2009 http://www.cdc.gov/media/transcripts/2009/t091001.htm (Accessed on October 14, 2011).
  139. World Health Organization. Pandemic influenza in pregnant women http://www.who.int/csr/disease/swineflu/notes/h1n1_pregnancy_20090731/en/index.html (Accessed on October 14, 2011).
  140. Maraví-Poma E, Martin-Loeches I, Regidor E, et al. Severe 2009 A/H1N1v influenza in pregnant women in Spain. Crit Care Med 2011; 39:945.
  141. Centers for Disease Control and Prevention (CDC). 2009 pandemic influenza A (H1N1) in pregnant women requiring intensive care - New York City, 2009. MMWR Morb Mortal Wkly Rep 2010; 59:321.
  142. Domínguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically Ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 2009; 302:1880.
  143. Pierce M, Kurinczuk JJ, Spark P, et al. Perinatal outcomes after maternal 2009/H1N1 infection: national cohort study. BMJ 2011; 342:d3214.
  144. Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009; 302:1872.
  145. Wenger JD, Castrodale LJ, Bruden DL, et al. 2009 Pandemic influenza A H1N1 in Alaska: temporal and geographic characteristics of spread and increased risk of hospitalization among Alaska Native and Asian/Pacific Islander people. Clin Infect Dis 2011; 52 Suppl 1:S189.
  146. Centers for Disease Control and Prevention (CDC). Deaths related to 2009 pandemic influenza A (H1N1) among American Indian/Alaska Natives - 12 states, 2009. MMWR Morb Mortal Wkly Rep 2009; 58:1341.
  147. Louie JK, Acosta M, Samuel MC, et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 2011; 52:301.
  148. Díaz E, Rodríguez A, Martin-Loeches I, et al. Impact of obesity in patients infected with 2009 influenza A(H1N1). Chest 2011; 139:382.
  149. Tsatsanis C, Margioris AN, Kontoyiannis DP. Association between H1N1 infection severity and obesity-adiponectin as a potential etiologic factor. J Infect Dis 2010; 202:459.
  150. Zhang AJ, To KK, Li C, et al. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J Infect Dis 2013; 207:1270.
  151. World Health Organization. Swine flu illness in the United States and Mexico - update 2, 26 April 2009 http://www.who.int/csr/don/2009_04_26/en/index.html (Accessed on October 14, 2011).
  152. Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009; 325:197.
  153. Trifonov V, Khiabanian H, Rabadan R. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N Engl J Med 2009; 361:115.
  154. Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009; 459:931.
  155. Cohen J. Swine flu outbreak. Out of Mexico? Scientists ponder swine flu's origins. Science 2009; 324:700.
  156. Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009; 459:1122.
  157. Morens DM, Taubenberger JK, Fauci AS. The persistent legacy of the 1918 influenza virus. N Engl J Med 2009; 361:225.
  158. Igarashi M, Ito K, Yoshida R, et al. Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. PLoS One 2010; 5:e8553.
  159. Chen H, Wen X, To KK, et al. Quasispecies of the D225G substitution in the hemagglutinin of pandemic influenza A(H1N1) 2009 virus from patients with severe disease in Hong Kong, China. J Infect Dis 2010; 201:1517.
  160. Bastien N, Antonishyn NA, Brandt K, et al. Human infection with a triple-reassortant swine influenza A(H1N1) virus containing the hemagglutinin and neuraminidase genes of seasonal influenza virus. J Infect Dis 2010; 201:1178.
  161. Zhang J, Zhang Z, Fan X, et al. 2009 pandemic H1N1 influenza virus replicates in human lung tissues. J Infect Dis 2010; 201:1522.
  162. Couch RB, Atmar RL, Franco LM, et al. Antibody correlates and predictors of immunity to naturally occurring influenza in humans and the importance of antibody to the neuraminidase. J Infect Dis 2013; 207:974.
  163. Agrati C, Gioia C, Lalle E, et al. Association of profoundly impaired immune competence in H1N1v-infected patients with a severe or fatal clinical course. J Infect Dis 2010; 202:681.
  164. Zhou J, To KK, Dong H, et al. A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J Infect Dis 2012; 206:495.
  165. Cheng Z, Zhou J, To KK, et al. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza. J Infect Dis 2015; 212:1214.
  166. Monsalvo AC, Batalle JP, Lopez MF, et al. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nat Med 2011; 17:195.