Epidemiology of Infectious Complications of H1N1 Influenza Virus Infection

Epidemiology of Infectious Complications of H1N1 Influenza Virus Infection Lyn Finelli, DrPH, MS Lead, Influenza Surveillance and Outbreak Response Epidemiology and Prevention Branch Influenza Division INFLUENZA DIVISION

Complications of Seasonal Influenza Respiratory Cardiac Neurologic Musculoskeletal Exacerbation of chronic disease INFLUENZA DIVISION

EID 2006;12(6):881 INFLUENZA DIVISION

Finelli L, et al. Pediatrics 2008 INFLUENZA DIVISION

CDC Emerging Infections Program (EIP) Surveillance for Influenza-Associated Hospitalizations Population-based surveillance system in 10 states 7% US population Case Definition: Hospitalized with laboratory confirmed influenza Case ascertainment by review of admission, discharge, laboratory and infection control logs Chart review conducted and analysis of ICD9 codes Emerging Infections Program Participating Counties INFLUENZA DIVISION

Influenza Associated Hospitalization Surveillance ICD 9 Codes indicating bacterial complications, 2003-04 through 2007-08 seasons Children N=4,097 Condition Number % All pneumonia 908 22% Influenza with pneumonia 672 16% Pneumonia organism NOS 169 4% Bacterial pneumonia, NOS 22 1% Specific bacterial pneumonia (S. aureus most common) 40 1% Empyema 5 0% All Sepsis 153 4% Sepsis/Septicemia/Bacteremia 110 3% Septic shock/shock 19 0% Other specific sepsis 12 0% INFLUENZA DIVISION

Influenza Associated Hospitalization Surveillance ICD 9 Codes indicating bacterial complications, 2003-04 through 2007-08 seasons Children N=4,097 Condition Number % Other Respiratory Infection 810 20% Otitis Media 349 9% Bronchiolitis 275 7% Strep pharyngitis 39 1% Sinusitis 35 1% Bronchitis 33 1% Conjunctivitis 28 1% Pharyngitis 18 0% Laryngitis 14 0% Tracheitis 13 0% Mastoiditis 3 0% Peritonsillar abscess 2 0% Epiglotitis 1 0% INFLUENZA DIVISION

Influenza associated hospitalization surveillance Bacterial pathogens identified from sterile sites in children, 2003-04 through 2007-08 seasons No./% Co-infection Organism 03-04 N=1306 30/2% 04-05 N=615 15/2% 05-06 N=712 16/2% 06-07 N=523 8/1.5% 07-08 N=859 19/2% Staphylococcus aureus 2 5 5 2 10 Streptococcus pneumoniae 4 1 2 0 4 Group A Streptococcus 0 2 2 0 2 Escherichia coli 2 0 2 1 0 Neisseria meningitidis 0 0 0 0 0 Haemophilus influenzae 3 0 0 0 0 Acinetobacter spp. (iwoffii) 1 0 0 0 0 Group B Streptococcus 0 0 1 0 0 Pseudomonas aeruginosa 1 0 0 1 0 Klebsiella oxytoca 1 0 0 1 1 Other assorted 16 7 4 3 2 INFLUENZA DIVISION

Influenza Associated Hospitalization Surveillance ICD 9 Codes indicating bacterial complications, 2005-06 through 2007-08 seasons Adults N=5,173 Condition Number % All Pneumonia 1757 34 Influenza with pneumonia 1075 21 Pneumonia NOS 324 6 Bacterial pneumonia, NOS 89 2 Specific bacterial pneumonia (Staph most common) 173 7 Pneumonitis 77 1 All Sepsis 610 12 Septicemia/Sepsis/Bacteremia 420 8 Septic Shock/Shock 93 2 Specific bacteria sepsis (Staph most common) 97 2 INFLUENZA DIVISION

Influenza Associated Hospitalization Surveillance ICD 9 Codes indicating bacterial complications, 2005-06 through 2007-08 seasons Adults N=5,173 Condition Number % Other Respiratory Infection 297 6 Bronchitis 155 3 URI 57 1 Sinusitis 54 1 Strep throat 12 0 Acute pharyngitis 9 0 Otitis media 7 0 Peritonsillar abscess 3 0 All GI/GU 491 9 UTI 367 7 Diarrhea (+/_) 81 2 Clostridium difficile 43 1 INFLUENZA DIVISION

Influenza associated hospitalization surveillance Bacterial pathogens identified from sterile sites in adults, 2005-06 through 2007-08 seasons No./% Co-infected Organism 2005-06 N=1228 43/3.5% 2006-07 N=756 41/5.4% Staphylococcus aureus (sens.) 9 8 43 Methicillin-resistant S. aureus 8 7 52 Streptococcus pneumoniae 7 5 13 Group A Streptococcus 3 4 4 2007-08 N=3071 143/4.7% Escherichia coli 0 4 7 Haemophilus influenzae 0 0 3 Neisseria meningitidis 0 1 0 Acinetobacter spp. (iwoffii) 1 1 1 Group B Streptococcus 1 0 1 Klebsiella oxytoca 1 1 0 Unknown pathogen 13 10 19 75-88% of bacterial cultures were identified within 48 hours of admission INFLUENZA DIVISION

Summary EIP Data Bacterial Complications of Seasonal Influenza Adults Pneumonia 34% Sepsis shock common 12% UTI 7% Resp Infection (assorted) 6% Diarrhea 3% Children Pneumonia 22% Resp Infection (assorted) 20% OM, sinusitis, pharyngitis bronchitis Sepsis 3% Sterile Sites S. aureus has increased in frequency and comprised approximately 50% of sterile site isolates in 2007-08 S. pneumoniae and GAS remain important in adults and children H. influenzae infections rare INFLUENZA DIVISION

Summary of 2009 pandemic H1N1 Events Between April 15-17, 2009, 2 cases of febrile respiratory illness residents of adjacent counties in southern California swine influenza A (H1N1) virus Worldwide pandemic ensued November 1, 2009 in US >1000 lab confirmed deaths >22,000 lab confirmed hospitalizations Estimated millions of symptomatic cases INFLUENZA DIVISION

10/3 10/17 9 8 7 6 5 4 3 2 1 0 Percentage of Visits for Influenza-like Illness (ILI) Reported by the Outpatient Influenza-like Illness Surveillance Network (ILINet), National Summary 2008-09 and Previous Two Seasons 11/1 11/15 11/29 12/13 12/27 1/10 1/24 2/7 2/21 3/7 3/21 4/4 4/18 5/2 5/16 5/30 6/13 6/27 7/11 7/25 8/8 8/22 9/5 9/19 Week Ending Dates 2006-07 2007-08 2008-09 National Baseline 8.0% 10/4 10/18 % of Visits for ILI

Weekly Influenza Activity Reported by State Health Departments

Weekly Influenza Activity Reported by State Health Departments

Brief Review of Published Literature

Hospitalized Patients with 2009 H1N1 Influenza US Complications N=272 % Death 19 7 Bloodstream infection (E.coli, S. pneumoniae, MRSA) 3/182 1.6 Bacterial infection other than blood (GAS, S. pneumoniae) 3 Radiologically confirmed pneumonia 100/249 40 Bilateral infiltrates 66/100 66 ICU Admission 67 25 ICU days 5 days median Mechanical Ventilation 42 17 Ventilator Days 9 days median ARDS 24 10 Patients who died or were admitted to ICU were more likely to have neurologic disorder, pneumonia and ARDS Jain, S et. al. Hospitalized Patients with H1N1 Influenza in the US, April June 2009. NEJM 2009;361

Critically Ill Patients with 2009 Influenza H1N1 Infection - Canada Characteristics and underlying conditions 168 confirmed or probable H1N1 infections Median age 32.3 years, 60% male, 30% < 18 years Major co-morbidity 30.4% (CHF. Renal ds, CVD, liver ds, malignancy) any co-morbidity 98.2% Most common co-morbidities: lung ds, obesity, hypertension, diabetes, h/o smoking Obesity 33.3% Outcomes 29 died (17%) Pneumonia 54 (32.1%), 41 patients with pathogen identified: 18 S. aureus and 5 S. pneumoniae ICU days median 12 days Ventilator days median 12 days Primary causes of death ARDS, hypoxemia, sepsis, multi-organ failure, and COPD Kumar A et al., Critically Ill Patients with 2009 Influenza H1N1 Infection in Canada, JAMA Express 2009 October 12, online

Hospitalized Adults and Children

Influenza Associated Hospitalization Surveillance Complications in hospitalized children 2009 H1N1 (Apr 15-Aug 31) (N=495) Complication No. % Respiratory Pneumonia 109 22 Hypoxemia 77 16 Acute Respiratory Failure 61 12 Empyema 4 1 Pleural effusion 13 3 Asthma exacerbation 10 2 Bronchitis 14 3 Otitis Media 34 7 Pharyng/Laryng/Tracheits/Sinusitis 13 3 Shock 15 3 Sepsis 8 2 Encephalopathy/encephalitis 4 1 Myositis 7 1 ICU Admission 20% Mechanical ventilation 7% Death 1%

Influenza Associated Hospitalization Surveillance Complications in hospitalized adults 2009 H1N1 (Apr 15-Present) N=976 Complication No. % Respiratory Pneumonia 141 19 Acute Respiratory Failure 149 19 Pleural effusion 15 2 Hemoptysis w pneumonia/itis 13 2 Bronchitis 23 3 Acute exacerbation of COPD 39 5 Asthma exacerbation 41 5 ICU Admission 22% Mechanical ventilation 13% Death 5% Shock/Septic Shock 35 5 Sepsis 99 13 Encephalopathy/encephalitis 14 2 Heart Failure 61 8 Rhabdomyolysis 14 2 Cardiomyopathy 16 2 Seizure 38 5 Myositis Acute Renal Failure 6 65 1 8

Organisms cultured from sterile sites in children and adults hospitalized with 2009 H1N1 influenza (April present) Children (N=8/13) n (%) Adults (N=22/26) n (%) S. aureus 6 (75) S. aureus 7 (32) S. pneumoniae 2 (25) S. pneumoniae 8 (36) GAS 0 GAS 6 (27) H. influenzae 0 H. influenzae 1 (5)

Deaths in Adults and Children

Characteristics of children with influenza-associated mortality -- seasonal and 2009 H1N1 influenza Seasonal Influenza N=336 2009 H1N1 Influenza Median age in years (range) 9 11 N=114 Median days from onset to death 4 6 Location of death: ED or home 37% 24% Location of death: ICU 54% 73% Arrested Outside Hospital 32% 20%

Complications among children with influenza-associated mortality -- seasonal and 2009 H1N1 influenza Seasonal Influenza N=244*/336 2009 H1N1 Influenza N=91*/114 % % CXR confirmed pneumonia 51 62 ARDS 33 43 Invasive Bacterial Co-Infection 21 25 Sepsis 16 18 Shock 20 23 Seizures 20 8 Encephalopathy/Encephalitis 11 10 Bronchiolitis 5 2 Croup 3 0 Viral Co-infection 8 0 Reye Syndrome 0 1 *Among children with known complications

Invasive organisms identified among children with influenza associated mortality, seasonal and 2009 H1N1 influenza Organism MRSA S. aureus methicillin sens S. aureus sensitivity unk. Group A Strep Enterococcus spp (VRE =1) Enterobacter cloaccae Klebsiella pneumoniae Pseudomonas aeruginosa Streptococcus viridans grp. Streptococcus spp. S. Pneumoniae Other Seasonal N=67* % 2009 H1N1 N=23/91 26 38.8% 7 30.4% 13 19.4% 2 8.7% 4 6.0% 2 8.7% 10 14.9% 2 8.7% 3 4.5% 1 4.3% 2 3.0% 0 0.0% 2 3.0% 1 4.3% 0 0.0% 1 4.3% 2 3.0% 0 0.0% 1 1.5% 5 21.7% 3 4.5% 3 13.0% 8 11.9% 2 8.7% % *Multiple bacterial pathogens identified in seven children Multiple bacterial pathogens identified in one child

Complications and Cause of Death among Fatal Cases N=299 78% admitted to ICU 78% ventilated Reported Cause of Death % Pneumonia 25 ARDS 12 Respiratory Failure 13 Cardiac Disease 9 Sepsis Syndromes 9 Organ Failure 6 Chronic Lung Disease 5

Updated Information on Pregnant Women with H1N1 (April 15-August 21, 2009) 700+ pregnant women with confirmed or probable 2009 H1N1 influenza ~ 100 pregnant patients admitted to ICU 28 deaths in pregnant women among 484 total H1N1 deaths (6%) >90% in third trimester Primary viral pneumonia with ARDS most common complication Jamieson DJ et al., Lancet 374:451-8, 2009, Siston A, unpublished data

Conclusions The majority of complications in children and adults are infectious All complications described are consistent with those in seasonal influenza Pneumonia, sepsis, URI, encephalitis, myositis Hemorrhagic viral pneumonia seems to occur with greater frequency than in seasonal influenza Persons at risk for complications are a little different from seasonal influenza Median age of those hospitalized and dying is younger Larger proportion of children and young adults and have significant underlying conditions, especially neurodevelopmental disorders in children

Conclusions Pregnant women are at high risk for severe outcome from seasonal and H1N1 influenza % with bacterial co-infection of those hospitalized and dying from 2009 H1N1 is similar to seasonal influenza S. aureus (MRSA and MSSA) and S. pneumoniae are predominant pathogens S. pneumo vaccination should be given to all patients with an indication Empiric antibacterial therapy should be directed at likely pathogens Best way to prevent influenza and its related complications is vaccination Efforts should be made to vaccinate patients for whom vaccination has been recommended Early antiviral treatment is important for those hospitalized and those at high risk for complications

Acknowledgements Seema Jain, MD Laurie Kamimoto, MD, MPH Ashley Fowlkes, MPH Lenee Blanton, MPH Lynnette Brammer, MPH Mackenzie Nowell, MPH Anna Bramley, MPH Matthew Biggerstaff, MPH Fatimah Dawood, MD Denise Jamieson, MD, MPH Alicia Siston, PhD David Swerdlow, MD