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Infectious Diseases Influenza What have we learned from the 2009 pandemic? Allison McGeer, MSc, MD, FRCPC Mount Sinai Hospital University of Toronto Disclosures Investigator initiated research funding: – Hoffman LaRoche, GlaxoSmithKline, Sanofi- Pasteur Advisory Boards – Novartis, GlaxoSmithKline, Sanofi-Pasteur, Pfizer, Hoffman-Laroche Honoraria for lectures – GlaxoSmithKline, Hoffman-Laroche, Gilead Biosciences Schematic diagram of the influenza viral life cycle. G Neumann et al. Nature 459, 931-939 (2009) doi:10.1038/nature08157 Viral shedding Annual Influenza in Canada (Pop 33M) 5 million (1 in 6) infected per year ~50,000 hospitalizations – 1% of those >65yrs; 0.5% of those <1yr 4,000 - 8,000 deaths (10 in children) 7% of children get otitis media 1.5 million work-days lost Antigenic drift Treanor J. N Engl J Med. 2004;350:218-220. Smith et al. 2004 Evolution of New Viruses 16 HAs 9 NAs Avian Human virus virus Reassortant Swine virus virus Figure from Smith et al. 2009 Nature. In press: doi:10.1038/nature08182. History Be an influenza virus, see the world Epidemic curvepandemic ofEpidemic (H1N1) 2009 cases,hospitalized Laboratory-confirmed cases ICU admissions and deaths Canada in by date of onset, as of ILI rate/1000 *Symptom onset date/specimen collection date was available for 98% date for was 98% and collection and cases available 99% ICU of hospitalized of admissions date/specimen onset deaths *Symptom & Lab %+ve 100 150 200 50 0 11-Apr-09 18-Apr-09 25-Apr-09 2-May-09 9-May-09 16-May-09 23-May-09 30-May-09 6-Jun-09 13-Jun-09 20-Jun-09 27-Jun-09 December 19, 2009* 4-Jul-09 Symptom onset date (or specimen collection date) 11-Jul-09 18-Jul-09 25-Jul-09 1-Aug-09 8-Aug-09 15-Aug-09 22-Aug-09 29-Aug-09 Lab %+ve ILI-rate/1000 Deaths ICU admissions Hospitalized cases 5-Sep-09 12-Sep-09 19-Sep-09 26-Sep-09 3-Oct-09 10-Oct-09 17-Oct-09 24-Oct-09 31-Oct-09 7-Nov-09 14-Nov-09 21-Nov-09 . 28-Nov-09 5-Dec-09 12-Dec-09 19-Dec-09 26-Dec-09 What’s next? - Pandemic There will be another pandemic – ~3% risk per year Severity of next pandemic is unpredictable Goal is planning that is: – Efficient (but recognizes that insurance is important) – Fills the gaps we identified in 2009 pandemic – Sustainable What’s next? - 2010/11 season Activity around the world is mixed – A(pH1N1) – A(H3N2) – B/Victoria So, 2010/11 season could be any strain Very few isolates so far, so no indication that season is starting Timing and Prevalence of Influenza Depends on Season Percent Positive Influenza Tests, Compared With Other Respiratory Viruses, Canada, by Reporting Week, 2005-2006 % Positive Tests 30 November - April 35 20 15 10 5 0 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 2005 Report Week 2006 % positive influenza virus % positive respiratory syncytial virus % positive parainfluenza virus % positive adenovirus Public Health Agency of Canada. FluWatch. August 13, 2006, to August 26 2006 (Week 33 & 34) . 18 What’s next? - 2010/11 season Patient messages about influenza vaccine – Made exactly the way we have always made seasonal influenza vaccines – More the 100M people around the world have been vaccinated with pH1N1 containing vaccines – Influenza continues to kill more Canadians than any other infectious disease – vaccination is the best prevention Motivation to Get the Flu Shot Ontarians would be more likely to get the flu shot if– There was a large outbreak in Ontario (73%) They were convinced the flu was a serious disease (73%) Their doctor recommended it (69%) It was offered in a convenient location (64%) They knew more about it and what it does (60%) Ontario Ministry of Health and Long-Term Care, August 2010 21 Why should Ontarians get the flu vaccine? Every year, Ontario’s Universal Influenza Immunization Program saves– – 300 deaths – 1,000 hospitalizations – 30,000 visits to hospital emergency departments – 200,000 physicians’ consultation for illness Kwong JC, et al. PLoS Med 2008;5:e211 What’s next? - 2010/11 season Patient messages about influenza vaccine – Made exactly the way we have always made seasonal influenza vaccines – More the 100M people around the world have been vaccinated with pH1N1 containing vaccines – Influenza continues to kill more Canadians than any other infectious disease – vaccination is the best prevention – Influenza vaccination does not make you sick Adverse Effects after Influenza Vaccine Symptom Percent reporting symptom in 7 days post- injection Fever 6.1 Tiredness 19.4 Malaise 17.5 Myalgia 5.7 Headache 14.4 Sore arm 24.1 Nichols et al. Arch Int Med, 1996;156:1546 Adverse Effects after Influenza Vaccine Symptom Placebo Vaccine Fever 6.1 6.2 Tiredness 19.4 18.9 Malaise 17.5 16.0 Muscle aches 5.7 6.2 Headaches 14.4 10.8 Sore arm 24.1 63.8 Nichols et al. Arch Int Med, 1996;156:1546 2010/11 Vaccination New for physicians More evidence on prevention of cardiac disease New evidence about GBS New evidence about influenza and vaccination in pregnancy 26 Flu Vaccine Associated with Reduced Rate of Acute MI UK: 16,012 pts >40 years with first acute MI vs. 62,694 matched controls1 Influenza vaccination associated with– – 19% reduction in acute MI when given within the past year – 20% reduction in acute MI when given within the flu season Greater reductions in MI seen with vaccination early (ie, Sept to mid-Nov) vs. later in the season (21% vs. 12% vs. no vaccination) Influenza vaccination should be encouraged wherever indicated, especially in people with existing CV disease, among whom there is often suboptimum vaccine uptake2 1. Siriwardena A, et al. CMAJ 2010 Sep 20. [Epub ahead of print] 2. Warren-Gash C, et al. Lancet Infect Dis 2009;9:601-10 27 Influenza Vaccine and GBS Guillain-Barré Syndrome (GBS) occurs in ~2 of 100,000 people per year, usually due to food-borne infection1 GBS occurrs in association with the flu vaccine - rarely – 1.2 cases per million doses1 2 Influenza infection itself can cause GBS Vaccination not associated with overall increase in the risk of GBS2,3 – Risk of GBS after ILI: 17 (9.4, 25) – Overall risk of GBS in vaccinated: 0.58 (0.18, 1.9) 1. PHAC. http://www.phac-aspc.gc.ca/alert-alerte/h1n1/pdf/Factsheet_Seniors.pdf 2. Sivadon-Tardy V, et al. Clin Infect Dis 2009;48:48-56 3. Tam CC, et al. PLoS One 2007;2:e344 Benefit of vaccinating pregnant women Outcome Reduction associated with influenza vaccine Influenza in infants 63% (5,85) Febrile respiratory illness 29% (7,46) in infants Febrile respiratory illness 36% (4,57) in mothers Zaman K, NEJM 2008;359:1555 Adjusted odds ratios of prematurity and small for gestational age by maternal influenza vaccine status (OR <1 imply a protective vaccine effect of ) Small for Gestational Premature Age Odds Ratio p Odds Ratio Analysis Period p value (95% CI) value (95% CI) All seasons/periods 0.8 (0.6-1.1) 0.18 0.9 (0.6-1.3) 0.66 Putative influenza season (Oct- 0.6 (0.4-0.9) 0.01 0.8 (0.5-1.3) 0.42 May) Period of at least local 0.5 (0.3-0.9) 0.02 0.7 (0.4-1.3) 0.24 influenza activity* Period of widespread influenza 0.3 (0.1-0.7) 0.01 0.4 (0.2-1) 0.04 activity* Influenza in pregnancy and birthweight RCT, Bangladesh, 2004/5 Difference in birth weights (vaccine vs. placebo) during intervals with no influenza – neonates of vaccinated moms babies were 0.25 gms heavier (P=.70) Difference in birth weights during intervals with influenza activity – neonates of vaccinated moms were 215 gms heavier (P=.004) Influenza vaccine in pregnancy Safety data No pregnancy associated adverse events with ANY inactivated vaccine, EVER Vaccine is recommended in pregnancy by NACI, CDC, SOGC, ACOG1,2 – Numerous safety studies, no evidence of teratogenicity No evidence to suggest that thimerosal given to mothers has any impact on fetus – Since 1998, US has recommended vaccination of pregnant women - 500,000 to 2 million/yr x 11 years Dosing of Influenza Vaccine for Children <9 Years of Age* Dose (ml) Number Site of doses† Anterolateral Age 6-11 months 0.25 ml 2 thigh Age 12-35 months, no previous dose any 0.25 ml 2 Deltoid SEASONAL influenza vaccine Age 12-35 months, at least one prior 0.25 ml 1 Deltoid dose any SEASONAL influenza vaccine Age 3-8 years, no previous dose any 0.5 ml 2 Deltoid SEASONAL influenza vaccine Age 3-8 years, at least one prior dose 0.5 ml 1 Deltoid any SEASONAL influenza vaccine *Adults and children over 9 years of age should receive a single 0.5 ml dose IM in deltoid †Doses should be given 4 weeks apart. NACI. Can Commun Dis Rep 2010;36(ACS­6):1-49 Key Messages About Influenza Prevention Get the flu shot Wash hands with soap and water at least 5 times per day Keep an alcohol-based hand sanitizer handy at work, home and in your car (minimum 60% alcohol) Cover the mouth and nose with a tissue to cough or sneeze and throw the tissue out. Cough into the upper sleeve if a tissue isn’t available Stay home when sick. Avoid crowds where viruses can spread easily Keep common surfaces and items clean New in Testing and Treatment Many cohorts from pH1N1 that find an association between treatment, especially early treatment, with antivirals, and increase survival Cohorts pH1N1 - I Antiviral efficacy Reference Patients NI impact Dominguez-Cherit Mexico, 58 OR survival if RX JAMA 2009;302:1883 critically ill 8.5 (1.2,63) Van Tam First 631 hosp OR for survival if Rx Thorax 2010;65:645 cases, UK NS (univ.
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