Influenza 2009: Not Yet The Perfect Storm

Transcription

1 Influenza 2009: Not Yet The Perfect Storm

2 What s needed for a pandemic strain? Novel virus (little to no immunity) Capable of causing disease in humans Highly pathogenic / virulent Capable of sustained person to person transmission

3 Influenza Competencies: at the end of this presentation, attendees should be able to 1. Explain to a normal person what all those letters and numbers used to name an influenza virus mean. 2. Find and understand relevant epidemiologic data so as to worry appropriately about the current and near future influenza situation. 3. Explain convincingly why (and which) people should be vaccinated. 4. Explain convincingly why (and which) people should receive antiviral drugs for influenza.

4 Influenza Virus

5 Influenza Virology: 1 Epidemiologically recognized for centuries: acute, febrile respiratory illness occurring in outbreaks of variable severity almost every winter. Influenza : from the 14 th century Italian notion that astrologic influences were responsible s: filtered swine mucus transmission implicated a virus s: Influenza isolated from humans.

6 INFLUENZA History Epidemics and pandemics: Most well known pandemic million deaths worldwide Subsequent pandemics 1957 Asian flu 1968 Hong Kong flu 1.5 million deaths Economic impact estimated at 32 billion dollars

7 Influenza Virology: 2 Family: Orthomyxoviridae. Three major antigenic types (A,B and C). RNA virus with linear, segmented (8), single stranded, negative-sense genome. Subtypes determined by H (hemagglutinin) and N (neuraminidase) glycoproteins. Subtypes differ by at least 30% amino acid sequence homology.

8 Influenza Virology: 3 M2 protein is an ion channel. Ionic flow acidifies vesicle and fuses viral and vesicle membrane together, leading to release of the virus into the host cell. Amantidine (Rimantidine) blocks this step.

9 Influenza nomenclature: Subtypes Type A is further subdivided by Hemagglutinin, 15 types exist H1-H15 Important for cell entry, immunity Neuraminidase, 9 types, N1-N9 Important for viral egress Target of Neuraminidase inhibitor drugs Host range depends on H and N Types B and C: human only, no pandemics

10 Transmission electron micrograph of influenza A virus, late passage. Source: CDC/Dr. Erskine Palmer

11 NIH web conf

12 Hot Virus Names This Year A/Brisbane/59/2007 (H1N1) is this year s vaccine strain. A/Brisbane/10/2007 (H3N2) is this year s vaccine strain. B/Florida/4/2006 is this year s vaccine strain. A/Swine/Mexico/?/2009 (H1N1) is also called p(h1n1), novel influenza A (H1N1), S-OIV etc.

13 NIH web conf

14 NIH web conf

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18 Diagnosis Clinical syndrome: ILI reporting network. NP DFA and culture: all HCWs. NP, tracheal secretions for PCR serology

19 How To Perform a Nasopharyngeal Swab Must collect a specimen with an adequate number of cells /DC1

20 DIRECT FLUORESCENT ANTIBODY STAINING IN HEP-2 CELLS a. Uninoculated. b. Influenza A. c. Parainfluenza (fine granules).

21 SHR Algorithm

22 Information Sources Public Health Agency of Canada: FluWatch. Your Provincial Lab. Rx Canada Inc. H1N1 Antiviral and OTC Weekly Report.

23 Images from the 1918 Influenza Epidemic National Museum of Heath and Medicine

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26 Number of cases N=385 Influenza in Saskatchewan, Number of cases by week Dec Dec 31-Dec 07-Jan 14-Jan 21-Jan 28-Jan 04-Feb 11-Feb 18-Feb 25-Feb 04-Mar 11-Mar Type A Type B Week ending

27 Number of positive tests 600 Pandemic H1N1 lab-confirmations in Saskatchewan since Sept 1, Sept 5 Sept 12 Sept 19 Sept 26 Oct 3 Oct 10 Oct 17 Oct 24 Oct 31 Nov 7 ph1n Collection week ending

28 Percent Percent ph1n1 lab confirmations by age group Week 44 cases Percent Age group

29 Number of tests Percent positive 1200 Respiratory lab tests and ph1n1positivity Saskatchewan Disease Control Laboratory Number of tests Percent ph1n May 16 May 23 May 30 Jun 6 Jun13 Jun 20 Jun 27 Jul 4 Jul 11 Jul 18 Jul 25 Aug 1 Aug 8 Aug 15 Aug 22 Aug 29 Sept 5 Sept 12 Sept 19 Sept 26 Oct 3 Oct 10 Oct 17 Oct 24 Oct 31 Nov 7 Week ending

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31 Case 1: 32 Year Old Male With Cough, Fever and SOB, day 1

32 Case 1, Day 3

33 Case 1, Day 5, 6

34 Case 1, Day 6 CT

35 Case 2: 29 Year Old Wife of Case 1, Admitted Day 5.

36 H1N1 S-OIV Influenza Why worry? It makes influenza more confusing. It has provided genetic material for the next human influenza pandemic. It has redefined our influenza season.

37 INFLUENZA PREVENTION VACCINE Inactivated Influenza Vaccine Live Attenuated Influenza Vaccine Vaccine Recommendations: not applicable in Future directions

38 Mortality For H1N1 Influenza A Regular Seasonal Strain Intensive Care Adult Patients With Severe Respiratory Failure Caused By Influenza A (H1N1)v In Spain Rello et al Crit Care Sep 11;13 (5): R patients who were ill enough to present to hospital and require ICU care. Age: mean 36 yo (range 31-52) 75% developed MOF. 8/32 died (2 were late deaths). Oseltamivir was given to all.

39 Mortality For H1N1 Swine-Associated Influenza Pneumonia and Respiratory Failure From Swine- Origin Influenza A (H1N1) in Mexico. Perez- Padilla et al NEJM 2009 Aug 13;361(7): patients admitted to hospital with pneumonia, 18 of them had S-OIV. Age range: half were yo. 12/18 required ICU and ventilation. 7/18 died.

40 INFLUENZA PREVENTION INACTIVATED INFLUENZA VACCINE First developed in US by Armed Services 1940 s Made of split viruses or viral subunits containing hemaglutinin and neuraminidase Contain 2 type A viruses and 1 type B virus Try to match what will most likely be in circulation each season Source: CDC

41 INFLUENZA PREVENTION INACTIVATED INFLUENZA VACCINE Strains circulating detected by WHO Global Surveillance Network (since 1948) Serologic studies to determine antigenicity 4-6 month egg based manufacturing process 18 Manufacturers worldwide 2 licensed in US in 2004 Source Aventis Pasteur

42 Prevention Beyond Vaccine Avoid close contact with people who are sick Cover Your Cough Frequent handwashing Avoid touching eyes, nose or mouth Antiviral drugs Stay home when you are sick!

43 Comparison of Laboratory-Confirmed Influenza Between the Surgical Mask and N95 Respirator Groups Loeb, M. et al. JAMA 2009;0: Copyright restrictions may apply.

44 INFLUENZA Management Primarily symptomatic, including hydration Antivirals: Adamantanes Amantadine, rimantidine decrease duration of symptoms by 50% if initiated within < 48 hours in trials Decrease in viral shedding Appearance and transmission of resistant virus Side effects predominantly CNS type, amantadine greater than rimantidine

45 INFLUENZA Management Side effects: Neuraminidase Inhibitors Oseltamivir nausea, vomiting, headache, cough Zanamivir not recommended for COPD, asthma because of bronchospasm No controlled trials comparing neuraminidase inhibitors to adamantanes

46 Oseltamivir Dosing Prophylaxis 75 mg po OD. For Cr Cl ml/min, 75 mg EOD or 30 mg suspension OD. No prophylaxis for residents who have recovered from lab confirmed influenza. Treatment 75 mg po BID X 5 days. No dosage recommendations exist for CrCl or those on HD. No treatment for those who have recovered from lab confirmed flu

47 Neuraminidase Inhibitors: Efficacy Original registration studies (mid 1990s) indicated that oseltamivir and zanamivir decreased duration of illness by about 24 hours. No indication for prevention of complications or hospitalization.

48 Neuraminidase Inhibitors: Efficacy Effect Of Oseltamivir On Influenza-Related Complications In Children With Chronic Medical Conditions Piedra et al Pediatrics 2009 Jul;124(1): Retrospective study of children 1-17 yo given oseltamivir within 24 hours of onset of symptoms of flu patients received therapy during 6 influenza seasons received no anti- flu medication.

49 Neuraminidase Inhibitors: Efficacy Effect Of Oseltamivir On Influenza-Related Complications In Children With Chronic Medical Conditions Piedra et al Pediatrics 2009 Jul;124(1): No death benefit but significantly reduced risk of respiratory illness other than pneumonia, otitis media, and all-cause hospitalization at 14 and 30 days.

50 Amantidine and Neuraminidase Inhibitor Susceptibility In Canada: Circulating human A(H1N1) is resistant to both amantidine and oseltamivir but sensitive to zanamivir. Circulating H3N2 is resistant to amantidine. S-OIV is sensitive both neuraminidase inhibitors and resistant to amantidine. Circulating B is sensitive to both neuraminidase inhibitors.

51 Dosing of Oseltamivir 75 mg po BID Based on Wpg data, no need to adjust for morbidly obese patients Extend out to 10 days rather than 5 for critically ill Consider 150 mg BID in severely ill, in fact, maybe everybody (resistance issues).

52 Treatment Guidelines Patient Mild disease Healthy individual Mild disease Pregnant woman (any trimester) Mild disease stable chronic disease Mild disease complex/unstable disease Moderate to Severe disease or SRI all individuals Self Manage ment & Home Isolation NP Swab Antiviral Treatment (Initiate if < 48 hours) Antiviral Treatment (Initiate even if > than 48 hours YES No No No YES CONSIDER YES YES YES No CONSIDER CONSIDER4 YES CONSIDER2 YES CONSIDER No YES YES YES