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Pandemic Influenza … …and the OHPIP Laboratory Working Group June 2005.

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Presentation on theme: "Pandemic Influenza … …and the OHPIP Laboratory Working Group June 2005."— Presentation transcript:

1 Pandemic Influenza … …and the OHPIP Laboratory Working Group June 2005

2 Objectives Review the flu Review the flu Pandemic Influenza Pandemic Influenza Laboratory Working Group Laboratory Working Group Public Health Laboratory Role Public Health Laboratory Role

3 Influenza negative sense single stranded RNA virus 8 gene segments, 10 gene products HA – protein necessary for attachment (15 subtypes) NA – protein necessary for release (9 subtypes) 3 types affecting humans: A B C Replicates in the respiratory tract epithelium Replicates in the respiratory tract epithelium

4 Mortality from Influenza IN CANADA Infectious diseases are cause of nearly 15 million of 57 million annual deaths worldwide (>25%) Infectious diseases are cause of nearly 15 million of 57 million annual deaths worldwide (>25%) Approximately 15-20% of all Canadians develop influenza annually Approximately 15-20% of all Canadians develop influenza annually Mortality due to influenza and pneumonia is the sixth leading cause of death in Canada Mortality due to influenza and pneumonia is the sixth leading cause of death in Canada Estimated 6,000-7,000 deaths per year in Canada ( million deaths worldwide) Estimated 6,000-7,000 deaths per year in Canada ( million deaths worldwide) 70,000-75,000 hospital admissions per year in Canada 70,000-75,000 hospital admissions per year in Canada 2. Statistics Canada, Health Statistics Division. Available at

5 Leading Causes of Death in Canada ( ) Cause of Death % Cancer 27.2 Heart Disease 26.6 Cerebrovascular Diseases 7.4 Chronic Obstructive Lung Disease and allied conditions 4.5 Accidents and Adverse Effects 4.0 Pneumonia and Influenza 3.7 Diabetes Mellitus 2.6 HIV Infection 0.3 HIV Infection Statistics Canada, Health Statistics Division. Available at

6 Laboratory-Confirmed Cases of Influenza by Age (1997–98 Season) Age (years) < >64 Unknown 8. CCDR Vol Influenza in Canada – season. Distribution (%)

7 Economic Cost of Influenza Outbreak Total annual costs of influenza are estimated at $1 billion in Canada Total annual costs of influenza are estimated at $1 billion in Canada Patients are only able to work 20% of their scheduled hours in the Patients are only able to work 20% of their scheduled hours in the first 7 days after onset 27. Jefferson T. Influenza in the workplace: Effect of oseltamivir on ability to perform usual activities and attendance at work [abstract]. 21 st International Congress of Chemotherapy. Birmingham, UK 1999.

8 Pandemic Influenza Associated with antigenic shift and/or emergence of new or recycled subtype Associated with antigenic shift and/or emergence of new or recycled subtype Little or no herd immunity Little or no herd immunity High attack rates High attack rates High morbidity and mortality in 1-3 waves High morbidity and mortality in 1-3 waves Interpandemic influenza Associated with antigenic drift of existing strains Associated with antigenic drift of existing strains Cross-reacting antibody in much of the population Cross-reacting antibody in much of the population Variable attack rates, sporadic infections and outbreaks Variable attack rates, sporadic infections and outbreaks Variable morbidity and mortality depending on age Variable morbidity and mortality depending on age

9 Influenza Pandemics 20 th Century Pandemics/ Distribution Influenza A Estimated Pandemics/ Distribution Influenza A Estimated large epidemicssubtype deaths large epidemicssubtype deaths 1889–1890Worldwide H 3 N 2 Unreported 1889–1890Worldwide H 3 N 2 Unreported (first documented (first documented pandemic) pandemic) 1918 Worldwide H 1 N 1 20–40 million 1918 Worldwide H 1 N 1 20–40 million "Spanish flu 1957 "Asian" fluWorldwide H 2 N 2 1 million 1957 "Asian" fluWorldwide H 2 N 2 1 million (initiated in China) (initiated in China) 1968 Hong Kong H 3 N 2 1 million 1968 Hong Kong H 3 N 2 1 million "Hong Kong" flu "Hong Kong" flu 1976 "Swine" fluNew Jersey, USA H SW N 1 Unreported 1976 "Swine" fluNew Jersey, USA H SW N 1 Unreported 7. Glezen WP. Emerging infections: Pandemic influenza. Epidemiol Rev 1996;18: Nöel GE. Life-threatening flu? Can J Diagnosis 1999; March: Taubenberger JK, Reid AH, Kraft AE, Bijwaard KE, Fanning TG. Initial genetic characterization of the 1918 Spanish influenza virus. Science. 1997;275: Tice DJ, Flu deaths rivaled, ran alongside World War I. Pioneer Planet. St. Paul, Mn:Pioneer Press. March 10, Available at Accessed May 26, 1999.http://www.pioneerplanet.com/archive/cent/dox/cent3.html

10 History of Influenza Viruses 17. Collier L, Mahy BWJ, ed. Virology. In:Topley and Wilsons Microbiology and Microbial Infections. 9 th ed. London, England:Arnold Publishers;1998;1: B H3N2H3N2 H1N1H1N1 H2N2H2N2 H3N8H3N8 H3N2H3N2 H1N1H1N1 Seroarcheology Virus Virus Isolation H5N1H5N1

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12 Influenza Type A (H 5 N 1 ) First appeared in humans in Hong Kong, 1997 First appeared in humans in Hong Kong, 1997 Primarily associated with avian species Primarily associated with avian species Fatal epidemic among Hong Kong poultry in 1997 Fatal epidemic among Hong Kong poultry in 1997 Pandemic (so far) avoided because strain not readily transmissible between humans Pandemic (so far) avoided because strain not readily transmissible between humans 13. WHO/OMS. Disease outbreaks reported. 13 April Influenza A (H9N2) in Hong Kong Special Administrative Region of China-update. Available at 18. Lee Y, Mak KH, Saw TA. The Avian Flu (H5N1): One Year On. Public Health and Epidemiology Bulletin. 1999;8:1-8.

13 December 2003 December 2003 –South Korea reported H5N1 had been isolated on a poultry farm At the end of March 2004 At the end of March 2004 –Infections in birds Cambodia, Cambodia, China, China, Japan, Japan, Laos, Laos, South Korea, South Korea, Thailand, Thailand, Vietnam Vietnam The First wave – 2004 SE Asia 12 infected; 8 dead Mortality: 67% 27 infected; 20 dead Mortality: 74%

14 The Second wave New outbreaks Late June and Early July 2004 New outbreaks Late June and Early July 2004 China, China, Thailand, Thailand, Vietnam Vietnam By September By September Indonesia, Indonesia, Malaysia, Malaysia, Thailand, Thailand, Vietnam Vietnam As of Oct. 25: 44 humans cases; 32 deaths Vietnam – 27 cases; 20 deaths Thailand – 17 cases; 12 deaths

15 Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO 19 May 2005 Date of onset Viet NamThailandCambodiaTotal casesdeathscasesdeathscasesdeathscasesdeaths Total Notes Total number of cases includes number of deaths. WHO reports only laboratory-confirmed cases. EmploymentEmployment | Other UN Sites | Search | Suggestions | RSS | Privacy © World Health Organization All rights reservedOther UN SitesSearchSuggestionsRSSPrivacy © World Health Organization All rights reserved

16 H5N1 in SE Asia million birds killed in Vietnam since million birds killed in Vietnam since 2003 Worlds 4 th largest poultry exporter Worlds 4 th largest poultry exporter 880 million USD loss during the first wave 880 million USD loss during the first wave Now ? enzootic in SE Asia and may take 2-3 yrs to burn out, if at all Now ? enzootic in SE Asia and may take 2-3 yrs to burn out, if at all Transmission by waterfowlproblematic. Reservoir. Transmission by waterfowlproblematic. Reservoir.

17 Avian Influenza H5N1 (HPAI) Signs: Signs: –Depression –Diarrhea –Cyanosis of wattles –Edema of head and face –Nervous signs

18 Bird flu Farmers look at an empty chicken coop in Kaliboto, Bitar, Indonesia on Jan. 27, This farm usually keeps around 5,500 chickens; 3,000 died from the flu, the 2,500 remaining were sick. A worker sprays chemicals at a bag containing chickens during a cleanup of a chicken farm in Supanburi, Thailand. A worker sprays chemicals at a bag containing chickens during a cleanup of a chicken farm in Supanburi, Thailand.

19 Potential for concern The Pandemic of The Pandemic of –Worldwide million deaths mainly in yr age group –Death rate 1.5% of all clinical cases The pandemic of The pandemic of –Total deaths > 1 million –Clinically typical; mortality 1/4000 The current H5N1 outbreak has high mortality rate! (>55%) The current H5N1 outbreak has high mortality rate! (>55%)

20 Pigs: the pandemic mixing vessel Pigs in China Pigs in China –Serologic evidence 4-8% of serum collected from pigs in two provinces had evidence of H5 infection 4-8% of serum collected from pigs in two provinces had evidence of H5 infection –Isolation of virus Two isolates from pigs Two isolates from pigs –Serial passage of avian influenza results in potential for human infection With time receptor specificity of avian influenza in pigs shifts With time receptor specificity of avian influenza in pigs shifts

21 Generation of Pandemic Influenza Antigenic Shift

22 Implications of H 5 N 1 Potential for pandemic infection by little-known pathogen Potential for pandemic infection by little-known pathogen Morbidity and mortality in both young and old Morbidity and mortality in both young and old No previous human exposure No previous human exposure No vaccine No vaccine Emphasizes the need for: Emphasizes the need for: –PANDEMIC READINESS PLAN 18. Lee Y, Mak KH, Saw TA. The Avian Flu (H5N1): One Year On. Public Health and Epidemiology Bulletin. 1999;8:1-8.

23 Laboratory Working Group Fall 2004 Fall 2004 Representation from all laboratory sectors; i.e. Public Health, Hospital, Community Representation from all laboratory sectors; i.e. Public Health, Hospital, Community Province Wide Membership Province Wide Membership

24 Steering Committee PHSC Laboratory Working Group OpSC

25 Objectives1 To develop and implement laboratory directives within OHPIP, including type and scope of testing, laboratory aspects of surveillance, and recommendations to improve and ensure expert and reliable laboratory services. To develop and implement laboratory directives within OHPIP, including type and scope of testing, laboratory aspects of surveillance, and recommendations to improve and ensure expert and reliable laboratory services.

26 Objectives2 To receive and review recommendations from other committees and working groups within OHPIP regarding refinements and amendments to the Laboratory portion of the plan. To receive and review recommendations from other committees and working groups within OHPIP regarding refinements and amendments to the Laboratory portion of the plan.

27 Objectives3 To provide on-going development and revision of the plan as necessary and to ensure that planning continues during inter-pandemic periods. To provide on-going development and revision of the plan as necessary and to ensure that planning continues during inter-pandemic periods.

28 Planning Across Sectors Representation on the LWG from public health, hospital & community sector medical laboratories Representation on the LWG from public health, hospital & community sector medical laboratories Recognition that role of the various sectors does differ Recognition that role of the various sectors does differ Pandemic planning has to take into account role differencesbuild on current strengths Pandemic planning has to take into account role differencesbuild on current strengths

29 Capacity for Integration and Adaptation Critical to planning is the capacity of the system to adapt and the level of integration already in place Critical to planning is the capacity of the system to adapt and the level of integration already in place E.g. currently >800,000 public health specimens are collected, documented and transported by community laboratories to PHLs for testing annually E.g. currently >800,000 public health specimens are collected, documented and transported by community laboratories to PHLs for testing annually Public Health Laboratories have the capacity for redirection of specimens for testing between sites freeing up capacity where and when needed Public Health Laboratories have the capacity for redirection of specimens for testing between sites freeing up capacity where and when needed Community laboratories provided the system surge capacity during SARS, performing testing for hospital outpatients, when those labs closed Community laboratories provided the system surge capacity during SARS, performing testing for hospital outpatients, when those labs closed Hospitals will need to maintain laboratory services in support of patient care (influenza and non-influenza related) at their sites. Hospitals will need to maintain laboratory services in support of patient care (influenza and non-influenza related) at their sites.

30 Lab Planning 1. Influenza Testing: Phase Based 1. Influenza Testing: Phase Based 2. Guidelines for the Suspension of Testing 2. Guidelines for the Suspension of Testing –Public Health Laboratories –Community Laboratories –Hospital Laboratories Planning follows the pandemic phases but is also tailored to address the severity of the attack Planning follows the pandemic phases but is also tailored to address the severity of the attack

31 Public Health Laboratories Testing in support of surveillance and detection of emerging and reportable diseases Testing in support of surveillance and detection of emerging and reportable diseases Diagnostic testing in support of patient care Diagnostic testing in support of patient care Routine and Reference Testing Routine and Reference Testing Pandemic: Pandemic: –Elective Testing Schedules –CL-3 Laboratories (Toronto and Ottawa) –Molecular (RT-PCR) Detection and Typing

32 Hospital Laboratories Diagnostic services in acute care setting Diagnostic services in acute care setting Variation in depth and breadth of services Variation in depth and breadth of services Academic/Teaching Centers versus Community Hospitals Academic/Teaching Centers versus Community Hospitals Pandemic: Laboratory Testing in support of patient population. Elective procedures, etc. suspended. Pandemic: Laboratory Testing in support of patient population. Elective procedures, etc. suspended.

33 Community Laboratories Provide the bulk of routine testing for primary health care providers. Provide the bulk of routine testing for primary health care providers. Pandemic: Pandemic: –Identified a list of tests required to support basic health care to whole population and to those affected by influenza in an extreme pandemic event. –Support of laboratory services at secondary sites.

34 Suspended Testing Guidelines SEVERE-MODERATE-MILD In a severe scenario, testing will be performed primarily for diagnostic purposes. In a severe scenario, testing will be performed primarily for diagnostic purposes. In a moderate scenario, a number of tests are added back as human and other resources allow. In a moderate scenario, a number of tests are added back as human and other resources allow. In a mild scenario, it is believed that, although suspension of some tests will be necessary, most testing can be offered with the exception of screening tests in low risk populations. In a mild scenario, it is believed that, although suspension of some tests will be necessary, most testing can be offered with the exception of screening tests in low risk populations.

35 Severe… ….e.g. high attack rate, or highly pathogenic strain, or both DIAGNOSTIC/Critical…Med Micro/ID physician TB TB HIV HIV Bacterial Culture, sterile sites Bacterial Culture, sterile sites Respiratory Respiratory Virus Culture Virus Culture Hepatitis Hepatitis C. trachomatis, GC C. trachomatis, GC Malaria Malaria Diagnostic Serology Diagnostic Serology Syphilis Syphilis Prenatal Prenatal Reference Testing Reference Testing Water Testing on order of MOH Water Testing on order of MOH

36 Moderate… In the event of a moderate scenario, a number of tests are added back as human and other resources allow…. In the event of a moderate scenario, a number of tests are added back as human and other resources allow…. –B. pertussis –Throat Culture –West Nile Virus

37 Mild/Low Although suspension of some tests will be necessary, most testing will be offered with the exception of screening tests in low risk populations…. Although suspension of some tests will be necessary, most testing will be offered with the exception of screening tests in low risk populations…. –Sputum Culture and Smear –Stool Culture –Mycology Culture –Antibiotic Sensitivity –Chlamydia Culture

38 INFLUENZA TESTING 8 week wave 8 week wave 35% attack rate 35% attack rate 4 million people in Ontario 4 million people in Ontario

39 Influenza Testing Weeks 1-3 Test all suspect cases, as possible, to confirm entry of pandemic strain into Ontario. Test all suspect cases, as possible, to confirm entry of pandemic strain into Ontario. Rapid testing. Rapid testing. Virus Culture. Virus Culture. Typing and anti-viral sensitivity testing. Typing and anti-viral sensitivity testing.

40 Natural History of Clinical Influenza Coryza Sore Throat Myalgia Headache Cough Anorexia Malaise Symptoms: Days after Onset C Oral temperature Onset of Illness in (log10 TCID50)/mlVirus Shed 21. Dulin, Ann Fam Phys, 1976

41 Local and Systemic Symptoms of Influenza Most symptoms associated with influenza are caused by the inflammatory response and correlate well with measurable levels of pro- inflammatory cytokines in respiratory tract mucous Most symptoms associated with influenza are caused by the inflammatory response and correlate well with measurable levels of pro- inflammatory cytokines in respiratory tract mucous Systemic symptoms include body and muscle aches, chills, malaise, fever, headache, photophobia, and ocular pain Systemic symptoms include body and muscle aches, chills, malaise, fever, headache, photophobia, and ocular pain Local symptoms include sore throat, dry cough, and runny nose Local symptoms include sore throat, dry cough, and runny nose

42 Clinical signs and symptoms predicting influenza infection. Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Arch Intern Med May 28;161(10): Clinical signs and symptoms predicting influenza infection. Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Arch Intern Med May 28;161(10): The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P<. 001). The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P<. 001).

43 Influenza Testing Weeks % clinical diagnosis 80% clinical diagnosis Number of clinical cases increasing Number of clinical cases increasing Capacity for testing decreasing Capacity for testing decreasing Limitations: reagents, supplies, human resources Limitations: reagents, supplies, human resources Molecular detection and typing: atypical or critical Molecular detection and typing: atypical or critical Rapid methods as available Rapid methods as available Culture for purposes of surveillance and for characterization of virus (e.g. sequencing, anti-viral sensitivity testing.) Culture for purposes of surveillance and for characterization of virus (e.g. sequencing, anti-viral sensitivity testing.) Surge capacity: redirection of work within PHLs and from Hospitals to Community and PHL sites as required. Surge capacity: redirection of work within PHLs and from Hospitals to Community and PHL sites as required.

44 Influenza Testing Weeks 6-8 Rapid molecular detection and sub-typing, and susceptibility testing to continue in this stage. Rapid molecular detection and sub-typing, and susceptibility testing to continue in this stage. Ramping up of virus detection activities to document decline of pandemic influenza and introduction of other respiratory viruses. Ramping up of virus detection activities to document decline of pandemic influenza and introduction of other respiratory viruses.

45 Summary Influenza viruses with pandemic potential are in circulation currently. Influenza viruses with pandemic potential are in circulation currently. Ontario Laboratories have developed testing guidelines in the event of a pandemic. Ontario Laboratories have developed testing guidelines in the event of a pandemic. Guidelines operate across Hospital, Community and Public Health Laboratory sectors. Guidelines operate across Hospital, Community and Public Health Laboratory sectors. Attack rate and virulence of the potential pandemic strain have been built into the guidelines. Attack rate and virulence of the potential pandemic strain have been built into the guidelines.

46 Next Steps Creation of well-defined protocols for pandemic periods. Creation of well-defined protocols for pandemic periods. Surveillance directives at the laboratory level. Surveillance directives at the laboratory level. Designation of testing sites for molecular detection and sub-typing. Designation of testing sites for molecular detection and sub-typing. Training of laboratory personnel. Training of laboratory personnel. Acquisition of supplies and equipment. Acquisition of supplies and equipment. Preparation of clear and concise communications around laboratory testing. Preparation of clear and concise communications around laboratory testing. Plans for laboratory support of secondary sites if required. Plans for laboratory support of secondary sites if required.

47 Gift Book Ideas Globe and Mail, December 2004


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