The Next Pandemic Brian J Ward MDCM Mc

The Next Pandemic Brian J Ward MDCM Mc. Gill Center for Tropical Diseases Mc. Gill Division of Infectious Diseases

Overview of Talk • Infectious agents spread by respiratory route • Classification & pandemic potential • Influenza A • Pandemic Influenza A • SARS • Canadian ‘Readiness’ & Emergency Response

Organisms Spread by the Respiratory Route Viruses (true airborne vs aerosol vs fomite) Adenoviridae Coronaviruses (SARS, common cold) Enteroviridae (poliomyelitis, Echo & Coxsackie) Herpesviridae (VZV) Myxoviridae (influenza viruses A, B and C) Paramyxoviridae (measles, mumps, RSV, PIV 1 -4) Pox viruses (smallpox) Rhinoviridae (common cold) … some hemorrhagic fever viruses (Junin, Lassa, CCF) … rabies virus … Bacteria Encapsulated (S. pneumonia, H. influenzae, N. meningitidis) Intracellular (Listeria, Mycoplasma, Chlamydia, Rickettsia) Granuloma-forming (Mycobacteria, brucellosis, meliodosis) Others (Bordatella), rare (tularemia, anthrax) & opportunists (Moraxella) Fungi Pneumocystis carinii Cocciodomycosis imitis, Cryptococcus neoformans Others (eg: Aspergillus)

Organisms with Pandemic Potential Factors the Influence Pandemic Risk R 0 Reproductive rate Number of secondary cases generated by primary case in a susceptible population Timing of Transmission The proportion of transmission that occurs prior to the development of obvious symptoms Tg Disease generation time Time between the infection of one person and the next in a chain of transmission

Reproduction Number (R 0) Asymptomatic Transmission ( ) Fraser C et al. Proc Natl Acad Sci U S A. 2004 Apr 20; 101(16): 6146 -51

Classification of Organisms Biohazard Safety Level and Pandemic Impact BSL 1 Low group/individual risk Healthy subjects unlikely to contract illness (E. coli) BSL 2 Moderate individual risk/Limited group risk Causes disease - exposure unlikely to be serious (eg: measles) BSL 3 High individual risk but limited group risk Usually causes serious disease (eg: F. tularensis) BSL 4 High individual and community risk Likely to cause severe disease, usually not treatable (MDR TB)

Influenza A

Influenza A: The facts • Influenza A virus ‘shared’ - humans, birds, pigs (& other species) • Two proteins critical for immune response - hemagglutinin (H) - neuroaminidase (N) • Humans: 3 H types and 3 N types • Birds: > 13 H and 9 N types • Genes for H and N readily mutate • Genes segregate independently Genetic Drift Genetic Shift Changes season-to-season Changes that cause pandemics

Influenza Morbidity & Mortality Non-Pandemic Years Attack Rates (/1000) (LR) 33 - 40 (HR) 62 - 116 Hospitalization Rates (LR) 0. 6 - 1. 3 (HR) 2 - 6. 1 Deaths (LR). 0015 - 0. 57 (HR). 0015 - 0. 57 Schopflocher DP et al. Ann Epidemiol 2004; 14: 73 -76 MMWR 2000

Influenza Morbidity & Mortality Pandemic Year (Based on CDC Flu. Aid Program) Arrival of pandemic strain in Canada 1 -5 weeks Peak infection rates 4 -6 months Attack rates ≥ 25% Outpatient Disease Rates (/1000) (LR) 60 - 198 (HR) 104 - 346 Hospitalization Rates (LR). 5 - 2. 5 (HR) 2. 9 - 8. 5 Deaths (LR) 0. 24 -. 42 (HR) 0. 22 - 4. 2 Health Canada Pandemic Planning Committee Schopflocher DP et al. Ann Epidemiol 2004; 14: 73 -76

Genetic Shift - Pandemic Influenza Human Strains Unknown Potential to ‘mix & match’ avian & human strain genes Avian Strains Unknown

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Pandemic Influenza • Arise due to Genetic Shift • Humans immunologically ‘naïve’ • 2 -3 pandemics per century

Pandemic Without Vaccine In Canada, if vaccine is unavailable, EXPECT: • 11, 000 to 58, 000 (~1%) deaths • 34, 000 to 138, 000 hospitalizations • 2 to 5 million outpatients • economic costs • health care: $330 M to $1. 4 B • societal: $5 B to $38 B Health Canada Pandemic Planning Committee

Avian Influenza 2003 -2004

H 5 N 1 Viruses • • Variably pathogenic in birds Emerged in Hong Kong 1997 -98 As yet unexplained hyper-mutation since them Re-emerged in all of Asia 2003 -04 Limited capacity to ‘jump’ to humans ? human-to-human spread documented (n=1) ~60% mortality (young and healthy) Recent evidence of infection in cats & pigs

Influenza Vaccines • Whole inactivated virion • ‘Split’-virus • egg protein content • thimerosal • Cold-adapted, live virus (Flu. Mist™) • Experimental vaccines - Proteosome (Flu. INsure™) - ISCOM-based - DNA, vectored, other

Vaccine Production Efforts • Surveillance 110 national influenza labs 4 regional reference centres • Generation of seed-strains adapted to growth in eggs (eg: PR 8) • Distribution of seed-strains to manufacturers • Two, 6 -month cycles ~250 x 106 doses (10 -20 doses/egg) Gerdil C. Vaccine 2003 www. alphaweb. org/docs/TAM_Teleclass_Pandemic_ Influenza_Local_MOHs_21 Oct_2003 -06_10_2003 -11_36_37. ppt

Issues with Current Vaccines • Egg-based Production - delays in adapting strains to eggs - problems with scale-up in the event of a pandemic - egg allergy Prevalence 0. 13 - 1. 6% Higher in young children Highest in kids with allergies (3 -40%) Zeigler RS. J Allergy Clin Immunol 2002; 110: 834 • Side-Effects - Guillain-Barré Syndrome (~1: 1 x 106 in some years) - Oculo-Respiratory Syndrome (ORS) • Pandemic Vaccine Supply - borders may close to product movement • Immune Response to Pandemic Strain - anticipate low antigenicity: may need two doses

Other concerns • Pattern of Pandemic - Big ‘bang’ - Grumble then explode • Anti-viral Drug Stockpiles - Resistant organisms - Priority list for distribution • Who is ‘in charge’? - FPT committee nominally in control - BGTD controls licensing - ? access to drugs/vaccine �� - graded travel advisories

SARS

2003 Epidemic/Pandemic

Epidemiology - Amoy Gardens • Amoy Gardens Appartment Complex (Hong Kong) • 131 cases of SARS (block E residents) • 241 asymptomatic residents quarantined • ariborne, droplet, water, environmental (cockroaches), etc • early index case with diarrhea • lived on top floors • subsequent cases on same ‘side’ of complex • ‘leak’ in sewage pipes so feces dried on pipes and blown into building

There are only 3 certainties in life. . . • Death • Taxes • That rents have gone down at the Amoy Gardens Apartment Complex

Etiology, Reservoir & Mortality • electron microscopy = coronavirus • civet cat = ? only reservoir • initial mortality estimates 2 -8% • recent WHO estimate 20 -50% • Hospital-based outbreak (CDN) will increase estimate • Even if 2% is true estimate 2% of 5 x 10 9 = 1 x 108 deaths

Clinical Disease - Imaging Wong KT, et al. Severe Acute Respiratory Syndrome: Radiographic Appearances and Pattern of Progression in 138 Patients. Radiology. 2003 May 20 55 -year-old healthy man with history of recent travel to Hong Kong. AP showing extensive bilateral ground-glass Opacities and poorly defined nodular pattern. 12 hours later Nicolaou S et al. AJR Am J Roentgenol. 2003; 180: 1247 -9

Will the Next Outbreak be Controllable? SARS Smallpox Influenza HIV Fraser C, Riley S, Anderson RM, Ferguson NM. Factors that make an infectious disease outbreak controllable. Proc Natl Acad Sci U S A. 2004 Apr 20; 101(16): 6146 -51

Infections with the Potential to Shape our World • HIV • Influenza virus • N meningitidis • Ebola (Reston) • Hendra & Nipah viruses • Prions (v. CJD)

The Hajj • Religious obligation • 1. 8 million (2001) - 63% Arab countries - 30% non-Arab Asia - 5% other African - 2% other • Al Haram - 356, 000 sq meters - 1 million pilgrims • Madinah - 165, 000 sq meters - 750, 000 pilgrims • Meningococcal epidemics (carriage as high as 80%) • 2000 Spread of W 135 serotype around globe

Issues, What Issues? Health Canada Santé Canada

Global Agenda for Influenza Surveillance and Control (WHO) Major Themes 1. Improvement in the quality and coverage of virological and epidemiological influenza surveillance 2. Improvement in the understanding of health and economic burden of influenza, including benefits from epidemic control and pandemic preparedness

Global Agenda for Influenza Surveillance and Control (WHO) Major Themes 3. Expansion in the use of existing vaccines, particularly in developing countries and in highrisk groups and acceleration in the introduction of new vaccines 4. Increase in national and global epidemic and pandemic preparedness, including vaccine and pharmaceutical supplies

WHO Pandemic Phases Phase 0, Level 0 - Inter-Pandemic period Phase 0, Level 1 - Novel virus identification in a human Phase 0, Level 2 - Human infection confirmed Phase 0, Level 3 - Human-to-Human transmission confirmed Phase 1 - Pandemic confirmed Phase 2 - Outbreaks in multiple geographic areas Phase 3 - End of first wave Phase 4 - Second or later waves Phase 5 - Post-Pandemic / Recovery

International Pandemic Preparedness Development of pandemic plans Approximately 30 countries worldwide have a plan Use of the WHO Pandemic Phases improves communication and consistency Requires national coordination and agreement on goals of pandemic preparedness and response National surveillance for influenza-like illness and influenza viruses Vaccine strategies Development of Stockpiles / Antiviral strategy

Canadian Planning Federal • CEPR - Center for Emergency Preparedness & Response - stockpiling of antiviral drugs - emergency supplies (tents/blankets/etc) • Division of Immunization & Respiratory Infection • Canadian Pandemic Planning Committee - pandemic influenza contract (ID Biomedical) - pandemic vaccine testing protocol Provincial &Territorial Planning Committees �

Thank you for you attention

Lessons Learned: Coordination and Operations Clear command structure required Provinces without well developed pandemic plans had to create structures immediately to deal with health emergency Dedicated team leadership is essential Need to strengthen human resource planning and surge capacity in emergency plans Psycho-social support: post traumatic stress

Lessons Learned: Disease Control Quarantine and isolation measures were generally acceptable to the public Cancellation of public gatherings will happen regardless of public health recommendations Multiple partners need to be involved in the implementation of public health measures Education and information dissemination media, NGOs, professional societies, businesses, schools… Blood and border issues will arise quickly

Lessons Learned: Surveillance Lack of integrated mechanisms and processes for surveillance Strengthen interface between hospital and public health Epidemiological, clinical and laboratory data linkage Establish case definitions with rationale Consistent use of definitions nationally AND strive for international consistency Pre-establish minimum dataset and data sharing agreements for emerging infectious diseases Establish mechanism for alerting public health and health care providers in real time

Lessons Learned: Outbreak Investigation Enhance epidemiological capacity at all levels multi-disciplinary outbreak investigation teams Improve ability to mobilize resources across jurisdictions Clarify or establish roles and responsibilities and collaboration mechanisms for a multi-jurisdictional response Increase training programs, including short courses that can be rapidly implemented

Lessons Learned: Communication Pre-established national networks worked; need to strengthen international networks Establish communication processes that permit optimal use of all participants time Human resources needed to translate science (particularly epidemiology) into public information Potential for case counts to become politicized Perception IS reality

Lessons Learned: Infection Control in Acute Care Settings Lack of trained infection control personnel Varying capacity for surveillance and need to coordinate with public health Negative impact of intensive SARS infection control measures Health care worker well-being Increase in other nosocomial infections e. g. MRSA, VRE Missed or not reported tuberculosis cases Ongoing training needed e. g. how to put on / remove personal protective equipment

Lessons Learned: Health Services Pandemic influenza guidelines useful Resource management Managing hospital triaging and transfers Dedicated SARS units Lack of supplies Staff exhaustion Security requirements Non-traditional sites / workers Sites administered through acute care setting City buses as screening units outside hospitals Lack of volunteers, no medical/nursing students