The Next PandemicBrian J Ward MDCM

McGill Center for Tropical DiseasesMcGill 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 RouteViruses (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, PIV1-4) 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

R0 Reproductive rateNumber of secondary cases generated by primary case in

a susceptible population Timing of Transmission

The proportion of transmission that occurs prior to the the development of obvious symptoms

Tg Disease generation timeTime between the infection of one person and the next in

a chain of transmission

Factors the Influence Pandemic Risk

Reproduction Number (R0)Asymptomatic Transmission ()

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

Classification of Organisms

BSL 1 Low group/individual riskHealthy 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)

Biohazard Safety Level and Pandemic Impact

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 Changes season-to-season Genetic Shift Changes that cause pandemics

Influenza Morbidity & MortalityNon-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: 73-76MMWR 2000

Influenza Morbidity & MortalityPandemic Year (Based on CDC FluAid Program)

Arrival of pandemic strain in Canada 1-5 weeksPeak infection rates 4-6 monthsAttack 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 CommitteeSchopflocher DP et al. Ann Epidemiol 2004; 14: 73-76

Genetic Shift - Pandemic Influenza

Human Strains

Avian Strains

Potential to ‘mix & match’ avian & human strain genes

Unknown

Unknown

subversity.blogspot.com

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

Year Interval(yrs) Subtype Severity

1889 -- H3N2 moderate

1918 29 H1N1 severe

1957 39 H2N2 severe

1968 11 H3N2 moderate

1977 9 H1N1 mild

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: $330M to $1.4B• societal: $5B to $38B

Pandemic Without Vaccine

Health Canada Pandemic Planning Committee

Avian Influenza2003-2004

• 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

H5N1 Viruses

Influenza Vaccines • Whole inactivated virion

• ‘Split’-virus• egg protein content• thimerosal

• Cold-adapted, live virus (FluMist™)

• Experimental vaccines - Proteosome (FluINsure™) - ISCOM-based - DNA, vectored, other

• Generation of seed-strains adapted to growth in eggs (eg: PR8)

• Distribution of seed-strains to manufacturers

• Two, 6-month cycles ~250x106 doses (10-20 doses/egg)

Gerdil C. Vaccine 2003www.alphaweb.org/docs/TAM_Teleclass_Pandemic_ Influenza_Local_MOHs_21Oct_2003-06_10_2003-11_36_37.ppt

Vaccine Production Efforts

• Surveillance110 national influenza labs4 regional reference centres

• Egg-based Production - delays in adapting strains to eggs - problems with scale-up in the event of a pandemic - egg allergy

• Side-Effects - Guillain-Barré Syndrome (~1:1x106 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

Issues with Current Vaccines

Prevalence 0.13 - 1.6% Higher in young childrenHighest in kids with allergies (3-40%)

Zeigler RS. J Allergy Clin Immunol 2002;110:834

• 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

Other concerns

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 5x10 = 1x10 deaths9 8

AP showing extensive bilateral ground-glass Opacities and poorly defined nodular pattern.

Nicolaou S et al. AJR Am J Roentgenol. 2003;180:1247-9

55-year-old healthy man with history of recent travel to Hong Kong.

12 hours later

Clinical Disease - ImagingWong KT, et al. Severe Acute Respiratory Syndrome: Radiographic Appearances and Pattern of Progression in 138 Patients. Radiology. 2003 May 20

Will the Next Outbreak be Controllable?

Influenza

SARS

Smallpox

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 (vCJD)

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 W135 serotype around globe

Issues, What Issues?

Health SantéCanada 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 high-risk 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 PhasesPhase 0, Level 0 - Inter-Pandemic periodPhase 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 wavePhase 4 - Second or later waves Phase 5 - Post-Pandemic / Recovery

International Pandemic PreparednessDevelopment 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 PlanningFederal • 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 requiredProvinces 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 ControlQuarantine 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 surveillanceStrengthen interface between hospital and public healthEpidemiological, clinical and laboratory data linkage

Establish case definitions with rationaleConsistent 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 jurisdictionsClarify 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-beingIncrease in other nosocomial infections e.g. MRSA, VREMissed or not reported tuberculosis cases

Ongoing training needed e.g. how to put on / remove personal protective equipment

Lessons Learned: Health ServicesPandemic influenza guidelines useful

Resource managementManaging hospital triaging and transfersDedicated SARS unitsLack of suppliesStaff exhaustionSecurity requirements

Non-traditional sites / workers Sites administered through acute care settingCity buses as screening units outside hospitalsLack of volunteers, no medical/nursing students