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The Next Pandemic
Brian J Ward MDCM
McGill Center for Tropical Diseases
McGill 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, 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
Factors the Influence Pandemic Risk
R0
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
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 (R0)
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 FluAid 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
subversity.blogspot.com
Pandemic Influenza
• Arise due to Genetic Shift
• Humans immunologically ‘naïve’
• 2-3 pandemics per century
Year
1889
1918
1957
1968
1977
Interval(yrs)
-29
39
11
9
Subtype
H3N2
H1N1
H2N2
H3N2
H1N1
Severity
moderate
severe
severe
moderate
mild
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: $330M to $1.4B
• societal: $5B to $38B
Health Canada Pandemic Planning Committee
Avian Influenza
2003-2004
H5N1 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 (FluMist™)
• Experimental vaccines
- Proteosome (FluINsure™)
- 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: PR8)
• Distribution of seed-strains to manufacturers
• Two, 6-month cycles ~250x106 doses (10-20 doses/egg)
Gerdil C. Vaccine 2003
www.alphaweb.org/docs/TAM_Teleclass_Pandemic_ Influenza_Local_MOHs_21Oct_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 (~1:1x106 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
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 5x10 9 = 1x108 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 (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
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