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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

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The Next Pandemic

Brian J Ward MDCM

McGill Center for Tropical Diseases

McGill Division of Infectious Diseases

overview of talk
Overview of Talk

• Infectious agents spread by respiratory route

• Classification & pandemic potential

• Influenza A

• Pandemic Influenza A


• Canadian ‘Readiness’ & Emergency Response

organisms spread by the respiratory route
Organisms Spread by the Respiratory Route

Viruses (true airborne vs aerosol vs fomite)


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 …


Encapsulated (S. pneumonia, H. influenzae, N. meningitidis)

Intracellular (Listeria, Mycoplasma, Chlamydia, Rickettsia)

Granuloma-forming (Mycobacteria, brucellosis, meliodosis)

Others (Bordatella), rare (tularemia, anthrax) & opportunists (Moraxella)


Pneumocystis carinii

Cocciodomycosis imitis,

Cryptococcus neoformans

Others (eg: Aspergillus)

organisms with pandemic potential
Organisms with Pandemic Potential

Factors the Influence Pandemic Risk

R0Reproductive 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

TgDisease generation time

Time between the infection of one person and the next in

a chain of transmission

reproduction number r 0 asymptomatic 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
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 the facts
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 & Mortality

Non-Pandemic Years

Attack Rates (/1000)

(LR) 33 - 40

(HR) 62 - 116

Hospitalization Rates

(LR) 0.6 - 1.3

(HR) 2 - 6.1


(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


(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
Genetic Shift - Pandemic Influenza

Human Strains


Avian Strains

Potential to ‘mix & match’ avian

& human strain genes


pandemic influenza
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


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


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 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

• Side-Effects

- Guillain-Barré Syndrome (~1:1x106 in some years)

- Oculo-Respiratory Syndrome (ORS)

•  PandemicVaccine Supply

- borders may close to product movement

• Immune Response toPandemic Strain

- anticipate low antigenicity: may need two doses

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


Other concerns

• Pattern of Pandemic

- Big ‘bang’

- Grumble then explode

• Anti-viralDrug 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

epidemiology amoy gardens

• 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


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

there are only 3 certainties in life
There are only 3 certainties in life ...

• Death

• Taxes

• That rents have gone

down at the Amoy Gardens

Apartment Complex

etiology reservoir mortality
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 deaths



clinical disease imaging
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
Will the Next Outbreak be Controllable?





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


• 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

Issues, What Issues?

Health SantéCanada Canada

global agenda for influenza surveillance and control who
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 who1
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 phases
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
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
Canadian Planning


• 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

lessons learned coordination and operations
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
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
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
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
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
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
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