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Lessons for Europe from past pandemics and the North American experience so far

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Title: Lessons for Europe from past pandemics and the North American experience so far


1
Lessons for Europe from past pandemics and the
North American experience so far
  • Evolution of the pandemic of A(H1N1)v influenza

European Centre for Disease Prevention and
Control Based on a talk given on 11 May 2009 in
Stockholm to ECDCs Advisory Forum
2
About this presentation
  • This is an open-access ECDC Educational
    PowerPoint presentation arranged in modules for
    use by professional explaining about the new
    A(H1N1)v virus to other professionals and policy
    makers. The slides should always be viewed with
    their accompanying notes, and cutting and
    pasting is not recommended.
  • A number of the slides will change with time. The
    slides are updated at intervals and the user
    should periodically check for updates available
    on the ECDC website
  • http//ecdc.europa.eu/
  • Comments on the slides and the notes are very
    much welcomed to be sent to influenza_at_ecdc.europa.
    eu.
  • Please state "Pandemic PowerPoints" in the
    subject line when writing to us.
  • ECDC thanks the National Institute of Infectious
    Diseases, Japan, for the original work on Slide
    3, and the Centers for Disease Control and
    Prevention, USA, for the original idea in Slide
    27.

3
Pandemics of influenza
Recorded human pandemic influenza(early
sub-types inferred)
2009 Novel influenza H1N1v
1889 Russian influenza H2N2
1968 Hong Kong influenza H3N2
1900 Old Hong Kong influenza H3N8
1918 Spanish influenza H1N1
1957 Asian influenza H2N2
Animated slide Press space bar
Reproduced and adapted (2009) with permission of
Dr Masato Tashiro, Director, Center for Influenza
Virus Research, National Institute of Infectious
Diseases (NIID), Japan.
4
The situation could be a lot worse for Europe!
(Situation circa summer 2009)
A pandemic emerging in SE Asia
  • A pandemic strain emerging in the Americas
  • Immediate virus sharing so rapid diagnostic and
    vaccines
  • Based on A(H1N1)v currently not that pathogenic
  • Some seeming residual immunity in a major large
    risk group
  • No known pathogenicity markers
  • Initially susceptible to oseltamivir
  • Good data and information coming out of North
    America
  • Arriving in Europe in the summer
  • Milder presentation initially

Delayed virus sharing
Based on a more pathogenic strain, e.g. A(H5N1)
No residual immunity
Heightened pathogenicity
Inbuilt antiviral resistance
Minimal data until transmission reached Europe
Arriving in the late autumn or winter
Severe presentation immediately
Contrast with what might have happened and
might still happen!
5
But no room for complacency (Situation and
information late May 2009)
  • Pandemics take some time to get going (1918 and
    1968).
  • Some pandemic viruses have turned nasty (1918
    and 1968).
  • Is the mildness and the lack of older patients
    because older people are resistant or because the
    virus is not transmitting much among them?
  • There will be victims and deaths as in the US
    in risk groups (young children, pregnant women
    and especially people with other underlying
    illnesses).
  • As the virus spreads south, will it exchange
    genes with seasonal viruses that are resistant
    A(H1N1)-H247Y, more pathogenic A(H3N2), or even
    highly pathogenic A(H5N1)?
  • An inappropriate and excessive response to the
    pandemic could be worse than the pandemic itself.

6
Idealised curve for planning
Initiation Acceleration Peak Declining
25
aths
20
15
Proportion of total cases, consultations,
hospitalisations or de
10
5
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Week
Single wave profile showing proportion of new
clinical cases, consultations, hospitalisations
or deaths by week. Based on London, 2nd wave
1918.
Animated slide Please wait
Source Department of Health, UK
7
One possible European scenario summer 2009
Initiation Acceleration Peak Declining
25
20
15
Proportion of total cases, consultations,
hospitalisations or deaths
10
5
0
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Jan
Feb
Mar
Apr
Month
In reality, the initiation phase can be
prolonged, especially in the summer months. What
cannot be determined is when acceleration takes
place.
Animated slide Please wait
8
  • How pandemics differ and why they can be
    difficult

9
For any future pandemic virus what can and
cannot be assumed?
  • What probably can be assumed
  • Known knowns
  • Modes of transmission (droplet, direct and
    indirect contact)
  • Broad incubation period and serial interval
  • At what stage a person is infectious
  • Broad clinical presentation and case definition
    (what influenza looks like)
  • The general effectiveness of personal hygiene
    measures (frequent hand washing, using tissues
    properly, staying at home when you get ill)
  • That in temperate zones transmission will be
    lower in the spring and summer than in the autumn
    and winter
  • What cannot be assumed
  • Known unknowns
  • Antigenic type and phenotype
  • Susceptibility/resistance to antivirals
  • Age-groups and clinical groups most affected
  • Age-groups with most transmission
  • Clinical attack rates
  • Pathogenicity (case-fatality rates)
  • Severity of the pandemic
  • Precise parameters needed for modelling and
    forecasting (serial interval, Ro)
  • Precise clinical case definition
  • The duration, shape, number and tempo of the
    waves of infection
  • Will new virus dominate over seasonal type A
    influenza?
  • Complicating conditions (super-infections)
  • The effectiveness of interventions and
    counter-measures including pharmaceuticals
  • The safety of pharmaceutical interventions

10
Some of the 'known unknowns' inthe 20th century
pandemics
  • Three pandemics (1918, 1957, 1968)
  • Each quite different in shape and waves
  • Some differences in effective reproductive number
  • Different groups affected
  • Different levels of severity including case
    fatality ratio
  • Imply different approaches to mitigation

11
Age-specific clinical attack rate in previous
pandemics
60
50
40
with clinical disease
30
20
10
0
0
20
40
60
80
Age (midpoint of age class)
Animated slide Press space bar
With thanks to Peter Grove, Department of Health,
London, UK
12
Different age-specific excess deaths in pandemics
4000
3500
3000
2500
Excess deaths
2000
1500
1000
Excess deaths, second wave, 1918 epidemic
500
0
lt1
1-2
2-5
5-10
10-15
15-20
20-25
25-35
35-45
45-55
55-65
65-75
75
Age group
16000
14000
12000
10000
Excess deaths
8000
6000
Excess deaths second wave 1969 pandemic, England
and Wales
4000
2000
0
0-4
5-9
10-14
15-19
20-24
25-34
35-44
45-54
55-64
65-74
75
Age group
Source Department of Health, UK
13
1918/1919 pandemic A(H1N1) influenza deaths,
England and Wales
1918/19 Influenza deaths, England and Wales.
The pandemic affected young adults, the very
young and older age groups.
Transmissibility estimated Basic Reproductive
Number (Ro)
Ro 2-3 (US) Mills, Robins, Lipsitch (Nature
2004) Ro 1.5-2 (UK) Gani et al (EID 2005) Ro
1.5-1.8 (UK) Hall et al (Epidemiol. Infect.
2006) Ro 1.5-3.7 (Geneva) Chowell et al
(Vaccine 2006)
Courtesy of the Health Protection Agency, UK
14
Estimated additional deaths in Europe if a
1918/19 pandemic occurred now a published
worst case scenario
Austria 13,000 Latvia 13,800 Netherlands 23,100
Belgium 14,900 Lithuania 18,800 Poland 155,200
Bulgaria 47,100 Germany 116,400 Portugal 25,100
Czech Rep 34,100 Greece 27,400 Romania 149,900
Cyprus 1, 900 Hungary 37,700 Slovenia 5,000
Denmark 7,300 Ireland 6,700 Slovakia 20,600
Estonia 6,100 Italy 95,200 Spain 87,100
Finland 8,100 Luxembourg 500 Sweden 13,300
France 89,600 Malta 1,100 UK 93,000
Iceland 420 Norway 5,800
EU total 1.1 million
Murray CJL, Lopez AD, Chin B, Feehan D, Hill KH.
Estimation of potential global pandemic influenza
mortality on the basis of vital registry data
from the 191820 pandemic a quantitative
analysis. Lancet. 2006368 2211-2218.
15
1957/1958 pandemic A(H2N2) especially
transmitted among children
1,000
800
600
influenza
Recorded deaths in England and Wales from
400
200
0
6
3
7
5
2
9
7
4
1
8
13
20
27
10
17
24
31
14
21
28
12
19
26
16
23
30
14
21
28
11
18
25
15
22
July
August
September
October
November
December
January
February
Week number and month during the winter of 1957/58
1957/58 Influenza deaths, England and Wales
Transmissibility estimated Basic Reproductive
Number (Ro)
Ro 1.8 (UK) Vynnycky, Edmunds (Epidemiol.
Infect.2007) Ro 1.65 (UK) Gani et al (EID
2005) Ro 1.5 (UK) Hall et al (Epidemiol.
Infect. 2006) Ro 1.68 Longini et al (Am J
Epidem 2004)
Courtesy of the Health Protection Agency, UK
16
1968/1969 pandemic A(H3N2) transmitted and
affected all age groups
Seasonalinfluenza
Initialappearance
1968/69 GP consultations, England and Wales
Transmissibility estimated Basic Reproductive
Number (Ro)
Ro 1.5-2.2 (World) Cooper et al (PLoS
Med.2006) Ro 2.2 (UK) Gani et al (EID 2005) Ro
1.3-1.6 (UK) Hall et al (Epidemiol. Infect.
2006)
Courtesy of the Health Protection Agency, UK
17
Differing attack rates determined by serology
serological attack rate observed in the UK
Courtesy of the Health Protection Agency, UK
18
Idealised curves for local planning
25
aths
20
15
Proportion of total cases, consultations,
hospitalisations or de
10
5
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Week
In reality, larger countries can experience a
series of shorter but steeper local epidemics.
Animated slide Press space bar
19
Numbers affected in seasonal influenza epidemics
and pandemics (overall clinical attack rate in
previous pandemics)
45
40
35
30
25
clinical attack rate ()
20
15
10
5
0
1918 New
1918
1918
1957 SE
1968
Seasonalinfluenza
York State
Leicester
Warrington
London
Kansas City
and Wigan
20
Seasonal influenza compared to pandemic
proportions of types of cases
Deaths
Requiring hospitalisation
Clinicalsymptoms
Deaths
Requiring hospitalisation
Asymptomatic
Seasonal influenza
Pandemic
21
  • Initial experience in North America 2009

22
Emerging themes in North America, early June
2009 (1)
  • Early epidemic
  • increased influenza-like illness reports due to
    increased consultations
  • many cases attributable to seasonal influenza
    until mid-May.
  • Infection rate for probable and confirmed cases
    highest in 5-24 year age group.
  • Hospitalisation rate highest in 0-4 year age
    group, followed by 5-24 year age group.
  • Pregnant women, some of whom have delivered
    prematurely, have received particular attention
    but data inadequate to determine if they are at
    greater risk from H1N1v than from seasonal
    influenza as already established.
  • Most deaths in 25-64 year age group most with
    known risks for severe disease.
  • Obesity suggested as risk but may be indicator
    for pulmonary risk.
  • Adults, especially 60 years and old, may have
    some degree of preexisting cross-reactive
    antibody to the novel H1N1 flu virus.
  • Transmission persists in several regions of the
    US with increased or rising incidence in New York
    area and northeastern US.

23
Emerging themes in North America, early June
2009 (2)
  • Containment impossible with multiple
    introductions and R0 1.4 to 1.6.
  • Focus on counting laboratory-confirmed cases
    changing to seasonal surveillance methods.
  • Outpatient influenza-like illness, virological
    surveillance (including susceptibility),
    pneumonia and influenza mortality, pediatric
    mortality and geographic spread.
  • Serological experiments and epidemiology suggest
    20082009 seasonal A(H1N1) vaccine does not
    provide protection.
  • Preparing for the autumn and winter when virus is
    expected to return
  • communications a pandemic may be 'mild' yet
    cause deaths
  • 25 of U.S. stockpile deployed to states
    (includes medication and equipment)
  • determining if and when to begin using vaccine
  • school closures being analyzed to determine
    effectiveness
  • other domestic and international investigations
    of public health questions.

24
  • Measuring the severity of a pandemic

25
There is an expectation that pandemics should be
graded by severity
  • But there are difficulties
  • severity varies from country to country
  • it can change over time
  • some relevant information is not available
    initially
  • key health information includes medical and
    scientific information
  • epidemiological, clinical and virological
    characteristics.
  • There are also social and societal aspects
  • vulnerability of populations
  • capacity for response
  • available health care
  • communication and
  • the level of advance planning.

26
What is meant by 'mild' and 'severe'? Not a
simple scale
  • Death ratio. Expectation of an infected person
    dying (the Case Fatality Ratio).
  • Number of people falling ill with respiratory
    illnesses at one time 'winter pressures'.
    Pressure on the health services' ability to deal
    with these very related to preparedness and
    robustness.
  • Critical service functioning. Peak prevalence of
    people off ill or caring for others.
  • Certain groups dying unexpectedly, e.g. children,
    pregnant women, young healthy adults.
  • Public and media perception
  • Conclusions. Not easy to come up with a single
    measure.
  • May be better to state what interventions/counterm
    easures are useful and justifiable (and what are
    not).

http//www.who.int/csr/disease/swineflu/assess/dis
ease_swineflu_assess_20090511/en/index.html and
http//www.who.int/wer/2009/wer8422.pdf
27
  • Arguments for and against just undertaking
    mitigation and not attempting delaying or
    containment

28
Policy dilemma mitigating vs. attempting
delaying (containing) pandemics?
  • Arguments for just mitigating and not attempting
    delaying or containment
  • Containment specifically not recommended by WHO
    in Phases 5 6.
  • Was not attempted by the United States for this
    virus.
  • Delaying or containment cannot be demonstrated to
    have worked would have seemed to have worked in
    1918 and 1968 without doing anything.
  • Very labour-intensive major opportunity costs.
  • Will miss detecting sporadic transmissions.
  • Overwhelming numbers as other countries light
    up.
  • When you change tactic, major communication
    challenge with stopping prophylaxis.

29
Policy dilemma mitigating vs. attempting
delaying (containing) pandemics?
  • Arguments for case-finding, contact tracing and
    prophylaxis
  • Countries are then seen to be doing something.
  • Recommended in one specific circumstance by WHO
    (the rapid containment strategy).
  • There are some places it would work in Europe
    (isolated communities).
  • It is what public health people do for other
    infections.
  • Public may expect it.

30
Aims of community reduction of influenza
transmission mitigation
  • Delay and flatten epidemic peak
  • Reduce peak burden on healthcare system and
    threat
  • Somewhat reduce total number of cases
  • Buy a little time

No intervention
Daily cases
Days since first case
Animated slide Press space bar
Based on an original graph developed by the US
CDC, Atlanta
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