Re: Lessons for Europe from past pandemics and the North American experience so far
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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
ECDC?s 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@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
H7
H5
H9*
1980
1997
Recorded new avian influenzas
1996
2002
1999
2003
1955
1965
1975
1985
1995
2005
H1N1
H2N2
1889
Russian
influenza
H2N2
H2N2
1957
Asian
influenza
H2N2
H3N2
1968
Hong Kong
influenza
H3N2
H3N8
1900
Old Hong Kong influenza
H3N8
1918
Spanish
influenza
H1N1
1915
1925
1955
1965
1975
1985
1995
2005
1895
1905
2010
2015
2009
Novel
influenza
H1N1v
Recorded human pandemic influenza
(early sub-types inferred)
Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research,
National Institute of Infectious Diseases (NIID), Japan.
Animated slide: Press space bar
H1N1
H1N1v
4
The situation could be a lot worse
for Europe! (Situation circa summer 2009)
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
A pandemic emerging in SE Asia
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
Single wave profile showing proportion of new clinical cases, consultations, hospitalisations or deaths by week. Based on London, 2nd wave 1918.
0%
5%
10%
15%
20%
25%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Week
Proportion of total cases, consultations, hospitalisations or de
aths
Source: Department of Health, UK
Initiation Acceleration Peak Declining
Animated slide: Please wait
7
One possible European scenario ? summer 2009
In reality, the initiation phase can be prolonged, especially in the summer months. What cannot be determined is when acceleration takes place.
0%
5%
10%
15%
20%
25%
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Jan
Feb
Mar
Month
Proportion of total cases, consultations, hospitalisations or deaths
Initiation Acceleration Peak Declining
Animated slide: Please wait
Apr
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' in
the 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
0%
10%
20%
30%
40%
50%
60%
0
20
40
60
80
Age (midpoint of age class)
% with clinical disease
1918 New York State
1918 Manchester
1918 Leicester
1918 Warrington & Wigan
1957 SE London
1957 S Wales
1957 Kansas City
1968 Kansas City
With thanks to Peter Grove, Department of Health, London, UK
Age-specific clinical attack rate in previous pandemics
Animated slide: Press space bar
12
Different age-specific excess deaths in pandemics
0
2000
4000
6000
8000
10000
12000
14000
16000
0-4
5-9
10-14
15-19
20-24
25-34
35-44
45-54
55-64
65-74
75+
Age group
Excess deaths
0
500
1000
1500
2000
2500
3000
3500
4000
<1
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
Excess deaths
Excess deaths, second wave, 1918 epidemic
Excess deaths second wave 1969 pandemic, England and Wales
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.
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
27
29
31
33
35
37
39
41
43
45
47
49
51
2
4
6
8
10
12
14
16
18
1918
1919
Week no. and year
Deaths in England and Wales
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
Transmissibility: estimated Basic Reproductive Number (Ro)
14
Estimated additional deaths in Europe if a 1918/19 pandemic occurred now ?
a published worst case scenario
5,800
Norway
420
Iceland
93,000
UK
1,100
Malta
89,600
France
13,300
Sweden
500
Luxembourg
8,100
Finland
87,100
Spain
95,200
Italy
6,100
Estonia
20,600
Slovakia
6,700
Ireland
7,300
Denmark
5,000
Slovenia
37,700
Hungary
1, 900
Cyprus
149,900
Romania
27,400
Greece
34,100
Czech Rep
25,100
Portugal
116,400
Germany
47,100
Bulgaria
155,200
Poland
18,800
Lithuania
14,900
Belgium
23,100
Netherlands
13,800
Latvia
13,000
Austria
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 1918?20 pandemic: a quantitative analysis. Lancet. 2006;368: 2211-2218.
15
1957/1958 pandemic: A(H2N2) ?
especially transmitted among children
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)
0
200
400
600
800
1,000
6
13
20
27
3
10
17
24
31
7
14
21
28
5
12
19
26
2
9
16
23
30
7
14
21
28
4
11
18
25
1
8
15
22
July
August
September
October
November
December
January
February
Week number and month during the winter of 1957/58
Recorded deaths in England and Wales from
influenza
1957/58: ?Influenza deaths?, England and Wales
Courtesy of the Health Protection Agency, UK
Transmissibility: estimated Basic Reproductive Number (Ro)
16
1968/1969 pandemic: A(H3N2) ? transmitted and affected all age groups
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)
1968/69: GP consultations, England and Wales
0
200
400
600
800
1,000
1,200
1,400
42
48
4
12
20
28
36
44
50
8
16
24
32
40
48
4
12
20
28
36
1967
1968
1969
1970
Week no. and year
GP 'ILI' consultations per week
Courtesy of the Health Protection Agency, UK
Initial
appearance
Seasonal
influenza
Transmissibility: estimated Basic Reproductive Number (Ro)
17
Differing attack rates determined by serology: serological attack rate observed in the UK
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0-9
10-19
20-29
30-39
40-49
50-59
60-69
70-79
1969 (first wave)
1970 (second wave)
1957
Courtesy of the Health Protection Agency, UK
18
Idealised curves for local planning
In reality, larger countries can experience a series of shorter but steeper local epidemics.
0%
5%
10%
15%
20%
25%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Week
Proportion of total cases, consultations, hospitalisations or de
aths
Animated slide: Press space bar
19
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
1918 New
York State
1918
Leicester
1918
Warrington
and Wigan
1957 SE
London
1968
Kansas City
clinical attack rate (%)
Numbers affected in seasonal influenza epidemics and pandemics (overall clinical attack rate in previous pandemics)
Seasonal
influenza
20
Seasonal influenza compared to pandemic ? proportions of types of cases
Asymptomatic
Clinical
symptoms
Deaths
Requiring
hospitalisation
Seasonal influenza
Pandemic
Asymptomatic
Clinical
symptoms
Deaths
Requiring
hospitalisation
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 2008?2009 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/countermeasures are useful and justifiable (and what are not).
http://www.who.int/csr/disease/swineflu/assess/disease_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
With interventions
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
Daily
cases
Days since first case
No intervention
Animated slide: Press space bar
Based on an original graph developed by the US CDC, Atlanta
