Lessons for Europe from the evidence to date
Evolution of the
H1N1 pandemic
European Centre for Disease Prevention and Control
Based on various talks given by ECDC staff
Version 31 July 2009
About this presentation
This is an open-access ECDC Educational PowerPoint presentation,
arranged in modules for use by professionals explaining about the
pandemic (H1N1) 2009 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.
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
Slides 4 and 36.
2
Pandemics of influenza
Recorded human pandemic influenza
(early sub-types inferred)
H2N2
H2N2
H1N1
H1N1
H3N8
1895 1905
1889
Russian
influenza
H2N2
1915
Pandemic
H1N1
H3N2
1925
1900
Old Hong Kong
influenza
H3N8
1955
1918
Spanish
influenza
H1N1
1965
1957
Asian
influenza
H2N2
1975
1985
2010
2015
H9* 1999
H5 1997 2003
H7 1980
Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research,
National Institute of Infectious Diseases (NIID), Japan.
2005
2009
Pandemic
influenza
H1N1
1968
Hong Kong
influenza
H3N2
Recorded new avian influenzas
1955
1995
1965
1975
1985
1996
1995
2002
2005
Animated slide: Press space bar 3
Genetic origins of the pandemic (H1N1)
2009 virus: viral reassortment
N. American H1N1
(swine/avian/human)
PB2
PB1
PA
HA
NP
NA
MP
NS
Eurasian
swine H1N1
PB2
PB1
PA
HA
NP
NA
MP
NS
Classical swine, N. American lineage
Avian, N. American lineage
Human seasonal H3N2
Eurasian swine lineage
PB2
PB1
PA
HA
NP
NA
MP
NS
Pandemic (H1N1)
2009, combining
swine, avian and
human viral
components
4
The situation could be a lot worse
for Europe! (Situation circa summer 2009)
A pandemic
 A pandemic strain emerging in the Americas.
emerging in SE Asia
 Immediate virus sharing so rapid diagnostic and
Delayed virus
sharing
vaccines.
Based on a more
 Pandemic (H1N1) currently not that
pathogenic strain, e.g.
pathogenic.
A(H5N1)
 Some seeming residual immunity in a major
No residual
large risk group (older people).
immunity
Heightened
 No known pathogenicity markers.
pathogenicity
Inbuilt antiviral
resistance
 Initially susceptible to oseltamivir.
Minimal data until
 Good data and information coming out of
transmission reached
Europe
North America.
Arriving in the late
 Arriving in Europe in the summer.
autumn or winter
 Mild presentation in most.
Contrast with what might
Severe presentation
immediately
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).
 When the pandemic wave affects Europe the health services will be
challenged
 There will be severely ill people and deaths — in risk groups (young
children, pregnant women and especially people with 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
Candidate objectives of pandemic
responses
 Protect citizens and visitors against the health and wider consequences
of the pandemic as far as this is possible.
 Through surveillance and rapid studies undertake early assessment to
determine the special features of this pandemic that will inform the
needed countermeasures.
 Identify and protect those most vulnerable to the pandemic.
 Deploy the known effective countermeasures and adapt and employ
other countermeasures so that they have a net positive effect.
 Apply countermeasures as effectively and equitably as possible.
 Organise and adapt health and social care systems to provide treatment
and support for those likely to suffer from influenza and its complications
whilst sustaining other essential care services.
 Support the continuity of other essential services and protect critical
infrastructure.
 Support the continuation of everyday activities as far as practical.
 Instill and maintain trust and confidence by ensuring that the
professionals, the public and the media are engaged and well informed.
 Promote a return to normality and the restoration of any disrupted
services at the earliest opportunity.
7
Proportion of total cases, consultations, hospitalisations or de aths
Idealised national curve for planning,
Europe 2009: Reality is never so smooth
and simple
25%
Initiation
Acceleration
Peak
Declining
20%
15%
10%
5%
0%
1
2
3
4
5
6
Week
7
8
9
10
11
12
Single-wave profile showing proportion of new clinical cases, consultations, hospitalisations or
deaths by week. Based on London, second wave 1918.
Source: Department of Health, UK
Animated slide: Please wait
8
Proportion of total cases, consultations, hospitalisations or deaths
One possible European scenario —
summer 2009
Initiation
25%
Acceleration
Peak
Declining
20%
15%
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: Press key
9
How pandemics differ —
and why they can be difficult
10
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
11
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.





12
Age-specific clinical attack rate in
previous pandemics
60%
1957 Kansas City
1957 S Wales
1957 SE London
1968 Kansas City
% with clinical disease
50%
1918 New York State
1918 Manchester
1918 Leicester
1918 Warrington & Wigan
40%
30%
20%
10%
0%
0
20
40
60
80
Age (midpoint of age class)
With thanks to Peter Grove, Department of Health, London, UK
Animated slide: Press space bar 13
Different age-specific excess deaths in
pandemics
4000
Excess deaths
3500
3000
2500
2000
1500
1000
Excess deaths, second wave,
1918 epidemic
500
0
<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
16000
Excess deaths
14000
12000
10000
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
14
1918/1919 pandemic: A(H1N1)
influenza deaths, England and Wales
18,000
Deaths in England and Wales
16,000
14,000
12,000
10,000
8,000
6,000
4,000
2,000
1918
Week no. and year
1918/19: ‘Influenza deaths’, England and Wales.
The pandemic affected young adults, the very young
and older age groups.
Courtesy of the Health Protection Agency, UK
18
16
14
12
10
8
6
4
2
51
49
47
45
43
41
39
37
35
33
31
29
27
0
1919
Transmissibility: estimated Basic Reproductive Number (R o)
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)
15
Estimated additional deaths in Europe if a
1918/19 pandemic occurred now –
a published worst case scenario
Austria
Belgium
Bulgaria
Czech Rep
Cyprus
Denmark
Estonia
Finland
France
13,000
14,900
47,100
34,100
1,900
7,300
6,100
8,100
89,600
Latvia
Lithuania
Germany
Greece
Hungary
Ireland
Italy
Luxembourg
Malta
Iceland
13,800
18,800
116,400
27,400
37,700
6,700
95,200
500
1,100
420
Netherlands
Poland
Portugal
Romania
Slovenia
Slovakia
Spain
Sweden
UK
Norway
23,100
155,200
25,100
149,900
5,000
20,600
87,100
13,300
93,000
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 1918–20 pandemic: a quantitative analysis. Lancet. 2006;368: 2211-2218.
16
1957/1958 pandemic: A(H2N2) —
especially transmitted among children
800
600
400
200
0
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
Recorded deaths in England and Wales from
influenza
1,000
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
Courtesy of the Health Protection Agency, UK
Transmissibility: estimated Basic Reproductive Number (R o)
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)
17
1968/1969 pandemic: A(H3N2) —
transmitted and affected all age groups
1,400
Seasonal
influenza
GP 'ILI' consultations per week
1,200
1,000
800
Initial
appearance
600
400
1967
1968
1969
36
28
20
12
4
48
40
32
24
16
8
50
44
36
28
20
12
4
48
0
42
200
1970
Week no. and year
1968/69: GP consultations, England and Wales
Transmissibility: estimated Basic Reproductive Number (R o)
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
18
Differing attack rates determined by
serology: serological attack rate observed
in the UK
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0-9
10-19
1969 (first wave)
Courtesy of the Health Protection Agency, UK
20-29
30-39
40-49
50-59
1970 (second wave)
60-69
70-79
1957
19
Proportion of total cases, consultations, hospitalisations or de aths
Idealised curves for local planning
25%
20%
15%
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 20
Numbers affected in seasonal influenza
epidemics and pandemics
45%
clinical attack rate (%)
40%
(Overall clinical attack rate in the first wave
of previous pandemics)
35%
30%
25%
20%
15%
10%
5%
0%
Seasonal
influenza
1918 New
York State
1918
Leicester
1918
Warrington
and Wigan
1957 SE
London
1968
Kansas City
21
Seasonal influenza compared to
pandemic — proportions of types of
cases
Deaths
Requiring
hospitalisation
Deaths
Requiring
hospitalisation
Clinical
symptoms
Asymptomatic
Seasonal influenza
Clinical
symptoms
Asymptomatic
Pandemic
22
Initial experience in
North America 2009
23
Emerging themes in North America,
late July 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 seem to at somewhat greater risk from
H1N1v than from seasonal influenza as already established.
 Most deaths in 25−64 year age group in people with chronic
underlying disease.
 Adults, especially 60 years and old, may have some degree of
preexisting cross-reactive antibody to the novel H1N1 flu virus.
 Transmission persisting in several regions of the US, but not all
areas are affected.
24
Emerging themes in North America,
early June 2009 (2)
 Containment with impossible with multiple introductions and R0 1.4
to 1.6.
 Initial focus on counting laboratory-confirmed cases has changed
to seasonal surveillance methods with:
– outpatient influenza-like illness, virological surveillance (including
susceptibility), pneumonia and influenza mortality, pediatric mortality
and geographic spread.
 Stopped issuing reports of numbers of infected persons as these were
meaningless.
 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;
– determining if and when to begin using vaccine;
– abandoned previous plans to use proactive school closures as this was
unworkable;
– looking at the southern hemisphere temperate countries.
25
Initial experience in Europe:
Planning assumptions
26
Revised European planning assumptions
for the pandemic – first wave, pandemic
(H1N1) 2009
Clinical attack rate
30%
Peak clinical attack rate
6.5% (local planning assumptions 4.5% to
8%) per week
Complication rate
15% of clinical cases
Hospitalisation rate
2% of clinical cases
Case fatality rate
0.1% to 0.2% (cannot exclude up to 0.35%)
of clinical cases
Peak absence rate
12% of workforce
These assumptions represent a reasonable worst case applying to one European country (the United Kingdom)
with data available as of July 2009. They should not be used for predictions.
Courtesy of Department of Health, UK, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_102892
27
Risk groups
28
Risk groups for the
A(H1N1) pandemic 2009
The following groups are considered more at risk of experiencing severe
disease than the general population should they become infected with the
pandemic A(H1N1) virus 2009:
 People with chronic conditions in the following categories:
–
–
–
–
–
–
–
chronic respiratory diseases;
chronic cardiovascular diseases (though not isolated mild hypertension);
chronic metabolic disorders (notably diabetes);
chronic renal and hepatic diseases;
persons with deficient immunity (congenital or acquired);
chronic neurological or neuromuscular conditions; and
any other condition that impairs a person’s immunity or prejudices their respiratory (breathing)
function, including severe or morbid obesity.
Note: These categories will be subject to amendment and development as more data become available. These are very similar underlying
conditions that serve as risk factors for seasonal influenza. What is especially different from seasonal influenza is that the older age
groups (over the age of 60 years) without underlying conditions are relatively unaffected by the pandemic strain.
 Pregnant women.
 Young children (especially those under two years).
Sources:
ECDC Pandemic 2009 Risk Assessment. Available from: http://www.ecdc.europa.eu/en/Health_topics/novel_influenza_virus/2009_Outbreak
Finelli L. CDC Influenza Surveillance. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jun09/15-2-inf.pdf
Nicoll A et al. Eurosurveillance, Volume 13, Issue 43, 23 October 2008. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19018
Jamieson D et al. Lancet 2009; July 29, 2009 DOI:10.1016/S0140-6736(09)61304-0
CDC 2009 ACIP Meeting, 31 July 2009. Novel influenza A(H1N1) epidemiology update. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jul09-flu/02Flu-Fiore.pdf
CDC 2009 ACIP Meeting, 31 July 2009. Vaccine workgroup considerations. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jul09-flu/11-FluFiore.pdf
29
Measuring the severity of a
pandemic
30
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.
31
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
32
Arguments for and against just
undertaking mitigation and not
attempting delaying or containment
33
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 and 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.
34
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.
35
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
With interventions
Days since first case
Based on an original graph developed by the US CDC, Atlanta
Animated slide: Press key
36