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
Pandemic
H3N8 H3N2 H1N1
1895 1905 1915 1925 1955 1965 1975 1985 1995 2005 2010 2015

1889 1900 1918 1957 1968 2009

Russian Old Hong Spanish Asian Hong Kong Pandemic
influenz Kong influenza influenza influenza influenza
a influenza H1N1 H2N2 H3N2 H1N1
H2N2 H3N8
Recorded new avian H9* 1999
influenzas H5 1997 2003
H7 1980 1996 2002

1955 1965 1975 1985 1995 2005

Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus
Research, Animated slide: Press space bar
3
National Institute of Infectious Diseases (NIID), Japan.
Genetic origins of the pandemic
(H1N1) 2009 virus: viral reassortment
N. American H1N1
(swine/avian/huma
n)
Eurasian
swine H1N1 PB2
PB
PB2
PB PA
1
PA H
1 N
H A
N
P
N
A
N MP
A
P N
MP
A
N S
S

PB2
PB
PA
1
H
N
A Pandemic
N
P
MP
(H1N1)
A
N 2009, combining
S
Classical swine, N. American
lineage swine, avian and
Avian, N. American lineage
Human seasonal H3N2
human viral
Eurasian swine lineage components
4
The situation could be a lot worse
for Europe! (Situation circa summer
2009)
 A pandemic strain emerging in the
A pandemic
emerging in SE
Asia
Americas.
Delayed virus
 Immediate virus sharing so rapid sharing
diagnostic and vaccines. Based on a more
 Pandemic (H1N1) currently not thatpathogenic strain,
e.g. A(H5N1)
pathogenic.
No residual
 Some seeming residual immunity in a immunity
Heightened
major large risk group (older people).
pathogenicit Inbuilt
y antiviral
 No known pathogenicity markers. resistance
 Initially susceptible to oseltamivir. Minimal data until
transmission
 Good data and information coming out of reached Europe

North America. Arriving in the late

autumn or winter
 Arriving in Europe in the summer.
Severe Contrast with what might
 Mild presentation in most. presentation have happened — and
immediately 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
 Idealised national curve for planning,
Europe 2009: Reality is never so
smooth and simple
Initiation Acceleration Peak Declining
25%
Proportion of total cases, consultations, hospitalisations oraths
de

20%

15%

10%

5%

0%
1 2 3 4 5 6 7 8 9 10 11 12
Week

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
One possible European
scenario — summer 2009
Proportion of total cases, consultations, hospitalisations or deaths

Initiation Acceleration Peak Declining

25%

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
50%
1918 New York State
% with clinical disease

1918 Manchester
1918 Leicester
40% 1918 Warrington & Wigan

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

3500

3000
Excess deaths

2500

2000

1500

1000

500 Excess deaths, second

0 wave, 1918 epidemic
<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

14000
Excess deaths

12000

10000

8000

6000

4000 Excess deaths second wave

2000 1969 pandemic, England
0 and Wales
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

16,000
Deaths in England and Wales

14,000

12,000

10,000

8,000

6,000

4,000

2,000

0
43
45
47
49
51
41
39
27
29

31
33
35
37

18
10

16
12
14
2
4
6
8
1918 Week no. and year 1919

1918/19: ‘Influenza deaths’, England and Wales. Transmissibility: estimated Basic Reproductive Number (Ro
Ro = 2-3 (US) Mills, Robins, Lipsitch (Nature 2004)
The pandemic affected young adults, the very Ro = 1.5-2 (UK) Gani et al (EID 2005)
young and older age groups. 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

15
 Estimated additional deaths in
Europe if a 1918/19 pandemic
occurred now –
a published
Austria 13,000 worst
Latvia case13,800Netherlands
scenario 23,100
Belgium 14,900Lithuania 18,800Poland 155,200
Bulgaria 47,100Germany 116,400Portugal 25,100
Czech Rep 34,100Greece 27,400Romania 149,900
Cyprus 1, Hungary 37,700Slovenia 5,000
900
Denmark 7,300Ireland 6,700Slovakia 20,600
Estonia 6,100Italy 95,200Spain 87,100
Finland 8,100Luxembourg 500Sweden 13,300
France 89,600Malta 1,100UK 93,000
Iceland 420Norway 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
1,000
Recorded deaths in England and Wales from

800

600
influenza

400

200

0
10
17

31

14
21
28

12

26

23
30

14

28
24

19

16

21
13
20

11

25

15
22
27

18
3

2
9

4
6

1
8
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

17
 1968/1969 pandemic: A(H3N2) —
transmitted and affected all age groups
1,400
Seasonal
1,200 influenza
GP 'ILI' consultations per week

1,000

800
Initial
600 appearance

400

200

0
28

36

44

16

24

40

48
12

20

50

32

12
42

48

20

28

36
4

4
1967 1968 1969 1970
Week no. and year
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

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 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

19
Idealised curves for local
planning
25%
Proportion of total cases, consultations, hospitalisations oraths
de

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% (Overall clinical attack rate in the first

40% wave of previous pandemics)
clinical attack rate (%)

35%
30%
25%
20%
15%
10%
5%
0%
Seasonal 1918 New 1918 1918 1957 SE 1968
influenza York State Leicester Warrington London Kansas City
and Wigan

21
Seasonal influenza compared to
pandemic — proportions of types of
cases

Deaths
Requiring
hospitalisation

Clinical
Deaths Requiring symptoms
hospitalisation

Clinical
symptoms

Asymptomatic
Asymptomatic

Seasonal influenza Pandemic

22
Initial experience in
North America 2009

23
Emerging themes in North America,

late
Early July 2009 (1)
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 6.5% (local planning assumptions 4.5%

rate to 8%) per week

Complication rate 15% of clinical cases

Hospitalisation rate 2% of clinical cases

0.1% to 0.2% (cannot exclude up to

Case fatality rate
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/02-Flu-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-Flu-Fiore.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