Lessons for Europe from the evidence to date

1
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
staffVersion 31 July 2009
2
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_at_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.

3
Pandemics of influenza
Recorded human pandemic influenza(early
sub-types inferred)
2009 Pandemic influenza H1N1
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
Genetic origins of the pandemic (H1N1) 2009
virus viral reassortment
N. American H1N1 (swine/avian/human)
Eurasian swine H1N1
Pandemic (H1N1) 2009, combining swine, avian
and human viral components
Classical swine, N. American lineage Avian, N.
American lineage Human seasonal H3N2 Eurasian
swine lineage
5
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.
• Pandemic (H1N1) currently not that pathogenic.
• Some seeming residual immunity in a major large
  risk group (older people).
• No known pathogenicity markers.
• Initially susceptible to oseltamivir.
• Good data and information coming out of North
  America.
• Arriving in Europe in the summer.
• Mild presentation in most.

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!
6
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.

7
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.

8
Idealised national curve for planning, Europe
2009 Reality is never so smooth and simple
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
Week
Single-wave profile showing proportion of new
clinical cases, consultations, hospitalisations
or deaths by week. Based on London, second wave
1918.
Animated slide Please wait
Source Department of Health, UK
9
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 Press key
10

• How pandemics differ and why they can be
  difficult

11
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

12
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.

13
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
14
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
15
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
16
Estimated additional deaths in Europe if a
1918/19 pandemic occurred now a published
worst case scenario
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.
17
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
18
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
19
Differing attack rates determined by serology
serological attack rate observed in the UK
Courtesy of the Health Protection Agency, UK
20
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
21
Numbers affected in seasonal influenza epidemics
and pandemics
45
(Overall clinical attack rate in the first wave
of previous pandemics)
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
22
Seasonal influenza compared to pandemic
proportions of types of cases
Deaths
Requiring hospitalisation
Clinicalsymptoms
Deaths
Requiring hospitalisation
Asymptomatic
Seasonal influenza
Pandemic
23

• Initial experience in North America 2009

24
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.

25
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
  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
• 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.

26

• Initial experience in Europe Planning assumptions

27
Revised European planning assumptions for the
pandemic first wave, pandemic (H1N1) 2009
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_1028
92
28

• Risk groups

29
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 persons
  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/n
  ovel_influenza_virus/2009_Outbreak
• Finelli L. CDC Influenza Surveillance. Available
  from http//www.cdc.gov/vaccines/recs/ACIP/downlo
  ads/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?A
  rticleId19018
• Jamieson D et al. Lancet 2009 July 29, 2009
  DOI10.1016/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/downlo
  ads/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/mt
  g-slides-jul09-flu/11-Flu-Fiore.pdf

30

• Measuring the severity of a pandemic

31
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.

32
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
33

• Arguments for and against just undertaking
  mitigation and not attempting delaying or
  containment

34
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.

35
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.

36
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 key
Based on an original graph developed by the US
CDC, Atlanta