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. About this presentation.

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Lessons for europe from past pandemics and the north american experience so far

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


About this presentation

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 [email protected]

  • 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.


Pandemics of influenza

H3N8

H2N2

H2N2

H1N1

H1N1v

H3N2

2015

2010

1915

1925

1955

1965

1975

1985

1995

2005

1895

1905

H1N1

H9*

Recorded new avian influenzas

1999

H5

1997

2003

H7

1980

1996

2002

1955

1965

1975

1985

1995

2005

Pandemics of influenza

Recorded human pandemic influenza(early sub-types inferred)

2009

Novel

influenza

H1N1v

1889

Russian

influenza

H2N2

1968

Hong Kong

influenza

H3N2

1918

Spanish

influenza

H1N1

1900

Old Hong Kong influenza

H3N8

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.


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

The situation could be a lot worse for Europe! (Situation circa summer 2009)

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

Contrast with what might have happened — and might still happen!

Severe presentation immediately


But no room for complacency situation and information late may 2009

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.


Idealised curve for planning

Idealised curve for planning

InitiationAccelerationPeakDeclining

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


One possible european scenario summer 2009

One possible European scenario — summer 2009

InitiationAccelerationPeakDeclining

25%

20%

15%

Proportion of total cases, consultations, hospitalisations or deaths

10%

5%

0%

Apr

Apr

May

Jun

Jul

Aug

Sep

Oct

Nov

Dec

Jan

Feb

Mar

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


Lessons for europe from past pandemics and the north american experience so far

  • How pandemics differ — and why they can be difficult


For any future pandemic virus what can and cannot be assumed

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


Some of the known unknowns in the 20th century pandemics

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


Age specific clinical attack rate in previous pandemics

1918 New York State

1918 Manchester

1918 Leicester

1918 Warrington & Wigan

1957 SE London

1957 S Wales

1957 Kansas City

1968 Kansas City

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


Different age specific excess deaths in pandemics

Different age-specific excess deaths in pandemics

4000

3500

3000

2500

Excess deaths

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

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


1918 1919 pandemic a h1n1 influenza deaths england and wales

18,000

16,000

14,000

12,000

Deaths in England and Wales

10,000

8,000

6,000

4,000

2,000

0

41

43

45

47

51

2

4

39

49

27

29

31

33

37

35

6

8

10

16

18

12

14

1918

1919

Week no. and year

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


Lessons for europe from past pandemics and the north american experience so far

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 1918–20 pandemic: a quantitative analysis. Lancet. 2006;368: 2211-2218.


1957 1958 pandemic a h2n2 especially transmitted among children

1957/1958 pandemic: A(H2N2) —especially transmitted among children

1,000

800

600

influenza

Recorded deaths in England and Wales from

400

200

0

3

7

5

2

9

7

4

6

1

8

10

17

24

31

14

21

28

12

19

26

16

23

30

14

21

28

13

20

27

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


1968 1969 pandemic a h3n2 transmitted and affected all age groups

1,400

1,200

1,000

800

GP 'ILI' consultations per week

600

400

200

0

8

4

4

12

20

36

44

50

16

24

32

40

48

28

12

20

36

42

48

28

1967

1968

1969

1970

Week no. and year

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


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

Differing attack rates determined by serology: serological attack rate observed in the UK

Courtesy of the Health Protection Agency, UK


Idealised curves for local planning

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


Lessons for europe from past pandemics and the north american experience so far

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


Seasonal influenza compared to pandemic proportions of types of cases

Clinicalsymptoms

Asymptomatic

Seasonal influenza compared to pandemic — proportions of types of cases

Deaths

Requiring hospitalisation

Clinicalsymptoms

Deaths

Requiring hospitalisation

Asymptomatic

Seasonal influenza

Pandemic


Lessons for europe from past pandemics and the north american experience so far

  • Initial experience in North America 2009


Emerging themes in north america early june 2009 1

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.


Emerging themes in north america early june 2009 2

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.


Lessons for europe from past pandemics and the north american experience so far

  • Measuring the severity of a pandemic


There is an expectation that pandemics should be graded by severity

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.


What is meant by mild and severe not a simple scale

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


Lessons for europe from past pandemics and the north american experience so far

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


Policy dilemma mitigating vs attempting delaying containing pandemics

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.


Policy dilemma mitigating vs attempting delaying containing pandemics1

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.


Aims of community reduction of influenza transmission mitigation

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

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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