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

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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] 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.

http://ecdc.europa.eu/

mailto:[email protected]

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Pandemics of influenza

H7

H5

H9*

1980

1997

Recorded new avian influenzas

1996 2002

1999

2003

1955 1965 1975 1985 1995 2005

H1N1

H2N2

1889Russianinfluenz

aH2N2

H2N2

1957Asian

influenzaH2N2

H3N2

1968Hong Konginfluenza

H3N2

H3N8

1900Old Hong

Kong influenza

H3N8

1918Spanishinfluenza

H1N1

1915 1925 1955 1965 1975 1985 1995 20051895 1905 2010 2015

2009Novel

influenzaH1N1v

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

Pro

port

ion

of

tota

l ca

ses,

con

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ati

on

s, h

osp

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ati

on

s or

de

ath

s

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

Pro

port

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of

tota

l ca

ses,

con

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ati

on

s, h

osp

italis

ati

on

s or

death

s

Initiation Acceleration Peak Declining

Animated slide: Please wait

Apr

8

How pandemics differ — and why they can be difficult

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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

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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

11

0%

10%

20%

30%

40%

50%

60%

0 20 40 60 80

Age (midpoint of age class)

% w

ith c

linic

al dis

ease

1918 New York State

1918 Manchester1918 Leicester1918 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


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 d

eath

s

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 d

eath

s

Excess deaths, second wave, 1918 epidemic

Excess deaths second wave 1969 pandemic, England and Wales

Source: Department of Health, UK

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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 1919Week no. and year

Death

s in

Engla

nd a

nd W

ale

s

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)

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Estimated additional deaths in Europe if a 1918/19 pandemic occurred now – a published worst case scenarioAustria 13,000 Latvia 13,800 Netherland

s 23,100

Belgium 14,900 Lithuania 18,800 Poland 155,200Bulgaria 47,100 Germany 116,400 Portugal 25,100Czech Rep

34,100 Greece 27,400 Romania 149,900

Cyprus 1,900

Hungary 37,700 Slovenia 5,000

Denmark 7,300 Ireland 6,700 Slovakia 20,600Estonia 6,100 Italy 95,200 Spain 87,100Finland 8,100 Luxembour

g 500 Sweden 13,300

France 89,600 Malta 1,100 UK 93,000Iceland 420 Norway 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.

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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

1,0006 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

Reco

rded d

eath

s in

Engla

nd a

nd W

ale

s fr

om

influenza

1957/58: ‘Influenza deaths’, England and Wales



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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

1,4004

2

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 'IL

I' co

nsu

ltati

ons

per

week


Initialappearance

Seasonalinfluenza


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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


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Idealised curves for local planning

In reality, larger countries can experience a series of shorter but steeper local epidemics.

0%

5%

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15%

20%

25%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Week

Pro

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0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

1918 NewYork State

1918Leicester

1918Warringtonand Wigan

1957 SELondon

1968Kansas City

clin

ical

atta

ck r

ate

(%)

Numbers affected in seasonal influenza epidemics and pandemics (overall clinical attack rate in previous pandemics)

Seasonalinfluenza

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Seasonal influenza compared to pandemic — proportions of types of cases

Asymptomatic

Clinicalsymptoms

Deaths

Requiring hospitalisation

Seasonal influenza Pandemic

Asymptomatic

ClinicalsymptomsDeaths

Requiring hospitalisation

21

Initial experience in North America 2009

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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

Dailycases

Days since first case

No intervention

Animated slide: Press space barBased on an original graph developed by the US CDC, Atlanta

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

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