0907 Influenza AH1N1 Likely Evolution of the Pandemic of The

8/3/2019 0907 Influenza AH1N1 Likely Evolution of the Pandemic of The

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Lessons for Europe from the evidence to date

Evolution of theH1N1 pandemicEuropean Centre for Disease Prevention and Control

Based on various talks given by ECDC staffVersion 31 July 2009


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About this presentation

This is an open-access ECDC Educational PowerPoint presentation,arranged in modules for use by professionals explaining about thepandemic (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 atintervals, and the user should periodically check for updates available onthe ECDC website:

http://ecdc.europa.eu/

Comments on the slides and the notes are very much welcomed to besent to [email protected]. Please state 'Pandemic PowerPoints'

in the subject line.

ECDC thanks the National Institute of Infectious Diseases, Japan, for the original work onSlide 3, and the Centers for Disease Control and Prevention, USA, for the original idea inSlides 4 and 36.


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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

1889Russianinfluenza

H2N2

H2N2

1957Asian

influenzaH2N2

H3N2

1968Hong Konginfluenza

H3N2

H3N8

1900Old Hong Kong

influenzaH3N8

1918Spanishinfluenza

H1N1

1915 1925 1955 1965 1975 1985 1995 20051895 1905 2010 2015

2009Pandemicinfluenza

H1N1

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

Pandemic

H1N1


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Genetic origins of the pandemic (H1N1)2009 virus: viral reassortment

PB2PB1PAHANPNA

MPNS

PB2PB1PAHANPNAMP

NS

PB2PB1PAHA

NPNAMPNS

Classical swine, N. American lineageAvian, N. American lineageHuman seasonal H3N2Eurasian swine lineage

Eurasianswine H1N1

N. American H1N1

(swine/avian/human)

Pandemic (H1N1)2009, combiningswine, avian andhuman viralcomponents


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

A pandemic strain emerging in the Americas.

Immediate virus sharing so rapid diagnostic andvaccines.

Pandemic (H1N1) currently not thatpathogenic.

Some seeming residual immunity in a majorlarge risk group (older people).

No known pathogenicity markers.

Initially susceptible to oseltamivir.

Good data and information coming out ofNorth America.

Arriving in Europe in the summer.

Mild presentation in most.

A pandemicemerging in SE Asia

Delayed virussharing

Based on a morepathogenic strain, e.g.A(H5N1)

No residualimmunityHeightenedpathogenicity Inbuilt antiviral

resistance

Minimal data untiltransmission reachedEurope

Arriving in the lateautumn or winter

Severe presentationimmediately

Contrast with what mighthave happened and mightstill happen!


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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 bechallenged

There will be severely ill people and deaths in risk groups (youngchildren, 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 pathogenicA(H3N2), or even highly pathogenic A(H5N1)?

An inappropriate and excessive response to the pandemic could beworse than the pandemic itself.


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Candidate objectives of pandemicresponses 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 theneeded 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 complicationswhilst sustaining other essential care services.

Support the continuity of other essential services and protect criticalinfrastructure.

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.


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Idealised national curve for planning,Europe 2009: Reality is never so smoothand simple

Single-wave profile showing proportion of new clinical cases, consultations, hospitalisations ordeaths by week. Based on London, second wave 1918.

Source: Department of Health, UK

0%

5%

10%

15%

20%

25%

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

Week

Pro

port

iono

ftotalcases,consu

lta

tions,

hosp

ita

lisa

tionsor

dea

ths

Initiation Acceleration Peak Declining

Animated slide: Please wait


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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

Proport

iono

ftotalcases,consu

ltations,

hosp

ita

lisa

tionsor

dea

ths

Initiation Acceleration Peak Declining

Animated slide: Press key

Apr


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How pandemics differ and why they can be difficult


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For any future pandemic virus whatcan and cannot be assumed?

What probably can be assumed:

Known knowns

Modes of transmission (droplet, directand indirect contact)

Broad incubation period and serialinterval

At what stage a person is infectious

Broad clinical presentation and casedefinition (what influenza looks like)

The general effectiveness of personalhygiene measures (frequent handwashing, using tissues properly, stayingat home when you get ill)

That in temperate zones transmission

will be lower in the spring and summerthan 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 seasonaltype A influenza?

Complicating conditions (super-infections) The effectiveness of interventions and

counter-measures includingpharmaceuticals

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 reproductivenumber.

Different groups affected.

Different levels of severity including case fatality

ratio. Imply different approaches to mitigation.


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0%

10%

20%

30%

40%

50%

60%

0 20 40 60 80

Age (midpoint of age class)

%w

ithcl

inica

ldisease

1918 New York State

1918 Manchester

1918 Leicester

1918 Warrington & Wigan

1957 SE London1957 S Wales

1957 Kansas City

1968 Kansas City

With thanks to Peter Grove, Department of Health, London, UK

Age-specific clinical attack rate inprevious pandemics

Animated slide: Press space bar


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Different age-specific excess deaths inpandemics

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

dea

ths

0

500

1000

1500

2000

2500

3000

3500

4000


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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 youngand 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

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49

51 2 4 6 8 1

012

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1918 1919Week no. and year

Dea

thsin

Eng

lan

dan

dWa

les

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 a1918/19 pandemic occurred now a published worst case scenario Austria 13,000 Latvia 13,800 Netherlands 23,100Belgium 14,900 Lithuania 18,800 Poland 155,200Bulgaria 47,100 Germany 116,400 Portugal 25,100Czech Rep 34,100 Greece 27,400 Romania 149,900Cyprus 1,900 Hungary 37,700 Slovenia 5,000Denmark 7,300 Ireland 6,700 Slovakia 20,600Estonia 6,100 Italy 95,200 Spain 87,100Finland 8,100 Luxembourg 500 Sweden 13,300France 89,600 Malta 1,100 UK 93,000

Iceland 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 basisof vital registry data from the 191820 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

1,000

613

20

2731

017

24

3171

421

2851

219

262 91

623

3071

421

2841

118

251 81

522

July August September October November December January February

Week number and month during the winter of 1957/58

Recorde

ddea

ths

inEng

lan

dan

dWa

les

from

influ

enza

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

1,400

42

48 4

1

2

2

0

28

3

6

4

4

5

0 81

6

2

4

3

2

4

0

4

8 412

20

28

36

1967 1968 1969 1970

Week no. and year

GP'ILI'

consu

lta

tionsperwee

k


Initial

appearance

Seasonalinfluenza



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Differing attack rates determined byserology: serological attack rate observedin 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 steeperlocal epidemics.

0%

5%

10%

15%

20%

25%

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

Week

Proport

iono

ftotalcases,consu

lta

tions,

hosp

ita

lisa

tionsor

dea

ths

Animated slide: Press space bar


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0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

1918 New

York State

1918

Leicester

1918

Warrington

and Wigan

1957 SE

London

1968

Kansas City

clinicalattackrate(%)

Numbers affected in seasonal influenzaepidemics and pandemics

Seasonalinfluenza

(Overall clinical attack rate in the first waveof previous pandemics)


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Seasonal influenza compared topandemic proportions of types ofcases

Asymptomatic

Clinicalsymptoms

Deaths

Requiringhospitalisation

Seasonal influenza Pandemic

Asymptomatic

ClinicalsymptomsDeaths

Requiringhospitalisation


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Initial experience inNorth America 2009


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Emerging themes in North America,late July 2009 (1) Early epidemic:

increased influenza-like illness reports due to increasedconsultations;

many cases attributable to seasonal influenza until mid-May.

Infection rate for probable and confirmed cases highest in 524year age group.

Hospitalisation rate highest in 04 year age group, followed by524 year age group. Pregnant women, some of whom have delivered prematurely, have

received particular attention seem to at somewhat greater risk fromH1N1v than from seasonal influenza as already established.

Most deaths in 2564 year age group in people with chronicunderlying disease.

Adults, especially 60 years and old, may have some degree ofpreexisting cross-reactive antibody to the novel H1N1 flu virus.

Transmission persisting in several regions of the US, but not allareas are affected.


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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 mortalityand geographic spread.

Stopped issuing reports of numbers of infected persons as these weremeaningless.

Serological experiments and epidemiology suggest 20082009seasonal A(H1N1) vaccine does not provide protection.

Preparing for the autumn and winter when virus is expected toreturn: 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 wasunworkable;

looking at the southern hemisphere temperate countries.


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Initial experience in Europe:Planning assumptions


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Revised European planning assumptionsfor the pandemic first wave, pandemic(H1N1) 2009

12% of workforcePeak absence rate

0.1% to 0.2% (cannot exclude up to 0.35%)of clinical cases

Case fatality rate

2% of clinical casesHospitalisation rate

15% of clinical casesComplication rate

6.5% (local planning assumptions 4.5% to8%) per week

Peak clinical attack rate

30%Clinical attack rate

Courtesy of Department of Health, UK, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/Publications PolicyAndGuidance/DH_102892

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.


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Risk groups


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Risk groups for theA(H1N1) pandemic 2009

The following groups are considered more at risk of experiencing severe

disease than the general population should they become infected with thepandemic 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 underlyingconditions that serve as risk factors for seasonal influenza. What is especially different from seasonal influenza is that the older agegroups (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_OutbreakFinelli L. CDC Influenza Surveillance. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jun09/15-2-inf.pdfNicoll A et al. Eurosurveillance, Volume 13, Issue 43, 23 October 2008. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19018Jamieson D et al. Lancet 2009; July 29, 2009 DOI:10.1016/S0140-6736(09)61304-0CDC 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.pdfCDC 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


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Measuring the severity of apandemic


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There is an expectation that pandemicsshould be graded by severityBut 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.


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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' abilityto deal with these very related to preparedness and robustness.

Critical service functioning. Peak prevalence of people off ill orcaring for others.

Certain groups dying unexpectedly, e.g. children, pregnantwomen, 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 usefuland justifiable (and what are not).

http://www.who.int/csr/disease/swineflu/assess/disease_swineflu_assess_20090511/en/index.html andhttp://www.who.int/wer/2009/wer8422.pdf


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Arguments for and against justundertaking mitigation and notattempting delaying or containment


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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 and1968 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 withstopping prophylaxis.

Policy dilemma mitigating vs. attemptingdelaying (containing) pandemics?


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Policy dilemma mitigating vs. attemptingdelaying (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 (therapid containment strategy).

There are some places it would work in Europe (isolatedcommunities).

It is what public health people do for other infections. Public may expect it.


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With interventions

Aims of community reduction ofinfluenza 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 keyBased on an original graph developed by the US CDC, Atlanta

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0907 Influenza AH1N1 Likely Evolution of the Pandemic of The