Lessons for Europe from the evidence to dateEvolution of the H1N1 pandemicEuropean Centre for Disease Prevention and ControlBased 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 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.

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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

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.

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H1N1Pandemic

H1N1

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

PB2PB1PAHANPNAMPNS

PB2PB1PAHANPNAMPNS

PB2PB1PAHANPNAMPNS

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

Eurasian swine H1N1

N. American H1N1(swine/avian/human)

Pandemic (H1N1) 2009, combining

swine, avian and human viral components

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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. 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.

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!

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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 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.

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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.

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

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

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

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Initiation Acceleration Peak Declining

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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.

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Initiation Acceleration Peak Declining

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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.

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0%

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Age (midpoint of age class)

% w

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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

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Different age-specific excess deaths in pandemics

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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.

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1918 1919Week no. and year

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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)

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July August September October November December January February

Week number and month during the winter of 1957/58

Reco

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influenza

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

Courtesy of the Health Protection Agency, UK

Transmissibility: estimated Basic Reproductive Number (Ro)

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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

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GP 'IL

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per

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Courtesy of the Health Protection Agency, UK

Initialappearance

Seasonalinfluenza

Transmissibility: estimated Basic Reproductive Number (Ro)

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

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Courtesy of the Health Protection Agency, UK

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Idealised curves for local planning

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

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0%

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1918 NewYork State

1918Leicester

1918Warringtonand Wigan

1957 SELondon

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Numbers affected in seasonal influenza epidemics and pandemics

Seasonalinfluenza

(Overall clinical attack rate in the first wave of previous pandemics)

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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

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Initial experience in North America 2009

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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.

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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 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.

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Initial experience in Europe: Planning assumptions

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Revised European planning assumptions for 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 casesCase fatality rate

2% of clinical casesHospitalisation rate

15% of clinical casesComplication rate

6.5% (local planning assumptions 4.5% to 8%) per week

Peak clinical attack rate

30%Clinical attack rate

Courtesy of Department of Health, UK, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/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 the A(H1N1) pandemic 2009The 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_OutbreakFinelli 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)61304-0CDC 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 a pandemic

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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.

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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' 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

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Arguments for and against just undertaking mitigation and not attempting 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 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) pandemics?

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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.

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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 keyBased on an original graph developed by the US CDC, Atlanta