1. The 2009-2010 A(H1N1v) pandemic Situation report Europe and forward look to the autumn Zsuzsanna Jakab, Director European Centre for Disease Prevention and Control Swedish Presidency Workshop, Jönköping, 2-3 July 2009

2. 2 Pandemics of influenza H7 H5 H9 * 1980 1997 Recorded new avian influenzas 19962002 1999 2003 195519651975198519952005 H1N1 H2N2 1889 Russian influenza H2N2 1957 Asian influenza H2N2 H3N2 1968 Hong Kong influenza H3N2 H3N8 1900 Old Hong Kong influenza H3N8 1918 Spanish influenza H1N1 19151925195519651975198519952005 18951905 2010 2015 2009 Novel influenza H1N1v 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

3. 3 Situation report Europe, as of 1 July 2009

4. 4 Cumulative distribution of confirmed cases of A(H1N1)v by day of reporting, as of 29 June 2009, log scale 1 10 100 1 000 10 000 100 000 26/04/0903/05/0910/05/0917/05/0924/05/0931/05/0907/06/0914/06/0921/06/0928/06/09 France Germany Spain UK Number of cases, logarithmic scale Animated slide: Press space bar Selected European countries

5. 5 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!

6. 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). 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.

7. 7 So far in Europe A mild disease in most people Easy to miss in surveillance Some severely ill and starting to see deaths – mostly in people with other underlying conditions Few cases in people over 60 years Spreading efficiently Out-breaks in schools (or easier to see in schools?)

8. 8 Initial experience in North America 2009 – the default position

9. 9 Emerging themes in North America, early June 2009 (1) Early epidemic about 1 million infected ( = 0.3% of population) – compared to minimum 25% expected attack rate Infection rate for probable and confirmed cases highest in 524 year age group. Hospitalisation rate highest in 04 year age group, followed by 524 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 2564 year age group; most with known risks for severe disease. –Morbid obesity a 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 persisting in several regions of the U.S. Expected to run on throughout the summer and then accelerate.

10. 10 Emerging themes in North America, end June 2009 (2) Containment impossible with multiple introductions and R 0 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. Communication difficulty a pandemic may be 'mild' yet cause deaths –25% of U.S. stockpile deployed to states (includes medication and equipment) –determining who to give vaccine, if and when to begin using vaccine –school closures being analysed to determine effectiveness

11. 11 Forward look for Europe

12. 12 Idealised curve for planning 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, 2nd wave 1918. 0% 5% 10% 15% 20% 25% 123456789101112131415 Week Proportion of total cases, consultations, hospitalisations or de aths Source: Department of Health, UK InitiationAccelerationPeakDeclining Animated slide: Please wait

13. 13 One possible European scenario summer and autumn 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% AprMayJunJulAugSepOctNovDecJanFebMar Month Proportion of total cases, consultations, hospitalisations or deaths InitiationAccelerationPeakDeclining Apr Animated slide: Press space bar

14. 14 One possible European scenario summer 2009 July August October Animated slide: Press space bar August September

15. 15 Some of the 'known unknowns' in the 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

16. 16 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. R o = 2-3 (US) Mills, Robins, Lipsitch (Nature 2004) R o = 1.5-2 (UK) Gani et al (EID 2005) R o = 1.5-1.8 (UK) Hall et al (Epidemiol. Infect. 2006) R o = 1.5-3.7 (Geneva) Chowell et al (Vaccine 2006) Courtesy of the Health Protection Agency, UK Transmissibility: estimated Basic Reproductive Number (R o )

17. 17 1957/1958 pandemic: A(H2N2) especially transmitted among children R o = 1.8 (UK) Vynnycky, Edmunds (Epidemiol. Infect.2007) R o = 1.65 (UK) Gani et al (EID 2005) R o = 1.5 (UK) Hall et al (Epidemiol. Infect. 2006) R o = 1.68 Longini et al (Am J Epidem 2004) 0 200 400 600 800 1,000 6 132027 3 10172431 7 142128 5 121926 29 162330 7 142128 4 111825 18 1522 JulyAugustSeptemberOctoberNovemberDecemberJanuaryFebruary Week number and month during the winter of 1957/58 Recorded deaths in England and Wales from influenza 1957/58: Influenza deaths, England and Wales Courtesy of the Health Protection Agency, UK Transmissibility: estimated Basic Reproductive Number (R o )

18. 18 So what can we expect in our countries? Some features from the ECDC risk assessment

19. 19 It will vary from place to place – and local can be more intense than national In reality, larger countries can experience a series of shorter but steeper local epidemics. 0% 5% 10% 15% 20% 25% 123456789101112131415 Week Proportion of total cases, consultations, hospitalisations or de aths Animated slide: Press space bar

20. 20 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 clinical attack rate (%) Numbers affected in seasonal influenza epidemics and pandemics (overall clinical attack rate in previous pandemics) Seasonal influenza

21. 21 Seasonal influenza compared to pandemic proportions of types of cases Asymptomatic Clinical symptoms Deaths Requiring hospitalisation Seasonal influenza Pandemic Asymptomatic Clinical symptoms Deaths Requiring hospitalisation There will be pressure on the primary and secondary health services – especially paediatric and intensive care.

22. 22 Good news Older people spared Sensitive to antivirals No pathogenicity markers But influenza is promiscuous – will it pick up any bad genes on its winter holiday in the south – primary oseltamivir resistance from seasonal flu or even pathogenicity genes from bird flu A(H5N1).

23. 23 Measuring the severity of a pandemic

24. 24 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.

25. 25 WHO: A(H1N1)v a moderate pandemic

26. 26 What is meant by 'moderate' and 'severe'? Not a simple scale What most people experience. Attributable risks? For most people its a mild self-limiting disease. Death ratio. Expectation of an infected person dying (the Case Fatality Ratio): < 0.5% of reported cases. Hospitalisation rate: Rates for children aged 0-23 months, 2-4 years, and 5-17 years were 1.1, 0.3, and 0.3 per 10,000, respectively. Rates for adults aged 18-49 years, 50-64 years, and >= 65 years were 0.1, 0.1, and 0.2 per 10,000, respectively. 1 Pathogenicity markers and animal studies. No markers but ferret data indicate somewhat more severe than seasonal flu. 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. Watch UK, Australia, Argentina, Chile, New Zealand. Critical service functioning. Peak prevalence of people off ill or caring for others. Watch Australia, Chile, New Zealand. 1 http://www.cdc.gov/flu/weekly/: 2008-2009 Influenza Season Week 24 ending June 20, 2009

27. 27 What is meant by 'moderate' and 'severe'? Not a simple scale Certain groups spared: older people. Certain individual dying unexpectedly, e.g. children, pregnant women, young healthy adults. Public and media perception: low perception of risk at present Conclusion Not easy to come up with a single measure of severity. May be better to state or agree 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

28. 28 Surveillance in a pandemic – future look This will be crucial to detect –Changes in the behaviour of the virus –Discover who is really at risk Will have to stop asking for numbers very soon Reliance on sentinel work – the previous EISS system through TESSy Reporting of severe disease especially important for informing the antiviral and vaccine priorities Special workshop 14-15 July in Stockholm

29. 29 Conclusions This pandemic will run through the rest of 2009- 2010. The first wave will probably start earlier than we might like. While this looks like a moderate pandemic - there will be surprises. Europe is better prepared than many other regions and a lot better prepared than we were in 2005. Final preparations will be very worthwhile. ECDC will be there to work with the Commission, EMEA and WHO to give every support to Member States.

30. Thank you!