1. 120 januari 2011 Influenza pandemic the use of antivirals Aura Timen, MD, PhD

2. 220 januari 2011 Content 1.the viruses 2.the disease 3.seasonal flu/pandemic 4.use of antivirals

3. Pandemie | 20 januari 2011 3 Influenza: the viruses Influenza A © 1998 American Museum of Natural History Neuraminidase: 9 subtypes : N1, N2…N9 Hemagglutinine: 16 subtypes: H1, H2,…H16 Oseltamivir: neuraminidase inhibitor

4. Pandemie | 20 januari 2011 4 4 Usually Acute onset Fever (>38ºC) Sore throat Dry cough Chills Muscle pain Severe disease, complications Dyspnea Chest pain Hemoptysis Prolonged or recurrent fever Altered mental status Seasonal influenza: clinical picture Copyright a.j.jacobi

5. Pandemie | 20 januari 2011 5 BRON: NIVEL

6. Pandemie | 20 januari 2011 6 PB2 PB1 PA HA NP NA MA NS PB2,PA: PB1: ~ 1998 ~ 1968~ 1998 HA, NP, NS: ~ 1918 NA, MA: ~ 1979 Classical swine Eurasian swine Triple reassortant A/California/4/2009 Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team*, New England Journal of Medicine, 2009 New virus: combination of genes from 4 viruses

7. Pandemie | 20 januari 2011 7 Pandemics of influenza 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 Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research, National Institute of Infectious Diseases (NIID), Japan. H1N1 H1N1v BRON: ECDC H7 H5 H9 * 1980 1997 Recorded new avian influenzas 19962002 1999 2003 195519651975198519952005

8. Pandemie | 20 januari 2011 8 Some of the 'known unknowns' in the 20th century pandemics ●Three pandemics (1918, 1957, 1968) ●Different shapes and waves ●Differences in effective reproductive number ●Different groups affected ●Different levels of severity including case fatality ratio ●Imply different approaches to mitigation New virus Efficient person-to- person transmission Significant disease No previous immunity Worldwide spread

9. Pandemie | 20 januari 2011 9 0% 10% 20% 30% 40% 50% 60% 020406080 Age (midpoint of age class) % with clinical disease 1918 New York State 1918 Manchester 1918 Leicester 1918 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 ECDC

10. Pandemie | 20 januari 2011 10 Differing attack rates determined by serology: serological attack rate observed in the UK 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0-910-1920-2930-3940-4950-5960-6970-79 1969 (first wave)1970 (second wave)1957 Courtesy of the Health Protection Agency, UK ECDC

11. Pandemie | 20 januari 2011 11 Different age-specific excess deaths in pandemics 0 2000 4000 6000 8000 10000 12000 14000 16000 0-45-910-1415-1920-2425-3435-4445-5455-6465-7475+ Age group Excess deaths 0 500 1000 1500 2000 2500 3000 3500 4000 <11-22-55-1010-1515-2020-2525-3535-4545-5555-6565-7575+ Age group Excess deaths Excess deaths, second wave, 1918 epidemic Excess deaths second wave 1969 pandemic, England and Wales Source: Department of Health, UK ECDC

12. Pandemie | 20 januari 2011 12 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 ECDC

13. Pandemie | 20 januari 2011 13 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

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18. Pandemie | 20 januari 2011 18 www.who.int

19. Pandemie | 20 januari 2011 19 www.who.int FASE 6

20. Pandemie | 20 januari 2011 20 Gezondheidsraad, publicatienr. 2005/05 Oseltamivir stockpile: 5.000.000 courses (assumption clinical AR = 30%) Treatment 2 dd 75 mg/5 days Prophylaxis 1 dd 75 mg/ 7 days

21. Pandemie | 20 januari 2011 21 v/d Wijngaard et al. NTVG

22. Pandemie | 20 januari 2011 22 Import Transmission in the Netherlands Laboratory confirmed cases of Novel Influenza A (H1N1), date of onset April 29 to August 14 (N=1564) US included in the case definition All countries with significant local transmission in the case definition Routine contact tracing stops

23. Pandemie | 20 januari 2011 23 v/d Wijngaard et al. Ned Tijdschr Geneeskd. 2009;153:A1053NTVG ●jaar oseltamivir zanamivir ●2005 14 158 353 ●2006 8 805 92 ●2007 1 048 58 ●2008 608 46 ●2009 (tot 1 juli) 9 069 92 Aantal verstrekkingen van oseltamivir en zanamivir per jaar via openbare apotheken in Nederland, in de periode 2005-2009 (bron: Stichting Farmaceutische Kengetallen) 1000 kuren door GGD’s

24. Pandemie | 20 januari 2011 24 Antivirals ●Containment: PHS –April 28-June 29: treatment of patients and prophylaxis in household contacts (in NL: 126 patients) –June 30-August 15: treatment of patients (in NL: > 1000 patients) ●Mitigation: GP’s, hospitals –August 15 – February 2010: treatment of patients from risk groups or with severe disease

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26. Pandemie | 20 januari 2011 26 Antivirale middelen (aug – dec) Zeer beperkt voorgeschreven Oseltamivir en indicatie: 72%

27. Pandemie | 20 januari 2011 27 Conclusions ●Incidents trigger an increase in consumption ●Prescribing behavior of GP’s and PHS is according to the guidelines ●Proper communication about indications ●Restricted demand from the public

28. Pandemie | 20 januari 2011 28 Influenza A (H1N1) 2009 pandemic in the Netherlands ●2193 patients admitted to hospital (50% with co-morbidity) ●63 notified deaths (90% with co-morbidity)

29. Pandemie | 20 januari 2011 29 Leeftijdsverdeling van patiënten met ziekenhuisopname IC opname Sterfte BRON: CIb

30. Pandemie | 20 januari 2011 30 Where do we stand now?