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

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

Pandemie | 20 januari 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

Pandemie | 20 januari 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

Pandemie | 20 januari BRON: NIVEL

Pandemie | 20 januari 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

Pandemie | 20 januari Pandemics of influenza H1N1 H2N Russian influenza H2N Asian influenza H2N2 H3N Hong Kong influenza H3N2 H3N Old Hong Kong influenza H3N Spanish influenza H1N 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 * Recorded new avian influenzas

Pandemie | 20 januari 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

Pandemie | 20 januari % 10% 20% 30% 40% 50% 60% 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

Pandemie | 20 januari Differing attack rates determined by serology: serological attack rate observed in the UK 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% (first wave)1970 (second wave)1957 Courtesy of the Health Protection Agency, UK ECDC

Pandemie | 20 januari Different age-specific excess deaths in pandemics Age group Excess deaths < 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

Pandemie | 20 januari % 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

Pandemie | 20 januari 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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Pandemie | 20 januari FASE 6

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

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

Pandemie | 20 januari 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

Pandemie | 20 januari v/d Wijngaard et al. Ned Tijdschr Geneeskd. 2009;153:A1053NTVG ●jaar oseltamivir zanamivir ● ● ● ● ●2009 (tot 1 juli) Aantal verstrekkingen van oseltamivir en zanamivir per jaar via openbare apotheken in Nederland, in de periode (bron: Stichting Farmaceutische Kengetallen) 1000 kuren door GGD’s

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

Pandemie | 20 januari 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

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

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

Pandemie | 20 januari Where do we stand now?