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

1 20 januari 2011

Influenza pandemicthe use of antivirals

Aura Timen, MD, PhD

2 20 januari 2011

Content1. the viruses 2. the disease3. seasonal flu/pandemic4. use of antivirals

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 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

Cop

yrig

ht a

.j.ja

cobi


5BRON: NIVEL


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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

Pandemics of influenza

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

2009Novel

influenzaH1N1v

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

1996 2002

1999

2003

1955 1965 1975 1985 1995 2005


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Some of the 'known unknowns' inthe 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


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0%

10%

20%

30%

40%

50%

60%

0 20 40 60 80

Age (midpoint of age class)

% w

ith c

linic

al dis

ease

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

ECDC


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

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79

1969 (first wave) 1970 (second wave) 1957

Courtesy of the Health Protection Agency, UK ECDC


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Different age-specific excess deaths in pandemics

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 d

eath

s

0

500

1000

1500

2000

2500

3000

3500

4000

<1 1-2 2-5 5-10 10-15 15-20 20-25 25-35 35-45 45-55 55-65 65-75 75+

Age group

Excess d

eath

s

Excess deaths, second wave, 1918 epidemic

Excess deaths second wave 1969 pandemic, England and Wales

Source: Department of Health, UKECDC


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0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

1918 NewYork State

1918Leicester

1918Warringtonand Wigan

1957 SELondon

1968Kansas City

clin

ical

atta

ck r

ate

(%)

Numbers affected in seasonal influenza epidemics and pandemics (overall clinical attack rate in

previous pandemics)

Seasonalinfluenza

ECDC


13

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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15


16


17


18

www.who.int


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www.who.intFASE 6


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Gezondheidsraad, publicatienr. 2005/05

Oseltamivir stockpile:

5.000.000 courses (assumption clinical AR = 30%)

Treatment2 dd 75 mg/5 days

Prophylaxis1 dd 75 mg/ 7 days


21

v/d Wijngaard et al. NTVG


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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

Notifi cation rules change

AH1N1 is comparable with seasonal flu


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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


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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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Tamifluverstrekking aan apotheken, ziekenhuizen en apotheekhoudende huisartsen (1 = 30 kuren)

-

20

40

60

80

100

120

140

160

33 34 35 36 37 38 39 40 41 42 43 44 45

Week

Hoe

veel

heid

kur

en


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Antivirale middelen (aug – dec)

• Zeer beperkt voorgeschreven

• Oseltamivir en indicatie: 72%


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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


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Influenza A (H1N1) 2009 pandemic in the Netherlands

● 2193 patients admitted to hospital (50% with co-morbidity)● 63 notified deaths (90% with co-morbidity)


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Leeftijdsverdeling van patiënten met ziekenhuisopname IC opname

Sterfte

BRON: CIb


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Where do we stand now?

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

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