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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
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
Cop
yrig
ht a
.j.ja
cobi
Pandemie | 20 januari 2011
5BRON: NIVEL
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
Pandemie | 20 januari 2011
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
Pandemie | 20 januari 2011
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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
Pandemie | 20 januari 2011
9
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
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%
0-9 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
Pandemie | 20 januari 2011
11
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
Pandemie | 20 januari 2011
12
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
Pandemie | 20 januari 2011
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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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www.who.int
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www.who.intFASE 6
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20
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
Pandemie | 20 januari 2011
21
v/d Wijngaard et al. NTVG
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
Notifi cation rules change
AH1N1 is comparable with seasonal flu
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
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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
Pandemie | 20 januari 2011
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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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26
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
Pandemie | 20 januari 2011
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Where do we stand now?