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Influenza pandemic
the use of antivirals
Aura Timen, MD, PhD
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20 januari 2011
Content
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20 januari 2011
the viruses
the disease
seasonal flu/pandemic
use of antivirals
Influenza: the viruses
Oseltamivir: neuraminidase inhibitor
Neuraminidase: 9 subtypes : N1, N2…N9
Hemagglutinine: 16 subtypes: H1, H2,…H16
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Influenza A
© 1998 American Museum of Natural History
Pandemie | 20 januari 2011
•Usually
Seasonal influenza: clinical picture
•Acute onset
•Fever (>38ºC)
•Sore throat
•Dry cough
•Chills
Copyright a.j.jacobi
•Muscle pain
•Severe disease,
complications
•Dyspnea
•Chest pain
•Hemoptysis
•Prolonged or recurrent fever
•Altered mental status
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4
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BRON: NIVEL
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New virus: combination of genes from 4 viruses
~ 1998
PB2,PA:
Triple reassortant
~ 1968
~ 1998
PB1:
~ 1918
HA, NP, NS:
~ 1979
NA, MA:
Classical swine
Eurasian swine
A/California/4/2009
PB2
PB1
PA
HA
NP
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team*, New
England Journal of Medicine, 2009
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NA
MA
NS
Pandemics of influenza
H2N2
H2N2
H1N1
H1N1
H3N8
1895 1905
1889
Russian
influenza
H2N2
1915
1925
1900
Old Hong Kong
influenza
H3N8
1955
1918
Spanish
influenza
H1N1
1965
1957
Asian
influenza
H2N2
1975
1985
2005
2010
2009
Novel
influenza
H1N1v
H9* 1999
H5 1997 2003
H7 1980
1955
1995
1968
Hong Kong
influenza
H3N2
Recorded new avian influenzas
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H1N1v
H3N2
1965
1975
1985
1996
1995
2002
2005
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Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research,
National Institute of Infectious Diseases (NIID), Japan.
BRON: ECDC
2015
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-toperson
transmission
•Significant
disease
•No previous
immunity
Worldwide
spread
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Age-specific clinical attack rate in previous
pandemics
60%
1957 Kansas City
1957 S Wales
1957 SE London
1968 Kansas City
% with clinical disease
50%
1918 New York State
1918 Manchester
1918 Leicester
1918 Warrington & Wigan
40%
30%
20%
10%
0%
0
20
40
60
80
Age (midpoint of age class)
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With thanks to Peter Grove, Department of Health, London, UK
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ECDC
Differing attack rates determined by serology:
serological attack rate observed in the UK
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0-9
10-19
1969 (first wave)
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Courtesy of the Health Protection Agency, UK
20-29
30-39
40-49
50-59
60-69
1970 (second wave)
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70-79
1957
ECDC
Different age-specific excess deaths in pandemics
4000
Excess deaths
3500
3000
2500
2000
1500
1000
Excess deaths, second wave,
1918 epidemic
500
0
<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
16000
Excess deaths
14000
12000
10000
8000
6000
Excess deaths second wave
1969 pandemic, England and
Wales
4000
2000
0
0-4
5-9
10-14
15-19
20-24
25-34
35-44
45-54
55-64
65-74
75+
Age group
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Source: Department of Health, UK
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ECDC
Numbers affected in seasonal influenza epidemics
and pandemics (overall clinical attack rate in
previous pandemics)
45%
clinical attack rate (%)
40%
35%
30%
25%
20%
15%
10%
5%
0%
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Seasonal
influenza
1918 New
York State
1918
Leicester
1918
Warrington
and Wigan
1957 SE
London
1968
Kansas City
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ECDC
Seasonal influenza compared to pandemic —
proportions of types of cases
Deaths
Requiring
hospitalisation
Deaths
Requiring
hospitalisation
Clinical
symptoms
Asymptomatic
Seasonal influenza
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Clinical
symptoms
Asymptomatic
Pandemic
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www.who.int
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FASE 6
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www.who.int
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Oseltamivir stockpile:
5.000.000 courses (assumption
clinical AR = 30%)
Gezondheidsraad, publicatienr. 2005/05
Treatment
2 dd 75 mg/5 days
Prophylaxis
1 dd 75 mg/ 7 days
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v/d Wijngaard et al. NTVG
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Notification rules change
AH1N1 is comparable with seasonal flu
Laboratory confirmed cases of Novel Influenza A (H1N1),
date of onset April 29 to August 14 (N=1564)
All countries with
significant local
transmission in the case
definition
Import
Transmission in the Netherlands
US included in the case
definition
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Routine contact tracing stops
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v/d Wijngaard et al.
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Ned Tijdschr Geneeskd. 2009;153:A1053NTVG
jaar
2005
2006
2007
2008
2009 (tot 1 juli)
oseltamivir
14 158
8 805
1 048
608
9 069
zanamivir
353
92
58
46
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)
160
140
Hoeveelheid kuren
120
100
80
60
40
20
33
34
35
36
37
38
39
40
41
42
43
Week
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44
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Antivirale middelen (aug – dec)
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•
Zeer beperkt voorgeschreven
•
Oseltamivir en indicatie: 72%
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Conclusions
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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
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BRON: CIb
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Where do we
stand now?
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