H1N1 - Bienvenue au CHR de la Citadelle

La Grippe, encore ?
Eric Firre
Médecine interne Hygiène hospitalière
CHR Citadelle Liège
H2N2
H2N2
H1N1
H1N1
H3N8
1895 1905
1889
Russian
influenza
H2N2
1915
Pandemic
H3N2
1925
1900
Old Hong
Kong influenza
H3N8
1955
1918
Spanish
influenza
H1N1
1965
1957
Asian
influenza
H2N2
1975
1985
2005
2010
2015
2009
Pandemic
influenza
H1N1
H9* 1999
H5 1997 2003
H7 1980
Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research,
National Institute of Infectious Diseases (NIID), Japan.
1995
1968
Hong Kong
influenza
H3N2
Recorded new avian influenzas
1955
H1N1
1965
1975
1985
1996
1995
2002
2005
Animated slide: Press space bar
Commissariat
interministériel
Influenza
 3 Types A, B et C
 8 segments génomiques
 3 protéines de surface :
• Hémagglutinine (HA)
• Neuraminidase (NA)
• Pompe à protons (M2)
Commissariat
interministériel
Influenza
Homme
Animal
H1, H1 et H3
H1 à H16
N1 et N2
N1 à N9
Transmission
surtout aérienne
Transmission
surtout oro-fécale

Epidémies saisonnières
épidémies
d’influenza A et B suite à des
mutations
=> “drift antigénique”

Pandémie
/ influenza A si antigène shift
=> nouveau sous type d’hémagglutinine
=> pas d’immunité dans la population
1918 H1N1 “Grippe Espagnole”
1957 H2N2 “Grippe asiatique”
1968 H3N2 “Grippe de Hong Kong”
20-40 million †
1-2 million †
700,000 †
1977 H1N1 Ré-émergence
Pas de pandémie
1997 H5N1 “grippe aviaire”
2009 H1N1 “grippe porcine”
Pas de pandémie
Pandémie ??? †
The Two Mechanisms whereby Pandemic Influenza Originates
Belshe R. N Engl J Med 2005;353:2209‐2211
N. American H1N1
(swine/avian/human)
PB2
PB1
PA
HA
NP
NA
MP
NS
Eurasian
swine H1N1
PB2
PB1
PA
HA
NP
NA
MP
NS
Classical swine, N. American lineage
Avian, N. American lineage
Human seasonal H3N2
Eurasian swine lineage
PB2
PB1
PA
HA
NP
NA
MP
NS
Pandemic (H1N1)
2009, combining
swine, avian and
human viral
components
The Influenza pandemics that might have been
45 MILLIONS DE PERSONNES
VACCINEES… 100 S. G-B !
20 MILLIONS DE POULETS TUES
Dr. R. Snacken ISSP
A distinguer :
Commissariat
interministériel
Influenza
Grippe saisonnière
(Maladie humaine)
Attendue chaque hiver
Cas humains de
grippe aviaire
(Zoonose)
Situation actuelle en Asie
Pandémie de grippe
(Zoonose évoluant
en maladie humaine)
En cours
Proportion of total cases, consultations, hospitalisations or deaths
Initiation
25%
Acceleration
Peak
Declining
20%
15%
10%
5%
0%
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Jan
Feb
Mar
Apr
Month
In reality, the initiation phase can be prolonged, especially in the summer months.
What cannot be determined is when acceleration takes place.
Animated slide: Press key
A pandemic
emerging in SE Asia
A
pandemic strain emerging in the
Americas.
Delayed virus
sharing
 Immediate
virus sharing so rapid
diagnostic and vaccines.
Based on a more
pathogenic strain, e.g.
A(H5N1)
 Pandemic
(H1N1) currently not that
pathogenic.
seeming residual immunity in a
major large risk group (older people).
No residual
immunity
 Some
 No
known pathogenicity markers.
 Initially
Heightened
pathogenicity
susceptible to oseltamivir.
 Good
data and information coming out of
North America.
 Arriving
 Mild
in Europe in the summer.
presentation in most.
Inbuilt antiviral
resistance
Minimal data until
transmission reached
Europe
Arriving in the late
autumn or winter
Severe presentation
immediately
Contrast with what might
have happened — and might
still happen!








What probably can be
assumed:
Known knowns
Modes of transmission (droplet, direct
and indirect contact)
Broad incubation period and serial
interval
At what stage a person is infectious
Broad clinical presentation and case
definition (what influenza looks like)
The general effectiveness of personal
hygiene measures (frequent hand
washing, using tissues properly,
staying at home when you get ill)
That in temperate zones transmission
will be lower in the spring and
summer than in the autumn and
winter
•
What cannot be assumed:
•
Known unknowns
•
•
•
•
•
•
•
•
Antigenic type and phenotype
Susceptibility/resistance to antivirals
Age-groups and clinical groups most affected
Age-groups with most transmission
Clinical attack rates
Pathogenicity (case-fatality rates)
‘Severity’ of the pandemic
Precise parameters needed for modelling and
forecasting (serial interval, Ro)
Precise clinical case definition
The duration, shape, number and tempo of the
waves of infection
Will new virus dominate over seasonal type A
influenza?
Complicating conditions (super-infections)
The effectiveness of interventions and countermeasures including pharmaceuticals
The safety of pharmaceutical interventions
•
•
•
•
•
•
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)
With thanks to Peter Grove, Department of Health, London, UK
Animated slide: Press space bar
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
Age group
Source: Department of Health, UK
45-54
55-64
65-74
75+
Austria
13,000
Latvia
Belgium
Bulgaria
Czech
Rep
Cyprus
Denmark
Estonia
Finland
14,900
47,100
34,100
Lithuania
Germany
Greece
18,800
116,400
27,400
1, 900
7,300
6,100
8,100
37,700
6,700
95,200
500
Slovenia
Slovakia
Spain
Sweden
5,000
20,600
87,100
13,300
France
89,600
Hungary
Ireland
Italy
Luxembou
rg
Malta
Iceland
1,100
420
UK
Norway
93,000
5,800
EU total: 1.1 million
Murray CJL, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of potential global pandemic influenza mortality on the basis
of vital registry data from the 1918–20 pandemic: a quantitative analysis. Lancet. 2006;368: 2211-2218.
13,800
Netherland
s
Poland
Portugal
Romania
23,100
155,200
25,100
149,900
Proportion of total cases, consultations, hospitalisations or de aths
25%
20%
15%
10%
5%
0%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Week
In reality, larger countries can experience a series of shorter but steeper
local epidemics.
Animated slide: Press space bar
Epidemiologic Curve of Confirmed Cases of Human Infection with Swine-Origin Influenza A
(H1N1) Virus with Known Date of Illness Onset in the United States (March 28-May 5, 2009)
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med
2009;10.1056/NEJMoa0903810
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med
2009;10.1056/NEJMoa0903810
Susceptibility of 37 Isolates of Swine-Origin Influenza A (H1N1) Virus to Neuraminidase Inhibitors
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med
2009;10.1056/NEJMoa0903810

Les premiers signes de la grippe A(H1N1) sont
de type grippal:





Fièvre soudaine supérieure à 38°C
Douleurs musculaires,
Toux
Maux de gorge et écoulements nasals
Céphalées parfois accompagnés de vomissements ou
de diarrhée.

Early epidemic:




Infection rate for probable and confirmed cases highest in
5−24 year age group.
Hospitalisation rate highest in 0−4 year age group, followed
by 5−24 year age group.




increased influenza-like illness reports due to increased
consultations;
many cases attributable to seasonal influenza until mid-May.
Pregnant women, some of whom have delivered prematurely, have
received particular attention seem to at somewhat greater risk from
H1N1v than from seasonal influenza as already established.
Most deaths in 25−64 year age group in people with chronic
underlying disease.
Adults, especially 60 years and old, may have some degree
of preexisting cross-reactive antibody to the novel H1N1 flu
virus.
Transmission persisting in several regions of the US, but not
all areas are affected.


Containment with impossible with multiple introductions
and R0 1.4 to 1.6.
Initial focus on counting laboratory-confirmed cases has
changed to seasonal surveillance methods with:




outpatient influenza-like illness, virological surveillance (including
susceptibility), pneumonia and influenza mortality, pediatric mortality
and geographic spread.
Stopped issuing reports of numbers of infected persons as these
were meaningless.
Serological experiments and epidemiology suggest 2008–
2009 seasonal A(H1N1) vaccine does not provide protection.
Preparing for the autumn and winter when virus is expected
to return:
communications: a pandemic may be 'mild' yet cause deaths;
determining if and when to begin using vaccine;
abandoned previous plans to use proactive school closures as this was
unworkable;
 looking at the southern hemisphere temperate countries.



•Clinical attack rate
•30%
•Peak clinical attack rate
•6.5% (local planning assumptions 4.5% to
8%) per week
•Complication rate
•15% of clinical cases
•Hospitalisation rate
•2% of clinical cases
•Case fatality rate
•0.1% to 0.2% (cannot exclude up to 0.35%)
of clinical cases
•Peak absence rate
•12% of workforce
These assumptions represent a reasonable worst case applying to one European country (the United Kingdom)
with data available as of July 2009. They should not be used for predictions.
Courtesy of Department of Health, UK, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_102892
The following groups are considered more at risk of experiencing severe disease than the general population
should they become infected with the pandemic A(H1N1) virus 2009:


People with chronic conditions in the following categories:







chronic respiratory diseases;
chronic cardiovascular diseases (though not isolated mild hypertension);
chronic metabolic disorders (notably diabetes);
chronic renal and hepatic diseases;
persons with deficient immunity (congenital or acquired);
chronic neurological or neuromuscular conditions; and
any other condition that impairs a person’s immunity or prejudices their respiratory (breathing) function, including severe or
morbid obesity.
• Pregnant women.
• Young children (especially those under two years).





Consultations en services d’urgence plus de 2X
supérieures que pendant le pic de l’hiver précédent
(Utah)
Unités de soins intensifs : environ 15-30 % des cas
nécessitant une hospitalisation admis en soins intensifs
(États-Unis, Canada)
Unité de soins intensifs : SDRA grave avec ventilation
mécanique besoins en personnel
Ventilation mécanique chez ~ 10 % des cas hospitalisés
(États-Unis, Canada)
4X la saison grippale habituelle pendant 2 mois







La vaccination des agents de santé est hautement
prioritaire (1-2 % de la population) Examen d’une
démarche progressive pour vacciner des groupes
particuliers : en fonction de l’épidémiologie des pays et
des objectifs
Femmes enceintes (2 % de la population mondiale)
Individus âgés > 6 mois souffrant d’une ou plusieurs
maladies chroniques (asthme et autres maladies
chroniques)
Jeunes adultes en bonne santé >15-49 ans
Enfants en bonne santé
Adultes en bonne santé >49-65 ans
Adultes en bonne santé >65 ans





Etude Etats-Unis du 15 avril au 16 juin 2009.
45 décès dont 6 femmes enceintes (13 %)
alors que celles-ci ne représentent qu’un peu
plus de 1 % de la population américaine.
Pas d’antécédents médicaux graves
(1 cas d’obésité morbide)
Toutes décédées d’une pneumonie virale sans
signes de surinfection bactérienne.
A noter que le traitement antiviral avait été
institué très tardivement chez ces patientes







difficulté respiratoire importante ou souffle
court
douleur ou pression dans la poitrine ou
l'abdomen
vertige soudain
confusion
vomissement grave ou persistant
diminution ou absence de mouvement de votre
bébé
fièvre élevée qui ne répond pas au Paracétamol.





Ne cessez pas d'allaiter si vous êtes malade
Ne pas tousser ou éternuer dans le visage du
bébé.
Lavez-vous souvent les mains avec de l’eau et
du savon.
Porter un masque.
Si trop malade pour allaiter, tirez le lait et
faites-le donner à votre bébé par quelqu’un
d’autre.




Relenza (de préférence) et Tamiflu
Egalement prescrits à titre préventif contre la
grippe A/H1N1, chez la femme enceinte en
contact étroit avec une personne malade. Ils
sont alors pris pendant 10 jours.
mères qui allaitent peuvent continuer à soigner
leurs bébés tout en étant traitées pour la grippe.
Le vaccin peut être administré aux femmes
enceintes ou qui allaitent




IFD et tests rapides
Biologie moléculaire
Sérologie
Culture
La prévention





Personnes malades: rester chez elles
Contagion 1 jour avant et jusqu’à 7 jours après
le début des symptômes
Mouchoirs à usage unique qui seront jetés
après chaque utilisation
Se couvrir le nez et la bouche avec ces
mouchoirs lorsqu’elles toussent ou éternuent
Se laver les mains régulièrement
Se tenir autant que possible à l’écart des
personnes bien portantes (> 1m50).



Actuellement pas de vaccin en vente pour
protéger l’homme contre la grippe A/H1N1.
En octobre, les premiers vaccins seront prêts et
seront livrés aux autorités qui les mettront
gratuitement à disposition des groupes à risque
de la population.
La protection contre la grippe saisonnière sera
assurée par un autre vaccin.
Le plan Grippe au CHR
10/09/2009
Aspects pédiatriques Dr Marc
Hainaut