Vaccinate! - Clinique Santé Voyage

Transcription

Vacciner en prévention
d‘infections neurologiques.
Grands enjeux.
Robert Steffen
Division of Epidemiology and Prevention of Communicable Diseases
Institute for Social- and Preventive Medicine, University of Zurich
WHO Collaborating Centre for Travellers‘ Health
Division of Epidemiology, Human Genetics & Environmental Sciences
University of Texas School of Public Health — Houston, TX
Hon. FFTM/ACTM (Australasia)
University of Zurich
GRID
Conflict of interest declaration
I have or had within the past few years financial relationships (grants for research
or to attend meetings, paid lectures, advisory boards) relevant to my presentation
with:
Vaccines
Bavarian-Nordic
Baxter
Crucell / Janssen / Johnson&Johnson
GlaxoSmithKline
Intercell
Novartis Vaccines and Diagnostics
Sanofi Pasteur
2
Drugs
DrFalk Pharma
Optimer
Santarus
Salix
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Rare: 1% of patients
Freedman DO et al. N Engl J Med 2006;354:119-30
3
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Travel-related diseases of the nervous system:
Non-infectious: more frequent than infectious!
●  Adverse events (neuropsychiatric)
–  Mefloquine and other antimalarials, vaccines (e.g. Yellow fever)
–  Repellents, insecticides (infants)
–  Recreational drugs
●  Nutritional poisoning, e.g. Ciguatera
●  Environmental
–  Acute mountain sickness ! cerebral edema
–  Diving ! decompression sickness
●  Motion sickness
●  Pressure palsies (post-flight)
●  Jet-lag exacebates tension headache
●  Sleep deprivation, jet-lag ! seizure
Hill DR. J Travel Med 2000;7:259-66
Potasman I et al. J Travel Med 2000;7:5-9
Toovey S. Travel Med Infect Dis 2009;7:2-6
Wilder-Smith EP & Wilder-Smith A in Tropical Diseases in Travelers, Schwartz E. ed., Wiley-Blackwell, 2009
4
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Imported cerebro-meningeal infections
French infectious disease unit, Saint-Mandé, near Paris (n=56)
Population:
● 
● 
● 
● 
45% tourists
27% military
16% immigrants
12% expatriates
Etiology confirmed:
●  Viral
● 
● 
● 
● 
35 M, 21 F, age 16 to 83 (mean 29) years
–  Enteroviruses
–  Herpesviridae
–  HIV
–  Dengue
–  Toscana
–  EBV
Bacterial
Parasitical
Helmints
Fungal
42 (75%)
24
11
8 (1 fatal with HSV-1)
2 (primary infections)
1
1
1
4 N. meningitidis, M. pneumoniae, S. typhi, Brucellosis
12 All malaria (many in intensive care)
1 Cysticercosis
1 Cryptococcosis
Rapp C et al. J Travel Med 2010;17:1-7
5
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Viral travel-related infectious diseases of the nervous system"
Vaccine preventable"
– 
– 
– 
– 
– 
– 
Rabies"
Japanese encephalitis"
Tick-borne encephalitis"
Poliomyelitis"
(Measles)"
(Influenza)"
Other"
– 
– 
– 
– 
– 
West Nile Virus (WNV) infections"
Rift Valley Fever (RVF)"
Toscana Virus infections"
Dengue fever"
Etc., etc."
6
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Rabies in Belfast, Northern Ireland
7
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Health risks abroad — 2012 estimates
Incidence rate per month of infections among travelers in developing countries
100%
Traveler’s diarrhea
10%
Influenza A or B
1%
Dengue infection (symptomatic)
Animal bite with rabies risk
PPD conversion
Malaria (overall West Africa)
0.1%
Hepatitis A
Typhoid (South Asia, N/W/Central-Africa)
Tick borne encephalitis (rural Austria)
Hepatitis B
Typhoid (other areas)
HIV-infection
Malaria (overall Central America/Carib.)
Fatal accident
Cholera
Legionella infection
0.001%
0.0001%
Japanese encephalitis
Meningococcal disease
Poliomyelitis
0.01%
8
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Incidence rate per month PLUS severity of
infections among travelers
Rabies
Dog (+) bite
Steffen R & Connor BA. J Travel Med 2005;12:26-35
9
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Rabies — global situation
Areas at risk of rabies
●  3.3 billion people exposed
●  55’000 - 70’000 deaths/year
– 
India 20,000 deaths
●  99% human deaths following a
dog bite
●  40% bitten by suspect animal
are children aged 5 to 14
years
●  Virtually 100% fatal in
non-immunes
●  100% preventable!!!
Global Alliance for Rabies Control, September 2011 (World Rabies Day)
WHO. Weekly epidemiol Record 2010;85:309-20.
WHO. International Travel and Health 2011:
http://gamapserver.who.int/mapLibrary/Files/Maps/Global_Rabies_ITHRiskMap.png
10
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NEW: Rabies on Bali and Flores
132 human cases since 2008
No tourists with rabies by 4/2012
11
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Rabies risk — transmission
MODE OF TRANSMISSION
Virus in the saliva of rabid animal
Transmission usually by bite, also
rarely by scratch, licking, spitting to mucus membrane
Virus does not enter bloodstream, but
is taken to nerve synapse ! brain
RISK ANIMALS: all mammals
Dogs: 98% worldwide
Other mammals, including monkeys
By bats: various parts of the world
CDC. Health Information for International Travel 2012.
12
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Risk of rabies exposure in travelers
●  BITES, etc. with potential risk
- U.S. Peace Corps: 4.4% per year
- Swiss expatriates: 1.8% per year
- Nepal: 0.19 (tourists) to 0.57 (expatriates)/year
Bernard K & Fishbein DB. Vaccine 1991;9:833-6.
Hatz CF et al. Vaccine 1995;13:811-5.
Pandey P et al. J Travel Med 2002;9:127-31.
Poet Junichi Kinoshita, Expatriate, Taipeh
● Postexposure prophylaxis
- STRESS! Rabies-IG difficult to find
- Number unknown!
- 45 PEP after stay in Bali
(since Nov. 2008 GeoSentinel, EuroTravNet)
Gautret P et al. Clin Microbiol Infect 2011;17:445-7.
13
Monkey Forest, Bali
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Panic after the bite or scratch
"  Hi ked999, when I was bitten by a domestic dog (my own
stupid fault) in Bali in Nov 2009 I started the injections, but
had to return to Australia within a week to have the
immunoglobin as it was not available in Bali at the time.
"  There is rabies in Bali. If you get bitten by a dog or a
monkey, you need to get to Singapore, Hongkong or
Bangkok ASAP for preventative treatment. You'll need a shot
of human immune globulin, which is not available on Bali...
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Particular risk for rabies
- Children*
-  Bicycle*/motorbike riders
-  Trekkers, hikers* (e.g. Nepal)
-  Prolonged stay*
-  Professionals with exposure*
-  Spelunkers*
* WHO: International Travel and Health, Geneva 2011
15
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Fatal rabies in travelers
Worldwide n = 42 (1990-2010), 64% after 2000
●  Bite: dog 37, fox 1, bat 1; unknown 3
●  Origin: Asia (India 6, Philippines 6) 19, Africa 14, Americas 8 (Mexico 5)
●  Age: 13 (31.7%) !18 y/o, 28 (60.3%) 19-64 y/o, 6 (14.6%) ! 65 y/o
●  Country of origin: EU 22, USA 13, former USSR 5, Japan 2 (1 VFR)
Malerczyk C et al. J Travel Med 2011;18:402-7.
16
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Rabies in illegaly imported dogs
Puppy (with documented rabies vaccination!) from Morocco
–  Search for 60 people in the Netherlands with suspected contact
Promedmail 21.2.12.
3-months old puppy Morocco ! France, unvaccinated
–  3 persons with bites, 26 other contacts ! 6 PEP
Eurosurveillance 2011;16:issue 33.
Puppy from India ! Alaska / from Iraq ! New Jersey
Zoonosis Public Health 2008;55:427-30.
MMWR 2008;57:1076-8.
Dog Sri Lanka ! United Kingdom
Vet Rec 2008;162:598.
France 2004: 3; delayed reports
France 1970-2012: 20 cases, 18 from Africa
17
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Options for prevention of rabies
in travelers
Avoid animal bites
#  do not pet / feed dogs, cats, monkeys, etc. etc.
#  be aware of surrounding — do not accidentally
surprise a stray dog
#  avoid contact with bats, monkeys, other wildlife
#  not carry or eat food while non-human primates are near
#  in caving or spelunking exposure to cave air is NOT a concern
Pre-exposure Prophylaxis (PrEP)
18
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WHO: pre-exposure vaccination
%  Intramuscular (IM), 0.5/1.0 ml depending on vaccine: deltoid / anterolateral thigh
%  Intradermal (ID), 0.1 ml — technically more demanding: Training / Supervision!
or
D0
D3
D7
D14
(D21)
D28
Not WHO!
$  AND upon exposure
D0
1 year?
5 years
D3
WHO. Wkly Epidemiol Rec. 2010;85:309-320.
Shiota S. et al. Vaccine 2008;26:6441-4 / Yanagisawa N et al. J Infect Chemother 2012;18:66-8.
19
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Traditional goals of pre-exposure prophylaxis
Modified from Plotkin S. et al. (eds). Vaccines, 5th ed., page 698 (2008)
20
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Rabies immunization recommendations
„Pre-exposure prophylaxis for those planning a visit to rabies endemic
country, especially if the visited area is far
from urban centres, where...“
„Rabies pre-exposure vaccine should generally be given to adults and
children who are at risk of rabies including those
●  travelling to remote areas where medical care is not readily available
●  undertaking higher risk activities (e.g. cycling, running)
●  travelling for long periods through rabies endemic countries
●  at occupational risk e.g. vets, animal handlers, and laboratory...“
„... rabies vaccine may be recommended based on
●  local incidence,
●  ... availability of appropriate anti-rabies biologicals,
●  intended activity and
●  duration of stay / repeat travel...“
21
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Rabies immunization recommendations
„Pre-exposure prophylaxis for those planning a visit to rabies endemic
country, especially if the visited area is far
from urban centres, where...“
f
„Rabies pre-exposure vaccine should generally be givendtooadults
and
e
e
children who are at risk of rabies including thoseut n
f
o
o
e
b
a is notnreadily
as available
●  travelling to remote areas where medical
care
s
c
r
e
i
l
is
ve cycling,
x
a
●  undertaking higher risk activities
(e.g.
running)
r
a
t
l
y
L
hendemic countries
Lthrough
p
A
o
●  travelling for long periods
rabies
r
t
c
p
u
e
r
t
e!and laboratory...“
r
r
s
u
u
n
s
I risk e.g.pvets,
●  at occupational
s
o animalphandlers,
o
x
e
t
s
po
ex
„... rabies vaccine may be recommended based on
●  local incidence,
●  ... availability of appropriate anti-rabies biologicals,
●  intended activity and
●  duration of stay / repeat travel...“
22
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Rare, but high impact neurological infections
in travelers: JE and meningococcal disease
Steffen R & Connor BA. J Travel Med 2005;12: 26-35.
23
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Basics on Japanese encephalitis (JE)
JE endemic areas 20103
●  Mosquito-borne flavivirus
●  Transmission mainly by Culex,
biting mainly in twilight / night
●  The leading cause of viral
neurological infection and disability
in Asia1
●  35,000–50,000 symptomatic cases
reported each year among residents
of endemic countries2
●  Outcome:
1/3 fatal, 1/3 sequelae, 1/3 full recovery
1. 
2. 
3. 
PATH. 2008. http://www.path.org/projects/JE_in_depth.php
Solomon T et al. Lancet 2003; 361: 821-826.
CDC. Health Information for International Travel, 2011, p.207
24
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Outbreaks of JE — often a surprise
India — recent years
7000
2500
Cases
6000
Deaths
2000
Cases
1500
4000
3000
Deaths
5000
1000
2000
500
1000
0
0
2001
2002
2003
2004
2005(P)
2006(P)
Year
Oya A ! & Kurane I. J Travel Med 2007;14:259-68"
www.namp.gov.in/je.html"
25
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Is there reliable information on the
season of transmission?
Precipitation
Infection in S Thailand
Buhl M.R. et al, J Travel Med 2009;16:217-19
26
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Risk of JE among travellers
FOREIGN POPULATION
Finnish / Swedish travellers
RATE
1 case / 300,000
Travellers from any nationality 1 case/million trips
Travellers, rural areas (CDC 1993)
US soldiers, Thailand
2-10 / 1000 / year
4,3 / 1000 / year
COMPARISON
Immunologically naïve locals
<0.1 ! 1/1000/y
Hills SL et al. Am J Trop Med Hyg 2010;82:930-6.
Buhl M & Lindquist L. J Travel Med 2009;16:217-9.
Shlim DR & Solomon T. Clin Infect Dis 2002;35;183-8.
WHO position paper. Wkly epidem Rec 2006;81:331-40.
Werlinrud AM et al. J Travel Med 2011; 18:411-13.
27
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Assessment of JE cases in travelers
●  1973 - 2008: total of 55 JE cases recorded
●  BUT
●  60% tourists — 16% expatriates, 11% soldiers
●  35% less than 1 month stay abroad
●  Some just beach vacation with excursion(s)
●  Thailand (n=19), Indonesia (8), China (7), etc.
●  18% case fatality rate / 44% with sequelae
28
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Lessons learned — recent reports:
JE transmission NOT limited to „rice fields“
— may also occur in:
•  Beach hotel tourists
(Bali, Thailand, Vietnam)
•  Tourists in cities (Angkor, Beijing, Hongkong)
•  VFRs (and refugees)
Werlinrud AM et al. J Travel Med 2011; 18:411-13.
Jeurissen A, Strauven T. Acta Neurol Belg 2011;111:143-5.
CDC. MMWR 2010;60:276-8.
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IXIARO / JESPECT vs. ”traditional” JE vaccine
Comparison of IXIARO and mouse-brain-derived vaccines
NOTE: all remaining doses of JE-Vax expired May 2011
Tauber E et al. Lancet 2007; 370: 1847-1853.
CDC. Health Information for International Travel 2012, p. 208.
30
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JE vaccine:
Basic characteristics of IXIARO = JESPECT*
●  Contains 6 mcg of inactivated Japanese encephalitis virus
(purified JEV proteins from attenuated strain SA14-14-2) "
●  Produced in Vero cells"
●  Adsorbed on aluminum hydroxide"
●  Primary vaccination series: 0, 28 ± 4 days (0.5 ml per dose)
●  Accelerated schedule: no data yet
●  Time to protection: 1 week after dose 2
–  NOTE: 1 dose results in limited seroconversion rates
●  Booster: after 1 to 2 years (?) / no data on booster after JE-Vax
"
* Name in Europe, Americas: IXIARO, in Australia: JESPECT"
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Utilisation d‘IXIARO
Série primaire: j0, j28 ± 4 (0.5 ml par dose)
Injection IM (ou SC en cas de risque de saignement)
Début de protection: 1 semaine après 2ème dose
NOTE: 1 dose resulte en seroconversion limité
Usage concomitant OK avec
●  Havrix
●  Twinrix
●  Typhim Vi
32
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Contre-indications
Hypersensibilité
–  Au principe actif
–  A l‘un des excipients ou autre composant
–  A l‘administration de la première dose
Maladie fébrile aiguë grave
Age < 18 ans
(Manque de données)
(Grossesse:
„only if needed“ / évitée)
(Allaitement:
„only if needed“ / évitée)
33
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Problèmes — incertitudes (1)
Enfants / adolescents " 17 ans: étude en route
(n = 1900 agés 2 mois à 17 ans, Philippines)
●  CDC / USA:
–  Enrol children in pediatric clinical trial (5 sites)
–  Administer IXIARO off-label 0.5 ml; age 2 months - 2 y: 0.25 ml
–  Refer children to travel clinic in Asia (Asian vaccines)
●  Suisse: procédures pragmatiques similaires
Kaltenbock A et al. Vaccine 2010;28:834-9.
www.cdc.gov/nci/dod/dvbid/jencephalitis/children.htm
Régistration pédiatrique: submission 2012 FDA/EMA
34
GRID
Problèmes — incertitudes (2)
Schéma accéléré: étude en route
Booster après IXIARO: 1 à 2 années (?)
Booster après JE-Vax: étude en route
Batch JEV09L37A, utilisé en France: protection?
(Délivré Juin 2010, périmé Août 2011)
35
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Global availability of IXIARO/JESPECT
As per Novartis Vaccines, February 2012:
– 
Europe: A, B, CH, CZ, D, DK, E, F, GB, H, IRE, I, NL, N, PL, P, S, SF
– 
Asia: Hongkong, Israel, Macau, (Singapore),
– 
Oceania: Australia, New Zealand
– 
Americas: Canada, U.S.A.
International Society of Travel Medicine
–  Global Travel Clinic Directory
–  Product Availability Listing
(Member benefit only, Q1/2013)
www.istm.org
36
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JE immunization recommendations
for travellers, 2011
Country/region
Criteria:
Experts:
Plan to live in endemic areas
World
USA
WHO
CDC
+
+
+
+
+
Long term residents
(>3 months)
U.K.
AUS
NaTHNac NH&MRC
+
Visiting rural areas:
>30 nights
>14 nights
- high risk (even <14 nights)
+ (*, **)
+ (*, **)
+ (***)
+ (**)
During season of transmission
+
+
+
(+)
*
**
***
+
(endemic)
+
+
PLUS
Extensive outdoor, evening and nighttime exposure in rural areas
High individual risk (farming, camping, no bed nets)
Itinerary through rice fields and marshland; activities including fieldwork, camping, cycling
Immunization is recommended
37
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JE vaccination decision algorithm
for travelers
Destination Asia where JE is transmitted?
No
Yes
Prolonged exposure
No JE vaccine indicated
Yes
Recommend
JE vaccination
pre-departure
Extensive outdoor exposure in rural area
•  Camping, hiking, bicycling
•  Occupational activities, especially
where flooding irrigation is practiced
•  Take into account host factors
Yes
Consider
JE vaccination
pre-departure
No
No
No JE vaccine indicated,
unless max protection requested
38
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JE vaccination decision algorithm
for travelers
Destination Asia where JE is transmitted?
No
Yes
Prolonged exposure
No JE vaccine indicated
Recommend
JE vaccination
pre-departure
#  Expatriates, students, pensioners (winter)
Yes
No
#  Repeat travellers: property owners, VFR, etc.
Extensive outdoor exposure in rural area
•  Camping, hiking, bicycling
•  Occupational activities, especially
where flooding irrigation is practiced
•  Take into account host factors
Yes
Consider
JE vaccination
pre-departure
No
No JE vaccine indicated,
unless max protection requested
39
GRID
Meningococcal disease
Caused by the bacterium Neisseria meningitidis
– Most epidemics caused by serogroups A, B, C, W-135 and X
– Spread from person to person
#  Incidence is highest in the
Meningococcal meningitis, countries at high risk*, 2009
“African Meningitis Belt” (AMB)
of sub-Saharan Africa
#  Outbreaks have occurred in
Hajj pilgrims (until 2003)
#  Symptomatic disease is fatal in
5–10% of cases
#  Up to 20% have permanent
neurological sequelae
WHO: International Travel and Health 2011, p.108. HPJ: NEUE LEGENDE UND SCAN DER KARTE
40
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Global Neisseria meningitidis
Serogroup Distribution
CANADA1
EUROPE4
14%
23% 59%
JAPAN9
USA2
14% 69%
TURKEY5
25% 35%
35%
31%
33% 29%
29%
AFRICAN
MENINGITIS
BELT6
78%
BRAZIL3
25%
10%
47%
SOUTH
ARGENTINA3
A
35% 50%
AUSTRALIA10
11%
68%
37% 52%
21% 57%
18%
17%
COLOMBIA3
TAIWAN8
B
W135
C
AFRICA7
X
Y
84%
NEW
ZEALAND11
11%
82%
Represents serogroups
not defined for each
individual country
References upon request.
41
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Changing N. meningitidis Serogroup Distribution (%)
Y increasing
N=261
N=122
Y increasing
N=167
N=110
C increasing
N=3624
N=N/A
C increasing
N=53
N=82
W increasing
N=9
N=209
11
23
Proportion of cases*
24
46
56
30
51
63
3
37
9
United States1,2
61
75
88
71
13
45
22
5
4
29
Colombia3
43
32
5
67
4
4
Czech
Republic6
Brazil4,5
2
36
21
6
B
C
W-135
Y
A
NG
Saudi
Arabia7
*Percentages represent proportions of cases due to each serogroup, not absolute incidence of disease.
42
GRID
Changing N. meningitidis Serogroup Distribution (%)
Y increasing
N=261
N=122
Y increasing
N=167
N=110
C increasing
N=3624
N=N/A
C increasing
N=53
N=82
W increasing
N=9
N=209
11
23
Proportion of cases*
24
46
56
30
51
63
3
37
9
61
75
88
71
13
45
22
5
4
29
43
32
5
4
2
36
21
6
67
B
C
W-135
Y
A
NG
4
Czech
Saudi
Changing
Serogroup
distribution
Republic
Arabia
*Percentages represent proportions of cases due to each serogroup, not absolute
of disease.
!incidence
broad
protection essential !
United States1,2
Colombia3
Brazil4,5
6
7
43
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Meningococcal disease –
Historical data in travelers
Population
Attack rate (per million)
CFR (%)
Travelers
0.4 to 3
>20
Pilgrims
77 to 2000
>20
Koch S & Steffen R, J Travel Med 1994;1:4-7
Jones DM & Sutcliffe EM, J Infect 1990;21:21-5
Moore PS et al, JAMA 1988;260:2686-9
44
GRID
Incidence of Meningococcal Disease
Europe, 2007
Incidence*/100,000 persons
≥4.00
2.00 to 3.99
1.00 to 1.99
0.50 to 0.99
<0.50
*Confirmed and probable meningococcal disease.
Czumbel I, et al. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. 2009.
45
GRID
Travel related environmental factors in
meningococcal disease
Dormitories
●  Educational institutions
●  Military
Bruce et al. JAMA 2001;286:688-93
Mimouni D et al. Am J Infect Control 2010;38:56-8
●  Trekking huts (Nepal 1980‘s)
CDC. MMWR 1985;34:119-25
Discotheque
Hauri AM et al. Epidemiol Infect 2000;124:69-73
Sport event (Rugby; not EURO, FIFA)
Orr H et al. Commun Dis Public Health 2001;4:316-8
Gonçalves G et al. Euro Surveill 2005;10:86-9
Refugee camps
Benca J et al. Neuro Endocrinol Lett 2007;28 Suppl 2:44
Pilgrimage
●  Hajj, Umrah
●  India (Prayag, Allahabad U.P.)
46
GRID
Anecdotal cases of meningococcal
disease in travelers, from 1996 (selection)
Type of traveler
Origin
Location
Outcome
Children
UK, Germany
Majorca, Spain
2 died, 2
recovered
PHLS. CDR Weekly 1996;6:191
(2 children died in same hotel)
Students (2)
Swiss / French Germany
1 died, 1
recovered
unknown
recovered
Zuscheid et al. Euro Surveill 2008,
Nov 6; Rapp C et al J Travel Med
2010;17:1-7
Athlete
Jaca, Spain
(1500 athletes from 43
countries)
Cummiskey J et al. J Sports Med
Phys Fitness 2008;48:125-8
Tourist
Swiss
Tirol, Austria
(only in public media)
Anonymous. NZZ 1 November 2006
Journalist
UK
Morocco > Japan recovered
> Singapore
Italy
Delhi, Chennai
Wilder-Smith A & Goh KT. J Travel
Med 2003;10:59-60 (W135)
Businessman
died
recovered
Lapadula G et al. Emerg Infect
2009;15:52-54
47
GRID
The Hajj and global spread
of disease
#  Annual pilgrimage
to Mecca, largest
gathering in the world
#  >2 million persons
from many countries
But no meningococcal disease from 2004
48
GRID
Exportation of Invasive W-135 Disease Among Pilgrims
and Contacts – From the Hajj to England and Wales
14
Pilgrim
Contact of pilgrim
No known contact with pilgrims
12
10
8
6
Hajj 2000
Hajj 2001
4
2
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19
2000
2001
Hahne SJ et al. Lancet. 2002;359:582-583.
Modified from: Prof. A. Wilder-Smith.
49
GRID
Post-Hajj carriage and
effect of polysaccharide vaccination
Carriage rates before and
after Hajj
Carriage rates amongst Hajj pilgrims
returning home, 1987
* Non-vaccinated adds up to 101% due to rounding errors
Moore PS et al, JAMA 1988;260:2686-9
Wilder-Smith A et al, Emerg Infect Dis 2003;9:123-6
50
GRID
Available Meningococcal Vaccines
Class
Polysaccharide
vaccines
Polysaccharide-protein
conjugates
Outer membrane
vesicle (OMV) vaccines
Serogroups
Available vaccines
A, C, W-135, Y
Menomune®, ACWY Vax®,
Mencevax®
A, C
Mengivac®, AC Vax®
C
Menjugate®, Meningitec®,
NeisVac-C®
A, C, W-135, Y
Menveo®, Menactra®
C (+ Hib)
Menitorix®
B*
MeNZB®, MenBvac™
B*
(+ C polysaccharide
capsule)
VA-MENGOC-BC®
Note: Availability of vaccines by country or region will vary.
*Strain specific.
Menomune and Menactra are registered trademarks of Sanofi Pasteur; AC Vax, ACWY Vax, Mencevax, and Menitorix are registered trademarks of GlaxoSmithKline; Mengivac is a
registered trademark of Aventis-Pasteur; Meningitec is a registered trademark of Wyeth; NeisVac-C is a registered trademark of Baxter Healthcare; VA-MENGOC-BC is a registered
trademark of Finlay Institute, Cuba; MenBvac is a trademark of Norwegian Institute of Public Health; Menjugate and MeNZB are registered trademarks of Novartis.
Granoff DM, et al. In: Plotkin S, et al, eds. Vaccines. 2008:chap 19.
51
GRID
Characteristics of Meningococcal Vaccines
Property
Polysaccharide
Conjugate
Effective in infants
No
Yes
Immune memory
No
Yes
Prolonged duration of
protection
No
Yes
Booster effect
No
Yes
Reduction of carriage
No
Yes
Contributes to herd effect
No
Yes
Hyporesponsiveness
with repeated dosing
Yes
No
This is based on MenC conjugate experience and all attributes descried for conjugates may not necessarily to apply to Menveo
Harrison LH. Clin Microbiol Rev. 2006;19:142-164.
52
GRID
Meningococcal Vaccine Recommendations
WHO
CDC
(USA)
CATMAT
(Canada)
NaTHNac
(UK)
DTG / SWI
(German /
Swiss)
Mandatory
Mandatory
Mandatory
Mandatory
Mandatory
N/A
N/A
Mandatory
N/A
Some required
At risk
N/A
N/A
N/A
N/A
Consider
Recommend
Consider
Risk groups
Consider
-
-
Recommend
-
Recommend
Consider
Recommend
Consider
-
Recommend
N/A
Recommend
Consider
-
-
At risk
Recommend
Consider
Indicated
Consider
-
At risk
-
-
-
Healthcare work
-
-
-
Indicated
-
VFRs
-
-
-
Indicated
-
Hajj / Umrah
Occupation KSA
Military
Sub-Sahara MB
All
Dry season
Epidemiology
Epidemic
Hyperendemic
Prolonged
contact w/locals
Other
Young children
53
GRID
Meningococcal vaccination decision
algorithm for travelers
Vaccination required?
Yes
No
• Hajj, Umrah
Last Mening‘ 4V vaccine <3y
No
Vaccinate!
•  Some occupations in
KSA
•  Some colleges in US,
Canada, UK
Yes
High risk occupation abroad?
Yes
• Disaster relief
• (College)
Recommend (or
consider) vaccine
No
Yes
High risk
destination
No
No meningococcal
vaccine indicated
54
GRID
Yes
No
• Hajj, Umrah
No
Vaccinate!
KSA
Canada, UK
Yes
Yes
relief aid
#  Disaster relief,• Disaster
humanitarian
• (College)
#  Military missions
#  Health professionals
Yes
Recommend (or
consider) vaccine
recommend
No
recommend
consider (§)
High risk
destination
No
No meningococcal
vaccine indicated
55
GRID
Yes
No
• Hajj, Umrah
No
Vaccinate!
KSA
Canada, UK
Yes
Yes
Recommend (or
consider) vaccine
No
Yes
•  Epidemic
•  AMB
High risk
destination
No
No meningococcal
vaccine indicated
56
GRID
Yes
• Hajj, Umrah
No
Vaccinate!
KSA
Canada, UK
Yes
No
Yes
No
Yes
High risk
Recommend (or
•  Epidemic destination
#  Epidemic / outbreak, anywhere consider) vaccine
recommend
#  African meningitis belt (AMB)
–  Prolonged contact with locals
(VFRs, backpackers, etc)
No meningococcal
–  Prolonged duration of stay
vaccine indicated
–  Host factors, e.g. immune deficiency
–  Request maximum protection
57
•  AMB
consider (for any season — §)
recommend
recommend
recommend
recommend
No
GRID
TBE Virus: Endemicity and vectors
European subtype
Siberian subtype
Far Eastern subtype
European subtype: Ix. ricinus
Siberian and Far Eastern subtypes: Ix. persulcatus
Tick-borne encephalitis
>10,000 cases/year
Courtesy: Prof. F.X. Heinz, Medical University of Vienna (amended)
58
GRID
L’encéphalite à tiques en Europe
Baxter 2011
59
GRID
L’encéphalite à tiques en Europe
:
s
t
n
bita
a
h
0
’00
.9;
0
6
0
e
i
1
n
r
a
u
h
t
i
s pa
L
,
le
5
a
.
7
4
m
,
i
e
2
i
x
n
e
ma
etto
ussi
s
,L
e
;R
4
.
c
.
9
n
,
0
41-6
2
9
e
1
:
6
8
d
;
ci
nie
nie
2011
In
Esto
é
Slov
id
y ep
l
k
e
e
O. W
Rec
WH
Baxter 2011
60
GRID
Evolution de l’endémicite en Suisse
1970 - 1978 vs. 2011
Krech T, thèse Université de Berne 1980
Bulletin, Office Fédéral de Santé Publique 2012
61
GRID
Transmission de l’encéphalite à tiques
Les tiques
grimpent
1 m 50
Les tiques ne sont
PAS
des parachutistes
62
GRID
L’essentiel sur les tiques (Europe Ixodes ricinus)
Piquent et peuvent transmettre des agents pathogènes aux
animaux des forêts (hérissons, souris, cervidés),
occasionnellement également aux animaux domestiques
(chien, chat) et aux êtres humains
–  (Méningo-) Encéphalite (verno-estivale) à tiques
–  Borréliose de Lyme, Ehrlichiose, Babésiose
Les tiques piquent, elles ne mordent pas
–  Exploration aveugle de l’hôte avec les organes sensoriels
–  La tique ’vomit’ en aspirant
–  La salive de la tique contient des substances
–  Antalgiques
–  Anticoagulantes
–  Piqûre souvent inaperçue (30 - 50%)
Conditions de vie
–  Hibernation entre des feuilles, reveil par 5-7°C au sol
–  Altitude maximale 1600 m
Süss J et al. J Travel Med 2008;15:39-45.
63
GRID
De la piqûre à la catastrophe
%
par 100’000 piqures
&  Tiques contaminées 0.5 - 5
1000
&  Maladie:
&  Symptôme ’grippe’
10 - 30
100 - 300
&  Encéphalite
6 - 10 (Asie 30)
6 - (100)
&  Sequelles neuropsy. 30
2 - (30)
&  Déces
Europe <1
1 -2 (Asie 20)
64
GRID
Chronologie de l’encéphalite à tiques
7-14 j (2-28)
Temps
d’incubation
1-8 jours
1-20 jours
Jours-semaines
Symptômes
grippaux:
fièvre, fatigue,
céphalées,
myalgies,
nausées,
Phase
intermédiaire
sans symptômes
malaise général
NOTE: Incubation après consommation de
lait, fromages d’animaux virémiques: 1-2
jours
10%
Maux de tête,
fièvre, fatigue,
paralysies,
troubles respiratoires,
crises d’épilepsie,
méningo-encéphalite
myélite
2%
90% guérit
Décès
Phase 2
Phase 1
WHO. Weekly epid Rec 2011;86:241-6.
65
GRID
Vaccins inactivés contre
l’encéphalite à tiques
"
"
"TicoVac "
"TicoVac "
"Encepur"
"
"
"Enfants "
"Adultes*"
"
"
"Adultes "
"= FSME-Immun
Age Indication
"≥16 years
"1-15 years
Virus strain
Amount of Ag
Al(OH)3 "
Stabilizer "
Traces "
Shelf life "
Volume "
Producer "
"Neudörfl "
"Neudörfl "
"2.4 µg "
"1.2 µg "
"1 mg
"
"0.5 mg "
"Human serum albumin
"
"Formaldehyde
"Formaldehyde
"24 months
"24 months
"0.5 ml "
"0.25 ml "
"Baxter, Austria
"Baxter, Austria
"= FSME-Immun Junior"
"≥12 years"
"K23"
"1.5 µg"
"1 mg"
"Sucrose"
"Antibiotics"
"24 months"
"0.5 ml"
"Novartis, Germany"
Autres vaccins: TBE Moscow, EnceVir (Russes; préparés de souches extrème-orientales), Chine (?)
Barrett PN et al, Chapter 32 in Plotkin et al, eds. 2008.
* Encepur Kinder 0.25 not marketed in France
66
GRID
Utilisation des vaccins contre
l’encéphalite à tiques
Série primaire:
●  Encepur:
–  Raccourci:
●  Ticovac:
–  Raccourci:
M0
M1-3* M10-15 (M9-12 après dose 2)
J0
J7*
M0
M1-3* M5-12
J0
J14*
J21
J365-540
M5-12
* Début de protection: 2 semaines après 2ème dose
NOTE: 1 dose resulte en seroconversion limité
Injection IM (ou SC en cas de risque de hémorrhagies)
Rappel:
●  Adultes, enfants:
●  Age >50 / 60 ans:
3 ! 5 ans, Suisse: 10 ans
tous les 3 ans, Suisse: 10 ans
67
GRID
Contre-indications
Hypersensibilité
–  A la substance active
–  A l’un des excipients ou autre composant
(Formaldéhyde, chlortétracycline, gentamycine, néomycine; protéines d’oeuf)
–  A l’administration de la première dose
Maladie fébrile aiguë grave
Grossesse:
que si .. protection .. est urgente
Allaitement:
que si .. protection .. est urgente
68
GRID
Efficacité de ces vaccins
Aucun essai clinique pour prouver l’efficacy
Vaccination de la population en Autriche prouve
l’ effectiveness (= outcome)
Estimations:
–  99% après vaccinations selon schéma
–  95% après vaccinations ’irrégulières’
Aucun corrélat sérologique fiable
Taux de protéction similaires des deux vaccins:
–  2 semaines après 2ème dose >90%
Heinz FX et al. Vaccine 2007;25:7559-67 and (2013 in preparation).
69
GRID
Tolerance profile of TBE vaccines
Mild local reactions as with any inactivated IM administered vaccine
Systemic Adverse Events:
–  Headache (Encepur 15% after first dose, 9% after third dose)
–  Fatigue, malaise, muscle and joint pain
–  Fever (TicoVac 0.8% ! 0.5%.
–  More frequently after first dose (Immune response may be protective?)
Similar safety profile in adults and children (young children more fever)
« It cannot be totally excluded that TBE vaccination may »
–  aggravate autoimmune diseases: multiple sclerosis, iridocyclitis
–  but no link to disease activity, clinical relapse or disease progression
RARE:
–  Myelitis, smell impairment, thrombocytopenic purpura reactivation
Ipatti P et al. Duodecim 2012;128:307-10.
Vodicka J et al. Vaccine 2010;28:886-8.
Benz R et al. Vaccine 2009;27:5172-3.
70
GRID
Tolerance profile of TBE vaccines
Mild local reactions as with any inactivated IM administered vaccine
Systemic Adverse Events:
ed
t
r
o
ep
,
r
y
l
n
mo
–  Fatigue, malaise, muscle and joint pain
m
o
g.
c
n
i
e
n
r
e
te 00977
–  Fever (TicoVac 0.8% ! 0.5%.
a
w
e
s
r
t
c
th n 21:CD0
e
f
e
f
f
i
e
l
a protective?)
–  More frequently after firstsdose
response
may
Jbe
r
e (Immune
o
009;
r
2
s
v
e
e
u
R
v
o
d
i
r
Syst
a
e
e
s
h
s andDchildren
a
Similar safetyug
profile in adults
(young children more fever)
e
atab
r
o
e
e
c
h
w Cochran
lt
e
A
n
.
o
« It cannot be totally
that TBE vaccination may »
n hexcluded
et al
V
i
l
e
–  Headache (Encepur 15% after first dose, 9% after third dose)
emic
D
–  aggravate autoimmune
diseases: multiple sclerosis, iridocyclitis
–  but no link to disease activity, clinical relapse or disease progression
RARE:
–  Myelitis, smell impairment, thrombocytopenic purpura reactivation
Ipatti P et al. Duodecim 2012;128:307-10.
Vodicka J et al. Vaccine 2010;28:886-8.
Benz R et al. Vaccine 2009;27:5172-3.
71
GRID
TBE in Austria 1979-2011
!"#$%&'('$)*$+,'-.)&$
/&%%)*&01*$%12(.&3($)*$+,'-.)&$4&-$5(&'-$6$2&%%)*&01*7$
Courtesy: Prof. F.X. Heinz, Medical University of Vienna
72
GRID
TBE in Austria 1979-2011
:
d
e
t
n
e
v
Pre cases s
0
e
s
0
a
0
c
l
>4
a
t
a
f
0
2
o
t
10
!"#$%&'('$)*$+,'-.)&$
/&%%)*&01*$%12(.&3($)*$+,'-.)&$4&-$5(&'-$6$2&%%)*&01*7$
Courtesy: Prof. F.X. Heinz, Medical University of Vienna
73
GRID
Risque pour les voyageurs
„Les voyageurs qui se rendent dans des pays ou zones à
risque en été sont particulièrement exposés lorsqu’ils font
de la randonnée ou campent dans les zones rurales ou
forestières. ...
La vaccination ne concerne que les voyageurs à risque.“
OMS: Voyages internationaux et santé 2011, p.100-2.
Encéphalite à tiques par mois d’exposition:
0,9 par 1000 pour l’US Army
0.1 par 1000 pour la population à risque en Autriche
Voyageurs: <50 cas publiés (78 millions de voyages)
Rendi-Wagner P. J Travel Med 2004;11:307-12.
Jensenius M. ISW-TBE 2009.
Reusken C et al. Euro Surveill 2011;16(44). pii 20003
74
GRID
Autres recommendations pour les
voyageurs
„La vaccination ne concerne que les voyageurs à risque.“
„Voyageurs concernés : Personnes à haut risque
uniquement“
OMS: Voyages internationaux et santé 2011, p.101-2.
Vaccine: No TBE vaccines ... in the U.S. ... Because the
routine primary vaccination series requires !6 months for
completion, most travelers to TBE-endemic areas will find
avoiding tick bites to be more practical than vaccination.
CDC Health Information for International Travel 2012;305-8.
75
GRID
Poliomyelitis — situation globale 2013
Last case in "
traveler 2007"
76
"
Stewardson AJ et al."
Emerg Infect Dis 2009;15:63-65."
GRID
Tetanus associated with travel
1 case only found: Spain to Germany
Werner GT. Sozial Präventivmed 1985;30:103-6
77
GRID
Conclusions
Travel related neurological infectious diseases are RARE
Underreporting! (often reporting not mandatory)
Often no zero risk
Some infections vaccine preventable — new vaccines = advantages
●  JE vaccine: replaces JE-Vax associated with adverse events
●  Meningococcal vaccines: conjugate, quadrivalent / B vaccine
Difficult to determine who will be exposed ! vaccine indicated
●  Rabies
●  Japanese Encephalitis (JE)
●  Meningococcal Disease
●  Tick Borne Encephalitis (TBE)
●  (Poliomyelitis) NOTE: vaccine recommended in all exposed...
78
GRID

Vaccinate! - Clinique Santé Voyage

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