ST60+/ST80+ ] · 概述 ST60+ 和 ST80+ Infrared Thermometers(以下简称“测温仪”)用于非 接触式温度测量。 这些测温仪通过测量物体表面辐射的红外能量来
Diagnose en surveillance van infectieuze …– Partly hospital-acquired (48h definition) –...
Transcript of Diagnose en surveillance van infectieuze …– Partly hospital-acquired (48h definition) –...
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Centre Culturel et de Congrès de Woluwé-St-Pierre
Diagnose en surveillance van infectieuze aanDoeningen
Diagnostic et surveillance Des malaDies infectieuses
26Ste Seminarie > 25 november 201026e Séminaire > 25 novembre 2010
Cultureel en Congrescentrum van St.-Pieters-
Woluwe Programme | Programma
Diagnosis maLDi-toF
surveillance Ca-mrSa influenza
risk & Prevention rotavirus vaccinal cover Helicobacter pylori
infection control Shigella Food-borne outbreaks
information | informatie
t +32 2 642 57 77inscription avant le 10 novembre 2010inschrijving vóór 10 november 2010sur | op www.wiv-isp.be/epidemio/labo
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24/11/2011
Emergence of CA-MRSA USA 300 as a cause of severe infections in Belgium
Dr Olivier DenisLaboratoire de référence des MRSA
ULB, Hôpital Erasme Brussels
Woluwé-St-Pierre25/11/2010
1
HOSPITAL
Other hospitals
Nursing homes (NH)Long-term care facilities (MRS)
Community
MRSA transmission between different sectors
Animals
Hospital-associated (HA-)MRSA
Community-associated (CA-)MRSA
Livestock-associated (CA-)MRSA
Infections with PVL positive (MR)SA strains can be severe
Necrotizingpneumonia
NecrotizingOsteomyelitis
These cases are rare and need specific treatment
2
Global dissemination of CA-MRSA
Europe
Hawaii
Taiwan
Africa
Australia
World distribution of PVL positive CA-MRSA clones
ST8
ST8
ST8
ST8
ST80
ST80
ST80
ST30
ST30
ST30
ST30
ST30
ST1
ST1
ST1
ST5
ST5
ST59ST59
ST59
ST30
Tristan A. et al. EID 2007
3
World distribution of PVL positive CA-MRSA clones
ST8
ST8
ST8
ST80
ST80
ST30
ST30
ST30
ST30
ST1
ST1
ST1
ST5
ST5
ST59ST59
ST59
ST30
Tristan A. et al. EID 2007
ST8 ST80
ST30
Panton-Valentine leukocidin
• Two-component pore-forming protein encoded by lukF-PV and lukS-PV genes– Cell membranes and mitochondria
• Target cells : polymorphonuclear neutrophils, monocytes and macrophages
• Necrosis and abcess +++• < 5% of S. aureus• Genes located on phages
– ϕ108PVL, ϕPVL, ϕSTL, ϕSa2mw
Kanero J et al. Biosc. Biotechnol. Biochem 2004 68:981Gillet Y et al. The Lancet 2002 359:753
4
Other virulence factors
• USA 300-ST8– ⇑ expression of agr, searRS, sarA, α-toxin (hla), PVL– Arginine Catabolic Mobile Element
• Integrated into orfX closed to SCCmec element• Encoding arginine deiminase• Enhanced ability to colonize the skin and secondly dissemination
• ST80 S. aureus– ⇑ binding to collagens of types I and IV; and to laminin
• Other– Phenol-soluble modulin (PSM) peptides– Activation and lysis human neutrophils humains
Montgomery C. et al. JID 2008 198:561De Bentzmann S. et al. JID 2004 190:1506Wang R. et al. Nature Med 2007 13:1510
CA-MRSA USA 300
• Isolated from patients on all continents• Most prevalent CA-MRSA in the USA
– Major cause of SSTIs and invasive infections
– Asymptomatic colonisation (17%) in the general population
• Molecular characteristics– ST8-SCCmec IV– Virulence factors : PVL and ACME
Moran GJ et al. NEJM 2006
5
100
50 100.
00
120.
00
140.
00
160.
00
180.
00
200.
00
220.
00
240.
00
300.
00
350.
00
500.
00
600.
00
700.
00
800.
00
900.
00 PFGE SCCmec ST PVL
A1 Ia 247 -A20 IV 8 -A23 IV 8 +L1 IV 22 -B2 IV 45 -G10 II 5 -J4 IV 30 +J1 II 36 -X1 IV 80 +X1 IV 80 +X1 IV 80 +X2 IV 80 +
Clonal linkage of Community and Hospital MRSA strains in Belgium
Secular trends of MRSA clonal distribution National Surveillance, hospitals, Belgium 1992-2008
% o
f ins
titut
ions
Deplano et al. CMI 2000; Denis et al. JAC 2002; MDR 2003; AAC 2004; AAC 2006; 17th ECCMID 2007
0
10
20
30
40
50
60
70
80
90
100
1992(n=62)
1995(n=85)
1997(n=90)
1999(n=33)
2001(n=100)
2003(n=112)
2005(n=116)
2008(n=109)
A1-ST247-SCCmec I B2-ST45-SCCmec IV C3-ST5-SCCmec IV
A20-ST8-SCCmec IV G10-ST5-SCCmec II L1-ST22-SCCmec IV
Years (number of hospitals)
6
Differences between
HA-MRSA– Endemic clones in each
country– No specific toxins– Co-resistant to AB– Nosocomial infections – Older patients with co-
morbidities
CA-MRSA– Same clones in Europe– Specific toxins
• PVL • Toxic shock syndrome toxin
– Susceptible to AB– Skin and soft tissue infections – Young healthy people
Liassine N et al JCM 2004;42:825-8Naimi T et al JAMA. 2003;290:2976-84.Vandenesch et al. EID, 2003;9:978-84
Surveillance programme of CA-MRSA in Belgium
• 2004 – 1st semester 2008– Antimicrobial susceptibility profile of the MRSA strain
• Cipro-S, fusidic acid-R
– Clinical manifestations : furunculosis, necrotizing pneumonia, …
• Since 2nd semester 2008– If MRSA isolated from outpatients or from inpatients
but within the first 48 hours of hospital admission– Clinical manifestations
7
CA-MRSA collected for toxine gene detection, (n = 516, 2004-2009)
0
10
20
30
40
50
60
70
80
90
100
2004 2005 2006 2007 2008 2009
Num
ber o
f str
ains
PVL-neg MRSAPVL-pos MRSA
YearsReference laboratory for staphylococci and MRSA
Origins of CA-MRSA strains(n = 95, 2008)
0
5
10
15
20
25
30
35
Skin/softtissue
Screening ENT Blood Other
Num
ber o
f str
ains
PVL-neg MRSAPVL-pos MRSA
YearsReference laboratory for staphylococci and MRSA
8
0
10
20
30
40
50
60
2003-04 2005 2006 2007 2008 2009Years
Num
ber o
f str
ains
OtherST8-IV (USA 300)ST8-IVST30-IVST80-IV
Genotype distribution of CA-MRSA PVL positive (n = 188), Belgium, 2003 to 2009
Reference laboratory for staphylococci and MRSA
Denis et al. JAC 2005; Brauner J et al. 19th ECCMID 2009, Naesens R. et al. JMM 2009
0
10
20
30
40
50
60
2003-04 2005 2006 2007 2008 2009 2010Years
Num
ber o
f stra
ins
OtherST8-IV (USA 300)ST8-IVST30-IVST80-IV
Genotype distribution of CA-MRSA PVL positive (n = 242), Belgium, 2003 to 2010
Reference laboratory for staphylococci and MRSA
Denis et al. JAC 2005; Brauner J et al. 19th ECCMID 2009, Naesens R. et al. JMM 2009
9
Origins of PVL-positive CA-MRSA strains (n = 242, 2004 – 2010)
77%
7%3% 2% 3% 8%
Skin and soft tissueCarriageBloodSputumOtherUnkown
MRSA reference laboratory, unpublished data
Clinical and demographic characteristics of patients with CA-MRSA USA 300, 2008
# familial cluster
Patients Age Sample site Clinic Cluster Contact with the USA
Evolution
1 35 Blood Meningitis Yes Dead2 48 Sputum Bronchitis Recovery3 6 Nose Furuncle Yes Recovery4 5 Nose Furuncle Recovery5 50 Skin Anal abcess Recovery6 35 Skin Mastitis Recovery7 1 Skin Furuncle Recovery8 40 Nose Carriage Yes Yes Recovery9 1 Skin Skin abcess Yes Yes Recovery10 21 Skin Furuncle Recovery11 10 Skin Furuncle Recovery12 48 Skin Wound Yes Recovery13 40 Nose Carriage Yes Recovery14 37 Blood Endocarditis Recovery
#
10
History and contact with health-care facilities in MRSA patients at their hospital admission
(n = 42 hospitals, 2009)
38%
11%15%
9%
18%
9%MRSA history
Transfer from hospital
Transfer from NH
Transfer from hosp. and NH
Community
Unkown
Source: B.Jans et al IPH surveillance report 2009
Occurrence of CA-MRSA isolatesby strain characteristics, 2003-08
• National hospital surveys, 2003 – 08– 1153 MRSA collected from >110 hospitals
• PVL-positive CA-MRSA– Low & stable frequency (<2 %)– Partly hospital-acquired (48h definition)– PVL-positive CA-MRSA: 10 isolates belonging predominantly to the
European clone ST80-SCCmec IV
Vandendriessche S. et al. 20th ECCMID, Vienna, April 2010
11
MLST-SCCmec
spa-type
year Resistance profile Resistance genes
n
ST80- IV t044 20082005 200820052008
KANTET, KANTET, KANTET, KAN, ERYTET, KAN, ERY, CLI
aphA3tetK, aphA3tetK, aphA3tetK, aphA3, ermCtetK, aphA3, ermC
11211
ST30-IV t019 20032005
//
NANA
12
ST5-IV t3196 2008 TET tetK 1
Profile of PVL-positive MRSA strains
Vandendriessche S. et al. 20th ECCMID, Vienna, April 2010
0
1
2
3
4
5
2003 2005 2008
% of MRSA
PVL-positve CA-MRSA
LA-MRSA
Trends in % PVL-positive CA-MRSA and LA-MRSA, 2003-2008
Years of survey
0.2
1.2 1.6
0.40.9 0.6
Vandendriessche S. et al. 20th ECCMID, Vienna, April 2010
12
Nasopharyngeal carriage of S. aureusin healthy kindergarten children
• Screening for S. aureus– Children 3-6 years from 11 kindergarten– Sequential nasopharyngal aspirates (autumn/winter/spring)
• Results– 830 samples from 333 children– 286 (34%) culture positive for S. aureus from 185 (55%) carriers– 14 MRSA isolated from 11 children (3%)– MRSA isolates multi-resistant to antimicrobials– No PVL
Blumental S. et al. ESPID 2010
Conclusions
• CA-MRSA infections in young population associated with SSTI but severe infections recently reported
• Predominance of European CA-MRSA ST80 clone up to 2007
• Progressive replacement by CA-MRSA USA 300 ST8– Small familial clusters, importation from the USA
• Low prevalence of PVL-positive MRSA in hospitals and in healthy children
• Epidemiological surveillance across healthcare sectors and community
13
Prevention and control
• Guidelines for general practice management of staphylococcal infection– Document severe or recurrent skin and soft tissue
infections– Adapt antibiotic treatment based on susceptibility testing– Standard precaution during the care of wound infections
• Guidelines to patients and families– Hand hygiene– Avoid sharing of potentially contaminated objects
Surveillance of Influenza in a Pandemic:
What’s different?
Françoise Wuillaume – Scientific Institute of Public health26th Seminary: Diagnosis and Surveillance of Infectious diseasesBrussels 2010
1
2
Content
1. Key points about Influenza & the 2009 pandemic
2. Objectives of the surveillances
3. Epidemiology and virology results
4. Measure of impact
5. Lessons learned & perspectives
3
Reminder
•Swine flu
•Mexican flu
•A flu, H1N1 flu
Pandemic Influenza
•Bird flu
•H5N1
Avian Influenza
•Influenza A, Influenza B
•A/H1N1, A/H3N2
Seasonal influenza
ILI = Influenza Like Illness (flu syndrome, clinical flu)
ARI = Acute respiratory infection
SARI = Severe acute respiratory infection
2
4
Influenza virus
Familly Orthomyxoviridae…….Genus Influenza (80-100 nm)
8 RNA segments3 Types (A, B, C)2 surface glycoproteins (HA, NA)
Hemagglutinin (16) Neuraminidase (9)
5
WHO pandemic criteria
A pandemic can start when three conditions have been met:
1. a new influenza virus subtype emerges; 2. it infects humans, causing serious illness; 3. and it spreads easily and sustainably among
humans.
http://www.who.int/csr/disease/avian_influenza/avian_faqs/en/
Examples of pandemics:• Plague (14th century)• Cholera El Tor• HIV• Spanish flu (1918 – H1N1), Asian flu (1957 – H2N2), Hong Kong flu (1968 – H3N2)
3
6
WHO pandemic phases (2009 revision)
August 2010
June 2009
H5N1
7
Historic background
4
8
Content
1. Key points about the 2009 pandemic
2. Objectives of the surveillance
3. Epidemiology and virology results
4. Measure of impact
5. Lessons learned & perspectives
9
Surveillance of Influenza
INFLUENZA surveillance
Measure impact
Detect changes
•Population
•Health services
•Work force
• Virulence
• Resistance
•Transmission
Measure impactDescribe
0
250
500
750
1000
1250
35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33
week
inci
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ie v
an g
riepa
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yndr
omen
(/1
00 0
00 in
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+ Evaluation of Control Measures
•Virus: type, sub-type
5
10
Surveillance in a pandemic (WHO)
Characterize the geographical spread, trend, intensity, impact, changes
Monitoring
Characterize the virological and clinical features & the risk factors
Assessment
Detect sustain human-to-human transmissionEarly detection
11
Demand of information in a pandemic
Communication
People
Health authorities
Health professional
Epidemiologist
How many …cases, deaths, pregnant women, persons at risk,
person vaccinated, ...
International partners
6
12
Items of the Influenza surveillance
YesNoUse of Tamiflu
n.a.NoVaccine effectiveness
+/-No Burden on health servicesYesNoAbsenteeismYesYesMortality
YesNoPaediatricians: ILI + biol. sampling
+/-
Yes
Yes
YesP
YesGeneral practitioners: ILI – ARI + biological sampling
Describe
No
No
Yes
S
Vaccination coverage Evaluation of control measures
SARI + HospitalisationsMeasure impactVirological surveillanceDetect changes
13
Content
1. Key points about the 2009 pandemic
2. Objectives of the surveillances
3. Epidemiology and virology results
4. Measure of impact
5. Lessons learned & perspectives
7
14
Epidemic Criteria
Yes-The neighbouring countries report an ILI activity
≥ 20 %QualitativeThe circulation of the virus is demonstrated
YesYesThe consultation rate is ≥ 141 ILI cases / 100,000 inhabitants / week during 2 consecutive weeks
PandemicSeasonal
15
Criteria 1 – ILI consultation rate ≥ 141/100,000 inh./week
ILI clinical Surveillance
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Trait. antiviraux
Grippe saisonnière
Grippe pandémique
ON
CasGroupes d'âge
Etat vaccinal
SYNDROMES GRIPPAUXUn syndrome grippal est une affection fébrile d’accès soudain, avec des symptômes respiratoires et des symptômes généraux
< 1 an1 - 4 ans
5 - 14 ans
15 - 19 ans
20 - 64 ans
65 - 84 ans
85 ans et +
ON
ON
Hospitalisation ON
8
16
Criteria 1 – ILI consultation rate ≥ 141/100,000 inh/week
Influenza Like Illnesses
Influenza – seasons 2009/2010 – Week 20/2010 - IPH
17
Criteria 1 – ILI consultation rate ≥ 141/100,000 inh/week
ILI per age groups
9
18
Criteria 2 – Proportion of positive samples ≥ 20 %
Proportion of positive samples
Exhaustive sampling
Systematic sampling
19
Criteria 3 – Neighbouring countries report ILI activity
International Notification – Week 40/2009
10
20
Season 2002-2003 B + H1N1 + H3N2
Season 2007-2008
Saison 2002-2003
Season 2005-2006
Season 2006-2007
Season 2004-2005
Season 2003-2004 H3N2
H3N2 + B B + H1N1
H3N2 H1N1 + B
Virology surveillance
21
Season 2008-2010 H3N2 + H1N1v
Virology surveillance
H3N2 + H1N1v
11
22
Content
1. Key points about the 2009 pandemic
2. Objectives of the surveillances
3. Epidemiology and virology results
4. Measure of impact
5. Lessons learned & perspectives
23
SARI = Hospitalised cases
12
24
Workload in consultations and hospitals
0.0
5.0
10.0
15.0
20.0
25.0
40 43 46 49 52 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 2
Weeks
Mea
n nu
mbe
r of c
ases
Mean ILI per GP Mean ILI per Pedia Mean SARI per Hospital
0
100
200
300
400
500
600
700
800
900
Wee
k 35
Week 3
6
Week
37
Wee
k 38
Wee
k 39
Week
40
Week
41
Wee
k 42
Week 4
3
Week4
4
Week
45
Wee
k46
Wee
k47
Week
48
Week
49
Wee
k50
Week5
1
Week
52
Wee
k53
Week
1
Wee
k2
Number of positive tests reported
influenza A influenza B Parainfluenza Adenovirus RSV Mycoplasma
?
8.0 7.05.8
25.0
11.7
25
Mortality: Be-Momo
Mortality 1999-2008 All-age population
1500
2000
2500
3000
1999w1 2001w26 2004w1 2006w26 2009w1year,week
nb predul
13
26
1.5
2
2.5
3
3.5
4
01/09
/2008
01/10
/2008
01/11
/2008
01/12
/2008
01/01
/2009
01/02
/2009
01/03
/2009
01/04
/2009
01/05
/2009
01/06
/2009
01/07
/2009
01/08
/2009
01/09
/2009
01/10
/2009
01/11
/2009
01/12
/2009
01/01
/2010
01/02
/2010
01/03
/2010
01/04
/2010
01/05
/2010
Mor
talit
y ra
te/1
00,0
00 in
hab/
day
Mortality rate Predicted mortality rate upper limit
Mortality: Be-Momo
Mortality 2008/2009 & 2009/2010Daily mortality rate, General population
27
15
16
17
18
19
20
21
22
23
38 39 40 41 42 43 44 45 46 47 48 49 50 51
Both sexs
Mortality: Be-Momo
Weekly mortality rates - All ages
Men Women
15
16
17
18
19
20
21
22
23
38 39 40 41 42 43 44 45 46 47 48 49 50 5115
16
17
18
19
20
21
22
23
38 39 40 41 42 43 44 45 46 47 48 49 50 51
Mortality rate
Baseline mortality
Upper limit
14
28
Mortality: Be-Momo
Cumulative weekly excess of deaths– week 38 to week 51
-200
-150
-100
-50
0
50
100
150
200
250
300
38 39 40 41 42 43 44 45 46 47 48 49 50 51
Age < 65
Age 65 - 84
Age 85+
-200
-150
-100
-50
0
50
100
150
200
250
300
38 39 40 41 42 43 44 45 46 47 48 49 50 51
Both sexs
-300
-200
-100
0
100
200
300
400
38 39 40 41 42 43 44 45 46 47 48 49 50 51
Men Women
29
System 1: Be-Momo
Excess mortality during Flu epidemic, 1999-2009
2131049200940 20092,614910200922009503810200832008403610200752007-2018132006620062,118131220055320041,272922004462003-31813200362003
1,30811102002522001-30810620014920003,3931162000481999
WeekYearWeekYearExcess
mortalityNumber of
weeksEndStart
15
30
Mortality: Be-Momo
Cumulated excess of mortalityH3N2(2009) / H1N1(2009)
-200
-100
0
100
200
300
400
500
600
700
800
900
-1 0 1 2 3 4 5 6 7 8 9 10 11 12
Men (season 2009) Women (season 2009)Men (pandemic) Women (pandemic)
-500
0
500
1000
1500
2000
2500
3000
-1 0 1 2 3 4 5 6 7 8 9 10 11 12
Season 2008/2009 Pandemic 2009
31
Mortality: Hospital reporting
Deaths Specific Reporting
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Week 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 1 2
Num
ber o
f dea
ths
0
100
200
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600
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800
900
ILI c
onsu
ltatio
n ra
te
nb deaths ILI consultation rate
16
32
… Could our epidemiologist calculate how many persons did get flu during the pandemic?
But finally….
33
Estimation of the number of infections
17 %5 %2 %Total
3 %1 %2 - 511 %65+
11 %4 %2 – 512 %15-64
53 %14 %2 – 51.3 – 25 %5-14
59 %16 %2 – 52 – 34 %< 5
% MaxEstimate
% Minestimate
Cor2(Asymp)
Cor1(consult)
GPsConsult
17
34
Content
1. Key points about the 2009 pandemic
2. Objectives of the surveillances
3. Epidemiology and virology results
4. Measure of impact
5. Lessons learned & perspectives
35
Lessons learnedThe GP sentinel network is a powerful tool in a pandemic, for both virology and epidemiology surveillance
To be able to monitor PH crisis, it is important to monitor the same indicators in non crisis situations
importance of historic baselines
Importance of networking with data providers (ED, ICU, gyneco…)
Virology and epidemiology are complementary and cannot be dissociated
Relative failure of exhaustive surveillance systems validation of sentinels networks
Relative failure in measuring the severity of the pandemichospital sentinel network
validation of severity indicators
18
36
Perspectives
An effective pandemic surveillance system would be a system for which no additional surveillance item is necessary when the pandemic starts:
1. GP sentinel network (virology + clinic)2. Hospital ED network (virology + clinic)3. Sentinel network of laboratories4. Mortality5. Social impact indicator (absenteeism?)
Those surveillance items are useful in any PH crisis.
37
We wish you a safe 2010/2011 Influenza season …
Week 46 in 2010
Specimen collectionSpecimen collection
Specimen Specimen analysis: analysis: Relevant Relevant pathogenspathogens
IdentificationIdentification
PatientPatient’’s s optimized optimized
managementmanagement
Cost effective and timely!!
ASTAST!!! Physician /bacteriologistdiscussion!!!
Single evolutionover the years:
Automation and miniaturization
Microflex MALDI‐TOF MS (Bruker Daltonics) Axima (Shimadzu)
Ions production in gas phase
Ions separationdepending m/z
Mass spectrumIon currentelectric current
In vacuum
1. Sample is mixed with excess matrix and dried on a MALDI plate.
2. Laser flash ionizes matrix molecules.
3. Sample molecules are ionized by proton transfer from matrix:
MH+ + A M + AH+.
1. Build up of an electromagnetic field:
Acceleration of ions
2. Separation in the flight tube:
•Small ions reach the detector before large ones.
•Measures the time for ions to reach the detector
ion detector
+
+ +
+
++
template
matrix/analytecrystals
accelerationzone
field-freedrift range
grid electrode
desorption
ionization
acceleration
separation
detection
mz =
2eUL²
t²
m: massz: chargeU: accelaration voltageL: path lengtht: timee: elemetary charge
DHB:Irregular crystallization
Requires more laser shots for quality spectrum
Spectra with 100-200 mass signals
Spectra with many signalsm/z > 10kDa
HCCA:Regular crystallization
Requires less laser shots for qualityspectrum
Spectra with 80-150 mass signals
Spectra with fewer signalsm/z > 10kDa
3000 5000 7000 9000 11000 13000m/z
Escherichia coli
Hafnia alvei
Leclercia adecarboxylata
Klebsiella pneumoniae
Proteus mirabilis
Enterobacter aerogenes
Possibility of enrichment of the database
!!! Caution: Bad discrimination of bacteria with similar proteinic profiles
1. Direct application of a thin layer on the MALDI plate
2. To overlay withmatrix3. Dry on air4. Introduction into the
spectrometer
direct
culturesuspension
(McFarland 1‐2)
suspensionin 25%
formic acid
optional:on‐target extractionwith 25% formic acid
addition of0.5 µL matrix solution
solvent evaporationat room temperature
automatedMS analysis
MALDI target
The sample preparation is easy...
....but requires ‐ some training‐ a well lit workplace‐ a calm hand‐ appropriate equipment
* Joan Barenfanger et al, Decreased mortality associated with prompt Gram staining of blood cultures , Am J Clin Pathol 2008;130:870‐876
Bacterial group Number of testedstrains
Acceptedidentifications usingthe algorithm (%)
Enterobacteriaceae 541 98,7
Non fermentative Gram‐negative bacteria
207 95,6
Staphylococcus 83 97,5
Streptococcus 110 89
Haemophilus / Moraxella 42 97,6
Neisseria sp. 4 100
Campylobacter sp. 5 100
Anaerobes 21 95,2
TOTAL 1013 96,7
Species Number of tested strains Accepted identifications using the algorithm (%)
Gram negative (No extraction)
K. pneumoniae 4 4 (100%)
P. rettgeri 1 1 (100%)
S. marcescens 2 2 (100%)
E. cloacae 1 1 (100%)
E. coli 4 4 (100%)
TOTAL Gram negative 12 12 (100%)
Gram Positive (Extraction)
S. aureus 3 3 (100%)
S. epidermidis 5 4 (80%)
S. hominis 1 0 (0%)
S. capitis 2 2 (100%)
E. faecium 1 1 (100%)
S. pneumoniae 3 0 (0%) (No pellet)
TOTAL Gram positive 15 10 (66%)
TOTAL 27 22 (81%)
MALDI‐TOF MS Phenotypicidentifications using
biochemicalcharacteristics
Molecular biology
Direct application Extraction
Preparationtime
5 minutes 20 minutes 1 to 20 minutes 60 minutes
Identification time
2 minutes 2 minutes 5 to 48 hours 45 minutes to 48 hours
Cost(consumables)
0,1 €/sample 0,5 €/sample
Sepsityper kit: 4€/sample
5 €/sample 30‐50 €/sample
Possible identifications
aerobic/anaerobic bacteriaYeasts
MycobacteriaFilamentousfungi
Rather frequentclinically relevant
species
All ones in theory
Requiredcompetence
Basic Moderate High
Comparison: MALDI‐TOF mass spectrometry vs other identification methods
CHU IntranetHospital hygiene
* Decreased mortality associated with prompt Gram staining of bloodcultures. Am J Clin Pathol 2008;130:870‐876
Becomes the essential bacterial identification method in any clinical microbiology lab
Gastric non-Helicobacter pylori helicobacters: distribution in animals and
significance for human health
Bram Flahou, Richard Ducatelle, Koen Chiers, Miet Vermoote, Kim Van Deun, Annemieke Smet, Lien De Cooman, Frank Pasmans,
and Freddy Haesebrouck
Dept. of Pathology, Bacteriology and Avian DiseasesFaculty of Veterinary Medicine
Ghent University
H. pylori infections in humans
+/- 50% of world’spopulation
Developed countries
Less developedcountries
Source:http://www.steadyhealth.com/articles/Helicobacter_pylori__The_Bacteria_that_Cause_Ulcers_a71.html
H. pylori
H. pylori infections in humans
Very important role in gastric pathology!
Source:http://www.steadyhealth.com/articles/Persistent_pain_in_the_upper_abdomen__Dyspepsia__Indigestion__Symptoms_and_Treatment_a1151.html
Source: http://www.healthgiants.com/2009/11/28/what-is-peptic-ulcer/
Gastric Helicobacter infections in humans
+/- 50% of world’spopulation
0.1 - 6% of people undergoinga gastroscopy
H. pylori
Source:http://www.steadyhealth.com/articles/Helicobacter_pylori__The_Bacteria_that_Cause_Ulcers_a71.html
non- Helicobacter pylorihelicobacters (NHPH)
Source: Jalava et al., 1997
• Very fastidious organisms, with a typical morphology
• “H. heilmannii” gastric non-H. pylori helicobacters (NHPH)
• Several species, mainly infecting animals but also a minority of humans
• Like H. pylori, also associated with:- gastritis (Stolte et al., 1994; Debongnie et al., 1995;…)
- gastric ulcers (Debongnie et al., 1998; Sykora et al., 2003;…)
- MALT lymphoma (Morgner et al, 2000; Stolte et al, 2002,…)
Gastric non-H. pylori Helicobacter(NHPH) infections in humans
• Molecular sequencing of various genes (16S rRNA, 23S rRNA, hsp60, urease A and B):
“H. heilmannii”
“H. heilmannii” type 1: “H. heilmannii” type 2H. suis H. felis
H. bizzozeroniiH. salomonisH. heilmanniiH. cynogastricusH. baculiformis
Gastric non-H. pylori Helicobacter(NHPH) infections in humans
“Helicobacter heilmannii” type 1 is identical to Helicobactersuis
Gastric non-H. pylori Helicobacter(NHPH) infections in humans
Source:http://www.steadyhealth.com/articles/Persistent_pain_in_the_upper_abdomen__Dyspepsia__Indigestion__Symptoms_and_Treatment_a1151.html
http://www.treknature.com/gallery/Asia/India/photo2986.htm
Source:http://blogs.orlandosentinel.com/features_lifestyle_animal/2009/05/im-guessing-those-kissapig-fundraisers-are-on-hold.html
Helicobacter infections in pigs
- 1990: first characterization
- large spiral-shaped bacteria in the stomach of slaughterhouse pigs
- colonisation: glandular stomach
- urease +
- “Gastrospirillum suis”
- Further genetic characterization: “Candidatus H. suis”
- successful isolation: Helicobacter suis
H. suis infections in pigs: prevalence
0102030405060708090
100
1 2 3 4
antrum fundus
1 suckling pigs 3 grow – finisher pigs
2 nursery pigs 4 adult pigs
Percentage positivity
H. suis infections in pigs: importance
- One of the risk factors for developing lesions in pars oesophagea (non-glandular part of the stomach)
normal hyperkeratosis
High prevalence ECONOMIC SIGNIFICANCE:
reduced growth rate
mortality due to bleeding
erosions
H. suis infections in pigs: importance
- Induces chronic gastritis in glandular part (mainly antrum)
- Induces a reduction in daily weight gain (> 20 g/day)
Treatment/eradication interesting for profits in pigindustry
• Molecular sequencing of various genes (16S rRNA, 23S rRNA, hsp60, urease A and B):
“H. heilmannii”
“H. heilmannii” type 1: “H. heilmannii” type 2H. suis H. felis
H. bizzozeroniiH. salomonisH. heilmanniiH. cynogastricusH. baculiformis
Gastric non-H. pylori Helicobacter(NHPH) infections in humans
“Helicobacter heilmannii” type 2
Different species colonizing mainly the canine and felinegastric mucosa:
H. felisH. bizzozeroniiH. salomonisH. heilmannii (previously “Candidatus H. heilmannii”)
culturable, however very fastidious
“”Helicobacter heilmannii” type 2
• One or more species of these helical bacteria in:
67 to 86% of clinically healthy dogs61 to 100 % of dogs showing chronic vomiting41 to 100 % of cats, slightly higher rate in animalspresented with chronic vomiting
Frequently mixed infections in dogs and catsAssociation with clinical symptoms species-dependent and still
controversial (H. felis: lymphocytic infiltrates )
Transmission between animals
• H. suis- Until now, no information concerning the epidemiologyof H. suis infections in pigs is available- Suggested routes of transmission:
gastric-oral route probably the main routes
oral-oral route
(faecal-oral): detection of H. suis in pig faeces
Prevalence in sows ↔ Prevalence in piglets (Protectiveeffect of milk???)
Transmission between animals• H. felis, H. bizzozeronii, H. salomonis, H. heilmannii
- Little information is available
- Transmission of H. salomonis from a dam to her puppies, as well as betweeninfected and non-infected pups (Hänninenet al., 1998)
- gastric/oral-oral transmission:
probably main route
- faecal-oral transmission:
probably NOT involved in transmission
(no isolation starting from faeces)Source: http://photobucket.com/images/cat%20licking/
Prevalence of NHPH in humans
• Percentage of patients undergoing gastroscopy:
- western populations: 0.1 % - 1.1 %, mostly around 0.3%
exceptions: Small Czech rural area : 2.0% ↕
More urban communities: 0.06% - 1.1 %
• Percentage of patients undergoing gastroscopy:
- eastern populations:
China: 1.73 % - 1. 9 % (Yang et al., 1998; Chen et al., 1993)
Thailand: 6.2 % (Yali et al., 1998)
- African populations: even higher?
Due to closer contact with animals?
Prevalence of NHPH in humans
Van den Bulck et al. (2005): as a percentage of NHPH-infected patients36.6%: H. suis most prevalent
In order of decreasing prevalence:
21.1%: H. salomonis14.6%: H. felis8.1%: H. heilmannii (provisionally)4%: H. bizzozeronii
Prevalence of NHPH in humans
Transmission NHPH animal man
• High NHPH prevalence in animals↔ animal reservoir?
Low NHPH prevalence in humans
Source:http://blogs.orlandosentinel.com/features_lifestyle_animal/2009/05/im-guessing-those-kissapig-fundraisers-are-on-hold.html
Source:http://www.funnyfidos.com/category/funny-dog-pictures/
Transmission NHPH animal manEpidemiological evidence
• Still not much data available• Retrospective study (Stolte et al., 1994):
- ‘normal’ German population: 37% pets63 % animal-free
- ‘NHPH’-infected population: 70.3% animal contact29.7% animal-free
Difference is statistically significant
• Questionnaire-based study (Meining et al., 1998):
NHPH - infected group: 86.5% animal contact
H. pylori - infected controls:48.2% animal contact
Transmission NHPH animal manEpidemiological evidence
• Questionnaire-based study (Meining et al., 1998):
- Contact with dogs, cats and especially pigs: risk factor for contracting NHPH (“H. heilmannii”) infection
Transmission NHPH animal manEpidemiological evidence
Source:http://blogs.orlandosentinel.com/features_lifestyle_animal/2009/05/im-guessing-those-kissapig-fundraisers-are-on-hold.html
• Presence of multiple “H. heilmannii” strains in an individual sufferingfrom ulcers and in his two cats (Dieterich et al., 1998)
• “H. heilmannii” gastritis caused by cat to child transmission (Van Loon et al., 2003)
genetic relatedness of human and feline strain• Acute gastritis associated with spiral organisms from cats (Lavelle et
al., 1994) • Transmission of “G. hominis” from a pet dog to a 12-year-old girl
(Thomson et al., 1994)
TEM + symptoms• Peptic ulcer disease associated with Helicobacter felis in a dog
owner (De Bock et al., 2007)
Transmission NHPH animal manCase studies
• Contamination of pig carcasses with H. suis:sampling in slaughterhouse
• 4 farms: 10 – 27% swabs: positive• Quantitative RT-PCR: 104 bacteria/swab• Transmission to humans through contaminated meat:
live bacteria? - On carcasses: yes- On meat products (raw mincedpork,…): to be investigated
Transmission NHPH animal manpork meat
Source: http://cric-projects.com/front/index.jsp?idProject=2
• Like H. pylori, also associated with:- gastritis, although less severe than that seen in a H. pylori infection (Stolte et al., 1994; Debongnie et al., 1995;…)
- gastric ulcers (Debongnie et al., 1998; Sykora et al., 2003;…)
- MALT lymphoma (Regimbeau et al, 1998, Morgner et al, 2000,…)
• Confirm in vitro and in vivo
Transmission NHPH animal manassociated pathologies
H. suis infection
Virulence of NHPHMongolian gerbils: chronic inflammation
Control
Virulence of NHPHMongolian gerbils: loss of parietal cells
H. suis
TEM In vivo: necrosis of parietal cells
Virulence of NHPHcell death
In vitro: H. suis-induced cell death in cell lines
Activated caspase-3: apoptosis
0
5
10
15
20
25
30
35
40
propidium iodide staining caspase-3 staining
% p
ositi
vity
in A
GS
cells
neg controlH. suis
Virulence of NHPHcell death
Important virulence factor: H. suis gamma-glutamyl transpeptidase, which degrades glutathione, generating pro-oxidant reactions
Research in our department
• Investigate virulence mechanisms
• Determine the current prevalence of NHPH in humans in Belgium and China (only just started)
• Identification up to the species and strain level
• Treatment/eradication of NHPH infections
Identification of NHPH to species level• Important for
- defining zoonoticimportance of different species- defining their association withdisease in humans and animals
• “H. heilmannii” type 2 bacteria: notdistinguishable based on 16S rRNAgene sequences
• Sequencing of urease A and B genes
• Multiplex PCR
H. felis
H. suis
Identification to species level: cultivation?
• Very fastidious organisms• “H. heilmannii” type 2:
- Succesful technique starting from gastric biopsiesfrom dogs and cats: H. felis, H. bizzozeronii, H.salomonis
- Only 2 isolates (H. bizzozeronii) from humangastric biopsies
• 2007: First succesful H. suis isolation starting from mucosalscrapings / mucus from the stomach of sows.
• 2010: First succesful H. heilmanniiisolation starting from mucosalscrapings / mucus from the stomach of cats.
• Important features- Activated charcoal- 20% serum- Acidic treatment of mucosa- Biphasic culture plates- Culturing at pH 4-6
Identification to species level: cultivation?
Identification to species level: cultivation?
H. suis
Identification to species level: cultivation?
H. suis cultivation successful starting from mucosalscrapings
Gastric biopsies???
Identification to strain level
HS1 atpa (0.0000)HS2 atpa (0.0008)
HS3 atpa (0.0000)HS4 atpa (0.0000)
HS5 atpa (0.0000)HS9 atpa (0.0000)
HS6 atpa (0.0000)HS7 atpa (0.0000)HS8 atpa (0.0000)
StrainAlleletype
SequenceType
atpA efp mutY ppa trpC ureI vhpCHS1 1 1 1 1 1 1 1 ST1HS2 2 1 2 1 2 1 1 ST2HS3 1 2 2 1 2 1 3 ST3HS4 1 2 3 1 3 1 4 ST4HS5 3 2 4 1 2 2 2 ST5HS6 1 3 5 1 1 1 5 ST6HS7 1 3 6 1 1 1 6 ST7HS8 1 4 7 1 1 1 1 ST8HS9 3 2 8 1 1 3 2 ST9
Multi Locus Sequence Typing for isolates, biopsies,…
Research in our department
• Investigate virulence mechanisms
• Determine the current prevalence of NHPH in humans in Belgium and China (near future)
• Identification up to the species and strain level
• Treatment/eradication of NHPH infections
D0 D21 D42 D70 D119
D21 D42 D70 D119
H. suisstomachhomogenate euthanasia
SC
IN
Eradication H. suis: vaccination trial in mice
Average urease
OD
SC IN
P<0.05 P<0.05 P<0.05
P<0.05
P<0.05
H. suis: vaccination trial in miceResults: Urease OD
SC IN
% positive animals
H. suis: vaccination trial in miceResults: PCR
Treatment H. suis: in vitro antimicrobial susceptibility
Combined agar and broth dilution method, followed by evaluation of bacterial growth after 48 incubation (microaerobic, 37°C) using a H. suis specific qPCR
H. suis-containing broth
Treatment H. suis: in vitro antimicrobial susceptibility
Antimicrobial agent No. of strains with a MIC (µg/ml) of:
≤0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 128Ampicillin 1 2 1 5
Ceftiofur 1 5 3
Clarithromycin 1 5 2 1
Enrofloxacin 4 4 1
Gentamicin 6 3
Lincomycin 1 2 5 1
Metronidazole 2 1 4 2
Tetracycline 3 3 2 1
Tylosine 4 5
Bimodal distribution: acquired resistance
Monomodal distribution with tailing: reduced susceptibility
Thank you for your kind attention!
HelicobacterHelicobacter pyloripylori infectioninfection
Fazia ManaKliniekhoofd gastro-enterologie
UZBrussel
1
25 November 2010
H. H. pyloripylori infectioninfection
TransmissionPrevalencePathologyTreatmentResistence
25 November 2010
About 50 % of world infected
Once aquired, lifelong
Only recognized and accepted reservoir = human stomach
H. H. pyloripylori infectioninfection: : introductionintroduction
2
25 November 2010
TransmissionTransmission
Still ?Infection primary in childhood
Schwarz S et al. PLOS pathogens 2008;4: e1000180
Vale F et al. Intern J Food Microbiol 2010
Perry S et al Emerg infect dis 2006
25 November 2010
TransmissionTransmission: : humanhuman to to humanhuman
Vertical person to person/horizontal person to person (sibling, outside family):
Gastro - oral (vomiting in childhood)Feco - oral (experiment with mice, after GE more infected)Oral - oral (controversial)
3
25 November 2010
Transmission: human environmentTransmission: human environment
Horizontal: environmentWater
Culture of HP from water, DNA en coccoid forms in water samplesMore infections if non-hygienic drinking water, no household bad and no sewage disposal facilitiesSurvival of HP in artificially contaminated water Coccoid form from water can colonize stomach of mice
Food (?, probably coccoid form survival in contaminated food, influence premastication)
25 November 2010
TransmissionTransmission
Rural areas: Horizontal transmission
Urban:Vertical transmission (Infection mother/child via genetic studies from HP)
4
25 November 2010
PrevalencePrevalence
Shangai 2009: 73 %serology, age 18-80
Guangzhou (China):1993: 62.5 %2003:49.3 %
Japan1993: 68.4 %2002: 52.5 %
South Korea1998: 66.9 %2005: 59.6 %
Alaska 2006: 24 %
25 November 2010
EpidemiologyEpidemiology childrenchildren 2121stst centurycentury
Belgium 2010: 9.4 %UBT, age 14 - 22
Brazil 2010: 28.7%Serology, age: 4–11
Uganda 2010: 44 %Stool test, age 0-11
Jordan 2006: 55 %Serology, age 6-9
Turkey 2006: 44 %Stool test, age 19-22
Germany 2003: 9 %Serology, age 7-20
Czech republic 2004: 7%Stool test, 0-15
Taiwan 12 %Serology, age 9-15
Saoudi Arabia 2006: 35 % UBT, medical students
Guangzhou (China): 19 %Children 1-5 y:1993: 30.82003:19.4
St-Petersburg: 13 %Children1995:44 %2005: 13 %
5
25 November 2010
PathologyPathology
H. pylori infection
Acute gastritis
Chronic gastritis
AsymptomaticAsymptomatic> 70 %> 70 %
Ulcer disease10 - 15 %
GastricCarcinoma
1 - 5 %
MALTlymphoma
< 1 %
25 November 2010
ExtradigestiveExtradigestive diseasesdiseases associatedassociated withwith H. H. pyloripylori infectioninfection
Vascular diseasesIschaemic heart diseasePrimary Raynaud's
phenomenonPrimary headache
Skin diseasesIdiopathic chronic
urticariaRosacea Alopecia areata
Autoimmune diseasesSjogren's syndromeAutoimmune thyroiditisAutoimmune
thrombocytopeniaHenoch-Schönlein
purpura
• Respiratory diseasesChronic bronchitisPulmonary tuberculosisBronchiectasisLung cancerBronchial asthma
• Other diseasesLiver cirrhosisGrowth retardationChronic idiopathicsideropeniaSudden infant deathDiabetes mellitus
6
25 November 2010
ITPITP IronIron deficiencydeficiencyanaemiaanaemia
dyspepsiadyspepsia
H. pylorigastritis
PathologyPathology
25 November 2010
Current concepts in the management of H. pylori infection: the Maastricht III Consensus report.
Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ.
2005 (published 2007)
ManagementManagement
7
25 November 2010
H. H. pyloripylori : diagnosis: diagnosis
Invasive tools
Histology
RUT
Culture
Non-invasivetools
UBT14C and 13C
Stool Ag test
Serology
Most efficient specand sens > 90 -95 %
Post treatment setting (monoclonal AB): +/- 92 % accuraat
Epidemiologicalstudies
25 November 2010
NonNon--invasiveinvasive tests tests UBT most accurate > 95 %Stool test (monoclonal AB): +/- 92 % accurate
Inconvenience of storage (-20°C), batch testing and acceptance of patients. Max 2 days room temperature ! New meridian rapid one-step test !
Serology only 80-85 % accurate. Locale validation necessary.
InvasiveInvasive teststestsRapid urea test (RUT): accuracy > 90 %
H. H. pyloripylori : diagnosis: diagnosis
8
25 November 2010
Advantages serology:
Results of serology not influenced by intake of PPI, antibiotics or by bleeding.
more accurate if low bacterial load (atrofie, MALT)
Easy to use for epidemiology
H. H. pyloripylori : diagnosis: diagnosis
25 November 2010
H. pylori: control after treatmentH. pylori: control after treatment
Control > 4 weeks
First choiceUBT
Second choicestool test (monoclonal > polyclonal)
9
25 November 2010
H. H. pyloripylori: : treatmenttreatment
whywhy ??
Recurrence of ulcers is decreased with + 90 %Healing of MALT lymphoma in early stagePrevention of gastric cancer if no precursor lesions of cancer are present at the moment of eradication
25 November 2010
Maastricht Maastricht guidelinesguidelines1996 1996 -- 2000 2000 -- 20052005
10
25 November 2010
A 11a Systematic review of randomised controlled trials (RCT) of good methodological quality and with homogenecity1b Individual RCT with narrow confidence interval1c Non-controlled studies
B 2 2a Systematic review of cohort studies (with homogenecity) 2b Individual cohort studies (including low quality RCT, eg <80%
follow-up) 2c Non-controlled cohort studies/ecological studies
33a Systematic review of case-control studies (with homogenicity)3b Individual case-control studies
C 4 Case series/poor quality cohort or case-control studies
D 5 Expert opinion without explicit critical appraisal or based on physiology, bench research or "first principles"
25 November 2010
Indications for treatment
11
25 November 2010
Maastricht III (2005) Maastricht III (2005) strong recommendations for eradication (unchanged))
A (5)Patients wishes
B (3b)First degree relatives of patients withgastric cancer
B (3b)After gastric cancer resection
B (2a)Atrophic gastritis
A (1C)MALToma
A (1a)DU/GU (active or not)
Recurrence of ulcers decrease with + 90 %
25 November 2010
Maastricht III (2005) Maastricht III (2005) unchanged recommendations for eradication
A (5)Patients wishes
B (3b)First degree relatives of patients withgastric cancer
B (3b)After gastric cancer resection
B (2a)Atrophic gastritis
A (1C)Low grade MALToma
A (1a)DU/GU (active or not)
Healing of MALT lymphoma in early stage (mucosa or submucosa) in 62 %
Not efficient: t(11,18) (q21;Q21) with fusion of MALT1 and API2
12
25 November 2010
Maastricht III (2005) Maastricht III (2005) unchanged recommendations for eradication
A (5)Patients wishes
B (3b)First degree relatives of patientswith gastric cancer
B (3b)After gastric cancer resection
B (2a)Atrophic gastritis
A (1C)MALToma
A (1a)DU/GU (active or not)
25 November 2010
Maastricht III (2005) Maastricht III (2005) unchanged recommendations for eradication
A (5)Patients wishes
B (3b)First degree relatives of patientswith gastric cancer
B (3b)After gastric cancer resection
B (2a)Atrophic gastritis
A (1C)MALToma
A (1a)DU/GU (active or not)
13
25 November 2010
Maastricht III (2005)Maastricht III (2005)
HP and ITP
HP and iron deficiency anemia
HP and aspirine
A (1b)HP and acute NSAID use
B (2b)HP and long term PPI
A (1a)HP and dyspepsia
25 November 2010
HP and ITP
HP and iron deficiency anemia
HP and aspirine
A (1b)HP and acute NSAID use
B (2b)HP and long term PPI
A (1a)HP and dyspepsia
Maastricht III (2005)Maastricht III (2005)
14
25 November 2010
HP and ITP
HP and iron deficiency anemia
HP and aspirine
A (1b)HP and acute NSAID use
B (2b)HP and long term PPI
A (1a)HP and dyspepsia
Maastricht III (2005)Maastricht III (2005)
25 November 2010
1HP and ITP
1HP and iron deficiency anemia
HP and chronic low dose aspirine use
A (1b)HP and acute NSAID use
B (2b)HP and long term PPI
A (1a)HP and dyspepsia
Maastricht III (2005)Maastricht III (2005)
Chan Fk et al. N Eng J Med 2001
Lai KC et al. N Eng J Med 2002
15
25 November 2010
1HP and ITP
1HP and iron deficiency anemia
HP and aspirine
A (1b)HP and acute NSAID use
B (2b)HP and long term PPI
A (1a)HP and dyspepsia
Maastricht III (2005)Maastricht III (2005)
Fe is better absorbed in acid environement
Competition in use of iron between host and H. pylori
Low vitamine C concentrations in H. pylori gastritis
Mist erosions or ulcers
?
25 November 2010
Maastricht III: statementsMaastricht III: statements
H. pylori and H. pylori and chronicchronic NSAID NSAID useuseBoth independent risk factors for ulcersPPI is better than eradication in the prevention of reccuring complicated ulcers
H. pylori and GERDH. pylori and GERDEradication has no effect on the efficacy of PPINo indication for eradication if no chronic PPINegative association between H. pylori en GERD: reason ?
16
25 November 2010
Statement Statement concerningconcerning gastricgastric cancercancer
H. pylori is a proven risk factor for non cardiac gastriccancer (65 % of all stomach cancers worldwide)
The risk depends on genetics of bacteria and host.
Other possible factors: nutrition, environment, medication
H. pylori eradication prevents the development of premalignant lesions and so decreases the risk of gastric cancer (1b and 1c evidence)
25 November 2010
Statement Statement concerningconcerning gastricgastric cancercancer
H. pylori is a proven risk factor for non cardiac gastriccancer (65 % of all stomach cancers worldwide)
The risk depends on genetics of bacteria and host.
Other possible factors: nutrition, environment, medication
H. pylori eradication prevents the development of premalignant lesions and so decreases the risk of gastric cancer (1b and 1c evidence)
17
25 November 2010
Statement Statement concerningconcerning gastricgastric cancercancer
The best timing for eradication is before the development of pre-malignant lesions = young age.
H. pylori eradication in the prevention of gastric cancer should be considered in high risk populations (china, japan).
25 November 2010
WhatWhat does does thisthis meanmean forfor BelgiumBelgium ??
WomanWoman:Breast cancer + 37 % (n = 9405)Colonic cancer + 13 % (n = 3408)Lung cancer + 7 % (n = 1540)Gastric cancer + 3 % (n = + 500 ) (cardia en non-cardia)Cervix + 3 % (n = 651)Esophageal cancer + 1,3 % (n = 224) (adeno and spino)
Man:Man:Prostate + 30 % (n = 9510)Lung cancer + 17 % (n = 5268)Colonic cancer + 13 % (n = 4111)Gastric cancer + 3 % (n = 846)Esophageal cancer + 2,3 % (n = 664)
18
25 November 2010
TotalTotal amountamount of of cancerscancers in in BelgiumBelgium 20052005
01000200030004000500060007000
80009000
10000
prostaat long cervixborst maag slokdarm
25 November 2010
EvolutionEvolution of of gastricgastric cancercancer in in BelgiumBelgium
0
200
400
600
800
1000
1200
1400
1600
1999 2002 2005
MenWomanTotal
19
25 November 2010
Incidentie van kanker bij vrouwen in Incidentie van kanker bij vrouwen in BelgiBelgiëë, 2005, 2005
0
200
400
600
800
1000
1200
1400
25 30 35 40 45 50 55 60 65 70 75 80 >85
maagkankercolonborstslokdarmcervixlong
leeftijd
Abs
oluu
t aan
tal
25 November 2010
Mass screening ?
Mass screening and treatment would also have effect on:
DyspepsiaGastric and duodenal ulcers
De H. pylori prevalence decreases (< 10 % in children and adults)
Point of no return ?
20
25 November 2010
Treatment
25 November 2010
Maastricht Maastricht IIIIII: : treatmenttreatment
New :
Effective treatment should achieveintention-to-treat eradication rate > 80%
21
25 November 2010
Maastricht III : Maastricht III : treatmenttreatment
First line
PPI bid +
clarithromycin 500mg bid+
amoxicillin 1g or metronidazole 500mg bid
1 week to 2 weeks
R < 15-20%
25 November 2010
Maastricht III : Maastricht III : treatmenttreatment
First line
PPI bid +
clarithromycin 500mg bid+
amoxicillin 1g or metronidazole 500mg bid
1 week to 2 weeks
R < 15-20%
XR < 40%
22
25 November 2010
Maastricht III : Maastricht III : treatmenttreatment
Alternative: Bismuth quadruple therapy ifavailable
25 November 2010
First choice:Bismuth quadruple therapy 10-14 days(Bismuth, tetracycline, metronidazole, PPI) Pylera R
No Bismuth available:PPI/tetracycline/metronidazole
Maastricht III : Maastricht III : treatmenttreatment
Second line:
23
25 November 2010
Maastricht III : Maastricht III : ““rescuerescue treatmenttreatment””
“Rescue treatment” depends onsusceptibility testing
Sequential therapy ? (further evaluationnecessary)
No advice on:levofloxacin (high and quick R)Rifampicin (only for TBC)Rifabutin (not in Belgium)
25 November 2010
SequentialSequential therapytherapy
Combination of the 3 currently usedantibiotics in a sequential way
Amoxi/clarithro/metro
10 days:PPI/ampi 5 daysPPI/ Clarithro/metro of tinidazole 5 days
24
25 November 2010
SequentialSequential therapytherapy: background: background
Combination ampi/PPI decreases the bacterial burden
Membrane distroyed by amoxi(decreases risk of developing R)
25 November 2010
Sequential therapy: efficiencySequential therapy: efficiency
RCT
first- line treatment versus sequential therapy: + 80 % versus + 90 %
If no R to clarithro: eradication rates =
10 day quadruple therapy (Amoxi/Metro/clarithro/PPI) versus sequential: both + 93 %
Wu DC, Clin Gastroenterol Hepatol. 2010 Jan;8(1):36-41
25
25 November 2010
SequentiSequentiëële therapiele therapie
Voordelen van de sequentiële behandeling ?
Betere eerste lijns resultaten (Minder nood aan 2de lijn)Compliantie =Niet meer neveneffecten
25 November 2010
SequentialSequential therapytherapy: : costscosts
Sequential: 37,5 euro
Classic (clarithro/metro/PPI 7 of 10 dagen):
34,5 euro
26
25 November 2010
FluoroquinoloneFluoroquinolone basedbased therapytherapy
Well tolerated, few side-effects, mixed results
1 st line: +/- 85 %2 nd line: 70 – 80 %3 rd line: 60 - 90 %
R is easily acquired R in Belgium: 25 % (Mana, Glupzcinsky, Miendje)
25 November 2010
OtherOther alternativesalternatives ??
27
25 November 2010
DoxicyclineDoxicycline basedbased therapytherapy
Different studies94 patients (cammarota et al 2004 – Rome-) 3rd line, R based116 patients (Realdi G et al.1999 – Italy -) 1line line270 patients (Perri et al 2002 – Italy) 1th line71 patients (Borody et al 1992 – australia-) 1 line189 patients, 3 groups (Taghavi SA et al 2008 –Iran-) 1 line
Success Respectively90 % / 58 % / 36 % / 65 % / 68 %
R testing,5 % tetra R, 0 % amoxi R, metro 100 %, claritro 95 %33 % doxi R, 26 % amoxi R, metro 30 %NDNDND
TreatmentOme, Amoxi 2 x 1 Bismuth, Doxi 2 x 100 mg 7 days -Ome, metro,Doxicycline 2 x 100 mg 7 daysLanso, Amoxi, doxi 2 x 100 14 daysBismuth citraat, metro, doxiDoxi, co-amoxiclav, ome
25 November 2010
Doxi, co-amoxiclav, ome
ND68 %189 (Iran)
Bismuth citraat, metro, doxi
ND65 %71(australia)
Lanso, Amoxi, doxi2 x 100 14 days
ND36 %270 (Italy)
Ome,metro,Doxicycline 2 x 100 mg 7 days
33 % doxi R, 26 % amoxi R, metro 30 %
58 %116 (Italy)
Ome, Amoxi 2 x 1 Bismuth, Doxi 2 x 100 mg 7 days
5 % tetra,, 100 %, metro 95 % claritro
90 %94 (Italy)
treatmentRresultspatients
Rabe, bismuth, doxy, furazolidone, 2x/d, 10 days
Only claritro failures83 %29 (Brazil)
DoxicyclineDoxicycline basedbased therapytherapy
28
25 November 2010
DoxicyclineDoxicycline basedbased therapytherapy
2 studies compared doxi with tetra(Realdi 1999 and Borody 1992)
Tetra > doxi91 % vs 58 %92 % vs 65 %
25 November 2010
IncreaseIncrease the the dosedose of PPI ?of PPI ?
Quick, intermediate and low metabolisers of PPI
Pos en negative studies
…….
Systemic review: omeprazole
A. VILLORIA et al. 2008. Aliment Pharmacol Ther 28, 868–877
29
25 November 2010
SituationSituation in in BelgiumBelgium ??
25 November 2010
R in R in adultsadults BelgiumBelgium
26 %28 %14 %Mana 2008
28 %-22 %Riga sept 2008Glupzcinsky)
16 %37 %15 %Miendje 2004-2007
17 %--Glupzcinsky 2003/4
-31 %3 %Aguemon 2002
levofloxacinmetronidazoleclarithromycin
30
25 November 2010
PrimPrim resistanceresistance in in childrenchildren BelgiumBelgium
6 – 16 %clarithro
18 %imidazole
Bontems1995 - 2000
Bontems P et al. Pediatr Infect Dis J 2001
25 November 2010
Algemene Algemene resitentieresitentie(multiple (multiple hospitalshospitals aroundaround BXL)BXL)
0
5
10
15
20
25
30
35
40
1997
2005
childrenclaritrochildrenmetroadultsclaritroadultsmetro
2005Y. Miendje
31
25 November 2010
International International resultsresults
1994-200522 %36 %(43 to 32 %)
France(children)
17 %35 %Korea
1989-’90 2005-’05
10 %20 %
Italy
1997-20021%(decreasing)
14 %Netherlands
200742 %90 %Cameroon
2000-200512 %36 %Wales
2000-20058,3 % (increasing)
28,6 % (increasing
England
200816 %TurkeyjaarR claritroR metroLand
25 November 2010
metameta--analysisanalysis standardstandard PAC 7PAC 7
81 %Untill 19981999Houben et al
Eradicationrate in %
Data rangePublicationAuthor
81 %Untill 19992000Gisbert et al
80 %1986 - 19981999Laheij et al
82 %Untill 19921992Chiba et al
32
25 November 2010
DISCUSSIE : DISCUSSIE : standardstandard PAC 7PAC 7
85 %S-Korea2009Jung et al
77 %Hungary2008Tulassay et al
92 %UK2008Ching et al
80 %Italie2007Zagari et al
86 %China2006Wang et al
79 %Finland2005Myllyluoma et al
85 %Australia1999Talley et al
82 %USA1999Schmid et al
92 %UK1998Stone et al
Eradicationrate in %
countryPublicationdate
Author
25 November 2010
DISCUSSIONDISCUSSION
Decreasing trends of eradication success ?
ITT > 90 % as a goal ?
Graham DY
Buzás GM, WJG, 2010
33
25 November 2010
DISCUSSIONDISCUSSION
Are cultures useful ?
Availability
expertise
Mixed resistanceCaristo E et al. Helicobacter 2008;13:557-563Kim J et al. Helicobacter 2003;8:202-206
Cost –benefit
Clinical relevance of metro R. Amoxi R ~ 0.rapid test clarithromycin resistance (FISH) ? - (spec en sens ?)
Before choosing levofloxacine based therapy
25 November 2010
ConclusionConclusion
Prevalence of Helicobacter pylori is falling dramatically in westernised countries Is decreasing in some developing countries
Transmission route is still not well known.
Mostly vertical in urban areas and horizontal in rural areas
34
25 November 2010
ConclusionConclusion
Most patients are asymptomatic and prevalence is falling but lethal pathologies like gastric cancer and ulcer disease are associated with H. pylori.
25 November 2010
ConclusionConclusion
Absolute indications for eradication
•DU/GU•Low-grade MALT•Pers or fam history of gastric cancer•Dyspepsia•Long term PPI use•IDA and ITP
35
25 November 2010
ConclusionConclusion
Prevention of gastric cancer
Eradication efficient if done before the development of pre-malignant lesions. Point of no return not known in other situations.
25 November 2010
ConclusionConclusion
Treatment:
First-line treatment efficacy has decreased but stays an acceptable treatment in Belgium.
Clarithromycin R has increased initially but seems to stabilize around 15 %
Metronidazole R is “relative” when translated to clinical practice.
36
25 November 2010
ConclusionConclusion
Treatment:
Levofloxacine R increases rapidly. Use in eradication only after culture and resistance profile.
In difficult situations: increase PPI, prolong treatment, find Bismuth, add H2-blokkers, culture (antrum and fundus).
25 November 2010
Don’t touch myHelicobacter ….
37
25 November 2010
Robin Warren and Barry Marshall1984
Nobel Nobel prizeprize medicinemedicine2005
Food-borne outbreaks caused by foodhandlers
Katelijne Dierick, DVM OD Communicable and Infectious diseasesNRL Food-borne outbreaksJuliette Wijtsmanstreet 141050 Brussels
Epilab, 25-11-2010
Rue Juliette Wytsmanstraat 14 | 1050 Brussels | BelgiumT +32 2 642 51 11 | F +32 2 642 50 01 | email: [email protected] | www.wiv-isp.be
1
Definitions
WHO definitions
Foodborne disease: a disease of an infectious or toxic nature caused by or thought to be caused by the consumption of foodor water
Outbreak: an incident in which 2 or more persons experience a similar illness after ingestion of the same food, or afteringestion of water from the same source, and whereepidemiological evidence implicates the food or water as the source of the illness.
The Zoonoses Directive (EC, 2003), transposed in KB-AR zoonoses22-5-2005, defines a food-borne outbreak as:
an incidence, observed under given circumstances, of two or more human cases of the same disease and/or infection, or a situation in which the observed number of human cases exceeds the expected number and where the cases are linked, or are probably linked, to the same food source’.
3 types
Food-borne infectionAfter ingestion of pathogen : direct interaction host-pathogen
• ex: SalmonellaFood-borne intoxication
After ingestion of toxine preformedin food: direct interaction host-toxin
• ex: StaphylococcusFood-borne toxi-infection
After ingestion of pathogen : Multiplication in the intestine of the
host with toxine production• ex: Clostridium perfringens
2
Trends and sources of zoonoses and zoonotic agents and food-borne outbreaksin the European union in 2008-april 2010
3
1032 436 37 154 48 175
48 134
2006
100709772
23
2008
851230383481057
6999
2007
10057 12 3 4 5
6 12
2006 persons affected% of total
43913Norovirus
841100Total17250unknown11810other
312Campylobacter109Bacillus cereus326Staphylococcus3910Salmonella20082007agent
% Reported food-borne outbreaks by agent and the total of affected persons in Belgium
Food is only a vehicle!Source:Infected animal
Infected raw material
Infected environment
Infected food handler
4
Toxi-infections caused byfood handler infection
PossibleSalmonellosisShigellosisHepatitis A
But most frequentlyNorovirusStaphylococcus aureus
Bacteria versus virusesBacteria : multiplication in food if favoral conditions
Viruses: need living cells: no multiplication
Stafylococcus aureusCoagulase positive staphylococci can produce enterotoxines:SET A, B, C, D,E, …… until O
Almost always S. aureus4 biotypes : A : human, B : poultry, pigs , C : cattle and sheep,D: hare
Origin of contaminationVery resistant , naturally occuring in air, water, soilmost important reservoir : humans, animals
Humans :• Healthy carriers ( throat, nose, skin: forehead, headskin,hands ) • Common cold infected with S.aureus• skin lesions : pus, acné, infected wounds ...
Animals:• pig : skin, nose, skin surrounding the eyes• milk : mastitis• Abcesses in meat( ex injection sites)
5
Stafylococcal intoxicationHealthy carriers milk – sick animalsdiseased people mastitis
Food preparation
Food-pH 7 -rich in protein -low AwContaminated food
multiplication of coagulase positive Staphylococci-Toxin (heatstable)production in food during exponential growrh phase(>105cfu/g)
Consumption of food
Absorption of the toxin preformed in the food
Food intoxication (nausea, vomiting, diarrhoea)Incubation time:2-4h
Duration: 24h
Stafylococcus
Food is contaminated by : • Poor personal hygiene during preparation• Contaminated milk or cream
Multiplication in food by:• non respect of cold or hot chain .
Sensitive food products : • Cooked product contaminated after preparation ( meat ,
fish, stews, vol au vent …• Crème patissière, ice cream, pastry• Products with low Aw : charcuterie, concentrated milk,
melkpowder
6
Case-study : Food-borne outbreak in a Barbecue in Brasschaat-1
22 out of 60 people sick and hospitalisedsevere vomiting.Food: steak, lamb chops, pork, chicken, sausage and potatoe salad.B.cereus: 104 – 107CFU/gcoagulase + Staphylococci: 103 -107CFU/g.
Food-borne outbreak in a Barbecue in Brasschaat-2:
BUT: •Presence of SET A in steak, pork, sausage and potatoe salad•SET toxin gen present in strains
PCR detection of the SET toxin genes sea, seb, sec and sed(toxines A-B-C-D-E detection with Vidas SET 2 – OxoidSET-RPLA) and the detection of the genes seg, seh, sei, sej, sek, sel, sem, seo and sen
PCR detection of the cereulide gen of B; cereus
•absence of cereulide gen in isolated strains•absence of emetic toxin cereulide
7
Norovirus
Very infectious• 100 virus particles can cause infection
Spread:• feco-orally• Person to person• Contaminated water or food water en voedsel (17% in NL)
Food at riskPrimary contamination
• Soft red fruits• Bivalve molluscs
Secundary contamination (by food handler)• Ready to eat meals• sandwiches• Complete meals (mixed)
Norovirus infections :seasonal influence
Foodborne outbreaks cumulative per month
0
5
10
15
20
25
1 2 3 4 5 6 7 8 9 10 11 12
month
cum
ulat
ive
num
ber
of fb
out
brea
k
Remaining outbreaks cumulative per month
0
20
40
60
80
100
120
140
1 2 3 4 5 6 7 8 9 10 11 12
month
cum
ulat
ive
num
ber
of o
utbr
eaks
not
rel
ate
to fo
od
FBO outbreaks Outbreaks not related to food
8
Zoönotic ??Primarycontamination
Food-handlers
Secondarycontamination
Contamination cycli of Norovirus
9
L. Baert et al , Epidemiol. Infect, 2009,137.316-325
10
L. Baert et al , Epidemiol. Infect, 2009,137.316-325
L. Baert et al , Epidemiol. Infect, 2009,137.316-325
11
Casus
Dilsen-Stokkem: VKSJ Vichte - 30/160 children illSunday 18/07/2010
Mon 19/07/2010: outbreak reported to NRL FBO by FAVV-AFSCA
Tue 20/07/2010: 5 food samples NRL FBO: start bacteriological analysis1 human sample: start bacteriological analysis and norovirus analysis
Thu 22/07/2010: first report human: positive norovirus GIIfood: bacteriology conform, start analysis norovirus
Mon 26/07/2010: final report human and food sampleshamburger positive for norovirus GII
Prevention
• Personal hygiene kitchen staff• T control of food before and after preparation
< 4° C > 65° C
• GMP (sector guide)• Vaccination (HAV)• Training!!!
12
Conclusion 1: Two parts in investigation:
Laboratory part : sampling very important!- Coproculture kitchen personnel- Swabs of nose or hands kitchen personnel- Environmental sampling- Leftovers of the meals- Ingredients-Raw materials
Epidemiological part- Food history- Disease history (also family, children, grand children)- Enquiry form!
Conclusion 2: Foodhandlers play an important role in the prevention of foodborne outbreaks
Foodhandler
Personal hygiene
Storage time/TemperatureAbuse
undercooking
Unprocessed orcontaminatedingredients
13
Thank you for your attention!
Thanks to our partners in Food-borne outbreakinvestigaton:
FAVV-AFSCAAgentschap Zorg en GezondheidSurveillance santé
Outbreak of Shigella sonneiinfections in the orthodox Jewish
community of AntwerpKoen De Schrijver, Sophie Bertrand, Ignacio Gutiérrez, Daniel Van den Branden, Jef Van
Schaeren
[email protected] Antwerpen
25 11 2010Diagnosis and surveillance Infectious Diseases WIV
Sint-Pieters-Woluwe
1
Onset
• In April 2008 informed on several isolatesof S. sonnei (notifiable disease)
• Young children, residing in Antwerp, members of the orthodox Jewishcommunity of Antwerp
Background I• 68% S. sonnei of 300 (2007)
– High antibiotic resistant strain• Shigellosis
– High infectiosity– Person to person– Mostly mild / dysentery– < 5 years
• Common source unfrequent– Sporadic cases – No custers before in Jewish
community in Antwerp
2
Background II
• Orthodox Jewishcommunity of Antwerp– Highly insular– Approx. 10,000 people– Frequent international
contact
Objectives of the study
• Describe the epidemic→Descriptive study• Detect the source of index patient and evaluate
relatedness of strains→Microbiological study• Assess riks factors for secondary transmission in
households→Secondary attack rate study in the households with identification of risk factors
• Stop spread of the epidemic→Control measures
3
Case definition• Confirmed case
– Person from Jewish community Antwerp– Culture confirmed S.sonnei– Ill between April-August 2008
• Probable case– Diarrhoea, and fever and abdominal cramps– Household of confirmed case– Within 7 days after index case– Same study period
• Secondary case– Within the week after contact with confirmed case in
the household
Descriptive study
– Standardized questionnaire• Demographical (… family contacts)• Clinical• Laboratorial• Exposure (travelling, family gatherings)
– Active case finding: visiting families and schools
4
Source tracing study
– Serotyping isolates (slide agglutination ) (Derbyshire UK)
– Susceptibility of strains (Disk diffusion Kirby-Bauer)(CLSI)
– PFGE (PulseNet method, XbaI) – Comparing strains from Israel 2000-2008) with strains
from Antwerp (FingerprintingII Informatix)– To compare the Israel strain we used the Dice
coefficient and unweighted – pair group method
Secondary attack rate study
– Identification of household contacts = 175– Secondary AR– Questionnaire and interview
• Number of children• Age of children• Presence of children with nappies• Children < 12 years assisting with cleansing other siblings• Antibiotics intake index Hospitalisation of index • Number of toilets• Hand washing after cleansing
– Uni- and multivariate RRs (95% CI) binomialregression model (StataCorp)
5
Patient data
• 42 cases (32 confirmed, 10 probable)• 32 cases notified and 10 case finding• 52% females• 55% < 5 years; 14% > 20 years• 43% dysentery type • 76% hospitalisation
N
10
5
17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 week 2008 2008
6
7
Secondary attack rate study
• 29 households• 175 household contacts• Secondary attack rate: (15/175) 8.5% (CI-
95% 4.3-12.7)
8
Control measures
• Parents were informed on need of handwashing.
• Schools informed on hygiene.• Symptomatic children excluded for a
minimum of 48 hours after clinicalrecovery, from day-care centres, pre-school and school attendance.
• Educational conference for parents, teachers, and caregivers.
9
Discussion and conclusion• 42 cases (32 S.sonnei) in Jewish community of Antwerp• Origine: Tel-Aviv
• Other outbreaks of S.sonnei in London, New York, Israel (1996-2008)– Calderon-Margalit et al.Epidemiol Infect. 2010;138:244-52
• Secondary attack rate: 8.5% comparable with other studies
• Risk factors: number of children (>3), young children (<5 y) and children (<12 y) helping parents independent risk factors
• High hospital admission rate 76%→ underdiagnosis
• Importance of collaboration between microbiology and epidemiology
• Importance of PFGE in comparing strains and in source tracing
Many thanksto
• Dr. Valinski ( Tel-Aviv)• Laboratories (Antwerp)
Vaccination coverage in Vaccination coverage in WalloniaWallonia
B. SwennenB. SwennenProvac Provac
ESPESP--ULBULB
Seminar : Diagnosis and surveillance of infectious diseases 25/11/2010
Immunization programme in Immunization programme in French community of BelgiumFrench community of Belgium
Target publicTarget public–– Children (0Children (0--18 y) in Wallonia18 y) in Wallonia–– Children (0Children (0--18 y) in Brussels followed by 18 y) in Brussels followed by
Private Private ““frenchfrench--speakingspeaking”” doctorsdoctorsPreventive structures Preventive structures
–– Office de la Naissance et de Office de la Naissance et de ll’’enfanceenfance (ONE)(ONE)–– Service Promotion santService Promotion santéé àà ll’é’écolecole (PSE)(PSE)
Vaccination Vaccination coveragecoverage
Impact Impact indicatorindicator : : –– proxy of the protection in the populationproxy of the protection in the population–– Vaccine Vaccine EfficacyEfficacy * vaccine * vaccine coveragecoverageProcessProcess indicatorindicator : : –– Is the programme Is the programme reachingreaching the the targettarget
population?population?–– Is Is immunizationimmunization scheduleschedule respectedrespected??
Immunization schedule in 2010:4 periods
Vaccination Vaccination coveragecoverage surveyssurveys in in French French communitycommunity of of BelgiumBelgiumChildrenChildren (18 (18 --24 24 monthsmonths) ) –– EveryEvery 3 3 yearsyears–– 8 8 surveyssurveys sincesince 19891989–– Last one in 2009Last one in 2009ScholarScholar population: 3 population: 3 yearsyears cyclecycle–– 2 2 th th elementaryelementary–– 6 6 th th elementaryelementary–– 4 4 th th secondarysecondary
Last Last SurveysSurveys
ChildrenChildren 18 18 -- 24 24 monthsmonths in in WalloniaWallonia 20092009ChildrenChildren 1818--28 28 monthsmonths in Brussels 2006in Brussels 2006AtAt SchoolSchool–– 4th 4th secondarysecondary in 2007in 2007--20082008–– 6th 6th elementaryelementary in in 20082008--20092009–– 2th 2th elementaryelementary inninn 20092009--20102010
Vaccination Vaccination coveragecoveragechildrenchildren 18 18 -- 24 24 monthsmonths in 2009in 2009
ChildrenChildren bornborn betweenbetween31 31 meimei and 30 and 30 novembernovember 20072007
ImmunizationImmunization scheduleschedule CSS 2007CSS 2007Age(1) 2 3 4 12 13 15 18 5-7 10-13 14-16
Vaccines month month month month month month month years years years
Polio(2) IPV IPV IPV IPV IPV
DiphteriaTetanus DTPa DTPa DTPa DTPa DTPa dTPertussis(3) dTpa
Haemophilus Hib Hib Hib Hibinfluenzae type b(4)
Hepatitis B(5) VHB VHB VHB VHB
MeaslesRubella RRO1 RRO1 RRO2 Mumps
Meningococcus C(7) MnC
Pneumococcus(8) Pn7V Pn7V Pn7V
Rotavirus ROTA ROTA (ROTA)
Range of period
Combined vzccine Control and catch-up if necessary
RRO2
12 vaccine preventable diseases
Modifications Modifications sincesince 20042004
Introduction Pn7VIntroduction Pn7V–– 3 3 dosisdosis regimenregimen–– Vaccine free of charge Vaccine free of charge sincesince januarijanuari 20072007RotavirusRotavirus vaccine vaccine recommendedrecommended–– InamiInami reimbursementreimbursement : 10,89: 10,89€€/dose for patient/dose for patient–– 2 vaccines 2 vaccines RotarixRotarix 2 doses, 2 doses, RotateqRotateq 3 doses3 dosesAtAt 12 12 monthmonth RRO + RRO + Pn7V 3Pn7V 3AtAt 15 15 monthmonth Hexa 4 + Hexa 4 + MenCMenC
MethodologyMethodology 1: the 1: the samplingsampling
Same methodolgy for 8 surveyssince1989Cluster sampling survey– 55 clusters of 12 children– 660 children
MethodologyMethodology 2: 2: data collectiondata collection
Home Home surveysurveyImmunizationImmunization information information notednoted fromfrom: : –– Carnet de lCarnet de l’’enfantenfant–– ImmunizationImmunization cardcardInterview of parents of the Interview of parents of the childrenchildrenInterviewers: Nurses Interviewers: Nurses fromfrom ONEONE
Distributed to all children bornsince 2000
660 Questionnaires
576 Contacts
526 Interviews
14 vaccinal Anamnesis
512 vaccinal charts
84 Non Contacts
50 Refusal
79.7%
8.7%
2.7%
12.7%87.3%
91.3%
97.3%
Taux de participationTaux de participation
Vaccine (n=512)
1 2 3 4
Hexavalent 98.0(502)96.9-99.2
98.0(502)96.9-99.2
96.9(496)95.5-98.3
90.0(461)87.4-92.7
MMR 92.4(473)90.2-94.6
/ / /
MéningococusC
91.2(467)88.7-93.7
0.2 (1)0-0.2
/ /
Pn7V 97.1(497)95.6-98.5
93.6(479)90.9-96.2
80.7(413)76.9-84.4
1.4 (7)0.4-2.4
Rotarix® 76.0(389)71.5-80.5
72.8(373)68.3-77.3
/ /
Rotateq® 6.1(31)4-8.1
5.7(29)3.7-7.7
4.5(23)2.6-6.3
/
DTaP-IPV 1.6(8)0.5-2.6
1.6(8)0.5-2.6
1.2(6)0.2-2.1
0.4(2)0-0.9
Hib 1.0(5)0.1-1.8
1.0(5)0.1-1.8
0.6(3)0-1.2
0.2(1)0-0.6
DTP 0.4(2)0-0.9
0.4(2)0-0.9
0.6(3)0-1.2
0.2(1)0-0.6
IPV / / / /
HBV 0.8(4)0-1.5
0.8(4)0-1.5
0.4(2)0-0.9
/
Vaccination coverage according vaccine disponible in FC
Vaccin (n=512) 1 2 3 4
Poliomyelitis 99.6 (510)99.1-100
99.6 (510)99.1-100
98 (502)(96.8-99.2)
90.4 (463)87.9-93
DiphtérieTetanus
Pertussis
100 (512) 100 (512) 98.6 (505) 97.6-99.6
90.6 (464)(88.1-93.1)
Hib 99.0 (507)98.2-99.9
99.0 (507)98.2-99.9
97.5 (499)96.1-98.8
90.2 (462)87.7-92.8
HBV 98.8 (506)97.6-99.8
98.8 (506)97.6-99.8
96.9 (496)95.4-98.4
90.4 (463)87.9-93
MMR 92.4(473)90.2-94.6
/ / /
Méningococcus C
91.2 (467)88.7-93.7
0.2 (1)0-0.2
/ /
Pn7V 97.1(497)95.6-98.5
93.6 (479)90.9-96.2
80.7 (413)76.9-84.4
1.4 (7)0.4-2.4
Rotavirus 82.0 (420)78.7-85.4
77.3 (396)*73.7-81.0
Vaccination coverage (%) in Wallonia in 2009
2006n= 493
2009n=512
n % IC 95% n % IC 95% dif férence2003-2006
Différence 2006-2009
Polio 4 dosis 468 94.9 93.0-96.9 463 90.4 87.9-93.0 2.6 -4.5 NS
DTP 4 dosis 467 94.7 92.8-96.7 464 90.6 88.1-93.1 2.0 -4.1 NS
Hib 4 dosis 461 93.7 91.6-95.8 462 90.2 87.7-92.8 6.3 -3.5 NS
VHB 3 dosis 456 92.7 90.2-94.8 462 90.2 87.7-92.8 27.9 -2.5 NS
MMR 439 89.0 86.3-91.8 473 92.4 90.2-94.6 6.5 +3.4 NS
Mén C 456 92.5 90.2-94.8 467 91.2 88.7-93.7 11.0 -1.3 NS
PN7V 145145 29.4 413 80.7 +51.3 **
Vaccine coverage evolution betwween 2006 et 2009 In WalloniaVaccine coverage evolution betwween 2006 et 2009 In Wallonia
8 surveys : 20 years of evolution8 surveys : 20 years of evolution
0
10
20
30
40
50
60
70
80
90
100
1989 1991 1993 1996 1999 2003 2006 2009
%
Polio complet
DTP-DT4
RRO
Hib
Hép. B
MénC
Prog.RROModif.RRO Hib
Recomm.Hib/VHB
Prog.VHB
OPV-IPVDTPa
Hib gratuit
MénC PnC
PnC
Evolution Evolution
In 2006 : increase due to hexavalent In 2006 : increase due to hexavalent vaccinevaccineIn 2009 : In 2009 : –– Stabilisation between 90% and 94% for Stabilisation between 90% and 94% for
hexavalenthexavalent–– MMR Progression (NS) but not yet 95%MMR Progression (NS) but not yet 95%–– Increase ** for Pn7V (3 dosis)Increase ** for Pn7V (3 dosis)–– Vaccine coverage decrease for the dose after Vaccine coverage decrease for the dose after
12 months of age 12 months of age
Vaccine coverage(%) : Vaccine coverage(%) : full schedule in 2009full schedule in 2009
Polio +DTPa + VHB +Hib + RRO + MenC+ Pn3
Polio +DTPa + VHB +Hib + RRO + MenC
74,1
84.0
70.0 -77.9
80.8– 87.2
Flanders2008
Wallonia2009
Brussels2006
Polio 95.3 90.4 90,0DTPa 95.2 90.6 90,0Hib 95.2 90.2 88,8HBV 95.1 90.2 88,4MMR 96.6 92.4 91,1MenC 95.6 91.2 91,7Pn7V 97.7 80.7 NA
Vaccine coverage in Belgium
Is the schedule right on time?Is the schedule right on time?
Before8 weeks
Between 8 – 10 weeks
Between 10 - 12 weeks
Between 12 - 16 weeks
After 16 weeks
Hexa1 1.2 57.8 26.8 9.8 4
14% 84,6%
Vaccinators in FCVaccinators in FCVaccinator MMR Rota1 Varicella*
n % n % n %
O.N.E.* 260 55.7 228 55.1 8 17.3
Pédiatere 170 36.4 152 36.7 30 65.2
GP 23 4.9 22 5.3 3 6.5
Hospi 14 3.0 12 2.9 5 10.9
Total 467 100 414 100 46 100
* 9% vaccine coverage for chickenpox
Bivariate analysis : study of the mother Bivariate analysis : study of the mother
Study Level Hexa 4 MMR
n % n
University 70 84.3 72 86.7
Other 385 91.4 395 93.8
* *
Bivariate analysis: Mother Bivariate analysis: Mother Nationality of originNationality of origin
Nationality Hexa 1 Rotavirus1 Rotavirus2
n % n % n %
Belgian 395 99 340 85.2 324 81.2Non belgian 100 94.3 76 71.7 74 69.8p value ** *** *
Bivariate analysis : Number Bivariate analysis : Number Chidren in the familyChidren in the family
Frères/ Sœurs
Rota1 Rota2 Pn7v (3)
n % n % n %
0 137 85.6 133 83.1 140 86.1
1 150 83.8 145 81.0 137 74.4
2 ou > 123 75.9 114 70.4 112 80.0
p value 0.055 * *
Bivariate analysis : Family IncomeBivariate analysis : Family Income
Income Rota1 Rota2n % n
0-1500 74 69.8 66 62.31500-3000 173 85.6 168 83.2>3000 117 85.4 114 83.2p value ** ***
Bivariate analysis: ParentsBivariate analysis: Parents’’s time s time at workat work
Rota1 Rota2
n % n
0-1 Full time 178 73.3 167 68.7
>1 Full time 238 90.5 233 88.3
p value *** ***
Day care Rota1 Rota2
n % n
Yes 268 86.7 259 83.9
No 150 75 141 70.5
p value *** ***
Bivariate analysis: Day care Bivariate analysis: Day care frequentationfrequentation
Bivariate analysis : ONE choice for Bivariate analysis : ONE choice for preventive carepreventive care
ONE (%)
Hexa4 RRO MénC Pn3 Rota1 Rota2
Yes 93.5 95.1 95.1 86.1 79.6 76.3
No 86.5 89.7 86.9 75.8 84.9 81
p value * * *** ** NS NS
Logistic regression for nonLogistic regression for non--vaccination factorsvaccination factors
Same model for Same model for –– Hexa 4Hexa 4–– MMRMMR–– Men CMen C–– Pn7V dose 3Pn7V dose 3–– RotavirusRotavirus
Vaccine free of charge
Hexavalent 4 MMR Men C PN7V 3 Rotavirus 2
Income>1500 1
< =1500 2.8(1.7-4.5) ***Rank in the fratry
1 1 1 1 1
>1 3.4 (1.5-8.5) ** 4.3 (1.5-12.7) ** 3.6 (1.4-8.9) ** 1.7(1-2.9) p=0.06
VaccinatorONE 1 1 1 1Other 3.6 (1.7-7.8) *** 2.2 (1- 4.8) * 3.7 (1.7-8) *** 2.4(1.4-4) ***
Study
High 1
≤secondary1.9 (0.9-4.2)
p=0.09
Day care
Nationality
Associated factors for non-vaccination (logistic regression, n=434,ORa)
ConclusionConclusion
Vaccine coverage remains stable since Vaccine coverage remains stable since 20062006Pn7V is well adoptedPn7V is well adoptedMMR1 still < 95% objectifMMR1 still < 95% objectifNo social inequities except for RotavirusNo social inequities except for RotavirusNo refusal for vaccination (cluster?)No refusal for vaccination (cluster?)Importance of the preventive structure Importance of the preventive structure ONE and free of charge vaccine to avoid ONE and free of charge vaccine to avoid inequitiesinequities
Vaccine coverage at school ageVaccine coverage at school age
MethodologyMethodology–– Random Sample of classes Random Sample of classes –– Information collected from medical chart in Information collected from medical chart in
school medical center (SPSE)school medical center (SPSE)–– April April ––mei each yearmei each year–– 3 year Cycle3 year CycleObjectivesObjectives–– Vaccine coverage, evolutionVaccine coverage, evolution–– Define new strategies for the programmeDefine new strategies for the programme
Immunization schedule in 2010:4 periods
Last Surveys Last Surveys
4th secondary in 20074th secondary in 2007--200820086th elementary in 6th elementary in 20082008--200920092th elementary inn 20092th elementary inn 2009--20102010
Vaccine coverage dT/dTaP Vaccine coverage dT/dTaP en 4 en 4 thth secondary (07secondary (07--08) 08)
before dTaP generalisationbefore dTaP generalisation
Vaccine coverage in 6th elementary
23,2225,24
30,53
44,8541,75
65,6
70,5
75,5
1,48
6,53 6,92
41,41
37,14
64,22
68,62
74,7
0
10
20
30
40
50
60
70
80
1996/1997 1997/1998 1998/1999 1999/2000 2000/2001 2003/2004 2005/2006 2008/2009
MMR2HBV
Vaccine coverage MMR2 Vaccine coverage MMR2 66th th Elementary / province in2009Elementary / province in2009
DTaPDTaP--IPV coverage evolution IPV coverage evolution 20042004--2010 in 2 Th elementary2010 in 2 Th elementary
69,173,1
74
0102030405060708090
100
2004-2005 2006-2007 2009-2010DTPaIPV
DTaPDTaP--IPV coverage /province IPV coverage /province and / vaccinator 2010 and / vaccinator 2010
14,3
55,7
10,1
2,4
58
9,1
8,8
50,5
9,7
14,6
47,3
16,4
1,5
59,1
8,4
9,5
49,8
13,1
0
10
20
30
40
50
60
70
80
90
Bruxelles Brabant Wallon Hainaut Liège Luxembourg NamurRégion/provinces
e
Identification non disponible
Autre vaccinateurMS
80,1
69,5 69
78,3
69 72,4
AcknowledgementsAcknowledgements
Provac Provac ––UlbUlb–– E RobertE Robert–– N da Costa MayaN da Costa Maya
Provac Provac ––UCL UCL –– A VermeerenA Vermeeren–– F GoffinF Goffin–– K LevieK Levie
Provac Provac ––ULGULG–– MC MiermansMC Miermans