Seminarie > 21 november 2013 Séminaire > 21 novembre 2013 · 2 4 • Sentinel network of 6...

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W:Halll Centre Culturel de Woluwé-St-Pierre

Diagnose en surveillance van infectieuze aanDoeningen

Diagnostic et surveillance Des malaDies infectieuses

29ste Seminarie > 21 november 201329e Séminaire > 21 novembre 2013

W:HalllCultureel centrum St.-Pieters-Woluwe

Programme | ProgrammaDiagnosis

respiratory infections

infection control HCai in elderly neonatalogy Tb

risk & Prevention Genomics mosquito-borne diseases vaccine coverage

surveillance emerging Zoonoses: •C.difficile •HEV Severe influenza

information | informatie

T +32 2 642 57 77inscription avant le 7 novembre 2013inschrijving vóór 7 november 2013sur | op www.wiv-isp.be/epidemio/labo

Medewerking en financiële steunCollaboration et appui financier

ISP : DO Santé publique et Surveillance│WIV : OD Volksgezondheid en Surveillance

Organiserend Comité │Comité Organisateur

Stands

Publicités │Advertenties

Dr J. Bots (GGC-CCC)

Dr P. Butaye (CODA-CERVA)

Dr B. Catry (WIV-ISP)

Dr G. Daube (ULg)

Dr K. De Schrijver (Vl. Gem.)

Mrs G. Ducoffre (WIV-ISP)

Dr G. Ieven (UZA)

Dr S. Jacquinet (FWB)

Dr P. Melin (ULg)

Dr E. Padalko (UGent)

Dr D. Pierard (UZ Brussel)

Dr C. Potvliege (CH Tivoli)

Dr H. Rodriguez-Villalobos (UCLouvain)

Dr Y. Van Laethem (CHU St-Pierre)

Dr H. Van Oyen (WIV-ISP)

Dr J. Verhaegen (UZ Leuven)

Dr K. Vernelen (WIV-ISP)

Voorzitter │Président : Dr. S. Quoilin (WIV-ISP)

Comité OrganisateurOrganiserend Comité

Alere Health

Becton Dickinson

BioMérieux Benelux

Bio-Rad Laboratories

Biotrading Belgium

Bruker Belgium

Cepheid Benelux

Elitech Benelux

Euribel

Forlab

HGR-CSS

Labconsult

Lameris Group

Meridian Bioscience Europe

Novartis

ThermoFisher

WIV-ISP

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Bio-Rad Laboratories

Biotrading Belgium

Cepheid Benelux

Meridian Bioscience Europe

Pfizer

Roche Diagnostics

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27/11/2014

Surveillance of severe influenza

Isabelle Thomas, National Reference Centre – InfluenzaFrançoise Wuillaume, Santé Publique et Surveillance

Novembre 21 2013Diagnostic et surveillance des maladies infectieuses

1

Influenza surveillance systems in BelgiumSurveillance of ILI (Sentinel network of GPs)

Surveillance of SARI (Sentinel network of hospitals)

Sentinel Laboratories

Non Sentinel surveillance focused on severe Influenza cases

3

Objectives of SARI surveillance To early detect signals of severity

During epidemic and pandemic

ICU, ECMO, mortality, pneumonia…

To identify risk factorsDescription of hospitalized patients : age, gender

Clinical condition at admission, co-morbidities

To identify viruses, subtypes or strains

Genotypic and phenotypic characterisationMonitoring changes in virus

Monitoring antiviral susceptibility

Monitoring known markers of virulence

2

4

• Sentinel network of 6 hospitals

• Screening of patients based on the case definition of SARI

• Respiratory samples sent to NRC Influenza • For influenza (sub)typing by real time PCR • Detection of other respiratory viruses

• Data of patients and results in a web base application

• CHU UCL (Mont-Godinne)

• CHU Saint-Pierre (Brussels)

• AZ St Jan (Brugge)

• UZ Brussel

• Jessa Ziekenhuis (Hasselt)

• Grand hôpital de Charleroi

Methods

5

SARI case definitionAn acute respiratory illness with onset within the last 7 days of

• History of fever or measured fever of ≥ 38C°

And

• Cough or dyspnea (shortness of breath or difficulty to breath)

And

• Requiring hospitalisation (24h or more)

Patients data• Date of admission, date of sampling, date of discharge or death

• Age, gender

• Symptoms (cough, fever, dyspnea, …..)

• Risk Factors (Chronic respiratory, chronic cardiovascular, pregnancy, …..)

• Indicators of severity ( ICU, ARDS, Death, critical state, ……)

• Vaccine status , …..

Methods

3

Laboratory tests for Influenza

Laboratory tests for other respiratory viruses

Co 229F ROX Boca Cy5

Co OC43 HEX PIV 4 HEX

Co NL63 Cy5 Paraecho ROX

Rhino FAM MERS CoV FAM

MIX 3 MIX 4

RSV A HEX PIV 1 ROX

RSV B ROX PIV 2 HEX

hMPV Cy5 PIV 3 FAM

EV FAM Adéno Cy5

MIX 1 MIX 2

Results SARI surveillance 2012‐2013

4

• 988 samples, of which 423 (42.8%) influenza positive: 224 (22.7%) influenza A and 201 (20.3%) influenza B.

• Co-circulation of A(H1N1) A(H3N2) and B Yam



5


• Influenza A and B : higher percentage of positivity

• RSV, hmpv, adéno and bocavirus more prevalent in children

• Coinfections: 121/988 (12.2%) (2 or more viruses up to 5 viruses)

• Influenza A + other viruses = 25.6%

• Influenza B + other viruses = 21.4 % ( 34% with RSV)

• 75.2% of coinfections in children less than 5 years

• No association with indicators of severity


6

!!! Effect of scale

% of risk factors


% ICU: 8.6%- In FLU +: 7.0%- In FLU -: 9.9%(NS, adjusted for age)- In children: 3.8%- In adults: 11.2%P < 0.001


FLU +

FLU -

7

% deaths: 4.1% (41/1002)- In FLU + : 3.6% (15/423)- In FLU - : 4.5% (26/579)(NS, adjusted for age)- In children: 0.8% (3/377)- In adults: 6.08 %(38/625)


FLU +

FLU -

ConclusionsSeason 2012-2013• Intense and long • No particular signs of severity clinically• Preliminary analysis shows similar influenza (sub)types circulate in mild and severe

influenza cases (detailed analysis ongoing)

Strenghts• Real time surveillance, complementary to ILI surveillance • Comparative virology of mild and severe influenza cases• Identify underlying conditions associated with severe influenza• Yearly recurrent surveillance allows comparison between seasons

• Alerting system for more severe season• Pandemic baseline data

• Direct contact between researchers and clinicians

We hope to continue the surveillance for the next seasons

Update on viral and atypical microorganisms in

LRTI and recommended diagnostic methods

M. Ieven21. 11. 2013

1

1

Why study the etiology in LRTI?

• Antibiotic resistance major public-health problem• 80% of antibiotics are prescribed in primary care• Acute RTIs most common reason for GP consultation• Evidence of over prescribing by GPs

Goossens et al, 365: 579-87, Lancet 2005

2

• Primary care physicians rely on symptoms and signs

• Not feasible to take samples for etiologic diagnosis in all LRTIs

• Little knowledge on etiologic causes of LRTI in this setting

Why an etiologic study in LRTI in the community?

2

3

Aetiology of lower respiratory tract infection in the community (%)

Reference n S. pn H. infl M. pn C.pn Virus

Boldy et al. 1990 42 3.0 3.0 8.0 0 21.0

Creer et al. 2006 80 18.8 6.3 1.2 61.3

Graffelman et al. 2004 145 6.2 9.0 9.0 1.3 39.0

Holm et al. 2007 364 6 4 3 <1 24

Hopstaken et al. 2005 247 2.9 13.8

Macfarlane et al. 1993 206 30.0 8.0 0.5 8.0

Macfarlane et al. 2001 316 17.1 9.8 7.3 17.4 19.3

Range 3-30 3-14 0.5-9 0-17 8-61

Woodhead M et al. Clin. Micribiol.Infect. 2011; 17, E1-E59

• Most studies are limited to only CAP patients• Early data on atypicals are largely based on serological analysis

4

GRACE: Etiologic diagnosis of LRTI in primary care: impact of RT-PCR

• EU FP6 Network of excellencewith overall aim to combat antimicrobial resistance

• From 10/2007 – 12/04/2010 - 3104 adult patients with LRTI- 2984 controls- 16 PCN in 12 countries

• Blood & respiratory samples taken, transported to Antwerp

3

5

Overview of Procedures

Sample/ Preparation at site Storage in Transport toSample Material the local lab the central lab

Label the UTMCollect the swab and place it in the UTM medium.

Nasopharyngeal swab in UTM

Store swab frozen until shipment.

Transport on dry ice

• Patient samples- First visit

• Serum • EDTA blood sample• Sputum• NPS in UTM• NPS in Skimmed milk

• Patient samples- Follow up visit

• Serum

• NPS in UTM• NPS in Skimmed milk

• Control samples- Visit 0

• EDTA blood sample• NPS in UTM• NPS in Skim milk

6

Flocked swabs or conventional rayon swabs?

Daley P. et al J Clin Microbiol. 2006; 44: 2265-7.

0

10

20

30

40

50

60

70

Conventional Swab New Swab

Nasal (N=16)

Nasopharyngeal(N=15)

Type of viralinfection

Total no. of cells/hpf No. of infected cells/hpf (95% CI)

Flocked swab Rayon swab Flockes swab Rayon swab

Influenza A virus (20)

67.2 29.3 15.8 (9.7-21.9) 7.2 (3.6-10.8)

RSV (21) 51.7 19.6 32.6 (18.7-46.7) 11.0 (6.1-15.9)

DFA negative (20) 82.4 24.8 0 0

Mean respiratory epthithelial cell yield among volunteers sampled by collecting NPS and NS using flocked or rayon

Mean of total and infected respiratory epithelial cells from NP samples by flocked and rayon swabs

4

7

Use of naso-pharyngeal swabs

From 98.5% of patients, both

NPSs were available!

8

Samples and Analysis Analysis in local lab Sputum sample

• Gram stain and cultureIf + for S. pneumoniae and/or Haemophilus spp: Store until shipment

Analysis in central lab Nasopharyngeal swab in UTM and swab in Skimmed milk

• Viral and atypical PCRs• Culture for S. pneumoniae and Haemophilus spp.

Serum sample• Serology for M. pneumoniae, C.pneumoniae and L. pneumophila• C-reactive protein,

• Lab based• POCT (Orion)

• Procalcitonin, • Kryptor (Brahms GmbH).

5

9

Bacterial infections in LRTI in GRACE

• Culture results from sputum and NPS for S. pneumoniae and H. influenzae

• PCR results from both sputum and NPS for atypicals• For M.pneumoniae and C.pneumoniae serology results included

In 22.5% of outpatients with LRTI, a common bacterial etiology is detected! Direct detection of S. pneumoniae and H. influenzae in adults treated in primary care is relatively uncommon

Etiologic agent n/total (%) in V1

S. pneumoniae

Haemophilus influenzae

M. pneumoniae

C. pneumoniae

B. pertussis

176/3058 (5.7%)170/3058 (5.5%)114/3058 (3.7%)133/3058 (4.3%)103/3058 (3.3%)

Creer DD et al. Thorax 2006; 61:75-79

10

Pathogen N (%) ofpatients with pos. results* (n=3116)

PCR from sputum (n=1666)

PCR from NPS (N=3023)

Serology (n=2433)

M. pneumoniae 114 (3.7) 28 9 82

C. pneumoniae 133 (4.3) 9 17 120

B. pertussis 103 (3.3) 34 39 61

*Total number of patients who received a diagnosis for one particular pathogen, irrespective of method used; a number of patients were positive by different methods used

A combination of methods is needed for early detection of M. pneumoniae cases

• M.pn detected in 2.5% by IgG seroconversion or significant IgG rise• Only 33% of IgG positive patients also positive for IgM• All (1.4%) sputum PCR positive patients also IgG positive

Combination of PCR and serology detects most cases

6

11

Mycoplasma pneumoniae infection in primary care in England and Wales

Chalker VJ et al., Eur J Clin Microbiol Infect Dis 12 February 2011

• M. pneumoniae detected by PCR in 1.7% samples (65/3987)

- 1.4% (41/2877) in adults vs- 3% (17/564) in children: 6% in 2005-2006 vs 2.2% in 2007-2009• incidence from 2005 to 2009 consistent with other observations in the

same period and consistent with hypothesis of four year epidemics• Mixed infections in 6.2% of all M. pneumoniae-positive cases

12

Incidence of Mycoplasma pneumoniae infections in Denmark 2004-2010

Rasmussen JN et al., Eurosurveillance 11.2010

GRACE 10.2007- 04.2010

• PCR based surveillance system for M. pneumoniae• Denmark From 2007 to 2010: average positivity rate of M. pneumoniae

in Denmark remained very low• Increase in positivity rate in late summer 2010 = end of GRACE

inclusions

7

13

Importance of PCR in the diagnosis of Mycoplasma pneumoniae infections

• PCR based detection: most sensitive• 28/32 (87%)

• Sensitivity of serology• 15/26 (58%)

• 7 patients only diagnosed by serology

• Combination of PCR and serology detects most casesDekeyser S et al., Pathol Biol 2011; 83-87

14

Molecular Methods used in GRACEBased on previous validation• Antwerp:

- Real-time mono PCRs (Lightcycler): M. pneumoniae, C. pneumoniae and L. pneumophila, Bordetella pertussis

• Leiden:- Real-time MX PCR (I-cycler):

• PIV1-4• hMPV, hRV• ADV

• Utrecht:- Real-time mono PCRs (Taqman):

• Inf A/B, • RSV A/B, • hCoV (229E, NL63, OC43)• new polyomaviruses WU and KI Loens K et al., ECCMID, 16.05.2009

8

15

Target Patient with LRTI Matched Control subjectprevalence prevalence n/total (%) n/total (%)

first visit follow up visit (n=3058) (n=2549) P-value (n=1680) P-value

Rhinovirus 590 (19.3) 111 (4.4) < 0.00001 72 (4.3) < 0.00001Influenza A/B 315 (10.3) 11 (0.4) < 0.00001 7 (0.4) < 0.00001Coronaviruses 233 (7.6) 71 (2.8) < 0.00001 29 (1.7) < 0.00001RSV 144 (4.7) 13 (0.5) < 0.00001 11 (0.7) < 0.00001Human MPV 142 (4.6) 7 (0.3) <0.00001 3 (0.2) < 0.00001Parainfluenza 1-4 83 (2.7) 13 (0.5) < 0.00001 8 (0.5) < 0.00001Human AV 47 (1.5) 44 (1.7) 0.26 25 (1.5) 0.68Polyomavirus WU 44 (1.4) 54 (2.1) 0.06 39 (2.3) 0.04Polyomavirus KI 27 (0.9) 29 (1.1) 0.51 17 (1.0) 0.77Bocavirus 18 (0.6) 11 (0.4) 0.96 16 (1.0) 0.21Total viruses 1643 (53.7) 364 (14.2) 227 (13.5)

Significance of etiologic agents?

16

Epidemiology of Respiratory agents in LRTI

• Significant prevalence of viral infection in LRTI,CAP in immonocompetent and in transplants:

- Flu > RSV > PI; hMPV 4.3%; rhino 18%Dare R et al. J Clin Microbiol 2007; 45:548-52Camps Serra M et al. Eur Resp J 2008; 31: 618-24

• Significant cause of pneumonia in hematological cancers - total 35 % of patients: RSV > Rhino > Influenza > PIV- HCoV increasingly important: 11 %

Van Elden L et al. Clin Infect Dis. 2002; 24: 177Van Elden L et al. J Infect Dis. 2004; 189: 653

• Acute RTI in elderly and children: up to 40%: - mostly rhino, RSV, hMPV, and influenza

Renwick et al 2007, Regamey et al 2008 Jartti et al 2008, Caram et al 2009, Jin et al 2009

9

17

Detection rates of viral etiologic agents

Presence viral etiologic agent • Visit 1: 1643/3058 (53.7%)• Visit 2: 364/2549 (14.2%)• Visit 0: 227/1680 (13.5%)

In more than 50% of outpatients’ samples presenting at the GP’s office with LRTI, a viral etiology is detected!

18

First visitprevalence n (%)

(n=3058)

Follow up visitprevalence n (%)

(n=2520)Rhinovirus 590 (19.3) 22 (3.7)

Influenza A/B 315 (10.3) 0 (0)

Coronaviruses 233 (7.6) 2 (0.8)

Respiratory syncytial virus 144 (4.7) 1 (0.7)

Human metapneumovirus 142 (4.6) 1 (0.7)

Parainfluenzaviruses 1-4 83 (2.7) 0 (0)

Persistance of viral RNA for +/- 3 weeks is uncommon

Viruses found in first visit but not in follow up: Influenza A/B, Paraflu,,Polyoma WU

Case analysis of viral detection during the acute phase and subsequent follow-up.

10

19

Target Patients with LRTI prevalence n (%)

First season1 Oct 2007-30April 2008

(n=777)

Second season1 Oct 2007-

30April 2008(n=1043)

Third season1 Oct 2007-30April 2008

(n=1058)

Parainfluenza 1- 4 16(2.1) 18 (1.7) 39 (3.7)Rhinovirus 135 (17.4) 200 (19.2) 204 (19.3)Human metapneumovirus 36 (4.6) 31 (3.0) 70 (6.6)Human adenovirus 10 (1.3) 14 (1.3) 20 (1.9)Bocavirus 5 (0.6) 1 (0.1) 12 (1.1)Respiratory syncytial virus 35 (4.5) 52 (5.0) 56 (5.3)

Influenza A/B 132 (17.0) 120 (11.5) 57 (5.4)Coronaviruses 52 (6.7) 90 (8.6) 86 (8.1)Polyomavirus WU 18 (2.4) 15 (1.4) 11 (1.0)Polyomavirus KI 8 (1.0) 2 (0.2) 13 (1.2)

Prevalence of respiratory viruses during 3 consecutive winter periods

20

05

1015202530354045505560

okt/0

7

nov/0

7

dec/0

7

jan/0

8

feb/

08

mrt/

08

apr/0

8

mei

/08

jun/0

8jul

/08

aug/

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/09

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/09

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Date of isolation

Num

ber o

f pos

sam

ples

Rhinovirus RSV Influenza_A_B

First season Second season Third season

Seasonal distribution of respiratory viruses

11

21

Influenza Like Ilnesses/ 100 000 inhabitants in Belgium

22

Target Patients with LRTI prevalence n (%)

After First season1 May 2008-30 Sept 2008

(n=92)

After Second season1 May 2009-30 Sept 2009

(n=84)

Parainfluenza 1- 4 6 (6.5) 3 (3.6)Rhinovirus 23 (25.0) 25 (29.8)Human metapneumovirus 2 (2.2) 2 (2.4)Human adenovirus 1 (1.1) 2 (2.4)

Bocavirus 0 (0.0) 0 (0.0)Respiratory syncytial virus 0 (0.0) 0 (0.0)Influenza A/B 2 (2.2) 3 (3.6)Coronaviruses 2 (2.2) 3 (3.6)Polyomavirus WU 0 (0.0) 0 (0.0)Polyomavirus KI 2 (2.2) 2 (2.4)

Prevalence of etiologic agents in V1 outside the winter season

12

23

Prevalence of respiratory viruses in different centers

0

10

20

30

40

50

60

70%

pos

itive

s

A B C D E F H I K O

Polyomavirus KIPolyomavirus WUCoronavirusesInfluenza A/BRespiratory syncytial virus BocavirusHuman adenovirusHuman metapneumovirusRhinovirusParainfluenza 4Parainfluenza 3Parainfluenza 2Parainfluenza 1

24

What is the role of bacterial and atypical bacterial infections?

Combined data on NPS, sputa and serology:• In +/- 23% of outpatients with LRTI, a bacterial aetiology is

detected! • In > 50% of outpatients with LRTI, a viral aetiology is

detected!

Overall, an etiologic agent has been detected in 75% of patients’ samples!!

13

25

Less than 50% of all bacterial infections occur as single infections

• Most dual infections are combined bacterial and viral infections

• 70.5% of all “significant” viral infections occur as single infections

• Viruses not considered as “causative” are detected as single agents in < 50% of the cases

Single or Dual viral Infections?

Clinical significance?? unclear at present- in some studies dual infections more severe- or some combinations more severe

hMPV + RSVSemple, 2005

Bacteria + virusesTempleton, 2006

26

Pathogens Total Single inf Combined viral Bacterial+viralRhinovirus 590 430 (72.9) 61 (10.3) 99 (16.8)Influenza A/B 315 218 (69.2) 34 (10.8) 63 (20.0)

Coronavirus 233 162 (69.5) 42 (18.0) 29 (12.5)

RSV 144 100 (69.4) 19 (13.2) 25 (17.4)Human MPV 142 94 (66.2) 23 (16.2) 25 (17.6)Paraflu 1-4 83 59 (71.1) 11 (13.3) 13 (15.7)Human AV 47 18 (38.3) 19 (40.4) 10 (21.3)Polyoma WU 44 13 (29.5) 26 (59.1) 5 (11.4)Polyoma KI 27 7 (25.9) 13 (48.1) 7 (25.9)Bocavirus 18 8 (44.4) 4 (22.2) 6 (33.3)

Single or Dual viral Infections?

70.5% of all “significant” viral infections occur as single infections

Viruses not considered as “causative” are detected as single agents in < 50% of the cases

14

27

Pathogen Age group N/total (%)<25

(n=211)25-65

(n=2221)>65

(n=626)P value<65->65

Rhinovirus 58 (27.5) 430 (19.4) 102 (16.5) 0.0002

Influenza A/B 25 (11.8) 257 (11.6) 33 (5.3) 0.000005

Coronaviruses 13 (6.2) 174 (7.8) 46 (7.3) NS

RSV 9 (4.3) 94 (4.2) 41 (6.6) 0.01

Human MPV 5 (2.4) 112 (5.0) 25 (4.0) NS

Parainfluenza 1- 4 9 (4.3) 60 (2.7) 14 (2.2) NS

Human adenovirus 5 (2.4) 36 (1.6) 6 (1.0) NS

Polyomavirus WU 3 (1.4) 27 (1.2) 14 (2.3) NS

Polyomavirus KI 3 (1.4) 18 (0.8) 6 (1.0) NS

Bocavirus 2 (0.9) 3 (0.3) 5 (0.8) NS

Total 132 (62.6) 1219 (54.9) 292 (46.7) 0.00008

Viruses in nasopharyngeal swabsper age groups

28

“CRP has additional diagnostic value in patients with an intermediate diagnostic risk of pneumonia as determined by symptoms and signs alone, especially in appropriately excluding pneumonia. PCT has no additional diagnostic value in primary care.”

15

29

Analysis of CRP and PCT results

CRP Routine

PCT

Absence of

bacterial infection

Bacterial infection unlikely

PossibleBacterial infection

Presence of

bacterial infection

Total

<2020-5050-100>100

213634914255

58302327

5318

2

211

2201382168101

Total 2682 138 17 15 2852

98.8% of all infections correlate with values indicating“absence of bacterial infection” or “bacterial infection unlikely”

30

Predictive value of serum PCT levels for bacterial infections?

• 2070/3059 patients with sputum samples (68%)• 484/2070 sputum samples: culture positive (23.4%)

- 362/2070 (17.5%): Haemophilus spp- 102/2070 (4.9%): Streptococcus pneumoniae- 20/2070 (1.0%): Haemophilus spp and S. pneumoniae

• PCT values <0.1 µg/L or 0.1-0.25 µg/L in: - 346/362 (95.5%) of Haemophilus spp positive sputa- 92/102 (90.2%): Streptococcus pneumoniae positive sputa- 20/20 (100%) of Haemophilus spp and S. pneumoniae positive sputa

PCT too insensitive to predict bacterial infectionNo distinction of bacterial and viral infections by PCT

16

31

Update on viral and atypical microorganisms in LRTI

• In >70% of adult outpatients’samples presenting with LRTI, an etiologic agent could be detected.

• Respiratory viruses are the predominant causes of LRTI, confirming that antibiotic treatment is not indicated in this setting.

• HRV accounted for the majority of viral LRTI followed by influenza and CoV; rhinoviruses are associated with respiratory symptoms throughout the year.

32

• RSV and hMPV are also prevalent in adult outpatients.

• Real-time NAATs results in a significant improvement in the detection of respiratory viruses in LRTI.

• During the GRACE study period, no epidemic of Mycoplasma pneumoniae was observed.

• Biomarkers such as CRP and PCT can not distinguish between bacterial and viral infections and are of limited use in this patient population.

Update on viral and atypical microorganisms in LRTI

17

33

Woodhead M et al Eur Resp J 2005;26:1138-1180

Woodhead M et al. Clin. Micribiol.Infect. 2011;17, E1-E59

Guidelines for the management of adult lower respiratory

tract infections. Clinical Microbiology and Infection 2011; 17: E1-E59

34

in the Community: • Microbiological investigations are not recommended

routinely (C1-3)

• Sputum examination to be considered for patients not responding to empirical AB therapy: gram stain and culture, if sputum is purulent and to be correlated with morphotype in gram stain (A3)

• Serologic investigations may be considered during outbreaks or epidemic mycoplasma years or in case of a particular epidemiological reason (A3)

Recommended diagnosticInvestigations for patients with LRTI

Woodhead M et al. Clin. Micribiol.Infect. 2011;17, E1-E59

18

35

In the hospital• Urinary L. pneumophila 1 Ag detection should be performed in

patients admitted to the hospital for reasons of severity and in other patients where this infection is clinically or epidemiologically suspected. (A3)

• Serology- More useful in epidemiologic studies (A3)- Not recommended for the management of the individual patient

(A3)Woodhead M et al . Eur. Resp. J. 2005;26:1138-80

• For atypicals and viruses: - molecular tests if well validated- initial and follow up serology for atypicals if no PCR available

Woodhead M et al . Eur. Resp. J. 2005;26:1138-80Ieven M and Loens K. Current Pediat Reviews, 2013, 9

Recommended diagnosticInvestigations for atypicals and viruses

36

19

37

Influenza A + B : 50% more RSV : 12% more PIV 1-2-3-4 : 64% more

• In >90% of severe CAP an etiology• In RVP 42% more viruses detected

Templeton K et al. J Clin Microbiol. 2004; 42: 1564-69; CID 2005; 41: 345, Mahony J et al. J Clin Microbiol 2007; 45: 2965-70

• Increase in diagnostic yield from 24% to 43% in children• Increase in diagnostic yield from 3.5% to 36% in adults

Van de Pol et al. J Clin Microbiol 2007;45: 2360-63

• Increase in diagnostic yield from 37% to 57%- Improved sensitivity for RSV, FluB and AdV- Main improvement: previously not detected viruses

Tiveljung-Lindell A et al. J Med Virol 2009; 81: 167-175

- Significant increase in diagnostic yield

Single Infection

Mixed infection

No infection

Single Infection

Mixed infection

No infection

Impact of molecular diagnostics compared to conventional diagnostics

38

Impact of molecular detection on the diagnosis of acute M. pneumoniaeinfection

M.pneumoniae carriage among asymptomatic persons is rare Persistance of M.pneumoniae DNA is common during +/- 7 weeks

• M. pneumoniae in 48/164 (29%) patients:• 45/164 (29%): PCR pos in first week

- 50% of cases still PCR positive after 54 days- 44/164 (27%): significant in IgG or + IgMBUT:

• 21% in 1st week• 56% during second week• 100% after 3rd week

PCR is superior to serology for diagnosis of M. pneumoniaeduring early phase of infection

Nilsson et al., BMC Microbiol 2008; 8: 93-100)

20

39

“Little and colleagues have generated convincing datathat should encourage physicians in primary care torefrain from antibiotic treatment in low-risk patients inwhom pneumonia is not suspected. … Guidance from measurements of specific blood biomarkers of bacterial infection might helpto identify the few individuals who will benefit fromantibiotics despite the apparent absence of pneumoniaand avoid the toxic effects and costs of those drugs andthe development of resistance in other patients.”

Antibiotics for non-pneumonic respiratory-tract infections

Editorial Published Online December 19, 2012Little P et al Lancet Infect Dis 2013;13: 123–29

“Tuberculosis in EU Cities.

Poverty and economic crisis”

Wouter Arrazola de Oñate, MDPublic healthMedical director VRGT ‐ BELTA

20‐1‐2014

1

• Public health is more than diagnostics and treatment (technology)

– also prevention and social determinants

• Epidemiology is more than statistics

• Misconceptions ‐ perceptions

• Policy advice EB

History

"Indien het belang van een ziekte voor de mensheid gemeten wordt aan de hand van het aantal sterfgevallen als gevolg van de ziekte, dan moet tuberculose als een veel ernstiger besmettelijke ziekte beschouwd worden als de pest, cholera en dergelijke. Eén op de zeven mensen sterft aan tuberculose. Indien men alleen de productieve leeftijdsgroep in beschouwing neemt, voert tuberculose éénderdevan de mensen af, vaak zelfs meer." (R. Koch)

20‐1‐2014

2

History

History VRGT

20‐1‐2014

3

Belgian Lung and Tuberculosis Association(BELTA) = Oeuvre National = Nationaal Werk

BELTA

Project:

BELTA ‐ TB net

VRGT(Flanders & Brussels)

Tuberculosiscontrol

Tobacco

FARES(Wallonia & Brussels)

Project BELTA‐Tbnet: WWW.BELTA.BE

Supported by RIZIV ‐ INAMI

20‐1‐2014

4

Tuberculosis in Belgium

Epidemiology

Poverty link: history Mortality

20‐1‐2014

5

2013: or Quiz

• Since ’70 with WHO and ECDC (Euro‐TB)

• Belgium:

– Mandatory notification

– Registration + epidemiology

– Contact investigation

20‐1‐2014

6

Evolution 1980 – 2012

28,028,8

26,9

22,2 21,8

19,819,2

18,0

16,1 16,615,8

14,613,3

14,9 15,1

13,6 13,312,7

11,812,4 12,8 12,9 12,7

10,911,8

11,0 10,79,7 9,4 9,5

10,39,5

8,9

0

5

10

15

20

25

30

1980 1985 1990 1995 2000 2005 2010

/100

000

projectie reele waarden

MEDIA ‐> PERCEPTION !

20‐1‐2014

7

Multi Drug Resistant TB (MDR‐TB) in Belgium(absolute numbers; % of all TB cases; % of TB cases whose strain got DST)

14

21

10

14

10

1918 18

15

1817

20

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

0

5

10

15

20

25

01 02 03 04 05 06 07 08 09 10 11 12

% of MDR‐TB cases

Number of MDR‐TB cases

MDR

% Total

% DST

Multi Drug Resistant TB (MDR‐TB)

7% 5% 6%11%

20% 11

%

24% 15

%

14%

5%10% 7%

20%

16% 6%

39%

40% 44

%

29%

20%

79% 95

%

90%

93%

80%

79% 89

%

50%

40%

44%

47%

65%

14 21 10 14 10 19 18 18 15 18 17 20

0%

20%

40%

60%

80%

100%

01 02 03 04 05 06 07 08 09 10 11 12

Other MDR

Pre‐XDR

XDR

X = extensively

20‐1‐2014

8

Regional differences

21,920,1

17,5 16,9 15,7 16,414,7

13,3 13,1 13,211,3 10,6

12,4 11,6 10,7 10,4 9,4 9,2 9,2 9,6 10,2 9,47,6

9,4 8,3 7,4 7,1 7,1 6,9 7,4 6,6 6,5

32,1 31,1

23,720,6 19,6

17,914,9

16,3 15,5 14,613,1 13,2

14,612,6 11,6 11,7 10,5

12,6 11,3 10,8 9,8 9,4 9,4 8,8 9 8,8 7,7 7,9 7,9 7,8 7,3

56,8

52,3

44,6

48,3

41,1

34,537,1 36,3

38,034,8

30,5

36,438,0

34,937,4 36,5

32,5 32,0

38,236,5

42,6

36,134,234,1

36,7

28,5 28,9 29,9

34,631,4

27,422,4

33,0

0

10

20

30

40

50

60

81 83 85 87 89 91 93 95 97 99 01 03 05 07 09 11

/100.000 Vlaams Gewest Waals Gewest Brussels Gewest

TB = Big City Problem

0

5

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15

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45

50

2001

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Brussel Antwerpen Brugge Gent Charleroi Luik Namen >100k anderen<100k

Vla=WaBE

20‐1‐2014

9

20‐1‐2014

10

Why EU Urban TB Control ?

2013: In Press 32 recommendations

Hard to reach, hard to hold+

Therapy hard to comply

20‐1‐2014

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• 1.2 Investigate and monitor inequalities and socio‐economic deprivation and their links with TB in order to intervene with a comprehensive public health approach (D)

• 1.3 Collaborate to promote suitable housing for homeless persons in order to prevent transmission of TB and promote cure in this population (D)

• 2.1 Implement a coordinated programme of education and training

• 4.3 Consider targeted radiographic screening (e.g. mobile or static digital X‐ray units) of urban high‐risk groups, especially homeless persons, persons with drug and alcohol misuse, and prisoners (C)

• 5.4 Consider provision of incentives and enablers, peer support workers

• 7.1 Complement routine surveillance activities and contact‐tracing with molecular epidemiology to identify unexpected spreading of TB and outbreaks, and to evaluate interventions (D)

• 8.5 Use involuntary isolation only as a measure of last resort under humane conditions (D).

Migration and TB

20‐1‐2014

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Tuberculosis: import disease ?

TB, migration and import

“Not a very common problem in Africa, before the European invasionwent looking for slaves and ivory” (ref: Janssens P, Kivits M, Vuylsteke J. Médecine et hygiène en Afrique Centrale de 1885 à nos jours. Brussel: Koning Boudewijnstichting, 1992.)

“TB imported by white Europeans on a mass scale to the continent.” Population “in contact for the first time with the white plague”

(ref: Gyselen A, Demedts M, Fortuin M, et al. Wat is er (nog) van de tuberculose? Brussel: VRGT ‐ Ministerie van de Vlaamse Gemeenschap, Administratie Gezondheidszorg. Brussel, 1996)

Continent hardest hit: Poverty and exploitation – HIV

DNA‐fingerprinting: very low levels of transmission frommigrant population toward resident population

‐ EU wide database of strains

20‐1‐2014

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20‐1‐2014

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“Aanzuigeffect” ‐ “L’ effet d’aimant” ‐ “Welfare magnet”= does not exist

Anecdotal cases of medical tourism

People seeking asylum in Belgium

Entry screening (CXR) at foreigners office, coverage 95 %

2012: detection rate at foreigners office 160,7 /100 000

18 times higher population in Belgium 8,9/100 000 (2012)

Register:

50 % of notified cases are of non‐Belgian nationality

So 50% among Belgians

Of all cases: 10,5 % asylum and 6,7 % non‐documented

82,8 % of all cases not among AS or non‐doc’s

20‐1‐2014

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Interferon‐ gamma Release Assays (IGRA)

Latent Tuberculosis Infection

Latent Infection vs. DiseaseLatent Tuberculosis Infection (LTBI):+ THT or IGRA without signs (clinical, radiological, microbiological) of active disease

90%

Active Disease: 10%

20‐1‐2014

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Andersen P et al. Lancet 2000; 356: 1099‐1104Pai M et al. Lancet Infect Dis 2004; 4: 761‐776

IGRA =Interferon‐γ Release Assay

European Consensus

20‐1‐2014

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Economic crisis and TB

Future

‐Association TB mortality + incidence AND whealth inequality, GDP, social protection

‐ Evolution of these parameters could predict epidemiology

‐Greece

20‐1‐2014

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Double dip: ‐ poverty + cases

‐ funds for PH

20‐1‐2014

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1

2

3

4

7

6

5

20‐1‐2014

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Conclusions + futur policy

Should we cut PH budgets in times of crisis ?

Should we cut budgets of Social Security ?

Investments in health, education, social protectionimprove economic recovery + ID epidemiology

Scientific community pro‐active role: advisingpolicy makers

Clostridium difficile: an emerging zoonotic pathogen

C. Rodriguez, B. Taminiau, V. Avesani, N. Korsak, J. Van Broeck, M. Delmée, G. Daube

Diagnostic et surveillance des maladies infectieuses21nd Novembre 2013

Centre culturel de Woluwé-St-Pierre

20/01/2014

1

Background• Since toxigenic C. difficile was recognized as the

major cause of antibiotic-associated diarrhea andpseudomembranous colitis in 1978, many outbreakshave been documented

• In the last years, an enhanced virulence andincreased antibiotic resistance of C. difficile strains(PCR-ribotype 078/NAP-1/B1) has been observed

• There are emerging data on the occurrence of C.

difficile infection in the community: non-hospitalizedand younger patients with absence of othertraditional risk factors

Hypothesis about a potential risk of foodborne infections linked to C. difficile

@google images 2013

Clements et al., 20102013

@google images 2013 @google images 2013

@google images 2013 @google images 2013

https://www.health.harvard.edu

• Patients with serious illnesses and prolonged hospitalizations are at particular risk, as

people above 65 years of age

• The increased risk of acquiring C. difficile in the elderly may be due to age-related

changes in intestinal flora, immune senescence or the presence of underlying diseases

• There is not much data describing the prevalence and molecular epidemiology of C.

difficile in nursing homes in absence of an epidemic situation

Background

Arvand, M., et al., 2012. High prevalence of Clostridium difficile colonization among nursing home residents in Hesse, Germany. Plosone, 7, e30183.

@google images 2013 @google images 2013@google images 2013

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Clostridium difficile Infection in Nursing homes

Arvand, M., et al., 2012. High prevalence of Clostridium difficile colonization among nursing home residents in Hesse, Germany. Plosone, 7, e30183.Birgand, G., et al., 2010. Investigation of a large outbreak of Clostridium difficile PCR-ribotypes 027 infections in northern France, 2006-2007 and associated clusters in 2008-2009. Eurosur, 24, 1-6.Marwick, C.A., et al 2013. Community-associated Clostridium difficile infection among older people in Tayside, Scotland, is associated with antibiotic exposure and care home residence: cohort study with nested case-control. J Antimicrob Chemoth, 3.Mylotte, J.M., et al., 2012. Surveillance for Clostridium difficile infection in nursing homes. J Am Geriatr Soc, 61, 122-5.Pa Patient Saf Advis., 2010. Clostridium difficile infections in nursing homes. Pennsylvania Patient Safety Advisory, 18, 10-5.Simor, A.E., et al., 1993. Infection due to Clostridium difficile among elderly residents of a long-term-care facility. Clin Infect Dis, 17, 672-8.Ryan, J., et alF., 2010. Asymptomatic carriage of Clostridium difficile in an Irish continuing care institution for the elderly: prevalence and characteristics. Ir J Med Sci, 179, 245-50.

@google images 2013

15%

2.1-8.1%

39%

10% 0.03%

8.9% 4.6%

Clostridium difficile in

animals and food

• In animals, C. difficileappears to be an important cause of enteric disease

• Asymptomatic carriage of C. difficile in animals has been also described

• C. difficile has been recently isolated from many types of meat products

• C. difficile meat isolates are correlated with the types implicated in human disease

@google images 2013

@google images 2013

@google images 2013

@google images 2013

@google images 2013

@google images 2013

@google images 2013

20/01/2014

3

The possibility that C. difficile infection has a food or animal origin has recently been evoked due to the presence of C. difficile strains in food animals and meat. These strains are similar to those found in

humans

@google images 2013

@google images 2013

@google images 2013

@google images 2013

@google images 2013

DDA-FMV-ULG

DDA-FMV-ULG DDA-FMV-ULG

Objectives

• Determine the presence of C. difficile in young animals on farms

• Determine the presence of C. difficile in intestinal contents and oncarcasses in animals at the slaughterhouse

• Evaluate the presence of C. difficile in retail meat

• Characterize the isolates by PCR-ribotype, presence of toxin genesand toxigenic activity in order to compare the strains with the mainPCR-ribotypes found in humans in Belgium

20/01/2014

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Study designFarm animals

From January to July 2011

o Piglets faecal samples• Samples from 23 piglets were collected from

3 different breeding farms• Piglets were stimulated to make them defecate

in individual tubes• The piglets don’t have diarrhea and were still suckling

o Calves faecal samples • Faecal samples of 18 calves were collected

from 5 different local farms • Calves were less than 3 months of age at the

time of sampling

@google images 2013

@google images 2013

Study designSlaughter animals

From January to July 2011

200 intestinal samples from cattle and pigs

were collected over 9 different visits to a

local slaughterhouse

All intestinal contents were collected from the

slaughter line, directly from the large intestine

in the viscera processing area

DDA-FMV-ULG

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5

Study design

Intestinal contents, carcass samples and meat

From September to June 2012

A total of 10o intestinal samples and

100 carcass samples from cattle and pigs

were collected. Carcasses were sampled

2 h after slaughter.

A total of 133 beef samples and

107 pork samples were collected

Belgian Royal Decree of 20 August 2002

DDA-FMV-ULG

DDA-FMV-ULG

Methodology• Direct and enrichment culture

Home-made cycloserine cefoxitin fructose taurocholate(Delmée et al., 1987. Epidemiology and prevention of Clostridium difficile in a leukaemia unit. E J Clin Microbiol, 6, 623-27)

• C. difficile latex agglutination rapid test Kit DR 1107A Oxoid• Detection of a species-specific internal fragment of tpi, detection of genes for toxin B,

toxin A and binary toxin (cdtA) by PCR et Genotype Cdiff test system(Lemée et al., 2004. Multiplex PCR targeting tpi (triose phosphate isomerase), tcdA (toxin A), and tcdB (toxin B) genes for toxigenic culture of Clostridium difficile. J Clin Microbiol, 42, 5710-14)

(Antikainen et al., 2009. Detection of virulence genes of Clostridium difficile by multiplex PCR. Acta Phat, Microbiol Inmuno Scand, 117, 607-13)

• Cytotoxicity assay using confluent monolayer MRC-5 cellsCytotoxic activity was confirmed using a specific C. difficile antitoxin kit (T500, TechLab, USA)

(Rodriguez et al., 2012. Clostridium difficile in young farm animals and slaughter animals in Belgium. Anaerobe, 18, 621-625)

• PCR-ribotyping• (Bidet et al.,1999. Development of a new PCR-ribotyping method based on ribosomal RNA gene sequencing. FEMS Microbiol Letters, 175, 261-66)

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Results and discussion:C. difficile in farm and slaughter animals

Prevalence 78.3% Prevalence 22.2%

Prevalence 6.9-9.9%Prevalence 0-1%

Farm

Slaughterhouse

Main PCR-ribotypes 078/002

Main PCR-ribotypes 078/UCL46

Main PCR-ribotypes 078/015

Main PCR-ribotypes 078/ Great variety of types (UCL5, 014, 002)

Similar prevalences and types were previously reported in other countries as Canada, The Netherlands, Slovenia or Spain

Costa et al., 2011. Clostridium difficile on a veal farm: prevalence, molecular characterization and tetracycline resistance. Vet Microbiol,152,379-84. Keessen et al., 2011. The relation between farm specific factors and prevalence of Clostridium difficile in slaughter pigs. Vet MicrobiolL,154,130-4. Hopman et al., 2011. Acquisition of Clostridium difficile by piglets. Vet Microbiol, 21,186-92. Avbersek et al., 2009. Diversity of Clostridium difficile and other animals in Slovenia. Anaerobe, 15, 252-5. Alvarez-Perez et al., 2009. Prevalence of Clostridium difficile in diarrhoeic and non-diarrhoeic piglets. Vet Microbiol, 137, 302-5.

@google images 2013

@google images 2013@google images 2013

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(0%)

Results and discussion:C. difficile on pigs and cattle carcasses

Prevalence 7%

Prevalence 7.9%

(2.2-2.5%)

(4%)

Susick et al., 2012. Longitudinal study comparing the dynamics of Clostridium difficile in conventional and antimicrobial free pigs at farm and slaughter. Vet Microbiol 25, 172-78.Rodriguez-Palacios et al., 2011. Transient faecal shedding and limited animal-to-animal transmission of Clostridium difficile by naturally infected finishing feedlot cattle. Appl Envir Microbiol 77, 3391-97.Harvey et al. , 2011. Clostridium difficile in retail meat and processing plants in Texas. Journal of Veterinary diagnostic investigation 23, 807-11.Hawkin,et al.,, 2012. Carriage and dissemination of Clostridium difficile and methicillin resistant Staphylococcus aureus in pork processing. Food Control, 31,433-37.Houser, et al., 2012. Prevalence of Clostridium difficile toxin genes in the faeces of veal calves and incidence of ground veal contamination. Foodborne Path dis., 9, 32-6.

(30%)

(15%)

There are similar studies

describing C. difficileon pig and

cattle carcasses at

the slaughterhouse

in North America and

Canada

Great variety of types (UCL5a/UCL16u)

Main PCR-ribotypes 014/081/UCL36

@google images 2013

@google images 2013

@google images 2013

First isolation in Europe

20/01/2014

7

Results and discussionC. difficile was found in retail meat with a prevalence

ranging between:

@google images 2013

@google images 2013

2.3% 4.7%

Main PCR-ribotypes 078/014 Main PCR-ribotypes 078/014/UCL57

Prevalence of C. difficile previously reported in meat• America: 1.8 - 20% of positives • Europe: 3% of positives• Main PCR-ribotypes in America 078 and 027

First isolation of PCR-Ribotypes 078 and 014 in retail meats in EuropeHensgens et al., 2012. Clostridium difficile infection in the community: a zoonotic disease? Clin Microbiol Infec Dis 18, 635-45.

Discussion: Ribotypes distribution in Belgian hospitals

• In 2011 in Belgium, the most prevalent

PCR ribotypes in hospitals were o 014***, 002*, 027, 078***, 020,

UCL46*, UCL16l*, UCL26, 001, 023*,

UCL23f, 012, UCL16b, 015*,

UCL5a**, UCL20a*, and UCL49 sorted

by decreasing values in number of

isolates.

Intestinal contents Carcasses Meat

• Overlap of PCR-ribotypes isolated

from meat and human samples (MLST)

1Delmée, M., 2012. Epidemiology of Clostridium difficile in Belgium. NRC Clostridium difficile-Yersinia.

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Conclusions

• This study documented that animals are carriers of C. difficile at

slaughter, and carcass contamination occurs inside the slaughterhouse

• PCR-ribotypes 014 and 078 were the most frequently identified. These

ribotypes were also the most common isolates from patients in Belgium

• The results obtained prove that toxigenic C. difficile is present in meat

in Belgium. However, the clinical relevance of ingesting spores with

food needs further investigation

ASSOCIATION OF CLASSICAL MICROBIOLOGY AND TARGETED METAGENOMIC ANALYSIS TO EVALUATE THE PRESENCE OF

CLOSTRIDIUM DIFFICILE IN A BELGIAN NURSING HOME

20/01/2014

9

Objectives• To evaluate and follow the prevalence of C. difficile

among older people in a nursing home

• To establish a relationship between other intestinal

bacterial populations and C. difficile colonization

• To evaluate the global evolutions of the total

microflora and the relation with the C. difficile

presence

@google images 2013

@google images 2013

@google images 2013

Nursing home study

Capacity: 110 beds• 34 nursing home• 61 nursing home and long-term

care• 15 day centers

Employees• 73

20/01/2014

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• During a 4-month period, stool samples from a group of 23 elderly care homeresidents were collected weekly

• Two samples per person were collected: the first sample was cultivated and examinedfor C. difficile by classical microbiological methods and the second one was used tostudy the microbial biodiversity of the faeces content by amplicon sequencing coupledto microbial metagenomic analysis .

Study designSTOOL SAMPLES

From March to June 2013

Metagenomics

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High throughput sequencing

Bioinformatics

20/01/2014

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Results: Prevalence of C. difficile in nursing home residents

• 7/23 (30.4%) residents were (at least one week) positive for C. difficile

• C. difficile was detected in 13/30 (43.3%) episodes of diarrhea and we found 25/47

(53.2%) samples positive but without diarrhea

• 4/13 (30.7%) residents positive for C. difficile had previously received an

antibiotic therapy. 10/13 (77%) positive residents didn’t get any antibiotic therapy

C. difficile recovery:

The results so far:

80 samples sequenced and analyzed: 6300 OTUs

Positive detection of Clostridium difficile :

n Microbiology Amplicon sequencing

20 + +

36 - -

19 + -

5 - +

C. difficile detection

20/01/2014

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0.000%

10.000%

20.000%

30.000%

40.000%

50.000%

60.000%

70.000%

80.000%

90.000%

100.000%

P1_week01

P1_week02

P1_week04

P1_week05

P1_week07

P1_week08

P1_week10

P2_week01

P2_week03

P2_week05

P2_week07

P2_week09

P13_week01

P13_week02

P13_week03

P13_week04

P13_week06

P13_week08

P13_week10

P15_week01

P15_week02

P15_week03

P15_week04

P15_week06

P15_week07

P15_week08

P15_week09

P18_week05

P18_week07

P18_week09

P19_week01

P19_week02

P19_week03

P19_week07

P19_week09

P19_week10

P24_week03

P24_week05

P24_week06

P24_week08

VictivallaceaeVibrionaceaeVerrucomicrobiaceaeVeillonellaceaeunclassifiedSynergistaceaeStreptococcaceaeStaphylococcaceaeSphingomonadaceaeRuminococcaceaeRikenellaceaeRhizobiaceaePseudomonadaceaePseudoalteromonadaceaePropionibacteriaceaePrevotellaceaePorphyromonadaceaePeptostreptococcaceaePasteurellaceaeOxalobacteraceaeMoraxellaceaeMicrococcaceaeMicrobacteriaceaeLactobacillaceaeLachnospiraceaeFusobacteriaceaeFlavobacteriaceaeFamily_XIII_Incertae_SedisFamily_XII_Incertae_SedisFamily_XI_Incertae_SedisEubacteriaceaeErysipelotrichaceaeEnterococcaceaeEnterobacteriaceaeDesulfovibrionaceaeCorynebacteriaceaeCoriobacteriaceaeComamonadaceaeClostridiaceaeCarnobacteriaceaeCampylobacteraceaeBifidobacteriaceaeBacteroidaceaeAlcaligenaceaeActinomycetaceae

Relative proportions of the differentbacterialfamiliesThere isa bacterialcomposition thatappearsstable alongthe weeks

The story so far• C. difficile prevalence of 30.4% in a Belgian nursing home

• The most common PCR-ribotype identified was 027

• Residents have all their microbiota print

• Metagenomics analysis can’t substitute targeted procotocols

• But It offers a global picture of the microbiota context:– With correlations– Identifications– Follow up

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Prof. Michel Delmée

Véronique Avesani

Johan Van Broeck

Eléonore Lyeza

Prof. Georges Daube

Dr. Bernard Taminiau

Dr. Nicolas Korsak

ACKNOWLEDGEMENTS

Nursing Home Sainte-Joséphine(Theux-Belgium)

Public slaughterhouse of Liège

Hepatitis E in Belgium: an imported disease or a local zoonosis? Diagnosis and surveillance of Infectious Diseases

21 November 2013

Rue Juliette Wytsmanstraat 14 | 1050 Brussels | BelgiumT +32 2 642 50 70 | F +32 2 642 56 92 | email: [email protected] | www.wiv-isp.be

Magali WautierNational Reference Center for Viral Hepatitis

Communicable and Infectious Diseases

1

Characteristics of HEV• ssRNA virus (7.2kb)

• non-enveloped

• Hepeviridae

• 5 genotypes

HEV genotype Geographic distribution1 (human) Asia, Africa

2 (human) Mexico, Africa

3 (human & animal) Europe, United States

4 (human & animal) China, Taiwan, Japan

5 (avian) Australia, United States

Symptoms• Similar to hepatitis A virus • Most cases: asymptomatic

Transmission• Historically

oro-faecal route → faecal contamination of drinking water

• Contamination caused by ingestion of uncooked deer or pork

• Transmission by blood transfusion

Characteristics of HEV

2

Endemic regions = developing countries

• Contaminated drinking water

= Waterborne-disease• Genotype 1 & 2

Non-endemic regions = industrialized countries

• Import infection : genotype 1 & 2• No recent travele.g.: The NetherlandsHEV suspected transmission from swine to human without travel history is increasing (gt 3 with 91-97% homology between human and Dutch pig strains)

= Food-borne infection • Zoonosis : genotype 3= swine/wild boar: animal reservoire.g.: Japan / FranceHEV transmission associated with eating of raw or undercooked wild boar and deer meat

Risk of transmission


Clinical Evolution• Liver disease• Acute self-limited• Few cases of fulminant hepatitis described• Chronic hepatitis in

organ transplant recipients immune depressed patients

• Mortality developing countries: 1-3%

pregnant women: 15-25%


3

Seroprevalence

• Blood donors: 1-16% • General population: 1.1-21%• Persons working with swine: prevalence much higher


4

Treatment• Absence of specific treatment

• Antivirals in chronical cases Ribavirin

Pegylated interferon alpha 2b


Prevention• Cooking the meat of swine, dear or wild boar

frying for 5 min at 191°C

boiling for 5 min

cooking for 20 min at 71°C

• Hygiene (water, personal)

• Disinfection autoclaving at 120°C

using disinfectants to enteric viruses

• Vaccination two vaccines successfully evaluated in phase 2-3 trials

not yet commercially available


5

Objectives of the study

• Demographic, clinical and molecular characterisation of HEV strains circulating in human and animal

• The animal work: in cooperation with the Veterinary Faculty of Liège (Prof. Dr. Thiry)

Establish zoonotic risk profile

MethodsPatients

• Sera from different clinical laboratories and the Institute of Tropical Medicine (Antwerp) Patients with clinical symptoms

Patients suspected of HE

Patients returning from HEV-endemic regions

6

Laboratory diagnosis• HEV IgG and IgM

Screening • ELISA by EtI-MAX 3000

• HEV RecomWell IgM and HEV RecomWel IgG (Mikrogen)

Confirmation • Immunoblot by Auto-Lipa

• HEV IgG/IgM recomblot (Mikrogen)

• HEV RNA Real-time PCR

• RealStar® HEV RT-PCR kit 1.0 (Altona Diagnostics)

Sequencing PCR • In-house method (primers in ORF 2 region)

Methods

Hepatitis E in Belgium: Results

Year Sera submitted for diagnosis

Seropositive (IgM+) Viropositive Total positive

2008 190 6/190 3/6 6/190

2009 245 8/245 5/15 9/245

2010 320 23/320 10/41 25/320

2011 494 30/494 24/76 31/494

2012 578 29/578 21/74 32/578

2013 379 16/379 14/51 23/379

7

Hepatitis E in Belgium: Results

2008 2009 2010 2011 2012 2013

Genotype

1 / 1/5 2/10 4/24 2/21 /

2 / / / / / /

3 1/3 2/5 4/10 14/24 10/21 12/14

4 / / 1/10 / / /

Phylogenetic tree

8

Conclusion

• 126 laboratory-confirmed cases with 53 genotyping

• 17% genotype 1

• 81.1% genotype 3 with 63 % 3f and 16% 3c : typical for European swine strains

In Belgium, most clinical hepatitis E cases are caused by genotype 3 and are probablyacquired locally

Future Challenges

• Further genotyping of HEV circulating in humans in Belgium

• Identification of HEV transmission and source of contamination

• Determination of the risk factors of clinical HEV infection in Belgium with a case control study design

• Determination of the full genome sequence of Belgian isolates of HEV from humans and animals

• HEV study in alcoholic patients in collaboration with Erasmus Hospital

Providing data to health autorities on the risk of zoonotic transmission of HEV in humans

9

Acknowledgments

The scientific team of the unit of viral diseases

Thank you for your attention!!!

Questions ?

Dynamic of vaccine coverage in Belgium and in Europa

B. Swennen, MD,MPHESP ULB

ISP-WIV 21 november 2013

20/01/2014

1

Vaccination coverageDefinition:

number of vaccinated / population of susceptibleGood Proxy of immunity level in the population

given that rates of primary and secondary vaccine failure are known

Dynamic nature of the relationship between Disease incidence Vaccine coverage Vaccine adverse events

21 november 2013 2

Chen 1994

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Two Goals of high vaccination coverage To prevent infections from occurring

Directly : in those being vaccinated

Indirectly : in unprotected individuals through herd immunity

To Eliminate or eradicate the pathogens

4 21 november 2013

Vaccination coverage and Vaccination programme Vaccine coverage must be considered as Impact indicator Process indicator

Vaccine coverage is measured for specific groups of population Children School age groups Adult Professional groups: HCW..

21 november 2013 5

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Vaccination coverage in Belgium in 2012 3 studies for Children 18 to 24 months of âge Wallonia : Provac ULB Brussels : ESP- ULB

Flanders :Centrum voor de Evaluatie van Vaccinaties (Vaccin &Infectieziekten Instituut) van de Universiteit Antwerpen en de Dienst Jeugdgezondheidszorg van de Katholieke Universiteit Leuven.

Vaccination Calendar : No change for children since 2010 Cluster sampling studies (Wallonia and Flanders) or

proportional sampling study (Brussels) Population based studies

21 november 2013 6

21 november 2013 7

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21 november 2013 8

Vaccinatiegraadstudie 2012-rapport

Vaccination coverage in Flanders 2012

Vaccination coverage (%) in Wallonia 2012

Vaccin (n=519) 1 2 3 4

Polio 99.8 (518)99.4-100

99.2 (515)98.5-100

99.2 (515)98.5-100

90.4 (469)87.8-92.9

DiphtérieTétanosCoqueluche

99.8 (518)99.4-100

99.2 (515)98.5-100

99.2 (515)98.5-100

90.4 (469)87.8-92.9

Haemophilus 99.2 (515)98.5-100

98.5 (511)97.4-99.5

98.5 (511)97.4-99.5

89.4 (464)86.8-92.1

Hépatite B 98.1 (509)96.9-99.3

97.2 (506)96.2-98.8

97.2 (506)96.2-98.8

89.2 (463)86.5-91.9

RougeoleRubéoleOreillons

94.4 (490)92.4-96.4 /

Méningocoque 89.6 (465)87.0-92.2 /

Pneumocoque 97.1 (504)95.7-98.6

95.4 (495)93.6-97.2

89.2 (463)86.5-91.9 /

Rotavirus 86.5 (449)83.6-89.5

80.2 (416)*76.7-83.6 /

Provac 2012

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Vaccination coverage (%) in Brussels 2012Vaccin (n=538) 1 2 3 4

Polio 99.6 (536)99.1-100

99.3 (534)98.5-100

98.7 (531)97.7-99.7

91.1 (490)88.7-9 3.5

DiphtérieTétanosCoqueluche

99.6 (536)99.1-100

99.3 (534)98.5-100

98.7 (531)97.7-99.7

91.1 (490)88.7-93.5

Haemophilus 97.2 (523)95.8-98.6

97.6 (525)(96.6-98.9)

96.7 (520)95.1-98.2

90.1 (485)87.6-92.7

Hépatite B 96.7 (520)95.1-98.2

96.8 (521)95.4-98.3

96.3 (518)94.7-97.9

89.6 (482)87-92.2

RougeoleRubéoleOreillons

94.1 (506)92.1-96.1 /

Méningocoque 89.4 (481)87.0-92.2 /

Pneumocoque 95.6 (521)93.9-97.3

94.0 (513)92.0-96

90.1 (485)87.6-92.2 /

Rotavirus 77.3 (416)73.8-80.9

72.7(391)68.9-76.4 /

ESP-ULB 2012

Vaccination coverage(%) : complete schedule

Wallonie Bruxelles

Polio +DTPa + VHB +Hib + RRO + MenC+ Pn3

81.8(78.6 - 85.2)

83.5(80.3-86.6)

Polio +DTPa + VHB +Hib + RRO + MenC+ Pn3 +Rota

70.1(66.2 - 74.1)

64.5(60.5 – 68.5)

11 21 november 2013

Provac 2012

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21 november 2013 12

Principal vaccinators of children in Flanders

Vaccinators (%) in Wallonia and Brussels

Hexa1 Hexa4 Rotarix1 Rotateq1

O.N.E. Wal 62.0 58.9 64.0 51.5

O.N.EK&G

Bxl 64.67.3

65.06.3

70.18.7

31.47.8

Pédiatre Wal 30.5 33.2 29.8 38.8

Bxl 21.4 23.2 16.2 52.9

Généraliste Wal 3.4 3.5 3.0 5.8

Bxl 1.6 2.3 1.7 0

Service hospitalier Wal 4.0 4.4 3.3 3.9

Bxl 2.6 2.3 2.5 3.9Provac 2012

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Vaccination coverage in European Countries Switzerland Netherland Germany France UK

21 november 2013 14

21 november 2013 15

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21 november 2013 16

Vaccinatie Coverage Birthtcohort since 1990 in Netherland

RIVM 2011

17

Coverage in Germany

Eurosurveillance 2012

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Vaccination coverage at 2 year In FranceVaccine Dose 1 Dose 3 Dose 4

DT polio 98.5 91.3

Pertussis 98.2 90.8

Hib 97.3 89.2

PCV 96.3 88.6

HBV 64.6

MMR 89.2

MenC 51.5

21 november 2013 18

Adopted from INVS 2012

19

Coverage at 2nd birthday in UK 2012-13

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20

Evolution MMR coverage in England

21 november 2013 21

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Conclusion Vaccination coverage No unique system of measurement Some registers methods (Vaccinnet and in the future e-vax) Certificate at 2 years of age (France…) Specific studies in Germany and Belgium

Level of coverage is one of the element for programme Need for other data -socio –economical status -level of refusal or hesitancy of the patients

21 november 2013 22

Mosquito born diseases in Belgium

Steven Callens, MD, PhD

Ghent University Hospital & University

20/01/2014

1

Outline of the presentation

• The Situation Room• Malaria

• The Q&A section• Is Belgium at risk of mosquito born diseases?

• If yes, which ones?

• What are the conditions that must be met?

• Are they met and will they be met?

• Which is the take home message?

A Typical Situation Room

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My Current Situation Room

My Current Situation Room

http://www.expatica.com/nl/news/dutch‐news/Asian‐tiger‐mosquito‐found‐in‐seven‐Dutch‐locations‐cleanup‐underway_271783.html

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The Current Situation: Malaria• Endogenous Malaria Case

• Belgium, Dec 2010• 64y old man, high fever, splenomegalia, thrombocytopenia

• Automated blood count: • “foreign body” inclusion• Plasmodium confirmed

• Thick smear, serology, PCR

• No contributive medical history• No foreign visits recently

• Visit daughter: B&B Rouen• One woman that stayed in Africa had visited

• One daughter had visited India in sept• No recent airport visits• No gardening, no frequent walk, no visit in

greenhouse, park like paradisio, tropical fair … • Repaired a chimney

• Autochtonous malaria in Belgium?• (Air)port related

• Autochtonous malaria in Europe?• 2001: Two cases of autochthonous P. falciparum malaria in Germany through A. plumbeus (2001).

• Cases Pl. vivax during winter in Finland.• 2009: 8 cases of autochthonous of P. vivaxmalaria were notified from the Peloponnese region, southern Greece.

The Current Situation: Malaria• Presence of vector:

• Identified in more than 100 sites in Belgium in urban site as well as in rural or natural sites. Initially confined to natural forest habitats,

• Strong population expansion all over Belgium and severe nuisance at a local scale.

• There is a habitat shift of this mosquito species:• From natural breeding site treeholes in forests to large manure collecting pits of abandoned and unclean pig stables or in band stores.

• Mosquitoes activity in November cannot be excluded if compatible conditions (ex.: dark, humid and wam as house, unclean pig stables, … ).

• The presence of this mosquito can have possible medical threat as it is vector for WNV or Pl falciparum.

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The Current Situation: Malaria

• Indigenous malaria or malaria acquired in endemic zones

• Induced malaria or non mosquito transmitted

• Odyssean malaria or acquired through imported exotic mosquitoes (suitcase malaria)

• Introduced malaria or autochtonous malaria• Anopheles plumbeus is largely observed in Belgium and has been describedas vector for Plasmodium falciparum but never as hibernating in adult stage.

• Anopheles atroparvus is rare in Belgium and has been described as hibernating in adult stage but never as vector for Plasmodium falciparum.

Risk Assessment

1 ‐ Unusual or unexpected? Unusual Autochthonous malaria can occur but this event is unusual as no risk factors have been identified.

2 ‐ Public health impact? Low/medium/high Low This event stays isolated but must be seen at level of

emerging vectorborne diseases.

3 ‐ Risk for dissemination? Low/medium/high Low No risk of malaria dissemination but must be seen at

level of already existing exotic mosquitoes in Belgium.

4 ‐ Limitation of international movement of goods? No

Considering this particular event, no immediate goods import restriction but it has to be discussed while taking into account the risk of exotic mosquitoes import. The Netherlands are already involved in ongoing surveillance (e.g.: in harbours, in neighbourhood of second‐hand tyres company or plant nursery (lucky bamboo).

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Is Belgium at risk of mosquitoborn diseases?

Europe: Vulnerable to Vector Borne diseases• Increased globalization, landscape management and changing socio economic behavior create suitable conditions for the (re)emergence of vector‐borne diseases in Europe

• Increased tourism

• Increased worldwide trade• Economic variable

• Demographic variable

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How (invasive) mosquitos may affect human health1. Concurrently harbouring novel pathogens

• 18th and 19th centuries in Europe: Ae. aegypti carrying YFV and DENV, causing disease outbreaks in ports

2. Transmitting native pathogens • Dirofilaria transmission in Italy in areas colonized by Ae. albopictus

3. Transmitting novel pathogens that were independently introduced• The most common one for disease emergence, (DENV and CHIKV)

• various time periods elapsed between the introduction of the vector and the first outbreak

• CHIKV transmission: 17 years after the establishment of Ae. albopictus in Italy, after 4 years in southern France

• Depending upon the global context (e.g. frequency and intensity of epidemics in dengue‐endemic areas).

Importation Routes of the Exotic AedineMosquitoes Established or Intercepted in Europe

DOI: 10.1089/vbz.2011.0814

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Abiotic and Biotic Factors

Math to the help!

• C = b m a2 pt/[‐ln(p)]• b = Vector competence (the proportion developing infective pathogen)

• m = Vector density in relation to host density

• a = Daily blood‐feeding rate

• p = Daily survival rate

• t = Duration of the pathogen’s extrinsic incubation period in days

• C = Vectorial capacity = specific to a species population in a defined natural context

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Climate Change… The small stuff

www.eea.europa.eu

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Which are mosquito born diseases?

• Protozoa• Plasmodium: Anopheles (low risk)

• Helminthiasis• Dirofilaria

DOI=10.3389/fphys.2012.00196

Which mosquito born diseases?

• Family Bunyaviridae• Genus Orthobunyavirus

• Bunyamwera virus

• California encephalitis virus

• La Crosse encephalitisvirus (LACV)

• Genus Phlebovirus• Rift Valley fever virus (RVFV)

• Family Flaviviridae• Genus Flavivirus

• Mosquito‐borne viruses

• Zika virus

• Dengue virus group

• Dengue virus (DENV)

• Japanese encephalitis virus group

• Japanese encephalitis virus (JEV)

• Murray Valley encephalitis virus (MVEV)

• St. Louis encephalitis virus (SLEV)

• West Nile virus (WNV)

• Yellow fever virus group

• Yellow Fever virus (YF)

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Which mosquito born diseases?

• Family Reoviridae• Subfamily Sedoreovirinae

• Genus Orbivirus• African horse sickness virus (AHSV)

• Bluetongue disease virus (BTV)• Equine encephalosis virus (EEV)

• Genus Seadornavirus• Banna virus (BAV)

• Family Togaviridae• Genus Alphavirus

• Eastern equine encephalitis virus (EEE)

• Ross River virus (RRV)

• Venezuelan equine encephalitis virus (VEE)

• Western equine encephalitis virus (WEE)

• Sindbis virus (SINV)

• Chikungunya virus (CHIK)

Pfff… (Remember my Situation Room…)

290 298 309

754 760

10071090

1209 1222 1275 1290

1674 1700

2220 2253 22672370

1551 1550 1602 1619

1832 1898

2078

2285

24802618

0

500

1000

1500

2000

2500

3000

1971 1974 1975 1976 1978 1979 1981 1982 1984 1987 1990 1991 1993 1995 1996 1997 1998 1999 1999 2002 2002 2004 2005 2008 2009 2011 2012

Taxonomy: Virus Species

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Japanese Encephalitis (in Europe)• Italy: JEV NS5 gene (expected size, 215 bp) were obtained from tissues of six birds collected in 2000

• Limited JEV circulation has occurred between birds and mosquitoes in Italy but no human cases have been observed, as in Australia since 1995.

• Relatively low availability of amplifying hosts (pigs) in that area• Low vector competence of European Culex pipiens• Low capability of local birds to maintain a persistent JEV circulation or other factors suppressing the JEV epidemic cycle, and

• Limited or absent human exposure.

• Laboratory differential diagnosis of neuroinvasive cases occurring in humans and horses during the mosquito season may have to include JEV in the panel of viruses

Euro Surveill. 2012;17(32):pii=20241 ‐Euro Surveill. 2012;17(32):pii=20242

West Nile Virus in a Belgian traveler• A 73‐year‐old Belgian woman, who had a medical history of lymphoma, traveled to Kavala city (Macedonia, Greece)

• Developed 6‐day history of fever, headache, malaise, nausea, confusion, decline of consciousness, and neck stiffness.

• Latest human cases reported from Italy, Montenegro. Spain reported cases in horses

http://www.ecdc.europa.eu/en/healthtopics/west_nile_fever/west‐nile‐fever‐maps/pages/index.aspx EID. Vol. 19, No. 4, April 2013

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http://www.ecdc.europa.eu/en/healthtopics/west_nile_fever/west‐nile‐fever‐maps/pages/index.aspx ‐ EID. Vol. 19, No. 4, April 2013

Dengue

• Promed Mail: 118 alerts• Dengue in Madeira:

• 3 February 2013: 2 164 cases of dengue infection (Figure 1) from the Autonomous Region of Madeira since 3 October 2012. All reported cases refer to the resident population of the island.

• No deaths or cases of severe dengue have been reported.

• Other cases:• 11 on the Continent [continental Portugal?]

• 70 in 13 European countries, all in returning travelers

http://www.ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?List=8db7286c‐fe2d‐476c‐9133‐18ff4cb1b568&ID=23&RootFolder=%2Fen%2Fpress%2Fnews%2FLists%2FNews&Web=86661a14‐fb61‐43e0‐9663‐0d514841605d Promed Mail 20130318.1591291

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Chikungunya: Italy 2007

Lancet 2007; 370: 1840–46

Which vectors are a threat?

Proven vector in the field

Found infected in field and laboratory. Competence studies having potential role as vector, but no proven vector in the field

Only laboratory. Competence studies having showed potential involvement in transmission

No vector or not known

Inya and Tahyna

DOI: 10.1089/vbz.2011.0814

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Anopheles plumbeus: shift of habitat and risk for autochtonous malaria in Belgium

http://www.belspo.be/belspo/SSD/science/Reports/FinalReport_MODIRISK%20ML.pdf

Anopheles plumbeus (Diptera: Culicidae) in Europe:a mere nuisance mosquito or potential malaria vector?• Contributes significantly to increase malaria transmission risk in Central‐Western Europe for both P. falciparum and vivax1. Proven competence for both parasites

2. Occurence high locally high population densities following exploitation of man made breeding habitats

3. The aggressiveness of the species to humans

4. Longevity for up to two months enabling the parasites to complete their development to the sporozoite stage

DOI 10.1111/1469‐0691.12189

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Climate Change… EAA assessment 2012• Besides invasive mosquitos:

• Ticks and the associated Lyme disease and tick‐borne encephalitis are moving into higher altitudes and latitudes.

• Changes in the geographical distribution of the sandfly vector are occurring in several European countries and there is a risk of human Leishmania cases further north.

• Projected temperature increases in the United Kingdom could increase the risk of local malaria transmission by 8 to 15 %; in Portugal a significant increase in the number of days suitable for the survival of malaria vectors is projected. However, the risk of localised malaria transmission is low.

Conclusion: Vectors are a concern…

• Concern is now rising as both vectors and pathogens are increasingly being introduced by international travel and trade.

• Some of these diseases are emerging or are reappearing after a long period of absence.

• Their occurrence is often associated with changes in ecosystems, human behavior, and climate

• There is a continued need for monitoring vectors…• VBORNET

• MODIRISK

DOI 10.1111/1469-0691.12189

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Conclusion: My (Future) Situation Room

Healthcare-associated infections in the elderly the ECDC supported HALT-2 project

Latour K., Jans B.

Rue Juliette Wytsmanstraat 14 | 1050 Brussels | BelgiumT +32 2 642 57 62 | email: [email protected]

20/01/2014

1

Contents

• Introduction• Why surveillance in LTCF?• The HALT project• Methods• Results

Healthcare-associated infections• Discussion

Introduction

• Surveillance of healthcare-associated infections (HAI) & antimicrobial resistance• In hospitals• In long-term care facilities (LTCF)

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Why surveillance in LTCF?Healthcare-associated infections

Antimicrobial resistanceAntimicrobial use

• Decrease length of stay• Earlier discharge to LTCF• Frequent patient transfers

Resident risk factors• Increased complexity of care (wounds,

catheters…)• Older adults• Decreased immune response• Comorbidities• Impaired functional & cognitive status• Frequent antimicrobial use• …

Institutional risk factors• Home-like character • Frequent contacts between residents &

healthcare workers• Less (qualified) staff, high workloads• No infection control team, no antimicrobial

committee• High number of visiting general practitioners• …

The HALT project

• ECDC funded project

• Healthcare-associated infections and Antimicrobial use in European Long-Term care facilities (HALT)

• To explore HAI & systemic antimicrobial use

• Point prevalence survey (PPS) design• Snapshot: data collected on one single day

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The HALT project

• HALT-1• May to September 2010• 722 LTCFs across 28 EU countries• 111 LTCFs in Belgium (107 nursing homes)

• HALT-2• April to May 2013• 1 181 LTCFs across 19 EU countries• 88 LTCFs in Belgium (87 nursing homes)

HALT-2: Methods

• Surveyor: • Local (i.e. person from LTCF) • External (i.e. person recruited by national centre)

• An institutional questionnaire to collect denominator data and information about antimicrobial policies and infection control resources in the LTCF

• A resident questionnaire for each resident using antimicrobials for systemic use (excl. antivirals) and/or presenting signs/symptoms of active HAI on the PPS day

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HALT-2: Methods

• Active HAI“An infection was active when signs and symptoms of the infection were present on the survey day or if signs and symptoms werepresent in the past but the resident was (still) receiving antimicrobial treatment for that infection on the survey day.”

• Onset of symptoms at least 48h after the resident was (re-)admitted to the LTCF (excluding infections already present or in incubation at the time of (re-)admission)

• All symptoms had to be new or acutely worse

• Exclusion of non-infectious causes of signs and symptoms

HALT-2: Methods

Stone MD, Ashraf MS, Calder J, et al. (2012) Surveillance definitions of infections in long-term care facilites: Revisiting the McGeer criteria. Infect Control Hosp Epidemiol. 10: 965-977

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HALT-2: Results

Belgium EuropeNumber of selected LTCFs1 87 1 051

Number of eligible residents 8 756 77 264Prevalence of residents with at least one HAI

3.6%(n=314)

3.4%(n=2 626)

Prevalence of residents with at least one systemic antimicrobial

5.1%(n=443)

4.4%(n=3 367)

1 Only general nursing homes, residential homes and mixed facilities

HALT-2: Results

Urinary tract infections

31.2%

Respiratory tract

infections36.6%

Skin infections

13.8%

Gastrointesti-nal

infections5.1%

Eye, ear, nose & mouth

infections5.8%

Bloodstream infections

0.3%

Unexplained fever2.8% Other

infections1.5%

Europe:RTI = 31.2%UTI = 31.2%Skin = 22.8%

Belgium%

Europe%

Urinary tract infections (UTIs)Confirmed UTIs 17.5 10.0

Probable UTIs 16.6 21.1Respiratory tract infections (RTIs)

Common cold/pharyngitis 10.8 9.0Flu 1.5 1.2

Pneumonia 3.1 2.6Other lower RTIs 21.2 18.3

Skin infectionsCellulitis/soft tissue/wound 13.2 20.0

Herpes simplex or zoster infections 0.3 0.5

Fungal infections 0.3 1.9Scabies 0.0 0.4

Gastrointestinal infectionsGastroenteritis 5.2 4.2

Clostridium difficile infection 0.9 0.9Eye, ear, nose and mouth

Conjunctivitis 3.1 4.6Ear infections 0.9 0.6

Sinusitis 0.3 0.2Oral candidiasis 0.3 0.5

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HALT-2: Results

Belgium EuropeEstimated number of LTCFs1 1 540 74 793

Estimated number of LTCF beds1 136 272 4 443 049

Prevalence of HAI3.6% 3.4%

Number of residents with a HAI on any given day2 4 660 143 510

Number of residents with a HAI each year3 170 090 5 238 115

1 Only general nursing homes, residential homes and mixed facilities2 Taken into account an occupation rate of 95%3 Taken into account an average duration of an infection episode of 10 days

HALT-2: Discussion• Low prevalence of HAI

• PPS in Belgian hospitals (n=52)• Prevalence of HAI = 7.1%• Pneumonia/lower RTI = 24%, UTI = 18%, surgical site = 18%

• Non-representative data, convenience sample

• Underestimation of the true HAI burden?• Data collected by local surveyors with less experience

in infection control • Not used to apply infection definitions• Seasonal variation?• Difficult to correctly diagnose infections in LTCFs

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HALT-2: Discussion• Underestimation of the true HAI burden?

• Infection diagnosis

• Older adults:• Signs/symptoms differ in older compared to younger adults• Symptoms can be blunted, altered or absent (e.g. fever)• Atypical symptoms (e.g. falls, loss of appetit, change in mental

status)• Communication problems (hearing loss, cognitive impairment)

• LTCF:• Physicians not always present on-site; diagnosis over the phone• Limited access to laboratory and radiological tests• Difficult to obtain specimens of high quality in persons who are

cognitively impaired and/or have physical constraints

HALT-2: Discussion

• Valuable information on HAI (and antimicrobial use) in LTCFs using a standardized and feasible methodology

• Raise awareness for HAI and antimicrobial resistance at European, national and local level

• Extremely motivated LTCF staffs• Despite high workload and lack of infection control

resources and skills• Voluntary participation, no financial incentives

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Thank you for your attention

Questions?

Surveillance of Hospital Acquired Infections in

Belgian NICUs:

the NeoKISS project

Ludo Mahieu, MD, PhD &

NeoKISS working group*

Intensive care = breech of barriers

2

Arterial catheter Endotracheal tube

Subclavian catheter

Nasogastric tube

L. Mahieu2

Why does it matter? Attributable Mortality:

Adults: 25% Neonates: 11% (CONS) Adverse Outcome: • Poor growth & severe Neurocognitive impairment at 2 years .

• Stoll BJ et al. JAMA 2004. • Duration of ventilation & Chronic lung disease

• Lahra M et al. Pediatrics 2009 • Early CRS & Hepatic fibrosis.

• Hermans D et al. J Pediatr Gastroenterol Nutr 2007 • Additional hospital stay (24d) and costs (12.000€)

• Mahieu L et al. J Hosp Infect 2001.

4 L. Mahieu

4

Introduction

• Newborn college: – National surveillance of neonatal morbidity &

mortality data: NICAUDIT report. – Supported by BSN & FOD. – HAI is major morbidity in VLBWI. – Aim: QI programmes (NeoKISS).

L. Mahieu U.Z. Antwerpen 5

Methods

• NeoKISS Germany as a reference – Voluntary to obligatory – VLBWI (< 1500 gram) – Nosocomial HAI

• Primary BSI (clinical, proven, CONS) • Pneumonia • NEC

• 2010 Pilot Fase (4 Belgian NICUs) – Development of a Web-based NEOKISS data entry system – Development of Web-based NEOKISS e-report

– Local incidence data – Benchmarking with National data – Benchmarking with other NICUs possible (anonymous ranking)


Methods

• Demographic • Device utilisation (/ 100 patient days)

– (CVC, PVC, ET, CPAP) • HAI (BSI, Pneumonia, NEC)

– Microbiology, type, source, case definitions, etc… • Calculations

– Incidence rate (/100 patients) – Incidence density (/1000 patient days)– Standardized infection risks (SIR)– Device specific infection density (/1000 device days)

• CVC, PVC, VAP, CPAP • Outcome

– Hospital stay – Mortality rate – AB utilisation (/100 patient days)


RESULTS

Primary Bloodstream Infections

Type of BSI in VLBWI in Belgian NICU* – (number/ 100 BSI).

46%

38%

15%

Percent of BSI

CONS BSIClinical BSIProven BSI

30

Incidence of Primary Bloodstream infections (BSI) - in VLBWI in Belgium*

Category Cumulative Incidence Incidence density/1000 patient days.

Birth weight

N Incidence rate/100 patients

Mean (SD) Median (Q1-Q3)

<500 g 6/8 75.0% 26.08 20 (0-37.97)

500-999 g 63/152 41.4% 10.83 10 (1.21-14.56)

1000 -1499 g 35/281 12.5% 4.62 4 (1.66-6.62)

All 104/441 23.6% 8.01 (5.2) 8 (1.25-11.61)

NICUs: Belgium (n = 7), 2011 data


Graph for Data presentation

7,8

0

2

4

6

8

10

12

14

16

18

13 10 09 Your NIC 11 19 12 02

Primary Bloodstream Infections (BSI) / 1000 patientdays anno 2011.


Standardized infection Rates

Expresses how each unit’s observed incidence deviates from what is expected on the basis of its specific patient case mix and

device use.

SIR >1 is higher then expected SIR < 1 is lower then expected

34

Primary Bloodstream infection (BSI) – Standardized Infection Rates (SIR)

Risk factors after multivariate analysis? Birth weight. CVC duration. Ventilation duration. PVC duration.

Karl Mertens, WIV 35

Primary Bloodstream Infections

Catheter associated.

Incidence Catheter associated BSI in VLBWI - Incidence /1000 catheter days

Category Incidence Density*

Type Catheter

Mean (SD) Median (Q1-Q3)

CVC 12.98 (8.9) 15 (1.52-16)

PVC 5.76 (3.3) 0 (0-9.17)

Overall (CVC+PVC) 11.77 13 (1.5-15.5)

*NICUs: Belgium (n = 7), 2011 Belgian NeoKISS data


Pneumonia

Ventilatory device Associated Pneumonia (ET + CPAP) in VLBWI in Belgium*

(Incidence density/1000 device days)

Category CPAP ET

Birth weight

Mean (SD) Median (Q1-Q3) Mean (SD) Median (Q1-Q3)

<500 g 0 (8) 0 (0-0) 12.5 (8) 0 (0-0.0)

500-999 g 1.58 (6.7) 0 (0-8.1) 8.1 (6.7) 4 (0-4.58)

1000 -1499 g 0.96 (4.6) 0 (0-0) 3.5 (4.6) 0 (0-5.19)

All 1.28 (3.9) 0 (0-1.7) 6.1 (5.3) 4 (0-5.19)

NICUs: Belgium (n = 7), 2011 data.


Trends &

Benchmarking with NeoKISS Germany

2011 vs. 2012

4,67

0,54 0,85

8,01

1,67 1,53

4,73

1,48 0,97

0123456789

BSI Pneumonia NEC

Trend of HAI in VLBWI 2011-2012 – incidence density/ 1000 patient days

German NeoKiss ref

2011

2012

-11%

-41%

-36%

64

Trend incidence density pneumonia in VLBWI: 2011-2012

0

6,1

1,28

0

2,45 1,84

0

1

2

3

4

5

6

7

Ventilator Intubator CPAP

NeoKISS20112012

-60%

+43%

66

Trend Length of stay (days) & AB utilization (/100 patientdays) in VLBWI in Belgium: 2011-2012

29,6

57,9

25,8

54,7

22,7

52

0

10

20

30

40

50

60

70

AB utilization LOS

Germand NeoKISSref20112012

-3.7%

-12%

69

Conclusions

• Benchmarking of HAI; – Beware for case mix (Use Adjusted SIRs).

• Surveillance a tool for Qaulity Improvement? – For Patient: decrease of HAI related morbidities – For National Health Insurance: decreases AB use and

LOS, thus cost of care!

• Data useful for priorities of prevention; – (CPAP) associated pneumonia an emerging problem? – Still more data are needed for better risk analysis!!

71

*Many thanks to …

• NeoKISS working group: – L. Mahieu, L, V. Cossey V, K. Mertens (WIV) , M. Gerard (BICS), C. Lacart,

C. Theyskens, C. Nguyenba, D. Haumont, E. Cavatorta, I. Vandenbossche, J-P Langhendries, M. Tackoen, P. Maton, W. Decaluwe, A. Clerckx (FBSH), G. Naulaers.

• Newborn-College working group: – Drs, Johansson, A. (HUDERF), Cools, F. (UZ Brussel), Plaskie, K., (GZA

Antwerpen), Lecart, C., (Grand Hôpital de Charleroi) , Rigo, J., (CHR Citadelle à Liège), Cornette, L., (AZ Sint-Jan, Brugge), Mathé, C., (CHR Haute Senne, Soignies), Naulaers, G., (UZ Leuven)

• All participating NICUs: – CHU St Pierre, UZ Antwerpen, UZ Leuven, UZ Brussel, AZ Brugge, GZ

Antwerpen, Clinique St Vincent CHC, CHU Tivoli, CHU de Charleroi, Grand Hôpital de Charleroi, Erasme ULB.

Hot topic

Diagnosis and surveillance of Infectious Diseases21 November 2013

Rue Juliette Wytsmanstraat 14 | 1050 Brussels | BelgiumT +32 2 642 54 04 | email: [email protected] | www.wiv-isp.be

20/01/2014

1

Meningococcal B vaccine 20134CMenB (Bexsero)

• Authorised for use by EMA January 2013, currently not available in Belgium

Major difficulties for decision making :• No data on Meningococcal Antigen Typing System (MATS) in

Belgium proportion of strains covered by vaccine is unknown• No data on clinical efficacy: surrogates not validated towards

clinical efficacy for 4CMenB• Duration of protection unclear need for further boosters?• Effect on transmission unclear (efficacy on carriage?)• Co-administration with other routine vaccines is problematic

(Fever, > 2 injections) endanger current program• No data yet on 2+1 schedule• Cost-effectiveness not yet assessed• Serogroup B evolution is unpredictable

Adapted from presentation at Eurovaccine 2013 by T. Grammens

Pertussis: increase in 2012

2

0

100

200

300

400

500

600

2004 2005 2006 2007 2008 2009 2010 2011 2012

Number of cases

Year

Sentinel labs National Reference Center

Why increase?• Change from whole

cell pertussis vaccin to acellularvaccine

• Waning immunity• Genetic changes

B.pertussis• Changes in

surveillance system & diagnosis

www.health.belgium.be > Hoge Gezondheidsraad/Conseil supérieur de la Santé

20/01/2014

2

Poliomyeltitis

Cases in Syria and Israel risk of importation in Europe:

• AFP surveillance • Enterovirussurveillance

• Environmental surveillance?

3WHO. Report of the 27th Meeting of the European Regional Certification Commission for Poliomyelitis Eradication (WHO, 2013)www.ECDC.europa.eu – Increased risk of polio in the EU

Mumps: increase 2012

4

0

50

100

150

200

250

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

Number of cases

week

Manadatory Notifications Flanders Mandatory Notifications Wallonia & Brussels

• Flanders: mandatory notification between 16/06/2012 -01/11/2013

• Brussels & Wallonia: still mandatory

• Mainly in age-group 15-24 years old• 2013: Surveillance through Sentinel Laboratory Network &

Sentinel Network of GP’s• 2013: National Reference Centre Mumps (WIV-ISP)• 2013: Seroprevalence study ongoing

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