CRYPTO study 2013-2016

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CRYPTO study 2013-2016 | 15-09-2015

Cryptosporidium: achtergrond informatie

● Verwekker waterdunne diarree

– Verschil in chronische sequela tussen types: C.hominis meer extra intestinale klachten (oa. gewrichtsklachten; beide relapses na aanvankelijk opknappen.)

● Therapie : geen effectieve therapie

● Risicogroep: immuungestoorden : hiv/aids; transplantatie/prednison hoge dosis

● Seizoen: najaar en kleinere voorjaarspiek

● Leeftijd: vooral jonge kinderen:

Cryptosporidium: in NL

● In NIVEL en SENSOR studie: ca. 2% van de cases; bijna niets in controles ( populatie en GP patiënten 1996-1998; microscopie)

● Weinig in eXplosie studie en KIZSS (Kinderdagverblijf 2010-2013 ( PCR))

● In Geops (ziekenhuisopnames GE): opvallend vaak (>7 %) maar vaak dubbelinfecties (PCR)

● GCC studie (GP patienten 4 labs, case controle; PCR)

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Dutch case control study GP population

organism Case Control

< 5yr 5-20 21-50 >50 < 5yr 5-20 21-50 >50

n= 152 313 557 493 104 200 445 428

Pos % Pos % Pos % Pos % Pos % Pos % Pos % Pos %

Giardia 14 9.2 24 7.7 24 4.3 23 4.7 4 3.8 15 7.2 10 2.2 4 0.9

Crypto 12 7.9 9 2.9 21 3.8 4 0.8 5 4.8 2 0.4 2 0.4 1 0.2

4

Bruijnesteijn van Coppenraet LE ea Case-control comparison of bacterial and protozoan microorganisms associated with gastroenteritis: application of molecular detection. Clin Microbiol Infect. 2015 Jun;21(6):. 7 592.e9-592.e19. Epub 2015

Table 4: Positivity for all targets by age category

Age difference detection Cryptosporidium in controls ; 50 yrs cases : 0.8 %; controls 0.2%

GCC study results parasites

5

0

1

2

3

4

5

6

7

8

9

50 yrs

Cryptosporidium % pos per age group

cases

controls

Cryptosporidium: DALYs and Cost of illness

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DALY’s Crypto: 72 DALYS per jaar; 3.1 DALYS per 1000 cases ( Giardia 127, Toxoplasma 3570, Campylobacter 3633) M.-J.J. Mangen et al. Cost-of-illness and disease burden Ranking of food-related pathogens in the Netherlands in 2011. International Journal of Food Microbiology 196 (2015) 84–93

ISIS lab surveillance 2001-2007

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0

10

20

30

40

50

60

70

80

90

100

1-4 5-8 9-12 13-16 17-20 21-24 25-28 29-32 33-36 37-40 41-44 45-48 49-52

Week

Aan

tal g

evallen

/ 1

0.0

00.0

00 in

wo

ners

2001 2002 2003 2004 2005 2006 2007 Cryptosporidium spp.

Incidentie van Cryptosporidium spp gerapporteerd door ISIS, 2001-2007.

ISIS lab surveillance 2001-2007

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0

100

200

300

400

500

600

700

800

900

1000

0 1-4 5-11 12-17 18-34 35-64 64+

Leeftijd

Aan

tal g

evallen

/ 1

0.0

00.0

00 in

wo

ners

Mannen Vrouwen Cryptosporidium spp.

Leeftijds- en geslachts-specifieke incidenties voor Cryptosporidium spp gerapporteerd door ISIS, 2001-2007

0

10

20

30

40

50

60

70

1 5 9 13 17 21 25 29 33 37 41 45 49 1 5 9 13 17 21 25 29 33 37 41 45 49 1 5 9 13 17 21 25 29 33 37 41 45

Week

Nb

2010 2011 2012

Number of Cryptosporidium positive faecal samples by week of confirmation in 4 laboratories*, Netherlands, January 2010 to November 2012

Weeks 36-38: 180 cases 20 in 2010 29 in 2011

Weeks 31-45: 472 cases

108 in 2010 92 in 2011

*CBSL (Hilversum), Haarlem, Saltro (Utrecht) and Labmicta (Enschede)

Nelly Fournet et all Euro Surveill. 2013

80 % C. hominis type IbA10G2 (dominant strain)

Sporadic Cryptosporidium - study design

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Regional GP Laboratories

GP Case patient

Patient visits GP with GI symptoms

GP sends sample to laboratory

1

2

RIVM (Epi&lab)

Laboratory sends B envelope to GP

GP forward A envelope to patient

Laboratory sends the sample for futher speciation/typing

3

3

4

Patient returns questionnaire

5

Cases are approached by email for follow up study of symptoms

6

Study objectives

• To describe the epidemiology of sporadic cryptosporidiosis in the Netherlands.

• To identify risk factors for sporadic cryptosporidiosis in the Netherlands in order to acquire information for control strategies.

4

Case and control definitions

Case definition

• Gastrointestinal illness between April 2 2013 to April 1 2016 and

laboratory confirmation (Cryptosporidium spp.)

Control recruitment

• 5 controls/ case prospectively selected from population register

• ‘Frequency matched’ according to age and area of residence of

cases

• Excluded if diarrhoea 2-4 weeks before

5

Data collection methods

Questionnaire with 200 items

• Symptoms

• Personal hygiene

• Day care attendance

• Travel

• Housing conditions

• Swimming

• Water consumption

• Outdoor activities

• Food history

• Animal contact (pets, farm animals)

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Laboratory and statistical methods

Microbiological

• Cryptosporidium specification by real-time PCR.

Statistical analysis

• Single variable and multivariable logistic regression

• Variables were included if P-value

Deelnemende laboratoria

In totaal 17 labs ● 'S-GRAVENHAGE

● AMSTERDAM

● DELFT

● ENSCHEDE/HENGELO

● GRONINGEN

● HAARLEM

● HEERLEN

● HILVERSUM

● LEEUWARDEN

● MAASTRICHT

● NIJMEGEN

● ROTTERDAM

● TERNEUZEN

● TILBURG

● UTRECHT/SALTRO

● VELDHOVEN

● WOERDEN

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Figure 1: Number of Cryptosporidium cases by date of sample collection and participating laboratory, IDS database (n=1218*). *167 with missing date of sample collection

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April 2013-aug 2015 (week 34)

Binnengekomen monsters 2015 bij RIVM-IDS (datum binnenkomst)

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0

10

20

30

40

50

60

70

80

90

100

jan feb mrt apr mei jun jul aug sep till

15/9)

number total received

number total received

Typering 2013 en 2014

2013 2014

C. hominis 16 % 8 %

C. parvum 84 % 92 %

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C.parvum IIaA15G2R1 meest voorkomend C.hominis IbA10G2 niet het meest voorkomend

30

5

4

11

3

2

1

1

1

1

Zomer 2013

5

3

1

1

1

C. parvum

C. hominis

IIaA15G2R1

IIaA17G1R1

IIaA16G3R1

IIaA15G1R1

IIaA19G3R1

IIaA14G1R1

IIaA14G2R1

IIaA16G1R1

IIaA16G2R1

IIaA20G1R1

IIaA20G2R1

IIdA17G1

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

C. parvum

IIaA19G1R1

4

1

1

1

C. hominis

C. hominis

C. hominis

C. hominis

C. hominis

IbA10G2

IbA9G3

IaA14

IeA11G3T3

IdA17

IdA25

Totaal 19 genotypes

C. parvum

Resultaten typering 132 samples 2015

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0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

jan feb mrt apr mei jun jul aug sep

% C hominis

% C.parvum

Binnengekomen /getest

Cryptosporidium study 2013 : by gender

21

0

5

10

15

20

25

30

female

male

Cryptosporidium study 2015 : by gender

22

0

5

10

15

20

25

2015w262015w272015w282015w292015w302015w312015w322015w332015w34

female

male

&

Project review module, August 2014

Risk factors for sporadic cryptosporidiosis in the Netherlands: a mid-term analysis

of an ongoing case-control study

Laura Nic Lochlainn EPIET Fellow National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Bilthoven, the Netherlands laura.nic.lochlainn@rivm.nl

//upload.wikimedia.org/wikipedia/en/5/5d/ECDC_logo.svgmailto:laura.nic.lochlainn@rivm.nl

Recruitment of participants April 2013- April 2014

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547 cases invited 2,350 controls invited

705 controls recruited

273 cases recruited

50% response

192 cases 587 controls 81 cases excluded due to travel

30% response

118 controls excluded due diarrhoea illness or travel

Factors associated with crypotosporidiosis: multivariable analysis

(na 1 jaar, vooral C.parvum)

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Characteristics Odds ratio* 95% CI

Swam in a river or lake 4.9 2.0-12.0

Had contact with cattle 3.8 2.0-7.0

Ate barbequed foods 3.8 2.4-6.1

Shared house with a case 1.8 1.1-3.0

Played in a sandbox 0.4 0.2-0.7

*Multivariable logistic regression adjusted for age, gender, season and excluding those who travelled

Characteristics of cases of cryptosporidiosis, the Netherlands, 2013-2014

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• 59% females (n=162)

• Median age of cases: 28 years (range 1-95)

0 50 100

Diarrhoea

Fatigue

Stomach pain

Loss of appetite

Weight loss

Headache

Vomiting

Dizziness

Joint pain

Proportion (%)

Komende analyses

● Chronische sequela

– Vragenlijst 4 maanden na begin

– 274 personen die een vragenlijst hebben ingevuld

– Geen gegevens uit NL;

– Paul Hunter in UK: C.hominis meer extra intestinale klachten

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Acknowledgements

RIVM Epidemiology Dept – Jussi Sane – Barbara Schimmer – Wilfrid Van Pelt – Rody Zuidema – Susan Hahné – Laura Nic Lochlainn – Lennard Pisa – Sofie Mooij

RIVM Laboratory Dept

– Titia Kortbeek – Jeroen Roelfsema – Sietze Brandes – Nahid Nozari – Denise Hoek

● Deelnemende labs – 'S-GRAVENHAGE

– AMSTERDAM

– DELFT

– ENSCHEDE

– GRONINGEN

– HAARLEM

– HEERLEN

– HILVERSUM

– LEEUWARDEN

– MAASTRICHT

– NIJMEGEN

– ROTTERDAM

– TERNEUZEN

– TILBURG

– UTRECHT/SALTRO

– VELDHOVEN

– WOERDEN

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Algoritme

● Wordt Cryptosporidium altijd bepaald – ook als het niet specifiek wordt aangevraagd?

– Wanneer wel/wanneer niet?

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Vragen?

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