1 23 January 2012

Disease burden and source attribution of food-borne illness with microbial subtyping, in Europe

Wilfrid van Pelt

2012 ILSI Annual Meeting,

Phoenix, Arizona, USA

23 January 20122

Thanks to ….RIVM, Bilthoven, the Netherlands● Arie havelaar (disease burden, expert elicitation)Havelaar et al. 2012. Int. J. of Food Microbiology; Havelaar AH, et al. Foodborne Pathog Dis 2008;5:649-59http://www.nationaalkompas.nl/gezondheidsdeterminanten/omgeving/milieu/voedselveiligheid/microbiologisch/incidentie-

sterfte-ziektelast-en-kosten-per-ziekteverwekker-en-blootstellingsroute/

DTU Food, Copenhagen, Denmark● Sara Pires (EU comparison Salmonella source attribution)

University of Oxford, UK● Martin Maiden, Noel McCarthy (Campylobacter source

attribution)

● And many many others

23 January 20123

ObjectivesDisease Burden food born illness● Provide decision makers at governmental level with a tool to

prioritise foodborne pathogens● Quantify the incidence and burden (e.g. DALYs) of pathogens

that can also be transmitted by foodSource attribution (of Disease Burden) of food born illness(microbial subtyping)● Estimate the fraction of cases transmitted by major pathways

food(-animals), environment, direct animal contact and human-human transmission and food groups within the food pathway

23 January 20124

Some EU work on Methods of attribution

● Microbiological approaches1. Microbial subtyping

2. Comparative Exposure Assessment (Evers, IJRAM 2008)

● Epidemiological approaches3. Sporadic case-control studies4. Outbreak data

● Expert elicitations (Havelaar AH, et al. Foodborne Pathog Dis 2008;5:649-59.)

Ad 1. Molecular subtyping– Campylobacter, MLST (Multi Locus Sequence Typing), Wilson 2008, Sheppard, 2009

– Listeria, AFLP (Amplified Fragment Lengths Polymorfism), Little et al. Foodborne Pathog Dis 2010;7(7)

– Salm. Typhimurium, MLVA (Multiple Loci VNTR Analysis), Pelt, unpublished

Salmonella Campylobacter

SalmonellaDK, UK, NE, SE, FR, GE, PLDK

World, world regionsEU, EU regions

Nice extensive overview: The EFSA Journal (2008) 764, 1-43.

MedVetNet WP28 work → Thesis and papers S.Pires DTU-Food

23 January 20125

Reconstructing the surveillance pyramid, 6 pathogens, 7 EU countries NL,DK,DE,SE,UK,IT,PLHaagsma et al. (2012) MedVetNet WPxx

● 6 pathogens causing infectious gastro-enteritis– Thermophilic Campylobacter spp.; Shiga-toxin producing

Escherichia coli O157; Enteropathogenic E. coli (EPEC); non-typhoidal Salmonella spp.; Yersinia enterocolitica

– Cryptosporidium spp.

23 January 20126

CaSa 2002/3: +/- 6500 / yr

Register study: +/46 / yr

Symptomatic Infected General population

General Practices

Laboratories

Hospital

†

NIVEL 1996/9: +/- 23.000 / yr

Sensor 1999:1x / 160 pyr

+/-8600 / yr

2900 / yr

+/- 690 / yr

+/- 52 / yr

GEOPS 2008/9 CaSa 2002/3: +/- 650 / yr

•Episodes gastro-enteritis/yr•Which pathogen (deficit)•Riskfactors•Disease burden/Costs

1x per320 pyr

Salmonella CampylobacterEpidemiological IID studies in NL

23 January 20127

CaSa 2002/3: 6500 / yr

Register study: +/46 / yr

Symptomatic Infected General population

General Practices

Laboratories

Hospital

†

NIVEL 1996/9: +/- 23.000 / yr

Sensor 1999:1x / 160 pyr1x per

320 pyr

+/-8600 / yr

2900 / yr

+/- 690 / yr

+/- 52 / yrGEOPS 2008/9CaSa 2002/3: +/- 650 / yr

Most expensive layer•Incidence pathogens/deficit•Riskfactors•Disease burden/Costs•Complications/comorbidity

Salmonella CampylobacterEpidemiological IID studies in NL

23 January 20128

CaSa 2002/3: 6500 / yr

Register study: +/46 / yr

Infected (sero-respons):symptomatic+a-symptomatic

Symptomatic Infected General population

General Practices

Laboratories

Hospital

†

NIVEL 1996/9: +/- 23.000 / yr

Sensor 1999:1x / 160 pyr

Infected (1996/2007):1x / 10 mnths

(lab x3000)

1x per320 pyrs

+/-8600 / yr

2900 / yr

+/- 690 / yr

+/- 52 / yr

Salmonella Campylobacter

GEOPS 2008/9 CaSa 2002/3: +/- 650 / yr

•Serological studies 1996, 2000, 2007•Also collaboration EU in MedVetNet

1x per3.5 yr(lab x1500)

Epidemiological IID studies in NL

23 January 20129

Cheese incident Salm. Typhimurium DT7Januari 2006 - April 2007, 297 extra lab-confirmed cases ST DT7

salmonellosis(tip of the iceberg).

Labconfirmed: 297 cases

Hospitalized: 60-75 cases

Death (<2yr): 5 - 6

Symptomatic InfectedGeneral population

General Practices

Laboratories

Hospital

†

Doctor visits: +/- 650General Population:+/- 4455 GE-cases

COI: € 1.2 mill

DALY: 54

23 January 201210

Disability Adjusted Life Years

DALY = YLL + YLD

● YLL – mortalitynumber of people,lost life years

● YLD – morbiditynumber of people,years and disability severity weight

Discounting: 0 and 1.5%

l

ll edYLL

l

lll wtnYLD

23 January 201211

Disease burden by pathogen, 2009Havelaar et al. 2012. Int. J. of Food Microbiology

23 January 201212

Ranking of pathogens: Total vs. Individual burdenIn

divi

dual

Bur

denSocietal Burden

23 January 201213

Source attribution using laboratory surveillance

“Pig”“Cattle” “Broilers” “Layers/Egg”“Layers/Egg”“Human”

Black Box•Prevalence contamination•Exposure (ao consumption/amount)•Dose-response (disease)•etc

Salmonellosis in humans

“ /

unknown

“travel/imported/unknown”

Salmonella typing

23 January 201214

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raw cattle productsST ft90,ft132

raw cattle productsST div.

SE Pt14b, Pt5,Pt4, Pt1, Newport monofas.

Manure transportsST DT104

Spanish egg imports

Source attribution using laboratory surveillanceSalmonella (Netherlands)

23 January 201215

Evaluation interventions (Denmark)

23 January 201216

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23 January 201217

Seasonality 2002-2005

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Source attribution subtyping Salmonella

23 January 201218

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Reptile/amfibian N=103

OutbreakN=682

Cattle N=1757

Pigs N=3166

Layers/Eggs

N=5074

Broilers/products N=2560

travel/other

N=1802

Source attribution subtyping Salmonella

Reptiles/Amphibians becoming pet animals

23 January 201219

Attributing human salmonellosis to sources in 24 EU countries using a microbial subtyping approach 2007-9Pires et al. (DTU-food), SCIENTIFIC / TECHNICAL REPORT submitted to EFSA, under review 2011.

23 January 201220

Data from EU countries●Salmonella data available from multiple sources

–Food-animal data:– Standardized Baseline surveys (EFSA)– Community Summary Reports

–Human cases:– European CDC (through EFSA)

–EU animal-food production and trade data– EUROSTAT

–Additional and surrogate data

23 January 201221

ResultsProp. (%) attributed to sources, EU

23 January 201222

ResultsProp. (%) attributed to sources, EU Regions

%

23 January 201223

Conclusion● Data availability for the source attribution model varied substantially among

EU MSs.

● Trade data difficult; Travel data underreported

● Results show– Layers/eggs: most important source of salmonellosis in the EU

– Austria, Czech Republic, Estonia, Germany, Greece, Hungary, Latvia, Lithuania, Luxembourg, Slovenia, Slovakia, Spain and the United Kingdom

– Pigs: second contributor– Most important in Belgium, Cyprus, Finland, France, Ireland, Italy,

Poland and Sweden– Turkeys: Denmark– Broilers: Portugal

23 January 201224

Source Attribution by Expert elicitation(Havelaar AH, et al. Foodborne Pathog Dis 2008;5:649-59)

● Estimates from 16 experts (microbiology, epidemiology, foodscience, foodsafety).

● 17 pathogensPoint of attribution: “kitchen door”● 5 Major pathways

– Food, Environment, Human, Animal, Travel

● 11 Food Groups– Beef/mutton, Pork, Poultry, Eggs, Dairy, Fish/shellfish, Fruit/vegetables, Beverages, Cereal

products, Other food, Human/animal

Source Attribution Campylobacter more difficult

23 January 201225

Source attribution Campylobacter by expert elicitation

Food; 42%

Environment; 21%

Human-Human; 6%

Animal-Human; 19%

Travel; 12%

Beef,Sheep; 4%Pig; 5%

Foodhandler etc; 5%

Composite; 3%

Grains; 2%

Beverages; 2%

Produce; 6%

(Shell-)Fish; 7%

Dairy; 9%

Eggs; 3%

Poultry; 54%

Main transmission routes

Attribution foods

Campylobacter

23 January 201226

Campylobacter sequence typingmulti locus (MLST) and antigen gene typing

Dingle KE, Colles FM, Wareing DRA, Ure R, Fox AJ, Bolton FJ, Bootsma, H.J., Willems, R.J.L. Urwin, R., Maiden, M.C.J. 2001. Multilocus sequence typing system for Campylobacter jejuni. J Clin Microbiol 39:14-23.

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23 January 201227

● Multiple potential sources.

● Different hosts have different Campylobacter types, so disease can be attributed to host sources.

Probabilistic assignment of human disease (o.a. Island model)Wilson et al. (2008). PLoS Genet 26, e1000203

1 2

Clinical isolate genotype probably came from chicken.

23 January 201228

Campylobacter source attributionby MLST typing (New Zealand)Mullner P, French N, et 2009). A Infect Genet Evol. 138

Left: Dutch modelMiddle: Adapted Hald modelRight: Island model

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23 January 201229

ScotlandSheppard, et al. (2009). Clin Infect Dis 48, 1072-1078.

UKWilson et al. (2008). PLoS Genet 26, e1000203.

Campylobacter source attribution by MLST typing

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C DC. jejuni C. coli

23 January 201230

Campylobacter source attribution by MLST typingNetherlandsSmid, et al. (unpublished)

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Down-weighted Pets-Environment

23 January 201231

Conclusions Attribution microbial subtyping● Quantifies role of most important zoonotic sources

+ Where to focus control strategies+ Evaluate intervention/developments over time+ Compare countries―No information transmission routes―Data intensive (representative collections…, up to date)― Pathogen: needs some source specificity

―Not too much sources/foods• Molecular subtyping

+ Allows genealogical source link/traceback (MLST, AFLP,…)―MLVA difficult, no real (short term) genealogical typing

23 January 201232

Conclusions – disease burden and costs● Toxoplasma gondii, Campylobacter spp, rotavirus, norovirus and

Salmonella spp. caused the highest burden of food-related pathogens

● The burden per case was highest for systemic infections: listeriosis and toxoplasmosis, hepatitis.

● Among enteric pathogens, STEC O157 caused the greatest burden per case

● The added burden of sequelae was high for Toxoplasma gondii, Campylobacter spp. and Salmonella spp.

● The cost were highest for rota- and norovirus and Campylobacter spp. (costs of PI-IBS, hepatitis viruses and Toxoplasma gondii unknown)

23 January 201233

Conclusions – foodborne disease in the Netherlands, 2009● There were approximately 650,000 cases of foodborne disease ● The most frequent causes of foodborne disease were toxins of S.

aureus, and C. perfringens, and norovirus● There were approximately 75 fatal cases of foodborne disease● The most frequent causes of death due to foodborne disease were

Salmonella spp., Campylobacter spp. and norovirus● The burden of foodborne disease was approximately 5800 DALYs● The greatest burden of foodborne disease was due to Toxoplasma

gondii, Campylobacter spp., Salmonella spp. and S. aureus toxin● The costs of foodborne disease were approximately 66 million euros● Pathogens causing the greatest costs of foodborne disease were S.

aureus toxins and Campylobacter spp.(costs of PI-IBS, hepatitis viruses and Toxoplasma gondii unknown)

● Two-thirds of the burden of foodborne disease was associated with foods of animal origin

23 January 201234

Conclusions – comparison with other infectious diseases

● 14 enteric pathogens and sequelae – 13,000 DALYs per year

● Lower than pneumonia (72,000)

● Similar to urinary tract infections (15,600) and upper respiratory infections (10,100)

● Higher than AIDS (3,800), meningitis (1,770), tuberculosis (610)

● Our food is safer than ever, but further prevention is warranted!