Campylobacter: is there light at the end of the tunnel?

Campylobacter: is there light at the end of the tunnel? Prof. Jaap A. Wagenaar, DVM, PhD Dept. Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands Central Veterinary Institute, Lelystad, The Netherlands WHO-Collaborating Center for Campylobacter/OIE Reference Laboratory for Campylobaceriosis j.wagenaar@uu.nl

Outline Campylobacter - some facts Source attribution Control options and expected effects Campylobacter in Europe Potential approach to reduce the burden Take home messages

The importance of Campylobacter for humans Campylobacter jejuni/coli is the most common cause of bacterial intestinal disease in Europe Estimated at 10 million cases per year in EU (costs: 2.4 billion) Serious outcome 35-45 per 100,000 ill (EU); 3.5-4.0 hospitalized; 0.15-0.30 fatal Sequelae Guillain Barré Syndrome, Irritable Bowel Syndrome, Reactive Arthritis => contributing heavily to the burden of illness Largest part of the world: no data

Campylobacter in poultry

Campylobacter in poultry newly hatched chicks are Campylobacter free colonisation < 10 days rare - maternal immunity? colonisation is age dependent (organic production) up to 10 9 cfu per gram cecal contents (amplification vessel) asymptomatic and lifelong for broilers, slight decline in older birds almost 100% of birds in a flock become positive within a few days strong seasonality only decline of counts after slaughterhouse

Source attribution Can we estimate the attribution from the different sources to human campylobacteriosis? and estimate the expected impact of control measures?

Human illness source attribution methods

Human illness source attribution methods Case control studies and outbreaks: 24-29% attributed to poultry meat

Human illness source attribution methods

Registered cases Campylobacteriosis incidence in Belgium 1000 900 800 700 600 500 400 300 200 100 0 Dioxin crisis April May June July 1998 1999

jun jul aug sep okt nov dec jan feb mrt apr mei jun jul aug sep okt nov dec jan feb mrt apr mei jun jul aug sep okt Weekly number of cases campylobacteriosis 140 120 Observed Expected Tolerance 100 80 Avian influenza outbreak 60 40 20 0 2002 2003 2004 data from Wilfrid van Pelt, RIVM

Source attribution based on different approaches Case control studies and outbreaks: 24-29% attributed to poultry meat Intervention studies: 40% attributed to poultry meat

Human illness source attribution methods

Multi Locus Sequencing Typing (MLST) DNA-sequence based method Strains from different sources (chicken, cattle, dog, human, pigs, environment) All information in 1 database (Oxford, UK) Mathematical modelling.. Outcome: what strains in humans are most likely from..

Source attribution based on different approaches Case control studies and outbreaks: 24-29% attributed to poultry meat Intervention studies: 40% attributed to poultry meat Microbial subtyping (MLST): 50-80% attributed to poultry

The goal is to estimate the relative contribution (%) of different (amplifying) reservoirs for Campylobacter to human infections It provides no information on the transmission pathways by which Campylobacter arrives to humans from the different reservoirs Source attribution information Casecontrol information

Results Source attribution

Interventions Intervention in the poultry meat production chain can prevent potentially 30-40% of the human infections at meat consumption level Intervention in the primary production can prevent potentially up to 80% of the human infections 20-30% 50-80% other sources

Interventions in the poultry meat production chain

What are we aiming for? Preferably absence in flocks, second best: reduced cecal concentration at slaughter If colonization cannot be prevented in primary production, the processing plant is in charge Eliminate the heavily contaminated carcasses Quantitative risk assessment models indicate that the incidence of campylobacteriosis associated with consumption of chicken meals could be reduced 30 times by introducing a 2 log reduction of the number of Campylobacter on the chicken carcasses

What measures in primary production? Prevention of introduction of Campylobacter into the broiler houses reduced fraction of positive flocks Increased resistance of broilers to become colonized reduced fraction positive flocks and (potentially) decreased Campylobacter counts/gram cecal contents Decreased concentration of Campylobacter in intestines just before slaughter Decreased concentration in gut contents associated with lower carcass counts.

Risk factors for farms to be Campylobacter positive (input for intervention) Positive association with colonization Thinning Other animals Other poultry houses Age Water supply Negative association with colonization Implementation of biosecurity measures

On-farm interventions Biosecurity (including fly screens) Thinning, consistently & rigorously applied, only indoor! Feed and water additives (acids, competitive exclusion, probiotics) Vaccination Phage therapy Genetic resistance Bacteriocines

Dr. Ruff Lowman Ruff Biosecure Inc.

cfu/g pfu/g Campylobacter colonization: bacteria only 1,00E+10 1,00E+09 1,00E+08 1,00E+07 1,00E+06 1,00E+05 1,00E+04 1,00E+03 1,00E+02 1,00E+01 1,00E+00 0 5 10 15 20 25 30 35 40 45 day Average CFU Average PFU Campylobacter inoculation

cfu/g pfu/g Campylobacter colonization: therapeutic treatment 1,00E+10 1,00E+09 1,00E+08 1,00E+07 1,00E+06 1,00E+05 1,00E+04 1,00E+03 1,00E+02 1,00E+01 1,00E+00 0 5 10 15 20 25 30 35 40 45 day Phage dosage Average CFU Average PFU Campylobacter inoculation

Quantification of measures

Effect of interventions based on QMRA (request from EFSA) 100% risk reduction can be achieved by irradiation/cooking > 90% risk reduction can be achieved by freezing for 2-3 weeks or reduction of the concentration in intestines at slaughter by > 3 log units; 50-90% risk reduction can be achieved by freezing for 2-3 days, hot water or chemical carcass decontamination with lactic acid, acidified sodium chlorite or trisodium phosphate 50-90% risk reduction by fly screens on farms (based on data from Denmark only) Up to 50% risk reduction by modifications of primary production, restriction of slaughter age to a max 28 days (only indoor flocks) discontinued thinning 39

Economic aspects http://ec.europa.eu/food/food/biosafety/salmonella/other_act_en.htm

Costs and benefits analysis

Campylobacter in Europe: EU data

EFSA-ECDC Zoonoses report 2011

Campylobacter trend EU

EU baseline study in 2008 Includes flocks and carcasses of broilers Objectives: 'baseline' prevalence in all member states in ceca and carcasses (neck skins) Enumeration of Campylobacter from neck skins Inclusion: 10,132 flocks in 561 slaughterhouses in 26 EU member states (+NO&CH)

Luxembourg

Luxembourg France UK

Dutch approach: process hygiene criterion To control contamination of end-products in industrial slaughter plants for broiler chickens (carcasses after chilling) Treshold based on risk assessment models 1000 cfu/gram neck/breast skin Not complying is a sign that hygiene of the slaughter plant should be improved (=> develop and implement a plan for improvement) Not complying batches will not withdrawn Discussion about introduction at EU-level 51 CONTROLLING CAMPYLOBACTER ON BROILER MEAT: THE DUTCH APPROACH March 13, 2013

FSA- UK

The FSA expects industry to focus its actions to: continue to improve the effectiveness of biosecurity measures on farms to prevent flock colonisation with campylobacter ensure that steps involved in slaughter and processing are effective in preventing contamination of carcasses continue to work on packaging and other initiatives that reduce cross contamination in the consumer and food service kitchen develop and implement new interventions that reduce contamination when applied at production scale

The role of the consumer!!!

Dr. Henk van der Zee, Food Inspectorate, the Netherlands

Take home messages Up to 80% of human campylobacteriosis is poultry derived with 20-40% through poultry meat Options for intervention in primary production are still (economically) limited and restricted to indoor production (animal welfare conflicting with food safety!) Efforts on primary production AND postharvest Elimination of the highly contaminated carcasses reduces the human burden considerably Potential approach: process hygiene criterium To survive as risk manager: do not make any promise for reduction for the future!

Thanks to... Albert de Boer Eelke Pothoven Ria van der Hulst Wilma Jacobs Frans Putirulan Nico Bolder Fimme Jan van der Wal Birgitta Duim Peter Willemsen Linda van der Graaf Conny van Solt Paulo de Boer Miriam Koene Esther Gaasbeek Rene Achterberg Ellard Kruijt Dik Mevius Alan Rigter Kees Veldman Jeroen Dijkstra Marga Japing Arie Havelaar Marcel van Bergen Joost Smid Twan van Gerwe WHO Global Food borne Infections Network Wilfrid van Pelt Hubert Endtz Diane Newell Lapo Mughini Gras Ingrid Friesema Nigel French Rob Tauxe Charles Hofacre Irving Nachamkin Ruwani Kalupahana Rob Lake Patrick McDermott Shaohua Zhao

April 2002.. 92 children and 3 teachers visited a farm 57 children and 3 teachers drunk fresh milk from the milktank

Six days after the farm visit.. 28 children ill (watery diarrhoea, some with blood and fever >40 C) common exposure: farm visit questionnaire: milk

Relationship milk/case Case: Yes No total Milk: Yes 28 29 57 No 2 33 35 Total 30 62 92

Dose-respons relation Case: yes no total %-case rel.risk Milk: No 2 33 35 6 1.0 1 swig 2 10 12 17 2.9 1/2 cup 7 11 18 39 6.8 1 cup 13 8 21 62 10.8 2 cups 6 0 6 100 17.5 total 30 63 92

Culture of Campylobacter 17 days after the visit 18 samples: 11 positive direct (all patients) 1 positive after enrichment (control) 6 negative (all controls) no sample from the milktank

Discussion Farmer was not convinced Milk can be contaminated with feces Many outbreaks described Consumption of raw milk?

The importance of Campylobacter Campylobacter jejuni/coli is the most common cause of bacterial intestinal disease in Europe Estimated at 10 million cases per year in EU27; costs 2.4 billion Incidence and consequences of infection are high 35-45 per 100,000 ill; 3.5-4.0 hospitalized; 0.15-0.30 fatal. Underreporting is common true rates 10-100X EFSA Journal 2010; 8(1):1437