foodborne illnesses and antibiotic resistance associated with zoonotic pathogens michael doyle

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Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

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Page 1: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Illnesses and Antibiotic Resistance Associated with

Zoonotic Pathogens

Michael Doyle

Page 2: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens

● Major zoonotic foodborne bacterial pathogens▲ Dissemination to foods▲ Prevalence in livestock and poultry▲ Prevalence in foods of animal origin

● Trends in foodborne illnesses caused by zoonotic pathogens

● Foodborne outbreak and sporadic case data● Public health issues associated with antibiotic-

resistant foodborne pathogens

Page 3: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens

● Types of antibiotic-resistant foodborne pathogens in USA

● Emergence and incidence of antibiotic-resistant foodborne pathogen infections▲ Risk factors associated with acquiring antibiotic

resistant foodborne microbial infections● Trends in prevalence of antibiotic-resistant zoonotic

foodborne pathogens in animals, foods and human illness

Page 4: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Major Bacteriological Causes of Enteric Foodborne Illness in USA

● Campylobacter jejuni - estimated 2.4 million cases/yr

● Salmonella sp. - estimated 1.4 million cases/yr

● E. coli O157:H7 - estimated 73,000 cases/yr

P. Mead et al. Emerging Infect. Dis. 5:607-625 (1999)

Page 5: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Reservoirs of Enteric Foodborne Pathogens

● Carried in intestinal tract of wild and domestic animals (including cattle, poultry, and swine) and/or symptomatic and occasionally asymptomatic people▲ Includes Salmonella, Campylobacter,

enterohemorrhagic E. coli O157:H7 (principally cattle)

Page 6: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Primary Sources of Enteric Foodborne Pathogens that

Contaminate Foods

● Animal manure ● Human feces

Page 7: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Transmission of Enteric Foodborne Pathogens to Foods

● Direct or indirect contact with animal or human feces▲ Fecal matter can contaminate foods through:

♦Use as a soil fertilizer in fields♦Polluted irrigation or processing water♦Defecation by animals in vicinity of produce fields or

processing areas♦Presence on contact surfaces of food handling equipment♦Transmission by insects such as flies♦Human carriers with poor personal hygiene harvesting or

handling foods

Page 8: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

The Manure Glut: A Growing Environmental Threat

● Five tons of animal manure is produced annually nationwide for every person living in the United States▲ The amount of animal manure is 130 times greater than

the amount of human waste produced▲ Cattle, hogs, chickens and turkey produced an estimated

1.36 billion tons of manure in 1997

Democratic Staff of U.S. Senate Agriculture Committee

(1998) “Animal Waste Pollution in America: An Emerging

National Problem”

Page 9: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Animal Solid Waste (Tons/yr)

Cattle 1,229,190,000

Hogs 116,652,300

Chickens 14,394,000

Turkeys 5,425,000

TOTAL 1.36 billion

The U.S. Manure Glut (1997 estimates)

Page 10: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Percentage of Great Britain Livestock Manures Contaminated with Zoonotic Microbes

Cattle Swine Poultry Sheep

Pathogen Fresha Storedb Fresh Stored Fresh Stored Fresh Stored

E. coli O157:H7 13.2 9.1 11.9 15.5 NDc ND 20.8 22.2

Salmonella 7.7 10.0 7.9 5.2 17.9 11.5 8.3 11.1

Campylobacter 12.8 9.8 13.5 10.3 19.4 7.7 20.8 11.1

a Fresh, collected from location in which depositedb Stored, collected from lagoon or farm yard manure heapc ND, not determined

M. L. Hutchison et al. Lett. Appl. Microbiol. 39:207-214 (2004)

Page 11: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Cell Numbers of Zoonotic Pathogens in British Livestock Manures

Cell No. (CFU/g) of pathogen

Cattle Swine Poultry Sheep

Pathogen Fresha Storedb Fresh Stored Fresh Stored Fresh Stored

E. coli O157

Geo Mean 1X103 3X102 4X103 1X103 NDc ND 8X102 3X102

Max 3X108 8X104 8X105 2X104 ND ND 5X104 5X103

Salmonella

Geo Mean 2X103 3X103 6X102 6X102 2X102 4X103 7X102 6X103

Max 6X105 7X106 8X104 2X103 2X104 8X103 2X103 6X103

Campylobacter

Geo Mean 3X102 5X102 3X102 2X103 3X102 6X102 4X102 1X102

Max 2X105 2X105 2X104 1X105 3X104 9X102 2X103 1X102

a Fresh, collected from location in which depositedb Stored, collected from lagoon or farm yard manure heapc ND, not determined

M. L. Hutchison et al. Lett. Appl. Microbiol. 39:207-214 (2004)

Page 12: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Factors Associated with Presence of Salmonella in Cattle on Conventional and Organic Dairy Farms

● Studied dairy cattle for 1 yr (2000 - 2001) on 129 conventional and organic farms in MN, WI, MI and NY

● Factors associated with Salmonella fecal shedding by cattle:▲ Farms with ≥ 100 cows more likely Salmonella-pos than

smaller farms (OR = 2.6; 95% CI, 1.4 - 4.6)▲ Cows designated sick by farm personnel (OR = 2.5; 95% CI,

1.7 - 3.7)▲ Cows within 14 days of calving (OR = 1.8; 95% CI, 1.1 - 2.8)▲ Cows due for culling within 14 days (OR = 1.9; 95% CI, 1.0 -

3.4)▲ Midwestern states were more likely to have Salmonella-

positive samples than NY▲ Highest Salmonella shedding in summer, then fall, spring and

winter

C. P. Fossler et al. Prev. Vet. Med. 67:39-53 (2005)

Page 13: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Factors Associated with Presence of Salmonella in Cattle on Conventional and Organic Dairy Farms

● Environmental samples more likely to be Salmonella-positive:▲ Samples from pens of sick cattle (OR = 7.4; 95% CI, 3.4 -

15.8)▲ Manure storage areas (OR = 6.4; 95% CI, 3.5 - 11.7)▲ Maternity pens (OR = 4.2; 95% CI, 2.2 - 8.1)▲ Haircoats of cattle to be culled (OR = 3.9; 95% CI, 2.2 - 2.7)▲ Milk filters (OR = 3.3; 95% CI, 1.4 - 5.7)▲ Cow waterers (OR = 2.8; 95% CI, 1.4 - 5.7)▲ Calf pens (OR = 2.7; 95% CI, 1.3 - 5.3)▲ Bird droppings from cow housing (OR = 2.4; 95%, CI 1.3 -

4.4)

C. P. Fossler et al. Prev. Vet. Med. 67:39-53 (2005)

Page 14: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Prevalence of Salmonella in Meat and Poultry Determined by USDA-FSIS Pathogen Reduction/HACCP Verification Testing Program

Calendar Year

Broiler Carcasses

Ground Chicken

Ground Turkey

Steer & Heifer Carcasses

Bull & Cow Carcasses

Ground Beef

Hog Carcasse

s

(% Positive)

Baseline

(Pre-1998) 20 44.6 49.9 1.0 2.7 7.5 8.7

1998 10.8 4.2 36.5 0 1.1 6.4 5.8

1999 11.4 16.2 31.6 0.3 2.2 4.3 9.8

2000 9.1 13.8 25.7 0.4 2.2 3.3 6.2

2001 11.9 19.5 26.2 0.6 2.4 2.8 3.8

2002 11.5 29.1 17.9 0.3 1.7 2.6 3.2

2003 12.8 35.5 25.4 0.4 1.5 1.7 2.5

2004 13.5 25.5 19.9 0.3 0.8 1.6 3.1

2005 16.3 32.4 23.2 0.6 1.3 1.1 3.7

2006 11.4 45.0 20.3 0.3 0.8 2.0 4.0

USDA-FSIS (http://www.fsis.usda.gov/OPHS/haccp/salm6year.htm)

Page 15: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Number of Confirmed E. coli O157:H7-Positive Ground Beef Samples by USDA-FSIS

Calendar Year No. Positive/No. Samples (% Positive)

2000 55/6,375 (0.86%)

2001 59/7,010 (0.84%)

2002 55/7,025 (0.78%)

2003 20/6,584 (0.30%)

2004 14/8,010 (0.17%)

2005 19/10,976 (0.17%)

2006 20/11,779 (0.17%)

USDA-FSIS (http://www.fsis.usda.gov/OPHS/ecoltest/tables1.htm)

Page 16: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Incidence of cases of Campylobacter, Salmonella, and Escherichia coli O157 infections under surveillance in the Foodborne Diseases Active Surveillance Network (Food Net), 2000 - 2006

National HealthPathogen Year No. of cases/100,000 persons Objective for 2010

Campylobacter 2000 15.72001 13.82002 13.42003 12.62004 12.92005 12.9 12.3

Salmonella 2000 14.42001 15.12002 16.12003 14.52004 14.72005 14.6 6.8

E. coli O157 2000 2.02001 1.62002 1.72003 1.12004 0.92005 1.1 1.0

U.S. Centers for Disease Control and Prevention

Page 17: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Sporadic Campylobacter jejuni Infections in Rural Michigan (2000 - 01)

● Risk factors identified:▲ Persons engaged in poultry husbandry had increased odds

of campylobacteriosis (OR = 6.88, 95% CI 1.44 - 33.0)♦Dose-response relationship between number of poultry

contacts and campylobacteriosis▲ Estimated 18% of Campylobacter cases occurring in rural

areas are attributable to poultry husbandry

R. Church Potter et al. Am. J. Publ. Health 93:2118-2123 (2003)

Page 18: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Sporadic Campylobacter Infections in the United States (1998 – 99)

Risk Factors

Odds

Ratio

Population Attributable Fraction (%)

Ate chicken prepared at a restaurant 2.2 24

Ate nonpoultry meat prepared at a restaurant 1.7 21

Had contact with animal stool 1.4 6

Had pet puppy 3.4 5

Had contact w/farm animals (person >12 yrs) 2.0 4

Ate turkey prepared at restaurant 2.5 4

Drank untreated water 3.3 3

Ate undercooked or pink chicken 2.1 3

Had contact w/farm animals (person 2<12 yrs) 21.0 2

Drank raw milk 4.3 1.5

C. Friedman et al. Clin. Infect Dis. 38(Suppl 3): S285 (2004)

Page 19: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Acquiring Salmonella Typhimurium Infection (1996 – 97)

● Risk factors identified in a multivariate model:▲ Receiving 1 antibiotic in the ACKSSuT group during the 4

weeks preceding onset of illness (OR = 3.1; 95% CI, 1.3 - 7.3)

▲ Traveling outside the United States during 5 days preceding illness (OR = 19.4; 95% CI, 2.2 - 172.4)

▲ Eating fried eggs prepared outside the home (OR = 4.2; 95% CI, 1.4 - 12.9)

M. K. Glynn et al. Clin. Infect. Dis. 38 (Suppl 3):S227-S236

(2004)

Page 20: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Sporadic Salmonella Enteritidis Infections in the United States (1996 – 97)

● Risk factor identified:▲ Chicken prepared outside the home (mOR = 2.8)

♦Accounted for 27% of SE cases

A. C. Kimura et al. Clin. Infect. Dis. 38 (Suppl 3): S244 (2004)

Page 21: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Sporadic E. coli O157:H7 Infections in the United States, 1996-1997

Risk Factors

Odds Ratio

Population Attributable Risk (%)

Ate at table-service restaurant 1.7 20

Ate pink hamburger at home 5.0 8

Ate pink hamburger away from home 5.0 7

Visited farm with cows (persons ≥ 6 yrs) 10 8

Lived on or visited farm (persons < 6 yrs) 5.2 6

Child ≤ 2 yrs of age in household (persons < 6 yrs) 5.4 6

Used an immunosuppressive medication (persons ≥ 6 yrs)

11 5

H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3): S271 (2004)

Page 22: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Fresh Produce

Fresh Vegetables and Fruits Have Become

Major Vehicles of Foodborne Pathogens,

especially E. coli O157:H7

Page 23: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Categories of U.S. Foodborne Outbreaks1996 - 2005

Food Category No. of Outbreaks No. of Cases

Processed Foods 44 2,957

Produce 64 8,151

Sprouts 25 1,565

Seafood 120 2,567

Eggs 234 6,572

FDA 2006

Page 24: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Outbreaks Related to Fresh Produce, 1973-1997: Specific Food Vehicles Implicated in

190 Outbreaks

● Generic or multiple: 105 outbreaks ● Lettuce 25● Melon 13● Seed sprouts 11● Apple or orange juice 11● Berry 9● Tomato 3● Green onion 3 ● Carrot 2● Other 8

S. Sivapalasingam et al. J. Food Protection 67:2342-2353 (2004)

88% of outbreakswith one specificvehicle

Page 25: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Outbreaks Reported to CDC1998-2002*: Spectrum of Produce Implicated

in 249 Outbreaks

● Generic or multiple 144 outbreaks

● Lettuce 22● Sprouts 14● Juice 10● Melon 9● Tomato 8● Berries 6● Cilantro 4● Mango 4● Other produce items 17

67% of outbreakswith single vehicle

(*Preliminary information) CDC

Page 26: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

E. coli O157:H7 Outbreak Associated with Bagged Fresh Spinach (Aug – Sept 2006)

● 205 cases of E. coli O157 infection in 26 states and Canada▲ 31 cases of HUS, 103 hospitalizations, 3 deaths

● Implicated vehicle – Bagged fresh spinach (Baby Spinach)▲ Outbreak E. coli O157 strain isolated from 13 bags of

baby spinach in 11 states▲ Grown in Salinas Valley, California

U.S. Food and Drug Administration (Sept 28, 06) www.fda.gov/bbs/topics/NEWS/2006/NEW01466.html

California Food Emergency Response Team. Final Report, Investigation of an Escherichia coli O157:H7 Outbreak Associated with Dole Pre-Packaged Spinach (March 21, 2007)

Page 27: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

E. coli O157:H7 Outbreak Associated with Bagged Fresh Spinach

● Traced to 50-acre plot on the Paicines Ranch in San Benito County, CA▲ Plot was in the second year of a 3-year transition to organic

production; most of land on this ranch used for cattle grazing (grass-fed beef)

▲ 45 of 351 (13%) of environmental samples in and around the Paicines Ranch were E. coli O157:H7-positive

♦Outbreak strain of E. coli O157 confirmed from 26 of 45 E. coli O157:H7-positive samples

♦These were from cattle feces (15 samples), wild pig (7 samples), stream water (2 samples) and soil (2 samples)

Page 28: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

E. coli O157:H7 Salinas Valley-Grown Spinach-Associated Outbreak

● Many creeks and streams near the Salinas Valley spinach fields were known to carry generic E. coli and E. coli O157:H7▲ Included were the Salinas River, Gabilan Creek, Towne

Creek, Tembladero Slough and Old Salinas River Estuary

▲ Some waterways had ≥ 12,000 E. coli/100 ml

M. Cone Los Angeles Times, Sept 21, 2006

Page 29: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

E. coli O157:H7 Outbreak Associated with Bagged Lettuce (Taco Johns) (December 2006)

● 81 cases of E. coli O157 infection in 3 states▲ 2 cases of HUS, 26 hospitalizations

● Implicated vehicle – Bagged, fresh-cut lettuce▲ Grown in California’s Central Valley▲ Outbreak E. coli O157:H7 strain isolated from 2

environmental samples from 2 dairy farms near lettuce-growing area

U.S. Food and Drug Administration

www.fda.gov/bbs/topics/NEWS/2007/NEW01546.html

Page 30: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Persistence of E. coli O157 on Vegetables and in Soil

● E. coli O157 survival on produce:▲ Parsley – 177 days▲ Carrots – 175 days▲ Onions – 84 days▲ Leaf Lettuce – 77 days

● E. coli O157 survival in soil:▲ Parsley – 217 days▲ Carrots – 196 days▲ Onions – 168 days▲ Leaf lettuce – 154 days

M. Islam et al., J. Food Protect. 67:1365 (2004); Food Microbiology 22:63 (2005)

Page 31: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

● Once E. coli O157:H7 are introduced into soil or onto seedlings, either via contaminated irrigation water or compost, these bacteria can contaminate for months the vegetables and soil in which vegetables are grown

Page 32: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Public Health Issues Associated with Antibiotic-Resistant Foodborne Pathogens

● May be failure of drug treatment by critical antibiotics needed for human therapy, especially important for systemic infections

● May be increased risk of infection to people taking antimicrobials to which pathogen is resistant

● May be more severe manifestations of illness associated with some drug-resistant pathogens▲ For example, longer duration of illness, and more

systemic infections and hospitalizations● Possible co-selection of virulence traits (e.g., toxin-encoding

genes) associated with antimicrobial-resistant microbes

Page 33: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Clinical Importance of Selected Antibiotics Associated with Foodborne Pathogens

● Ceftriaxone -- drug choice (cephalosporin) for treatment of severe salmonellosis in humans, especially children

● Ceftiofur -- only cephalosporin approved for systemic use in food animals in the United States▲ Ceftiofur-resistant microbes exhibit decreased

susceptibility for extended-spectrum cephalosporins● Erythromycin -- drug of choice for treatment of severe

campylobacteriosis● Ciprofloxacin -- used for the empirical treatment of

gastroenteritis and is recommended for treatment of infections caused by macrolide (erythromycin) resistant campylobacters

Page 34: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Examples of Antibiotic-Resistant Foodborne Pathogens in the United States

● Multidrug-Resistant Non-Typhi Salmonella▲ Salmonella Typhimurium DT104 - R-type: ACSSuT

♦Five agents: ampicillin, chloramphinicol, streptomycin, sulfamethoxazole, tetracycline

▲ Salmonella Newport - R-type: MDR-Amp C♦Nine agents: ampicillin, chloramphenicol,

streptomycin, sulfamethoxazole, tetracycline, amoxicillin-clavulanic acid, cephalothin, cefoxitin, ceftiofur, (and decreased susceptibility to ceftriaxone)

● Ciprofloxacin-resistant Campylobacter

Page 35: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Examples of Antibiotic-Resistant Foodborne Pathogens in the United States (Cont’d)

● NOT issue with E. coli O157:H7▲ Antibiotic treatment is contraindicated because of

potential exacerbation of manifestations of illness (renal failure)

● Vancomycin-resistant Enterococcus faecium and E. faecalis▲ Largely hospital-acquired infections in intensive care

units; food not identified as major vehicle of transmission in USA

Page 36: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Antibiotic Treatment of Salmonella Infection

● Not needed for mild diarrhea

● Used to prevent complications in neonates, immunosuppressed, and persons > 50 years of age

● Life-saving in invasive infections (e.g., meningitis)

● Important antibiotics include amoxicillin, ceftriaxone, ciprofloxacin, trimethoprim-sulfa

Page 37: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Dominant Multidrug-Resistant Salmonella from Humans in United States, 2002

● Four multidrug-resistant strains accounted for 8% (169/2009) of non-Typhi Salmonella isolates from humans assayed by CDC NARMS▲ S. Typhimurium R-type ACSSuT (21% of all isolates of S.

Typhimurium), includes MDR DT104▲ S. Newport MDR-Amp C (22% of all isolates of S. Newport)▲ S. Typhimurium R-type AKSSuT (6% of all S. Typhimurium)▲ S. Heidelberg R-type AClCfCp (8% of all S. Heidelberg)

Centers for Disease Control and Prevention National Antimicrobial

Resistance Monitoring System for Enteric Bacteria, 2002

Page 38: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Acquiring Multidrug-Resistant Salmonella Typhimurium DT104 Infections in the

United States

● Case-control study using FoodNet data for MDR S. Typhimurium infections between 1996 - 1997

● Risk factors identified in a multivariate model:▲ Receiving an antibiotic(s) in the ACKSSuT group during

the 4 weeks before illness (OR = 5.5; 95% CI, 6.3 - 23.8)▲ Consuming eggs prepared outside the home during 5

days preceding illness (OR = 4.4; 95% CI, 1.2 - 16.6)

M. K. Glynn et al. Clin. Infect. Dis. 38 (Suppl 3):S227-S236

(2004)

Page 39: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Factors for Acquiring Salmonella Typhimurium DT104 Infection in Canada

● Case-control study between 1999 - 2000 of sporadic Canadian cases of diarrheal illness caused by S. Typhimurium DT104

● Risk factors included:▲ Antibiotics taken within 4 wks before illness (OR = 5.2,

95% CI 1.8 - 15.3)▲ Living on a livestock farm (OR = 4.9, 95% CI 1.9 -

18.9)▲ Recent travel outside Canada (OR = 4.1, 95% CI 1.2 -

13.8)

K. Doré et al. Epidemiol. Infect. 132:485-493 (2004)

Page 40: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Multidrug-Resistant Salmonella Newport

● Increase in human cases of MDR-S. Newport infections from 0% in 1996 to 3% in 2002 of non-Typhi Salmonella cases

● Increase in S. Newport isolates associated with human infections that were MDR-Amp C, from 0% in 1996-97 to 22% in 2002

Page 41: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Emergence of MDR Salmonella Newport Infections Resistant to Cephalosporins in the United States

● In Massachusetts, isolation of S. Newport MDR-Amp C among S. Newport isolates from humans increased from 0% in 1998 to 53% in 2001

● Case-control study revealed Newport MDR-Amp C was:▲ Domestically acquired▲ Associated with exposure to a dairy farm

A. Gupta et al. J. Infect. Dis. 188:1707-1716 (2003)

Page 42: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Vehicles of Outbreaks of S. Newport MDR-Amp C Infection

● Outbreaks first reported in 1999 in United States

● Examples of food vehicles▲ Unpasteurized cream▲ Cheese made from unpasteurized milk▲ Ground beef▲ Tomatoes▲ Turkey▲ Cilantro▲ Dish containing goat’s blood

Page 43: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Emergence of Multidrug-resistant Salmonella Newport in United States

● The incidence of S. Newport human illness increased markedly in the late 1990s

● The increase in human S. Newport illness has been driven by an increase in a highly resistant strain, "Newport MDR-AmpC"

● Illness due to Newport MDR-AmpC is also emerging in cattle● Risk factors for human illness include contact with cattle and

consumption of bovine products (e.g., ground beef, unpasteurized cheese)

Patricia Griffin, Centers for Disease Control and Prevention, CSTE Annual Meeting 2002

Page 44: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Comparison of S. Typhimurium DT104 with S. Newport MDR-Amp C

S. Typhimurium DT104 S. Newport MDR-Amp C

● Illness in cattle ● Illness in cattle

● Illness in persons in contact with

cattle

● Illness in person in contact with

cattle

● Bovine food vehicles (cheese,

ground beef)

● Bovine food vehicles (cheese,

ground beef

● R-type: ACSSuT ● R-type: ACSSuT plus

● Resistance genes on chromosome ● Resistance genes on plasmid

● Epidemic in Europe (esp. 1990 -

2002) and present in USA

● Largely confined to USA

Page 45: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Recommendation by Some Public Health Scientists

● Establish “zero tolerance” for antibiotic-resistant Salmonella in ground beef

Page 46: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

MDR Salmonella Paratyphi B var. Java Outbreak in Cattle

● MDR S. Java outbreak occurred in cattle in the United Kingdom▲ MDR S. Java associated with tropical fish from Thailand

put in cattle drinking water tanks to control algae♦Thailand aquaculture does not normally apply

antibiotics directly to ponds► Fish are fed chicken manure and chickens are fed

antibiotics■Antibiotics inducing drug resistance likely

present in chicken feces fed to fish

John Threlfall, Society for General Microbiology Annual Meeting, Edinburgh, Scotland, April 2005

Page 47: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Changes in the incidence of foodborne illness, and corresponding changes in prevalence of antibiotic-resistant foodborne pathogens causing human illnesses in U.S.

Year(s) Organism

Human

case rate

(per 100,000)

Relative

decrease

or increase % Resistant

Human

case rate

(per 100,000)

Relative

decrease or

increase

1996-98 Salmonella 15.9 31% (2 or more antibiotics, 1996)

4.9

2004 Salmonella 14.7 8% decrease 16% (2 or more antibiotics, 2002)

2.4 51% decrease

1996-98 Salmonella Typhimurium

4.9 34% (ACSSuT, 1996) 1.7

2004 Salmonella Typhimurium

2.9 41% decrease 21% (ACSSuT, 2002) 0.6 65% decrease

1996-98 Salmonella Newport

1.2 8% (2 or more antibiotics, 1996)

0.1

2004 Salmonella Newport

1.7 41% increase 25% (2 or more antibiotics, 2002)

0.4 300% increase

1996-98 Campylobacter 18.7 13% (ciprofloxacin resistance, 1997)

2.4

2004 Campylobacter 12.9 31% decrease 20% (ciprofloxacin resistance, 2002) 17.7% (ciprofloxacin resistance, 2003)

2.6 8% increase

Page 48: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Analysis for Regulatory Decisions on Antimicrobial Usage: Example of

Unintended Consequences?

● Risk management action in Europe to eliminate use of antibiotics for feed efficiency and growth promotion may have resulted in increased intestinal disease in animals and concomitant use of more therapeutic antibiotics with resultant increase in resistance▲ Resistance among some pathogens (tetR S. Typhimurium,

ampR S. Typhimurium, tetR C. jejuni, cryR C. jejuni, ampR E. coli) have increased in Europe

Page 49: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Analysis for Regulatory Decisions on Antimicrobial Usage: Example of

Unintended Consequences?

▲ Example, Denmark banned in 1998 use of antibiotics for growth promotion of animals

♦Total use of antibiotics in animals in Denmark decreased 30% between 1997 (before ban) and 2004, there was a 41% increase in therapeutic uses between 1999 (after ban) and 2004

► Between 1999-2004, tetR and ampR of S. Typhimurium from pigs increased, from chickens increased from 0% in 1997 to 17% in 2004 and from ill humans increased from 18% to 46%

Page 50: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Risk Analysis for Regulatory Decisions on Antimicrobial Usage

● EU banned antibiotic use in feed for growth promotion on the basis of the precautionary principle which is employed when scientific information is insufficient, inconclusive or uncertain▲ Sweeping risk management measures that are proposed

for a certain classification of use (e.g., growth promotion) can be draconian and without predictable results

▲ Analysis would best be carried out on a case-by-case basis and driven by product-specific, science-based risk assessments

● IFT Expert Panel concluded that thorough risk assessments should be used to guide selection of risk management actions so that unintended consequences are minimized

Page 51: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Concluding Comments

● Salmonella, Campylobacter and E. coli O157:H7 are major causes of foodborne illness

● Livestock and poultry are important vehicles for transmitting these pathogens to foods and on to humans

● Manure is a major vehicle for transmitting zoonotic pathogens to food

● Salmonella contamination of poultry, especially ground products, is considerably greater than that of beef and pork

● E. coli O157:H7 and Salmonella contamination of produce (likely from direct or indirect exposure to manure) is a growing concern

Page 52: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Concluding Comments

● Growing public health concerns regarding antimicrobial-resistant zoonotic foodborne pathogens▲ MDR Salmonella comprise ca. 10% of non-Typhi Salmonella

isolates from humans▲ Major increase in incidence of human cases of MDR S.

Newport infections (ca. 300%)▲ Major decrease in incidence of human cases of

Campylobacter enteritis (ca. 31%) but increase in incidence of ciprofloxacin-resistant Campylobacter cases (ca. 8%)

However:▲ Major decrease in incidence of human cases of S.

Typhimurium DT104 infections (ca. 65%) and in prevalence of S. Typhimurium DT104 in livestock and poultry (ca. 10%)

Page 53: Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Concluding Comments

Putting the Antibiotic Resistance Issue in Livestock in

Perspective

● Minimizing the use of antimicrobials in agriculture should be weighed against the likelihood of increasing the level of pathogens in food

● Sick animals must be treated for humanitarian reasons

● Prudent use of antibiotics in both human and animal medicine is essential

● Thorough risk assessments should be used to guide risk management actions