Is C. difficile a Foodborne Disease?

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1 Is C. difficile a Foodborne Disease? Brandi Limbago, Ph.D. Deputy Chief Clinical and Environmental Microbiology Branch IAFP 24 July 2012 Disclaimer: The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

2 We know it s an important healthcare-associated pathogen Anaerobic spore-forming bacillus - Produces toxins: A & B, binary, others Clostridium difficile Infection(CDI) - diarrhea, pseudomembranous colitis, sepsis, death Fecal-oral transmission via spores - contaminated environment - hands of healthcare personnel Receipt of antimicrobials is the primary risk factor for disease - Suppression of normal flora of the colon - Acquisition and growth of C. difficile Clindamycin, penicillins, cephalosporins, fluoroquinolones Healthy colon Pseudomembranous colitis

3 Hospitalizations, Deaths and Costs Linked to CDI CDI hospitalizations 1 3 fold increase from May be leveling off Deaths linked to CDI 2 ~14,000 deaths in 2007 Medical Costs 3, billion in excess healthcare costs in U.S. facilities in 2003 Reports of increasing Community-associated CDI 1. Lucado J et al. Healthcare Cost and Utilization Project, Stat. Brief # Hall AJ et al.. Clin Infect Dis May 22. [Epub ahead of print] 3. Dubberke ER et al. Emerg Infect Dis Jul;14: O'Brien JA et al. Infect Control Hosp Epidemiol Nov;28: Slide courtesy of Fernanda Lessa

4 CDI is an Emerging Cause of Communityassociated Infection 23 patients (70%) Community-associated (CA-CDAD) No inpatient hospital exposure in prior 3 months Pregnant women Young patients without serious underlying disease Median age: 23 yrs 8/23 (35%) had no antibiotic exposure in prior 3 months What is the source of Community CDI?

5 Country United States United States PA Reports of C. difficile in Retail Foods Product Ground beef, pork, turkey, sausage Ground beef, buffalo, chicken, lamb, turkey, pork, veal, sausage n pos/ n cultured % Pos. PCR Ribotypes Reference 37/ , 078 Songer et al / Curry et al Brand A pork sausage* 13/ * Ground pork, beef, chicken, United States TX 23/ ** Harvey et al turkey, pork & beef sausage United States PA Veal 3/50 6 ND Houser et al. Canada (Ontario, Quebec) Canada (nationwide) Ground beef & veal 12/ , M31, 014, M26 Median: 6.3% Rodriguez-Palacios et al Ground beef 10/ M26, 077, 014, others Rodriguez-Palacios Veal chops (likely an overestimate) 3/ M26, J, K et al Canada (Ontario) Ground beef, pork 14/ , 027, C, E, Y Weese et al Canada (Ontario) Fish & seafood 5/ , nontox. Metcalf et al Canada (Ontario) Root vegetables 5/ , 077 Metcalf et al Italy Shellfish < 9/ , 005, 009, 010, 056, 066 Pasquale et al Scotland Salad 3/ , 001 Bakri et al Sweden Pork, beef, lamb, poultry 2/ Netherlands Beef, pork, veal, lamb, chicken 8/ types de Boer et al. 2011

6 FoodNet Retail Meat Surveillance for C. difficile 12 mos surveillance at FoodNet sites trained in use of a standardized protocol Tested by State Public Health Laboratories Meat type Total Sampled Potential C. difficile* Confirmed C. difficile Ground Beef Ground Turkey Chicken Breast Pork Chops Total mos. Surveillance Performed at CDC lab Total Sampled Confirmed C. difficile Not tested 0 Not tested 60 0 Submitted for publication

7 Clostridium species isolated from meats Ground Beef (n=10) Ground Turkey (n=10) C. sporogenes 3 10 C. cadaveris 0 3 C. perfringens 2 0 C. bifermentans 0 1 C. septicum 1 0 C. difficile 0 0 Other Clostridium spp. 2 0 Total Clostridium isolates 8 14 Total meat samples positive for Clostridium * 6 10 *2 ground beef and 4 ground turkey samples contained more than one Clostridium species What else could be driving CA-CDI? Submitted for publication

8 No. of CDI case-patients Community Onset CDI Relative to Previous Discharge, North Carolina, 2005 (N=348) // // * Time (in weeks) Adapted from Kutty PK, et al. Infect Control Hosp Epidemiol. 2007;29:

9 EIP Surveillance of Clostridium difficile Infection Admission Discharge 0-12 weeks 48 h > 12 weeks * HO-HCFA CO-HCFA CA-CDI Time HO: Hospital (Healthcare) onset CO-HA: Community Onset Healthcare-associated CA: Community Associated *CO-HA vs. CA, depending on whether patient was discharged within previous 12 weeks CDAD Surveillance Working Group. Infect Control Hosp Epidemiol 2007; 28:

10 Surveillance for CDI Through the Emerging Infections Program (EIP) Active, population-based, and laboratory-initiated surveillance for CDI Began in 2009 Public health network State health departments, CDC, local health departments and academic institutions Goals of EIP CDI surveillance Determine population-based incidence of community- and healthcare-associated CDI Describe epidemiology of CA-CDI and generate hypotheses for future research activities Characterize C. difficile strains that cause CDI with a focus on strains from community-associated cases More information on EIP CDI:

11 Distribution of CDI Cases from EIP CDI Surveillance, 2010 CDI Cases (N=10,342)* 32% are CA-CDI > 20% 28% previously reported from US 1, Sweden 2,3 and Canada 4 CO-HCFA 19% CO-CA 32% Hospitalonset 23% Nursinghome onset 26% * EIP Sites: California, Colorado, Connecticut, Georgia, Minnesota, New York, Oregon, and Tennessee CDC unpublished EIP CDI data 1. Kutty et al. Emerg Infect Dis Norén et al. J Clin Microbiol Karlström et al. Clin Infect Dis MMWR (09); Lambert et al. Infect Control Hosp Epi Slide courtesy of Fernanda Lessa

12 Strains Represented among EIP C. difficile Isolates Convenience sample of all CDI cases PFGE performed on 2002 isolates received since fall from from from 2011 HCFO % COHCFA % CA % UNK 20 1% NAP1-related 3% NAP3 1% NAP2 2% NAP1 26% NAP5 1% NAP4 10% NAP7 3% NAP6 7% unnamed* 32% NAP8 0% NAP9 2% NAP10 2% NAP11 9% NAP12 2% CDC unpublished EIP CDI data *Includes 250 distinct patterns

13 Is There a Difference in Strains Causing Disease in Healthcare vs. Community Settings? 35% 30% 25% 20% CA COHCFA HCFO 15% 10% 5% 0% CDC unpublished EIP CDI data

14 Conclusions C. difficile can be found in retail foods Low levels contamination, uneven distribution C. difficile is an emerging cause of disease in the community Strains causing CA-CDI cases are very similar to those causing in healthcare Argues against a novel source of the organism in CA-CDI Most patients with CA-CDI have exposure to healthcare settings and/ or antibiotics Only ~5% have no healthcare/ antibiotic exposures

15 FoodNet project L. Hannah Gould, Angela D. Thompson Duncan MacCannell Sharon A. Greene J. Scott Weese J. Glenn Songer Charles E. MacGowan Stephanie Estes Beverly Jolbitado Henrietta Hardin Emerging Infections Program Lydia Anderson Duncan MacCannell J. Kamile Rasheed Fernanda Lessa Jessica Cohen Scott Fridkin Dale Gerding & Hines VA lab EIP sites CA, CO, CT, GA, MD, MN, NM, NY, OR, TN, Strain typing collaborators Jane Marsh Ed Kuijper Mark Wilcox Michael Mulvey For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA Telephone, CDC-INFO ( )/TTY: Web: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

16 Thank you!

17 Minimum Spanning Tree: Human, Animal and Food Isolates 97 C. difficile isolates obtained through the CDC - 45 human isolates (maj. from US and Canada) - 26 animal isolates, bovine and swine from US - 26 food isolates, mostly pork and beef PFGE, toxinotyping and tcdc deletion analysis 60 PCR ribotype PCR ribotype (A) 6 2 (B) NY CN CN ,11 MD 17 CN CN 16 CN CN 10 CT ME TN PA 18 (C) ME CN ME 20 CN Marsh JW, et al. Anaerobe 17:156-60, , A 25 Z food NC , 30 31, 32 (D) animal Hu-CDI CA-CDI GA 3 TN TN CT MD 6 5 TN 3 IT 6 CO MA 4 SP 7 MD CT 6 SP CN MD MN MN NC Slide courtesy of Jane Marsh

18 MLVA Analysis of PCR Ribotype 027 Food, Animal and Human Isolates (A) (B) (C) 10, Lo Source c 1 human NJ 2 braunsch ground 3 beef 4 braunsch 5 bovine 6 S. sausage MLVA genotype Source Loc MLVA genotype 9 equine 10 grnd pork 11 grnd beef grnd beef 13 chorizo 14 braunsch Source Loc MLVA genotype Canad 17 human a 18 grnd beef Canad a grnd beef Canad a 20 grnd beef Canad a food Identity across 7 tandem repeat loci is rarely observed Serial isolates from CDI patients show variability animal Hu-CDI Marsh JW, et al. Anaerobe 17:156-60, 2011 Slide courtesy of Jane Marsh

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