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Bacterial Enteric Infections and the Food Chain

Bacterial Enteric Infections and the Food Chain. Demystifying Medicine. Stephen J. Savarino, MD, MPH Enteric Disease Department Naval Medical Research Center Silver Spring, MD. National Institute of Health February 3, 2009. DON’T EAT ME!. Photograph courtesy of J. Besser, MN Dept Health.

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Bacterial Enteric Infections and the Food Chain

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  1. Bacterial Enteric Infections and the Food Chain Demystifying Medicine Stephen J. Savarino, MD, MPH Enteric Disease Department Naval Medical Research Center Silver Spring, MD National Institute of Health February 3, 2009

  2. DON’T EAT ME! Photograph courtesy of J. Besser, MN Dept Health

  3. Outline • Perspective on food and health • Case vignette 1: ‘1 of 1400’ • Epidemiology, burden and control of foodborne diseases, U.S. • Case vignette 2: ‘from bad to worse’ • Complications and sequelae • Contributory host factors • Burden of enteric infections, developing countries • Consideration of future directions

  4. too little food • too much food • bad food Food and Health

  5. Context human-microbial community food chain environment individual crops harvest storage/processing microbiota distribution population humans animals

  6. Case Vignette 1 • 46 yr old Minnesota man presents to his physician on 06/16/08 complaining of bloody diarrhea • 3 days prior, began with belly cramps, watery then bloody diarrhea and occasional vomiting and chills • No history of recent travel out of state • Physical exam remarkable for temp. 102.5°F and mild dehydration; stool exam reveals gross blood • Supportive therapy started as outpatient • Stool culture grows Salmonella enterica (06/23) courtesy of E. Hedican, MN Department of Health

  7. Case Vignette 1 (cont) • On follow-up, patient still ill and started on course of oral ciprofloxacin (6/23) • Patient interviewed by MDH on 6/28, a day after S. enterica serotyped as subspecies Saintpaul • Reported eating in Restaurant A (6/14) 2 d before illness began: bean burrito, pico de gallo, onion, guacamole, diced jalapeño/red pepper garnish • One of 33 eventual MN S. Saintpaul diarrhea cases • Experienced uncomplicated recovery after 12 d courtesy of E. Hedican, MN Department of Health

  8. Multistate Salmonella saintpaul Outbreak, 2008 50 National tomato alert (6/07) 1st multistate study (started 5/26) 2nd multistate study (started 6/26) 40 CDC notified (5/22) National jalapeño alert (7/09) 30 Numer of cases Household-based study (began 7/11) 20 Outbreak end (8/28) 10 1 8 16 22 29 6 13 20 27 3 10 17 24 1 8 16 22 29 5 12 Apr May Jun Jul Aug Date of illness onset MMWR 2008;57(34):929

  9. Multistate Salmonella saintpaul Outbreak, 2008 MMWR 2008;57(34):929

  10. Multistate Salmonella saintpaul Outbreak, 2008 • Over 4 months, > 1,400 cases; 43 states, D.C., and Canada; 286 hospitalizations; 2 deaths • Jalapeño & serrano peppers confirmed vehicles with traceback to single farm in Tamaulipas, Mexico • No definite confirmation of tomatoes as vehicles • Cooperation between CDC&P, State Health Depts, FDA, USDA, and others; FoodNET, PulseNET

  11. Salmonella saintpaul Outbreak:Lessons Learned • Effectiveness of epidemiological investigations • High degree of cooperation/communication between state and federal health authorities • Improvements to surveillance infrastructure to facilitate rapid, standardized investigation of potential foodborne disease cases • Improved system for traceback by FDA • Collateral costs from outbreak • Tomato industry lost $100-500 M* • Consumer confidence in fresh produce shaken *http://www.nowpublic.com/health/tomatoes-after-500-million-losses-fda-appears-wrong

  12. How Safe is Our Food? Clippings from Washington Post, Jan 22-29, 2009

  13. Ten Leading Causes of Death in the U.S.,vs. 1900 1997 pneumonia heart disease tuberculosis cancer diarrhea/enteritis stroke heart disease chronic lung disease stroke unintentional injury liver disease pneumonia/flu injuries diabetes cancer HIV infection senility suicide diphtheria chronic liver disease 40 30 20 10 0 0 10 20 30 40 percentage of all annual deaths MMWR 1999;48:621

  14. Fall and Rise of Reported Salmonella Infections, U.S. 1920-2002 • sewer systems • water treatment • milk pasteurization • Industrialization of food supply • non-typhi Salmonella • E. coli O157:H7(STEC) • Campylobacter R. Tauxe, CDC, National Notifiable Diseases Surveillance Data

  15. Changes in Food Production and ConsumptionLate 20th Century • Mass production and distribution of foods • Concentrated livestock operations • Increasing availability of fresh food and produce • Increasing international trade • Proliferation and increasing patronage of commercial food establishments

  16. Estimated Annual Burden of FoodborneGI Illnesses in the U.S., 1996-7 Total Unknown pathogens Known pathogens Mead PS et al, Emerg Infect Dis 1999;5:607-625

  17. Economic Impact of Foodborne IllnessesU.S., 1995 Buzby JC and Roberts T (ERS, USDA) Food Review 1996, Sep-Dec, 20-25 • Seven pathogens (~2.8% cases) • Campylobacter jejuni • Salmonella spp. • Escherichia coli O157:H7 • Clostridium perfringens • Listeria monocytogenes • Staphylococcus aureus • Toxoplasma gondii • Economic impact (1995 dollars) • Cost, $6.5-$34.9 Billion

  18. Preventing Foodborne Diseases • On-farm safety practices (GAP) • Inspection • Hazard analysis critical control points (HACCP) • Microbial monitoring • Tracing • Restaurant code • Consumer education • Disease surveillance, outbreak investigation farm transport, processing, distribution preparation adapted from J. Besser, MN Dept Health

  19. Reportable Foodborne Disease Surveillance Case reports Clinical microbiology Public Health specimens isolates Case interviews Prevention / control activities adapted from J. Besser, MN Dept Health

  20. U.S. FoodNET Surveillance System • Active, population-based surveillance network initiated in 1996 • Estimate illness burden • Monitor trends for 10 specific pathogens • Develop and assess interventions to reduce burden • CDC, FDA, FSIS (USDA), State Health Depts • Ten sites in U.S. FoodNET Burden of Illness Pyramid

  21. National Molecular Subtyping Network for Foodborne Disease Surveillance Area labs National database FoodNET sites FDA, USDA labs J. Besser, MN Dept Health

  22. PulseNET Pulse-field gel electrophoresis • Standardized laboratory methods (PFGE) • Dynamic, internet accessible pattern database • Data analysis, cluster detection software • Communication network • Refines the foodborne disease case definition • Increases the sensitivity of cluster detection • Strengthens measures of association • Increases the speed of outbreak investigation

  23. Largest U.S. Food Recalls involvingPulseNET

  24. Relative Disease Rates forSelected Bacterial Pathogens, 1996-2005 2.0 Vibrio Salmonella 1.0 Relative rate 0.9 Campylobacter 0.8 0.7 O157:H7 E. coli 0.6 Listeria 0.5 1996-8 1999 2000 2001 2002 2003 2004 2005 Year Scallan A, ClinInfectDis 2007;44:718-725; and MMWR 2006;55(14):392-395

  25. Emerging Foodborne Pathogens, MN • Novel Pathogens Project • 1996-2004 • Sentinel surveillance • Twin cities HMO lab (A) • Rural, hospital lab (B) • Case-control studies • Molecular methods • PCR-based methods • Viral microarray • Arcobacter butzleri • Aeromonas spp. • Bacillus cereus • Brachyspira spp. • Campylobacter spp. • Clostrid perfringens • E. coli O157:H7 • E. coli, e-aggregative • E. coli, e-pathogenic • E. coli, e-toxigenic • E. coli, e-invasive • E. coli, shiga-toxin • Escherichia alberti • Edwardsiella tarda Known/suspected bacterial pathogens • Enterobacter sakazaki • Hafnia alvei • Helicobacterspp. • Lawsonia intracellularis • Listeria monocytogenes • Salmonella spp. • Shigellaspp. • Staph. aureus • Tropheryma whipplei • Vibriospp. • Yersiniaspp. J. Besser, MN Dept Health (unpublished data)

  26. Labs A and B, 1996-2002, Bacterial Enteric Pathogens (n=20,616 plates) ETEC ETEC testing initiated Non-O157 STEC Reportable Bacterial Pathogens 8.3% 9 7.4% 8 6.5% 6.3% 6.2% 7 5.5% 6 4.9% 5 Percent Positive 4 3 2 5.0% 6.3% 5.4% 4.5% 6.3% 5.4% 4.4% 1 0 1996 1997 1998 1999 2000 2001 2002 J. Besser, MN Dept Health (unpublished data)

  27. Urban HMO Lab (A), 2000-2004 n = 9,799 Number positive 2.7% 1.9% 1.4% 1.0% 0.6% C. jejuni ETEC Shigella Salmonella STEC J. Besser, MN Dept Health (unpublished data)

  28. ETEC Emergence as a Foodborne Pathogen, Minnesota • ETEC infrequent agent in U.S. community-based studies in 1980s • Increasing number of outbreaks reported over past decade • Probable factors • Increasing free trade • Greater international travel • Harbinger for emergence in other states? • Infant and travelers’ diarrhea in developing countries • Virulence factors • Fimbrial colonization factors • Heat stable (ST) and heat labile (LT) enterotoxins Petri WA et al, JCI 2008;118:1277

  29. Case Vignette 2 • 10 yr old boy presented with generalized muscle weakness • Short episode of diarrhea five days before weakness noticed • Father and brother reported acute diarrhea 8 and 3 days before onset of patient’s complaints • Family attended a barbecue and consumed chicken two days before members developed diarrhea • No other guests including mother developed illness CW Ang et al, JNeuroimmunol 2000;111:229

  30. Case Vignette 2 (cont) • Boy was admitted to hospital for diagnostic evaluation • Examination remarkable for generalized muscle weakness, normal sensory and cranial nerve exams • Electrophysiology study results • Very low compound muscle action potentials in lower limbs • Normal compound sensory nerve action potentials • Patient met diagnostic criteria for Guillain-Barré syndrome (GBS) • Never required ventilatory support and made full neurological recovery CW Ang et al, JNeuroimmunol 2000;111:229

  31. Pertinent Laboratory Results CW Ang et al, JNeuroimmunol 2000;111:229

  32. Guillain-Barré Syndrome and C. jejuni • Most common cause of acute flaccid paralysis in humans • 1-2 cases per 100,000 per year • Acute inflammatory polyradiculoneuropathy • Gastrointestinal illness often precedes onset by 1-3 weeks • C. jejuni most common antecedent infection • ~35% of cases • Less common antecedents: cytomegalovirus (~15%), Epstein-Barr virus (~8%), and Mycoplasma pneumoniae (~5%) • Sialyltransferases involved in synthesis of ganglioside-like epitopes of lipooligosaccharide on surface of C. jejuni

  33. Ganglioside mimicry in C. jejuni LOS and pathogenesis of Guillain-Barré Syndrome Guerry P and Szymanski C, Trends Microbiol 2008;16:428

  34. Annual Health Burden due to GBS in US, 2004

  35. Leading Zoonotic Foodborne Pathogens, U.S. Annual Disease Burden and Sequelae Adapted from DuPont HL, ClinInfectDis 2007;45:1353

  36. Foodborne DiseasesHost and Environmental Factors • Host factors • Age • Chronic illness • Immunodeficiency • Physiological or anatomic abnormalities • Genetic predisposition • Environmental factors • Crowding • Poor sanitation • Poverty Vulnerable subpopulations in the U.S. Reynolds K, RevEnvironContamToxicol 2008

  37. Global Distribution of Diarrhea-related Deaths in Children <5 years of age, 2000 • of 10 million children < 5 years dying each year • 1.6-2.1 million deaths due to diarrheal diseases • repeated infection in survivors associated with impaired growth and development Petri WA et al, J Clin Invest 2008;118:1277-1290

  38. Consideration of future directions • Short-term (now) • Set achievable goals for further reduction in foodborne disease incidence (post-Healthy People 2010) • Establish and implement best practices for food safety, surveillance and control of foodborne pathogens • Maximize coordination and marshal needed resources from government and industry • Improve education: consumers, food industry, policymakers • Leverage information technology and institute workable systems that expedite, accurate food/produce traceback

  39. Consideration of future directions • Medium-term (5-10 years) • Define UNKNOWN pie slice: existing and emerging pathogens and relative contributions to foodborne disease, providing basis for future priorities in disease control and prevention • Quantify both acute and long-term morbidity associated with foodborne gastrointestinal infections, with quality-adjusted life years (QALYs) • Develop improved methods for pathogen detection in food chain (e.g., molecular, biosensor technology) • Accelerate vaccine development for selected pathogens

  40. Consideration of future directions • Long-term (10-25 years) • Foster radical, sustainable sanitary and food safety improvements in developing countries, trading partners • Harness expanding knowledge of pathogenomics, microbiomics; human immunology, genetics and mucosal biology to develop new interventions that promote gut health and disease resistance • Nutritional interventions, probiotics

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