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STEPHEN J. SAVARINO, MD, MPHSTEPHEN J. SAVARINO, MD, MPH
ENTERIC DISEASE DEPARTMENTENTERIC DISEASE DEPARTMENT
NAVAL MEDICAL RESEARCH CENTERNAVAL MEDICAL RESEARCH CENTER
SILVER SPRING, MDSILVER SPRING, MD
Bacterial Enteric
Infections and the Food Chain Demystifying
Medicine
National Institute of HealthFebruary 3, 2009
Photograph courtesy of J. Besser, MN Dept Health
Outline
Perspective on food and healthCase vignette 1: ‘1 of 1400’Epidemiology, burden and control of
foodborne diseases, U.S.Case vignette 2: ‘from bad to worse’Complications and sequelaeContributory host factorsBurden of enteric infections, developing
countriesConsideration of future directions
Food and Healthtoo little
food
too much food
bad food
Context
individual
population
human-microbial community environment
harvestcrops
storage/processing
humans animals
distribution
food chain
microbiota
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
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 dcourtesy of E. Hedican, MN Department of
Health
10
30
20
40
50
Nu
mer
of
case
s
1 8 1622 29 6 132027 3 10 1724 1 8 16 2229 5 12Apr May Jun Jul Aug
Date of illness onset
Multistate Salmonella saintpaul Outbreak, 2008
CDC notified (5/22)
1st multistate study (started
5/26)
National tomato alert (6/07)
2nd multistate study (started 6/26)
Household-based study (began 7/11)
National jalapeño alert (7/09)
MMWR 2008;57(34):929
Outbreak end (8/28)
MMWR 2008;57(34):929
Multistate Salmonella saintpaul Outbreak, 2008
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
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
How Safe is Our Food?
Clippings from Washington Post, Jan 22-29, 2009
Ten Leading Causes of Death in the U.S.,vs.1900 1997
0 10 20 30 4040 30 20 10 0
pneumoniatuberculosis
diarrhea/enteritisheart disease
strokeliver disease
injuriescancersenility
diphtheria
heart diseasecancer
strokechronic lung diseaseunintentional injurypneumonia/flu
diabetesHIV infectionsuicidechronic liver disease
MMWR 1999;48:621percentage of all annual deaths
Fall and Rise of Reported Salmonella Infections, U.S. 1920-2002
0
5
10
15
2025
30
35
40
45
50
1920 1930 1940 1950 1960 1970 1980 1990 2000
Years
Incidence per 100,000 population
Typhoid fever Non-typhoid salmonellosis
R. Tauxe, CDC, National Notifiable Diseases Surveillance Data
sewer systems water treatment
milk pasteurization
Industrialization of food supply
non-typhi Salmonella E. coli O157:H7(STEC)
Campylobacter
Changes in Food Production and Consumption
Late 20th CenturyMass 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
Estimated Annual Burden of FoodborneGI Illnesses in the U.S., 1996-7
Total
Known pathogens Unknown pathogens
Mead PS et al, Emerg Infect Dis 1999;5:607-625
Economic Impact of Foodborne Illnesses
U.S., 1995
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
Viruses
ParasitesBacteria
Unknown
Viruses
ParasitesBacteria
Unknown
Buzby JC and Roberts T (ERS, USDA) Food Review 1996, Sep-Dec, 20-25
Preventing Foodborne Diseases
On-farm safety practices (GAP)InspectionHazard analysis critical control points (HACCP)Microbial monitoringTracingRestaurant codeConsumer educationDisease surveillance, outbreak investigation
farm transport, processing, distribution
preparation
adapted from J. Besser, MN Dept Health
Reportable Foodborne Disease Surveillance
State and local Agriculture and Veterinary Labs
Clinical microbiology Public Health
Prevention / control activities
Case interviews
Case reports
isolatesspecimens
adapted from J. Besser, MN Dept Health
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
Area labs
National databaseFoodNET sites
FDA, USDA labs
National Molecular Subtyping Network for Foodborne Disease Surveillance
J. Besser, MN Dept Health
PulseNET
938
748684
495
372
288241219210
8461563930
1 2 3 4 5 6 7 8 9 10
938
748684
495
372
288241219210
8461563930
1 2 3 4 5 6 7 8 9 10
Standardized laboratory methods (PFGE)Dynamic, internet accessible pattern databaseData analysis, cluster detection softwareCommunication networkRefines the foodborne disease case definition
Increases the sensitivity of cluster detectionStrengthens measures of association Increases the speed of outbreak investigation
Pulse-field gel electrophoresis
Largest U.S. Food Recalls involvingPulseNET
Year Pathogen FoodFood
recall(lbs)
2006Salmonella Tennessee
peanut butter 345,000,000
1998 L. monocytogeneshot dogs, deli meats
35,000,000
2002 L. monocytogenesready-to-eat poultry products
27,400,000
1997 E. coli O157:H7 frozen ground beef 25,000,000
2007 E. coli O157:H7 ground beef 21,700,000
2002 E. coli O157:H7 ground beef 18,600,000
2000 L. monocytogenesready-to-eat poultry products
16,900,000
2008SalmonellaSaintpaul
tomatoes, jalapeño, serrano peppers
unknown
Relative Disease Rates forSelected Bacterial Pathogens, 1996-
2005R
ela
tive
rate
0.5
0.6
0.7
0.80.91.0
2.0
1996-8 1999 2000 2001 2002 2003 2004 2005
Year
Vibrio
Salmonella
Campylobacter
ListeriaO157:H7 E. coli
Scallan A, ClinInfectDis 2007;44:718-725; and MMWR 2006;55(14):392-395
Emerging Foodborne Pathogens, MNNovel 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
Enterobacter sakazaki
Hafnia alvei Helicobacterspp. Lawsonia intracellularis
Listeria monocytogenes
Salmonella spp. Shigellaspp. Staph. aureus Tropheryma whipplei
Vibriospp. Yersiniaspp.
Known/suspected bacterial pathogens
J. Besser, MN Dept Health (unpublished data)
Labs A and B, 1996-2002, Bacterial Enteric Pathogens (n=20,616 plates)
J. Besser, MN Dept Health (unpublished data)
Perc
en
t P
osi
tive
0123456789
1996 1997 1998 1999
5.0% 6.3% 5.4% 4.5%
5.5%6.5%
6.2%4.9%
ETEC
Non-O157 STEC
Reportable Bacterial Pathogens
2000 2001 2002
6.3% 5.4% 4.4%
8.3%7.4%
6.3%
ETEC testing initiated
Urban HMO Lab (A), 2000-2004
C. jejuni
ETEC Shigella
Salmonella
STEC
Nu
mb
er
posi
tive
2.7% 1.9% 1.4% 1.0% 0.6%
n = 9,799
J. Besser, MN Dept Health (unpublished data)
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
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
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
Patient Father Brother Mother
Diarrhea + + + -
C. jejuni serology + + + -
C. jejuni culture - + +
Anti-LOS antibodies (IgG)1 + - - -
Anti-ganglioside antibodies
~IgM
-GM1 800 - - -
-GM2 200 - 200 -
-GD1b 200 - - -
-Asialo-GM1 >1600 100 - -
~IgG
-GM1 400 - - -
-Asialo-GM1 >1600 - - -
Pertinent Laboratory Results
CW Ang et al, JNeuroimmunol 2000;111:229
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
Ganglioside mimicry in C. jejuni LOS and pathogenesis of Guillain-Barré Syndrome
Guerry P and Szymanski C, Trends Microbiol 2008;16:428
Measure Estimate (95% CI)
Inpatient care
Community hospitalizations 6,008 (5,510-6,506)
Community hospital patients 5,473 (4,951-5,995)
Discharges to rehabilitation facility 1,009 (837-1,181)
Discharges to long-term care facility 161 (105-217)
Discharges to nursing home 720 (606-834)
Outpatient care
Physician visits 19,728 (0-103,506)
Physical therapy visits 147,182 (0-309,820)
Occupational therapy visits 7,821 (0-29,553)
Lost productivity
Permanently disabled workers 574 (512-636)
Deaths
GBS underlying cause of death 247 (216-278)
Annual Health Burden due to GBS in US, 2004
Leading Zoonotic Foodborne Pathogens, U.S. Annual Disease Burden and Sequelae
Morbidity & Mortality
Campylobacter jejuni
non-typhoidal Salmonella
Shiga-toxin producing E.
coli
No. cases1.4 – 2.5 Million
1.4 Million 100,000
No. hospitalized
13,000 > 15,000 2,000
No. deaths 100 400-600 91
Complicationssepsis, meningitis
hemorrhagic colitis
Sequelaereactive arthritis
reactive arthritis
hemolytic-uremic syndrome (HUS)
Guillain-Barré syndrome
Irritable bowel syndrome
Irritable bowel syndrome
Adapted from DuPont HL, ClinInfectDis 2007;45:1353
Foodborne DiseasesHost and Environmental Factors
Host factors Age Chronic illness Immunodeficiency Physiological or
anatomic abnormalities Genetic predisposition
Environmental factors Crowding Poor sanitation Poverty
Population Number
Persons > 65 y 35,061,000
Children< 5 y 20,186,469
Persons with diabetes
18,200,000
Cancer patients 15,000,000
Pregnant women 6,000,000
AIDS patients 1,039,000
Organ transplants 123,120
Vulnerable subpopulations in the U.S.
Reynolds K, RevEnvironContamToxicol 2008
Global Distribution of Diarrhea-related Deaths in Children <5 years of age,
2000
Petri WA et al, J Clin Invest 2008;118:1277-1290
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
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
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
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
