Robert Tauxe, MD, MPH

Transcription

1 Robert Tauxe, MD, MPH Deputy Director, Division of Foodborne, Waterborne and Environmental Diseases National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention

2 Theodor Escherich Studied normal infants Discovered: Bacterium coli commune now Escherichia coli Kiyoshi Shiga Studied epidemic dysentery Discovered: Shiga s bacillus (Shigella dysenteriae Type 1) and Shiga toxin

3 What Theodor Escherich saw

4 Some E. coli do cause disease Enteroinvasive E. coli (EIEC) Enteropathogenic E. coli (EPEC) Enterotoxigenic E. coli (ETEC) Enteroaggregative E. coli (EAggEC) Enterohemorrhagic E. coli (EHEC) Shiga toxins Extraintestinal pathogenic E. coli (ExPEC) Urinary pathogenic E. coli (UPEC)

5 The Shiga-toxin producing E. coli How do they cause disease? Traverse the stomach (acid resistance) Attach to bowel wall (adherence factor, intimin, eae) Produce Shiga toxins, absorbed into bloodstream Targets and kills cells that line blood vessels in large bowel kidney brain Treatment = early rapid fluid therapy

6 E. coli O157:H7, the most common Shiga toxin producing E. coli (STEC) The first decade 1982: 2 outbreaks of bloody diarrhea - undercooked ground beef - E. coli O157:H7 identified 1984: Nebraska outbreak: Papillion nursing home ground beef Very severe illness. 34 ill, 14 hospitalized, and 4 died 1985: Canadian study linked hemolytic uremic syndrome and verotoxin-producing E. coli US workers identify the toxin as a Shiga-like toxin 1986: E. coli O157:H7 North Carolina outbreak: spread in a child care center 3 children got HUS 1986: Isolated E. coli O157 from calves and heifers on two farms associated with HUS

7 1993 Western States E. coli O157 Outbreak 726 cases 55 HUS 4 deaths Outbreak detected Meat recall 39 d

8 Impact of the 1993 outbreak on food safety E. coli O157:H7 made a notifiable infection in all states 1996: PulseNet launched: The national subtyping network for bacterial foodborne pathogens. DNA fingerprinting of all E. coli O157 by public health. Greatly improved outbreak detection and investigation : Pathogen Reduction Act transforms meat and poultry safety at processing. 1996: FoodNet launched: Active public health surveillance collects data about cases from 10 sites. Burden and trend monitoring.

9 Reported outbreaks of E. coli O157:H7 infections in the United States Rangel et al, EID 11: , 2005

10 Managing E. coli O157 in ground beef 1994: E. coli O157:H7 declared an adulterant in ground beef 1996: Pathogen reduction act, FSIS began testing carcasses : No substantive change in E. coli O157 illnesses tracked by CDC s FoodNet; outbreaks traced to ground beef. Late 2002: New guidance to grinders: Include E. coli O157 in HACCP plans for ground beef. FSIS tests more ground beef 2003: Frequency of ground beef + for E. coli O157 drops 50% Human infection with E. coli O157 drops 40% 10

11 FSIS: Year-to-year comparison of % of ground beef samples yielding E. coli O157:H7 p = 0.89 p = 0.32 p = 0.03 Naugle, 2005, J Food Protect 68:2504-5

12 FoodNet trends Since , Vibrio infections are up by 47% Salmonella - 8% Campylobacter - 31% Listeria - 40% E. coli O157-42% MMWR 2005; 54: (April 15, 2005)

13 By the end of the second decade - E. coli O157:H7 Predominant source was beef, especially ground beef Interventions in processing worked 0.9 diagnosed infections per 100,000 persons each year (2004) ~ 2,700 diagnosed infections per year The national objective for 2010 was 1.0 per 100,000 Still a problem remained in fresh produce petting zoos child care centers untreated water 13

14 Incidence of culture-confirmed O157 STEC infections, FoodNet, * Cases per 100,000 popula/on Goal for 2010 *CDC, preliminary FoodNet data, 2013 Year

15 Health burden of E. coli O157 infections In 2010, compared to the late 1990 s, can estimate we averted: 58,500 illnesses 1,900 hospitalizations 20 deaths Current annual burden of illness from STEC O157: 96,000 illnesses 3,300 hospitalizations 30 deaths About 70% is foodborne, 8% due to live animal contact Scallan 2011 Emerg Infect Dis 17:1-7 15

16 North Carolina State Fair outbreak 2004, and Aedin s Law Visitors to 2004 state fair 108 ill, mostly children, 15 cases of HUS Visiting the petting zoo (sheep, goats) Illness associated with contact with manure, hand-to-mouth behavior 80% of samples from dirt yielded O Legislature passed Aegin s law: State inspection of petting zoos Mandatory handwashing facilities Signs required Goode 2009 Arch Ped Adol Med:

17 Incidence of culture-confirmed O157 STEC infections, FoodNet, * Cases per 100,000 popula/on Goal for 2010 = 1.0 Goal for 2020 = 0.6 *CDC, preliminary FoodNet data, 2013 Year

18 Percent of STEC O157 foodborne illnesses attributed to specific food categories (outbreaks: ) Painter 2013 EID 19: Online table 4

19 E. coli O157:H7 and baby spinach cases in 26 states. 31 HUS, 3 deaths Linked by PulseNet Bagged baby spinach Traced back to 4 farms One farm environment had outbreak strain of E. coli O157 Outbreak strain of E. coli O157:H7 from cattle 0.5 miles upstream stream sediment wild pig feces soil on farm

20 E. coli O157:H7 and shredded lettuce outbreak: 36 cases, 2 states National taco chain Shredded lettuce from California farm Fields adjacent to two dairy farms Pipes could connect manure lagoons and irrigation system 10 samples with outbreak strain of O157 - from both dairies - from three fields

21 E. coli O157:H7 and strawberries Oregon, ill, 4 HUS, 2 deaths Linked by PulseNet Strawberries sold at roadside stands From one farm in Oregon Deer frequent the farm Outbreak strain found in all 5 strawberry fields sampled 10/50 samples with deer scat Laidler 2013 Clin Infect Dis 57:

22 Bacteria manipulate leaf stomata and get inside Stomata are tiny respiratory pores on surface of leaves Plant stomata close in the presence of bacteria Some plant pathogens have mechanisms to open them up again E. coli O157:H7 have Type 3 Secretion Systems One attaches to the human gut, and causes disease there Another is specific to plants it opens the stoma, so E. coli can colonize the stomal pore Similar capacity in some strains of Salmonella? Melotto. Cell 2006; 126: , 2006 Saldana. Frontiers in Microbiol; May 2011 vol 2, article 119. doi: /fmicb

23 Do some enteric bacterial pathogens have a life cycle in both plants and animals? Fruit/leaf/seed Plant Feces Colonizing plants that herbivores eat makes evolutionary sense The plant is eaten by an herbivore, that excretes the bacteria somewhere else in feces (often with seeds) Colonizing next generation of plants Brings the bacteria to the next generation of herbivores We omnivores can be infected from either animals or plants Fletcher 2013 Phytopathology 103:

24 Connections between ruminant animal reservoirs and field or orchard may be key for Lettuce Spinach Strawberries Apple cider Hazelnuts Alfalfa seeds for sprouting Wheat seeds (flour)

25 Focused on-farm control efforts can prevent foodborne illness in three ways Less contamination of meat at slaughter Less contamination of produce in nearby environments Less spread to children and others in contact with those animals

26 Detecting of E. coli O157 E. coli O157 Do not rapidly ferment sorbitol, so look clear (not pink) Readily identified if selective and differential agar used usually Sorbitol MacConkey +/- cefixime and tellurite

27 Detection of STEC by enzyme immunoassay (EIA) Take aliquot at 16-24h Stool Specimen Enrichment broth Shiga toxin EIA or lateral flow assay Some labs stop when test is positive

28 Clinical laboratory testing guidelines: Best Practices For all stools submitted from patients with acute communityacquired diarrhea or suspected HUS simultaneously culture for O157 and assay for non-o157 STEC with a test that detects Shiga toxin Report and send to a public health laboratory ASAP O157 isolates and Shiga toxin positive broths h"p://

29 Increase in reported non-o157 STEC mirrors increase in toxin testing, FoodNet, Number of non- O157 STEC cases reported Number of clinical labs that perform Shiga toxin EIA tes/ng Non-O157 Cases Number of Labs Hoefer, Foodborne Pathog Dis, 2011; CDC, unpublished preliminary data, 2010

30 Incidence of culture-confirmed O157 and non-o157 STEC infections, FoodNet, * Cases per 100,000 popula/on *CDC, preliminary FoodNet data, 2013 Year

31 Non-O157 STEC by serogroup, FoodNet, N=1318 isolates 63 serogroups <1.5% each preliminary data; an additional 85 isolates had missing O group information

32 Non-O157 STEC by Serogroup, FoodNet, N=1318 isolates 81% 63 serogroups <1.5% each preliminary data; an additional 85 isolates had missing O group information

33 Modes of transmission in 41 single-etiology non-o157 STEC outbreaks Outbreaks (n=41) Mode % Foodborne 34 Person- to- person 39 Mixed 7 Water 5 Animal contact 3 Unknown 12 Implicated food vehicles Bear jerky Beef BBQ pork Berries Lettuce Milk Punch Preliminary data; excluded outbreaks with more than one non-o157 STEC or another pathogen isolated

34 Severity of illness: O157 vs non-o157 STEC infections, in FoodNet O157 infec/ons Non- O157 infec/ons Feature % % Hospitalized HUS 11 1 Shiga toxin 1 only 2 74 Shiga toxin 2 only Shiga toxins 1 & All HUS cases were associated with E. coli producing Shiga toxin type 2

35 Times are changing star/ng in January Campylobacter 2. E. coli O Shiga toxin 1 and 2 4. Salmonella 5. Shigella 6. Cryptosporidium 7. Enterotoxigenic E. coli (ETEC) 8. Norovirus 9. Clostridium difficile Toxin A/B 10. Rotavirus 11.Giardia 11 pathogens in 5 hours PosiAve results require confirmaaon State health departments will be noafied as clinical labs adopt test

36 Culture-independent diagnostic tests: the time frame Many clinical laboratories will be switching to non-culture diagnostic tests within a few years Reduce costs by adopting this technology May or may not send specimens for culture Then they will move on to newer tests based on rapid DNA sequencing Within 5-10 years it will be possible to routinely get whole DNA sequence straight from clinical specimens ( metagenomics )

37 What happens if labs drop cultures and do not forward the specimen to public health? Won t know serotype (lab simply reports Shiga toxin detected ) but clinician needs to know if it s O157 because of virulence and public health needs serotype information to detect outbreaks and follow trends Won t know DNA fingerprint subtype (PulseNet PFGE pattern) but subtype is important to public health for outbreak detection PCR test might just be detecting non-pathogenic STEC It could be a false positive It could be a false negative

38 What are we doing at CDC? 2014: Advanced Molecular Diagnostics (5 year initiative) Improve pathogen identification and characterization Develop new diagnostics to meet evolving public health needs Support states current and future reference testing needs Implement enhanced, integrated laboratory information systems Develop tools for prediction, modeling and early recognition of emerging infectious diseases

39 STEC in the 21 st century A continuing challenge to public health Expanding array of serotypes, food vehicles Better outbreak detection has pushed systemic change Changes at processing have made a major impact On-farm interventions are needed to further reduce risk Laboratory-based surveillance methods will evolve as we move to a post-culture era

40 Thank you 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

41 E. coli O157 and raw cookie dough ill, 35 hospitalized, 10 HUS No deaths 30 states Median age 15 y old 75% female Eating one brand of raw cookie dough New food habit in this demographic Source unclear Intense sampling found O157 in dough Heat treated flour used since Neil 2012 Clin Infect Dis 54:

42 E. coli O104 and fenugreek sprouts Germany, ill, 769 HUS, 42 deaths 14 countries Unusual strain O104:H4 STEC and EnteroaggregativeEC Mostly Germany, one outbreak in France Linked to sprouts of imported fenugreek seeds No disinfection step Some sprouted at home Buchholz 2011 NEJM 365: ; ECDC website