1. Prevent Disease – Promote Wellness – Improve Quality of Life Patricia A. Somsel, DrPH Director, Division of Infectious Diseases Bureau of Labs, MDCH Detection of S-TEC: New Guidelines for Clinical and Public Health Labs MI ClinLabNetwork, 11/2009

2. Prevent Disease – Promote Wellness – Improve Quality of Life WHY?

3. Prevent Disease – Promote Wellness – Improve Quality of Life 1982 Cases of “hemorrhagic colitis” first recognized as a distinct entity Oregon, Feb-Mar 25 cases; mean age 28 yrs (8-76) Michigan, May-June 18 cases; mean age 17 yrs (4-58) Illness associated with consumption at Chain A restaurant of sandwiches with beef patty, rehydrated onions, pickles E coli O157:H7 isolated from cases and one lot of meat served in Michigan NEJM 1983; 308:681-5

4. Prevent Disease – Promote Wellness – Improve Quality of Life Spontaneous Resolution (~85%) HUS (~15%) -3-201234567 Diarrhea Bloody diarrhea Culture + culture Adapted from: Lancet 2005; 365:1073

5. Prevent Disease – Promote Wellness – Improve Quality of Life Estimated Foodborne illness in US* % of total Shigella 0.6%0.7% *Mead et al, 1999. Emerg Infect Dis 5(5):607-625 (Shiga toxin-producing E.coli)

6. Prevent Disease – Promote Wellness – Improve Quality of Life Frequency of pathogens in diarrheal stools, New Mexico study, Apr – Oct 2000* *All stools from acute, community-acquired diarrhea were tested in study 2.3 1.1 0.9 CampylobacterSalmonellaSTECShigella

7. Prevent Disease – Promote Wellness – Improve Quality of Life Estimates of annual STEC infections in the US E.coli O157 –73,000 acute illnesses –2,200 hospitalizations –61 deaths Non-O157 STEC –36,700 acute illnesses –1,100 hospitalizations –30 deaths Mead et al, 1999. Emerg Infect Dis 5(5):607-625

8. Prevent Disease – Promote Wellness – Improve Quality of Life HUS: Incidence Estimates in US Estimate 4,400 cases per year due to O157 –Roughly estimate 310 – 880 cases per year due to Non-O15 68% of cases occur in children < 5 years of age. Estimate 96 cases per week in all ages from all serotypes. One child in the US develops HUS each day. *Mead et al, 1999. Emerg Infect Dis 5(5):607-625

9. Prevent Disease – Promote Wellness – Improve Quality of Life The Cost? Outpatient physician care: $440 Hosp, spontaneous resolution: $5,600 Hosp, HUS w/o ESRD: $31,000 Hosp, HUS, ESRD: $5,100,000 Frenzen PD J Food Protect 2005

10. Prevent Disease – Promote Wellness – Improve Quality of Life MI STEC Study: 2001-2005 Manning SD et al. 2007. Surveillance for Shiga toxin-producing Escherichia coli, Michigan, 2001-2005. Emerg Infect Dis. Feb; 13(2):318-21.

11. Prevent Disease – Promote Wellness – Improve Quality of Life Evaluation of the enhanced surveillance using EIA on all stools Overall, 66 additional cases were identified that would not have otherwise been detected from 2001-05 –Among these 66, 31 (47%) were non-O157 27 of 64 (42%) were less than 18 years old 22 of 51 (43%) were hospitalized 39 of 51 (76%) had bloody diarrhea MI STEC Study: 2001-2005

12. Prevent Disease – Promote Wellness – Improve Quality of Life

15. Barriers to Full and Prompt Recovery of STEC* Acute disease not easily defined –~25% in the MI study NOT bloody –WBC’s may/may not be present –Generally not associated with fever –Seasonality not predictable with changing ‘menu’ of implicated foods *Without full recovery of STEC, the true burden of Non-O157 STEC disease is hidden

16. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d Physicians may not think of STEC in patient w/out classic ‘bloody diarrhea’ Physicians may not know what testing clinical labs routinely perform (and they may use multiple labs) Physicians often do not understand the role of non-O157 E.coli and the testing necessary to demonstrate it

17. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d Clinical laboratories typically test for STEC: –Upon request of physician, or hx of bloody diarrhea –Only in summer/fall, if at all –If specimen bloody (stools come in transport which is often red!)

18. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d Clinical labs typically test for STEC by culture, which can only detect E.coli O157 –Other serotypes also produce disease –Culture and prelim identification requires 24-48 hours –Media and serotyping reagents expensive and may outdate if testing rarely ordered, so many labs may ‘send-out’ this testing to commercial labs, resulting in additional delay of 1-2 days

19. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d EIA (toxin) detects all serotypes, but –Clinical labs unsure if they can do both culture and EIA and get reimbursed –Confusion about appropriate billing for EIA –Some PHLabs will not accept broths –Subculture of broth to solid media may result in delayed result –EIA may not fit into the ‘routine’ as easily as SMAC plate –False Positives? –Workforce issues

20. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d Once a likely STEC is isolated, it must be shipped to a PHLab for further characterization, including PFGE and uploading to PulseNet. –Effective Oct 2, 2009 STEC isolates MUST by law be submitted in MI –STEC is a Category A agent, which requires special handling and extra expense. –Labor, materials, and shipping costs for public health purposes not reimbursable

21. Prevent Disease – Promote Wellness – Improve Quality of Life Barriers, cont’d Specimens sent to commercial laboratories which may not be in the state of the patient residence, so STEC recovered may not go to the PHLab in the state responsible for follow- up/investigation Unless STEC isolates reach PH for complete characterization, the full picture of STEC disease is unrecognized, investigations are incomplete and appropriate interventions are hampered.

22. Prevent Disease – Promote Wellness – Improve Quality of Life Response

23. Prevent Disease – Promote Wellness – Improve Quality of Life Importance of Culture Confirmation of Shiga Toxin-producing Escherichia coli Infection as Illustrated by Outbreaks of Gastroenteritis — New York and North Carolina, 2005 Morbidity and Mortality Weekly Report September 29, 2006 / Vol. 55 / No. 38

24. Prevent Disease – Promote Wellness – Improve Quality of Life Conclusion: Rapid tests can facilitate the detection of outbreaks of STEC, but when used alone may produce false positive results Described the investigation of two outbreaks of gastroenteritis in which laboratories used non-culture methods to detect Shiga toxin.

25. Prevent Disease – Promote Wellness – Improve Quality of Life Health care providers should notify clinical labs if STEC is suspected Clinical labs should strongly consider adding STEC O157 to routine enteric cultures Ideally clinical labs should screen all stools for STX using an EIA AND culture for O157 Clinical labs that use an EIA only should sub positives ASAP for STEC O157 All STEC O157 isolates and positive broths from which O157 has not been recovered should be forwarded ASAP to PHLabs Clinical and PHLabs work together for correct diagnosis and follow-up Recommendations:

26. Prevent Disease – Promote Wellness – Improve Quality of Life Results of a 2007 Survey of Clinical Labs in MI (69/123) 26% (18) offered testing on-site* ~50% of these tested all stools for O157 ~20% of these tested bloody stools only ~20% tested only when requested *if didn’t offer testing on-site, sent to reference laboratory upon request #2009 update: approximately 30 clinical labs in MI now perform EIA; not clear if this is on all stools. Barriers, cont’d

27. Prevent Disease – Promote Wellness – Improve Quality of Life Why this didn’t work Published in MMWR - Did not reach target audience – effected little change in clinical practice Difficulties in reimbursement All PHLabs not on the same page –Commercial/reference laboratories might have multiple, mutually exclusive requirements to meet for PHLabs in different states –Requirements of PHLabs not always accomadating of clinical lab reality

28. Prevent Disease – Promote Wellness – Improve Quality of Life Meeting Convened at CDC in 2007: Role of Commercial Diagnostic and Public Health Laboratories in Enteric Disease Surveillance and Response

29. Prevent Disease – Promote Wellness – Improve Quality of Life Issues Identified Reimbursement problems Lack of communication to clinical labs Inconsistent requirements from PHLabs Inconsistent cooperation from diagnostic labs

30. Prevent Disease – Promote Wellness – Improve Quality of Life Needs Identified Establish a standard of practice for detection of STEC by clinical labs Establish consistent expectations for PHLabs Establish consistent expectations for clinical, commercial/reference labs

31. Prevent Disease – Promote Wellness – Improve Quality of Life Plan of Action Produce a new MMWR to establish standards of practice diagnostic labs Produce a companion piece detailing standards of practice for PHLabs Follow-up with broad dissemination of guidelines via conferences and additional publications to reach non-doctoral level microbiologists, pathologists, physicians

32. Prevent Disease – Promote Wellness – Improve Quality of Life Authored by 15 microbiologists from clinical, commercial and public health labs, as well as ID physicians – a consensus document Presents evidence to support culture and toxin testing of ALL stools submitted for routine culture. Details implementation of guidelines Describes the performance characteristics of commercially available assays, and acceptable specimens New MMWR ~ October 16, 2009 MMWR Vol 58:RR-12. October 2009.

33. Prevent Disease – Promote Wellness – Improve Quality of Life Will establish a standard against which microbiology practices might be compared Will establish an expectation for reimbursement for culture AND toxin testing

34. Prevent Disease – Promote Wellness – Improve Quality of Life How?

35. Prevent Disease – Promote Wellness – Improve Quality of Life Clinical Lab Recommendations Culture to selective and differential media (e.g.,SMAC) Enzyme ImmunoAssay (EIA) to detect TOXIN AND All Stool Specimens

36. Prevent Disease – Promote Wellness – Improve Quality of Life O157 STEC Pos EIA with no O157 isolate suggesting non- O157 STEC OR isolate broth Category A UN 2814 PHL Clinical Lab Recommendations ASAP

37. Prevent Disease – Promote Wellness – Improve Quality of Life PHLab Recommendations Remove barriers to rapid submission of isolates and broths Expedite testing to rapidly recognize/report presence of Stx-2 Organize testing to rapidly submit isolate patterns to PulseNet

38. Prevent Disease – Promote Wellness – Improve Quality of Life Public Health Recommendations -Details If receive isolates of O157 STEC: confirm biochemically as E. coli serotype (O and H antigens) characterize Shiga toxin type stx gene specific PCR an antibody/antigen assay that can distinguish between Shiga toxin 1 and 2 PFGE and upload to PulseNet

39. Prevent Disease – Promote Wellness – Improve Quality of Life If Receive Clinical Sample/broth: Cefixime and Tellurite Sorbitol MacConkey (CT-SMAC) OR a chromogenic agar (e.g. CHROM™ Agar] AND Sorbitol MacConkey agar (SMAC) OR Washed sheep’s blood agar Public Health Recommendations…

40. Prevent Disease – Promote Wellness – Improve Quality of Life If no colonies resemble O157 STEC Test for the presence of Shiga toxin via colony sweep of the growth using EIA, Vero Cell Culture, or PCR Public Health Recommendations…..

41. Prevent Disease – Promote Wellness – Improve Quality of Life If this Stx screen is negative: STOP If the Stx screen is positive: screen up to 10 individual colonies for Shiga toxin EIA, Vero Cell Culture or PCR Evidence indicates STEC may be isolated 90% of the time when 10 isolates are screened Public Health Recommendations…..

42. Prevent Disease – Promote Wellness – Improve Quality of Life Once a STEC is identified: biochemically confirm as E. coli serotype the isolate O antigen only: O26, O103, O111, O121, and O157 If not one of the above, forward to the CDC E. coli Reference Laboratory If an STEC is not identified after 10 isolates are tested forward to the CDC E. coli Reference Laboratory Public Health Recommendations…..

43. Prevent Disease – Promote Wellness – Improve Quality of Life Perform PFGE on all STEC isolates Public Health Recommendations….. Upload to PulseNet

44. Prevent Disease – Promote Wellness – Improve Quality of Life STEC PHLab Best Practice EIA Positive Broth Selective culture Screen colonies for O157 STEC If no O157 – Screen for Shiga toxin by PCR Negative Screen = stop work up Serogroup PFGE Positive Screen = search up to 20 colonies for STEC

45. Prevent Disease – Promote Wellness – Improve Quality of Life Special consideration for specimens from HUS patients If the recommended guidelines do not produce an isolate: IMS – Immunomagnetic Separation Technique Key to work with physicians, clinical laboratories and epidemiology to get samples quickly Public Health Recommendations…..

46. Prevent Disease – Promote Wellness – Improve Quality of Life Companion Public Health Laboratory Guidelines, expected Fall 2009 –Authored by 17 public health microbiologists (state and federal) –Details Best Practices for PHLabs to support the clinical labs in their jurisdictions to assure rapid and comprehensive recognition of STEC

47. Prevent Disease – Promote Wellness – Improve Quality of Life STEC MMWR Workgroup L. Hannah Gould 1 Cheryl Bopp 1 Nancy Strockbine 1 Robyn Atkinson 2 Vickie Baselski 3,4 Barbara Brody 5 Roberta Carey 1 Claudia Crandall 6 Sharon Hurd 7 Ray Kaplan 8 Marguerite Neill 9 Shari Shea 10 Patricia Somsel 11 Melissa Tobin-D’Angelo 12 Patricia M. Griffin 1 Peter Gerner-Smidt 1 1 CDC, 2 TN Dep’t Hlth, 3 ASM, 4 Univ of TN Hlth Sci Ctr, 5 LabCorp, 6 CA Dept Hlth, 7 CT Emerg Inf Prog, 8 Quest Diagnostics, 9 Brown Univ,Wareen Alpert Sch of Med, 10 Assoc of Pub Hlth Labs, 11 MI Dept Comm Hlth, 12 GA Div of Pub Hlth

48. Prevent Disease – Promote Wellness – Improve Quality of Life APHL STEC Work Group: John Besser – MNCami Hartley - NC Chris Carlson – SDClaudia Crandall - CA Cindy Fisher – UTDebbie Rutledge - DE Karim George – KYPatricia Somsel - MI Steve Gladbach – MOTim Monson - WI Hugh Maguire – COL. Hannah Gould - CDC Nancy Strockbine – CDCCheryl Bopp – CDC Peter Gerner-Smidt – CDCSharon Shea - APHL

49. Prevent Disease – Promote Wellness – Improve Quality of Life Acknowledgements MDCH –Kendra Anspaugh –Barbara Evans –Robbie Madera –James Rudrik, PhD –Bill Schneider –Hao T. Trihn MSU –Late Tom Whittam, PhD –Shannon Manning* –Microbial Evolution Lab *STEC surveillance project conducted by Dr. Manning during an EID fellowship