1. Fungal Infections Associated with Contaminated Methylprednisolone Acetate in Michigan, 2012-2013 Joseph R. Coyle, MPH Michigan Department of Community Health Exserohilum rostratum

2. Michigan Outbreak Response Team: ▫ Brenda Brennan ▫ Jim Collins ▫ Joe Coyle ▫ Jay Fiedler Michigan Pain Clinics and Staff Michigan Hospitals- Administrators, Clinicians, IPs State Health Departments Centers for Disease Control and Prevention ▫ Jennie Finks ▫ Shannon Johnson ▫ Jevon McFadden ▫ Mawuli Nyaku ▫ Many others… Acknowledgements 2

3. Outline Outbreak Timeline Role of the MDCH Michigan Pain Clinics ▫ Patient Notification Identifying and Counting Cases ▫ Surveillance definitions Characterization and Epidemiology of Fungal Infections in Michigan Summarizing the MDCH Contribution 3

4. Case Count October 8 th, 2012 Case Count June 3 rd, 2013 Outline 4

5. 5

6. Outbreak Timeline September 18 th, 2012 – Tennessee Department of Health (TDH) receives report of 56-year old patient with Aspergillus meningitis September 25 th, 2012 – TDH identified an additional 7 patients with meningitis ▫ All TN patients received an epidural steroid injection from a common Ambulatory Surgery Center ▫ All injections were from three lots of methylprednisolone acetate (MPA) from the New England Compounding Center (NECC) 6

7. September 26 th, 2012 – NECC voluntarily recalls three lots of MPA (05212012, 06292012, and 08102012) September 27 th, 2012 – North Carolina Department of Health and Human Services identifies a patient with meningitis also exposed to one of the three recalled lots of MPA TN and NC patients had similar presentations (sub- acute meningitis with pleocytosis) with a common exposure (NECC MPA) Outbreak Timeline 7

8. September 28 th, 2012 – Growing evidence of connection between meningitis cases and NECC MPA shared on multi-state call with CDC October 1 st, 2012 –NECC customer invoice list shared with the Michigan Department of Community Health (MDCH) Bureau of Epidemiology October 2 nd, 2012 – MDCH begins contacting Michigan clinics who were recipients of recalled lots of NECC MPA Outbreak Timeline 8

9. 9

10. Maintaining daily contact with CDC (Epi, Lab, and Clinical) Retrospectively and prospectively identifying cases and maintaining case count / line list Coordinating with Michigan hospitals and clinicians Sharing information via the Michigan Health Alert Network (MIHAN) Updating media via press releases and our PIO Collection of specimens to be forwarded to CDC lab for testing MDCH Role 10

11. MDCH Role Chart abstraction and data collection Patient Notification and Coordinating with Michigan Clinics: ▫ Re-enforcing recall and instructing clinics to pull any recalled product from circulation ▫ Identifying a point-of-contact at each pain clinic ▫ Working with clinics to determine a list of patients potentially exposed to a recalled lot of NECC MPA ▫ Assisting clinics with direct patient notification:  Direct contact via phone (voicemail not sufficient)  Registered letter 11

12. 12

13. Michigan Pain Clinics LocationRecalled Product ReceivedExposures* Lot NumberAmountProductPatientsInjections Clinic A06292012400 vialsMPA 80mg/mL – 5mL PF638759 Clinic B 052120121,000 vialsMPA 80mg/mL – 1mL PF 1,0321,668 06292012500 vialsMPA 80mg/mL – 1mL PF Clinic C 05212012100 vialsMPA 80mg/mL – 1mL PF 102114 06292012100 vialsMPA 80mg/mL – 1mL PF 08102012100 vialsMPA 80mg/mL – 1mL PF Clinic D0521201225 vialsMPA 80mg/mL – 1mL PF3240 MI TOTAL2,225 vials1,8042,581 13 *Estimates

14. Michigan Pain Clinics LocationRecalled Product ReceivedExposures* Lot NumberAmountProductPatientsInjections Clinic A06292012400 vialsMPA 80mg/mL – 5mL PF638759 Clinic B 052120121,000 vialsMPA 80mg/mL – 1mL PF 1,0321,668 06292012500 vialsMPA 80mg/mL – 1mL PF Clinic C 05212012100 vialsMPA 80mg/mL – 1mL PF 102114 06292012100 vialsMPA 80mg/mL – 1mL PF 08102012100 vialsMPA 80mg/mL – 1mL PF Clinic D0521201225 vialsMPA 80mg/mL – 1mL PF3240 MI TOTAL2,225 vials1,8042,581 14 *Estimates

15. Michigan Shipments of NECC MPA Lot NumberMichigan (mLs)Nationwide (mLs) 1 MI % of Nation 052120121,12511,6229.7% 062920122,60010,66524.4% 081020121004,3032.3% TOTAL3,82526,59114.4% 15

16. Michigan Shipments of NECC MPA Lot NumberMichigan (mLs)Nationwide (mLs) 1 MI % of Nation 052120121,12511,6229.7% 062920122,60010,66524.4% 081020121004,3032.3% TOTAL3,82526,59114.4% 1 Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. Preliminary data analysis indicated lot 06292012 had the highest attack rate of the three recalled lots 1,2 2 Kainer et al. “Fungal Infections Associated with Contaminated Methylprednisolone in Tennessee”. New England Journal of Medicine 367(23):2194-203 16

17. Objectives: ▫ Explain patient’s exposure and evaluate individual for current signs and symptoms of meningitis or localized infection ▫ If the patient is symptomatic:  Refer patient to receive immediate medical evaluation ▫ If the patient is asymptomatic:  Discuss signs and symptoms of disease  Inform patients to receive immediate medical evaluation if they experience symptoms in the future ▫ Answer any other questions or concerns patients might have Patient Notification 17

18. MDCH staff helped a Clinic A place phone calls on 10/6 MDCH and Local Health Department staff dispatched to Clinic B from 10/8 to 10/10 to aid in contacting patients Patients hard to reach by phone sent registered letter Patient Notification 18

19. 19

20. Case Definitions (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html An individual potentially exposed to one of the three recalled lots of NECC MPA who meets one of the following criteria: Meningitis - Meningitis of unknown etiology Stroke - Posterior circulation stroke without a cardioembolic source and without documentation of a normal cerebrospinal fluid (CSF) profile Paraspinal Infection - Osteomyelitis, abscess or other infection (e.g., soft tissue infection), in the spinal or paraspinal structures at or near the site of injection Joint Infection - Osteomyelitis or worsening inflammatory arthritis of a peripheral joint (e.g., knee, shoulder, or ankle) 20

21. Case definitions are not mutually exclusive ▫ e.g. a patient could have both meningitis and a para- spinal infection Cases were counted in the state where they received their injection ▫ e.g. Michigan residents who received NECC injections in Indiana are counted as Indiana cases Deaths reported are from all causes among persons who meet at least one of the case definitions ▫ Deaths are not necessarily directly attributed to a fungal infection or treatment complications Case Identification (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html 21

22. Determination of infection was made by clinical teams, including neuroradiologists and infectious disease specialists, who interpreted findings in the context of patient signs and symptoms For example: ▫ Clinical judgment – determining what is an infectious versus non-specific enhancement on MRI ▫ Patient judgment – determining new or worsening pain beyond baseline MDCH counted cases, but did not ‘call’ cases Case Identification (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html 22

23. 23

24. Case Count (as of June 3 rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 24

25. 25 Case Count (as of June 3 rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

26. Case Count (as of June 3 rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 26

27. Case Breakdown a 16 deaths among persons meeting one of the case definitions b 83 (31.8%) cases laboratory confirmed by culture, histopathology or molecular assay 27

28. Case Count (as of June 3 rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 28

29. 29 Michigan N=264 Virginia N=54 Case Breakdown

30. Patients Exposed 1 Patients Infected Michigan Nationwide Case Count (as of June 3 rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 30 1 Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012.

31. Epi Curve Change in case presentation from meningitis to primarily para- spinal infections around late October prompted one hospital to recommend screening MRIs for all asymptomatic patients potentially exposed at Clinic A 31

32. Screening MRIs Approach initiated by a single Michigan hospital 414 asymptomatic patients targeted as part of outreach ▫ Preliminary data on 292 patients who received MRI screens Represents approximately 50 patients who may not have been otherwise identified 32

33. Infection Timeline 33 N=5 N=41

34. 34 Infection Timeline N=73 N=214

35. 35 Infection Timeline N=255

36. Case Demographics Age (n=264) Median66 Range28-89 Sex (n=264) Female15458.3 % Male11041.7 % Race (n=264) American Indian / Alaskan Native10.4 % Asian10.4 % Black / African American41.5 % Caucasian24793.6 % Unknown114.2 % 36

37. Clinic Attack Rates LocationRecalled Product ReceivedExposures*Infections Lot Number Amount (vials) ProductPatientsCases Attack Rate Clinic A06292012400MPA 80mg/mL – 5mL63821233.2 % Clinic B 052120121,000MPA 80mg/mL – 1mL 1,032525.0 % 06292012500MPA 80mg/mL – 1mL Clinic C 05212012100MPA 80mg/mL – 1mL 10200.0 % 06292012100MPA 80mg/mL – 1mL 08102012100MPA 80mg/mL – 1mL Clinic D0521201225MPA 80mg/mL – 1mL3200.0 % MI Total2,2251,80426414.6 % Nationwide26,591 1 13,534 2 745 3 5.5 % 1 Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. 2 http://www.cdc.gov/hai/outbreaks/infographic.html http://www.cdc.gov/hai/outbreaks/infographic.html 3 http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 37 *Estimates

38. LocationRecalled Product ReceivedExposures*Infections Lot Number Amount (vials) ProductPatientsCases Attack Rate Clinic A06292012400MPA 80mg/mL – 5mL63821233.2 % Clinic B 052120121,000MPA 80mg/mL – 1mL 1,032525.0 % 06292012500MPA 80mg/mL – 1mL Clinic C 05212012100MPA 80mg/mL – 1mL 10200.0 % 06292012100MPA 80mg/mL – 1mL 08102012100MPA 80mg/mL – 1mL Clinic D0521201225MPA 80mg/mL – 1mL3200.0 % MI Total2,2251,80426414.6 % Nationwide26,591 1 13,534 2 745 3 5.5 % 1 Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. 2 http://www.cdc.gov/hai/outbreaks/infographic.html http://www.cdc.gov/hai/outbreaks/infographic.html 3 http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html 38 Clinic Attack Rates *Estimates

39. Michigan had the highest number of potentially exposed patients 1 Michigan received a disproportionate amount of the 06292012 ‘Hot Lot’ Potentially higher contamination in 5mL vials of MPA? Enhanced surveillance and MRI screenings may have identified cases that might have otherwise been missed Factors contributing to burden of cases in Michigan 1 Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. 39

40. 40

41. Contributions from MDCH MDCH dedicated ~4,000 hours during the first three months of the outbreak (equivalent of two FTEs) Case report form completion – over 10,000 pages of hospitalization information from fungal cases abstracted from medical records sent to CDC: ▫ 264 case report forms, each a minimum of 27 pages in length – totaling ~7,128 pages ▫ 277 additional admission case report forms, each a minimum of 12 pages in length – totaling ~3,324 pages Sharing information to help inform national guidelines and recommendations 41

42. Providing hospital assistance and support clinical decision making: ▫ MDCH Certificates of Need through Licensing and Regulatory Affairs  Allowed hospital to obtain an additional mobile MRI  Allowed hospital to open an additional operating suite ▫ Redirected patients to hospitals with lower burden of infected patients ▫ Assisted with staffing augmentation at overburdened facilities  FEP Volunteer Management expedited out-of-state nurse licensure Contributions from MDCH 42

43. Facilitated patient notification which led to early diagnosis and treatment Contributions from MDCH 43 http://www.cdc.gov/hai/outbreaks/infographic.html

44. 44 Thanks!

45. 45 Questions?