Joseph R. Coyle, MPH Michigan Department of Community Health

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

2. Acknowledgements • Jennie Finks • Shannon Johnson • Jevon McFadden • Mawuli Nyaku • Many others… • 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

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

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

5. Outbreak Timeline

6. Outbreak Timeline • September 18th, 2012 – Tennessee Department of Health (TDH) receives report of 56-year old patient with Aspergillus meningitis • September 25th, 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)

7. Outbreak Timeline • September 26th, 2012 – NECC voluntarily recalls three lots of MPA (05212012, 06292012, and 08102012) • September 27th, 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)

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

9. Role of the Michigan Department Community Health

10. MDCH Role • 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

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

12. Michigan Pain Clinics

13. Michigan Pain Clinics *Estimates

14. Michigan Pain Clinics *Estimates

15. Michigan Shipments of NECC MPA

16. Michigan Shipments of NECC MPA 1Smith 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 lots1,2 2Kainer et al. “Fungal Infections Associated with Contaminated Methylprednisolone in Tennessee”. New England Journal of Medicine367(23):2194-203

17. Patient Notification • 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

18. Patient Notification • 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

19. Identifying and Counting Cases

20. Case Definitions (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)

21. Case Identification (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html ) • 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

22. Case Identification (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html ) • 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

23. Epidemiology of Fungal Infections in Michigan

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

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

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

27. Case Breakdown a16 deaths among persons meeting one of the case definitions b83 (31.8%) cases laboratory confirmed by culture, histopathology or molecular assay

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

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

30. Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html) Patients Exposed1 Patients Infected 1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. Michigan Nationwide

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

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

33. Infection Timeline N=5 N=41

34. Infection Timeline N=73 N=214

35. Infection Timeline N=255

36. Case Demographics

37. Clinic Attack Rates 1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. *Estimates 2http://www.cdc.gov/hai/outbreaks/infographic.html 3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

38. Clinic Attack Rates 1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. *Estimates 2http://www.cdc.gov/hai/outbreaks/infographic.html 3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

39. Factors contributing to burden of cases in Michigan • Michigan had the highest number of potentially exposed patients1 • 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 1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012.

40. Summary

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

42. Contributions from MDCH • 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

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

44. Thanks!

45. Questions?