1. Economic Evaluation of 2012 Fungal Meningitis Outbreak in New River Valley Nargesalsadat Dorratoltaj, MS, MPH Department of Population Health Sciences, Virginia Tech, Blacksburg, VA Margaret O'Dell, MD, MFA New River Health District, Virginia Department of Health, Christiansburg, VA Page Bordwine, MPH, MT(ASCP) New River Health District, Christiansburg, VA Thomas Kerkering, MD, FACP, FIDSA Carilion Clinic, Virginia Tech Carilion School of Medicine, Roanoke, VA Kerry Redican, PhD, MPH, MSPH, CHES Department of Population Health Sciences, Virginia Tech, Blacksburg, VA Kaja Abbas, PhD, MPH Department of Population Health Sciences, Virginia Tech, Blacksburg, VA

2. Conflict of Interest: None We declare that we have no conflict of interest, and we comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines.

3. Learning objectives Identify the costs and effectiveness of 2012 fungal meningitis outbreak response in New River Valley, Virginia. Evaluate the incremental cost-effectiveness ratio of the fungal meningitis outbreak response. Assess the incremental cost-effectiveness ratio to prioritize the limited resources of the local health department.

4. Study Objective

5. The objective of this study is : To conduct an economic evaluation of fungal meningitis outbreak response from local health department and clinical facilities perspectives.

6. Background What is fungal meningitis? Nationwide outbreak Outbreak in Virginia

7. What is fungal meningitis? Fungus spread through blood to the spinal cord Swelling of protective membranes, covering brain, and spinal cord Not contagious Signs and symptoms: Fever Headache Stiff neck Nausea and vomiting Photophobia (sensitivity to light) Altered mental status Treatment is with long courses of high dose antifungal medications Voriconazole

8. Pathogenesis Predominant Pathogen: Exserohilum rostratum (a brown-black mold) Index case Infection: Aspergillus fumigatus Common in the Environment Risk factors: Immunocompromised patients Loss of immunity associated with age

9. Started in September 2012 at Tennessee Methylprednisolone Acetate (MPA) used for Epidural Spinal Injections (ESI) Contaminated MPA lots were produced in a Compounding pharmacy in MA. Nationwide outbreak

10. Contaminated injections put 13,000 people at risk of fungal meningitis. Final count: 751 cases, 64 deaths, 20 states States received contaminated MPA lots: States with confirmed cases: Source: CDC

11. Contaminated lots in Virginia Two facilities in Virginia received the contaminated lots: Insight Imaging, Roanoke Valley New River Valley Surgery Center, Christiansburg VA Local Health Departments started their surveillance in October 2012 to control the outbreak.

12. Public Health Significance

13. Virginia with 54 cases and 5 deaths affected significantly by the outbreak. Cost effectiveness analysis assists the local health department to prioritize its resources effectively and efficiently.

14. Methods New River Health District surveillance system Incremental Cost Effectiveness Ratio (ICER)

15. New River Health District surveillance system

16. Incremental Cost Effectiveness Ratio (ICER) Used in economic evaluation of health programs Useful approach for making decisions about new interventions Ratio of the change in the costs to incremental benefit of an intervention

17. Costs Cost of new intervention o Local health department cost New River Health District o Local clinical facilities cost Lewis Gale o Montgomery o Salem o Pulaski Roanoke Carillion Cost of control o No intervention from local health department.

18. Effectiveness: Disability Adjusted Life Years(DALY) averted

19. Results Local health department cost Clinical facility cost Effectiveness Incremental Cost-Effectiveness Cost (ICER)

20. Local health department costs NRHD DivisionTotal Cost Epidemiologists $16,748.5 Director of Health District $6,746.9 Planner $1,558.7 EH Manager $511.0 Clerical $372.8 Admin $240.0 Nurse Epi $575.5 Volunteers $3,739.5 Total $30,492.9

21. Clinical facilities costs New River Valley had more than 90 exposed patients 14 patients: CSF cultured 12 patients: Lumbar Puncture Test 9 patients: Have admission records at local clinical facilities Total Cost: $41,667

22. Effectiveness ParameterEstimation DALY2.87+97.65=100.52 YLL(With treatment) # of potential cases Case fatality Average life expectancy in Virginia Average age of exposed patients YLL (Without treatment) # of potential cases Case fatality Average life expectancy in Virginia Average age of exposed patients YLL 10.15 years 7 10% 79 years 57 years 107.8 years 7 70% 79 years 57 years |10.15-107.8|= 97.65 YLD(With treatment) Disability weight Average duration of Disease YLD(Without treatment) YLD 2.87 years 0.615, [0.613,0.616] 8 months [3 months- 1yr] 0 2.87

23. Incremental Cost Effectiveness Ratio

24. Discussion

25. The cost effectiveness ratio of this outbreak response from the local health department and clinical facilities perspective, is $718 per DALY averted.

26. Cost effectiveness thresholds

27. Public Health Implications

28. The results of this study can help decision makers at local health departments to prioritize among different outbreak responses in resource limited areas.

29. Limitations

30. No confirmed case of fungal meningitis Estimation of clinical facility cost Cost of control for clinical facilities Estimation of fungal meningitis characteristics

31. Future Work

32. Future work Add state and federal level to the ICER calculation. Apply the ICER calculation in health district with confirmed cases Multi-layered response to the fungal meningitis outbreak

33. Acknowledgements Public Health Program

34. References [1] Kainer, M. A., Reagan, D. R., Nguyen, D. B., Wiese, A. D., Wise, M. E., Ward, J., & Jones, T. F. (2012). Fungal infections associated with contaminated methylprednisolone in Tennessee. New England Journal of Medicine, 367 (23), 2194-2203. 2] Centers for Disease Control and Prevention. Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a single compounding pharmacy - united states, 2012. MMWR. Morbidity and mortality weekly report, 61(41):839{8 42, October 2012. PMID: 23076093. [3] Center for Disease Control and Prevention. Multistate fungal meningitis outbreak investigation. http://www.cdc.gov/HAI/outbreaks/meningitis.html. [Accessed 15 August 2013] http://www.cdc.gov/HAI/outbreaks/meningitis.html [4] Smith, R. M., Schaefer, M. K., Kainer, M. A., Wise, M., Finks, J., Duwve, J., & Park, B. J. (19). December 2012. Fungal infections associated with contaminated methylprednisolone injections—preliminary report. N. Engl. J. Med.[Epub ahead of print.] doi, 10. [5] Kauffman, C. A., Pappas, P. G., & Patterson, T. F. (2013). Fungal infections associated with contaminated methylprednisolone injections. New England Journal of Medicine, 368 (26), 2495-2500. [6] Measure of America, 2013-2014. [7] Rosenstein, N. E., Perkins, B. A., Stephens, D. S., Popovic, T., & Hughes, J. M. (2001). Meningococcal disease. New England Journal of Medicine, 344 (18), 1378-1388. [8] Meningitis Causes, Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/meningitis/basics/causes/con-20019713, accessed on March 31, 2014http://www.mayoclinic.org/diseases-conditions/meningitis/basics/causes/con-20019713 [9] Mathers, C., Fat, D. M., & Boerma, J. T. (2008). The global burden of disease: 2004 update. World Health Organization. [10] Centers for Disease Control and Prevention (CDC). (2012). Multistate fungal meningitis outbreak investigation interim treatment guidance for central nervous system and/or parameningeal infections associated with injection of potentially contaminated steroid products [11] Case Definitions for Fungal Meningitis and Other Infections. (2013, October 23). Centers for Disease Control and Prevention. Retrieved April 16, 2014, from http://www.cdc.gov/hai/outbreaks/clinicians/index.html http://www.cdc.gov/hai/outbreaks/clinicians/index.html [12] Grosse, S. D. (2008). Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. [13] Lumbar Puncture, Healthcare Bluebook, from https://www.healthcarebluebook.com/page_Results.aspx?id=375&dataset=MD [14] Barenfanger, J., Lawhorn, J., & Drake, C. (2004). Nonvalue of culturing cerebrospinal fluid for fungi. Journal of clinical microbiology, 42 (1), 236-238. [15] Caldwell, N., Srebotnjak, T., Wang, T., & Hsia, R. (2013). “How Much Will I Get Charged for This?” Patient Charges for Top Ten Diagnoses in the Emergency Department. PloS one, 8 (2), e55491.

35. Thank you! Contact: Narges Dorratoltaj nargesd@vt.edu

36. Benefits DALY = Years of Life Lost (YLL) + Years of Life Lost due to Disability (YLD) YLL= Number of potential cases x case fatality x (Average life expectancy- Average Age at time of death) YLD = Number of cases x Disability Weight x Average duration of the disease until remission or death