Thirteen Year Summary of Primary Amebic Meningoencephalitis in Texas

1. Thirteen Year Summary of Primary Amebic Meningoencephalitis in Texas Heather K. Noble Public Health Internship Program University of Texas at Austin Mentors: Karen Moody and Marilyn Felkner Texas Department of State Health Services

2. Introduction

3. A New Disease • 1965:4 Australian patients die of acute amebic meningitis • Fowler and Carter identify trophozoites in olfactory bulbs and frontal lobes • 1966:Butt coins term ‘primary amebic meningoencephalitis’ (PAM) • 1970:Carter demonstrates that organism in CSF of infected individuals is unique species • Naegleria fowleri

4. Naegleria fowleri • Ubiquitous in nature • Feeds on coliform bacteria • Three forms depending on environment Trophozoite Flagellate Cyst Visvesvara et al., 2007, FEMS Immunol Med Microbiol

5. N. fowleri Trophozoite Marciano-Cabral & Cabral, 2007, FEMS Immunol Med Microbiol • Infectious form • 10-25 µm • Prominent nucleolus and vacuoles • Amoebastome food cups with toxic naegleriapores

6. Exposure • Warm, untreated freshwater reservoirs • Municipal water supplies • Lakes, ponds, rivers, and runoff streams • Improperly maintained pools

7. Forceful Entry Behaviors: • Inhalation of water • Swimming • Diving • Active water sports • Skiing • Tubing • Scuba diving • Wake boarding

8. Pathogenesis • Attachment to nasal epithelium • Invasion of brain via olfactory nerves and cribiform plate • Infection of grey matter and tissue necrosis • Severe inflammation

9. Incubation: 3 to 10 days Illness duration: Days to weeks Clinical Presentation: Headache Nausea/vomiting Fever Loss of taste and smell Confusion Seizures Disease Characteristics

10. Laboratory Diagnosis • Procedure: • CSF collection • CSF examination • Wet preparation • Flagellation Test • Culture • E. coli seeded plate • PCR Ahmad, 2007, Int J Pathol

11. Treatment • Amphotericin B • Antifungal • Binds ergosterol to form pore • Collateral damage to human cells • Rifampin • Antibiotic • Inhibits RNA polymerase • Efficacy questioned

12. Knowledge of PAM • Rare but highly lethal • Estimated to affect 1 in 2.6 million exposed • 95% fatality rate • Case studies • Pertinent history • Symptoms and hospital course • Laboratory and autopsy data

13. Cases reported in: United States Puerto Rico Mexico Panama Venezuela New Guinea Australia New Zealand Great Britain Czech Republic Belgium Italy Nigeria Uganda India Thailand PAM Case Reports: Worldwide

14. PAM Case Reports: US 1962-2008 Yoder et al., 2009, Epidemiol Infect

15. PAM Case Reports: Texas 1966-1995

16. Purpose • To describe confirmed PAM cases that occurred in Texas between 1996 and 2009 • To identify potential risk factors for disease and guide Texas healthcare professionals in the identification and treatment of PAM cases

17. Methods

18. Study Population • All confirmed Texas PAM cases that occurred between 1996 and 2009 • Only Texas residents • Confirmation required isolation and positive identification of N. fowleri in a CSF specimen

19. DSHSRecords Hospital Charts Media Reports Data Sources Identify Confirmed Cases Request Hospital Records

20. Variables Analyzed • Age • Sex • Race • Dates of illness • Exposure • Date and site • Patient history • Symptoms • Laboratory findings • Treatment

21. Data Analysis • Tools: • Excel • Access • Epi Info • Measures: • Frequencies • Means

22. Results

23. TX PAM Cases, 1996-2009 • 11 PAM cases on file, but only 10 were Texas residents • Reviewed media and hospital reports: 10 total unique Texas PAM cases identified

24. Demographic Data Gender Race/Ethnicity n = 10 n = 10

25. Age Distribution of PAM Cases • Victim Age Distribution

26. PAM Case Reports by Year, 1996-2009 • PAM Incidence in Texas from 1996-2009

27. Month and Date of Symptom Onset 6 of the 10 recorded cases began in the first week of August for their respective years (1998, 2001*, 2002, 2007, 2008)

28. N. fowleri Exposure Sites for Texas PAM Cases, 1996-2009 • N. fowleri Reservoirs • Pie Chart n = 10

29. Texas PAM Case Reports by County of Residence, 1996-2009

30. Mechanisms of Exposure

31. Incubation Ranges

32. Disease Presentation

33. Laboratory Results: CSF

34. Laboratory Results: Blood

35. Treatments by Drug Class

36. Illness Duration • Victim Illness Duration

37. Conclusions

38. Conclusions • Young males (ages 5-14) at greatest risk • PAM cases tend to occur during the warmest summer months, particularly August • Untreated freshwater reservoirs • History of recreational water activities, especially swimming

39. Conclusions • Incubation: 4-16 days • Common symptoms: disorientation, vomiting • PAM laboratory profiles resemble bacterial meningitis, although amebae present in CSF • Illness duration: 3-10 days

40. Recommendations • During the warmest summer months: • Swimmers should be warned of risks associated with untreated waters • All recreational water users should plug noses • Doctors should maintain high index of suspicion for PAM

41. Limitations • Small sample size • Rarity of disease • Archived hospital records • Difficult to retrieve • Sometimes incomplete • Questionable legibility of copies

42. Future Studies • Retrieve remaining archives • Complete study • Study virulence of N. fowleri from new confirmed cases • Correlate virulence with lethality and illness duration • LD50 in mice • Perform in-depth analysis of treatment regimens • Which therapeutic agents have had success? • How important is quick initiation of therapy? • Which patient variables may affect therapy?

43. Acknowledgements • TDSHS • Ms. Karen Moody • Dr. Marilyn Felkner • UT Austin • Dr. Leanne Field • Ms. Nancy Elder • Dr. Diane Kneeland

44. Acknowledgements • I would also like to thank the generous program sponsor: Association of Public Health Laboratories