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 TrophozoiteFlagellateCyst Visvesvara et al., 2007, FEMS Immunol Med Microbiol

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

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

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. PAM Case Reports: Worldwide 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

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. Data Sources Identify Confirmed Cases Hospital Charts DSHS Records Media Reports 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 n = 10 GenderRace/Ethnicity

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) Month of OnsetCases July1 August8 September1 Date of Onset Cases 1-108 11-201 21+1

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 Water ActivitiesCases Swimming7 Skiing2 Tubing1 Wake Boarding1 Unspecified Recreation3

31. Incubation Ranges Case NumberDays 60-6 54 74-7 35, 10-14 26 105-9 80-16

32. Disease Presentation Reported SymptomsCases Disorientation7 Vomiting7 Fever5 Headache5 Lethargy5 Neck pain/stiffness4 Agitation3 Loss of consciousness3 Photophobia3 Seizure3

33. Laboratory Results: CSF Patient2348910 ColorStrawN/A BloodyNoneStraw AppearanceHazyN/AHazyOpaqueHazyClear WBC (cells/mm 3 )2501080750175022540 PMNs (%)816983575250 Lymphs (%)172517294611 Monos (%)26N/A1423 RBC (cells/mm 3 )5201263803075099235 Glucose (mg/dL)<171<1041228 Protein (mg/dL)550.5148>300424313602

34. Laboratory Results: Blood Patient2348910 Sodium (mEq/L)129N/A141133138150 Potassium (mEq/L)3.4N/A4.44.04.14.5 Chloride (mEq/L)98N/A11597101122 CO2 (mEq/L)19N/A2024 21 Glucose (mg/dL)173N/A198166135469 WBC (cells/mm 3 )8,90020,50022,90017,40016,80012,400 PMNs (%)87N/A968693 Lymphs (%)8N/A14.934 Monos (%)5N/A27.442

35. Treatments by Drug Class

36. Illness Duration Victim Illness Duration

37. Conclusions

38. 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 –LD 50 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