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Thirteen Year Summary of Primary Amebic
Meningoencephalitis in Texas
Heather K. NoblePublic Health Internship Program
University of Texas at Austin
Mentors:Karen Moody and Marilyn Felkner
Texas Department of State Health Services
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Introduction
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
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
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
Exposure• Warm, untreated freshwater reservoirs
– Municipal water supplies– Lakes, ponds, rivers, and runoff streams– Improperly maintained pools
Forceful Entry
Behaviors:• Inhalation of water• Swimming• Diving• Active water sports
– Skiing– Tubing– Scuba diving– Wake boarding
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Pathogenesis
• Attachment to nasal epithelium
• Invasion of brain via olfactory nerves and cribiform plate
• Infection of grey matter and tissue necrosis
• Severe inflammation
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
Laboratory Diagnosis
• Procedure:– CSF collection– CSF examination– Wet preparation
• Flagellation Test
– Culture• E. coli seeded plate
– PCR
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Ahmad, 2007, Int J Pathol
Treatment
• Amphotericin B– Antifungal– Binds ergosterol to
form pore– Collateral damage to
human cells
• Rifampin– Antibiotic– Inhibits RNA
polymerase– Efficacy questioned
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
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
PAM Case Reports: US 1962-2008
Yoder et al., 2009, Epidemiol Infect
PAM Case Reports: Texas 1966-1995
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
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Methods
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
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Data Sources
Identify Confirmed Cases
Hospital Charts
DSHS Records Media
Reports
Request Hospital Records
Variables Analyzed
• Age• Sex• Race• Dates of illness• Exposure
– Date and site
• Patient history• Symptoms• Laboratory findings• Treatment
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Data Analysis
• Tools:– Excel– Access – Epi Info
• Measures:– Frequencies– Means
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Results
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
Demographic Data
3
7
Female Male
1
7
2
White Hispanic Not Available
n = 10 n = 10
Gender Race/Ethnicity
Age Distribution of PAM Cases
• Victim Age Distribution
0
1
2
3
4
5
6
0-4 5-9 10-14 15-19 20-24
Years
Cases
PAM Case Reports by Year, 1996-2009
• PAM Incidence in Texas from 1996-2009
0
1
2
3
4
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009Year
Number of Cases
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 Onset Cases
July 1
August 8
September 1
Date of Onset Cases
1-10 8
11-20 1
21+ 1
N. fowleri Exposure Sites for Texas PAM Cases, 1996-2009
• N. fowleri Reservoirs• Pie Chart
7
12
Creek
Lake
River
n = 10
Texas PAM Case Reports by County of Residence, 1996-2009
Mechanisms of Exposure
Water Activities Cases
Swimming 7
Skiing 2
Tubing 1
Wake Boarding 1
Unspecified Recreation 3
Incubation Ranges
Case Number Days
6 0-6
5 4
7 4-7
3 5, 10-14
2 6
10 5-9
8 0-16
Disease PresentationReported Symptoms Cases
Disorientation 7
Vomiting 7
Fever 5
Headache 5
Lethargy 5
Neck pain/stiffness 4
Agitation 3
Loss of consciousness 3
Photophobia 3
Seizure 3
Laboratory Results: CSF
Patient 2 3 4 8 9 10
Color Straw N/A N/A Bloody None Straw
Appearance Hazy N/A Hazy Opaque Hazy Clear
WBC (cells/mm3) 250 1080 750 1750 22 540
PMNs (%) 81 69 83 57 52 50
Lymphs (%) 17 25 17 29 46 11
Monos (%) 2 6 N/A 14 2 3
RBC (cells/mm3) 520 126 380 30750 99 235
Glucose (mg/dL) <1 71 <10 4 12 28
Protein (mg/dL) 550.5 148 >300 424 313 602
Laboratory Results: Blood
Patient 2 3 4 8 9 10
Sodium (mEq/L) 129 N/A 141 133 138 150
Potassium (mEq/L) 3.4 N/A 4.4 4.0 4.1 4.5
Chloride (mEq/L) 98 N/A 115 97 101 122
CO2 (mEq/L) 19 N/A 20 24 24 21
Glucose (mg/dL) 173 N/A 198 166 135 469
WBC (cells/mm3) 8,900 20,500 22,900 17,400 16,800 12,400
PMNs (%) 87 N/A 96 86 93 93
Lymphs (%) 8 N/A 1 4.9 3 4
Monos (%) 5 N/A 2 7.4 4 2
Treatments by Drug Class
0
1
2
3
4
5
6
Antifungal Antibiotic Antiviral Diuretic Anticonvulsant
Drug Class
Cases
Illness Duration
• Victim Illness Duration
0
1
2
3
4
3 4 5 6 9 10
Days
Number of Cases
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Conclusions
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
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
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
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Limitations
• Small sample size– Rarity of disease
• Archived hospital records– Difficult to retrieve– Sometimes incomplete– Questionable legibility
of copies
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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?
Acknowledgements
• TDSHS– Ms. Karen Moody– Dr. Marilyn Felkner
• UT Austin– Dr. Leanne Field– Ms. Nancy Elder– Dr. Diane Kneeland
Acknowledgements
• I would also like to thank the generous program sponsor: Association of Public Health Laboratories
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