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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