Thirteen Year Summary of Primary Amebic Meningoencephalitis in Texas Heather K. Noble Public Health...

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



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



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





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



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



Data Analysis

• Tools:– Excel– Access – Epi Info

• Measures:– Frequencies– Means





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





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



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



Thirteen Year Summary of Primary Amebic Meningoencephalitis in Texas Heather K. Noble Public Health...

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