eMedicine Specialties > Infectious Diseases > CNS Infections

Naegleria Infection: Differential Diagnoses & Workup

Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Coauthor(s): Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Diane H Johnson, MD, Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine
Contributor Information and Disclosures

Updated: Aug 3, 2009

Differential Diagnoses

Other Problems to Be Considered

Bacterial meningoencephalitis
Viral meningoencephalitis
Cryptococcal meningoencephalitis in immunocompromised individuals

Workup

Laboratory Studies

The diagnosis of primary amebic meningoencephalitis (PAM) is always parasitic and is based on detection and identification of N fowleri trophozoites in the CSF or brain biopsy samples.

Specimens

The CSF is the specimen of choice for demonstration of the amebae.

Direct wet-mount microscopy

The CSF is centrifuged at 150 xg for 5 minutes. The supernatant is aspirated, and the sediment is suspended in the remaining fluid. A drop of sediment suspension is kept on a slide and mounted with a coverslip and is examined with compound light microscopy using 10X and 40X objectives. The specimen is best examined with phase contrast microscopy. This may show trophozoites with lobopodia extension and retraction.

The amebae are detected based on their active directional movements. Close observation is important because PAM can be diagnosed based on the observation of trophozoites; however, these have been confused with WBCs in reported cases. Cyst and flagellated stages are not found in CSF samples; if both cysts and trophozoites are found in CSF, it is highly suggestive of Acanthamoeba infection, ruling out Naegleria PAM.

Examination of stained CSF smear

CSF Gram stain findings are usually negative. RBCs are present. Wright-Giemsa–stained CSF may show trophozoites with large karyosome and may show a contractile vacuole. Direct fluorescent antibody staining of CSF smears is useful for demonstrating N fowleri in the CSF.

Culture

Naegleria species can be readily cultivated on either nonnutrient agar or agar media containing low concentrations of nutrients (eg, peptone 0.05%, yeast extract 0.05%, glucose 0.1%) in the presence of living or killed bacteria. In general, the bacteria of choice include nonmucoid strains of Klebsiella pneumoniae, Enterobacter species (Enterobacter aerogenes and Enterobacter cloacae), and Escherichia coli. After several days, the plate is microscopically inspected; Naegleria cysts are identified by trails left by migrating amebae in the lawn of the bacteria. Various molecular methods can be used for final confirmation of the identity of the species.

Serodiagnosis

Serologic testing has no role in the diagnosis of acute PAM, since little time is available from onset to death to mount an antibody response. In one survivor, detectable antibody persisted for more than 4 years.

Molecular diagnosis

PCR is available at some research sites using numerous primers. Molecular characterization of strains is also useful in tracking infections to a source and in recognizing potential risks for swimmers or bathers in particular locales. A species-specific DNA probe is available to identify N fowleri in environmental samples, followed by restriction fragment length polymorphism (RFLP) analyses of whole-cell DNA for confirmation. Epidemiologic typing of N fowleri was used in an analysis of the 5.8S rRNA gene and the internal transcribed spacer (ITS) of clinical isolates. In a study performed in the United States, a rapid, sensitive, and specific assay for the detection of N fowleri was developed using Mp2C15 probe in a nested PCR assay format.11 A nested PCR assay has also been applied to detect the presence of the parasite in domestic water sources.12

Recently, flow cytometry has been used for the diagnosis of N fowleri infection.13

Histology

Both immunofluorescence and immunoperoxidase methods are useful for demonstrating N fowleri trophozoites in the histologic sections of the brain biopsy samples.

Imaging Studies

Head CT scanning yields nonspecific findings, showing a loss of the subarachnoid space and diffuse gray material enhancement.

Other Tests

CSF studies show the following:

  • Sanguinopurulent or bloody CSF, showing a nonspecific polymorphonuclear (PMN) neutrophil–predominant neutrophilia
  • Increased opening pressure
  • PMN pleocytosis
  • Elevated RBC count or frank hemorrhagic CSF
  • Normal to low CSF glucose level
  • Elevated protein level

Procedures

Lumbar puncture: Wet-mount examination of CSF is the main diagnostic tool in PAN.

Histologic Findings

N fowleri infection produces lesions mainly in the base of the brain, brain stem, and cerebellum. The olfactory mucosa and bulbs are the most commonly affected areas. The lesions consist of an acute necrotizing meningoencephalitis associated with moderately purulent exudates. Only trophozoites are found in the CNS lesions, not cysts.

More on Naegleria Infection

Overview: Naegleria Infection
Differential Diagnoses & Workup: Naegleria Infection
Treatment & Medication: Naegleria Infection
Follow-up: Naegleria Infection
Multimedia: Naegleria Infection
References
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References

  1. Schuster FL. Cultivation of pathogenic and opportunistic free-living amebas. Clin Microbiol Rev. Jul 2002;15(3):342-54. [Medline].

  2. Centers for Disease Control and Prevention (CDC). Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. May 30 2008;57(21):573-7. [Medline].

  3. Parija SC, Jayakeerthee SR. Naegleria fowleri: a free living amoeba of emerging medical importance. J Commun Dis. Sep 1999;31(3):153-9. [Medline].

  4. Cervantes-Sandoval I, Serrano-Luna Jde J, García-Latorre E, Tsutsumi V, Shibayama M. Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion. Microbiology. Dec 2008;154(Pt 12):3895-904. [Medline].

  5. Jung SY, Kim JH, Song KJ, Lee YJ, Kwon MH, Kim K. Gene silencing of nfa1 affects the in vitro cytotoxicity of Naegleria fowleri in murine macrophages. Mol Biochem Parasitol. May 2009;165(1):87-93. [Medline].

  6. Factsheet of Naeglaria fowleri. Available at http://www.cdc.gov/ncidod/dpd/parasites/Naegleria/factsht_naegleria.htm.

  7. Jamerson M, Remmers K, Cabral G, Marciano-Cabral F. Survey for the presence of Naegleria fowleri amebae in lake water used to cool reactors at a nuclear power generating plant. Parasitol Res. Apr 2009;104(5):969-78. [Medline].

  8. Naegleria fowleri. Wikipedia. Available at http://en.wikipedia.org/wiki/Naegleria_fowleri. Accessed 9/25/2008.

  9. Parija SC. Amoebae. In: Textbook of Medical Parasitology: Protozoology & Helminthology. 3rd ed. New Delhi, India: All India Publishers and Distributors; 2006:26-61.

  10. Rai R, Singh DK, Srivastava AK, Bhargava A. Primary amebic meningoencephalitis. Indian Pediatr. Dec 2008;45(12):1004-5. [Medline].

  11. Réveiller FL, Cabanes PA, Marciano-Cabral F. Development of a nested PCR assay to detect the pathogenic free-living amoeba Naegleria fowleri. Parasitol Res. May 2002;88(5):443-50. [Medline].

  12. Marciano-Cabral F, MacLean R, Mensah A, LaPat-Polasko L. Identification of Naegleria fowleri in domestic water sources by nested PCR. Appl Environ Microbiol. Oct 2003;69(10):5864-9. [Medline].

  13. Johnson PE, Deromedi AJ, Lebaron P, Catala P, Havens C, Pougnard C. High throughput, real-time detection of Naegleria lovaniensis in natural river water using LED-illuminated Fountain Flow Cytometry. J Appl Microbiol. Sep 2007;103(3):700-10. [Medline].

  14. Vargas-Zepeda J, Gómez-Alcalá AV, Vásquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F. Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin. Arch Med Res. Jan-Feb 2005;36(1):83-6. [Medline].

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Further Reading

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Keywords

Naegleria fowleri, Naegleria infection, N fowleri, primary amebic meningoencephalitis, PAM, purulent meningoencephalitis, N fowleri meningoencephalitis, Naegleria fowleri meningoencephalitis, Naegleria australiensis, Naegleria italica, Naegleria philippinensis, N australiensis, N italica, N philippinensis

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Contributor Information and Disclosures

Author

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Subhash Chandra Parija, MBBS, MD, PhD, FRCPath is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences, India, and Royal College of Pathologists
Disclosure: Jawaharlal Institute of Postgraduate Medical education & Research , Pondicherry , India Salary Employment

Coauthor(s)

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences
Disclosure: Nothing to disclose.

Diane H Johnson, MD, Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine
Diane H Johnson, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Women's Association, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Daniel R Lucey, MD, MPH, Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences
Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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