Acanthamoeba and Naegleria

Acanthamoeba and Naegleria are the most common free-living amoebae associated with human disease. Balamuthia mandrillaris and Hartmannella species are also free-living amoebae but less commonly cause clinically significant infections. Pathogenic species may cause fatal central nervous system (CNS) disease.

Epidemiology

Incidence
- Acanthamoeba keratitis – 0.3-1/100,000
- Naegleria, Balamuthia, Hartmannella – 4/1,000,000
Transmission – contaminated water or soil

Organisms

Acanthamoeba
- Pathogenic species that infect humans
  - A. culbertsoni
  - A. castellanii
  - A. polyphaga
  - A. astronyxis
- The life cycle of Acanthamoeba includes both a trophozoite stage and a dormant cyst stage
  - Cysts are highly resistant to antimicrobial agents
Naegleria pathogenic species
- N. fowleri is only species known to infect humans
Balamuthia mandrillaris
Hartmannella species
Sappinia pedata

Risk Factors

Acanthamoeba infection
- Keratitis
  - Soft contact lens wearers with poor hygienic practices
  - Patients exposed to contaminated water
- Meningitis
  - Almost exclusively in immunocompromised patients
Naegleria infection
- Correlates with history of swimming in lakes or brackish water
- Aspiration of contaminated water, inhalation of contaminated dust
Immunosuppression is a risk factor for infection from all free-living amoebae
- Naegleria fowleri and Balamuthia mandrillaris cause infection in immunocompetent patients also

Clinical Presentation

Acanthamoeba
- Chronic granulomatous amoebic encephalitis
  - Fever, nausea, headache, vomiting, stiff neck, cranial nerve involvement, hemiparesis, ataxia
  - Fatality ratio of >90%
- Ocular
  - Corneal ulcers, punctuate keratitis, anterior uveitis
  - Complications
    - Secondary glaucoma
    - Cataract
    - Iris atrophy
- Chronic granulomatous skin lesions
Balamuthia mandrillaris
- Amoebic encephalitis
- Chronic granulomatous skin lesions (papulonodular, erythematosus, possible ulceration)
- Oral cavity lesions (palate deformity)
Naegleria fowleri
- Primary amoebic meningoencephalitis (PAM)
  - Acute onset of fever, nausea, vomiting, headache, stiff neck, cranial nerve involvement
  - Almost always fatal within 4-6 days
Sappinia pedata
- Amoebic encephalitis

Indications for Testing

Patients with symptoms of meningitis/encephalitis where cerebrospinal fluid examination is negative for routine organisms or patient does not respond to conventional antibiotic therapy
Contact lens wearer with acute keratitis
- Suspected herpetic keratitis that is not responding to therapy
- Failure to respond to antimicrobial treatment

Laboratory Testing

Initial testing for meningoencephalitis
- Lumbar puncture with CSF analysis
  - Typically demonstrates elevated protein and elevated WBC count with lymphocyte predominance; elevated RBCs with disease progression in primary amoebic meningoencephalitis
  - Culture
  - CSF examination for trophozoites with Wright or Giemsa stain
  - Consider viral panel testing to rule out most common viral etiologies (including HSV)
- CBC – usually without leukocytosis
Initial testing for keratitis
- Culture of eye specimen

Histology

Histopathological diagnosis (brain or skin biopsy) using traditional hematoxylin and eosin, lactophenol cotton blue stain, fluorescence with calcofluor white dye, or molecular assays

Differential Diagnosis

CNS disease
- Viral encephalitis
- Bacterial leptomeningitis
- Fungal meningitis
- M. tuberculosis meningitis
Corneal disease
- Herpes simplex virus
- Atypical mycobacteria
- Adenovirus
- Varicella-zoster virus
- Ophthalmic manifestations of autoimmune disease
- Ophthalmic rosacea
Skin disease
- Dimorphic fungal infections
- Mycobacterial infections

Tests generally appear in the order most useful for common clinical situations

Test name: Acanthamoeba and Naegleria Culture and Stains, CSF

ARUP #: 2002584

Methodology: Qualitative Culture/Microscopic Identification/Calcofluor Stain/Giemsa Stain

Use:

Detect Acanthamoeba spp, Naegleria spp and other free-living amoebae

CSF specimens are examined by calcofluor white and Giemsa stains upon receipt in addition to setup for culture

Limitations:

Culture does not detect Balamuthia mandrillaris; stain does

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Rule out bacterial meningitis

Test name: Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001765

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Use:

Panel includes California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, West Nile virus, measles, mumps, varicella-zoster virus, HSV-1 and/or -2, and lymphocytic choriomeningitis antibodies

Additional Tests Available

Test name: Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001764

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Chemiluminescent Immunoassay

Comments:

Panel includes California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, West Nile virus, measles, mumps, varicella-zoster virus, HSV type 1 and/or 2, and lymphocytic choriomeningitis antibodies

Test name: Amoeba Calcofluor Stain

ARUP #: 0060250

Methodology: Qualitative Calcofluor White/Microscopic Exam

Comments:

Detect Acanthamoeba spp, Naegleria fowleri and other free-living amoebae

Test name: Acanthamoeba and Naegleria Culture

ARUP #: 0060245

Methodology: Qualitative Culture/Microscopic Identification

Comments:

Diagnose Acanthamoeba spp, Naegleria spp and other free-living amoebae in CSF, corneal scrapings or tissue, or vitreous fluid specimens

CSF specimens are stained with calcofluor White and Giemsa upon receipt in addition to setup for culture