Acanthamoeba and Naegleria

Diagnosis

Indications for Testing

• Patients with symptoms of meningitis/encephalitis where cerebrospinal fluid (CSF) 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

• CDC – Acanthamoeba testing recommendations
• CDC - Naegleria testing recommendations
• 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

Clinical Background

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 – highly resistant to antimicrobial agents
• Naegleria pathogenic species
  • N. fowleri – 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 can also infect immunocompetent patients

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
    • 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 Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001764 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay	Use to rule out most common viral etiologies 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
Amoeba Calcofluor Stain 0060250 Method: Qualitative Calcofluor Stain/Microscopy	Detect Acanthamoeba spp, Naegleria fowleri and other free-living amoebae
Acanthamoeba and Naegleria Culture 0060245 Method: Qualitative Culture/Microscopy	Diagnose Acanthamoeba spp, Naegleria spp and other free-living amoebae in CSF, corneal scrapings or tissue, or vitreous fluid specimens CSF specimens stained with calcofluor White and Giemsa upon receipt in addition to setup for culture