- Free-living ameba: Acanthamoeba spp, Naegleria fowleri, Balamuthia mandrillaris, Sappinia pedata.
- Ubiquitous in nature: isolated from air, soil, fresh water, salt water, chlorinated swimming pools, sewage, heating and ventilation systems.
- Two-stage life cycle
- Actively feeding & dividing trophozoites (14-40 μm in diameter)
- Dormant cysts (double-walled 10-25 μm in diameter); cysts resistant to chlorine, low temperature, antibiotics, pH extremes.
- Three groups (I, II, III) of Acanthamoeba spp described, division based on cyst morphology.
- Encystation occurs under environmental stress: food deprivation, desiccation, change in temperature.
- Transmission: inhalation most common route; direct inoculation of skin
- Described as “Trojan horses” as they can harbor intracellular bacteria.
- Cause of granulomatous amebic encephalitis, chronic sinusitis, otitis, cutaneous lesions in pts with AIDS.
- Disseminated disease more common with advanced immunosuppression; immunity is predominantly T-cell mediated.
- Granulomatous amebic encephalitis (GAE):
- sub-acute onset of headache, confusion, stiff neck; CT & MRI show nonspecific enhancing lesions, usually in midbrain, brainstem, & cerebellum.
- CSF with lymphocytic pleocytosis, normal to low glucose, and elevated protein; wet mount of CSF (trophozoites resemble macrophages); H&E staining; Calcofluor white flourescently stains cysts and trophozoites in tissue section; special growth medium & cell Cx can be used.
- Cutaneous lesions: erythematous nodules that become ulceronecrotic with indurated borders; Bx with staining and Cx.
- Real time PCR assays validated for diagnosis of keratitis.
SITES OF INFECTION
- Skin: most common manifestation in AIDS; painful, ulcerated nodules on trunk or extremeties; may be due either to direct inoculation or hematogenous spread; 73% mortality. Leukocytoclastic vasculitis reported.
- CNS: GAE; CD4 usually < 200; fulminant course; mortality high.
- ENT: chronic sinusitis & otitis.
- Eyes: painful, chronic corneal ulcers associated with use of contact lenses or eye trauma in immunocompetent host.
- Bone: osteomyelitis.
- Lungs: may be primary portal of entry; pneumonia.
- Clinical suspicion leading to early Dx yields best chance of cure.
- Combination therapy is the rule for treating infections
- Drug susceptibility varies between species and strains of species, susceptibility testing recommended.
- Drugs must be cysticidal to prevent recurrence from dormant cysts.
- Prognosis may be improved with immune restoration due to ART.
- Combination therapy for CNS and disseminated disease:
- pentamidine 4 mg/kg IV qd
- pentamidine-associated side effects are nephrotoxicity, leukopenia, elevated LFTs, and hypoglycemia.
- sulfadiazine 1.5 g PO q6h
- flucytosine 37.5 mg/kg PO q6h (max 150 mg/kg/d)
- fluconazole 12 mg/kg IV qd
- miltefosine < 45 kg: 100 mg PO qd (in 2 divided doses); ≥45 kg: 150 mg PO qd (in 3 divided doses)
- contraindicated in pregnancy and breastfeeding.
- Voriconazole and miltefosine combined therapy of GAE reported in immunocompetent and immunosuppressed hosts.
- Widespread cutaneous infection does not necessarily imply disseminated infection.
- IV pentamidine 4 mg/kg/d + topical chlorhexidine + topical ketoconazole successful for cutaneous disease without CNS involvement.
- Refer to ophthalmologist immediately.
- For AK: polyhexamethylene biguanide (PHMB, 0.02%) +/- chlorhexidine 0.02% +/- propamidine isethionate (Brolene) 0.1% +/- hexamidine 0.1%.
Selected Drug Comments
Use for disseminated disease.
Consider adding in disseminated disease.
Investigational New Drug expanded access via CDC.
Use for disseminated/cutaneous disease.
Use for disseminated disease.
Used in combination for disseminated disease.
Basis for recommendation
- Centers for Disease Control and Prevention (CDC): Investigational Drug Available Directly from CDC for the Treatment of Infections with Free-Living Amebae. MMWR Morb Mortal Wkly Rep 62:, 2013 [PMID:23965830]
Comment: Miltefosine (hexadecylphosphocholine), an antineoplastic agent also used to treat leishmaniasis, is available via an expanded access investigational new drug (IND) protocol from CDC for treatment of free-living amebae infections. Miltefosine is generally well-tolerated, gastrointestinal adverse effects are reported. CDC Emergency Operations Center offers diagnostic assistance, specimen collection and shipping directions, and treatment recommendations. Contact at 770-488-7100.
The Medical Letter on Drugs and Therapuetics. Drugs for Parasitic Infections, 3rd Edition. New Rochelle, NY; 2013. www.medicalletter.org.
Comment: Recommended treatment for GAE updated to include recommended dosing for pentamidine, sulfadiazine, flucytosine, fluconazole, and miltefosine. Miltefosine is contraindicated in pregnancy and breastfeeding. AK treatment recommendations discuss use of topical or oral voriconazole in patients who fail PHMB, chlorhexidine and hexamidine.
- Venkatesan A et al: Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 57:1114, 2013 [PMID:23861361]
Comment: Consensus statement on case definitions and diagnostic algorithms in encephalitis includes comment on role of free-living amoeba and treatments undergoing investigation, Table 5.
- Visvesvara GS: Infections with free-living amebae. Handb Clin Neurol 114:153, 2013 [PMID:23829906]
Comment: Comprehensive review of biology of free-living amebae includes clinical data, diagnostic data, and epidemiology. Detailed discussion of granulomatous amebic encephalitis and other manifestations of Acanthamoeba infection. Author describes Acanthamoeba spp as "Trojan horse" because of their ability to act as hosts for a wide variety of pathogenic bacteria.
- Centers for Disease Control and Prevention website; Accessed 10/9/13, http://www.cdc.gov/parasites/acanthamoeba/biology.html
Comment: Website details life cycle of organism and clinical presentation of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Images of cysts and trophozoites found at: http://www.dpd.cdc.gov/dpdx/HTML/FreeLivingAmebic.htm
- Gee SN et al: Tender ulceronecrotic nodules in a patient with leukemia. Cutaneous acanthamebiasis. Arch Dermatol 147:857, 2011 [PMID:21768491]
Comment: Case report of 64 yo woman with chronic lymphocytic leukemia (CLL) presenting with painful erythematous, indurated plaques that progressed to ulceronecrotic 1-3 cm nodules on arms, abdomen, back and thighs. Histopathology showed suppurative inflammation and necrotic areas of numerous amebas with thick ruffled cell walls. Initial treatment included flucytosine, sulfadiazine, pentamidine, and fluconazole. Eight days after dx, regimen was changed to include miltefosine, voriconazole, flucytosine, and sulfadiazine. Although lesions were resolving 7 wks of tx, she transferred to hospice care due to CLL.
- Ikeda Y et al: Assessment of real-time polymerase chain reaction detection of Acanthamoeba and prognosis determinants of Acanthamoeba keratitis. Ophthalmology 119:1111, 2012 [PMID:22381810]
Comment: Data show high sensitivity of quantitative real-time PCR for Acanthamoeba keratitis and correlation between copy numbers of Acanthamoeba spp. and stage of AK based on slit-lamp biomicroscopy. AK was divided into 5 stages of disease severity: (1) epitheliitis, (2) epitheliitis with radial neuritis, (3) anterior stromal disease, (4) deep stromal keratitis, and (5) ring infiltrate or extra corneal inflammation.
- Carter WW et al: Disseminated Acanthamoeba sinusitis in a patient with AIDS: a possible role for early antiretroviral therapy. AIDS Read 14:41, 2004 [PMID:14959703]
Comment: Authors report successful treatment of a 35 yr-old woman who presented with sinusitis that progressed to disseminated acanthamebiasis as initial manifestation of AIDS. Initiation of ART may have had impact on positive outcome.
- Page MA, Mathers WD: Acanthamoeba keratitis: a 12-year experience covering a wide spectrum of presentations, diagnoses, and outcomes. J Ophthalmol 2013:, 2013 [PMID:23840938]
Comment: Review of 372 cases of Acanthamoeba keratitis diagnosed from 1999-2010 by confocal microscopy.
- Pietrucha-Dilanchian P et al: Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with neurotoxoplasmosis coinfection in a patient with advanced HIV infection. J Clin Microbiol 50:1128, 2012 [PMID:22170911]
Comment: Case report of 53 yo HIV+ man, CD4 cell count 25 cells/μL, HIV VL 75,000 c/ml presenting with progressive weakness, confusion and fall. PMHx significant for homelessness. Brain MRI showed 2.5cm ring-enhancing lesion treated presumptively for toxoplasmosis. Further work up including serum serology, H&E stains of brain tissue, and real-time PCR confirmed diangosis of Balamuthiamandrillaris and Acanthamoeba spp. in addition to brain tissue examination and PCR confirming T. gondii.
- Visvesvara GS, Moura H, Schuster FL: Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 50:1, 2007 [PMID:17428307]
Comment: Recent summary of free-living amoebae-associated infection, reviews types of disease and diagnostic methods.
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