Amebic meningoencephalitides and keratitis: Challenges in diagnosis and treatment

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Current Opinion in Infectious Diseases (Impact Factor: 5.01). 12/2010; 23(6):590-4. DOI: 10.1097/QCO.0b013e32833ed78b
Source: PubMed


Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri, although free-living amebae, also cause devastating diseases in humans leading to death. Acanthamoeba spp. and B. mandrillaris cause granulomatous amebic encephalitis, cutaneous and nasopharyngeal as well as disseminated infection. Acanthamoeba also causes a vision-threatening infection of the cornea, Acanthamoeba keratitis, principally in contact lens wearers. N. fowleri causes an acute, fulminating infection of the central nervous system, primary amebic meningoencephalitis, in healthy children and young adults who indulge in aquatic activities in fresh water. This review focuses on the recent developments in the diagnosis and treatment and clinical management of the diseases caused by these amebae.
Development of a multiplex real-time PCR test has made it possible to simultaneously detect all the three free-living amebae in a sample. It is a rapid assay with a short turn-around time of just 4-5 h. An early diagnosis would be helpful in initiating potentially effective treatment. A recent study reported exciting results indicating that loading of rokitamycin in chitosan microspheres improves and prolongs the in-vitro anti-Acanthamoeba activity of the drug.
Diagnoses of these infections are challenging and antimicrobial therapy is empirical, which often results in fatalities. Further research is needed to explore the possibility of a better drug delivery system that crosses the blood-brain barrier and effectively reach the central nervous system.

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Available from: Govinda Visvesvara
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    • "Departamento de Morfologia, Laboratório de Entomologia e Parasitologia Tropical, Universidade Federal de Sergipe, Av. Marechal Rondon, s/n, Roza Elze, CEP 49100-000 São Cristóvão, Sergipe, Brazil (Clarke and Niederkorn 2006; Khan and Siddiqui 2009; Lorenzo-Morales et al. 2015; Petry et al. 2006; Scheid et al. 2008; Visvesvara 2010). Treatment of granulomatous amoebic encephalitis has been performed with a combination of different pharmacological agents, including pentamidine, isothionate, sulfadiazine, flucytosine, and fluconazole or itraconazole. "
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    ABSTRACT: Amoebic keratitis and granulomatous amoebic encephalitis are caused by some strains of free-living amoebae of the genus Acanthamoeba. In the case of keratitis, one of the greatest problems is the disease recurrence due to the resistance of parasites, especially the cystic forms, to the drugs that are currently used. Some essential oils of plants have been used as potential active agents against this protist. Thus, the aim of this study was to determine the amebicidal activity of essential oils from plants of the genus Lippia against Acanthamoeba polyphaga trophozoites. To that end, 8 × 10(4) trophozoites were exposed for 24 h to increasing concentrations of essential oils from Lippia sidoides, Lippia gracilis, Lippia alba, and Lippia pedunculosa and to their major compounds rotundifolone, carvone, and carvacrol. Nearly all concentrations of oils and compounds showed amebicidal activity. The IC50 values for L. sidoides, L. gracilis L. alba, and L. pedunculosa were found to be 18.19, 10.08, 31.79, and 71.47 μg/mL, respectively. Rotundifolone, carvacrol, and carvone were determined as the major compounds showing IC50 of 18.98, 24.74, and 43.62 μg/mL, respectively. With the exception of oil from L. alba, the other oils evaluated showed low cytotoxicity in the NCI-H292 cell line. Given these results, the oils investigated here are promising sources of compounds for the development of complementary therapy against amoebic keratitis and granulomatous amoebic encephalitis and can also be incorporated into cleaning solutions to increase their amebicidal efficiency.
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    • "The loss of dcsa-alone from Ppal is sufficient to prevent any viable cysts from being formed, highlighting an absolutely essential role for cellulose in cyst differentiation. While Ppal and most dictyostelids are harmless soil inhabitants, this is not the case for other Amoebozoa such as Acanthamoeba and Balamuthia sp. which can cause blinding keratitis and lethal amoebic encephalitis (Trabelsi et al. 2012; Visvesvara 2010). Even the encysting dictyostelid D. polycephalum was shown to be responsible for a case of keratitis (Reddy et al. 2010). "
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    ABSTRACT: Amoebas and other freely moving protists differentiate into walled cysts when exposed to stress. As cysts, amoeba pathogens are resistant to biocides, preventing treatment and eradication. Lack of gene modification procedures has left the mechanisms of encystation largely unexplored. Genetically tractable Dictyostelium discoideum amoebas require cellulose synthase for formation of multicellular fructifications with cellulose-rich stalk and spore cells. Amoebas of its distant relative Polysphondylium pallidum (Ppal), can additionally encyst individually in response to stress. Ppal has two cellulose synthase genes, DcsA and DcsB, which we deleted individually and in combination. Dcsa- mutants formed fruiting bodies with normal stalks, but their spores and cyst walls lacked cellulose, which obliterated stress-resistance of spores and rendered cysts entirely non-viable. A dcsa-/dcsb- mutant made no walled spores, stalk cells or cysts, although simple fruiting structures were formed with a droplet of amoeboid cells resting on an sheathed column of decaying cells. DcsB is expressed in prestalk and stalk cells, while DcsA is additionally expressed in spores and cysts. We conclude that cellulose is essential for encystation and that cellulose synthase may be a suitable target for drugs to prevent encystation and render amoeba pathogens susceptible to conventional antibiotics.
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    • "Several of the approximately 24 identified species of the genus Acanthamoeba have been linked to human disease, including Acanthamoeba castellanii, Acanthamoeba polyphaga, Acanthamoeba astronyxis, Acanthamoeba hatchetti, Acanthamoeba culbertsoni, Acanthamoeba healyi, and Acanthamoeba byersi (Visvesvara et al., 2007; Corsaro and Venditti, 2010; Visvesvara, 2010; Qvarnstrom et al., 2013). The growing importance of Acanthamoeba spp. in medical care and research during the last decade is due to their potential to infect human hosts, causing severe diseases, such as granulomatous amoebic encephalitis (GAE), a chronic brain infection that occurs more frequently in immunosuppressed individuals; "
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    ABSTRACT: Acanthamoeba polyphaga is a free-living protozoan pathogen, whose infective trophozoite form is capable of causing a blinding keratitis and fatal granulomatous encephalitis in humans. The damage caused by A. polyphaga trophozoites in human corneal or brain infections is the result of several different pathogenic mechanisms that have not yet been elucidated at the molecular level. We performed a comprehensive analysis of the proteins expressed by A. polyphaga trophozoites, based on complementary 2-DE MS/MS and gel-free LC-MS/MS approaches. Overall, 202 non-redundant proteins were identified. An A. polyphaga proteomic map in the pH range 3-10 was produced, with protein identification for 184 of 370 resolved spots, corresponding to 142 proteins. Additionally, 94 proteins were identified by gel-free LC-MS/MS. Functional classification revealed several proteins with potential importance for pathogen survival and infection of mammalian hosts, including surface proteins and proteins related to defense mechanisms. Our study provided the first comprehensive proteomic survey of the trophozoite infective stage of an Acanthamoeba species, and established foundations for prospective, comparative and functional studies of proteins involved in mechanisms of survival, development, and pathogenicity in A. polyphaga and other pathogenic amoebae.
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