Recent Advances in the Treatment of<i>Acanthamoeba</i>Keratitis

Kumar, Raman; Lloyd, David

doi:10.1086/341487

Cited by 81 publications

(49 citation statements)

References 72 publications

(81 reference statements)

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“…Indeed, in a recent study, we found that tears of healthy individuals contain antibodies against Acanthamoeba MBP, and oral immunization with rMBP protects against Acanthamoeba keratitis in a hamster animal model and this protection correlates with the appearance of MBP-specific IgA in tears of immunized animals. 3 The MBP-specific IgA in tears is likely to provide protection by preventing the parasite binding to the corneal epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…Granulomatous amoebic encephalitis is nearly always fatal because of the lack of an effective treatment. In immunocompetent individuals, Acanthamoebae provoke a debilitating vision-threatening corneal infection known as Acanthamoeba keratitis (AK) 1 (3)(4)(5). AK is characterized by intense pain and a slowly worsening clinical course.…”

mentioning

confidence: 99%

“…AK is characterized by intense pain and a slowly worsening clinical course. Contact lens wear is a major risk factor (3,6,7). In the developed world, ϳ85% of the cases are diagnosed in contact lens wearers (7).…”

mentioning

confidence: 99%

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Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

Gárate

Cao

Bateman

et al. 2004

Journal of Biological Chemistry

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Acanthamoebae produce a painful, blinding infection of the cornea. The mannose-binding protein (MBP) of Acanthamoeba is thought to play a key role in the pathogenesis of the infection by mediating the adhesion of parasites to the host cells. We describe here the isolation and molecular cloning of Acanthamoeba MBP. The MBP was isolated by chromatography on the mannose affinity gel. Gel filtration experiments revealed that the Acanthamoeba lectin is a ϳ400-kDa protein that is constituted of multiple 130-kDa subunits. Cloning and sequencing experiments indicated that the Acanthamoeba MBP gene is composed of 6 exons and 5 introns that span 3.6 kb of the amoeba genome and that MBP cDNA codes for a precursor protein of 833 amino acids. That the cloned cDNA encodes authentic MBP was demonstrated by showing that: (i) recombinant MBP possesses mannose binding activity, and (ii) polyclonal antibodies prepared against Acanthamoeba MBP bound to the recombinant protein. Sequence analysis revealed that the MBP contains a large N-terminal extracellular domain, a transmembrane domain, and a short C-terminal cytoplasmic domain. Despite extensive BLAST searches using the MBP sequence, no significant matches were retrieved. The most striking feature of the Acanthamoeba MBP sequence is the presence of a cysteine-rich region containing 14 CXCXC motifs within the extracellular domain. In summary, we have isolated, cloned, and characterized a novel MBP from Acanthamoeba. Because the presence of antibodies to MBP in tears provides protection against infection, the availability of the MBP cDNA sequence and rMBP should help develop: (i) a tear-based test to identify individuals who are at risk of developing the keratitis and (ii) strategies to immunize high-risk individuals.Acanthamoebae are causative agents of two distinct disease entities. In immunocompromised individuals, this protozoan parasite produces chronic granulomatous amoebic encephalitis and disseminating infections including dermatitis and pneumonitis (1, 2). Granulomatous amoebic encephalitis is nearly always fatal because of the lack of an effective treatment. In immunocompetent individuals, Acanthamoebae provoke a debilitating vision-threatening corneal infection known as Acanthamoeba keratitis (AK) 1 (3-5). AK is characterized by intense pain and a slowly worsening clinical course. Contact lens wear is a major risk factor (3, 6, 7). In the developed world, ϳ85% of the cases are diagnosed in contact lens wearers (7). However, in the developing countries, where contact lens use is infrequent, the disease is more commonly found in non-contact lens wearers (8). The mechanism by which Acanthamoebae produce granulomatous amoebic encephalitis and AK has not been fully elucidated. It is generally accepted that the two major predisposing factors in the pathogenesis of AK are minor corneal trauma caused by contact lens wear or other noxious agents and exposure to contaminated solutions including lens care products and tap water (9, 10). The adhesion of parasites to the host cells ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

Gárate

Cao

Bateman

et al. 2004

Journal of Biological Chemistry

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“…Polyhexamethylene biguanide has been demonstrated to be effective, especially if applied in conjunction with other agents. Chlorhexidine applied hourly is also effective, and kills both cysts and trophozoites (20). A successful outcome in patients treated medically is noted in up to 88%, the remainder requiring corneal debridement and possibly penetrating keratoplasty.…”

Section: Case Presentationmentioning

confidence: 99%

AcanthamoebaSpecies Keratitis in a Soft Contact Lens Wearer Molecularly Linked to Well Water

Mubareka

Alfa

Harding

et al. 2006

Canadian Journal of Infectious Diseases and Medical Microbiolog

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An otherwise-healthy 14-year-old female soft contact lens wearer, who lived in a rural area where the tap water source for the home was a well, presented to a community hospital with a four-week history of progressive redness, swelling and blurred vision of her left eye despite treatment with topical neomycin and corticosteroids. A dendritiform corneal epithelial lesion, corneal edema and inflammation in the anterior chamber were noted on initial examination, and treatment for herpes simplex keratouveitis with oral valacyclovir and topical trifluridine 1% was initiated. There was no clinical improvement, and six weeks after the onset of symptoms she was referred to a corneal specialist for evaluation and further management. The patient's visual acuity was 20/80 and her corneal sensation was intact; slit-lamp examination revealed diffuse corneal edema, areas of punctate epithelial staining, poorly defined subepithelial and anterior stromal infiltrates, a partial ring infiltrate and 2+ cell and flare in the anterior chamber (Figure 1). The patient underwent corneal debridement, and scrapings were sent for viral, bacterial and Acanthameoba culture. She was admitted to the hospital, and polyhexamethalene biguanide 0.02% and diamidine propamidine isothianate eye drops were added to antiviral therapy and topical neomycin. Over the next few days, her visual acuity decreased to hand movement only, the corneal edema intensified, and midstromal peripheral vascularization developed. Her corneal epithelium healed promptly following debridement. Treatment with oral itraconazole, topical chlorhexidine 0.02% and topical ciprofloxacin were added after Acanthameoba species were isolated from corneal scrapings. Over the next few months, the patient improved markedly (her left visual acuity was 20/50) despite significant corneal vascularization and persisting central stromal opacity.Clinical samples, including corneal scrapings, contact lenses, contact lens solution, tap water and well water, were inoculated directly onto non-nutrient agar with Escherichia coli overlay (1), as well as sheep's blood agar, MacConkey agar and chocolate agar. The non-nutrient agar with E coli overlay was incubated at room temperature. The agar surface of the plates was examined daily with an inverted microscope at 10× magnification. On day 5 after planting, the plates inoculated by corneal scrapings were positive for both the cyst (Figure 2) and trophozoite forms of Acanthamoeba species. In addition, Serratia marcescens and Stenotrophomonas maltophilia were isolated from corneal scrapings that were inoculated onto sheep's blood agar, MacConkey agar and chocolate agar. Environmental samples consisting of well water and tap water from the patient's home, in addition to samples from the contact lens case, were also positive for Acanthamoeba species. Acanthamoeba species isolates were forwarded to the Ohio State University Department of Molecular Genetics (Columbus, Ohio, USA), where molecular epidemiological analysis was undertaken. This consisted of amp...

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“…In the present study, we demonstrate that oral immunization with recombinant MBP ameliorates AK in a hamster animal model and that this protection is associated with the presence of elevated levels of anti-MBP immunoglobulin A in the tear fluid of the immunized animals.Acanthamoeba castellanii keratitis (AK) is a rare but painful and devastating infection of the cornea that is difficult to diagnose and treat (2,4,8,11,13,16). We have recently shown that acanthamoebae express a mannose-binding protein (MBP) that mediates the adhesion of the amoebae to corneal epithelial cells (3,5,6,18) and that anti-MBP immunoglobulin A (IgA) antibodies are present in the human tear fluid of healthy individuals…”

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confidence: 99%

Oral Immunization withAcanthamoeba castellaniiMannose-Binding Protein Ameliorates Amoebic Keratitis

et al. 2006

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Acanthamoeba castellanii mannose-binding protein (MBP) mediates adhesion of the amoebae to corneal epithelial cells, a key first step in the pathogenesis of Acanthamoeba keratitis (AK), a devastating corneal infection. In the present study, we demonstrate that oral immunization with recombinant MBP ameliorates AK in a hamster animal model and that this protection is associated with the presence of elevated levels of anti-MBP immunoglobulin A in the tear fluid of the immunized animals.Acanthamoeba castellanii keratitis (AK) is a rare but painful and devastating infection of the cornea that is difficult to diagnose and treat (2,4,8,11,13,16). We have recently shown that acanthamoebae express a mannose-binding protein (MBP) that mediates the adhesion of the amoebae to corneal epithelial cells (3,5,6,18) and that anti-MBP immunoglobulin A (IgA) antibodies are present in the human tear fluid of healthy individuals

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Recent Advances in the Treatment ofAcanthamoebaKeratitis

Cited by 81 publications

References 72 publications

Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

AcanthamoebaSpecies Keratitis in a Soft Contact Lens Wearer Molecularly Linked to Well Water

Oral Immunization withAcanthamoeba castellaniiMannose-Binding Protein Ameliorates Amoebic Keratitis

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