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1.
Exp Parasitol ; 218: 108008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979343

RESUMO

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebicidas/administração & dosagem , Nanopartículas/administração & dosagem , Acanthamoeba/crescimento & desenvolvimento , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Amebíase/tratamento farmacológico , Amebíase/mortalidade , Amebíase/parasitologia , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/mortalidade , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/administração & dosagem , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Sistemas de Liberação de Medicamentos , Imunocompetência , Hospedeiro Imunocomprometido , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/mortalidade , Encefalite Infecciosa/parasitologia , Nanopartículas/classificação , Nanopartículas/uso terapêutico , Trofozoítos/efeitos dos fármacos
2.
Rev. cuba. oftalmol ; 33(2): e824, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1139081

RESUMO

RESUMEN Se reporta el uso del crosslinking como tratamiento de la queratitis por Acanthamoeba en una serie de 7 pacientes quienes acudieron al Servicio de Córnea por queratitis multitratadas. Se les realizó biopsia corneal, la cual se cultivó en solución de Page. Los pacientes fueron tratados con un protocolo de PACK-CXL durante más de 5 minutos y fueron sometidos a la exposición a la luz UV-A. El edema del nuevo epitelio era de 2 cruces a las 24 horas, y desapareció a las dos semanas del procedimiento en todos los casos. El porcentaje de desepitelización basal al momento del diagnóstico fue de 75,7 por ciento. La agudeza visual mejor corregida fue de entre 20/20 y 20/30. Se concluye que el uso de crosslinking en pacientes con Acanthamoeba en fases inicales pudiera ser una opción terapéutica segura y efectiva(AU)


ABSTRACT A report is presented of the use of crosslinking as treatment for Acanthamoeba keratitis in a series of 7 patients attending the Cornea Service for multitreated keratitis. Corneal biopsy was performed, which was cultured in Page solution. The patients were treated with a PACK-CXL protocol for more than 5 minutes and subjected to UV-A light exposure. Edema of the new epithelium was 2 crosses at 24 hours and disappeared 2 weeks after the procedure in all cases. Basal de-epithelialization percentage at diagnosis was 75.7 percent. Best corrected visual acuity ranged between 20/20 and 20/30. It is concluded that the use of crosslinking in patients with Acanthamoeba keratitis in its initial stages could be a safe and effective therapeutic option(AU)


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Acanthamoeba/citologia , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Relatório de Pesquisa , Literatura de Revisão como Assunto , Bases de Dados Bibliográficas
3.
Parasitol Res ; 119(6): 1943-1954, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32385711

RESUMO

Acanthamoeba causes diseases such as Acanthamoeba keratitis (AK) which leads to permanent blindness and granulomatous Acanthamoeba encephalitis (GAE) where there is formation of granulomas in the brain. Current treatments such as chlorhexidine, diamidines, and azoles either exhibit undesirable side effects or require immediate and prolonged treatment for the drug to be effective or prevent relapse. Previously, antifungal drugs amphotericin B, nystatin, and fluconazole-conjugated silver with nanoparticles have shown significantly increased activity against Acanthamoeba castellanii. In this study, two functionally diverse tetrazoles were synthesized, namely 5-(3-4-dimethoxyphenyl)-1H-tetrazole and 1-(3-methoxyphenyl)-5-phenoxy-1H-tetrazole, denoted by T1 and T2 respectively. These compounds were evaluated for anti-Acanthamoeba effects at different concentrations ranging from 5 to 50 µM. Furthermore, these compounds were conjugated with silver nanoparticles (AgNPs) to enhance their efficacy. Particle size analysis showed that T1-AgNPs and T2-AgNPs had an average size of 52 and 70 nm respectively. After the successful synthesis and characterization of tetrazoles and tetrazole-conjugated AgNPs, they were subjected to anti-Acanthamoeba studies. Amoebicidal assay showed that at concentration 10 µM and above, T2 showed promising antiamoebic activities between the two compounds while encystation and excystation assays reveal that both T1 and T2 have inhibited differentiation activity against Acanthamoeba castellanii. Conjugation of T1 and T2 to AgNP also increased efficacy of tetrazoles as anti-Acanthamoeba agents. This may be due to the increased bioavailability as AgNP allows better delivery of treatment compounds to A. castellanii. Human cell cytotoxicity assay revealed that tetrazoles and AgNPs are significantly less toxic towards human cells compared with chlorhexidine which is known to cause undesirable side effects. Cytopathogenicity assay also revealed that T2 conjugated with AgNPs significantly reduced cytopathogenicity of A. castellanii compared with T2 alone, suggesting that T2-conjugated AgNP is an effective and safe anti-Acanthamoeba agent. The use of a synthetic azole compound conjugated with AgNPs can be an alternative strategy for drug development against A. castellanii. However, mechanistic and in vivo studies are needed to explore further translational values.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Nanopartículas Metálicas , Prata/farmacologia , Tetrazóis/farmacologia , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Acanthamoeba castellanii/genética , Acanthamoeba castellanii/isolamento & purificação , Amebicidas/síntese química , Amebicidas/toxicidade , Clorexidina/farmacologia , Genótipo , Células HeLa , Humanos , Tetrazóis/síntese química , Tetrazóis/toxicidade
4.
Exp Parasitol ; 215: 107915, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32461112

RESUMO

Acanthamoeba castellanii is an opportunistic protozoan responsible for serious human infections including Acanthamoeba keratitis and granulomatous amoebic encephalitis. Despite advances in antimicrobial therapy and supportive care, infections due to Acanthamoeba are a major public concern. Current methods of treatment are not fully effective against both the trophozoite and cyst forms of A. castellanii and are often associated with severe adverse effects, host cell cytotoxicity and recurrence of infection. Therefore, there is an urgent need to develop new therapeutic approaches for the treatment and management of Acanthamoebic infections. Repurposing of clinically approved drugs is a viable avenue for exploration and is particularly useful for neglected and rare diseases where there is limited interest by pharmaceutical companies. Nanotechnology-based drug delivery systems offer promising approaches in the biomedical field, particularly in diagnosis and drug delivery. Herein, we conjugated an antihyperglycemic drug, metformin with silver nanoparticles and assessed its anti-acanthamoebic properties. Characterization by ultraviolet-visible spectrophotometry and atomic force microscopy showed successful formation of metformin-coated silver nanoparticles. Amoebicidal and amoebistatic assays revealed that metformin-coated silver nanoparticles reduced the viability and inhibited the growth of A. castellanii significantly more than metformin and silver nanoparticles alone at both 5 and 10 µM after 24 h incubation. Metformin-coated silver nanoparticles also blocked encystation and inhibited the excystation in Acanthamoeba after 72 h incubation. Overall, the conjugation of metformin with silver nanoparticles was found to enhance its antiamoebic effects against A. castellanii. Furthermore, the pretreatment of A. castellanii with metformin and metformin-coated silver nanoparticles for 2 h also reduced the amoebae-mediated host cell cytotoxicity after 24 h incubation from 73% to 10% at 10 µM, indicating that the drug-conjugated silver nanoparticles confer protection to human cells. These findings suggest that metformin-coated silver nanoparticles hold promise in the improved treatment and management of Acanthamoeba infections.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Metformina/administração & dosagem , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Anti-Infecciosos Locais/farmacologia , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/farmacologia , Células HeLa , Humanos , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/parasitologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Microscopia de Força Atômica , Encistamento de Parasitas/efeitos dos fármacos , Prata , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
5.
Parasit Vectors ; 13(1): 123, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32143731

RESUMO

BACKGROUND: Acanthamoeba spp. are ubiquitous pathogens which cause granulomatous amoebic encephalitis and disseminated infection. Moreover, Acanthamoeba spp. infection of the cornea leads to Acanthamoeba keratitis. Our previous study showed that the infection of an eyeball may also take place via the migration of trophozoites through the optic nerve from the brain to the eyes. The aim of the study was to analyze the activity of enzymatic antioxidants and the concentration of non-enzymatic antioxidant in the eyes of immunocompetent and immunocompromised mice with disseminated acanthamoebiasis. RESULTS: In the immunocompetent mice infected with Acanthamoeba spp. we noted a significant decrease in catalase activity at 8 and 16 days post-infection (dpi). Glutathione reductase activity was significantly lower at 16 dpi compared to the control group and glutathione concentration was statistically higher at 24 dpi than in the control group. In the immunosuppressed mice, a statistically significant increase in glutathione concentration in the eye samples was found at 16 dpi compared to those not infected with Acanthamoeba spp. In the immunosuppressed mice infected with Acanthamoeba spp., glutathione peroxidase activity was statistically lower at 8 dpi, and glutathione concentration was statistically significantly higher at 16 dpi compared to the control group. CONCLUSIONS: The inflammatory response in the eyes of hosts with experimental acanthamoebiasis led to changes in the activity of enzymatic antioxidants and the content of non-enzymatic antioxidant. Therefore, the dysregulation of antioxidants may play a role in the pathomechanism of Acanthamoeba eye infection.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/metabolismo , Acanthamoeba/metabolismo , Antioxidantes/farmacologia , Hospedeiro Imunocomprometido , Acanthamoeba/imunologia , Ceratite por Acanthamoeba/parasitologia , Ceratite por Acanthamoeba/patologia , Animais , Antioxidantes/uso terapêutico , Catalase/metabolismo , Modelos Animais de Doenças , Olho/imunologia , Olho/patologia , Glutationa , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Camundongos , Oxirredução
6.
J Fr Ophtalmol ; 43(4): 330-333, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151474

RESUMO

Acanthamoeba keratitis due to a genus of free-living amoebae is a severe corneal infection. Treatment of this disease is based on the combined use of antiseptics and other drugs, including azoles. We tested isavuconazole, the latest marketed azole, in vitro, against A. castellanii, A. lenticulata and A. hatchetti. Our results show that isavuconazole presents slight amoebistatic activity against A. castellanii trophozoites but no cysticidal activity. Isavuconazole could be used only in association for management of AK due to A. castellanii.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Acanthamoeba/efeitos dos fármacos , Nitrilos/farmacologia , Piridinas/farmacologia , Triazóis/farmacologia , Acanthamoeba/classificação , Acanthamoeba/crescimento & desenvolvimento , Acanthamoeba/fisiologia , Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba castellanii/efeitos dos fármacos , Acanthamoeba castellanii/crescimento & desenvolvimento , Acanthamoeba castellanii/fisiologia , Animais , Relação Dose-Resposta a Droga , Humanos , Nitrilos/uso terapêutico , Encistamento de Parasitas/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Trofozoítos/efeitos dos fármacos
9.
J Formos Med Assoc ; 119(1 Pt 2): 211-217, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31076316

RESUMO

PURPOSE: To analyze the outcomes of Acanthamoeba keratitis (AK) in terms of different clinical presentations in a tertiary hospital in Taiwan over a 20- year period. METHODS: This is a retrospective case series. Patients with AK diagnosed at the National Taiwan University Hospital between January 1996 and December 2015 were identified. A diagnosis of AK was made on the basis of positive Acanthamoeba smear/cultures or pathological identification of Acanthamoeba cysts on keratoplasty specimens. Patient demographics, clinical presentations, treatment courses, and final visual outcomes were collected and analyzed. Visual acuity, postoperative complications and graft survivals were measured as outcomes. RESULTS: Of the 62 patients with AK in our study, 64.5% were medically treated while 35.5% underwent surgical treatment. In those with ring infiltrate, 52.4% patients could be successfully treated with medications. In eyes receiving penetrating keratoplasty, postoperative complications were more common in therapeutic penetrating keratoplasty (TPK) than those in optical penetrating keratoplasty (OPK) group (82.4% versus 40%, p = 0.04). The graft size was larger in TPK than that in OPK group (8.56 versus 7.83 mm, p = 0.002). Furthermore, post-operative glaucoma, which was the major complication, was found to be associated with larger graft size (p = 0.02) and dilated pupil/iris atrophy (p = 0.01). CONCLUSION: Even in advanced cases with ring infiltrate, eradication of infection with anti-amoebic drugs is possible. In those requiring keratoplasty, the surgical timing should be made meticulously considering graft size and signs of dilated pupil/iris atrophy in terms of post-operative glaucoma.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/cirurgia , Ceratoplastia Penetrante , Ceratite por Acanthamoeba/diagnóstico , Adolescente , Adulto , Idoso , Criança , Feminino , Glaucoma/etiologia , Sobrevivência de Enxerto , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taiwan , Centros de Atenção Terciária , Acuidade Visual , Adulto Jovem
10.
Br J Ophthalmol ; 104(4): 575-581, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31401556

RESUMO

AIMS: To test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data. METHODS: A retrospective cohort study of 227 patients developing AK between 25 July 1991 and 10 August 2012. Inclusion criteria required a complete record of AAT treatment for both the primary outcome of a medical cure rate at 12 months and the secondary outcome of Snellen visual acuity ≤6/24 and/or surgical intervention. Analysis used multivariable regression to control for differences in baseline disease characteristics for both primary and secondary outcomes with unadjusted analyses for other outcomes. Subjects were categorised for analysis both by the AAT used at baseline and also by mutually exclusive AAT (patients exposed to all the drugs in each group, and no others, for some period). AAT categories were PHMB monotherapy, PHMB+diamidine, PHMB+chlorhexidine+diamidine, diamidine monotherapy and other AAT. RESULTS: Analysis by baseline AAT showed no notable difference between treatments for both a medical cure at 12 months in 60.79% (138/227) or for a poor outcome in 49.34% (112/227). When AATs were analysed by mutually exclusive groups, PHMB monotherapy provided the best outcomes. These findings are subject to bias requiring careful interpretation. Overall cure rates for the 214 subjects with resolved outcomes were 94.27% (214/227), median time to cure 5 months (IQR 3.25-9.00 months) and range 1-26.24 months. CONCLUSION: PHMB 0.02% monotherapy for the initial treatment of AK is as effective as biguanide+diamidine combination therapy. Chlorhexidine monotherapy was too infrequent for comparison. The outcome data are the most detailed available.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/fisiopatologia , Antiprotozoários/uso terapêutico , Acuidade Visual/fisiologia , Adolescente , Adulto , Idoso , Biguanidas/uso terapêutico , Clorexidina/uso terapêutico , Desinfetantes/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Pentamidina/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
11.
Eye Contact Lens ; 45(5): 301-305, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442212

RESUMO

PURPOSE: To compare the infectious contact lens-related corneal ulcer (CLRU) and non-CLRU cases at Saint Louis University. METHODS: Retrospective review of corneal ulcer cases identified by search of the ophthalmology and microbiology department databases between 1999 and 2016. RESULTS: Six hundred seventy-seven cases of corneal ulcers were identified, of which 46% were CLRU. CLRU cases were seen more commonly in younger patients (P<0.001) and women (P=0.03) than non-CLRU cases. Many of the infections were vision-threatening as defined by central/paracentral location (73% CLRU and 71% non-CLRU [P=0.60]) and large size of ulcer >2 mm in 36% CLRU and 51% non-CLRU (P=0.002). Causative pathogen in cultured CLRU was predominately Pseudomonas species (44%, P<0.001 vs. the non-CLRU group), other gram-negative (6%), gram-positive (33%), fungi (13%), and Acanthamoeba (5%). Comparatively, cultured non-CLRU was predominately gram-positive (64%, P<0.001 vs. the CLRU group), gram-negative (26%), and fungi (11%). The combined oxacillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus isolates were 35% and 34%, respectively. Despite the progressive increase in the number of corneal ulcers seen, the annual trend for any one particular organism for either CLRU cases or non-CLRU cases did not change significantly. CONCLUSIONS: Most of the cases were non-CLRU. CLRU was disproportionately associated with Pseudomonas species and non-CLRU with Staphylococcal species. Fungal infections were predominately caused by filamentous organisms in both groups. Acanthamoeba keratitis was exclusively associated with CL use.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Lentes de Contato/microbiologia , Lentes de Contato/parasitologia , Úlcera da Córnea/microbiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/parasitologia , Centros Médicos Acadêmicos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Criança , Pré-Escolar , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Cornea ; 38(10): 1309-1313, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306283

RESUMO

PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 µg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/isolamento & purificação , Amebicidas/farmacologia , Infecções Oculares Parasitárias/tratamento farmacológico , Voriconazol/farmacologia , Acanthamoeba/efeitos dos fármacos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/parasitologia , Animais , Antifúngicos/farmacologia , Sinergismo Farmacológico , Infecções Oculares Parasitárias/parasitologia , Humanos , Testes de Sensibilidade Parasitária
13.
Cornea ; 38(7): 914-917, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31170106

RESUMO

PURPOSE: Acanthamoeba keratitis is a rare, vision-threatening disease. Commercially available antiamoebics are poorly cysticidal and highly toxic, and therapeutic keratoplasties can be complicated by recurrence or graft failure. We aimed to discuss the use of oral miltefosine for treatment of recalcitrant Acanthamoeba keratitis. METHODS: A 44-year-old contact lens wearer presented with a 2-week history of red painful eye and decreasing vision. After poorly responding to topical corticosteroid on the presumptive diagnosis of anterior uveitis, she developed radial keratoneuritis. Corneal scraping was positive for Acanthamoeba. No clinical response to treatment was observed with topical chlorhexidine 0.02%, polyhexamethylene biguanide 0.02%, and oral voriconazole. She then underwent 2 therapeutic keratoplasties with prompt recurrence of the disease in the keratoplasty graft. RESULTS: Oral miltefosine was added to the treatment. She underwent a third penetrating keratoplasty 8 months later. The excised button was negative for amoeba. She continued miltefosine for 3 more months. No recurrence was observed after 30 months. CONCLUSIONS: This case shows resolution of recalcitrant Acanthamoeba keratitis with oral miltefosine in an immunocompetent patient. Further clinical evidence would be needed to possibly incorporate this medication in the antiamoebic armamentarium.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/administração & dosagem , Fosforilcolina/análogos & derivados , Administração Oral , Adulto , Quimioterapia Adjuvante , Lentes de Contato Hidrofílicas/efeitos adversos , Feminino , Humanos , Ceratoplastia Penetrante , Fosforilcolina/administração & dosagem , Resultado do Tratamento
14.
Parasitol Res ; 118(6): 1953-1961, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31069536

RESUMO

The genus Acanthamoeba can cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage that many times causes infection relapses. In an attempt to add new agents to our chemotherapeutic arsenal against acanthamebiasis, two Acanthamoeba isolates were treated in vitro with newly synthesized biguanide dendrimers. Trophozoite viability analysis and ultrastructural studies showed that dendrimers prevent encystment by lysing the cellular membrane of the amoeba. Moreover, one of the dendrimers showed low toxicity when tested on mammalian cell cultures, which suggest that it might be eventually used as an amoebicidal drug or as a disinfection compound in contact lens solutions.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/efeitos dos fármacos , Amebicidas/farmacologia , Biguanidas/farmacologia , Clorexidina/análogos & derivados , Dendrímeros/farmacologia , Encefalite/tratamento farmacológico , Acanthamoeba/classificação , Acanthamoeba/isolamento & purificação , Animais , Linhagem Celular Tumoral , Clorexidina/farmacologia , Soluções para Lentes de Contato , Encefalite/parasitologia , Células HeLa , Humanos , Trofozoítos/efeitos dos fármacos
15.
Parasitol Res ; 118(8): 2443-2454, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144032

RESUMO

Acanthamoeba keratitis (AK) is a devastating, painful corneal infection, which may lead to loss of vision. The development of resistance and failure of the currently used drugs represent a therapeutic predicament. Thus, novel therapies with lethal effects on resistant Acanthamoeba are necessary to combat AK. In the present study, the curative effect of Nigella sativa aqueous extract (N. sativa) and chitosan nanoparticles (nCs) and both agents combined were assessed in experimentally induced AK. All inoculated corneas developed varying grades of AK. The study medications were applied on the 5th day postinoculation and were evaluated by clinical examination of the cornea and cultivation of corneal scraps. On the 10th day posttreatment, a 100% cure of AK was obtained with nCs (100 µg/ml) in grades 1 and 2 of corneal opacity as well as with N. sativa 60 mg/ml-nCs 100 µg/ml in grades 1, 2, and 3 of corneal opacity, highlighting a possible synergistic effect. On the 15th day posttreatment, a 100% cure was reached with N. sativa aqueous extract (60 mg/ml). Moreover, on the 20th day posttreatment, N. sativa (30 mg/ml) provided a cure rate of 87.5%, while nCs (50 µg/ml) as well as N. sativa 30 mg/ml-nCs 50 µg/ml yielded a cure rate of 75%; the lowest percentage of cure (25%) was obtained with chlorhexidine (0.02%), showing a non-significant difference compared to the parasite control. The clinical outcomes were in agreement with the results of corneal scrap cultivation. The results of the present study demonstrate the effectiveness of N. sativa aqueous extract and nCs (singly or combined) when used against AK, and these agents show potential for the development of new, effective, and safe therapeutic alternatives.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/administração & dosagem , Nigella sativa/química , Extratos Vegetais/administração & dosagem , Acanthamoeba/efeitos dos fármacos , Acanthamoeba/fisiologia , Ceratite por Acanthamoeba/parasitologia , Adulto , Animais , Antiprotozoários/química , Quitosana/química , Quitosana/farmacologia , Quitosana/uso terapêutico , Clorexidina/farmacologia , Córnea/parasitologia , Feminino , Humanos , Masculino , Nanopartículas/química , Extratos Vegetais/química , Ratos , Resultado do Tratamento
16.
Parasitol Res ; 118(7): 2295-2304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093751

RESUMO

Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 µM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 µM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Nanopartículas Metálicas/química , Ácido Oleico/farmacologia , Ceratite por Acanthamoeba/parasitologia , Amebicidas/química , Animais , Olho/parasitologia , Humanos , Microscopia de Força Atômica , Ácido Oleico/química , Prata/química , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
17.
Cornea ; 38(8): 1011-1016, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30932935

RESUMO

PURPOSE: N-chlorotaurine (NCT) is an anti-infective belonging to the class of chloramines and an investigative drug for the topical treatment of keratoconjunctivitis. The aim of the present study was to demonstrate its efficacy against Acanthamoeba and Candida in corneas infected ex vivo. METHODS: Corneal buttons from porcine eyes were contaminated with Acanthamoeba castellanii trophozoites or Candida albicans Centraalbureau voor Schimmelcultures 5982 and incubated for 7 and 3 days, respectively. Subsequently, they were treated with 1% NCT for 5 to 120 minutes. After further incubation for 2 days in the absence of NCT in tests with A. castellanii, the buttons were homogenized, and the amoebae grown for a further 5 days before they were counted in a light microscope. For C. albicans, quantitative cultures were performed from corneal homogenates. RESULTS: Incubation of 120 minutes in NCT completely inhibited the regrowth of A. castellanii and reduced the number of C. albicans colony-forming unit counts by 4 log10. In addition, at 60 minutes, significant reductions of both pathogens could be observed. Histology showed penetration of pathogens into the stroma of the corneal buttons. CONCLUSIONS: NCT inactivates A. castellanii and C. albicans in corneal tissue.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Candidíase/tratamento farmacológico , Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Parasitárias/tratamento farmacológico , Taurina/análogos & derivados , Ceratite por Acanthamoeba/microbiologia , Acanthamoeba castellanii/isolamento & purificação , Acanthamoeba castellanii/fisiologia , Animais , Candida albicans/isolamento & purificação , Candida albicans/fisiologia , Candidíase/microbiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/microbiologia , Modelos Biológicos , Suínos , Taurina/uso terapêutico
18.
Cont Lens Anterior Eye ; 42(5): 506-511, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31018907

RESUMO

PURPOSE OF THE STUDY: To report an observational study of Acanthamoeba Keratitis (AK) in University Hospital Coventry & Warwickshire (UHCW), Coventry, UK and determine risk factors, outcomes as well as incidence rates. METHODS: A retrospective analysis was done of consecutive patients who were treated for AK by the corneal service at UHCW from January 2017 to January 2018. Cases were identified from 2 sources; the department of microbiology and the hospital pharmacy. Patient data was collected by 3 of the authors using both paper and electronic medical records. Information was also gathered over the telephone using a predefined questionnaire. The primary endpoint used for assessing duration of disease was time to resolution after the initial diagnosis. RESULTS: 9 eyes were identified over the 12-month period, a drastic increase from previous years. All were contact lens (CL) wearers and 3 used daily disposable CL's. 8 out of 9 patients had an improvement in best corrected visual acuity (BCVA) which was consistent with their baseline levels pre-infection. The average length of treatment was 107.25 days for the 8 resolved cases. 1 case is still having ongoing treatment. No case has required surgical treatment. Several patients admitted to exposing their CL to unsterile water either via swimming, showering or tap water. All patients had purchased their lenses from contact lens practitioners. CONCLUSION: Overall, our study shows excellent outcomes. Almost all patients had resolution of symptoms with medical treatment and an improvement in visual acuity. Several contributing factors have aided us in achieving this including early diagnosis, a robust treatment protocol and diagnostic modalities such as Polymer Chain Reaction (PCR) and Confocal Microscopy (CFM). However, the increased incidence compared to previous years is a worrying trend and there will be an ongoing analysis looking at patterns of incidence in the future.


Assuntos
Ceratite por Acanthamoeba/epidemiologia , Hospitais de Ensino/estatística & dados numéricos , Acanthamoeba/genética , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Adulto , Anti-Infecciosos Locais/uso terapêutico , Antiprotozoários/uso terapêutico , Benzamidinas/uso terapêutico , Biguanidas/uso terapêutico , Clorexidina/uso terapêutico , Lentes de Contato/efeitos adversos , DNA de Protozoário/genética , Desinfetantes/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologia , Acuidade Visual/fisiologia , Adulto Jovem
19.
Am J Ophthalmol ; 201: 31-36, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721687

RESUMO

PURPOSE: To ascertain the incidence of Acanthamoeba keratitis and the coexistence of Acanthamoeba and fungi in microbial keratitis. DESIGN: Prospective cross-sectional study. METHODS: Patients presenting with stromal keratitis were additionally tested for Acanthamoeba irrespective of the clinical diagnosis. Culture positivity was the gold standard. RESULTS: Of the 401 cases included in the study, 40 were positive for Acanthamoeba (10%); of these 40, 16 were positive for both Acanthamoeba and fungi (4.5% of the study group was Acanthamoeba and fungal keratitis positive); 5 were positive for Acanthamoeba and bacteria; and 2 had triple infection with Acanthamoeba, fungi, and bacteria. Ring infiltrates and stromal edema are frequently associated with Acanthamoeba keratitis, as well as in Acanthamoeba coinfections. Ring infiltrates in particular were more frequently seen in the Acanthamoeba and fungal keratitis group (8/16) and they were often yellowish with hyphate edges (vs ring infiltrates only, which are seen in the patients with Acanthamoeba alone). Only 2 patients were contact lens wearers: however, they presented with history of trauma. CONCLUSIONS: Acanthamoeba coinfections are much more frequent and are not restricted to contact lens users. Anticipating coinfections is necessary for establishing a diagnosis as well as for appropriate and timely therapeutic interventions.


Assuntos
Ceratite por Acanthamoeba/epidemiologia , Coinfecção/epidemiologia , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/parasitologia , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Parasitárias/epidemiologia , Acanthamoeba/isolamento & purificação , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/microbiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Bactérias/isolamento & purificação , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Lentes de Contato/microbiologia , Lentes de Contato/parasitologia , Substância Própria/microbiologia , Substância Própria/parasitologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Estudos Transversais , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/tratamento farmacológico , Infecções Oculares Parasitárias/microbiologia , Feminino , Fungos/isolamento & purificação , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
Cornea ; 38(4): 463-468, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30640249

RESUMO

PURPOSE: Acanthamoeba keratitis (AK) is a severe vision-threatening ocular infection that is frequently a diagnostic challenge. Treatment course is lengthy and often not fully effective. Contact lens wear has been recognized as the prime risk factor for AK. In vivo confocal microscopy (IVCM) is a noninvasive imaging modality that allows direct visualization of potential causative pathogens in real time with an established utility in the diagnosis of AK. In this study, we aim to assess the utility of IVCM in monitoring disease progression in contact lens wearers with culture-confirmed keratitis. METHODS: Fourteen eyes from 11 patients with culture-confirmed AK were included in this retrospective study. IVCM was performed during the patient's initial visit and all follow-up visits. All available confocal sequences were reviewed and graded in a masked fashion. Density of Acanthamoeba cyst infiltration and changes in the cyst density as a percentage of baseline cyst density measured at each patient's initial visit were calculated. A univariate regression analysis was performed to assess the association between treatment and changes in cyst density per month of treatment. RESULTS: Acanthamoeba cysts were identified by IVCM in all of these culture-confirmed cases of keratitis. Mean cyst density in the central cornea at presentation was 99 ± 64.9 cells per square millimeter (range, 38-255/mm). Cyst density in our study population significantly decreased by approximately 5.3% with each month of antiamebic treatment (P = 0.001; R = 0.41). CONCLUSIONS: Reduction in Acanthamoeba cyst density with treatment can be monitored by IVCM, which in turn can be used clinically in prognostication and disease monitoring of AK.


Assuntos
Ceratite por Acanthamoeba/diagnóstico por imagem , Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/citologia , Antiprotozoários/uso terapêutico , Técnicas de Diagnóstico Oftalmológico , Microscopia Confocal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lentes de Contato/efeitos adversos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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