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1.
Microbiol Spectr ; 10(1): e0156921, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35171015

RESUMO

Human mastadenovirus (HAdV), a linear double-stranded DNA (dsDNA) virus, is the causal agent of several diseases, including pharyngoconjunctival fever, epidemic keratoconjunctivitis, and hemorrhagic cystitis, in immunocompromised individuals. There are more than 100 reported types of adenoviruses, but the pathogenicity of many HAdVs remains unknown. Brincidofovir (BCV) is a hexadecyloxypropyl lipid conjugate of cidofovir (CDV) that is active against dsDNA viruses. Clinical effectiveness of BCV against certain HAdV species has been reported; however, its activity against novel HAdV types remains unknown. We investigated the half-maximal inhibitory concentration (IC50) values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. The mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs, including the novel types. IMPORTANCE We investigated the IC50 values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. In addition, the mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs.


Assuntos
Infecções por Adenoviridae/virologia , Infecções por Adenovirus Humanos/virologia , Citosina/análogos & derivados , Ceratoconjuntivite/virologia , Mastadenovirus/efeitos dos fármacos , Organofosfonatos/farmacologia , Infecções por Adenoviridae/imunologia , Infecções por Adenovirus Humanos/imunologia , Cistite , Citosina/farmacologia , Humanos , Hospedeiro Imunocomprometido , Ceratoconjuntivite/imunologia , Mastadenovirus/classificação , Mastadenovirus/genética , Mastadenovirus/fisiologia
2.
J Med Virol ; 93(8): 4840-4845, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33543795

RESUMO

Conjunctivitis is a frequent ocular disorder caused by human adenoviruses (HAdVs). Only a few of the 45 HAdV-D species are associated with epidemic keratoconjunctivitis, including HAdV-D8. Nosocomial outbreaks due to HAdV-D8 have been rarely described, because keratoconjunctivitis cases are clinically diagnosed and treated without having to characterize the causative agent. Moreover, molecular typing is tedious when using classical techniques. In this study, a hospital outbreak of conjunctivitis caused by HAdV-D8 was characterized using the recently developed whole-genome sequencing (WGS) method. Of the 363 patients attending the Ophthalmology Department between July 13 and August 13, 2018, 36 may have acquired intrahospital conjunctivitis. Also, 11 of 22 samples sent to the Virology section were selected for WGS analysis. The WGS results revealed that 10 out of 11 HAdV-D8 strains were closely related. The remaining strain (Case 28) was more similar to a strain from an outbreak in Germany obtained from a public sequence database. WGS results showed that outbreak HAdV-D8 strains had a minimum percentage of identity of 94.3%. WGS is useful in a clinical setting, because it avoids carrying out viral culture or specific polymerase chain reaction sequencing. The public availability of sequence reads makes it easier to compare clusters in circulation. In conclusion, WGS can play an important role in standard routines to describe viral outbreaks.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Genoma Viral/genética , Ceratoconjuntivite/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/virologia , DNA Viral/genética , Feminino , Humanos , Ceratoconjuntivite/virologia , Masculino , Pessoa de Meia-Idade , Filogenia , Espanha/epidemiologia , Centros de Atenção Terciária , Sequenciamento Completo do Genoma
3.
Ocul Immunol Inflamm ; 29(7-8): 1627-1632, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-32643975

RESUMO

Purpose: To examine the effects of treatments performed on children with adenoviral conjunctivitis.Methods: 50 children with Adenoviral keratoconjunctivitis (AK) were evaluated. Patients were divided into four groups according to the medical treatment agents that were used previously. AK symptoms were clinically scored and analyzed. The diagnosis of all children was confirmed by an in-office lateral flow immunoassay.Results: Fifty patients with AK were included in the study. 24 (48%) were female and 26 (52%) were male. The mean age was 12.88 ± 2.66 (8-17). In PVP-I groups clinical findings shows faster improvement than other groups (p < .05).Conclusions: Conjunctival irrigation with 2.5% PVP-I is very effective for the treatment of adenoviral conjunctivitis in childhood. Ganciclovir ophthalmic gel 0.15% increases the effect of 2.5% PVP-I on AK, but this was not statistically significant.


Assuntos
Infecções por Adenovirus Humanos/tratamento farmacológico , Anti-Infecciosos Locais/uso terapêutico , Antivirais/uso terapêutico , Infecções Oculares Virais/tratamento farmacológico , Ganciclovir/uso terapêutico , Ceratoconjuntivite/tratamento farmacológico , Povidona-Iodo/uso terapêutico , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/virologia , Administração Oftálmica , Adolescente , Criança , Sinergismo Farmacológico , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/virologia , Feminino , Humanos , Imunoensaio/métodos , Ceratoconjuntivite/diagnóstico , Ceratoconjuntivite/virologia , Masculino , Soluções Oftálmicas , Estudos Retrospectivos
4.
Eur J Ophthalmol ; 31(2): 379-384, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31813297

RESUMO

PURPOSE: The aim of this study was to test the antiviral effectivity of potassium peroxymonosulfate (RUBYSTA®, KYORIN) against five epidemic keratoconjunctivitis-related types of Human adenovirus D in vitro. METHODS: Five types of Human adenovirus D (8, 37, 53, 54 and 56) were incubated with 1% potassium peroxymonosulfate, 0.1% sodium hypochlorite (NaClO) or alcohol-based disinfectant for 30 s or 1 min. These solutions were subjected to measurements of viral titres by infection assays in A549 cells. At day 6 post-infection, both, supernatants and cells, were collected and the viral genome was assessed by real-time polymerase chain reaction analysis. RESULTS: Treatments with 1% potassium peroxymonosulfate led to significant reduction in all tested Human adenovirus D types comparable to disinfecting effects by 0.1% NaClO. Overall, potassium peroxymonosulfate demonstrated sufficient inactivation of the major epidemic keratoconjunctivitis-causing Human adenovirus D to be considered for disinfection and prevention purposes in ophthalmological clinics and hospitals. CONCLUSION: This study demonstrated that potassium peroxymonosulfate is a promising disinfectant for the prevention of epidemic keratoconjunctivitis nosocomial infections in ophthalmological clinics.


Assuntos
Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/efeitos dos fármacos , Desinfetantes/farmacologia , Ceratoconjuntivite/virologia , Oxidantes/farmacologia , Peróxidos/farmacologia , Células A549 , Infecção Hospitalar/prevenção & controle , Epidemias , Humanos , Replicação Viral/efeitos dos fármacos
5.
J Med Virol ; 93(6): 3969-3973, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33135807

RESUMO

We report a large epidemic (n = 126) of keratoconjunctivitis predominantly with two lineages of adenovirus (AdV) type D8 in patients seen in eye casualty between march and August 2019. Other AdV species identified by viral sequencing included B, C, and E. Despite various features of more severe eye disease being present, these were not significantly different between the different AdV species, with similar rates of pseudomembrane formation and keratitis observed in patients with AdV species B as for those with AdV species D.


Assuntos
Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Surtos de Doenças , Ceratoconjuntivite/epidemiologia , Ceratoconjuntivite/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/patogenicidade , Adolescente , Adulto , Infecção Hospitalar/epidemiologia , Olho/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Adulto Jovem
6.
Rev Esp Salud Publica ; 942020 Sep 08.
Artigo em Espanhol | MEDLINE | ID: mdl-32896840

RESUMO

OBJECTIVE: Ocular infections caused by human adenovirus are highly contagious and can cause outbreaks, especially in nursing homes. In this work, we describe the epidemiological and analytical research as well as the control measures carried out for a conjunctivitis outbreak. METHODS: Descriptive epidemiological study. Cases with a symptom onset date prior to oficial communication were analyzed retrospectively. The rest was analyzed prospectively. Conjunctival smears were collected for microbiological study. Virological analysis was performed by detecting adenovirus by PCR and genotyping. A data questionnaire that collected clinical and epidemiological information was designed. Possible risk factors associated with infection were studied by calculating the Odds Ratio. RESULTS: On June 11, 2019, the Epidemiological Surveillance Section of the Provincial Health Department of Albacete was notified of the existence of a large number of cases of conjunctivitis in a geriatric center. 54 cases were declared: 43 internal residents, 3 day center assistants and 8 workers. Attack rates were 35.8%, 12.5% and 8.4% respectively. Three risk factors were associated with the disease: patient´s lack of autonomy, being a resident at the nursing home and having their room assigned on the first floor. Human adenovirus serotype 8 was detected in the patients' samples. CONCLUSIONS: A high attack rate was observed in internal residents and the disease was associated with patient´s lack of autonomy and having their room assigned on the first floor of the nursing home. The outbreak was caused by human adenovirus serotype 8.


OBJETIVO: Las infecciones oculares causadas por adenovirus humanos son altamente contagiosas y pueden causar brotes, especialmente en residencias de ancianos. El objetivo de este trabajo fue exponer las investigaciones epidemiológicas y analíticas realizadas para el estudio del brote de queratoconjuntivitis epidémica y las medidas establecidas para su control. METODOS: Se realizó un estudio epidemiológico descriptivo. Se analizaron de forma retrospectiva los casos con fecha de inicio de síntomas anterior a la comunicación oficial, y de forma prospectiva el resto. Se recogieron frotis conjuntivales para estudio microbiológico. El análisis virológico fue realizado mediante la detección de adenovirus por PCR y genotipado. Se diseñó un cuestionario de datos que recogía información clínica y epidemiológica. Se estudiaron posibles factores de riesgo asociados a la infección mediante el cálculo de la Odds Ratio. RESULTADOS: El 11 de junio de 2019 se notificó a la Sección de Vigilancia Epidemiológica de la Dirección Provincial de Sanidad de Albacete la existencia de un número elevado de casos de conjuntivitis en un centro geriátrico. Se declararon 54 casos: 43 entre residentes internos, 3 entre asistentes del centro de día y 8 entre personal laboral. Las tasas de ataque fueron del 35,8%, 12,5% y 8,4%, respectivamente. La falta de autonomía, el ser residente interno y estar ubicado en la primera planta fueron factores asociados a la enfermedad. Se detectó adenovirus humano serotipo 8 en las muestras correspondientes a enfermos. CONCLUSIONES: Se observó una elevada tasa de ataque en residentes internos y la enfermedad se asoció con la falta de autonomía y la localización en la primera planta. El brote fue causado por adenovirus humano serotipo 8.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Surtos de Doenças , Controle de Infecções/métodos , Ceratoconjuntivite/epidemiologia , Ceratoconjuntivite/virologia , Casas de Saúde , Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/prevenção & controle , Adenovírus Humanos/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ceratoconjuntivite/diagnóstico , Ceratoconjuntivite/prevenção & controle , Masculino , Estudos Retrospectivos , Fatores de Risco , Sorogrupo , Espanha/epidemiologia
7.
Klin Monbl Augenheilkd ; 237(5): 675-680, 2020 May.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-32375197

RESUMO

PURPOSE: To perform a systematic analysis of articles on the ophthalmological implications of the global COVID-19 pandemic. METHODS: PubMed.gov was searched for relevant articles using the keywords "COVID-19", "coronavirus", and "SARS-CoV-2" in conjunction with "ophthalmology" and "eye". Moreover, official recommendations of ophthalmological societies were systematically reviewed, with a focus on the American Academy of Ophthalmology (AAO) and the Royal College of Ophthalmologists (RCOphth). RESULTS: As of April 16, 2020, in total, 21 peer-reviewed articles on the ophthalmological aspects of COVID-19 were identified. Of these, 12 (57.1%) were from Asia, 6 (28.6%) from the United States of America, and 3 (14.3%) from Europe. There were 5 (23.8%) original studies, 10 (47.6%) letters, 3 (14.2%) case reports, and 3 (14.2%) reviews. These articles could be classified into the topics "Modes and prevention of (ocular) transmission", "Ophthalmological manifestations of COVID-19", "Clinical guidance concerning ophthalmological practice during the COVID-19 pandemic", and "Practical recommendations for clinical infrastructure". Practical recommendations could be extracted from official statements of the AAO and the RCOphth. CONCLUSION: Within a short period, a growing body of articles has started to elucidate the ophthalmological implications of COVID-19. As the eye can represent a route of infection (actively via tears and passively via the nasoacrimal duct), ophthalmological care has to undergo substantial modifications during this pandemic. In the eye, COVID-19 can manifest as keratoconjunctivitis.


Assuntos
Infecções por Coronavirus , Ceratoconjuntivite , Ducto Nasolacrimal/virologia , Oftalmologia , Pandemias , Pneumonia Viral , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Lágrimas/virologia , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Humanos , Ceratoconjuntivite/virologia , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , SARS-CoV-2
9.
Jpn J Infect Dis ; 73(5): 349-353, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32350225

RESUMO

Seven human mastadenovirus (HAdV) species (A-G) are known with more than 100 reported types. HAdV is highly resistant to common hand sanitizers. Epidemic keratoconjunctivitis and pharyngoconjunctival fever are caused by HAdV, which can be explosively transmitted in a confined space, resulting in outbreaks, such as nosocomial infections. Given the absence of an antiviral agent against the HAdV infection, it is important to prevent the spread of the infection by using disinfectants. Ozone has already been well-known for its bactericidal and virucidal effects. ALTANT is an ozonated alcohol preparation developed by E-TECH Co., Ltd. (Kobe, Hyogo, Japan). In this study, we mixed ALTANT with different HAdV types at a ratio of 9:1 and determined HAdV viability after instantaneous reactions for varying periods (flash to 5 minutes) using the TCID50 assay. The assay results demonstrated that the HAdV viability decreased by 1/10 to 1/100 within 1 minute after the reaction; additionally, slight differences in the reactivity were observed among the HAdV types. HAdV viability decreased by a factor of > 4log10, and the virus was eliminated within 3 minutes. This study demonstrated the potent HAdV disinfection effect of ALTANT.


Assuntos
Infecções por Adenovirus Humanos/prevenção & controle , Desinfetantes/farmacologia , Etanol/farmacologia , Mastadenovirus/efeitos dos fármacos , Ozônio/farmacologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/farmacologia , Proliferação de Células/efeitos dos fármacos , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/virologia , Surtos de Doenças , Desinfetantes/química , Etanol/química , Humanos , Japão , Ceratoconjuntivite/prevenção & controle , Ceratoconjuntivite/virologia , Mastadenovirus/patogenicidade , Testes de Sensibilidade Microbiana , Ozônio/química
10.
Antivir Chem Chemother ; 28: 2040206620921319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345035

RESUMO

Human adenovirus type 19 (HAdV-19) is a major cause of the epidemic keratoconjunctivitis. Outbreaks of keratoconjunctivitis are problematic to human health, especially for infants, the elderly, and immunocompromised individuals. However, the development of anti-HAdV drugs has been hampered by inconvenient screening systems; therefore, development of a simple screening method is highly desirable. In this study, we identified that HAdV-19 can infect a human lymphoid cell line transformed with human T-cell leukemia virus (MT-2 cells). MT-2 cells supported HAdV-19 replication and showed apparent cytopathic effects within five days post-infection. Using a thiazolyl blue tetrazolium bromide (MTT)-based colorimetric assay on MT-2 cells, we were able to detect the anti-HAdV-19 activities of previously reported nucleoside/tide compounds, including (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir), 2',3'-dideoxycytidine (zalcitabine) and 3'-deoxy-3'-fluorothymidine (trifluridine). Compared with previous methods, this system represents a more simple and rapid method to screen anti-HAdV-19 agents.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Antivirais/farmacologia , Cidofovir/farmacologia , Linfócitos/efeitos dos fármacos , Zalcitabina/farmacologia , Adenovírus Humanos/genética , Células Cultivadas , Humanos , Ceratoconjuntivite/tratamento farmacológico , Ceratoconjuntivite/virologia , Linfócitos/virologia , Testes de Sensibilidade Microbiana
11.
Jpn J Ophthalmol ; 64(3): 312-320, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32125553

RESUMO

PURPOSE: To characterize the virological features of adenovirus type 54 (Ad54) causing nationwide outbreak of severe epidemic keratoconjunctivitis (EKC) in Japan, we comparatively analysed the viral propagation phenotype of Ad54 and other Ads: type 37 (Ad37), 64 (Ad64), and 5 (Ad5), in A549 cells quantitatively. STUDY DESIGN: Laboratory investigation. METHODS: We compared the growth rate of Ads using copy numbers and cytopathic effect observation during propagation in A549 cell lines. Expressions of mRNA of E1 gene were also calculated and compared. Phylogenetic analysis of the region, including putative promoter of E1 gene and E1 open reading frame (ORF), were performed. RESULTS: Increases in viral loads, growth rate, and viral propagation were slower for Ad54 than for other Ads. The expression level of the E1 gene per infected cell was lower for Ad54 than for other Ad types on post-infection day 1. Phylogenetic analysis of the E1 gene putative promoter and ORF revealed Ad54 was the closest to Ad type 8. CONCLUSION: The propagation of Ad54 in A549 is slow compared with Ad37, Ad64 and Ad5. This slow propagation could have been caused by slow genomic replication resulting from delayed viral entry or E1 transcription initiation. The EKC caused by Ad54 needs more attention because the slow propagation of Ad54 may contribute to prolonged disease duration.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/fisiologia , Surtos de Doenças , Infecções Oculares Virais/epidemiologia , Ceratoconjuntivite/epidemiologia , Células A549/virologia , Proteínas E1 de Adenovirus/genética , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Técnicas de Cultura de Células , Linhagem Celular , Efeito Citopatogênico Viral , Variações do Número de Cópias de DNA , DNA Viral/genética , Infecções Oculares Virais/virologia , Humanos , Japão/epidemiologia , Ceratoconjuntivite/virologia , RNA Mensageiro/genética , Carga Viral , Cultura de Vírus
12.
J Refract Surg ; 36(1): 55-61, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917852

RESUMO

PURPOSE: To assess visual and refractive outcomes and recurrence rates of subepithelial infiltrates after corneal surface ablation with mitomycin C (MMC) 0.02% for the treatment of chronic corneal scars following epidemic keratoconjunctivitis and to compare these results with a control group receiving only medical treatment. METHODS: This was a retrospective case series enrolling patients with central corneal scars following epidemic keratoconjunctivitis. Patients were divided into two groups: (1) control with clinical follow-up and refractive correction with glasses or rigid gas-permeable contact lenses when necessary and (2) transepithelial phototherapeutic keratectomy (PTK) with MMC 0.02%, combined with photorefractive keratectomy (PRK) in selected cases (treatment group). Signs and symptoms, corrected distance visual acuity (CDVA) in logMAR units, manifest and cycloplegic refraction, and depth of the corneal opacities were assessed. RESULTS: Thirty-five eyes of 27 patients (11 men [40.7%] and 16 women [59.3%]) were enrolled, with a mean follow-up of 54.4 ± 19.7 and 27.5 ± 22.8 months in the control and treatment groups, respectively. Mean improvement in CDVA was 0.13 ± 0.17 logMAR (P = .007) in the control group and 0.29 ± 0.24 logMAR (P = .001) in the treatment group. Intergroup comparison showed a greater improvement in the treatment group (P = .041). Mean hyperopic shift induced in the treatment group was +0.46 ± 1.20 diopters. The recurrence rate of subepithelial infiltrates was 77.7% in the control group and 11.7% in the treatment group throughout the follow-up (54.4 ± 19.7 and 27.5 ± 22.8 months, respectively). CONCLUSIONS: Corneal surface ablation with MMC 0.02% was efficient in treating corneal scars following adenoviral epidemic keratoconjunctivitis, with greater visual improvement in comparison to clinical treatment and a decreased rate of infiltrate recurrence. [J Refract Surg. 2020;36(1):55-61.].


Assuntos
Técnicas de Ablação/métodos , Infecções por Adenovirus Humanos/complicações , Lesões da Córnea/terapia , Infecções Oculares Virais/complicações , Ceratoconjuntivite/complicações , Mitomicina/farmacologia , Acuidade Visual , Infecções por Adenovirus Humanos/virologia , Adulto , Córnea/patologia , Lesões da Córnea/diagnóstico , Lesões da Córnea/etiologia , Topografia da Córnea , Infecções Oculares Virais/virologia , Feminino , Humanos , Ceratoconjuntivite/virologia , Masculino , Inibidores da Síntese de Ácido Nucleico/farmacologia , Refração Ocular , Estudos Retrospectivos , Resultado do Tratamento
13.
Prog Retin Eye Res ; 76: 100826, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31891773

RESUMO

Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to the specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos , Túnica Conjuntiva/virologia , Córnea/virologia , Infecções Oculares Virais/epidemiologia , Ceratoconjuntivite/epidemiologia , Infecções por Adenovirus Humanos/virologia , Epidemias , Infecções Oculares Virais/virologia , Saúde Global , Humanos , Ceratoconjuntivite/virologia
14.
Tunis Med ; 97(5): 639-643, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31729734

RESUMO

INTRODUCTION: The adenoviral keratoconjunctivitis infiltrates may be a source of significant visual impairment justifying the use of various therapeutic means. AIM: Evaluate the efficiency and safety of use of cyclosporine A 0,5% eye drop in the treatment of subepithelial infiltrates. METHODS: It was a prospective study of 37 eyes of 22 patients with adenoviral keratoconjunctivitis with subepithelial infiltrates treated with cyclosporine A 0,5% eye drop. Cyclosporine A 0,5% was prepared from the injectable form of cyclosporine (Sandimmun®) and artificial tears. The cyclosporine A 0,5% was first administered at 4 drops per day for 15 days, then at a rate of 2 drops per day for a variable period ranging from 15 days to 6 months. The use of this molecule has been motivated by the presence of a persistent dazzlement, by visual acuity under 6/10 or an astigmatism superior to 1 diopter. RESULTS: At the end of follow, dazzlement disappeared in all patients; the final average visual acuity was 8/10 and corneal astigmatism average was of 0.75 diopter. The slit lamp examination showed a marked decrease in the number and density of subepithelial infiltrates from the 15th day. A 29-year-old patient, however, presented some intercostal vesicles due to zonal recrudescence but with spontaneous and quick resolve in the same time of taking topical cyclosporine. No local complications were observed in our patients. The average follow-up was 13 months. CONCLUSION: Topical cyclosporine A is an effective and well-tolerated alternative to corticosteroids in the subepithelial infiltrates occurring as sequelae of adenoviral keratoconjunctivitis.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Ciclosporina/administração & dosagem , Ceratoconjuntivite/tratamento farmacológico , Ceratoconjuntivite/virologia , Adulto , Ciclosporina/efeitos adversos , Feminino , Humanos , Masculino , Soluções Oftálmicas , Estudos Prospectivos , Resultado do Tratamento
15.
FEBS Lett ; 593(24): 3583-3608, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31769017

RESUMO

Human adenovirus commonly causes infections of respiratory, gastrointestinal, genitourinary, and ocular surface mucosae. Although most adenovirus eye infections are mild and self-limited, specific viruses within human adenovirus species D are associated with epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular surface infection, which can lead to chronic and/or recurrent, visually disabling keratitis. In this review, we discuss the links between adenovirus ontogeny, genomics, immune responses, and corneal pathogenesis, for those viruses that cause EKC.


Assuntos
Adenovírus Humanos/patogenicidade , Evolução Biológica , Proteínas do Olho/genética , Interações Hospedeiro-Patógeno/genética , Ceratite/genética , Ceratoconjuntivite/genética , Proteínas Virais/genética , Adenovírus Humanos/genética , Adenovírus Humanos/imunologia , Animais , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Túnica Conjuntiva/virologia , Córnea/imunologia , Córnea/metabolismo , Córnea/patologia , Córnea/virologia , Modelos Animais de Doenças , Proteínas do Olho/imunologia , Regulação da Expressão Gênica , Genômica/métodos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Ceratite/imunologia , Ceratite/patologia , Ceratite/virologia , Ceratoconjuntivite/imunologia , Ceratoconjuntivite/patologia , Ceratoconjuntivite/virologia , Filogenia , Proteínas Virais/imunologia , Tropismo Viral/genética , Tropismo Viral/imunologia
16.
Diagn Microbiol Infect Dis ; 95(4): 114885, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31607514

RESUMO

Adenoviral epidemic keratoconjunctivitis (EKC) is a major cause of ocular morbidity worldwide and specific antiviral therapies are not available. EKC is primarily caused by Human adenovirus D (HAdV-D) types 8, 37, 53, 54, 56 and 64. Considering the genomic variation in HAdV-D, we hypothesized that clinical signs could be differentiated by virus type. The hypothesis was retrospectively tested with clinical signs recorded from 250 patients with ocular infections visiting an ophthalmological clinic in southern Japan between 2011 and 2014. The results showed that conjunctival opacity, corneal epithelial disorders and pre-auricular lymphadenopathy, were more frequently associated with EKC than other ocular infections. Furthermore, HAdV types 8, 37 and 54, caused corneal complications and longer infections significantly more frequently than infections by types 53 and 56 (P < 0.05). Our descriptive results supported that symptoms severity vary with the infecting type, however, further research is needed to improve diagnosis of EKC.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/patologia , Adenovírus Humanos/fisiologia , Ceratoconjuntivite/epidemiologia , Ceratoconjuntivite/patologia , Células A549 , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Efeito Citopatogênico Viral , Humanos , Lactente , Japão/epidemiologia , Ceratoconjuntivite/virologia , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Retrospectivos , Adulto Jovem
18.
BMC Infect Dis ; 19(1): 624, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307413

RESUMO

BACKGROUND: Two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively with an interval of 5 days in two primary boarding schools in Weixi Lisu Autonomous County, Diqing, and Tibetan Autonomous Prefecture, Yunnan. The aims of this study were to determine the intensity and characteristics of the outbreaks, as well as the clinical manifestations in the patients, the risk factors for infection and the pathogen responsible for the two outbreaks. METHODS: An outbreak investigation was conducted in two primary schools, and a case-control study including patients from the Weixi County Ethnic Primary School was performed. Relevant specimens were collected according to the case definition, and next-generation sequencing was employed to identify the pathogen. An epidemiological investigation method was used to analyse the related epidemiological characteristics, such as risk factors. The phylogenetic tree was constructed by MEGA 7.0. RESULTS: A total of 331 acute conjunctivitis cases, including probable cases of EKC, were reported in the two schools, and the attack rates were 30.59% (171/559, 95%CI: 26.76-34.42) and 20.41% (160/784, 95%CI: 17.58-23.24), respectively. Cases occurred in all grades and classes in both schools, and only one staff member in each school presented illness. The epidemics lasted for 54 days and 45 days, respectively. The patients had typical manifestations of EKC, such as acute onset, follicular hyperplasia, pseudomembrane formation, preauricular lymphadenopathy, corneal involvement and blurred vision, and a relatively long disease course (average 9.40 days, longest 23 days and shortest 7 days). The risk factor for infection was close contact with a patient or personal items contaminated by a patient. The pathogen responsible for the outbreaks was HAdV-8. The virus was highly similar to the 2016 HAdV-8 strain from Tibet, China. CONCLUSIONS: This study strongly suggests that HAdV-8 could lead to serious consequences. This is the second report of a HAdV-8-associated EKC outbreak in mainland China. Tibetan HAdV-8 might be circulating in southwest China; therefore, it is necessary to monitor the pathogens causing acute conjunctivitis in this area.


Assuntos
Infecções por Adenovirus Humanos/diagnóstico , Adenovírus Humanos/isolamento & purificação , Ceratoconjuntivite/diagnóstico , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , China/epidemiologia , DNA Viral/isolamento & purificação , DNA Viral/metabolismo , Surtos de Doenças , Feminino , Humanos , Ceratoconjuntivite/epidemiologia , Ceratoconjuntivite/virologia , Masculino , Filogenia , Fatores de Risco , Instituições Acadêmicas , Análise de Sequência de DNA , Adulto Jovem
19.
Viruses ; 11(5)2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035532

RESUMO

Human adenoviruses (HAdV) are the most common cause of ocular infections. Species B human adenovirus type 3 (HAdV-B3) causes pharyngoconjunctival fever (PCF), whereas HAdV-D8, -D37, and -D64 cause epidemic keratoconjunctivitis (EKC). Recently, HAdV-D53, -D54, and -D56 emerged as new EKC-causing agents. HAdV-E4 is associated with both PCF and EKC. We have previously demonstrated that HAdV-D37 uses sialic acid (SA)-containing glycans as cellular receptors on human corneal epithelial (HCE) cells, and the virus interaction with SA is mediated by the knob domain of the viral fiber protein. Here, by means of cell-based assays and using neuraminidase (a SA-cleaving enzyme), we investigated whether ocular HAdVs other than HAdV-D37 also use SA-containing glycans as receptors on HCE cells. We found that HAdV-E4 and -D56 infect HCE cells independent of SAs, whereas HAdV-D53 and -D64 use SAs as cellular receptors. HAdV-D8 and -D54 fiber knobs also bound to cell-surface SAs. Surprisingly, HCE cells were found resistant to HAdV-B3 infection. We also demonstrated that the SA-based molecule i.e., ME0462, designed to bind to SA-binding sites on the HAdV-D37 fiber knob, efficiently prevents binding and infection of several EKC-causing HAdVs. Surface plasmon resonance analysis confirmed a direct interaction between ME0462 and fiber knobs. Altogether, we demonstrate that SA-containing glycans serve as receptors for multiple EKC-causing HAdVs, and, that SA-based compound function as a broad-spectrum antiviral against known and emerging EKC-causing HAdVs.


Assuntos
Infecções por Adenovirus Humanos/metabolismo , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/fisiologia , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Receptores Virais/metabolismo , Tropismo Viral , Células A549 , Sequência de Aminoácidos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Humanos , Ceratoconjuntivite/metabolismo , Ceratoconjuntivite/virologia , Análise de Sequência de DNA
20.
Viruses ; 11(3)2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30870979

RESUMO

Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Ceratoconjuntivite/virologia , Receptores Virais/metabolismo , Suramina/farmacologia , Ligação Viral/efeitos dos fármacos , Células A549 , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/virologia , Sítios de Ligação , DNA Viral , Reposicionamento de Medicamentos , Genoma Viral , Humanos , Ceratoconjuntivite/tratamento farmacológico , Filogenia , Estudo de Prova de Conceito , Análise de Sequência de DNA
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