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1.
J Zoo Wildl Med ; 50(4): 1012-1015, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926539

RESUMO

Adenoviruses have been reported to affect a broad range of host species, tend to be species specific, and often affect the respiratory system. This report describes the isolation of an adenovirus from deep nasal swabs of two wild North American porcupines (Erethizon dorsatum) with respiratory diseases that presented to a wildlife hospital. Partial sequences of the deoxyribonucleic acid polymerase gene of the isolated virus were identical to skunk adenovirus (SkAdV-1), also known as pygmy marmoset adenovirus. Both porcupines survived and were released back to the wild after successful medical treatment and rehabilitation. The significance of the adenovirus isolated from these porcupines is unknown; however, this is the first report of an adenovirus in porcupines, and the first report of SkAdV-1 in a rodent.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/classificação , Porcos-Espinhos , Infecções Respiratórias/veterinária , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/virologia , Animais , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Broncodilatadores/uso terapêutico , Enrofloxacina/uso terapêutico , Masculino , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Terbutalina/uso terapêutico
2.
FEMS Microbiol Rev ; 43(4): 380-388, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916746

RESUMO

The symptoms of human adenovirus infections are generally mild and self-limiting. However, these infections have been gaining importance in recent years because of a growing number of immunocompromised patients. Solid organ and hematopoietic stem cell transplant patients are subjected to severe immunosuppressive regimes and cannot efficaciously eliminate virus infections. In these patients, adenovirus infections can develop into deadly multi-organ disseminated disease. Presently, in the absence of approved therapies, physicians rely on drugs developed for other purposes to treat adenovirus infections. As there is a need for anti-adenoviral therapies, researchers have been developing new agents and repurposing existing ones to treat adenovirus infections. There are several small molecule drugs that are being tested for their efficacy against human adenoviruses; some of these have reached clinical trials, while others are still in the preclinical phase. Besides these compounds, research on immunotherapy against adenoviral infection has made significant progress, promising another modality for treatment. The availability of an animal model confirmed the activity of some drugs already in clinical use while proving that others are inactive. This led to the identification of several lead compounds that await further development. In the present article, we review the current status of anti-adenoviral therapies and their advancement by in vivo studies in the Syrian hamster model.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenovírus Humanos/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/uso terapêutico , Desenvolvimento de Medicamentos , Mesocricetus , Animais , Cricetinae , Modelos Animais de Doenças
3.
Sci Rep ; 9(1): 17, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626902

RESUMO

The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/farmacologia , Reposicionamento de Medicamentos , Niclosamida/farmacologia , Oxiclozanida/farmacologia , Rafoxanida/farmacologia , Células A549 , Adenoviridae/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Células HEK293 , Humanos
4.
J Infect Chemother ; 25(5): 371-375, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30642772

RESUMO

BACKGROUND: Disseminated adenovirus (ADV) infection is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, it is rare following autologous peripheral blood stem cell transplantation (auto-PBSCT) or chemotherapy alone. CASE: A 66-year-old Japanese female with relapsed and refractory multiple myeloma (RRMM) received auto-PBSCT, achieving partial response. To obtain a greater response, pomalidomide/dexamethasone was started on day 28 after auto-PBSCT, but was stopped on day 41 due to thrombocytopenia, fever, and gross hematuria. Additionally, she complained of abdominal pain on day 46. Blood tests revealed elevation of transaminases and alkaline phosphatase. There was no evidence of bacterial or fungal infections or progression of MM. ADV titer in urine and serum were 3.41 × 105 copies/mL and 6.76 × 103 copies/mL, respectively. CT scans revealed cystitis, urethritis, and peritonitis. Since more than two organs were infected with ADV, she was diagnosed with disseminated ADV disease. After 5 weeks of supportive care, all symptoms resolved. ADV titer decreased to 5.90 × 102 copies/mL in urine and became negative in serum on day 80. However, she succumbed to the MM a little more than a month later. CONCLUSION: Disseminated ADV infection can occur even in non-allogeneic transplant settings, such as in severely immunocompromised patients with MM who receive auto-PBSCT and repeated salvage therapies. Although it is a rare event, the mortality rate of this disease is very high, and hence, early diagnosis and interventions are needed in suspected cases.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Terapia de Salvação/métodos , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/etiologia , Idoso , Dexametasona/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Evolução Fatal , Feminino , Humanos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Transplante Autólogo/efeitos adversos
5.
Pharmacotherapy ; 38(12): 1260-1266, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30403300

RESUMO

BACKGROUND: Infections with adenoviruses (ADVs) can result in considerable mortality and morbidity in solid organ transplant (SOT) recipients. Standard therapy for ADV infections in transplant recipients is not established. At our institution, intravenous cidofovir and immunoglobulin have been used to treat disseminated or invasive ADV in SOT and hematopoietic stem cell transplant recipients. METHODS: A retrospective case series of SOT recipients treated with cidofovir and intravenous immunoglobulin was performed. RESULTS: Five SOT recipients (four renal and one heart transplant) with adenovirus infection were treated successfully with cidofovir and immunoglobulin. Cidofovir was discontinued after the first negative ADV viral load and resolution of clinical symptoms, given the concern for nephrotoxicity in renal transplant recipients. Renal tubular acidosis type 2 and iritis were observed in two patients receiving therapy. CONCLUSION: Symptom resolution and a single negative ADV viral load may be indicators for cidofovir discontinuation.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/administração & dosagem , Cidofovir/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Transplantados , Infecções por Adenoviridae/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/fisiologia
6.
PLoS One ; 13(10): e0200043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30332435

RESUMO

Infection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi's sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.


Assuntos
Acrilamidas/farmacologia , Hidrazinas/farmacologia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Carioferinas/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Viroses/tratamento farmacológico , Infecções por Adenoviridae/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Infecções por Citomegalovirus/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Fibroblastos/virologia , Cobaias , Células HEK293 , Infecções por HIV/complicações , Células HeLa , Humanos , Camundongos , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Reprodutibilidade dos Testes , Sarcoma de Kaposi/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Viroses/complicações
7.
BMC Infect Dis ; 18(1): 529, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30348093

RESUMO

BACKGROUND: Adenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child's long-term clinical outcomes. CASE PRESENTATION: We present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation. CONCLUSIONS: Adenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation.


Assuntos
Infecções por Adenoviridae/diagnóstico , Aneuploidia , Antivirais/uso terapêutico , Bronquiolite Obliterante/patologia , Cidofovir/uso terapêutico , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/virologia , Bronquiolite Obliterante/complicações , Bronquiolite Obliterante/diagnóstico por imagem , Cromossomos Humanos Par 9 , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Mosaicismo , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
9.
Antiviral Res ; 159: 77-83, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30268911

RESUMO

The repurposing of drugs approved by the regulatory agencies for other indications is emerging as a valuable alternative for the development of new antimicrobial therapies, involving lower risks and costs than the de novo development of novel antimicrobial drugs. Adenovirus infections have showed a steady increment in recent years, with a high clinical impact in both immunosuppressed and immunocompetent patients. In this context, the lack of a specific drug to treat these infections supports the search for new therapeutic alternatives. In this study, we examined the anti-HAdV properties of mifepristone, a commercially available synthetic steroid drug. Mifepristone showed significant in vitro anti-HAdV activity at low micromolar concentrations with little cytotoxicity. Our mechanistic assays suggest that this drug could affect the microtubule transport, interfering with the entry of the virus into the nucleus and therefore inhibiting HAdV infection.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenovírus Humanos/efeitos dos fármacos , Antivirais/uso terapêutico , Reposicionamento de Medicamentos , Mifepristona/uso terapêutico , Células A549 , Animais , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL
11.
J Neonatal Perinatal Med ; 11(3): 335-338, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30010146

RESUMO

Neonatal adenovirus infection is infrequent, but in most cases the outcome of the infection is fatal. In this case report we describe the hospital course of a 3 day old newborn patient presenting with bloody stools and thrombocytopenia that remained clinically stable and had a benign course following Adenovirus 40/41 infection detected in stool. Neonatal adenovirus infection should be considered in the differential diagnosis of neonatal sepsis and pneumonia but also in patients that present with hematochezia, thrombocytopenia and/or other less specific signs and symptoms of viral illness.


Assuntos
Infecções por Adenoviridae/congênito , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Hemorragia Gastrointestinal/microbiologia , Gentamicinas/uso terapêutico , Trombocitopenia/microbiologia , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/microbiologia , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento
12.
Curr Opin Organ Transplant ; 23(4): 395-399, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29846196

RESUMO

PURPOSE OF REVIEW: Adenoviruses (AdVs) infection is a self-limited disease in the majority of immunocompetent children and adults, but can cause disseminated and life-threatening illness in immunocompromised hosts. This article will discuss therapeutic strategies for AdV infection in the pediatrics transplant recipient. RECENT FINDINGS: Currently, there is no FDA approved antiviral therapy for AdV infection. Accordingly, the primary initial therapy would be decreasing immunosuppression, whenever possible. Cidofovir (CDV) is an antiviral drug whose use has been associated with significant reductions of AdV viral load and, in some series improved survival in recipients of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). However, its use is also associated with significant toxicity. Brincidofovir (BCV) is a lipid formulation of CDV, which has an improved oral bioavailability and favorable toxicity profile compared with CDV. However, studies have only shown modest benefit from BCV for AdV disease or viremia. Immunotherapy is a growing field in the management of this virus infection on HSCT patients with promising results. SUMMARY: Current evidence support the use of CDV and BCV, as rescue therapy, on SOT and HSCT transplant patients. Immunotherapy had only been proven successful in HSCT patients, as an option for refractory cases or rescue therapy for AdV infection.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Órgãos/efeitos adversos , Infecções por Adenoviridae/imunologia , Criança , Cidofovir/uso terapêutico , Citosina/efeitos adversos , Citosina/análogos & derivados , Citosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Pediatria , Transplantados
13.
J Pediatr Hematol Oncol ; 40(6): e364-e368, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29846280

RESUMO

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenoviridae , Citosina/análogos & derivados , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Meduloblastoma/terapia , Organofosfonatos/efeitos adversos , Viremia/tratamento farmacológico , Infecções por Adenoviridae/patologia , Autoenxertos , Pré-Escolar , Colo/patologia , Colo/virologia , Citosina/administração & dosagem , Citosina/efeitos adversos , Humanos , Masculino , Meduloblastoma/patologia , Octreotida/administração & dosagem , Organofosfonatos/administração & dosagem , Viremia/patologia
14.
Turk Kardiyol Dern Ars ; 46(3): 231-233, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29664432

RESUMO

Presently described is a case of disseminated adenovirus infection in a heart-kidney transplant recipient that was successfully treated with cidofovir. There are several reports of adenovirus infections in adult solid organ transplant recipients and the prognosis is usually poor, with mortality rates of 40% to 60%. Severe disseminated adenovirus infections have been associated with increased risk of adverse transplant events, such as rejection, ventricular dysfunction, allograft vasculopathy, graft loss, and the need for re-transplantation. The patient's lack of clinical improvement, the onset of hemorrhagic cystitis and acute kidney injury were factors in our decision to temporarily discontinue administration of immunosuppressive agents and start an antiviral agent. It is important to suspect adenovirus in transplant patients when they do not respond to antibiotics and cultures are negative. Early diagnosis and treatment are critical to improving outcomes in immunocompromised patients.


Assuntos
Infecções por Adenoviridae , Transplante de Coração , Imunossupressores/efeitos adversos , Transplante de Rim , Adenoviridae , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/etiologia , Idoso , Antivirais/uso terapêutico , DNA Viral/sangue , Humanos , Rim/patologia , Masculino , Carga Viral
15.
Pediatrics ; 141(Suppl 5): S475-S480, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29610175

RESUMO

Two infants with disseminated adenoviral infections are described. Both these infants had a similar clinical course and were also diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH). Previous reports of immunocompromised adults with adenovirus-associated HLH are in the literature; however, this is the first report that we are aware of with this pathology occurring in infants. These cases are used to demonstrate the importance of thinking about HLH in patients who are diagnosed with adenovirus and exhibit prolonged fevers that are unresponsive to antimicrobial agents with hepatosplenomegaly and cytopenias.


Assuntos
Infecções por Adenoviridae/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/imunologia , Antivirais/uso terapêutico , Cidofovir/uso terapêutico , Dexametasona/análogos & derivados , Dexametasona/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/imunologia , Metilprednisolona/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia
16.
Pharmacotherapy ; 38(4): 470-475, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29457839

RESUMO

BACKGROUND: Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or U.S. Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. AIMS: We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy. RESULTS: The first patient was a 44-year-old woman who developed adenoviral enteritis 1 month after transplantation, which resolved with ribavirin therapy. Two weeks later, the infection recurred, and brincidofovir was initiated. While receiving this therapy for 3 months, she developed severe acute rejection, which was managed with rabbit antithymocyte globulin followed by infliximab. Eventually, complete resolution of the rejection and adenoviral enteritis was achieved. At 12 months posttransplantation, the patient was healthy and tolerating enteral feeding. The second patient was a 28-year-old man who had undergone isolated intestinal transplantation 6 years before he presented with generalized weakness and an increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance immunosuppression was reduced, and brincidofovir was started. The infection resolved with a month of therapy. Six months after the infection, he was healthy and tolerating enteral feeding. CONCLUSION: This is the first publication, to our knowledge, to describe two cases in which brincidofovir was used to successfully treat adenovirus infection in intestinal transplant recipients. Thus, these cases demonstrate that brincidofovir appears to be a safe and effective option in the management of adenoviral enteritis in these patients.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/uso terapêutico , Citosina/análogos & derivados , Hospedeiro Imunocomprometido , Organofosfonatos/uso terapêutico , Transplantados , Adulto , Citosina/uso terapêutico , Feminino , Humanos , Masculino , Terapia de Salvação
17.
Antiviral Res ; 152: 84-93, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29421320

RESUMO

Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus-host interactions, and several key host molecules involved in the HAdV infection process were identified. The RARß (retinoic acid receptor ß) molecule, one of the upstream regulatory factors of differentially expressed genes (DEGs), played important roles in HAdV replication. The results of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that RARß mRNA and protein were downregulated by HAdV infection in the A549 cells. The knockdown of RARß by RARß siRNA increased the HAdV production and the overexpression of RARß decreased the HAdV production. Furthermore, FDA-approved Tazarotene, which is an RAR selective agonist with relatively more selectivity for RARß, was found to inhibit HAdV replication in vitro. Taken together, our study presents a key host molecule in adenovirus infection, which could be developed as a potential host target to an anti-adenovirus drug. In addition, this study provides evidence for the re-exploitation of an FDA-approved small molecule for therapeutic applications in adenovirus replication.


Assuntos
Infecções por Adenoviridae/metabolismo , Adenovírus Humanos/fisiologia , Receptores do Ácido Retinoico/metabolismo , Replicação Viral/efeitos dos fármacos , Células A549 , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/virologia , Adenovírus Humanos/efeitos dos fármacos , Adenovírus Humanos/genética , Antivirais/farmacologia , Regulação para Baixo/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/genética
19.
Cutan Ocul Toxicol ; 37(1): 15-18, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28393562

RESUMO

PURPOSE: To evaluate the results of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP) in infants with active adenoviral keratoconjunctivitis (AKC). MATERIAL AND METHODS: A retrospective analysis was performed using the medical records of all infants treated with intravitreal injections of anti-VEGF agents during an AKC outbreak previously reported in the literature at a tertiary center for treatment of ROP. The infants were divided into two groups. Group 1 included nine infants (18 eyes) with AKC, while Group 2 included 13 infants (26 eyes) without AKC. RESULTS: During the AKC outbreak, 22 infants were treated with anti-VEGF agents for treatment-requiring ROP. In all patients in both groups, the ROP and plus disease displayed a significant regression within 2 days after the intravitreal injections. Moreover, no serious complications such as endophthalmitis, retinal detachment, cataract or intravitreal hemorrhage were observed after the treatment and there were no statistically significant differences between the groups in terms of postoperative complications. CONCLUSION: Immediate and appropriate intervention is very important in cases of treatment-requiring ROP otherwise it can result in blindness. However, laser treatment for ROP is technically difficult in infants with active AKC. The results of this study showed that favorable outcomes without serious ocular complications could be obtained via intravitreal injections of anti-VEGF agents in infants with active AKC.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Ceratoconjuntivite/tratamento farmacológico , Retinopatia da Prematuridade/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Feminino , Humanos , Lactente , Recém-Nascido , Injeções Intravítreas , Masculino
20.
J Clin Virol ; 96: 73-79, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29017084

RESUMO

BACKGROUND: Adenovirus infection is a recognized complication following haematopoietic stem cell transplantation. We present a review of our experience of these infections in our transplant cohort over 10 years including 3 patients treated with the novel antiviral brincidofovir. OBJECTIVES: We aimed to describe the presentation, response to treatment and outcomes of adult stem cell transplant patients with disseminated adenovirus infection. STUDY DESIGN: All adult cases of disseminated adenovirus infection following haematopoietic stem cell transplant in our unit between 2005 and 2015 were identified. Transplant details and data on timing of diagnosis, course of infection, viral co-infection and treatment were collected. RESULTS: Of 733 patients transplanted, 10 patients had disseminated infection, including 4 male and 6 female patients with median age of 36.5 (range 19-59) years. 6/10 received an allograft from an unrelated donor. Median post-transplant time to detection of viraemia was 67days (range 20-1140days). Median peak viral load was 3133 copies/ml (352-11,000,000) in survivors received cidofovir alone, one cidofovir then brincidofovir and two brincidofovir alone. 8/10 p and 1,580,000 copies/ml (41,999-3,000.000) in those who died. Five patientsatients had a decrease in viral load following antivirals and/or reduction in immunosuppression including all on brincidofovir. Three died on treatment. CONCLUSIONS: Disseminated adenovirus infection is uncommon in adult transplant patients and uncertainties remain surrounding effective treatment. In our cohort, brincidofovir has shown promise in treatment of adenoviral infection. However, randomized controlled studies are required to confirm this impression.


Assuntos
Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/tratamento farmacológico , Antivirais/uso terapêutico , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Organofosfonatos/uso terapêutico , Transplante Homólogo/efeitos adversos , Infecções por Adenoviridae/patologia , Adulto , Estudos de Coortes , Citosina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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