Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.382
Filtrar
1.
Comput Biol Med ; 175: 108529, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718667

RESUMO

Many health challenges are attributed to viral infections, which represent significant concerns in public health. Among these infections, diseases such as herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) infections have garnered attention due to their prevalence and impact on human health. There are specific antiviral medications available for the treatment of these viral infections. Drugs like Cidofovir, Valacyclovir, and Acyclovir are commonly prescribed. These antiviral drugs are known for their efficacy against herpesviruses and related viral infections, leveraging their ability to inhibit viral DNA polymerase. A molecular descriptor is a numerical value that correlates with specific physicochemical properties of a molecular graph. This article explores the calculation of distance-based topological descriptors, including the Trinajstic, Mostar, Szeged, and PI descriptors for the aforementioned antiviral drugs. These descriptors provide insights into these drugs' structural and physicochemical characteristics, aiding in understanding their mechanism of action and the development of new therapeutic agents.


Assuntos
Antivirais , Antivirais/uso terapêutico , Antivirais/química , Antivirais/farmacologia , Humanos , Aciclovir/uso terapêutico , Aciclovir/química , Aciclovir/farmacologia , Biologia Computacional/métodos , Cidofovir/uso terapêutico , Cidofovir/química , Citosina/análogos & derivados , Citosina/uso terapêutico , Citosina/química , Valaciclovir/uso terapêutico
2.
J Dermatolog Treat ; 35(1): 2328180, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38493799

RESUMO

Purpose: Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition which presents with widespread asymptomatic or pruritic, skin-colored papules with white protruding keratin spiculations in immunocompromised individuals. Due to its rarity, there is little data to guide treatment decisions. The purpose of this article is to report a case of TS that completely resolved after treatment with topical cidofovir.Materials and methods: A 19-year-old immunosuppressed female presented with widespread painful, itchy bumps on the nose and face. Upon examination, there were erythematous papules with hyperkeratinized spicules affecting the central face. Biopsy of the lesions was consistent with TS which was confirmed via PCR analysis. The tenderness of this patient's eruption was highly atypical for TS. Once daily topical application of compounded 1% cidofovir cream was prescribed.Results: The patient's symptoms resolved completely after 4 weeks of therapy with topical cidofovir 1% cream, without reduction of immunosuppression.Conclusions: Topical cidofovir 1% cream may be a valuable treatment for this rare disease.


Assuntos
Infecções por Polyomavirus , Dermatopatias , Feminino , Humanos , Adulto Jovem , Cidofovir/uso terapêutico , Hospedeiro Imunocomprometido , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/terapia , Prurido , Dermatopatias/patologia
3.
Eur J Obstet Gynecol Reprod Biol ; 296: 131-139, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432019

RESUMO

OBJECTIVE: The present study aims to evaluate the efficacy and effect of localized delivery of drugs in the treatment of high-grade squamous intraepithelial lesion (HSIL) based on a meta-analysis. STUDY DESIGN: Databases including Cochrane Library, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from their inception till August 2022. Randomized controlled trials (RCTs) that compared the efficacy of drugs and surgery in the treatment of HSIL were collected. A meta-analysis was performed using the software of Review Manager (version 5.4.1). RESULTS: Eight RCTs involving 523 patients were included in the meta-analysis. For HSIL, the rate of cervical lesions histological regression was 69.85 % in the surgery group and 59.88 % in the drug group, there was no significant difference between the two groups [OR = 0.45, 95 % CI (0.07, 3.03), P = 0.41]. The histological regression rate of cervical lesions in the placebo group was 37.76 %, and the difference between the drug group and the placebo group was statistically significant [OR = 4.94, 95 % CI (2.65, 9.20), P < 0.00001]. CONCLUSION: A total of four drugs were involved in the eight RCTS included in this study, which were imiquimod, 5-fluorouracil (5-FU), cidofovir and interferon. The results showed that although drug administration was effective in the histological regression of HSIL, the efficacy was less than about 10% of surgical treatment. Considering the recurrence of the disease after surgery and the problems of abortion, premature delivery and premature rupture of membranes after cervical conization in reproductive women, drug therapy can be used as a supplement to surgery or conservative treatment to promote the histological regression of cervical lesions in patients with HSIL.


Assuntos
Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Doenças do Colo do Útero , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Preparações Farmacêuticas , Displasia do Colo do Útero/patologia , Imiquimode , Cidofovir , Neoplasias do Colo do Útero/patologia
4.
Iran J Med Sci ; 49(1): 1-9, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38322157

RESUMO

Monkeypox is an infectious and contagious zoonotic disease caused by the Orthopoxvirus species and was first identified in Africa. Recently, this infectious disease has spread widely in many parts of the world. Fever, fatigue, headache, and rash are common symptoms of monkeypox. The presence of lymphadenopathy is another prominent and key symptom of monkeypox, which distinguishes this disease from other diseases and is useful for diagnosing the disease. This disease is transmitted to humans through contact with or eating infected animals as well as objects infected with the virus. One of the ways to diagnose this disease is through PCR testing of lesions and secretions. To prevent the disease, vaccines such as JYNNEOS and ACAM2000 are available, but they are not accessible to all people in the world, and their effectiveness and safety need further investigation. However, preventive measures such as avoiding contact with people infected with the virus and using appropriate personal protective equipment are mandatory. The disease therapy is based on medicines such as brincidofovir, cidofovir, and Vaccinia Immune Globulin Intravenous. The injectable format of tecovirimat was approved recently, in May 2022. Considering the importance of clinical care in this disease, awareness about the side effects of medicines, nutrition, care for conjunctivitis, skin rash, washing and bathing at home, and so on can be useful in controlling and managing the disease.


Assuntos
Exantema , Mpox , Humanos , Animais , Administração Intravenosa , África , Benzamidas , Cidofovir
6.
Saudi Med J ; 45(2): 205-210, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309731

RESUMO

OBJECTIVES: To study the clinical evaluation of recurrent respiratory papillomatosis (RRP) patients and the factors associated with the improvement in the Derkay's score as a measure of disease severity. METHODS: A retrospective cohort that included all juvenile RRP patients who were admitted to King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between September 2015 and June 2022 and underwent surgical debulking. RESULTS: A total of 16 patients were eligible to join our study. Among them, 7 patients were males. Hoarseness of voice was the most frequent symptom. The median period of the follow-up was 56 months. Complete remission was achieved in 31.3%. The univariate linear regression model revealed that the cidofovir-treated patients had a significant reduction in the change value of Derkay's score compared to those without treatment (regression coefficient= -5.83, 95% confidence interval [CI]: [-11.5 to -0.143], p=0.045). Also, the increased first Derkay's score decreased the change value and subsequently increased the improvement chance of the disease (regression coefficient= -0.424, 95% CI: [-0.764 to -0.083], p=0.018). However, in the multivariate regression model, both variables showed non-significant results. CONCLUSION: cidofovir treatment and higher Derkay's scores affected the disease improvement.


Assuntos
Organofosfonatos , Infecções por Papillomavirus , Infecções Respiratórias , Masculino , Criança , Humanos , Feminino , Cidofovir/uso terapêutico , Arábia Saudita/epidemiologia , Organofosfonatos/uso terapêutico , Citosina/uso terapêutico , Estudos Longitudinais , Estudos Retrospectivos , Centros de Atenção Terciária , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico
7.
Antiviral Res ; 222: 105799, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38190973

RESUMO

Adenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. Presently, there is no drug specifically approved for the treatment of adenovirus infections by the FDA. The state-of-the-art treatment of such infections is the off-label use of cidofovir, an acyclic nucleotide phosphonate. While cidofovir inhibits adenovirus replication, it has dose-limiting kidney toxicity. There is an apparent need for a better compound to treat adenovirus infections. To this end, we have been developing acyclic nucleotide phosphonate prodrugs that utilize an amino acid scaffold equipped with a lipophilic modifier. Here, we compare the antiviral potential of two prodrugs of HPMPA that differ only in the amino acid-based promoiety: USC-087, based on an N-hexadecyl tyrosinamide, and USC-093, based on an N-hexadecyl serinamide. Oral administration of both compounds was very efficacious against disseminated HAdV-C6 infection in immunosuppressed Syrian hamsters, suppressing virus replication and mitigating pathology even when treatment was withheld until 4 days after challenge. We saw only marginal efficacy after respiratory infection of hamsters, which may reflect suboptimal distribution to the lung. Importantly, neither compound induced intestinal toxicity, which was observed as the major adverse effect in clinical trials of brincidofovir, a prodrug of cidofovir which also contains a C-16 modifier. Notably, we found that there was a significant difference in the nephrotoxicity of the two compounds: USC-087 caused significant kidney toxicity while USC-093 did not, at effective doses. These findings will be valuable guidepoints in the future evolution of this new class of potential prodrugs to treat adenovirus infections.


Assuntos
Adenina/análogos & derivados , Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Organofosfonatos , Pró-Fármacos , Tirosina/análogos & derivados , Cricetinae , Animais , Humanos , Infecções por Adenovirus Humanos/tratamento farmacológico , Cidofovir/farmacologia , Cidofovir/uso terapêutico , Mesocricetus , Antivirais/uso terapêutico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Adenoviridae , Replicação Viral , Organofosfonatos/farmacologia , Organofosfonatos/uso terapêutico , Infecções por Adenoviridae/tratamento farmacológico , Citosina/farmacologia , Citosina/uso terapêutico , Aminoácidos/farmacologia , Nucleotídeos/uso terapêutico
8.
Viruses ; 16(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257837

RESUMO

A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient's HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant.


Assuntos
Infecções por Adenoviridae , Transtornos Linfoproliferativos , Pré-Escolar , Humanos , Masculino , Adenoviridae , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/tratamento farmacológico , Cidofovir/uso terapêutico , Genótipo , Transplante de Células-Tronco
9.
Ann Pharmacother ; 58(3): 286-304, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37272472

RESUMO

OBJECTIVE: To describe the use of cidofovir (CDV) for viral infections in immunocompromised children (IC) and provide guidance on dosing and supportive care. DATA SOURCES: A PubMed search was conducted for literature published between 1997 and January 2022 using the following terms: cidofovir, plus children or pediatrics. STUDY SELECTION AND DATA EXTRACTION: Limits were set to include human subjects less than 24 years of age receiving intravenous (IV) or intrabladder CDV for treatment of infections due to adenovirus, polyomavirus-BK (BKV), herpesviruses, or cytomegalovirus. DATA SYNTHESIS: Data were heterogeneous, with largely uncontrolled studies. Conventional dosing (CDV 5 mg/kg/dose weekly) was commonly used in 60% (31/52) of studies and modified dosing (CDV 1 mg/kg/dose 3 times/week) was used in 17% (9/52) of studies, despite being off-label. Nephrotoxicity reported across studies totaled 16% (65/403 patients), which was higher for conventional dosing 29 of 196 patients (15%) than modified dosing 1 of 27 patients (4%). Saline hyperhydration and concomitant probenecid remain the cornerstones of supportive care, while some regimens omitting probenecid are emerging to target BKV. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: To our knowledge, this is the first comprehensive review of CDV use (indications, dosing, supportive care, response, and nephrotoxicity) in pediatric IC. CONCLUSIONS: Effective utilization of CDV in IC remains challenging. Further prospective studies are needed to determine the optimal CDV dosing; however, less aggressive dosing regimens such as modified thrice weekly dosing or low dosing once weekly omitting probenecid to enhance urinary penetration may be reasonable alternatives to conventional dosing in some IC.


Assuntos
Organofosfonatos , Viroses , Humanos , Criança , Cidofovir/efeitos adversos , Antivirais/uso terapêutico , Probenecid , Organofosfonatos/uso terapêutico , Citosina/efeitos adversos , Viroses/tratamento farmacológico
10.
Indian J Pediatr ; 91(4): 398-400, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37620591

RESUMO

The authors present a 16-mo-old boy with flu like symptoms, not responding to supportive management and progressed to severe hypoxemic pneumonia. Adenovirus was detected in the nasopharyngeal aspirate. He showed rapid improvement after intravenous cidofovir administration.


Assuntos
Infecções por Adenoviridae , Organofosfonatos , Pneumonia Viral , Masculino , Humanos , Cidofovir/uso terapêutico , Antivirais/uso terapêutico , Organofosfonatos/uso terapêutico , Citosina/uso terapêutico , Infecções por Adenoviridae/diagnóstico
11.
Curr Pharm Biotechnol ; 25(4): 411-425, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37711132

RESUMO

Monkeypox is a disease caused by the monkeypox virus, which is a type of orthopox virus that comes from the virus family Poxviridae. Its first case reported in animals and humans was in 1958 and 1970, respectively. It is a viral zoonosis disease with two modes of transmission: animal to human (via direct contact or eating the meat of an infected animal) and human to human (via contact or contact with skin lesions, body fluids, and infected person's contaminated objects). The literature depicts that monkeypox is less contagious among individuals in contrast to smallpox; the infection chain of monkeypox is nearly five to six patients approximately. It has two clades, the West African and the Central African (the Congo basin). The Congo basin subgroup of monkeypox is highly transmissible and severe. The symptoms of monkeypox include fever, lethargy, headache, lymphadenopathy, myalgia, myodynia, fainting, shivers, backache, and rashes on the face and extremities. The most common symptom of monkeypox is lymphatic hyperplasia or, lymph adenopathy or swollen lymph nodes. It is proven to be very useful in the diagnosis of monkeypox. The antiviral drugs that are used for its treatment are tecovirimat, brincidofovir and cidofovir. Tecovirimat has fewer side effects and it shows better therapeutic action in comparison to brincidofovir and cidofovir. For the prevention of monkeypox, the Center for Disease Control and Prevention recommends the administration of the same vaccine used for smallpox named INVAMUNE, which is currently in its third generation. Its first and second generations have adverse side effects in patients having HIV or atopic dermatitis.


Assuntos
Citosina/análogos & derivados , Mpox , Organofosfonatos , Varíola , Vírus da Varíola , Animais , Humanos , Mpox/diagnóstico , Mpox/tratamento farmacológico , Cidofovir
12.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2055-2065, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37837475

RESUMO

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.


Assuntos
Citosina/análogos & derivados , Mpox , Organofosfonatos , Humanos , Cidofovir , Benzamidas
14.
Pediatr Infect Dis J ; 43(3): 198-202, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38011019

RESUMO

BACKGROUND: Cidofovir (CDV), a nucleoside phosphonate analogue, exhibits activity against severe cytomegalovirus and adenoviral (ADV) infection. Nevertheless, reports of elevated nephrotoxicity rates limited its use to highly vulnerable cases, mainly immunocompromised children with fulminant infection. Limited data exists regarding CDV safety in immunocompetent children. OBJECTIVE: To evaluate CDV-related toxicity, mainly nephrotoxicity, in immunocompetent children with severe ADV/cytomegalovirus infection. METHODS: We conducted a retrospective review of medical records for all immunocompetent children under 18 years of age treated with intravenous CDV from January 2005 to December 2019. RESULTS: Among the 23 patients identified, 21 were diagnosed with severe ADV infection. Median age was 15 months. Twenty-one (91%) children were admitted to the pediatric intensive care unit. Eighteen patients (78%) received standard CDV protocol (5 mg/kg CDV weekly for 2 weeks), 4 (17%) according to nephroprotective low-dose protocol and 1 patient transitioned. The median duration of CDV treatment was 14 days (range: 1-21 days). All patients received hyperhydration and probenecid with each infusion. Acute kidney injury was recorded in 1 patient (with concurrent septic shock) during CDV treatment. Two children exhibited acute kidney injury before CDV initiation, but renal function normalized during CDV treatment. One patient developed transient neutropenia (600 cells/L), apparently as a result of sepsis. No other major adverse effects were noted. Mortality rate was 3/23 (13%), unrelated to CDV toxicity. CONCLUSIONS: Our findings suggest that CDV-related nephrotoxicity rate in immunocompetent children may be lower than previously reported, perhaps lower than in the severely immunocompromised population.


Assuntos
Injúria Renal Aguda , Infecções por Adenoviridae , Infecções por Citomegalovirus , Infecções Oportunistas , Humanos , Criança , Adolescente , Lactente , Cidofovir/efeitos adversos , Antivirais/efeitos adversos , Citosina/efeitos adversos , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente
15.
Eur Arch Otorhinolaryngol ; 281(2): 601-627, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37831132

RESUMO

BACKGROUND: Specific HPV types cause recurrent respiratory papillomatosis (R.R.P.). When administered intralesionally, cidofovir, an antiviral agent, has shown favorable outcomes in reducing papilloma. Bevacizumab, an angiogenesis inhibitor, has demonstrated improved R.R.P. However, both treatments lack FDA approval for R.R.P. Our study aims to evaluate the efficacy and safety of intralesional Cidofovir and Bevacizumab for R.R.P. and compare the two interventions. METHODS: We searched five electronic databases to find relevant studies. After the screening, data were extracted from the included studies. Pooled ratios with 95% confidence intervals (CIs) were used for categorical outcomes, and mean difference (MD) was used for continuous outcomes. Statistical heterogeneity was evaluated using the chi-squared test for I2 statistics. The Cochrane Risk of Bias assessment tool was used to assess the methodological quality of randomized controlled trials (RCTs), while the National Institutes of Health's tool was used for observational studies. Analysis was done by Review Manager software. RESULTS: In our comprehensive meta-analysis of 35 articles involving 836 patients, cidofovir demonstrated an overall remission ratio of (0.90 [95% CI: 0.83, 0.98], p = 0.01), while bevacizumab (0.92 [95% CI: 0.79, 1.07]), p = 0.3). The complete remission ratio for cidofovir was (0.66 [95% CI: 0.57, 0.75], p > 0.0001), while bevacizumab was (0.29 [95% CI: 0.12, 0.71], p = 0.07). In partial remission, Bevacizumab showed a higher ratio than Cidofovir 0.74 [0.55, 0.99] vs. 0.40 [0.30, 0.54]. Bevacizumab had a pooled ratio of 0.07 [95% CI: 0.02, 0.30] in terms of no remission, indicating better outcomes compared to Cidofovir with a ratio of 0.28 [95% CI: 0.16, 0.51]. Additionally, Cidofovir showed a favorable decrease in the Derkay Severity Score (DSS) with a mean difference (MD) of 1.98 [95% CI: 1.44, 2.52]. CONCLUSION: Cidofovir had a higher impact on complete remission compared to Bevacizumab. Both showed partial remission, with Bevacizumab having a higher ratio. Moreover, Cidofovir showed a significant decrease in DSS. Bevacizumab had lower rates of no remission and recurrence and fewer adverse events compared to Cidofovir. However, the difference between the two treatments was not significant, except for partial remission.


Assuntos
Infecções por Papillomavirus , Infecções Respiratórias , Humanos , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/uso terapêutico , Cidofovir/uso terapêutico , Injeções Intralesionais , Infecções por Papillomavirus/tratamento farmacológico
16.
Pharmacol Res Perspect ; 12(1): e01164, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38149674

RESUMO

Monkeypox (mpox), a virus belonging to the orthopoxvirus family, can cause a zoonotic infectious disease with morbidity and cosmetic complications. Therefore, effective antiviral drugs with appropriate safety profiles are important for the treatment of patients with mpox. To date, there is no FDA-approved drug for the treatment of mpox. However, tecovirimat, brincidofovir, and cidofovir are the candidate therapies for the management of mpox. Given the safety concerns following the use of these medications, we aimed to review evidence on the clinical considerations of mpox antiviral medications that will be useful to guide clinicians in the treatment approach. Based on the current evidence, tecovirimat has favorable clinical efficacy, safety, and side effect profile and it can be considered as first-line treatment for mpox.


Assuntos
Mpox , Humanos , Mpox/tratamento farmacológico , Antivirais/efeitos adversos , Cidofovir , Benzamidas , Isoindóis
17.
Exp Clin Transplant ; 22(1): 29-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38149668

RESUMO

OBJECTIVES: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. MATERIALS AND METHODS: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. RESULTS: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. CONCLUSIONS: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.


Assuntos
Vírus BK , Nefropatias , Transplante de Rim , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Masculino , Criança , Feminino , Leflunomida/efeitos adversos , Cidofovir/efeitos adversos , Transplante de Rim/efeitos adversos , Viremia/diagnóstico , Estudos Retrospectivos , Creatinina , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/tratamento farmacológico , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/cirurgia , Nefrite Intersticial/complicações , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/tratamento farmacológico , Transplantados
18.
Transpl Immunol ; 81: 101953, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37931665

RESUMO

BACKGROUND: The selection of antiviral therapy for BK polyomavirus (BKPyV) infection has been extensively debated. Our study aimed to assess the efficacy and safety of various treatments for BKPyV infection. METHODS: We searched PubMed, EMBASE, and Web of Science databases for relevant studies regarding drug treatments for BKPyV viremia/DNAemia published between January 1, 1970 and September 30, 2022. Two independent authors screened the published studies, extracted pertinent data, and evaluated their methodological quality. A meta-analysis was performed using the RevMan software version 4.2.2. RESULTS: A total of 33 published studies involving 986 patients were included in the meta-analysis. Overall, therapeutic interventions comprised immunosuppression reduction alone or in combination with leflunomide, intravenous immunoglobulin (IVIG), cidofovir, or mTOR inhibitor (mTORi) therapy. The meta-analysis revealed that the efficacy of immunosuppression reduction alone for serum BKPyV clearance was 68% (95% confidence interval [CI]: 0.58-0.77; I2 = 78%). Moreover, the efficacy of immunosuppression reduction in combination with leflunomide, cidofovir, IVIG, or mTORi therapy for serum BKPyV clearance was 61% (95% CI: 0.47-0.74; I2 = 83%), 71% (95% CI: 0.63-0.78; I2 = 0), 87% (95% CI: 0.82-0.93; I2 = 45%), and 80% (95% CI: 0.59-1.00; I2 = 58%), respectively. Compared to immunosuppression reduction alone, immunosuppression reduction combined with IVIG therapy offered a statistically significant benefit in serum BKPyV clearance (P < 0.01) with minimal adverse reactions, whereas other adjunctive drug treatments did not demonstrate considerable effects. CONCLUSIONS: Reducing immunosuppression remains the primary approach for treating BKPyV infection. Although the combination treatment with IVIG proved to be most effective, other agents might offer varied antiviral advantages of high heterogeneity, which should be substantiated in future long-term randomized controlled trials.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Cidofovir/farmacologia , Cidofovir/uso terapêutico , Leflunomida/uso terapêutico , Leflunomida/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Transplantados
19.
Transpl Infect Dis ; 25 Suppl 1: e14173, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37846850

RESUMO

Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III-IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥102-3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virus-specific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.


Assuntos
Infecções por Adenoviridae , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Cidofovir , Estudos Prospectivos , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/epidemiologia , Fatores de Risco , Fatores Imunológicos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
20.
Curr Drug Targets ; 24(13): 1032-1045, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842888

RESUMO

BACKGROUND: There have been several neglected infectious pathogens that have reemerged in the last few decades, including the monkeypox virus, a virus from the orthopoxviral genus that causes monkeypox and is transmitted between animals and humans. The human monkeypox outbreak has spread to several different countries. Because of the outbreak's unusually high case count and lack of connections to endemic nations, there are concerns that the monkeypox transmission pattern may have changed. OBJECTIVE: The current study aimed to provide recent advancements in the prevention and management of the monkeypox virus in humans. METHODOLOGY: We have highlighted recent advancements in the prevention and management of the monkeypox virus in humans in this work. RESULTS: For the treatment and prevention of monkeypox, new medications and vaccinations are being used, and more study is needed to understand the epidemiology, biology, and ecology of the virus in endemic regions and stop future global outbreaks. Vaccines available in the market for the treatment of viruses are JYNEOS and ACAM2000. Some of the antiviral drugs, such as tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin, are used for the treatment of the monkeypox virus. Some of the vaccines, such as NIOCH-14, Cidofovir, CMX-001, and ST-246, are currently in clinical trials. CONCLUSION: We have, herein, covered features of monkeypox viral biology that are important for risk assessment and getting ready for an outbreak of the monkeypox virus, with a focus on recent advances in knowledge of the virus's host range, evolutionary potential, and potential targets for neutralization.


Assuntos
Mpox , Vacinas , Animais , Humanos , Monkeypox virus , Mpox/tratamento farmacológico , Mpox/epidemiologia , Mpox/prevenção & controle , Cidofovir , Antivirais/farmacologia , Antivirais/uso terapêutico , Benzamidas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA