Prevenção de doenças víricas, vacinas e drogas antivirais. D.J. Wise and G.R. Carter, (Translated: Nov; Last updated: Mar). In: A Concise. A profilaxia com drogas antivirais reduz a citomegalovirose e a mortalidade associada ao CMV em pacientes que receberam transplante de órgãos sólidos. b Laboratório Experimental de Drogas Antivirais e Citotóxicas, Instituto de Microbiologia Professor Paulo de Góes, UFRJ,. , Ilha do Fundão, Rio de.
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BK polyomavirus BKPyV is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid antiviraus progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months.
The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits.
Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review. BK polyomavirus BKPyV belongs to the family Polyomaviridae former Papovaviridae and are small nmnonenveloped virus with an icosahedral capsid and a core of circular double-stranded DNA in association drobas histones. The geographic distribution of the subtypes antiviraiss a close relationship between BKPyV and migration of human populations, although without any apparent clinical significance.
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BKPyV is ubiquitous in human population. Primary infection in healthy children is usually asymptomatic, but may manifest as a common cold. Replication of BKPyV occurs during states of immune suppression. Viruria occurs in pregnancy, cancer, HIV infection, diabetes, and transplantation.
BKPyV infections in immunosuppressed individuals can lead to distinctive pathological entities in different patient groups: BKVN is the result of viral replication dtogas renal tissue, and is characterized by a histologically manifest renal allograft infection with BKPyV and deteriorating graft function. The gold standard for BKVN is still a renal biopsy. In addition, BKPyV is also possibly related antivirsis pneumonia, encephalitis and several types of cancer. The methods used to detect and quantify BKPyV are based on the pathogenesis of the infection.
The onset for each event is variable: In general, viruria-based methods are considered valuable tools for BKPyV screening high negative predictive value, NPV but weakly indicative of kidney or urinary tract diseases low positive predictive value, PPVsince less than a half of all patients with viruria will progress to the viremia stage. Decoy cells are epithelial cells with enlarged nuclei and large basophilic ground-glass intranuclear inclusions. Electronic microscopy methods are based on the detection of viral particles or “Haufen”, defined qntivirais discrete, tightly clustered, cast-like aggregates of a minimum of six polyomaviruses with an unequivocal three-dimensional architecture.
In addition, BKVN with detectable viruria without viremia has been reported. Given its overall performance, BKPyV viremia testing without urine became the method drogzs choice in many diagnostic centers and also recommended by the KDIGO Transplant Work Group in31 although viruria screening prior to viremia quantitation is considered cost-saving. However, due to the precocity of BKPyV viremia in most cases, the tendency has been driven for condensed screening in the first months. Current screening strategies relies on two basic principles: Despite methodological variations, both strategies showed to be droyas effective in detecting BKPyV infection, allowing for timely intervention.
As previously mentioned, viruria can be assessed drigas electronic microscopy, decoy cytology drovas qPCR.
However, performing these techniques simultaneously seems do not add useful clinical information. After, it will be performed monthly until the sixth month. Then, every 2 or 3 months until 2 years post-transplant, and anytime during any allograft dysfunction. Quantitative measurement of viremia is not indicated in patients without viruria. In both cases immunosuppression reduction is recommended even in the absence of BKPyV in biopsy see ref. Currently, reduction of immunossupression is the keystone of therapy for BKVN.
Since late diagnosis of BKVN is usually associated with an irreversible decline of graft function anrivirais33 and most of patients with viremia will eventually develop BKVN, regular screening for BKPyV reactivation, mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is the usual procedure adopted by transplant centers. When viremia is detected, a graft biopsy is usually indicated before reducing immunossupression, mainly in case of renal function deterioration, to distinct BKVN from rejection.
Even if kidney function is unchanged, biopsy should be considered for those patients at a higher immunological risk in order to exclude a sub-clinical rejection episode.
There is no clear evidence to support any specific modification of the immunosuppressive therapy. However, in vitro analyses suggest that reduction or withdrawn of calcineurin inhibitors should be the first step in immunossupression modification due to its effects on T cells.
After reduction of immunossupression, renal function should be closely monitored due to the risk of rejection. While reducing immunosuppression is a logical first line therapy, a second line option is not well defined.
For these patients who fail to decrease viremia after reduction of immunossupression, the use of immunoglobulin, cidofovir and fluoroquinolone has been attempted despite unclear benefits. Among those options, the use of fluoroquinolones was more extensively studied. In vitro analyses have shown that fluoroquinolones could have antiviral properties by inhibiting BKV replication.
Benefits of ciclofovir in patients with BKVN were described only in small non-controlled studies. Thus, it is expected that immunoglobulin contains antibodies against this virus. The use of immunoglobulin seems especially attracting when the diagnosis of allograft rejection cannot be ruled out. In this case, the use of massive dose of immunoglobulin could be useful for both rejection and BKVN.
However, there is a paucity of studies addressing the use of immunoglobulin in the treatment BKVN 43 – 45 and randomized clinical trials are needed. Repeat transplantation is a feasible option after graft loss due to BKVN.
A study of patients who underwent repeat kidney transplantation after graft loss due to BKVN showed a 3-year graft survival rate of Viremia clearance after BKVN in the initial transplant was significantly associated with a lower risk of recurrence after repeat transplantation.
The advent of newer, more potent immunosuppressive agents may contribute to an apparently increasing incidence of BKVN in kidney transplant recipients. The optimal screening method and timing to detect BKPyV remains to be determined and cutoff values, especially for quantitative tests, need to be defined and standardized.
Currently, early diagnosis and reduction of immunosupression therapy seems to be the most srogas treatment for BKPyV infection. BK polyomavirus in Kidney transplant recipients: BKPyV events following renal transplantation. Cell Mol Life Sci ; Phylogenetics, evolution, and medical importance of polyomaviruses. Infect Genet Evol ;9: BK virus infection in transplant recipients: Neth J Med ; Evolution of the BK polyomavirus: Rev Med Virol ; J Gen Virol ; The rapidly expanding family antuvirais human polyomaviruses: J Med Virol ; The role of polyomaviruses in human disease.
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Patholog Res Int ; A cornucopia of human polyomaviruses. Nat Rev Microbiol ; Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy based on prospective monitoring of BK viremia: Detection of polyomavirus Antigirais reactivation after renal transplantation using an intensive decoy cell surveillance program is cost-effective.
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In vitro anti-HMPV activity of meroditerpenoids from marine alga Stypopodium zonale (Dictyotales).
Cost-efficient screening for BK virus in pediatric kidney transplantation: Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients. Transpl Infect Dis ; Histologic versus molecular diagnosis of BK polyomavirus-associated nephropathy: Clin J Am Soc Nephrol ;1: BK polyomavirus in solid organ transplantation. Am J Transplant ; Presence of urinary Haufen accurately predicts polyomavirus nephropathy.
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