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儿科移植受者中的腺病毒感染:有效的抗病毒药物即将问世吗?

Adenovirus infection in pediatric transplant recipients: are effective antiviral agents coming our way?

作者信息

Lopez Santiago M C, Michaels Marian G, Green Michael

机构信息

Division of Infectious Diseases, Children's Hospital of Pittsburgh of UPMC.

Pediatrics/Surgery and Thomas E. Starlz Transplant Institute, University of Pittsburgh, Pennsylvania, USA.

出版信息

Curr Opin Organ Transplant. 2018 Aug;23(4):395-399. doi: 10.1097/MOT.0000000000000542.

Abstract

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.

摘要

综述目的

腺病毒(AdV)感染在大多数免疫功能正常的儿童和成人中是一种自限性疾病,但在免疫功能低下的宿主中可导致播散性和危及生命的疾病。本文将讨论儿科移植受者腺病毒感染的治疗策略。

最新发现

目前,尚无FDA批准的用于腺病毒感染的抗病毒治疗方法。因此,首要的初始治疗方法是尽可能降低免疫抑制。西多福韦(CDV)是一种抗病毒药物,其使用与腺病毒载量的显著降低相关,并且在一些系列研究中,实体器官移植(SOT)和造血干细胞移植(HSCT)受者的生存率有所提高。然而,其使用也与显著的毒性相关。布林西多福韦(BCV)是CDV的脂质制剂,与CDV相比,其口服生物利用度有所提高,毒性特征较好。然而,研究仅显示BCV对腺病毒疾病或病毒血症有适度益处。免疫疗法在HSCT患者病毒感染管理中是一个不断发展的领域,取得了有前景的结果。

总结

目前的证据支持在SOT和HSCT移植患者中使用CDV和BCV作为挽救疗法。免疫疗法仅在HSCT患者中被证明是成功的,可作为难治性病例或腺病毒感染挽救疗法的一种选择。

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