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UL97磷酸转移酶基因L595S突变导致肾移植受者出现复发性和持续性巨细胞病毒感染。

Recurrent and persistent cytomegalovirus infection in a kidney recipient caused by the L595S mutation in UL97 phosphotransferase gene.

作者信息

Peixoto Maíra, Mascarenhas Lays, Cunha André, Dutra Margarida, Miranda Eva, Silva Ivo, Costa Sandra, Galvão Bernardo, Cunha Andréa

机构信息

Laboratório Avançado de Saúde Pública, Oswaldo Cruz Fundation, Salvador, Brazil.

出版信息

Antivir Ther. 2012;17(3):585-8. doi: 10.3851/IMP1938. Epub 2011 Oct 27.

Abstract

Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug-resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a CMV-seropositive donor (D(+)/R(-)), and who developed clinical GCV resistance, confirmed by mutation in viral UL97 phosphotransferase responsible for GCV activation. Under prophylactic therapy with intravenous GCV for 6 weeks post-transplantation, he developed severe anaemia and hepatic enzyme increases, probably due to drug side effects. At this moment, the drug was discontinued and he started to be monitored by pp65 antigen test. At week 10 post-transplantation, he presented fever, myalgia, thrombocytopenia and neutropaenia, with a positive CMV antigen test. During treatment with intravenous GCV, antigenaemia assay demonstrated a higher number of positive cells, requiring GCV at higher doses. Pre-emptive therapy lasted for 31 days and he started the maintenance therapy with oral GCV. However, antigenaemia assay demonstrated an extremely high number of positive cells, and he was rehospitalized and prescribed intravenous GCV. Severe leukopaenia led to GCV interruption, but immunosuppressive dose reduction helped to control the active CMV infection. GCV-resistant CMV infection resulted in increased morbidity, rehospitalization episodes and increased costs; therefore, implementation of resistance diagnostic tests in the transplantation routine is of great importance. We documented the first case of GCV-resistant CMV infection due to the L595S mutation in UL97 phosphotransferase gene in a kidney recipient from Bahia state, Brazil.

摘要

更昔洛韦(GCV)是巴西巴伊亚州实体器官移植受者预防和治疗活动性巨细胞病毒(CMV)感染的首选治疗药物。长期和反复使用GCV治疗可能导致耐药病毒,与进行性和播散性疾病相关。我们报告一例年轻男性肾移植受者的病例,该受者CMV血清学阴性,供者为CMV血清学阳性(D(+)/R(-)),其出现临床GCV耐药,通过负责GCV激活的病毒UL97磷酸转移酶突变得以证实。移植后静脉注射GCV预防性治疗6周时,他出现严重贫血和肝酶升高,可能是药物副作用所致。此时停用该药物,开始通过pp65抗原检测进行监测。移植后第10周,他出现发热、肌痛、血小板减少和中性粒细胞减少,CMV抗原检测呈阳性。静脉注射GCV治疗期间,抗原血症检测显示阳性细胞数量增加,需要更高剂量的GCV。抢先治疗持续31天,然后他开始口服GCV维持治疗。然而,抗原血症检测显示阳性细胞数量极高,他再次住院并接受静脉注射GCV治疗。严重白细胞减少导致GCV中断,但降低免疫抑制剂量有助于控制活动性CMV感染。GCV耐药的CMV感染导致发病率增加、再次住院次数增多和费用增加;因此,在移植常规中实施耐药诊断检测非常重要。我们记录了巴西巴伊亚州一名肾移植受者因UL97磷酸转移酶基因L595S突变导致GCV耐药CMV感染的首例病例。

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