Slifkin Michelle, Doron Shira, Snydman David R
Division of Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts, USA.
Drugs. 2004;64(24):2763-92. doi: 10.2165/00003495-200464240-00004.
Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu season'.
病毒病原体已成为对实体器官移植(SOT)受者产生有害影响的最重要微生物因子。抗病毒化学预防是指使用药物来阻止活动性病毒感染的传播、避免其重新激活或防止其发展为疾病。巨细胞病毒(CMV)是对SOT受者产生负面影响的主要微生物病原体。CMV可引起感染性疾病综合征,增强医源性免疫抑制,并且通常与机会性二重感染相关。CMV还与排斥反应的发病机制有关。CMV的化学预防方案包括中高剂量的口服阿昔洛韦、静脉注射和口服更昔洛韦,以及前体药物伐昔洛韦和缬更昔洛韦。CMV预防策略应分层进行,高危患者应接受最“强效”的预防方案。单纯疱疹病毒(HSV)在SOT受者中的重新激活更为频繁,可能变得更具侵袭性,愈合时间更长,并且比在免疫功能正常的宿主中更有可能传播至内脏器官。CMV的预防方案对HSV也有有效的化学预防作用;在没有CMV预防的情况下,对于血清阳性受者,应使用阿昔洛韦、伐昔洛韦或泛昔洛韦作为HSV预防药物。SOT后的原发性水痘-带状疱疹病毒(VZV)感染很少见,由于VZV的流行病学特点,最常见于儿童移植人群。带状疱疹发生在5%-15%的患者中,通常在移植后第六个月之后。由于疾病发病较晚且受影响个体比例较低,SOT后带状疱疹的预防方案既不实用也不具有成本效益。所有SOT受者在接触水痘或带状疱疹后都应接受VZV免疫球蛋白治疗。爱泼斯坦-巴尔病毒在SOT中作为移植后淋巴增殖性疾病发生的诱发因素具有最显著的影响。可能有效的抗病毒药物与用于CMV的药物相同,但预防的指征和有效性尚不明确。乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)作为移植指征,是SOT人群中的重要病原体。肝移植后所谓的复发性HBV和HCV“预防”存在争议,是抑制性而非预防性的,并且可能是终身的。SOT后的流感感染是通过人与人之间的接触获得的。在流感流行期间,移植人群的感染频率相对较高,并且流感对免疫抑制的SOT受者的不利影响可能比对免疫功能正常的个体更大。除了每年接种疫苗外,在流感流行和医院内暴发等情况下,以及在“流感季节”接触有症状个体后,应将预防流感的抗病毒药物作为暴露后预防措施给予SOT受者。