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  中国感染控制杂志  2023, Vol. 22 Issue (7): 853-855   DOI: 10.12138/j.issn.1671-9638.20233640
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李祥, 宁永忠. 感染性疾病抢先预防研究进展[J]. 中国感染控制杂志, 2023, 22(7): 853-855. DOI: 10.12138/j.issn.1671-9638.20233640.
[复制中文]
LI Xiang, NING Yong-zhong. Research progress in preemptive prevention of infectious diseases[J]. Chin J Infect Control, 2023, 22(7): 853-855. DOI: 10.12138/j.issn.1671-9638.20233640.
[复制英文]

作者简介

李祥(1982-),男(汉族),江苏省扬州市人,副主任技师,主要从事临床微生物学研究

通信作者

宁永忠  E-mail: 13167306676@163.com

文章历史

收稿日期:2022-11-30
感染性疾病抢先预防研究进展
李祥 , 宁永忠     
清华大学附属垂杨柳医院检验科,北京 100022
摘要:随着医学的不断发展、进步,出现了一些新的医疗理念,衍生出新的医学术语,如抢先预防。本文介绍抢先预防的概念、内涵、方法等,着重阐述抢先预防在感染性疾病领域的应用。分析抢先预防与其他相似术语如普通预防、靶向预防的区别和联系,为广大医务人员临床应用该理论提供一定的指导意义。
关键词抢先预防    感染    抢先治疗    抢先监测    
Research progress in preemptive prevention of infectious diseases
LI Xiang , NING Yong-zhong     
Department of Laboratory Medicine, Chuiyangliu Hospital Affiliated to Tsinghua University, Beijing 100022, China
Abstract: With the continuous development and progress of medicine, new medical concepts and terms have emerged, such as preemptive prevention. This paper introduces the concept, connotation and methods of preemptive prevention, and focuses on the application of preemptive prevention in the field of infectious diseases. The diffe-rences and connections among preemptive prevention and other similar terms such as general prevention and targeted prevention are analyzed, providing guidance for the clinical application of this theory to medical personnel.
Key words: preemptive prevention    infection    preemptive treatment    preemptive monitoring    

词组“preemptive prevention”或“pre-emptive prevention”偶见于文献,可译作“抢先预防”。是指先于临床表现的、基于客观证据的处置,防止相关疾病的发生。相对于普通预防,抢先预防则更快一步,更有针对性,效果更好。该词在非感染性疾病领域、感染性疾病领域都有应用。非感染性疾病领域中如关于全髋关节置换术后新发抑郁症危险因素的研究[1]提到,医生应该利用患者术前信息、术后并发症信息来识别高风险患者,以便采取抢先预防(pre-emptive prevention)策略。感染性疾病角度主要是病毒学领域,也涉及真菌学、寄生虫学领域。本文主要就该词在感染性疾病领域的含义进行综述。

感染性疾病领域里,抢先预防一词既见于临床实践指南,也见于一般性研究论文、综述等。临床实践指南如美国移植感染病学会实践社(American Society of Transplantation Infectious Diseases Community of Practice)关于移植后爱泼斯坦-巴尔病毒(Epstein-Barr virus,EBV)感染、移植后淋巴增生性疾病(post-transplant lymphoproliferative disorders,PTLD)的指南[2]。该指南摘要中明确指出,低质量证据支持早期EBV+PTLD的抢先预防(preemptive prevention)策略,即在EBV血清阴性受者中使用需要进一步结果验证的分析方法来测量外周血中的EBV-DNA,并结合干预措施来降低病毒载量。

抢先预防的含义包括两方面。主要是抢先治疗(preemptive/pre-emptive therapy/treatment),其次是抢先监测(preemptive/pre-emptive monitoring)。抢先预防包含抢先治疗,看似矛盾,实则不然。抢先治疗是指在临床症状未出现时,对通过针对性检查发现的异常给予治疗,不同于临床症状已经发生后的治疗,本质上属于预防。而抢先监测是指为了获得有效的客观证据进行的监测,目的是对疾病的预防。例如对产科患者进行B群链球菌筛查,阳性则给予治疗,实际上也属于抢先预防的范畴,其行为包含了抢先监测和抢先治疗两个方面。著名的新英格兰医学杂志发表的一篇论文中最早出现抢先治疗(preemptive therapy)一词[3],是对另一篇论文的评价,是一篇随机对照双盲试验(RCTs)研究,研究同种异体骨髓移植后应用更昔洛韦以预防巨细胞病毒(CMV)感染[4]。采用的技术手段是移植后第35天进行支气管肺泡灌洗液CMV培养,培养阳性则给予更昔洛韦治疗。该词目前在非感染性疾病领域也有应用,如血液病领域[5]、过敏和免疫学领域[6]

概括而言,“抢先”指先于临床表现的、基于客观证据的处置。在感染性疾病领域里,抢先治疗的含义一直没有大的改变,持续到目前[7]。当然也会有一些具体的不同,包括:免疫力受损与否;临床表现变化,如有无临床感染症状、体征;技术手段包括培养、聚合酶链式反应(PCR)、基因芯片等;启动时间因病毒、基础性疾病的不同而异;用药因病毒、基础性疾病、药代动力学和药效学、非临床因素等不同而异。病毒感染领域里,目前该词一般用于免疫受损患者,主要是移植后、艾滋病等状态。多数没有临床表现,技术手段主要是PCR。常见的病毒如EB病毒、CMV、BK病毒、单纯疱疹病毒、水痘带状疱疹病毒等,也包括各种呼吸道病毒[8]、肝炎病毒等[9]

从感染的病程来看,包括新发生的感染、得到控制的感染再激活两种情况。移植后最开始的感染多数属于前者;免疫受损时反复出现的感染,部分属于后者;一些病毒性感染性疾病的复发,也属于后者,如乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染的情况[9]

基于相似的理念,抢先治疗从病毒学领域逐渐扩展到真菌学[10-11]、寄生虫学[12]、细菌学领域。真菌学领域用得略多,细菌学领域抢先治疗的理念实际有应用,但明确用“抢先治疗”这个词的较少[13]

抢先监测指为了抢先预防、抢先治疗所进行的监测。在新英格兰医学杂志发表论文[3]中最早作为一种专业方式被应用。作为一个明确的词组,2002年见于非感染性疾病领域[14],而感染性疾病领域到2010年才出现[15-16],即上述抢先治疗里涉及的技术手段,对其进行特化、归纳成为专业词组。具体监测方式如病毒培养[4]、PCR、抗原检测[10]等。近期发展增加了2个角度,一个是方便使用的自测平台[17];一个是免疫监测,即患者免疫功能监测,其临床实用性还有待研究[18]。因此,抢先监测可以初步分为微生物学监测和免疫学监测两类。

随着抢先预防的概念逐渐明确且实用,预防性用药分为3种情况:普遍预防(universalprophylaxis)、靶向预防(targetedprophylaxis)、抢先预防/抢先治疗[11, 19]。普遍预防指没有明确的客观证据,基于流行病学对多种病原体进行预防,如术前抗菌药物使用,一般是针对某部位常见病原体进行用药覆盖。靶向预防指无明确的客观证据,基于流行病学对一种病原体[一般是种的水平,特殊的可以是属,如针对曲霉属;或型/群,如耐甲氧西林金黄色葡萄球菌(MRSA)]进行预防,如艾滋病患者服用磺胺类抗菌药物预防耶氏肺孢子菌感染。靶向预防时有时使用广谱抗微生物药物,目的是靶向预防,实际上部分起到了普遍预防的效果。而抢先预防则基于客观证据。早期有文献将抢先治疗和靶向预防两者等同[20],此观点欠妥,当然一般理解上,抢先预防/抢先治疗可以看作是特殊的靶向预防;而从严格的专业角度,应有所区分。

感染性疾病领域文献中相关表达方式较多,除了上述以外,汇总如下:抢先策略(preemptive strate-gy)[2]、抢先处置(preemptive management)[2]、抢先干预(preemptive prevention)[2]、抢先方式(preemptive approach)[21]、抢先给药(pre-emptive administration)[22]、抢先筛查(preemptive scree-ning)[23]、抢先地(preemptively)[2]、抢先(使用)的(preemptive rituximab)[2],含义相同、类似或相关,上述词汇本质上都属于抢先预防的范畴,属于含义相近的表述,适用于不同的医疗行为,有些仅仅是表述上的差异。

综上所述,作为感染性疾病领域的专业词汇,抢先预防的定义明确,主要是指在临床事件未发生之前及时进行预判,获取先于临床表现的基于客观的证据,尽早采取相应的预防措施,防止不良事件的发生。抢先预防一词的界定清楚(相对于普遍预防、靶向预防)、概念明确(基于证据,先于临床表现)、包含有限(包括抢先治疗、抢先监测两部分)、应用广泛(多个内科领域)、表达多样(十余种表达方式)。某些情况下,甚至大多数情况下,抢先预防和抢先治疗可以视作同义词。

利益冲突:所有作者均声明不存在利益冲突。

参考文献
[1]
Wilson JM, Schwartz AM, Farley KX, et al. Preoperative patient factors and postoperative complications as risk factors for new-onset depression following total hip arthroplasty[J]. J Arthroplasty, 2021, 36(3): 1120-1125. DOI:10.1016/j.arth.2020.10.009
[2]
Allen UD, Preiksaitis JK, AST Infectious Diseases Community of Practice. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019, 33(9): e13652.
[3]
Rubin RH. Preemptive therapy in immunocompromised hosts[J]. N Engl J Med, 1991, 324(15): 1057-1059. DOI:10.1056/NEJM199104113241509
[4]
Schmidt GM, Horak DA, Niland JC, et al. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group[J]. N Engl J Med, 1991, 324(15): 1005-1011. DOI:10.1056/NEJM199104113241501
[5]
Skou AS, Juul-Dam KL, Ommen HB, et al. Peripheral blood molecular measurable residual disease is sufficient to identify patients with acute myeloid leukaemia with imminent clinical relapse[J]. Br J Haematol, 2021, 195(3): 310-327. DOI:10.1111/bjh.17449
[6]
Adachi T, Kainuma K, Asano K, et al. Strategic outlook toward 2030: Japan's research for allergy and immunology-se-condary publication[J]. Allergol Int, 2020, 69(4): 561-570. DOI:10.1016/j.alit.2020.04.006
[7]
Raval AD, Kistler KD, Tang YX, et al. Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: a systematic literature review of real-world evidence[J]. Transpl Infect Dis, 2021, 23(2): e13483.
[8]
Hijano DR, Maron G, Hayden RT. Respiratory viral infections in patients with cancer or undergoing hematopoietic cell transplant[J]. Front Microbiol, 2018, 9: 3097. DOI:10.3389/fmicb.2018.03097
[9]
Takikawa H. Viral hepatitis[J]. Gan To Kagaku Ryoho, 2020, 47(5): 744-749.
[10]
Xu XL, Zhao T, Harypursat V, et al. Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies[J]. Chin Med J (Engl), 2020, 133(23): 2859-2866. DOI:10.1097/CM9.0000000000001134
[11]
Bitterman R, Marinelli T, Husain S. Strategies for the prevention of invasive fungal infections after lung transplant[J]. J Fungi (Basel), 2021, 7(2): 122. DOI:10.3390/jof7020122
[12]
Rauwolf KK, Floeth M, Kerl K, et al. Toxoplasmosis after allogeneic haematopoietic cell transplantation—disease burden and approaches to diagnosis, prevention and management in adults and children[J]. Clin Microbiol Infect, 2021, 27(3): 378-388. DOI:10.1016/j.cmi.2020.10.009
[13]
宁永忠. 细菌性感染性疾病的诊断分级[J]. 中华传染病杂志, 2015, 33(1): 49-52.
Ning YZ. Diagnostic grading of bacterial infectious diseases[J]. Chinese Journal of Infectious Diseases, 2015, 33(1): 49-52.
[14]
Besarab A. Preventing vascular access dysfunction: which po-licy to follow[J]. Blood Purif, 2002, 20(1): 26-35. DOI:10.1159/000046982
[15]
Ram S, Vajpayee P, Shanker R. Enterotoxigenic Escherichia coli in sewage-impacted waters and aquatic weeds: quantitative PCR for culture-independent enumeration[J]. J Appl Micro-biol, 2010, 108(3): 1007-1014. DOI:10.1111/j.1365-2672.2009.04501.x
[16]
McGillicuddy JW, Weimert NA, Taber DJ, et al. Can preemptive cytomegalovirus monitoring be as effective as universal prophylaxis when implemented as the standard of care in patients at moderate risk?[J]. Transplantation, 2010, 89(10): 1218-1223. DOI:10.1097/TP.0b013e3181d54ba6
[17]
Haidar G, Boeckh M, Singh N. Cytomegalovirus infection in solid organ and hematopoietic cell transplantation: state of the evidence[J]. J Infect Dis, 2020, 221(Suppl 1): S23-S31.
[18]
Stern A, Papanicolaou GA. CMV prevention and treatment in transplantation: what's new in 2019[J]. Curr Infect Dis Rep, 2019, 21(11): 45. DOI:10.1007/s11908-019-0699-0
[19]
Dinubile MJ. Universal prophylaxis, targeted prophylaxis, and/or preemptive therapy for opportunistic infections at the time of initiation of combination antiretroviral therapy for patients with advanced HIV Infection[J]. Clin Infect Dis, 2009, 49(5): 808-811. DOI:10.1086/605289
[20]
Kusne S, Shapiro R, Fung J. Prevention and treatment of cytomegalovirus infection in organ transplant recipients[J]. Transpl Infect Dis, 1999, 1(3): 187-203. DOI:10.1034/j.1399-3062.1999.010307.x
[21]
Paccoud O, Guitard J, Labopin M, et al. Features of Toxoplasma gondii reactivation after allogeneic hematopoietic stem-cell transplantation in a high seroprevalence setting[J]. Bone Marrow Transplant, 2020, 55(1): 93-99. DOI:10.1038/s41409-019-0641-y
[22]
Bethea ED, Gaj K, Gustafson JL, et al. Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study[J]. Lancet Gastroenterol Hepatol, 2019, 4(10): 771-780. DOI:10.1016/S2468-1253(19)30240-7
[23]
Schwenk HT, Khan A, Kohlman K, et al. Toxoplasmosis in pediatric hematopoietic stem cell transplantation patients[J]. Transplant Cell Ther, 2021, 27(4): 292-300. DOI:10.1016/j.jtct.2020.11.003