切换至 "中华医学电子期刊资源库"

中华实验和临床感染病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (06) : 526 -532. doi: 10.3877/cma.j.issn.1674-1358.2017.06.002

综述

人巨细胞病毒感染及母婴传播阻断临床研究进展
张雨1, 曾慧慧1,()   
  1. 1. 100026 北京,首都医科大学附属北京妇产医院新生儿科
  • 收稿日期:2017-02-27 出版日期:2017-12-15
  • 通信作者: 曾慧慧
  • 基金资助:
    首都医科大学附属北京妇产医院、北京妇幼保健院中青年学科骨干培养专项(No. fycc201614)

Progress of clinical research on human cytomegalovirus infection and maternal-infant interruption

Yu Zhang1, Huihui Zeng1,()   

  1. 1. Neonatal Intensive Care Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
  • Received:2017-02-27 Published:2017-12-15
  • Corresponding author: Huihui Zeng
引用本文:

张雨, 曾慧慧. 人巨细胞病毒感染及母婴传播阻断临床研究进展[J/OL]. 中华实验和临床感染病杂志(电子版), 2017, 11(06): 526-532.

Yu Zhang, Huihui Zeng. Progress of clinical research on human cytomegalovirus infection and maternal-infant interruption[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2017, 11(06): 526-532.

人巨细胞病毒(HCMV)为dsDNA病毒,其囊膜糖蛋白和基质蛋白诱导人体产生免疫反应。HCMV通过直接损伤和免疫病理损伤,导致多器官损害。人感染HCMV以潜伏性和再次激活为特征,临床症状与免疫力状态有关。本文旨在对HCMV感染的流行病学、临床表现及母婴感染特点、实验室检查手段及评价、抗HCMV治疗及母婴阻断措施作一综述。我国育龄妇女HCMV血清学阳性率为95%以上,妊娠期原发感染率为1%~4%,其中24%~75%通过垂直传播引发宫内胎儿感染,导致其发育畸形、流产、死胎或新生儿出生缺陷甚至死亡,建议实施规范感染控制措施预防孕期CMV感染。先天性CMV感染可累及多脏器,常见于神经系统和网状内皮系统损害。HCMV检测包括分子技术与非分子技术,抗-HCMV亲和力的测定有助于原发感染的诊断。目前不能将抗病毒治疗和超免疫球蛋白作为预防孕期先天性CMV感染常规手段。抗病毒药阿昔洛韦、伐昔洛韦、泛昔洛韦无致畸作用,但仍有必要评价其孕期治疗的安全性和有效性。巨细胞病毒免疫球蛋白是防治HCMV感染的有效制剂,单克隆抗体的研制是防治HCMV感染的研究热点之一。

Human cytomegalovirus (HCMV), a double-stranded DNA virus, whose envelope glycoproteins and matrix proteins may induce immune responses in humans. HCMV caused multiple organs damage through direct injury and pathological damage. Latency and reactivation are defining characteristics of HCMV. Clinical symptoms of HCMV infection are related to immune status of the host. This review summarized the epidemiology, clinical manifestations, characteristics of vertical transmission, laboratory test and evaluation, anti-HCMV treatment and mother-to-child blocking methods of HCMV infection. The positive rate with serology in women of childbearing age was over 95%. The rates of primary HCMV infection during pregnancy was 1% to 4%, and 24% to 75% of them could cause intrauterine fetal infection through vertical transmission, resulting in malformations, miscarriages, stillbirths, birth defects or even death. Therefore, it is suggested that standard control measures should be taken to prevent CMV infection during pregnancy. Congenital CMV infection involves multiple organs, most common in nervous system or reticuloendothelial system. HCMV detection included both molecular and non-molecular techniques. The determination of avidity of HCMV antibodies is helpful in the diagnosis of primary infection. Antiviral therapy and immunoglobulin may not be routinely used to prevent congenital CMV infection during pregnancy at this stage. Although there was no teratogenic effect of the following antiviral drugs, acyclovir, valaciclovir and famciclovir, it was still needed to evaluate the safety and efficacy of them used in pregnancy. Cytomegalovirus immunoglobulin is an effective preparation for the prevention and treatment of HCMV infection. The development of monoclonal antibody to HCMV is one of research hotspots in prevention and treatment filed.

表1 先天性CMV感染胎儿异常产前超声表现
[1]
Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle[J]. J Clin Invest,2011,121(5):1673-1680.
[2]
Tomtishen JP, 3rd. Human cytomegalovirus tegument proteins (pp65, pp71, pp150, pp28)[J]. Virol J,2012,9(1):1-9.
[3]
Fortunato EA, Dell’Aquila ML, Spector DH. Specific chromosome 1 breaks induced by human cytomegalovirus[J]. Proc Natl Acad Sci USA,2000,97(2):853-858.
[4]
赵杨, 闻良珍. 妊娠期人巨细胞病毒感染的研究现况[J]. 中华围产医学杂志,2004,7(2):121-122.
[5]
Maidji E, Percivalle E, Gerna G, et al. Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts[J]. Virology,2002,304(1):53-69.
[6]
Korndewal MJ, Mollema L, Tcherniaeva I, et al. Cytomegalovirus infection in the Netherlands: seroprevalence, risk factors, and implications[J]. J Clin Virol,2015,63:53-58.
[7]
Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection[J]. Rev Med Virol,2010,20(4):202-213.
[8]
Yan XC, Wang JH, Wang B, et al. Study of human cytomegalovirus replication in body fluids, placental infection, and miscarriage during the first trimester of pregnancy[J]. J Med Virol,2015,87(6):1046-1053.
[9]
王芳, 马骏, 李芬. 人巨细胞病毒宫内感染的研究进展[J]. 现代妇产科进展,2005,14(1):56-58.
[10]
北京地区母婴巨细胞病毒感染课题组. 北京地区新生儿先天巨细胞病毒感染状况研究[J]. 中国新生儿科杂志,2012,27(1):5-9.
[11]
Enders G, Daiminger A, Bader U, et al. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age[J]. J Clin Virol,2011,52(3):244-246.
[12]
Davis NL, King CC, Kourtis AP. Cytomegalovirus infection in pregnancy[J]. Birth Defects Res,2017,109(5):336-346.
[13]
Rawlinson WD, Boppana SB, Fowler KB, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy[J]. Lancet Infect Dis,2017,17(6):e177-e188.
[14]
Malcolmson C, Ng K, Hughes S, et al. Impact of matrix-assisted laser desorption and ionization time-of-flight and antimicrobial stewardship intervention on treatment of bloodstream infections in hospitalized children[J]. J Pediatric Infect Dis Soc,2017,6(2):178-186.
[15]
郭丽丽, 许红梅. 人巨细胞病毒感染的流行病学研究进展[J]. 山东医药,2017,31(12):1131-1133.
[16]
姜毅. 先天性巨细胞病毒感染母婴传播及诊断[J]. 中国新生儿科杂志,2009,24(5):261-265.
[17]
Guerra B, Lazzarotto T, Quarta S, et al. Prenatal diagnosis of symptomatic congenital cytomegalovirus infection[J]. Am J Obstet Gynecol,2000,183(2):476-482.
[18]
姚丽, 张梅, 郭先成. 孕妇巨细胞病毒感染载量与胎儿宫内感染的相关性分析[J]. 中华医院感染学杂志,2015,(15):3550-3552.
[19]
张立群, 巩振华, 李毅. 孕中期巨细胞病毒宫内感染的临床研究[J/CD]. 世界最新医学信息文摘(连续型电子期刊),2015,15(3):76-78.
[20]
李淑涓, 曹云. 早产儿经母乳获得性巨细胞病毒感染的研究进展[J]. 中华围产医学杂志,2014,17(11):773-777.
[21]
Lanzieri TM, Dollard SC, Josephson CD, et al. Breast milk-acquired cytomegalovirus infection and disease in VLBW and premature infants[J]. Pediatrics,2013,131(6):e1937-e1945.
[22]
Dioverti MV, Razonable RR. Cytomegalovirus[J]. Microbiol Spectr,2016,4(4):97-125
[23]
Society for Maternal-Fetal Medicine (SMFM), Hughes BL, Gyamfi-Bannerman C. Diagnosis and antenatal management of congenital cytomegalovirus infection[J]. Am J Obstet Gynecol,2016,214(6):B5-B11.
[24]
Marsico C, Kimberlin DW. Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment[J]. Ital J Pediatr,2017,43(1):38.
[25]
桑洪爱, 王琳琳, 刘振平, 等. 孕妇巨细胞病毒感染对胎儿及新生儿的影响[J/CD]. 中国产前诊断杂志(电子版),2015(1):36-39.
[26]
王晓红. 婴儿巨细胞病毒感染与胆道闭锁的关系[J]. 实用儿科临床杂志,2005,3(20):274-275.
[27]
左江成, 曾一芹, 向希映, 等. 母乳期婴儿巨细胞病毒感染现状与传播途径分析[J]. 实用医学杂志,2015,31(1):140-143.
[28]
Hayden RT, Yan X, Wick MT, et al. Factors contributing to variability of quantitative viral PCR results in proficiency testing samples: a multivariate analysis[J]. J Clin Microbiol,2012,50(2):337-345.
[29]
Gleaves CA, Smith TF, Shuster EA, et al. Comparison of standard tube and shell vial cell culture techniques for the detection of cytomegalovirus in clinical specimens[J]. J Clin Microbiol,1985,21(2):217-221.
[30]
赵缜, 李敏, 彭奕冰, 等. 人巨细胞病毒pp65抗原血症检测方法的建立和初步临床应用[J]. 检验医学,2004,19(1):36-39.
[31]
Razonable RR, Paya CV, Smith TF. Role of the laboratory in diagnosis and management of cytomegalovirus infection in hematopoietic stem cell and solid-organ transplant recipients[J]. J Clin Microbiol,2002,40(3):746-752.
[32]
St George K, Rinaldo CR, Jr. Comparison of cytomegalovirus antigenemia and culture assays in patients on and off antiviral therapy[J]. J Med Virol,1999,59(1):91-97.
[33]
Pass RF, Zhang C, Evans A, et al. Vaccine prevention of maternal cytomegalovirus infection[J]. N Engl J Med,2009,360(12):1191-1199.
[34]
Nigro G, Adler SP, La Torre R, et al. Congenital Cytomegalovirus Collaborating Group: Passive immunization during pregnancy for congenital cytomegalovirus infection[J]. N Engl J Med,2005,353(13):1350-1362.
[35]
Revello MG, Lazzarotto T, Guerra B, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus[J]. N Engl J Med,2014,370(14):1316-1326.
[36]
Buxmann H, Stackelberg OM, Schlosser RL, et al. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis[J]. J Perinat Med,2012,40(4):439-446.
[37]
Nigro G, Capretti I, Manganello AM, et al. Primary maternal cytomegalovirus infections during pregnancy: association of CMV hyperimmune globulin with gestational age at birth and birth weight[J]. J Matern Fetal Neonatal Med,2015,28(2):168-171.
[38]
Jacquemard F, Yamamoto M, Costa JM, et al. Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection[J]. Bjog,2007,114(9):1113-1121.
[39]
Visentin S, Manara R, Milanese L, et al. Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age[J]. Clin Infect Dis,2012,55(4):497-503.
[40]
Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group[J]. N Engl J Med,1999,340(19):1462-1470.
[41]
Hou B, Zhang Y. Risk of birth defects after use of acyclovir, valacyclovir, and famciclovir in the first trimester[J]. JAMA,2010,304(20):2242-2243.
[42]
Leruez-Ville M, Ghout I, Bussieres L, et al. In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase Ⅱ study[J]. Am J Obstet Gynecol,2016,215(4):462.e461-462. e410.
[43]
Whitley RJ, Cloud G, Gruber W, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase Ⅱ study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group[J]. J Infect Dis,1997,175(5):1080-1086.
[44]
Kimberlin DW, Lin CY, Sanchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial[J]. J Pediatr,2003,143(1):16-25.
[45]
Kimberlin DW, Jester PM, Sanchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease[J]. N Engl J Med,2015,372(10):933-943.
[46]
Revello MG, Lazzarotto T, Guerra B, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus[J]. N Engl J Med,2014,370(14):1316-1326.
[47]
Funaro A, Gribaudo G, Luganini A, et al. Generation of potent neutralizing human monoclonal antibodies against cytomegalovirus infection from immune B cells[J]. BMC Biotechnol,2008,8(1):85.
[1] 钱警语, 郑明明. 《2024意大利妇产科学会非侵入性和侵入性产前诊断指南》解读[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 486-492.
[2] 黄蓉, 梁自毓, 祁文瑾. NLRP3炎症小体在胎膜早破孕妇血清中的表达及其意义[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 540-548.
[3] 何霞, 黄蓉, 祁文瑾. 胎膜早破孕妇胎盘与胎膜菌群丰度的高通量测序研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 549-555.
[4] 谢江燕, 王亚菲, 贺芳. 妊娠合并血栓性血小板减少性紫癜2例并文献复习[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 556-563.
[5] 韩肖燕, 杨桦. 中孕期孕妇血清胎盘生长因子水平低与胎儿不良预后的关系[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(04): 398-402.
[6] 杜佳丽, 鲍睿, 乔春红, 韩伟. 中孕期宫颈功能不全孕妇经阴道紧急宫颈环扎术后不良妊娠结局预测模型构建[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(04): 403-409.
[7] 徐婷婷, 詹泳池, 王晓东, 刘兴会. 电子胎心监测结果出现正弦波形的胎母输血综合征围生期结局分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(04): 382-389.
[8] 谭娟, 谭建新, 邵彬彬, 王艳, 许争峰. 胎儿单基因遗传病无创产前检测的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 245-250.
[9] 张禾璇, 杨雪, 王侣金, 李林洁, 刘兴宇. 新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查及基因突变特征分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 200-208.
[10] 林雪, 陈锰, 杨梅琳, 刘兴会, 周红雨. 妊娠合并重症肌无力患者的围产结局和重症肌无力病情恶化的影响因素分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 125-132.
[11] 陈义思, 梁敏, 李红雨, 夏雪, 刘燕茜, 李晨曲, 王丹. 妊娠合并慢性肾病围产期多学科团队管理价值研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 133-139.
[12] 贾赛君, 张英, 万佳义. 妊娠合并亚临床甲状腺功能减退孕妇的妊娠结局[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 140-147.
[13] 马海月, 南晓琴. 网织红细胞百分比/未成熟网织红细胞指数联合胆红素与白蛋白比值对新生儿溶血病的病情评估意义[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(01): 89-96.
[14] 张艳兰, 徐琳, 王彩英, 杨洪玲, 庞琳. 56例先天性梅毒新生儿的临床特征及预后[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(03): 163-169.
[15] 路长贵, 唐维兵. 新生儿及小婴儿先天性胆管扩张症临床特征分析及微创治疗[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(02): 76-82.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?