巨细胞病毒宫内感染状态与母婴垂直传播之间的关系

目的研究巨细胞病毒（HCMV）宫内感染状态即活动性与非活动性感染与母婴垂直传播之间的关系。方法对85例HCMV-IgM或HCMV-DNA阳性的母血标本用RT-PCR方法检测即刻早期（IE）mRNA和晚期（L）mRNA,并用PEP-PCR方法检测母血标本中分离出的胎儿细胞的HCMV-DNA。结果 85例母血标本中检测到IE-mRNA或L-mRNA的有57例,其中胎儿细胞HCMV-DNA呈阳性的有37例,宫内垂直传播率为64.91%。未检测到IE-mRNA和L-mRNA的28例样本中胎儿细胞HCMV-DNA呈阳性的有4例,宫内垂直传播率为14.29%。两组的垂直传播率经χ2检验有统计学差异（P〈0.001）。结论巨细胞病毒宫内感染处于活动期状态时,其发生母婴垂直传播的危险性显著高于非活动期感染状态,这对于采取正确的治疗措施和评估预后有重要的指导意义。     

人巨细胞病毒宫内感染与孕龄的关系

目的研究孕龄与人巨细胞病毒宫内感染的垂直传播率之间的关系。方法分别应用ELISA方法和PCR方法检测273例不同孕龄的孕妇外周血标本中的HCMV-IgM和HCMV-DNA,新生儿血样或胚胎组织用PCR方法检测HCMV-DNA以诊断先天性HCMV感染。结果孕早期妇女外周血中的HCMV-IgM和HCMV-DNA的阳性率均低于孕中期和孕晚期妇女,差异有显著性(P<0.005)。孕中期和孕晚期妇女宫内感染的垂直传播率显著高于孕早期妇女,差异有统计学意义(P<0.001)。结论孕中期和孕晚期妇女发生宫内感染的几率和垂直传播率均显著大于孕早期妇女,应加强对孕中期和孕晚期HCMV感染孕妇的监测和治疗。     

母血中胎儿有核红细胞计数与宫内感染的关系

目的探讨母血中胎儿有核红细胞数量与巨细胞病毒宫内感染之间的关系。方法收集54例巨细胞病毒宫内感染孕妇和68例非感染孕妇的外周血样本,富集胎儿有核红细胞后计数。每例样本取2个胎儿有核红细胞并用PEP-PCR技术证实其胎源性。结果宫内感染组的胎儿有核红细胞数量与100个有核细胞数的比值显著高于非感染组(P<0.05)。结论巨细胞病毒宫内感染孕妇外周血中的胎儿有核红细胞数量比正常妊娠者增高,对进一步阐明该病的病生机制具有一定的意义。     

巨细胞病毒宫内感染与预后研究现状

巨细胞病毒(cytomegalovirus,CMV)是一类在自然界普遍存在但又有严格种属特异性的病毒,属β疱疹病毒亚科,致人类疾病的为人巨细胞病毒(CMV)人群中感染非常普遍,但大多数呈临床不显性感染或潜伏感染,多数人在儿童期或少年期受HCMV感染后获得免疫.HCMV宫内感染可导致胎儿畸形、智力低下和发育迟缓等,严重者可引起全身性感染综合征,称为巨细胞包涵体病(cytomegalic inclusion diseses,CID).     

巨细胞病毒孕期感染的免疫学变化与宫内传播

人巨细胞病毒（humancytomegalovirus，HCMV）是引起胎儿宫内感染最常见、最危险的病原体，能导致流产、死胎、畸形、智力发育落后等严重后果。我国是HCMV感染高度流行国家，正常育龄妇女IgG抗体阳性率高达７６．３％９８％，孕妇HCMV活动性感染不仅引起孕妇更强烈、更严重的疾病过程，且严重影响胎儿和新生儿健康。近年研究认为，孕期CMV感染所致宫内传播、母体及胎儿损害与妊娠和CMV导致机体免疫尤细胞免疫抑制有密切关系，本文就其机制和宫内感染的早期诊断作一综述。一、HCMV感染的免疫学变化１．体液免疫：体液免疫在机体抗…     

孕妇与胎儿巨细胞病毒感染

人类巨细胞病毒感染是一种全身感染性疾病,也是一种性传播疾病.HCMV是最常见的机会性感染病毒,对成人是低致病性,对胎儿却危害极大,比风疹更加严重.HCMV感染可引起泌尿生殖系统、中枢神经系统、血液循环系统、肝脏和肺脏等病变,并与动脉粥样硬化和宫颈癌等恶性肿瘤发生有关.胎儿感染病毒后,可引发胎儿宫内发育迟缓(objective intrauterine growth restriction,IUGR)、流产、死胎、死产和新生儿死亡.约10%新生儿出现低体重、黄疸、紫癜、肝脾肿大、智力低下和小头畸形等.大部分感染胎儿在出生后数周内因黄疸和溶血性贫血而死亡,偶有存活者,也会发生脑积水、永久性耳聋、失明和痉挛性截瘫等多种残疾.     

经胎盘接种小鼠巨细胞病毒宫内感染模型建立

目的应用小鼠巨细胞病毒宫内感染模型,观察母鼠妊娠结局。方法用ELISA筛选无MCMV感染史性成熟期小鼠,雌雄同笼受孕。孕龄12.5天时,模型组胎盘显微注射MCMV,对照组注射生理盐水,空白对照组不做任何处理。部分在孕龄18.5天处死母鼠,部分待母鼠自然分娩,观察母鼠妊娠结局及子代感染情况。结果模型组36.62%(26/71)和生理盐水对照组29.85%(20/67)的死胎率,χ2=0.711,P>0.05。分别和空白对照组0.00%(0/68),P<0.01。比较三组组畸胎率分别为22.54%(16/71)、0.00%(0/67)和0.00%(0/68),P<0.01。空白对照组和生理盐水对照组未发现胎盘和胎仔感染,模型组胎盘感染率63.27%(31/49)、胎仔感染率为32.65%(16/49),χ2=0.136,P<0.01。结论小鼠巨细胞病毒宫内模型的建立为其发病机理研究、选择宫内感染的干预介入点提供了新的靶点。     

先天性巨细胞病毒感染胎儿的临床研究

目的探讨先天性巨细胞病毒(human cytomegalovirus, HCMV)感染与胎儿先天畸形和孕妇合并异常妊娠的关系.方法追踪42例孕期诊断为宫内HCMV感染胎儿的妊娠结局,应用PCR技术于生后1w内检测新生儿血、尿或唾液HCMV DNA;对孕母的妊娠史加以回顾性分析.结果 HCMV感染可损害多器官,脑和肾是HCMV感染最常攻击的靶器官,各占先天畸形胎儿的28%,与其他器官损害相比差异有显著意义;HCMV感染不是产前诊断HCMV宫内感染的唯一指征,73.9%宫内诊断为HCMV感染的胎儿其孕母合并异常妊娠. 结论先天性HCMV感染与胎儿畸形和孕妇合并异常妊娠关系密切.脑、肾是HCMV感染最常攻击的靶器官,合并异常妊娠史的孕妇宫内HCMV感染率较高.临床上对于合并胎儿先天畸形和异常妊娠史的孕妇,尤其胎儿脑、肾畸形者,应常规检查有无宫内HCMV感染.     

套式聚合酶链反应检测豚鼠巨细胞病毒宫内感染

人巨细胞病毒(HCMV)宫内感染是导致出生缺陷的重要因素之一，其致病机制迄今尚未阐明。本研究建立豚鼠巨细胞病毒(GPCMV)宫内感染模型，将灵敏性和特异性均较高的套式聚合酶链反应(N-PCR)用于研究检测，报道如下。     

Molecular epidemiology of primary human cytomegalovirus infection in pregnant women and their families

The source of human cytomegalovirus (HCMV) infection was investigated in 29 pregnant women with primary HCMV infection by comparing DNA sequences of UL146, UL144 and a portion of UL55 gene of HCMV strains circulating within each family. Thirteen families were identified in which the pregnant woman, the husband and/or a child were shedding HCMV. In three of these families, both the woman and the husband suffered from a concomitant primary HCMV infection. Phylogenetic analysis of UL146, UL144, and UL55 genes indicated that strains circulating within each family were identical, whereas strains from different families appeared to be distinct. However, identical UL146, UL144, and UL55 DNA sequences were observed sporadically among unrelated strains. A child rather than the husband was the virus source for the great majority of pregnant women. No association was observed between UL144 polymorphisms and intrauterine transmission.     

实时荧光定量PCR在检测孕妇血HCMV感染中的研究

目的探讨实时荧光定量PCR(FQ-PCR)检测孕妇血中巨细胞病毒(HCMV)感染的应用。方法采用FQ-PCR技术,对临床疑为HCMV病毒感染的326名孕妇(观察组)和健康孕妇(对照组)210名进行检测。结果观察组和对照组的检出率分别为42.33%、3.81%,观察组HCMV感染率明显高于对照组(χ2=95.6305,P<0.01),两者之间有显著差异。结论FQ-PCR检测HCMV具有方法简单、快速、特异性强、定量准确等优点,应推荐作为检测孕妇血中HCMV感染的首选方法。     

孕妇巨细胞病毒感染对胎儿影响的前瞻性研究

用酶联免疫吸附试验（ＥＬＩＳＡ）及聚合酶链反应（ＰＣＲ）方法对沈阳市４５０名孕妇进行巨细胞病毒（ＣＭＶ）筛查，并前瞻性追查到其婴儿１００名ＣＭＶ感染状况。结果孕妇９７．１１％为既往感染，０．８９％为原发感染，１１．１１％为复发感染，仅２％为易感者。４５０例中感染组孕妇有畸形儿３例，流产３例，其胎儿感染率与致畸率明显高于对照组。１００例母婴检查结果：感染组孕妇所生先天性感染儿比对照组多１．４３倍（ＲＲ＝１．４３），感染组有２名低智儿，对照组无。本组早孕原发感染对胎儿危害最大，其宫内传播率为３３．３％。感染组孕妇９例感染儿中２例巨细胞包涵体病，７例无症状。为了早期诊断达到优生目的，对孕妇进行ＣＭＶ筛查是必要的，但筛查过程中发现有活动感染时处理要慎重，最好追查到羊水阳性时考虑终止妊娠。     

Primary human cytomegalovirus infections: Kinetics of ELISA-IgG and neutralizing antibody in pauci/asymptomatic pregnant women vs symptomatic non-pregnant subjects

BackgroundHuman cytomegalovirus infections are mostly asymptomatic in infants and young children, while they are often associated with overt clinical symptoms in adults.ObjectivesTo verify whether the antibody response to HCMV is more potent in symptomatic non-pregnant adults as compared to asymptomatic/paucisymptomatic pregnant women.Study designOverall, 36 consecutive pregnant women with primary HCMV infection were compared with 10 consecutive symptomatic non-pregnant subjects with primary HCMV infection and overt clinical symptoms. Levels of IgG antibody responses to HCMV-infected cell lysate and the pentamer gH/gL/pUL128L, gH/gL and gB HCMV glycoprotein complexes as well as neutralizing antibodies preventing infection of epithelial cells (ARPE-19) and human embryonic lung fibroblast (HELF) cells were compared at intervals of 1–30, 31–60, 61–90, 91–180 and 181–360 days after onset of infection. In parallel, viral load was quantified by real-time PCR.ResultsIn symptomatic non-pregnant subjects, the IgG responses to HCMV lysate as well as to gH/gL and ARPE-19 neutralizing antibodies were significantly higher from 31 to 60 through 180 days after infection onset. In the same patients, the IgG antibody responses to the pentamer and HELF-neutralizing antibody were significantly higher starting 90 days post-infection.ConclusionsThe presence of overt clinical symptoms is associated with a significantly higher antibody response (concomitantly with a higher viral load) in non-pregnant subjects with symptomatic primary HCMV infection as compared to pregnant women with paucisymptomatic/ asymptomatic primary infection (and lower viral load).     

HBV阳性孕妇DC—SIGN／DC—SIGNR基因多态性与宫内感染关系的研究

目的分析HBV阳性孕妇DC—SIGN与DC—SIGNR的表达水平及其编码基因的多态性与HBV宫内感染相关性。方法应用PCR技术、琼脂糖凝胶电泳检测HBV阳性孕妇DC—SIGN与DC—SIGNR基因的颈区重复序列分型,然后用卡方检验分析DC—SIGN与DC—SIGNR基因各亚型出现的频率在两组中的差异。结果①29例宫内感染组DC—SIGN基因型全部为7／7型的纯合子基因,54例非宫内感染组中出现2例7／5型的基因,其他52例均为7／7型的基因,两组之间差异无统计学意义（P=0．54）。②29例宫内感染组发现4种DC—SIGNR基因型,分别为7／7型、7／5型、9／7型、6／5型,基因型频率分别为0．3793、0．3448、0．2414、0．0345。54例非宫内感染组发现6种基因型,为7／7型、7／5型、9／5型、9／7型、7／6型、6／5型,基因型频率分别为0．5186、0．1481、0．0926、0．1852、0．0370、O．0185。7／5型基因型在宫内感染组（29例）和非宫内感染组（54例）中的分布的差异有统计学意义（P=0．038）,其他基因型两组之间差异无统计学意义（P〉0．05）。结论①DC—SIGN编码基因存在个体基因变异,但变异相对较少,在HBV阳性产妇宫内感染组和非宫内感染组中DC—SIGN基因型分布无明显差异。②DC—SIGNR编码基因存在个体基因变异,变异相对较大,DC—SIGNR基因型“7／5型”在HBV阳性产妇宫内感染组和非宫内感染组中分布差异有统计学意义（P=0．038）,可能是影响宫内感染的易感基因。     

孕妇传染病感染标志物的检测及临床意义

目的了解孕妇乙肝、丙肝、梅毒及艾滋病的感染状况,探讨检测的临床意义。方法对我院2002年1月~2004年12月住院孕妇进行乙肝病毒血清标志物(HBV-M)、抗-HCV、-TP及-H IV检测,共2782例。结果HBsAg阳性率为12.80%,三年来乙肝阳性率变化不大,各年阳性率相互间比较无显著性差异(P>0.05);丙肝、梅毒阳性率分别为0.32%和1.40%,阳性率显逐年上升趋势,2004年与2002年梅毒阳性率比较,差异具有显著性意义(χ2=4.07,P<0.05);抗-H IV全为阴性。结论对孕妇进行4种传染病感染标志物检测是及早发现传染病和防止传染病母婴垂直传播的有效防治措施之一。     

早期先兆流产孕妇HCMV感染与血清PAPP-A水平的相关性研究

目的探讨早孕妇女妊娠相关血浆蛋白A(PAPP-A)水平与人巨细胞病毒(HCMV)活动性感染的相关性以及二者在早期自然流产发病机制中的作用。方法应用酶联免疫吸附试验(ELISA)和逆转录PCR(RT-PCR)筛选HCMV活动性感染早孕先兆流产妇女,定量检测其外周血血清PAPP-A水平,并与相同孕周的非HCMV活动性感染的先兆流产孕妇及健康孕妇进行比较分析。结果早期先兆流产妇女中HCMV活动性感染者、非活动性感染者、健康孕妇血清PAPP-A分别为:(0.4924±0.088)m lU/m l,(0.805±0.213)m lU/m l和(2.479±1.020)m IU/m l(F=93.98,P<0.01)。结论早孕妇女HCMV活动性感染和PAPP-A水平密切相关,并可能在早期自然流产的发病机制中占据相当重要的地位。     

HCMVpp65抗原、HCMV mRNA和IgM抗体检测在诊断HCMV活动性感染中的比较

目的比较人巨细胞病毒（HCMV）pp65抗原、HCMV mRNA和血清HCMV—IgM抗体检测3种方法在诊断HCMV活动性感染中的实用意义。方法采集医院TORCH检查HCMV—IgM阳性的病人外周血（60份）。将标本分2份2ml和3ml,别用于HCMV mRNA和pp65检测。将三者结果进行比较。结果pp65抗原检测的结果与IgM抗体检测的阳性符合率为81．67％。与HCMV mRNA检测相比pp65抗原检测法的符合率、特异度和敏感度分别为81．67％,81．81％和81．63％。而且高pp65抗原血症与患者的临床症状密切相关。结论pp65抗原血症反映该病毒活动状况,可监测HCMV活动性感染,联合HCMV—IgM的检测可以提高临床的诊断率并可用于指导临床用药及监测药物疗效。     

Detection of human cytomegalovirus (HCMV) pp67-mRNA and pp65 antigenemia in relation to development of clinical HCMV disease in renal transplant recipients

Objective   To evaluate the performance of the recently introduced method based on detection of human cytomegalovirus (HCMV) pp67 mRNA in blood by the nucleic acid sequence-based amplification (NucliSens), in comparison to semiquantitative detection of pp65 HCMV antigen in white blood cells, in relation to development of clinical HCMV disease.
Methods   Thirty patients, recipients of renal transplants, were monitored prospectively for the presence of pp67 mRNA, the presence and level of pp65 antigenemia, IgG and IgM antibodies, and the development of clinical HCMV disease. A total of 148 samples were examined during the observation period.
Results   Twenty-five samples were positive for pp67-mRNA and 45 samples contained at least one pp65 positive cell, with 68% agreement between the two assays. Both assays predicted correctly the development of clinical disease in five patients, giving a sensitivity of 100%. However, the specificity of the pp67-mRNA test was 72%, and of the pp65 antigenemia test from 20 to 64%, depending on the level of antigenemia chosen for cut-off. pp67-RNA appeared somewhat earlier than pp65 antigenemia, and responded earlier to treatment. Sero-conversion and appearance of IgM antibodies were of very little clinical value.
Conclusion   Both the pp67-mRNA and the pp65 antigenemia assay predicted correctly the development of clinical HCMV disease in renal transplant recipients. However, the specificity of both tests with respect to development of HCMV disease, especially the pp65 antigen test was moderate. Significantly positive tests not necessarily prove the development of clinical disease. Testing for pp67-mRNA may improve the diagnosis and management of HCMV disease in renal transplant patients.