妊娠后期应用替比夫定阻断HBV高载量孕妇母婴传播效果及安全性

目的评价妊娠后期应用替比夫定(LdT)阻断HBV高载量孕妇母婴传播的疗效及安全性。方法选择185例2012年5月1日至2013年4月30日在余姚市人民医院门诊就诊及住院的HBsAg阳性、HBV DNA≥2.0×105 IU/mL、肝功能正常的妊娠妇女,按照患者意愿分为治疗组(127例,自孕28周至产后30d口服LdT 600mg/d)和对照组(58例,未服药)。两组孕妇均在孕26~27周、分娩时及产后30d检测HBV DNA。两组婴儿在出生后6h内、30d、6个月注射乙型肝炎疫苗10μg,同时在婴儿出生后6h内及产后30d注射乙型肝炎免疫球蛋白200IU。在婴儿7~8月龄时检测HBsAg情况。结果治疗组孕妇在分娩时及产后30dHBV DNA滴度明显下降,HBV DNA的阴转率为22.04%,在分娩时HBV DNA水平与对照组相比差异有统计学意义(P=0.001);治疗组婴儿HBsAg阳性率为0.00%,对照组为5.17%(3例感染),两组比较差异有统计学意义(P=0.01)。两组患者在剖宫产率、产后出血率、早产率、新生儿先天畸形率、正常体重儿等方面差异无统计学意义。结论 HBV DNA高载量孕妇在妊娠后期实施抗病毒治疗,能有效抑制孕妇体内HBV DNA水平,降低HBV母婴垂直传播率。     

免疫预防阻断乙型肝炎病毒母婴传播效果的观察

阻断乙型肝炎病毒(HBV)母婴传播是控制乙型肝炎的重大问题。为探讨免疫预防对阻断HBV母婴传播的效果及影响因素,对667例HBV表面抗原(HBsAg)阳性孕妇及其婴儿进行研究。这些孕妇按HBVe抗原(HBeAg)和HBVDNA检测结果,分为HBeAg阳性组及阴性组、DNA阳性组及阴性组;按是否于孕晚期注射乙型肝炎免疫球蛋白(HBIG),分为注射组及未注射组。婴儿于出生24h内均肌内注射HBIG100IU,并按0、1、6方案注射10μg重组酵母HBV疫苗;8～12月龄后随访婴儿,并进行HBV标志物(HBV-M)检测。667个婴儿中,20例感染HBV,免疫阻断失败率为3.0%。孕妇HBeAg阳性组免疫阻断失败率为8.7%,阴性组为0.2%,两组差异显著(P<0.001);两组婴儿对疫苗免疫应答率分别为83.0%和83.1%,无显著差异(P=0.988)。孕妇DNA阳性组免疫阻断失败率为8.1%,HBVDNA均≥6log10copies/ml。孕期注射与未注射HBIG组婴儿免疫阻断失败率分别为3.7%和2.7%,无显著差异(P=0.479);两组婴儿对疫苗免疫应答率分别为84.4%和82.4%,无显著差异(P=0.519)。孕妇HBeAg阳性注射HBIG组与未注射组的免疫阻断失败率分别为8.4%和8.9%,无显著差异(P=0.892)。孕妇HBeAg阴性注射与未注射HBIG组的免疫阻断失败率分别为0.0%和0.3%,也无显著差异(P=0.538)。11例免疫阻断失败的婴儿中,10例出生时血清HBsAg已为阳性;8～12个月后随访,HBsAg仍持续阳性,提示为宫内感染。本研究证实,孕期注射HBIG未能提高婴儿对HBV疫苗加HBIG的免疫阻断效果。宫内感染可能是疫苗加HBIG免疫阻断失败的主要原因。采用降低孕妇血清HBVDNA的措施,如对孕妇进行抗HBV治疗,也许能降低HBV宫内感染率。     

胎盘Hofbauer细胞在HBV母婴垂直传播的作用

目的:探讨胎盘Hofbauer细胞在乙型肝炎病毒(HBV)母婴垂直传播的作用。方法:垂直传播组(母亲及其新生儿血HBsAg和HBV-DNA均为阳性)、非垂直传播组(母亲血HBsAg和HBV-DNA阳性而新生儿阴性)和对照组(母亲及其新生儿血HBsAg和HBV-DNA均为阴性)各30例,透射电了显微镜观察其胎盘Hofbauer细胞超微结构变化及其与HBV颗粒的关系。结果:①对照组未发现Hofbauer细胞:在垂直传播组和非垂直传播组,Hofbauer细胞散在分布于胎盘间质中。②在垂直感染组,Hofba-uer细胞肿胀,胞浆突起减少,胞浆空泡变大;粗面内质网及高尔基复合体萎缩,线粒体缩小,溶酶体少见;胞核增大,染色质浓缩、边聚。在非垂直感染组,Hofbauer细胞呈圆形或卵圆形,细胞表面有大量胞浆突起,排列着微吞饮小体,细胞胞浆内有圆形空泡;线粒体呈杆状,峭排列紧密,溶酶体较多,高尔基体及粗面内质网欠发达;胞核偏位,核仁显著,染色质分布均匀。③在Hofbauer细胞胞质空泡、细胞间隙内存在单个或多个成熟病毒颗粒、病毒包涵体和病毒抗原颗粒。结论:HBV可引起胎盘Hofbauer细胞超微结构改变,并经Hofbauer细胞介导引起母婴垂直传播。     

乙型肝炎疫苗接种与康泰疫苗事件引发的思考

<正>乙型肝炎(乙肝)是由乙型肝炎病毒(乙肝病毒)引起的严重危害人民健康的传染病,主要通过血液、医源、性生活和母婴等途径传播,是急慢性肝炎、肝硬化及肝癌的重要原因.成人感染乙肝病毒多数都可以痊愈,但婴幼儿感染则多数成为慢性持续性感染者.1979年全国乙肝流行病调查人群中乙肝病毒表面抗原(hepatitis B surface antigen,HBsAg)平均携带率为9.76%,儿童4岁时HBsAg携带率就已达或接近高     

PI3K 与乙型肝炎病毒宫内感染的相关研究

慢性乙型肝炎病毒(Hepatitis B virus,HBV)感染是全世界关注的公共卫生问题。我国是乙肝高流行区,每年约有150万乙肝病毒携带者分娩,近半数胎儿通过母婴垂直传播感染乙肝。由于婴幼儿期感染乙肝后形成的免疫耐受,往往成为慢性甚至终身携带者,逐渐发展为肝硬化、肝癌。近年来的研究发现,PI3-Akt信号通路与妊娠生及或病理过程关系密切,在感染HBV的胎盘组织中发现PI3K-Akt信号通路中相关蛋白表达异常增高,且HBx Ag干扰该通路调节凋亡功能。推断HBx Ag通过调节PI3K-Akt信号通路活性影响胎盘功能,是HBV宫内感染的一种重要分子机制。为今后阻断HBV宫内感染提供新的研究方向。     

乙型肝炎病毒宫内感染危险因素的病例对照研究

目的:探讨与乙型肝炎病毒宫内感染相关的产妇孕期危险因素.方法:采用病例对照的研究方法,选择连续收集的2005年10月至2006年10月在陕西省妇幼保健院产科行孕期检查并分娩的113例乙型肝炎病毒表面抗原(HBsAg)阳性产妇及其所产新生儿为研究对象,以出生时血清HBsAg阳性的新生儿为病例组,其余均为对照组,收集产妇孕期及产时的相关资料,采用单因素分析、对数线性模型等方法分析与宫内感染相关的因素.结果:113例新生儿有3例发生宫内感染.病例组产妇孕中期有性行为、HBVDNA阳性与对照组之间存在统计学差异(P＜0.05),且交互作用分析显示二者之间符合相乘模型,OR值及95%CI为127.00(4.73-340.51),有协同作用.其他因素与HBV宫内感染无统计学关联.结论:孕中期性行为及产妇HBV DNA阳性可能增加新生儿HBV宫内感染的危险性.     

新生儿乙肝疫苗减剂接种的五年随访观察

<正>资料表明,乙肝病毒(HBV)感染在出生前后就可确定,而且常常导致慢性肝病。因此,阻断母婴垂直传播是预防HBV携带状态的最重要的步骤。 出生时被动接种免疫球蛋白(HBIg)以预防乙肝是普遍公认的,但接种程序复杂。几次有关减少接种次数的效果评价证明减剂接种亦具有合乎要求的免疫原性。相反,首次接种的年龄却是一个有争议的问题:一方面由于分娩是HBV感染的关键时     

抗乙型肝炎病毒单克隆抗体药物的临床前药效学评价

由乙型肝炎病毒（HBV）感染导致的病毒性肝炎是世界范围内的一个重大公共卫生问题,抗HBV抗体药物乙型肝炎免疫球蛋白（HBIG）是阻断乙型肝炎母婴传播和移植性感染的主要用药。但HBIG本身存在一些问题,而重组抗HBV单克隆抗体能成为其有效替代物。在重组抗HBV抗体技术相对成熟的情况下,重组抗HBV单克隆抗体药物功能性评价体系的缺失成为阻碍抗HBV单克隆抗体药物研发的重要因素。本文就现有的抗HBV单克隆抗体药物的评价方法和体系进行综述。     

免疫抑制剂地塞米松可明显延长乙型肝炎病毒抗原在水动力法转染HBV小鼠模型中的表达

建立基于高压水动力法的乙型肝炎病毒(HBV)转染小鼠模型,并进一步建立和优化乙肝动物模型研究方法。首先构建了含腺相关病毒倒转末端重复序列元件与包含1.3个拷贝HBV基因组(ayw亚型)的HBV表达质粒(pAAV-HBV1.3);并将pAAV-HBV1.3质粒经高压水动力法尾静脉注射C57BL/6小鼠,不同时间点采集血液和肝组织标本,ELISA检测血清HBsAg、HBeAg表达;Real-time PCR检测血清及肝组织病毒载量;HE染色、免疫组化染色检测肝组织病理学改变及病毒抗原在肝组织中的定位及表达;最后采用免疫抑制剂地塞米松注射液(DEX)腹腔注射小鼠,建立免疫功能抑制小鼠模型,在此基础上制备乙肝病毒转染小鼠模型,并进行血清HBsAg、HBeAg检测。结果是正常免疫状态下,小鼠转染pAAV-HBV1.3 10d时血清及肝组织HBV相关抗原阳性,30d后HBV相关抗原检测阴性,但30d和60d血清及肝组织病毒载量检测均为阳性,且与对照组差异显著(P0.01,P0.05);经地塞米松注射后处于免疫抑制状态下的高压水动力法建立的乙肝病毒转染小鼠,则在60d仍可检测到HBsAg、HBeAg的表达。以上结果表明通过高压水动力法建立了急性乙肝小鼠模型,通过抑制小鼠免疫状态,可延长病毒在小鼠体内存留时间。该模型建立为HBV疫苗评价、药物开发及乙肝相关致病机理研究奠定了基础。     

父系HBeAg 阳性流产胚胎绒毛中HBV-DNA 的表达

目的:探讨在父系HBeAg阳性的流产胚胎中,乙型肝炎病毒在绒毛中的表达。方法:募集仅父系感染乙型肝炎病毒组合,即母HBsAg(-)且父HBsAg(+)流产胚胎。按以下组合将入选对象分为4组:组1为父HBeAg(+)母HBsAb(+);组2为父HBeAg(+)母HBsAb(-);组3为父HBeAg(-)母HBsAb(+);组4为父HBeAg(-)母HBsAb(-),采用酶联免疫吸附实验(ELISA)对胎儿父、母亲血清进行乙肝抗原、抗体检测,并使用荧光定量PCR法对胚胎绒毛进行HBV DNA检测。结果:父系感染乙型肝炎病毒的142例胚胎中,仅在父系HBeAg阳性组别(1、2组)84例胚胎中发现3例绒毛HBV-DNA升高,阳性率为3.57%。其中父HBeAg(+)母HBsAb(-)组合中2例,父HBeAg(+)母HBsAb(+)组合中1例。父系HBeAg均阳性,母系HBsAb阳性与阴性组间子代绒毛HBV-DNA升高率差异无显著性(P>0.05)。结论:HBeAg阳性父亲可能更容易导致乙肝父婴垂直传播。     

Mother-to-child transmission of HIV in Botswana: an ethical perspective on mandatory testing

Mother-to-child transmission (MTCT) of HIV represents a particularly dramatic aspect of the HIV epidemic with an estimated 600,000 newborns infected yearly, 90% of them living in sub-Saharan Africa. Since the beginning of the HIV epidemic, an estimated 5.1 million children worldwide have been infected with HIV. MTCT is responsible for 90% of these infections. Two-thirds of the MTCT are believed to occur during pregnancy and delivery, and about one-third through breastfeeding. As the number of women of child bearing age infected with HIV rises, so does the number of infected children. It is apparent that voluntary testing in Botswana has made some valuable inroads in decreasing perinatal HIV transmission, but the statistics showing the increased rate of HIV infection among women 15-24 years of age are not very promising. After reviewing all the pertinent scientific data it is clear that mandatory HIV testing of all pregnant women in conjunction with the implementation of a full package of interventions would save thousands of lives -- mothers, newborns and others who could be infected as a result of these women not being aware of their HIV status. If the protection and preservation of human life is a priority in Botswana, then it is time to allow for mandatory HIV testing of all pregnant women, before it is too late for those who are the most vulnerable. To do less would be medically inappropriate and ethically irresponsible.     

Mother-to-child transmission of HIV-1 in sub-Saharan Africa: past, present and future challenges

HIV prevalence continues to be high among women of reproductive age in sub-Saharan Africa. In 2007 the HIV prevalence among pregnant women attending antenatal clinics was >20% in the southern African counties of Botswana, Swaziland, South Africa and Lesotho. Mother-to-child transmission (MTCT) of HIV can occur in-utero, intrapartum or postnatally. Without any preventive measure the overall rate of the MTCT of HIV in breastfeeding women could be 25-45%. Prior to the discovery of successful antiretroviral interventions to prevent the MTCT of HIV in sub-Saharan Africa (before 1999), innovative research determined the magnitude of the problem, the impact of the HIV epidemic on mothers and children, and the main risk factors associated with MTCT. Non-antiretroviral interventions conducted before 1999 such as washing the birth canal with antiseptics and antenatal supplementation with vitamin A did not reduce the MTCT of HIV. However, during the period 1999 to present, major successes were made in the prevention of the MTCT of HIV. The use of single-dose nevirapine prophylaxis to the mother and infant reduced the MTCT of HIV to ~12%. Subsequently, longer prophylaxis and combined antiretroviral regimens were shown to be highly effective and very low HIV transmission rates comparable to those in developed countries were reported in some clinical trial settings in sub-Saharan Africa. The future is promising but challenges remain. The current successful intervention modalities are entirely dependent on antiretrovirals and breastfeeding continues to be vital for the survival of the child in the African setting. Reviewing past and present achievements assists in focusing future research and development of prevention programs.     

白细胞介素17 在妊娠合并乙肝中的表达

目的：观察白细胞介素17（Interleukin-17,IL-17）在乙肝孕妇和正常孕妇胎盘中表达差异来反映胎盘内的细胞免疫应答的情 况,为外源性细胞因子在增强机体免疫、清除病毒及阻断和治疗HBV宫内感染提供新的科学依据。方法：选择择期剖宫产的足月 妊娠妇女46 例,其中血清HBsAg（+）30 例,血清HBsAg（-）的对照组16 例,采用免疫组化方法检测胎盘组织IL-17 的表达。结 果：IL-17 主要表达在胎盘绒毛的合体滋养层细胞胞浆、毛细血管内皮细胞胞浆以及基质中。血清HBsAb（+）孕妇与HBsAb（-）孕 妇比较,无显著差异（P＞0.05）,HBsAg（+）乙肝孕妇与对照组的表达比较差异有统计学意义（P＜0.05）,HBeAg（+）孕妇与HBeAg （-）孕妇的表达比较差异有统计学意义（P＜0.05）。结论：IL-17 在乙肝孕妇胎盘组织中的表达高于正常孕妇,IL-17 的表达不但加 强了机体的防御功能,且能促进炎性反应。     

High Endemicity and Low Molecular Diversity of Hepatitis B Virus Infections in Pregnant Women in a Rural District of North Cameroon

Background

A program, supported by the GEMHEP (Groupe d''étude Moléculaire des Hépatites), was established in 2007 in the sanitary district of Tokombéré, to prevent perinatal transmission of hepatitis B virus (HBV). It comprises screening for HBV surface antigen (HBsAg) in all pregnant women and vaccinating the newborn if tests are positive.

Methods/Principal Findings

1276 women were enrolled in the study after providing informed consent. Demographic data and blood samples were available for 1267 of the enrolled patients. HBsAg was determined locally using a rapid test (Vikia HBsAg, Biomerieux). Tests for HBV and HDV virological markers (HBeAg, anti-HDV antibodies (Ab), HBV-DNA, HDV-RNA, HBV and HDV genotypes) were performed on the confirmed HBsAg-positive samples in the virology unit of the Angers University Hospital (France). HBsAg was found in 259 of the 1267 pregnant women (20.4%) between January 2009 and April 2010, of whom 59 were HBeAg-positive (22.7%) with high levels of HBV-DNA. Anti-HDV Ab were found in 19 (7.3%) of the HBsAg-positive women. The prevalence rates of HBsAg and HDV were not age-dependent whereas HBeAg carriers were statistically younger than non carriers. Basal core promoter (BCP) and precore (PC) mutations and genotypes were determined by sequencing. Of 120 amplified sequences, 119 belonged to HBV genotype E (HBV/E) and the 9 HDV strains belonged to HDV clade 1. In the PC region, 83/228 patients (36.4%) harbored a G1896A mutant or mixed phenotype virus. In the BCP region, the double mutation A1762T/G1764A and the G1757A substitution were detected respectively in 26/228 patients (11.4%) and 189/228 patients (82.8%).

Conclusions

Our results confirm the high prevalence and low molecular diversity of HBV in Far Northern Cameroon; more than 20% of the infected women were highly viremic, suggesting a high rate of HBV perinatal transmission and supporting the WHO recommendation to vaccinate at birth against hepatitis B.     

Prevalence of human T‐lymphotropic virus type 1 carriers among pregnant women in Hokkaido,Japan

As there is a risk of MTCT of HTLV‐1, the HSGP HTLV‐1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV‐1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5 467 000 and 39 392 newborns in 2011, the HSGP HTLV‐1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti‐HTLV‐1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33 617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33 563 (99.8%) women were judged to be HTLV‐1 carriers and non‐carriers, respectively. It was concluded that the prevalence rate of HTLV‐1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV‐1 in Hokkaido.     

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis

Background

The World Health Organization (WHO) has called for the “virtual elimination” of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe.

Methods and Findings

We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines'' “Option A” (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO “Option B” (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning.The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%–7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%.

Conclusions

Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the “virtual elimination” of pediatric HIV in Zimbabwe. Please see later in the article for the Editors'' Summary     

Correlation between Vertical Transmission of Hepatitis B Virus and the Expression of HBsAg in Ovarian Follicles and Placenta

Background

The aim of this study was to investigate the correlation between the expression of hepatitis B surface antigen (HBsAg) in human ovary and placenta and the vertical transmission of hepatitis B virus (HBV).

Methodology/Principal Fidnings

Ovarian and placental tissue specimens of pregnant women infected with HBV were collected during cesarean section and immunostained for HBsAg. The sera of the corresponding newborns were tested for HBV markers and HBV DNA. HBsAg was detected in 15 out of 33 (45%) placental tissues and was further detected in capillary endothelial cells in 4 specimens (26%), of which 3 (75%) corresponding infants were infected with HBV in utero. Out of the 33 ovarian tissues, 7 (21%) were positive for HBsAg, of which 2 (28%) showed HBsAg in ovarian follicles and the 2 corresponding infants (100%) had intrauterine HBV infection.

Conclusions/Significance

HBsAg expression in cells of the ovarian follicle or placental capillary endothelium signal a higher risk for intrauterine HBV infection.     

严格消毒注射器输液器械及针灸针以控制农村婴幼儿乙型肝炎病毒感染

在婴幼儿HBV高感染村,实施一人一针一管一用一消毒的严格措施后,使一岁儿童HBV感染率下降53.0％,HBsAg阳性率下降55.5％,使HBsAg阴性母亲的1～2岁儿童HBV感染率下降64.6％～76.4％,HBsAg阳性率降低78.6％～81.9％。     

Congenital Chagas disease: an update

Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of children born from chronically infected mothers in endemic areas, with variations depending on the region. This presentation aims to focus on and update epidemiological data, research methods, involved factors, control strategy and possible prevention of congenital infection with T. cruzi. Considering that etiological treatment of the child is always effective if performed before one year of age, the diagnosis of infection in pregnant women and their newborns has to become the standard of care and integrated into the surveillance programs of syphilis and human immunodeficiency virus. In addition to the standard tests, polymerase chain reaction performed on blood of neonates of infected mothers one month after birth might improve the diagnosis of congenital infection. Recent data bring out that its transmission can be prevented through treatment of infected women before they become pregnant. The role of parasite genotypes and host genetic factors in parasite transmission and development of infection in foetuses/neonates has to be more investigated in order to better estimate the risk factors and impact on health of congenital infection with T. cruzi.