Update on the management of hepatitis B and C infections in the neonatal period

Hepatitis B virus and hepatitis C virus have received a significant amount of attention in recent years, and both viruses share a significant amount of similarities with one another beyond just that they both primarily target the liver. In recent years, cases of both infections have been fueled by a nationwide epidemic of injection drug use. Most relevant to this audience, they are both transmitted from mother to child. The increased cases in young adults combined with mother to child transmission translate into more exposed infants that will need to be managed and followed. Screening of pregnant women for hepatitis B infection coupled with appropriate treatment and prophylaxis measures are incredibly effective to preventing transmission. Prevention of hepatitis C infection is not yet possible, but advances in antiviral therapy make interruption of transmission a future possibility.     

The chasm between public health and reproductive research: what history tells us about Zika virus

Zika transmission from mother to fetus and its possible sexual transmission have become a media focus in the past months as a major public health concern. While mother-to-fetus transmission, fetal neurologic manifestations or sexual transmission have never been documented for this virus before, other viruses that belong to the same family are very well known to reproductive health workers, clinicians, and researchers. As a member of Flaviviridae family, including hepatitis C and bovine viral diarrhea virus (BVDV), Zika’s pathogenesis may have some parallels with these infections which may pose future questions for public health and research. Vertical transmission of hepatitis C virus from mother to child is known to occur in up to 10 % of pregnancies. BVDV, a member of Pestivirus genus of Flaviviridae family is not known to be transmitted to humans but is known for its vertical transmission in cattle. BVDV infection at different stages of gestation may lead to a spectrum of adverse pregnancy outcomes, including pregnancy loss and neurologic manifestations (including deformations such as hydrocephalus and microcephaly) in the offspring. Similar to hepatitis C, which is a virus of Hepacivirus genus, BVDV is capable of persistent infection, meaning that virus may stay in mother and future generations of calves may be infected as well, which may, in turn, result in persistence of infection in offspring. Would this be a case with Zika virus? Along with mother-to-fetus transmission, sexual transmission is a concerning implication for Zika virus. Would woman become a persistent career or male be able to persistently carry virus with its sperm is yet unknown; yet, there is a concern for the reservoir of infection. Animal models of the disease are urgently needed not only to demonstrate the mother-to-fetus transmission and confirm the fetal neurologic manifestations but also to address the effects of virus on life-long host’s immunity and reproductive health. Along those lines, women desiring pregnancies who are identified to travel, have a partner traveling to, or living in the areas of Zika infections should be encouraged to have a preconception consultation with maternal-fetal medicine.     

孕妇的输血传播病毒感染及母婴垂直传播

目的 探讨广州市妊娠妇女的输血传播病毒（ＴＴＶ）感染情况和ＴＴＶ透过胎盘屏障进行入胎儿体内（垂直传播）的可能性。方法 应用套式ＰＣＲ对２５２例广州市发及其新生铁配对血清标本进行ＴＴＶＤＮＡ扩增。结果 ３９例孕妇血清和４例新生儿脐血清检测出ＴＴＶＤＮＡ,孕母ＴＴＶ感染率为１５．５％,母婴垂直传播率为１０．２％。结论 妊娠妇女存在下ＴＴＶ感染且可经胎盘传递给胎儿     

Mother-to-child transmission of hepatitis C virus: recent news about the benefit of caesarean sections

The rate of mother-to-infant transmission for hepatitis C virus is estimated to be around 5% of viraemic mothers and represents an important route of HCV infection among children. Transmission is possible in utero but the highest risk of infection is at or near the time of delivery because of an important blood transmission of hepatitis C virus. Mothers with high levels of HCV-RNA and co-infected for human immunodeficiency virus are documented to have risk factors for vertical transmission of HCV. Thus, for these, the mode of delivery must be discussed even if there are no precise recommendations. Among obstetrical risk factors, the results of literature fail to prove a benefit of elective caesarean delivery in the aim to reduce the vertical transmission of HCV. However, obstetrical situations with a high risk of blood contact between mother and foetus must be considered and if possible evicted.     

Hepatitisinfektion in der Schwangerschaft und bei der Geburt

The most common cause of jaundice in pregnancy is viral hepatitis, potentially accompanied by temporary dysfunction of the liver. Whereas acute viral hepatitis in pregnancy frequently describes an asymptomatic course, thereby only rarely affecting the fetus, some of the known hepatitis viruses might cause severe morbidity in the neonatal period particularly when the infection is noted near term or sub partu. However, efforts have been made in order to reduce the number of acute neonatal infections (hepatitis B immune globulin and vaccine). Conversely, no immunoprophylaxis for hepatitis C is available yet, although the vertical transmission rate is low. Perinatal transmission of hepatitis E is unusual, but maternal disease is often severe. The clinical relevance of the commonly found hepatitis G virus remains unknown. Liver inflammation caused by other viruses, toxic agents or autoimmune hepatitis are rare conditions in pregnancy.     

HIV-1 Infection in Pregnancy: Prevention of Mother-to-child Transmission

There are over 22 million people worldwide infected by the HIV virus. Most HIV infections are sexually acquired, and women, mainly in the reproductive age, account for a large proportion of cases. The HIV-1 virus can be vertically transmitted during pregnancy, delivery or through breast feeding. Perinatal transmission is the main cause of paediatric HIV infections. The aim of the present review is to discuss the prevention of vertical transmission of the HIV virus from the mother to her child.The strength of evidence supports the administration of antenatal, intrapartum and neonatal zidovudine or other antiretroviral drugs. High maternal HIV load during pregnancy was found to be associated with an increased risk of vertical transmission. Zidovudine was shown to reduce the risk of vertical HIV transmission by 68 percent in a double-blind placebo-controlled randomized trial (P < 0.001). Caesareon section increases the risk of maternal complications, with a possible, albeit unproved benefit of reducing vertical transmission, and should be discussed with the mother. Other alternative methods (condom use, smoking cessation, vaginal cleansing at delivery) are more readily available worldwide. They have a positive influence on maternal health, but their role in decreasing the risk of vertical transmission awaits confirmation. Education, the use of antiretroviral therapies and safe infant bottle feeding should be made accessible to HIV-infected women whenever possible.     

乙型肝炎病毒宫内感染机理的研究

目的　探讨乙型肝炎病毒 (HBV)宫内感染的可能机理。方法　应用PCR技术检测 5 9例乙型肝炎病毒表面抗原 (HBsAg)阳性孕妇的羊水、阴道分泌物及其新生儿脐血清中HBVDNA(研究组 ) ,10例乙型肝炎病毒标志物 (HBVM )阴性的正常孕妇及其新生儿为对照组。采用免疫组化ABC染色法检测两组孕妇胎盘组织中的HBsAg及乙型肝炎核心抗原 (HBcAg)的阳性率。 结果　 ( 1)研究组孕妇的羊水、阴道分泌物、新生儿脐血清中HBVDNA阳性率分别为 4 7 5 % ( 2 8/ 5 9)、5 2 5 % ( 31/5 9)、4 5 8% ( 2 7/ 5 9) ;对照组孕妇的羊水、阴道分泌物、新生儿脐血清中均未检出HBVDNA。 ( 2 )研究组孕妇胎盘组织中HBsAg及HBcAg的阳性率 ,呈现出由蜕膜细胞 ( 76 3%及 5 9 3% )、滋养层细胞 ( 72 9%及 5 5 9% )、绒毛间质细胞 ( 6 2 7%及 5 0 8% )至绒毛毛细血管内皮细胞 ( 5 2 5 %及 4 4 1% )依次递减的趋势 ;但其中有 4例孕妇胎盘组织中HBsAg及HBcAg的分布与上述特点相反。研究组孕妇有 32例羊膜细胞中检出HBsAg及HBcAg。对照组孕妇胎盘组织中的HBsAg及HBcAg检出率为零。结论　孕妇血中HBV主要是通过感染胎盘导致胎儿感染 ;但也可能存在胎盘以外的感染途径。     

Viral hepatitis during pregnancy

Viral hepatitis is one of the most common liver diseases appearing during pregnancy. Prevention against hepatotropic viruses is restricted due to lack of vaccines being effective in induction of efficient immunization in the majority of these microorganisms. In general, there is no possibility of active immunization against hepatotropic viruses except type A and B viral hepatitis. An issue of viral hepatitis in pregnancy as an aspect of potential risk factor connected with infection of pregnant women and a fetus has been described in this paper. Furthermore, the most important topics in the field of the epidemiology, prophylaxis and possible treatment options of viral hepatitis A, B, C, D, E and G have been discussed. The newest reports of pregnant women lamivudine therapy as a preventive treatment against vertical transmission during delivery have been reviewed. Rarly diagnosed viral hepatitis caused by herpes simplex virus, cytomegalovirus, Epstein-Barr virus and adenoviruses have been characterized as well.     

Management of HIV infection during pregnancy

Optimal management of HIV infection in pregnancy requires maternal use of potent antiretroviral therapy to prevent disease progression in the mother and vertical transmission to the newborn. Combination antiretroviral therapy substantially reduces the risk of perinatal HIV transmission and appears to be more effective than zidovudine monotherapy. The administration of single dose nevirapine to mother intrapartum and infant postpartum effectively reduces vertical HIV transmission and is less costly and cumbersome than zidovudine regimens. Elective cesarean section reduces vertical transmission of HIV but its benefit is less clear when antiretroviral therapy decreases maternal plasma HIV viral load to low levels at delivery. If possible, HIV-infected mothers should avoid breastfeeding. The present review discusses the importance of early identification of maternal HIV infection, strict adherence to combination antiretroviral regimens to prevent drug resistance, developing a better understanding of antiretroviral pharmacokinetics in pregnancy and short/long term safety of anti-HIV drugs.     

Vertical transmission of HIV from mother to child in sub-Saharan Africa: modes of transmission and methods for prevention

The impact of the human immunodeficiency virus (HIV) epidemic in sub-Saharan Africa on future mortality rates of infants, children, and mothers, life expectancy, and economic growth is profound. Vertical transmission of HIV, transmission from mother to child, is a major factor in the increasing rates of HIV infection in sub-Saharan Africa. Vertical transmission of HIV occurs in utero, intrapartum during labor and delivery, and postpartum during breast-feeding. Because of the large numbers of HIV-infected mothers in developing countries, the majority trials regarding prevention of vertical transmission of HIV have been conducted in sub-Saharan Africa. Thus, sub-Saharan Africa has become a human laboratory, which demonstrates both the successes and failures of preventative methods to reduce vertical transmission of HIV. This review summarizes the body of research dedicated to understanding the pathophysiology of vertical transmission of HIV and pharmacology of inhibition of vertical transmission of HIV. While many debate the ethics of conducting trials in developing countries where effective prevention modalities have been slow to be implemented for economic, social and political reasons, studies continue and researchers continue to discover therapies and preventative methods, which may reduce the future devastation of HIV both in sub-Saharan Africa and throughout the world.     

HIV exposure: neonatal considerations

The presence of human immunodeficiency virus (HIV) in pregnant women puts infants at risk for exposure through placental infection and contact with contaminated maternal blood and genital secretions. Efforts to combat this inevitably fatal disease continue to focus on preventing transmission of the virus from a mother who has HIV to her newborn during the prenatal, intrapartum, and postnatal periods. Prophylaxis against transmission and vigilant assessment for indicators of infection are hallmarks of appropriate health care for infants exposed to HIV.     

Viral infections in pregnancy

Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae.     

Viral infection,proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection

Purpose

Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus.

Methods

Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants.

Results

Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation.

Conclusions

Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.

     

妊娠晚期三种病毒活动性感染与低出生体重儿先天性感染率调查研究

目的观察妊娠晚期三种病毒活动性感染对低出生体重儿的垂直传播及先天性感染率。方法观察组为出生体重＜２５００ｇ早产儿和足月小于胎龄儿（ＳＧＡ）,对照组为同期出生单胎足月正常新生儿;两组均与生母配对分别于分娩后４８小时采血,用间接法ＥＬＩＳＡ检测巨细胞病毒（ＣＭＶ）、风疹病毒（ＲＶ）、单纯疱疹病毒Ⅱ型（ＨＳＶ－Ⅱ）、特异性ＩｇＧ和ＩｇＭ抗体。结果产妇三种病毒活动性感染率观察组和对照组差异无显著性意义（Ｐ＞００５）;但母婴传播率早产组三种病毒均明显高于对照组（直接概率＜００２５）。三种病毒先天性感染率早产儿组均明显高于足月儿组（Ｐ＜００５）,胎龄愈小,出生体重愈低先天性感染率愈高。结论妊娠晚期孕母病毒活动性感染,小胎龄早产儿胎盘屏障发育不完善,病毒容易通过胎盘传播给胎儿,因而早产儿组先天性感染率高于足月儿组。     

Role of placental tissues in the intrauterine transmission of hepatitis B virus

OBJECTIVE: The purpose of this study was to determine the mechanism of intrauterine transmission of hepatitis B virus. STUDY DESIGN: Placental tissues from 158 pregnant women who tested positive for hepatitis B surface antigen were examined for hepatitis B virus markers, Fc gamma receptors, and hepatitis B surface antigen-anti-hepatitis B surface antigen in different layers of cells. RESULTS: It was shown that the hepatitis B virus infection rate among different layers of placental cells gradually decreased from the maternal side to the fetal side. Furthermore, the closer the infected cell layer was to the fetal side, the higher the risk of intrauterine hepatitis B virus infection. Fc gamma receptors were found on cells of both hepatitis B surface antigen positive and negative placentas; Fc gamma receptors III were found on trophoblastic cells and villous mesenchymal cells, and Fc gamma receptors II were found on only villous mesenchymal cells. Hepatitis B surface antigen-antibodies to hepatitis B surface antigen was detected in the cytoplasm and on the membrane of trophoblastic cells and villous mesenchymal cells in 2 hepatitis B surface antigen-positive placentas. CONCLUSION: The results support the hypothesis that intrauterine hepatitis B virus transmission could be caused through "cellular transfer" in the placenta. One of the means of cellular transfer could be through Fc gamma receptor III-mediated entry of hepatitis B surface antigen-antibodies to hepatitis B surface antigen into cells.     

Hepatitis C-Implications in Pregnancy

Hepatitis C is a single-stranded RNA virus chat is transmitted primarily through transfusion of blood or blood products, or through the sharing of contaminated needles among injection-drug users. Heterosexual transmission of the virus has been reported. It is uncommon. Vertical transmission of the virus from mother to infant has also been reported but there are no large scale studies evaluating this. The literature suggests a vertical transmission rate of about six percent, but there is some recent evidence to suggest chat wornen with high titres of virus (which is uncommon) may transmit at a higher rate. Treatment for chronic persistent hepatitis C is currently interferon-alpha, but its use has not been investigated in pregnancy. Pregnant patients in high risk groups (intravenous drug users, recipients of multiple transfusions, undiagnosed hepatitis) should be screened for hepatitis C. Currently, there are no proven regimens available to decrease the likelihood of transmission. Investigators have not been able to isolate the hepatitis C virus from breast milk, therefore, there is no good evidence to advise women to avoid breastfeeding.     

HIV infection in women

Human immunodeficiency virus (HIV) infection is caused by an RNA retrovirus. The virus is trophic for CD₄ lymphocytes. By attacking and ultimately destroying these cells, the virus causes a severe deficiency in cell-mediated immunity, rendering the host susceptible to a myriad of opportunistic infections and malignancies. HIV infection occurs in a continuum, ranging from the initial, acute retroviral illness to florid acquired immunodeficiency syndrome (AIDS). At the present time, more than 400,000 Americans have been afflicted with AIDS. Approximately 1 million Americans are in pre-AIDS stages of their illness. In the United States, 12–15% of patients with HIV infection are women. Among women, the two most important risk factors for HIV infection are intravenous drug use and heterosexual contact with a high-risk male. Factors that increase the risk of sexual transmission of HIV infection include multiple partners, receptive anal intercourse, concurrent use of intravenous drugs or crack cocaine, and ulcerated genital tract lesions. Approximately 90% of all cases of HIV infection in children result from direct perinatal transmission from an infected mother. Transplacental dissemination and intrapartum transmission are the two most important mechanisms of perinatal infection. HIV infection can also be transmitted by breast-feeding and by close personal contact following delivery. The approximate frequency of perinatal transmission is 20–30%. The risk of transmission can be reduced significantly by treating HIV-infected patients and their neonates with zidovudine. Because HIV infection is such a severe and, usually, fatal illness, great emphasis should be placed on preventive measures.     

HTLV-I transmission from mother to child

Human T-lymphotropic virus type I (HTLV-I), a causative agent of adult T-cell leukemia, (ATL) is transmitted from mother to child. ATL cells originate from the CD4 subset of peripheral T cells. The main route of mother-to-child transmission is postnatal breast-feeding. Refraining from breast-feeding or limiting the duration of breast-feeding can reduce the risk of mother-to-child transmission. Other than postnatal breast-feeding, there seem to be two routes of HTLV-I transmission from mother to child. One is intrauterine transmission, and the other is via saliva. Intrauterine transmission is rare, although proviral DNA is detected in cord blood samples. HTLV-I proviruses in the cord blood may be defective. HTLV-I proviral DNA and antibodies against HTLV-I are also detected in saliva. However, no report has been published so far which showed direct evidence of HTLV-I transmission via saliva. The placenta can be infected by HTLV-I, but infection does not reach the fetus, possibly apoptosis of placental villous cells because it is induced by HTLV-I infection.     

Management of the infant born to a mother infected with human immunodeficiency virus type 1 (HIV-1): current concepts

Despite the use of highly active antiretroviral therapy (HAART) and the success of protocol PACTG-076 in decreasing perinatal transmission of HIV infection in many industrialized countries, a total of 5,600,000 new cases of HIV infection were diagnosed worldwide in 1999. Of those cases, more than 10% are children under 15 years of age. The vast majority of pediatric HIV infection is due to perinatal transmission. More than 95% of HIV-infected people live in the developing world. Different studies are currently being conducted with modifications of the original PACTG-076, especially shorter courses of zidovudine (ZDV), combinations of antiretrovirals (ZDV and 3TC), or comparison of a modified version of the standard ZDV course vs. a single dose of nevirapine for the mother intrapartum and also for the newborn. The results of these studies may provide more affordable, alternative regimens to prevent maternal-to-child HIV-1 transmission for developing countries than the PACTG-076 protocol. It is very important that physicians and physician extenders (nurse practitioners and physician assistants) caring for infants born to HIV-infected mothers have an understanding of the pathophysiology of vertical HIV-1 infection transmission. They should be familiar with the conditions associated with an increased risk of transmission, interventions available to decrease this risk, current medications, and laboratory resources.     

Viral hepatitis: from A to E, and beyond?

Identification of hepatitis viruses A-E has enabled researchers to investigate the epidemiology, pathogenesis, sequelae, and possible means of prevention of these infections. This knowledge also provides a basis for further study of the pathological significance of candidate hepatitis viruses. With improvements in hygiene in many parts of the world, hepatitis A virus infection has decreased markedly. However, this success has the unintended consequence of rendering a large percentage of the younger population susceptible to hepatitis A virus infection. Fortunately, effective active immunization for hepatitis A virus is now available. Hepatitis B remains a common condition, especially in Asia and Africa which have high prevalences of chronic infection. Chronic hepatitis B carriers serve as reservoirs of infection for the community and are at risk of chronic liver disease and hepatocellular carcinoma. A mass immunization program in Taiwan has been remarkably successful in reducing the prevalence of chronic hepatitis B infection. Genotypes of the hepatitis B viruses may be associated with the severity of liver disease and the responses to therapies. Hepatitis C is another important cause of death worldwide. The infection easily becomes refractory and the chronicity contributes to the development of cirrhosis and hepatocellular carcinoma. Although no effective immunization is currently available for hepatitis C, it can be controlled by preventative measures and recently developed interferon-based treatments, especially in combination with ribavirin. The prevalence of hepatitis D has markedly decreased in the last decade and new cases are now rarely encountered. Hepatitis E is endemic in limited areas and travel to these areas appears to be the main risk factor for contracting the infection. Several new candidate hepatitis viruses have been identified, including GB virus-C, TT virus, and SEN virus, but none of these has been shown to cause hepatitis, and they may be passenger viruses.