Perinatal transmission of the hepatitis b virus and of the hbv-associated delta agent from mothers to offspring in northern italy

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P <.01) yet consistent risk of infection. 2. HBs antigenernia is usually prolonged and symptomatic in babies born to HBeAg–positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:10³) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.     

Efficacy of hepatitis-B immunoglobulin and hepatitis-B vaccine in prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg

Combined prophylaxis of perinatal transmission of hepatitis B virus (HBV) with hepatitis-B immunoglobulin (HBIG) and hepatitis-B vaccine was investigated in 40 infants born to HBeAg positive carrier mothers. The efficacy of two combined prophylaxis schedules was compared to 78 similar infants in the control group receiving no treatment, by following the HBV markers at regular intervals up to one year of age. In both schedules, the HBIG and HBV vaccine were given at birth, followed by HBV vaccine given at 30 days and 60 days (group I) or 180 days (group II) of age. The incidence of persistent HBsAg carrier in infants born to HBeAg positive carrier mothers was significantly reduced from 92.6 percent at one year of age in the control group to zero percent (group I) and 11.5 percent (group II) in the treated groups. There was no statistical significant difference in the efficacy of these two combined prophylaxis schedules. HBIG given at birth did not interfere with infant immune response to the hepatitis B vaccine. At twelve months of age, anti-HBs could be detected in 77.8 percent of infants in group I and 89.5 percent in group II with mean titre of 621.4 and 1148.0 in group I and group II respectively. It was concluded that combined prophylaxis with HBIG and hepatitis-B vaccine immediately after birth is the best method for prevention of HBV perinatal transmission from HBeAg positive carrier mothers to their infants.     

Reduced doses of hepatitis B immune globulin in the prevention of perinatal transmission of hepatitis B

From October 1982 to May 1983, newborn infants of 79 hepatitis B surface antigen (HBsAg)-positive women were enrolled in a study of the efficacy of hepatitis B immune globulin (HBIG) in the prophylaxis of perinatal transmission of hepatitis B virus (HBV) infection. HBIG 0.5 ml or 0.25 ml was given to the newborn within 15 minutes of birth and at 3 and 6 months. The mother-infant pairs were followed-up every 3 months for at least 9 months. Similar observations of untreated infants were used for comparison. Among infants of hepatitis B e antigen (HBeAg)-positive carrier mothers, the HBsAg carrier rates at 3 months were similar in the 0.5-ml and 0.25-ml HBIG dose groups. At 12 months the difference--17.7% of 17, 40% of 15--did not reach statistical significance, but the differences between these rates and that of the untreated control-85.7% of 35--did. Among infants of HBeAg-negative carrier mothers, HBV infection rates in both dose groups were similar to those of untreated infants. In the treated groups at 12 months about 45% of infants of HBeAg-positive mothers and 90% of infants of HBeAg-negative mothers were still negative for HBsAg and anti-HBs. Vaccination to induce active antibody is necessary to prevent postnatal infection and chronic carriage of HBV. To reduce the cost of combined passive and active hepatitis B immunoprophylaxis in children born to HBeAg-positive carrier mothers, 0.25 ml of HBIG could be used instead of the usually recommended 0.5 ml.     

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.     

Prevention of perinatal transmission of hepatitis B virus (HBV): a comparison of two prophylactic schedules

Perinatal transmission of hepatitis B virus (HBV) from HBsAg carrier mothers who were HBeAg+, antiHBe+, or negative for both HBe markers, was interrupted using either 4 doses of vaccine, or one dose of hepatitis B immunoglobulin (HBIG) at birth, combined with 4 doses of vaccine. In those infants who received HBIG at birth, the antiHBs titre was significantly higher at 1 and 2 months old, but at 6, 9, and 18 months old, there was no significant difference. Among the infants of carrier mothers who did not display HBeAg (i.e., were antiHBe+, or negative for both HBe markers), a transient subclinical infection would have been expected in around 10% had there been no intervention. No evidence of such infection was detected, and no difference in outcome was found between the two treatment groups. Amongst infants born to HBeAg+ carrier mothers, infection occurred in 1 out of 8 who had received HBIG and vaccine, and in 3 of 8 who had received vaccine only. The difference in outcome was not statistically significant, but the numbers analysed were small. The infections which occurred in spite of prophylaxis may be attributable to in utero infection, poor response to vaccine by the infant, or to the mother having a particularly high HBV-DNA level. HBIG given at birth to infants of HBeAg+ carrier mothers may enhance the protection of infants who are destined to be poor responders to vaccine.     

Perinatal transmission of hepatitis B virus in high-incidence countries

Hepatitis B is a serious public health problem throughout the world. Hepatitis B virus (HBV) induces acute hepatitis with a case-fatality rate of about 1%. Even more important, 5-10% of patients infected with HBV become chronic carries and about 25% of these will die due to cirrhosis and hepatocellular carcinoma. The reservoir of HBV chronic carriers in the world is estimated at more than 200 million people and 80% of them reside in Asia and the western Pacific. In high-incidence areas, such as south-east Asia, perinatal transmission of HBV from carrier mothers to newborns appears to be the most important factor for the high prevalence of HBV infection and 70-90% of infants born to HBsAg/HBeAg-positive mothers become chronic carriers. Three possibilities of transmission of HBV from carrier mothers to newborns are suggested: (a) transplacental transmission in utero - it was estimated that such transmission occurred in 5-15% of newborns; (b) transmission during delivery, which is considered the main mode of perinatal transmission; (c) postnatal transmission from mother to newborn, which is not common. HBeAg is the main maternal factor in determining whether infection of newborns will occur; the expression of this antigen seems to be determined genetically. Recently it has shown that immunoprophylaxis is highly effective in preventing the development of the carrier state in infants born to HBsAg/HBeAg-positive mothers. Only 5-10% of high-risk infants are not protected by vaccination. If it becomes possible to immunize the entire world population including all babies born to carrier mothers at birth, and if our knowledge of the mechanisms of perinatal transmission of HBV is accurate, the carriers and acute cases of HB ought to disappear in two to three generations.     

乙型肝炎病毒母婴阻断长期效果的随访研究

目的观察乙型肝炎病毒母婴阻断长期效果,探讨HBsAg阳性孕妇生产儿童发生慢性HBV感染的相关影响因素。方法随访和收集于2004--2006年在北京地坛医院出生的HBsAg阳性母亲所生,并在出生时进行200单位乙肝免疫球蛋白（HBIG）注射和经过乙肝疫苗10μg,0、1和6个月的完整免疫接种程序的儿童静脉血,采用Abbott微粒子化学发光法检测其HBsAg、抗-HBs抗体、抗-HBc抗体,分析母婴阻断和乙肝疫苗接种的长期效果及其影响因素。结果收集和调查306名儿童年龄3—6（4．84）岁,其母亲生产时HBeAg阳性198人,HBeAg阴性92人。10（3．27％）名儿童发生慢性HBV感染。除慢性HBV感染者外,其余296名儿童,20．27％抗-HBs〈10mlU／ml;44．26％抗-HBs≥10—100mlU／ml;27．03％抗-HBs≥100～1000mlU／ml和8．45％抗-HBs≥1000mlU／m,抗-HBs保护率为79．73％（236／296）。抗-HBc阳性率为7．43％（22／296）。10例感染儿童的母亲生产时HBeAg均为阳性,HBVDNA均在10。拷贝／ml以上,其中8例超过10^8拷贝／ml。结论在进行乙肝疫苗加HBIG注射的HBV母婴传播阻断措施下,HBV母婴阻断失败和慢性H13V感染发生在HBeAg阳性和高病毒载量产妇所生婴儿,在有效阻断后仍需进行抗HBs监测并加强免疫接种。     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.     

Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk.

Israel has no official prevention policy at present against perinatal and horizontal transmission of hepatitis B virus (HBV) infection in newborns and children at risk. The present study was designed to assess the prevalence of HBV carrier state in a population of 11,123 pregnant women at term. Among this population (mean age 29.7 +/- 5.9), 98 women (0.88%) were found to be asymptomatic HBsAg+ carriers, and 97% of these carriers were anti-HBe+. Evidence for HBV replication, as determined by serum HBV-DNA, was established in 6.6% of the HBsAg+/anti-HBe+ population. The HBsAg carrier rate was strongly influenced by religion, continent, and country of birth of the carrier mothers. The highest relative carrier rate was found among women of Moslem origin (4.3%), as compared to Jewish women (0.67%). Most carrier women were born in Israel (56.1%) to mothers who had emigrated from regions with intermediate or high endemicity of HBV, such as North Africa or the Middle East. In these groups, the HBsAg carrier rate ranged between 1.2 and 3.0%. Ninety-three percent of newborns receiving passive/active vaccination against HBV developed protective levels of anti-HBs. Finally, evidence for horizontal transmission of HBV was found in 19.3% of 83 non-vaccinated children in families of HBsAg carriers. The present study therefore establishes HBsAg prevalence rates in specific risk groups of women at term and confirms the need for an official policy on immunization against HBV in Israel. Since over 50% of women at term belong to the defined risk groups, universal active vaccination of the entire newborn population each year is suggested as the most rational and needed policy in Israel.     

重组酵母乙肝疫苗对新生儿免疫效果的评价

目的研究新生儿接种国产5μg重组酵母乙肝疫苗的免疫效果及影响因素。方法从东莞市石碣医院预防接种门诊登记的,2005年7～12月出生的,按规定接种程序完成乙肝疫苗接种的新生儿中随机抽取303名进行横断面调查研究。结果新生儿免疫后抗-HBs几何平均滴度（GMT）为（201.36±14.89）mIU/ml。母亲乙肝HBsAg阳性/阴性、母亲乙肝HBeAg阳性/阴性、男/女、是否出生低体重、是否早产、本地/外地的新生儿之间抗-HBs抗体GMT差别无统计学意义（P〉0.05）。抗-HBs阳转率为97.69%,达到卫生部规定的免疫成功率指标（85%）（t=6.19,P〈0.001）;母亲HBsAg阳性/阴性、HBeAg阳性/阴性的新生儿之间抗-HBs阳转率差别有统计学意义。新生儿HBsAg阳性率0.33%,母亲乙肝HBeAg阳性/阴性的新生儿HBsAg阳性率差别有统计学意义（P〈0.05）。免疫后母婴传播阻断保护率为96.16%。结论新生儿接种国产5μg重组酵母乙肝疫苗具有良好的免疫效果,与乙肝免疫球蛋白100 IU联合使用,有良好的母婴传播阻断保护作用。母亲乙肝感染状况（HBsAg、HBeAg阳性）是影响新生儿乙肝抗-HBs阳转率的危险因素;母亲乙肝HBeAg阳性是影响新生儿乙肝疫苗母婴传播阻断保护率的危险因素。     

Hepatitis b e antigen and antibody: detection by radioimmunoassay in chimpanzees during experimental hepatitis b

Hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) were evaluated using a sensitive radioimmunoassay (RIA) in weekly serum samples obtained from nine chimpanzees experimentally infected with hepatitis B virus (HBV). In two chimpanzees with HBV infection with detectable hepatitis B surface antigen (HBsAg) for less than five weeks, and in one chimpanzee with documented HBV infection with no detectable HBsAg, HBeAg was not detected; in all three, anti-HBe became detectable early in the infection. In six chimpanzees in which HBsAg was detected for 16 weeks or longer, HBeAg was detected early in the infection; in five, anti-HBe became detectable and HBeAg unde-tectable prior to the clearance of HBsAg. The sixth remained HBsAg-positive and HBeAg-positive for more than two years and never developed anti-HBe. These results confirm the sensitivity of this RIA and its value in predicting the course of HBV infections.     

新生儿不同时期静脉血HBsAg含量对HBV母婴传播阻断失败的预测研究

目的探讨HBV慢性感染孕妇新生儿出生后不同时期静脉血HBsAg含量变化对ItBV母婴传播阻断失败的预测价值。方法以HBsAg、HBeAg双阳性、血清HBVDNA含量≥10^5拷贝／ml慢性HBV感染孕妇所娩新生儿150例为研究对象,出生后立即注射乙肝免疫球蛋白200Iu,并按0、1和6个月程序接种乙肝疫苗10～20μg。分别于新生儿出生时、生后1个月、生后7个月采取静脉血检测HBV血清学指标,分析新生儿不同时期静脉血HBsAg含量对HBV母婴传播阻断失败的预测。结果共有11例新生儿发生HBV母婴阻断失败。新生儿出生时、生后1个月、生后7个月HBsAg阳性率分别为41．26％、10．49％、7．69％,HBeAg阳性率分别为97．90％、65．75％、13．29％。以出生时I-IBsAg≥O．05和HBsAg≥1IU／ml预测HBV母婴传播阻断失败,阳性预测价值分别为18．64％和70％;生后1个月HBsAg〉~O．05和HBsAg≥1IU／ml的阳性预测价值分别为73．33％和100％。结论出生时静脉血HBsAg含量≥1IU／ml时应高度怀疑HBV母婴传播的失败。生后1个月HBsAg≥1IU／ml对母婴传播阻断失败有高度的预测价值,如何提高出生时和生后1个月静脉血HBsAg阳性新生儿的HBV感染阻断率是以后研究的重点。     

Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies

It is well documented that perinatal transmission is the major cause of chronic HBV infection in China. However, the mechanisms of HBV perinatal transmission are not defined clearly. It is not known whether hepatitis B e antigen can cross the human placenta, and the rate of HBeAg decay in babies with and without HBV breakthrough has not been studied. In this study, HBV serological markers were investigated in 95 hepatitis B surface antigen positive pregnant women. These markers were also studied in the babies at birth and at the age of 6 months and 12 months. The data show that 7.4% (7/95) children were infected with HBV during the first year after birth despite receiving passive-active immunoprophylaxis with hepatitis B immune globulin and hepatitis B vaccine. The surface gene fragment of HBV DNA was cloned and sequenced following PCR amplification in 7 cases of HBsAg positive babies and their mothers. All babies had the same sequences as their mothers, although two babies also had sequences that would produce an amino acid substitution within the "a" determinant. Furthermore, we measured HBeAg titers and HBV DNA levels by using Abbott AxSYM system and LightCycler-based real-time fluorescence quantitative PCR in 54 mother-infant pairs. Thirty-three mothers were HBeAg positive, and 21 mothers were HBeAg negative. Seventy percent (23/33) of neonates from HBeAg-positive mothers were HBeAg positive at birth compared with 0% (0/21) of neonates from HBeAg negative mothers. HBeAg was present at higher titer in the birth sera of the babies with HBV breakthrough than in babies without breakthrough. HBeAg was cleared from the serum in all 19 babies without breakthrough. In 17 of these 19 babies, the HBeAg was cleared within 6 months, and in two babies clearance took 12 months. The mean serum HBV DNA level in the mothers of the 4 infants with HBV breakthrough was significantly higher than in the mothers of babies who did not become infected. In conclusion, this data suggests that HBeAg can cross the human placenta, and disappears from serum within 6 months in most babies. HBV DNA levels in hepatitis B carrier mothers are associated with the failure of HBIG and vaccine immunization, and the additional influence of transmitted HBeAg cannot be excluded.     

HBV viremia in newborns of HBsAg(+) predominantly Caucasian HBeAg(−) mothers

BackgroundHepatitis B virus infection is an important public health problem worldwide and eliminating mother-to-infant transmission is important to decrease the prevalence of chronic HBV-infection. Although, immunoprophylaxis given at birth largely prevents mother-to-infant transmission, perinatal HBV viremia has been reported in HBsAg(?) newborns born mainly to HBeAg(+) women in endemic areas.ObjectivesTo examine the incidence of perinatal HBV viremia in newborns of HBsAg(+) predominantly HBeAg(?) mothers.Study designPeripheral blood was obtained at birth from 109 HBsAg(+) mothers and their newborns before the administration of active–passive immunoprophylaxis. Infants were prospectively followed and appropriately vaccinated.ResultsAlthough most (92.7%) of the HBsAg(+) mothers were HBeAg(?), 73.4% had detectable HBV viremia. Neonatal viremia was detected in 3/8 (37.5%) and 24/101 (23.8%) newborns of HBeAg(+) and HBeAg(?) mothers, respectively (p = 0.386). However, HBV–DNA levels were significantly higher in newborns of HBeAg(+) mothers (p = 0.025). No child developed chronic HBV infection, but one child had evidence of subclinical hepatitis.ConclusionsAlthough the clinical significance of low viremia levels in almost one in four newborns of HBsAg(+) mothers in a low endemicity area is unclear, it may enhance our understanding of HBV mother-to-infant transmission.     

Reversed passive hemagglutination test fails to detect HBsAg in a number of HBeAg positive sera

In endemic areas of hepatitis B virus (HBV) infection, perinatal transmission from asymptomatic HBsAg carrier mothers to infants plays a major role in the transmission of HBV. HBeAg indicates a high level of viral replication and infectivity. Most of the infants born to HBeAg positive mothers become carriers. Prenatal screening of HBsAg would identify infected mothers and thus allow preventive administration of immunoglobulin and immunization to the newborns. Reversed passive hemagglutination assay (RPHA) is commonly used in Thailand for HBsAg screening. However this method has low sensitivity and gives false negative results. Therefore, infants born to HBsAg false negative mothers would not receive proper immunization. This study reveals the rate of false negative results for HBsAg by RPHA in high infectivity sera. Of 985 sera which were HBsAg positive by ELISA, 70 (7.1%) were negative for HBsAg by RPHA. Of these 70 false negative sera, 7 (10%) were HBeAg positive. Our results indicate that RPHA is a less sensitive method for detection of HBsAg than ELISA. RPHA can give false negative results even in sera with high HBV infectivity. Therefore, RPHA should be replaced by EIA for prenatal HBsAg screening or any other screening for HBV infection whenever possible.     

Field evaluation of the efficacy and immunogenicity of recombinant hepatitis B vaccine without HBIG in newborn Vietnamese infants

A study involving more than 2,000 infants was conducted in Vietnam to assess the field effectiveness and immunogenicity of recombinant hepatitis B vaccine given at birth, 1 month, 2 months, without concomitant hepatitis B immune globulin (HBIG). All received a 5 microg dose of H-B-VAX II at birth. Infants born to non-carrier mothers (Group 1; N = 1798) then received 2.5 microg doses at 1 and 2 months of age, while infants of HBeAg-negative (Group 2; N = 125) or HBeAg-positive (Group 3; N = 88) carrier mothers received 5 microg doses. No Group 1 or 2 vaccinees were infected. In Group 3, 12 (14.6%) of 82 infants did become infected (estimated efficacy 84%). 98.0-98.6% of uninfected infants who were tested for anti-HBs developed a seroprotective concentration > or = 10 IU/L. In hyperendemic Vietnam, where routine maternal screening and passive-active prophylaxis of high-risk infants with vaccine plus HBIG is not feasible, administration of vaccine alone to all newborns may control effectively HBV infection.     

Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area

One hundred eleven newborn infants born of Spanish hepatitis B surface antigen (HBsAg) carrier mothers were consecutively assigned to one of three treatment groups. Group A was treated with three or four doses of hepatitis B immune globulin (HBIG) in one of three different schedules. Group B received one dose of hepatitis B vaccine (Hevac-B, Pasteur) at birth and at 1, 2 and 12 months. Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth. Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months. The three immunization protocols were equally effective, since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection. There were five transient and subclinical infections among children who received only HBIG (group A), one transient infection in group B, and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection, since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months. Although the percentage of responders in the two vaccinated groups did not differ significantly, children who received only vaccine reached higher antibody levels than those who also received HBIG. Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious.     

Dynamics and impact of perinatal transmission of hepatitis B virus in North India

The magnitude and significance of perinatal transmission of hepatitis B virus (HBV) were assessed in infants of 8,575 women, of whom 3.7% were seropositive for HBV surface antigen (HBsAg). The e antigen of HBV (HBeAg) was found in 7.8% of these carriers, the antibody to HBeAg (anti-HBe) was found in 30.1% of them, and HBsAg alone was found in 62.1% of them. The estimated incidence of HBsAg positivity by 6 months of age in infants of carrier women was significantly (P less than .001) higher than in controls (18.6% vs 3.0%). Transmission was most frequent (87.5%) if the carrier mother was HBeAg positive and was much less so if she was positive for anti-HBe (17.5%) or for HBsAg alone (9.6%). Toward the end of infancy incidence of HBsAg positivity among offspring of carriers and among controls was not different. Most infants positive for HBsAg and HBeAg continued with the infection beyond 6 months of age. It is estimated that about one-third of the adult asymptomatic HBV carriers in India evolve directly from perinatal infection, while the majority become infected during childhood or early adulthood.     

Sequence analysis of hepatitis B virus genomes from an infant with acute severe hepatitis and a hepatitis B e antigen-positive carrier mother

It is well known that fulminant hepatitis B can occur in infants born to hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers, whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis B born to a HBeAg-positive mother. The aim of this study was to determine whether HBV variants contribute to the pathogenesis of fulminant hepatitis and severe hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence of HBV genomes from the infant and his HBeAg-positive carrier mother was analyzed. All HBV isolated from the infant and his mother were subtype adr. The sequences of the cloned HBV genomes, each including a part of the X and precore/core regions, isolated from the infant were almost identical (homology of 99.1-99.9%) to those from his mother. There was no mutation in any of the 17 clones examined at nucleotides 1762 and 1764 in the core promoter, which is reported to be associated with fulminant hepatitis. A point mutation at nucleotide 1758 in the second AT-rich region of the basic core promoter was present in all clones. None of the clones had a point mutation at nucleotide 1896 of the precore region. In this study, no specific HBV variants contributing to the development of neonatal severe hepatitis were found. There is a possibility that host factors rather than viral factors play an important role in some cases of severe neonatal hepatitis B.