Hepatitis B immunization in high risk neonates born from HBsAg positive mothers: comparison between plasma derived and recombinant DNA vaccine

A half dose recombinant hepatitis B vaccine (HBVax II, MSD, 5 micrograms) was investigated for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers as compared to the half-standard dose regimen of plasma derived hepatitis B vaccine (HBVax, MSD, 10 micrograms). Forty infants born to carrier mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either the recombinant or plasma derived hepatitis B vaccine. The infants were randomly divided into two groups of 20 infants each. The plasma derived vaccine (10 micrograms) was given to group I, while infants in group II received the recombinant vaccine (5 micrograms) at birth, 1 and 6 months of age. There were no statistically significant differences in the efficacy and the seroconversion rate of these two combined prophylaxis regimens. The protective efficacy rate of both kinds of HBV vaccine was found to be 94.6 and 89.2 percent in group I and group II respectively. At twelve months of age, the anti-HBs seroconversion rates were 95.0 percent in group I and 84.2 percent in group II. However, the geometric mean titres in group I (179.55 mIU/ml) was significantly higher than those in group II (42.2 mIU/ml) but the anti-HBs titre was still above protective level (10 mIU/ml) in most of the infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers

To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers.     

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.     

Hepatitis B e antigen seroconversion: effects of lamivudine alone or in combination with interferon alpha

Seroconversion of hepatitis B e antigen (HBeAg) is an important marker for resolution of active hepatitis B virus (HBV) infection and for a long-term positive response to treatment. Lamivudine, a nucleoside analogue, is the first effective oral treatment for chronic hepatitis B in patients with evidence of viral replication and liver disease. When appropriate patient groups are compared, treatment with lamivudine for 1 year leads to HBeAg seroconversion in a similar proportion of patients as a standard course of interferon (IFN) alpha therapy. Seroconversion increases during prolonged therapy (up to 3 years), and is sustained post-treatment in more than three-quarters of patients. Response rates are related to the pretreatment level of serum alanine aminotransferase (ALT) and reach 65% in those patients with serum ALT > 5 x upper limit of normal (ULN) after one year. For patients with pretreatment ALT > 2 x ULN, response was seen in 38% after one year, rising to 65% after 3 years. To date, combination with IFN and lamivudine has not been shown to confer additional benefit compared with lamivudine monotherapy. Lamivudine is effective and appropriate for use in a greater proportion of HBV infected patients than IFN alpha, particularly those infected at birth or in early childhood. Furthermore, because seroconversion after lamivudine is not normally associated with a severe flare of liver disease, as seen with IFN, it is more suitable for use in patients with active liver disease and cirrhosis. In conclusion, lamivudine is more suitable than IFN for a broad range of patients, including those with severe liver disease, recurrent flares, pre-core mutant HBV and those who have failed previously IFN treatment or are immunosuppressed. Lamivudine is also better tolerated than IFN.     

Trial of hepatitis B prophylaxis in children born to mothers carrying HBs antigen in New Caledonia

A prophylaxis trial of hepatitis B at birth was carried out in New Caledonia. Ninety-nine newborns from women carrying hepatitis B antigen during pregnancy were immunized. The prophylaxis protocol was as follows: anti-HBs immunoglobulin and the first dose of vaccine at birth if the mother was HBe Ag+ or HBe Ag- without anti-HBe, only vaccination if the mother showed anti-HBe antibodies. 73.8% had anti-HBs antibodies when checked at 6 months; at the age of one year, this figure was 60.4%. Four months after the booster injection, 68.3% were anti-HBs positive. Among all these children, three of them were born to HBe Ag+ mothers became HBs Ag/HBe Ag positive. The control group studied showed that mother-infant vertical transmission was not the only route of contamination in children in New Caledonia.     

Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.     

Hepatitis B immunization in high risk neonates born from HBsAg and HBeAg positive mothers: comparison of standard and low dose regimens

A reduced dose of plasma derived hepatitis B vaccine (Hevac B) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers. Forty newborn infants born of these mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either standard or reduced doses of HBV vaccine. The infants were divided into two groups of 20 infants each. The standard dose of HBV vaccine (5 micrograms) was given to group I, while infants in group II received reduced dose (2 micrograms) at birth and at 1, 2 and 12 months of age. There was no statistically significant difference in the efficacy and antibody responses of these two combined prophylaxis regimens. The protective efficacy rate of HBV vaccine was found to be 94.0 and 93.2 percent in group I and group II, respectively. At twelve months of age, the anti-HBs seroconversion rates were 80.0 percent in group I and 86.7 percent in group II, with geometric mean titres of 84.57 mlU/ml and 78.56 mlU/ml, in group I and group II, respectively. One month after a booster at one year of age, anti-HBs could be detected in 86.7 percent of the infants in both groups. The geometric mean titres were 429.04 and 664.81 mlU/ml, in group I and group II, respectively. Anti-PreS2 antibody was detected in high titre as early as 4 months after the first dose of HBV vaccine, with a geometric mean titre of 116.30 mlU/ml and 107.97 mlU/ml, in group I and group II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoregulation of the in vitro anti-HBs antibody synthesis in chronic HBsAg carriers and in recently boosted anti-hepatitis B vaccine recipients.

We report a study on immunoregulation of in vitro antibody to hepatitis B surface antigen (anti-HBs) synthesis induced by pokeweed mitogen (PWM) from peripheral blood mononuclear cells (PBMC) in chronic hepatitis B surface antigen (HBsAg) carriers and in 'high responders', (anti-HBs RIA ratio greater than or equal to 20 in serum), recently boosted with anti-hepatitis B vaccine. Anti-HBs was detected in 11 days PBMC supernatants (SN) from 24 out of 36 'high responders', but in none from 31 chronic HBsAg carriers, despite detectable amounts of polyclonal IgG and antibody to hepatitis B core antigen (anti-HBc) were produced. The lack of anti-HBs production by chronic HBsAg carriers did not seem to be determined by suppressor influences because T lymphocytes from the majority of chronic HBsAg carriers, co-cultured with 'high responders' PBMC did not suppress anti-HBs production. Co-cultures between HBsAg carriers T4 positive (helper/inducer) cells and allogenic 'high responder' non-T cells produced anti-HBs antibody, indicating that HBsAg carrier T cells are not deficient in this allogenic helper function under PWM stimulation. Allogenic cocultures between HBsAg carrier non-T cells and 'high responder' T4 positive cells failed in anti-HBs production: a specific B lymphocyte defect might be involved in the lacking anti-HBs synthesis in chronic HBV patients. Antigen-induced specific anti-HBs synthesis experiments indicate that B cells themselves seem to be the target for HBsAg-induced suppression of anti-HBs antibody response.     

A novel hepatitis B virus mutant coexisting with wild type virus in a carrier with negative HBsAg yet positive HBeAg and anti-HBs

BackgroundOccult infection of hepatitis B virus (HBV) has important impacts on both public health and clinical medicine.ObjectivesTo characterize the sequences of HBV S region in a chronic carrier with occult HBV infection.Study designSerological markers for HBV were tested by commercial kits. Western blotting was performed to detect HBsAg. PCR was used to amplify HBV S region; the resultant products were sequenced directly and cloned and then sequenced.ResultsTests with commercial kits showed that the carrier was HBsAg negative yet HBeAg positive. HBsAg was positive in Western blotting analysis. Although anti-HBs titers were as high as 5356–11,578 mIU/ml, serum HBV DNA was positive, ranging from 370 to 491 copies/ml. Wild type and mutant HBV coexisted in circulation. The mutant virus had mutations in both preS2 and S genes: the preS2 ATG mutated to ATA, and the S gene had a 15-nucleotide repeat insertion in the a determinant. By Blast search in the GenBank, the mutant virus had not been identified before. Nevertheless, the carrier had no signs of liver dysfunction during follow-up period.ConclusionWe identified a novel mutant HBV coexisted with wild type virus in a carrier with negative HBsAg and positive HBeAg and high level of anti-HBs.     

A novel hepatitis B virus mutant coexisting with wild type virus in a carrier with negative HBsAg yet positive HBeAg and anti-HBs

BackgroundOccult infection of hepatitis B virus (HBV) has important impacts on both public health and clinical medicine.ObjectivesTo characterize the sequences of HBV S region in a chronic carrier with occult HBV infection.Study designSerological markers for HBV were tested by commercial kits. Western blotting was performed to detect HBsAg. PCR was used to amplify HBV S region; the resultant products were sequenced directly and cloned and then sequenced.ResultsTests with commercial kits showed that the carrier was HBsAg negative yet HBeAg positive. HBsAg was positive in Western blotting analysis. Although anti-HBs titers were as high as 5356–11,578 mIU/ml, serum HBV DNA was positive, ranging from 370 to 491 copies/ml. Wild type and mutant HBV coexisted in circulation. The mutant virus had mutations in both preS2 and S genes: the preS2 ATG mutated to ATA, and the S gene had a 15-nucleotide repeat insertion in the a determinant. By Blast search in the GenBank, the mutant virus had not been identified before. Nevertheless, the carrier had no signs of liver dysfunction during follow-up period.ConclusionWe identified a novel mutant HBV coexisted with wild type virus in a carrier with negative HBsAg and positive HBeAg and high level of anti-HBs.     

Experiences with radioimmunoassay in the detection of HBsAg in the presence of anti-HBs.

Interference from anti-HBs present during hepatitis B antigenemia caused the appearance of several false negative reactions in a competition radioimmuno-precipitation procedure. The results indicate that such interference is considerably less in the solid-phase radioimmunoassay (Ausria II) and probably causes few false negative tests. The use of pepsin treatment as a means to destroy interfering antibodies is discussed.     

Effect of amphotericin B alone or in combination with rifampicin or clarithromycin against Candida species biofilms

Effectiveness of amphotericin B alone or in combination with rifampicin or clarithromycin on the killing of Candida species biofilms was investigated in vitro. Amphotericin B was assayed at 0.005 to 10 mg/ml. Rifampin and clarithromycin were assayed at 10 mg/ml. We studied 7 Candida albicans, 3 Candida parapsilosis, 3 Candida glabrata, 3 Candida krusei and 2 Candida tropicalis strains. Biofilms were developed in 96-well, flat-bottomed microtiter plates for 48 hours. A synergistic effect between amphotericin B and clarithromycin was demonstrated against 66.6% of C. parapsilosis, 66.6% of C. glabrata, and 42.8% of C. albicans biofilms. A synergistic effect between amphotericin B and rifampin was demonstrated against 66.6% of C. parapsilosis, 42.8% of C. albicans, and 33.3% of C. glabrata biofilms. No synergistic effect was observed against C. krusei or C. tropicalis biofilms with any of the combinations. Rifampin or clarithromycin alone did not exert any effect on Candida species biofilms. Rifampin or clarithromycin combinations with amphotericin B might be of interest in the treatment of Candida biofilm-related infections.     

乙型肝炎核酸疫苗NV—HB／s肌注小鼠后HBsAg的表达和抗 …

目的 研究乙型肝炎核酸疫苗肌注小鼠后在体内的表达及小鼠体液免疫应答的规律,同时观察接种局部组织的病理变化。方法 以乙型肝炎核酸疫苗ＮＶ－ＨＢ／ｓ肌注小鼠,然后定期分批处死,采集肌注局部组织检测ＨＢｓＡｇ（ＡＢＣ免疫组化法）,采集外周血标本检测ＨＢｓＡｇ和抗－ＨＢｓ（ＥＬＩＳＡ法０,并常规病理检查。     

Markers of hepatitis-viral infection in children born of mothers with hepatitis B

Sixty-two women suffering from hepatitis B (HB) and their newborn babies were examined by a highly sensitive radioimmunoassay (RIA). The fluorescent antibody technique was also used to examine autopsy specimens of livers of 7 fetuses, 1 stillborn, and 3 babies dying in the first days of life whose mothers during pregnancy or delivery had experienced HB. Frequent infection of babies (77.8%) was observed at high concentrations of HBsAg in mothers in labor with subsequent development of persisting HBs-antigenemia, and in half of the babies of chronic hepatitis. HBsAg was detected in the first days of life not only in the blood serum, but also in the liver tissue which may be explained by intrauterine infection. At low concentrations of HBsAg in mothers the babies were infected less frequently (26.1%) and half of them were shown to have anti-HBs in the umbilical blood and blood serum in the first days and months of life. Anti-HBc transmission from mothers was also demonstrated. In babies born to convalescents after HB in the absence of HBsAg, anti-HBs in combination with anti-HBc were determined.     

Response to hepatitis B vaccine in family members of HBsAg carriers

The family members of HBsAg carriers have an increased risk of hepatitis B virus (HBV) infection. 214 subjects from 98 families with no HBV markers were randomized to receive hepatitis B vaccine: HEVAC B (Institute Pasteur) or GCC VAC (Green Cross Corporation) at 0, 1, and 5 months. Of those who completed the course, 87.8% had an anti-HBs response of greater than 10 mIU/ml at 6 months. The response rate was similar for both sexes. There was a decrease in response rate and anti-HBs titre with age. The response rate for HEVAC B was 92.5% and GCC VAC 84.3%. The offspring had comparable response to the spouses who were not blood relatives of the index carriers, but this could be related to their younger age. Discriminant analysis showed that a higher anti-HBs titre was associated with HEVAC B, younger age, and less direct relationship with the index carrier.     

Low-Level Viremia and Intracellular Expression of Hepatitis B Surface Antigen (HBsAg) in HBsAg Carriers with Concurrent Hepatitis C Virus Infection

Assays of hepatitis B virus (HBV) replication and antigen expression in HBV surface antigen (HBsAg) carriers with concurrent hepatitis C or D virus (HCV or HDV) infection revealed that HCV and HDV can suppress HBV replication but that HCV also substantially suppresses HBV surface protein expression. HBsAg carriers with concurrent HCV infection thus have low-level viremia and intracellular HBsAg.