Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers

OBJECTIVE: To assess the presence of antibody to hepatitis B surface antigen (anti-HBs) at postvaccination testing in Minnesota health care workers receiving recombinant hepatitis B vaccines, and to identify risk factors for lacking anti-HBs following hepatitis B vaccination. DESIGN: Retrospective cohort study. SETTING: Ten acute care hospitals in Minnesota. PARTICIPANTS: A total of 595 health care workers who had received hepatitis B vaccine (Recombivax HB or Engerix-B) between June 1987 and December 1991 and who underwent postvaccination testing for anti-HBs within 6 months after receiving the third dose of vaccine. MAIN OUTCOME MEASURE: Presence or absence of anti-HBs following hepatitis B vaccination. RESULTS: Five variables were independently associated with lacking anti-HBs by multivariate analysis: vaccine brand, smoking status, gender, age, and body mass index. Stratifying by vaccine brand demonstrated that age (P = .01), body mass index (P < .01), and smoking status (P < .01) were associated with lacking anti-HBs only for Recombivax HB recipients; and gender (P = .03) was associated with lacking anti-HBs only for Engerix-B recipients. After controlling for smoking status, age, gender, and body mass index, recipients of Recombivax HB were more likely to lack anti-HBs than recipients of Engerix-B (relative risk, 2.3; 95% confidence interval, 1.1 to 4.7; P = .02). CONCLUSIONS: Results indicate that certain populations of health care workers are at increased risk of not responding to hepatitis B vaccination. Further studies evaluating immunogenicity of currently available recombinant hepatitis B vaccines in persons at high risk for primary vaccine failure are needed.     

Immune status in preschool children born after mass hepatitis B vaccination program in Taiwan

A mass hepatitis B vaccination program began in Taiwan in 1984. In order to determine the immune status of hepatitis B virus (HBV) infection among preschool children, a total of 25 kindergartens in 20 townships and metropolitan precincts in central Taiwan were randomly selected through stratified sampling. Serum specimens of 2130 healthy preschool children aged 2-6 years old were screened for the HBV markers and liver function in 1996. HBV surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against HBV core antigen (anti-HBc) were tested by reverse passive hemagglutination (RPHA), enzyme immunoassay (EIA) and radioimmunoassay (RIA) using commercial kits. HBV vaccination rate of the preschool children was 98%, and complete vaccination rate (three or four doses of HBV vaccine) was 94%. The HBsAg seropositive rate was 4.5% among incomplete vaccinees and 1.3% among complete vaccinees. The anti-HBs was detectable in 1637 of 2000 complete vaccinees (81.9%) and in 53 of 88 incomplete vaccinees (60.2%). The overall prevalence rate of anti-HBc was 2.4% (52 of 2130). The older the age, the lower the anti-HBs seropositive rate. The anti-HBs seropositive rats for complete vaccinees were 100% at 2 years old and 75% at 6 years old. There were no significant differences in HBsAg-seropositive rates and anti-HBs-seropositive rates among different residential areas or ethnic groups. There were three children who were seropositive on HBsAg, anti-HBs and anti-HBc, whether they were infected by the vaccine-induced escape mutant of HBV deserves scrutiny.     

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in neonates

BACKGROUND: Most of the licensed hepatitis B vaccines produced by recombinant DNA contain the S protein component of the hepatitis B virus surface antigen particle but lack two important components, Pre-S1 and Pre-S2. These components have recently been shown to play an important immunogenic role by enhancing the hepatitis B surface antibody (anti-HBs) titers, stimulating response and circumventing genetic nonresponsiveness. OBJECTIVE: To assess safety, tolerability and immunogenicity in neonates of a novel recombinant HBV vaccine (Bio-Hep-B) containing the S, Pre-S1 and Pre-S2 components compared with a licensed recombinant vaccine (Engerix-B) containing the S component only. METHODS: Healthy neonates were randomized to receive either Bio-Hep-B (2.5 micrograms/dose) or Engerix-B (10 micrograms/dose) at ages < 24 h, 1 month and 6 months. Blood was obtained at ages 0, 1, 7 and 12 months. Tolerability was assessed by diary cards filled by the parents for 5 successive days after immunization. Immunogenicity was assessed by determination of anti-HBs antibody. RESULTS: Of 205 neonates 153 were in the Bio-Hep-B group and 52 were in the Engerix-B group. Both vaccines were well-tolerated and all infants became seroprotected (anti-HBs > 10 mIU/ml). After the first dose a significantly higher proportion of neonates seroconverted in the Bio-Hep-B group than in the Engerix-B group (83% vs. 34%; P < 0.001); this difference in seroresponse was even more pronounced for those achieving seroprotective concentrations (> 10.0 mIU/ml) after the first dose: 54% vs. 7%, respectively (P < 0.001). Geometric mean concentrations were significantly higher at all points in the Bio-Hep-B group. CONCLUSION: Both vaccines were well-tolerated and immunogenic. Bio-Hep-B, despite its low dose, was significantly more immunogenic and elicited more rapid antibody response. This finding has implication for future vaccine programs in regions where maternal screening for hepatitis B virus surface antigen and administration of hepatitis B immunoglobulin are not routinely practiced at birth for infants of hepatitis B virus carrier mothers.     

Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and Sprague-Dawley brains

BACKGROUND: Primary liver cancer is an important health problem in Korea, where hepatitis B virus (HBV) infection is prevalent. The authors conducted a prospective cohort study to evaluate the protective effect of HBV vaccination against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30 comprised the study population. They were clinically free of liver diseases, and had not been vaccinated against HBV at enrolment. The results of HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of the vaccination programme which took place during 1985 were used for the construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094 were anti-HBs positive, and 273,277 were negative for both. Among the candidates for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated against HBV during 1985. Cases of liver cancer were ascertained by record linkage and from medical records covering 1986-1989. A multivariate log-linear model was used to test statistical significance and to estimate relative risks (RR). RESULTS: The total follow-up period was 1,404,566 person-years, with an average of 3 years and 10 months. A total of 302 incident cases were ascertained. The overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With reference to the incidence level among the unvaccinated and uninfected, the RR of primary liver cancer among the chronically infected and that of the unvaccinated and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60), respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09). CONCLUSIONS: This study suggested that artificial immunization through HBV vaccination, even in adulthood, reduces the risk of liver cancer. It might also offer a practicable means of primary prevention, especially in areas with hyperendemicity of HBV infection.     

Long-term persistence of anti-HBs after vaccination with a recombinant DNA yeast-derived hepatitis B vaccine: 8-year results

The aim of this study was to evaluate the persistence of antibodies 7 years after hepatitis B booster administration in healthy adult volunteers who were vaccinated in 1986. In October 1986, 188 seronegative, healthy adult volunteers (117 men and 71 women) were vaccinated with a 20 micrograms dose recombinant DNA yeast-derived hepatitis B vaccine. Mean age of the study group was 23.3 years (+/- 0.28). Immunisation was carried out according to a 0-1-2 month vaccination schedule, with a booster dose at 12 months. Of the 159 subjects who received the full vaccination course, 63 (40%) had a blood sample taken 8 years after the first vaccination. Of these 63 subjects, five were excluded from the analysis due to an irregular vaccination schedule and four subjects did not complete the accompanying questionnaire on possible booster administration. So, 54 subjects remained available for further analysis. Fourteen individuals had received an additional booster of hepatitis B vaccine sometime between 1989 and 1994. The geometric mean titre (GMT) at month 13 for these 14 individuals was 1494 mIU ml-1, compared with 3103 mIU ml-1 for those who did not receive an interim booster. Forty subjects, who received no additional booster dose besides that of month 12, met the inclusion criteria of the follow-up study. Of these, all subjects except one were seropositive for anti-HBs at month 96 (GMT: 215.9 mIU ml-1). All subjects were still anti-HBc negative at that time. Distribution of individual antibody titres revealed that overall 92.5% of subjects retained protective antibody levels (> or = 10 mIU ml-1); 72.5% of vaccinees retained high levels of anti-HBs (> or = 100 mIU ml-1) as compared to 99.2 and 97.0% at month 13, respectively. A positive correlation was found between the subjects' titres at month 13 and month 96. A 0-1-2 dose vaccination course with a booster dose administered at month 12, induces a protective immune response which lasts at least until 7 years after the full vaccination course of the subjects. A positive correlation was found between the anti-HBs antibody titres at month 13 and month 96.     

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.     

Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences. 1. Safety and immunogenicity in young, healthy adults

The safety and immunogenicity of a yeast-derived recombinant hepatitis B virus (HBV) vaccine containing surface antigen (S) and selected preS1 and preS2 sequences (S-L*) were compared with those of a vaccine prepared with S alone (Engerix-B). S-L* consisted of composite particles containing S and L* at a ratio of 70/30. L* encompassed amino acid residues 12-52 of preS1 residues 133-145 of preS2, and the entire S domain. A total of 100 healthy, HBV-seronegative, young adults were randomized to receive 20 micrograms/dose of either S-L* or Engerix-B under double-blind conditions according to a 0-, 1-, 2-, 12-month schedule. In vivo humoral and in vitro lymphoproliferative responses to S and preS regions were monitored. Addition of the selected preS sequences to S did not enhance the in vivo humoral anti-HBs response but improved the in vitro stimulating capacity of the antigen (L*) in S-L* primed subjects.     

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.     

Antenatal diagnosis of esophageal atresia with tracheoesophageal fistula

We have studied the antibody response to hepatitis B vaccine in 42 hemodialysis patients; 8 of them were diagnosed as having HCV infection before vaccination. Hemodialysis patients received four doses of recombinant HB vaccine (Engerix-B, SKB, 40 micrograms per dose). Seroconversion occurred in 71.4% of all hemodialysis patients; in 79.4% of HCV-negative and in 37.5% of HCV-positive patients. Effective immunity (anti-HBs titer higher than 100 m IU/ml) was observed in 12.5% of HCV positive and in 35.3% of HCV-negative patients. We conclude that HCV infection may modify or postpone the response to hepatitis B vaccine.     

The direction of bladder displacement by adnexal masses

BACKGROUND: Vaccination against the hepatitis B virus (HBV) of health care staff during their studies would have the advantage of early prevention when the prevalence of infection is presumably low. METHODS: The population to be protected is made up of 1533 medical and nursing students. In those who accepted, anti-HBc was determined and information was obtained concerning circumstances of exposure to HBV. Vaccination was offered to all the cases of negative anti-HBc. Individuals receiving 3 doses of the vaccination (20 micrograms at 0, 1 and 6 months) were seen at 4-7 months of the last dose to determine the anti-HBs titers achieved. RESULTS: One thousand sixty-five students (70%) accepted inclusion into the prevaccination anti-HBc study and 1,029 (3.4%) were anti-HBc negative. Only older age and previous transfusions and jaundice were significantly associated to greater prevalence of infection by HBV. The adherence to 1, 2 or 3 doses of the vaccination was 96%, 94% and 87%, respectively. Following the 3 doses, > or = 10 UI/I of anti-HBs were detected in 97% of the cases studied with geometric measurement of the responders being 1580 U/I. The titer had an inverse relation which was not significant with age. CONCLUSIONS: The high participation in the program of anti-hepatitis B vaccination and the excellent immune response observed leads to the recommendation of systemic vaccination to future health care professionals during their study period. Furthermore, the low prevalence of previous HBV infection advises against previous detection of anti-HBc with immunization of the whole collective being more effective.     

Feasibility study of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine, and comparison of clinical reactions and immune responses with diphtheria-tetanus-acellular pertussis (DTPa) and hepatitis B vaccines applied as mixed or injected into separate limbs

The feasibility of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine was assessed and a comparison made of immunogenicity and reactogenicity to DTPa and HBV vaccines mixed in one syringe and to concomitant but separate injections as a primary vaccination course in three groups of infants at 3, 4.5 and 6 months of age. All subjects attained protective levels of anti-HBs antibodies 1 month after the primary course with higher geometric mean titres (GMTs) in the combined or mixed vaccinations. GMTs for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) were as good or better in the groups administered the combined formulation and the extemporaneously mixed vaccines than the separate administration. No serious adverse event related to the vaccination was reported in this study. Neither the combined formulation of DTPa and HBV vaccines nor the extemporaneous mixture increased the incidence or severity of adverse reactions compared with the separate administration of DTPa. This study shows the feasibility of a combined DTPa-HBV vaccine and the data support, in the interim, the mixing of DTPa and HBV vaccines which are tested in clinical trials for infant immunization.     

Infectivity of hepatic allografts with antibodies to hepatitis B virus

BACKGROUND: Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS: Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS: From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS: Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.     

Juvenile offenders and hepatitis B: risk, vaccine uptake and vaccination status

OBJECTIVE: To determine the hepatitis B vaccination status of juvenile offenders in a custodial setting, their perceived risk of hepatitis B infection, and factors influencing vaccine uptake. DESIGN: 130 males aged 14-17 years resident at the Melbourne Juvenile Justice Centre for at least one week between mid-January and mid-December 1996 were invited to participate; 90 (69%) completed a doctor-administered questionnaire, and blood for serological testing was obtained from 83 of these participants. MAIN OUTCOME MEASURES: Whether hepatitis B vaccine had been offered; whether hepatitis B vaccine had been given; the presence of antibodies to hepatitis B and C; risk factors and self-perceived risk of hepatitis B. RESULTS: About a quarter of participants (22/83) had protective levels of antibody to hepatitis B surface antigen (anti-HBs). Forty (44%) participants reported having been offered hepatitis B vaccine; they were more likely to be vaccinated and have protective levels of anti-HBs. Perceived risk for bloodborne virus infection was low, although two-thirds of participants were at high risk of hepatitis B infection. On serological testing, 6.4% (5/78) were positive for antibody to hepatitis B core antigen (anti-HBc), and a further 2.6% (2) had equivocal antibody levels. Of the 71 who were negative for anti-HBc, 51 (71.8%) were negative for anti-HBs. CONCLUSIONS: The targeted hepatitis B vaccination program has not adequately protected this group at high lifetime risk of hepatitis B. Failure to deliver vaccine may reflect lack of contact with healthcare services, oversight in offering vaccine and reluctance of youth to participate in preventive healthcare measures, often through not seeing themselves to be at risk. Universal approaches to vaccination may be more successful in vaccinating this group.     

Kinetics of hepatitis B surface antigen-specific immune responses in acute and chronic hepatitis B or after HBs vaccination: stimulation of the in vitro antibody response by interferon gamma

Because cellular and humoral immune responses against the hepatitis B virus (HBV) surface antigen (HBs) might be crucial to overcome HBV infection, HBs-specific B- and T-cell responses of HBV patients and HBs vaccine recipients were analyzed quantitatively and functionally. In patients with acute hepatitis B (AHB), transient high anti-HBs-secreting B-cell frequencies were observed early after clinical onset, whereas 1 patient who probably developed chronic infection and chronic HBV carriers had absent or weak B- and T-cell responses. In HBs vaccine recipients, maximal HBs-specific B- and T-cell responses were detected after the first injection that decreased gradually before anti-HBs antibodies appeared in serum. Years after vaccination, anti-HBs-secreting B cells were enriched in the bone marrow. After in vitro stimulation with HBsAg, peripheral blood mononuclear cells (PBMC) of only 1 of 5 acute and 1 of 6 chronic HBV patients, but of all 6 vaccine recipients, secreted varying amounts of interferon gamma (IFN-gamma), but no interleukin-4 (IL-4) or IL-5. Furthermore, the addition of IFN-gamma, but not of IL-2, -4, -12, or IFN-alpha, resulted in strong increases of anti-HBs-secreting B cells in vaccine recipients and chronic carriers. In conclusion, circulating anti-HBs-secreting B cells were significantly higher in early acute hepatitis B or early after HBs vaccination than in chronic hepatitis B and decreased in the follow-up as a result of compartmentalization to lymphoid tissues. Release of IFN-gamma by antigen-stimulated T cells might be critical for anti-HBs formation.     

Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy children: results after 5 years

Long-term persistence of hepatitis A virus (HAV) serum antibody in vaccinated children has not been demonstrated in previous studies. To study the long-term immunogenicity to HAV vaccine, three doses of strain HM 175 HAV vaccine with 360 enzyme-linked immunosorbent assay units were administered to 107 children, aged from 1.0 to 6.8 years, at 0, 1, and 6 months. The administration of one vaccine dose induced seropositivity (anti-HAV titer > or = 20 mIU ml-1) in 95% of all vaccinees at month 1. All subjects remained seropositive until month 6. The titers of HAV antibody remained above 20 mIU ml-1 in all subjects followed up to 60 months. The geometric mean titer (GMT) reached its peak (3802 mIU ml-1) at month 7, i.e. 1 month after the booster dose, and then declined until the end of follow-up at month 60 (661 mIU ml-1). A trend of higher GMT in female subjects persisted up to month 60. The changes of the GMT over time were best described by the regression equation: log (GMT) = 3.26-0.08 x (age in years) (r = -0.95, P = 0.014). According to this equation, the geometric mean concentration would reach 20 mIU ml-1 at around 24.5 years after the beginning of vaccination. In conclusion, those who completed the recommended three-dose inactivated HAV vaccination series remained seroprotective for at least 5 years. Theoretically, such a vaccination program can provide a protective period of over 20 years in children. This paper may be the first to describe at least 5-year immunogenicity of inactivated HAV vaccination in healthy children.     

Three-week hepatitis B vaccination provides protective immunity

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.     

Hepatitis B component does not interfere with the immune response to diphtheria, tetanus and whole-cell Bordetella pertussis components of a quadrivalent (DTPw-HB) vaccine: a controlled trial in healthy infants

The aim of this single-blind, parallel trial was to assess whether the hepatitis B (HB) component of a DTPw-HB vaccine interferes with the immune response to the other three components when administered at 3, 5 and 7 months of age. One hundred and six infants were randomized to receive three doses of DTPw or DTPw-HB vaccines. Seroprotection (or seroresponse) rates and geometric mean titers (GMT) of antibodies were assessed 3-6 weeks after the third dose. Anti-diphtheria, anti-tetanus and anti-Bordetella pertussis antibodies were measured by ELISA and anti-HBs by radioimmunoassay. Local and general signs and symptoms were recorded for a 4-day follow-up period after each vaccination. After the full vaccination course all subjects in both groups had seroprotective titers (> or = 0.1 IU ml-1) against diphtheria and tetanus and seroresponded (titers > or = 15 EL.U ml-1) to B. pertussis, and there was no significant difference between groups in relation to GMT. All subjects vaccinated with DTPw-HB had seroprotective levels (> or = 10 mIU ml-1) of anti-HBs antibodies after the third dose (GMT of 2318 mIU ml-1). Overall there were no significant differences between groups in relation to the incidence of local and general symptoms. These results show that the HB component did not interfere with the immune response to the other three components of the vaccine.     

Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B

BACKGROUND/AIM: During the course of persistent hepatitis B virus infection, viral replication markedly decreases after acute exacerbation of liver inflammation accompanied by emergence of antihepatitis B e antibody (anti-HBe) and/or anti-hepatitis B surface antibody (anti-HBs). In some cases, however, persistent viral replication continues even after such exacerbation with or without HBeAg/anti-HBe seroconversion. The aim of the present study was to investigate the extent of genetic variations of HBV in this phenomenon. METHODS: Full-length HBV genomes were amplified by polymerase chain reaction from sera of three patients before and after acute exacerbation and were directly sequenced. RESULTS: In the whole genomes of 3215 nucleotides, only six nucleotide mutations for six amino acid substitutions (2 in the surface gene, 2 in the X gene, 1 in the core gene and 1 in the polymerase gene) were observed in patient 1, 15 mutations for 14 amino acid substitutions (1 in the pre-core codon 28, 4 in the surface gene, 4 in the core gene and 5 in the polymerase gene) were observed in patient 2, and 5 mutations for 6 amino acid substitutions (2 in the surface gene, 2 in the X gene, pre-core stop codon mutation and 1 in the polymerase gene) were observed in patient 3. Substitution in the a determinant of the surface gene, which encodes target epitopes for neutralizing antibodies, as well as those in the pre-core/core gene, which encodes epitopes for cytotoxic T cells, were mainly found. CONCLUSION: HBV that remained after the emergence of anti-HBe and anti-HBs are considered to possess mutations in epitopes for both humoral and cellular immunity. These mutant HBV may be involved in the pathogenesis of persistent hepatic injury after acute exacerbation.     

Comparative genotoxicity of halogenated acetic acids found in drinking water

20 years after the introduction of the hepatitis-B vaccine the question still remains unsolved as to how the 2 to 5 per cent of the vaccinees who, after basic immunisation, respond with no anti-HBs levels (0-10 IU/l nonresponder, NR) or low levels (11-99 IU/l low-responder, LR) should be boostered to acquire sufficient and long-lasting protective anti-HBs levels. In a retrospective analysis of booster results we found in 75 NR and LR that the probability for long-lasting protection is very low for NR, but better for LR (60%). In a second part of this publication, the efficacy of intradermal and intramuscular hepatitis-B boosters was examined by retrospective analysis of booster results among 26 NR and LR. A slight advantage of the intradermal application was found concerning post-booster anti-HBs increase and the maximal HBs values reached. Long-lasting protective anti-HBs values could not be established for either way of application. Finally, a survey of the literature summing up true results of intradermal hepatitis-B basic immunisations with reduced doses (mostly 2 micrograms), shows that whereas the seroconversion rates achieved by this method are almost compatible with those after regular basic vaccination, the GMT values were far lower than those after regular basic vaccination. Prospective and randomised studies are needed to show which kind of booster is most efficient for nonresponders and low-responders.     

Molecular epidemiology of HIV-1 infection in the Philippines, 1985 to 1997: transmission of subtypes B and E and potential emergence of subtypes C and F

OBJECTIVES: to identify the risk factors for hepatitis B (HBV) and hepatitis C (HCV) virus infections in drug users attending two drug treatment centres in Northwest England, and to evaluate the effect of both needle exchange and hepatitis B vaccination on the prevalence of hepatitis B and hepatitis C infections. METHODS: a retrospective, cross-sectional study performed at the Regional Infectious Disease Unit and a Primary Care Centre for drug users in Liverpool. The study population included 773 drug users who had hepatitis serology performed between January 1992 and April 1996. Information on risk factors was obtained from clinical records; hepatitis serology data were obtained from the Liverpool Public Health Laboratory database. RESULTS: the overall seroprevalences of exposure markers for HBV (anti-HBc antibody) and HCV (anti-HCV antibody) were 48% and 67%, respectively. Duration of injecting drug use was the strongest predictor of HCV infection, with a crude odds ratio of 8.9 (95% confidence interval (CI): 4.5-17) for >10 compared to <3 years of injecting, and was also a strong predictor of HBV infection, with an adjusted odds ratio (controlled for the effects of HBV vaccination) of 5.7 (95% CI: 3.2-10) for >10 compared to <3 years' injecting. Vaccination against HBV was associated with greatly reduced HBV seroprevalence (crude odds ratio 0.11, 95% CI: 0.06-0.18). Overall, HCV was acquired earlier in the injecting career than HBV, but drug users who were not vaccinated against HBV acquired markers for HBV even more rapidly than for HCV. We found no independent protective effect for either anti-HBc or anti-HCV acquisition after the introduction of a needle-exchange scheme. CONCLUSIONS: hepatitis C is highly prevalent among Merseyside drug users and is likely to prove difficult to control because of rapid acquisition early in the injecting career. Vaccination against hepatitis B is the best means of protecting drug users from hepatitis B, and should be offered before injecting is commenced.