A mathematical model of hepatitis B virus transmission and its application for vaccination strategy in china.
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BACKGROUND: Before universal infant immunization against hepatitis B virus (HBV) in 1986 China was a region endemic for HBV infection. The prevalence of HBV infection in the population was about 60% and the proportion of chronic HBV carriers around 10%. These HBV carriers could progress to chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma. Since 1976, large-scale sero-surveys of HBV infection have been carried out and a lot of data have been collected. METHOD: This paper describes a mathematical model developed to predict the dynamics of HBV transmission and to evaluate the long-term effectiveness of the vaccination programme. We used a compartment model expressed by a set of partial differential equations based on the characteristics of HBV infection. RESULTS: All parameters, expressed in the model as a non-linear function of age and time since vaccination, were estimated using sero-survey data. The model fits well with both pre-vaccination and post-vaccination sero-surveys. The observed and estimated age-specific prevalence rates of HBV infection and HBV carriage agree with each other. According to our model, if all newborns are vaccinated according to schedule, the rate of HBV carriage will decline sharply over time to 0.2% in 70 years. By then, the ratio of acute hepatitis B will be less than 0.5% and the ratio of chronic hepatitis B will be around 5%. CONCLUSIONS: The results suggest that HBV infection in China can be controlled in just one generation, and eventually eliminated. Our model shows that vaccination coverage is the most important indicator for the elimination of HBV transmission. The higher the vaccination coverage, the better the long-term effectiveness of immunization. Thus, the key to controlling and eliminating HBV transmission in China is to find ways to immunize all infants throughout the country, especially in poor, rural areas. (+info)
Update: expanded availability of thimerosal preservative-free hepatitis B vaccine.
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Thimerosal, a mercury-based compound, is no longer used as a preservative in any of the pediatric hepatitis B vaccines licensed in the United States. On March 28, 2000, SmithKline Beecham Biologicals (Rixensart, Belgium) received approval from the Food and Drug Administration of a supplement to its hepatitis B license to include the manufacture of single-antigen, preservative-free hepatitis B vaccine (Engerix-B, pediatric/adolescent); distribution of this product has begun. A single-antigen, preservative-free hepatitis B vaccine (Recombivax HB, pediatric) from Merck Vaccine Division (West Point, Pennsylvania) had earlier received similar approval (1). A preservative-free Haemophilus influenzae type b (Hib)/hepatitis B combination vaccine (Comvax) from Merck Vaccine Division also is available. An adequate supply of preservative-free hepatitis B vaccine is available for all infant and childhood vaccinations. Thimerosal preservative-containing hepatitis B vaccines may continue to be used for vaccination of adolescents and adults as recommended (2). (+info)
Association of hepatitis B virus infection with other sexually transmitted infections in homosexual men. Omega Study Group.
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OBJECTIVES: This study determined the prevalence and factors associated with hepatitis B virus (HBV) infection among men who have sex with men. METHODS: At the baseline visit of an HIV study among men who have sex with men, we asked about HBV vaccination status and tested for HBV markers. RESULTS: Of 625 subjects, 48% had received at least 1 dose of HBV vaccine. Of 328 unvaccinated men, 41% had 1 or more HBV markers. HBV prevalence increased markedly with age and was associated with many sexual and drug-related behaviors. In a multivariate model, 7 variables were independently associated with HBV infection: ulcerative sexually transmitted diseases (odds ratio [OR] = 10.1; 95% confidence interval [CI] = 2.6, 54); injection drug use (OR = 5.2; 95% CI = 1.2, 26); gonorrhea or chlamydia (OR = 4.0; 95% CI = 1.9, 8.9); sexual partner with HIV/AIDS (OR = 3.6; 95% CI = 1.8, 7.1); 50 or more casual partners (OR = 3.4; 95% CI = 1.6, 7.1); received money for sex (OR = 3.0; 95% CI = 1.2, 7.8); and 20 or more regular partners (OR = 2.5; 95% CI = 1.1, 6.1). CONCLUSIONS: In Montreal, men who have sex with men are at risk for HBV infection, but a substantial proportion remain unvaccinated; new strategies are required to improve coverage. Men who have sex with men and who have a sexually transmitted infection, especially a genito-ulcerative infection, appear to be at particularly high risk for HBV infection. (+info)
Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization.
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CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human D(b) (HHD) mice, which are deficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) D(b-/-)) and transgenic for a chimeric HLA-A*0201/D(b) molecule covalently bound to the human beta(2)-microglobulin (HHD(+/+)). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secreting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients. (+info)
Maintenance of immune memory to the hepatitis B envelope protein following adoptive transfer of immunity in bone marrow transplant recipients.
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Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has been documented in mice and humans. In the present study, we report long-term follow-up of antibodies to HBsAg in humans who received allogeneic bone marrow transplantation (BMT) from donors immunized with HBsAg. BM donors were immunized with recombinant HBsAg. BM or PB cells were transplanted to HLA matched recipients. Recipients were followed for anti-HBs seroconversion. Control groups included non-immunized or rHBsAg immunized healthy adults as well as individuals that had had hepatitis B and recovered spontaneously. PBLs were stimulated in vitro with rHBsAg and stimulation was expressed as stimulation index. Adoptive transfer of immunity to HBsAg was initially documented in 12 recipients of BM from anti-HBc+/anti-HBs+ donors. An almost 4 year follow-up showed detectable protective anti-HBs levels (>10 mIU/ml) in 50% of patients. Immunity to HBV was also documented in 22/35 BMT recipients (62%), who received their bone marrow from actively immunized donors. In 7/9 of these BMT recipients, anti-HBs antibodies levels were documented 25 months following BMT. In 6/8 (75%) of patients who received only PBLs from HBV immune donors, adoptive transfer of immunity to HBV, and seroconversion to HBsAg+, were documented within 2 months of i.v. injection. Evidence for specific cellular immune response with increased SIs was documented for healthy vaccinees, and BMT recipients, and in none of the healthy non-vaccinated controls. These results suggest that adoptive transfer of immunity to HBV is a useful method for providing long-lasting protection for BM recipients. (+info)
Results of hepatitis B vaccination in sarcoidosis.
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BACKGROUND: Sarcoidosis is known to be associated with defects in cellular immunity, especially in reference to T helper lymphocytes. Anergy to a tuberculin skin test is most characteristic of this disease. OBJECTIVES: To further the data on impaired immunity, we studied the antibody response to hepatitis B vaccination in patients with sarcoidosis. METHODS: Serologic markers of hepatitis B virus (HBV) (HBsAg, anti-HBs, anti-HBc) were studied in 40 patients with sarcoidosis (32 female, 8 male; mean age: 45 +/- 11 years, range: 25-66 years) with a mean duration of disease of 6 years. While all the markers were negative in 22 patients (55%), 2 had isolated anti-HBc positivity and 16 had both anti-HBc and anti-HBs antibodies. Thirty-five age- and sex-matched healthy subjects were studied as controls. Recombinant HBV vaccines (Genhevac B Pasteur, 20 microg) were administered (at 0, 1, and 6 months) to 16 of the seronegative cases and the controls and antibody titres were measured 1 month after the last dose. The tuberculin skin test was negative in all cases. RESULTS: While none of the vaccinees in the diseased group responded, the control group yielded an antibody response rate of 85. 7% (30/35), with a mean titre of 257.9 mIU/ml. CONCLUSIONS: Patients with sarcoidosis were invariably unresponsive to standard vaccination, while some of the diseased subjects had already mounted a natural antibody response, either before or after the development of the original disease. Cellular immunodeficiency in sarcoidosis could be a suitable model for studying immunological interactions between HBV and the host. (+info)
Hepatitis B immunization coverage among Vietnamese-American children 3 to 18 years old.
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OBJECTIVE: Persons with chronic hepatitis B virus (HBV) infection are at increased risk of chronic hepatitis, cirrhosis, and liver cancer. Although HBV infection is relatively uncommon in the United States, the disease is endemic in persons born in Southeast Asia, including Vietnamese-Americans. Current US infant immunization recommendations and state-mandated school-entry programs have left many nontargeted age-cohorts unvaccinated and at risk of infection. To assess the need for catch-up hepatitis B immunizations, this study reports the hepatitis B immunization rates of Vietnamese-American children 3 to 18 years old living in the metropolitan areas of Houston and Dallas, Texas, and the Washington, DC, area. DESIGN: We conducted 1508 telephone interviews with random samples of Vietnamese households in each of the 3 study sites. We asked for hepatitis B immunization dates for a randomly selected child in each household. Attempts were made to verify immunization dates through direct contact with each child's providers. Low and high estimates of coverage were calculated using reports from providers when reached (n = 720) and for the entire sample (n = 1508). RESULTS: Rates of having 3 hepatitis B vaccinations ranged from 13.6% (entire sample) to 24.1% (provider reports, Dallas), 10. 3% to 26.4% (Houston), and 18.1% to 37.8% (Washington, DC). Children living in the Texas sites, older children, children whose families had lived in the United States for a longer time, and children whose provider was Vietnamese or who had an institutional provider were less likely to have been immunized. The odds of being immunized were greater, however, for children who had had at least 1 diphtheria, tetanus toxoid, and pertussis shot, and whose parents had heard about HBV infection, and were married. CONCLUSIONS: The low rates of hepatitis B vaccine coverage among children and adolescents portend a generation which, too old to benefit from infant programs and school entry laws, will grow into adulthood without the protection of immunization. Increased efforts are needed to design successful catch-up campaigns for this population. (+info)
Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines.
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To study the regulation of the human cellular immune response to HBsAg we produced a series of HBsAg-specific T cell lines from good and poor responders to the hepatitis B vaccine. All T cell lines expressed CD4 on their membrane and could therefore be considered of the helper/inducer phenotype. The different HBsAg-specific T cell lines were restricted by HLA-DRB5*0101, DRB1*1201, -DRB1*0701, -DRB1*0301, -DPB1*0201, -DPB1*0402, and -DPB1*0901. In good responders to the hepatitis B vaccine different HLA molecules could act as restricting element. In poor responders the diversity of HLA class II restriction determinants was more limited. This leads us to conclude that the immune response to HBsAg is multispecific and polyclonal in good responders and paucispecific and oligoclonal in poor responders to the hepatitis B vaccine. By using a panel of synthetic peptides representing selected sequences of the HBsAg, the fine specificities of each of these T cell lines could be determined. Strikingly, the majority of the identified T cell epitopes was located in and around the first hydrophobic transmembranous region of the HBsAg. This was observed in T cell lines from good and poor vaccine responders, without distinction. The remarkable T cell immunogenicity of this region may reside in its richness in binding motifs for a variety of HLA class II determinants. (+info)