Infant Hepatitis B Virus Vaccination Research Articles

Hepatitis B prevalence and risk factors among adults living with HIV in South Africa: a clinic-based cohort study

BackgroundPeople living with HIV (PLHIV) may have concurrent Hepatitis B Virus (HBV) infection, and certain antiretroviral therapies are recommended for HBV-HIV co-infected individuals. Routine screening for Hepatitis B virus may influence management of antiretroviral therapy for PLHIV, but risk factors for co-infection have not been well defined. The objective of this study was to identify risk factors for HBV infection among PLHIV in South Africa.MethodsWe conducted a cross-sectional analysis of a prospective, clinic-based cohort study of adults seeking HIV testing from 2013–2017 in Umlazi township, South Africa. Patients newly diagnosed with HIV were enrolled and subsequently tested for Hepatitis B surface antigen positive (HBsAg +). We used a Poisson linear regression model to assess which factors, pertaining to sociodemographic status, medical history, clinical symptoms, mental health were associated with HBV.ResultsAmong 3,105 PLHIV participants in South Africa, 6% were positive for HBV. Males had a higher HBV prevalence (10.4%) than females (5.2%). Within the HBV-positive group, the mean age was 33.2 years, with 38.3% females and 43.9% having completed high school or higher. About 39.9% reported alcohol use, 24.7% had a smoking history, and 8.3% reported substance use in the past year. Older participants born before 1995, when routine infant HBV vaccination was introduced, were more likely to have HBV. In multivariable analyses, smoking history increased HBV risk in females (aPR = 2.58; 95% CI 1.47–2.52), while alcohol use decreased HBV risk in males (aPR = 0.36; 95% CI 0.19–0.70).ConclusionsIn a South African cohort, roughly one in 16 PLHIV had HBV co-infection, and this rate was higher in males. The most prominent risk factors for HBV infection in PLHIV were alcohol use, higher income, and smoking history, which may help inform targeted treatment and prevention strategies. Creating HBV-specific screening and prevention strategies for PLHIV may be useful for reducing HBV infections.

ABO blood types, but not Secretor or Lewis blood types, influence strength of antibody response to Hepatitis B vaccine in Black South African children.

Subunit vaccines for the Hepatitis B virus (HBV) have greatly reduced the prevalence of infection and morbidity through HBV-related liver cirrhosis and cancer. However, strength of immune response to vaccination varies considerably. While it is known that ABO blood types may influence HBV infection risk, the role of ABO and related blood types in strength of immune response to HBV vaccine has not been investigated. We examined 16 polymorphisms in the ABO, FUT2, and FUT3 genes and their related phenotypes for associations with strength of antibody response to HBV vaccine in Black South African infants. Anti-HBc and anti-HBs antibody levels were measured by CMIA assay 1-3months after the last dose of HBV vaccine. Prior infection occurred in 8/207 individuals (3.86%) who were removed from further study. Of the remaining 199 individuals, 83.4% individuals were strong responders (anti-HBs≥100 mIU/ml, median 973 mIU/ml), another 15.6% were weak responders (anti-HBs<100 mIU/ml, median 50 mIU/ml) and 1% were non-responders (anti-HBs<10 mIU/ml). The frequency of weak responders to HBV vaccine was not significantly affected by sex, birthweight, use of an additional booster dose of vaccine or cohort of origin. We characterised patterns of genetic variation present at the ABO, FUT2 and FUT3 loci by use of MassArray genotyping and used these data to predict ABO, Secretor and Lewis phenotypes. We observed significant association of ABO blood type with strength of antibody response to HBV vaccine in a Black South African cohort (p=0.002). In particular, presence of rs8176747G and expression of B antigen (whether in B blood type or AB blood type) was associated with decreased antibody response to HBV vaccine. Secretor and Lewis blood types were not associated with antibody response to HBV vaccine. This work increases our understanding of the impact that host genetic variation may have on vaccine immunogenicity.

Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050.

The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.

Hepatitis B prevalence in women giving birth in the Northern Territory, Australia, 2005-2015.

Hepatitis B virus (HBV) vaccination in the Northern Territory (NT) was funded for all Aboriginal and Torres Strait Islander newborns in 1988 and for all newborns in 1990. The prevalence of HBV in the Northern Territory was found to be higher in Aboriginal and Torres Strait Islander women than in non-Indigenous women across 2005-2010. We examined more recent data to assess whether the gap remains. We linked data from two routinely collected registries, the NT Perinatal Register and the NT Notifiable Diseases System, to investigate the prevalence of HBV infection, according to eligibility for infant HBV vaccination, in women giving birth during 2005-2015. There were 22,781 women recorded as giving birth in public hospitals in the Northern Territory during 2005-2015. Hepatitis B virus prevalence was highest in Aboriginal and Torres Strait Islander (1.8%) and overseas-born women (1.8%). Among Aboriginal and Torres Strait Islander women, estimated hepatitis B virus prevalence was significantly higher in those born before the implementation of the vaccination program than in those born afterwards (2.4% versus 0.3%). Prevalence was highest amongst those living in very remote areas, both overall (2.2%) and within the birth cohort eligible for HBV vaccination. Hepatitis B virus prevalence in Northern Territory Aboriginal and Torres Strait Islander women appears to be declining as more individuals vaccinated as part of infant vaccination programs reach adulthood. Prevalence remains highest in remote areas, highlighting the importance of ongoing monitoring and of promoting vaccination in these regions.

A systematic review and meta-analysis of the prevalence of hepatitis B virus infection among pregnant women in Nigeria.

BackgroundNigeria has a high burden of hepatitis B virus (HBV) infection, commonly acquired through vertical transmission. However, there is a lack of an efficient surveillance system for monitoring and understanding the epidemiology of HBV among pregnant women. Building on a previous review on the prevalence of HBV in Nigeria (2000–2013), we conducted a systematic review and meta-analysis of HBV prevalence among pregnant women in Nigeria.MethodsFour electronic databases PubMed, Embase, Global Health, and Scopus were systematically searched from January 2014 to February 2021. We also searched the African Journal Online and manually scanned the reference lists of the identified studies for potentially eligible articles. Observational studies that reported the prevalence of HBsAg and/or HBeAg among pregnant women in peer-reviewed journals were included in the study. We performed a meta-analysis using a random-effects model. We defined HBV infection as a positive test to HBsAg.ResultsFrom the 158 studies identified, 20 studies with a total sample size of 26, 548 were included in the meta-analysis. The pooled prevalence of HBV infection among pregnant women across the studies was 6.49% (95% confidence interval [CI] = 4.75–8.46%; I2 = 96.7%, p = 0.001; n = 20). The prevalence of HBV was significantly lower among pregnant women with at least secondary education compared with those with no education or primary education (prevalence ratio = 0.7, 95% CI = 0.58–0.87; n = 10). However, the prevalence of HBV was not significantly different by age, religion, marital status, or tribe. The prevalence of HBV was not significantly different among pregnant women with previous surgery, blood transfusion, multiple lifetime sex partners, tribal marks, tattoos, scarification, or sexually transmitted infections, compared with those without these risk factors. From a total sample size of 128 (n = 7), the pooled prevalence of HBeAg among HBV-infected pregnant women was 14.59% (95% CI = 4.58–27.99%; I2 = 65.5%, p = 0.01). Subgroup analyses of HBV infection by study region and screening method, and meta-regression analysis of the study year, sample size, and quality rating were not statistically significant.ConclusionsThere is an intermediate endemicity of HBV infection among pregnant women in Nigeria. Interventions, such as routine antenatal HBV screening, antiviral prophylaxis for eligible pregnant women, and infant HBV vaccination should be scaled up for the prevention of perinatal transmission of HBV infection in Nigeria.

Moderate Heat-Assisted Gene Electrotransfer for Cutaneous Delivery of a DNA Vaccine Against Hepatitis B Virus.

An estimated 350 million people are living with chronic Hepatitis B virus (HBV) worldwide. Preventative HBV vaccination in infants has reduced the disease burden; however, insufficient immunization programs and access obstacles leave vulnerable populations at risk for infection in endemic regions. Gene electrotransfer (GET) using a noninvasive multielectrode array (MEA) provides an alternative platform for DNA vaccination in the skin. DNA vaccines are nonlive and nonreplicating and temperature stable unlike their counterparts. In addition, their simple engineering allows them to be manufactured quickly at a low cost. In the current work, we present the combination of GET and moderate heating for delivery of a DNA vaccine against HBV. Our laboratory has previously shown the synergy between moderate tissue preheating at 43°C and GET with the MEA as a means to reduce both the applied voltage and pulse number to achieve similar if not higher gene expression than GET alone. In this study, we expand upon this work, by optimizing the plasmid dose to achieve the highest level of expression. Using the reporter gene luciferase, we found that an intradermal injection of 100 μL at 1 mg/mL induced the highest expression levels across all tested GET conditions. We then evaluated our moderate heat-assisted GET platform for the intradermal delivery of a plasmid encoding Hepatitis B surface antigen (pHBsAg) via a prime and prime plus boost vaccination protocol. At 18 weeks, following the prime plus boost protocol, we observed that a high-voltage low-pulse GET condition with moderate heating (45 V 36 p+heat) generated antibodies against Hepatitis B surface antigen (HBsAb) at peak measuring 230-fold over injection of plasmid DNA alone with moderate heating. HBsAbs remained robust over the 30-week observation period. These data suggest that moderate heat-assisted GET has the potential to induce strong immune responses, an attractive feature for development of an alternative vaccine delivery platform.

The Impact of Universal Infant Hepatitis B Immunization on Reducing the Hepatitis B Carrier Rate in Pregnant Women.

The hepatitis B virus (HBV) status of pregnant women affects HBV vaccine failure in their offspring. This study is aimed to investigate the impact of the universal infant HBV vaccination program on the long-term hepatitis B surface antigen (HBsAg) rate in pregnant women. Using the National Immunization Information System, we examined a 32-year period of cross-sectional data on a maternal HBsAg and hepatitis B e antigen (HBeAg) screening program launched in July 1984. An age-period-cohort model analysis of 940 180 pregnant women screened for July 1996-June 1997 and the years 2001, 2006, 2011, and 2016 was applied. The annual HBsAg- and HBeAg-seropositive rates decreased from 13.4% and 6.4%, respectively, for the period 1984-1985 to 5.9% and 1.0% in 2016 (P for both trends < .0001). Pregnant women with birth years after July 1986 (the HBV vaccination cohort) had the lowest relative risk (0.27 [95% confidence interval, .26-.28]) of HBsAg positivity compared with birth years before June 1984. The birth cohort effect in relation to the universal infant HBV immunization program has effectively reduced the HBV carrier rate in pregnant women and the burden of perinatal HBV infection on the next generation.

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(−) mothers: a nested case–control study

ObjectivesTo investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis...

Persistence of Hepatitis B Immunity Following 3-dose Infant Primary Series in HIV-infected Thai Adolescents and Immunologic Response to Revaccination.

HIV infection may alter immunologic response and the establishment of immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to determine the need to revaccinate perinatally HIV-infected Thai adolescents. Cross-sectional serologic tests for HBV, including hepatitis B surface antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core antibody (anti-HBc), were performed in perinatally HIV-infected adolescents. Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune reconstitution from highly active antiretroviral therapy (HAART) were revaccinated using regular (10 μg) 3-dose schedule given intramuscularly at 0-, 2- and 6-month intervals. Of 193 adolescents who received 3-dose infant HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc (indicating breakthrough infection), of which 4 (2%) had positive hepatitis B surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and 97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects responded to the first dose with anti-HBs antibody ≥100 mIU/mL had a shorter median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months; P = 0.049). Only half of perinatally HIV-infected adolescents were able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination with 3-dose schedule is required in perinatally HIV-infected adolescents who did not initiate HAART at the time of infant vaccination.

Effects of Interleukin-4 and Interleukin-12b Gene Polymorphisms on Hepatitis B Virus Vaccination

Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Association of HLA-DP variants with the responsiveness to Hepatitis B virus vaccination in Korean Infants

Recently, HLA-DP single nucleotide polymorphisms (SNPs) have been reported to be related to responsiveness to hepatitis B virus (HBV) vaccination. The aim of this study was to investigate associations between HLA-DP SNPs and responsiveness to HBV vaccine in Korean infants. A total of 290 healthy Korean infants who were registered to Seoul Metropolitan Public Cord Blood Bank during the period of February 2007 to December 2011 were enrolled. Anti-HBs antibody level was analyzed after three doses of HBV vaccination. Genotyping of HLA-DPA1 SNPs (rs3077 and rs3830066) and HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were performed by PCR-sequencing. HLA-A, -B, and –DRB1 genotyping was also performed by PCR-sequence-specific oligonucleotide probe kits. HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were associated with HBV vaccine response. Allele frequencies of rs7770370 A, rs7770501 C, rs3128961 G, and rs9277535 A were significantly higher in responders than in non-responders (all p<0.01). Anti-HBs antibody levels were different according to genotypes of DPB1 rs7770370, rs7770501, rs3128961, and rs9277535 (all p<0.01). In multivariate analysis, HLA-DPB1 rs7770370 AA genotype was significantly associated with HBV vaccine response (relative risk, RR=2.5, p=0.033) and high-titer vaccine response (RR=2.7, p<0.001). In conclusion, HLA-DPB1 SNPs were significantly associated with responses to HBV vaccination in Korean infants.

Hepatitis B virus vaccination booster does not provide additional protection in adolescents: a cross-sectional school-based study.

BackgroundCurrent consensus does not support the use of a universal booster of hepatitis B virus (HBV) vaccine because there is an anamnestic response in almost all children 15 years after universal infant HBV vaccination. We aimed to provide a booster strategy among adolescents as a result of their changes in lifestyle and sexual activity.MethodsThis study comprised a series of cross-sectional serological surveys of HBV markers in four age groups between 2004 and 2012. The seropositivity rates of hepatitis B surface antigen (HBsAg) and its reciprocal antibody (anti-HBs) for each age group were collected. There were two parts to this study; age-specific HBV seroepidemiology and subgroup analysis, including effects of different vaccine types, booster response for immunogenicity at 15 years of age, and longitudinal follow-up to identify possible additional protection by HBV booster.ResultsWithin the study period, data on serum anti-HBs and HBsAg in a total of 6950 students from four age groups were collected. The overall anti-HBs and HBsAg seropositivity rates were 44.3% and 1.2%, respectively. The anti-HBs seropositivity rate in the plasma-derived subgroup was significantly higher in both 15- and 18-year age groups. Overall response rate in the double-seronegative recipients at 15 years of age was 92.5% at 6 weeks following one recombinant HBV booster dose. Among the 24 recipients showing anti-HBs seroconversion at 6 weeks after booster, seven subjects (29.2%) had lost their anti-HBs seropositivity again within 3 years. Increased seropositivity rates and titers of anti-HBs did not provide additional protective effects among subjects comprehensively vaccinated against HBV in infancy.ConclusionsHBV booster strategy at 15 years of age was the main contributor to the unique age-related phenomenon of anti-HBs seropositivity rate and titer. No increase in HBsAg seropositivity rates within different age groups was observed. Vaccination with plasma-derived HBV vaccines in infancy provided higher anti-HBs seropositivity at 15–18 years of age. Overall booster response rate was 92.5% and indicated that intact immunogenicity persisted at least 15 years after primary HBV vaccination in infancy. Booster vaccination of HBV did not confer additional protection against HBsAg carriage in our study.

Association of HLA alleles with the responsiveness to hepatitis B virus vaccination in Korean infants

Hepatitis B virus (HBV) vaccination is the most effective means of countering HBV-related morbidity and mortality, and individuals who do not respond to vaccination (non-responders) are problematic. The aim of the present study was to investigate associations between HLA and responsiveness to HBV vaccine in Korean infants. A total of 944 healthy Korean infants 9–12 months old were enrolled, and HLA distribution was compared among subgroups in accordance with the response to HBV vaccination. The HLA distribution of the subjects was similar to known Korean population data and did not deviate from the HWE proportions. The alleles that showed positive associations with non-responsiveness (<10mIU/mL) or low antibody titer (<100mIU/mL) were HLA-A*33, B62, DRB1*04, and DRB1*07, while the alleles A*02 and DRB1*08 showed negative associations. Among these alleles, B62, DRB1*07 and DRB1*08(−) showed significant associations with a poor or decreased response to vaccination even after correction (OR=1.83, 1.99, 5.63; pc<0.05) and also showed dose effects. After stratification by other associated alleles at different loci, B62 and DRB1*07 were independently associated with non-responsiveness, but A*02(−) and DRB1*08(–) lost their individual associations. The combined association of A*02(–)–DRB1*08(–) and B62–DRB1*08(–) was significant (OR=25.2 and 24.5; pc<0.05). Although the hierarchy is not clear, we can assume the following: (i) B62 and DRB1*07 have independent effects, (ii) DRB1*08(–) has a very strong and synergic effect, and (iii) there is probability of a third factor controlling A*02(–) and DRB1*08(–) with an effect on non-responsiveness to HBV vaccination in Korean infants.

Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986–90) and in the nationwide immunisation program

BackgroundGambian infants were not routinely vaccinated against hepatitis B virus (HBV) before 1986. During 1986–90 the Gambia Hepatitis Intervention Study (GHIS) allocated 125,000 infants, by area, to vaccination or not and thereafter all infants were offered the vaccine through the nationwide immunisation programme. We report HBV serology from samples of GHIS vaccinees and unvaccinated controls, and from children born later.MethodsDuring 2007–08, 2670 young adults born during the GHIS (1986-90) were recruited from 80 randomly selected villages and four townships. Only 28% (753/2670) could be definitively linked to their infant HBV vaccination records (255 fully vaccinated, 23 partially vaccinated [1–2 doses], 475 not vaccinated). All were tested for current HBV infection (HBV surface antigen [HBsAg]) and, if HBsAg-negative, evidence of past infection (HBV core-protein antibody [anti-HBc]). HBsAg-positive samples (each with two age- and sex-matched HBsAg-negative samples) underwent liver function tests. In addition, 4613 children born since nationwide vaccination (in 1990-2007) were tested for HBsAg. Statistical analyses ignore clustering.ResultsComparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy. Among unvaccinated individuals, the prevalence was higher in males (p = 0.015) and in rural areas (p = 0.009), but adjustment for this did not affect estimated vaccine efficacy. Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001. Chronic active hepatitis was not common: the proportion of HBsAg-positive subjects with abnormal liver function tests (ALT > 2 ULN) was 4.1%, compared with 0.2% in those HBsAg-negative. The prevalence of antibodies to hepatitis C virus was low (0.5%, 13/2592). In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990–97, and 0.3% (9/35150) in those born between 1998–2007.ConclusionsInfant HBV vaccination achieves substantial protection against chronic carriage in early adulthood, even though approximately a quarter of vaccinated young adults have been infected. This protection persists past the potential onset of sexual activity, reinforcing previous GHIS findings of protection during childhood and suggesting no need for a booster dose. Nationwide infant HBV vaccination is controlling chronic infection remarkably effectively.

Population-based interventions to reduce the public health burden related with hepatitis B virus infection in the gambia, west Africa.

In The Gambia, West Africa, the prevalence of chronic hepatitis B virus (HBV) infection in adults exceeds eight percent and hepatocellular carcinoma (HCC) has been the most frequent type of malignancy. Two population-based intervention studies to control HBV infection, namely, GHIS (Gambia Hepatitis Intervention Study) and PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa), are discussed. The GHIS started in 1986 as a nation-wide trial of the HBV vaccine to evaluate the effectiveness of infant HBV vaccination in preventing HCC in adulthood. The vaccine was progressively introduced into the Expanded Program of Immunization (EPI) of The Gambia over four years in a phased manner, called the “stepped-wedge” design. This was because instantaneous universal vaccination in the country was impossible for logistic and financial reasons. However, this design also allowed the study to have an unvaccinated control group which consisted of the newborns of the areas where HBV vaccine has not yet been incorporated in the EPI. To assess the outcome, a national cancer registry was founded and all HCC patients in this birth cohort are linked with the vaccine trial database. The study is still ongoing to answer whether the HBV vaccine in infancy prevent HCC in adulthood in The Gambia. Although the universal HBV vaccination since 1990 has been successful in reducing the prevalence of chronic HBV infection in young Gambians, the number of HCC cases may not decline over the next decades as people infected prior to the immunization program are likely to continue to develop the diseases. To reduce the HCC incidence through community-based screening of HBV infection and provision of antiviral therapy, the PROLIFICA project started in 2011. Study hypothesis and design of these two studies, GHIS and PROLIFICA, are further discussed.

Update on epidemiology of hepatitis B and C in China

A high rate of chronic hepatitis B virus (HBV) infection in China is mainly caused by perinatal or early childhood transmission. Administration of universal HBV vaccination in infants has led to a dramatic decrease in HBV epidemiology, with hepatitis B surface antigen (HBsAg) prevalence declining from 9.75% in 1992 to 7.18% in 2006. The major HBV genotypes are B and C, with B being more prevalent in the southern part and C more prevalent in the northern part of China. A national survey carried out in 1992 showed that the hepatitis C virus (HCV) infection rate was 3.20% in general population in China. After implementation of mandatory HCV screening for blood transfusion and other precautions to prevent blood-borne disease since 1993, the new cases of HCV infection associated with blood or blood product has become very rare. Although the anti-HCV prevalence would be much higher in high-risk groups, a survey carried in 2006 showed that the anti-HCV prevalence rate was only 0.43% in general population. This sharp decline in HCV infection rate was mainly due to stringent administration and monitoring of blood donors and blood products, but may also be related to the remarkably improved specificity of anti-HCV test. The predominant HCV genotype in China is genotype 1b (60-70%), and the host interleukin-28b rs12979860 CC genotype is very frequent in Chinese population (over 80%).

Maternal immunization promotes the immune response of neonates towards hepatitis B vaccine

Infants infected with hepatitis B virus (HBV) face the risk of developing severe complications. Unfortunately, in spite of universal vaccination programmes, 5% or more of vaccinated newborns still do not achieve protective levels of anti-hepatitis B virus surface antigen titres (anti-HBs). The aim of this study was to use animal experiments and population-based research to determine whether maternal vaccination against HBV affects the outcome of neonatal vaccination. Six sows and 53 newborn piglets were used for this study and randomly assigned to the vaccination group (three 20 μg doses of recombinant HBV vaccine). All the piglets were followed up to 10 weeks of age, and peripheral blood was withdrawn for measurement of anti-HBs. A cross-sectional study was also conducted on 449 mothers with infants. A structured questionnaire was used to collect demographic, medical and maternal data, and their peripheral blood was collected for measurement of anti-HBs. The results of animal experiments demonstrated that nonvaccinated piglets born to vaccinated sows and nonvaccinated piglets born to nonvaccinated sows were negative for anti-HBs. Repeated measures analysis of variance showed that the titres of anti-HBs in vaccinated piglets born to vaccinated sows were significantly higher than in vaccinated piglets born to nonvaccinated sows (P < 0.05). In a population-based study, a cumulative logistic regression analysis showed that the strongest influences on neonatal anti-HBs titres were delay of the first vaccination dose [OR = 3.02(95% CI: 1.72-5.30)] and maternal anti-HBs titres [OR = 2.48(95% CI: 2.03-3.04)]. In conclusion, high maternal anti-HBs titres can enhance the response to HBV vaccination in infants.

Genetic effects have a dominant role on poor responses to infant vaccination to hepatitis B virus

The objective of this study was to investigate the overall contribution of genetic and environmental effects on poor response to hepatitis B virus (HBV) vaccination in Chinese infants. One-year-old healthy twins were recruited from child-care settings. Parental factors, neonates' condition at birth, postnatal infant feeding history and growth measurements during the 12 months were investigated by conducting an interview and checking the medical records. HBV-related markers were examined at 1 year of age. Heritability of surface antibody to HBV (anti-HBs) concentrations (ordinal variable) among twins was estimated using MX software. The role of perinatal environmental factors on poor vaccine response (anti-HBs<100 mIU ml(-1)) was analyzed using XTGEE (fit population-averaged panel-data models by using GEE) programs. Overall, 172 out of 225 recruited twin pairs were analyzed for heritability, including 82 pairs (47.67%) of monozygotic twins and 90 pairs of dizygotic twins, which consisted 43 pairs of (25.0%) opposite sex twins, 29 pairs of male twins and 18 pairs of female twins. Seventy-one (19.9%) of 370 twins showed poor responses to HBV vaccine. An additive genetic (0.91 of the variance)-random environmental (0.09 of the variance)-model best fit the variation of anti-HBs response. Risk factor analysis showed that with a smoking father and low birth weight, the infants were associated with an increased risk of poor response to HBV vaccination (odds ratio (OR)=4.50, 95% confidence interval (CI): 2.52-8.03 and OR=2.55, 95% CI: 1.33-4.87, respectively). Higher Apgar score and gaining more body weight in the first year of life reduced this risk. Genetic factors have a dominant role in determining infant HBV vaccination responses (91%) compared with perinatal environmental factors.

Immunity to Hepatitis B Virus (HBV) Infection Two Decades after Implementation of Universal Infant HBV Vaccination: Association of Detectable Residual Antibodies and Response to a Single HBV Challenge Dose

Most persons who receive hepatitis B vaccine during infancy will have a level of antibody to hepatitis B surface antigen (anti-HBsAg) of <10 IU/liter 10 to 15 years later; however, most will demonstrate immune memory by an anamnestic response to a vaccine challenge dose. To determine whether there was a difference in anamnestic response among college students vaccinated during infancy, we compared anti-HBsAg levels after a 20-μg dose of Engerix-B in those with a residual anti-HBsAg level of 0 IU/liter and those with levels of 1 to 9 IU/liter. Anti-HBsAg was measured before (baseline) and 2 weeks after a challenge dose; a response was defined as a level of ≥10 IU/liter after the dose among those with <10 IU/liter at the baseline. Of the 153 students who completed the study, 130 (85%) had an anti-HBsAg level of <10 IU/liter at the baseline, 72 had a level of 0 IU/liter, and 58 had levels ranging from 1 to 9 IU/liter. Students with a levels of 1 to 9 IU/liter were more likely to respond to the challenge dose than those with a baseline anti-HBsAg level of 0 IU/liter (83% versus 50%; P < 0.001). The presence of any detectable anti-HBsAg among persons vaccinated in the remote past may indicate the persistence of immune memory.

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

BackgroundHepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.MethodsTo evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.ResultsOf the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.ConclusionsThe national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.