Toward reaching hepatitis B goals: hepatitis B epidemiology and the impact of two decades of vaccination, Georgia, 2021.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand.

BACKGROUND: This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine]. METHODS: Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports. RESULTS: Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group. CONCLUSIONS: This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.

Sero-prevalence of hepatitis B virus and compliance with hepatitis B vaccination schedules among outpatient clinic attendees in Nairobi.

BACKGROUND: Hepatitis B is becoming a growing public health problem in Kenya. To combat the threat, HBV vaccination should be recommended, particularly for individuals who are not covered by the national immunization program. Vaccination provides sero-protection rates approaching 95% among healthy adults after completing the three-dose vaccination course, but decreases to 87% among those who receive only two doses, emphasizing the importance of completing the three-dose vaccination course. However, data on adult adherence to HBV multi-dose vaccines in Sub-Saharan Africa are limited, despite the fact that this information is critical for prevention. As a result, more research on HBV vaccine dose completion is required. The purpose of this study is to estimate the prevalence of hepatitis B virus infection among out-patient clinic attendees in Nairobi, Kenya, as well as to identify beneficiaries of free vaccination and barriers to completing the recommended vaccine doses. METHODS: Between July 30th and September 30th, 2015, 2644 outpatient clinic attendees aged ≥ 4 were recruited from three hospitals in Nairobi County, Kenya: Mama Lucy, Riruta, and Loco. Self-administered questionnaires were used to collect socio-demographic information, and blood samples were tested for hepatitis B surface antigen (HBsAg) using the KEMRI HEPCELL Rapid® (Hepatitis B Detection kit) test kit. Individuals who tested negative for HBsAg were given a free course of three doses of HBV vaccine. The vaccination register provided information on the number of doses administered. RESULTS: The average age of the study population was 31.4 years (range: 4-66), with females accounting for 59.2%. 1.82% (48/2644) of the participants tested positive for HBsAg. Among the 2596 individuals eligible for vaccination, 66% (1720/2596) received at least one dose, and 51.8% (1345/2596) received all three doses. Vaccination acceptance increased with age, with older patients more likely to return for subsequent dose (OR>1 for second and third dose). Unavailability and failure to contact client were cited as significant (p<0.0001) barrier to vaccination completion by 53.7% (666/1226, 95% CI 0.5-0.6) and 37% (454/1226, 95% CI 0.3-0.4) of respondents respectively. CONCLUSION: The prevalence of HBV infection among outpatient clinic attendees highlights the importance of expanding HBV immunization programs in Kenya. However, given the low vaccination completion rate, there is a need for public awareness of the vaccine's importance in preventing HBV and HBV-related complications.

Dissolving Microneedle Arrays as a Hepatitis B Vaccine Delivery System Adjuvanted by APC-Targeted Poly (Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

The objective of this study is to develop a new hepatitis B surface antigen (HBsAg) delivery system by coating soluble microneedle arrays with mannose-modified PLGA nanoparticles (MNPs). MNPs of different sizes were synthesized. The effects these nanoparticles on the maturation of dendritic cells were studied by flow cytometry. HBsAg-containing MNPs (HBsAg/MNPs) of the appropriate sizes were coated into water-soluble microneedle arrays. The in vitro characteristics of microneedles arrays and the immune responses after subcutaneous administration in mice were studied. The results showed that PLGA nanoparticles with an average size of about 800 nm showed the most significant effects in stimulating the maturation of dendritic cells. In the water-soluble microneedle array, the targeted PLGA nanoparticles containing HBsAg were distributed discretely with a maximum distribution height of about 280 µm with a drug load of 0.98 ± 0.05 µg/mg. The drug-containing microneedle arrays exhibited excellent mechanical properties and improved biosafety. The results of immune responses in vivo showed that the subcutaneous administration of the microneedle arrays induced the proliferation of splenocyte, secreted specific IL-12 and IFN-γ, and promote the production of IgG in mice. This study verifies the feasibility of soluble composited microneedles administration in hepatitis B immunization, and provides new ideas for the development and application of non-injectable vaccine delivery systems.

Perceptions and Cues to Action as Predictors of Nurses' Vaccination Intentions at Two Primary Health Care Facilities in Ghana.

Uptake of hepatitis B vaccination by health care providers remains suboptimal in Ghana, although it is considered an effective strategy against the hepatitis B virus. This study aimed to identify the predictors of nurses' hepatitis B vaccination intentions at two municipal health care facilities in Ghana. A descriptive cross-sectional survey was adopted. A section of the health belief model-based questionnaire was administered to 181 nurses conveniently sampled from the two facilities. Data analysis was done using Statistical Product and Service Solutions software version 23.0. Frequencies and percentages were used to assess the demographic characteristics of participants. Pearson r coefficients were used to assess the intercorrelations between individual perceptions, and the cues to action on vaccination intentions. Simple and multiple regression was used to estimate the prediction of individual perceptions, and the cues to action on hepatitis B vaccination intentions of nurses. The findings showed that nurse-perceived benefits and cues to action were positive and significantly related to hepatitis B vaccination intentions of nurses (r = 0.14, P < 0.05; r = 0.17, P < 0.05). Perceived susceptibility and perceived barrier were negative and significantly related to vaccine intentions (r = -0.13, P < 0.05; r = -0.24, P < 0.01). Notably, perceived barrier predicted hepatitis B vaccination intentions (ß = -0.22, t = -2.48, P = 0.01). Nurses' vaccination behavioral intentions were positive. It was recommended that perceived barriers to hepatitis B vaccination such as vaccination ineffectiveness, time constraints, high costs, and side effects should be addressed to increase nurses' vaccination uptake.

Assessing the impact of hepatitis B immune globulin (HBIG) on responses to hepatitis B vaccine during co-administration.

INTRODUCTION: A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered. METHODS: Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed. RESULTS: Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration CONCLUSION: Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site.

Impact of the national hepatitis B immunization program in China: a modeling study.

BACKGROUND: Elimination of hepatitis B virus (HBV) is a striking challenge for countries with high or moderate disease burden. Therefore, using China as a practical case to share experiences for similar countries may accelerate the achievement of the WHO 2030 target of 90% reduction in HBV-related incidence. We aim to evaluate the impact of national HBV immunization strategies in China; and the feasibility to achieve WHO 2030 targets under different scenarios. METHODS: We constructed an expanded Susceptible-Exposed-Infectious-Recovered (SEIR) model and decision tree-Markov model to estimate the epidemic of HBV in China, assess the feasibility of 2030 Elimination Goals through the projections and conduct the economic analysis. Least square method was used to calibrate the expanded SEIR model by yearly data of laboratory-confirmed HBV cases from 1990 to 2018. Two models were separately used to evaluate the impact and cost-effectiveness of HBV vaccine by comparing prevalence of chronic HBV infections, quality-adjusted life-years (QALYs), incremental cost effectiveness ratio and benefit-cost ratio (BCR) under various intervention options, providing a basis for exploring new containment strategies. RESULTS: Between 1990 and 2020, the number of chronic HBV infections decreased by 33.9%. The current status quo would lead to 55.73 million infections (3.95% prevalence) in 2030, compared to 90.63 million (6.42% prevalence) of the "Without the NIP" scenario (NIP: National Immunization Program), 114.78 million (8.13% prevalence) without any interventions. The prevention of mother to child transmission (PMTCT) strategy showed a net benefit as 12,283.50 dollars per person, with BCR as 12.66, which is higher than that of universal vaccination at 9.49. Compared with no screening and no vaccination, the PMTCT strategy could save 7726.03 dollars for each QALY increase. CONCLUSIONS: Our findings proved the HBV vaccination has demonstrated a substantial positive impact on controlling the epidemic of HBV in terms of effectiveness and economy after about 30 years of implementation of the national hepatitis B immunization program which also provided containment experience for high or medium burden countries. As for China, the next step should focus on exploring strategies to improve diagnosis and treatment coverage to reduce the burden of HBV-related deaths and ultimately eliminate HBV.

Intradermal Hepatitis B Vaccination in Non-responder People Living with Human Immunodeficiency Virus in Japan.

We performed a pilot study to assess the immunogenicity and safety of intradermal hepatitis B (HB) virus vaccines in people living with HIV (PLWH). This single-center prospective study was conducted in Yokohama, Japan. Adult PLWH with serum antibodies against HB surface antigen (anti-HBs) <10 mIU/mL at all time points after standard HB vaccination were included. We administered HB surface antigen (total dose of 10 µg) at 5 separate sites intradermally at baseline, one month, and 6-9 months and measured anti-HBs 1-3 months after administration. Eleven PLWH were included in this study. The mean age was 36 years, and all patients were men. At baseline, all patients were on antiretroviral therapy, and the mean CD4+ lymphocyte count was 588 /µL and plasma HIV-RNA was <20 copies/mL, except for one patient. Anti-HB levels were elevated to >10 mIU/mL in one patient after one dose, 6 patients after 2 doses, and 4 patients after 3 doses of the intradermal vaccines. Eight patients experienced grade 1 local adverse events. Additional vaccination via the intradermal route induced an anti-HBs level >10 mIU/mL in all patients, without serious adverse events.

Genetic variants of NTCP gene and hepatitis B vaccine failure in Taiwanese children of hepatitis B e antigen positive mothers.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccine failure remains a hurdle to the global elimination of HBV infections in the vaccination era. We aimed to elucidate the relationships between HBV entry receptor sodium taurocholate co-transporting polypeptide (NTCP) and vaccine failure in children born to highly infectious mothers. METHODS: The genetic variants rs7154439, rs4646285, rs4646287, and rs2296651 were genotyped in 170 children with chronic HBV infections and 138 control children of mothers positive for hepatitis B e antigen (HBeAg). All children received hepatitis B immunoglobulin and complete HBV vaccination. Total RNAs from 82 adult non-tumor liver tissues were quantified for NTCP, type I interferons and interferon-induced transmembrane protein 3 (IFITM3) levels. RESULTS: A higher rate of the GA/AA genotype (28.3% vs. 15.3%, p = 0.006) of the genetic variant rs4646287 in intron 1 of the NTCP gene was detected in control children compared to the carrier children. The rs4646287 G > A genotype was associated with younger ages at which spontaneous HBeAg seroconversion occurred (10.8 ± 8.4 vs. 14.6 ± 8.7 years, p = 0.003) in chronic HBV-infected children. Unique correlation patterns of NTCP and innate immunity-related genes (type I interferons and IFITM3) were found in HBV-infected liver tissues with the rs4646287 G > A genotype. CONCLUSION: The rs4646287 G > A genotype of the NTCP gene may be associated with lower risk for HBV vaccine failure in children born to highly infectious mothers. The protective effect of rs4646287 G > A was also present in carrier children, evidenced by earlier spontaneous HBeAg seroconversion.

[Non/hypo-response to hepatitis B vaccination and influencing factors in HIV-infected patients in the context of different immunization schedules].

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ2 test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction.

Importance: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. Objective: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. Design, Setting, and Participants: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). Exposures: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. Main Outcomes and Measures: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. Results: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, -0.19 [95% CI, -0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). Conclusions and Relevance: In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

Hepatitis vaccination adherence and completion rates and factors associated with low compliance: A claims-based analysis of U.S. adults.

Poor compliance with multi-dose vaccine schedules by adults for whom hepatitis (Hep) A and B vaccines are recommended contributes to major Hep A and B disease burdens among high-risk U.S. adults. Evidence on hepatitis vaccine series adherence, completion, timeliness of completion, and factors associated with these outcomes, is limited and not readily generalizable for U.S. adults. This retrospective, observational study examined adherence, completion, its timeliness, and the impact of sociodemographic and clinical factors on these outcomes among a large, geographically representative sample of U.S. adults. We analyzed the Optum Clinformatics SES administrative claims database (1/1/2010-6/30/2020) for recipients of 2-dose (HepA, HepB2) or 3-dose (HepB3, HepAB) hepatitis vaccines. Adherence was defined as receipt of booster doses within specified assessment periods, per label-recommended schedules. Completion (receipt of all doses) was assessed at 6, 12, 18, and 24 months.The study included 356,828 adults ≥19 years old who were continuously enrolled in a medical benefit plan for one (HepB2), six (HepB3; HepAB), or 18 months (HepA) prior to and following the index date (first observed vaccine dose). Adherence and 24-month completion rates were: HepA (27.0%, 28.4%), HepB2 (32.2%, 44.8%), HepB3 (14.3%, 37.3%), HepAB, (15.3%, 33.8%). Kaplan-Meier completion curves plateaued after about 6 months for HepB2 and about 12 months for HepA, HepB3, and HepAB vaccines. Logistic regression analyses showed risk for low adherence/completion was generally associated with male gender, younger age, Black or Hispanic race/ethnicity, lower educational or household income attainment, and more comorbidities. Adherence and completion rates for all hepatitis vaccine series are low, especially for males, younger adults, those with lower socio-economic status and more comorbidities. To our knowledge, this is the largest claims-based analysis of adherence and completion rates for U.S. adults initiating all currently available HepA and HepB vaccines. Findings may inform hepatitis vaccination programming.

Antibody levels and protection after Hepatitis B vaccine in adult vaccinated healthcare workers in northern Uganda.

Hepatitis B vaccine has contributed to the reduction in hepatitis B virus infections and chronic disease globally. Screening to establish extent of vaccine induced immune response and provision of booster dose are limited in most low-and-middle income countries (LMICs). Our study investigated the extent of protective immune response and breakthrough hepatitis B virus infections among adult vaccinated healthcare workers in selected health facilities in northern Uganda. A cross-sectional study was conducted among 300 randomly selected adult hepatitis B vaccinated healthcare workers in Lira and Gulu regional referral hospitals in northern Uganda. Blood samples were collected and qualitative analysis of Hepatitis B surface antigen (HBsAg), Hepatitis B surface antigen antibody (HBsAb), Hepatitis B envelop antigen (HBeAg), Hepatitis B envelop antibody (HBeAb) and Hepatitis B core antibody (HBcAb) conducted using ELISA method. Quantitative assessment of anti-hepatitis B antibody (anti-HBs) levels was done using COBAS immunoassay analyzer. Multiple logistic regression was done to establish factors associated with protective anti-HBs levels (≥ 10mIU/mL) among adult vaccinate healthcare workers at 95% level of significance. A high proportion, 81.3% (244/300) of the study participants completed all three hepatitis B vaccine dose schedules. Two (0.7%, 2/300) of the study participants had active hepatitis B virus infection. Of the 300 study participants, 2.3% (7/300) had positive HBsAg; 88.7% (266/300) had detectable HBsAb; 2.3% (7/300) had positive HBeAg; 4% (12/300) had positive HBeAb and 17.7% (53/300) had positive HBcAb. Majority, 83% (249/300) had a protective hepatitis B antibody levels (≥10mIU/mL). Hepatitis B vaccine provides protective immunity against hepatitis B virus infection regardless of whether one gets a booster dose or not. Protective immune response persisted for over ten years following hepatitis B vaccination among the healthcare workers.

Re-examining Hepatitis B Postexposure Prophylaxis Following Pediatric Community-acquired Needle-stick Injury in an Era of a National Immunization Registry.

BACKGROUND: Long-term hepatitis B immunity has been demonstrated following the completion of the primary vaccination series in childhood. Some guidelines recommend a hepatitis B surface antibody (anti-HBs) directed approach following community-acquired needle-stick injury (CANSI) to inform hepatitis B postexposure prophylaxis (PEP) management. We assessed the utility of anti-HBs testing post-CANSI, as well as the costing of, and adherence to PEP at a pediatric hospital. METHODS: Children presenting to an Australian tertiary pediatric hospital post-CANSI (2014-2019) were identified retrospectively using medical and laboratory records. Immunization status was obtained from the Australian Immunisation Registry. RESULTS: Fifty-six children with CANSI were identified. Of those with immunization records, all had completed hepatitis B vaccinations (n = 52). At presentation, 44% (n = 23) had anti-HBs <10 IU/L, which was more likely in older (≥6 years, 68%) versus younger children (OR 4.59, P < 0.02). HBIG and hepatitis B vaccine adherence was 65% (15/23) and 78% (18/23), respectively. All children (n = 14) with anti-HBs ≥4 weeks postvaccination ±HBIG, demonstrated an anamnestic response. No hepatitis B infections were detected. Using completed immunizations versus anti-HBs levels as a marker of immunity to direct PEP resulted in a projected cost savings of AUD$ 4234. CONCLUSION: Anti-HBs levels <10 IU/L, despite previous vaccinations, were frequent in children post-CANSI, with many demonstrating an anamnestic response. Adherence to postexposure HBIG and hepatitis B vaccine was suboptimal using an anti-HBs directed approach. These data support re-evaluating PEP in an era of the national immunization registry; completion of hepatitis B vaccinations as a marker of immunity provides a practical approach, ensuring optimized care for pediatric CANSI.

Non/hypo-response to hepatitis B vaccination and influencing factors in HIV-infected patients in the context of different immunization schedules / 中华流行病学杂志

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ2 test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.

Implementation of a neonatal hepatitis B immunization program in rural Karenni State, Myanmar: A mixed-methods study.

BACKGROUND: Hepatitis B infection is a major health concern in Myanmar. Hepatitis B birth dose vaccination to prevent mother-to-child transmission is not universal, especially in births outside of health care facilities. Little is documented about delivery of immunization programs in rural Myanmar or in conflict-affected regions. To address this gap, this study describes the implementation of a novel community delivered neonatal hepatitis B immunization program in rural Karenni State, Myanmar. METHODS: A mixed-methods study assessed the effectiveness and feasibility of hepatitis B birth dose immunization program. 1000 pregnant women were screened for hepatitis B virus (HBV) infection using point of care testing. Neonates of HBV positive mothers were immunized with a three dose HBV vaccine schedule at birth, 1, and 6 months of age. HBV testing was completed for children at 9 months to assess for infection. Descriptive statistics were collected including demographic data of mothers, neonatal vaccination schedule completion, and child HBV positivity at 9 months. Qualitative data examining barriers to implementation were collected through semi-structured interviews, participant-observation, and analysis of program documents. Themes were codified and mapped onto the Consolidated Framework for Implementation Research. RESULTS: 46 pregnant women tested HBV positive leading to 40 live births. 39 women-child dyads were followed until the 9-month age mark. With the exception of two neonates who received their birth dose past 24 hours, all children received their vaccines on time. None of the 39 children tested positive for HBV at nine months. Themes regarding barriers included adaptability of the program to the rural setting, friction with other stakeholders and not meeting all needs of the community. Identified strengths included good communication and leadership within the implementing ethnic health organization. CONCLUSION: A community delivered neonatal HBV vaccination program by ethnic health organizations is feasible and effective in rural Myanmar.

[Immunization effect and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell levels].

Objective: To explore the immunogenicity and persistence of hepatitis B vaccine in HIV-infected patients with different CD4+T cell (CD4) levels, and analyze the influence effect of CD4 levels on immunization response. Methods: A total of 182 HIV-infected patients who participated in a randomized controlled trial of 20 µg and 60 µg hepatitis B vaccination at month 0, 1, and 6 in 2014 by Guangxi Zhuang Atonomous Region CDC and Ningming county CDC were surveyed. Six months later after the first dose and 1 month, 6 months, 1 year, and 3 years later after the full course of the vaccination, 5 ml of the venous blood of the patients was collected, and the anti-HBs was detected by Chemiluminescent Microparticle Immunoassay (CMIA). On the basis of previous studies, this study focused on analyzing the immunogenicity and persistence of hepatitis B vaccine under different CD4 levels. Results: One month later after the whole course of hepatitis B vaccination, the anti-HBs geometric mean concentration (GMC), anti-HBs positive rate (≥10 mIU/ml) and strong positive rate (≥100 mIU/ml) in HIV patients with CD4 <350 cells/µl were 442.50 mIU/ml, 71.05% (27/38) and 44.74% (17/38), respectively, which were significantly lower than those HIV-infected patients with CD4 ≥350 cells/µl [583.90 mIU/ml, 92.13% (117/127) and 77.95% (99/127)] (P<0.05). After controlling the confounding factors, the probability of being anti-HBs positive induced by hepatitis B vaccine in patients with CD4 <350 cells/µl was 0.14 times higher than in those with CD4≥350 cells/µl (95%CI: 0.03-0.62), and patients with CD4 <350 cells/µl had higher risk of no response. From 6 months to 3 years after the whole course of the vaccination, the anti-HBs GMC (195.00-27.55 mIU/ml vs. 300.10-45.81 mIU/ml), the positive rate (56.67%-36.67% vs. 78.57%- 51.58%) and the strong positive rate (33.33%-6.67% vs.44.64%-15.79%) in patients with CD4 <350 cells/µl gradually declined, lower than the levels in those with CD4 ≥350 cells/µl. Conclusions: HIV-infected patients with CD4 <350 cells/µl have high risk of no response to hepatitis B vaccination and poor immune persistence. It is necessary to strengthen the anti-HBs monitoring in HIV-infected patients, with special attention to those with CD4 <350 cells/µl. When anti-HBs is negative, hepatitis B vaccine should be injected as early as possible.

The impact of the timely birth dose vaccine on the global elimination of hepatitis B.

In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.

Hepatitis B Vaccine Non-Responders Show Higher Frequencies of CD24highCD38high Regulatory B Cells and Lower Levels of IL-10 Expression Compared to Responders.

Background: The cellular mechanisms involved in the lack of protective antibody response after hepatitis B vaccination are still rather unclear. Regulatory B cells (Breg) known as modulators of B-and T-cell responses may contribute to poor vaccine responsiveness. The current study aimed to investigate the role of regulatory B cells (Breg) in hepatitis B vaccine non-responsiveness after immunization with second- or third-generation hepatitis B vaccines. Method: We performed comparative phenotypic and frequency analysis of Breg subsets (CD24+CD27+ and CD24highCD38high Breg) in second-generation hepatitis B vaccine non-responders (2nd HBvac NR, n = 11) and responders (2nd HBvac R, n = 8) before (d0), on day 7 (d7), and 28 (d28) after booster vaccination. Cryopreserved peripheral blood mononuclear cells were stimulated ex vivo with a combination of CpG, PMA, and Ionomycin (CpG+P/I) and analyzed for numbers and IL-10 expression levels of Breg by flow cytometry-based analyses. Results: Flow cytometry-based analyses revealed elevated frequencies of CD24+CD27+ Breg at all time points and significantly higher frequencies of CD24highCD38high Breg on d0 (p = 0.004) and 28 (p = 0.012) in 2nd HBvac NR compared to 2nd HBvac R. In parallel, we observed significantly lower levels of CpG+P/I-induced IL-10 expression levels of CD24+CD27+ and CD24highCD38high Breg (d0: p < 0.0001; d7: p = 0.0004; d28: p = 0.0003 and d0: p = 0.016; d7: p = 0.016, respectively) in 2nd HBvac NR compared to 2nd HBvac R before and after booster immunization. Frequencies of CD24+CD27+ and CD24highCD38high Breg significantly decreased after third-generation hepatitis B booster vaccination (d7: p = 0.014; d28: p = 0.032 and d7: p = 0.045, respectively), whereas IL-10 expression levels of both Breg subsets remained stable. Conclusion: Here we report significantly higher frequencies of CD24highCD38high Breg in parallel with significantly lower IL-10 expression levels of CD24+CD27+ and CD24highCD38high Breg in 2nd HBvac NR compared to 2nd HBvac R. Anti-HBs seroconversion accompanied by a decrease of Breg numbers after booster immunization with a third-generation hepatitis B vaccine could indicate a positive effect of third-generation hepatitis B vaccines on Breg-mediated immunomodulation in hepatitis B vaccine non-responders.

Hepatitis B vaccination status and associated factors among students of medicine and health sciences in Wolkite University, Southwest Ethiopia: A cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) infection is a significant global public health problem. Health care providers and medical students in developing countries including Ethiopia are at an increased risk of contracting HBV due to the high burden of this infection. The most effective way of prevention against HBV infection is vaccination of health care providers. However, there is a paucity of data on the HBV vaccination coverage among students of health science in Ethiopia. Therefore, this study aimed to determine HBV vaccination coverage and associated factors, level of knowledge, attitudes, and practices (KAP) towards HBV among students of medicine and health science at Wolkite University. MATERIALS AND METHODS: A cross-sectional study was conducted at Wolkite University among 417 study participants from November to December 2020. The study participants were recruited by using a simple random sampling technique. Data were collected using a self-administered structured questionnaire and analyzed using SPSS version 21. A binary logistic regression model was used to determine the factors associated with full-dose vaccination status. Statistical significance was set at P-value <0.05. RESULTS: Out of the 417 study participants, 5.8% (95%CI: 3.8-7.9) received a full-dose of the HBV vaccine in this study. Unavailability and high cost of the vaccine were frequently mentioned reasons for not being vaccinated against HBV. About 73.6%, 36.2%, and 47% of participants had good knowledge, positive attitudes, and good practices towards HBV, respectively. Being male gender (AOR: 8.8; 95%CI: 2.9-27), rural residence (AOR: 3.6; 95%CI:1.2-10.6), positive attitude (AOR: 0.44; 95%CI: 0.1-1.1), good practice (AOR: 0.17; 95%CI: 0.05-0.5), medicine department (AOR: 5.9; 95%CI: 1.2-29), being second-year student (AOR: 11.7; 95%CI: 2.7-50.9), third-year student (AOR: 19; 95%CI: 4.25-45), and fourth-year student (AOR: 27; 95%CI: 5.8-56) were significantly associated factors with full-dose vaccination status. CONCLUSION: Our study revealed that only small proportions (5.8%) of study participants received full-dose HBV vaccination. Vaccinations of students before starting clinical attachments, provisions of training for students on infection prevention mechanism and universal precautions particularly on HBV, increasing the uptake of the HBV vaccine, creating awareness on attitude and practice of students towards HBV to enhance uptake of the vaccine are recommended.