Immunization status and factors influencing hepatitis B vaccination of preterm infants in three provinces of China, 2019 to 2021.

BACKGROUND: Premature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population. METHODS: We obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019-2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression. RESULTS: There were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage. CONCLUSIONS: HepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

An Observational Prospective Cohort Study of Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection of an Aerosolized, Inhaled Adenovirus Type 5-Vectored Coronavirus Disease 2019 Vaccine Given as a Second Booster Dose in Guangzhou City, China.

Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.

Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.

BACKGROUND: Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet. METHODS: This multicentre, open-label phase 3 trial, done in 15 centres in six provinces (Jiangsu, Hunan, Anhui, Chongqing, Yunnan, Shandong) in China, aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV in healthy adults (members of the general population with no acute febrile disorders, infectious disease, serious cardiovascular diseases, serious chronic diseases or progressive diseases that cannot be controlled) at least 18 years old, who had received two doses of inactivated COVID-19 vaccine as their primary regimen. This study contained a non-randomly assigned safety cohort and a centrally randomly assigned (1:1) immunogenicity subcohort. The patients in the immunogenicity subcohort received aerosolised Ad5-nCov (aerosolised Ad5-nCoV group) or inactivated vaccine (inactivated COVID-19 group) The primary endpoints were the incidence of adverse reactions within 28 days following the booster vaccination with aerosolised Ad5-nCoV in the safety population (collected through a daily record of any solicited or unsolicited adverse events filled by each participant) and the geometric mean titre of neutralising antibodies at day 28 after the booster dose in the immunogenicity subcohort (measured with a pseudovirus neutralisation test). This study was registered with ClinicalTrials.gov, NCT05204589. FINDINGS: Between Jan 22, 2022, and March 12, 2022, we recruited 11 410 participants who were screened for eligibility, of whom 10 267 (99·8%) participants (5738 [55·9%] men, 4529 [44·1%] women; median age 53 years [18-92]) received the study drugs: 9847 (95·9%) participants in the open-label cohort to receive aerosolised Ad5-nCoV, and 420 (4·1%) in the immunogenicity subcohort (212 in the aerosolised Ad5-nCoV group and 208 in the inactivated vaccine group). Adverse reactions were reported by 1299 (13%) of 10 059 participants within 28 days after receiving the booster vaccination with aerosolised Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants in the aerosolised Ad5-nCoV group had a significantly higher level of the neutralising antibodies against omicron BA.4/5 (GMT 107·7 [95% CI 88·8-130·7]) than did those in the inactivated vaccine group (17·2 [16·3-18·2]) at day 28. INTERPRETATION: The heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Association of vaccine policy with virus infection and awareness of hepatitis B in Fujian, China.

China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9-9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43-0.62), 0.10 (0.08-0.12), and 0.015 (0.01-0.023) among the 1981-1991, 1992-2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00-1.57), 0.39 (0.26-0.58), and 0.019 (0.006-0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (ß = -0.25, SE = 0.08, P = .001, and ß = -0.20, SE = 0.08, P = .017 for 1992-2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public's awareness of hepatitis B vaccination in the context of great achievements.

A case-case study on the effect of primary and booster immunization with China-produced COVID-19 vaccines on prevention of pneumonia and viral load among vaccinated persons infected by Delta and Omicron variants.

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.

Epidemiological distribution of hepatitis B virus genotypes in 1-29-year-olds in the mainland of China.

BACKGROUND: To analyze the epidemiological distribution of Hepatitis B virus (HBV) genotype in the mainland of China following the implementation of effective preventive measures. METHODS: Five hundred and seventeen HBsAg-positive subjects aged 1-29 years surveyed in the 2014 national HBV sero-survey in the mainland of China were enrolled in the study. The full-length HBV genome was obtained by PCR amplification and sequencing. The HBV genotype was determined by phylogenetic analysis. Combined with questionnaire information, HBV genotype distribution was analyzed. RESULTS: Of the 517 HBsAg-positive subjects, 369 (71.4%) were included in the analysis. HBV genotypes found were B (45.0%), C (36.6%), D (6.0%), C/D (9.8%), B/C (2.2%), and I (0.5%). Geographic differences in HBV genotype were significant for seven regions. Three serotypes were found: adw (47.2%), adr (35.5%), and ayw (17.3%). B2 (43.9%) and C2 (25.2%) were the two major subgenotypes. The predominant genotypes differed between the Han group and the other ethnic groups. No statistical differences in genotype distribution were found by gender, age group, or hepatitis B (HepB) vaccination history. CONCLUSION: The prevalence of HBV genotype B was higher than that of genotype C with subgenotypes B2 and C2 endemic in 1-29-year-olds in the mainland of China, after HBV prevalence has reduced significantly due to the implementation of preventive measures. HepB vaccination or other factors did not interfere with HBV genotype distribution. The surveillance of HBV genotype was essential for responding to the potential changes and impact on the preventive policies in the future.

Factors predicting clinical pregnancy rate of in vitro fertilization-embryo transfer (a STROBE-compliant article).

The aim of this study was to investigate the factors predicting clinical pregnancy rate of in vitro fertilization-embryo transfer (IVF-ET).The data of 9960 patients receiving IVF-ET fresh cycle at our Reproductive Center from January 2009 to December 2017 were first divided into pregnant group and non-pregnant group to find the clinical pregnancy rate-related factors. According to the serum HCG levels at 36 hours and 12 hours after HCG trigger, all patients were divided into 4 groups including <50 mIU/ml, ≥50 and <100 mIU/ml, ≥100 and <200 mIU/ml, and ≥200 mIU/ml groups to know whether the HCG levels at 36 hours and 12 hours affect the pregnancy rate. According to the serum HCG ratio at 36 hours to 12 hours (36 h/12 h) after HCG trigger, all patients were divided into three groups including <0.88, 0.88-1.06 and >1.06 groups to observe whether the serum HCG ratio (36 h/12 h) affects the clinical pregnancy rate. According to different assisted pregnancy modes, all patients were divided into 3 groups including IVF, ICSI, and IVF/ICSI groups to observe whether the assisted pregnancy mode affects the clinical pregnancy rate. The correlation of the clinical pregnancy rate with pregnancy rate-related factors obtained above was analyzed using logistic regression analysis model.The clinical pregnancy rate significantly increased (P < .01) in the HCG ratio (36 h/12 h) >1.06 group as compared with the HCG ratio (36 h/12 h) < 0.88 and 0.88-1.06 groups. The serum estrogen (E2) level at 36 hours was significantly lower and the number of retrieved oocytes was significantly higher in the HCG ratio (36 h/12 h) >1.06 group than in the HCG ratio (36 h/12 h) <0.88 and 0.88-1.06 groups (P = .000).The serum HCG ratio (36 h/12 h) may be used as a predictor of IVF-ET clinical pregnancy rate. High clinical pregnancy rate is probably associated with E2 down-regulation in the HCG ratio (36 h/12 h) >1.06 group.

Changes in the epidemiology of hepatitis A in three socio-economic regions of China, 1990-2017.

BACKGROUND: Hepatitis A (HepA) vaccination and economic transitions can change the epidemiology of HepA. China's Gross Domestic Product (GDP) per capita was known to be inversely associated with the incidence of HepA, but a deeper understanding of the epidemiology of HepA in different socio-economic regions is lacking. We compare the changing epidemiology of HepA in three socioeconomic-geographic regions of China. METHODS: We obtained data on all HepA cases reported through the National Notifiable Disease Reporting System and assessed trends and changes in age-specific incidence rates by age quartile and season. We categorized the country into three regions, the sequential years into five era, compared the incidence, quartile age, seasonal intensity and coverage of HepA of the three regions. Linear regression was performed to analyse trends in incidence of HepA and to analyse the association between coverage and incidence. RESULTS: The annual mean incidences of HepA in the eastern, central, and western regions decreased from 63.52/100 000, 50.57/100 000 and 46.39/100 000 in 1990-1992 to 1.18/100 000, 1.05/100 000 and 3.14/100 000 in 2012-2017, respectively. Decreases in incidence were seen in all age groups in the three regions; the incidence was highest (9.3/100 000) in the youngest age group (0-4 years) of the western region, while in the central region, the age group with the highest incidence changed from 0 to 9 years to adults ≥60 years old. In 2017, the median age of HepA cases was 43 years (Q1-Q3: 33-55), 47 years (Q1-Q3: 32-60) and 33 years (Q1-Q3: 9-52) in the eastern, central, and western provinces, respectively. Seasonal peaks became smaller or were nearly elimination nationwide, but seasonality persisted in some provinces. After the Expanded Program on Immunization (EPI) included HepA vaccine into the routine schedule in 2007, HepA coverage increased to > 80% in the three regions and was negatively association with the HepA incidence. CONCLUSION: The incidence of HepA decreased markedly between 1990 and 2017. A socioeconomic inequity in coverage of HepA vaccine was almost eliminated after HepA vaccine was introduced into China's EPI system, but inequity in incidence still existed in lower socio-economic developed region.

Compliance among infants exposed to hepatitis B virus in a post-vaccination serological testing program in four provinces in China.

BACKGROUND: Mother to child transmission of hepatitis B virus (HBV) remains the most common form of HBV infection in China. Prevention of HBV vertical transmission involves timely administration of the complete hepatitis B vaccine (HepB) series and hepatitis B immunoglobulin. Post-vaccination serological testing (PVST) is utilized to determine an infant's outcome after HBV exposure and completion of HepB series. We aim to determine the frequency of compliance with a PVST testing cascade for HBV infected mothers and analyze factors associated with infant lost to follow up (LTFU). METHODS: We conducted a retrospective cohort review of previously collected data in Fujian, Jiangxi, Zhejiang and Chongqing provinces in China from 1 June 2016-31 December 2017. The study population included all HBV-exposed infants and their mothers. SAS software was used for statistical analyses. Bivariate and multivariate regression analyses (presented in odds ratio [OR] with 95% confidence intervals [CI]) were used to compare the proportional differences of factors associated with PVST not being completed. RESULTS: Among enrolled 8474 target infants, 40% of them transferred out of the study provinces without further information and 4988 were eligible for PVST. We found 20% (994) of infants were not compliant with the testing cascade: 55% of LTFU occurred because parents refused venous blood sample collection or failure of sample collection in the field, 16% transferred out after 6 months of age, and 10% of families chose to have independent, confidential PVST completed without reporting results. High PVST noncompliance rates were more likely to be from Fujian (aOR = 17.0, 95% CI: 9.7-29.9), Zhejiang (aOR = 5.7, 95% CI: 3.2-10.1) and Jiangxi (aOR = 1.9, 95% CI: 1.0-3.4), and from HBV e antigen positive mother (aOR = 1.2, 95% CI: 1.1-1.4). CONCLUSIONS: This study found that the LTFU rate reached 20% in PVST program, which was a significant problem. We recommend implementing a national electronic information system for tracking HBV at risk mother-infant pairs; encourage further research in developing a less invasive means of completing PVST, and take effective measures nationally to reduce HBV stigma. Without reducing the loss to follow up rate among infants eligible for PVST, elimination of vertical HBV transmission will be impossible.

Hepatitis B vaccine alone may be enough for preventing hepatitis B virus transmission in neonates of HBsAg (+)/HBeAg (-) mothers.

BACKGROUND AND AIM: To prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers. METHODS: Combined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (-) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (-) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6months with or without HBIG at birth. RESULTS: At 7months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p=1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p=0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7months of age (1555.3mIU/mL vs. 654.9mIU/mL, p<0.0001). At 12months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p=0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7mIU/mL vs. 297.0mIU/mL, p=0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12months of age. CONCLUSIONS: Vaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers.

Hepatitis B Immunoprophylactic Failure and Characteristics of the Hepatitis B Virus Gene in Mother-Infant Pairs in Parts of China.

OBJECTIVE: To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes. METHODS: HBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software. RESULTS: The immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5.76% (32/556). High sequence homology (99.8%-100%) was observed in 8 of the 10 mother-infant pairs. We identified 19 subgenotype C2 strains, 9 subgenotype B2 strains, and 2 subgenotype C1 strains. Three serotypes were detected: adr (19/30), adw (9/30), and ayw (2/30). The frequency of amino acid mutation of the 'a' determinant region was 16.67% (5/30), including that of Q129H, F134Y, S136Y, and G145E. We detected 67 amino acid mutations in the basal core promoter, precore, and core regions of the genome. CONCLUSION: The immunoprophylactic failure rate in infants born to HBV-infected mothers is low in the regions of China examined during this study. Moreover, HBV mutation in the 'a' determinant region could not account for immunoprophylactic failure for all infants.

Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study.

OBJECTIVE: Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort. METHODS: A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5. RESULTS: All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20-3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003). CONCLUSIONS: HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed.

The immunogenicity in healthy infants and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10µg recombinant yeast-derived Hepatitis B vaccine (Hep-KSC).

BACKGROUND AND AIMS: To evaluate immunogenicity and efficacy of a 10µg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns. METHODS: Overall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10µg Hep-KSC, 10µg Engerix-B or 5µg Hep-KSC and those in PM group received 10µg Hep-KSC or 10µg Engerix-B at 0, 1 and 6 months, with an additional 200IU HBIG at birth for the latter. RESULTS: For NM Group, 10µg Hep-KSC paralleled 10µg Engerix-B but outperformed 5µg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p=0.0077) and anti-HBs geometric mean concentration (GMC) (798.87mIU/ml vs 790.16mIU/ml vs 242.04mIU/ml, p<0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000mIU/ml was higher in 10µg Hep-KSC than 5µg Hep-KSC group (45.77% vs 11.93%, p<0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10µg Hep-KSC and 10µg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10µg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10µg Engerix-B group. The anti-HBs GMC was comparable between 10µg Hep-KSC and 10µg Engerix-B group at 7 and 12 months (575.31mIU/ml vs 559.64mIU/ml; 265.79mIU/ml vs 264.48mIU/ml). CONCLUSIONS: 10µg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.

An economic analysis of adult hepatitis B vaccination in China.

BACKGROUND AND OBJECTIVE: With the universal infant hepatitis B vaccination (HepB) program, China has made remarkable achievements to prevent and control hepatitis B. In order to further reduce hepatitis B virus (HBV) infection, the Chinese government is considering implementing a widespread adult HBV vaccination campaign. We performed an economic analysis of two different adult HepB vaccination strategies for 21-59-years-olds: vaccination without screening and screening-based vaccination. METHODS: Cost-benefit analyses were conducted. All 21-59-year-olds were divided into two groups: young adults (ages 21-39) and middle-aged adults (ages 40-59). Costs and benefits were estimated using the direct cost and societal (direct and indirect costs) perspectives. All costs and benefits were adjusted to 2014 US dollars, where future values were discounted at a 3% annual rate. We calculated benefit-cost ratios (BCRs) of the two vaccination strategies for the two different age groups. Sensitivity analyses varied key parameters within plausible ranges. RESULTS: Among young adults, the direct and societal BCRs for a vaccination campaign with no screening would be 1.06 and 1.42; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 1.19 and 1.73. Among middle-aged adults, the direct and societal BCRs for a vaccination campaign without screening would be 0.59 and 0.59; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 0.68 and 0.73. CONCLUSION: The results of our study support a HepB vaccination campaign for young adults. Additionally, a vaccination campaign with screening appeared to provide greater value than a vaccination without screening.

Amino acid polymorphism in the reverse transcriptase region of hepatitis B virus and the relationship with nucleos(t)ide analogues treatment for preventing mother-to-infant transmission.

A high maternal serum hepatitis B virus (HBV) DNA level is associated with vaccine failure. The administration of nucleos(t)ide analogues (NAs) in pregnancy for decreasing serum HBV is regarded as an effective and safe method to reduce HBV perinatal transmission. However, the effect of NAs treatment is closely related to amino acid polymorphisms in the HBV reverse transcriptase (RT) region. The full-length RT coding region of 334 HBV isolates from untreated Chinese women of childbearing age with persistent HBV infection were sequenced and amino acid polymorphic analysis was performed to evaluate its impact on NAs treatment for decreasing HBV perinatal transmission. Of the 334 isolates, 36 (10.8%) harbored NAs resistance (NAr) mutations which were mainly putative drug mutations related to lamivudine. The primary drug mutation rtA181T/V was detected in three HBeAg-negative women with an HBV DNA level of <4 log IU/ml. These NAr mutations were rarely detected in women with an HBV DNA level of ≥7 log IU/ml (P = 0.014) or in women younger than 35 years (P = 0.001). The NAr mutation rate among young women (<35 years) who had a high HBV DNA level (≥7 log IU/ml) was significantly lower than in women who had lower HBV DNA levels (<7 log IU/ml) or who were older (≥35 years; P = 0.017). These results suggest that younger women with a high HBV DNA level harbor fewer NAr mutations and that this population may respond to NAs treatment for the prevention of mother-to-infant transmission.

[Study on the risk of HBV infection among spouses of HBsAg carriers].

OBJECTIVE: To investigate the risk of HBV infection among the spouses of hepatitis B virus surface antigen (HBsAg) carriers and to provide a reference for developing strategies on hepatitis B control and prevention. METHODS: A case-control study including HBsAg carriers aged 20 - 45 years-old from the nationwide sero-epidemiological survey for Hepatitis B in both Guangdong and Jiangxi provinces in 2006, together with their spouses were selected as case group, while. HBsAg negative persons and their spouses were among the control groups, under the same residential areas, gender, age and age of marriage to the HBsAg carriers. Questionnaire survey and hepatitis B serological markers detection were carried out, together with the HBV genotype detection among the HBsAg positive couples between husband and wife by PCR. RESULTS: Among the spouses of HBsAg carriers, the positive rate of HBsAg was 13.21%, while the rate was 6.29% for the spouse of HBsAg negative population, with difference statistically significant (χ² = 4.23, P < 0.05). HBsAg positive rate among spouses of the case group was higher than that in the control group. Among the spouses of HBsAg carriers, the HBsAg rate was positively correlated with the age of marriage, frequency of sexual intercourse and condom use. There were 21 pairs of HBsAg carriers between husband and wife, and HBV were isolated among 13 pairs, and there were 11 pairs carrying the same HBV genotype, accounting for 84.62%. HBV genotypes would include 8 pairs of type B and 3 pairs of type C. However, only 2 pairs were infected with different HBV genotype. CONCLUSION: High risks of HBV infection existed in the spouses of HBsAg carriers. It was important to ask the HBsAg carriers to take the initiative in informing their spouses, and carrying out the appropriate measures, such as safe sex or timely hepatitis B vaccination for the spouse of HBsAg carriers etc., so as to reduce the HBV transmission between husband and wife.

[Estimation on the intangible cost and influencing factors for patients with hepatitis B-related diseases].

OBJECTIVE: To estimate the intangible cost and associated factors on patients with hepatitis B-related diseases, so as to explore the differences of the three elicitation techniques on the 'willingness to pay approach' (WTP). METHODS: Face-to-Face interviews were conducted to collect health economics-related information by trained investigators, using a structured questionnaire. WTP was employed to estimate the intangible cost while an open-ended question format, together with iterative bidding game and payment card were respectively used to elicit WTP for the hypothetical cure of hepatitis B-related diseases. A Multiple linear stepwise regression model was determined to identify those factors potentially affecting the intangible cost. RESULTS: A total of 564 subjects from 641 patients with hepatitis B-related diseases were identified for the inclusion of this study. The average annual intangible cost of patient with hepatitis B-related diseases was 54 320.4 Yuan (Ren Minbi). The intangible cost accounted for 53.0% of the total cost, which was much more than the proportions of the direct and indirect costs (38.5% and 8.5%, respectively). Among annual personal and the household income of the patient, proportions of intangible cost were 262.6% and 67.6% respectively, suggesting that the patients were under huge spiritual and psychological pressure. Response rate of the approach, combined open-ended questions with iterative bidding game, was the highest (76.6%) among the three elicitation formats. Considered the characteristics of data being gathered, the approach seemed to be more reasonable. Further studies were needed to examine the results yielded from other WTP elicitation formats. We also noticed that the progression of disease was associated with the increase of direct and indirect costs, but not with the intangible cost. Data from the multiple linear stepwise regression analysis indicated that the types of hospital and commercial medical insurance were significantly different in explaining the variation of the intangible cost. CONCLUSION: Measures should be taken to reduce the intangible cost of hepatitis B-related diseases. The approach regarding the combination of open-ended questions with iterative bidding game should be recommended when carrying our further WTP studies of this kind.

[Evaluation on the efficacy of recombinant hepatitis B vaccine booster immunization in 2789 children aged over 10 years].

OBJECTIVE: To study the efficiency of booster immunization with different recombinant hepatitis B vaccines. METHODS: 2789 children aged over 10 years who had completed the basic immunization of hepatitis B vaccine under 1 year old were selected. All the sampled children were classified into four groups (A, B, C and D) and immunized with different hepatitis B vaccines produced by different companies respectively. Before booster immunization, their blood plasma specimens were detected for hepatitis B virus (HBV) surface antigen (HBsAg), antibodies to HBV surface antigen (anti-HBs) and antibodies to HBV core antigen (anti-HBc) by chemiluminescence. In each group, the anti-HBs positive children were immunized with one dosage and anti-HBs negative children were immunized three dosages of the same vaccine. Their blood specimens were collected again after 1 month, and detected for anti-HBs. RESULTS: The anti-HBs positive rates of A, B, C and D group were 36.43%, 37.59%, 42.91% and 46.46% respectively before immunization while 89.20%, 91.52%, 90.96% and 85.45% respectively after immunization with one dosage, 99.12%, 99.47%, 98.87% and 98.85% respectively after immunization with three dosages. The differences of anti-HBs positive rates in the four respective groups showed statistical significances between any two rates of pre-immunization, post-immunization with one dosage and post-immunization with three dosages (all P < 0.05). The anti-HBs positive conversion rates of four groups were 83.01%, 86.41%, 84.16% and 72.82% respectively after immunization with one dosage. The anti-HBs positive conversion rate of four groups were 98.62%, 99.16%, 98.03% and 97.84% respectively after immunization with three dosages and the difference of positive conversion rates in each group showed statistical significances between booster immunization with one dosage and booster immunization with three dosages. The average GMTs in anti-HBs positive children in the four groups were 2853.21, 6254.23, 3581.40 and 3021.32 mIU/ml respectively after immunization with one dosage. The average GMTs of anti-HBs negative children in the four groups were 273.08, 648.52, 387.87 and 245.36 mIU/ml respectively after immunization with one dosage, and were 632.30, 2341.14, 563.97 and 394.08 mIU/ml respectively after immunization with three dosages. CONCLUSION: Our data showed that it would be suitable to anyone to use the four vaccines for anti-HBs positive children aged over 10 years with one dosage and for anti-HBs negative children aged over 10 years with three dosage booster immunization.