[Strategic considerations in health economics for the complete treatment of patients with chronic HBV infection].

The World Health Organization (WHO) released the Global Health Sector Strategy 2016, which explicitly proposes a 90% reduction in the new hepatitis B virus (HBV) infection rate and a 65% reduction in HBV-related mortality by 2030. However, at present, there are still 296 million chronic hepatitis B virus-infected patients worldwide, and nearly 900,000 patients die every year from cirrhosis and liver cancer caused by HBV infection. Antiviral treatment for chronic hepatitis B virus infection can effectively inhibit HBV replication, reduce liver inflammation and necrosis, effectively block and reverse liver fibrosis, and even early cirrhosis, thereby lowering cirrhosis-related complications, liver cancer, and liver disease-related mortality. Although the domestic and foreign guidelines have gradually eased antiviral treatment indications for chronic hepatitis B, there are still a considerable number of chronic hepatitis B patients with nonconformity who cannot receive antiviral treatment because they do not meet the existing standards, resulting in the progression of more severe diseases. This study analyzed the prevalence of hepatitis B, the therapeutic effect of antiviral drugs, domestic and international guideline treatment standards, the assessment of key indicators changes in the guidelines, comprehensively considered the coverage rate and treatment standards for antiviral treatment, and explored the changes in disease burden and cost-effectiveness following increasing the coverage rate and reducing treatment thresholds in order to achieve the global strategic goal of eliminating hepatitis B as soon as possible as a public health threat.

[Evolution and regional differences in the supportive environment for influenza vaccination among the elderly population in China].

Seasonal influenza leads to a significant disease burden, and older people infected with influenza are susceptible to various complications. Influenza immunization can prevent infection effectively and significantly reduce the risk of complications and severe cases. Creating a supportive environment for vaccination is crucial in advancing the influenza vaccination rate among the elderly population. In China, the present environment for supporting influenza vaccinations among the elderly is primarily comprised of policies for free vaccination and expense reimbursement, which exhibit noteworthy regional variations across cities and regions. This study systematically analyses the supportive environment and regional disparities associated with influenza vaccination among the elderly in China. It aims to comprehend the opportunities for influenza prevention and control resulting from the current background of influenza vaccination and to identify potential health inequality challenges caused by regional differences. The findings should inform the introduction of relevant national policies and programs to protect the health and well-being of the elderly population.

[Progress in prevention and control of viral hepatitis since the establishing of the People's Republic of China].

China has the highest disease burden of viral hepatitis. After understanding the epidemic characteristics of viral hepatitis in China and putting forward scientific prevention and control strategies, the Chinese government has been effectively practicing the policy of "prevention first with combination of prevention and control". Over the past 40 years, China has taken effective measures to promote vaccination, strengthen blood screening, standardize diagnosis and treatment services and strengthen supervision, and achieved remarkable success. The incidence of hepatitis A decreased from 52.6 per 100,000 in 1990 to 1.38 per 100,000 in 2019, the HBsAg prevalence among children under 5 years of age decreased from 9.67% in 1992 to 0.32% in 2014, and the cure rate of chronic hepatitis C patients has reached more than 95%. The incidence of hepatitis E is also on the decline. However, in 2019, the estimated diagnosis rate for hepatitis B patients is 25% and treatment rate is 17%; hepatitis C diagnosed rate is 30% and only 9% of the diagnosed were treated. This still falls far from the target of 90% diagnosis rate and 80% treatment rate by 2030. Relevant policies should be implemented as soon as possible, health promotion should be carried out, and screening and diagnosis and treatment services should be strengthened to promote timely treatment for more chronically infected people.

The epidemiology of hepatitis B virus infection in women of reproductive age in highly endemic areas in China.

We describe the epidemiology of hepatitis B virus (HBV) infection among women of reproductive age residing in areas of China that are highly endemic for chronic HBV, and provide evidence useful for decision-makers to guide strategies for preventing mother-to-child transmission of HBV, and assess the impact of perinatal transmission PMTCT by projecting HBsAg prevalence trends without interventions. We conducted a cross-sectional HBV serological survey of women, 15-49 years of age, residing in Fujian, Guangdong, Guangxi and Hainan provinces. Demographic and other subject-level data were collected in face-to-face interviews, after which we obtain blood specimens. Specimens were tested for HBV sero-markers by ELISA (Beijing Wantai Biological Pharmacy), and HBV DNA was tested with PCR (Hunan Sansure Biotech). Weighted HBsAg and HBV (either HBsAg+ or anti-HBc+ indicating either present or past infection) prevalences were 11.82% and 57.16%, respectively. Among the HBsAg-positive women, 27% were also HBeAg positive. The proportion of individuals with HBV DNA loads >105 IU/mL declined with increasing age. Among HBsAg-negative women, 0.9% had occult HBV infection. The prevalence of chronic HBV infection among reproductive women in these highly endemic provinces is high, posing a threat to maternal health and risk of mother-to-child transmission. Prevention of mother-to-child transmission remains critically important.

[Endoscopic neurosurgery combined with intraventricular lavage for pyogenic ventriculitis].

Objective: To investigate the efficacy of endoscopic neurosurgery combined with intraventricular lavage for pyogenic ventriculitis. Methods: A retrospective analysis of 45 patients with pyogenic ventriculitis in six hospitals which included Beijing Shijitan Hospital and Peking Union Medical College Hospital from 2001 to 2017. Twenty-four patients (non-endoscopic group) were treated with external ventricular drainage combined with intraventricular antibiotics administration from 2001 to 2009. Twenty-one patients (endoscopic group) was treated by endoscopic neurosurgery combined with intraventricular antibiotics lavage from 2010 to 2017. The drainage time, mortality, and modified Rankin score (mRS) after 6 months of follow-up were compared between the two groups. Results: Drainage time: (20±6) days in the endoscopic group, and (42±10) days in the non-endoscopic group. There was a significant difference between the two groups (P<0.001). Days in hospital: (29±7) days in the endoscopic group, and (51±11) days in the non-endoscopic group. There were significant differences between the two groups (P<0.001). Mortality: 8 patients (33.3%) died in the non-endoscopy group, and 1 patient (4.76%) died in the endoscopy group. There was a significant difference between the two groups (P=0.017). After 6 months of follow-up, patients of mRS≤3 were 14 cases (66.67%) in the endoscopy group, and 7 cases (29.17%) in the non-endoscopic group. There was a significant difference between the two groups (P=0.001). Conclusion: Endoscopic neurosurgery combined with intraventricular antibiotics saline lavage for pyogenic ventriculitis is an effective assessment and treatment method, and it is worth further promotion and application.

[The risk of hepatitis B virus infection in people with diabetes mellitus: a meta-analysis].

Objective: To evaluate the relevance of diabetes mellitus and hepatitis B virus(HBV) infection in people by Meta-analysis. Methods: Databases we searched included CNKI, VIP China Science and Technology Journal Database, Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library and Web of Science Core Collection database. Publication time was from January 1997 to May 2017. The Languages were limited to Chinese and English. English search terms include: diabetes, diabetes mellitus, hepatitis B and risk. Chinese search terms include: diabetes mellitus, hepatitis B and risk. We included all observational studies on diabetes and HBV infection. Firstly, the Newcastle-Ottawa Scale and the evaluation criteria of Cross-sectional study recommended by Agency for Healthcare Research and Quality were used to evaluate the quality of articles. Secondly, RevMan 5.3 software was used for heterogeneity testing. Subgroup analysis, random effects model and Mantel-Haenszel method were used to calculate the combined OR value. Finally, Stata 14.0 software was used to conduct the sensitivity analysis, and Begg rank correlation method was used to detect the publication bias. Results: A total of 12 studies were included, comprising 6 cross-sectional studies and 6 case-control studies. But the 12 articles were heterogeneous (χ(2)=42.10, P<0.001). After subgroup analysis, cross-sectional studies of diabetes and HBV infection were still heterogeneous (χ(2)=28.21, P<0.001), whose combined odds ratio (OR) was 1.36 (95%CI: 1.03-1.80). But the heterogeneity of case-control studies was not statistically significant (χ(2)=10.32, P=0.070), whose combined odds ratio (OR) was 1.55 (95%CI: 1.10-2.17). After the sensitivity analysis, the 95%CI of the combined OR of the 7 studies did not fluctuate, and the lower limit was above 1.07. No publication bias was detected in the cross-sectional study subgroup (Z=1.35, P=0.176) and the case-control study subgroup (Z=1.69, P=0.091). Conclusion: Patients with diabetes are more likely to be infected with HBV than those without diabetes. Diabetes mellitus is likely to be a risk factor for HBV infection.

[The epidemiological characteristics of HBV susceptibility in 1-29 years old young people in China in 2006 and 2014: based on the national sero-survey data analysis].

Objective: To analyze the epidemiological characteristics of HBV susceptible people in 1-29 years old people in 2006 and 2014 in China. Method: Data is from the 2006 and 2014 national sero-survey, and both of them were conducted in 160 disease surveillance points of 31 provinces (excluding Hong Kong, Macao Special Administrative Region and Taiwan province) in China. We used the centralized face-to face investigation method to collect basic information including birth date, gender, ethnicity, resident place, hepatitis B vaccination (HepB) history and so on, and 5 ml venous blood was collected for all subjects to test the sero-markers of HBsAg, anti-HBs and anti-HBc. We definite the HBV susceptible people as the HBsAg, anti-HBs and anti-HBc all negative together. And we use chi-square to analyze the epidemiological characteristics of HBV susceptibility in 1-29 years old young people in 2006 and 2014, and use multiple factors logistic regression to analyze the affect factors on HBV susceptible appearing in people with HepB vaccination. Result: In 2006 and 2014 sero-surveys, the investigated 1-29 year-old people were 49 849 and 31 713, respectively. And compared with 2006, the proportion of HBV susceptible people with HepB among 1-29 in 2014 increased from 20.87% (10 401) to 28.55% (9 055) (χ(2)=630.69, P<0.001); and the proportion of susceptible people without HepB decreasing from 15.02% (7 485) to 7.66% (2 460) (χ(2)=953.73, P<0.001). Compared with Han nationality, the high risk of susceptible appearing in minority people after HepB vaccination (OR=1.38). And compared with less than 3 doses HepB vaccination, the more than 3 doses vaccination could reduce the anti-HBs disappearing rate (OR=0.68); Compared with one year after last dose vaccination, the 2-4 years interval (OR=3.33) and more than 5 years interval (OR=6.53) would have high risk for anti-HBs disappearing. All above were P<0.001. In western area, the proportion of susceptible people without HepB (9.58%, 1 047/2 460) was higher than the proportion in eastern (6.30%, 657/2 460) and middle area (7.30%, 756/2 460) (P<0.001). Conclusion: The HepB coverage maintained in high level in 1-4 years old children. The HBV susceptible proportion mainly concentrated in 15-29 years old people, and the immunization gap was in western, rural areas and minority peoples.

[Analysis on sero-epidemiological characteristics of hepatitis B virus among people born during 1994-2001 before and after hepatitis B vaccine catch-up vaccination, China].

Objective: To analyze the sero-epidemiological characteristics of hepatitis B virus among people born during 1994-2001, conducted by the national hepatitis B sero-epidemiological surveys in 2006 and 2014. Methods: Based on the data of the two national hepatitis B sero-epidemiological surveys in 2006 and 2014, people born during 1994-2001 were included into our analysis as this study subjects. The two surveys were conducted in 160 disease surveillance points of 31 provinces (not including Hong Kong, Macao and Taiwan) in China. Face-to-face interviews with the subject by door to door or on the investigation site were conducted by trained staff using standard questionnaires to obtain basic information including birth date, sex, ethnicity, resident place and so on. And then 5 ml venous blood was collected. Enzyme-linked immunosorbent assay (ELISA) reagents were used for HBsAg, anti-HBs and anti-HBc measurements and Abbott micro-particle enzyme immunoassay (MEIA) reagents was used to confirm test. We analyzed HBsAg, anti-HBs and anti-HBc positive rate by gender, ethnicity, urban/rural, eastern/central/western region, birth years and compared the distribution of serum epidemiological characteristics in 2006 and 2014. Results: 19 821 and 4 712 people born during 1994-2001 were involved in 2006 and 2014 national serosurveys of China, respectively. For the people born during 1994-2001, HBsAg positive rate were 2.02% (95% CI: 1.82%-2.21%) in 2014 and 1.95% (95% CI: 1.56%-2.35%) in 2006. Anti-HBc positive rate were 7.94% (95%CI: 7.17%-8.71%) in 2014 and higher than that in 2006 (6.49%, 95%CI: 6.15%-6.83%), especially for the female (8.31%, 95% CI: 7.20%-9.43%), urban (7.45%, 95% CI: 6.38%-8.52%), western region (11.25%, 95%CI: 9.79%-12.71%), minority people (16.02%, 95%CI: 13.47%-18.57%) in 2014 were higher than that of the female (6.29%, 95% CI: 5.81%-6.78%), urban (4.82%, 95% CI: 4.40%-5.24%), western region (7.97%, 95% CI: 7.31%-8.63%), minority people (11.88%, 95% CI: 10.66%-13.00%) in 2006 respectively. Anti-HBs positive rate were 57.80% (95%CI: 57.11%-58.48%) in 2014 and 59.13% (95%CI: 57.72%-60.53%) in 2006. Anti-HBs positive rate of rural (58.80%, 95% CI: 56.83%-60.78%),western region (58.50%, 95% CI: 56.23%-60.78%), minority people (57.20%, 95% CI: 53.76%-60.63%) in 2014 was higher than of rural (52.62%, 95% CI: 51.64%-53.61%),western region (51.73%, 95% CI: 50.54%-52.96%),minority people (41.14%, 95%CI: 39.28%-43.00%) in 2006. Conclusion: Anti-HBc positive rate among people born during 1994-2001 in 2014 survey showed a rising tendency than in 2006. The risk of HBV infection was existed. Hepatitis B vaccine catch-up in childhood was necessary.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among low-responder infants following primary vaccination: 4-year of follow-up].

Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T(0)), four years (T(1)) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T(0) and it decreased to 16.51% (149/529) at T(1). The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T(0) to T(1). Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T(0) were significantly higher at T(1). The positive rate at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T(0) were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T(0) were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T(1). The b value (95% CI) of GMC was 0.86 (0.04-1.68). Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.

[Recognition of the vaccination: a key and important strategy in controlling vaccine preventable diseases].

China has achieved an outstanding accomplishment in combating infectious diseases, which has contributed to health improvement and prolongation of life expectancy, and health development globally. Among strategies for combating infectious diseases, vaccination is a key component. However, immunization rates have fallen sharply as a result of false information, inconvenient access to vaccination, and distrust which together can lead to "vaccine hesitancy", eventually resulting in the risk of endemic vaccine-preventable disease. By analyzing the importance of vaccination and its determinants, it should be recognized that vaccination is necessary to protect children's health, and considered as a key national policy with forceful strategies for the control of vaccine-preventable diseases.

[Anti-HBs persistence following primary vaccination with three doses of hepatitis B vaccine among normal and high-responder adults: a 3-year follow-up study].

OBJECTIVE: To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 µg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. RESULTS: A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100% at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI: 1 358.86-1 470.30) mU/ml to 60.33 (95%CI: 56.97-63.90) mU/ml. When comparing with those vaccinated 20 µg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 µg HepB-SC, 10 µg HepB-SC and 10 µg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20 µg HepB-SC, 10 µg HepB-SC and 10 µg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92- -0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was -0.31 (-0.47- -0.15) and -0.24 (-0.39- -0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2. CONCLUSIONS: Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.

[Antibody persistence following primary vaccination with hepatitis B vaccine among normal and high-responder adults: a 5-year follow-up study].

OBJECTIVE: To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 µg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula polymorpha (HepB-HP). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and the risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. RESULTS: Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI: 1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI: 32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20 µg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 µg HepB-SC group and 10 µg HepB-HP group. The OR (95% CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 µg HepB-SC and 10 µg HepB-HP. The b (95%CI) was -0.20 (-0.28- -0.12) and -0.36 (-0.44- -0.29) , respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group; the b (95%CI) was -0.10(-0.18- -0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs at T2 was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2. CONCLUSION: Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1.

[Anti-HBs persistence following revaccination with three doses of hepatitis B vaccine among low-responsive adults after primary vaccination: a 4-year follow-up study].

OBJECTIVE: To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 µg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs <10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis. RESULTS: A total of 529 participants were identified from 892 low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI: 466.72-629.56) mU/ml to 27.69 (95% CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 µg HepB was significantly higher than those revaccinated 20 µg HepB-CHO, 10 µg HepB-SC and 10 µg HepB-HP. The b (95% CI) was -0.40 (-0.78--0.02), -0.57 (-1.01- -0.15) and -0.63 (-1.03- -0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95% CI) was 0.93 (0.53-1.33) and 3.31 (2.88-3.73) respectively. CONCLUSION: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among non-responsive adults: a 4-year of follow-up study].

OBJECTIVE: To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months schedule: 20 µg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively. RESULTS: Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95% CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI: 12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively. CONCLUSION: The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.

Comparison between the EQ-5D-5L and the EQ-5D-3L in patients with hepatitis B.

OBJECTIVES: The purpose of the study was to compare psychometric properties of the EQ-5D-5L (5L) and the EQ-5D-3L (3L) health outcomes assessment instruments in patients with hepatitis B in China. METHODS: Patients, including hepatitis B virus carriers and those with active or inactive chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis or hepatocellular carcinoma, answered a questionnaire composed of 5L, socio-demographic information, 3L, and the visual analog scale (VAS), respectively. After 1 week, a retest was conducted for inpatients. We compared acceptability, face validity, redistribution properties, convergent validity, known-group validity, discriminatory power, ceiling effect, test-retest reliability, and responsiveness of 5L and 3L. RESULTS: A total of 369 outpatients and 276 inpatients were recruited for the first interview. Of the inpatients, 183 were used in the retest. Most patients preferred 5L-3L. The 3L-5L response pairs had an inconsistency rate of 2.4%. Correlation with the VAS was greater with 5L than with 3L. Age, education, and comorbidity were associated with health-related quality of life (HRQoL). 5L discriminated more infectious conditions than 3L. In all dimensions, the Shannon's index from 5L was larger while in three dimensions the Shannon's evenness index from 5L was slightly larger. The ceiling effect was reduced in 5L. In patients with stable health states, no significant difference was detected in the weighted kappa between 5L and 3L, but intraclass correlation coefficient of 5L was higher than that of 3L. In patients with improved health states, HRQoL was seen as increased in both 5L and 3L, without significant difference. CONCLUSIONS: The EQ-5D-5L was more suitable than the EQ-5D-3L in the patients with hepatitis B in China.

[Progress in epidemiological research of norovirus infection].

With characteristics of high infectivity, diverse transmission routes and high variation, norovirus is the main pathogen of sporadic cases and outbreaks of acute gastroenteritis, resulting in a serious disease burden. This paper summarizes the latest progress in epidemiological research of norovirus infection from aspects of disease burden caused by acute gastroenteritis, virus variation and predominant strains, prevention and control measures, and immunization and vaccine development.

[Introduction of World Health Organization Strategies and the Technical Advisory Committee actions on viral hepatitis control and status of the elimination of viral hepatitis in China].

Viral hepatitis has been causing big threat to public health globally. The number of annual deaths caused by hepatitis surpassed the deaths caused by AIDS, tuberculosis, and malaria. World Health Organization (WHO) issued the global health sector strategy on viral hepatitis 2016-2020 (GHSS) to control its epidemic. It established the Strategies and Technical Advisory Committee on HIV, viral hepatitis, and sexually transmitted infections (STAC). This paper summarizes the GHSS goals and the keynote of the 2020 STAC meeting, analyzes the challenges and opportunities faced by China in eliminating viral hepatitis, and provides the comments on the papers on this issue, which could guide further actions.

[Review on immunogenicity, safety and social value of combined vaccines for children used both at home and abroad].

Combined vaccines contain two or more antigens. Research suggested that combined vaccines could prevent multi diseases and reduce the frequency of vaccination. This article focus on combined vaccines for children used both at home and abroad, such as diphtheria-pertussis-tetanus vaccine (DTaP), measles-rubella-mumps vaccine (MMR), etc. and summarizes their immunogenicity, safety and social values, including benefits to families, vaccination workers and health services, to provide evidence for promoting the research, development and use of combined vaccines in China. We found that combined vaccines can not only ensure the immunogenicity and safety, but also give convenient and lower cost vaccination to families, and using combined vaccines can improve the work efficiency of vaccination workers, reduce the impact of the epidemic on immunization services and improve vaccination coverage and timeliness. At present, the promotion of combined vaccines in China is restricted by many technical bottlenecks, high prices, and low awareness among people. It is recommended that research on the safety, effectiveness and health economics of combined vaccines should be strengthened, and the value of combined vaccines should be scientifically evaluated; the public's awareness and trust in combined vaccines should be enhanced, as well as the development and application of multi-linked multivalent vaccines should be promoted. The government should improve regulations to assist the development and application of combined vaccines.

[Development and outlook on human challenge trial of vaccine].

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

[Hesitancy of parents towards vaccines in national immunization program in three regions in China: a cross-sectional study].

Objective: To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program. Methods: A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys. Results: A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%). Conclusions: The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.