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.

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.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Association of the dietary inflammation index (DII) with the prevalence of chronic kidney disease in patients with type-2 diabetes mellitus.

Chronic kidney disease (CKD) is a major complication of diabetes mellitus (DM). Inflammation is an essential component in the process of CKD progression in patients with DM. Diet is a significant determinant of systemic inflammation levels. However, the association between the dietary inflammatory index (DII) and CKD in individuals with DM remains largely unknown; therefore, the aim of this study was to explore whether the DII is linked to the prevalence of CKD in patients with DM. The research method was as follows: first, data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were obtained. There were 7,974 participants in our study. These individuals were then classified into three groups according to DII tertiles (T1-T3), with each group consisting of 2,658 participants. Logistic regression analysis was employed to examine whether there was a connection between the DII and CKD. We observed a significant association between the DII and the prevalence of CKD in individuals with DM. After full adjustment for age, sex, ethnicity, smoking, drinking, body mass index (BMI), triglyceride (TG), total cholesterol (TC), metabolic equivalents (METs), energy intake, hypoglycemic medications, hypertension, and cardiovascular disease (CVD), the group with a higher DII had a greater frequency of CKD (T2 group: OR: 1.40; 95% CI: 1.10-1.76; p = 0.006; T3 group: OR: 1.67; 95% CI: 1.29-2.17; p < 0.001). The implementation of an anti-inflammatory diet could serve as an intervention strategy for patients with DM to prevent the onset of CKD.

Changing Epidemiology of Hepatitis A in China: Evidence From Three National Serological Surveys and the National Notifiable Disease Reporting System.

BACKGROUND AND AIMS: China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine. APPROACH AND RESULTS: Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts. CONCLUSIONS: The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.

Evaluating the independent influence of sexual transmission on HBV infection in China: a modeling study.

BACKGROUND: The long-term impact of sexual transmission on the hepatitis B virus (HBV) infection in China remains unclear. This study aims to estimate the independent influence of sexual transmission on HBV infection. METHODS: Based on the natural history of HBV infection and three national serosurvey data of hepatitis B in China, we developed an age- and sex-specific discrete model to describe the transmission dynamics of HBV. The initial conditions of the model were determined according to the age- and sex-specific national serosurvey data in 1992. Based on the national survey data of hepatitis B in 1992 and 2006, by using the Markov Chain Monte Carlo (MCMC) method, we estimated the age- and sex-specific seroclearance rates of hepatitis B surface antigen (HBsAg) and the horizontal transmission rates as well as their 95% confidence intervals (CI). Then we used the age- and sex-specific national serosurvey data of hepatitis B in 2014 to test the accuracy of our model-based estimation. Finally, we evaluated the independent impact of sexual transmission on HBV infection and discussed the long-term effect of promotion of condom use in China. RESULTS: We estimated that the annual rates of HBsAg seroclearance for males and females aged 1-59 years were respectively 1.04% (95% CI, 0.49-1.59%) and 1.92% (95% CI, 1.11-2.73%). Due to sexual transmission, in 2014, the total number of chronic HBV infections in people aged 0-100 years increased 292,581, of which males increased 189,200 and females increased 103,381. In 2006, the acute HBV infections due to sexual transmission accounted for 24.76% (male: 31.33%, female: 17.94%) and in 2014, which accounted for 34.59% (male: 42.93%, female: 25.73%). However, if the condom usage rate was increased by 10% annually starting in 2019, then compared with current practice, the total number of acute HBV infections from 2019 to 2035 would be reduced by 16.68% (male: 21.49%, female: 11.93%). The HBsAg prevalence in people aged 1-59 years in 2035 would be reduced to 2.01% (male: 2.40%, female: 1.58%). CONCLUSIONS: Sexual transmission has become the predominant route of acute HBV infection in China, especially for men. The promotion of condom use plays a significant role in reducing the cases of acute HBV infection.

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies.

BACKGROUND: The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. METHODS: During 2014-2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. RESULTS: (1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. CONCLUSIONS: HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

Effects of ACE Inhibitors and Angiotensin Receptor Blockers in Normotensive Patients with Diabetic Kidney Disease.

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing the progression of albuminuria and risk of cardiovascular events in hypertensive patients with diabetic kidney disease (DKD) is well-documented. However, the efficacy and safety of these agents in normotensive patients with DKD are still controversial. MEDLINE, Embase, and Cochrane Library were searched for relevant random controlled trials. The odd risk (OR) reductions were calculated with a random-effects model. Decrease in albuminuria, changes in eGFR, major cardiovascular events, and drug-related adverse events were analyzed. Thirteen RCTs including 1282 patients were retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs significantly decreased albuminuria (MD -80.28 mg/d, 95% CI -104.79 mg/d to -55.77 mg/d), and the efficacy is independent of changes in blood pressure and systolic blood pressure at baseline. The result of subanalysis showed the declining of albuminuria was more significantly in normotensive DKD patients with 2DM (p=0.005). No significant differences were found with regard to the declining of evaluated glomerular filtration rate (eGFR) (MD -0.29 ml/min/1.73 m2, 95% CI -2.99 to 2.41 ml/min/1.73 m2). There were no significant differences in the side effect of the drugs such as hypotension and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can decrease albuminuria to varying degree in normotensive patients with DKD, and better response occurred in patients with 2DM.

Using a hepatitis B surveillance system evaluation in Fujian, Hainan, and Gansu provinces to improve data quality and assess program effectiveness, China, 2015.

BACKGROUND: Monitoring hepatitis B surveillance data is important for evaluating progress towards global hepatitis B elimination goals. Accurate classification of acute and chronic hepatitis infections is essential for assessing program effectiveness. METHODS: We evaluated hepatitis B case-reporting at six hospitals in Fujian, Hainan and Gansu provinces in 2015 to assess the accuracy of case classification. We linked National Notifiable Disease Reporting System (NNDRS) HBV case-reports with hospital information systems and extracted information on age, gender, admission ward and viral hepatitis diagnosis from medical records. To assess accuracy, we compared NNDRS reported case-classifications with the national HBV case definitions. Multivariable logistic regression was used to identify factors associated with misclassification. RESULTS: Of the 1420 HBV cases reported to NNDRS, 23 (6.5%) of the 352 acute reports and 648 (60.7%) of the 1068 chronic reports were correctly classified. Of the remaining, 318 (22.4%) were misclassified and 431 (30.4%) could not be classified due to the lack of supporting information. Based on the multivariable analysis, HBV cases reported from Hainan (aOR = 1.8; 95% CI: 1.3-2.4) and Gansu (aOR = 12.7; 95% CI: 7.7-20.1) along with reports from grade 2 hospitals (aOR = 1.6; 95% CI:1.2-2.2) and those from non-HBV related departments (aOR = 5.3; 95% CI: 4.1-7.0) were independently associated with being 'misclassified' in NNDRS. CONCLUSIONS: We identified discrepancies in the accuracy of HBV case-reporting in the project hospitals. Onsite training on the use of anti-HBc IgM testing as well as on HBV case definitions and reporting procedures are needed to accurately assess program effectiveness and ensure case-patients are referred to appropriate treatment and care. Routine surveillance evaluations such as this can be useful for improving data quality and monitoring program effectiveness.

Self-motivated medical care-seeking behaviors and disease progression in a community-based cohort of chronic hepatitis B virus-infected patients in China.

BACKGROUND: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. METHODS: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. RESULTS: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. CONCLUSION: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

BACKGROUND: IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. METHODS: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. RESULTS: Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25-0.71, p < 0.001) and reducing proteinuria (SMD: -0.58 g/day, 95% CI -0.80 to -0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids' type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. CONCLUSION: This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution.

Comparison of hepatitis E virus seroprevalence between HBsAg-positive population and healthy controls in Shandong province, China.

BACKGROUND: Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls. METHODS: A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group. RESULTS: In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47-11.09) in Zhangqiue and 38.06% (95% CI: 35.07-41.19) in Rushan (P < 0.001); the corresponding rates of IgM were 0.1% (95% CI: 0.002-0.54) and 1.57% (95% CI: 0.90-2.53), respectively (P < 0.001). HEV IgG seroprevalence was similar between CHB group and the control group in both counties (P = 0.21, P = 0.47, respectively) and the same results were found for the positive rate of IgM (P = 0.103, P = 0.262, respectively). Multivariable analysis showed the status of HBsAg was not independently associated with the status of anti-HEV IgG in either Zhangqiu or Rushan [P = 0.187, OR = 1.23(95% CI: 0.90, 1.68); P = 0.609, OR = 1.05 (95% CI: 0.87, 1.26)]. CONCLUSIONS: The seroprevalence of HEV varies greatly in different geographic areas, but the seroprevalence is similar between populations with and without CHB. CHB patients residing in high HEV endemic areas might be at higher risk for HBV-HEV superinfection.

Robust Antibody and Cytokine Response to Hepatitis B Vaccine Among Not-in-Treatment Patients With Chronic Hepatitis C: An Open-Label Control Study in China.

Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial. Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups. Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05). Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment. Clinical Trials Registration: NCT 02898922.

Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China.

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of age, the decline was 97%. China's HBV prevention program, targeted toward interrupting perinatal transmission, has been highly successful and increasingly effective. However, this progress must be sustained for decades to come, and elimination of HBV transmission will require augmented strategies.

The independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, 1992-2006: A mathematical model analysis.

OBJECTIVE: To evaluate the independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, from its introduction in 1992 to 2006. METHODS: An age- and time-dependent discrete dynamic model was developed to simulate HBV transmission in China under the assumptions of no any change in interventions and only with newborn vaccination introduction, respectively. The initial conditions of the model were determined according to the national serosurvey in 1992. The simulated results were compared with the observed results of the national serosurvey in 2006, and the contribution rate of newborn vaccination on reducing HBV prevalence was calculated overall and by birth cohort. RESULTS: The total HBV prevalence would remain stable through the 14-year period if no any change in interventions, but decrease year by year if only with newborn vaccination introduction. Newborn vaccination could account for more than 50% of the reduction of the total HBV prevalence, although the full 3-dose and timely birth dose vaccination coverage rates were low in the early years. The results by birth cohort showed that the higher the two coverage rates, the higher contribution rate on reducing HBV prevalence. For the 2005 birth cohort which had high levels in the two coverage rates, the contribution rate could reach more than 95%. CONCLUSION: Newborn hepatitis B vaccination from 1992 to 2006 in China had played the most important role in reducing HBV prevalence. Newborn vaccination with high full 3-dose and timely birth dose coverage rates is the decisive factor in controlling hepatitis B in China.

[Analysis of the hepatitis B report data on pilot surveillance in 200 counties in China, 2013].

OBJECTIVE: To analyze the information of the supplementary card for hepatitis B and the laboratory confirmed result of immunoglobulin M antibody to hepatitis B virus (HBV) Core Antigen (anti-HBc IgM) for the suspected acute hepatitis B to evaluate the hepatitis B report data on pilot surveillance. METHODS: 200 counties were established in China for hepatitis B pilot surveillance and 63 641 cases were reported. We added a supplementary card in National Notificable Disease Reporting System (NNDRS) and all the reported hepatitis B cases in NNDRS were required to fill the supplementary card. Venous blood 5 ml was collected and a confirmed test of anti-HBc IgM was made for suspected acute hepatitis B. We made confirmed diagnosis for the suspected acute hepatitis B according to the supplementary card information of the reporting card and the confirmed test result of anti-HBc IgM. RESULTS: 63 641 hepatitis B cases were reported in 200 hepatitis B pilot surveillance counties in 2013. Among 1 723 cases which were filled with the HBsAg positive within six months in supplementary card, 735 cases were reported as chronic hepatitis B, the proportion was 42.66%. Among 4 582 cases which were filled with anti-HBc IgM positive in supplementary card, 2 436 cases were reported as acute hepatitis B, the proportion was 53.16%. 1 829 cases were reported as chronic hepatitis B, the proportion was 39.92%. The validity cases of the information for liver puncture and the HBV surface antigen (HBsAg) transform during the recovery period in supplementary cards for all the reporting cases were 579 and 4 961, and the rate were 0.91% and 7.80%, respectively. 4 302 suspected acute cases were made confirmed diagnosis, and 1 197 cases (27.82%) were confirmed acute and 2 590 cases (60.20%) were confirmed chronic. CONCLUSION: Clinical doctors failed to make full use of the information of supplementary cards to make classification diagnose for hepatitis B. Suspected acute hepatitis B with anti-HBc IgM positive should be pay attention to follow up and further distinguish acute or chronic hepatitis B according to the HBsAg transform.

[Seroepidemiological analysis of hepatitis B among children aged 1-14 in 3 counties of Guangdong province in 2013].

OBJECTIVE: To investigate the epidemic status of Hepatitis B in children aged 1-14 in 3 counties of Guangdong province in 2013, and to evaluate the effect of hepatitis control in children aged 1-14 after hepatitis B vaccine was integrated into the national immunization program in 2002 and catch-up vaccination was conducted from 2009 to 2011. METHODS: A multi-stage stratified random sampling was designed to survey 1 621 children aged 1-14 in rural area of Nanxiong county, Haifeng county and Xinxing county by questionnaires including general information, medical history and risk factors. The samples were tested with chemiluminescence method to detect hepatitis B virus (HBV) surface antigen (HBsAg), antibody to HbsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc). Chi-square test was used to compare the positive rate of HBV serum markers in different age groups, vaccine histories, birth weight and HBV infection status of mother. RESULTS: Among the children aged 1-14 in 3 counties rural regions of Guangdong province, the positive rate of HBsAg, anti-HBs, and anti-HBc was 1.11% (18/1 621), 60.69% (982/1 618) and 1.92% (31/1 617), respectively. The HBsAg positive rate of vaccinated children (0.84%, 13/1 547) was lower than that of unvaccinated children (1/13) or children with unknown vaccination status (6.56%, 4/61) (χ² = 22.64, P < 0.001). The HBsAg positive rate (0.45%, 5/1 118) of the children with birth-dose given within 24 hours was lower than those that of children given beyond 24 hours (2.63%, 61/190) (χ² = 10.21, P < 0.001). The HBsAg positive rate (5/18) of children with birth weight under 2 kilogram was higher than that of children with birth weight above 2 kilogram (0.78%, 12/1 548) (χ² = 120.8, P < 0.001). The HBsAg positive rate of children born to HBsAg-positive mothers (2.80%, 3/107) was higher than that of children born to HBsAg-negative mothers (0.21%, 1/470) (χ² = 8.50, P = 0.004). With the age increasing, the coverage and timely birth-dose coverage of Hepatitis B vaccine (HepB) decreased, and the positive rate of anti-HBs gradually decreased. CONCLUSION: After the catch-up vaccination was conducted in unvaccinated children aged 1-14 years from 2009 to 2011, the HBsAg and anti-HBc positive rate decreased, while the anti-HBs positive rate increased significantly.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccines among non-responsive adults: 24-month of follow-up].

OBJECTIVE: To access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-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 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). 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 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. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. 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 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24. CONCLUSION: Anti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.