Ning Miao

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.

Evaluation of policies and practices to prevent mother to child transmission of hepatitis B virus in China: results from China GAVI project final evaluation.

BACKGROUND Mother to Child Transmission (MTCT) has remained a leading cause of HBV infection in China, accounting for 40% of total infections. Providing hepatitis B vaccine (HepB) to all infants within 24h of birth (Timely Birth Dose, TBD), and subsequent completion of at least 3 vaccine doses is key to preventing perinatal HBV infection. In 2002, with the financial support of the Global Alliance on Vaccine and Immunization (GAVI) targeted to Western region and 223 poverty-affected counties in Central region, hepatitis B vaccine was provided for free. In 2010, we evaluated the China GAVI project in terms of its activities to prevent perinatal infections. OBJECTIVE The objectives of the evaluation were to (1) measure achievements in the China GAVI project in terms of TBD coverage, and (2) describe practices for HBsAg screening of pregnant women and HBIG use outside the GAVI China project. METHODS We used the methods recommended by WHO to select a cluster sample of health care facilities for the purpose of an injection safety assessment. We stratified China into three regions based on economic criteria, and selected eight counties with a probability proportional to population size in each region. In each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. In each hospital, we abstracted 2002 through 2009 records to collect information regarding birth cohorts, hospitals deliveries, vaccine management, hepatitis B vaccination delivery, HBsAg screening practices and results, and HBIG administration. In addition, in all hospitals, we abstracted records regarding the delivery of TBD. RESULTS We visited 244 facilities in the three regions, including 24 county hospitals and 220 township hospitals. We reviewed 837,409 birth summary records, 699,249 for infants born at county or township hospitals. Hospital delivery rates increased from 58% in 2002 to 93% in 2009. Surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 (+31%). Surveyed TBD coverage among children born in hospitals increased from 73% in 2002 to 98% in 2009. Between 2002 and 2009, the proportion of pregnant women screened for HBsAg increased from 64% in 2002 to 85% in 2009. In 2009, the proportion of infants born to women screened and found to be HBsAg positive who did not receive any immunization within 24h after birth ranged from 0% to 0.7% across regions. CONCLUSIONS Increased availability of hepatitis B vaccine, along with efforts to improve hospital deliveries, increased TBD coverage in China. This decreased perinatal HBV transmission and will reduce disease burden in the future. Screening for HBsAg to guide HBIG administration has begun, but with heterogeneous immuno-prophylaxis practices and a poor system for follow up.

Preventing hepatitis B though universal vaccination: Reduction of inequalities through the GAVI China project

OBJECTIVE In order to measure hepatitis B coverage and progress in equality with respect to protection against hepatitis B in poverty-affected areas funded by the Global Alliance on Vaccine and Immunization project funded in poverty-affected counties. METHODS We reviewed routinely reported coverage data and conducted a national stratified, validation, cross-sectional survey in October 2010, according to WHO recommended sampling method. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county. RESULTS We visited 244 townships as part of the final evaluation (71 in the East, 86 in the Center and 87 in the West). Overall, in these 244 townships, surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 and surveyed three dose of hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009. Overall, in the GAVI supported areas, the HepB3/DTP3 ratio increased from 57% in 2002 to 94% in 2009. CONCLUSION Pro-poor GAVI approach was an effective way to reduce inequity among children through provision of free vaccination. When vaccine and AD syringes were provided for free, they closed the gap between Eastern and Western regions and between the rich and the poor.

Comparing live attenuated and inactivated hepatitis A vaccines: An immunogenicity study after one single dose

INTRODUCTION While three types of hepatitis A vaccines are available in China, little data are available to compare them in terms of early antibody response. We conducted a trial to compare antibody response at 7, 14 and 28 days. METHODS We randomized primary school children in Gansu and Jilin provinces into four groups to receive either (1) Chinese live attenuated hepatitis A vaccine (H2 strain), (2) domestic inactivated hepatitis A vaccine (Healive(®)), (3) imported inactivated hepatitis A vaccine (Havrix(®)) or (4) hepatitis B vaccine (Control group). We compared groups at 7, 14 and 28 days in terms of proportion of sero-conversions (≥10 mUI/ml), and Geometric Mean Concentration (GMC) of antibodies measured with a Microparticle Enzyme Immunoassay (MEIA). We compared rates of self-reported adverse events following immunization (AEFI) in the first three days. RESULTS 204 children received the H2 vaccine, 208 received Healive(®), 214 received Havrix(®), and 215 received hepatitis B vaccine (no differences across groups in terms of age, sex, weight and height). At seven days, sero-conversion proportions were 25%, 35%, 27% and 2% (p<0.0001) with GMC of 6 mIU/ml, 8 mIU/ml, 6 mIU/ml and 3 mIU/ml, respectively for the four groups. At 28 days, sero-conversion proportions were 98%, 100%, 93% and 3% (p<0.0001) with GMC of 47 mIU/ml, 71 mIU/ml, 67 mIU/ml and 3 mIU/ml, respectively. AEFI were benign and did not differ across groups (p=0.94). CONCLUSIONS While our study was not able to identify differences between Havrix(®), Healive(®) and H2 vaccine in terms of sero-conversion proportion and GMC between seven and 28 days, further studies should evaluate non-inferiority or equivalence of the Chinese vaccines, particularly with respect to the GMC concentration for the H2 vaccine since it could affect long-term protection.

Cost-effectiveness analysis of a hepatitis B vaccination catch-up program among children in Shandong Province, China

Objective: The aim of the study was to estimate long-term cost‑effectiveness of a hepatitis B vaccination catch-up program among children born between 1994 and 2001 (when they were 8‑15 y old) in Shandong province, China, to provide information for nationwide evaluation and future policy making. Methods: We determined the cost-effectiveness of the catch-up program compared with the status quo (no catch-up program). We combined a Decision Tree model and a Markov model to simulate vaccination and clinical progression after hepatitis B virus (HBV) infection. Parameters in the models were from the literature, a field survey, program files, and the National Notifiable Disease Reporting System (NNDRS). The incremental cost‑effectiveness ratio (ICER) was used to compare the 2 alternative strategies. One-way sensitivity analysis, 2-way sensitivity analysis, and probability sensitivity analysis were used to assess parameter uncertainties. Results: The catch-up program was dominant compared with the status quo. Using a total of 5.53 million doses of vaccines, the catch-up program could prevent 21,865 cases of symptomatic acute hepatitis B, 3,088 carrier states with positive hepatitis B surface antigen (HBsAg), and 812 deaths due to HBV infection. The catch-up program could add 28,888 quality-adjusted life years (QALYs) and save

An economic analysis of adult hepatitis B vaccination in China.

192.01 million in the targeted population in the future. The models were robust, considering parameter uncertainties. Conclusion: The catch-up program in Shandong province among children born between 1994 and 2001 was ‘very cost-saving.’ It could save life years and reduce total future costs. Our study supported the desirability and impact of such a catch-up program throughout China.

Evaluation of immunization injection safety in China, 2010: Achievements, future sustainability

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.

Effectiveness of prevention of mother-to-child transmission practice in three provinces of Southern China

OBJECTIVE The study objectives were to evaluate injection practices in China in the post GAVI project era and provide guidance for policy makers to update national standards for injection practices and further improve vaccination services. METHODS We conducted a national stratified, cross-sectional survey in October 2010, according to WHO recommended sampling methods. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. RESULTS With respect to the risk to the patient, we never observed open injection equipment lying around or needles left in the septum of multi-dose vials. We never observed sterilizable injection devices syringes in any of the facilities. The proportion of facilities using sharps containers was highest in the East (85%), intermediate in the West (79%) and lowest in the Central region (56%). In 2009, auto-disable syringes and safety boxes were used in 78% and 79% facilities in GAVI supported areas of the Western region, respectively. Only one facility presented evidence of attempts to re-sterilize disposable injection equipment in the Eastern region. CONCLUSIONS Use of AD syringe and sharps containers increased in vaccination services in China, especially in GAVI supported areas, leading to sustainable progress in terms of elimination of reuse of injection devices. However, risk to patients still existed, including persisting use of standard disposable syringes and attempts to re-use disposable devices.

Economic evaluation on infant hepatitis B vaccination combined with immunoglobulin in China, 2013.

Vaccination in prevention mother-to-child transmission (PMTCT) of hepatitis B has been recommended since plasma-derived hepatitis B vaccines became available in China in 1986; however, less study evaluated practice effectiveness of PMTCT systematically. We conducted a prospective survey to evaluate the effectiveness of PMTCT practices in 3 provinces of southern China. We selected prefectures with low timely birth dose coverage in Yunnan, Guangxi, and Hunan provinces. Infants born to HBsAg positive mothers were evaluated at 7–12 months of age. We tested hepatitis B virus (HBV) surface antigen (HBsAg) and HBV e antigen (HBeAg) of mothers and tested HBsAg of infants born to HBsAg positive mothers using Enzyme-linked Immunosorbent Assay (ELISA) at provincial CDC laboratories. We used logistic regression analysis to analyze the risk factors for HBV infection. Among 3,094 infants born to HBsAg positive mothers, 172 were positive for HBsAg (5.6%). HBeAg status of pregnant women, timely birth dose (TBD) of hepatitis B vaccine were major predictors for HBV infection of infants. PMTCT practices greatly reduced the prevalence of HBsAg among infants born to HBsAg positive mothers China. However, the effectiveness of strategies used in PMTCT varied. HBsAg screening for pregnant women, monitoring of infants born to HBsAg positive mother should be enhanced to evaluate the effectiveness of program.

Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China

Hepatitis B virus (HBV) infection was highly endemic before the introduction of hepatitis B vaccine (HepB) in China, with HBV surface antigen (HBsAg) prevalence being 9.75% in the general population in 1992. HBsAg prevalence among children <4 years old (9.67%) was nearly the same as the prevalence among adults, which means transmission during birth and early childhood was the predominant mode of HBV transmission in China. Ninety percent of newborns infected with HBV would become chronic carriers, leading to a substantial disease burden of chronic liver disease. China has made substantial progress in reducing HBV mother-to-child transmission (MTCT), but challenges remain. In 1992, HepB was first recommended by the Ministry of Health (MOH) for routine vaccination of infants, with the first dose to be administered within 24 hours of birth and subsequent doses at ages 1 and 6 months. In 2002, China integrated HepB into the Expanded Progamme on Immunization (EPI), with the government providing free 5mg/0.5ml/dosage HepB for all infants. In 2011, China changed the HepB dosage form to 10mg/0.5ml/dosage to improve vaccine immunogenicity. Joint HBV immune prophylaxis with HepB vaccine and hepatitis B immunoglobulin (HBIG) after birth could generally interrupt HBV MTCT, and it is recommended by the World Health Organization (WHO), the World Gastroenterology Organization (WGO), and the US Centers for Disease Control and Prevention (CDC). At the end of 2010, China implemented a program for preventing mother-to-child transmission (PMTCT) of HIV, syphilis, and hepatitis B, where all children born to HBsAg positive mothers could receive free 100IU HBIG at birth. Economic analysis of universal infant hepatitis B vaccination has been carried out by several studies in China. However, previous studies were focused on the economic analysis of 5mg vaccine used in China. Most of the previous studies did not include screening for pregnant women and HBIG injection. Some of these studies also did not include costs for adverse events following immunization (AEFI) and productivity losses due to HBVrelated diseases. The objective of this study is to provide an updated and comprehensive economic evaluation of infant HepB vaccination with 10ug vaccine and HBIG. Results from this study will be important and useful for making future policy decisions regarding HepB vaccination.