Xiaohong Gong

Epidemiological serosurvey of Hepatitis B in China-Declining HBV prevalence due to Hepatitis B vaccination

OBJECTIVE To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants. METHODS National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA. FINDINGS The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other). CONCLUSIONS China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

Evaluation of the Impact of Hepatitis B Vaccination among Children Born during 1992–2005 in China

BACKGROUND Endemic hepatitis B virus (HBV) infection is a serious health problem in China. Hepatitis B vaccination of infants was introduced in 1992 and was progressively expanded during the subsequent 15 years. METHODS We conducted a national serosurvey, with participants selected by multiple-stage random sampling. Demographic characteristics and hepatitis B vaccination history were collected by a questionnaire and a review of vaccination records, and serum specimens were tested for hepatitis B surface antigen, antibody to hepatitis B core antigen, and hepatitis B surface antibody by enzyme-linked immunosorbent assay. RESULTS Hepatitis B vaccine coverage (3 doses) increased from 30.0% for children born in 1992 to 93.4% for children born in 2005. Receipt of a timely birth dose increased from 22.2% to 82.6% for children born during this interval. Multivariate analysis showed that older age, western and rural residence, birth at home, and certain ethnicities were risk factors for under vaccination with both full vaccine series and timely birth dose. The prevalence of hepatitis B surface antigen was reduced to 2.1% among all children and 1.0% among children born after 1999. The efficacy of hepatitis B vaccination with a timely birth dose was 88.3%. CONCLUSIONS Hepatitis B vaccine has been successfully integrated into routine infant immunization in China, now reaching most infants within 24 h after birth, and the prevalence of hepatitis B surface antigen has been greatly reduced among children born after 1992.

Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992-2005.

BACKGROUND In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination. METHODS We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth. RESULTS Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992-1997 to 93.2% for children born in 2002-2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992-2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose (p=0.04), birth after 1998 (p<0.001), living in an urban setting (p=0.008) and hospital birth (p=0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87). CONCLUSIONS Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.

Hepatitis A surveillance and vaccine use in China from 1990 through 2007.

Background Hepatitis A vaccines have been highly effective in preventing hepatitis A. To investigate the epidemiology of hepatitis A in China after hepatitis A vaccine became available, we reviewed reported cases of hepatitis A and the use of hepatitis A vaccine in China during the period from 1990 through 2007. Methods Data from the National Notifiable Disease Reporting System from 1990 to 2007 and the Emergency Events Reporting System from 2004 to 2007 were reviewed and epidemiologic characteristics analyzed. Hepatitis A vaccine distribution between 1992 and 2007 was also reviewed. Results The incidence of hepatitis A has declined by 90% since 1990, from 56 to 5.9 per 105/year. Declines in age-specific incidence were seen in all age groups, most dramatically among children younger than 10 years. Disease incidence still varies substantially: poorer western provinces have had the highest incidences since 2000. In high-incidence provinces, children younger than 10 years continue to have a high disease incidence. Only 50% of cases were laboratory-confirmed, and only 3% occurred in reported local outbreaks. Over 156 million doses of hepatitis A vaccine have been distributed since 1992, and use has continued to increase since 2003. Conclusions Incidence of hepatitis A has decreased in all age groups, likely due to changing socioeconomic conditions and increasing hepatitis A vaccine use. Nevertheless, western populations remain at high risk, with transmission predominantly occurring among children. The epidemiology of hepatitis A transmission is not well understood. Improved surveillance with better laboratory confirmation is needed to monitor the impact of universal hepatitis A vaccination of young children; this strategy began to be implemented in 2008.

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

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

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.

Surface antibody and cytokine response to recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine

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.