Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis.

OBJECTIVE: To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. METHODS: We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. FINDINGS: We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. CONCLUSION: Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.

Long-term seropositivity, safety, and impact of inactivated and live, attenuated hepatitis a vaccines in China - A cross-sectional study.

BACKGROUND: In 2008, China introduced live, attenuated hepatitis A vaccine (L-HepA, licensed in 1992) and inactivated hepatitis A vaccine (I-HepA, licensed in 2002) nationwide, and is currently the only country using L-HepA in routine immunization. We assessed seropositivity and its duration following vaccination, safety, and association with hepatitis A incidence and population seroprevalence for I-HepA and L-HepA. METHODS: We obtained seroprevalence data from two nationwide serosurveys (in 1992 and 2014), vaccination status from the 2014 serosurvey, and vaccine safety and disease incidence data from the national surveillance system. We compared long-term HAV seropositivity among vaccine recipients and described safety profiles of both vaccines. We categorized the 31 provinces into those predominately using I-HepA and achieving high coverage (n = 4), those predominately using L-HepA achieving high coverage (n = 4), and those predominately using L-HepA achieving lower coverage (n = 23). We compared population HAV seropositivity, coverage, and disease incidence among the three groups. RESULTS: One year after vaccination, seropositivity from I-HepA was significantly higher than from L-HepA (97.8% vs 90.7%), and seropositivity declined to 73.5% for L-HepA and 75.4% for I-HepA after 10 years - not significantly different by vaccine. The annual incidence of serious AEFI was <0.5/100 000 for both vaccines. Prior to licensure of either HepA vaccine, provinces that would go on to predominantly use I-HepA had lower incidences of hepatitis A and lower seropositivity levels to HAV than provinces that would go on to use L-HepA. By 2014, these differences were significantly diminished. Regardless of vaccine selection, all three province groups had lower immunity to HAV among individuals born during the 10 years prior to nationwide vaccine introduction - individuals who were 10 to 24 years old in 2014. CONCLUSION: Evidence of good immunogenicity, safety, and impact on incidence supports continued use of both I-HepA and L-HepA in the EPI system. These results may be useful for countries considering integrating HepA vaccines into their routine programs.

The impact of hepatitis B vaccine in China and in the China GAVI Project.

The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB) vaccine to infants born in the less developed areas of China including the Western provinces and poverty counties of Middle provinces, to prevent the consequences of hepatitis B virus infection. By 2009, the project areas had raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90% among infants, comparable to those in wealthier Eastern provinces, and reduced HBV prevalence to <1% among children in these areas. We estimated the impact in disease prevented by HB vaccine in China between 1992, when the vaccine was routinely recommended, and 2009, and in CGP areas for the years 2003-2009, when the CGP was active. A published model was used to estimate the burden of chronic and acute HBV infection and death prevented due to HB vaccination in China and the CGP areas using data from national serosurveys in China in 1992 and 2006, and HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling to estimate vaccine coverage nationally, regionally, and CGP areas. We also estimated the incremental impact of the CGP on HB vaccine coverage in those underserved areas. Our findings suggest that between 1992 and 2009, HB vaccination in China has prevented 24 million chronic HBV infections and 4.3 million future deaths due to cirrhosis, hepatocellular carcinoma and acute hepatitis. During the CGP between 2003 and 2009, an estimated 3.8 million chronic HBV infections and 680,000 deaths were prevented in CGP areas. We found that the CGP funding increased HB vaccine coverage in project areas by 4-15% for HB3 and 4-27% for timely birth dose beyond the coverage expected without the CGP. The CGP represents a highly successful public health collaboration between the national government and international partners.