Scaling up hepatitis B vaccination with the support of GAVI in China : lessons learned for introduction of new vaccines and for the future of hepatitis B control

Background: Hepatitis B virus (HBV) infection is a leading cause of illness and death in China. In 1992, 60% of the population had a history of HBV infection and 9.8% were chronically infected with HBV. Each year, an estimated 263,000 persons died from HBV-related hepatocellular carcinoma or cirrhosis, accounting for 37%-50% of HBV-related deaths worldwide before 1992. In 1992, the Ministry of Health introduced hepatitis B vaccine into the management system of the Expanded Programme on Immunization (EPI) as a cost-effective way to prevent HBV infection. The schedule included a timely birth dose (within 24 hours of birth, to prevent perinatal infections that are most strongly associated with long term chronic infections and adverse outcomes) and subsequent doses at one month and six months. However, this introduction into the EPI management system only meant that the Government took responsibility over administration and coverage monitoring, but not funding support: The cost of vaccination was covered out of pocket. As a result, coverage was lower in rural areas, in Western provinces (low economic status) and among females. In 2002, the Ministry of Health fully integrated free hepatitis B vaccine into EPI with funding from the Global Alliance for Vaccines and Immunization (GAVI). The GAVI China project financially supported vaccine and auto-disable syringes in Western provinces and poverty-affected counties of Central provinces (Chapter 1). As the GAVI China project was completed in 2010, we compiled all evaluation work conducted to understand how input and process lead to output and outcomes that impacted the heavy HBV associated burden in China.
Methods: We compiled data from GAVI China project areas between 2002 and 2009, reviewed cross-sectional studies conducted in 2004 and 2006 and conducted a final evaluation survey in 2010. These investigations covered input (funds invested into the project for vaccine and AD syringes), process (integration of the vaccine in EPI, increase in institutional births, introduction of auto-disable syringes for vaccination and training), output (immunization coverage for third dose and timely birth dose, use of auto-disable syringes for immunization), outcome (immunity in the population, safe injection practices) and impact (prevalence of HBV surface antigen among children included in the vaccination cohort).
Results: With respect to hepatitis B immunization, input included 27 million USD provided by the GAVI China project to funds hepatitis B vaccine between 2002 and 2007. These funds came from the international GAVI Alliance (50%) and the Government of China (50%). In addition, the Chinese government provided an additional 21.5 million USD in government co-funding of subsidies from central to provincial to health care workers in provinces between 2007 and 2009 so that the vaccine could be administered without user fees. The health system efficiently processed these resources. First, in GAVI-supported areas, the increase in the HepB3/DPT3 ratio (increased from 57% in 2002 to 94% in 2009), indicated indicating that EPI absorbed well the new vaccine. Second, institutionalized deliveries increased to reach 96% nationwide in 2009, indicating that maternal and child health services created conditions to maximize coverage of the timely birth dose. As a result, from 2002 to 2009, the national three-dose hepatitis B vaccine coverage progressed from 71% to 93% (Chapter 5) and the timely birth dose coverage progressed from 60% to 91% (Chapter 7) with a reduction of inequities between Eastern and Western areas. Both of these resulted in immunity among vaccinated cohorts (85% of anti-HBs among children 12 to 23 months of age in the national 2006 serological survey) (Chapter 2). One key factor strongly associated with being HBsAg negative is receiving timely birth dose of hepatitis B vaccine as early as possible (Chapter 4).
With respect to injection safety, input included 14 million USD of GAVI funds to supply auto-disable syringes, safety boxes and needle cutters. In 2009, auto-disable syringes and safety boxes were used in 78% and 79% facilities in GAVI supported areas of the Western areas, respectively (Chapter 6). In terms of output, sterilizable injection devices disappeared and attempts to re-use disposable injection equipment became rare (0% in the 2010 final evaluation). However, no data regarding the incidence of injection-associated infections were available to evaluate the outcome of the progress in injection safety.
With respect to social mobilization and training, 10 million USD were assigned to training between 2002 and 2009. Most of those were not directly funded by GAVI China. These funds were provided by the Government because of the leverage effect of the GAVI China project. These were used in 28,753 training workshops for health care workers that resulted in better knowledge among health care workers (In 2010, 98% of them knew that hepatitis B virus can be transmitted from mother to child) and guardians (In 2010, 89% of them knew that the first dose of hepatitis B vaccine had to be given in the first 24 hours of life). This higher level of knowledge also contributed to higher immunization coverage and safer injections.
Ultimately, the elements of the GAVI China project combined at the impact level to prevent HBV infections. The 2006 national serological survey documented these achievements and pointed to 1% prevalence of HBsAg among children under five years of age, a decrease of 90% from the 9.8% prevalence in the same age group in 1992 (Chapter 3). These infections prevented will lead to the future prevention of cirrhosis, hepatocellular carcinoma. Those should result in early deaths prevented and benefits in terms of disability-adjusted life years (DALYs). However, in 2010, it was too early to measure these longer term effects and the final impact of the project on HBsAg prevalence had not yet been quantified.
Conclusion: The introduction of hepatitis B vaccine into the national immunization programme was successful and the strategies and policy used for the GAVI China project provided a successful case study for the introduction of other new vaccines in China. The determinants of the success of the GAVI China included (1) a well documented disease burden, (2) a good collaboration between the government of China and the international GAVI Alliance that resulted in a strong national GAVI China project, (3) local production of vaccine and AD syringes, (4) solid processes for implementation and (5) leverage of additional support through national and provincial levels co-funding. Remaining challenges include (1) the persistence of an estimated 80,000 perinatal HBV infections each year in China, (2) the lack of homogeneous regulations to harmonize injection practices, (3) the absence of a scaled implementation for the national policy that recommends vaccination of health care workers, (4) the weak specificity and sensitivity of acute hepatitis B surveillance and (5) the absence of policy and plans for the management of chronic hepatitis B infection. We recommended that China (1) maintain universal hepatitis B infant vaccination, with a high priority to reach all infants, especially for those living in remote, mountain areas (2) make additional efforts to strengthen the health system and further improve hospital delivery rates to increase timely birth dose coverage and decrease perinatal HBV transmission, (3) develop clear surveillance guidelines to monitor acute hepatitis B rates (4) immunize health care workers, with an emphasis on pre-service delivery (5) collect manage sharps waste in a way that is safe for the health care workers, the community and the environment, and (6) screen pregnant women to administer adapted immuno-prophylaxis (including hepatitis B immune globulin, HBIG) for children born to those HBsAg positive. These should prepare the country for the next phase of a policy for the prevention and control of hepatitis B, which should ultimately include screening and treatment of patients with chronic infections, particularly those of older age cohorts who were born before the era of universal immunization