Program Evaluation Key Outcomes and Addressing Remaining

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Key outcomes and addressing remaining challenges—Perspectives from a ﬁnal

ଝ

evaluation of the China GAVI project

a,1 a,1 a,1 a,1 b c

Weizhong Yang , Xiaofeng Liang , Fuqiang Cui , Li Li , Stephen C. Hadler , Yvan J. Hutin ,

d a,∗

Mark Kane , Yu Wang

Chinese Center for Disease Control and Prevention, Beijing, China

Centers for Disease Control and Prevention, Atlanta, USA

Europe Center for Disease Control and Prevention, Stockholm, Sweden

Mercer Island, Washington, USA

r t a b

i c s t

l r

e i n f o a c t

Article history: During the China GAVI project, implemented between 2002 and 2010, more than 25 million children

Received 6 June 2012

received hepatitis B vaccine with the support of project, and the vaccine proved to be safe and effective.

Received in revised form 24 July 2012

With careful consideration for project savings, China and GAVI continually adjusted the budget, addi-

Accepted 24 September 2012

tionally allowing the project to spend operational funds to support demonstration projects to improve

timely birth dose (TBD), conduct training of EPI staff, and to monitor the project impact. Results from the

ﬁnal evaluation indicated the achievement of key outcomes. As a result of government co-investment,

Keywords:

human resources at county level engaged in hepatitis B vaccination increased from 29 per county on

GAVI

Project average in 2002 to 66 in 2009. All project counties funded by the GAVI project use auto-disable syringes

Outcomes for hepatitis B vaccination and other vaccines. Surveyed hepatitis B vaccine coverage increased from 71%

Challenges in 2002 to 93% in 2009 among infants. The HBsAg prevalence declined from 9.67% in 1992 to 0.96% in

2006 among children under 5 years of age. However, several important issues remain: (1) China still

accounts for the largest annual number of perinatal HBV infections (estimated 84,121) in the WHO WPR

region; (2) China still lacks a clear national policy for safe injection of vaccines; (3) vaccination of high risk

adults and protection of health care workers are still not implemented; (4) hepatitis B surveillance needs

to be reﬁned to more accurately monitor acute hepatitis B; and (5) a program for treatment of persons

with chronic HBV infection is needed. Recommendations for future hepatitis B control include: using

the lessons learned from the China GAVI project for future introductions of new vaccines; addressing

unmet needs with a second generation hepatitis B program to reach every infant, including screening

mothers, and providing HBIG for infants born to HBsAg positive mothers; expanding vaccination to high

risk adults; addressing remaining unsafe injection issues; and improving monitoring of acute hepatitis

B. This paper describes ﬁndings and discusses perspectives from a ﬁnal project evaluation, a national

stratiﬁed validated cross-sectional survey done in October 2010.

1. Introduction for Vaccines and Immunization Project on hepatitis B immuniza-

tion (China GAVI project) implemented from 2002 in 22 of the

China received GAVI support in 2001 because of the high dis- 31 provinces was designed to (a) increase coverage of hepatitis

ease burden of hepatitis B and a strong government commitment B vaccine through a pro-poor approach targeting all counties of

to protect infants at risk. The Ministry of Health/Global Alliance the 12 Western provinces and poverty counties of the 10 Central

provinces, (b) accelerate integration of hepatitis B vaccine into rou-

tine immunization, and (c) assure immunization injection safety

[1]. The central and sub-national levels shared a common respon-

ଝ

Disclaimer: The ﬁndings and conclusions of this report are those of the authors sibility and complemented each other’s functions.

and do not necessarily represent the ofﬁcial position of the United States Centers

In collaboration with GAVI, the government of China imple-

for Disease Control and Prevention (USCDC).

∗ mented a number of activities, including (1) increasing awareness

Corresponding author.

of the importance of a timely birth dose (TBD) of hepatitis B vac-

E-mail address: [email protected] (Y. Wang).

These authors contributed equally to this paper. cine among providers and parents, (2) intensifying training for

J74 W. Yang et al. / Vaccine 31S (2013) J73–J78

Box 1: Summary of key indicators of input, process, output, outcome and impact for the GAVI project, China, 2002–2010.

Elements Immunization against hepatitis B Social mobilization and training Injection safety

Input - 27 million USD disbursed by GAVI for - 10 million USD disbursed by the government - 14 million USD disbursed by China GAVI for

hepatitis B vaccine in 2002–2010 for training activities AD syringes in 2002–2007

- 21.5 million USD disbursed by the - 100,000 USD disbursed by China GAVI for

government to subsidize health care workers safety boxes and needle cutters in 2002–2007

for vaccination 2007–2009

Process - HepB3/DTP3 target ratio increased from 57% - 28,753 training workshops held from 2002 to - 0% of facilities using sterilizable equipment

in 2002 to 94% in 2009 2009 - 78% of facilities using AD syringes in

- Hospital delivery rates increased from 78% in GAVI-supported areas

2002 to 96% in 2009 - 79% of facilities using safety boxes in

- TBD/DTP1 ratio increased from 0.83 in 2002 to supported areas

0.98 in 2009

Output - Surveyed TBD coverage increased from 60% - 98% of healthcare workers know about - 0% of injections for which there is an attempt

in 2002 to 91% in 2009 perinatal HBV transmission to reuse syringe and/or needle

- Surveyed HepB3 coverage increased from - 89% of the guardians aware of the need of the - Safety boxes used in 79% of facilities

71% in 2002 to 93% in 2009 ﬁrst hepatitis B vaccine within 24 h of life

Outcome - Prevalence of Anti-HBs: 85% among children - No data to determine whether or not

12–23 months of age in 2006 injection-associated infections occur

Impact - Prevalence of HBsAg decreased from 9.67% in 1992 to 0.96% in 2006

- No data on cirrhosis and hepatocellular carcinoma

- No data on mortality reduction

- No data on DALY averted

health care workers (HCWs), (3) monitoring and supervision of vac- of the success and identify remaining issues (Box 1). With respect to

cination activities, (4) improving hospital delivery rates through hepatitis B immunization, inputs included 76 million USD provided

provisions of subsidies to parents to encourage hospital deliv- by the China GAVI project to fund hepatitis B vaccine between 2002

ery of infants, (5) building collaborative bridges between delivery and 2007, and 21.5 million USD of additional China government

services (maternal and child health, MCH) and vaccination service subsidies to health care workers between 2007 and 2009. The

(EPI), and (6) subsidizing providers as a incentive for providing health system efﬁciently utilized these resources. First, the increase

timely birth dose and three doses of hepatitis B vaccine along with in the HepB3/DPT3 ratio (reaching 94% in 2009) indicated that

other EPI vaccines [1]. EPI effectively implemented hepatitis B immunization. Second, the

Initially, GAVI project funds were only used to procure vaccine increase in the proportion of institutionalized deliveries (reaching

and safe injection equipment. However, provision of insufﬁcient 96% in 2009) indicated that Maternal and Child Services created

operational costs in some provinces was identiﬁed as a bottleneck conditions that maximized TBD coverage. As a result, from 2002 to

for implementation. Hence, from 2007 onwards, China GAVI project 2009, three doses of hepatitis B vaccine coverage increased from

savings were assigned to support operational costs in low perform- 71% to 93% and TBD coverage increased from 60% to 91% based on

ing areas, with ﬂexibility given for expenditures so that human national survey data [3]. Both of these factors resulted in immunity

resources could also be covered. This paper describes ﬁndings among vaccinated cohorts as 85% of children 12–23 months of age

and perspectives from a ﬁnal project evaluation which included were anti-HBs+ in the 2006 serological survey [5].

a national stratiﬁed, validated cross-sectional survey conducted in With respect to injection safety, inputs included 14 million USD

October 2010. of China GAVI funds to supply AD syringes, safety boxes and nee-

dle cutters. In 2009, AD syringes and safety boxes were used in

2. Final evaluation process 78% and 79% facilities in the GAVI-supported areas of the Western

areas, respectively. In terms of output, sterilizable injection devices

We used the methods recommended by WHO to select a cluster disappeared and attempts to re-use disposable injection equip-

sample of 244 health care facilities for the purpose of injec- ment became rare (0% in the 2010 ﬁnal evaluation) [4]. However,

tion safety assessments [2]. The design of this assessment, which no data regarding the incidence of injection-associated infections

included both vaccine coverage and injection safety assessments, were available to evaluate the outcome of the progress in injection

is described in other papers in this supplement [1,3]. safety.

With respect to social mobilization and training, 10 million USD

2.1. Key outcomes were assigned to training between 2002 and 2009. Most of these

funds were not directly funded by GAVI alliance but by the govern-

Results of China GAVI project ﬁnal evaluation suggest that in ment, through a leverage effect of the China GAVI project support.

2010, the project goal of 85% coverage of three doses was reached in Funding was used in 28,753 workshops to train health care work-

98% of China GAVI project counties that together accounted for 99% ers resulting in better knowledge among health care workers (in

of the target population [3].. The 75% timely birth dose (TBD) project 2010, 98% knew that hepatitis B virus can be transmitted from

goal was reached in 80% of counties that together accounted for 79% mother to child) and guardians (in 2010, 89% knew that the ﬁrst

of the target population. Auto-disable (AD) syringes were success- dose of hepatitis B vaccine had to be given in the ﬁrst 24 h of life).

fully introduced in all GAVI-supported areas, although standard This also contributed to higher immunization coverage and safer

disposable syringes remained in use in non-GAVI supported areas injections.

in Central and Eastern provinces [4]. Ultimately, the elements of the China GAVI project combined

The China GAVI project ﬁnal evaluation went further than a at the impact level to prevent HBV infections. The 2006 national

review of the initial goals and examined all the components of the serological survey documented these achievements and pointed

China GAVI project as per the logic model to understand the causes to a 0.96% prevalence of HBsAg among children under ﬁve years

W. Yang et al. / Vaccine 31S (2013) J73–J78 J75

events with hepatitis B vaccine in China was lower than the global

incidence worldwide as reported by WHO [10].

During January 2006 to March 2007, the monitoring system

of sudden public health events in China reported 10 cases of

infant death after vaccination with hepatitis B vaccine. They were

comprehensively analyzed by on-site investigation, clinical exami-

nation and/or autopsy. Among 6 cases that were subject to autopsy,

one case was attributed to acute allergic shock induced by vac-

cination with hepatitis B vaccine, while ﬁve were attributed to

coincidence. Among 4 cases that were not subject to autopsy, one

was possibly due to acute allergic shock induced by vaccination

[10–12]. While the AEFI monitoring system in China did not allow

a formal relation to a denominator expressed in terms of doses

used, we used approximations to estimate a rate based on the birth

Fig. 1. The prevalence of HBsAg among population aged 1–59 years in China 1979,

1992 and 2006. cohort (16 million) and vaccine coverage in a year. Using these cal-

culations, the death rate following AEFIs associated with hepatitis

B vaccine (2/16 million) was 0.1/million, lower than the one quoted

of age in China (a decrease of 90% from the 9.67% prevalence in

by UNICEF [13]. All these data suggested that hepatitis B vaccine is

the same age group in 1992), and a 1.26% prevalence among chil-

very safe. Reactions usually include minor local pain and/or mild

dren under ﬁve years of age in GAVI-supported areas [5,6]. These

fever, and recovery occurs without any treatment [14,15].

improvements will lead to the future prevention of cirrhosis and

hepatocellular carcinoma which should result in the prevention of

3.3. Maintaining hepatitis B vaccination (2011 onwards)

early deaths and morbidity from chronic hepatitis B, cirrhosis, and

liver cancer.

Since 2007, the China/GAVI project has not made additional

investments for hepatitis B vaccine and AD syringes because the

3. The beneﬁt of vaccination: impact China central government has assumed ﬁnancial responsibility for

hepatitis B vaccination and injection safety for all newborns in

3.1. The effectiveness of hepatitis B vaccine China. Hepatitis B vaccine became one of the vaccines integrated

into the national immunization program, with all costs fully funded

The results from the 2006 serosurvey indicated that the preva- by the government of China including vaccine, syringes, subsidy for

lence of HBsAg was 7.18% overall. However, there were large vaccination, salaries of HCWs, cold chain and operational funds.

variations in prevalence by age, ranging from 0.96% among chil-

dren 1–4 years of age, to 2.42% among children 5–14, and 8.57%

4. Challenges and remaining issues after China GAVI project

among persons 15–59. This age-speciﬁc prevalence proﬁle show-

ing low prevalence among children and high prevalence among

4.1. Persistence of perinatal HBV infections

adults is new for China. The 1979 and 1992 surveys showed little

variation in the prevalence by age, with a slight decrease in preva-

Despite great achievements in terms of the elimination of peri-

lence among older age groups (probably reﬂecting selective higher

natal HBV infection, in 2010, China still accounted for the largest

mortality in HBsAg positive persons). In contrast with these earlier

annual number of perinatal HBV infections (estimated 84,121) in

proﬁles, the age-speciﬁc prevalence of HBsAg from the 2006 survey

the WHO WPR region. Two factors explain the difﬁculties that

featured a marked reduction among younger age groups who were

China is facing when trying to eliminate remaining perinatal HBV

exposed to the immunization program (Fig. 1) [5–7].

transmission. First, the efﬁcacy of hepatitis B vaccine alone for pre-

Overall, the HBsAg prevalence was 7.18% in 2006, compared

vention of perinatal HBV transmission ranges from 85% to 95% [16]

with 9.75% in 1992 (a decrease of 26%). The classiﬁcation criteria

overall but there will still be some infants infected by HBeAg pos-

of the World Health Organization (WHO) specify that a prevalence

itive mothers despite receiving a TBD. The inclusion of HBIg into

of HBsAg >8% indicated high endemicity, 2–8% intermediate ende-

the protocol of immune-prophylaxis increases vaccine effective-

micity and <2% low endemicity areas. Hence, China should now

ness to 95% [16]. Second, challenges remain in the ﬁeld of TBD

be listed as an intermediate prevalence area [8]. The prevalence of

administration among certain rural, remote, and poorer popula-

HBsAg among children under 5 has already reached the WPRO goal

tions. Vaccination coverage was lower among children born at

(less than 2% by 2012), allowing for China to be veriﬁed as reaching

home, especially in remote areas [17]. Thus, in the future, China

the WHO goals [9]. Based on the results of the 1992 and 2006 sero-

must identify mechanisms to address these two issues and reach

epidemiological studies, we estimated that since 1992, nearly 80

more children with more effective prophylactic regimens. This will

million children under the age of 15 had averted an HBV infection,

require increasing TBD through increased births in hospitals or

and that 19 million had averted a chronic HBV infection [5].

delivering a timely birth dose to those born at home, and increasing

HBsAg screening of pregnant women so that HBIg can be provided

to infants of HBV carrier mothers along with the TBD.

3.2. Safety of hepatitis B vaccination

In 2005, China established a system to monitor Adverse Events 4.2. Remaining unsafe injection issues

Following Immunization (AEFI) in 10 provinces, and expanded it

to 16 provinces in 2008. The monitoring data from 16 provinces Despite the large scale introduction of AD syringes in China

indicated that 252 AEFI following hepatitis B vaccine were reported because of the China GAVI project and development of an industry

between 2005 and 2008. This accounted for 5.16% of the total num- in China to produce them, the Eastern region and some non-project

ber of reported AEFIs. The reported incidence was 2.28/100,000, areas in the Central areas still do not use AD syringes [4]. This leaves

including allergic rash, allergic purpura, vascular edema, Arthus a risk of reuse of injection equipment in the absence of steriliza-

reaction and thrombocytopenic purpura. The incidence of adverse tion. Management of sharps waste has made progress in China.

J76 W. Yang et al. / Vaccine 31S (2013) J73–J78

However, some grassroots level (village clinic) facilities and pri- varying funding capacity of provinces [20], this is not universally

vate hospitals still engage in unsafe sharps waste management that implemented and inequity remains. Although safe and effective

may (1) expose the community to sharps injuries or (2) generate anti-viral drugs are now available and widely used in China, costs

toxic fumes. In addition, sharps waste collection and management are directly charged to patients and not subsidized by the govern-

suffers from lack of standardization, which exposes health care ment. Therefore, China should have eligible medicines integrated

workers and the community to needle-stick injuries. Finally, some into the national health insurance system, which will beneﬁt many

health care workers remain unprotected with the hepatitis B vac- patients with chronic infections and increase equities in access to

cine. Without a clear national policy that includes a regulatory care in the long run. A national guideline should frame screening,

framework, technical guidelines and implementation funds, this case management, counseling, medical treatment, and follow-up.

situation will not change.

5. Recommendations for future hepatitis B control

4.3. Vaccination of high risk adults and protection of health care

workers

5.1. Transferring knowledge for introduction of new vaccines

China has successfully completed a catch-up campaign to vacci-

The success of the introduction of hepatitis B vaccine into China’s

nate children under 15 years of age who previously had not received

EPI was based upon careful preparation that addressed all criti-

the hepatitis B vaccine. The next phase in China could consider vac-

cal points. In the future, to ensure the successful introduction of

cinating high-risk adults. Health care workers are universally at

new vaccines into China’s EPI, preparatory work should address

high risk for HBV infection. Two WHO resolutions in 2007 [18] and

(1) burden of disease, (2) cost-effectiveness, (3) ﬁnancing and (4)

2010 [19] recommended vaccinating health care workers against

local production of the vaccine. In view of its developing economy,

hepatitis B. Aside from health care workers, WPRO has a guideline

China is no longer eligible for GAVI alliance support. Therefore, in

for hepatitis B vaccination of high-risk adults [9]. These resolu-

the future, if a new, locally produced, cost-effective vaccine for a

tions and recommendations provide general guidance to China.

disease with a high burden is considered for introduction in the

However, the WPRO guidelines recommend using national data to

EPI, the cost of the new vaccine should be funded using domestic

identify high-risk populations so that the national guidelines for

funds. With domestic production in mind, the experience from the

the vaccination of high-risk adults are based upon evidence. Thus,

China GAVI project could be used to generate delivery and ﬁnancing

a sound surveillance system is needed to identify risk factors for

mechanisms that will ensure equitable coverage (Table 1).

infection and frame the groups that could beneﬁt from immuniza-

The China GAVI project provides a model for how to scale up

tion.

the introduction of a new vaccine into routine immunization in

collaboration with the GAVI alliance. The China GAVI experience

4.4. Surveillance challenges for incident disease

with respect to hepatitis B vaccine in recent years can be compared

to the current situation of other new vaccines in China (Table 1).

The Chinese National Notiﬁable Disease Reporting System

For hepatitis B vaccine, documentation of a large burden of disease,

(NNDRS) offers a solid foundation for good hepatitis surveil-

demonstration of cost effectiveness, and the presence of large-scale

lance. Viral hepatitis has been a national notiﬁable disease since

domestic vaccine production led to a strong government commit-

1959, with reporting by type since 1990. Health care workers

ment. This government commitment progressively led to universal,

use a national case deﬁnition system to report cases through the

equitable ﬁnancing. This experience is similar to the Chinese expe-

electronic NNDRS. The basic demographic and epidemiological

rience with Japanese encephalitis [21,22], for which information

characteristics are routinely compiled. The system is implemented

on burden of disease [5,6] and cost effectiveness [23,24] com-

nationally in a uniform manner, is Internet-based and person cen-

bined with the availability of a good national vaccine [25] triggered

tered. All diagnosed hepatitis B cases are entered into system, and

national introduction into the EPI in 2007. Overall, these experi-

then county, prefecture, province and national level staff can access

ences point to a number of criteria with respect to introduction

the data.

of new vaccines that could be of use to National Immunization

However, both acute and chronic hepatitis B cases are included

Technical Advisory Groups (NITAGs) in China and other countries.

in the system and are not differentiated. This hides potential

These NITAGs should consider epidemiologic, economic and other

new risks and does not accurately reﬂect the occurrence of new

issues to assist Ministries of Health with the decision-making pro-

infections. Therefore, China should reﬁne the surveillance system,

cess around new vaccine introduction. When a new vaccine is

according to appropriate case deﬁnitions, so that acute and chronic

ready to be introduced, NITAGs may beneﬁt from collaboration

infections can be separated. This will need to take into consider-

with international partners, including the WHO Strategic Advi-

ation the ﬁeld aspects of disease diagnosis, laboratory diagnosis,

sory Group of Experts (SAGE) on Immunization, the WHO group

epidemiologic case investigation and data collection and transmis-

on New and Under-utilized Vaccines Implementation (NUVI), the

sion.

SIVAC initiative (i.e., Supporting National Independent Immuniza-

tion and Vaccine Advisory Committees and the GAVI in eligible

4.5. Burden of chronic infections among adults

countries). NITAGs can then consider these elements to recommend

a mechanism for equitable and sustainable ﬁnancing for universal

China, having managed the most pressing problem of incident

introduction when the right conditions are met.

perinatal and early childhood infections, is now faced with tack-

ling the prevalent burden of HBV-infected patients among adults

(8.57% of the population). Since the burden of chronic infections 5.2. Implementation of a second generation hepatitis B program

is large, the approach to case management needs to address cost

effectiveness and willingness to pay. In addition to economic issues, 5.2.1. Immunization

standards of care, evidence-based treatment guidelines, availability Immunization system. The future of hepatitis B immunization in

of appropriate and affordable drugs needs to be addressed as well. China must include maintaining high levels of universal infant vac-

Pilot population-based projects in selected settings may provide cination. Vaccinating all infants in a timely manner remains the

useful guidance on the way to proceed. In addition, China is devel- highest priority, especially for those living in remote, mountain

oping a new reformed health system for treatment, but due to the areas. To this effect, the program must (1) regularly analyze data

W. Yang et al. / Vaccine 31S (2013) J73–J78 J77

Table 1

Lessons learned from hepatitis B vaccine introduction in China with respect to the introduction of other new vaccines, China GAVI project evaluation, 2002–2009.

Elements to consider for Hepatitis B vaccine in Situation in 2011 with respect to other vaccines

introduction of a new vaccine China

HIb Rotavirus Pneumococcal conjugate

vaccine

Burden of disease - Extensive documentation - Based on extrapolation of - Large burden of diarrheal - Based on extrapolation of

documentation using local data global data disease global data

- Large burden - Difﬁcult technically - Low mortality - Difﬁcult technically

Vaccine effectiveness - Documented in China - Studies conducted outside - Studies conducted in China - Studies conducted outside

of China of China

Cost effectiveness - Documentation on the - Studies conducted outside - Studies conducted outside - Studies conducted outside

basis of studies conducted of China of China of China

outside of China were

sufﬁcient

Local vaccine production - From 1985 - Available in 2003 - Available in 2000 - Available in 2006 for adults

- Multiple producers - Two producers - One producer (PPSV23), but not for

- Sufﬁcient supplies - Insufﬁcient supplies for children

nationwide use

Equitable ﬁnancing - Progressively acquired, No No No

with key milestones in

1992, 2002, 2005 and 2007

to identify the difﬁcult to reach, (2) make vaccines available in all Waste management. Management of waste could be achieved

villages or townships (which could have implications in terms of through national legislation, regulation or law making, which

cold chain), (3) assign the responsibility to vaccinate to the village should be implemented in the entire country, and cover all health

heath care worker (instead of relying on the township hospitals), units. As heterogeneity of solutions facilitates the adoption of sub-

(4) conduct regular supervision and (5) provide hands on training standard choices, precise guidance should deﬁne what is acceptable

for health care workers. and what is not.

Perinatal infections. With respect to the prevention of the trans-

mission from mother to children, China ﬁrst should conduct

5.2.3. Surveillance for acute HBV disease

additional efforts to strengthen the health system and further

China should develop clear guidelines for the surveillance of

improve hospital delivery rates. This increases TBD coverage and

hepatitis B including clear differentiation of acute and chronic

decreases perinatal HBV transmission, which results in reduction

hepatitis B. Key aspects to address include (1) guiding hospital

of disease burden. Tibet, Guizhou and Yunnan should be the prior-

professionals to make the right diagnosis and report according to

ity areas. Screening for HBsAg in pregnant mothers and provision of

the right case deﬁnition, (2) testing specimens appropriately in the

HBIG for those born to HBsAg positive mothers would be the second

laboratory, (3) case investigation and effective data management.

step, which will further decrease new infections among suscepti-

Reliable reporting of acute hepatitis B will allow identiﬁcation of

ble infants. As screening and HBIG to infants of carrier mothers is

risk factors for use in policy making. Such work should to be done

already done in many provinces, at cost to parents, China needs a

in pilot projects ﬁrst, before expanding to a national scale. Evidence

national guidance to support and promote this policy.

generated could guide vaccination of high-risk adults.

Catch-up campaigns. As China has already completed catch-

up vaccination for children under 15 years old (birth cohorts

5.2.4. Toward screening and treatment

since 1994), the strategy will now evolve toward routine activities

As time will progressively unveil the impact of hepatitis B immu-

through school entry checks in primary school or middle school,

nization on the incidence of cirrhosis/hepatocellular carcinoma

plus provision of routine vaccination in all vaccination sites. Rais-

cases, China will need to set up a system that will be able to measure

ing the target age for catch-up campaigns would lead to smaller

these health events to calculate the number of deaths prevented

returns in terms of cost-effectiveness [26].

and Disability Adjusted Life Years (DALYs) averted.

Health care worker protection. In addition to the routine

In the meantime, China will have to address the issue of the

immunization of infants, catch-up campaigns for children and vac-

current burden of chronic infections among older age groups.

cination for high-risk adults, pre-service vaccination for students in

These chronically infected persons have not beneﬁtted from the

medical, nursing and other health care related schools and univer-

immunization of newborns. A China CDC study already monitors

sity should be addressed [27,28]. Hence, health care workers would

morbidity and mortality outcomes among HBV-infected patients

be protected before exposure. This is a cost-effective way to protect

identiﬁed during the 2006 serological survey [5]. This is a ﬁrst doc-

health care workers [29,30].

umentation step for future programs of management. In the future,

developing pilot approaches for population-based screening for

5.2.2. Addressing remaining unsafe injection issues

management could be an easy ﬁrst step to identify how China could

Injection practices. China needs to have clear safe injection guide-

provide long term care and support for the large population already

lines that would be mandatory for all injections. For vaccination,

infected. It is through these kinds of small-scale pilot projects that

use of AD syringes should be generalized. This could be achieved

the ﬁrst chapters of the great hepatitis B immunization success

through training, supervision, national legislation, regulation or

story were written some thirty years ago in China.

law making. A Chinese expert committee could review the WHO

best practices and the recent national evidence to deﬁne best prac-

tices for China. China should develop national guidelines for safe Conﬂict of interest statement

injections that require that all vaccinations to be given using AD

syringes. The authors state that there is no conﬂict of interest.

J78 W. Yang et al. / Vaccine 31S (2013) J73–J78

References [17] Cui FQ, Wang XJ, Cao L, et al. Progress in hepatitis B prevention through

universal infant immunization—China: 1997–2006. MMWR 2007;56(18):

441–5.

[1] Liang F, Cui F, Hadler S, Wang X, et al. Origins, design and implementation of

[18] WHO. Worker’s health:global plan of action. In: The sixtieth world health

the China GAVI project. Vaccine 2013;31:J8–14.

assembly. 2007. WHA60.26.

[2] WHO. Tool for the assessment of injection safety. WHO/V&B/01.30; 2001.

[19] WHO. Viral hepatitis, A63/15. In: Sixty-third world health assembly. 2010.

[3] Cui F, Liang X, Gong X, et al. Preventing hepatitis B though universal vac-

[20] Ding S, Li Z. The analysis on Chinese new health reforming system and

cination: reduction of inequities through the China GAVI Project. Vaccine

2013;31:J29–35. it’ssustainability. Xiamen: Xiamen Medical University Express; 2008.

[21] Ding D, Kilgore PE, Clemens JD, Wei L, Zhi-Yi X. Cost-effectiveness of routine

[4] Wu Z, Cui F, Chen Y, et al. Evaluation of immunization injection safety in China,

immunization to control Japanese encephalitis in Shanghai: China. Bull World

2010: achievements, future sustainability. Vaccine 2013;31:J43–8.

Health Organ 2003;81(5):334–42.

[5] Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in

[22] Yin Z, Wang H, Yang J, et al. Japanese encephalitis disease burden and clinical

China—declining HBV prevalence due to hepatitis B vaccination. Vaccine

2009;27(47):6550–7. features of Japanese encephalitis in four cities in the People’s Republic of China.

Am J Trop Med Hyg 2010;83(4):766–73.

[6] Xia GL, Liu CB, Cao HL, et al. Prevalence of hepatitis B and C virus infections

[23] Wu GY, Gong YL, Yu SL, Shao RT, Qin HJ. Study on the cost-effectiveness: beneﬁt

in the general Chinese population. Results from a nationwide cross-sectional

and utility analysis on the infant inoculation hepatitis B vaccine in Shanghai.

seroepidemologic study of hepatitis A, B, C, D, and E virus infections in China,

Zhonghua Liu Xing Bing Xue Za Zhi 2004;25(6):474–8.

1992. Int Hepatol Commun 1996;5:62–73.

[24] Pruss-Ustun A, Rapiti E, Hutin Y. Estimation of the global burden of disease

[7] Qu Z. An epidemiological study on the distribution of HBsAg and anti-HBs in

attributable to contaminated sharps injuries among health-care workers. Am J

China. Chin J Microbiol Immunol 1986;(Suppl.):19–47.

Ind Med 2005;48(6):482–90.

[8] WHO. Hepatitis B vaccine, WHO position paper. Wkly Epidemiol Rec

2009;84:405–20. [25] Cui F, Gong X, C.Hen Y, et al. Evaluation on impact of hepatitis B vaccine inte-

grated into routine immunization in Ministry of Health/Global Alliance for

[9] WPRO. Progress towards meeting the 2012 hepatitis B control milestone: WHO

Vaccine and Immunization GAVI cooperation project areas, P.R. China. Chin

Western Paciﬁc Region, 2011. Wkly Epidemiol Rec 2011;86(19):180–8.

J Vacc Immun 2009;15(4):289–93.

[10] Wu WD, Liu DW, Wu BB. Study on the surveillance of adverse events following

[26] Hutton DW, So SK, Brandeau ML. Cost-effectiveness of nationwide hepatitis

immunization in China: 2007–2008. Chin J Vacc Immun 2009;15(6):481–90.

B catch-up vaccination among children and adolescents in China. Hepatology

[11] Liu D, Guo B, Cao L, et al. Study on the surveillance of adverse events following

2010;51(2):405–14.

immunization in China: 2005–2006. Chin J Vacc Immun 2007;13(6):505–13.

[27] Talaat M, Kandeel A, El-Shoubary W, et al. Occupational exposure to needlestick

[12] Wang F, Cui F, Liu D, et al. Analysis on the adverse events following immu-

injuries and hepatitis B vaccination coverage among health care workers in

nization of 10 infants death after hepatitis B vacciantion. Chin J Vacc Immun

2009;15(1):52–7. Egypt. Am J Infect Control 2003;31(8):469–74.

[28] Mayo Ferreiro F, Smyth Chamosa E, Figueiras A. Vaccination for the hepatitis B

[13] UNICEF. Building trust and responding to adverse events following immuniza-

virus in primary care health staff: prevalence, affecting factors and need. Aten

tion in south Asia; 2005.

Primaria 1998;22(1):13–20.

[14] WHO. Hepatitis B vaccines: WHO position paper—recommendations. Vaccine

2010;28(3):589–90. [29] Sangfelt P, Uhnoo I, Reichard O, Weiland O. A low-dose intradermal hepatitis

B vaccine programme in health-care workers and students is highly effective

[15] Progress towards meeting the 2012 hepatitis B control milestone: WHO West-

and cost saving: a retrospective follow-up survey in the clinical setting. Scand

ern Paciﬁc Region, 2011. Wkly Epidemiol Rec 2011;86(19):180–8.

J Gastroenterol 2008;43(4):465–72.

[16] Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn

[30] Lanphear BP. Hepatitis B immunoprophylaxis: developing a cost-effective

infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst

program in the hospital setting. Infect Control Hosp Epidemiol 1990;11(1):

Rev (Online) 2006;2. CD004790. 47–50.