Hepatitis B Control Through Immunization: A Reference Guide

(1)

Box 2: Whyasdf asdfsdf

Hepatitis B Control

Through Immunization:

A Reference Guide

WHO

(2)

(3)

Hepatitis B Control

Through Immunization:

A Reference Guide

(4)

Hepatitis B Control Through Immunization: A Reference Guide

1. Hepatitis B – prevention and control. 2. Hepatitis B vaccines. 3. Immunization programs. 4. Regional health planning. I. World Health Organization Regional Office for the Western Pacific.

ISBN 978 92 9061 669 6 (NLM Classification: WC 536)

All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264;

fax: +41 22 791 4857; email: bookorders@who.int).

Requests for permission to reproduce or translate WHO publications – whether for sale or for non-commercial distribution – should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). For WHO Western Pacific Regional Publications, request for permission to reproduce should be addressed to Publications Office, World Health Organization, Regional Office for the Western Pacific, P.O. Box 2932, 1000, Manila, Philippines (fax: +632 521 1036, email:

publications@wpro.who.int).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication.

However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for

(5)

ACKNOWLEDGEMENTS ii ABBREVIATIONS ii FOREWORD iii

SUMMARY iv

1. INTRODUCTION 1

1.1 Purpose and focus 2

1.2 Control strategies 3

1.3 Progress made in the Western Pacific Region 3 2. REGIONAL GOAL AND INDICATORS 9 2.1 The regional hepatitis B control goal 10

2.2 Strategic areas of focus 11

3. VACCINATION OF INFANTS 13 4. VACCINATION OF PRIORITY ADULT POPULATION GROUPS 21 5. VACCINE SUPPLY, QUALITY AND SAFETY 25 6. ADVOCACY AND SOCIAL MOBILIZATION 29 7. MEASUREMENT OF PROGRAMME PERFORMANCE AND IMPACT 33 7.1 Monitoring programme performance – vaccine coverage 34 7.2 Measuring programme impact – seroprevalence surveys 35 8. VERIFICATION FRAMEWORK 39

8.1 Verification criteria 40

8.2 Verification thresholds and indicators 40 8.3 Structure and function of the Expert Resource Panel (ERP) 41

8.4 Verification procedure 42

8.5 Post-verification 42

9. SELECTED RESOURCES AND GUIDANCE DOCUMENTS 43

ANNEX 1: HEPATITIS B VIRUS 46

ANNEX 2: HEPATITIS B VACCINE 48 ANNEX 3: HEPATITIS B VACCINATION COVERAGE AND CHRONIC

INFECTION PREVALENCE 50

AEFI adverse event following immunization Anti-HBs antibodies to hepatitis B surface antigen Anti-HBc antibodies to hepatitis B core antigen CTC controlled temperature chain DPT diphtheria-pertussis-tetanus vaccine ELISA enzyme - linked immunosorbent assay EPI Expanded Programme on Immunization ERP Hepatitis B Expert Resource Panel HBcAg hepatitis B core antigen

HBeAg hepatitis B ‘e’ antigen HBIG hepatitis B immunoglobulin HBsAg hepatitis B surface antigen HBV hepatitis B virus

HepB hepatitis B vaccine

Hib Haemophilus influenzae type B RED Reaching Every District TAG Technical Advisory Group UNICEF United Nations Children’s Fund

US CDC United States Centers for Disease Control and Prevention VVM vaccine vial monitor

ABBREVIATIONS

Hepatitis B Control Through Immunization: A Reference Guide was produced by the Expanded Programme on Immunization (EPI) unit of the WHO Regional Office for the Western Pacific and Ms Stephanie Shendale. Many National Immunization Programme managers and WHO EPI country staff provided valuable comments during the development of this document. The WHO Regional Office for the Western Pacific hepatitis B Expert Resource Panel members reviewed several drafts of the document and provided valuable feedback. The Technical Advisory Group (TAG) on Immunization and Vaccine-Preventable Diseases in the Western Pacific Region and WHO headquarters also provided technical input.

ACKNOWLEDGEMENTS

(7)

Hepatitis B prevention and control is a high priority for me as the World Health Organization Regional Director for the Western Pacific — the Region which has historically had the highest hepatitis B burden.

Hepatitis B infection causes deadly cirrhosis and cancer of the liver. The best protection from this deadly virus is three doses of vaccine in infancy, with the first dose administered within 24 hours of birth. Extremely safe and effective, the vaccine is the best tool we have for protecting children.

Member States have prioritized hepatitis B vaccination. Now millions of infants receive the complete series every year, and hepatitis B infection among infants and children has fallen dramatically, and continues to decline.

Indeed, the success of the Western Pacific Region has been remarkable. Since 2003, 10 million chronic hepatitis B infections have been prevented in the Region, saving an estimated 2.5 million people from hepatitis B-related deaths.

This milestone is the result of national actions to control hepatitis B. By 2012, 30 countries and areas in the Region had reduced prevalence among children to less than 2% — compared to prevalence rates higher than 6% in the pre-vaccine era.

In October 2013, the Regional Committee for the Western Pacific passed a resolution to further reduce hepatitis B — to less than 1% chronic infection prevalence among children by 2017.

This latest goal will save millions more in the Region from the devastating effects of hepatitis B.

To support Member State efforts to reach this goal, I am pleased to introduce Hepatitis B Control Through Immunization: A Reference Guide, which provides guidance and targets for

hepatitis B control.

The Western Pacific Region was the first to establish a hepatitis B control goal. With close cooperation and strong government leadership, the Region can also become the first to reduce the disease’s deadly toll to historic lows.

As always, I welcome the opportunity to work with each Member State towards the achievement of our shared goal.

Shin Young-soo, MD, Ph.D.

Regional Director for the Western Pacific

World Health Organization

iii

FOREWORD

(8)

Hepatitis B Control Through Immunization: A Reference Guide is intended to provide a handy compilation of available guidance for hepatitis B vaccination programs in countries and areas of the Western Pacific Region. The Western Pacific Region, despite being home to approximately 28% of the global population, bears a disproportionate burden of hepatitis B virus (HBV)- related mortality and morbidity, accounting for almost half of all chronic hepatitis B infections worldwide.¹ With an estimated 160 million chronic HBV carriers living in the Region, hepatitis B is responsible for nearly 900 deaths per day, a mortality rate comparable to that of tuberculosis.¹ Most countries had a chronic HBV infection rate of more than 10% before the introduction of vaccination.² Of the 325 000 estimated annual deaths caused by HBV infection in the Region, nearly all are consequences of chronic infection, mostly decades after the initial infection at birth or in early childhood. Hepatitis B, therefore, is an important regional public health priority.

Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life has been proven to be the most effective strategy for the prevention and control of hepatitis B. In 2005, the Western Pacific Region achieved the distinction of being the first WHO region to incorporate infant hepatitis B immunization in the national immunization programmes of all its Member States.

In 2003, the fifty-fourth session of the WHO Regional Committee for the Western Pacific set a goal to reduce the prevalence of chronic hepatitis B infection among 5-year- old children to less than 1% (WPR/RC54.R3) in 2005 an interim milestone of reducing chronic HBV infection among children to less than 2% by 2012 was established (WPR/

RC64.R5). By 2012, the Region as a whole and 30 countries and areas were estimated to have met the milestone. Striving to build upon these gains, in 2013, the sixty-fourth session of the WHO Regional Committee for the Western Pacific has now resolved to meet the goal of reducing chronic HBV infection to less than 1% among 5-year-old children by 2017 (WPR/RC64.R5). Achievement of this goal will translate to an additional 60 000 hepatitis B-related deaths averted per birth cohort in the Region.

There are five key strategic areas for hepatitis B prevention through vaccination.

1. Vaccination of infants

•

Strengthening of routine immunization services to achieve and sustain at least 95%

coverage with three doses of hepatitis B vaccine by 1 year of age in each birth cohort at the national level, and at least 85% coverage in each district.

•

Delivery of a timely birth dose (within 24 hours of birth), with a target of reaching at least 95% of births at the national level and at least 85% coverage in each district.

•

Coordination with maternal and child health programmes to improve access to immunization and other neonatal care interventions for births outside of health facilities.

Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life has been proven to be the most effective strategy for the prevention and control of hepatitis B.

SUMMARY

1 Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 2005;34:1329–39.

2 Rani M, Yang B, Nesbit R. Hepatitis B control by 2012 in the WHO Western Pacific Region: rationale and implications. Bull

(9)

v 2. Vaccination of priority adult population groups

•

Immunization of high-risk population groups including health workers, men who have sex with men, sex workers, people who inject drugs, frequent recipients of blood/

plasma transfusions, and any other population groups coming in regular contact with blood and blood products.

•

Advocacy of national policies requiring free and universal hepatitis B vaccination of health-care workers.

3. Vaccine supply and quality

•

Elimination of vaccine stock-outs at the national and district levels through improved training in vaccine management.

•

Prevention of vaccine freezing through improved training in temperature monitoring.

•

Promotion of use of controlled temperature chain for delivery of hepatitis B birth dose.

4. Advocacy and social mobilization

•

Increasing awareness among decision-makers, health workers and caretakers of the risks and consequences of HBV infection and the need for hepatitis B vaccination through:

n community and civil society engagement,

n use of media outlets,

n education materials, and

n mass awareness campaigns such as World Hepatitis Day and World Immunization Week.

5. Measurement of programme performance and impact

•

Measurement of programme performance through monitoring of immunization coverage rates, including establishment of systems to monitor hepatitis B birth dose coverage at the district level.

•

Impact measurement through hepatitis B surface antigen (HBsAg) seroprevalence surveys.

•

Verification.

(10)

(11)

1. INTRODUCTION

AFP

(12)

INTRODUCTION

1.1 PURPOSE AND FOCUS

The Western Pacific Region, despite being home to approximately 28% of the global population, bears a disproportionate burden of HBV-related mortality and morbidity, accounting for almost half of all chronic hepatitis B infections worldwide.³ With an estimated 160 million chronic HBV carriers living in the Region, hepatitis B is responsible for nearly 900 deaths per day, a mortality rate comparable to that of tuberculosis.⁴ Most countries had a chronic HBV infection rate of more than 10% before the introduction of vaccination.⁵Of the 325 000 estimated annual deaths caused by HBV infection in the Region, nearly all were consequences of chronic infection, mostly decades after the initial infection at birth or in early childhood. Hepatitis B, therefore, is an important regional public health priority.

Striving to build upon the gains achieved in immunization systems during the poliomyelitis eradication initiative, the Western Pacific Region has adopted hepatitis B control through immunization as one of the pillars for strengthening immunization service delivery systems. In 2005, the WHO Regional Committee for the Western Pacific established an interim milestone of reducing chronic HBV infection prevalence to less than 2% among children aged 5 years old by 2012, with a future goal of reaching less than 1% infection prevalence in the Region.⁶ The Region as a whole and 30 countries and areas achieved the milestone of less than 2%

prevalence by 2012, a remarkable achievement in a region with a disproportionately high burden from hepatitis B. Based on this success, in October 2013, the Regional Committee resolved to meet the goal of reducing chronic HBV infection to less than 1% prevalence in 5-year-old children by 2017.

Since the 2007 hepatitis B regional plan was developed, the hepatitis B programme has reached a new level of maturity, most notably: hepatitis B vaccination has been introduced nationwide across the Region for more than five years; the three-dose series of hepatitis B is provided as part of a combined diphtheria–pertussis–tetanus (DPT) vaccine in the majority of countries; and hepatitis B surface antigen (HBsAg) prevalence among children has decreased dramatically. In addition, the target year for meeting the goal has been set for 2017. As of January 2014, 11 countries and areas have been verified as having achieved the goal of less than 1% HBsAg prevalence among 5-year-old children. In light of these developments, in 2013, the Technical Advisory Group (TAG) on Immunization and Vaccine- Preventable Diseases in the Western Pacific Region recommended updating the hepatitis B regional guidance to reflect the current status of the programme.

This regional reference guide for hepatitis B synthesizes WHO guidance documents published since the last plan was released, namely: Guidelines for certification of achievement of hepatitis B control goal in the Western Pacific Region,⁷an updated WHO position paper on hepatitis B vaccination (2009),⁸a WHO review of practices to improve birthdose coverage (2013) and a regional WHO guidance document on vaccination of health-care workers (2013).⁹ This new guide also incorporates the recommendations made by TAG during its

4 Rani M, Yang B, Nesbit R. Hepatitis B control by 2012 in the WHO Western Pacific Region: rationale and implications. Bull World Health Organ. 2009;87:707–13.

5 Clements CJ, Baoping Y, Crouch A, Hipgrave D, Mansoor O, Nelson CB, et al. Progress in the control of hepatitis B infection in the Western Pacific Region. Vaccine. 2006;24:1975–82.

6 Measles elimination, hepatitis B control and poliomyelitis eradication. Manila: World Health Organization Regional Office for the Western Pacific; 2005 (WPR/RC56.R8; http://www2.wpro.who.int/rcm/en/archives/rc56/rc_resolutions/wpr_rc56_r08.htm).

7 Guidelines for certification of achievement of hepatitis B control goal in the Western Pacific Region. Manila: World Health Organization Regional Office for the Western Pacific; 2007 (www.wpro.who.int/entity/immunization/documents/docs/

HepBControlCertifGuidelines.pdf).

8 Hepatitis B vaccines: WHO position paper. Wkly Epidemiol Rec. 2009;84(40):405–19.

9 Vaccinating health-care workers against hepatitis B. Manila: World Health Organization Regional Office for the Western Pacific;

The Region as a whole and at least 30 countries and areas achieved the milestone of less than 2% prevalence by 2012.

(13)

INTRODUCTION

3 22nd meeting in June 2013, the WHO Regional Committee for the Western Pacific at its

sixty-fourth session in October 2013, and the Second Hepatitis B Expert Resource Panel Consultation held in December 2013.

The guide is intended to provide a handy compilation of available guidance for hepatitis B vaccination programmes in countries and areas of the Western Pacific Region. It provides an update on the progress made since 2007, regional goals, programmatic strategies and indicators, processes for monitoring and verifying achievement of the

hepatitis B control goal, and references to additional WHO resources.

1.2 CONTROL STRATEGIES

Universal infant immunization with three doses of hepatitis B vaccine, with the first dose provided within 24 hours of birth, is the most cost-effective prevention and control strategy.

This strategy provides the earliest possible protection to future birth cohorts and reduces the pool of chronic carriers in the population. Timely vaccination of newborn infants (ideally within 24 hours of birth) can prevent perinatal transmission of hepatitis B. Catch-up vaccination of children born before the introduction of vaccine and vaccination of adults at high risk for HBV infection are additional preventive strategies that can help to protect older susceptible birth cohorts.

Non-immunization control options include ensuring the safety of blood and blood products through regular screening of donors, promotion of safe sex, and ensuring injection safety. These control strategies will have positive public health benefits, not only in terms of hepatitis B control, but also for other bloodborne infections, such as HIV. WHO has developed a comprehensive framework for global action on the prevention and control of viral hepatitis, which provides further guidance on non-vaccination control strategies for viral hepatitis including diagnosis and treatment.¹⁰

Notwithstanding the merits of these additional strategies, however, this updated reference guide focuses specifically on hepatitis B control through immunization.

1.3 PROGRESS MADE IN THE WESTERN PACIFIC REGION

Since the publication of the 2007 hepatitis B regional plan, substantial progress in hepatitis B control has been made in the Region, including the achievement of the 2012 milestone of reducing chronic infection prevalence among 5-year-old children to less than 2%. Since 2005, all Member States in the Region, except Japan,¹¹ have been providing hepatitis B immunization for all infants nationwide. Since 2007, all Member States, except Japan and New Zealand,¹²have included a birth dose within 24 hours in their official immunization schedules. Reported coverage for hepatitis B birth dose and third dose has improved dramatically in the Region, although data quality remains a concern. The dramatic impact that vaccination programmes have had on reducing chronic infection prevalence in the Region is illustrated in Figures 1 and 2, and regional trends in vaccination coverage can be seen in Figure 3.

Universal infant immunization with three doses of hepatitis B vaccine, with the first dose provided within 24 hours of birth, is the most cost- effective prevention and control strategy.

10 Prevention and control of viral hepatitis infection: framework for global action. Geneva: World Health Organization; 2012 (WHO/

HSE/PED/HIP/GHP 2012.1; www.who.int/csr/disease/hepatitis/Framework/en/).

11 Japan has a policy of screening all pregnant women and providing hepatitis B vaccination to infants born to HBsAg- positive mothers.

12 Japan and New Zealand provide the birth dose to newborn infants born to HBsAg-positive women.

(14)

INTRODUCTION

Figure 1. Prevalence of chronic HBV among children before vaccine introduction

Chronic HBV prevalence before vaccine

>6% prevalence >2% - 6% prevalence <2% prevalence Mongolia

China Japan

Republic of Korea

Lao People’s Democratic

Republic Hong Kong SAR (China)

Cambodia

Singapore Malaysia

Viet Nam Macao SAR (China)

Australia

Commonwealth of Northern Mariana

Islands

Marshall Islands Federated States

of Micronesia Philippines

Guam

Brunei Darussalam

Palau

Papua New Guinea

Nauru

Kiribati

Vanuatu

New Zealand Solomon

Islands

New Caledonia

Wallis and Futuna

Tuvalu

Tonga

Cook Islands Fiji

Tokelau

American Samoa

French Polynesia Niue

Samoa

Chronic HBV prevalence in 2012

China Japan

Republic of Korea

Republic

Hong Kong SAR (China)

Cambodia

Singapore Malaysia

Australia

Islands

Guam

Brunei Darussalam

Palau

Papua New Guinea

Nauru

Kiribati

Vanuatu

New Zealand Solomon

Islands

New Caledonia

Wallis and Futuna

Tuvalu

Tonga

Cook Islands Fiji

Tokelau

American Samoa

Samoa

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimination of its fronteriers and boundaries.

Pitcairn Islands Pitcairn Islands

Chronic HBV prevalence before vaccine

China Japan

Republic of Korea

Republic Hong Kong SAR (China)

Cambodia

Singapore Malaysia

Australia

Islands

Guam

Brunei Darussalam

Palau

Papua New Guinea

Nauru

Kiribati

Vanuatu

New Zealand Solomon

Islands

New Caledonia

Wallis and Futuna

Tuvalu

Tonga

Cook Islands Fiji

Tokelau

American Samoa

Samoa

Chronic HBV prevalence in 2012

China Japan

Republic of Korea

Republic

Cambodia

Singapore Malaysia

Australia

Islands

Guam

Brunei Darussalam

Palau

Papua New Guinea

Nauru

Kiribati

Vanuatu

New Zealand Solomon

Islands

New Caledonia

Wallis and Futuna

Tuvalu

Tonga

Cook Islands Fiji

Tokelau

American Samoa

Samoa

Dotted lines on maps represents approximate border lines for which there may not yet be full agreement © WHO Regional The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimination of its fronteriers and boundaries.

Pitcairn Islands Pitcairn Islands

Figure 2. Prevalence of chronic HBV among children in 2012

(15)

INTRODUCTION

As of 2012, the Region as a whole and at least 30 countries and areas have successfully reduced chronic infection rates in children to less than 2%. As of January 2014, 11 countries and areas were officially verified as achieving the goal of reducing infection rates in children to less than 1%: Australia, Brunei Darussalam, China, Hong Kong SAR (China), Cook Islands, Macao SAR (China), Malaysia, Mongolia, New Zealand, Palau and the Republic of Korea. See Figure 4.

5

Figure 3. Immunization coverage with hepatitis B birth dose and third dose, Western Pacific Region, 1990–2013

Immunization coverage (%)

0 20 40 60 80 100

2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990

Year

Timely birth dose coverage (<24 hours) 3-Dose hepatitis B coverage

Program Improvements Required (8) Ready for Verification (3) Serosurvey Planned (14) Verified (11) Mongolia

China

Japan Republic of Korea

Lao People’s Democratic Republic

Cambodia

Singapore Malaysia

Australia

Northern Mariana Islands

Marshall Islands

Federated States of Micronesia Philippines

Guam

Brunei Darussalam

Palau

Papua

New Guinea Kiribati

Vanuatu

New Zealand Solomon

Islands

New Caledonia

Wallis and Futuna Tuvalu

Tonga Cook Islands Fiji

American Samoa

Samoa Tokelau Nauru

Pitcairn Islands

Figure 4. Hepatitis B control verification status, 2013

(16)

INTRODUCTION

Partners Global action or

recommendation Regional action or

recommendations Country or

regional progress

Key Milestones

Hepatitis B (HB) ^{HB fact}

Plasma-derived hepatitis B vaccine becomes the first ever cancer preventing vaccine licensed (the recombinant hepatitis B vaccine in use today was licensed in 1986).

AusAID, NZAID, WHO and UNICEF implement a project to increase hepatitis B vaccination in Pacific island countries.

GAVI support for hepatitis B vaccine introduction becomes available for GAVI-eligible countries.

WHO recommends hepatitis B birth dose vaccination for all newborn infants.

Hong Kong SAR (China) and Malaysia verified as having reached the 1% hepatitis B control goal. Tonga verified as having reached the 2% hepatitis B control milestone.

2%

The Western Pacific Region as a whole and at least 30 countries and areas meet the 2% hepatitis B milestone. Australia, China, Mongolia and New Zealand verified as having reached the 1% hepatitis B control goal.

The Western Pacific Region adopts 2017 as the target year to meet the 1% goal. Palau verified as having reached the 1% hepatitis B control goal^#. The Victorian

Infectious Diseases Reference Laboratory (VIDRL) becomes the hepatitis B reference laboratory for the Western Pacific Region. CDC supports WHO Regional Office for the Western Pacific in hepatitis B control. The World

Health Organization recommends hepatitis B vaccination for all infants.

Macao SAR (China) and the Republic of Korea are the first countries and areas officially verified as having reached the 1% hepatitis B control goal. 100%

All countries and areas in the Region include hepatitis B vaccination as part of their national immunization policies (Japan has targeted vaccination).

The Western Pacific Region sets a goal to reduce hepatitis B infection among children to less than 1% with a milestone of less than 2% by 2012*.

All countries and areas in the Region adopt hepatitis B birth dose vaccination for all newborn infants with the exception of Japan and New Zealand, which conduct targeted vaccination.

100% ^100%

1%

(17)

INTRODUCTION

7

Partners Global action or

recommendation Regional action or

recommendations Country or

regional progress

Key Milestones

Hepatitis B (HB) ^{HB fact}

Plasma-derived hepatitis B vaccine becomes the first ever cancer preventing vaccine licensed (the recombinant hepatitis B vaccine in use today was licensed in 1986).

AusAID, NZAID, WHO and UNICEF implement a project to increase hepatitis B vaccination in Pacific island countries.

GAVI support for hepatitis B vaccine introduction becomes available for GAVI-eligible countries.

WHO recommends hepatitis B birth dose vaccination for all newborn infants.

Hong Kong SAR (China) and Malaysia verified as having reached the 1% hepatitis B control goal.

Tonga verified as having reached the 2%

hepatitis B control milestone.

2%

The Western Pacific Region as a whole and at least 30 countries and areas meet the 2% hepatitis B milestone.

Australia, China, Mongolia and New Zealand verified as having reached the 1%

hepatitis B control goal.

The Western Pacific Region adopts 2017 as the target year to meet the 1% goal.

Palau verified as having reached the 1% hepatitis B control goal^#. The Victorian

Infectious Diseases Reference Laboratory (VIDRL) becomes the hepatitis B reference laboratory for the Western Pacific Region.

CDC supports WHO Regional Office for the Western Pacific in hepatitis B control.

The World Health Organization recommends hepatitis B vaccination for all infants.

Macao SAR (China) and the Republic of Korea are the first countries and areas officially verified as having reached the 1%

hepatitis B control goal.

100%

All countries and areas in the Region include hepatitis B vaccination as part of their national immunization policies (Japan has targeted vaccination).

The Western Pacific Region sets a goal to reduce hepatitis B infection among children to less than 1% with a milestone of less than 2% by 2012*.

All countries and areas in the Region adopt hepatitis B birth dose vaccination for all newborn infants with the exception of Japan and New Zealand, which conduct targeted vaccination.

100% ^100%

1%

* WPR/RC56.8

# WPR/RC64.R5

(18)

INTRODUCTION

Further information

n More information on HBV, the consequences of HBV infection, and HBV epidemiology can be found in Annex 1.

n Additional information on hepatitis B vaccine can be found in Annex 2, and in the following resources:

l WHO position paper on hepatitis B vaccines (2009): http://www.who.int/wer/2009/

wer8440.pdf

l Introducing hepatitis B vaccine into national immunization services (WHO/V&B/01/28): http://whqlibdoc.who.int/hq/2001/WHO_V&B_01.28.pdf

l Introduction of hepatitis B vaccine into childhood immunization services. Management guidelines, including information for health workers and parents (WHO/V&B/01.31): http://whqlibdoc.who.int/hq/2001/WHO_V&B_01.31.pdf

l The Immunological Basis for Immunization Series: Hepatitis B (2012):

http://apps.who.int/iris/bitstream/10665/77755/1/9789241504751_eng.pdf

n Hepatitis B data profiles for the countries and areas of the Western Pacific Region, including demographic data, vaccination policies, childbirth delivery types, reported vaccination coverage during 2008–2012, and vaccination coverage and seroprevalence survey summaries, can be found in the following document:

l Hepatitis B control: strategic information and country profiles. Manila: World Health Organ- ization; 2013 (http://www.wpro.who.int/hepatitis/resource/hepbcountryprofile.pdf).

•

• o

(19)

Box 2: Whyasdf asdfsdf

9

Western Pacific Regional Strategic Action Plan For Hepatitis B Control Through Immunization 2014–2019

2. REGIONAL GOAL AND

STRATEGIC AREAS OF FOCUS

WHO

(20)

REGIONAL GOAL & INDICA

TORS

2.1 REGIONAL HEPATITIS B CONTROL GOAL

Eleven countries and areas in the Western Pacific Region have already been verified as achieving the regional goal of less than 1% HBsAg seroprevalence.

13 Measles elimination, hepatitis B control and poliomyelitis eradication. Manila: World Health Organization Regional Office for the Western Pacific; 2005 (WPR/RC56.R8; http://www2.wpro.who.int/rcm/en/archives/rc56/rc_resolutions/wpr_rc56_r08.htm).

14 Hepatitis B control through vaccination: setting the target. Manila: World Health Organization Regional Office for the Western Pacific; 2013 (WPR/RC64.R5)

Box 1: Why is hepatitis B infection measured in terms of HBsAg seroprevalence rather than clinical disease outcomes?

Vaccine-preventable diseases with strong active surveillance systems such as measles and polio:

l are acute in nature, meaning the impact of the vaccination programme is immediately visible in the same year on the disease burden in the targeted age group (for example, infants); and

l have distinct clinical signs and symptoms, which allow for the development of a simple case definition that can be used for detection of potential cases. This, coupled with laboratory confirmation, can achieve a highly sensitive surveillance system.

Neither of the above criteria applies to hepatitis B. Transmission of HBV among infants, the key target group for hepatitis B immunization programmes, is usually asymptomatic.

Nevertheless, infants and younger children are highly prone to HBV infection from perinatal and horizontal transmission, and are more likely than adults to become chronically infected with HBV. These children are not only likely to die from cirrhosis or liver cancer in their 30s to 50s, but also serve as an infectious pool to sustain the transmission of HBV infection among the general population.

Therefore, surveillance for symptomatic hepatitis B disease among children (as practised for other vaccine-preventable diseases) is unlikely to show any impact of the vaccination programme.

The first indicator to be affected by a vaccination programme is the seroprevalence of HBsAg among the vaccinated cohorts, as fewer children become infected. Therefore, a reduction in chronic HBV infection can be verified by a decrease in the seroprevalence of serological markers (HBsAg) rather than a reduction in the incidence of cirrhosis or hepatocellular carcinoma, which would take several decades to observe.

GOAL: Reduce HBsAg seroprevalence to less than 1% in 5-year-old children by 2017.

The ultimate goal of the WHO Regional Office for the Western Pacific’s Hepatitis B Programme is to protect each and every child from HBV infection. In September 2005, the Region pledged a commitment to reducing chronic HBV infection rates (as measured by HBsAg seroprevalence among children aged 5 years) to less than 2% by 2012.¹³

Having achieved that milestone in 2012, the sixty-fourth Regional Committee in 2013 resolved to meet the goal of reducing HBV infection in children to less than 1% prevalence by 2017 as measured by serological surveys (Boxes 1 and 2).¹⁴

Eleven countries and areas in the Western Pacific Region (Australia, Brunei Darussalam, China, Cook Islands, Hong Kong SAR [China], Macao SAR [China], Malaysia, Mongolia, New Zealand, Palau and the Republic of Korea) have already been verified as achieving the regional goal of less than 1% HBsAg seroprevalence. After verification, it is important to sustain high vaccination coverage, address pockets of low coverage, and strive to ensure that all new birth cohorts are completely protected from hepatitis B infection.

(21)

REGIONAL GOAL & INDICATORS

2.2 STRATEGIC AREAS OF FOCUS

The key strategic areas for hepatitis B prevention through vaccination are as follows:

l vaccination of infants;

l vaccination of priority adult population groups;

l vaccine supply and quality;

l advocacy and social mobilization; and

l measurement of programme performance and impact.

11

15 Goldstein ST, Zhou F, Hadler S, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol, 2005, 34:1329–39.

Box 2: Why is the goal set among 5-year-old children?

Children have a 90% chance of developing chronic HBV infection if infected at birth, a 30%

chance if infected between the ages of 1 and 5 years, and only a 5–10% chance if infected after 5 years of age. In settings that are hyperendemic for hepatitis B, as is the case in most countries of the Western Pacific Region, most chronic infections are acquired by age 5.¹⁵ As such, measuring the goal among children aged 5 years or older will take into account the complete exposure period when the risk of horizontal transmission and likelihood of becoming chronically infected are highest. Setting the goal among children under 5 years of age may overestimate the impact of vaccination programmes if some of the children who are uninfected and unprotected at the time of evaluation later become infected by age 5.

(22)

(23)

3. VACCINATION OF INFANTS

WHO

(24)

VACCINATION: INFANTS

Strengthening routine immunization services to achieve and sustain high coverage of each birth cohort with at least three doses of hepatitis B vaccine before the age of 1 year is the most important strategy for hepatitis B control. Mathematical modelling suggests that extremely high vaccination coverage is needed to interrupt hepatitis B transmission.¹⁶ While it is difficult to know the exact coverage that is necessary to interrupt transmission of hepatitis B, the goal should be to protect the entire birth cohort to ensure equity in health access. When the Regional Committee set 2017 as the target year for achieving the goal of 1% hepatitis B prevalence, vaccination coverage targets were also endorsed. Based on the 2013 hepatitis B resolution, and the Regional Framework for Implementation of the Global Vaccine Action Plan, the coverage targets for both hepatitis B third dose and timely birth dose are at least 95% coverage at the national level, and at least 85% coverage in all districts.¹⁷

Delivery of a timely birth dose (within 24 hours of birth) is critical to prevent mother-to-child transmission of HBV.

17 Hepatitis B control through vaccination: setting the target. Manila: World Health Organization Regional Office for the Western Pacific; 2013 (WPR/RC64.R5, http://www.wpro.who.int/about/regional_committee/64/resolutions/en/).

19 Lee C, Gong Y, Brok J, BOxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review). The Cochrane Collaboration; John Wiley & Sons, Ltd; 2008 (http://www.who.int/immunization/sage/Lee_

review_HepBinf_CD004790.pdf ).

Target: Minimum third dose coverage of 95% at the national level and at least 85%

coverage in each district.

Target: Minimum birth dose coverage of 95% at the national level and 85% coverage at the district level.

The three-dose schedule for hepatitis B vaccine is combined with the schedules of DPT and Haemophilus influenzae type B (Hib) vaccine in the majority of countries of the Region.

Monitoring hepatitis B third dose coverage is therefore an indicator of the overall strength of the routine immunization system in countries (Table 1).

Delivery of a timely birth dose (within 24 hours of birth) is critical to prevent mother- to-child transmission of HBV, a high priority in a region where women of childbearing age have chronic infection prevalence greater than 8% and prevalence of hepatitis B ‘e’ antigen (HBeAg) is high among those who are HBsAg positive.¹⁸ A high percentage of chronic infections in the Region may be acquired through mother-to-child transmission during childbirth. The baby of an HBsAg-positive (carrier) mother has a 70–90% risk of infection if the mother is HBeAg positive, and a 5–20% (~10%) risk if she is HBeAg negative. Post- exposure prophylaxis with hepatitis B vaccine within 24 hours of birth dramatically reduces the risk of infection. A meta-analysis of randomized control trials found that birth dose vaccination reduced the incidence of hepatitis B chronic infection by 72% among infants

born to HBsAg positive women.¹⁹

(25)

Box 3: Why is a birth dose for all newborn infants recommended?

WHO recommends a policy of universal neonatal vaccination within 24 hours of birth to ensure that all babies are provided initial protection at birth. Hepatitis B vaccination at birth provides benefits in terms of a “safety net”, not only for prevention of perinatal infection, but also against early horizontal transmission from household contacts or other sources.²¹ In addition, administration of a birth dose has been associated with higher rates of on-time completion of the hepatitis B vaccine series and, in certain settings, improved completion rates for all other infant vaccines.

Antenatal screening programmes can be useful for identifying HBV infection among pregnant women. However, even where robust screening programmes are in place, country experiences have shown that targeted vaccination of babies of HBsAg positive mothers fails to capture all at-risk newborn babies due to incomplete screening, inaccurate test results, and errors in medical records. Therefore, universal birth dose vaccination is the most effective policy to prevent mother-to-child transmission.

Given the importance of early protection, timely delivery of the first dose of vaccine (within 24 hours of birth) for all newborn infants is the primary strategy for preventing perinatal transmission (Box 3). Where resources allow, hepatitis B immunoglobulin (HBIG) (passive immunity) may be given in addition to the vaccine to children born to HBsAg positive mothers. However, the option for HBIG is conditional on the existence of comprehensive antenatal screening programmes for hepatitis B infection and resources, and will be of limited value in settings with poor antenatal coverage. Where screening programmes exist, post-vaccination serological testing may be useful to assess the effectiveness of the programme in preventing mother-to-child infection. It is effective to conduct post-vaccination testing for HBsAg and anti HBs after completion of the vaccine series, between the ages of 9 and 18 months.

WHO in the Western Pacific Region has developed operational field guidelines for the delivery of the hepatitis B birth dose.²⁰ Countries may refer to this document when developing national action plans for delivery of the hepatitis B birth dose.

The birth dose should ideally be given within 24 hours of birth, as the earlier the vaccine is given the more likely it is that infection will be prevented. With limited data to establish when a birth dose is “too late” to protect the newborn infant, the birth dose should be administered on first possible postnatal contact, even if missed at birth. If the baby is due for the first combination dose (DTP-Hib-hepB) at the first contact, then the combination dose should be given rather than the monovalent birth dose.

15

20 Preventing mother-to-child transmission of hepatitis B: Operational field guidelines for delivery of birth dose of hepatitis B vaccine. Manila: WHO Regional Office for the Western Pacific; 2006.

21 Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine.

2013;31(21):2506–16.

Delivery of timely hepatitis B birth dose provides an opportunity to link immunization delivery systems with maternal health programmes (Box 6). It is effective for immunization services to work with maternal services work with maternal and neonatal care services to ensure that hepatitis B vaccine is included in the essential care package for newborn infants (Box 4), and to harmonize training and programmatic issues such as where, when, and by whom the birth dose will be given.

(26)

Provision of the hepatitis B birth dose within 24 hours of birth provides special challenges, especially in countries where a substantial proportion of births occur at home.

In many cases, home deliveries are handled by traditional birth attendants, most of whom receive no formal training. Collaboration with maternal and child health programmes to promote facility births and access to skilled birth attendants and postnatal care is of utmost importance, as well as engagement of village health volunteers and community leaders to increase access to outreach services available.

Ensuring population confidence in the safety of the vaccine is critical to achieving high vaccination coverage. Apprehensions about the timing and safety of administering vaccine immediately after birth, such as concerns about false contraindications and potential adverse reactions, must be addressed through education and training of health workers, as well as through information and communication aimed at the community, to avoid missed opportunities to vaccinate.

Low birth weight and premature delivery are NOT contraindications for the administration of hepatitis B vaccine within 24 hours of birth (Box 5). However, the birth dose should not interfere with any urgent clinical care needs that may present, and should only be given after the baby is stable. Studies have shown that the immunogenic response to the birth dose may be reduced in low-birth-weight babies. This should NOT prevent the administration of vaccine within 24 hours; however, it is crucial to ensure that low-birth- weight babies receive a full three-dose series of hepatitis B vaccine, in addition to the birth dose (a total of four doses).

The early postnatal period is a fragile time, and, in many developing countries, neonatal mortality remains high for various reasons. Over half of neonatal deaths occur within the first 24 hours of life,²² increasing the likelihood of a coincidental association between birth dose vaccination and neonatal complications or death due to other causes. Is is effective to train health-care providers to be able to answer questions about vaccine safety and address concerns about coincidental adverse events following immunization (AEFIs).

Box 4. Hepatitis B as part of the Essential Newborn Care package

It is effective to include Hepatitis B vaccination in the essential newborn care package, so that it is part of the series of standard procedures that a baby receives at birth:

l Hepatitis B birth dose should be given after immediate newborn care (that is, drying baby, checking for breathing, skin-to-skin contact with mother, cord-cutting, initiation of breastfeeding, eye care) and only when the baby is stable (that is, baby scores 6 or higher on the Apgar test (if test is done) and is able to breastfeed soon after birth.

l Medications for the mother and baby should never be kept on the same tray to avoid programmatic errors.

l Hepatitis B birth dose can be administered along with other essential newborn care interventions such as BCG vaccination, vitamin K prophylaxis and weighing.

l Low birth weight and Caesarean sections are not contraindications for hepatitis B vaccination, although immunogenicity can be lower for low-birth-weight babies and for babies weighing less than 2,000 grams the birth dose and three additional doses are needed to provide complete protection.

22 Newborn death and illness. Geneva: The Partnership for Maternal, Newborn & Child Health, World Health Organization; 2011 (http://www.who.int/pmnch/media/press_materials/fs/fs_newborndealth_illness/en/index.html, accessed in September 2014).

(27)

Catch-up immunization of older children

The first priority is protecting infants through strengthening routine immunization services. Catch-up immunization for older children who missed immunization as infants is recommended as a secondary strategy after routine infant vaccination reaches target levels if countries have additional financial and human resources for enhanced hepatitis B control, and should be based on careful epidemiological and economic analysis. It is up to each country to prioritize other groups for publicly funded immunization.

Effective Strategies:

1. Use tools, such as the Reaching Every District (RED) strategy (re-establishing outreach services, supportive supervision at all levels, linking services with communities, monitoring and use of data for action, and planning and management of resources) to streamline and strengthen routine immunization services to reach each and every child. For more information on tools and guidance for immunization service delivery, including the RED strategy, visit WHO’s Service Delivery webpage.²⁵

2. Collaborate with maternal and child health programmes to coordinate immunization services with broader maternal and neonatal care; improve policies, training and supervision; increase

17

Box 5. Contraindications and precautions

Extensive evidence has documented that the hepatitis B vaccine is extremely safe for neonates and infants.^23,24 Given the inherent fragility of the early neonatal period, however, health workers often hold misconceptions regarding contraindications for hepatitis B birth dose vaccination. It is therefore critical to improve education and training for health-care workers so that opportunities for immunization are not missed due to misinformation.

There are no absolute contraindications for timely hepatitis B birth dose vaccination.

Low birth weight, premature delivery, Caesarean sections and HIV status are NOT contraindications for the administration of the vaccine. However, the timing of vaccine administration should not interfere with treatment of any urgent neonatal care, and should be given only after the baby is stable.

Table 1. Typical schedule of hepatitis B (HepB) and pentavalent (DTP-Hib-hepB) vaccination in the Western Pacific Region*

Age** Vaccine

At birth (within 24 hours) HepB monovalent

6 weeks DTP–HepB–Hib1

* While three doses are sufficient to induce immunity, for programmatic reasons most countries in the Region use a combination vaccine, resulting in a four-dose schedule.

** Ages given are recommended as the earliest possible, but they are flexible. Immunization programmes should emphasize vaccination at birth and completing the hepatitis B series by 6 months of age.

23 Lewis E, Shinefield HR, Woodruff BA, Black SB, Destefano F, Chen RT, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect Dis J. 2001;20(11):1049–54.

24 Eriksen EM, Perlman JA, Miller A, Marcy SM, Lee H, Vadheim C, et al. Lack of association between hepatitis B birth immunization and neonatal death: a population-based study from the vaccine safety datalink project. Pediatr Infect Dis J.

2004;23(7):656–61.

25 Immunization, vaccines and biological: service delivery (webpage). Geneva: World Health Organization; 2014 (http://www.who.

int/immunization/programmes_systems/service_delivery/en/)

Hepatitis B Control Through Immunization: A Reference Guide

Hepatitis B Control

Through Immunization:

A Reference Guide

Hepatitis B Control

Through Immunization:

A Reference Guide

CONTENTS

ABBREVIATIONS

ACKNOWLEDGEMENTS

FOREWORD

•

•

•

SUMMARY

•

•

•

•

•

•

•

•

•

1. INTRODUCTION

Key Milestones

2%

1%

Key Milestones

2%

1%

2. REGIONAL GOAL AND

STRATEGIC AREAS OF FOCUS

3. VACCINATION OF INFANTS