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Progress Toward Hepatitis B Control and Elimination of Mother-to-Child Transmission of Hepatitis B Virus — Western Pacific Region, 2005–2017
Weekly / March 1, 2019 / 68(8);195–200
Joseph Woodring, DO1; Roberta Pastore, MD1; Anne Brink, MBBS2; Naoko Ishikawa, MD, PhD2; Yoshihiro Takashima, MD, PhD1; Rania A. Tohme, MD3 (View author affiliations)
View suggested citationHepatitis B vaccine (HepB), which has been available since 1982, provides lifelong protection against hepatitis B virus (HBV) infection and the associated 20%–30% increased lifetime risk for developing cirrhosis or hepatocellular carcinoma among >95% of vaccine recipients (1). Before HepB introduction into national childhood immunization schedules, the estimated hepatitis B surface antigen (HBsAg) prevalence in the World Health Organization (WHO) Western Pacific Region (WPR)* was >8% in 1990 (2). In 2005, the WPR was the first WHO region to establish a hepatitis B control goal, with an initial target of reducing HBsAg prevalence to <2% among children aged 5 years by 2012. In 2013, the WPR set more stringent control targets to achieve by 2017, including reducing HBsAg prevalence to <1% in children aged 5 years and increasing national coverage with both timely HepB birth dose (HepB-BD) (defined as administration within 24 hours of birth) and the third HepB dose (HepB3) to ≥95% (3). All WPR countries/areas endorsed the Regional Action Plan for Viral Hepatitis in the Western Pacific Region 2016–2020 in 2015 (4) and the Regional Framework for the Triple Elimination of Mother-to-Child Transmission of human immunodeficiency virus (HIV), Hepatitis B and Syphilis in Asia and the Pacific 2018–2030 (triple elimination framework) in 2017 (5). These regional targets and strategies are aligned with program targets established by the WHO Global Health Sector Strategy on Viral Hepatitis 2016–2021 that aim to reduce HBsAg prevalence among children aged 5 years to ≤1% by 2020 and to ≤0.1% by 2030 (6). This report describes progress made to achieve hepatitis B control in the WPR and the steps taken to eliminate mother-to-child transmission (MTCT) of HBV during 2005–2017. During this period, regional timely HepB-BD and HepB3 coverage increased from 63% to 85% and from 76% to 93%, respectively. As of December 2017, 15 (42%) countries/areas achieved ≥95% timely HepB-BD coverage; 18 (50%) reached ≥95% HepB3 coverage; and 19 (53%) countries/areas as well as the region as a whole were verified to have achieved the regional and global target of <1% HBsAg prevalence among children aged 5 years. Continued implementation of proven vaccination strategies will be needed to make further progress toward WPR hepatitis B control targets. In addition to high HepB-BD and HepB3 coverage, enhanced implementation of complementary hepatitis B prevention services through the triple elimination framework, including routine HBsAg testing of pregnant women, timely administration of hepatitis B immunoglobulin to exposed newborns, and antiviral treatment of mothers with high viral loads, will be needed to achieve the global hepatitis B elimination target by 2030.
Immunization Activities
HepB-BD and HepB3 coverage data are reported annually to WHO and the United Nations Children’s Fund (UNICEF) from 36 of the 37 WPR countries and areas.† WHO and UNICEF estimate vaccination coverage for 27 countries in the region, using annual government-reported survey and administrative data; for the remaining areas and territories, government-reported coverage data are used. By 2005, all countries/areas in the region had introduced at least three HepB doses into national immunization schedules. By 2012, 34 (94%) of 36 countries/areas provided universal HepB-BD (Table 1); since 1987, Japan and New Zealand have provided selective administration of timely HepB-BD to infants born to mothers who are HBsAg-positive or whose HBsAg status is unknown. During 2005–2017, regional HepB-BD coverage increased from 63% to 85%, and HepB3 coverage increased from 76% to 93%. In 2017, 15 (42%) of 36 countries/areas achieved ≥95% timely HepB-BD coverage, and 18 (50%) countries/areas reached ≥95% HepB3 coverage.
HBsAg seroprevalence surveys
Surveillance for acute hepatitis B infection and its sequelae cannot fully capture the population prevalence of HBV infections, because most infants and children remain asymptomatic during acute infection. Nationally representative HBsAg seroprevalence surveys allow countries to assess the prevalence of chronic HBV infection among children born after the introduction of hepatitis B vaccine in the national immunization schedule and track progress toward achievement of regional hepatitis B control targets. In 1990, before HepB was introduced into childhood immunization schedules in most WPR countries/areas, HBsAg seroprevalence among children aged 5 years was estimated to be >8% in 22 (61%) of 36 countries/areas (2), a level of chronic infection considered to be highly endemic (1). As of December 2017, all countries/areas in the WPR had completed serosurveys except for Nauru and New Caledonia; seven countries/areas conducted serosurveys before 2009 (Table 2). By December 2017, HBsAg seroprevalence among children aged 5 years declined to <1% in 25 (69%) countries/areas based on national serosurveys (Table 2). Notably, China, which has the largest birth cohort in the region, was successful in decreasing the prevalence of HBV infection among children to <0.5%. In Laos, Papua New Guinea, Vietnam, and several of the Pacific Island countries, estimated HBsAg prevalence among children aged 5 years still exceeds 2%.
Regional Verification of Hepatitis B Control Goal
In 2007, the WPR established the Hepatitis B Immunization Expert Resource Panel that independently advises on the status of and strategies for achieving the regional hepatitis B control goal.§The Expert Resource Panel is an interdisciplinary team of 10–15 experts recognized in the field of hepatitis B, and members have expertise in immunization, epidemiology, virology, and hepatology. The Expert Resource Panel convenes verification panels to assess whether countries have met established regional control targets. The verification process includes review of data from nationally representative serosurveys conducted among children aged 5 years, who have already passed through the period of highest risk for perinatal and horizontal transmission of HBV. Panel members also review national and subnational HepB coverage data and supporting evidence of countries’ progress in monitoring and targeting high-risk populations including HBsAg-positive mothers and their exposed newborns. As of December 2017, 19 (53%) of the 36 countries/areas were verified by the Expert Resource Panel as having met the regional <1% prevalence target based on serosurvey and vaccination coverage data (Table 2).
Progress Toward Elimination of Mother-to-Child Transmission of HBV
In 2017, the WPR established a goal for elimination of mother-to-child transmission (MTCT) of HBV by 2030, defined as achievement of a 90% reduction in new cases of chronic HBV infection, equivalent to 0.1% HBsAg seroprevalence among children aged 5 years, as part of the triple elimination framework. Key components of the WPR’s strategy to achieve elimination of MTCT of HBV include achieving ≥95% HepB-BD and HepB3 coverage, screening ≥95% of pregnant women for chronic HBV infection, administering hepatitis B immunoglobulin (HBIG) to infants born to HBsAg-positive mothers, and treating pregnant women eligible for treatment with antiviral drugs (5). As of December 2017, 19 (53%) of 36 countries/areas had developed national plans for viral hepatitis prevention; 26 (70%) countries/areas reported having established integrated routine antenatal screening programs for HIV and syphilis (data not shown); and 20 (56%) countries/areas had a national policy for routine antenatal HBsAg testing (Table 3). However, only two (6%) countries reported testing ≥95% pregnant women for HBsAg, and eight countries (22%) reported providing antivirals to infected mothers. In addition to providing timely HepB-BD and HepB3 vaccination for HBV-exposed infants, 10 (28%) countries/areas administered HBIG to newborns of HBsAg-positive mothers, and seven (19%) provided postvaccination serologic testing to determine the infection status of exposed infants.
Discussion
During 2005–2017, the WPR achieved remarkable progress toward the regional hepatitis B control goal and elimination of MTCT of HBV. HepB has been introduced in all countries/areas; almost all countries/areas provide universal HepB-BD; coverage with HepB-BD and HepB3 increased by 35% and 22%, respectively; and 19 (53%) countries/areas were verified to have achieved the 2017 regional control target by December 2017. This success was corroborated by a 2016 disease modeling study that estimated regional prevalence to be 0.93% among children born in 2012.¶ This model also showed that immunization programs in the region prevented more than 37 million cases of chronic HBV infection, and averted more than seven million deaths related to hepatitis B that would have occurred in the lifetime of children born between 1990 and 2014 had hepatitis B vaccination programs not been established (2).
Interventions implemented to increase HepB-BD vaccination coverage included promoting community awareness about the need for HepB vaccination, especially the administration of a timely HepB-BD; building capacity and knowledge of health care staff to administer a timely birth dose; using HepB-BD outside the cold chain; and promoting institutional deliveries (7). WPR countries/areas have extensive experience using the highly heat stable monovalent HepB-BD outside the cold chain in areas that lack a reliable cold chain or have high home birth rates with limited health facility access. This use of the HepB-BD outside the commonly recommended storage temperatures of 35°F–46°F (2°C–8°C) for limited periods under monitored and controlled conditions, has been demonstrated to be safe and effective, with WHO suggesting outside-the-cold-chain use in settings where HepB-BD administration is restricted by access to cold storage (1). HepB-BD use outside the cold chain has been used to increase timely HepB-BD administration by 27% in Laos, 70% in China, and 150% in the Solomon Islands (7,8). Cambodia and China have national policies that encourage pregnant women to deliver in health facilities to reduce maternal and neonatal mortality by ensuring that mothers and newborns are examined by health care professionals within 24 hours of delivery. Institutional delivery also facilitates coordination of postnatal care services between maternal, neonatal, and child health programs and national immunization programs that can improve timely HepB-BD coverage (7,9).
To reach the global hepatitis B elimination goal of ≤0.1% HBsAg prevalence among children aged 5 years by 2030, WPR countries/areas need to achieve elimination of MTCT of HBV, because perinatal transmission accounts for a high proportion of chronic HBV infections among children (1). The triple elimination framework provides guidance for a coordinated delivery of services for immunization, HIV, sexually transmitted infections, and reproductive, maternal, neonatal, and child health to ensure that a timely HepB-BD is administered and high HepB3 coverage is achieved. The framework also provides guidance for implementation of complementary interventions in addition to vaccination to prevent perinatal HBV transmission, including routine testing of pregnant women and timely administration of hepatitis B immunoglobulin to exposed newborns. In addition, the framework suggests possible administration of antiviral drugs to mothers with high viral loads, while awaiting global guidance on its use to prevent MTCT of HBV (5).** In Cambodia, a modeling analysis indicated that offering an integrated package of services through the triple elimination platform could reduce MTCT of HBV by 76%, from 14.1% to 3.4%; syphilis by 51%, from 9.4% to 4.6%; and HIV by 8%, from 6.6% to 6.1%. It could prevent approximately 3,200 infant HBV infections annually at a cost of $114 USD per disability-adjusted life-year (10).
The WPR has significantly decreased the incidence of chronic HBV infection, with a few countries still requiring programmatic improvement in vaccination to achieve hepatitis B control. As the WPR expands implementation of interventions for elimination of MTCT of HBV, global and regional guidance is needed on 1) the use of monitoring indicators to assess the effect of these interventions on elimination of MTCT, 2) the appropriate frequency of costly serosurveys for verification of achievement of low HBsAg seroprevalence targets, and 3) the use of models to estimate infection prevalence from programmatic data to support countries in their control efforts and the elimination of MTCT verification process.
Corresponding author: Joseph Woodring, woodringj@who.int, +329285036370.
1Western Pacific Regional Office, Expanded Programme on Immunization, World Health Organization, Manila, Philippines; 2Western Pacific Regional Office, HIV, Hepatitis and Sexually Transmitted Infections, World Health Organization, Manila, Philippines; 3Global Immunization Division, Center for Global Health, CDC.
All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.
* The Western Pacific Region, one of the six regions of the World Health Organization, consists of 37 countries and areas with a total population of approximately 1.8 billion, including American Samoa (USA), Australia, Brunei, Cambodia, China, Commonwealth of the Northern Mariana Islands (USA), Cook Islands, Federated States of Micronesia, Fiji, French Polynesia (France), Guam (USA), Hong Kong (China), Japan, Kiribati, Laos, Macao (China), Malaysia, Marshall Islands, Mongolia, Nauru, New Caledonia (France), New Zealand, Niue, Palau, Papua New Guinea, Philippines, Pitcairn Islands (UK), Samoa, Singapore, Solomon Islands, Republic of Korea, Tokelau (New Zealand), Tonga, Tuvalu, Vanuatu, Vietnam, and Wallis and Futuna (France).
† The Pitcairn Islands, with a population of approximately 50 persons, does not have an immunization program and does not report immunization coverage data to WHO/UNICEF.
§ At the September 2018 Expert Resource Panel meeting (https://iris.wpro.who.int/bitstream/handle/10665.1/14321/RS-2018-GE-37b-PHL-eng.pdf), two new interim goals were proposed: 1) to reduce HBsAg prevalence to <1% among children aged 5 years in all countries and areas by 2025; and 2) in countries and areas that already have <1% HBsAg prevalence in children aged 5 years, to further reduce HBsAg prevalence to <0.3% by 2025. These are intended to be interim targets for countries to reach the hepatitis B elimination target of <0.1% HBsAg prevalence among children aged 5 years by 2030.
¶ Cambodia, Commonwealth of the Northern Mariana Islands, Federated States of Micronesia, French Polynesia, Guam, Niue, and Tokelau presented serosurvey evidence of reaching the <1% HBsAg prevalence target among children aged 5 years after 2016, suggesting that regional prevalence might have further declined.
** World Health Organization. Guidelines for the prevention, care, and treatment of persons with chronic hepatitis B infection. https://apps.who.int/iris/bitstream/handle/10665/154590/9789241549059_eng.pdf.
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