Progress Toward Elimination of Mother-to-Child Transmission of Hepatitis B Virus — Region of the Americas, 2012–2022

In 2022, an estimated 5 million persons in the World Health Organization Region of the Americas (AMR) were living with chronic hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma and cirrhosis worldwide. Most chronic infections are acquired through mother-to-child transmission (MTCT) or horizontal transmission during childhood and are preventable with hepatitis B vaccination, including a birth dose (HepB-BD), followed by 2-3 additional doses (HepB3) in infancy. The Pan American Health Organization (PAHO) Elimination of MTCT of HBV infection strategy is intended to reduce chronic HBV infection (measured by hepatitis B surface antigen [HBsAg] seroprevalence) to ≤0.1% among children by achieving 1) ≥95% coverage with HepB-BD and HepB3; and 2) ≥80% of pregnant women received testing for HBsAg, and provision of hepatitis B immunoglobulin to HBV-exposed neonates. By 2012, all 51 AMR countries and territories (countries) provided HepB3 nationwide, and by 2021, 34 (67%) provided HepB-BD nationwide. Mathematical models estimate that HBsAg seroprevalence in children is ≤0.1% in 14 (28%) of 51 countries and at the regional level. Three (6%) of 51 countries met the 95% coverage targets for both HepB3 and HepB-BD during both 2021 and 2022. Of these, two have likely met criteria for the elimination of MTCT of HBV infection. However, in 2022, HepB3 coverage had declined by ≥10 percentage points in 15 (37%) of 41 countries with 2012 coverage data for comparison. These declines in HepB3 coverage, as well as the absence of HepB-BD in the routine immunization schedules in 17 countries, threaten PAHO's progress toward the elimination of MTCT of HBV infection. Efforts to introduce HepB-BD and maintain high HepB3 and HepB-BD coverage are needed.


Introduction
Globally, chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma and cirrhosis (1).In 2022, an estimated 5 million persons in the World Health Organization (WHO) Region of the Americas (AMR)* had chronic HBV infection, and approximately 20,000 died from hepatitis B-related causes (2).Most chronic HBV infections are acquired through mother-to-child transmission (MTCT) or horizontal transmission during early childhood (1).Infections acquired at age ≤5 years are more likely to become chronic than are those acquired later in life (1).To prevent chronic HBV infection, WHO recommends that all infants receive a timely birth dose of hepatitis B vaccine (HepB-BD), defined as receipt within the first 24 hours of life, with 2-3 additional doses (HepB3) preferably administered during the first months of life, simultaneous with vaccines containing diphtheria, tetanus, and pertussis (1).
In 1999, the Pan American Health Organization (PAHO) recommended that the 51 countries and territories (countries) in AMR provide HepB3 vaccination for all infants nationwide (universal vaccination) and, in 2011, recommended the inclusion of a universal HepB-BD (3,4).In 2017, PAHO expanded its strategy for achieving the elimination of MTCT of HIV and syphilis to include HBV infection and Chagas disease (EMTCT Plus) (5).PAHO's EMTCT Plus strategy includes the impact target of reducing hepatitis B surface antigen (HBsAg) seroprevalence (a marker for chronic HBV infection) to ≤0.1% among children aged 4-6 years, and several programmatic targets: 1) achieving high coverage (≥95% nationally and >85% in all provinces or areas) with timely HepB-BD and HepB3; and 2) increasing HBsAg testing among pregnant women and provision of hepatitis B immunoglobulin (HBIG) to HBV-exposed neonates to ≥80% (5).The WHO global criteria for the elimination of MTCT of HBV infection are similar and include achieving ≤0.1% HBsAg seroprevalence among children aged ≤5 years †  with timely HepB-BD and HepB3 for the two most recent, consecutive years (6).This report describes progress toward the elimination of MTCT of HBV infection in AMR during 2012-2022 (3,5,6).

Vaccination Activities
Hepatitis immunization schedules, year of hepatitis vaccine introduction nationwide (universal), and WHO/UNICEF National Immunization Coverage estimates or administrative immunization coverage for timely HepB-BD and HepB3 among children aged <1 year were compiled from PAHO, UNICEF, and WHO immunization data portals, unless otherwise indicated (3).WHO/UNICEF National Immunization Coverage estimates are based upon annual country reports submitted via the WHO/UNICEF Joint Reporting Form on Vaccination and coverage surveys.

HBsAg Seroprevalence
WHO recommends population-based, nationally representative HBsAg serosurveys among children aged ≤5 years to monitor progress toward the elimination of MTCT of HBV infection (6).Examples of representative serosurveys (national or subnational) in children or cohorts born after introduction and widespread use of hepatitis B vaccine in the AMR were identified through a search of literature published after 2016 and were reviewed (3).Mathematical modeling estimates of HBsAg seroprevalence in children published by the Global Burden of Disease Collaborators, § The Global Health Observatory, ¶ and the Center for Disease Analysis/Polaris Observatory Collaborators** were reviewed and compiled.

Additional Indicators for EMTCT Plus
Data on the proportion of pregnant women with at least four prenatal care visits and of births at health facilities were compiled from PAHO's Core Indicator Portal.Data describing the presence of policies for universal testing for HBV in antenatal care and provision of HBIG to HBV-exposed newborns were compiled from published literature and PAHO and country websites describing strategies for hepatitis B control and the elimination of MTCT of HBV infection.This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.
HepB3 coverage in 2022 declined by ≥13 percentage points from that in 2012 in the Andean Area, Central America, and Southern Cone and Brazil subregions (Table 1) and declined by ≥10 percentage points in 15 (37%) of 41 countries reporting data for both 2012 and 2022 (3).Coverage in Haiti and Suriname never exceeded 68% and 81%, respectively, during the reporting period.Twelve countries met the global target of ≥90% HepB3 coverage during both 2021 and 2022; among those, five met the PAHO target of ≥95% coverage.

HBsAg Seroprevalence
Estimates from three mathematical models suggest that regional HBsAg seroprevalence among children aged ≤5 years is <0.1% (Table 2).Among 26 countries for which three modeled estimates are available, the estimated seroprevalence from all three models is ≤0.1% in 14 (54%) countries, among which two (Chile and Cuba) reported both HepB3 and HepB-BD coverage ≥95% during both 2021 and 2022.Recently published nationally representative HBsAg serosurveys that included children and vaccine-eligible cohorts conducted in Haiti, Mexico, and the United States corroborate the 2022 estimates for these countries.In addition, recently published HBsAg serosurvey results from population-based subnational surveys conducted in AMR show that decades of vaccination against HBV have led to reductions in the seroprevalence of HBsAg among cohorts that have been age-eligible for vaccination compared with seroprevalence among older cohorts.

Additional Indicators for EMTCT Plus
According to reports received by PAHO from 35 countries, as of 2020, 19 (54%) had national goals for the elimination of  * Year of introduction refers to the year the country or territory established universal HepB vaccination (HepB3 or HepB-BD) policies (i.e., HepB vaccination is recommended for all children throughout the country or territory according to schedule).† All years of HepB3 introduction and all years of HepB-BD introduction before 2016 were compiled from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392937.Years of HepB-BD introduction during and after 2016 were compiled from https://data.unicef.org/resources/immunization-country-profiles,https://paho-cim.shinyapps.io/immunization-dashboard,https://immunizationdata.who.int/global/wiise-detail-page/introduction-of-hepb-birth-dose?ISO_3_CODE = PRY&YEAR =, or directly from the JRF.§ HepB vaccination schedules were compiled from https://immunizationdata.who.int/.Canada's provinces have varying schedules; some include a birth dose, and some initiate vaccination after 1 year of life.Details by Canadian province are available online (https://www.canada.ca/en/public-health/services/provincialterritorial-immunization-information.html).For the United States (including Puerto Rico), the HepB vaccination schedule was extracted from https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf.¶ If not available at https://immunizationdata.who.int/ or as indicated in footnote above, HepB vaccination schedules were compiled from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392937.** Annual HepB3 and HepB-BD national coverage values are WUENIC prepared using data from the JRF; they were compiled from https://immunizationdata.who.int.
Timely administration of HepB-BD is defined as administration within 24 hours of birth.Data were not collected in Puerto Rico during some of the reporting years.In addition, even when data were collected, sample size was sometimes too small to calculate reliable coverage estimates.HepB3 and HepB-BD subregional and regional coverage estimates were generated using data from the 10-year period (2012-2022) for the 51 countries or territories using WUENIC estimates or official coverage.Countries or territories not reporting coverage or that have not adopted universal HepB-BD vaccination policies were assumed to have no coverage.HepB3 and HepB-BD subregional and regional coverage values were weighted coverage based upon the number of average annual births for 2012-2022, as available, from the United Nations population estimates.† † Where annual WUENIC were not available, values are from official or administrative national immunization coverage as reported on the country or territory's JRF (https://paho-cim.shinyapps.io/immunization-dashboard).Any reported coverage exceeding 100% was considered 100%.§ § Where annual WUENIC and official or administrative national immunization coverage as reported on the country or territory's JRF were not available, values are those provided in a previous report.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392937¶ ¶ Vaccination data for some territories within the Region of the Americas are not consistently reported to the World Health Organization separately from their associated countries.MTCT of HBV infection (5).Forty-three countries reported data on prenatal care visits by pregnant women; in 21 (49%) countries, ≥90% of pregnant women had at least four prenatal visits.In 27 of 30 (90%) countries with data on delivery location, ≥91.5% of births were at health facilities.Twenty-seven (84%) of 32 countries with data reported providing universal antenatal HBV testing, and 24 (75%) of 32 reported providing HBIG for neonates born to mothers with high levels of HBV DNA; however, the extent of coverage with these interventions is unknown in many AMR countries.

Discussion
Substantial progress has been made toward the elimination of MTCT of HBV infection in AMR.PAHO has supported vaccination against hepatitis B in the region since the 1990s by 1) advocating for vaccination to stakeholders, 2) providing technical support for the development of national vaccination policies, 3) building health care worker capacity, and 4) facilitating vaccine procurement.§ § Mathematical models estimate the prevalence of chronic HBV infection among children aged ≤5 years, as measured by HBsAg seroprevalence, to be <0.1% regionally, and 14 countries met both regional and global impact targets for the elimination of MTCT of HBV infection (5,6).Among the 14 countries identified as likely to have met the HBsAg seroprevalence target, two reported HepB-BD and HepB3 coverage ≥95% during both 2021 and 2022, meeting both the regional and global programmatic targets for the elimination of MTCT of HBV infection, and both implemented antenatal and maternal and child health policies supporting the elimination of MTCT of HBV infection (5,6).§ § https://www.paho.org/en/revolving-fund

TABLE 2. Estimated hepatitis B surface antigen seroprevalence among children aged <5 years, coverage of reproductive health and maternal and child health services, and policies of interventions for the prevention of mother-to-child transmission of hepatitis B, by country or territory and region -Region of the
FIGURE.Annual estimated coverage with the third dose of hepatitis B vaccine and timely hepatitis B birth dose* among children aged <1 year -Region of the Americas, World Health Organization, 1993-2022 Globally, WHO has defined the target as ≤0.1% HBsAg seroprevalence in children aged ≤5 years.In countries with a long history of sustained, high hepatitis B vaccination coverage, flexibility exists to conduct surveys among children aged >5 years.In AMR, PAHO has set the target age group for hepatitis B serosurveys to be children aged 4-6 years. †

TABLE 1 . (Continued) Year of introduction of hepatitis B vaccine,* , † hepatitis B vaccination schedules, §, ¶ and annual estimated or official coverage with third dose of hepatitis B vaccine and a timely hepatitis B birth dose** , † †, § § among children aged <1 year, by country or territory, subregion, and region -Region of the Americas, World Health Organization, 2012, 2017, and 2019-2022 Abbreviations:
B = at birth; HepB = hepatitis B-containing vaccine; HepB3 = third dose of HepB; HepB-BD = birth dose of HepB; JRF = World Health Organization/ UNICEF Joint Reporting Form on Vaccination; NA = not applicable; NR = data not reported; WUENIC = World Health Organization/UNICEF estimates of national immunization coverage.
For the United States, coverage estimates were determined as follows for HepB3 and HepB-BD: 2016-2018 estimates are among children aged 19-35 months during the previous survey year (e.g., 2018 estimate is from survey year 2017 data); 2019-2022 estimates are among children by age 24 months.The 2019 estimate is from combined 2015-2016 birth cohort, the 2020 estimate is from combined 2016-2017 birth cohort, the 2021 estimate is from combined 2017-2018 birth cohort, and the 2022 estimate is from combined 2018-2019 birth cohort.For Puerto Rico, HepB3 estimates are among children by age 24 months, by birth cohort; HepB-BD estimates are among children on the first day of life, by birth cohort.