4.1.1. Prevalence of HBV infection

WHO recommends universal immunization of infants against hepatitis B starting with a timely birth dose in all settings (6), regardless of HBV endemicity. Where the prevalence of HBV infection is intermediate (2–8%) or high (>8%), universal immunization of infants has had a large impact and is cost effective (37). The results of the impact model and cost–effectiveness analysis that was conducted for these guidelines suggest that in settings with high endemicity, high coverage with a timely birth dose followed by two or three additional doses of vaccine would lead to the greatest impact at the lowest cost (see Web annex 3). Some countries with low endemicity have, however, chosen selective strategies to prevent mother-to-child transmission that are based on testing pregnant women to identify those infected. These countries have already been implementing interventions similar to the peripartum prophylaxis recommended in these guidelines, even though they did not implement universal use of hepatitis B immunization in accordance with WHO recommendations.

4.1.2. Prevalence of HBeAg positivity in HBV-infected women of childbearing age

Among women of childbearing age with chronic HBV infection, the prevalence of HBeAg positivity that correlates with high HBV DNA viraemia varies across regions (38). As a result, the risk of perinatal transmission also varies (11, 12). Historically, the African and the Western Pacific regions have the highest prevalence of HBV infection (1) but differ in the prevalence of HBeAg positivity. The prevalence of HBeAg positivity in HBV-infected women of childbearing age is generally higher in the Western Pacific Region compared to other regions, while the African Region has a lower prevalence (38, 39). The introduction of hepatitis B vaccine as part of the Expanded Programme on Immunization (EPI) has led to improved prevention of horizontal transmission in the past decades. As a result, the proportion of chronic HBV infections attributable to horizontal transmission has decreased. Perinatal infection now accounts for a higher proportion of the remaining transmission, both in the Western Pacific and African regions.

4.1.3. Infant immunization coverage

In 2018, the global coverage of the third dose of hepatitis B vaccine was high (84%) (8). However, there were outliers and some countries still struggle to reach high coverage. Where the third dose coverage remains low, increasing coverage is key to eliminating horizontal transmission. Of the six WHO regional offices, three (Western Pacific, Europe and South-East Asia) have mechanisms in place to verify achievements of the better to use hepatitis B control goal through immunization (40, 41). The Eastern Mediterranean Region is still establishing their process. The African Region, however, is first working on the establishment of birth dose policies. In the Region of the Americas, pilot testing of verification of the 0.1% elimination goal has started.

4.1.4. Timely birth dose coverage

In 2018, the coverage of the timely birth dose remained heterogeneous (from 4% in the African Region to 83% in the Western Pacific Region). Where coverage of the timely birth dose remains low, increasing coverage is a priority for two reasons. First, a timely birth dose followed by two or three additional doses is the intervention that leads to the greatest impact at the lowest cost (see Web annex 3). Second, studies demonstrating the efficacy of antiviral prophylaxis have been conducted only in the setting of routine use of infant vaccination (including a timely birth dose) (see Web annex 1). At present, the efficacy of peripartum antiviral prophylaxis in the absence of a timely birth dose is unknown. However, future research in the field could address this knowledge gap.

4.1.5. Availability of commodities

The availability of medicines and diagnostics needed for peripartum antiviral prophylaxis varies. TDF is no longer protected by any patent, and therefore should be available for procurement in any country of the world for US$ 2.5/month or less (42). In practice, in some countries, the absence of national programmes may lead to fragmented procurement, high in-country mark-ups and higher overall prices. HBV DNA testing can be procured for as little as US$ 15/test. The best current market price for laboratory-based HBeAg testing is US$ 7.5 and for RDTs to detect HBeAg, the price ranges between US$ 0.5 and US$ 1.3. However, the in vitro diagnostic infrastructure differs from country to country. Finally, HBIG availability and prices vary. In sub-Saharan Africa, availability is particularly limited. It is mostly available in the private sector at high prices.

4.1.6. Experience with peripartum prophylaxis

Several countries that used to be highly endemic for HBV infection have achieved major progress in hepatitis B control through high coverage of infant hepatitis B vaccination, including timely birth dose (43). Because breakthrough infections in children born to women with high HBV DNA and who received a timely birth dose followed by two or three additional doses now constitute a source of residual perinatal infections (43, 44), programmes for peripartum prophylaxis have been initiated in most regions (15, 45). In some regions, however, particularly the African Region, experience with peripartum prophylaxis is still limited.

4.2.1. African Region

The African Region is characterized by high endemicity of HBV infection, but lower prevalence of HBeAg positivity among women of childbearing age than in the South-East Asia Region, suboptimal routine infant vaccination coverage, low hepatitis B birth dose vaccine coverage, and limited availability of in vitro diagnostic infrastructure and commodities (including HBIG). In this context, initial efforts to implement hepatitis B vaccine birth dose policies would lead to the greatest impact at the lowest cost (see Web annex 3). Initially, efforts to introduce a timely birth dose may start in women delivering in health-care facilities (in 2019, 59.5% of pregnant women delivered in a health-care facility) (46). Additional efforts will be needed to reach women who deliver in the community. From 2021, the support of Gavi, the Vaccine Alliance, should facilitate introduction of a birth dose of hepatitis B vaccine in the EPI schedule (47). The cost of a mono-dose of hepatitis B vaccine is low (US cents 13), under the threshold of national co-payment for Gavi-sponsored vaccines (47). Therefore, financial support from Gavi under the current policy will be primarily directed at operations rather than at vaccine procurement. While efforts to prevent mother-to-child transmission of HBV in the African Region should focus on timely birth dose, implementation of pilot projects for peripartum prophylaxis would also allow experience to be gained in the field. Research projects examining the efficacy of peripartum prophylaxis in the absence of HBIG and/or timely birth dose could also open new programmatic options in the future.

4.2.2. Region of the Americas

The Region of the Americas is characterized by low endemicity of HBV infection, with pockets of high endemicity, particularly among indigenous populations. The estimated regional prevalence of HBsAg in children at 5 years of age is <0.1%. The prevalence of HBeAg among women of childbearing age varies. By 2018, 26 countries and territories had introduced universal hepatitis B birth dose vaccine into their national immunization schedules with an estimated regional coverage of 72%. In 2019, four additional countries introduced a universal birth dose, representing nearly 92% of the total birth cohort in the Region. In 2016, the Pan American Health Organization endorsed “EMTCT Plus”, a Framework for elimination of mother-to-child transmission of HIV, Syphilis, Hepatitis B, and Chagas (48). In recent years, the national context allowed initial experiences of peripartum prophylaxis in a few countries. In 2017, 24 countries were routinely testing pregnant women for HBsAg, while 22 countries provide HBIG for exposed newborns. Implementation of the present guidelines for peripartum prophylaxis would facilitate the prevention of more perinatal HBV infections.

4.2.3. Eastern Mediterranean Region

The Eastern Mediterranean Region is characterized by intermediate endemicity of HBV infection and low prevalence of HBeAg among HBV-infected women of childbearing age. Overall, third dose coverage with the hepatitis B vaccine is high (82%) and the birth dose coverage is low (33%). Experience with peripartum prophylaxis is limited. In this context, efforts to increase timely birth dose coverage should be prioritized.

4.2.4. European Region

The European Region is characterized by low-to-intermediate endemicity of HBV infection in most of its Member States, and low prevalence of HBeAg among HBV-infected women of childbearing age. However, several countries in the south Caucasus and central Asia, and a few countries in eastern and central Europe had high endemicity profiles before universal immunization was introduced. In addition, migrants born in high-endemicity countries have a higher prevalence of HBV infection. Overall, vaccination coverage with the third dose of hepatitis B vaccine is high (84%) but in 2019, four Member States had not implemented universal immunization of infants against hepatitis B nationally because of their low endemicity (1). Some Member States of the WHO European Region (mostly high-income countries with low baseline prevalence of HBV infection) do not implement universal hepatitis B vaccination but rely on targeted prevention of perinatal transmission through testing all pregnant women and providing the birth dose to children born to HBsAg-positive mothers.

Implementation of the present guidelines for peripartum prophylaxis would further facilitate the prevention of perinatal HBV infections, particularly in countries that are not using universal hepatitis B immunization.

4.2.5. South-East Asia Region

The South-East Asia Region is heterogeneous with respect to the epidemiology of HBV infection. Some countries have intermediate or low endemicity for HBV infection (e.g. Sri Lanka). Some countries have high endemicity for HBV infection with a high prevalence of HBeAg positivity among HBV-infected women of childbearing age (e.g. Democratic People’s Republic of Korea, Indonesia, Thailand). Also, in intermediate-endemicity settings, there are indigenous people with a higher prevalence of HBV infection (49). The 2018 coverage of the third dose of hepatitis B vaccine was high (89%) and the coverage of the birth dose was intermediate (48%). Eight out of 11 Member States provide a universal birth dose. However, two of the four Member States that have already reached the 1% goal of HBsAg prevalence in children 5 years of age did not have a timely birth dose in their immunization schedule (50). There is experience of peripartum prophylaxis where HBV is highly endemic and perinatal transmission common, as in Thailand (15). Implementation of the present guidelines for peripartum prophylaxis would facilitate the prevention of perinatal HBV infections, especially in Member States that may decide against adoption of birth dose vaccine in view of the low prevalence of HBsAg that has already been achieved with existing three doses of hepatitis B vaccine.

4.2.6. Western Pacific Region

In the Western Pacific Region, an estimated 115 million people were living with HBV infection in 2015 and the regional prevalence of chronic HBV infection was estimated at 6.2% (1). When hepatitis B vaccination was introduced in the 1990s, most Member States had a high endemicity of HBV infection and a high prevalence of HBeAg positivity (51). The Region was the first to decide on a target for the control of HBV infection through immunization, aiming at 2% prevalence of HBsAg in children aged 5 years by 2012 (52). In 2018, the coverage of the birth dose and third dose of hepatitis B vaccine was high overall (83% and 90%, respectively), though a number of Member States still had challenges in achieving high coverage (53). In 2018, nine out of 25 reporting Member States and areas had achieved 95% coverage for the timely birth dose while 13 of 27 Member States and areas had achieved 95% coverage of the third dose of vaccination. As a whole, the Region achieved the 2017 target of 1% prevalence of HBsAg in children 5 years of age. However, as a result of large populations and with some Member States having a very high HBV prevalence in the general population, breakthrough infections still account for a large number of perinatal infections. In 2017, the Regional Committee for the Western Pacific Region endorsed the Regional Framework for the Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific, 2018–2030 (54). The Framework proposes a coordinated approach towards achieving triple elimination of mother-to-child transmission of HIV, HBV and syphilis through access to quality reproductive, maternal, newborn and child health services. A number of Member States in the Western Pacific Region have spearheaded efforts to further reduce mother-to-child transmission, including through the use of antiviral prophylaxis and follow up of exposed infants (55, 56). In China, universal antenatal testing for HIV, hepatitis B and syphilis have been offered since 2011, and modelling studies in 2015 to estimate the impact of interventions on the HBV epidemic catalysed discussions on the possibilities of enhancing tightening the HBV prevention strategy toward elimination. In 2017, comprehensive interventions for EMTCT of HBV were established in three provinces as part of pilot projects on triple elimination. In 2018, Malaysia initiated pilot projects for EMTCT of HBV in four states. In 2019, Mongolia updated its national guidelines for EMTCT to include HBV and HCV. Cambodia and Viet Nam have developed national action plans for triple elimination and Philippines and Papua New Guinea are in the process of developing national frameworks. The present guidelines will support countries in introducing and scaling up antiviral prophylaxis to further reduce mother-to-child transmission of HBV.

TABLE. 1

Key elements of the context to guide policies for the prevention of mother-to-child transmission of HBV in the six WHO regions.