Game changing: hepatitis B vaccine in a controlled temperature chain
Authors: Minal K Patel, Anna-Lea Kahn
Journal: The Lancet Global Health (2018)

WHO recommends that every child should receive at least three doses of hepatitis B virus (HBV) vaccine, with the first dose being given ideally within 24 h of birth (referred to as HBV birth dose vaccine), regardless of burden of disease in the country.1WHOHepatitis B vaccines: WHO position paper—July 2017.Wkly Epidemiol Rec. 2017; 92: 369-392PubMed Google Scholar However, despite this recommendation, only 101 (52%) of the 194 WHO member states provide universal HBV birth dose vaccination, with nine (19%) of 47 countries in the African region providing the vaccine.2Implementation of hepatitis B birth dose vaccination—worldwide, 2016.Wkly Epidemiol Rec. 2018; 93: 61-72PubMed Google Scholar Furthermore, for those countries providing universal HBV birth dose vaccination, a significant positive correlation exists, as is expected, between coverage levels of HBV birth dose vaccine and institutional delivery rates and skilled birth attendant rates.3Allison RD Patel MK Tohme RA Hepatitis B vaccine birth dose coverage correlates worldwide with rates of institutional deliveries and skilled attendance at birth.Vaccine. 2017; 35: 4094-4098Crossref PubMed Scopus (21) Google Scholar The more home births that occur, the lower the coverage. Therefore, new strategies need to be implemented to reach home births while not neglecting the fact that countries should simultaneously be trying to increase institutional delivery rates because they are the safest for the mother and newborn baby. In The Lancet Global Health, Nick Scott and colleagues4Scott N Palmer A Morgan C et al.Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling study.Lancet Glob Health. 2018; 6: e659-e667Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar have provided evidence that the controlled temperature chain (CTC) strategy is financially smart for many countries. Using a mathematical model of perinatal HBV transmission and disease progression, they find that beyond the health benefits in all regions, a CTC strategy would be cost-effective in the East Asia and Pacific, Latin America and the Caribbean, sub-Saharan Africa, and North Africa and the Middle East regions. Savings ranged from US$890 (95% CI 430–1490) per 1000 births in Latin America and the Caribbean to US$1920 (1540–2140) in sub-Saharan Africa, where an estimated 167 (95% CI 136–198) disability-adjusted life-years (DALYs) per 1000 births would be averted through the CTC strategy. This method builds on the existing body of evidence suggesting that use of the CTC could help to improve the coverage, equity, and timeliness of delivery of HBV birth dose vaccine by overcoming barriers associated with compromised access to vaccines due to cold chain constraints.5Petit D Tevi-Benissan C Woodring J Hennessey K Kahn AL Countries' interest in a hepatitis B vaccine licensed for the controlled temperature chain; survey results from African and Western Pacific regions.Vaccine. 2017; 35: 6866-6871Crossref PubMed Scopus (10) Google Scholar However, several programmatic issues need to be considered alongside this data. First, many countries have yet to introduce HBV birth dose vaccination. One barrier has been cost—even though the vaccine is inexpensive, the start-up costs can be high including training of delivery and newborn care staff on vaccine administration and handling, and expanding cold chain infrastructure in delivery wards. Additionally, although the monovalent hepatitis B vaccine was financed for many years by Gavi, the Vaccine Alliance, their switch to supporting the pentavalent vaccine reduced the in-country availability of the monovalent vaccine needed for the HBV birth dose vaccine. As Gavi embarks on a new round of its Vaccine Investment Strategy, a renewed opportunity will arise to expand funding to include the introduction of HBV birth dose vaccine in Gavi-eligible countries. Many of these countries are in the African region, have a high proportion of home births, and would benefit the most from a CTC strategy. Second, creation of a CTC outreach strategy has other potential benefits for the mother and newborn baby, beyond preventing HBV infection. WHO recommends that postnatal care is provided for home births within 24 h of birth because of the many benefits including the reduction of maternal and neonatal mortality.6WHOWHO recommendation on postantal care of the mother and newborn. World Health Organization, Geneva2014Google Scholar Lifesaving postnatal care can be provided, as well as education on exclusive breastfeeding, clean cord care, and the importance of routine immunisations.7Li XF Fortney JA Kotelchuck M Glover LH The postpartum period: the key to maternal mortality.Int J Gynaecol Obstet. 1996; 54: 1-10Crossref PubMed Scopus (187) Google Scholar, 8Darmstadt GL Marchant T Claeson M et al.A strategy for reducing maternal and newborn deaths by 2015 and beyond.BMC Pregnancy Childbirth. 2013; 13: 216Crossref PubMed Scopus (35) Google Scholar Therefore, we estimate that the cost-savings per DALY averted would be higher when viewed broadly. Third, although the authors focus on the outreach strategy for home births, at least 20% of health facilities in low-income and middle-income countries do not have sufficient cold chain for the daily provision of HBV birth dose vaccination.9WHOUnited Nations Children's FundWHO/UNICEF Joint Statement: achieving immunization targets wtih the comprehensive effective vaccine management (EVM) framework. World Health Organization and United Nations Children's Fund, Geneva and New York2016Google Scholar Furthermore, the CTC can facilitate access to vaccines by allowing delivery wards to keep HBV birth dose vaccines in the delivery room, overcoming previously documented barriers such as inadequate access to vaccines after hours. Thus again, the impact would be greater than that outlined by Scott and colleagues,4Scott N Palmer A Morgan C et al.Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling study.Lancet Glob Health. 2018; 6: e659-e667Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar as the CTC strategy could also be implemented in these health facilities. However, the uptake of the CTC for HBV birth dose vaccines is not without its own set of challenges. Despite a confirmed interest in CTC by countries such as the Solomon Islands and Laos, pilot studies on the use of HBV birth dose vaccines outside the cold chain showed that one challenge was a paucity of regular vaccine delivery to remote health facilities.10Breakwell L Anga J Dadari I Sadr-Azodi N Ogaoga D Patel M Evaluation of storing hepatitis B vaccine outside the cold chain in the Solomon Islands: identifying opportunities and barriers to implementation.Vaccine. 2017; 35: 2770-2774Crossref PubMed Scopus (20) Google Scholar, 11Kolwaite AR Xeuatvongsa A Ramirez-Gonzalez A et al.Hepatitis B vaccine stored outside the cold chain setting: a pilot study in rural Lao PDR.Vaccine. 2016; 34: 3324-3330Crossref PubMed Scopus (28) Google Scholar Ensuring a stable, regular supply of vaccine to use in the CTC is not always possible, especially to more remote areas or those with difficult access. However, this type of barrier is not insurmountable; countries need to create plans for supplying all health facilities and doing CTC outreach. All the benefits of the CTC will never come to fruition if no manufacturer exists with a product licensed and prequalified for CTC use. The thermostability of HBV vaccine has been documented since the early 1990s, and yet almost 30 years later, no CTC-compatible product exists. Although HBV vaccine storage in the CTC has the potential to save many lives and money, few manufacturers have been willing to commit to the stability testing and label variation needed for relicensure. Consequently, global efforts to support the development of appropriate CTC incentives for manufacturers are needed; additionally, the assessment, quantification, and effective communication of the demand for CTC should be communicated to manufacturers by countries as well as other global stakeholders. We declare no competing interests. Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling studyA CTC outreach strategy that improves the timing and coverage of the HBV birth dose vaccination is likely to be cost-saving and reduce the burden of HBV infection associated with perinatal transmission. Full-Text PDF Open Access