Hepatitis A virus (HAV) causes inflammatory liver disease that may progress to fulminant liver failure. HAV is transmitted primarily via the fecal/oral route through ingestion of contaminated food and water, or through direct contact with an infectious person (for example, contact with a case within a household). The incidence of HAV infection correlates with socioeconomic indicators, decreasing with increasing income, and access to clean water and adequate sanitation.
In line with the WHO classification, levels of endemicity are based on HAV seroprevalence: high (≥90% by age 10 years); intermediate (≥50% by age 15 years with <90% by age 10 years); low (≥50% by age 30 years with <50% by age 15 years); and very low (<50% by age 30 years).
Data from 2019 regarding the global burden of disease estimated 159 million acute HAV infections, resulting in 39,000 deaths and 2.3 million disability-adjusted life years worldwide; with 97% of hepatitis A deaths occurring in low- and lower-middle-income countries. Preventive strategies such as low-cost vaccination plans are needed for vaccine equity reasons in these countries.
Following the successful propagation of HAV in cell culture in 1979, several hepatitis A vaccines have been developed – being inactivated HAV vaccines (IHVs) the most widely used worldwide.
IHVs are licensed for use in subjects aged ≥12 months, to reduce the potential of interference with pre-existing maternal antibodies. A complete vaccination schedule usually consisted of 2 doses administered intramuscularly with an interval of 6-12 months between doses. Compliance and costs of a 2-dose schedule can make it unfeasible to introduce IHVs to the immunization calendar in many low-middle income countries worldwide.
High efficacy of post-exposure prophylaxis with IHVs is well documented. In Israel, a community wide HAV outbreak in a low socioeconomic setting was completely interrupted within a few weeks following administration of a single dose of IHV administered to >90% of the pediatric population.
But what about incorporating a single dose into the regular HAV immunization schedule for children?
The impact of 1-dose IHV programs has been increasingly demonstrated in diverse settings, including in Argentina, Brazil, and Russia. Specifically in Argentina, HAV had been the leading cause of fulminant hepatic failure and liver transplantation in children in the assessed pre-vaccination period. After the introduction of universal single-dose childhood vaccination in 2005, not a single case of liver failure or transplantation due to hepatitis A was observed, thus demonstrating the favorable impact of vaccination on these critical outcomes.
A review of studies assessing long-term protection of a single dose (1-dose) of IHV as part of the national immunization program, found that protective anti-HAV antibody levels can persist for more than 10 years, and that antibody titers can increase or reappear after booster vaccination. Furthermore, detectable antibodies are estimated to persist for up to 30 years with single-dose schedules based on mathematical modeling and on anti-HAV kinetic studies.
The WHO recommends introducing vaccination against HAV into national immunization schedules for individuals aged 12 months and older. For children, the vaccine can be administered as a single-dose or a two-dose schedule.
Long-term HAV-specific memory humoral and cellular responses have been demonstrated in single-dose vaccinated pediatric populations. This response was independent of demographic characteristics or plasma antibody levels and suggests that individuals with waned Ab titers may still be protected. It has recently been demonstrated that T cells protect against HAV-mediated liver injury. The CD8+ T cell responses are relevant by these cells’ antiviral cytokine production and direct cytolytic activity, while CD4+ T cells act by making antiviral cytokines or helping cytotoxic T lymphocytes.
Recently Brazil reported that one-dose inactivated hepatitis A vaccination was effective in controlling hepatitis A at a national level, with the target-NIP population (children aged 1–4 years) receiving the greatest benefit.
A single dose of IHV provides a great impact on public health, anyway – long- term follow up of protection/effectiveness against Hepatitis A of children receiving a single dose of IHV is a must.
Policy makers in other Latin American countries may utilize these 1-dose schedule to tailor their universal vaccination strategies for hepatitis A.
Bibliography
- Jacobsen KH et al. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010;28(41):6653–7.
- See https://who.int /publications/m/item/sage-hepatitis-a-vaccines-systematic-review-2022.
- The Institute for Health Metrics and Evaluation. Acute hepatitis A — Level 4 cause (https://www.healthdata.org/results/gbd_summaries/2019/acute-hepatitis-a-level4-cause, accessed June 2022)
- Martin A et al. Hepatitis A virus: from discovery to vaccines. Hepatology. 2006;43(2 Suppl 1):S164–72.
- Dagan R et al. Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibody. Pediatr Infect Dis J. 2000;19(11):1045–52.
- Ott JJ et al. Long-term protective effects of hepatitis A vaccines. A systematic review. Vaccine. 2012;31(1):3–11.
- Vizzotti C et al. Impact of the Single-dose Immunization Strategy Against Hepatitis A in Argentina. Pediatric Infectious Disease Journal. 2014;33(1):84–8.
- Espul C et al. Persistence of immunity from 1 year of age after one or two doses of hepatitis A vaccine given to children in Argentina. Hepat Med. 2012;4:53–60.
- Hepatitis A WHO Position Paper – WEEKLY EPIDEMIOLOGICAL RECORD, NO 40, 7 OCTOBER 2022
- Urueña, A. et al. Humoral and cellular immune memory response 12 years following single dose vaccination against hepatitis A in Argentinian children. Vaccine 40, 114–121 (2022)
- Bierrenbach AL, Choi Y, Batista PM, Serra FB, Parellada CI, Julian GS, Nakajima K, Moreira TDNF. The Impact of an Inactivated Hepatitis A Vaccine with One Dose in Brazil: A Retrospective Time-Series. Vaccines (Basel). 2021 Apr 20;9(4):407. doi: 10.3390/vaccines9040407. PMID: 33924029; PMCID: PMC8072696.
