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Melenko Svitlana Romanivna,
PhD, Associate Professor of the Department of Infectious Diseases and Epidemiology
Bukovinian State Medical University Cherniievych Bohdan Oleksandrovych,
student
Bukovinian State Medical University
Nykoliuk Mariia Volodymirivna
student
Bukovinian State Medical University DOI: 10.24412/2520-6990-2023-8167-46-48 HEPATITIS A VACCINATION IN THE WORLD.
Abstract.
Hepatitis A is one of the most important healthcare issues. The first licensed vaccine against hepatitis A (HepA) was in 1992. Both live attenuatedHepA (HepA-L) and inactivatedHepA (HepA-I) are highly immunogenic and well tolerated, and immune protection post-vaccination can last for more than 18 years. HepA is effective for both postexposure and preexposure prophylaxis, especially among young adults and children. During the last 25 years, many countries have witnessed a significant reduction in the incidence of hepatitis A. However, outbreaks of hepatitis A continue to occur frequently among high-risk populations and individuals who have not been included in universal child vaccination programs in recent years. To better understand the changes in the epidemiology of hepatitis A, it is recommended to conduct disease surveillance and serosurveys. Additionally, further research should be carried out to examine the long-term effectiveness of a single dose of HepA in providing immune protection, and to evaluate the cost-effectiveness of different strategies for HepA vaccination. Taking into account this evidence, the recommendation for HepA vaccination should be scientifically based and updated in a timely and well-implemented manner.
Keywords: Immune protection post-vaccination , vaccine against hepatitis A, vaccination strategy, Hepatitis
A.
Introduction: Hepatitis A is a viral infection that spreads primarily through the fecal-oral route. The first reported case of hepatitis A in the United States was in 1973. In 1988, the world's largest outbreak of hepatitis A occurred in Shanghai, China, with over 310,000 cases and 8,000 hospitalizations. Since the first introduction of the hepatitis A vaccine (HepA) in 1992, its effectiveness in controlling the spread of the disease has been demonstrated in numerous countries. However, despite these efforts, over 7,000 people worldwide died from hepatitis A in 2016. In 2016, the World Health Organization (WHO) set a goal of eliminating
viral hepatitis by 2030, and continued efforts are necessary to achieve this objective. This review provides an overview of the global use of HepA vaccination, with the aim of identifying strategies to achieve this goal as scheduled.
Development of HepA : During the 20th century, the development of HepA was made possible due to the success of HAV cultivation in cell lines that are suitable for vaccine production. Nowadays, both inactivated HepA (HepA-I) and attenuated live HepA (HepA-L)
«<g©yL©(MUM~JOy©MaL» #®»7)), 2023 / MEDICAL SCIENCES
are available worldwide, which contain HAV propagated in various human and nonhuman mammalian cells.
A combined HepA and hepatitis B vaccine (HepAB) offers the possibility of preventing both hepatitis A and B simultaneously, potentially saving cost and logistical resources. Currently, there are two types of combined vaccines containing HepA distributed worldwide: combined hepatitis A and B vaccines (Bil-ive™, Twinrix™) and combined hepatitis A and typhoid vaccines (Viatim®). However, no new HepA vaccine has been newly licensed or developed in the last decade.
Administration of hepatitis A vaccine: HepA-I can be given through intramuscular injection in two doses, with a flexible interval of 6 months to 4-5 years (usually 6-18 months) between the first and second dose. The timing of the second dose is not crucial, and a similar anti-HAV titer can be achieved regardless of whether the interval is 6 months, 12 months, or 18 months. Even if the interval between the two doses of HepA-I is up to 2 years, high immunogenicity can still be detected. In some countries, such as Argentina, Brazil, Chile, Paraguay, Colombia, and Tunisia, a singledose HepA-I schedule is used in routine universal vaccination of children for cost considerations. In contrast, HepA-L is mainly used in China and India, and a single subcutaneous dose is administered. Although a high se-roconversion rate can be achieved with a single dose of HepA-I or HepA-L, the duration of immunity after a one-dose schedule may be shorter compared to the two-dose schedule.
The immune system's production of antibodies in response to Hepatitis A vaccination: The immune protection induced by HepA vaccination involves both cellular and humoral pathways. To assess the effectiveness of the vaccine, the most commonly used indicators are the geometric mean concentration (GMC) and sero-conversion rate of anti-HAV. Detection of anti-HAV can be done using enzyme-linked immunosorbent assays (ELISA) and microparticle enzyme immunoassay (MEIA), but the sensitivity of the test may vary depending on the method used. The minimum protective level of anti-HAV IgG is still unknown, and different studies have used different serological cutoffs for seroconver-sion rate (ranging from 10 mIU/ml to 40 mIU/ml). Almost all children can achieve seroconversion of anti-HAV after receiving two doses of HepA-I vaccine, regardless of the manufacturer. The seroconversion rate could be around 95% within 14-30 days after the first dose of HepA-I, and the second dose can significantly increase the anti-HAV level. One-dose HepA-I and HepA-L vaccinations showed a similar seroconversion rate among children and adults, but the GMC was much higher after two doses of HepA-I compared to one-dose of HepA-I or HepA-L. Understanding the prompt immune response after HepA vaccination is important for using it as post-exposure prophylaxis.
Nearly 30 years have passed since HepA vaccination was first introduced, and the issue of long-term immunity following vaccination has become increasingly important. Studies have demonstrated that two or three doses of HepA-I can provide a protective level of anti-
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HAV (^20 mIU/mL) that can last for more than 20 years in both children and adults. A mathematical model suggests that immunity following a two-dose regimen of HepA-I could persist for at least 33 years in 95% of vaccinated individuals. The duration of anti-HAV postvaccination is closely associated with the peak antibody level.
Factors associated with immunogenicity of HepA: There are various factors that may impact the immune response to Hepatitis A (HepA) vaccination. Firstly, the dosage of HepA administered is a significant factor affecting its immunogenicity. In the early stages of HepA-L production, the dose administered was between 105.0-5.5 TCID50, resulting in a seroconversion proportion of 30-40%. However, when the dose was increased to 106.52 TCID50, 106.83 TCID50 and 107.0 TCID50, the seroconversion rates increased to 90.4%, 94.8% and 97.5%, respectively. Currently, the Chinese Pharmacopoeia requires a HepA-L dose above 106.5 TCID50. A similar trend is observed with HepA-I.
Secondly, age has been found to be a crucial factor affecting the immunogenicity of HepA. The immuno-genicity of HepA decreases with increasing age, and vaccinees over 40 years of age tend to have lower anti-HAV following HepA vaccination compared to younger adults. This is the primary reason why immu-noglobulin (IG) is recommended for elderly individuals for PEP during Hepatitis A outbreaks in some countries.
Thirdly, obesity and smoking have been reported to reduce the antibody response to HepA. Additionally, maternal anti-HAV can also influence the antibody response post-HepA. Infants born to mothers with immunity after natural infection may have reduced immu-nogenicity to HepA due to interference with the antibody response, which lasts for 12 months in infants.
Lastly, previous studies suggest that the immuno-genicity of HepA is consistent across different ethnic groups and races.
Ensuring safety after Hepatitis A vaccination:
HepA-I and HepA-L have been found to be highly safe for both children and adults. The majority of adverse events following HepA vaccination are minor in nature. It has been reported that the occurrence of both solicited and unsolicited adverse events is slightly greater following the first dose of HepA-I as compared to the second dose. The primary issue with HepA-L is the potential spread of vaccine strain viruses from vaccinated individuals to unvaccinated individuals. In the initial study of HepA-L derived from the H2 strain, attenuated hepatitis A virus (HAV) was found in the stool samples of vaccinated individuals who received the vaccine 830 days prior. This suggests that attenuated HAV was excreted in the stool, albeit at a much lower level than the wild type virus.
Conclusion: Both HepA-I and HepA-L have demonstrated high immunogenicity and tolerance, with immune protection lasting for at least 20 years postvaccination. The implementation of HepA vaccination and improved sanitary conditions have resulted in a global decrease in hepatitis A incidence, particularly in regions where HepA is introduced into Universal
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Childhood Vaccination Programs (UCVP). However, outbreaks of hepatitis A continue to occur frequently among high-risk populations and age groups that are not covered by UCVP. Furthermore, globalization of economic markets has made the transmission of hepatitis A virus (HAV) across countries much easier.
To achieve the goal of eliminating hepatitis A as scheduled in the near future, the following issues should be emphasized. In highly endemic regions, efforts must be made to improve sanitary and hygienic conditions, including access to clean drinking water and food, which are critical in reducing the incidence of foodborne infectious diseases such as hepatitis A. UCVP should be considered for countries that are tran-sitioning from highly endemic to intermediately endemic regions. In countries with intermediate endemicity, it is important to carefully analyze the long-term immunity protection after HepA and the need for booster doses, especially in regions where only one dose of HepA is introduced in UCVP, to avoid an increase in hospitalization and death due to HAV infection, particularly among young people and adults. In low endemic regions, the focus should be on high-risk populations, including travelers, drug users, and homeless persons, to prevent HAV infection.
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