This study describes epidemiological patterns of HAV infection and predicts the impact of vaccination strategies in a region from central-west Tunisia that accounts among the regions with lowest economic level in the country. Anti-HAV prevalence by age-groups showed a rapid increase during childhood and adolescence. Starting from 31.5% in children aged 5–9 years, it increases with age to reach 50.0, 68.1 and 96.9% in peoples aged 10–14, 15–19 and 20–29 years, respectively. In fact, previous studies conducted in Tunisia and in Jordon and Nicaragua, countries having high/ intermediate HAV endemicity level, showed also that the seroprevalence rate of HAV is high among adolescence and it can reach up to 100% especially in advanced ages [
20,
21,
34,
35]. These results classify the study region as of intermediate endemicity, according to the World Health Organization (WHO) criteria: < 90% at 10 years and ≥ 50% at 15 years of age [
36]. These results also suggest the transition pattern of HAV from high to intermediate endemicity, probably for the whole of Tunisia, previously classified among countries with high endemicity [
19]. Similar epidemiological changes, associated with improved living conditions, are now being observed in many developing countries from the MENA region, such as Algeria, Kuwait, Saudi Arabia, the Emirates and Egypt [
13,
14,
37‐
40] as well as others countries in Africa, Asia, Europe and Latin America [
10‐
16,
34,
35,
41‐
48]. Since older patients are usually symptomatic, the higher occurrence of infection during adolescence and adulthood results in an increased number of symptomatic cases and may lead to serious outbreaks. Therefore, vaccination stands out as the best measure to prevent hepatitis A and is now recommended by WHO for countries showing transition from high to intermediate endemicity. The high effectiveness of hepatitis A vaccines was shown in reducing disease burden and HAV outbreaks [
15,
41,
42]. Many countries such as Argentina, Bahrain, Brazil, China, Greece, Panama, the US and Uruguay; as well as regions of Belarus (Minsk City), Canada (Quebec), Italy (Puglia) and Spain (Catalonia) had introduced HAV vaccine in their universal immunization programs [
40,
43,
49‐
56]. As of May 2019, 34 countries used or were planning to introduce hepatitis A vaccine in routine immunization of children nationally [
57]. In Tunisia, during the past 3 years, many cases of hepatitis A were notified to the ministry of health; most of them were children attending schools and aged over 6 years. Field investigations showed that the majority of the schools where these cases occurred have bad sanitary conditions in terms of access to safe drinking water and the availability of water in the sanitary blocs. In addition to measures aiming the improvement of hygiene in schools, systematic vaccination strategies against HAV were also considered.
At the international level, both inactivated and live attenuated vaccines are now available. Inactivated vaccines were developed since 1992. A complete vaccination schedule consists of 2 doses administered at 6–36 months interval [
36,
58], although several studies showed that a single dose is sufficient [
32,
59,
60]. Inactivated vaccines generally produce comparable immune responses with a protective efficacy of 94% [
33,
36]. They have been introduced in the national immunization program of many countries: two doses in Mongolia (14 months and 2 years), Turkey (18 and 24 months), Israel (18 and 24 months), Uruguay (15 and 21 months), Bahrain (15 months and 2 years), Saudi Arabia (15 months and 2 years), Panama (12 and 18 months), Kazakhstan (2 and 2.5 years) and Qatar (12 and 18 months) and a single dose in Brazil (15 months), Argentina, Colombia and Mexico, for children aged 12 months in the three latter countrie s[
61]. Live attenuated HAV vaccines were more recently developed and are licensed for a single subcutaneous administration in children aged ≥1 year. They provide a protective efficacy of 95% and are mainly used in China and few other countries (India, Thailand, Philippines, Guatemala, Bangladesh) [
62].
Presently, the WHO encourages introduction of HAV vaccine in the immunization schedule of countries with intermediate endemicity and in countries experiencing increased morbidity and mortality [
36]. In the United States of America, the Advisory Committee on Immunization Practices recommends vaccination of children aged 12–23 months together with catch-up vaccination of older children and vaccination of persons at high risk [
20]. In Tunisia, inactivated vaccines were available with a relatively expensive cost and used for around 10% of children vaccinated in the private sector. In the past few years, inactivated vaccine was given to the contacts of confirmed cases to limit the spread of the virus during outbreaks and, since October 2018, it is given to 6 years-old children at school entry. However, other vaccination strategies are still under discussion within the NITAG and the results of the present study will help to choose the best strategies. Although a strategy including a first dose at 12 months of age and a one-time catch-up vaccination for children aged 1–6 years would be the most effective, this was considered as non-feasible for financial considerations. The only possible schemes would consist in the introduction of only one dose or, at most, of two doses. According to the current national vaccination schedule, the best time to deliver this single dose of vaccine may be 12 months of age, together with the 1st dose of Measles/Rubella vaccine, or 6 years at school entry together with the Polio booster vaccine. Due to the recent outbreaks in school-aged children, it was proposed to deliver this vaccine at school entry to rapidly reduce the infection rate among school attendees and interrupt the epidemic trend of the disease. In this study, we developed an age structured epidemiological model to assess the impact of the introduction of vaccination with 3 scenarios: a single dose at 12 months, a single dose at 6 years of age, and one dose at 12 months with a dose at 6 years of age during 6 years. Vaccinating at 12 months of age (scenario 2) is the standard scheme and the most widely used scenario in the world. Vaccination at 6 years of age (scenario 3) is more efficient to interrupt rapidly the epidemic trend among school attendants. Scenario 1 combines the two scenarios allowing a systematic protection of all neonates starting from the earliest recommended age for HAV vaccine and a vaccination at school entry to rapidly reduce the burden of the disease in schools. Scenario 1 will thus offer a catch-up vaccination of children aged 1 to 6 years during a period of 6 years. Our results showed that the three strategies can significantly reduce the incidence of hepatitis A infection and that the reduction will be faster with Scenario1. With regard to the vaccinations strategies using only one dose, our results show that vaccination at school entry induces a more rapid decrease of the fraction of susceptible among school attendants and adolescents but keeps a fraction of susceptible among children less than 6 years of age which will not provide an optimal long-term efficacy of the vaccination strategy.