Evolving trends in hepatitis A epidemiology: Shifting patterns, emerging risks, and future strategies

Abstract

Hepatitis A, a vaccine-preventable liver infection caused by the hepatitis A virus, is undergoing significant epidemiological shifts worldwide. Traditionally considered a disease of childhood in endemic regions, improved sanitation, economic development, and widespread vaccination have led to a decline in incidence, particularly in developed nations. However, this decline has resulted in a growing population of susceptible adults, increasing the risk of severe outbreaks. Additionally, changes in travel patterns, urbanization, and socioeconomic disparities have altered disease distribution, leading to sporadic outbreaks in low-endemicity regions and a rising burden in certain high-risk populations. This review explores the evolving epidemiology of hepatitis A, emphasizing the transition from endemic childhood infections to adult susceptibility. We examine the impact of changing risk factors, including shifting demographics, increased international travel, and regional disparities in vaccination coverage. Furthermore, the review highlights the emergence of new viral strains and their potential implications for disease control. Updated vaccination policies, including targeted immunization strategies and their role in preventing outbreaks, are also discussed. Given these dynamic changes, continued surveillance and public health preparedness tailored to evolving risk groups are crucial for sustained hepatitis A control. By synthesizing recent epidemiological data and policy updates, this review provides insights into the future of hepatitis A prevention and control, offering guidance for clinicians, researchers, and public health professionals.

Key Words: Disease outbreak; Emerging infectious disease; Hepatitis A vaccine; Fulminant hepatic failure; Endemic diseases

Core Tip: The epidemiology of hepatitis A is undergoing a profound shift, driven by changing socioeconomic conditions, living standards worldwide and ongoing viral evolution. This has resulted in a shift in epidemiology, with decreasing exposure to the virus among children, leaving adolescent and adult populations susceptible to more clinically significant disease. This change leads to more severe disease in older populations, highlighting the need for updated vaccination guidelines targeting susceptible adults, vigilant surveillance to monitor viral evolution and antigenic variation, and strengthened public health measures including enhanced hygiene and outbreak prevention strategies.

INTRODUCTION

Hepatitis A virus (HAV) affects tens of millions of people and continues to be a significant global health concern, with recent estimates indicating approximately 14 million cases and 28000 deaths annually, according to a 2024 Food and Agriculture Organization of the United Nations/World Health Organization (WHO) review of viral foodborne diseases[1]. This marks a notable rise from the 7134 deaths reported in 2016, highlighting the enduring and possibly increasing burden of HAV in both developing and developed settings[2]. Despite the availability of an effective vaccine for several decades now and ability to control viral spread with simple measures such as providing access to sanitation and food hygiene measures, one review estimates an increase in global incident cases from 1990 to 2019 by 13.9%, from 139.54 million to 158.94 million, with persistence of high endemicity levels in certain parts of the developing world and sporadic outbreaks occurring even in the developed world, even as the world transforms in other ways with medical and scientific breakthroughs[3]. The goal of eliminating viral hepatitis by 2030 was put forward by WHO in 2016, and much needs to be done to achieve this[4].

HAV is a non-enveloped, icosahedral virus with a linear, single-stranded, positive-sense RNA genome, classified under the Picornaviridae family[5]. The Picornaviridae family includes several medically important viruses such as poliovirus, echovirus, rhinovirus, and coxsackievirus[6]. It is transmitted via the fecal-oral route, often through contaminated shellfish which includes oysters, clams and other filter feeding molluscan shellfish[7]. Although seafood continues to be a common source, a growing number of cases are now associated with imported frozen products such as fruits, vegetables, and ready-to-eat meals[3]. International travellers from low-endemic regions are at increased risk of hepatitis A infection when visiting high-endemic areas, particularly if they lack prior immunity to the virus[8]. Additionally, person-to-person transmission is prominent in high-risk settings such as nursing homes, prisoners and among men who have sex with men[9,10]. Laboratory diagnosis relies on the detection of anti-HAV immunoglobulin M (IgM) antibodies, which indicate recent infection. Anti-HAV IgG antibodies appear soon after and confer lifelong immunity[11]. In suspected cases with initially negative results, repeat testing after 7-10 days is recommended to exclude delayed seroconversion. In selected cases, HAV RNA detection by reverse transcription polymerase chain reaction in serum or stool can provide early confirmation of infection, especially during the seronegative window period, and is also useful for outbreak tracing and identifying transmission chains. Molecular assays further allow genotype determination most commonly genotypes IA, IB, and IIIA in human infections which contributes to understanding viral origin, regional circulation, and epidemiologic links. False-positive IgM results may occasionally occur in autoimmune or other viral conditions, so molecular confirmation may be warranted in equivocal cases[12]. HAV infection is typically asymptomatic in children but often presents with symptoms in adults which includes fever, malaise, anorexia, abdominal discomfort and jaundice[13]. After an incubation period of about 28 days (range 15-50 days), the illness typically progresses through prodromal, icteric, and convalescent phases. The clinical spectrum ranges from mild, anicteric illness to severe acute hepatitis, with most patients achieving complete recovery[14]. However, in 15%-20% of individuals, a cholestatic or relapsing form may develop, characterized by prolonged jaundice, pruritus, and recurrent elevations of aminotransferases after apparent recovery[15]. In rare cases, especially among individuals with pre-existing chronic liver diseases or co-infection with hepatitis B virus, HAV can lead to fulminant hepatic failure[16]. Extrahepatic manifestations, though uncommon, have been reported and include vasculitis, cryoglobulinemia, and thrombocytopenia[17]. Table 1 clearly demonstrates clinical course and manifestations of HAV Infection[14].

Table 1 Clinical course and manifestations of hepatitis A virus infection.

Phase	Approximate duration	Key clinical manifestations	Laboratory/virological findings
Incubation	2-6 weeks (mean 28 days)	Asymptomatic	HAV replication in liver; high virus in stool and blood; normal ALT
Prodromal (pre-icteric)	3-10 days	Fatigue, anorexia, nausea, low-grade fever, right upper quadrant discomfort, diarrhea in children	Rapid ALT/AST rise (> 1000 IU/L); HAV in stool; start of IgM anti-HAV appearance
Icteric phase	1-3 weeks	Jaundice, dark urine, pale stools, pruritus; fever and malaise subside	Peak ALT/AST; elevated bilirubin; IgM anti-HAV positive
Convalescent/recovery	Several weeks-months	Gradual improvement; residual fatigue	Enzyme levels normalize; IgM declines; IgG persists lifelong

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HAV: Hepatitis A virus; Ig: Immunoglobulin.

The case fatality rate of acute hepatitis A varies significantly with age with approximately 0.1% in children and reaching 2.1% in adults aged 40 years and older. In Africa, however, the case fatality rate tends to be higher in adults aged 50 years and above, it increases substantially, ranging from 1.8% to 5.4%. These age-related disparities in mortality highlight the increased vulnerability of older adults and the critical importance of early vaccination and targeted public health interventions, especially in regions with limited healthcare infrastructure[18,19]. In the United States, between 2016 and 2022, more than 44600 cases and over 400 deaths were recorded during large-scale HAV outbreaks across multiple states[20]. This underscores the continued threat posed by communicable diseases, including hepatitis A, which remains a significant cause of morbidity and mortality especially in resource-limited settings[21]. This review explores the changing global epidemiology of hepatitis A, recent outbreak patterns, key risk factors, critical need for improved surveillance, expanded vaccination programs, emergence of new viral strains and targeted preventive stratergies.

ENDEMICITY AND EPIDEMIOLOGY OF HEPATITIS A

Hepatitis A epidemiology in the pre-vaccine era

Hepatitis A existed worldwide, with endemicity levels correlating with socioeconomic status and sanitation[22]. The geographical distribution for hepatitis A was split into high, intermediate, low, and very low endemicity areas according to seroprevalence rates of hepatitis A. The WHO classifies endemicity levels based on the age-specific seroprevalence of HAV in the general population (Table 2)[23].

Table 2 Endemicity levels based on the age-specific seroprevalence of hepatitis A virus in the general population.

Endemicity level	Age-specific seroprevalence
High	90% by 10 years of age
Intermediate	50% by 15 years, with < 90% by 10 years
Low	50% by 30 years
Very low	< 50% by 30 years

In areas of high endemicity, lower overall disease rates and rare outbreaks of HAV have been reported in adult populations since most infections occur in early childhood when asymptomatic infection predominates, with almost the entire population having been infected before reaching adolescence[24,25]. Less frequent infection rates were observed in regions of moderate endemicity, due to improved sanitation and living standards, increasing in average age of infection[26]. Paradoxically, these regions would face a heightened risk of large hepatitis A outbreaks because of a larger population of susceptible adolescents and adults who did not have immunity after exposure and were more likely to have a symptomatic illness[27]. Tunisia's 2015 nationwide study (n = 6322) revealed 78.8% HAV seroprevalence, with seropositivity rising sharply from 16% in children (5-9 years) to > 90% in adults ≥ 25 years, indicating late-adolescence age at midpoint of population immunity (AMPI). Prevalence was significantly higher in rural areas (P < 0.001) and varied regionally, showing intermediate-to-high endemicity linked to socioeconomic and sanitation factors, informing vaccination strategies. In North America, Western Europe, and other developed areas, the endemicity of HAV infection was low. Fewer children were exposed, and the incidence of disease was low. Most cases occurred as community-wide outbreaks with transmission among preschool and school-age children and their adult contacts[28-31]. Other regions, for example, Scandinavia, were classified as very low endemicity, with most cases occurring in defined risk groups, such as travelers returning from endemic areas and injection drug users[32]. Figure 1 represents schematic representation of HAV endemicity.

Figure 1 Global hepatitis A virus endemicity map. HAV: Hepatitis A virus.

Vaccine development, use, and implementation strategies

The first hepatitis A vaccines, licensed for use in the United States in 1992 and 1993 respectively, were the following inactivated single antigen vaccines: (1) HAVRIX (GlaxoSmithKline Biologicals, Rixensart, Belgium); and (2) VAQTA (Merck and Company Inc., Whitehouse Station, NJ, United States)[33,34]. Subsequently, more inactivated and live hepatitis vaccines have been developed and licensed[35]. In addition, combination vaccines containing hepatitis A and B (Twinrix™ and Bilive™) and another containing typhoid and hepatitis A (Viatim^®) have also been licensed[36]. Strategies have included targeted vaccination among high-risk groups, regional childhood vaccination, and universal childhood vaccination[35]. A dynamic modelling study demonstrated that universal hepatitis A vaccination is cost-effective in both developed (United States) and developing (Rio de Janeiro) settings, significantly reducing disease incidence and increasing quality-adjusted life years. These findings support the adoption and expansion of universal vaccination policies globally[37]. As of May 2019, 28 countries had introduced routine universal hepatitis A vaccination in children, with two more countries planning the inclusion according to a WHO report[38]. These include 10 countries in the Americas, 5 in the Eastern Mediterranean, 8 in Europe, and 5 in the Western Pacific[38]. According to WHO position paper in October 2022, hepatitis A vaccination strategies should be tailored based on a country's endemicity level, with universal childhood vaccination recommended in transitioning countries, targeted vaccination in low-endemic areas, and thorough risk benefit analyses before implementation in highly endemic regions. High-risk groups including travellers, men who have sex with men, people who inject drugs, migrants, and those with chronic liver disease should be prioritized for vaccination to reduce morbidity and mortality[39]. In addition, the vaccine was recommended among people who were experiencing homelessness in the United States due to outbreaks in this population[40]. Table 3 clearly demonstrates global variation in HAV provision and access[12,41-56].

Table 3 Global variation in hepatitis A vaccine provision and access.

Vaccine policy	Cost coverage	Equity/operational notes	Ref.
Routine childhood vaccination; targeted adult vaccination (VFC program)	Free under VFC; OOP for adults without insurance	Outbreaks in PEH and drug-using adults; gaps in adult uptake	Nelson et al[41], United States
Targeted (indigenous, travelers, PEH)	Provincial programs; partial coverage	Uneven uptake across provinces	Palaisy[42], Canada
Universal childhood vaccination (≥ 12 months)	Government-funded	High coverage; regional disparities in remote areas	Brito and Souto[43], Brazil
Integrated in national schedule (since 2023)	Free public sector	Rapid rollout post-urban outbreaks	Guzman-Holst et al[44], Mexico
Universal single-dose schedule	Government-funded	Successful herd immunity; sustained low incidence	Flichman et al[45], Argentina
Targeted (travelers, men who have sex with men, PEH)	National Health Service covers high-risk groups	Limited adult awareness	Johnson et al[46], United Kingdom
Recommended (travelers, men who have sex with men, laboratory staff)	Reimbursed by insurance	Stable low incidence; high cost limits universal rollout	Szucs[47], Germany
Universal since 2003 in several regions	Government-funded	Decline in hepatitis A virus cases; regional autonomy causes inconsistency	Bechini et al[48], Italy
Targeted vaccination	Regional funding	Good outbreak response; inequity across regions	Urbiztondo et al[49], Spain
Included in routine childhood schedule in 2008	Government-funded	High coverage; rare outbreaks	Ryani[50], Saudi Arabia
Universal childhood (since 2011)	Fully subsidized	Excellent coverage nationwide	Yigit and Kalayci[51], Turkey
Targeted vaccination (private market)	Mostly OOP	High-cost limits uptake; growing private sector use	Shah et al[52], India
Targeted; not yet universal	OOP except high-risk groups	Declining seroprevalence; debate on adding to National Immunisation Programme	Poovorawan et al[53], Thailand
Universal childhood vaccination since 2008	Government-funded	Dramatic incidence decline; urban-rural gap remains	Yan et al[54], China
Targeted (travelers, men who have sex with men)	OOP	Low uptake; periodic import-linked outbreaks	Kanda et al[12], Japan
Targeted (travelers, laboratory staff)	OOP	Low uptake due to cost; increasing adult outbreaks	Patterson et al[55], South Africa
Not routine; private market only	OOP	High endemicity; vaccine not prioritized	Ahmed and Nashwan[56], Pakistan

OOP: Out of pocket; PEH: People experiencing homelessness; VFC: Vaccines for Children.

Endemicity in the era of vaccination and improving living standards

With the introduction of childhood vaccinations for hepatitis A and improved sanitation, there has been a global trend of decrease in average seroprevalence rates, particularly among children[57]. The seroprevalence rates correlate with socioeconomic status and access to clean water and sanitation[57]. With the implementation of routine childhood hepatitis A vaccination since 1999 in high-risk United States areas significantly reduced infection rates[58]. Notably, Poovorawan et al[59] observed a declining HAV seroprevalence among Thai youth, reflecting increased susceptibility due to reduced natural exposure highlighting the risk of outbreaks in unvaccinated cohorts. As sanitation improved, several countries began transitioning to intermediate endemicity, delaying exposure to adolescence or adulthood when symptomatic disease is more common and severe. For instance, Chakravarti and Bharara[60] in 2019 described how improved hygiene delayed natural HAV exposure, raising susceptibility in older age groups. Study conducted by Mantovani et al[61] further demonstrated that socioeconomic inequities continue to drive HAV infections among children in under-resourced regions like the Western Brazilian Amazon. HAV epidemiology is clearly depicted in pre vaccine and vaccine era in Figure 2.

Figure 2 Impact of vaccination on hepatitis A transmission dynamics. MSM: Men who have sex with men.

Jacobsen et al[62] demonstrated that older ages indicate less childhood exposure and a lower endemicity level by refining the use of AMPI. AMPI indicates the age by which 50% of a population has HAV antibodies[62]. Table 4 demonstrates examples from recent studies showing AMPI of HAV seroprevalence reflecting transition of HAV endemicity with either improved sanitation, socioeconomic disparities or implementation of vaccination strategies[63-66].

Table 4 Age-stratified seroprevalence and age at midpoint of population immunity estimates reflecting hepatitis A virus endemicity transitions.

Country	Overall seroprevalence	Age at midpoint of population immunity (years)	Endemicity level	Key findings	Ref.
Iran	86%	21	High to intermediate	Declining natural immunity in younger cohorts due to improved sanitation	Lankarani et al[63]
Jordan	38.3%	21-30	Intermediate to low	Introduction of HAV vaccine resulted in epidemiological shift of HAV seroprevelance	Kareem et al[64]
Turkey	67.23% over all; 35.9% in 15-18 years	Estimated 25-30	Intermediate	Low seroprevelance in youth is due to the fact that these individuals were not included in routine vaccination	Karabey et al[65]
Vietnam	69.2% (total), 57.9% (urban), 80.7% (rural)	29	High to intermediate	Socio-economic disparities and unsafe drinking water contribute to geographic difference	Cam Huong et al[66]

HAV: Hepatitis A virus.

Cost and effectiveness of hepatitis A vaccination

Universal childhood immunization substantially reduces incidence, hospitalization and outbreak-related costs. Several recent studies reinforce the cost-effectiveness of hepatitis A vaccination, particularly in settings transitioning from high to intermediate endemicity. A modeling analysis by Abimbola et al[67] in 2023 estimated an incremental cost-effectiveness ratio of United State dollar 48000 for full two-dose vaccination in their setting, highlighting that expanded vaccination must be justified by disease burden and budget constraints. In contrast, in India, Gurav et al[68] in 2024 demonstrated that routine vaccination of children aged 1 year is cost-saving both from societal and payer perspectives. Moreover, a systematic review by Gurav et al[69] found that 81.8% of economic evaluations in middle-income countries supported universal vaccination without screening as cost-effective. Across studies, sensitivity analyses often show vaccine unit cost, outpatient care costs, hospital costs, and productivity losses as key drivers of cost-effectiveness[70]. These recent results underscore that as endemicity shifts and adult susceptibility grows (reflected by rising AMPI), vaccine cost-effectiveness becomes more favorable and strategic choices (dose schedule, target age groups) matter even more.

Changing epidemiology of hepatitis A

With improved sanitation and food hygiene, fewer children are exposed to hepatitis A in childhood. The lack of exposure to HAV during childhood leads to higher susceptibility and a shift in the incidence of disease later in life, resulting in increases in symptomatic cases since age is a risk factor for the severity of HAV infections[22,71]. This was seen previously in high-income countries, but the same trend is now emerging in lower and middle-income countries. An increase in the average age of infection has been seen. For example, studies conducted in 2005 and 2006 in urban areas in Armenia and Kazakhstan found a mean age of infection in the early 20s[72,73]. This increase in the average age of infection is accompanied by an increased incidence of clinically significant and severe presentation. A review and a large retrospective study from India show that this epidemiological shift has led to an increased incidence of symptomatic infection and an increased risk of complications including liver failure[74,75]. South Korea continues to face an epidemiological shift in HAV infection which has contributed to recurrent outbreaks, including a major spike in 2019 that primarily affected individuals aged 30-44 years[76]. Recent country-level data further support this trend: In China (2007-2021), HAV incidence remains low but is shifting toward older age groups, reflecting a rising AMPI and lingering adult susceptibility[77]. A 2025 study from a tertiary hospital in Pakistan reported a rising trend of acute hepatitis A among adults over the past five years, accounting for 59% of viral hepatitis cases in 2024[78].

In addition to the change in average age and symptom severity of cases, there is a change in classification of regions with high endemicity to intermediate endemicity, such as countries in Latin America and Middle East and North Africa region as shown by reviews of seroprevalence data[79,80]. With this change, the susceptible population of adolescents and young adults who may develop symptomatic illness increases, leading to a paradoxical increase in reported incidence. A socioeconomic and rural-urban divide can also be seen in the shift in epidemiology. These factors present a complex and heterogeneous picture of hepatitis exposure among different populations in the same countries. A significant increase in seroprevalence associated with a lower socioeconomic status was seen in a study from Egypt, Vietnam and Tunisia[66,81,82].

Rising global incidence and outbreaks

The incidence of hepatitis A presents a complex global picture, with both increases and decreases in different regions and demographics. The overall global declining seroprevalence rates are paralleled by a seemingly paradoxical increase in clinical incident cases of hepatitis A[83]. One explanation for this may be due to increased population growth, especially in low-income and middle-income countries, with China and India accounting for a third of global cases in 2019[22]. Another explanation for the increase is that the reported incidence of hepatitis A can increase in low-endemicity areas due to an increase in the average number of infections resulting in symptomatic illness[84]. In many low-income countries, the endemic levels of hepatitis A remain high, with poor sanitation and food hygiene being a major reason[22]. High-income countries, despite showing decreasing seroprevalence rates and low endemicity, have also seen sporadic outbreaks particularly among unvaccinated high-risk groups such as men who have sex with men, people who inject drugs, or those experiencing homelessness amplified by imported contaminated food[85-87]. Overall, the data shows persistent high levels of hepatitis A in hyperendemic regions and the emergence of frequent outbreaks in low-endemic regions[57]. A recent meta-analysis showed that hospitalization rate related to foodborne outbreak has shown a significant upward trend over time (P = 0.002)[88]. Table 5 demonstrates examples of HAV outbreaks[89-108].

Table 5 Outbreaks related to hepatitis A virus infection.

Group	Region	Key details	Ref.
Men who have sex with men	Europe, United States, Israel, Chile, Poland, Barcelona	1400 cases in 16 European Union/European Economic Area countries; three HAV strains; linked outbreaks in Israel/Chile; mostly non-immune men who have sex with men engaging in high-risk sexual behaviour, increase risk with concomitant HIV infection	Ndumbi et al[89], Enkirch et al[90], Raczyńska et al[91], Dabrowska et al[92]
Patient who inject drugs	California, Michigan, Kentucky, Utah, London, Ontario	Increased HAV cases among persons who inject drugs or homelessness due to low vaccination coverage, syndemic involving concomitant HIV, HCV, HAV and group A streptococcal infection	Foster et al[93], Turner[94]
Foodborne	Europe, Italy, Sweden, Austria, United States, Michigan	Large European Union and Italy outbreak from frozen berries; Sweden, Austria, Michigan linked to imported strawberries; outbreaks from contaminated food or infected food handlers	Fallucca et al[95], Authority[96], Hutin et al[97], Greig and Ravel[98]
Travelers/migration	France, United States of America (United States)	Travel-related cases account for approximately 30%-46% of HAV cases in United States/Europe; 254 cases of hepatitis A in international travellers, with most cases occurring in unvaccinated individuals	Migueres et al[99], Balogun et al[100]
Homelessness	San Diego (United States), San Francisco (United States)	People experiencing homelessness had 3.3 × higher odds of infection, higher hospitalization and death rates; prevalence increased with years of homelessness, injection drug use, and foreign-born status	Peak et al[101], Hennessey et al[102]
Community transmission	Brazil, Germany	Person-to-person transmission common in enclosed spaces; 34.3% of household contacts infected; outbreak among Ukrainian war refugees and volunteer caregiver	Lima et al[103], Krumbholz et al[104]
HIV positive patients	Iran, Warsaw, Poland	97.7% HAV seroprevelance; outbreaks in HIV positive men who have sex with men	Dabrowska et al[92], Omidifar et al[105]
Chronic liver disease (HBV and HCV)	Italy, Argentenia	HAV superinfection causes severe disease, fulminant hepatitis; higher fatality in coinfected patients; HAV outbreaks among men who have sex with men show high rates of HIV, syphilis and HBV co-infection	Vento et al[106], Marciano et al[107]
Metabolic dysfunction associated steatotic liver disease	United States	Increase odds of liver fibrosis	Vassilopoulos et al[108]

HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus.

Emerging strains and antigenic variation in HAV

HAV is characterized by a single serotype, which supports the continued efficacy of existing vaccines, and categorized into six genotypes (I-VI), with human disease mainly caused by genotypes I, II, and III, each further subdivided into subgenotypes such as IA, IB, IC, IIA, IIB, IIIA, and IIIB[109]. Recent evidence points to the emergence of antigenic variants. These are strains with minor genetic mutations, particularly in the viral protein 1 (VP1) region. Genomic comparisons indicate greater quasispecies diversity and a higher frequency of non-synonymous mutations in VP1 among vaccinated individuals, suggesting vaccine-driven selective pressure[110]. A molecular analysis of HAV isolates from Tunisia (2003) found two novel antigenic variants within sub-genotype IA: (1) One with a 38 amino acid deletion in a known neutralization region; and (2) Another with a unique amino acid substitution linked to fulminant hepatitis[111]. From 2018 to 2022, Florida reported 5491 hepatitis A cases, with genotyping showing predominance of subgenotype IB (69%) which carries over fourfold higher mortality risk, highlighting the importance of molecular surveillance in outbreak management[112]. While most analyses rely on partial VP1/2A sequences, whole-genome sequencing offers greater accuracy and resolution to detect antigenic variants and vaccine escape mutations[113].

PREVENTION AND SURVEILLANCE OF HEPATITIS A

Prevention and the need for future surveillance and effective vaccination strategies

In the recent position paper on hepatitis A vaccination, WHO recommends that vaccination against HAV be introduced into national immunization schedules for individuals aged ≥ 12 months, based on: (1) An increasing trend over time of acute hepatitis A disease, including severe disease, among older children, adolescents or adults; (2) Changes in the endemicity of the region from high to intermediate; and (3) Cost-effectiveness. In this position paper, WHO does not recommend childhood vaccination in areas with very high endemicity as most individuals are asymptomatically infected with HAV in childhood, which prevents clinical hepatitis A in adolescents and adults. In areas with low and very low endemicity, the WHO recommends targeted vaccinations in high-risk groups[39]. Following this phenomenon of decreasing endemicity leading to increased incidence of clinical disease, the WHO recommends the implementation of universal childhood vaccination in regions with changes in endemicity from high to intermediate[39]. This underscores the need for incidence and seroprevalence surveillance to recognize this shift, especially in low-income and middle-income countries that have been previously classified as high-endemicity regions. The role of urbanization and socioeconomic status also must be considered during surveillance as there can also be significant heterogeneity within populations, among urban and rural areas and areas of different socioeconomic backgrounds. Thailand provides a compelling example of this epidemiological transition. Historically, HAV infection was highly endemic in Thailand, with most individuals acquiring natural immunity during childhood. However, rapid economic development and improvements in water and sanitation infrastructure have markedly reduced HAV transmission. A recent national seroprevalence study in 2024 demonstrated a significant decline in population immunity, with the median age for seropositivity increasing from 36 years in 2004 to 47 years in 2024[114]. In addition, the continued outbreaks in low and very low endemicity areas highlight the need for surveillance and targeted vaccination campaigns in high-risk populations, as well as strategies to identify and prevent outbreaks related to contamination of the food supply chain[85]. A recent systematic review by Trucchi et al[115] analysed 32 outbreaks linked to food handlers and found that, despite most outbreaks being small, delayed detection, asymptomatic infections, and poor vaccination uptake among food service staff significantly hindered control efforts. The authors suggested that targeted vaccination of food handlers, particularly in high-risk or seasonal employment settings, along with environmental hygiene and good sanitation could represent a cost-effective strategy to prevent foodborne HAV transmission and strengthen biological risk management within the food industry[115]. Apart from vaccination, a single 0.2 mL/kg dose of intramuscular immunoglobulin provides protective anti-HAV levels for at least 60 days with acceptable safety and tolerability in healthy individuals, offering short-term passive protection when administered within two weeks of exposure particularly for close contacts, infants under 12 months, or immunocompromised individuals although its effectiveness is often reduced by delayed outbreak detection and logistical challenges[116]. However, its effectiveness is reduced by delayed outbreak detection and logistical challenges, underscoring the importance of timely reporting and rapid public health response. As several outbreak investigations have shown, including those summarized by Nicholls et al[117], Fortin and Milord[118], and Jones et al[119], late administration substantially diminishes protective benefit. Investigation of transmission dynamics across foodborne, waterborne, and person-to-person routes, especially in under-researched or travel-related contexts can be used to guide prioritizing public health interventions[120]. Serological studies can be conducted which may offer a powerful complement to traditional surveillance, capturing the often-overlooked dynamics of asymptomatic infections and immunity[121]. Advances in molecular surveillance, such as multiplex polymerase chain reaction-based next-generation sequencing for whole-genome sequencing of HAV directly from serum samples, now allow rapid strain identification and phylogenetic tracking even in low-titer infections. Phylogenetic and gene-level analyses confirmed its reliability for molecular epidemiology, revealing clear geographic clustering which can accelerate outbreak detection, enable real-time tracing of transmission routes, and inform targeted vaccination and control strategies[122]. Additionally integrating genomic, wastewater and routine surveillance into a hybrid early-warning system can improve detection speed and source tracing, enabling faster targeted vaccination and immunoglobulins[123]. Health awareness campaigns play a vital role in the prevention and control of HAV, particularly in regions with low vaccination coverage or poor sanitation infrastructure. World Hepatitis Day, observed annually on July 28, serves as a key global platform for raising awareness about viral hepatitis, including hepatitis A. As part of broader health promotion efforts, such campaigns help educate the public on prevention strategies, including hygiene practices and vaccination[124].

CONCLUSION

The incidence of hepatitis A presents a complex global picture, with both increases and decreases in different regions and demographics. The overall global declining seroprevalence rates are paralleled by a seemingly paradoxical increase in clinical incident cases of hepatitis A among adults necessitating adult vaccination and measures to mitigate the risk of HAV transmission in communities by strengthening surveillance programs including genomic and food-supply traceability combined with public education and environmental hygiene measures to meet the WHO 2030 hepatitis-elimination target.