H epatitis A virus (HAV) is a small, nonenveloped RNA virus belonging to the family Picornaviridae. Its biology and transmission cycle have been reviewed elsewhere (1,2) and are therefore only briefl y introduced. Six genotypes and 1 serotype have been described; genotypes I-III circulating in humans and IV-VI circulating in nonhuman primates. Virions exist in either of 2 forms (3): lipid-associated (main form in blood, also referred to as quasi-enveloped) or truly nonenveloped (main form in stool). Although parenteral transmission has also been reported, the predominant transmission route is the fecal-oral through contact with infected persons or uptake of contaminated food and water. Infection might involve an early, as of yet poorly characterized, extrahepatic replication phase (e.g., in gut epithelial cells [4]); from the gut, virions are then transported through the blood to their primary replication site, the liver. The transmission cycle ends with a transport of viral progeny via the bile to the gut, leading to massive virus shedding in stool (2). Although the course of disease is generally self-limiting, several serious complications can occur, especially in older persons or in combination with risk factors.Since 1995, when the fi rst HAV vaccine was licensed in the United States, the annual US incidence rate of acute hepatitis A has decreased tremendously (1,5). During 2015, the National Notifi able Diseases Surveillance System of the Centers for Disease Control and Prevention (CDC) recorded an annual average of 0.4 cases/100,000 inhabitants (5). However, since 2016, the downward trend has reversed (6). In mid-2016-early 2017, Michigan, California, Kentucky, and Utah began to report local personto-person HAV outbreaks, which have since become a national concern: 38,031 cases affecting 35 states (status as of February 2021) (7). In 2018, the annual US incidence rate was 3.8 cases/100,000 population, and the true rate was estimated to be twice as high because of under-ascertainment and under-reporting (6). The current outbreak is enhanced by the fact that most (≈74%) of US-born adults are susceptible to HAV (8). This pattern is typical for industrialized countries that have good standards of sanitation and hygiene and a history of restrictive (mostly infant-targeted or risk group-targeted) vaccination practices (9). HAV genotype IB has been the most common genotype during this outbreak, whereas before 2017, most cases in the United States involved genotype IA (10).
