MONIQUE A. FOSTER, MD, MPH

Although hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide, cases in the United States have been steadily declining since 1996, after the vaccine became available, until recent years.

 As of 2016, widespread outbreaks of hepatitis A infections have caused over 27,000 cases in the United States.

Twenty-five years ago, large community outbreaks were driven by infections among children, most of whom are asymptomatic when infected with HAV.

 Initial vaccine recommendations focused on children in high-prevalence counties but in 2006 were expanded to recommend that all children be vaccinated with 2 doses of vaccine starting at 12 months of age. As a result, the epidemiology of hepa&shy;titis A has shifted, reflecting a higher proportion of adults susceptible to infection compared with children, particu&shy;larly adults reporting certain risk behaviors and exposures.

 This article describes the changing epidemiology of hepa&shy;titis A and the community-wide person-to-person outbreaks of hepatitis A infections occurring among adults in the United States.

HEPATITIS A IN THE PREVACCINE ERA (1966-1995) 

HAV is a single-stranded RNA virus in the picornavirus family that replicates in the liver and is then excreted as bile into the stool.

 Illness is typically acute and self-limited. Clinical symptoms are indistinguishable from other infectious and noninfectious causes of hepatitis.

 The average incubation time after exposure to HAV is 28 days but can range from 15 to 50 days.

 Children under the age of 6 years are typically asymptomatic, and an infected person can excrete virus in stool for up to 2 weeks prior to experiencing symptoms, making identification of exposures and early detection of outbreaks particularly difficult.

Hepatitis A epidemiology varies worldwide. In endemic regions, up to 90% of children have been infected by 10 years of age.

 Outbreaks among older children and adults are rare in HAV-endemic countries because the majority of infections occur in early childhood, which confers life&shy;long immunity.

 As countries transition to lower ende&shy;micity through improved sanitation and hygiene and access to clean water, the overall susceptibility of the older populations increases.

 Because susceptible adults are more likely to present with symptoms when infected with HAV, outbreaks are more commonly observed in low-endemicity countries.

The United States transitioned to a low-endemicity country during the last century.

 Prior to the licensing of single-antigen hepatitis A vaccine in the United States in 1995, the highest hepatitis A incidence rates were among children, and most cases occurred in the context of community-wide epidemics in which the virus was trans&shy;mitted from person to person.

 Community-wide epidemics lasted 6 to 18 months and exhibited bimodal age-spe&shy;cific attack rates (ages 5-9 years and 20-24 years).

 The cyclic nature of these outbreaks resulted from the periodic increase in sufficient numbers of susceptible children to sustain transmission.

Epidemics from the 1920s through the 1990s suggested that preschool-aged children were the principal sources, because school-based outbreaks were unusual.

 The cyclic pattern also suggested that children under 10 years were most likely the group driving transmis&shy;sion, because sufficient numbers were susceptible enough to be primary sources.

The bimodal age distribution among hepatitis A cases in the prevaccine era was likely due to infections among chil&shy;dren and infections among adults at risk—namely, persons who use drugs (PWUDs) and men who have sex with men (MSM).

 Illicit drug use was reported in many community-wide hepatitis A outbreaks prior to the avail&shy;ability and widespread use of the vaccine.

 During the prevaccine era, outbreaks of hepatitis A occurred relatively frequently among MSM.13,18,19 Behaviors associated with infec&shy;tion included high-risk sexual practices (eg, >1 anonymous sex partner, group sex, oral-anal sex).

 Seroprevalence studies showed that a greater number of sex partners, longer duration of sexual activity, and serological evidence of other sexually transmitted infec&shy;tions were also associated with HAV infection.

 As an important source of HAV transmission during previously reported outbreaks, improving vaccine coverage among PWUDs and MSM is critical to reducing the frequency and duration of community-wide outbreaks.

 The main chal&shy;lenge was and remains amassing the resources early enough in an outbreak response to maxi&shy;mize their impact.

In 1996, after the vaccine was licensed, in an effort to control ongoing outbreaks, the Advisory Committee on Immunization Practices (ACIP) recommended vaccinating children in communities with high rates of hepatitis A, PWUDs, and MSM. In 1999, it was recommended that children living in regions with double the national incidence rate of 10 per 100,000 be vaccinated.

HEPATITIS A DURING THE VACCINE ERA (1996-PRESENT) 

During 1987-1997, the national average HAV incidence rate was 10.8 cases per 100,000 population, with a total of 11 states, mostly in the West, having an average annual rate of ≥20 cases per 100,000 population.

 After the recommendations to vaccinate adults at risk and routine vaccination for children living in states that had consistently elevated hepatitis A incidence rates, incidence rates declined 78% during 1990-2003, with 90% of that decline occurring after 1997.

 Although most vaccinations went to children, incidence rates declined in all age groups.

 The observed decline in hepatitis A incidence could not be solely attributed to vaccination, given the historical cyclic pattern of the disease and the absence of vaccination coverage data in at-risk adults.

 During this time, large-community outbreaks that had accounted for the majority of reported cases virtually disappeared.

 Although vaccination of children resulted in fewer adult cases, those that occurred were commonly associated with contact with chil&shy;dren.

 Transmission among at-risk adults continued, likely due to low vaccination coverage.

 Although overall case counts were decreasing, the cases that were identified were increasingly identified among adults, in partic&shy;ular those in high-risk groups.

The main challenge to control HAV transmission among at-risk adults involves providing outreach and vaccination due to societal marginaliza&shy;tion.

 Vaccinations provided through drug treatment facilities, HIV counseling and testing sites, homeless shelters, syringe exchange programs, and correctional facilities have proved to be successful interventions in containing outbreaks within these groups.

There was also a shift in the reported poten&shy;tial sources of infection, with a declining proportion of adults reporting exposure to infected children and an increasing proportion reporting exposure to contaminated food.

FOOD-ASSOCIATED HEPATITIS A OUTBREAKS (2000-2016) 

The epidemiologic shift from community-wide outbreaks driven by infected children to an increasing number of outbreaks associated with contaminated food occurred around the year 2000.

 In general, food-associated hepatitis A outbreaks are difficult to detect because of the many factors involved, including the long incu&shy;bation period, difficulty recalling food histories during the exposure period, challenges in iden&shy;tifying focal contamination of a food product, varying immunity among exposed individuals, geographically scattered cases, and inability to determine if case-patients were infected through person-to-person transmission.

 Although HAV contamination of food can occur at any point during harvesting, processing, distribution, or preparation, HAV infections among food handlers decreased, mirroring the overall decline observed nationally after wide&shy;spread adoption of childhood hepatitis A vacci&shy;nation recommendations.

After the year 2000, all the major (n >100 cases) food-associated outbreaks of HAV that occurred in the United States were associ&shy;ated with food items that were imported from endemic countries and were likely contaminated prior to distribution.

 In 2003, over 600 indi&shy;viduals were infected by hepatitis A—contami&shy;nated green onions imported from Mexico and served in multiple dishes at a single restaurant.

The next large HAV food-associated outbreak occurred 10 years later. In 2013, the CDC iden&shy;tified 165 individuals from 10 states infected by consuming HAV-contaminated pomegranate arils imported from Turkey.

 The arils were sold in a frozen berry mix from a single retailer. The retailer maintained information systems that included itemized sales data, purchase dates, and customer information, which aided the ability to identify the contaminated product and offer postexposure prophylaxis.

Just 3 years later, the CDC investigated 2 large food-associated HAV outbreaks: HAV-contaminated frozen scallops imported from the Philippines served in Hawaii (n = 292)

 and HAV-contaminated frozen straw&shy;berries imported from Egypt and served in multiple states along the East Coast (n = 144).

 In both outbreaks, the contaminated food items were served uncooked from multiple locations of implicated restaurant chains.

None of these outbreak investigations could determine at what point in harvesting or processing the contamination occurred.

 Shellfish may be contaminated because of harvesting near known sources of sewage or discharge of sewage near shellfish beds.

RETURN OF PERSON-TO-PERSON HEPATITIS A OUTBREAKS (2016-PRESENT) 

A large population of susceptible, unvacci&shy;nated adults remains vulnerable to infection, and certain groups remain at particularly high risk because of behaviors that increase risk of person-to-person transmission. HAV transmis&shy;sion among people who report drug use, people experiencing homelessness, and MSM can result from inadequate sanitary conditions or specific sexual contact or practices or through sharing drug paraphernalia.

 Despite the long-standing recommendations that PWUDs and MSM receive hepatitis A vaccination, vaccina&shy;tion coverage rates are estimated to be low.

Since 2016, the United States has experienced unprecedented person-to-person outbreaks of hepatitis A infections, primarily involving adults reporting drug use or homelessness and MSM.

 These outbreaks started in California, Utah, and Kentucky but have affected at least 30 states, with more than 26,000 reported outbreak cases.

 Hospitalization rates have been high (60%), and novel vaccination strate&shy;gies requiring substantial public health resources have been required to stop transmission.

Vaccination is the cornerstone of outbreak control.38 Identifying and targeting groups at risk early in outbreaks can be logistically diffi&shy;cult and costly; therefore, public health officials recommend proactive vaccination of groups at highest risk because this is the most effective strategy for preventing outbreaks.

 Transient housing, economic instability, anonymous sexual contact that impedes contact tracing, limited access to health care, and distrust of govern&shy;ment services make outbreaks among these at-risk populations more difficult to control, requiring tailored comprehensive public health interventions that address their specific circum&shy;stances and needs.

Although the United States transitioned from high hepatitis A endemicity to low endemicity over the past century, the most at-risk populations continue to evolve.

 Introduction and widespread use of a safe and effective hepatitis A vaccine decreased overall incidence of hepatitis A infections, but community-wide outbreaks continue to occur, particularly among adults at risk.

 Continued efforts to increase hepatitis A vaccination coverage among the ACIP-identified at-risk groups is vital to halting the current ongoing hepatitis A outbreaks, preventing large community outbreaks in the future, and reducing overall hepatitis A inci&shy;dence in the United States.

*The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the CDC.

Foster serves as the epidemiology lead for hepatitis A in the Division of Viral Hepatitis at the US Centers for Disease Control and Prevention (CDC). She is a graduate of East Carolina University in Greenville and Eastern Virginia Medical School in Norfolk and received her MPH from Vanderbilt University in Nashville, Tennessee. Foster completed her pediatric residency at the University of Tennessee Health Science Center and a pediatric infectious disease fellowship at Vanderbilt University before joining the CDC as an epidemic intelligence service officer with the Division of Viral Hepatitis in 2014.

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An epidemiologist explores the changing epidemiology of a familiar disease.
 

MONIQUE A. FOSTER, MD, MPH

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