Hepatitis A Outbreaks on the Rise in the US
An epidemiologist explores the changing epidemiology of a familiar disease.
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.1 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.2 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 hepa­titis A has shifted, reflecting a higher proportion of adults susceptible to infection compared with children, particu­larly adults reporting certain risk behaviors and exposures.3 This article describes the changing epidemiology of hepa­titis 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.4 Illness is typically acute and self-limited. Clinical symptoms are indistinguishable from other infectious and noninfectious causes of hepatitis.5,6 The average incubation time after exposure to HAV is 28 days but can range from 15 to 50 days.6 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.7,8
Hepatitis A epidemiology varies worldwide. In endemic regions, up to 90% of children have been infected by 10 years of age.9 Outbreaks among older children and adults are rare in HAV-endemic countries because the majority of infections occur in early childhood, which confers life­long immunity.9 As countries transition to lower ende­micity through improved sanitation and hygiene and access to clean water, the overall susceptibility of the older populations increases.9 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.2 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 trans­mitted from person to person.2,10 Community-wide epidemics lasted 6 to 18 months and exhibited bimodal age-spe­cific attack rates (ages 5-9 years and 20-24 years).11 The cyclic nature of these outbreaks resulted from the periodic increase in sufficient numbers of susceptible children to sustain transmission.11 Epidemics from the 1920s through the 1990s suggested that preschool-aged children were the principal sources, because school-based outbreaks were unusual.11,12 The cyclic pattern also suggested that children under 10 years were most likely the group driving transmis­sion, because sufficient numbers were susceptible enough to be primary sources.11
The bimodal age distribution among hepatitis A cases in the prevaccine era was likely due to infections among chil­dren and infections among adults at risk—namely, persons who use drugs (PWUDs) and men who have sex with men (MSM).10,11,13 Illicit drug use was reported in many community-wide hepatitis A outbreaks prior to the avail­ability and widespread use of the vaccine.2,14-17 During the prevaccine era, outbreaks of hepatitis A occurred relatively frequently among MSM.13,18,19 Behaviors associated with infec­tion included high-risk sexual practices (eg, >1 anonymous sex partner, group sex, oral-anal sex).13,20 Seroprevalence studies showed that a greater number of sex partners, longer duration of sexual activity, and serological evidence of other sexually transmitted infec­tions were also associated with HAV infection.13 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.11 The main chal­lenge was and remains amassing the resources early enough in an outbreak response to maxi­mize their impact.11,15
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.2,21
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.2 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 1997.21,22 Although most vaccinations went to children, incidence rates declined in all age groups.2 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.22,23 During this time, large-community outbreaks that had accounted for the majority of reported cases virtually disappeared.22,23 Although vaccination of children resulted in fewer adult cases, those that occurred were commonly associated with contact with chil­dren.22 Transmission among at-risk adults continued, likely due to low vaccination coverage.22 Although overall case counts were decreasing, the cases that were identified were increasingly identified among adults, in partic­ular those in high-risk groups.3,24,25
The main challenge to control HAV transmission among at-risk adults involves providing outreach and vaccination due to societal marginaliza­tion.11,26 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.11
There was also a shift in the reported poten­tial sources of infection, with a declining proportion of adults reporting exposure to infected children and an increasing proportion reporting exposure to contaminated food.10
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 2000.10 In general, food-associated hepatitis A outbreaks are difficult to detect because of the many factors involved, including the long incu­bation period, difficulty recalling food histories during the exposure period, challenges in iden­tifying 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.27 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 wide­spread adoption of childhood hepatitis A vacci­nation recommendations.27,28
After the year 2000, all the major (n >100 cases) food-associated outbreaks of HAV that occurred in the United States were associ­ated with food items that were imported from endemic countries and were likely contaminated prior to distribution.29-31 In 2003, over 600 indi­viduals were infected by hepatitis A—contami­nated green onions imported from Mexico and served in multiple dishes at a single restaurant.29
The next large HAV food-associated outbreak occurred 10 years later. In 2013, the CDC iden­tified 165 individuals from 10 states infected by consuming HAV-contaminated pomegranate arils imported from Turkey.30 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.30
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)31 and HAV-contaminated frozen straw­berries imported from Egypt and served in multiple states along the East Coast (n = 144).32 In both outbreaks, the contaminated food items were served uncooked from multiple locations of implicated restaurant chains.32
None of these outbreak investigations could determine at what point in harvesting or processing the contamination occurred.27,29,31,32 Shellfish may be contaminated because of harvesting near known sources of sewage or discharge of sewage near shellfish beds.27
RETURN OF PERSON-TO-PERSON HEPATITIS A OUTBREAKS (2016-PRESENT)
A large population of susceptible, unvacci­nated 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 transmis­sion 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.18,33 Despite the long-standing recommendations that PWUDs and MSM receive hepatitis A vaccination, vaccina­tion coverage rates are estimated to be low.8,34
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.35 These outbreaks started in California, Utah, and Kentucky but have affected at least 30 states, with more than 26,000 reported outbreak cases.36 Hospitalization rates have been high (60%), and novel vaccination strate­gies requiring substantial public health resources have been required to stop transmission.37
Vaccination is the cornerstone of outbreak control.38 Identifying and targeting groups at risk early in outbreaks can be logistically diffi­cult and costly; therefore, public health officials recommend proactive vaccination of groups at highest risk because this is the most effective strategy for preventing outbreaks.8 Transient housing, economic instability, anonymous sexual contact that impedes contact tracing, limited access to health care, and distrust of govern­ment services make outbreaks among these at-risk populations more difficult to control, requiring tailored comprehensive public health interventions that address their specific circum­stances and needs.16,35,39
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.2,9 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.35,40 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 inci­dence in the United States.8
*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.
- Franco E, Meleleo C, Serino L, Sorbara D, Zaratti L. Hepatitis A: Epidemiology and prevention in developing countries. World J Hepatol. 2012 Mar;4(3):68-73. doi: 10.4254/wjh.v4.i3.68.
- Murphy TV, Denniston MM, Hill HA, et al. Progress toward eliminating hepatitis A disease in the United States. MMWR Suppl. 2016 Feb;65(1):29-41. doi: 10.15585/mmwr.su6501a6.
- Klevens RM, Denniston MM, Jiles-Chapman RB, Murphy TV. Decreasing immunity to hepatitis A virus infection among US adults: Findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012. Vaccine. 2015 Nov;33(46):6192-6198. doi: 10.1016/j.vaccine.2015.10.009.
- Ciocca M. Clinical course and consequences of hepatitis A infection. Vaccine. 2000 Feb;18(suppl 1):S71-74. doi: 10.1016/s0264-410x(99)00470-3.
- Hofmeister MG, Foster MA, Teshale EH. Epidemiology and transmission of hepatitis A virus and hepatitis E virus infections in the United States. Cold Spring Harb Perspect Med. 2019 Apr 1; 9(4). Pii: a033431. doi: 10.1101/cshperspect.a033431.
- Lemon SM. Type A viral hepatitis: epidemiology, diagnosis, and prevention. Clin Chem. 1997 Aug;43(8, pt 2):1494-1499.
- Lemon SM, Ott JJ, Van Damme P, Shouval D. Type A viral hepatitis:Aa summary and update on the molecular virology, epidemiology, pathogenesis and prevention. J Hepatol. 2017 Sep 5, pii:S0168-8278(17)32278-X. doi: 10.1016/j.jhep.2017.08.034.
- Fiore AE, Wasley A, Bell BP; Advisory Committee on Immunization Practices. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 May 19;(RR-7); 1-23.
- Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010 Sep 24;28(41):6653-6657. doi: 10.1016/j.vaccine.2010.08.037.
- Craig AS, Watson B, Zink TK, Davis JP, Yu C, Schaffner W. Hepatitis A outbreak activity in the United States: Responding to a vaccine-preventable disease. Am J Med Sci. 2007 Sep;334(3):180-183. doi: 10.1097/MAJ.0b013e3181425411.
- Shaw FE Jr, Sudman JH, Smith SM, et al. A community-wide epidemic of hepatitis A in Ohio. Am J Epidemiol. 1986 Jun 12;123(6):1057-1065. doi: 10.1093/oxfordjournals.aje.a114334.
- Venczel LV, Desai MM, Vertz PD, et al. The role of child care in a community-wide outbreak of hepatitis A. Pediatrics. 2001 Nov;108(5):E78. doi: 10.1542/peds.108.5.e78.
- Cotter SM, Sansom S, Long T, et al. Outbreak of hepatitis A among men who have sex with men: Implications for hepatitis A vaccination strategies. J Infect Dis. 2003 Apr;187(8):1235-1240. doi: 10.1086/374057.
- CDC. Epidemiologic notes and reports hepatitis A among drug abusers. MMWR Morb Mortal Wkly Rep. 1988;37(19):297-300,305.
- James TL, Aschkenasy M, Eliseo LJ, Olshaker J, Mehta SD. Response to hepatitis A epidemic: Emergency department collaboration with public health commission. J Emerg Med. 2009 May;36(4):412-416. doi: 10.1016/j.jemermed.2007.10.001.
- Schade CP, Komorwska D. Continuing outbreak of hepatitis A linked with intravenous drug abuse in Multnomah County. Public Health Rep. 1988 Sep-Oct;103(5):452-459.
- Villano SA, Nelson KE, Vlahov D, Purcell RH, Saah AJ, Thomas DL. Hepatitis A among homosexual men and injection drug users: more evidence for vaccination. Clin Infect Dis. 1997 Sep;25(3):726-728. doi: 10.1086/513757.
- Sansom SL, Cotter SM, Smith F, et al. Costs of a hepatitis A outbreak affecting homosexual men: Franklin County, Ohio, 1999. Am J Prev Med. 2003 Nov;25(4):343-346. doi: 10.1016/s0749-3797(03)00209-5.
- Corey L, Holmes KK. Sexual transmission of hepatitis A in homosexual men: incidence and mechanism. N Engl J Med. 1980 Feb 21;302(8):435-438. doi: 10.1056/NEJM198002213020804.
- Bialek SR, Barry V, Bell BP, et al. Seroprevalence and correlates of hepatitis a among HIV-negative American men who have sex with men. Sex Health. 2011 Sep;8(3):343-348. doi: 10.1071/SH10162.
- CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1996;45 (RR15):1-30.
- Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA. 2005 Jul;294(2):194-201. doi: 10.1001/jama.294.2.194.
- Bell BP, Shapiro CN, Alter MJ, et al. The diverse patterns of hepatitis A epidemiology in the United States-implications for vaccination strategies. J Infect Dis. 1998 Dec;178(6):1579-1584. doi: 10.1086/314518.
- Klevens RM, Miller JT, Iqbal K, et al. The evolving epidemiology of hepatitis a in the United States: incidence and molecular epidemiology from population-based surveillance, 2005-2007. Arch Intern Med. 2010 Nov;170(20):1811-1818. doi: 10.1001/archinternmed.2010.401.
- Ly KN, Klevens RM. Trends in disease and complications of hepatitis A virus infection in the United States, 1999-2011: a new concern for adults. J Infect Dis. 2015 Jul 15;212(2):176-182. doi: 10.1093/infdis/jiu834.
- Thorburn KM, Bohorques R, Stepak P, Smith LL, Jobb C, Smith JP. Immunization strategies to control a community-wide hepatitis A epidemic. Epidemiol Infect. 2001 Dec;127(3):461-467. doi: 10.1017/s0950268801006008.
- Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis. 2004;38(5):705-715. doi: 10.1086/381671.
- Sharapov UM, Kentenyants K, Groeger J, Roberts H, Holmberg SD, Collier MG. Hepatitis A infections among food handlers in the United States, 1993-2011. Public Health Rep. 2016 Jan-Feb;131(1):26-29. doi: 10.1177/003335491613100107.
- Wheeler C, Vogt TM, Armstrong GL, et al. An outbreak of hepatitis A associated with green onions. N Engl J Med. 2005 Sep 1;353(9):890-897. doi: 10.1056/NEJMoa050855.
- Collier MG, Khudyakov YE, Selvage D, et al; Hepatitis A Outbreak Investigation Team. Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study. Lancet Infect Dis. 2014 Oct;14(10):976-981. doi: 10.1016/S1473-3099(14)70883-7.
- Viray MA, Hofmeister MG, Johnston DI, et al. Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw-Hawaii, 2016 [published online October 17, 2018]. Epidemiol Infect. doi: 10.1017/S0950268818002844.
- Centers for Disease Control and Prevention. Multistate outbreak of hepatitis A linked to frozen strawberries (final update). CDC website. cdc.gov/hepatitis/outbreaks/2016/hav-strawberries.htm. Published December 16, 2016. Accessed October 9, 2019.
- Collier MG, Drobeniuc J, Cuevas-Mota J, Garfein RS, Kamili S, Teshale EH. Hepatitis A and B among young persons who inject drugs--vaccination, past, and present infection. Vaccine. 2015 Jun 4;33(24):2808-2812. doi: 10.1016/j.vaccine.2015.04.019.
- Williams WW, Lu PJ, O'Halloran A, et al. Surveillance of vaccination coverage among adult populations - United States, 2015. MMWR Surveill Summ. 2017 May 5;66(11):1-28. doi: 10.15585/mmwr.ss6611a1.
- Foster MA, Hofmeister MG, Kupronis BA, et al. Increase in hepatitis A virus infections - United States, 2013-2018. MMWR Morb Mortal Wkly Rep. 2019 May 10;68(18):413-415. doi: 10.15585/mmwr.mm6818a2.
- Foster M, Ramachandran S, Myatt K, et al. Hepatitis A virus outbreaks associated with drug use and homelessness - California, Kentucky, Michigan, and Utah, 2017. MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1208-1210. doi: 10.15585/mmwr.mm6743a3.
- Wooten DA. Forgotten but not gone: learning from the hepatitis A outbreak and public health response in San Diego. Top Antivir Med. 2019;26(4):117-121.
- Craig AS, Sockwell DC, Schaffner W, et al. Use of hepatitis A vaccine in a community-wide outbreak of hepatitis A. Clin Infect Dis. 1998 Sep;27(3):531-535. doi: 10.1086/514700.
- Latash J, Dorsinville M, Del Rosso P, et al. Notes from the field: increase in reported hepatitis A infections among men who have sex with men - New York City, January-August 2017. MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):999-1000. doi: 10.15585/mmwr.mm6637a7.
- Centers for Disease Control and Prevention. Viral hepatitis surveillance, United States 2016. cdc.gov/hepatitis/statistics/2016surveillance/pdfs/2016HepSurveillanceRpt.pdf. Accessed: October 9, 2019.