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What is the history of Hepatitis A in America and other countries?


disease history

Hippocrates described outbreaks of jaundice in 5th Century B.C. and medical historians believe this is likely the first reported cases of hepatitis A infections. 1  Throughout more recent history, reports of the disease were often associated with wars, and descriptions of outbreaks, often referred to in medical literature as infectious hepatitis or epidemic jaundice, have been documented since the Napoleonic Wars.2

By the early part of the 20th century, physicians believed that transmission of infectious hepatitis occurred through food and water sources and from person to person.3 By 1931, it was hypothesized that outbreaks of this epidemic jaundice were caused by an “ultra-microscopic virus which is pathogenic only to man.”4

In the 1940’s, experiments on the transmission of hepatitis A were conducted in Germany, the United States, and the Middle East. In Germany, human subjects involved in these experiments were fed duodenal juice. In the United States, researchers fed hepatitis A contaminated stool or serum filtrate to 12 conscientious objectors who volunteered for the experiment in lieu of military service. In the Middle East, volunteers were injected with blood or serum from patients with jaundice. From these experiments, researchers were able to determine the incubation period of infectious hepatitis, as well as the difference in the incubation periods between infectious hepatitis, now referred to as hepatitis A, and serum hepatitis, now hepatitis B.5

In the mid 1940’s, researchers discovered that gamma globulins (immunoglobulins) could help in the prevention of illness, including hepatitis A. Small amounts of hepatitis A gamma globulins were found to prevent illness for up to nine months.6 This treatment continues to be an option for hepatitis A prevention even today. 7

Human experimentation with Hepatitis A continued in the United States in the 1950’s, most notably at the Willowbrook State School on Staten Island, New York. In 1956, Dr. Saul Krugman began experimenting on children with developmental and intellectual disabilities residing at the state run school.  Krugman wanted to learn more about the hepatitis virus as well as the available gamma globulin’s ability to reduce the risk of infection. As high rates of infectious hepatitis were well documented at Willowbrook, the institution was considered to be the perfect environment for Krugman to conduct further research. Krugman’s hepatitis experiments lasted for 14 years, and involved exposing new residents to the current circulating strain of infectious hepatitis found at the state school. Krugman, along with his assistant, Dr. Joan Giles, intentionally exposed intellectually disabled residents to the feces and serum of children who were known to have had the infection and proceeded to monitor their health status in an attempt to learn more information about the virus. Experiments performed by Krugman and Giles were not focused on treating the infection, but rather on observing the symptoms of hepatitis A infection for scientific gain. Krugman justified the experiments by reporting that the children of Willowbrook would most likely be exposed to the virus anyway due to the high rates of infection at the school, and that all children participating in the experiments would receive proper care and monitoring on a special hepatitis unit. Parental consent for participation was obtained, however, in many cases, parents who applied to have their children admitted to Willowbrook were informed that openings were only available for the particular unit where hepatitis experiments were taking place.8 9 10

Willowbrook was an overcrowded and unsanitary facility and few attempts were made to improve the living conditions of the residents. The facility lacked adequate staffing and residents often came from poor and minority families, most of whom had no other housing alternatives available for their children due to their financial situation or as a result of racial discrimination.11 Robert Kennedy visited Willowbrook in 1965 and called it a “snakepit,” 12  noting that children were living in filth. He recommended that changes be implemented to improve the living conditions, however, no improvements were ever made to the facility.13

In 1971, several physicians publicly condemned the ongoing experiments on intellectually disabled children and voiced serious ethical concerns. In letters published by The Lancet in 1971, concerns expressed by physicians critical of the study included the ethics of experimentation on intellectually disabled children, the fact that the experiments would offer no improvement to the health of the child, the lack of any attempt to control the outbreak of infectious hepatitis by improving sanitation within the school, and more.14 15 16 In 1972, investigative reporter Geraldo Rivera exposed the horrors of Willowbrook in an award winning documentary aired on ABC news. Rivera’s news report prompted the families of Willowbrook’s residents to take action and file a class action lawsuit against the State of New York. The hepatitis experiments were halted following public outcry and eventually federal laws were passed to protect the rights of individuals living in institutions.17

While the experiments that took place at Willowbrook resulted in a gain in scientific knowledge about the hepatitis virus, including the confirmation of a distinction between infectious hepatitis, now known as hepatitis A, and serum hepatitis, or hepatitis B, as well as the differentiation between their modes of transmission,18 the ethics of Krugman’s experiments continue to be questioned today.19

In 1973, the hepatitis A virus was finally detected and isolated in the feces20 and additional techniques to adequately test samples to definitively determine a diagnosis of hepatitis A infection and differentiate it between hepatitis B were also developed during this time.21 Hepatitis A vaccine development began following virus isolation, and by 1991, the first published research on the use of an inactivated hepatitis A vaccine in humans appeared in medical literature.22

Hepatitis became a reportable disease in the early 1950’s23 and in 1961, there were 72,651 reported cases of both infectious and serum hepatitis reported to the CDC. 24 In 1961, the CDC reported on an increase in the number of cases, noted it to be “the largest number reported since hepatitis was added to the list of notifiable diseases ten years ago.”25 It was also reported that there was a seven year interval between high rates of hepatitis infection, and most cases were reported in the later part of the winter and the early part of spring.26

In 1966, the CDC began differentiating between infectious hepatitis, now referred to as hepatitis A, and serum hepatitis, or hepatitis B. Prior to 1966, the CDC collected data on the rates of both types of hepatitis infection, however, no distinction was made between the two. In 1966, there were 32,859 reported cases of hepatitis A and 1,497 reported cases of hepatitis B, an over 50 percent decrease from the number of reported cases five years earlier.27

Between 1966 and 1995, the year prior to the Food and Drug Administration’s (FDA) approval of the inactivated hepatitis A vaccine (1996), reported rates of hepatitis A infection varied between a high of 59,606 in 1971, and a low of 21,532 in 1983,28 with higher numbers of outbreaks occurring in the U.S. approximately every 10 years.29 Hepatitis A infection rates were noted to be highest among Alaskan Natives and American Indians and more prevalent in the western part of the United States. Children under the age of fifteen were found to have the highest rates of infection, with 30 percent of cases occurring within this population.30 Outbreaks occurred most frequently between family members or sexual contacts, daycare workers, and international travelers. Only between two and three percent of all hepatitis A infections were the result of an identified water or food source and 50 percent of all reported cases had no identified source of infection. 31

It was also reported in 1996 that one third of all Americans had lifelong hepatitis A immunity due to previous exposure to the virus and exposure to hepatitis A directly correlated to age. 75 percent of adults over the age of 70 were found to be immune to hepatitis A, whereas only 10 percent of children under the age of 10 had previous exposure to the virus and determined to be immune. 32

At the time of the CDC’s Advisory Committee on Immunization Practices (ACIP) recommendation of the newly available hepatitis A vaccines, VAQTA, and HAVRIX in 1996, ACIP acknowledged that the number of cases of hepatitis A had declined over the past several decades primarily as a result of an improvement in sanitation and hygiene practices.33 In 1996, there were 31,032 cases of hepatitis A infection reported to the CDC.34

In 2007, one year following the ACIP’s recommendation for routine administration of two doses of hepatitis A vaccine for all children beginning at 12 months of age,35 there were 2,979 reported cases of hepatitis A infections reported.  At this time, it was noted that hepatitis A infections were highest among adults between the ages of 25 and 39 and lowest in children under the age of five. However, as children under the age of five are often asymptomatic when exposed to hepatitis A, infection rates in young children may have actually been much higher than reported. 18 percent of all cases of hepatitis A were attributable to international travel with approximately 85 percent of all travel-related cases associated with trips to Mexico and Central or South America. Six percent of cases occurred in men who had sex with other men, and one percent of cases involved injectable drug users. Information on risk factors for hepatitis A infection were absent from nearly half of the reported cases.36

The number of reported hepatitis A infections steadily decreased until 2013, when a large multistate outbreak occurred in association with imported pomegranate arils from Turkey resulted in 165 reported infections,37 and put the total number of reported cases for the year at 1,781.38 In 2016, reported rates of hepatitis A infection increased yet again as a result of two separate outbreaks associated with contaminated food, with one in Hawaii linked to raw scallops imported from the Philippines39 and a second multi-state outbreak linked to frozen strawberries imported from Egypt.40 There were 2,007 reported cases of hepatitis A infections in 2016,41 including 418 cases linked to the contaminated food sources.42 The CDC reported that only 1,026 of the 2,007 reported cases of hepatitis A infection included clinical data pertaining to death, and from these reported cases, seven deaths were associated with hepatitis A.43

Between 1998 and 2017, 97 hepatitis A outbreaks associated with either food or water sources have been reported. These outbreaks resulted in 2,896 infections, 399 hospitalizations and 8 deaths.44 Imported foods continue to be a source of potential hepatitis A infections.45

In the United States, risk factors for acquiring hepatitis A infection include international travel, exposure to a person with hepatitis A infection, employment at a day care center, being a man who has sex with another man, being an injection drug user, or becoming exposed from a contaminated food or water source. It is important to note that in 2014, only 7 percent of reported cases of hepatitis A infection listed a risk factor, with the overwhelming majority of cases missing information or reporting no known etiology for the infection.46 

Since 2016, several states have reported hepatitis A infections that have primarily impacting persons who use drugs or who are experiencing homelessness. Over 15,000 cases, 8,500 hospitalizations and 140 deaths have been attributed to this outbreak. In October of 2018, the CDC added homelessness as a risk factor for developing hepatitis A and recommended hepatitis A vaccination for this particular population.47

What Is the Incidence of Hepatitis A in the Rest of the World?

Globally, hepatitis A is the most common form of acute hepatitis, with an estimated 1.5 million clinical cases occurring each year. 48  Hepatitis A infections are often cyclical and closely associated with sanitation and hygiene practices. In developing countries that lack adequate sanitation and where hygiene habits are poor, most children become infected with hepatitis A prior to the age of ten. As infection in most young children tends to be asymptomatic, outbreaks are uncommon as most individuals have been exposed to the virus early in life and have lifelong immunity.49

In countries that are developing and may have varying conditions of sanitation and personal hygiene, hepatitis A exposure may be avoided in childhood and delayed until an older age during which infection will often be symptomatic. As a result, these countries are noted to have higher rates of hepatitis A infection.50

In developed countries, such as the United States, Canada, Western Europe, Japan, and Australia, where good hygiene and sanitation practices exist, rates of hepatitis A infection are very low, and occur mainly as a result of international travel, exposure in residential or childcare centers, or by water or food borne contamination. Risk factors for hepatitis A infection in developed countries include men who have sex with other men, drug users, international travelers, and persons experiencing homelessness.51 52

Hepatitis A infection does not result in chronic liver disease and rarely results in death. When death occurs, it is often a result of fulminant hepatitis or acute liver failure.53

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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References

1 Krugman S, The Gordon Wilson Lecture. The ABC's of viral hepatitis. Trans Am Clin Climatol Assoc. 1992; 103: 145–156.

2 Conrad ME, Infectious Hepatitis: An Unsolved Military Problem. Mil. Med. 1965 Jun; 130(6) 594–600

3 Cuthbert JA, Hepatitis A: Old and New. Clin Microbiol Rev. 2001 Jan;14(1):38-58.

4 Ibid

5 Ibid

6 Ibid

7 CDC Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis. MMWR. Sept 15, 2017; 66(36);959–960

8 Ely, M Disinterestedness at Willowbrook. COLFA Conference. University of Texas at San Antonio, Spring 2014

9Stephen Goldby, Saul Krugman, M.H. Pappworth, and Geoffrey Edsall: The Willowbrook Letters, “Criticism and Defense”; Paul Ramsey, “Judgment on Willowbrook” Published on Philosophy at TAMUCC. No Date

10 Diamond, EF The Willowbrook Experiments The Linacre Quarterly. 1973 May; 40 (2)9 133-137

11 Ely, M Disinterestedness at Willowbrook. COLFA Conference. University of Texas at San Antonio, Spring 2014

12 Dugger, CW. Big Day for Ex-Residents Of Center for the Retarded. The New York Times. Mar. 12, 1993

13 Ibid

14Stephen Goldby, Saul Krugman, M.H. Pappworth, and Geoffrey Edsall: The Willowbrook Letters, “Criticism and Defense”; Paul Ramsey, “Judgment on Willowbrook” Published on Philosophy at TAMUCC. No Date

15 Goldby S. Experiments at the Willowbrook State School. Lancet. 1971 Apr 10;1(7702):749.

16 Pappworth MH, THE WILLOWBROOK EXPERIMENTS. Lancet. 1971 June 5; 297(7710);1181

17 Gunderman D, Revisiting the atrocities that once consumed the halls of Willowbrook State School in Staten Island – WARNING GRAPHIC CONTENT. The New York Daily News. Apr. 9 , 2017

18 Krugman S, The Gordon Wilson Lecture. The ABC's of viral hepatitis. Trans Am Clin Climatol Assoc. 1992; 103: 145–156.

19 Carroll TM, Gutmann MP, The Limits of Autonomy: The Belmont Report and the History of Childhood. J Hist Med Allied Sci. 2011 Jan; 66(1): 82–115.

20 Feinstone SM, Kapikian AZ, Purceli RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science. 1973 Dec 7;182(4116):1026-8.

21 Cuthbert JA, Hepatitis A: Old and New. Clin Microbiol Rev. 2001 Jan;14(1):38-58.

22 Sjogren MH, Hoke CH, Binn LN et al. Immunogenicity of an inactivated hepatitis A vaccine. Ann Intern Med. 1991 Mar 15;114(6):470-1.

23 CDC December-1951 Bulletin. Dec. 1951. vol. X, no. 12.

24 CDC Annual Supplement: Reported Incidence of Notifiable Diseases in the United States, 1961. MMWR. Oct 31, 1962; 10 (53); 1-29

25 Ibid

26 Ibid

27 CDC Reported incidence of notifiable diseases in the United States 1966. MMWR. Nov. 1967. 15(53); 1-60

28 CDC Table 1a. Reported number and rate per 100,000 population of cases of acute, symptomatic, viral hepatitis, by type and year, United States, 1966-2008. June 25, 2010

29 CDC Prevention of Hepatitis A Through Active or Passive Immunization MMWR Dec 27, 1996; 45 (RR-15)

30 Ibid

31 Ibid

32 Ibid

33 Ibid

34 CDC Summary of Notifiable Diseases, United States 1996. MMWR. Oct. 31, 1997; 45(53);1-87

35 CDC Prevention of Hepatitis A Through Active or Passive Immunization Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. May 19, 2006; 55(RR07);1-23

36 CDC Surveillance for Acute Viral Hepatitis – United States, 2007. MMWR. May 22, 2009; 58 (3) 1-27

37 CDC Multistate outbreak of hepatitis A virus infections linked to pomegranate seeds from Turkey (Final Update). Oct. 28, 2013

38 CDC Summary of Notifiable Infectious Diseases and Conditions — United States, 2013. MMWR Oct. 23, 2015; 62(53);1-119

39 CDC Outbreak of hepatitis A in Hawaii linked to raw scallops. Aug. 19, 2016

40 CDC 2016 - Multistate outbreak of hepatitis A linked to frozen strawberries (Final Update). Dec. 16, 2016

41 CDC National Notifiable Infectious Diseases and Conditions: United States – Table 2g. Reported cases of notifiable diseases, by region and reporting area- United States and U.S. territories, 2016 Atlanta, GA. CDC Division of Health Informatics and Surveillance, 2017

42 CDC National Outbreak Reporting System (NORS) – NORS Dashboard. Dec. 10, 2018. See Etiology – Hepatitis; Year – 2016.

43 CDC Table 2.2. Select clinical characteristics of hepatitis A cases* reported in the United States, 2016. Apr. 16, 2018

44 CDC National Outbreak Reporting System (NORS) – NORS Dashboard. Dec. 10, 2018. See Etiology – Hepatitis.

45 Gould L, Kline J, Monahan C, Vierk K. Outbreaks of Disease Associated with Food Imported into the United States, 1996–2014. Emerg Infect Dis. 2017;23(3):525-528.

46 CDC. Surveillance Manual – Chapter 3: Hepatitis A. – Background. May 18, 2018

47  CDC Emergency Preparedness and Response - Update: Widespread Outbreaks of Hepatitis A among People Who Use Drugs and People Experiencing Homelessness across the United States. Health Alert Network. Mar. 25, 2019

48  Franco E, Meleleo C, Serino L, et al. Hepatitis A: Epidemiology and prevention in developing countries. World J Hepatol. 2012 Mar 27; 4(3): 68–73.

49 WHO Hepatitis A Sep. 19, 2018

50 Ibid

51 Franco E, Meleleo C, Serino L, et al. Hepatitis A: Epidemiology and prevention in developing countries. World J Hepatol. 2012 Mar 27; 4(3): 68–73.

52 CDC Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Persons Experiencing Homelessness MMWR Feb.15, 2019; 68(6);153–156

53 WHO Hepatitis A Sep. 19, 2018


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