Hepatitis A

Ian D. Gust

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315894072
• eBook ISBN: 9781351090070
• Topic: Ciencias biológicas
• Subtopic: Biología

In the present volume, current knowledge of Hepatitis A is reviewed and the sequence of events, that led to each of the major advances in the field, traced.

Chapter 1
HISTORY

I. INTRODUCTION

A. General

Today, when at least five different forms of acute viral hepatitis are recognized, it is difficult to imagine that the disease was not considered to be a distinct clinical entity until this century and that it was not until the 1940s that physicians realized that more than one form of hepatitis existed.

It is often said that hepatitis A was known at the time of Hippocrates¹ because of his description of benign epidemic jaundice which appears in the “De internis affectionibus”.² “This type of jaundice is called epidemic because it occurs in all seasons. It is caused above all else by overindulgence, excesses of wine and after a chill. From the first moment, the body changes color and becomes yellow; the eyes become markedly jaundiced; the disease appears under the hair and under the nails. There are chills and low grade fever. The patient is weak. The head aches; the urine is yellow and thick. This form of jaundice is less dangerous and is cured if treated quickly.”

While the symptoms that are described could be due to hepatitis A they are scarcely diagnostic! Caution should be exercised in ascribing this and later descriptions of epidemic jaundice to hepatitis A as a number of other diseases such as yellow fever may cause outbreaks of jaundice often associated with a high-case fatality rate. The earliest outbreaks of hepatitis which were almost certainly hepatitis A, were documented in Europe in the 17th and 18th centuries. In 1886, Hirsh compiled a list of 34 epidemics of jaundice, the earliest of which took place in Minorca in 1745.³ A more extensive list was produced by Bachman in 1952⁴ including two epidemics in the 17th century, 25 in the 18th, and 53 from 1802 to 1874. While not all of these were due to hepatitis A, some undoubtedly were. The earliest recorded outbreak in the U.S. seems to have occurred in Norfolk, Va. in 1812.⁵ Brief accounts of the disease can be found over the next 50 years although it appears to have been uncommon until the outbreak of the Civil War when large numbers of cases occurred among Union troops.

B. Catarrhal Jaundice

Sporadic cases of jaundice were also recognized in the 19th century. From 1855 the disease became known as “catarrhal jaundice” as a result of a misconception about its etiology which was first suggested by Bamberger and perpetuated by the eminent pathologist Virchow.⁶

Bamberger and Virchow believed that “catarrhal jaundice” was due to inflammation of the biliary tract which resulted in the common bile duct becoming blocked by a plug of inspissated mucus. This belief was so firmly entrenched that patients were sometimes treated with magnesium sulfate which it was thought would assist in dislodging the plug.

Although many physicians, including Sir William Osler, subscribed to this theory, Bamberger and Virchow’s views did not go unchallenged. Various workers suggested that epidemic and sporadic jaundice had a common etiology, that the cause of both diseases was acute inflammation of the liver and that they were caused by an infectious agent.

In 1912, Cockayne⁷ published a review in which he suggested that the sporadic and epidemic forms of jaundice were probably manifestations of the same disease. Although this view was echoed by Blumer,⁸ it received little attention in the medical community.

In 1922, Eppinger⁹ propounded the view that the primary lesion was not obstruction but hepatocellular necrosis, a view which received support from pathologists in Britain, Scandinavia, and the U.S.^10–12 Although Eppinger felt that the most probable cause was a liver toxin, contemporaries thought that the disease was infectious, a view which gained support when Inada and his colleagues¹³ showed that some outbreaks of jaundice in Japan were due to infection with leptospira. Although a number of enteric bacteria were isolated from the feces of patients with “catarrhal jaundice” no particular strain was consistently implicated which led McDonald¹⁴ in 1908 to postulate that a virus might be involved.

C. Serum Hepatitis

The first indication of the existence of a second form of hepatitis which was spread by a different route and had a different epidemiology came from the observations of Lurmann who described an outbreak of hepatitis among shipyard workers in Bremen in 1833.¹⁵ Lurmann observed 191 cases of jaundice in a group of 1289 shipyard workers 2 to 8 months after they had been vaccinated against smallpox with a particular batch of human glycerinated lymph. By contrast, no cases of jaundice were observed among 500 of their colleagues who were vaccinated at the same time with a different batch of vaccine. A second similar episode occurred in Germany later that year.’¹⁶ The disease, which became known as “serum hepatitis” was assumed to be due to a blood-borne infectious agent but was regarded as a medical curiosity of no general importance. Over the next 50 years however, a number of outbreaks with similar features were observed in a variety of settings. In the 1920s, outbreaks of jaundice were described in groups of American and German patients who were being treated for syphilis with injections of the arsenical preparation, salvarsan.¹⁷ Although these outbreaks were carefully documented, the mechanism of infection was not defined and no thought appears to have been given to the possible role of syringes and needles in transmission of the disease. A few years later Flaum et al.¹⁸ reported an outbreak of jaundice among diabetics attending a clinic to receive insulin injections. In an outstanding paper, they produced evidence that reuse of needles and syringes was responsible for transfer of the disease and suggested that in view of its prolonged incubation period “serum hepatitis” was caused by a different agent to the one responsible for “catarrhal jaundice.”

In 1937, two additional outbreaks of serum hepatitis were reported by British workers. In the first, several groups of school children who had received injections of pooled convalescent serum as prophylaxis against measles developed jaundice.^19,20 Of 191 children immunized with a particular serum pool, 37 developed hepatitis and 7 died. In each instance the incubation period between receipt of the pooled serum and onset of symptoms was several months. A second outbreak of jaundice occurred among adults who had been injected with yellow fever vaccine.²¹ Findlay and MacCallum,²² who investigated the outbreak, concluded that the disease was caused by the presence of a contaminating virus, which had been introduced either in the tissue cultures in which the yellow-fever virus was propagated, or in batches of human serum used to stabilize the vaccine. In an effort to prevent contamination they changed the method of vaccine production and the strain of virus which was used. Following these changes no cases of jaundice were detected among the next 5000 vaccinees.

Although by 1939 there was excellent evidence that viral hepatitis was an infectious disease caused by two etiologically distinct agents with separate modes of transmission and distinctive epidemiologies, these concepts were outside the mainstream of medical thought. It required the impetus of World War II and massive outbreaks of disease among troops and civilians to alter this situation.

II. Hepatitis In The Military

A. 18th and 19th Centuries

Epidemic hepatitis is an old camp follower and has been a problem among troops for centuries. Epidemics of hepatitis were frequently described by military surgeons in accounts of battles fought in Europe during the 18th and 19th centuries. The disease occurred during the Seven Years War, both in Germany and the low countries.²³ So many epidemics occurred among German garrison and field troops between 1842 and 1856, that the disease became known as “Kriegsickterus,” “Kriegsgelbsucht,” or “Soldatengelbsucht” just as French soldiers in the Napoleonic Wars referred to it as “jaunisse des camps.”

Hepatitis has been a problem in the American army since the Mexican War and was well documented among both white and black troops in the Union Army during the American Civil War, where it was reported to have caused more than 70,000 cases and attack rates were as high as 13 cases per 1000 troops.²⁵

Although the disease was recognized to be infectious, its etiology was not known. A variety of causes were suggested, including infection with leptospira and certain strains of Salmonellae.^26,27

B. World War I

During World War I large epidemics of hepatitis occurred in the British, French, German, and Rumanian armies.²⁸ Starting in July, 1915 among British troops in Alexandria, the disease spread to Gallipoli, Thessalonia, and Mesopotamia. Epidemics also occurred among French troops in the Dardenelles and German and Rumanian troops in Rumania^26,29 while the American army was largely unaffected.

Willcox,³⁰ who described the epidemic in British troops, observed that “the epidemic jaundice of campaigns appears to start as a gastrointestinal infection, … is almost certainly conveyed by the alimentary tract and contamination of food … probably plays an important part. Flies … may convey infection to food; but they are probably not the main cause of the spread of the disease”. He also speculated that the disease could be transmitted by contaminated water. It was 30 years before these ideas were proven to be true.

C. World War II

Although infectious hepatitis was a major cause of morbidity among both Allied and Axis forces throughout the entire conflict, it was not until a major outbreak of serum hepatitis occurred among American troops that the magnitude of the problem was realized. As a direct result of this outbreak, army authorities in Britain and the U.S. sponsored a number of studies which were aimed at determining the etiology of the disease and developing means of controlling it.

1. The Serum Hepatitis Epidemic in American Troops

By 1940, immunization had become an accepted means of prophylaxis against yellow fever. As the problem of post-vaccination jaundice seemed to have been overcome, it seemed logical to immunize troops who might be required to fight in endemic areas. The decision to immunize American troops was put into effect in 1941 using a vaccine produced by the Rockefeller Foundation containing the 17D strain of yellow fever vir...

Table of contents

• Cover
• Title Page
• Copyright Page
• INTRODUCTION
• THE EDITORS
• DEDICATION
• Contents
• Chapter 1 History
• Chapter 2 Identification Of Hepatitis A Virus
• Chapter 3 The physiochemical properties of hepatitis a virus
• Chapter 4 Animal Models
• Chapter 5 Features of Hepatitis A in Experimentally Infected Nonhuman Primates
• Chapter 6 Biology of hav in cell culture
• Chapter 7 Molecular Biology
• Chapter 8 Clinical Features
• Chapter 9 Epidemiology
• Chapter 10 General Preventative Measures
• Chapter 11 Active Immunization
• Chapter 12 Enterically Transmitted Non-A, Non-B Hepatitis
• Index