At a cataclysmic moment in history, millions of years after the earth’s crust had solidified, atoms of hydrogen, oxygen, nitrogen and carbon came together to constitute life. One of the first forms of this ‘life’ to develop was the lowly amoeba. Eons passed, and the amoeba evolved into different species - one of them the Entamoeba Histolytica. In the waters of the earth it waited, through millenniums, for the advent of man! Man evolved, roamed the earth, drank its water and sometimes developed amoebiasis, occasionally an amoebic liver abscess. Ignorant of the cause, he stoically suffered the disease cause by this microscopic predator until 1887 when the culprit was finally identified.

The condition
Although Sushruta described "Atisaar" (Amoebic dysentery) no clear explanation of hepatic involvement is available in ancient literature.¹
Hippocrates (460-377 B.C.)², contemporary of Herodotus and Socrates, and considered to be the first to reject superstition about diseases and to base practice of medicine on observation and study, has described large hepatic abscesses which must have been amoebic in nature.³ In his ‘Aphorisms’, it is apparent that he considered hepatic abscesses to be of two types : one with pus which "was pure and white" and the other with pus which "resembles the less of oil as it flows".⁴ He also noted that the latter condition was associated with a higher mortality. (It is interesting to note however, that just as the Hippocratic oath, although bearing his name was probably not written before 200 A.D.², so also many other observations, attributed to him were actually made later).
Shortly after the death of Hippocrates, in 356 B.C. Alexander the Great was born. When still young, he became King of Macedonia and Emperor of a vast empire. In his eastern campaign, he reached as far as the Indus and for a short while stepped into an area where amoebiasis must have been endemic. Badly exhausted by sickness, insomnia and injured in ferocious fighting against the Brahmanic people, he made his way back over the Gedrosia desert and died at the young age of 33 years⁵ at Babylon⁶ probably of an amoebic liver abscess.
The association of a hepatic disease with dysentery has been suspected since the time of Galen⁷. In 1776, during an epidemic of dysentery in Mexico, Joaquin Pio Eguia y Lugo observed that many deaths were due to a liver disease.⁸ Ballingall^l9 in 1818 made note of an officer in a Madras establishment who while fighting a duel, had an abscess of liver opened by a fortunate shot and thus obtained a complete cure.
When Ballingall practised in Madras, Napoleon Bonaparte, Emperor of France, was exiled in the tropical island of St. Helena by the British after his defeat at Waterloo.¹⁰ Now bloody dysentery (amoebiasis?) was very common on this island and Napoleon soon contracted what was diagnosed by two successive naval surgeons as tropical hepatitis.¹¹ However, as it was not in the interest of the Tory Government, then in England, to disclose the true nature of Napoleon’s disease, these two surgeons were arrested, court-martialed and struck off the Navy list.¹² On Napoleon’s demand, his family appointed a special physician, Antomarchi, to whom we owe most of our knowledge of Napoleon’s last illness. After an attack suggestive of amoebic liver abscess (pain and tender swelling in the epigastrium associated with fever and diarrhoea) he finally died in 1821,¹³ shortly after a violent attack of vomiting, haematemesis and melaena. At the post-mortem Antommarchi noticed a "cancerous ulcer which had its centre at the superior part along with the small curve of the stomach communicating with the liver".¹⁴ It thus appears that Napoleon died, not as it commonly supposed due to cancer of the stomach,¹² but of an amoebic liver abscess of the left lobe which had ruptured into the stomach!
At the other end of the earth, in India, the high incidence of dysentery prompted workers to deal amply with it. Annesley (1828)¹⁵ in his book "Researches on the diseases of India" mentioned that out of 51 patients of dysentery on whom post-mortem was done, 26 had a tropical liver abscess. Parks, also working in India, acknowledged a certain relationship between dysentery and hepatitis.⁸
However, it is Charles Morehead, Professor of Medicine and the first principal of Grant Medical College, Bombay, who is accredited⁸ with have reported the first case of hepatic abscess in 1848.
Later he described a similar case in a patient with dysentery. By a strange coincidence, one hundred and thirty-one years later, the author, who has also been a Professor of Medicine at the Grant Medical College, Bombay, for over twenty years, has contributed this monograph on the same disease. Sir Charles Morehead, in his book, ‘Clinical Researches on diseases in India’¹⁶ has given a detailed and masterly discourse on liver abscess. Reading his dissertation, one is astounded by wealth of clinical material presented. The observations and comments made are as relevant today, as they were over a hundred years ago.
He stated that hepatic abscess is not ‘exceedingly rare among ‘Asiatics’ and from his clinical material concluded that "the co-existence of tropical hepatic abscess and ulceration of the mucous membrane of the large intestine was frequently observed". He has described the pus as being of a "reddish colour and thick" and has enumerated almost all the known complications of this condition with vividly illustrative case histories. This, pleuropulmonary, pericardial, peritoneal and other complications have been described.¹⁶

The culprit
While clinical research was being conducted on tropical liver abscess, dramatic events, which would soon lead to the discovery of the etiological agent in such an abscess, were taking place in a totally different field of science. Antony Van Leeuwenhoek discovered protozoa. Rosel van Rosenhof, an amateur lens grinder and microscopist, in 1775, described a microscopic being that was constantly changing its shape. Hence he called it "the little proteus".⁸ In 1849, Gros¹⁷ described the first amoeba living as a parasite in man - the amoeba Gigivalis. Later, in 1875, Fredor Alekshandrevitch Losch¹⁸ of St. Petersburg (now Leningrad) found amoebae in the stools of a patient with dysentery and suggested it as the causative factor.
In 1887, after centuries of impunity, the amoeba was finally identified as the etiological agent in tropical liver abscess. The honour of this discovery goes to none other than the famous Robert Koch¹⁹ who while studying cholera in Egypt and India, came across 2 cases of dysentery complicated by an abscess of the liver. He demonstrated E. Histolytica in the walls of capillaries near the abscess which were similar to those found in the stool.⁸ The etiological relationship between amoebic dysentery and tropical hepatic abscess was soon confirmed by Kartulis²⁰ in Egypt (1887) when he found amoebae in twenty cases of tropical abscess. The idea of suppuration being caused by amoebae was inconceivable to him. He therefore postulated that amoebae carried bacteria from the colon to the liver causing suppuration.³
There still existed, however, a school of though (Andrew Duncan at the London School of Tropical Medicine) which denied the general association between amoebic dysentery and tropical liver abscess. This was probably due to the failure to demonstrate amoebae in the pus of larger abscesses.⁷
The scholarly monograph of Councilman and Lafleur²¹, in 1891 on intestinal and hepatic amoebiasis substantiated the contentions of Koch and Kartulis. In their monograph, they insisted on the occurrence of hepatic abscess as a complication of dysentery even in patients who did not have symptoms of the latter disease⁸. They also coined the present term '‘Amoebic abscess of the liver'’
Leonard Roger, in 1902, published a paper based on thirty seven cases of amoebic liver abscess.²² In 35 of them amoebae were demonstrated. However, inspite of similar reports by numerous workers, especially those in India, Sir Philip Manson²³ (1914) comments: "to what extent the amoeba is concerned in the production of tropical liver abscess, it is as yet impossible to state".
Excellent work done by Ochsner and DeBakey²⁴ (1939), Lamont and Pooler²⁵ (1958), Paul Milroy³ (1960); Wilmot²⁶ (1962) and many others have clarified many aspects of amoebic liver abscess. Thus, what Charles Morehead and others have observed decades previously, was finally a medical ‘fact’ and the ‘tropical’ hepatic abscess was proved to be associated etiologically with ‘tropical’ dysentery.²⁷ The culprit had been identified, the war had begun!

The cure
Hippocrates was well aware of drainage of liver abscess as a form of therapy. Although he insisted that the physician must assist nature’s own tendency to heal the sick and take great care that "his treatment shall at least do no harm"², he also stated "Desperate diseases need desperate remedies!"⁴
Amoebic liver abscess is, even to-day, considered a ‘desperate disease’ and it is no wonder that many ‘desperate’ measures, however empirical, have been tired in an attempt to cure this condition. In the late eighteenth and early nineteenth century ‘depletion’ was a common form of therapy. This was achieved rapidly by ‘blood letting’ (a simple procedure of making a nick in a vein): if one required slower ‘depletion’, the use of leeches applied to the abdomen or the use of a ‘blister’ over the liver area could be resorted to. Moreover in this era the administration of laxatives and mercurial purgatives in large doses, was routine. The treatment in those early days was gruesome, to say the least.²⁸
Throughout the nineteenth century, surgical procedures like open drainage and later, trocar aspiration were commonly utilised. Ballingall⁹ even recommended the introduction of a seton (a strip of linen or stand of horse hair used as a drain) as a curative measure for such abscesses. As might be expected, with the then prevailing surgical techniques and standards of asepsis the mortality rate was appallingly high.
The use of quinine was also tried in few such cases.¹⁶
Although ipecacuanha was known as a patent remedy for ‘bloody flux’ among the indigenous population of Brazil in the sixteenth century it was not routinely used in the therapy of amoebic liver abscess until after the definite association between amoebiasis and liver abscess was established. Rogers, whose work in amoebiasis is legend, is credited with having revived the use of ipecacuanha to replace the unsatisfactory surgical treatment then in vogue.
Later in 1912 he introduced emetine²⁹ in the treatment of amoebic abscess. In this book "The Salts of Emetine", he recounted the early history of ipecacuanha, the isolation of its alkaloid emetine by Pelletier and the discovery of the rapid cure of amoebic dysentery and liver abscess with hypodermic injections of the alkaloid.

Conclusion
Hippocrates firmly believed that order reigned in nature and that the earnest seeker may discover its character by patient investigation. This remains as true today as it was over two thousand years ago. As more advanced facilities for investigation are now available, a more concrete picture of amoebic liver abscess is slowly evolving. Much work, however, remains to be done. What is required now is patience and a lot of dedication. The story has not ended: it has only just begun.

References

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