CHAPTER X

AMOEBIC DYSENTERY

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—Lambl, in 1859, was the first one to note the presence of amoebae in man, these being found in the stools of a child affected with diarrhoea. It was Lösch, however, who, in 1875, first accurately described the parasite which he found in the intestinal ulcerations as well as in the stool of a patient with chronic dysentery and was able to produce dysenteric ulcerations in the dog, by injecting amoebae-containing faeces into the dog’s rectum.

In 1879 Grassi noted the encysted forms of amoebae, but as he found them in well people, he denied their pathogenic importance. Cunningham found amoebae in the stools of cholera patients and Perroncito in those of typhoid cases, both of these authorities, however, viewing the question of their pathogenicity as did Grassi.

This was the general attitude of the medical mind until Koch, in 1883, while investigating cholera in Egypt, was impressed with the striking penetration of amoebae in the walls of intestinal ulcers and considered that this fact favored the view that amoebae were pathogenic.

Kartulis continued the work of Koch and in 1886 published his findings in 150 cases of dysentery, noting the presence of amoebae in the stools of all these cases. In 1887 he noted the presence of amoebae in liver abscess. In 1891, Lutz noted that amoebae in dysentery contained red cells. In the same year Councilman and Lafleur came to the conclusion that there were two species of amoebae in man, one harmless and the other, which was found in the submucosa of intestinal ulcers, pathogenic, Casagrandi and others put forward the view that amoebae only acted as carriers for bacteria, but in 1893 Kruse and Pasquale injected all the bacterial species isolated from a dysenteric stool into a cat’s rectum with negative result. Hlava and Kartulis first produced dysenteric lesions in cats by injecting per rectum, amoebic stools. Kruse and Pasquale produced dysentery in cats by injecting per rectum bacteria-free pus from a liver abscess which however contained amoebae.

A stumbling block as to the connection between amoebae and dysentery was the fact that many cases of typical dysentery failed to show amoebae. In 1898 Shiga settled this matter by reporting a group of bacilli which were concerned in the production of dysentery. His findings were confirmed all over the world and the distinction gradually obtained of cases of dysentery from bacillary as well as from amoebic infections.

In 1903 Schaudinn reported the existence of two species of amoebae, one harmless and named _Entamoeba coli_, the other pathogenic and named _E. histolytica_. In 1907 Viereck described a pathogenic amoeba which, by reason of its four nuclei in the encysted stage, he called _E. tetragena_.

As the result of the work of Hartmann, Whitmore, Darling, Wenyon and the recent conclusive findings of Walker we now hold the view that Schaudinn was working with _E. tetragena_ and not with a separate species, so that by the law of priority we must drop the name _E. tetragena_ and accept _E. histolytica_.

=Geographical Distribution.=—Amoebic dysentery seems to be especially prevalent in Indo-China, China and the Philippines, as well as in parts of India. It is also very common in Egypt and Northern Africa. In South America, especially Brazil, it is common, as is also true of the West Indies and Central America. It is an important disease in the Southern States of the United States, as well as in Italy and other parts of Southern Europe. On the whole it is probable that it exists in greater or less degree in most of the tropical and subtropical parts of the world.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—For a long time the authorities in Manila held that it was impracticable to differentiate between a pathogenic and nonpathogenic species, taking the view that the principal factor in the production of dysentery was that of symbiosis between amoebae and suitable bacteria, it having been thought that they observed in cultures of amoebae evidences of both symbiosis and antagonism on the part of amoebae to certain species of bacteria. They furthermore were convinced that pathogenic amoebae could be cultured on a medium of about 1/10th the strength of ordinary nutrient bouillon or agar and that dysentery could be produced by such cultural amoebae. Such views had an important bearing on epidemiology as it was thought that where amoebae could be cultured from green vegetables, fruit, or water supply there was positive evidence of the possibility of infection with amoebic dysentery from such a source.

The above views are no longer entertained and, due to Walker, working in Manila with experiments on man, we now know that cultural amoebae are without effect in the production of dysentery and that there are certainly two well known species of amoebae having man for a host, the one pathogenic, _Entamoeba histolytica_, and the other a harmless commensal, _Entamoeba coli_. Two other species, _Endolimax nana_ and _Iodamoeba bütschlii_, have recently been described but are generally considered nonpathogenic.

Some authorities prefer the generic names _Löschia_ and _Endamoeba_ to _Entamoeba_.

Schaudinn, in 1903, described the pathogenic amoeba, which he named _E. histolytica_, as follows: 1. Distinct, highly refractile and tenacious ectoplasm. He considered this tough external portion of the cytoplasm as the explanation of the ability of the pathogenic amoeba to bore its way into the intestinal submucosa. 2. Eccentric nucleus which was indistinct by reason of little chromatin. 3. Reproduction by peripheral budding in which small aggregations of chromatin reached the periphery of the cytoplasm and, enclosed in a resistant capsule, broke off from the parent amoeba and constituted the infecting stage.

[Illustration: FIG. 59.—_Entamoeba histolytica_. The same living individual drawn at brief intervals while moving. (From Doflein after Hartmann.)]

For the nonpathogenic _E. coli_ he noted: (1) No distinction between a granular endoplasm and refractile ectoplasm; (2) centrally placed and sharply outlined nucleus, rich in chromatin; and (3) encystment with the formation of eight nuclei, which cysts with their nuclei or amoebulae form the infecting stage.

The pseudopodia of _E. histolytica_ are actively projected as long finger-like processes which show the ectoplasm quite distinctly, while the pseudopodia of _E. coli_ are lobose and sluggishly projected and show a uniformly opaque grayish color. In dysenteric stools _E. histolytica_ tends to show contained red cells. _E. coli_ never contains them but instead shows bacteria and food

## particles.

In 1907 Viereck and later Hartmann recognized a pathogenic amoeba with four nuclei in its encysted form, to which was given the name _E. tetragena_.

All authorities now consider that Schaudinn made an error in observation as to the existence of peripheral budding for _E. histolytica_, so that we recognize but two types of encystment, one with a larger cyst and thicker cyst wall, with eight nuclei and an absence of chromidial bodies—_E. coli_—the other, smaller, with a thin cyst wall one to four nuclei and chromidial bodies in the encysted stage, the pathogenic amoeba, _E. histolytica_. Synonym, _E. tetragena_.

In the vegetative stage the human amoebae are best differentiated by the nuclear structure as shown in stained specimens. In _E. coli_ the nucleus is vesicular with a thick nuclear membrane and the chromatin chiefly deposited on the under surface of the nuclear membrane. This chromatin often seems deposited in quadrant aggregations. The karyosome is eccentric.

For the pathogenic amoeba we recognize a _histolytica_ type of nucleus, which is found in dysenteric stools, and a _tetragena_ type, which is found in diarrhoeal or more or less normal stools. Dobell does not recognize this differentiation.

[Illustration: FIG. 60.—The more important intestinal amoebae of man showing nuclear structure when stained. 1. _E. histolytica._ 1(a). _E. histolytica_ cyst. 2. _E coli._ 2(a). _E. coli_ cyst. 3. _E. nana._ 3(a). _E. nana_ cyst. 4. _I. bütschlii._ 4(a). _I. bütschlii_ cyst. (After Dobell.)]

The histolytica nucleus has a thin nuclear membrane and is poor in chromatin while the tetragena nucleus has more chromatin, showing radial projections from the inner surface of the nuclear membrane, and a loose central spherical karyosome, which contains a central chromatin dot or centriole, with a clear halo surrounding it. Dobell states he has not been able to note this centriole.

The preëncysted _E. histolytica_ has a nucleus resembling that of _E. coli_. The smaller size and chromidial bodies are differentiating.

Animal experimentation upon kittens with _E. coli_ by Schaudinn, Craig and Wenyon have been unsuccessful as to production of dysenteric manifestations. On the other hand all of these experimenters produced typical lesions and dysenteric manifestations in kittens injected rectally or fed with material containing pathogenic amoebae.

Wenyon as previously stated produced a liver abscess in one of his experiments.

Darling has been so successful in his experimental work with kittens that he compares the colon of a kitten to a test tube and suggests the procedure of rectal injections of material containing amoebae as a means of differentiating the two human amoebae.

On the other hand Walker was unable to infect kittens and monkeys with material containing pathogenic amoebae and he makes the statement that such failures would indicate the greater susceptibility of man to infection, as he was able to infect 17 out of 20 men with one feeding of such material.

Sellards and Baetjer note that inoculation of kittens per rectum or by feeding dysenteric stools rich in amoebae has resulted in infection in about 50% of experiments.

By inoculating the material directly into the caecum they were able to infect every one of their kittens. They were also able to propagate a strain of amoebae through a series of animals for several months.

The intracaecal inoculations yielded positive results in diagnosis of human amoebiasis when the clinical manifestations were obscure and the amoebae in the discharges so few and atypical as to make such an examination unsatisfactory.

_Other Intestinal Amoebae._—It is a remarkable fact that one of the most common of the intestinal amoebae, _Endolimax nana_, has only recently been reported (Wenyon and O’Conner in 1917). In the examination of the stools of American soldiers Kofoid found it present in 28% of his examinations while _E. coli_ was present in 23% of cases and _E. histolytica_ in 9.3%. In examining 156 British soldiers Dobell noted its presence in 33% of them. The general view is that it is not pathogenic but its great importance is in the possibility of its being mistaken in its cyst form for _E. histolytica_. The living amoeba averages about 8 microns but in stained specimens it is somewhat smaller. In freshly passed faeces the amoeboid motion is sluggish and the nucleus indistinct. This amoeba is best identified by haematoxylin stained specimens when the nucleus shows a measurement of about 2 microns with a large eccentric karyosome which exhibits a variety of form. Unless perfectly fresh material is stained the degenerative changes in the amoebae may give a signet ring appearance of karyosome and ring nucleus. Such an appearance may suggest the limax nucleus. The mature cysts are usually oval, but sometimes round, and contain 4 nuclei, but when newly formed may only have one nucleus. The nucleus is large in the uninucleate form (up to 3 microns) but in the quadrinucleate forms it is about 1.2 microns with a large eccentric mass of chromatin. Chromidial bodies are rarely, if ever, present in these cysts.

_Iodine Cysts._—These bodies which stain a deep brown colour when treated with iodine are now recognized as amoebae and have been named _Iodamoeba bütschlii_. They are most probably nonpathogenic. It is a small amoeba (9 to 13 microns, rarely up to 20 microns) and shows the sluggish movements of _E. coli_. The nucleus is very difficult to discern, thus differing from _E. coli_. In stained specimens it has a vesicular nucleus about 2 microns in diameter with a fairly large central karyosome. The cysts are spherical or oval, often of irregular outline and are about 10 microns in diameter. The nucleus is large and eccentrically placed and has a karyosome which tends to show as a peripherally placed mass. There is almost always present a large glycogen mass in the cyst which stains intensely with iodine.

_Dientamoeba Fragilis_ (Jepps and Dobell 1918).—A rare binucleate amoeba averaging 8-9 microns in size. Nuclei show a fairly large, central granular karyosome and no peripheral chromatin. Strands of linin may be seen radiating from karyosome to nuclear wall. This organism is said to be frequently mistaken for Blastocystis when the vacuoles coalesce leaving a thin ring of cytoplasm. Cysts unknown. Considered nonpathogenic. Recently Kofoid and Swezy reported another species of amoeba parasitic in man, _Councilmania lafleuri_. The adult and cystic stages resemble in many respects the _E. coli_. Adult said to ingest red blood cells. Stated to be pathogenic but that more evidence is needed on this point.

=Human Experiments.=—Recently Walker and Sellards have published a most important paper.

The experiments were made in men who had been under observation for years at Bilibid Prison, whose food was cooked and the water they drank distilled. Moreover, there were complete records of examination for intestinal parasites, including entamoebae. They were under complete control and the existence or possibility of natural infection with amoebae was reduced to a minimum. All the men fed pathogenic amoebae were volunteers and each signed, in his native dialect, an agreement to the conditions of the experiment.

The first series of experiments was with cultural amoebae, in order to refute statements that amoebae cultivated from water or other nonparasitic sources, as well as from dysenteric stools, are capable of living in man parasitically or of producing dysenteric symptoms. Twenty feeding experiments on ten men were made by Walker and Sellards with cultures of amoebae without the development in a single instance of dysentery or the finding of such amoebae in the stools upon microscopical examination. In 13 cases they recovered the amoebae in cultures from the faeces from the first to the sixth day, but never afterwards. They stated definitely that cultural amoebae are nonpathogenic.

The next experiments were with _Entamoeba coli_. In the 20 cases fed with material containing _Entamoeba coli_ there was a uniform failure to recover them culturally and in no instance was dysentery produced. Seventeen became parasitized as the result of a single feeding in from one to eleven days, the entamoebae being found in the stools and persisting in their appearance in the stools for extended periods. They concluded that _Entamoeba coli_ is an obligate parasite, nonpathogenic, and cannot be cultured.

The third series of 20 feedings, carried on by Walker alone, was with _Entamoeba histolytica_. The material was mixed with powdered starch or magnesium oxide and given in gelatin capsules. In these experiments they obtained tetragena cysts in the stools of men fed only motile _Entamoeba histolytica_, and motile _Entamoeba histolytica_ in the stools of men who were fed only tetragena cysts and, finally, an alternation of motile _E. histolytica_ and tetragena cysts in the stools of a man having a recurrent attack of amoebic dysentery.

=Results.=—Seventeen of the men became parasitized after the first feeding; 1 required three feedings, and 2, who did not become parasitized at the first feeding, were held as controls. The average time for parasitization was nine days. Only 4 of the 18 parasitized men developed dysentery, which came on after twenty, fifty-seven, eighty-seven, and ninety-five days, respectively, after the ingestion of the infecting material.

In 4 cases fed with material from acute dysenteric stools or from amoebae-containing pus from liver abscess, and containing motile amoebae, there was no resulting dysentery, the 4 cases of experimental dysentery resulting from feeding of material from normal stools of carriers.

As regards the cases which became parasitized, but did not develop dysentery, it is suggested that the amoebae live as commensals in the intestine of the host and only penetrate the intestinal mucosa and become tissue parasites when there occurs depression of the natural resistance of the host or as the result of some lesion of the intestine. That the pathogenic amoebae are more than harmless commensals, however, is shown by the fact that they alone, and not the nonpathogenic _Entamoeba coli_, are capable of penetrating a possibly damaged intestinal mucosa.

=Epidemiology.=—The chief factor in the spread of amoebic dysentery would seem to be the encysted amoebae in the stools of convalescents, or symptomless carriers, rather than the motile amoebae in dysenteric stools. When such carrier has to do with the preparation of food, he becomes a particular source of danger.

This probably explains the endemic rather than the epidemic characteristics of the spread of amoebic dysentery because, if the innumerable vegetative amoebae in dysenteric stools were equally operative with the more sparsely eliminated cysts, there would be epidemics of amoebic dysentery similar to those of bacillary dysentery. The old idea that water, fruit or vegetables, from which one can isolate amoebae on culture, are sources of infection must be abandoned, as such cultural amoebae are known to have no pathogenic relation to man.

Vegetative amoebae undergo disintegration in a short time after the stool is passed, so that they are probably rarely concerned in amoebic infections but the resisting cysts may be washed from a dried stool into a water supply or even be transported in dust to lodge on unprotected foodstuffs.

Flies may possibly act as transmitting agents. As bearing on the probable importance of such flies as _Musca domestica_ and _Fannia canalicularis_ in transmitting amoebic infections may be noted the findings of Wenyon that the faeces of such flies, as well as _Lucilia_ and _Calliphora_, after feeding on cyst-containing human faeces, teem with such cysts. In a dissection of 1027 house flies caught in Mesopotamia Buxton found ova of parasites of man in 4.09%. The percentage of infection with _E. histolytica_ cysts was O.3%.

PATHOLOGY

Wenyon thinks that the pathogenic amoebae work their way into the tubular glands of the intestines and multiply and subsequently, either by pressure of their pseudopodia or through the disintegrating

## action of some toxic substance elaborated by them, they force their

way into the underlying submucosa. In this location they produce a gelatinous, oedematous necrosis, which shows a marked absence of polymorphonuclears, but a proliferation of connective tissue cells. The process is regenerative rather than inflammatory.

Small hemispherical elevations of the overlying mucosa mark the location of the deeper-lying necrotic process. With the multiplication of the amoebae and the extension of the necrotic process in the submucosa we have thrombi formed in the terminals of the portal vein and possibly in those of the mesenteric arteries, which in the former case may result in emboli being swept up the portal vein to lodge in the liver and form a starting point for a similar necrosing process there or, as the result of interference with the blood supply of the overlying mucosa, cause this to undergo necrosis and be cast off as a slough, leaving an oval or irregular ulcer with deeply undermined edges and a floor formed by the muscular coat. The ulcers may be no larger than a pin’s head or they may be 1 or 2 inches in diameter or by coalescence be still larger. The gelatinous necrosis in the submucosa always extends beyond the limits of the necrosis of the mucosa, thus explaining the undermining. At times the muscular coats of the intestines are involved thus leading to a slough which involves all coats except the serous one. Bacterial infection, with coagulation necrosis of the mucosa overlying the amoebic process, is also responsible for some of the tissue destruction.

The amoebic ulcerations rarely extend above the ileo-caecal valve but may involve the entire large intestine. Rogers and Lafleur found the lesions most often in the caecum and ascending colon, often limited to this area.

The appendix was involved in 7% of the Manila autopsies. Often mild cases may only show lesions in the caecum. When there is a tendency to perforation the omentum will often be drawn over to the location of the threatened perforation. There is often thickening of the intestine in one place with cicatricial contraction of the lumen and thinning in another, so that there is an appearance of great irregularity.

SYMPTOMATOLOGY

The great majority of cases of amoebic dysentery run a chronic course with periods of improvement alternating with recurrences of pains and dysenteric stools. From Walker’s experiments the period of incubation would appear to be from one to three months. The onset in such cases is very insidious and the patient may complain more of diarrhoeal than dysenteric manifestations. Such patients often give a history of passing three or four pultaceous stools daily and complain of tenderness in the region of the caecum or along the course of the large intestine. One may determine some thickening of the colon in a thin subject.

Fever is absent and there are very few of the toxic manifestations which often accompany bacillary dysentery, such as headache, nausea and a mildly delirious state. There is progressive loss of weight and strength with the development of neurasthenic symptoms. The skin becomes dry and earthy and we have the picture of a more or less marked secondary anaemia. It is in these cases that we should be on the lookout for grayish green or grayish brown mucoid masses which can usually be found during an exacerbation. Sloughs of the gelatinous-like necrosis in the submucosa usually contain amoebae.

The X-ray has been utilized to give location of amoebic ulcerations. Bismuth is used for several days prior to taking the photograph and fills the sites of ulceration.

Such cases usually show a moderate leucocytosis in which the percentage of large mononuclears is increased and a very important point is that with tenderness about the caecum, plus a leucocytosis, one may diagnose appendicitis and operate on a normal appendix. Autopsy records however have shown that the appendix is not infrequently invaded by amoebae but in some of these cases, other than finding amoebae in the lumen of the appendix, I have been unable to note any change. Cases of amoebiasis confined to caecum and ascending colon may only show symptoms of slight anaemia.

Besides the more common insidious chronic type we may have amoebic dysentery setting in quite acutely with severe griping and frequent scanty grayish green to reddish brown mucoid stools.

Such cases may show anorexia and nausea with some fever but there is not present the manifestations of toxemia one associates with a severe case of bacillary dysentery in the tropics.

Very confusing cases are those in which a bacillary dysentery sets in upon an amoebic one and this possibility should always be thought of when a severe bacillary dysentery does not respond to serum therapy or an amoebic one to emetine.

Gangrenous lesions may occur in amoebic dysentery although more common in bacillary infections. Such cases will show extreme prostration and even give the clinical picture of cholera.

=Complications.=—By far the most important and serious complication of amoebic dysentery is liver abscess, which occurs in about 20% of cases. This condition is treated of separately. Besides liver abscess quite a number of cases of amoebic abscess of the brain have been reported, 26 such cases occurring in Egypt alone. These abscesses almost always occur in those cases which have developed liver abscess and may appear after the liver abscess has healed.

The pus of such abscesses is viscid and blood-tinged, resembling liver abscess pus. The amoebae are found in the abscess wall. The symptoms are those of brain tumor, meningitis not occurring. Necrotic processes of skin and muscles have also been reported in which amoebae have been found.

Perforation of the large intestine is not rare, Strong having noted 12 perforations in 77 autopsies. These usually occur in the region of the sigmoid flexure.

Adhesions are common complications of amoebic dysentery.

DIAGNOSIS

=Clinical Diagnosis.=—In the clinical diagnosis it is well to remember that many cases of chronic tropical diarrhoeas are really due to amoebic ulcerations of the intestines.

We can as a rule differentiate bacillary from amoebic dysentery by the more sudden and acute onset of the former together with fever and other evidences of toxaemia. The pulse rate is more rapid in bacillary than amoebic dysentery. Again the number of stools in bacillary dysentery is usually greater and the amount of each stool less in quantity. The stool of bacillary dysentery is of a milky whiteness from the large number of pus cells or composed of gelatinous, reddish mucus, while that of amoebic dysentery is tinged with disintegrated blood giving it a grayish-green or brown color. The mucopurulent mass in bacillary dysentery may be flecked or streaked with blood. The therapeutic results following emetine injections are of value in diagnosis.

Gangrenous types of dysentery are similar whether due to bacillary or amoebic infection. Chronic dysentery of bacillary origin is much like amoebic dysentery clinically.

Manson-Bahr and Gregg recommend the use of the sigmoidoscope in the diagnosis of chronic amoebic ulcerations. In the evening the patient takes ½ ounce of castor oil and the next morning a soap and water enema is given followed by 15 minims of laudanum. The patient is put in the lithotomy position. No anaesthetic is used. The pain in introducing the instrument is greater in chronic bacillary ulceration cases than in amoebic ones. Scrapings can be made for microscopic examinations. Nisbet has reported the diagnosis of a case of balantidial ulceration by use of the sigmoidoscope.

=Laboratory Diagnosis.=—The mucoid mass of amoebic dysentery is often brownish. The pathogenic amoeba shows active finger-like processes and in acute attacks often shows contained red cells. In the fresh specimen of the milky mucopurulent mass of bacillary dysentery one observes large numbers of pus cells and particularly very large phagocytic cells which greatly resemble amoebae. Upon staining with Gram’s stain one may find numerous Gram-negative bacilli in the cytoplasm of this cell.

These large cells which resemble amoebae are often vacuolated, thus intensifying the similarity. They are nonmotile, however, and do not show the small ring nucleus which is so characteristic of the vegetative human amoebae. The nucleus of the confusing cells is also larger, approximating one-fourth the size of the cell.

Bacillary dysentery stools show an absence of Charcot-Leyden crystals which are often present with amoebic stools.

For bringing out the nuclear characteristics of human amoebae Walker recommends fixation of thin moist smears in Giemsa’s sublimate alcohol (absolute alcohol 1 part, sat. aq. sol. bichloride 2 parts) for 10 to 15 minutes. These smears are then well washed with water and stained with alum haematoxylin for five minutes. The nuclear characteristics are noted under etiology. In such staining the preparations, which are best made on cover-slips, should never be allowed to become dry.

An excellent iron haematoxylin method is that of Rosenbusch:

Rapidly smear out with a toothpick a small particle of faeces or other material containing protozoa and, while still moist, fix by Giemsa’s method and, after getting rid of the mercury with iodine solution followed by 95% alcohol, treat smears with a 3.5% solution of iron-alum in distilled water for one-half hour or overnight, then wash thoroughly in distilled water.

Then stain from five to twenty minutes in the following haematoxylin stain: (1) 1% solution of haematoxylin in 95% alcohol. It takes at least ten days to ripen. (2) A saturated solution of lithium carbonate. Add to 10 cc. of the haematoxylin solution 5 to 6 drops of the lithium carbonate one. Next wash well and differentiate with about 1% solution of the iron-alum. Again wash in water, pass through alcohols to xylol and mount in balsam. With vegetative amoebae I have obtained beautiful results with vital staining which can best be done by tinging the faeces emulsion with a 1% aqueous solution of neutral red. I have also had good results by emulsifying the faeces in a drop of 1 or 2% formalin and then adding a drop of 2% acetic acid. The mixture is then tinged with either neutral red or methyl green.

For distinguishing the encysted form of _Entamoeba coli_ one can obtain excellent results by emulsifying the faeces in Gram’s iodine solution. Owing to the glycogenic reaction given by _E. coli_, the round amoeba, with its 8 nuclei stands out very distinctly.

For diagnosing the 4-nucleated cyst of the pathogenic amoeba one gets better results with haematoxylin as this brings out not only the 4 nuclei but the chromidial bodies as well. It was formerly customary to recommend the administration of salts prior to examining for amoebae. Walker warns that such a procedure gives us amoebae which are difficult to differentiate, the nuclear characteristics of _E. coli_ and the tetragena nucleus of _E. histolytica_ being much alike as they both contain much chromatin. In a dysenteric stool the histolytica type of nucleus, containing but little chromatin, does not resemble the nucleus of _E. coli_.

He prefers the examination of formed stools obtained without a purgative.

DIFFERENTIATING CHARACTERISTICS OF PATHOGENIC AMOEBAE (AFTER DOBELL AND O’CONNOR). MOTILE STAGE

-----+----------------+-----------------+----------------+---------------- | Entamoeba | Entamoeba coli | Endolimax nana | Iodamoeba | histolytica | | | bütschlii -----+----------------+-----------------+----------------+---------------- Size | 20-30µ | 20-30µ | 6-12µ | 9-13µ -----+----------------+-----------------+----------------+---------------- Moti-|Very character- |Usually sluggish |Slow progressive|Slight motility lity| istic. Flows in| but may show | movement when | with movements | almost straight| considerable | freshly passed.| similar to | line across | activity when | Later slight | E. coli. | field. Later | freshly passed. | changes of | Quickly | becomes less |The movement | shape. Soon | degenerates | active pushing | consists chiefly| rounds and | and dies. | out a few, | in changes of | dies. | | large blunt, | shape without | | | blade-like | progression. | | | pseudopodia | | | | which are per- | | | | fectly hyaline | | | | being composed | | | | entirely of | | | | ectoplasm. | | | -----+----------------+-----------------+----------------+---------------- Cyto-|Endoplasm finely|Endoplasm had a |Endoplasm finely|Endoplasm finely plasm| granular and | bulky granular | granular with | granular and | uniform in | appearance and | numerous minute| homogeneous. | appearance. May| contains numer- | food vacuoles |Usually contains | contain red | ous food | containing | numerous food | blood cells but| vacuoles charged| bacteria. |vacuoles charged | bacteria | with bacteria |No sharp line as| with minute | probably never | and vegetable | a rule between | bacteria. Cysts | seen in normal | débris. Never | the endoplasm | of this amoeba | individuals. | contains red | and ectoplasm. | have previously |Ectoplasm clear | blood cells. No | | been described | and well | sharp line be- | | been described | developed. | tween endoplasm | | as “iodine | | and ectoplasm. | | cysts.” -----+----------------+-----------------+----------------+---------------- Nuc- |4-7µ. A delicate| 4-7µ. |1-3µ. Vesicular |2-3.5µ. Small leus | vesicle incon- | Distinguishable.| with delicate | vesicle with | spicuous or | Stained shows | membrane. | distinct mem- | invisible. | larger beads of |Stained shows | brane. Stained |Stained shows | chromatin lining| wall free from | shows wall free | fine beads of | wall. Karyosome | chromatin. All | from chromatin | chromatin | spherical, | chromatin cont-| as a rule. | lining wall. | eccentric and | ained in large,|Typically |Karyosome small,| larger than | irregular, | chromatin cont- | spherical and | that of | eccentric | ained in large, | central. | E. histolytica. | karyosome. | central | | |Variations in | spherical | | | shape of | karyosome. Zone | | | karyosome | between nuclear | | | characteristic.| wall and | | | | karyosome | | | | filled with | | | | single layer of | | | |small granules. -----+----------------+-----------------+----------------+----------------

(Part 1 of 2) ----------------------------------------------------------------- ENCYSTED STAGE -----------+------------------------+---------------------------+ | Entamoeba histolytica | Entamoeba coli | -----------+------------------------+---------------------------+ Size | 7-15µ | 15-20µ | -----------+------------------------+---------------------------+ Shape | Round. | Round. | -----------+------------------------+---------------------------+ Wall | Thin. | Thicker than E. | | | histolytica. | -----------+------------------------+---------------------------+ Nuclei |Typically shows four |Typically shows eight | |nuclei. May show one to |nuclei. May show one to | |four. Nuclei at rest |twenty. Structurally | |structurally similar to |similar to adult nucleus. | |that of adult nucleus. | | | | | -----------+------------------------+---------------------------+ Chromatoids|Large chromatoids |Large chromatoids may be | |common. |present but usually absent.| -----------+------------------------+---------------------------+ Glycogen |Diffuse but not |Relatively abundant in the | |abundant. |early stages. Scanty or | | |absent in mature cysts. | -----------+------------------------+---------------------------+

(Part 2 of 2) ----------------------------------------------------------------- ENCYSTED STAGE -----------+---------------------------+------------------------- | Endolimax nana | Iodamoeba bütschlii -----------+---------------------------+------------------------- Size | 7-9µ | 9-12µ -----------+---------------------------+------------------------- Shape | Usually oval. | More or less rounded. -----------+---------------------------+------------------------- Wall | Thin. | Relatively thick. | | -----------+---------------------------+------------------------- Nuclei |Very small. May show from |One relatively larger |one to four nuclei. Rarely |nucleus. Differs struct- |eight. Structurally similar|urally from the adult |to adult type of nucleus. |type in that the granules | |in the clear zone become | |massed at one pole giving | |an eccentric karyosome. -----------+---------------------------+------------------------- Chromatoids|Absent. |Absent. | | -----------+---------------------------+------------------------- Glycogen |Rarely present. |Dense glycogen mass is | |characteristic. | | -----------+---------------------------+-------------------------

Walker also notes the advantages of examining a specimen with a ⅔ inch objective as encysted amoebae are easily picked up. In opposition to the usual recommendation of text-books to report only on motile amoebae, he recommends the making of a differential diagnosis on nonmotile encysted forms. This however is now generally accepted by experienced workers as true.

The preëncysted _E. histolytica_ has a nucleus much resembling that of _E. coli_. The presence of the same chromidial bodies one notes in the cysts is an aid in recognizing this stage. The 4 nuclei of the cysts are much smaller than the nucleus of the preëncysted or vegetative stage.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—The main consideration is a knowledge of the importance of the carrier problem. The stools of all persons preparing food in localities where amoebic dysentery is prevalent should therefore be examined for the 4-nucleated cyst of the pathogenic amoeba. It must be remembered that while emetine controls the dysenteric manifestations of amoebiasis it does not seem to cause the disappearance of the parasite, so that patients who have had amoebic dysentery tend to become carriers.

As a matter of fact there is a question as to the possibility of the emetine treatment acting as a factor for the increase of carriers.

Vedder considers that while emetine will kill the amoebae deeply placed in the submucosa it has no effect on the more superficially located cysts and suggests that it may be possible to treat carriers by colonic irrigations with quinine or silver salts.

Emetine bismuth iodide has recently been highly recommended as our best agent for eradication of _E. histolytica_ cysts of carriers.

=Treatment.=—The emetine treatment may now be considered as the specific one for amoebic dysentery. In Brazilian ipecac about 72% of the total alkaloids is emetine, so that it is better than Carthagena ipecac which contains only about 40% of emetine. Emetine was recommended for dysentery as long ago as 1817, but owing to the impossibility of differentiating between bacillary and amoebic dysentery, until recently, this method of treatment was little advocated.

In 1910 Vedder found that emetine was practically without power in its action on dysentery bacilli but that it would kill amoebae, even in dilutions of 1 to 100,000. He also found that deëmetized ipecac was quite inert in its action on amoebae.

In 1912, Rogers, who had for years been an ardent advocate of the ipecac treatment of amoebiasis, took up the treatment of amoebic dysentery and its liver complications with emetine. Reports from all over the world now attest the value of this drug in the treatment of the acute manifestations of amoebiasis but unfortunately note the inefficacy of this treatment on the encysted forms of amoebae.

It is usual to give from ⅓ to ⅔ grain of emetine hydrochloride, dissolved in sterile saline, by hypodermic injection into the subcutaneous tissues. Some now give as high as 1 grain daily for about ten days, but Vedder prefers ⅓ grain repeated 3 times daily. In these doses there is practically no nausea.

It was found by Baermann and Heinemann that subcutaneous injections of from 2 to 2½ grains daily caused indisposition and anorexia. The subcutaneous injections are less painful than the intramuscular ones.

Rogers has used emetine intravenously in doses of 1 grain without bad effect.

Vedder calls attention to the fact that the minimal fatal dose of emetine is several times less when administered to rabbits intravenously than when given subcutaneously, so that after seeing rabbits die with what was apparently centric paralysis immediately after intravenous doses of comparatively small amounts of emetine hydrochloride he would hesitate before administering 1 grain intravenously in a human case.

Levy and Rowntree think emetine should not be given intravenously except in extreme cases. Among ill effects of emetine they note peripheral neuritis. Kilgore has reported such cases where even wrist-drop was seen.

Low has treated cases successfully with keratin-coated tabloids of emetine hydrochloride, giving ½ grain every night. Vedder has not obtained satisfactory results with the drug by mouth.

Rogers considers that 15 grains of emetine is the fatal dose for an adult man and as there is possibly a cumulative action it would seem safer to continue the drug only for ten days and then later repeat the course of hypodermics. Of course emetine cannot cure the ulcerative lesions of amoebic colitis and as bacillary infections are apt to set in when damaged tissues are present and, as such infections do not yield to emetine, one must be prepared for failure in treatment of symptoms in such cases.

Recognizing the great importance of immediate treatment to prevent extension of the ulcerative process, as well as against abscess, the rule was adopted in the medical care of the English forces, in the Mediterranean, to give emetine so soon as a case of dysentery was seen, not waiting for a determination of etiology. The treatment ordered was 1 grain of emetine, hypodermically, every day for ten days, or ½ grain morning and evening for ten days. There must not be any intermission of a single day.

Before the introduction of emetine the usual treatment was with ipecac.

It was customary to give 20 to 50 grains of powdered ipecac in capsule, cachet or keratin-coated pills to a patient with an empty stomach and who had had a dose of morphine or laudanum about 20 minutes before the time for giving the ipecac. The salol-coated ipecac pills are generally used in America. The patient should be in bed and should try to yield to the soporific influences of the opiate. Any flow of saliva should be removed with gauze as its swallowing would provoke nausea. Some use a mustard poultice to the epigastrium. It is remarkable the change which this treatment will effect in the number and character of the stools.

Many now think it advisable to give emetine hypodermically to reach the amoebae deeply seated and, at the same time, to give ipecac by mouth to destroy more superficially situated ones, or those in the lumen of the gut. Alcresta ipecac has been recommended as a good method of giving ipecac by mouth.

We do not have now the same confidence in emetine injections that we formerly entertained. In Egypt the combination of emetine injections with ½ grain keratin coated tablets of emetine by mouth seemed to give better results in the more chronic stages of amoebiasis.

Very favorable reports have come from the use of emetine bismuthous iodide. This drug is given by mouth in doses not exceeding 3 grains in a day. It is put up in gelatine capsules and a course of treatment is one 3 grain capsule each night for 12 nights. It is supposed that there is no action on the drug in the stomach as it is insoluble in dilute acid but as a matter of fact nausea and vomiting frequently occur and slight purging is common after its administration. During the twelve-day course of treatment the patient should remain in bed and be given a milk diet.

We have recently had success with the administration of ipecac by the duodenal tube and it might be that bismuthous emetine iodide could be given in the same way.

Ross thinks that the flushing action of salines, thus washing away amoebae and necrotic material, is of advantage in amoebic as well as in bacillary dysentery. He also thinks liquid petrolatum of value. Some advise the bismuth treatment recommended by Deeks of giving a large teaspoonful of bismuth subnitrate, in a glass of water, 3 or 4 times during the day.

A decoction made by boiling for 15 minutes one teaspoonful of powdered chaparro in 8 ounces of water and given one-half hour before each meal has been reported on favorably. The powdered roots, stems and leaves of “Chaparro amargosa” are used. This is a plant of Texas and is named _Castela nicholsoni_. A decoction of about one-half strength of that taken by mouth is recommended for enemata. Simaruba bark is recommended by some practitioners. Its action is similar to chaparro. Benzyl benzoate is recommended for the pains and tenesmus of amoebic dysentery as well as bacillary dysentery. Twenty drops of the 20% alcoholic solution are given three times daily.

Many drugs have been recommended for colon irrigation of which the favorite is probably quinine muriate in dilution of 1 to 1000 or 1 to 2500. Inject 2 or 3 pints slowly by gravity. Protargol in 1 to 500 solution is better than silver nitrate in 1 to 2000. Emetine enemata do not seem to be of much value.

In very serious cases, particularly when gangrenous change in the mucosa may be present, the operation of appendicostomy seems indicated, following which a catheter is inserted and the large intestine irrigated with a 1% solution of bicarbonate of soda to wash away the mucus and later with a boracic acid solution of 1 to 125 or 1 to 10,000 of potassium permanganate.

In a discussion as to certain surgical considerations in connection with appendicostomy Muller notes that the right rectus incision is to be avoided on account of danger of gangrene from pressure of rectus on the stitched-up appendix. He also thinks that appendicostomy is much safer than caecostomy on account of the frequent thinning of the walls of the caecum. For irrigation he prefers a 1 to 500 solution of collargol.

In treating dysentery cases rest in bed and the use of a nonirritating diet are advisable.

The return of the increase of large mononuclears to normal may be used as an index to cure.

Walker and Emrich have recently reported success in treatment of cyst carriers by giving oil of chenopodium in 3 hourly doses of 16 minims, followed by castor oil and preceded by a dose of magnesium sulphate.

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