Biliary Fever in the Horse

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BILIARY FEVER IN THE HORSE. By ALEXANDER EDINGTON, M.D., F.R.S.E., Director of the Government BacteriQlogical Institute, Grahamstown, Cape Colony. THE malady in horses to which the above name is commonly applied in the Cape Colony would seem to have existed for very many years. As my duties necessitate my presence in the laboratory, I am compelled to fall back, for a description, on what has been stated in regard to it by variOl.js veterinary surgeons. At the same time, I may state that, in the course of inoculations whidi I have made into horses, CODditions have. been produced which are not unlike those described as pertaining to biliary fever. Before, however, describing these experiments, it may be of service to quote the published observations made by veterinary surgeons in the field. In 1883 my colleague, Mr D. Hutcheon, the Colonial Veterinary Surgeon, described it in the following terms: "The disease to which I refer is very clearly described by Mr \Viltshire, Colonial Veterinary Surgeon for Natal, in his Report on Anthrax in the Natal Almanack for 1883. He terms it anthrax fever. Now, although I am inclined to differ in opinion with Mr Wiltshire respecting the nature of the disease, yet the symptoms of it as described by him correspond exactly with symptoms of the disease attributed to bots in this Colony. The following are the symptoms of the disease to which I refer. At first the horse appears dull, lacking his ordinary energy, and when feeding manifests a disrelish for his food." Mr Hutcheon then refers to the fact that the lining membrane of the eye-lids, the conjunctiva, is of a dull brownish colour," marked with a few dark spots or streaks," which, as Mr Hutcheon remarked, "often get larger, and in bad cases give a deep claret colour to the whole conjunctival membrane." He then states that the animal gets drowsy, stands or walks with head depressed, and eats or picks in a listless manner. He may, however, "appear uneasy, paws with his forefeet, bites at his sides, rubs himself against other horses, and manifests symptoms of abdominal irritation. This is succeeded by delirium. The animal will wander about the veldt in a heedless and stupid manner . . . the chances are that he will tumble over some krantz or into a deep sluit. " In most cases the action of the bowels is arrested . .. It would appear, however, that constipation is by no means a constant symptom of the disease." Mr Hutcheon states" that diarrhcea was a constant accompaniment of it in 1879. The urine is generally high-coloured; in one case that I saw it was as dark asclaret.'i Mr Hutcheon, in describing the post-mortem appearances, states that the symptoms may vary a little, "depending a good deal on whether the horse has suffered from any previous disease." He then mentions the following as among the conditions found: "The abdomen generally contains a variable quantity of a brownish fluid; liver enlarged and congested . .. The spleen is generally enlarged and somewhat pulpy. The mucous lining of the upper portion of the small intestine

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is often congested and contains a quantity of viscid mucus . .. A small quantity of a straw-coloured fluid is generally found in the chest and heart bag; the lungs are more or less congested, and the interlobular tissue contains a variable quantity of a yellow, jelly-looking serum, exactly similar to what is found in great abundance in the real horse-sickness." Dr Theiler, in the Transvaal Agricultural Journal for April 1903, in the course of an article on biliary fever, emphasises the observation of the yellow staining of all visible mucous membranes (jaundice), and adds that this continues for a considerable time and only disappears gradually. "The animal's temperature rises considerably, and is then accompanied by a very marked depression. Head and ears hang down and the eyes close. At this stage the symptoms may increase very suddenly and become alarming in their intensity. Death ensues, preceded by coma." Among the conditions found on post-mortem examination are," a brownish-yellow discoloration of the flesh . .. The liver is increased in size and shows discoloration. The spleen, with very few exceptions, is considerably enlarged . .. The pulp is dark brown in colour, and usually softened. All the lymphatic glands are more or less enlarged and of an cedematous character. The kidneys are pale and often enlarged. The lungs are pale and with a few exceptions normal. The heart is usually distinctly attacked, its flesh having a boiled appearance and very friable on the outside and inside lining; blood spots and blood streaks may frequently be observed. The heart ventricles are full of coagulated blood." In the description by Mr Hutcheon it is stated that a serous exudation is found in the chest cavity and in the heart bag, and that a jelly-like exudation is found in the interlobular tissue. For the purpose of differentiation these facts are of the utmost importance, but in Dr Theiler's description they do not occur. He states that he has failed to produce the disease by inoculating sound animals, and that doses of 50 to 100 cc. injected into the jugular vein has always failed to produce any effect. He argues that either it only occurs in imported animals or the parasite is obliged" to pass through a phase of development outside the body of the horse, in the insect, before it is able to infect a fresh animal." In the Report by Colonel Joshua Nunn, A.V.D., now DeputyDirector-General of the I mperial Veterinary Department, dated 16th October 1888, he states: "Four forms of horse-sickness have come under my observation, viz. : the 'acute' or 'pulmonary'; 'blue tongue' ; 'dikkop,' which is the Dutch for a big or swollen head, and the' subacute,' or what Mr Rutherford calls the bilious form." After describing the form er three, he states: "The subacute or bilious form comes on gradually, the animal being off his feed . . . The bowels are constipated, and f
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serum." He regards such swellings as of evil omen, and states that such cases usually terminate fata1ly. In my Annual Reports for I90r and 1902, I have given the details of a long investigation made by me into this subject, and I now propose, in alluding to these, to bring forward additional observations and conclusions which have been made during the year. (1.) I have produced the disease by inoculation in more than forty horses. This fact abundantly testifies to the fact that the disease can be transmitted by inoculation. (2.) I have produced it in animals born and bred in this district, thus showing that local horses are liable to the malady. (3.) The majority of the deaths in the" protection camps" of this area occurred among animals from the Karroo. This suggests that Karoo animals are more liable to infection than coast-bred animals. (4.) I have found that coast-bred animals are more or less protected. (5.) The evidence I propose to bring forward will serve to show that many, if not most, animals running near the coast owe their seeming insusceptibility to the fact that they are already infected. My first experience with this disease arose when I inoculated locally bred animals with the blood of a donkey that had been inoculated with horse-sickness blood ten days previously. Since then my former reports showed that the disease has been readily produced in clean horses by the inoculation of the blood of "salted" horses which had been inoculated with horse-sickness blood ten days previously. At a later date I found that the blood of the same " salted" horse would still produce the fever when drawn one hundred days after inoculation with horse-sickness blood. Still later I determined that the blood of an "unsalted" horse could induce fever if the animal had recently been inoculated with the blood of the salted horse. In this case, however, the fever produced was not so severe as that obtained from a " salted" horse that had been recently reinoculated. I now desired to determine whether the blood of sound but " unsalted" animals, which had been running in the veldt of this district for some time, could convey infection. For this purpose I borrowed a horse which had been running in the veldt at night and working during the day. By means of a hypodermic needle some of the blood was drawn from the jugular vein into a bottle containing a very small quantity of sterile neutral citrate of potash. Twenty cubic centimetres of this blood were injected subcutaneously into two clean horses, which I had received from the military authorities, and which had been under observation for several weeks after their arrival, previous to this inoculation. In both animals about twenty-four hours after the temperature had risen I found parasites in the blood, and they continued in varying degrees to be present during all the febrile stages. This experiment, therefore, fully justifies me in concluding that horses running in these areas are more or less generally infected with this disease. As a corollary to the foregoing, and also by way of determining if I could raise the virulence, the following experiment was undertaken. I borrowed another horse in Grahamstown, and in the same

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manner as before drew some blood. Forty cc. of this was injected subcutaneously into a clean horse (No.3) on the 23rd December. A rise of temperature was seen on the seventh day. On the eighth day after the first inoculation 20 cc. of the same blood were injected subcutaneously and a similar amount intravenously. On the 5th and 6th January, being the fourteenth and fifteenth days after the inoculation of horse NO.3, I bled it, and with the blood inoculated horse NO.4 by injecting 20 cc. intravenously on each day. Some slight fever was observed on the third day, which gradually increased, with very little remission. On the tenth day a further inoculation was made by injecting 20 cc. of the fresh blood of hcrse NO.3 subcutaneously. On the following day the temperature fell, but rose again on the twelfth day. The animal died on the thirteenth day. During the period when the temperature was highest there was a distinct hcematuria, the urine being of a deep port-wine colour. On making a post-mortem examination immediately after death I found the following conditions: As the animal lay on the table with the head and neck hanging down, a small amount of yellow gelatinous serous exudation ran from the nose. This'material most evidently came from the trachea, in which some also was found. On dissecting the skin over the neck a small amount of gelatinous redema was seen to lie around and to follow the course of the great vessels in the neck. On opening the chest almost half a gallon of dark yellow serous exudation was found. Both lungs were slightly congested, and some yellow gelatinous exudation was found under the pleural membrane covering the lungs and also in the interlobular tissue. The interlobular exudation was best seen in the left lung, and particularly towards the free edges. Along the posterior aorta a considerable amount of gelatinous redema was found, and numerous petechice were seen lying somewhat superficially. About four ounces of yellow serous exudation was found in the pericardium. The outside of the heart showed numerous petechiae over the left ventricle and auricle, while in a lesser degree they were found over the right side. The base of the heart over the right ventricle was occupied by a large gelatinous redema. The interventricular groove was occupied by the same redema, while the blood vessels in this situation were infiltrated in the outer coat, appearing as white opaque lines. The spleen was enlarged, somewhat softer than normal on section, and covered with discrete petechice. The kidneys were pale and contained a small amount of gelatinous redema in the pelvis. The liver looked as if boiled. There was evidence of old standing disease in the f(lrm of chronic venous congestion, while small discrete areas of necrosis were found throughout the organ. Taking the post-mortem examination as a whole, the resemblance to horse-sickness was exceedingly great. The cedema of the pelvis of the kidney and the condition of the spleen are some''''hat in excess of what one usually finds in horse-sickness, yet in some cases of that disease I have found in my experiments conditions exactly similar. In my Report for 1898 I showed that when a dose of serum, taken from a horse which had recovered from horse-sickness and been subsequently reinoculated on several occasions, was given to a horse in which the fever of horse-sickness was just beginning to appear or had already set in, a hcematuria appeared about forty-eight hours later.

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After such a condition had appeared the animal died in less than forty-eight hours. The post-mortem examinations in these ,cases were absolutely identical with that just described. The serum then used was prepared in the following manner. Horses which had been" salted" to horse-sickness were reinoculated periodically with increasing doses of virulent horse-sickness blood until doses of 200 cc. could be given without producing any evil effect. Some little time thereafter these animals were bled, and the serum was then filtered through a Berkefeld filter (which keeps back all organisms which are visible under the microscope), and thereafter 0'5 per cent of carbolic acid was added to it and the whole filtered again. The serum was frequently used some weeks after having been made, and this fact, taken in conjunction with the mode of preparation, completely precludes the idea that it could have been the means of conveying a gross malarial infection. The interest in the case, however, lay in the remarkable fact that the serum possessed no power to produce harm in healthy animals. \V'hen given, however, to animals suffering from horse-sickness, it produced the remarkable h~molysis to which I have alluded. It is noteworthy that Dr Koch found the serum from recovered Rhodesian redwater cattle to possess this same remarkable property. As already stated, I considered the condition I produced experimentally as a malarial form of horse - sickness, and that it agrees with Colonel Nunn's description of the" bilious form of horsesickness." In the cases where I produced it by inoculating with the blood of healthy horses, I considered it as identical with the so-called biliary fever. When these latter animals recovered they were then inoculated with the blood of a recently reinoculated" salted" horse. Since no fever resulted therefrom, I am disposed to consider the conditions produced as identical, and that the condition denominated by me as the malarial form of horse-sickness is the same as that known as biliary fever.l In my Report for 1902 details of experiments are given which strongly support my view that the malarial condition is one phase of horse-sickness. If, however, a critical investigation were required to prove the matter absolutely, it would be necessary to carry these out in a country where the natural infection does not obtain, so as to eliminate any fallacy from any occult malaria.

Protective Inoculation against so-called Biliary rever. During my experiments I have attempted the production of the fever in fifty horses, of which the results may be summarised as follows : (I.) Sixteen prQved absolutely insusceptible. (2.) Twenty - four showed high fever, and were thereafter insusceptible. (3.) Three showed slight fever, and were thereafter insusceptible. (4.) Three showed slight fever, and after a second inoculation the fever increased. (5.) Two showed no fever until the second inoculation. I

"Journal of Hygiene," Vol. IV., No.1, 1H04

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(6.) Two showed slight fever, which was continued after the second inoculation. From the above, therefore, it is see!) that as a rule one attack renders the animal thereafter insusceptible. Where second attacks are seen to have arisen in the foregoing experiments, it deserves to be noted that the second inoculations were made within a month of the first, and that experience has shown that the malarial fever is not always completely ended by that time. Under such circumstances, and seeing that, as a rule, no serious illness follows the inoculated disease, I can confidently recommend inoculation to be practised in such areas as the disease commonly occurs in. For this purpose I propose to supply blood drawn from properly prepared animals and at a moderate cost. I would recommend a dose of twenty cubic centimetres to be injected subcutaneously, and the animal thereafter permitted to rest for a month before being worked. Farmers should note that the blood must be used as soon as possible, and that the animal must be stabled during its month's rest.

IMPLANTATION OF TISSUE AND ITS RELATION TO CANCER/

By EDWARD H. NICHOLS, M.D., (Assisting Visiting Surgeon, the Boston City Hospital; Assistant Professor of Surgical Pathology, the Harvard Medical School.) (From the Surgical Laboratory of the Harvard Medical School.) BELOW are presented the results of a series of implantations of tissue in sixty-two animals. For implantation both adult and fcetal tissues were used. The implanted tissues were chiefly epithelial, although some mesenchymal tissues were used. The experiments were undertaken to see if epithelial or mesenchymal tissues, set free from their normal environment, could acquire a power of unlimited growth and give rise to the formation of metastases. . In some cases the implanted tissues proliferated, maintained their vitality, and produced nodules analogous to dermoid cysts or teratomata, and some of the nodules were of large size. In no case was any nodule produced with unlimited growth or the formation of local or glandular metastases. This line of experimentation was undertaken because, from a previous study of the inclusions in cancer cells, from experiments with the so-called" cancer yeasts," from a study of various lesions claimed to be due to protozoic infection, and from a study of the literature on the infectiousness of cancer, it was believed that there was less evidence that cancer was due to a parasite than that it was due to some inherent character of the epithelial cells. A critical review of the reasons which led to this belief follows. The investigators 0'[ the subject of the origin of cancer and other 1

Reprinted from the " Journal of Medical Research " Jan. 1905.