human and bovine tuberculosis

7
37 2 ABSTRACTS AND REPORT. mucous membrane of the small intestine, congestion of the kidneys with slight nephritis, spleen packed with small tumours about the size of a pea, liver normal. There was a small amount of blood-tinged serous fluid in the pleural sacs; pleura congested but lungs and trachea normal. At the base of the heart there was an irregular mass of tumours, the weight of which was estimated to be 9 or 10 kilogrammes. Some of the glands at the entrance to the chest showed tumours about the size of a hen's egg, from which a milky juice escaped on section; others were healthy. The heart was hypertrophied. The other organs (nasal cavities, larynx, etc.) were normal. Structun of the GrozlIths.- The neoplasms were enclosed in fairly thick capsules of connective tissue, the outer surface showing prominences that varied in size from a nut to an apple. When cut open they were seen to contain a considerable amount of fluid. The cut surface was yellowish-white in colour and had a lobulated appearance, with streaks in places. The lobules were clearly marked off by strands of connective tissue derived from the capsule. Microscopical examination showed a considerable amount of connective-tissue matrix surrounding groups of cells of various shapes and sizes. The peripheral groups were narrow, as if compressed by the growth of the tumour. The matrix was rich in blood vessels. There was a considerable amount of "cancer juice" saturating the groups of cells. In some places the cells were disposed in a stratified manner around the periphery of the groups. The origin of the primary tumour is doubtful; possibly it arose from the epithelial cells of the intestine, considering the number of connections it had with that organ. Generalisation appeared to have taken place via the lymphatic system, as is usual with epithelial tumours. (Gay and Roquet, Bulletin et Memoires, Soci!:te der Sciences Vf:tf:rillaires de Lyon, NO.5, p. 363, 1908.) HUMAN AND BOVINE TUBERCULOSIS} KOCH'S paper (see p. 303) was followed 'by a number of communications from Smith, Boston; Woodhead, Cambridge; Arloing" Lyons; Fibiger, Copenhagen; Raw, Liverpool; Ravenel, Madison, Wis., in which endea v urs were made to shake Koch's standpoint. A real discussion did not take place in this session. To make a discussion successful a special session was held two days later, on the proposal of Koch, before an invited audience, about fifty gentlemen having attended. Biggs, New York, was in the chair. Koch introduced the proceedings with the following remarks :- "A great difference of views seems to prevail with regard to the question of human and bovine tuberculosis, and I am glad that we have an occasion to enter into the subject in detail. I trust we may be able to prepare an understanding in the matter, although I do not believe that perfect agreement of the various views will be obtainable, as each author, having taking much time to build up his opinion, will be inclined to cling to it until his life's end. What mostly impedes an understanding is the difference of languages and the necessity to translate the remarks of the various orators into several languages, so that a possibility of incorrect interpretation can arise. I would, therefore, urgently beg the various gentlemen to make their remarks as concise as possible, and to keep strictly to the subject without any superfluous additions. "I would specially propose two points for discussion, the first referring to the remarks of Mr Fibil'er, who contends that bovine tuberculosis is very 1 Report of a discURsion at the International Congress, 'VaRhington, Septemher 1908.

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Page 1: Human and Bovine Tuberculosis

37 2 ABSTRACTS AND REPORT.

mucous membrane of the small intestine, congestion of the kidneys with slight nephritis, spleen packed with small tumours about the size of a pea, liver normal.

There was a small amount of blood-tinged serous fluid in the pleural sacs; pleura congested but lungs and trachea normal. At the base of the heart there was an irregular mass of tumours, the weight of which was estimated to be 9 or 10 kilogrammes. Some of the glands at the entrance to the chest showed tumours about the size of a hen's egg, from which a milky juice escaped on section; others were healthy. The heart was hypertrophied. The other organs (nasal cavities, larynx, etc.) were normal.

Structun of the GrozlIths.-The neoplasms were enclosed in fairly thick capsules of connective tissue, the outer surface showing prominences that varied in size from a nut to an apple. When cut open they were seen to contain a considerable amount of fluid. The cut surface was yellowish-white in colour and had a lobulated appearance, with h~morrhagic streaks in places. The lobules were clearly marked off by strands of connective tissue derived from the capsule. Microscopical examination showed a considerable amount of connective-tissue matrix surrounding groups of cells of various shapes and sizes. The peripheral groups were narrow, as if compressed by the growth of the tumour. The matrix was rich in blood vessels. There was a considerable amount of "cancer juice" saturating the groups of cells. In some places the cells were disposed in a stratified manner around the periphery of the groups.

The origin of the primary tumour is doubtful; possibly it arose from the epithelial cells of the intestine, considering the number of connections it had with that organ.

Generalisation appeared to have taken place via the lymphatic system, as is usual with epithelial tumours. (Gay and Roquet, Bulletin et Memoires, Soci!:te der Sciences Vf:tf:rillaires de Lyon, NO.5, p. 363, 1908.)

HUMAN AND BOVINE TUBERCULOSIS}

KOCH'S paper (see p. 303) was followed 'by a number of communications from Smith, Boston; Woodhead, Cambridge; Arloing" Lyons; Fibiger, Copenhagen; Raw, Liverpool; Ravenel, Madison, Wis., in which endeav urs were made to shake Koch's standpoint. A real discussion did not take place in this session. To make a discussion successful a special session was held two days later, on the proposal of Koch, before an invited audience, about fifty gentlemen having attended. Biggs, New York, was in the chair. Koch introduced the proceedings with the following remarks :-

"A great difference of views seems to prevail with regard to the question of human and bovine tuberculosis, and I am glad that we have an occasion to enter into the subject in detail. I trust we may be able to prepare an understanding in the matter, although I do not believe that perfect agreement of the various views will be obtainable, as each author, having taking much time to build up his opinion, will be inclined to cling to it until his life's end. What mostly impedes an understanding is the difference of languages and the necessity to translate the remarks of the various orators into several languages, so that a possibility of incorrect interpretation can arise. I would, therefore, urgently beg the various gentlemen to make their remarks as concise as possible, and to keep strictly to the subject without any superfluous additions.

"I would specially propose two points for discussion, the first referring to the remarks of Mr Fibil'er, who contends that bovine tuberculosis is very

1 Report of a discURsion at the International Congress, 'VaRhington, Septemher 1908.

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A,BSTR_\CTS AND REPORT. 373

frequent in man. I wish to state again on this occasion that I have never denied that bovine tuberculosis is found in man, but I contend that these cases are rare. Secondly, I would refer to' the statement I made on Wednesday last in the Congress to the effect that not one single authentic case of phthisis has ever been found in man where for any long period of time bovine tubercle bacIlli have been coughed out by the respective patient. I would specially ask the question, whether any case of pulmonary tuber­culosis exists in which tubercle bacilli of the bovine type were found, not ,once but repeatedly.

"I propose that we should discuss this second point first, and I ask: Has any of the gentlemen present ever seen such a case of bovine tuberculosis in man? (Pause.) It appears that nobody knows of such a case. The German Commission for research, that much is known to the members present, found no such case among twenty-two cases investigated. As regards the work of the British Commission, I may mention the fact that one of the animals became diseased of bovine tuberculosis after being fed with human sputum, but that this case cannot be given weight as proof. Moreover, it appears that in these experiments a large number of sputa, obtained from a plurality of patients, have been given. Perhaps Dr Woodhead may be in a position to furnish full information on the subject, and make definite statements on these senes of experiments. A number of experiments with sputum collected from many consumptives have been made in which the results were negatIve."

Adoing here stated that he had observed a case where on post-mortem examination bovine type was found in a cavern.

Koch: "The case thereon which Prof. Arloing reports and his contentions have come to my knowledge, but the finding of one single case of bovine tuberculosis in a cavern cannot be considered as proof; the case would only show proof if the bovine tubercle bacillus had been found repeatedly and durmg a certain period of time. In this connection I would call attention to the possibility of accidental contamination with milk or butter or other food substances, which must always be kept in vIew. Even if the bovine tubercle bacilli are found in a cavern after death, the possibility must always be thought of that the patient in the course of his last hours of life may have inhaled particles of vomited contents of the stomach or contents of the mouth cavity, and that the infection of a tuberculous cavern of the bovine type may have come to pass in that way. One isolated observation of this kind has not the necessary power of proof, and only experiments of utmost exactness and excluding every possibility of secondary contamination can be taken into account."

Woodhead considered Koch's scepticism towards one single case or a small group of cases as justified. He gave information on the sputum feeding experiments at Brompton Hospital in London, and referred to the details con· tained in the British report. A sure observation in the sense of the question asked by Koch had not been made.

Adoing emphasised once more that in his case a large quantity of bacilli of the bovine type were found in the lung, which proved, at least, that the. human tissue is a suitable medium for the cultivation of the bovine type,

Koch: "There seems to be a misunderstanding between Prof. Arloing and myself. I do not doubt that he has found the bacilli of the bovine type in the lung, but this is only an isolated case. I repeat that we may be dealing here with an accidental admixture."

Arloing admitted that his researches did not comply with all conditions stipulated by Koch, but called attention to the fact that in the case mentioned by him the bacilli were" found during lifetime and not in the agony. Hf"

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repeated that the multiplication of the bacilli of the bovine type pointed to · the adaptability of the human tissue.

Theobald Smith considered Koch's requirements as justified, and the repeti­tion of experiments in the direction stated by Koch as necessary. The case mentioned by Arloing did not seem to him to be valid for proof.

Ravenel: "Am I right or wrong in understanding that the German Com­mission has ascertained the bovine type of the bacillus to be the cause of a case of miliary tuberculosis of the lungs?"

Koch: "I asked whether any case exists of tubercle bacilli of the bovine type 10 pulmonary tuberculosis and not in miliary tuberculosis."

Ravenel: "Am I right or wrong in saying that the German Commission. has published a case of that kind?"

Bang: "I think you are nght." Smith: "These are two qUite different things. Generalised tuberculosis·

can cause death long before any tubercle bacilli are ripe for settlement in a case of pulmonary tuberculosis."

Ravenel: "That may be correct; but is not acute miliary tuberculosis of the lungs phthisis? "

Koch: "No, it is not." Flbiger: "I would ask whether Prof. Koch remembers an authentic case

of bovine tuberculosis in man which is descnbed by Dutch authors." Koch: "I know that case very well. It is a case of this type; but it suffers

from the defects which have been inherent to the former investigations. Besides, the same apprehensions apply to this case as to that mentioned by Prof. Arloing, viz., that the case relJresents but one single finding. In order to arrive at definite conclusions the greatest care with reference to the con­ditions stipulated by me must be taken in future in all cases investigated and reported. I do not consider this question settled either in one sense Of in the other before all inexact cases which afe unsuitable for proof are absolutely cleared up."

The President asked the meeting to discuss now the question of the­frequency of infection.

Koch: "I would ask the following question: How often does primary intestinal tuberculosis or tuberculosIs of the mesenteric glands occur in children? It has been said by some that primary intestinal tuberculosis occurring in children is due to bacilli of bovine tuberculosis. I contend that this form of tuberculosis is not frequent, and in support of this assertion I refer to Virchow, Orth, Albrecht, Baumgarten and others as authorities who have ~aid and still say that primary intestinal tuberculosis is an extra­ordinarily rare disease." (Koch reads the following passage from the newest work of C. Fliigge-Die Ve1'breitungs1I.Ieise und Bekampfimg der Tuberkulose auf Grund experimmtaler UntersUcllU1igen im hygienischett Institut der Kiinigl. Universitiit Bnslau-The propagation of and the combat against tuberculosis on the basis of experimental researches carried out at the Hygienic Institute of the Royal University of Breslau-1908, p. 411):-

" , If some few authors are of a different view, and Fibiger and Jensen, for instance, find primary intestinal tuberculosis in the case of about 6 per cent. of all patients, and of about I I per cent of all tuberculous patients, and in children even of 16 per cent., Baumgarten considers this figure" as far too high," and says: "Primary intestinal infection is very rare accordmg to my experience, and most pathologic anatomists agree with this view." Virchow. Orth, Ribbert, Albrecht and many others have expressed their opinions in quite the same sense. Orth found among J 3 1 children only 1'5 p(r cent. of undoubted tuberculosis of the in;estinal and mesenteric glands; Biedert among 3104 sections of tuberculous children had sixteen times primary

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intestinal tuberculosis, i.e., five cases in 1000. Baginsky found no case in 933, Grosser only one case among 1407 sections of tuberculosis in the Pathologic Institute of Tubingen.'

., Thus it is seen that the views of the pathological anatomists widely differ from each other. I have discussed the question with Orth among others; his personal view certainly differs from that of Heller's assistants, as far as autopsies in Berlin are in question.

"I would now ask: Whence comes this great difference? Are there local differences in the pathological material of the various localities, or must the differences of opinion be looked for in the subjective understanding or subjective interpretation on the part of the various prosectors and patho­logical anatomists who carry out the autopsies? This question remains undecided in the meantime. The question of the frequency of primary intestinal tuberculosis I consider as settled in the sense that, in my opinion and in that of other authorities, the occurrence is a very rare one. If we consider that eleven-twelfths of the tuberculous deaths are due to pulmonary tuberculosis and only one-twelfth is caused by all the other forms of tuberculosis together, if we take into account that of these again only a small part can be due to primary intestinal tuberculosis, and that once more only a part of them belongs to bovine infection, we must admit that bovine infection is a rare clinical occurrence."

Woodhead: "I must say that, when Prof. Koch stated in London that primary feeding tuberculosis was very rare and actually seldom or never occurred ... "

Koch: "I said it was rare." . Woodhead considered the question of the frequency to be a difficult one.

According to his observations made in the eighties he had thought a pretty frequent occurrence had been proved, and he was surprised by the small figures reported from Germany. Later experiments, on which he gives some detailed information, have shown that abdominal tuberculosis is not at all as rare as stated in the statistics mentioned by Koch. Nobody would con­tend that intestinal tuberculosis, produced by the bacillus of the bovine type, was nearly as important as pulmonary tuberculosis, but, according to British experience, that form must not be neglected. He was glad to hear that Koch intends to carry out himself experimental researches on the question whether the bovine type has anything to do with pulmonary tubercu­losis. As regards practical measures, he was of opinion that rather something too much than something too little should be done.

Calmette placed the infection through the digestive tract in the foreground. The bacilli of the bovine type are, in his opinion, rarely retained in the mesenteric glands of young children, but penetrate into the organism and, on being localised in the lungs, undergo such changes with regard to their morphological and biological properties tp~~ they may be taken for the human type. Polymorphism of that kind so often occurs in bacteriology that one ought not to deny it on examining the tubercle bacillus.

Tendeloo has examined more than 1200 corpses and has arrived at the conviction that primary mesenteric tuberculosis is extremely rare. Much depends on the method of examination, especially in the case of the lung. Many centres easily escape notice. If one excludes all cases where with primary mesenteric infection small centres are found in the lungs, only a small number of surely primary intestinal tubercle bacilli remains. As regards the assertion of Calmette that bacilli of the bovine kind are found in mesenteric glands without having produced any local lesions and that they migrate along to the lungs and produce tuberculous lesions there, he does not believe in that possibility. In his view, the experiments made by

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Cornet, with more than 3000 animals, offer good proof; these experiments are far too little valued, especially by the searchers who have themselves carried out but few animal experiments. It is difficult to understand how the bacillus of the bovine type could stay in the mesenteric glands without producing any lesions, while further on in distant organs it should produce tuberculosis. Calmette's own experiments do not appear to sufficiently support Cal mette's hypothesis. The results of post-mortem examinations on human corpses fully agree with the results of the experiments made by Cornet. The experiments made by Ravenel, who injected large quantities of bacilli and found bacilli in the lungs after a short period of time, are correct; but they must be interpreted in a different manner. It is known that foreign bodies are retained in the lymph glands; but the filtering capacity of the glands is limited. If the stress put on this capacity is too heavy, the surplus passes through the glands. This is the case with the Ravenel experiments, where the masses of injected and therefore excessive bacilli have not been retained, but carried away in the lymph circulation. But under natural conditions such things do not happen.

Fibiger, on the basis of the results obtained by the Board of Health of Berlin, by the British Commission, and by himself together with Jensen, maintained his contention that a considerable number of cases of bovine in­fection occur in children, especially of cases of intestinal and cervical gland tuberculosis. There is a tendency to be noted that such cases are gradually found more and more frequently. Thus, some of the authors whose older work Koch had referred to have mentioned more frequent cases in their recent reports. Fibiger referred in this connection to Baginsky, Hansemann, Benda, Orth, Nebelthau, Harbitz, Lubarsch, and others. The difference of opinion is difficult to explain. The difference of nutrition, the habit of taking boiled or unboiled milk, might perhaps be made responsible for it. Accord­ing to the figures published in recent years, and derived from the hospitals of Kie1, Berlin, and Copenhagen, primary mesenteric tuberculosis is ascer­tained post-mortem in every sixth or seventh child. Supposing that every third case thereof must be placed to the account of the bovine type, then every eighteenth child, i.e., 5 per cent. of all children examined post-mortem, has been a victim to infection by primary intestinal tuberculosis of the bovine type. "Prof. Koch stated that the number of these cases is small. If 5 per cent. of all deceased children is not a high figure, which figure may then be considered as high?" '

Koch: "Notwithstanding, I am not convinced. The result of the question 510 far ascertained is that some pathological anatomists say that the figures are high and others that they are low. I am of opinion that the cases of primary mesenteric tuberculosis are rare, as also results from the considerable amount of information tendered just now by Prof. Tendeloo. The question is not how many cases of primary intestinal tuberculosis are found, but how many -cases thereof are due to the tubercle bacillus of the bovine type. I refer to the statistics published by Gaffky, who in the course of the last two years examined 300 children that had died in the hospital of Baginsky, whom Mr Fihiger refers to as having gradually brought out higher figures than formerly. Among the cases mentioned in the above statistics there were fifty-three deaths from tuberculosis, while four cases were doubtful; among those fifty-three cases there was n~t one single case of bovine tuberculosis, the patients having all been victims to human tuberculosis. Ought this special difference:: perhaps to be explained by supposing that there is less bovine tuberculosis in Berlin than in Copenhagen? This question must in the meantime remain un­decided.

"As regards the view expressed by Culmette, I have expected long since

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that 'somebody would put forward the argument that the bacilli change their <:haracter on the way from the mesenterium to the lungs. But this, gentle­men, is a mere hypothesis supported by nothing. On the contrary, every­thing we know at present on this subject speaks against this hypothesis; for it is a proved fact that the bovine tubercle bacillus keeps its character for a very long time. I have repeatedly found virulent bovine tubercle bacilli in old, healed-up, strictly localised and partly calcified glands, where these bacilli must have remained capable of life for a very long time. I have likewise had occasion repeatedly to examine typical wart-like swellings on the hands of workmen employed in the slaughter of tuberculous cattle. Even where such noduies on the fingers of the patients had existed for years, bacilli of the unmistakable bovine type could be isolated from them.

"Considering the great confusion which apparently exists with regard to the whole problem in question, I would urgently warn you not to draw con­clusions from a hypothesis which is absolutely unsupported."

Theobald Smith, with regard to the migration of the tubercle bacilli through the digestive tract to the lungs without stoppage in the mesenteric glands, referred to the tuberculosis of the lungs caused in pigs through feeding with milk. This always shows in the shape of miliary tuberculosis, which proved that the bacilli are retained in the regional lymph glands, where they increase, and whence they penetrate later on into the blood circulation. In experi­mental feeding one must object to (I) feeding a very large number of tubercle baCilli; (2) using bacilli which have changed their relation to the tissues of the experimental animal in consequence of artificial cultivation; (3) using dogs, because their relation to human and bovine tuberculosis is uncertain; {4) killing the experimental animals too early after feeding, t·.e, before the bacilli have had time to settle in the mesenteric glands.

Adami (Montreal) recalled that Koch in his paper had placed himself upon the practical and not the theoretical point of view; at the same time he had promised to devote himself for the next two or three years to examinations to see whether the human or the bovine type occurs in pulmonary tubercu­losis. The orator himself was convinced that Koch would find all cases are caused by the human type. "But, I would ask, what practical value is there to be looked for in these examinations and delays? In the end we shall still stand before the same problem, to extirpate bovine tuberculosis, because, as Koch has admitted here and in London, a certain number of cases in man, though they are not pulmonary tuberculosis, are due to the bovine tubercle bacillus."

Koch: "I would again call attention to the fact that human tuberculosis is the principal point of attack, because eleven-twelfths of the patients perish through this type of the infection. I admit that bovine infection can occa­sionally occur, and I desire not to be understood in the sense as though I disregarded the endeavours to extirpate bovine tuberculosis, as far as these endeavours are dictated by agricultural and economical reasons.· But I mean that it would be wrong to give to these proposals the leading place in front ,of the efforts to combat human tuberculosis."

Fibiger objected to a statement made by Koch to the effect that the figures mentioned by him, the orator, were selected cases. He stated that the statistics of Gaffky made use of by Koch were not published, and referred to the communication made by Kleine, who has described cases of infection on the hands.

Koch: "I object to the interpretation of this latter finding, as it is evidently not conclusive in any respect; for we might be dealing here with cases of infection by human bacilli, as we frequently find them, in the shape of primary lesions, with pathological anatomists. In that case such a finding very much

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differs from the cases mentioned by myself, where very virulent bovine tubercle bacilli were found in primary tuberculous lesions after many years.'~

The Chairman asked whether it was possible to come to an understanding for a resolution.

Flick pointed out that according to the decision of the Congress Committee no resolution could be passed on scientific problems.

Koch: "Gentlemen, we are dealing here exclusively with a purely scientific subject, and the questions proposed cannot be settled by any resolution. We are speaking of objective facts and not of subjective views. I, for my part, most earnestly refuse to join in any resolution on this subject."

Woodhead recommended an understanding from the practical point of view.

Eastwood (London) was of opinion that a resolution ought to be passed and afterwards placed before the Congress in the closing meeting on the following three practical questions: (I) Is the danger from the tubercle bacillus of the bovine type so slight for human health that it may practically be disregarded? (2) Does the consumption of milk containing bovine tubercle bacilli cause an increase of morbidity or mortality in children? (3) Is the institution of a supply of milk free from bovine tubercle bacilli a means that can efficiently assist the struggle against human tuberculosis?

Koch: "We have not at all discussed this subject; how can resolutions of purely practical importance be brought about in this meeting on things which we have not discussed to-day? I repeat, I shall abstain from any resolution."

Pearson seconded the motion of Eastwood, and pointed out that according to the general impression Koch had estimated in 1901 in London the transmissibility of bovine tuberculosis to man so low that measures against bovine tuberculosis would be without importance for the public health. If, as Fibiger has explained from the statistics of Baginsky, the cases of primary intestinal tuberculosis have considerably increased in Berlin since then, the question would have to be asked whether any negligence of precautionary measures in connection with the consumption of milk has occurred in consequence of the London statement.

A lengthy discussion ensued, in which Messrs Flick, Smith, Ravenel, Arloing, and Eastwood took part, on the question whether and how the results of the Conference ought to be brought before the public.

Several orators pointed out the necessity to publish something on the Session. Finally, it was proposed to place the shorthand minutes before the public.

Koch: "I have not the slightest objection to the publication of an exact report of this meeting. Why should I object to the statement that I recognise the transmissibility of bovine tuberculosis to man? I have never denied it. I propose, therefore, that a report shall be published. after the shorthand notes have been seen and signed by each orator; but the report is only to be a mere reproduction of the spoken word, of the facts stated and of the opinions expressed, and is in no way to take the­shape of any resolution, especially not on any questions which we have not at all discussed."

In this sense a decision was arrived at, and the Chairman closed the meeting. (Tuberculosis, Vol. VII., p. 496.)