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ON AN OUTBREAK OF DIARRHŒA IN THE WARDS OF ST. BARTHOLOMEW'S HOSPITAL,
8 against any other article of diet than the These facts constitute a strong presumption rice-puddings. that the in the production of the outbreak was main agency OUTBREAK OF DIARRHŒA IN THE the pudding, that it was variably toxic in different wards at WARDS OF ST. BARTHOLOMEW’S the time of its consumption, and that in some 7 per cent. of the cases some accessory toxic agency was at work. I will now pass to the bacteriological evidence, which will PROBABLY CAUSED BY INFECTION OF RICE-PUDDING WITH be found to confirm the presumption just mentioned and BACILLUS ENTERITIDIS SPOROGENES. possibly to explain the discrepancies. I must first briefly BY F. W. ANDREWES, M.D. OXON., F.R.C.P. LOND., allude to the investigations carried out by Dr. Klein in the PATHOLOGIST AND LECTURER ON PATHOLOGY TO ST. BARTHOLOMEW’S preceding outbreaks and published in full by him in reports HOSPITAL. to the Local Government Board (1895-96 and 1897-98). In the first outbreak, which occurred in October, 1895, he found WITHIN the past three years the wards of St. Bartholo- abundantly in the stools of the patients suffering from diarmew’s Hospital have been thrice visited by a mild form of rhœa a peculiar spore-bearing anaerobic bacillus which he named bacillus enteritidis sporogenes. This organism differs epidemic diarrhoea. The outbreaks have all been of similar from any previously described pathogenic species in several character, occurring suddenly in a single night and passing important respects, and it most nearly resembles the organism off as suddenly. In one instance as many as 146 persons described by Botkin as bacillus butyricus, which, howThe cases have occurred almost ever, is non-pathogenic. The special features which diswere attacked in one night. are: 1. Its energetic action when entirely amongst the patients; the sisters and nurses, with tinguish Klein’s bacillus in milk. The milk is quickly curdled anaerobically grown The great majority very few exceptions, have escaped. with copious evolution of gas, the spongy broken curd of the attacks have been mild-merely abdominal pain folfloating in a fairly clear, transparent whey. 2. Its intense lowed by a few loose actions of the bowels-but in a few of virulence when inoculated subcutaneously in certain animals, the more severe cases blood and mucus were passed. Vomit- especially guinea-pigs. Death occurs in from one to three ing has almost always been absent. No fatal case has days, with severe hasmorrhagic oedema and gangrene of the occurred and, indeed, no case has been so serious as to excite subcutaneous tissues spreading widely from the point of alarm, except where the patient was previously very ill. inoculation. The virulence varies in intensity in different On each occasion, besides the actual attacks of diarrhoea cases and is lost in old cultures; recent milk cultures are there were instances of abdominal pain alone and there was the most virulent. 3. It stains well by Gram’s method. This further noted a general tendency to looseness of the bowels- distinguishes it from the bacillus of malignant oedema; e.g., patients who were habitually constipated had their moreover, it has terminal spores of an oval shape. During bowels opened naturally. The distribution of the attacks in the past three years a considerable amount of evidence has the different wards of the hospital has been very capricious. accumulated rendering it highly probable that this organism The first outbreak was on the night of Sunday, Oct. 27th, is concerned with the causation of epidemic diarrhoea. In all 1895, when there were 59 attacks distributed over 15 wards the fatal cases of "English cholera"which I have had the out of 28; the second was on the night of Sunday, March 6th, opportunity of examining it has been abundantly present in 1898, when there were 146 attacks distributed over 22 wards full virulence, and it has also been present in the majority of out of 28 ; and the third was on the night of Friday, cases of severe and mild diarrhceas which I have investiAugust 5th, 1898, and affected 86 persons, distributed over gated. It is a widely distributed saprophyte and may be found in cultivated soil, in the excrement of animals, and 16 of the 20 wards then open. In each epidemic the facts irresistibly suggested a poison- sometimes in that of man, though in very sparse numbers ing by some article of food and I carefully investigated as compared with those found in diarrhoeal conditions; the matter from this point of view. A bacterial infection it is very abundant in sewage In occurs also with great rather than a chemical poisoning was suggested by the frequency in milk, even in that of good quality, at least incubation period. In the first two epidemics no special during warm weather; the conditions under which cows article of diet could be incriminated and I was reduced are commonly milked readily explain this. In many ways, Of indeed, the characters of the unknown poison demanded by to the more general ones-milk, bread, and butter. these milk came the most strongly under suspicion in Ballard in his well-known hypothesis as to the causation of each case and the bacteriological evidence to which I will epidemic diarrhoea are satisfactorily fulfilled by the bacillus refer later confirmed this suspicion. The third outbreak, enteritidis sporogenes. It is, however, not yet clear under to which I wish to draw special attention in this paper, what conditions it attains virulence. In the first outbreak differed from the two preceding outbreaks in being definitely of diarrhoea at St. Bartholomew’s Hospital this bacillus was traceable to an article of diet (rice-pudding) made with milk readily obtained from the milk supplied to the establishIn the second outbreak, in March, 1898, the rather than directly to the milk itself. I will shortly detail ment. same organism was present in every stool of patients the facts supporting this statement. The epidemic began about 10 P.M. on August 5th, 1898, suffering from diarrhoea which was examined both by and fresh cases occurred up to 6 or 8 A.M. on August 6th. Dr. Klein and myself. It was also present in the milk All were of a mild nature; 84 patients and 2 nurses were supplied to the hospital on the day preceding the outattacked. Only 4 wards in the hospital escaped (one block break. It is worthy of note that the two first outbreaks was closed for alterations), but individual wards were affected occurred on Sunday nights; there is no second delivery of in very different measure. On investigating the diets of the nilk on Sundays and hence there is unusual opportunity for persons attacked I was at once struck with the overwhelming ihe multiplication of any living poison present, since the evidence against the rice-puddings which had been consumed nilk supplied early on Sunday morning has to suffice for The vast majority of the attacks twenty-four hours’ consumption. In the third outbreak, in on the previous day. occurred in patients on"half diet," all of whom which the rice-pudding fell under suspicion, I obtained the Patients on "full ;tools of 3 patients suffering from diarrhoea, taken at random had partaken of rice-pudding. diet" had been provided with suet-pudding, while those on rom three different wards, and submitted them to micro"milk diet"had, as a rule, no pudding, and in these two copic and bacteriological examination. CASE 1.-A boy, aged fifteen years, who was convalescent classes very few attacks had occurred. Only 6 patients rom pneumonia and pericarditis, had eaten rice-pudding in out of the 86, or some 7 per cent., had not eaten ricepudding. In certain wards every patient who had eaten rice- he middle of the day on August 5th. During the following pudding suffered, while every one who had not eaten it iight he had mild colic and diarrhoea, passing three brown escaped. The two nurses who were attacked had both par- iquid stools. The attack was over by the next day. Covertaken of the patients’ rice-pudding. The largest number of ;lass preparations of one of the stools, stained by Gram’s cases in any one ward was 14 and in this ward 20 out of 22 fiethod, showed amongst other organisms a fair number of patients had eaten rice-pudding. Moreover, in many wards large bacilli resembling the bacillus enteritidis sporogenes. the puddings were noticed by the sisters as unpleasant to the spores were present in a few of the bacilli. The bacillus nteritidis sporogenes was readily obtained on cultivation. smell or the taste, and in one ward they were on this account CASE 2.-The patient was a woman, aged forty-seven not served out. No diarrhoea occurred in that ward. On the other hand, in certain wards the puddings were appaears, who was suffering from bronchitis, emphysema, and rently of the normal good quality and in many cases were icrbus cordis. She had not eaten rice-pudding on August eaten without the slightest ill-effect. There was no evidence th, but custard-pudding prepared at the same time and from to be obtained
ON AN
HOSPITAL,
9 the same milk. Diarrhoea began at 4 A.M. on August 6t]h guinea-pig died and showed changes resembling those proand three loose stools were passed, the last one containingg duced by the bacillus enteritidis sporogenes, but with absence blood and mucus. The attack passed off in a few hours3. of any marked accumulation of fluid. This is often the case As in the preceding case bacilli resembling the bacillu;.s when death does not occur within the first two or three days. enteritidis sporogenes were found microscopically in thee The bacilli present were granular and degenerate; they were stools. Only a few of them were sporing, but the organisnn not very numerous either locally or in the spleen. The second guinea-pig showed in two days a considerable was obtained readily enough on culture. CASE 3.-The patient was a man, aged twenty-five years, effusion of fluid into the subcutaneous tissue over the It was killed on the third day who was convalescent from typhoid fever, and who had beeiaabdomen and the thorax. previously constipated. He partook of rice-pudding at mid-da3y and all the changes characteristic of infection by bacillus on Aug. 5th and had diarrhoea during the succeeding night., enteritidis sporogenes were found. It may therefore be passing four brown liquid stools. The attack ceased duringo, taken as reasonably certain that the bacilli which were the next day. The specimen of stool examined was crowdec microscopically demonstrable in the rice-pudding were truly with typical bacillus enteritidis sporogenes, most of whict1 bacillus enteritidis sporogenes, although their virulence was bore oval terminal spores, and there were also largEe less intense than in the case of the bacilli obtained numbers of free spores. The bacillus was readily obtainecI from the stools of the patients affected by the diarrhœa. on cultivation. In all three cases the cultures of bacillus enteritidiss It may be urged that the process of cooking would destroy sporogenes proved highly virulent. They were made ini any germs in the pudding derived from the milk with which the usual manner-that devised by Dr. Klein. Freshiit was made. To test this point I visited the hospital kitchen sterile milk tubes were inoculated with two or three3 with a thermometer and ascertained the temperatures platinum loops of the stool and then heated to 80° C. attained at different stages in the cooking. The mass was for ten minutes in order to destroy everything except the first boiled" in a large copper, and I found its temperature spores. They were then cooled and incubated anaerobicallyr about 70’C. in the upper layers and from 80° to 85° C in the at 37°C. in Buchner tubes. In forty-eight hours all threei deeper parts. The pudding was then baked in small dishes milk tubes showed energetic coagulation and gas-formation- in an oven. I tested one removed hot and bubbling from a ragged clot floating in clear whey. Microscopically theyrthe oven and found its temperature to average from 90° to appeared to be pure cultures of the bacillus enteritidisi 92° C., and nowhere to exceed 98° C. Now, the spores of sporogenes. Guinea-pigs were inoculated subcutaneously ini the bacillus enteritidis sporogenes, like those of Botkin’s the groin with 1 c.c. of the whey from each milk tube. One bacillus butyricus, are amongst the most resistant known and died in less than twenty-one hours and the other two inwill stand 100’C. for a considerable period, and I therefore less than forty-eight hours. All showed similar appear- find no difficulty in believing that such spores, originally ances-an intense hæmorrhagic oedema and gangrene spread- present inthethe milk, may have escaped in certain parts of puddings-an assumption which might explain ing over the abdomen and the thorax. The bloody fluid some of teemed with the bacilli which also were found in the heart- their variably toxic character. I consider that these epidemics and the above facts in blood and spleen in smaller numbers. I was unfortunately not able to obtain a specimen of the connexion with them are worth placing on record for more milk which had been supplied to the hospital on August 5threasons than one. I imagine that similar outbreaks are not as all had been used or thrown away. (I have no doubt, uncommon in large institutions though they are not often however, that I should have found the bacillus enteritidis: recorded. The occurrence of three precisely similar sporogenes in it. A week or two later on six consecutive, epidemics in three years at St. Bartholomew’s Hospital is a days I tested the milk supplied and found the organism striking circumstance. Bacterial infection through the present on five days out of the six.) In one ward, however, a channel of hot baked rice-pudding is not quite what might sample of the rice-pudding eaten on August 5th had been have been looked for, yet I think the evidence points in that preserved for me. In this ward there had been several cases direction in the case of the last of the three epidemics. It of diarrhoea which seemed clearly attributable to the is, however, as a contribution to the study of epidemic pudding. The pudding, then twenty-four hours old, was diarrhoea and its causation that the facts are best worth sour to the smell and acid to litmus. Cover-glass films recording. There may be those who will disagree with the prepared from it stained by Gram’s method and in other interpretation which I have placed upon the facts, and, ways showed amongst other organisms a large number of indeed, there are several points which are by no means large bacilli precisely resembling the bacillus enteritidis clear. Why, for instance, should the rice-pudding sporogenes in size and shape, but in none could any spores made with milk have been capable of setting up be detected. The other organisms present were cocci and diarrhoea while the milk from which it was made caused small bacilli resembling the lactic acid bacillus. I did not no such symptoms ?? It may be that the process of further investigate the nature of these. A number of cooking, by destroying all competing microbes, gave a cultures were made from the pudding, some aerobic and freer hand to the bacillus enteritidis sporogenes. Yet it some anaerobic, some after heating to 800 C. for ten can hardly have had time for the exercise of such unreminutes and some unheated. The heated cultures stricted activity, since the puddings were for the most part all failed, as I anticipated, since no spores were consumed hot from the oven. It may be, again, that present. The unheated ones were necessarily impure, but all its toxic powers were in some way enhanced by the showed evidence of the presence of the bacillus enteritidis process of cooking. We know little or nothing of the consporcgenes. An unheated milk culture, incubated anaerobi- ditions under which the organism attains virulence. It is a cally, behaved quite like a culture of that organism, showing common saprophyte and it is probably habitually consumed in forty-eight hours a dense coagulum honeycombed with gas in milk with no deleterious effect, yet under certain circumbubbles and a clear whey in which were present both enteri- stances it becomes highly pathogenic. If it be true, as it tidis-like bacilli and small bacilli like the bacillus acidi lactici. would appear, that an organism so virulent to guinea-pigs is Some of the unheated rice-pudding, incubated anaerobically almost constantly to be found in association with acute at 37°C., showed precisely similar changes and the whey diarrhoea and is not found, or is only exceptionally found, teemed with enteritidis-like bacilli. A large guinea-pig was under conditions in which the intestine is normal, it is inoculated subcutaneously with 1t c.c. of the whey from difficult to avoid the conclusion that this organism has a this milk culture which contained both the bacillus enteritidis direct connexion with diarrhœa-presumably a causal consporogenes and other bacilli. In twenty-four hours it was nexion. Yet it is so common and so widely distributed a very ill, with much local swelling over the belly wall, and saprophyte that it seems clear that its mere presence in the in forty-eight hours it was worse, and in the region of the intestine cannot alone be the effective cause of diarrhoea. inoculation the abdominal wall was thickened and con- There must be certain conditions under which its virulence tracted. On the third day I extracted a drop of fluid becomes highly exalted, and the nature of these conditions from the swelling with a sterilised hypodermic syringe. is a very promising field for future research. Meanwhile, I This fluid showed fat droplets and fragments of necrotic must be content to have shown, as I believe, that in a given tissue and a moderate number of degenerate-looking bacillus extensive outbreak of mild diarrhœa the bacillus enteritidis enteritidis sporogenes. An anaerobic milk culture was made sporogenes of Klein was present in virulent form in the stools from it and grew in the characteristic manner. With the which were examined, that the channel of infection was in whey from this culture which contained other organisms all probability rice-pudding, and that the rice-pudding besides the bacillus enteritidis sporogenes a second guinea-pig contained the bacillus in question. was inoculated. Meanwhile on the fourth day the first Highgate, N. .
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ON AN
HOSPITAL,
9 the same milk. Diarrhoea began at 4 A.M. on August 6t]h guinea-pig died and showed changes resembling those proand three loose stools were passed, the last one containingg duced by the bacillus enteritidis sporogenes, but with absence blood and mucus. The attack passed off in a few hours3. of any marked accumulation of fluid. This is often the case As in the preceding case bacilli resembling the bacillu;.s when death does not occur within the first two or three days. enteritidis sporogenes were found microscopically in thee The bacilli present were granular and degenerate; they were stools. Only a few of them were sporing, but the organisnn not very numerous either locally or in the spleen. The second guinea-pig showed in two days a considerable was obtained readily enough on culture. CASE 3.-The patient was a man, aged twenty-five years, effusion of fluid into the subcutaneous tissue over the It was killed on the third day who was convalescent from typhoid fever, and who had beeiaabdomen and the thorax. previously constipated. He partook of rice-pudding at mid-da3y and all the changes characteristic of infection by bacillus on Aug. 5th and had diarrhoea during the succeeding night., enteritidis sporogenes were found. It may therefore be passing four brown liquid stools. The attack ceased duringo, taken as reasonably certain that the bacilli which were the next day. The specimen of stool examined was crowdec microscopically demonstrable in the rice-pudding were truly with typical bacillus enteritidis sporogenes, most of whict1 bacillus enteritidis sporogenes, although their virulence was bore oval terminal spores, and there were also largEe less intense than in the case of the bacilli obtained numbers of free spores. The bacillus was readily obtainecI from the stools of the patients affected by the diarrhœa. on cultivation. In all three cases the cultures of bacillus enteritidiss It may be urged that the process of cooking would destroy sporogenes proved highly virulent. They were made ini any germs in the pudding derived from the milk with which the usual manner-that devised by Dr. Klein. Freshiit was made. To test this point I visited the hospital kitchen sterile milk tubes were inoculated with two or three3 with a thermometer and ascertained the temperatures platinum loops of the stool and then heated to 80° C. attained at different stages in the cooking. The mass was for ten minutes in order to destroy everything except the first boiled" in a large copper, and I found its temperature spores. They were then cooled and incubated anaerobicallyr about 70’C. in the upper layers and from 80° to 85° C in the at 37°C. in Buchner tubes. In forty-eight hours all threei deeper parts. The pudding was then baked in small dishes milk tubes showed energetic coagulation and gas-formation- in an oven. I tested one removed hot and bubbling from a ragged clot floating in clear whey. Microscopically theyrthe oven and found its temperature to average from 90° to appeared to be pure cultures of the bacillus enteritidisi 92° C., and nowhere to exceed 98° C. Now, the spores of sporogenes. Guinea-pigs were inoculated subcutaneously ini the bacillus enteritidis sporogenes, like those of Botkin’s the groin with 1 c.c. of the whey from each milk tube. One bacillus butyricus, are amongst the most resistant known and died in less than twenty-one hours and the other two inwill stand 100’C. for a considerable period, and I therefore less than forty-eight hours. All showed similar appear- find no difficulty in believing that such spores, originally ances-an intense hæmorrhagic oedema and gangrene spread- present inthethe milk, may have escaped in certain parts of puddings-an assumption which might explain ing over the abdomen and the thorax. The bloody fluid some of teemed with the bacilli which also were found in the heart- their variably toxic character. I consider that these epidemics and the above facts in blood and spleen in smaller numbers. I was unfortunately not able to obtain a specimen of the connexion with them are worth placing on record for more milk which had been supplied to the hospital on August 5threasons than one. I imagine that similar outbreaks are not as all had been used or thrown away. (I have no doubt, uncommon in large institutions though they are not often however, that I should have found the bacillus enteritidis: recorded. The occurrence of three precisely similar sporogenes in it. A week or two later on six consecutive, epidemics in three years at St. Bartholomew’s Hospital is a days I tested the milk supplied and found the organism striking circumstance. Bacterial infection through the present on five days out of the six.) In one ward, however, a channel of hot baked rice-pudding is not quite what might sample of the rice-pudding eaten on August 5th had been have been looked for, yet I think the evidence points in that preserved for me. In this ward there had been several cases direction in the case of the last of the three epidemics. It of diarrhoea which seemed clearly attributable to the is, however, as a contribution to the study of epidemic pudding. The pudding, then twenty-four hours old, was diarrhoea and its causation that the facts are best worth sour to the smell and acid to litmus. Cover-glass films recording. There may be those who will disagree with the prepared from it stained by Gram’s method and in other interpretation which I have placed upon the facts, and, ways showed amongst other organisms a large number of indeed, there are several points which are by no means large bacilli precisely resembling the bacillus enteritidis clear. Why, for instance, should the rice-pudding sporogenes in size and shape, but in none could any spores made with milk have been capable of setting up be detected. The other organisms present were cocci and diarrhoea while the milk from which it was made caused small bacilli resembling the lactic acid bacillus. I did not no such symptoms ?? It may be that the process of further investigate the nature of these. A number of cooking, by destroying all competing microbes, gave a cultures were made from the pudding, some aerobic and freer hand to the bacillus enteritidis sporogenes. Yet it some anaerobic, some after heating to 800 C. for ten can hardly have had time for the exercise of such unreminutes and some unheated. The heated cultures stricted activity, since the puddings were for the most part all failed, as I anticipated, since no spores were consumed hot from the oven. It may be, again, that present. The unheated ones were necessarily impure, but all its toxic powers were in some way enhanced by the showed evidence of the presence of the bacillus enteritidis process of cooking. We know little or nothing of the consporcgenes. An unheated milk culture, incubated anaerobi- ditions under which the organism attains virulence. It is a cally, behaved quite like a culture of that organism, showing common saprophyte and it is probably habitually consumed in forty-eight hours a dense coagulum honeycombed with gas in milk with no deleterious effect, yet under certain circumbubbles and a clear whey in which were present both enteri- stances it becomes highly pathogenic. If it be true, as it tidis-like bacilli and small bacilli like the bacillus acidi lactici. would appear, that an organism so virulent to guinea-pigs is Some of the unheated rice-pudding, incubated anaerobically almost constantly to be found in association with acute at 37°C., showed precisely similar changes and the whey diarrhoea and is not found, or is only exceptionally found, teemed with enteritidis-like bacilli. A large guinea-pig was under conditions in which the intestine is normal, it is inoculated subcutaneously with 1t c.c. of the whey from difficult to avoid the conclusion that this organism has a this milk culture which contained both the bacillus enteritidis direct connexion with diarrhœa-presumably a causal consporogenes and other bacilli. In twenty-four hours it was nexion. Yet it is so common and so widely distributed a very ill, with much local swelling over the belly wall, and saprophyte that it seems clear that its mere presence in the in forty-eight hours it was worse, and in the region of the intestine cannot alone be the effective cause of diarrhoea. inoculation the abdominal wall was thickened and con- There must be certain conditions under which its virulence tracted. On the third day I extracted a drop of fluid becomes highly exalted, and the nature of these conditions from the swelling with a sterilised hypodermic syringe. is a very promising field for future research. Meanwhile, I This fluid showed fat droplets and fragments of necrotic must be content to have shown, as I believe, that in a given tissue and a moderate number of degenerate-looking bacillus extensive outbreak of mild diarrhœa the bacillus enteritidis enteritidis sporogenes. An anaerobic milk culture was made sporogenes of Klein was present in virulent form in the stools from it and grew in the characteristic manner. With the which were examined, that the channel of infection was in whey from this culture which contained other organisms all probability rice-pudding, and that the rice-pudding besides the bacillus enteritidis sporogenes a second guinea-pig contained the bacillus in question. was inoculated. Meanwhile on the fourth day the first Highgate, N. .
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