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Tuberculous Infection in Children
80
ABSTRACTS.
Clinical Bacteriology and Vaccine Therapy. By William Scott, F.R.e. V.S. London: Bailliere, Tindall & Cox. 1913. Price 7S. 6d. net. AN eminent medical authority some years ago prophesied that the physician of the future would bo:: an immunisator, and the author of this work has a like opinion regarding the role of the future veterinary surgeon. There is, however, a distinction, for, whereas it has generally been understood that the medical man whom the prophet had in view would merely administer the vaccine, the author of this work thinks that the veterinary practitioner ought to make his own bacteriological diagnosis, isolate and identify the causal organism, make and standardise his own vaccine, and where necessary control its use by periodic determinations of the patient's opsonic index. Mr Scott, who conducts a large country practice, would have the reader believe he already does all this, and, indeed, he declares that his object in writing the book was to show how other busy practitioners can do likewise. It is not encouraging to a reviewer with any knowledge of bacteriology to find such grotesque opinions in the preface, and a perusal of the text does nothing to remove the bad impression. The author somewhat plaintively appeals to the reader's indulgence on the ground that much of the matter was written in the small hours of the morning, but one cannot help feeling that he would have been better in bed and asleep. It is difficult to imagine :my more appalling prospect for veterinary therapeutics than the one which the author would like to see realised.
TUBERCULOUS INFECTION IN CHILDREN} THE first series of investigations recorded in this Report were carried out in the Pathological Laboratory of the Local Government Board hy Drs Eastwood and F. Griffith. The object of the enquiry was to investigate the incidence of tuberculous infection in a series of children dying from all causes between the ages of two and ten years, and to determine whether the bacilli found were of the bovine or of the human type. Materials from 150 children were examined. All these children had died in hospitals in or near London, none of which were especially devoted to the treatment of tuberculosis. The investigations supplement those carried out by the Royal Commission 1 "Reports to the Local Government Board on Public Health and Medical Subjects.' New Series No. 88:I. The Incidence and Bacteriological Characteristics of Tuberculous Infection in Children. By Arthur Eastwood, M.D., and Fred Griffith, M.B. II. An Enquiry, based on a Series of Autopsies, into the Occurrence and Distribution of Tuberculous Infection in Children, and its Relation to the Bovine and the Human Types of Tubercle Bacilli respectively. By A. Stanley Griffith, M.D. Printed under the Authority of His Majesty's Stationery Office by Darling & Son, Ltd., 1914. Price 2s. 3d. To be purchased through any Bookseller. .
ABSTRACTS.
81
on Tuberculosis in that they are based upon materials obtained from unselected cases. It was arranged that every case within the age-period mentioned which terminated fatally should be examined until 150 had been collected. Method of Invlstigation.-At the post-mortem examinations special care was taken not to cut into the bronchial and mesenteric glands. When either of these groups of glands showed any that were enlarged and obviously tuberculous some of the caseous material was removed with all necessary precautions to prevent contamination and used for the inoculation of egg· medium and of guinea-pigs. In cases in which the glands were not enlarged as many as possible were removed, emulsified, and inoculated intraperitoneally into guinea-pigs, not less than three being used when no evidence of tuberculosis could be discovered in them. Cultivation and animal inoculation were also resorted to in the case of other organs: (a) when they contained tuberculous lesions and none were found in the bronchial or mesenteric glands; (b) to clear up the diagnosis of a doubtful nodule; and (c) in certain cases where it was thought of interest to ascertain whether the tubercle bacilli obtained from various parts of the body all possessed the same characteristics. The guinea-pigs were killed six weeks after inoculation, if not obviously tuberculous at an earlier date, and cultures were made from the lesions found. The cultural characters of the bacilli obtained either directly or from the guinea-pigs were tested upon various media and their virulence for rabbits was determined by inoculation of weighed quantities of culture grown upon pure bovine serum. From a tabulated summary of the general results obtained the following details may be gathered : In fifty-six cases there was no evidence of infection with tubercle bacilli, and the inoculation experiments with emulsions of the bronchial and mesenteric glands were negative. In the remaining ninety-four cases, or 62·7 per cent., evidence of infection was found, with, in the majority of cases, the formation of visible tuberculous lesions from which the bacilli were recovered in culture. In sixteen of these cases, although tuberculous lesions were present and tubercle bacilli were in most instances demonstrable by microscopic examination, the bacilli were apparently dead, as neither cultivation upon artificial media nor animal inoculation yielded positive results. In seventy-eight of the ninety· four cases tubercle bacilli were isolated and cultivated. In five of these cases there was no macroscopic evidence of tuberculosis, tubercle bacilli being cultivated from apparently healthy glands. Bovine bacilli were isolated from three of these cases, in two instances from the mesenteric glands, and in the third from the bronchial glands. In the other two cases the bacilli were of the human type, and were isolated in one of them from the cervical, bronchial, and mesenteric glands and in the other from the mesenteric glands only. Examples of tubercle bacilli lying latent in mesenteric or bronchial glands of children showing tuberculosis in some other part of the body were encountered in twenty-two cases. In five of these the bacilli were of the bovine type, and they occurred in the mesenteric glands (once) and in the bronchial glands (four times). Of the seventeen instances in which human tubercle bacilli were found, thirteen showed latent infection of the mesenteric glands and four of the bronchial glands. F
ABSTRACTS.
The total number of cases in which death was due to tuberculosis was sixty-one, other causes being responsible in the remaining thirty-three instances. Since in sixteen instances the bacilli present in obvious lesions appeared to be dead, it was possible to distinguish between bovine and human infections in only seventy-eight of the ninety-four cases. Of these seventyeight cases sixty-five were due to bacilli of the human type, and tuberculosis was the cause of death in fifty-two of them. Bacilli of the bovine type were responsible for the infection in the remaining thirteen cases, and of these nine died from tuberculosis. In one instance in which the bronchial glands were free from tubercle bacilli a culture was obtained from the mesenteric glands which was found to resemble the bovine type of bacillus as regards its cultural characters, but which was of low virulence for rabbits. Reference to the tabulated information shows that the lesions present in the child from which this virus was obtained were: Spinal caries, tuberculous rib with discharging sinus, cas eo-calcareous tubercles in the mesenteric glands and the spleen. Attempts to cultivate tubercle bacilli from the spleen failed. This virus is included among those considered to be of the bovine type. As already stated, in thirteen cases bacilli of the bovine type were isolated, and in three of these none of the tissues showed any macroscopic evidence of tuberculous disease. From a survey of the remaining ten cases it may be gathered that in no case was disease found in the lungs without visible lesions in the intestine or its associated glands. In one of these cases there was tuberculous meningitis and a few grey foci in the liver, the mesenteric glands appearing normal, but tubercle bacilli were cultivated from both the liver and the mesenteric glands. In four of these cases there were visible lesions involving the abdominal organs, but none in the thoracic organs. In the course of examining tuberculous lesions found in children, observations were recorded as to the appearances and numbers of the tubercle bacilli found in smear preparations. After the type of bacillus present had been determined by cultural and inoculation methods, these records were analysed with a view to determining how far a forecast of the type of bacillus can be based upon the microscopic characters, on the assumption that long, beaded forms were characteristic of the human type, and short, uniformly stained forms, without admixture of the long, beaded forms, indicated the bovine type. 121 smears were recorded. In sixty· one cases no inference as to type could be drawn. In fifty-two cases (forty-seven human and five bovine), a correct inference was drawn, and in eight cases (six human and two bovine) the inferences drawn proved to be incorrect. The authors found in every case that cultures obtained, either directly or through the guinea-pig, from different situations in the same body were identical in growth upon corresponding media. For the purpose of comparison with the condition found in the series of children, and with particular reference to the question whether tubercle bacilli can pass through the alimentary tract and set up lesions in distal organs without leaving evidence of infection at the portal of entry, the results obtained in 462 feeding experiments carried out by the Royal Commission on Tuberculosis are given in tabular form. From these it may be gathered that distal lesions without lesions at the portal of entry were exceedingly rare except in the case of the dog. For the purpose of obtaining further data, feeding experiments were carried out upon eighteen pigs. In all cases except two the pigs were fed with bovine cultures mixed with milk. In the two instances human cultures were used.
AIiSTRACTS.
The pigs were killed after the lapse of from 84 to 167 days, the post-mortem examination being supplemented in many instances by inoculation tests with apparently normal tissues. The tabulated results show: (I) That uncertainty attaches to feeding experiments in which small doses ('01 milJigramme or less) are used; (2) that, as in children, tubercle bacilli may occasionally be found by experiment in apparently healthy tissues; and, especially (3) that distal lesions were entirely absent in all cases in which no infection of the alimentary tract or its glands was found. THE second series of investigations detailed in the report were carried out on behalf of the Local Government Board by Dr A. Stanley Griffith, with the object of ascertaining, (1) the frequency of tuberculous infection, latent or manifest, in childhood; (2) the distribution of the disease within the body; and (3) the relative incidence of the bovine and the human types of the tubercle bacillus. In this investigation also no selection of cases for examination was made, every fatal case in children under twelve years of age occurring in the institutions assisting in the enquiry was investigated. In all cases, whether there were macroscopic lesions or not, the mesenteric and bronchial glands were examined, and in some instances the cervical glands and other tissues. The glands were removed from the associated tissues with every possible precaution to prevent accidental contamination and were emulsified with salt solution, the emulsion being used for the intraperitoneal inoculation of from two to four guinea pigs. In all cases where there was suitable material an attempt was made to get cultures direct. The inoculated guinea-pigs, unless showing obvious evidence of tuberculosis at an earlioer date, were killed six weeks after inoculation. Egg medium was used in all cases to raise primary cultures, sub-cultures being made upon serum, and only serum cultures were used for the virulence tests. The tests employed to distinguish between the human and bovine types of bacilli were the cultural characters shown by growths upon glycerinised media and the virulence for certain species of animals. Attention is drawn to certain important factors in carrying out the virulence tests. If rabbits are inoculated intravenously the dose should not be too large, since large doses of human tubercle bacilli sometimes produce an acute tuberculosis in rabbits, not easily distinguishable from that set up by bovine bacilli. A suitable dose is '01 mg. of culture. If subcutaneous inoculation be resorted to, the dose should not be smaller than 10 mg., since smaller doses may produce slowly progressive disease instead of the acute and rapidly fatal infection. In all, ninety-one strains from various sites in the bodies of thirty-five children were tested; of these strains twenty-one were obtained direct and seventy through the guinea-pig. Seventy-two strains from twenty-eight cases exhibited the cultural characters of the human tubercle bacillus, and sixteen strains from six cases grew like bovine tubercle bacilli. In every case from which two or more strains were isolated the cultural characters of the strains were identical. In one case, a child aged five years who died from meningitis, both human and bovine bacilli were proved to have been present in the bronchial glands. The cultures in this case were obtained through guinea-pigs.
ABSTRACTS.
The pathogenicity of the various strains has been tested upon the rabbit only. From the thirty-five children examined the human type of bacillus was isolated in twenty-eight cases, the bovine type in six, and in the remaining case the infection was mixed. None of the bovine strains were isolated from children over four years of age. In four of the six cases death was due to tuberculosis-meningitis in three and abdominal tuberculosis in one. Death in the other two cases was due respectively to scalds and measles with broncho-pneumonia. In one of these the tuberculous disease was limited to the intestine and the mesenteric glands, and in the other to the mesenteric and bronchial glands. In all six cases the primary seat of infection was the intestines or mesenteric glands, and in one case there was extensive tuberculous ulceration of the pharynx. Bacilli of the human type were isolated from twenty-six diseased children and from two that were apparently healthy. In sixteen of the twenty-six the bronchial glands were most severely affected. In nine of these cases the lesions in the mesenteric glands were miliary, and were most probably caused by bacilli disseminated from the thoracic lesions. In four cases, of which two showed intestinal ulceration, they were partly or wholly caseous, and in the author's opinion they were due to the ingestion of bacilli at about the same time as the infection of the thorax occurred. The grounds for this opinion are that there were no disseminated lesions of similar size elsewhere in the body, and there were no ulcerated lesions in the lungs from which tubercle bacilli could be coughed up and swallowed. In six cases the infection was apparently primary in the lungs. In all these cases there was tuberculosis of the intestine and mesenteric glands, which could be amply accounted for by the condition of the lungs. In two cases infection caused by the human type of bacillus appeared to be certainly of alimentary origin. In two cases the portal of entry was uncertain. In five children dying from other causes isolated caseous and calcareous tuberculous lesions were found which did not produce tuberculosis in guineapigs. In four instances the disease was localised in the mesenteric glands, and in the fifth in the bronchial glands. Only one set of glands was implicated in each case. In these cases the apparently healthy glands failed to produce tuberculosis in guinea-pigs. Microscopic examination was positive in one case, negative in two, and not recorded in two. Attention is drawn to the evidence furnished by one case of the tendency for tubercle bacilli to die and not remain latent in retrogressive lesions. The subject was a boy of eight and a half years of age, who died of shock after an operation for tuberculous disease of the vertebrre and ilio-sacral joint. At the post-mortem examination calcareous nodules were found in the mesenteric and bronchial glands which failed to infect guinea-pigs. This is an example of arrest and cure of tuberculosis in gland tissue capable of destroying tubercle bacilli and progression of the disease in bony tissue less capable of destruction of the bacilli. In another case there was localised tuberculosis of the bronchial glands, which were caseous and softened. Numerous tubercle bacilli were discoverable in the caseo-purulent material, but only one of three inoculated guinea-pigs died. The majority of the bacilli were dead. Guinea-pigs were inoculated with material derived from apparently healthy
ABSTRACTS.
bronchial and mesenteric glands obtained from children showing no macroscopic evidence of tuberculosis. In two cases only were tubercle bacilli detected by this means, and they proved to be of the human type_ Both strains were isolated from bronchial glands. Reference is made to the findings in a number of investigations regarding the presence of tubercle bacilli in apparently healthy tissues, and it is pointed out that these discoveries furnish no evidence as to how long tubercle bacilli may remain in tissues before visible lesions are produced. With regard to the portal of entry the following points may be noted : Of eight cases in which the intestines or mesenteric glands were the seats of the primary lesions, six were caused by bovine bacilli and two by the human type. Of twenty-two cases in which the primary lesions were intrathoracic the whole were due to human tubercle bacilli. Since there is no recorded instance of a child suffering from primary thoracic tuberculosis caused by the bovine bacillus, and since there are no grounds for assuming that the two types behave differently, it must be held that the evidence tends to prove that in those cases in which primary thoracic tuberculosis caused by the human bacillus exists the path of infection has been the respiratory tract.
THE INFECTION OF CHILDREN WITH THE BOVINE TYPE OF TUBERCLE BACILLUS. THE author's investigations were carried out with the object of obtaining definite statistical evidence as to the relative frequency of the bovine and human types of tubercle bacilli in cases of disease of the cervical glands in children. Seventy-two consecutive cases were studied, and the results obtained show that in sixty-five of these the bacillus responsible was of the bovine type and in the remaining seven of the human type. As direct cultivation from materials obtained by operation proved to be too uncertain, the author resorted to the inoculation of · guinea-pigs, the lesions developing in these serving as the seed material for cultures. In all cases plain egg and glycerin egg media were used for the raising of primary cultures. These media, together with glycerin agar and glycerin serum, were also used for the classification of the cultures_ The necessity of using media containing glycerin for the differentiation of cultures is emphasised. Two distinct groups of tubercle bacilli were isolated, to which the author applies the names "eugonic" and "dysgonic," as suggested by the Royal Commission on tuberculosis. The dysgonic group contained sixty-five viruses, and these were all of the bovine type. The remaining seven viruses formed the eugonic group and were of the human type. The division into eugonic and dysgonic viruses was found to correspond in all cases with the differences in virulence for rabbits. A general description is given of the cultural characters of these two groups of viruses.
ABSTRACTS.
Clinical Bacteriology and Vaccine Therapy. By William Scott, F.R.e. V.S. London: Bailliere, Tindall & Cox. 1913. Price 7S. 6d. net. AN eminent medical authority some years ago prophesied that the physician of the future would bo:: an immunisator, and the author of this work has a like opinion regarding the role of the future veterinary surgeon. There is, however, a distinction, for, whereas it has generally been understood that the medical man whom the prophet had in view would merely administer the vaccine, the author of this work thinks that the veterinary practitioner ought to make his own bacteriological diagnosis, isolate and identify the causal organism, make and standardise his own vaccine, and where necessary control its use by periodic determinations of the patient's opsonic index. Mr Scott, who conducts a large country practice, would have the reader believe he already does all this, and, indeed, he declares that his object in writing the book was to show how other busy practitioners can do likewise. It is not encouraging to a reviewer with any knowledge of bacteriology to find such grotesque opinions in the preface, and a perusal of the text does nothing to remove the bad impression. The author somewhat plaintively appeals to the reader's indulgence on the ground that much of the matter was written in the small hours of the morning, but one cannot help feeling that he would have been better in bed and asleep. It is difficult to imagine :my more appalling prospect for veterinary therapeutics than the one which the author would like to see realised.
TUBERCULOUS INFECTION IN CHILDREN} THE first series of investigations recorded in this Report were carried out in the Pathological Laboratory of the Local Government Board hy Drs Eastwood and F. Griffith. The object of the enquiry was to investigate the incidence of tuberculous infection in a series of children dying from all causes between the ages of two and ten years, and to determine whether the bacilli found were of the bovine or of the human type. Materials from 150 children were examined. All these children had died in hospitals in or near London, none of which were especially devoted to the treatment of tuberculosis. The investigations supplement those carried out by the Royal Commission 1 "Reports to the Local Government Board on Public Health and Medical Subjects.' New Series No. 88:I. The Incidence and Bacteriological Characteristics of Tuberculous Infection in Children. By Arthur Eastwood, M.D., and Fred Griffith, M.B. II. An Enquiry, based on a Series of Autopsies, into the Occurrence and Distribution of Tuberculous Infection in Children, and its Relation to the Bovine and the Human Types of Tubercle Bacilli respectively. By A. Stanley Griffith, M.D. Printed under the Authority of His Majesty's Stationery Office by Darling & Son, Ltd., 1914. Price 2s. 3d. To be purchased through any Bookseller. .
ABSTRACTS.
81
on Tuberculosis in that they are based upon materials obtained from unselected cases. It was arranged that every case within the age-period mentioned which terminated fatally should be examined until 150 had been collected. Method of Invlstigation.-At the post-mortem examinations special care was taken not to cut into the bronchial and mesenteric glands. When either of these groups of glands showed any that were enlarged and obviously tuberculous some of the caseous material was removed with all necessary precautions to prevent contamination and used for the inoculation of egg· medium and of guinea-pigs. In cases in which the glands were not enlarged as many as possible were removed, emulsified, and inoculated intraperitoneally into guinea-pigs, not less than three being used when no evidence of tuberculosis could be discovered in them. Cultivation and animal inoculation were also resorted to in the case of other organs: (a) when they contained tuberculous lesions and none were found in the bronchial or mesenteric glands; (b) to clear up the diagnosis of a doubtful nodule; and (c) in certain cases where it was thought of interest to ascertain whether the tubercle bacilli obtained from various parts of the body all possessed the same characteristics. The guinea-pigs were killed six weeks after inoculation, if not obviously tuberculous at an earlier date, and cultures were made from the lesions found. The cultural characters of the bacilli obtained either directly or from the guinea-pigs were tested upon various media and their virulence for rabbits was determined by inoculation of weighed quantities of culture grown upon pure bovine serum. From a tabulated summary of the general results obtained the following details may be gathered : In fifty-six cases there was no evidence of infection with tubercle bacilli, and the inoculation experiments with emulsions of the bronchial and mesenteric glands were negative. In the remaining ninety-four cases, or 62·7 per cent., evidence of infection was found, with, in the majority of cases, the formation of visible tuberculous lesions from which the bacilli were recovered in culture. In sixteen of these cases, although tuberculous lesions were present and tubercle bacilli were in most instances demonstrable by microscopic examination, the bacilli were apparently dead, as neither cultivation upon artificial media nor animal inoculation yielded positive results. In seventy-eight of the ninety· four cases tubercle bacilli were isolated and cultivated. In five of these cases there was no macroscopic evidence of tuberculosis, tubercle bacilli being cultivated from apparently healthy glands. Bovine bacilli were isolated from three of these cases, in two instances from the mesenteric glands, and in the third from the bronchial glands. In the other two cases the bacilli were of the human type, and were isolated in one of them from the cervical, bronchial, and mesenteric glands and in the other from the mesenteric glands only. Examples of tubercle bacilli lying latent in mesenteric or bronchial glands of children showing tuberculosis in some other part of the body were encountered in twenty-two cases. In five of these the bacilli were of the bovine type, and they occurred in the mesenteric glands (once) and in the bronchial glands (four times). Of the seventeen instances in which human tubercle bacilli were found, thirteen showed latent infection of the mesenteric glands and four of the bronchial glands. F
ABSTRACTS.
The total number of cases in which death was due to tuberculosis was sixty-one, other causes being responsible in the remaining thirty-three instances. Since in sixteen instances the bacilli present in obvious lesions appeared to be dead, it was possible to distinguish between bovine and human infections in only seventy-eight of the ninety-four cases. Of these seventyeight cases sixty-five were due to bacilli of the human type, and tuberculosis was the cause of death in fifty-two of them. Bacilli of the bovine type were responsible for the infection in the remaining thirteen cases, and of these nine died from tuberculosis. In one instance in which the bronchial glands were free from tubercle bacilli a culture was obtained from the mesenteric glands which was found to resemble the bovine type of bacillus as regards its cultural characters, but which was of low virulence for rabbits. Reference to the tabulated information shows that the lesions present in the child from which this virus was obtained were: Spinal caries, tuberculous rib with discharging sinus, cas eo-calcareous tubercles in the mesenteric glands and the spleen. Attempts to cultivate tubercle bacilli from the spleen failed. This virus is included among those considered to be of the bovine type. As already stated, in thirteen cases bacilli of the bovine type were isolated, and in three of these none of the tissues showed any macroscopic evidence of tuberculous disease. From a survey of the remaining ten cases it may be gathered that in no case was disease found in the lungs without visible lesions in the intestine or its associated glands. In one of these cases there was tuberculous meningitis and a few grey foci in the liver, the mesenteric glands appearing normal, but tubercle bacilli were cultivated from both the liver and the mesenteric glands. In four of these cases there were visible lesions involving the abdominal organs, but none in the thoracic organs. In the course of examining tuberculous lesions found in children, observations were recorded as to the appearances and numbers of the tubercle bacilli found in smear preparations. After the type of bacillus present had been determined by cultural and inoculation methods, these records were analysed with a view to determining how far a forecast of the type of bacillus can be based upon the microscopic characters, on the assumption that long, beaded forms were characteristic of the human type, and short, uniformly stained forms, without admixture of the long, beaded forms, indicated the bovine type. 121 smears were recorded. In sixty· one cases no inference as to type could be drawn. In fifty-two cases (forty-seven human and five bovine), a correct inference was drawn, and in eight cases (six human and two bovine) the inferences drawn proved to be incorrect. The authors found in every case that cultures obtained, either directly or through the guinea-pig, from different situations in the same body were identical in growth upon corresponding media. For the purpose of comparison with the condition found in the series of children, and with particular reference to the question whether tubercle bacilli can pass through the alimentary tract and set up lesions in distal organs without leaving evidence of infection at the portal of entry, the results obtained in 462 feeding experiments carried out by the Royal Commission on Tuberculosis are given in tabular form. From these it may be gathered that distal lesions without lesions at the portal of entry were exceedingly rare except in the case of the dog. For the purpose of obtaining further data, feeding experiments were carried out upon eighteen pigs. In all cases except two the pigs were fed with bovine cultures mixed with milk. In the two instances human cultures were used.
AIiSTRACTS.
The pigs were killed after the lapse of from 84 to 167 days, the post-mortem examination being supplemented in many instances by inoculation tests with apparently normal tissues. The tabulated results show: (I) That uncertainty attaches to feeding experiments in which small doses ('01 milJigramme or less) are used; (2) that, as in children, tubercle bacilli may occasionally be found by experiment in apparently healthy tissues; and, especially (3) that distal lesions were entirely absent in all cases in which no infection of the alimentary tract or its glands was found. THE second series of investigations detailed in the report were carried out on behalf of the Local Government Board by Dr A. Stanley Griffith, with the object of ascertaining, (1) the frequency of tuberculous infection, latent or manifest, in childhood; (2) the distribution of the disease within the body; and (3) the relative incidence of the bovine and the human types of the tubercle bacillus. In this investigation also no selection of cases for examination was made, every fatal case in children under twelve years of age occurring in the institutions assisting in the enquiry was investigated. In all cases, whether there were macroscopic lesions or not, the mesenteric and bronchial glands were examined, and in some instances the cervical glands and other tissues. The glands were removed from the associated tissues with every possible precaution to prevent accidental contamination and were emulsified with salt solution, the emulsion being used for the intraperitoneal inoculation of from two to four guinea pigs. In all cases where there was suitable material an attempt was made to get cultures direct. The inoculated guinea-pigs, unless showing obvious evidence of tuberculosis at an earlioer date, were killed six weeks after inoculation. Egg medium was used in all cases to raise primary cultures, sub-cultures being made upon serum, and only serum cultures were used for the virulence tests. The tests employed to distinguish between the human and bovine types of bacilli were the cultural characters shown by growths upon glycerinised media and the virulence for certain species of animals. Attention is drawn to certain important factors in carrying out the virulence tests. If rabbits are inoculated intravenously the dose should not be too large, since large doses of human tubercle bacilli sometimes produce an acute tuberculosis in rabbits, not easily distinguishable from that set up by bovine bacilli. A suitable dose is '01 mg. of culture. If subcutaneous inoculation be resorted to, the dose should not be smaller than 10 mg., since smaller doses may produce slowly progressive disease instead of the acute and rapidly fatal infection. In all, ninety-one strains from various sites in the bodies of thirty-five children were tested; of these strains twenty-one were obtained direct and seventy through the guinea-pig. Seventy-two strains from twenty-eight cases exhibited the cultural characters of the human tubercle bacillus, and sixteen strains from six cases grew like bovine tubercle bacilli. In every case from which two or more strains were isolated the cultural characters of the strains were identical. In one case, a child aged five years who died from meningitis, both human and bovine bacilli were proved to have been present in the bronchial glands. The cultures in this case were obtained through guinea-pigs.
ABSTRACTS.
The pathogenicity of the various strains has been tested upon the rabbit only. From the thirty-five children examined the human type of bacillus was isolated in twenty-eight cases, the bovine type in six, and in the remaining case the infection was mixed. None of the bovine strains were isolated from children over four years of age. In four of the six cases death was due to tuberculosis-meningitis in three and abdominal tuberculosis in one. Death in the other two cases was due respectively to scalds and measles with broncho-pneumonia. In one of these the tuberculous disease was limited to the intestine and the mesenteric glands, and in the other to the mesenteric and bronchial glands. In all six cases the primary seat of infection was the intestines or mesenteric glands, and in one case there was extensive tuberculous ulceration of the pharynx. Bacilli of the human type were isolated from twenty-six diseased children and from two that were apparently healthy. In sixteen of the twenty-six the bronchial glands were most severely affected. In nine of these cases the lesions in the mesenteric glands were miliary, and were most probably caused by bacilli disseminated from the thoracic lesions. In four cases, of which two showed intestinal ulceration, they were partly or wholly caseous, and in the author's opinion they were due to the ingestion of bacilli at about the same time as the infection of the thorax occurred. The grounds for this opinion are that there were no disseminated lesions of similar size elsewhere in the body, and there were no ulcerated lesions in the lungs from which tubercle bacilli could be coughed up and swallowed. In six cases the infection was apparently primary in the lungs. In all these cases there was tuberculosis of the intestine and mesenteric glands, which could be amply accounted for by the condition of the lungs. In two cases infection caused by the human type of bacillus appeared to be certainly of alimentary origin. In two cases the portal of entry was uncertain. In five children dying from other causes isolated caseous and calcareous tuberculous lesions were found which did not produce tuberculosis in guineapigs. In four instances the disease was localised in the mesenteric glands, and in the fifth in the bronchial glands. Only one set of glands was implicated in each case. In these cases the apparently healthy glands failed to produce tuberculosis in guinea-pigs. Microscopic examination was positive in one case, negative in two, and not recorded in two. Attention is drawn to the evidence furnished by one case of the tendency for tubercle bacilli to die and not remain latent in retrogressive lesions. The subject was a boy of eight and a half years of age, who died of shock after an operation for tuberculous disease of the vertebrre and ilio-sacral joint. At the post-mortem examination calcareous nodules were found in the mesenteric and bronchial glands which failed to infect guinea-pigs. This is an example of arrest and cure of tuberculosis in gland tissue capable of destroying tubercle bacilli and progression of the disease in bony tissue less capable of destruction of the bacilli. In another case there was localised tuberculosis of the bronchial glands, which were caseous and softened. Numerous tubercle bacilli were discoverable in the caseo-purulent material, but only one of three inoculated guinea-pigs died. The majority of the bacilli were dead. Guinea-pigs were inoculated with material derived from apparently healthy
ABSTRACTS.
bronchial and mesenteric glands obtained from children showing no macroscopic evidence of tuberculosis. In two cases only were tubercle bacilli detected by this means, and they proved to be of the human type_ Both strains were isolated from bronchial glands. Reference is made to the findings in a number of investigations regarding the presence of tubercle bacilli in apparently healthy tissues, and it is pointed out that these discoveries furnish no evidence as to how long tubercle bacilli may remain in tissues before visible lesions are produced. With regard to the portal of entry the following points may be noted : Of eight cases in which the intestines or mesenteric glands were the seats of the primary lesions, six were caused by bovine bacilli and two by the human type. Of twenty-two cases in which the primary lesions were intrathoracic the whole were due to human tubercle bacilli. Since there is no recorded instance of a child suffering from primary thoracic tuberculosis caused by the bovine bacillus, and since there are no grounds for assuming that the two types behave differently, it must be held that the evidence tends to prove that in those cases in which primary thoracic tuberculosis caused by the human bacillus exists the path of infection has been the respiratory tract.
THE INFECTION OF CHILDREN WITH THE BOVINE TYPE OF TUBERCLE BACILLUS. THE author's investigations were carried out with the object of obtaining definite statistical evidence as to the relative frequency of the bovine and human types of tubercle bacilli in cases of disease of the cervical glands in children. Seventy-two consecutive cases were studied, and the results obtained show that in sixty-five of these the bacillus responsible was of the bovine type and in the remaining seven of the human type. As direct cultivation from materials obtained by operation proved to be too uncertain, the author resorted to the inoculation of · guinea-pigs, the lesions developing in these serving as the seed material for cultures. In all cases plain egg and glycerin egg media were used for the raising of primary cultures. These media, together with glycerin agar and glycerin serum, were also used for the classification of the cultures_ The necessity of using media containing glycerin for the differentiation of cultures is emphasised. Two distinct groups of tubercle bacilli were isolated, to which the author applies the names "eugonic" and "dysgonic," as suggested by the Royal Commission on tuberculosis. The dysgonic group contained sixty-five viruses, and these were all of the bovine type. The remaining seven viruses formed the eugonic group and were of the human type. The division into eugonic and dysgonic viruses was found to correspond in all cases with the differences in virulence for rabbits. A general description is given of the cultural characters of these two groups of viruses.