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A contribution to the study of tuberculous infection in infancy and childhood
A CONTRIBUTION TO THE STUDY OF TUBEIICULOUS INFECTION llq" INFANCY AND CHILDHOOD. By ~. C. :HENDRIE, M.D.Glas., D.:P.:H.Birm. Ifi the general practice of medicine in a busy industrial area the relative frequency and u n i f o r m mortality of tubercular nmningitis in children is impressive. The subject is also of outstanding importance from'the :Public :Health standpoint, and Sir George Newman [1] in a memorandum has drawn attention to the special n e e d o( a searching investigation on the subject of tuberculous infection in childhOOd. Tuberculosis is also of great economic importance to the community , and it is rather remarkable that if as many children were to die each year of smallrpox or typhoid there would be a public outcry. : Whereas in the case of tuberculosis, owing to the fact that we are dealing with a disease w h i c h does not appear to cause so m u c h consternation in the public mind, observations lead one t o believe that adequate measures of control and prevention of aerogenous dissemination of tuberculous disease from adults to children have received insufficient attention. The plan of action in studying the subiect has included u review of various factors Causing or contributing to infection, the methods Of the transmission of tuberculous disease to and within the juvenile population. INHALATION INFECTION. I n the general commun!ty cases o f " o p e n " tuberculosis form a most serious menace to public health. Droplet infection is considered to be the important means ~/hereby tuberculous material is aerogenously disseminated. Fliigge many years ago was a~ble to show by experimental methods that under n m d e r n conditions of life droplet infection was the common mode of transmission of tuberculous disease within the h u m a n race. Careful research has shown that the air exhaled by consumptives during ordinary and quiet breathing is usually free from tubercle bacilli, whereas the moist droplets exhaled whilst coughing, talking or sneezing often contain living tubercle bacilli which may remain suspended in the atmosphere for a variable period of time. :Flfigge in his original experiments placed guinea-pigs in near contact with tuberculous patients, and in a high percentage of cases pulin0nary tuberculous disease developed in the animals. The results of animal experiments are of great interest in view of the'relationship of inhalation to infants and young children. It is no'w recognised that " carriers" of s o m e of the less frequently severe diseases, e.g., scarlet fever, by transmitting sub-clinical doses of infection to individuals in their immediate neighbourhood may act beneficially therein by activating immunity mechanisms. Under era.rain conditions, as Surgeon Commander Sheldon: Dudley has pointed out, a high " carrier" rate synchronises with the decline of an existing epidemic disease. There is no suggestion or proof that a n y comparable conditions exist in the case o f tuberculous infection, and the evidence points to the fact that an " o p e n " case of tuberculosis in a family on the contrary frequently leads to one or more deaths in the juvenile members of the household, from transmitted aiirogenous infection. The relationships of 13
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the " soil" and the " s e e d " in tuberculous infection is crowded with, at present, unknown quantities. Therefore one must assume that any infant or child exposed to tuberculous infection would possibly develop the disease in a generalising form with tragic results. It is only safe to conclude at this juncture that 100 per cent. of infants are highly susceptible to the tubercle bacillus, and especially so to the human type bacillus, and there are no definite means available which can be relied upon to indicate the inherent defensive capacity in any given individual child. This being so, the main object of this paper is to illustrate that the only means of adequate protection of the y o u n g child against what even from the comlnencement might be a fatal illness, is the rigid necessity of protection of such young individuals from a tuberculous infectious environment. F. Hamburger [2] records the placing of a feeble-minded boy, aged 9 years, i n a room in which three tuberculous girls lived. Because of the 9 mental state of the boy, the girls avoided him and never came into close contact with him. H e remained free from tuberculous infection, as shown by the negative, clinical examination and negative tuberculin reaction for seven months. On the other hand, in a room i n Which a tuberculous patient was harboured, four children aged 9,, 4, 5 and 10 years respectively, were brought in. Within four weeks all the four children, who, prior to coming into the room, were tuberculin negative, showed a positive reaction to tuberculin. There are certain periods of life in which the risk of a tuberculous infection becoming generalised is great, and this, combined with the very considerable susceptibility characteristic of infancy, is a matter of great importance. It is thus obvious that when contact with the consumptive is close and prolonged, which in ordinary life occurs not uncommonly in the domestic relationships of mothers and suckling infants, droplet infection may be ~ serious menace, and as will be shown later, this ~principle is of great significance. CONGENITAL TUBERCULOSIS. It is ~ remarkable fact that although transference of tuberculous infection from mother to the fcetus in utero may happen, it occurs so extremely rarely as to be of no more than academic interest only. An interesting inquiry was conducted by Debr6 and Lelong, into the incidence of tubercle bacilli or tuberculous lesions in 98 placentm of tuberculous women. I n none did they find any evidence whatever of tuberculous infection, and, furthermore, careful autopsies of 15 still-born infants, born of tuberculous mothers, were examined very closely, both histologically and by animal inoculation, with negative results. The placenta appears to act as a formidable barrier and a powerful line of defence between the tuberculous mother and the foetus. In connection with this point the writer had facilities for studying the post-mortem record, and for seeing specimens obtained from a case of tuberculosis of the newly born infant (19 days old) in the Baudelocque Hospital, :Paris, in June of 1932. The details of the case were provided by Dr. L a c o m m e ; they ar~ as follows : A primipara, aged 95, suffering from I~ott's disease, developed at the 9eighth month of pregnancy n~liary tuberculosis with tubercular meningitis. The child was removed by C~esarean section, and presented no
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abnormal features externally. Skin reaction to tuberculin on the seventh day was negative. On the sixteenth day its temperature rose a little, and it lost weight. Auscultation showed a few scattered rhles in both lungs. The child died on the nineteenth day. At the autopsy numerous fine tuberculous granulations were found scattered throughout the parenehyma of the organs. Bacteriological examination carried out by hi. hi7. Coulaud and Valtis showed tubercle bacilli to be present, and in the internal organs were seen typical changes characteristic of miliary tuberculosis. This appears to have resulted from infection of the infant's blood-stream immediately prior to, or at its birth, i.e., at a time when the mother herself was actually suffering from tubercular septicmmia. This must fortunately be a rare occurrence, and the case is only mentioned to show the extreme rarity of true congenital tuberculosis. The work of L6on Bernard also depends upon his belief that tuberculosis is not a congenital disease, and the great success of his prophylactic Work bears out the view he holds, viz., that infection practically always arises from contact after birth with an infectious " o p e n " case. It can, without doubt, be assumed that an infant born of a mother who has local pulmonary tuberculosis only at the time of labour will not be infected except by aerial contagion: that this is so can be exemplified by another case from the Baudelocque Hospital. The details are as follows: A inother with caseous bilateral puhnonary .tuberculosis--sputum T.B. + + m g a v e birth to an infant of normal weight on August 3, 1923. I t was normal in appearance and separated at birth. It was immediately placed in a different pavilion from that containing the mother. Unfortunately the mother, on going out of hospital a month later, obtained the permission of a nurse to embrace her child, the contact lasting for a short period of time. During the first three months, the child's weight curve continued satisfactory. At the end of three months, digestive troubles supervened, the child lost weight and developed febrile attacks. A cough appeared and auscultation revealed a few fine rAles at the left base. The loss of weight was suspicious. A staphylococcal infection of the. skin supervened, and death occurred on November 25, 1923. At autopsy, bilateral caseous bronchopneumonia w a s found, with three or four large tracheo-bronchial glands equally caseous. A few miliary tubercles were found on the pleura and on the peritoneum. ~-~.CQUIRED TUBERCULOSIS---THE CxHON'S TUBERCLE.
The simplest form of tuberculosis of the lung is found in infants in whom no complex resistance has been developed to impede the course of the infection. The ideas of Ghon as to the primary puhnonary focus have been amply confirmed : the Ghon tubercle probably represents the primary focus of localisation within the lung of tubercle bacilli received by the aerogenous route. It is commonly pyramidal in shape, with the base towards the pleura, and shows dense puhnonie consolidation and caseation. The size of such focus varies considerably in different cases and it may or may nog be easily detected on ordinary macroscopic examination of the lung; the Ghon's tubercle may be present in any part of the lung, and although it commonly exists singry, two such foci may be detectable. It shows no special selective situation in either lung, and is as commonly seen
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in the lower lobe as the upper. If the search be c.ontinued, sometimes an erosion of the caseous node into the associated bronchiole will be observed. The lymph nodes at the corresponding lung hilum are always enlarged and caseous; sometimes direct lymphatic extension from" the intrapuhnonary focus to the hilum glands can be easily demonstrated. Development of the localised Ghon lesion seems to indicate that tubercle bacilli were originally aspirated deep into the lung substance of the hitherto uninfected child. If the initial bacterial dos• is not overwhelniing, it would appear there exists even in 'the infant a capacity of the lung tissue to localise the infection with the ultimate result of the formation of a Ghon's tubercle. There is, however, a very strong tendency in the infant for bacilli to escape into the lymphatic channels of the hilus and tracheo-bronchiallymph glands. Thus it is ahnost a rule to find in the association of the primary intrapulmonary nodule a caseative reactionary disease in the corresponding lymph nodes. It is well recognised that even circumscribed and partially calcified tuberculous loci may still harbour the tubercle bacillus in an active and virulent form. A direct proof of this statement is indicated by the modern utilization of material removed from the stomach by aspiration, in cases in which such tuberculous feel exist in the lung and associated lymph glands. The presence of living and active tubercle bacilli has been thus frequently demonstrated. Also since it is almost the rule for infants and young children to swallow such infected secretions, autogenous infection of the alimentary tract is not an uncommon feature. There is no doubt that numerous factors may arise in the individual which will in themselves, singly or collectively, contribute towards the tendency on the one hand to maintain the primary intrathoracic lesion in a state of response , and on the other hand to allow one or other of the various forms of dissemination locally, or to distant parts of the body, to occur. It i s of outstanding importance to regard re-infection from an external source as likely to be of extreme danger to a child who is already infected with the tubercle bacillus, as this is probably the factor which, by a combination of the removal of processes of established resistance and the precipitation of sensitising factors, allows a rapid decline of the bodily defence as a whole, thus favouring generalisation of the disease. DETERMINATION
OF T H E P R I M A R Y I'{OUTE OF T U B E R C U L O U S IN INFANTS A N D CHILDREN.
INFECTION
In the living child clinical investigation ,nay give clear evidence regarding the site of the primary distribution in the body of tile infecting agent, but since the establishment of exact and conclusive evidence by such means is difficult in many cases, careful post-mortem examination in fatal cases is more likely to produce conclusive evidence. Direct bacteriological analysis has not been possible in regard to the primary or secondary feet, and hence for the purposes of, this paper approach to the problem has been made by means of careful study of the anatomical distribution of m acroscopical lesions in any given case. It has been regarded that, where the hilum and tracheo-bronchial lymph glands were the site of a recognisable tuberculous process, the original infective agent gained admission to the body by means of the pulmonary system. In each such case the possibility of a more unusual route such as connec-
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tion with a primary tuberculous cervical adenitis or an extension upwards from the abdomen by means of the thoracic duct or its connections has been carefully eliminated. In what has been considered to be the primary case of intrathoracic tuberculosis, there has been detected at post-mortem examination a tuberculous process in the lung, bearing the feature described by Ghon and associated with caseous tuberculous mediastinal adenitis. It is surprising how frequently this clear-cut picture has presented itself. I t is true, however, that in some instances the absence of any macroscopically visible primary intrapulmonary tuberculous focus has been striking. However, the presence in such cases of massive tuberculous disease in the mediastinal glands and more typically in the hilum glands of one lung, with the absence of tuberculous foci in other parts of the body (excluding miliary lesions), has Ied to the only conclusion possible that the original infection was by way of inhalation infection but no recognisable permanent intrapuhnonary damage was effected. It has been observed in many of the primary thoracic cases studied, that together with definite clinical evidence of abdominal tuberculosis, or where no such clinical suspicion was aroused, a variable degree of active tuberculous involvement within the alimentary tract and its associated lymphatic system, more especially the mesenteric lymph glands, has been detected by necropsy examination. It has been striking how frequently such lesions below the diaphragm were associated with tuberculous lesions above the diaphragm. In any given case, the problem set was to decide on what anatomical evidence could the sequence of events be analysed. This in certain cases presented some difficulty, but in the large majority an accurate analysis could be made. Points which have been taken were (1) the extent of the lesi0ns found in the thorax and in the abdomen; (2) the relative ages of the tuberculous reaction in the respective parts of the body ; (3) the anatomical disassociation of the diseased tissues: and (4) a careful study of the intervening lymphatic system where two or more areas of tuberculous reaction were detectable--the latter being typically exemplified by examination of the main trunk connections of the mesenteric lymphatics and the mediastinal lymphatic system. I~,ECOGNITION OF I)RIMARY TtIOBACIC INFECTION.
Tubercle bacilli often escape into the respirator), secretions in cases even where intrapulmonary and mediastinal gland lesions appear to be in a closed condition. The fact is utilised by clinicians when investigating cases suspected of thoracic tuberculosis. By testing the resting gastric contents (which in children represents to some extent swallowed respiratory secretions) tubercle bacilli are quite frequently detected in cases where definite clinical or even radiological evidence of a conclusive nature has not been obtained. In any child debilitated by tuberculous infection, the acid gastric secretion is minimised and tubercle bacilli may pass readily into the intestinal tract. The intestinal and mesenteric involvement thus obtained may be of greater degree and extent than might at first sight be suggested by the relative minority of the primary intrathoracic foci. Therefore, in some instances careful judgment is required on the available
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necropsy findings to reach a satisfactory conclusion concerning the p r i m a r y origin of infection in the case. I t is evident t h a t the e x t e n t of the abdominal lesion p e r se cannot by any means~be eonclusive o f p r i m a r y infection by ingestion. T h e age of the lesions in the thor/tx m a y be obviously greater t h a n t h a t of those in the abdomen, irrespective of their differences in extent. T h e presence of a well-marked isolated easeating G h o n ' s tubercle, in t h e light of the k n o w n pathology of the genesis of such a lesion, cannot be considered to arise in any secondary way to a p r i m a r y abdominal tuberculous d i s e a s e . Ileal difficulty arises w h e r e t h e r e is a massive and anatomically continuous tuberculous involvement of t h e whole abdominal l y m p h a t i c system, including the thoracic duct origin and connection in the thorax. I n such cases it m u s t be granted t h a t secondary mediastinal glandular tubercle might, and in fact does, to our knowledge, arise very occasionally by this means. U n d e r these circumstances, f u r t h e r extension into t h e p u l m o n a r y system has also been k n o w n to occur. B y the breakdown of i n t r a p u l m o n a r y fool, f u r t h e r reinfection of the bowel m a y take place. I n fact, a cyclical infection and reinfection is thus established. I n v e r y advanced cases of this kind a retrospective diagnosis of the origin and site of the p r i m a r y infection m a y be almost impossible. Although bacteriological investigation to. d e t e r m i n e w h e t h e r the h u m a n or bovine type of bacillus is present would be helpful, it would not, in itself, necessarily be completely conclusive to this end. I t is reasonable, therefore, to believe t h a t w h e r e a c o m b i n a t i o n of i n t r a p u l m o n a r y and thbracic glandular infection exists, t o g e t h e r w i t h intestinal and m e s e n t e r i c involvement and w h e r e t h e m a i n i n t e r v e n i n g l y m p h a t i c connections of these two systems are free from t u b e r c u l a r disease, t h e n the p r i m a r y focus existed above t h e d i a p h r a g m and not w i t h i n the abdomen. I n o r d e r to illustrate the above considerations a few selected cases from t h e whole group studied are outlined as follows : ~ . Case A.--W. BI., female, aged 2 years ,5 months. First child of two. ClinicM History.--Listless and out of sorts for a short time. Vomiting occurred,
later pain was present in the eye; convulsions appeared. Child became increasingly drowsy. She was admitted to hospital in coma, showing the characteristic features of meningitis. Examination of the lungs showed impaired percussion note, just inside the angle of the left scapula, with harsh breath sounds of ,~ bronchial type in the neighbouring lung. .Post.morlem 17~ndings.--Glands at the left hilum were considerably enlarged and caseating. In the lung substance of the left upper lobe, an area of caseating lymphatic tuberculosis, the size of a cherry, was detected. This was apparently well circumscribed, and not of recent formation. Careful examination within the abdomen showed no evidence of any tuberculous disease, beyond the presence of visceral miliary tubercles in common with their presence in all the other organs and meninges. Case B . - - B . ~V., female, aged 6 years. First clfild of two. Clinical Hislorg.--Convulsions for six days, repeated vomiting and marked constipa-
tion, with progressive pallor and eyanosis. Admitted to hospital in conditidn of severe dehydration and showing characteristic meningeal signs. The only abnormal physical signs in lungs were those of diminishcd air entry into the right lung fields. Cerebrospinal fluid showed the characteristic cellular and bio-chemical changes of tuberculous meningitis. l'ost-~mrtem F i n d i n g s . ~ A small tubcrculoma present in the upper part of the thynms gland. Towards the posterior aspcct of the right lung, a chronic tuberculous focus, the siz9 of a hazel nut was found. Several of the lymph nodes at tlm right hilum and the
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gland at tlle bifurcation of the trachea were involved in cascating tuberculous disease. No tuberculous process was detected anywhere within the alimentary tract, or in the abdominal lymphatic system. All the viscera showed presence of typical miliary tubercles, and characteristic tubercular meningltls was demonstrated.
Case C.--R. S,, male, aged 5 months. Third child in family of three (one of which was dead of tuberculous meningitis). Clinical Hisfory.--Although the case under review was only 5 months old, ig had been observed that the infant had suffered from spasmodic cough for two months, and symptoms suggesting " asthma " had appeared from time to time. The terminal illness was vague and rapid, miliary tuberculous disease was not; suspected, and in fact, was only detected at post mortem. CMnically there were no definite abnormal physical signs in the lungs to suggest tuberculous disease. Post-morteJJ~ Findlngs.--The necropsy revealed enlarged and caseating lymphatic.glands in the superior mediastinum. An intrapulmonary tuberculous lesion which appeared to be of at least several weeks' duration, and prob,~bly more, was found towards the centre of the right middle lobe. This focus was the size of a hazel nut. No tuberculous disease was found within the alimentary tract, or in the abdominal lymphatics. All the intcrnal organs showed numerous fine miliary tubercles. The meninges revealed characteristic tuberculous basic meningitis. Case D.--W. B., male, aged 1 year 9 months. Seventh child of a family of eight. Two children dead, one acute diarrhoea and vomiting, and one of an obscure puhnonary condition ? " ipneumonia." Clinical History.---Occasional attacks of diarrhoe~ and vomiting. A shor~ time before coming under observation at hospital, rapid loss of weight was noticed. Aftei" admission drowsiness was detected, combined with neck rigidity and other signs of meningitis, which diagnosis was confirmed by lumbar puncture, bacteriological, and cytological examination of cerebrospinal fluid. Careful examination of chest; revealed no abnormal physical signs. There was some simple distension of the abdomen. Post-mortem ffindi~gs.--Therc were considerably enlarged caseating lymph glands at the hilton of the left lung, but a continuity of these lesions was not traceable to a small isolated area of tuberculous disease in the posterior aspcct of the left middle lobe of the lung. No indication of any abdominal tuberculous disease was detected. The thoracic and abdominal viscera together with the meninges revealed the characteristic features of terminal miliary tuberculosis. Case ~ . - - R . B., male, oged 5 years. Second child of two. ,~[other's sister died of tuberculosis and mother's brother also died of tuberculosis. History.--Pale and thin for one year. For two weeks before admission failure of general health with development of severe constipation. Clinical Hislor~j.--Condition on admission to hospital : neck rigid, Kernig's sign and other clinical evidence of meningitis was detected. Several miliary tubercles in the retinm. No unusual phenomena could be detected in the thorax. Post-morlcm Findi~zgs.~Largc caseating tubcrculous lymph glands present at right lung hilum. An isolated patch of tuberculous disease was detected towards the periphery, at the posterior parb of the right lower lobe, one-third of an inch in diameter, entirely caseous. The left lung and corresponding left hilum glands were not involved and no intestinal or abdominal glandular disorder.was present. An old tubcrculomc~ was discovered in the right island of Rcil; this appeared to be quite encapsulated, and not connected with the tuberculous meningitic process. The viscera and meningeal tissues" revealed the usual signs of miliary tuberculosis. Case F . m A . F., male, aged 5 months. Second child of two. History.--Cough for a few days, vomiting, twitching of face and bands.
Observation in hospital revealed a meningeal posture in bed, and strabismus; marked spasticity of legs developed, and meningeal signs became very pronounced. Cliuical diagnosis of tuberculous meningitis was confirmed by bacteriological, cytological, and biochemical examination of cerebrospinal fluid.
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Post-mortem Findings.~In the substance of the upper lobe of the righg lung, several yellowish areas of tuberculous consolidationwere found, one of these areas revealing cavity the size of t~hazel nut, full of soft caseous material, and lined with granulation tissue. In the lung substance immediately surrounding was found a caseating form of pneumonia. The bronchial and mcdiastinal lymph glands were enlarged and advancedly caseous. There was no abdominal tuberculosis beyond the presence of terminal miliary tubercles, which wcre also secn in the thoracic viscera and in the characteristic meningitic exudate. Commentary.inCases A, ]3, C, D, E and F, as briefly outlined above, are considered to be examples of individuals receiving without doubt a primary infection of the lung by inhalation of tubercle bacilli. I n each instance an intrapulmonary tuberculous focus of some duration was detected in association with caseative tuberculous disease in the anatomically related lymph glands. I n two instances, Cases C and F, the patients were only aged 5 months. I t is therefore obvious that some approximation of the time element in these lesions can be deduced. In the Case F, the intrapulmonary lesion was of remarkably advanced degree, and w h e n considered with the age of the infant, it must be assumed that the primary infection had taken place within the first three months of life. I n Case C, as the description relates, an old lesion was present in the lung substance, the age being deduced from the well-marked caseative change with reactive encapsulation, t t e r e again it can be logically understood that a primary infection occurred soon after the neo-natal period of life. I t is therefore evident that even at this early age in life definite and recognisable intrathoracic lesions can be discovered as evidence of direct infection by way of the respiratory tract, which is an important observation to be realised when searching f o r the means of contagion in the infant. It is interesting to observe even in this snmll series of cases that the intrapulmonary primary tuberculous focus frequently exists singly, and may be disposed of at any place within the lung substance or immediately subpleural in position. There may be some significance in this observation. It suggests that the infection has been by one or two tubercle bacilli initially, which have settled in the bronchial tissue, where the Ghon's tubercle is later discovered. It is readily understood how the local and general resistance of the child, when infected with a small single dose of tubercle bacilli, nmy defend itself by the formation of the local lung lesion, even though the hilar and mediastinal lymph glands are called on to assist in this defence mechanism. Thus it would appear that the tragic sequence of miliary tuberculosis is determined in such cases where superaddcd reinfection from without, or some temporary influence of an endogenous nature, disorganises the resistance of the unfortunate infant. Case E bears some points meriting special comment. Some time relationships of the infection responsible for the intrapuhnonary caseating lesion may be gathered from the fact that the child was exposed for a period of time, in all probability some years previously, to active tuberculous disease in a relative. So far as is known, the child had not been exposed t o any further infection by inhalation since that time. Corroborative evidence concerning the time of original infection may be gathered by the
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fact t h a t an encapsulated intracerebra! t u b e r e u l o m a was present also, the latter being regarded as a m e t a s t a t i c extension f r o m the original intrap u l m o n a r y focus. I t would appear, therefore, evident t h a t the initial sites of reaction are easily detectable for a considerable period of time after their formation, a n d yet w h e r e judged by clinical methods, such lesions appear to be quiescent, and miliary tuberculosis m a y still make its dread appearance. T h e G h o n tubercle, therefore, while being of considerable value in an investigation of this kind, w h e r e evidence is s o u g h t for the direction of p r i m a r y infection, mus~ also be considered o f some potential d a n g e r to the patieng. This is especially so since active caseating t u b e r culous disease is almost "invariably found in the a n a t o m i c a l l y related l y m p h glands at the same time. F r e q u e n t l y , the mediastinal glandular disease, w h i c h has no d o u b t arisen by a similar process, exists without t h e r e being a residual d e m o n s t r a b l e i n t r a p u h n o n a r y lesion. I t has been outlined that a secondary extension of tuberculous disease to ghe intestinal t r a c t m a y occur as a result of the a u t o m a t i c swallowing of b r o n c h o - p u l m o n a r y secretions in a child w h o is suffering from a p r i m a r y intrathoracic focus of tuberculosis. T h e following g r o u p of cases illustrates examples of this type : ~ Case G.IK.]3., nmle, aged 2 years. Second child of two. First child died of tuberculou s meningitis. History.--Breast fed. Twelve days restlessness, unusual involvement of the right ann, with vomiting rLttacks and head retraction. On admission to hospital, recent emaciKtion was evident, and characteristic signs of meningitis were present. Papilloedema was seen, and cerebrospinal fluid showed the usual features present in tuberculous meningitis. No unusual physical signs in chest were elicited. 1)ost-mortem 17indings.~Extcnsive thoracic glandular tuberculosis, more especially at hilum of the right lung, and in the substance of the middle lobe of the right hng, a diffuse form of cascativc pneunmnie consolidation were seen. Left lung showed no such change. A careful examination of the intestinal mucosa showed no visible ulceration, but section of the lymph glands in relation to the small intestine showed recent tuberculous invasion. Typical miliary tubercles were present in the viscera and meninges. Case H.--]3. C., female, aged 8 months. Fifth child of five. History.--Three months prior to admission lef~ hip-joint noticed not to be normal. When brought to hospital, evidence of arthritis was definite. The child had had ~ cough for some time. A few days after admission to hospitM, early signs of meningitis appeared and rapidly progressed. _Post-mortem 17indings.~A large fibro.caseating mass was found in the lower portion of the right lung. The corresponding hilum glands were much enlarged and caseating. In the mucous lnembrane of the ileum, two small recent tuberculous ulcers were detected with some involvement also of the lymphoid tissue in the region of tim ileo-cmcal valve. There was an absence of involvement of the mesenterie lymph nodes. Numerous miliary tuberclcs present in ~he viscera and meningitic exudate was present. Tuberculous involvement of the synovial membrane of tlm left hip-joint was demonstrated. Case L--J. S., female, aged 2 years 3 months. History.--Operation for simple mastoiditis three mouths before admission to the Children's ttospita]. Recent illness consisted of irritability for a few days, pyrexia, drowsiness and vomiting. Case clinically rccognised as tuberculous meningitis and diagnosis confirmed by examination of ccrcbrospinal tluid. 1)osl-morlcm 1,'indings.--At thc peripheral part of the right upper lobe, an old tuberculous area, the size of a large pea, was detce.tcd. Lymph glands at the hilum, corresponding to this part of the lung, shmved c'ascative disease. Several very recent tuberculous ulcers were detected in the jejunal and ileal mucosm, these ulcers being 88in. to ~ in. in diameter,
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showing only slight thickening. There was more extensive recent ulceration at the ileocmcal junction. The mesenterie lymph glands, however, revealed no macroscopic tuberculous invasion. The usual evidence of miliary tuberculosis and tubercular meningitis was detected.
Case J . - - l l . W., male, aged 2 years 10 months. F i r s t child of two. Previous health of this child appeared to be good. Clinical History.--Fourteen days before hospital observation, vomiting, severe headache, restlessness and photophobia present, o n admission, convulsions with rapid development of complete picture of tubercular meningitis supervened. Post-morlem F~nr~ings.--An old caseating lesion, size of a florin was found, situated in the lower part of the left lung, and although the glands at the root of this lung were extremely large and caseous, no direct anatomical continuity of the two diseased areas could be detected. The right lung was free from intrapuhnonary discase. Tuberculous ulceration could not bc detected in any part of the intestinal tract, but careful section of some of the slightly enlarged mesenterie lymph glands revealed an early invasion with tubercle bacilli. Scattered miliary tubercles present in the viscera and in the meningeal exudate. Case K.--C. B., male, aged 8 months. :Fed on cow's milk. Second child of two. Clinical History.--:Facial paresis observed, and two days later developed signs of mastoiditis. cardia.
Pyrexia and general physical deterioration occurred with extreme tachy-
Posl-mortem Findings.--In the right lung, a large caseating are~ with commencing cavitation was found. The size of this focus was about that of a plum. Situated in the upper lobe and in the immediately surrounding lung tissue was congestive eonsolidation. I n the ileum a few small tuberculous ulcers ~ in. diameter were found together with early invasion of the local mescnteric lymph glands. Dissection of the brain revealed three tuberculomata situated respectively in the cerebellum, the left parietal region, and in the right cerebral sub-cortex. Characteristic evidence of terminal general miliary invasion was seen in the organs and meninges. CaseL.~G. C., 2 years. Second child of two. Breast fed. Measles three months prior to hospital observation. Clinical I~istory.--For two months secmed easily tired and languid. Cough troublesome, occasionally febrile. :Rapid pulse noted. Markcd physical'signs of tuberculous disease detected in the chest, suggesting bilateral patchy consolidation. There was no expectoration, bu~ numerous T.B. were present in the stools. :Radiological examination of the chest showed " a diffuse mottling of the right lung." Post.morlem FindiT~gs.--The retrosternal and upper mediastinal lymph glands were extensively involved in a cascating ttiberculous process, nmtting together the mediastinal structures. The pericardium was clear, but adherent to the left pleura. The whole of the left pleura was adherent to the thoracic wall by tuberculous fibrinous exudate which also involved the interlobar septa. The lung surfaces were granular. The hilus of each lung was matted by tuberculous glands, sonm breaking down by caseation. On section the lung showed a diffuse caseating tuberculous process of broncho-pneumonia distribution, with a cavity occurring aro~md the hilum of theleft lung. The whole of thelymphatic system extending into the abdomen, including the thoracic duct, was involved in the tuberculous process. There was no pleural effusion on the right side. The heart showcd no tuberculous process. I n the abdomen numerous tuberculous ulcers were found throughout the intestinal trac~, and a number of mesentcrio lymph glands showcd a tuberculous reaction. BIiliary tubercles were present in other viscera. C o m m e n t a r y . - - C a s e s t l a n d I s e r v e as i n s t a n c e s to s h o w t h e site a n d n a t u r e of t h e l e s i o n s w h e r e t h e i n f e c t i o n i n t h e b o w e l h a s u n d o u b t e d l y a r i s e n s e c o n d a r y to t h e p r i m a r y t h o r a c i c d i s o r d e r . T h e t u b e r c u l o u s i m p l a n t a t i o n w a s f o u n d i n t h e l o w e r p a r t of t h e s m a l l i n t e s t i n e , a n d m u s t haye arisen at a comparatively short t i m e before general miliary dissemina t i o n took place, i n a m h u c h a-s, a l t h o u g h t h e i n t e s t i n a l u l c e r a t i o n w a s q u i t e d e f i n i t e , n o e x t e n s i o n to t h e r e l a t e d l y m p h a t i c g l a n d s h a d a p p e a r e d .
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Cases G and J revealed an curly active tuberculous process in some of the mesenteric lymph glands, and from a survey of the whole pathology it would appear conclusive that tubercle bacilli had reached the glands, after passing directly through the mucous membrane of the intestine. I t is probable that this latter phenomenon is a f r e q u e n t occurrence, where infection is received indirectly from the thoracic foei. Case K, by virtue of the presence of intestinal ulceration and involvement of the corresponding mesenteric lymph glands, indicates the progression of effects which is commonly noted as a result of initial infection by inhalation. This was especially so in this child, aged 8 months, where time and circumstance had not allowed the development of any distinct process of resistance. Case L. Here special consideration is given to show the extreme degree of abdominal tuberculosis which may arise, secondarily to primary thoracic tuberculosis. In fact, by such means the complete circle of infection and reinfection is set up. The primary puhuonary lesion is aggravated and possibly extended by means of thoracic duct involvement in the extensive lymphatic connections within the mediastinum. I t is, therefore, evident that abdominal tuberculosis in infancy and childhood is easily determined as a secondary effect to thoracic tuberculosis. In fact, this extension in itself may be the all important factor in determining the issue of the case, apart from the grave danger in miliary tuberculosis supervening. The potential dangers, therefore, of even a small focus of primary intrapulmonary tuberculosis in the young child may produce illeffects in a widely varied clinical, anatomical, and pathological range. In a small group of cases studied above, all of which have died as a result of terminal miliary tuberculosis, definite primary foci of infection could be determined within t h e thorax. On analysis, however, of a large number of cases of miliary tuberculosis, ~ certain percentag6 will fail to reveal, even by extremely careful search, any evidence to show previously localised tubercular infection anywhere within the body. This is very disconcerting, inasmuch as it may be indicative that a certain proportion of the juvenile population possesses no capacity for resisting and localising an initial dosage. The following two cases are mentioned here to illustrate the pathology of this occurrence. D. G., male, aged 5 months. Only child. Breast fed. Clinical History.--Well till onc and ~ half days before admission. On that morning he began to vomit for the first time in his life, became restless and irrltablc, crying a good deal, and worldng his head to and fro. Rapidly progressive meningeal inflamm.~tion, leading to coma, supervcncd. No clinical abnormality detected in the thorax or abdomen. The clinical nature of the illness was that of rapidly progressive infection in a previously healthy child. Post.mortem I~Tndings.--Characteristic tuberculous meningitis was found. The internal organs revealed the usual evenly distributed miliary tubercles, characteristic of the disease. Extensive and extremely careful search in the thorax, abdomen and elsewhere, for some clue for the recognition of a previous are,% of tuberculous disease failed.
Com~zentary.--The facts in this case appear to be clear. There was no doubt that the infant was in perfect health before the final acute illness, and this is confirmed by the neerepsy details, which indicate the complete absence of any detectable chronic form of disease. Since the child was
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breast fed and the mother was apparently in good health, the possibility of infection .by ingestion of tubercle bacilli is practically eliminated. I n all probability, the whole illness had arisen by inhalation of virulent tubercle bacilli, which with extreme rapidity, gained access to the infant's circulation to produce a miliary tuberculous state, ab i~zitio. A similar case, but occurring in an older child, was as follows : M. II., female, aged 2 ycars, 5 months. Secondchild of two. Breast fed. History.--Ill for four weeks, dry cough, ? bronchitis. For one week head rolling, and dazed condition present. Clinical History.--On admission, the child was well nourished, tIead retraction was present and also a well-marked squint. No abnormal features were noted in the chest. Biochemical changes in the eerebrospinal fluid confirmed the suspected nature of the process, viz., tuberculous meningitis. t)ost-mortem I~indilzg.--~.Iiliary tuberculosis with tubercular meningitis. ~o primary lesion could be detected.
Commentary.--The only essential difference between the first and the second case is one of the age of the children. The rapid dLffusion o f the infecting organism following an apparent primary exposure to infection seems equally possible in infancy and in childhood. (To be continved.)
h UNIVERSAL STRETCHER SPLINT FOR TREATMENT OF SURGICAL TUBERCULOSIS. By •. PORTEOUS, ~[.B., Ch.B. Late 13radford City Sa~zalori~tm, Grassi~zgton, Yorkshire. 5[OST authorities are agreed upon the principles of non-operative treatment of hip, spine, knee-joint or bone tuberculosis. Some form of splint is necessary, and it would be an advantage if a splint could be devised suitable for either hip, spine, or knee, and made in two sizes, one for adults and one for children. Standardisation in medical treatment is an impossibility, but standardisation in the application of fundamental principles, with facilities for simple improvisations for individual cases, seemed to the writer to be worthy of some thought. The ingenuity of the medical attendant is often taxed to provide apparatus for individual cases and multiplication becomes expensive, even if the apparatus is made on the premises. The medical superintendent receiving occasional cases of surgical tuberculosis is at a great disadvantage, for the standard hospital bed is t h e m o s t awkward piece of furniture to which to attach any apparatus which will give consistent results. I t was in the hope of p~roviding a more suitable apparatus t h a t t h e stretcher splint illustrated and about to be described was designed.
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the " soil" and the " s e e d " in tuberculous infection is crowded with, at present, unknown quantities. Therefore one must assume that any infant or child exposed to tuberculous infection would possibly develop the disease in a generalising form with tragic results. It is only safe to conclude at this juncture that 100 per cent. of infants are highly susceptible to the tubercle bacillus, and especially so to the human type bacillus, and there are no definite means available which can be relied upon to indicate the inherent defensive capacity in any given individual child. This being so, the main object of this paper is to illustrate that the only means of adequate protection of the y o u n g child against what even from the comlnencement might be a fatal illness, is the rigid necessity of protection of such young individuals from a tuberculous infectious environment. F. Hamburger [2] records the placing of a feeble-minded boy, aged 9 years, i n a room in which three tuberculous girls lived. Because of the 9 mental state of the boy, the girls avoided him and never came into close contact with him. H e remained free from tuberculous infection, as shown by the negative, clinical examination and negative tuberculin reaction for seven months. On the other hand, in a room i n Which a tuberculous patient was harboured, four children aged 9,, 4, 5 and 10 years respectively, were brought in. Within four weeks all the four children, who, prior to coming into the room, were tuberculin negative, showed a positive reaction to tuberculin. There are certain periods of life in which the risk of a tuberculous infection becoming generalised is great, and this, combined with the very considerable susceptibility characteristic of infancy, is a matter of great importance. It is thus obvious that when contact with the consumptive is close and prolonged, which in ordinary life occurs not uncommonly in the domestic relationships of mothers and suckling infants, droplet infection may be ~ serious menace, and as will be shown later, this ~principle is of great significance. CONGENITAL TUBERCULOSIS. It is ~ remarkable fact that although transference of tuberculous infection from mother to the fcetus in utero may happen, it occurs so extremely rarely as to be of no more than academic interest only. An interesting inquiry was conducted by Debr6 and Lelong, into the incidence of tubercle bacilli or tuberculous lesions in 98 placentm of tuberculous women. I n none did they find any evidence whatever of tuberculous infection, and, furthermore, careful autopsies of 15 still-born infants, born of tuberculous mothers, were examined very closely, both histologically and by animal inoculation, with negative results. The placenta appears to act as a formidable barrier and a powerful line of defence between the tuberculous mother and the foetus. In connection with this point the writer had facilities for studying the post-mortem record, and for seeing specimens obtained from a case of tuberculosis of the newly born infant (19 days old) in the Baudelocque Hospital, :Paris, in June of 1932. The details of the case were provided by Dr. L a c o m m e ; they ar~ as follows : A primipara, aged 95, suffering from I~ott's disease, developed at the 9eighth month of pregnancy n~liary tuberculosis with tubercular meningitis. The child was removed by C~esarean section, and presented no
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abnormal features externally. Skin reaction to tuberculin on the seventh day was negative. On the sixteenth day its temperature rose a little, and it lost weight. Auscultation showed a few scattered rhles in both lungs. The child died on the nineteenth day. At the autopsy numerous fine tuberculous granulations were found scattered throughout the parenehyma of the organs. Bacteriological examination carried out by hi. hi7. Coulaud and Valtis showed tubercle bacilli to be present, and in the internal organs were seen typical changes characteristic of miliary tuberculosis. This appears to have resulted from infection of the infant's blood-stream immediately prior to, or at its birth, i.e., at a time when the mother herself was actually suffering from tubercular septicmmia. This must fortunately be a rare occurrence, and the case is only mentioned to show the extreme rarity of true congenital tuberculosis. The work of L6on Bernard also depends upon his belief that tuberculosis is not a congenital disease, and the great success of his prophylactic Work bears out the view he holds, viz., that infection practically always arises from contact after birth with an infectious " o p e n " case. It can, without doubt, be assumed that an infant born of a mother who has local pulmonary tuberculosis only at the time of labour will not be infected except by aerial contagion: that this is so can be exemplified by another case from the Baudelocque Hospital. The details are as follows: A inother with caseous bilateral puhnonary .tuberculosis--sputum T.B. + + m g a v e birth to an infant of normal weight on August 3, 1923. I t was normal in appearance and separated at birth. It was immediately placed in a different pavilion from that containing the mother. Unfortunately the mother, on going out of hospital a month later, obtained the permission of a nurse to embrace her child, the contact lasting for a short period of time. During the first three months, the child's weight curve continued satisfactory. At the end of three months, digestive troubles supervened, the child lost weight and developed febrile attacks. A cough appeared and auscultation revealed a few fine rAles at the left base. The loss of weight was suspicious. A staphylococcal infection of the. skin supervened, and death occurred on November 25, 1923. At autopsy, bilateral caseous bronchopneumonia w a s found, with three or four large tracheo-bronchial glands equally caseous. A few miliary tubercles were found on the pleura and on the peritoneum. ~-~.CQUIRED TUBERCULOSIS---THE CxHON'S TUBERCLE.
The simplest form of tuberculosis of the lung is found in infants in whom no complex resistance has been developed to impede the course of the infection. The ideas of Ghon as to the primary puhnonary focus have been amply confirmed : the Ghon tubercle probably represents the primary focus of localisation within the lung of tubercle bacilli received by the aerogenous route. It is commonly pyramidal in shape, with the base towards the pleura, and shows dense puhnonie consolidation and caseation. The size of such focus varies considerably in different cases and it may or may nog be easily detected on ordinary macroscopic examination of the lung; the Ghon's tubercle may be present in any part of the lung, and although it commonly exists singry, two such foci may be detectable. It shows no special selective situation in either lung, and is as commonly seen
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in the lower lobe as the upper. If the search be c.ontinued, sometimes an erosion of the caseous node into the associated bronchiole will be observed. The lymph nodes at the corresponding lung hilum are always enlarged and caseous; sometimes direct lymphatic extension from" the intrapuhnonary focus to the hilum glands can be easily demonstrated. Development of the localised Ghon lesion seems to indicate that tubercle bacilli were originally aspirated deep into the lung substance of the hitherto uninfected child. If the initial bacterial dos• is not overwhelniing, it would appear there exists even in 'the infant a capacity of the lung tissue to localise the infection with the ultimate result of the formation of a Ghon's tubercle. There is, however, a very strong tendency in the infant for bacilli to escape into the lymphatic channels of the hilus and tracheo-bronchiallymph glands. Thus it is ahnost a rule to find in the association of the primary intrapulmonary nodule a caseative reactionary disease in the corresponding lymph nodes. It is well recognised that even circumscribed and partially calcified tuberculous loci may still harbour the tubercle bacillus in an active and virulent form. A direct proof of this statement is indicated by the modern utilization of material removed from the stomach by aspiration, in cases in which such tuberculous feel exist in the lung and associated lymph glands. The presence of living and active tubercle bacilli has been thus frequently demonstrated. Also since it is almost the rule for infants and young children to swallow such infected secretions, autogenous infection of the alimentary tract is not an uncommon feature. There is no doubt that numerous factors may arise in the individual which will in themselves, singly or collectively, contribute towards the tendency on the one hand to maintain the primary intrathoracic lesion in a state of response , and on the other hand to allow one or other of the various forms of dissemination locally, or to distant parts of the body, to occur. It i s of outstanding importance to regard re-infection from an external source as likely to be of extreme danger to a child who is already infected with the tubercle bacillus, as this is probably the factor which, by a combination of the removal of processes of established resistance and the precipitation of sensitising factors, allows a rapid decline of the bodily defence as a whole, thus favouring generalisation of the disease. DETERMINATION
OF T H E P R I M A R Y I'{OUTE OF T U B E R C U L O U S IN INFANTS A N D CHILDREN.
INFECTION
In the living child clinical investigation ,nay give clear evidence regarding the site of the primary distribution in the body of tile infecting agent, but since the establishment of exact and conclusive evidence by such means is difficult in many cases, careful post-mortem examination in fatal cases is more likely to produce conclusive evidence. Direct bacteriological analysis has not been possible in regard to the primary or secondary feet, and hence for the purposes of, this paper approach to the problem has been made by means of careful study of the anatomical distribution of m acroscopical lesions in any given case. It has been regarded that, where the hilum and tracheo-bronchial lymph glands were the site of a recognisable tuberculous process, the original infective agent gained admission to the body by means of the pulmonary system. In each such case the possibility of a more unusual route such as connec-
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tion with a primary tuberculous cervical adenitis or an extension upwards from the abdomen by means of the thoracic duct or its connections has been carefully eliminated. In what has been considered to be the primary case of intrathoracic tuberculosis, there has been detected at post-mortem examination a tuberculous process in the lung, bearing the feature described by Ghon and associated with caseous tuberculous mediastinal adenitis. It is surprising how frequently this clear-cut picture has presented itself. I t is true, however, that in some instances the absence of any macroscopically visible primary intrapulmonary tuberculous focus has been striking. However, the presence in such cases of massive tuberculous disease in the mediastinal glands and more typically in the hilum glands of one lung, with the absence of tuberculous foci in other parts of the body (excluding miliary lesions), has Ied to the only conclusion possible that the original infection was by way of inhalation infection but no recognisable permanent intrapuhnonary damage was effected. It has been observed in many of the primary thoracic cases studied, that together with definite clinical evidence of abdominal tuberculosis, or where no such clinical suspicion was aroused, a variable degree of active tuberculous involvement within the alimentary tract and its associated lymphatic system, more especially the mesenteric lymph glands, has been detected by necropsy examination. It has been striking how frequently such lesions below the diaphragm were associated with tuberculous lesions above the diaphragm. In any given case, the problem set was to decide on what anatomical evidence could the sequence of events be analysed. This in certain cases presented some difficulty, but in the large majority an accurate analysis could be made. Points which have been taken were (1) the extent of the lesi0ns found in the thorax and in the abdomen; (2) the relative ages of the tuberculous reaction in the respective parts of the body ; (3) the anatomical disassociation of the diseased tissues: and (4) a careful study of the intervening lymphatic system where two or more areas of tuberculous reaction were detectable--the latter being typically exemplified by examination of the main trunk connections of the mesenteric lymphatics and the mediastinal lymphatic system. I~,ECOGNITION OF I)RIMARY TtIOBACIC INFECTION.
Tubercle bacilli often escape into the respirator), secretions in cases even where intrapulmonary and mediastinal gland lesions appear to be in a closed condition. The fact is utilised by clinicians when investigating cases suspected of thoracic tuberculosis. By testing the resting gastric contents (which in children represents to some extent swallowed respiratory secretions) tubercle bacilli are quite frequently detected in cases where definite clinical or even radiological evidence of a conclusive nature has not been obtained. In any child debilitated by tuberculous infection, the acid gastric secretion is minimised and tubercle bacilli may pass readily into the intestinal tract. The intestinal and mesenteric involvement thus obtained may be of greater degree and extent than might at first sight be suggested by the relative minority of the primary intrathoracic foci. Therefore, in some instances careful judgment is required on the available
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necropsy findings to reach a satisfactory conclusion concerning the p r i m a r y origin of infection in the case. I t is evident t h a t the e x t e n t of the abdominal lesion p e r se cannot by any means~be eonclusive o f p r i m a r y infection by ingestion. T h e age of the lesions in the thor/tx m a y be obviously greater t h a n t h a t of those in the abdomen, irrespective of their differences in extent. T h e presence of a well-marked isolated easeating G h o n ' s tubercle, in t h e light of the k n o w n pathology of the genesis of such a lesion, cannot be considered to arise in any secondary way to a p r i m a r y abdominal tuberculous d i s e a s e . Ileal difficulty arises w h e r e t h e r e is a massive and anatomically continuous tuberculous involvement of t h e whole abdominal l y m p h a t i c system, including the thoracic duct origin and connection in the thorax. I n such cases it m u s t be granted t h a t secondary mediastinal glandular tubercle might, and in fact does, to our knowledge, arise very occasionally by this means. U n d e r these circumstances, f u r t h e r extension into t h e p u l m o n a r y system has also been k n o w n to occur. B y the breakdown of i n t r a p u l m o n a r y fool, f u r t h e r reinfection of the bowel m a y take place. I n fact, a cyclical infection and reinfection is thus established. I n v e r y advanced cases of this kind a retrospective diagnosis of the origin and site of the p r i m a r y infection m a y be almost impossible. Although bacteriological investigation to. d e t e r m i n e w h e t h e r the h u m a n or bovine type of bacillus is present would be helpful, it would not, in itself, necessarily be completely conclusive to this end. I t is reasonable, therefore, to believe t h a t w h e r e a c o m b i n a t i o n of i n t r a p u l m o n a r y and thbracic glandular infection exists, t o g e t h e r w i t h intestinal and m e s e n t e r i c involvement and w h e r e t h e m a i n i n t e r v e n i n g l y m p h a t i c connections of these two systems are free from t u b e r c u l a r disease, t h e n the p r i m a r y focus existed above t h e d i a p h r a g m and not w i t h i n the abdomen. I n o r d e r to illustrate the above considerations a few selected cases from t h e whole group studied are outlined as follows : ~ . Case A.--W. BI., female, aged 2 years ,5 months. First child of two. ClinicM History.--Listless and out of sorts for a short time. Vomiting occurred,
later pain was present in the eye; convulsions appeared. Child became increasingly drowsy. She was admitted to hospital in coma, showing the characteristic features of meningitis. Examination of the lungs showed impaired percussion note, just inside the angle of the left scapula, with harsh breath sounds of ,~ bronchial type in the neighbouring lung. .Post.morlem 17~ndings.--Glands at the left hilum were considerably enlarged and caseating. In the lung substance of the left upper lobe, an area of caseating lymphatic tuberculosis, the size of a cherry, was detected. This was apparently well circumscribed, and not of recent formation. Careful examination within the abdomen showed no evidence of any tuberculous disease, beyond the presence of visceral miliary tubercles in common with their presence in all the other organs and meninges. Case B . - - B . ~V., female, aged 6 years. First clfild of two. Clinical Hislorg.--Convulsions for six days, repeated vomiting and marked constipa-
tion, with progressive pallor and eyanosis. Admitted to hospital in conditidn of severe dehydration and showing characteristic meningeal signs. The only abnormal physical signs in lungs were those of diminishcd air entry into the right lung fields. Cerebrospinal fluid showed the characteristic cellular and bio-chemical changes of tuberculous meningitis. l'ost-~mrtem F i n d i n g s . ~ A small tubcrculoma present in the upper part of the thynms gland. Towards the posterior aspcct of the right lung, a chronic tuberculous focus, the siz9 of a hazel nut was found. Several of the lymph nodes at tlm right hilum and the
: F e b r u a r y , 193&]
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gland at tlle bifurcation of the trachea were involved in cascating tuberculous disease. No tuberculous process was detected anywhere within the alimentary tract, or in the abdominal lymphatic system. All the viscera showed presence of typical miliary tubercles, and characteristic tubercular meningltls was demonstrated.
Case C.--R. S,, male, aged 5 months. Third child in family of three (one of which was dead of tuberculous meningitis). Clinical Hisfory.--Although the case under review was only 5 months old, ig had been observed that the infant had suffered from spasmodic cough for two months, and symptoms suggesting " asthma " had appeared from time to time. The terminal illness was vague and rapid, miliary tuberculous disease was not; suspected, and in fact, was only detected at post mortem. CMnically there were no definite abnormal physical signs in the lungs to suggest tuberculous disease. Post-morteJJ~ Findlngs.--The necropsy revealed enlarged and caseating lymphatic.glands in the superior mediastinum. An intrapulmonary tuberculous lesion which appeared to be of at least several weeks' duration, and prob,~bly more, was found towards the centre of the right middle lobe. This focus was the size of a hazel nut. No tuberculous disease was found within the alimentary tract, or in the abdominal lymphatics. All the intcrnal organs showed numerous fine miliary tubercles. The meninges revealed characteristic tuberculous basic meningitis. Case D.--W. B., male, aged 1 year 9 months. Seventh child of a family of eight. Two children dead, one acute diarrhoea and vomiting, and one of an obscure puhnonary condition ? " ipneumonia." Clinical History.---Occasional attacks of diarrhoe~ and vomiting. A shor~ time before coming under observation at hospital, rapid loss of weight was noticed. Aftei" admission drowsiness was detected, combined with neck rigidity and other signs of meningitis, which diagnosis was confirmed by lumbar puncture, bacteriological, and cytological examination of cerebrospinal fluid. Careful examination of chest; revealed no abnormal physical signs. There was some simple distension of the abdomen. Post-mortem ffindi~gs.--Therc were considerably enlarged caseating lymph glands at the hilton of the left lung, but a continuity of these lesions was not traceable to a small isolated area of tuberculous disease in the posterior aspcct of the left middle lobe of the lung. No indication of any abdominal tuberculous disease was detected. The thoracic and abdominal viscera together with the meninges revealed the characteristic features of terminal miliary tuberculosis. Case ~ . - - R . B., male, oged 5 years. Second child of two. ,~[other's sister died of tuberculosis and mother's brother also died of tuberculosis. History.--Pale and thin for one year. For two weeks before admission failure of general health with development of severe constipation. Clinical Hislor~j.--Condition on admission to hospital : neck rigid, Kernig's sign and other clinical evidence of meningitis was detected. Several miliary tubercles in the retinm. No unusual phenomena could be detected in the thorax. Post-morlcm Findi~zgs.~Largc caseating tubcrculous lymph glands present at right lung hilum. An isolated patch of tuberculous disease was detected towards the periphery, at the posterior parb of the right lower lobe, one-third of an inch in diameter, entirely caseous. The left lung and corresponding left hilum glands were not involved and no intestinal or abdominal glandular disorder.was present. An old tubcrculomc~ was discovered in the right island of Rcil; this appeared to be quite encapsulated, and not connected with the tuberculous meningitic process. The viscera and meningeal tissues" revealed the usual signs of miliary tuberculosis. Case F . m A . F., male, aged 5 months. Second child of two. History.--Cough for a few days, vomiting, twitching of face and bands.
Observation in hospital revealed a meningeal posture in bed, and strabismus; marked spasticity of legs developed, and meningeal signs became very pronounced. Cliuical diagnosis of tuberculous meningitis was confirmed by bacteriological, cytological, and biochemical examination of cerebrospinal fluid.
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TUBEnCaE
[February, 1934
Post-mortem Findings.~In the substance of the upper lobe of the righg lung, several yellowish areas of tuberculous consolidationwere found, one of these areas revealing cavity the size of t~hazel nut, full of soft caseous material, and lined with granulation tissue. In the lung substance immediately surrounding was found a caseating form of pneumonia. The bronchial and mcdiastinal lymph glands were enlarged and advancedly caseous. There was no abdominal tuberculosis beyond the presence of terminal miliary tubercles, which wcre also secn in the thoracic viscera and in the characteristic meningitic exudate. Commentary.inCases A, ]3, C, D, E and F, as briefly outlined above, are considered to be examples of individuals receiving without doubt a primary infection of the lung by inhalation of tubercle bacilli. I n each instance an intrapulmonary tuberculous focus of some duration was detected in association with caseative tuberculous disease in the anatomically related lymph glands. I n two instances, Cases C and F, the patients were only aged 5 months. I t is therefore obvious that some approximation of the time element in these lesions can be deduced. In the Case F, the intrapulmonary lesion was of remarkably advanced degree, and w h e n considered with the age of the infant, it must be assumed that the primary infection had taken place within the first three months of life. I n Case C, as the description relates, an old lesion was present in the lung substance, the age being deduced from the well-marked caseative change with reactive encapsulation, t t e r e again it can be logically understood that a primary infection occurred soon after the neo-natal period of life. I t is therefore evident that even at this early age in life definite and recognisable intrathoracic lesions can be discovered as evidence of direct infection by way of the respiratory tract, which is an important observation to be realised when searching f o r the means of contagion in the infant. It is interesting to observe even in this snmll series of cases that the intrapulmonary primary tuberculous focus frequently exists singly, and may be disposed of at any place within the lung substance or immediately subpleural in position. There may be some significance in this observation. It suggests that the infection has been by one or two tubercle bacilli initially, which have settled in the bronchial tissue, where the Ghon's tubercle is later discovered. It is readily understood how the local and general resistance of the child, when infected with a small single dose of tubercle bacilli, nmy defend itself by the formation of the local lung lesion, even though the hilar and mediastinal lymph glands are called on to assist in this defence mechanism. Thus it would appear that the tragic sequence of miliary tuberculosis is determined in such cases where superaddcd reinfection from without, or some temporary influence of an endogenous nature, disorganises the resistance of the unfortunate infant. Case E bears some points meriting special comment. Some time relationships of the infection responsible for the intrapuhnonary caseating lesion may be gathered from the fact that the child was exposed for a period of time, in all probability some years previously, to active tuberculous disease in a relative. So far as is known, the child had not been exposed t o any further infection by inhalation since that time. Corroborative evidence concerning the time of original infection may be gathered by the
February, 1934]
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201
fact t h a t an encapsulated intracerebra! t u b e r e u l o m a was present also, the latter being regarded as a m e t a s t a t i c extension f r o m the original intrap u l m o n a r y focus. I t would appear, therefore, evident t h a t the initial sites of reaction are easily detectable for a considerable period of time after their formation, a n d yet w h e r e judged by clinical methods, such lesions appear to be quiescent, and miliary tuberculosis m a y still make its dread appearance. T h e G h o n tubercle, therefore, while being of considerable value in an investigation of this kind, w h e r e evidence is s o u g h t for the direction of p r i m a r y infection, mus~ also be considered o f some potential d a n g e r to the patieng. This is especially so since active caseating t u b e r culous disease is almost "invariably found in the a n a t o m i c a l l y related l y m p h glands at the same time. F r e q u e n t l y , the mediastinal glandular disease, w h i c h has no d o u b t arisen by a similar process, exists without t h e r e being a residual d e m o n s t r a b l e i n t r a p u h n o n a r y lesion. I t has been outlined that a secondary extension of tuberculous disease to ghe intestinal t r a c t m a y occur as a result of the a u t o m a t i c swallowing of b r o n c h o - p u l m o n a r y secretions in a child w h o is suffering from a p r i m a r y intrathoracic focus of tuberculosis. T h e following g r o u p of cases illustrates examples of this type : ~ Case G.IK.]3., nmle, aged 2 years. Second child of two. First child died of tuberculou s meningitis. History.--Breast fed. Twelve days restlessness, unusual involvement of the right ann, with vomiting rLttacks and head retraction. On admission to hospital, recent emaciKtion was evident, and characteristic signs of meningitis were present. Papilloedema was seen, and cerebrospinal fluid showed the usual features present in tuberculous meningitis. No unusual physical signs in chest were elicited. 1)ost-mortem 17indings.~Extcnsive thoracic glandular tuberculosis, more especially at hilum of the right lung, and in the substance of the middle lobe of the right hng, a diffuse form of cascativc pneunmnie consolidation were seen. Left lung showed no such change. A careful examination of the intestinal mucosa showed no visible ulceration, but section of the lymph glands in relation to the small intestine showed recent tuberculous invasion. Typical miliary tubercles were present in the viscera and meninges. Case H.--]3. C., female, aged 8 months. Fifth child of five. History.--Three months prior to admission lef~ hip-joint noticed not to be normal. When brought to hospital, evidence of arthritis was definite. The child had had ~ cough for some time. A few days after admission to hospitM, early signs of meningitis appeared and rapidly progressed. _Post-mortem 17indings.~A large fibro.caseating mass was found in the lower portion of the right lung. The corresponding hilum glands were much enlarged and caseating. In the mucous lnembrane of the ileum, two small recent tuberculous ulcers were detected with some involvement also of the lymphoid tissue in the region of tim ileo-cmcal valve. There was an absence of involvement of the mesenterie lymph nodes. Numerous miliary tuberclcs present in ~he viscera and meningitic exudate was present. Tuberculous involvement of the synovial membrane of tlm left hip-joint was demonstrated. Case L--J. S., female, aged 2 years 3 months. History.--Operation for simple mastoiditis three mouths before admission to the Children's ttospita]. Recent illness consisted of irritability for a few days, pyrexia, drowsiness and vomiting. Case clinically rccognised as tuberculous meningitis and diagnosis confirmed by examination of ccrcbrospinal tluid. 1)osl-morlcm 1,'indings.--At thc peripheral part of the right upper lobe, an old tuberculous area, the size of a large pea, was detce.tcd. Lymph glands at the hilum, corresponding to this part of the lung, shmved c'ascative disease. Several very recent tuberculous ulcers were detected in the jejunal and ileal mucosm, these ulcers being 88in. to ~ in. in diameter,
202
Tun~,az5z
[ F e b r u a r y , 1934
showing only slight thickening. There was more extensive recent ulceration at the ileocmcal junction. The mesenterie lymph glands, however, revealed no macroscopic tuberculous invasion. The usual evidence of miliary tuberculosis and tubercular meningitis was detected.
Case J . - - l l . W., male, aged 2 years 10 months. F i r s t child of two. Previous health of this child appeared to be good. Clinical History.--Fourteen days before hospital observation, vomiting, severe headache, restlessness and photophobia present, o n admission, convulsions with rapid development of complete picture of tubercular meningitis supervened. Post-morlem F~nr~ings.--An old caseating lesion, size of a florin was found, situated in the lower part of the left lung, and although the glands at the root of this lung were extremely large and caseous, no direct anatomical continuity of the two diseased areas could be detected. The right lung was free from intrapuhnonary discase. Tuberculous ulceration could not bc detected in any part of the intestinal tract, but careful section of some of the slightly enlarged mesenterie lymph glands revealed an early invasion with tubercle bacilli. Scattered miliary tubercles present in the viscera and in the meningeal exudate. Case K.--C. B., male, aged 8 months. :Fed on cow's milk. Second child of two. Clinical History.--:Facial paresis observed, and two days later developed signs of mastoiditis. cardia.
Pyrexia and general physical deterioration occurred with extreme tachy-
Posl-mortem Findings.--In the right lung, a large caseating are~ with commencing cavitation was found. The size of this focus was about that of a plum. Situated in the upper lobe and in the immediately surrounding lung tissue was congestive eonsolidation. I n the ileum a few small tuberculous ulcers ~ in. diameter were found together with early invasion of the local mescnteric lymph glands. Dissection of the brain revealed three tuberculomata situated respectively in the cerebellum, the left parietal region, and in the right cerebral sub-cortex. Characteristic evidence of terminal general miliary invasion was seen in the organs and meninges. CaseL.~G. C., 2 years. Second child of two. Breast fed. Measles three months prior to hospital observation. Clinical I~istory.--For two months secmed easily tired and languid. Cough troublesome, occasionally febrile. :Rapid pulse noted. Markcd physical'signs of tuberculous disease detected in the chest, suggesting bilateral patchy consolidation. There was no expectoration, bu~ numerous T.B. were present in the stools. :Radiological examination of the chest showed " a diffuse mottling of the right lung." Post.morlem FindiT~gs.--The retrosternal and upper mediastinal lymph glands were extensively involved in a cascating ttiberculous process, nmtting together the mediastinal structures. The pericardium was clear, but adherent to the left pleura. The whole of the left pleura was adherent to the thoracic wall by tuberculous fibrinous exudate which also involved the interlobar septa. The lung surfaces were granular. The hilus of each lung was matted by tuberculous glands, sonm breaking down by caseation. On section the lung showed a diffuse caseating tuberculous process of broncho-pneumonia distribution, with a cavity occurring aro~md the hilum of theleft lung. The whole of thelymphatic system extending into the abdomen, including the thoracic duct, was involved in the tuberculous process. There was no pleural effusion on the right side. The heart showcd no tuberculous process. I n the abdomen numerous tuberculous ulcers were found throughout the intestinal trac~, and a number of mesentcrio lymph glands showcd a tuberculous reaction. BIiliary tubercles were present in other viscera. C o m m e n t a r y . - - C a s e s t l a n d I s e r v e as i n s t a n c e s to s h o w t h e site a n d n a t u r e of t h e l e s i o n s w h e r e t h e i n f e c t i o n i n t h e b o w e l h a s u n d o u b t e d l y a r i s e n s e c o n d a r y to t h e p r i m a r y t h o r a c i c d i s o r d e r . T h e t u b e r c u l o u s i m p l a n t a t i o n w a s f o u n d i n t h e l o w e r p a r t of t h e s m a l l i n t e s t i n e , a n d m u s t haye arisen at a comparatively short t i m e before general miliary dissemina t i o n took place, i n a m h u c h a-s, a l t h o u g h t h e i n t e s t i n a l u l c e r a t i o n w a s q u i t e d e f i n i t e , n o e x t e n s i o n to t h e r e l a t e d l y m p h a t i c g l a n d s h a d a p p e a r e d .
February, 1934]
TUBERCULOSIS
IN I N F A N C Y
AND
CHILDHOOD
203
Cases G and J revealed an curly active tuberculous process in some of the mesenteric lymph glands, and from a survey of the whole pathology it would appear conclusive that tubercle bacilli had reached the glands, after passing directly through the mucous membrane of the intestine. I t is probable that this latter phenomenon is a f r e q u e n t occurrence, where infection is received indirectly from the thoracic foei. Case K, by virtue of the presence of intestinal ulceration and involvement of the corresponding mesenteric lymph glands, indicates the progression of effects which is commonly noted as a result of initial infection by inhalation. This was especially so in this child, aged 8 months, where time and circumstance had not allowed the development of any distinct process of resistance. Case L. Here special consideration is given to show the extreme degree of abdominal tuberculosis which may arise, secondarily to primary thoracic tuberculosis. In fact, by such means the complete circle of infection and reinfection is set up. The primary puhuonary lesion is aggravated and possibly extended by means of thoracic duct involvement in the extensive lymphatic connections within the mediastinum. I t is, therefore, evident that abdominal tuberculosis in infancy and childhood is easily determined as a secondary effect to thoracic tuberculosis. In fact, this extension in itself may be the all important factor in determining the issue of the case, apart from the grave danger in miliary tuberculosis supervening. The potential dangers, therefore, of even a small focus of primary intrapulmonary tuberculosis in the young child may produce illeffects in a widely varied clinical, anatomical, and pathological range. In a small group of cases studied above, all of which have died as a result of terminal miliary tuberculosis, definite primary foci of infection could be determined within t h e thorax. On analysis, however, of a large number of cases of miliary tuberculosis, ~ certain percentag6 will fail to reveal, even by extremely careful search, any evidence to show previously localised tubercular infection anywhere within the body. This is very disconcerting, inasmuch as it may be indicative that a certain proportion of the juvenile population possesses no capacity for resisting and localising an initial dosage. The following two cases are mentioned here to illustrate the pathology of this occurrence. D. G., male, aged 5 months. Only child. Breast fed. Clinical History.--Well till onc and ~ half days before admission. On that morning he began to vomit for the first time in his life, became restless and irrltablc, crying a good deal, and worldng his head to and fro. Rapidly progressive meningeal inflamm.~tion, leading to coma, supervcncd. No clinical abnormality detected in the thorax or abdomen. The clinical nature of the illness was that of rapidly progressive infection in a previously healthy child. Post.mortem I~Tndings.--Characteristic tuberculous meningitis was found. The internal organs revealed the usual evenly distributed miliary tubercles, characteristic of the disease. Extensive and extremely careful search in the thorax, abdomen and elsewhere, for some clue for the recognition of a previous are,% of tuberculous disease failed.
Com~zentary.--The facts in this case appear to be clear. There was no doubt that the infant was in perfect health before the final acute illness, and this is confirmed by the neerepsy details, which indicate the complete absence of any detectable chronic form of disease. Since the child was
20~
TUBERCLE
[February, 1934
breast fed and the mother was apparently in good health, the possibility of infection .by ingestion of tubercle bacilli is practically eliminated. I n all probability, the whole illness had arisen by inhalation of virulent tubercle bacilli, which with extreme rapidity, gained access to the infant's circulation to produce a miliary tuberculous state, ab i~zitio. A similar case, but occurring in an older child, was as follows : M. II., female, aged 2 ycars, 5 months. Secondchild of two. Breast fed. History.--Ill for four weeks, dry cough, ? bronchitis. For one week head rolling, and dazed condition present. Clinical History.--On admission, the child was well nourished, tIead retraction was present and also a well-marked squint. No abnormal features were noted in the chest. Biochemical changes in the eerebrospinal fluid confirmed the suspected nature of the process, viz., tuberculous meningitis. t)ost-mortem I~indilzg.--~.Iiliary tuberculosis with tubercular meningitis. ~o primary lesion could be detected.
Commentary.--The only essential difference between the first and the second case is one of the age of the children. The rapid dLffusion o f the infecting organism following an apparent primary exposure to infection seems equally possible in infancy and in childhood. (To be continved.)
h UNIVERSAL STRETCHER SPLINT FOR TREATMENT OF SURGICAL TUBERCULOSIS. By •. PORTEOUS, ~[.B., Ch.B. Late 13radford City Sa~zalori~tm, Grassi~zgton, Yorkshire. 5[OST authorities are agreed upon the principles of non-operative treatment of hip, spine, knee-joint or bone tuberculosis. Some form of splint is necessary, and it would be an advantage if a splint could be devised suitable for either hip, spine, or knee, and made in two sizes, one for adults and one for children. Standardisation in medical treatment is an impossibility, but standardisation in the application of fundamental principles, with facilities for simple improvisations for individual cases, seemed to the writer to be worthy of some thought. The ingenuity of the medical attendant is often taxed to provide apparatus for individual cases and multiplication becomes expensive, even if the apparatus is made on the premises. The medical superintendent receiving occasional cases of surgical tuberculosis is at a great disadvantage, for the standard hospital bed is t h e m o s t awkward piece of furniture to which to attach any apparatus which will give consistent results. I t was in the hope of p~roviding a more suitable apparatus t h a t t h e stretcher splint illustrated and about to be described was designed.