a clinical study of the human and bovine types of tuberculosis in man

2
319 A CLINICAL STUDY OF THE HUMAN AND BOVINE TYPES OF TUBERCULOSIS IN MAN. BY JOHN T. MORRISON, M.B. EDIN., F.R.C.S. ENG., HON. SURGEON, ROYAL SOUTHERN HOSPITAL, AND CONSULTING SURGEON, CITY SANATORIA FOR TUBERCULOSIS, LIVERPOOL. THE investigations out of which this paper developed were originally undertaken by Prof. J. M. Beattie, of the University of Liverpool, to determine whether the incidence of human and bovine tuberculosis was the same in Liverpool as in other parts of the country. The bacteriological work has all been carried out by him from clinical material supplied from the City Sanatoria, the Royal Liverpool Children’s Hospital, the Liverpool Stanley Hospital, and private practice. It is therefore fairly representative of all types of non-pulmonary tuberculosis and of various ages and social strata. The correlation of the clinical conditions with the bacteriological findings brought out many points of interest which are important in so far as they contribute to a more accurate knowledge of the disease. My conclusions should be regarded as indications rather than demonstrations of the truth. So far as they go, I think they are justified by ascertained facts, but larger numbers are needed before generalisations can be made. Of necessity a certain amount of selection has crept in. The material is from consecutive cases, but since, as a rule, it is the more hopeful cases that reach the operating-theatre the mortality results are of no absolute value. On the other hand, a certain amount of comparison between different groups is permissible. One hundred cases were investigated bacteriologi- cally during the years 1923-24-25. One or two have been excluded as certainly not tuberculous. Some patients cannot be traced, and so final con- clusions cannot be drawn about them, although previous notes render them useful for certain statistics. Inoculation Failures. A considerable number of cases inoculated, although clinically undoubted cases of tuberculosis, gave no result in the test animals. Of these "negative " results one should be eliminated, as the patient had a severe streptococcal infection and the animals died of streptococcal septicaemia. This leaves 31 cases, almost one-third, for inquiry. The material used in these 31 cases was : in 66 per cent. the caseous debris of softening glands or actual pus ; in 25 per cent. caseating bone foci and peritoneal fluid and tuberculous granulation tissue in 4 per cent. each. As the proportions are practically identical in the series of cases proved definitely bovine, it seems that the source of the material and its physical properties have no important bearing on its failure to produce disease in animals. In other words, although pus was used in a considerable percentage of cases-and tuberculous pus is notoriously deficient in tubercle bacilli-the negative results cannot be attributed to this factor, as pus was used in just as many cases which gave positive results. So far as it goes. this is an argument against the criticism that paucity of organisms in the material used was responsible for the absence of tuberculosis in the laboratory animals. It may be said that such organisms as were present were enfeebled by exposure to powerfully antagonistic bodies in the serum of patients highly immunised against tuberculosis. If this be so, the high state of immunity is not reflected in the clinical progress of the patients. In those under consideration the recovery-rate (or proportion of apparent cures) was only 73 per cent. None of the 18 cases of undoubted bovine tuberculosis traced for two years or over showed any signs of active disease-i.e., the recovery-rate was 100 per cent. I do not think that the effects of general immunity in the patient are of any great importance here. On the other hand, local conditions seem to have a bearing upon the results. It is conceivable that fibrosis, for instance, is inimical to the organisms in lesions in one part of the body, while in other parts the disease might even be progressive. The average duration of the lesion in the cases giving " no result " was 4-3 years (though several cases had apparently relatively short histories), while the " human " cases had lasted 2-3 years and the " bovines " only just over one year. That the results were not merely fortuitous is shown by the fact that repetition of the inoculations confirmed the original negative finding in several instances. In case it should be pleaded that these patients were not tuberculous at all, those in whom any clinical doubt arose have been excluded. The proportion of cases of actinomycosis and syphilis which -simulate tuberculosis is very small. No case giving a positive Wassermann reaction has been included. The table shows that, in the distribution of the disease over the different organs and systems, the " no result " cases represent almost exactly the average between those of definitely human and bovine origin. The negative cases, therefore, are probably derived fairly equally from both types of infections, so that it cannot be said that one type of bacillus is more frequently at fault, or is more easily influenced by the local curative actions of the body, than the other. For this reason the ’’ no result " cases have been ignored in the statistical inquiries into the human and bovine cases. Regional Distribution. The bovine bacillus is found to account for 75 per cent. of the cases of tuberculous glands in the neck. That is rather less than has been found in certain other districts, where the percentage has been placed as high as 90 per cent. Inquiry into the age incidence may account for this apparent variation. Bovine infections were present in only about 28 per cent. of the bone cases. The figures relating to abdominal and genito-urinary cases-mainly because they are relatively seldom submitted to operation- are so small as to be valueless. In the main the figures are comparable to those for the country generally. I A study of the age factor throughout the whole series shows that 65 per cent. of the human infections were over 12 at the age of apparent onset, while 35 per cent. were 20 or over when symptoms first appeared.: Among the bovine cases, on the other hand, only 15 per cent. were over 12 when attention was drawn to the disease. Of these 15 per cent., although the infection was bovine, three out of the five were not only over 12 but actually between 20 and 25 when evidence of tuberculosis was first obtained. While, roughly, 75 per cent. of all bone tuberculosis is due to the human bacillus, in patients over 15 the figure rises to 82 per cent., and in those under 15 about 70 per cent. is human in origin. This figure is one of great significance. Of the cases of lymphatic gland infection in children 16 per cent. yielded the human type of organisms and 84 per cent. the bovine. This more closely approximates to the 90 per cent. quoted above from the published results of work done entirely amongst children. Nevertheless, the fact remains that in Liverpool 16 per cent. of cases of glandular tuberculosis are due to human bacilli-i.e., infection from active cases of phthisis. In contrast to this 62 per cent. 1 A. P. Mitchell : Infection of Children with Bovine Tubercle Bacillus, Brit. Med. Jour., 1914, i., 125.

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Page 1: A CLINICAL STUDY OF THE HUMAN AND BOVINE TYPES OF TUBERCULOSIS IN MAN

319

A CLINICAL STUDY OF THE

HUMAN AND BOVINE TYPES OF

TUBERCULOSIS IN MAN.

BY JOHN T. MORRISON, M.B. EDIN., F.R.C.S. ENG.,HON. SURGEON, ROYAL SOUTHERN HOSPITAL, AND CONSULTING

SURGEON, CITY SANATORIA FOR TUBERCULOSIS, LIVERPOOL.

THE investigations out of which this paper developedwere originally undertaken by Prof. J. M. Beattie,of the University of Liverpool, to determine whetherthe incidence of human and bovine tuberculosis wasthe same in Liverpool as in other parts of the country.The bacteriological work has all been carried outby him from clinical material supplied from the

City Sanatoria, the Royal Liverpool Children’sHospital, the Liverpool Stanley Hospital, and privatepractice. It is therefore fairly representative of all

types of non-pulmonary tuberculosis and of variousages and social strata. The correlation of the clinicalconditions with the bacteriological findings broughtout many points of interest which are importantin so far as they contribute to a more accurateknowledge of the disease. My conclusions shouldbe regarded as indications rather than demonstrationsof the truth. So far as they go, I think they arejustified by ascertained facts, but larger numbersare needed before generalisations can be made.Of necessity a certain amount of selection has creptin. The material is from consecutive cases, butsince, as a rule, it is the more hopeful cases that reachthe operating-theatre the mortality results are ofno absolute value. On the other hand, a certainamount of comparison between different groups ispermissible.One hundred cases were investigated bacteriologi-

cally during the years 1923-24-25. One or twohave been excluded as certainly not tuberculous.Some patients cannot be traced, and so final con-clusions cannot be drawn about them, althoughprevious notes render them useful for certainstatistics.

Inoculation Failures.A considerable number of cases inoculated,

although clinically undoubted cases of tuberculosis,gave no result in the test animals. Of these"negative " results one should be eliminated, as thepatient had a severe streptococcal infection and theanimals died of streptococcal septicaemia. Thisleaves 31 cases, almost one-third, for inquiry. Thematerial used in these 31 cases was : in 66 per cent.the caseous debris of softening glands or actual pus ;in 25 per cent. caseating bone foci and peritonealfluid and tuberculous granulation tissue in 4 per cent.each. As the proportions are practically identicalin the series of cases proved definitely bovine, itseems that the source of the material and its physicalproperties have no important bearing on its failureto produce disease in animals. In other words,although pus was used in a considerable percentageof cases-and tuberculous pus is notoriously deficientin tubercle bacilli-the negative results cannot beattributed to this factor, as pus was used in just asmany cases which gave positive results. So far as itgoes. this is an argument against the criticism thatpaucity of organisms in the material used was

responsible for the absence of tuberculosis in thelaboratory animals.

It may be said that such organisms as werepresent were enfeebled by exposure to powerfullyantagonistic bodies in the serum of patientshighly immunised against tuberculosis. If thisbe so, the high state of immunity is not reflectedin the clinical progress of the patients. In thoseunder consideration the recovery-rate (or proportionof apparent cures) was only 73 per cent. None ofthe 18 cases of undoubted bovine tuberculosis tracedfor two years or over showed any signs of activedisease-i.e., the recovery-rate was 100 per cent.

I do not think that the effects of general immunityin the patient are of any great importance here. Onthe other hand, local conditions seem to have abearing upon the results. It is conceivable thatfibrosis, for instance, is inimical to the organisms inlesions in one part of the body, while in other partsthe disease might even be progressive. The averageduration of the lesion in the cases giving " no result "was 4-3 years (though several cases had apparentlyrelatively short histories), while the " human " caseshad lasted 2-3 years and the " bovines " only justover one year. That the results were not merelyfortuitous is shown by the fact that repetition of theinoculations confirmed the original negative findingin several instances.

In case it should be pleaded that these patients werenot tuberculous at all, those in whom any clinicaldoubt arose have been excluded. The proportion ofcases of actinomycosis and syphilis which -simulatetuberculosis is very small. No case giving a positiveWassermann reaction has been included. The tableshows that, in the distribution of the disease over thedifferent organs and systems, the " no result " casesrepresent almost exactly the average between those

of definitely human and bovine origin. The negativecases, therefore, are probably derived fairly equallyfrom both types of infections, so that it cannot besaid that one type of bacillus is more frequentlyat fault, or is more easily influenced by the localcurative actions of the body, than the other. Forthis reason the ’’ no result " cases have been ignoredin the statistical inquiries into the human and bovinecases.

Regional Distribution.The bovine bacillus is found to account for 75 per

cent. of the cases of tuberculous glands in theneck. That is rather less than has been found incertain other districts, where the percentage has beenplaced as high as 90 per cent. Inquiry into the ageincidence may account for this apparent variation.Bovine infections were present in only about 28 percent. of the bone cases. The figures relating toabdominal and genito-urinary cases-mainly becausethey are relatively seldom submitted to operation-are so small as to be valueless. In the main the figuresare comparable to those for the country generally.

I A study of the age factor throughout the whole seriesshows that 65 per cent. of the human infections wereover 12 at the age of apparent onset, while 35 percent. were 20 or over when symptoms first appeared.:Among the bovine cases, on the other hand, only15 per cent. were over 12 when attention was drawnto the disease. Of these 15 per cent., although theinfection was bovine, three out of the five were notonly over 12 but actually between 20 and 25 whenevidence of tuberculosis was first obtained. While,roughly, 75 per cent. of all bone tuberculosis is dueto the human bacillus, in patients over 15 the figurerises to 82 per cent., and in those under 15 about70 per cent. is human in origin. This figure is one ofgreat significance.

Of the cases of lymphatic gland infection in children16 per cent. yielded the human type of organismsand 84 per cent. the bovine. This more closelyapproximates to the 90 per cent. quoted above fromthe published results of work done entirely amongstchildren. Nevertheless, the fact remains that inLiverpool 16 per cent. of cases of glandular tuberculosisare due to human bacilli-i.e., infection from activecases of phthisis. In contrast to this 62 per cent.

1 A. P. Mitchell : Infection of Children with Bovine TubercleBacillus, Brit. Med. Jour., 1914, i., 125.

Page 2: A CLINICAL STUDY OF THE HUMAN AND BOVINE TYPES OF TUBERCULOSIS IN MAN

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c’f glandular disease in adults is due to the humantubercle bacillus. In fact, in adults about 72 percent. of all surgical tuberculosis is the result ofinfection with the human organism. That impliesthat a very large proportion of cases of adult non-pulmonary tuberculosis have also a pulmonary focus-active or latent. This should increase the gravityof the prognosis in these cases, should make prolongedafter-care imperative, and should be a warningagainst the indiscriminate use of general anaesthetics,which may aggravate pulmonary disease. An X rayof the chest should always be taken before operationon any adult with surgical tuberculosis.

Family History.It was thought that a study of the family history

would in many instances give a clue to the typeof disease present-i.e., that a history of phthisis ina member of the older generation would be found ininfections with the human bacillus, and that inbovine infections the older generation would behealthy, and other members of the same generationdiseased. Here, however, great difficulties are

encountered. There is a very widespread feelingthat it is disgraceful to have a case of tuberculosisin the family. Unfortunately, the sense of disgracedoes not lead to the general adoption of a morehygienic way of life, the use of non-tuberculous milk,and stricter measures to prevent the spread ofinfection, but only to concealing the shameful factor to heaping up mounds of sand ’in which to burythe head, so that at least the horrid thing is out ofsight. Infection of collateral members of the familyis surprisingly seldom reported in bovine infections,though, of course, striking instances do occur. Thisis another indication that the soil is at least asimportant as the seed in the development of tuber-culosis. In human cases, on the contrary, a bador decidedly suspicious history of pulmonary diseasewas found in 31 per cent. Over and over again onecan elicit nothing more than " grandmother alwayshad a cough and mother died of pneumonia."Apart from a study of the family history, attempts

at determining the portal of entry were singularlyunsuccessful. It was definitely recorded that, amongthe bovine cases, two apparently originated in glandsdraining the area. in which an open wound hadexisted a short time before. In bovine cases themilk naturally falls under special suspicion. Infour cases, one of which was in a well-to-do intelligentfamily, it was stated that the milk had always beenboiled. This, of course, proves nothing, for suchmatters are often left to maids, who may be untrust-worthy. Moreover, other articles of diet, such asbutter and cream, may be carriers of the bacillus.The tonsils were diseased and the teeth carious in

many patients with cervical glandular disease, butin several others they were not obviously at fault.Little weight, unfortunately, can be attached to thisobservation as, apart from the possibility of tuber-culous infection passing through a tonsil withoutleaving indisputable evidence behind, it has beendefinitely shown that naked-eye examination is nocriterion as to the presence or absence of actualtuberculous disease in a tonsil.l

Results of Treatment.The results of treatment are strikingly different

in the different groups. For instance, as alreadystated, all the 18 bovine cases traced were found ingood health, and their lesions quiescent, while no lessthan 18-75 per cent. of the human cases were deadwithin three years ; 68-75 per cent. were cured orapparently cured. I do not think this necessarilymeans that the bovine infections are harmless, whilethe human are deadly. Apart from the long periodof illness, the expense of treatment, and the permanentcrippling often caused by bovine infections, manypatients die in the early years of life from meningeal,"pulmonary, and abdominal tuberculosis, and are

never seen by the surgeon.2 2 The course of the two

2 Dr. Louis Cobbett’s evidence, Report of Royal Commissionon Tuberculosis, 1907.

infections is apparently very different. Those dueto the bovine organism begin, as a rule, early in life,though not necessarily in the very earliest years,and may lead to a comparatively acute and virulentprocess. Should this not prove fatal, the manifes.tations of the disease become more and more chronicuntil after early adult life it practically disappears.Many believe that the human infection is contractedearly-i.e., within the first four years of life-andthat thereafter, if not rapidly fatal, it lies latent,perhaps for many years. Be that as it may, in" surgical cases " the disease is one that tends toattack those of maturer years (65 per cent. over

12 at the time of apparent onset) and, unlike thebovine type, it never disappears, and all ages areliable to suffer. It may become very chronic, butthe immunity established evidently falls far shortof that produced by the bovine organism, as is shownby the very considerable mortality in the humanvariety.

_______________

SOURCES OF INFECTION IN NON-PULMONARY TUBERCULOSIS.

BY C. O. STALLYBRASS, M.D. LOND.,D.P.H. LIVERP.,

ASSISTANT MEDICAL OFFICER OF HEALTH FOR THE CITYOF LIVERPOOL.

FOR the past seven years I have noted, from thereports of our sanitary inspectors on cases of non-pulmonary tuberculosis, whether there was a historyof exposure of the patient to a pulmonary case

occurring in the patient’s family. In all these patientsthere is a considerable presumption that the infectionwas of human origin. The total number of casesso examined is now 4469, and these are presented inTable I., separated according to the anatomical site, onthe usual classification. The numbers are sufficientlylarge to have some statistical validity.

TABLE I.

City of Liverpool.-Cases of non-pulmonary tuberculosis in1921-27, divided into Group A-those with no history ofexposure, and Group B-those with a history of exposure toopen cases of tuberculosis occurring within the family of thepatient.

I * This column gives the excess (or defect) of the percentage ofcases occurring in Group B over the percentage of cases occurringin Group A.

The significance of these figures lies in the last twocolumns, which give (1) the excess or deficiency ofthe percentage of cases having a history of exposure toinfection in comparison with the percentage of caseshaving no such history, and (2) the probable error ofthis difference in percentage. The usual criterion ofthe significance of a difference of two rates is that itshould be three or more times its probable error.

With this proviso the following deductions may bemade from the table. In Liverpool-

1. Tuberculosis of the bones and joints is significantlymore frequent in those having no history of exposure toa human source of infection.

2. Tuberculosis of meninges and abdominal tuberculosisare significantly more frequent in those having a historyof exposure.