Experiences of the Mantoux test in dispensary work

EXPERIENCES OF THE MANTOUX TEST IN DISPENSARY-WORK.~ B y NOR3IAN TA'r'rERSAT,5, 5I.D.; B.S: Chief Clilzical Tubercztlosis O~icer. City of Leeds. :BEFORE discussing actual experiences I think we will all be agreed on the following points, substantiated by many workers, that: (1) Tuberculin hypersensitiveness is constantly associated with tuberculous infection. (2) By adult life the majority o f the urban working class population give a positive response. (3) A positive skin reaction only indicates that the individual has at some time been injected by the tubercle bacillus and cannot of itself decide whether the disease process is active or ext:inct. t 9 ,, (4) A "genuine n e c~,atlve, i.e., to 1 : 10, excludes present ( a n d p r o b a b l y past) tuberculosis within a very small margin of error (2 per cent.). :For to-day's discussion I am confining my remarks to observations on 452 children tested in 1931 and the early part of 1932, thus allowing a iollow-up period of two and ~ half to four years. It was not considered practicable to do complete graduated tests in this large number and the majority were tested once only with 0"l c.c. of 1 : 1,000 old tuberculin. A number of the youngel/ children, especially if close contacts to positive cases, were tested with 0"1 c.c. of 1 : 1 0 , 0 0 0 tuberculin, following this up with the 1 : 1,000 dilution if the weaker tests were negative. It follows from this that some of our " n e g a t i v e " results cannot be called "genuine ne,,atlves as they might have reacted to the lower dilutions of 1 : 100 or 1 : 10. On the other hand, H a r t has shown that the error in using a 1 : 1 , 0 0 0 dilution is only 4 per cent., and that by testing up to the 1 : 10 strength the error is still ~ per cent., so that for practical purposes in dispensary work I would suggest that the standard test should be 0"1 e.c. o! 1 : 1,000 dilution. W e rarely test: out patients with the more concentrated dilutions except when under institutional treatment. Results are read in forty-eight or seventy-two hours after the test. Of the 452 children in this series 147 (approximately one-third) were 5 ),ears old and under, 214 (nearly half) were aged 6 to 10, and 91 aged 11 to 1 4 . All, of course, were c l i n i c a l l y e x a m i n e d ~ m a n y of them on several occasions--and 352 (80 per cent.) were also X-rayed. Of the total of 452 practically half (2'21) were contacts to T . B . + cases, and only 62 (14 :per cent.) gave no history of Contact. The final clinical diagnosis in these ,15'2 children (taking all the evidence, clinichl, X-ray, skin and 'other tests, and in some, institutional observation) was : Definite evidence of tuberculosis _(sufificient to justify notification)61 (58 p u h n o n a r y - 3 nou-puhnonary; negative for Tb. 391. The results of the h[antoux tests (grouping all ages together) were : - P.ositive 307 (68 per cent.) ; negative 145 (32 per cent.). When the cases are reviewed according to age-groups and contact history t h e followin~ results are obtained : - - . i Abstract of a paper read to the Yorkshire Tuberculosis Society. December 14, 193-t. 19

290

TUBERCL]~

Positive

m. All ages 0-14

[April, 1935

Contacts to T . B . q .. Contacts to T . B . - - or I'I.P. IRon.Contacts .. 9 ..

Age Contacts to T.B.--I-

9. 3ontacts to r . B . - - or N o n PulmonaryT.B.

0 to 5 6 to 10 11 to 14

Age 0 to 5 6 to 10 11 to 14

.'1"

189 (88 per cent.) 87 (51 ,, ) 39. ( 5 1 .

,,

Positive

)

Negative 33 (12 per cent.) 82 (49 ,, )

3o (49

,,

Negative

58 (90 per cent.) 91 (86 per cent.) 39 (80 per cent.)

8 (10 per cent.) 15 (14 per cent.) 10 (20 per cent.)

Positive

Negative

'29 ( 5 0 p e r c e n t . ) 39 (50 per cent.) 19 (5i per cent.)

)

28 (501)ercent.) 38 (50 per cent.) 16 (46 per cent.)

The figures for the 62 non-contact children are too small to divide into age-groups but they correspond in total Very closely to the contacts to sputum negative or non-pulmonary cases--32 positive and 30 negative (approximately 50-50). These figures merely confirm the findings of many other workers. They show on the one hand the very early tubereulisation of the contacts to sputum positive cases (90 per cent. positive under 5 years of age) and also suggest that contacts to sputum negative and non-puhnonary cases are not tuberculised to a greater extent than children in whom there is no known exposure. There are, however, one or two further observations to be made about the value of the positive reaction in diagnosis. H a r t summarises these as follows :-(1) A positive reaction indicates that infection has taken place. (2) Its chief clinical value is in infancy--the younger the age the worse the prognosis--though even in infants the positive test must be taken only as contributory evidence of clinical tuberculosis. Under 2 years of age a positive test, even without symptoms, indicates need for observation, with a guarded but optimistic prognosis. Up to 5 years of age a positive test with obscure and persistent symptoms is strong presumptive evidence of clinical tuberculosis. :Now in dispensary work We see comparatively few children of 2 years old and under (personally I discourage them). However, it'~ the cases under review there were o0 children aged fi years and under who were Mantoux tested, k follow up of these children (2~ to nearly 4 years after the test) should throw some light on whether the above conclusions are correct, and this has been done. Of these 20 infants 11 gave a positive test and 9 were negative. The follow up of the 11 positive reactors shows 7 alive and well, 2 have developed Tb. glands (slight), 2 cannot be traced (owing to removal following death of parent). The 9 negative reactors show 7 alive and well, 1 dead (broncho-pneumonia), 1 no trace.

April, 1935]

/dAlqTOUX TEST Ilq DISPENSARY WO1RK

.291

These results, although only a smail series, hardly confirm the rather grave views just quoted. Can we learn anything else from the positive reacting group? Does the intensity of reaction have much significance (i.e., are the + + and + + - k reactors more likely to show evidence of clinical tuberculosis than the milder positive reactors or is their hyperallergy a good prognostic sign) ? It is difficult to answer this question, but as far as my observations go they suggest that in the very young children (0 to 5 age-group) strong reactions tend to be associated with signs aud slight symptoms suggestive of clinical disease. In older children, those nearing the school-leaving age, my records suggest that these strong reactions are good rather than bad in their prognostic significance, and that the child who is shortly to face the stresses of work and outside contact is in a safer position with a + + reaction than with a negative or mildly positive result (though I doubt if this holds with continued home contact to a sputum-positive case). One final observation i n c o n n e c t i o n with the positive reactors is this. If a young child, and especially if more than one child from the same family,, gives a strongly positive response and yet home contact is denied or unknown, it is worth while getting the adults from the home up for review. In considering the value of a negative reaction we are at once on much safer ground, even when the test is used only up to the 1 : 1,000 dilution, for as I have already stated, a negative result excludes the presence of tuberculosis with a margin of error of not more than 4 per cent., and since we are considering eases of slight symptoms and signs, rather than the very toxic group whose reaction is lowered, probably the margin of error is nearer .2 per cent. than 4 per cent. In :Leeds, except in contacts to sputum-positive eases, we find that up to 14 years of age there are 50 per cent. negative reactors. It follows that when a child is referred witla chest signs or s y m p t o m s - - t h e multitudino as coughs, eatarrhs, bronchitis, asthma, bronchiectasis, post-pneumonic and other conditionsmthere is a reasonable chance of finding him :Mantoux negative, and therefore excluding at once the question of tuberculosis in the diagnosis. I should imagine that if in :Leeds, where housing is deplorable, there are 50 per cent. negative, many of you must be working in areas where the percentage of negatives is higher and therefore the test more valuable, and probably it will be found to be of increasing value amongst adults as the tubereulisation of the eommmfity diminishes. W h a t has already been said about pulmonary lesions and hIantoux re'sting applies equally, if not more so, to non-puhnonary eases. W e often see doubtful eases of bone and joint disease, X-ray findings doubtful ~or negative, signs very suspicious. In quite a number of these the finding of k~negative sldn reaction has been the deciding point in making a negative diagnosis. :RADIOLOGY AND i~ANTOUX TESTING.

3Vith a view to trying to establish some correlation between ~[antoux findings and chest X-rays, practically all the positive reactors were X-rayed, also a certain number of the negative reactors, especially such as were contacts t o T . B . + . Thus, out of 307 positive reactors "295 were X-rayed

292

TU~.R0r~E

[April, 1935

(96 per cent.), while o n l y 57 out of 145 negative reactors were radiographed. (150 (approx. 50 per (14 per cent.} : I 0,o coo .} : 51 (95 per cent.} : Negative Mantoux cases--57 films 3 (5 per cent.} : Positive ~Iantoux cases--205 films

cent.} : Negative X-ray Definite evidence o[ Tb. omc abnorm l t,--,os ,b Negative X-ray Some abnormality

In reading the X-ray films, clinical findings and Mantoux tests are always (in the first instance) ignored, and an attempt is made to assess the fihn on its own merits. Unfortunately there is still very wide divergence of opinion as to what is suggestive of Tb. in a radiograph, especially in children. I cannot attempt to-day to indicate our criteria for positive X-ray opinions--all I would say is that the 14 per cent. in whom we found "definite X-ray evidence" were mainly : - (1) " Infiltrations," mostly in the upper chest, with characteristics we have found associated with Tb. (2) Primary lung feel, with or withou~ secondary glands. (3) Unmistakable tracheo-bronchial glands. (4) Thickened pleura. Many of you will be familiar with D e w and Lloyd's publication of 1932 on this subject. That paper gives a statement of their criteria for " a h n o r m a l " films, but they do not attempt to any extent to indicate which of their " a b n o r m a l " fihns are considered as showing evidence of tuberculosis, and which are not--all are called "abnormal." hi?any of our "N%atlve X-rays show abnormalities," but if the changes seen are not; like those we recognise as "probably T b . " - - a n d can be explained by other illness (bronchiectasis, post,pneumonic changes, &c.)--we call them negative. This, I believe, explains how it is that in the Brompton 1Report 35 per cent. of the non-reactors to tuberculin had what they call "positive" (or abnormal) radiograms, whereas in my own series only 5 per cent. of negative reactors slmw X-ray abnormalities. I fully9agree with Lloyd 9 many " infiltrations" seen in ehiid X-rays are non-tuberculous, but I would suggest; that a close study of their characteristics enables one to decide on radiologieal grounds which are and which are not tuberculous with a considerable degree o[ accuracy. Lloyd states that 22 out of 51 Children in his series showed "calcified traeheo-bronehial glands," but gave a ~zegative skin test. This did not occur in a single one of my own series and I would suggest that his criteria of what are "calcified tracheo-bronehial glands" were inaccurate--in fact he suggests himself that such is the case in his final conclusions.~ In explaining why 50 per cent. of the positive skin-reactors show negative X-rays one must not forget that in many of these cases there probably is no chest lesion at all, and the infection is hidden away in abdominal or cervical glands, &e.--a fact supported by the Brompton postmortem figures which .Dew and Lloyd quote in their paper. Is there a~y relation between the inte~lsity of skin reaction and the radiological findings ? I have tried to find whether any type of X-ray appearance was con-

April, 1935]

MANTOUX~'EST IN I)ISPnNSAa~" won~

293

sistently accompanied by strong skin-reactions, b u t have not found any close relationship. Some of the strongest reactions, with vesiculation and even slight febrility, have shown no X-ray findings at all in the chest. On the other hand, those cases, not very cmnmon, of what we call " E p i t u b e r culosis," do seem to give )vithout exception a strong skin response. This would appear quite rational if we are correct in interpreting these X-ray appearances as indicating a strong allergic response to a reinfection around some small local focus. ~INAL OBSERVATIONS. It must be remembered that there is a " l a t e n t period" between primary infection and secondary skin reactivity. This varies from a few weeks to several months, and therefore, even if contact has beeu broken, a second test some months later is necessary before one can state that a child has not been infected. Another point I should like to raise is one of Hart's final conclusions which I cammt at present reconcile with my own ideas and experience. H e stresses, and quite rightly, the importance of separation of infants from iJffeetious parents before infection occurs, and then states " I f infcction has already occurred the advantage of separation is less certain." Cummins, in his most interesting work on the South African natives, shows quite clearly that those natives who arrive at the mines already tuberculised, and extremelyhypersensitive to high dilutions of tuberculin, develop clinical disease 0f an acute type when they meet fresh infection. The higher their tuberculin sensitivity the greater their risk of the disease. I t is not proven that this applies equally in Europeans, but it does seem to me that the continued exposure to infection of already allergic children is running a grave r~sk of severe reactions which may precipitate acute disease. There are many other problems on which further study of skin sensitiveness may.throw light and which it has not been possible to discuss to-day. ~Ve want to know more about the skin reactions in young adults l~rior to their developing the acute forms of disease we see so commonly to-day. Are they hypcrallergic, and if so could anything be done to dcscnsitise the hyperallergic cases by a course of tuberculin at about the school-leaving age, or are they negative and in need of such protection as B.C.G. is claimed to give? I believe that the question of densensitisation is going to be a matter of great importance before long. The recent work o f Professor Rich (:Baltimore) and other workers, chiefly in America, has shown that allergy, although frequently accompanying immunity, is not in itself an indication of immunity. They have shown that an animal which has been rendered both immune a n d allergic can be desensitised and so lose its allergy without auy loss of i m m u n i t y . :Now one of our greatest difficulties is that when acute young adult disease arises, the destruction of tissue and permanent damage is extremely rapid. These cases suggest that a fresh implantation of bacterial protein has occurred in highly sensitised tissues, with an intensely necrotic effect on the tissues. W e see these cases develop, with their influenzal onset, in healthy-looking young adults, especially from contact families. Could this destructive onset be prevented by desensitisation with tuberculin ? If we can prove that these cases arise especially in those" who appear ~i:ell,

929J

TUBERCLE

[April, 1935

but give a strong skin reaction, much useful preventive work might be done, as all this recent work points to the fact that such immunity as they have would persist unimpaired after desensitisation, but the allergy which leads to the extensive local damage wouht be removed. A recent leader in the British Medical Journal calls attention to the possibilities of epidemiological surveys and the problems of latent infection ; another wide field for investigation by skin testing. If the Tuberculosis Service is to push its attack home, to get to the root of the problem as to why this infected person dies of tuberculosis whilst that one lives to a ripe old age, and whether the infected person needs desensitising or the non-infected person requires a minimal infection--if we are to solve problems such as these, most of the spade work must be done in the daily routine of the dispensary, and I believe that much of the light to be focussed on these problems may come through an intelligent appreciation of what we may learn from such tests as we have been discussing to-day.

INTI~ATHOI~ACIC TUBERCULOSIS AMONGST THE CHINESE, WITH $PEGIAL REFEI~EIqCE TO THE PROVINCE OF SZECHUAN. By H. G. ANDERSON, M.D., M.R.C.P. Itcnry Lcstcr Institutv of Medical l{esearch, Shanghai, and West ChiTin Union University, Chengtu.

(Contin,ted fl'om p. ~56.) DETAILED STATISTICAL IPRESENTATION OF FINDINGS.

In general the findings presented in the following chart may have been said to have been recorded on first attendance at clinic, or in the case of in-patients at such time as the results of the physical strain of the iourney to hospital had subsided. A Inaiority of the cases were at an early stage of their disease or ambulant. Owing to a Chinese superstition that illluck enters a house with a corpse, the majority of moribund patients go home to die; contrary to the case of hospitals catering for Chinese coolies in the hIalay Peninsula, whoso inmates were too far from their homes to make the journey. One word of caution needs to be uttered with regard to Group A, and that is that tubercle bacilli in the s p u t u m may have their origin in a primary tuberculosis of the nasopharynx. W h e r e this is first excluded then tubercle bacilli in the sputum may be said to present final proof of tuberculosis of the lower respiratory tract. As far as possible the numbers in any given series have been presented; little serious claim is made for percentages stated in the absence of such a measure of their statistical accuracy. Percentages have been determined with a 10-inch slide rule, and are therefore subject to the slight inaccuracies of such a method. "Incidence" is based on a threshold value of positivity necessarily