42

Tuberculin

Tuberculin surveys play art important pa~t in the attack on the tuberculosis problem. Although main attention has to be devoted to those very important sources of informa- tion, the tuberculosis mortality and morbidity rates, nevertheless tuberculin surveys are able to provide vaIuable additional infor- mation, not otherwise available, concerning the frequency of tuberculous infection.

Tuberculin surveys usually at tempt to assess the incidence of tuberculization of a group. The nation as a whole may be investigated, to obtain a broad picture of the national tuberculosis problem, and to as- certain whether there has been any change in the incidence of infection with changing social and economic conditions. [For this purpose fully representative groups have to be selected. I t may be desired, however, to examine a particular group of people, e.g. an urban or rural community, or a particular age or occupational group of the population. Similar or dissimilar groups of people may be tested and compared. Particular groups may be retested after a period to assess the effects of changing conditions, passage of time, improved public health services, pro- longed association with cases of tuberculosis, or any other factor which may have a bearing on the tuberculosis problem.

In practice, in this country, it has been found difficult to select reliable samples of the general population, and most published surveys describe the reactions of special groups, selected in various ways, and not fully representative of the nation as a whole. I t is obvious, of course, that some national populations live under such varying circum- stances that nalional surveys will only have a limited value. The isolated shepherd or fisherman of North Wales has very different opportunities of contact with tuberculous infection, compared with those of the aver- age inhabitant of one of our large cities.

Surveys and the Tuberculin Test* BY B. COUTS,

Tuberculosis Offcer, Hefts C.C.

have been without bias in some part{cular direction, if enough surveys are done, a reasonable estimate can be made of the national state of affairs. This has been the case in the United States, partictilarly for the younger age groups. Most British surveys are concerned with 'hospital populations' or tuberculosis contacts. In Denmark, however, all the school children have been tested, and in Norway and Sweden small districts have been completely covered.

Tuberculin surveys have been made, using all the various tuberculin tests. The accm'acy of the results varies with the test used, and with the potency of the prepara- tion of tuberculin. In the case of the MantouX test, the dilution used is, of course, of great importance. It will be seen therefore that each survey has to be judged on its own merits, and in fact, it is found that many surveys are unreliable, or give incomplete informatiot:).

In a large number of reported surveys, radiographic examination of the lungs has also been made of each subject tested, or occasionally, of each person found to be tuberculin sensitive. These examinations are of great value, particularly in case-finding programmes, but are not really essential to the main purpose of a tuberculin sm'vey. Only a proportion of those sensitized to tuberculin, show any typical radiographic changes, and the frequency of tuberculous infection cannot be accurately estimated in this way.

Tuberculin surveys have of course been made for many years. One of the first was carried ont by Metchnikoff in 191i among the Kalmuck people of South Russia. He was followed by very many investigators, in most parts of the world, particularly in Europe. These surveys tended to show that among the poorer classes of many industrial

*Part of an M.D, thesis sub,nitted to the University of Glasgow,

March I947 T t3 s

cities of Europe, extensive tuberculization occurred at early ages, and that by puberty most children were positive reactors. For instance, by I2 years almost all children in a Viennese survey were sensitized (Hamburger, 19o9), as were three-quarters of the children in a Prague hospital (Ganghofner, 19o8 ).

The results of these surveys were confirmed by much clinical and pathological experience and it was generally accepted that most persons living in urban areas had encoun- tered infection by the age of puberty and been sensitized to tuberculin.

In clinical diagnosis, except for infants and very young children, the positive tuber- culin test was not likely to be helpful, since most patients of the hospitaI class were posi- tive reactors, whether suffering from clinical tuberculosis or other conditions.

Tuberculosis continued to be extremely widespread, particularly during and follow- ing the first World War, when a phase of improvement in the West European countries was seriously interrupted. With the gradual passing of the hardships tbllowing the war, with improving food and housing, and better knowledge of the prevention ofd~sease, the numbers of new cases and of deaths began again to fall.

In Britain, as in many other countries, the decrease in the death rate from tuberculosis began again about I925, and the figures showed progressive improvement until the outbreak of war in I939. I t seems likely that where national statistics show the numbers of new cases and of deaths to be decreasing each year, the opportunities for tuberculiza- tion become less frequent, particularly in those households where no member of the thmily is excreting tubercle bacilli. Tuber" culin reactions might therefore be expected to become less frequently positive, with possibly a change in the rate at which the young become tuberculized.

In this country, of course, the recent war reversed the downward trend of the tubercu- losis figures. The anxiety, intense over- crowding, lack of ventilation due to the 'blackout,' excessive hours of work, and re-

lzr< CL~ 43

strictions in the lbod supply have all played their part, coupled with the dispersal of tuberculosis patients in the early years of the war, and the increasing shortage of hospital and sanatorium accommodation.

The situation has therefore deteriorated since I939, particularly as regards tubercu- losis in children, but not to such art extent as to take us back to the state of affairs in I93~, when the most authoritative English tubercu- lin survey was published by P. D'Arcy Hart.

In the years I942 and i943, the writer per- formed a tuberculirt survey, among childrer~ and adults under 30 years, in Cambridge- shire. 5oo persons were tested, composed of 35 ° patients examined at the chest clinic, of whom 24 were cases of active tuberculosis, and I5O factory workers. Tests were made, usually by the Mantoux test (o'o 1 - I rag. O.T.) but many children had the patch test applied, negative reactions being confirmed by the intradermal method.

A parallel investigation was carried out in the neighbouring county of Hertfordshire, in I944 and i945. 700 children under 15 years were tested, 3oo of these being contacts of sputum-positive cases. None of the children had active tuberculosis. The Mantoux test was used in a dosage of o.I mg. O.T. (I : I,ooo). Only where clinical findings were suggestive, was a dose of I mg. (I :IOO) employed. Many of the childrer~ had jelly tests performed in addition.

The main aims of the investigations were to gain some idea of the frequency of tuber- culin sensitivity in normal groups of the population and to ascertain whether tuber- culir~ tests were likely to be of clinical value in adults.

Cambridgeshire Survey II1 Table I the figures are given of the results of testing 485 persons under 3 ° years, seen at the Cambridge clinic. These included cases of tuberculosis and contact persorts, and the results therefore cannot be taken as typical of the general population. The table does indi- cate, however, what routine testing in tuber- culosis dispensaries may be expected to show, that even in this selected population only

44

55 per cent & t h e children aged io-I 4 years are tuberculin positive, and that over io per cent of the adults are non-reactors.

From the total number examined were extracted all those who were clinical cases of tuberculosis or who had been in contact with such cases (Table II). T h e remainder, ~7 o in all, of whom more than one-half had been tested as part of a routine medical examina- tion, were considered as fairly representative of the population of the area. Indeed, by the exclusion of cases and contacts, they might well have been less tuberculized than the general population.

Non-Contacts For children under 15 years, the numbers are small and too much reliance cannot be placed on them. I t is, however, likely that the figures of 2~ per cent positive reactors for all children under 15 years, and 42 per cent for children between IO and 15 years,

TABLE I,--TuBm~OULIN REACTIONS OF TOTAL NUMBER TESTED (CAMBRIDOESHIRE)

Positive Negative Age No. reactors reactors

o-4 33 I3 (39'4%) ~o (60.6%) 5-9 67 ~6 (38.8%) 41 (6i,~%)

Io-I 4 82 45 (54"9%) 37 (45"I%) ~5-~9 97 7~ (74'~%) 25 (25"8%) 2o-o 4 r58 r14 (8e.6%) 24 (I7"4%) =5-~9 68 58 (85.3%) lO (I4"7%)

o-I4 ~82 84 (46.2%) 98 (53'8%) I5-29 303 244 (8o'5%) 59 (I9'5%)

o '29 485 3~8 (67'6%) 557 (32'4%)

TABLE II.--TuBEItCULIN REACTIONS IN 270 ~]~-ON-OONTAOT NON-TUBERCULOUS' PERSONS

. . . . . (CA~m~nm~.smRE) Positive Negative

Reactors Reactors Probable Age No. (%) ( % ) error

0-4 8 o ioo 5-9 53 9 91 i 3 ' 4

7o-I4 33 42 58 ~6 ;8 ~5-r~9 64 64q 35'9 --t:4 "° o- o-~4 76 8~ '9 17' r ~ 2 "9 25-29 56 82.I 17'9 :t:3"5

0 - I 4 74 ~2.I 77"9 i 3 " 3 I5-29 I96 76'5 23"5 i ~ ' o o-29 27o 61.8 38.~ ~2 .o

T v ~ ~. g c L E March 1947

are fairly significant. Less than one-half of ' the children of the latter group are tuber-

culin positive, and testing is therefore a very useful procedure.

As regards the older subjects tested, it is seen that one-third of those between 15 and 20 years were still tuberculin negative, and of those between 20 and 3o years, nearly one- fifth had escaped infection. This is quite a substantial proportion of the total, and shows that the theory that tuberculization is inevitable and universal, is not true. In clinical cases where the diagnosis is in doubt, it will be worth while in the Cambridge area to test with tuberculin all adults up to 30 years, there being, in persons free from tuberculosis and not in contact with a case of tuberculosis, a 20 per cent chance of a negative reaction.

Contacts Examination of the figures for the persons in contact with cases of tuberculosis showed a familiar picture (Table III). Those in con- tact with sputum-negative cases, although few in number in this series, gave figures higher than those obtained from the 'non- tuberculous non-contact' group, but much lower than those given by the subjects in contact with sputum-positive cases. These last persons showed a high incidence of positive reactors, over 60 per cent for child- ren more than 5 years old, rising to over 80 per cent in adult life. The latter figure was identical with that obtained from the same age-group in the 'non-tuberculous non- contact' series.

In view of the discussion in the past on the difference in tuberculization between town

a n d countryside, it was considered that Cambridgeshire, with its very marked con- t rast in living conditions between the busy overcrowded town o f Cambridge and the sparsely inhabited, isolated rural areas sur- rounding it, might give information of interest. Subjects were therefore divided into the three categories of those living in Cam- br idge, those living in the rural area, and those who had lived mainly o u t s i d e t h e County (Table IV).

IVfarch 1947 T U n ~. R c L ~

'I'ABLE III.--CoMPARISON OF FREQUENCY OF POSITIVE I~EACTIONS IN 47o CONTACT AND NON'CONTACT PERSONS IN CAMBRIDGESIrIIRE

Contacts of sputum-positive Contacts of sputum- cases negative eases Non-contacts

Age No, Positive reactors jVo. Positive reactors No. Positive reactors

45

°-4 I° 5 (4 I'7%) I2 4 (33'3%) 5--9 15 II (78"3%) 41 II (26'8%)

IO-I4 28 18 (64'3%) 4 o 21 (52"5%) I5-I 9 26 24 (92'4%) 68 45 (66'2%) 2°-"4 44 37 (84'~%) 82 69 (84'1%) 25-29 7 7 58 48 (82.8%)

o-I4 55 34 (61.8%) 19 7 (37"0%) 93 36(38'7%) I5-~9 77 68 (88.4%) i8 ~5 (83'3%) o08 i62 (77"9%)

o-~.9 132 io2 (77'3%) 37 22 (59'5%) 3oi i98 (66.0%)

TABLE IV.--CoMPARISON OF FREQUENCY OF POSITIVE I~EACTIONS IN PERSONS LIVINO MAINLY IN CAMBRIDGE~ CAMBRIDGESHIRE, AND OUTSIDE CAMBRIDOESHIRE

Cambridge (borough) Cambridgeshire (rural) Outside Cambridgeshire Age No. Positive reactors No. Positive reactors No. Positive reactors

o-I4 9 ° 35 (39'I%) 56 I5-29 I43 i2o (83.9%) 6i

o-~9 ~33 i55 (66.5%) 117

Although the figures for the complete age- groups showed almost identical results in all the categories, consideration of the results of the tests in childhood and adult life revealed three important findings.

First, the surprising fkct emerged that under 15 years of age, the level of infection was more than so per cent higher in the rural areas than in Cambridge itself. It is probable that bovine infection was re- sponsible for this high level of tuberculization in the rural children, and indeed it was seen at the clinic that many of the cases of glandu- lar tuberculosis were in children from the countryside.

Secondly, in the age-group I5-~ 9 years, the frequency of infection was 17 per cer~t lower in the rural areas than in Cambridge. This was in conformity with the suggestion that rural life in Cambridgeshire offered less opportunity for infection.

Thirdly, the results of the tests in those persons who had lived mainly outside the County, showed a remarkable similarity to the findings for the town of Cambridge. It is likely, therefore, that in spite of its many

36 (62'5%) 36 I3 (36'I%) 4~ (67""%) 99 83 (83'9%)

77 (65"8%) I35 96 (7I'I%)

advantages, Cambridge does not show a lower level of tuberculization than other areas, mainly in Southern England, from which the persons tested were drawn.

The Hertfordshire Survey In the part of the work performed in Hert- fordshire, all examinations were made in the course of ordinary dispensary work. As in the previous part, the results were collected of the tuberculin tests of those persons free from tuberculosis and not in contact with cases of the disease (Table V). This again is a selected group with the bias towards pro- ducing a favourable impression of the degree of tuberculization.

For the children under z 5 years, of this group, the percentage of positive reactors was 25.5, while for children between IO and z 5 years the percentage was 45"3.

lit the case of 2o0 children, in contact with sputum-positive cases, the correspond- ing figures were 64"3, and 78'6 respectively, Indeed the youllgest children, under 5 years, showed a percentage of 5e'6 positive re- actors (Table VII).

46

Difference in Reactions According to Sex Analysis of the incidence of reactions showed a lesser frequency, not statistically significant, among the female subjects tested.

TABL~ V. - -TuBERCULIN I~.EACTIONS IN 5 10 'NoN-CONTACT NON-TUBERCULOUS" CHILDREN

(H~:R'rro~-DSmRE) Positive Negative Probable reactors reactors error

Age No. (%) (%) (%)

T U B E R C L E

1 0 0

0- 4 z31 Io. 7 89- 3 =~I'8 5-9 ~42 22 "3 77 "7 ± 5.8

lO-54 I37 45"3 54"7 :k2'8

o-z4 55o 25"5 74"5 J=z '3

T A B L E VI.- -Tu]~ERCULIN RF.ACTIONS IN 196 ~HILDREN, ~ONTACTS OF SPUTUM-POSITIVE

CAs~s (Hr~'rroRDszm~)

Age No.

Positive Negative reactors reactors (%) (%)

0-4 74 52.6 47 "4 5-9 66 63.6 36'4

IO-X4 56 78"6 ~r'4

o-I4 I96 64"3 35"7

Comparison of Results in Cambridgeshire and Hertfordshire

C )mparison of the surveys is complicated by the fact that, as already mentioned, the method of testing varied in the two areas. The use of the intradermal test with I mg. Old Tubercul in in Cambridgeshire, showed a certain number of reactors missed by a less intensive search, such as occurred in Hert- fordshire. In spite o f this, the results show lower figures irl the former area in several of the groups tested, and it is probable that tuberculization occurs less often in early childhood in Cambridgeshire than in Hert- fordshire.

It is possible to compare two classes in the two courLties. In the case of the 'non-tuber- culous non-contact ' groups (Table VII) , Cambridgeshire numbers are very few, but do suggest that the incidence of infection is lower in that county in the children under t o years, than in Hertrordshire. The figures for cliildrell between io and 15 years, and ibr the whole group, are similar in the two

8o-

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March i947

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surveys. It is probable that these findings, that approximately 25 per cent of all child- ren under 15 years of age, and 45 per cent of children bctwcen io and z 5 years are positive reactors, are valid for areas other than the two counties, since other surveys have shown similar findings. (Fig. I).

TABLE VII.--ColvlPARISON OF INCIDENCE OF POSITIVE REACT5ON8 AMONG '1\ToN-CONTACT NON-TUBERCULOUS' CHILDREN IN CAMBRIDGE-

SHIRE AND HERTFORDSHIRE Cambridgeshire Hertfordshire

Positive Positive reactors reaclors

Age No. (%) No. (%)

0- 4 8 o I3I lO. 7 5-9 33 9 242 22.3

IO-I4 33 42 I37 45'3

o-I4 74. ~7 55o 25'5

Comparisoll of the results of testing child- ten in contact with 'open' cases of phthisis

March 1947

showhigh figures inbo th areas, over 60 per cent being reactors in both surveys (Table VII I ) .

TABLE V I I I . - - C o M P A R I S O N OF INCIDENCE OF POSITIVE REACTIONS AMONG CHILDREN, CON- TACTS OF SPUTUM-POSITIV~ CASES~ IN CAM-

BRIDCESHIRE AND HERTFORDSHIRE

Cambridgeshire Hertfordshire Positive Positive reactors reactors

Age No. (%) No. (%) o- 4 12 41 "7 74 52'6 5-9 I5 73'3 66 63.6

~o-I4 a8 64. 3 56 78.6 o-I4 55 6i .8 i96 64. 3

Comparison with other Tuberculin Surveys It is instructive to compare the results ob- tained with the findings of other writers. The incidence of positive reactors was much higher in the surveys performed by D ' A r c y

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:r u s E R c:: L E 47

Har t (I932), Kaync (I934) , Tattersall (I935) and Blacklock (I936). Gory's figures ob- tained from children in orthopaedic hospitals in I934 tended to be lower, while Brad- shaw's results (t939) were similar to those of the presertt writer. Both Price (I939) and Jones Davies (I943), working with chi ldren with rural backgrounds, found much lower levels of infection. The results of tests in Glasgow in I943 by Flemir~g showed a striking similarity to the writer's findings although tuberculous children were in- cluded. In the work of Simpson (I944) the percentages were higher for the children under I o years, but similar for children over this age. The Bournemouth survey by Heimann and Patersor~ (I945) showed results very like those of this writer in the younger groups, al though for older persons, their figures were much lower. Fig. 2.

In his study of the Papworth children, Brieger (1944) reports a higher frequency of tuberculization, inevitable ir~ a Tuberculosis Settlement.

Turning to foreign countries, the picture is more varied. Many surveys, particularly those performed about ten years ago, on the Continer~t and in the United States, show a state of affairs similar to that revealed by the present work (S6derstr6m, i932; Groth- Petersen, I936 ), More recent irLvestigations, howe#er, particularly in Scandinavia, the Uni ted States and Canada, reveal lower levels of tuberculization, especially marked in the older children and young adults (see T6rnell, I943; Rich, I944; Pedley, I943). Some areas still show a high level of tuber- culization, and this is usually an indication of a backward communi ty (Mencig, I939; Lal, I943). (Fig. 3, see next page).

Discussion It may be deduced that we are, in this country, in an intermediate position as re- gards tuberculization, that we have pro- gressed in the last fifteml years, but have not reached the low levels found ia certain other comttries. This finding is in keeping with the changes in tuberculosis mortality and mor- bidity rates observed in rccetlt years.

4.8 T U B E R C L E

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Fro. 3.

An important factor in this country in maintaining the incidence of positive re- actors (and, of course, of tuberculous disease), must be the frequently contaminated milk supply. This danger has become particularly pressing, now that school children are en- couraged to drink increased quantities of milk, often in the early war years neither pasteurized nor boiled. (It ha s been thought by some American writers that the very low but persistent a m o u n t of tuberculization (.circa Io per cent) found in some surveys of rural American children was due to bovine milk infection.)

T h e tendency for tuberculization to be- come less frequent in the younger members of the communi ty means that pr imary in- fection is being postponed until adolescence or adu]t life. This tendency is even more .marked in many other countries. The de- cline in the incidence of infection is not always striking from a mathematical point of view, especially when compared with tlle corresponding decline in tubercu!osis mortal-

March i947

ity and morbidity rates. On analysis, however, it is unreasonable to expect the figures of sensitization to show the same decrease as have, for instance, the mortality rates in the last .forty years. Since infec- tion may be the result of random arLd even single encoumer with a~ infec- tious case, and the result- ant sensitization, in the vast majority of cases, lasts for many years, it will be seen that ~ the tendency for positive tuberculin reactors to become fewer in number will not be marked over short periods of time, unless a striking diminution in the oppor-

so tunities of infection has occurred.

In some measure, then, the tuberculin sur- vey, with its information concerning the tuberculization of the community, is a better indication of the widespread danger of tuber- culous infection than the mortality and mor- bidity rates, and is a useful corrective to over-optimistic views. It is probably true to say that only when the majority of the com- munity pass through life without a primary infection will the tuberculosis problem really have been overcome. New problems will no doubt confi'ont us as tuberculin sensitization becomes less frequent and in- creasing numbers of adults are at risk of undergoing primary infection.

Summary The incidence of sensitization to tuberculin in Cambridgeshire and Hertfordshire is de- scribed, there being some evidence of a decline as compared with previous surveys in this country. This was particularly marked in the younger ctfildren, and among the adults in Cambridgeslxire, where tubercu- lizatiozl was not found to be complete.

March I947 T u

The incidence of positive tuberculin re- actions is still much higher itl this country than in many other areas, particularly N. America and Scandinavia.

The value of the tuberculin test is in- creasing, since a reasonable prospect exists, in young non-tuberculous persons, of a nega- tive tuberculin reaction being obtained.

References Blacklock, J. W. S. (1936) Brit. zned. J., n, 304. Bradshaw, D. B. (1939) Ibid., i, 805. Brieger, E. M. (! 944) 'The Papworth Fafnilies,'

London. Cory, J. W. E. (1934) Archly. Dis. Child., ix, 177. Davies, T. E. Jones (1943) 'A Study of Tuber-

culous Infection in the County of Radnor.' Llandrindod Welis.

Fleming, G. B. (i943) Lancet, ii, 58o. Ganghoi'ner, F. (I9O8) Wien. Min. Wchnschr., xxi,

14o3.

r~ c L x 49

Groth-Petersen, E. (1936) Acta tuberc. Stand., x, I I I , I3I,

Hamburger, F. (I91o) Die Tuberkulose des Kindesalters, Leipzig, pp. 38, I88.

Hart, P. D'Arcy (1932) Med. Res. Oounc. London, Spec. Rep. Ser. No. 164.

Heimann, F. A., and Paterson, H. R. (i945) ~ied. Offzeer, LxxIv, 209.

Kayne, G. G. (I943) Lancet, 1I, i333. Lal, R. B., Majumdar, S. M., and Ahmed, J.

(1943) Ind. reed. Gaz., LXXln, 477. Mencik, J. R., Kahn, IV[. 0., and Mayer, E.

(1939) Amer. Rev. Tuber., XL, 5e2. Metehnikoff, E., Burner, E., and Taressevkch,

L. (19II) Ann. Inst. Past., xxv, 785 . Pedley, F. G. (1943) Canad. reed. Ass. J., XLW11, 05. Price, D. (I939) Irish J. reed. Sci., 6th Set'., lO 4. Rich, A. R. (i 944) 'The Pathogenesls of Tuber-

culosis,' Baltimore. Simpson, E. J. (1944) Brit. reed. J . , I, 286. S6derstr6m, H.J. (193 o) Acta Pedlar., xm, 433. Tattersall, N. (i935) Tubercle, xvi, 289. T6rnell, E. (1943) A eta tuberc. Scand., xv11, 2611

The Treatment of Minimal Tuberculous Chest Lesions* A Comparative Study

BY R. H E L L E R From the Hounslow Chest Clinic.

The significance and treatment of minimal tuberculous chest lesions is becoming a question of considerable importance, owing to the detection of an increasing number of these cases by mass radiography surveys.

Preliminary Survey of Literature This problem has recently been studied to some extent in America. Reisner and Downes observed 469 untreated patients, which they classified into four groups according to the radiological appearances: 'Exudative,' 'Exudative-Productive,' 'Pro- ductive and Fibrotic' and 'Fibro-Calcific' lesions. One will probably not be far wrong in assuming tlaat their 'Exudative' and 'Exudative-Productive' ]esions represented the cases with radiological evidence of activity, while the last two groups, especially the 'Fibro-Calcific' lesions contained the cases which appeared radiologically quie- scent. The authors found that about one haIf

of the 'Exudative' and 'Exudative-Produc- rive' cases showed evidence of activity during an observation period of five years.

Stein and Israel observed 66 consecutive untreated patients with minimal lesions and found that by the end of one year after diagnosis, 3 ° cases (i.e. about 5 ° per cent) showed evidence of progression.

Bobrowitz followed up i~ 9 patients who had routine sanatorium treatment and found that 2o per cent had progressed during the period of observation. He included in his series at least 8o patients who probably would not have received sanatorium treat- ment in this country at the present time, e.g. 42 patients with a 'small localized area of fibrosis,' 13 patient s with 'increased lung markings' and even 3 patients with khick pleura without infiltration.'

Kruger, Potter and Jaffin observed 185 patients who had been treated by bed rest

*Paper read at a meeting Of the Middlesex Tuberculosis Associatiml on December I8, I946.