Tuberculosis in Young Adults: Report on the Prophit Tuberculosis Survey, 1935-44

Abstract

In 1932 the Royal College of Physicians of London received a legacy from the late Mr. J. M. G. Prophit, to be devoted to research into tuberculosis, and decided that an investigation should be made of large numbers of nurses, medical students, contacts of tuberculous persons, adolescents in the Royal Navy, and controls, and that the results of the numerous tests involved, and of the observations made over a long period of time, should be correlated with the conditions in which these persons lived and with any other relevant facts. Work was started in 1935. A Prophit Scholar was appointed (Ridehalgh 1935-39, Hall 1940-41, Daniels 1942-45, Springett [assistant] 1943-45) and arrangements were made for collaboration with the appropriate commercial and public bodies, including teaching hospitals in London and elsewhere. The aim at first was to examine five groups, each of 5, 000 persons, but the war prevented the accomplishment of this object; in the event, 10, 100 were studied in all. Table 1, from Section A, gives the relevant data. It will be observed that all the persons studied were free from X-ray evidence of tuberculosis; those found on first examination to have such evidence are not included in the survey. The nurses form the largest group. Most of them were English, but there were about 1, 000 Irish or Welsh. Nurses were employed in general hospitals to which tuberculous persons were admitted (Group A), or in general hospitals to which such patients were not usually admitted (Group B); it is made clear [img 1T231446A.tif] that there were some admissions of tuberculous patients to Group B hospitals, but that they were very much less frequent than, in Group A. More of the Irish and Welsh nurses were employed in Group A than in Group B hospitals. The mean age at entry into the survey was 21 years for controls, medical students and nurses, 18 for contacts and 16 for Navy boys. (Section B.) Intradermal tuberculin tests were performed on all the subjects of this investigation, the doses varying from 0.001 to 1.0 mgm. OT. The tuberculin was diluted with the following borate buffer solution, in which no loss of potency occurred for a month at 40 degrees F. [img 1T231446B.tif] This is bacteriostatic and does not interfere with the biological properties of the tuberculin. [Unfortunately, in the text on p. 217, three symbols (g., grm. and gr.) are used in the same paragraph to represent grammes.] At the initial test, on entry into the investigation, (discussed in Section C), the percentages positive to one or other of these dilutions were 83.9 and 85.4 for female and male controls; 64.2 for Navy boys; 82.8 and 84.5 for female and male medical students; 80.2 for nurses; and 92.3 and 93.3 for female and male contacts. These rates are compared with those reported on persons of comparable ages in various countries, by different authors; in general, the European rates tend to be higher than those reported from the United States. In the Prophit survey the incidence of sensitization is some 7-10 per cent, higher at the age of 23 than at 18. An interesting finding is that the degree of sensitivity in positive reactors is higher in contacts and in the groups in which the proportion of positive reactors is high, than in the groups in which that proportion is low, except in the case of Irish and Welsh nurses. All (except a very few) of the subjects were examined radiologically on entry into the investigation (Section D). Pulmonary tuberculosis was then found in 1.6 and 1.9 per cent, of female and male controls; 0.5 per cent, of Navy boys; 0.7 and 0.8 of medical students; 1.2 per cent, of nurses other than Irish or Welsh; 2.9 of Irish or Welsh nurses; and 9.9 and 5.6 per cent, of female and male contacts. Calcined primary lesions, pleural changes and miscellaneous lesions are listed also, in the proportions in which they occurred. Most of the lesions of pulmonary tuberculosis were found in the upper zones of the lungs, and there was a preponderance of right-lung lesions. Pulmonary tuberculosis was infrequent in those under the age of 18. The incidence was higher in contacts of sputum-positive persons than in contacts of sputum-negative (tuberculous) persons, but even in the latter group it was much higher than in controls. Paradoxically, the incidence of pulmonary tuberculosis and of calcified foci in the lungs was highest in the Irish and Welsh nurses, who, as a group, showed the lowest incidence of positive tuberculin reactions on entry. There was no linear relationship between the incidence of calcified foci and of pulmonary tuberculosis, which suggests that pulmonary tuberculosis is not always a recrudescence of endogenous infection. In Section E the authors consider the changes observed in tuberculin sensitivity during the period of observation. Of those initially negative to tuberculin, 26 per cent, of female controls, 36 per cent, of male medical students, 54 per cent, of nurses in Group B hospitals, and 80 per cent, of nurses in Group A hospitals became positive during the first year of observation, but the degree of sensitivity after conversion from negative to positive was lower than that registered in persons initially positive a year after entry. Moreover, a number of persons initially positive, especially nurses of Group A hospitals, became more sensitive to tuberculin during the first year of observation. These findings lead the authors to the conclusion that repeated reinfection from outside may take place in persons already infected, and that such repeated reinfection is one of the factors which maintains or increases sensitivity. The point is made that over 70 per cent, had no symptoms of note at the time of conversion from tuberculin negative to positive, and that in 782 conversions only 14 cases of erythema nodosum were observed. The other symptoms associated with conversion are set out in a table; they were usually rather vague. In Section F, on the clinical analysis of cases of tuberculosis, the authors state that as they were not themselves on the staff of any of the hospitals concerned, and although as a matter of courtesy they were allowed to conduct certain investigations, they were not in a position to ensure that all persons were radiographed at the requisite times, or to make alj. the exact examinations and observations which would have been desirable. This was inevitable in a survey big enough to provide statistically adequate results. In persons who were negative to tuberculin on first examination, there were 71 who subsequently developed tuberculosis (including pleural effusion and non-pulmonary disease). Of these, 6 showed lesions which were attributed to the primary focus, [img 1T231446C.tif] 25 showed pleural effusion only, 7 showed post-primary dissemination, 22 showed reinfection lesions (but it was not possible to determine whether they were endogenous or exogenous), and 3 were unclassified. None of the 8 Navy boys in this group could be analysed, because the particulars available were too scanty. In persons who were positive to tuberculin on first examination, there were 124 who subsequently developed tuberculosis; 97 developed pulmonary lesions, and of these 7.1 were minimal (in that the radiological shadow did not occupy more than two interspaces, or not more than the two apices). There were 12 cases of pleural effusion only, and 7 of non-pulmonary tuberculosis. Again, the cases among the Navy boys could not be analysed. In addition, there were 15 cases in persons whose initial tuberculin reactions were not completed, or not read. When lesions were closely related in time to the primary infection, they were usually accompanied by symptoms, whereas the majority of reinfection lesions, in persons initially tuberculin-negative or tuberculin-positive, were clinically latent when they were discovered radiologically. The incidence and the morbidity rates were as above [taken from Table 66, Section G, p. 134]. The authors make the point that it would be unwise to compare these figures with the notification rates for the general population, because of differences in composition and in case-finding methods. They do compare them, however, with results reported in surveys from other countries, in which incidence rates varying from 0.4 to 11.3 per cent, have been recorded. An important analysis (below) shows the rates in persons other than controls: -[img 1T231446D.tif] The differences are significant, and even if pleural effusions and retrogressive lesions are excluded, they are still significant, for both male and female groups. Similar evidence, that nurses and students negative to tuberculin are particularly liable to tuberculosis, is quoted from several other, well known, sources, but the Prophit figures are lower than most. There is evidence which suggests that nurses who became strongly positive to tuberculin at the time of Mantoux conversion were more prone to develop overt disease than those who were less strongly positive; the difference is not significant in the technical sense, but it is suggestive. The morbidity rate in nurses in Group A hospitals was consistently higher than the rate in Group B hospitals, irrespective of initial tuberculin reaction, race, or variations between individual hospitals. The disease tended to appear early in nurses initially tuberculin negative, incidence being high in the first year and low in succeeding years, whereas in those initially tuberculin positive the rate was low in the first two years, and subsequently rose. Morbidity in contacts was much higher than in any other group; it was 20.5 times as high in Irish and Welsh nurses as in other nurses, irrespective of initial tuberculin reaction. There were 97 cases which arose during the survey and which were regarded as minimal; 60 per cent, of these lesions were infraclavicular and 25 per cent, apical. One quarter showed cavitation at some time, and one half required sanatorium, care. '' There is some ind