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Pulmonary mycetoma as a late complication of tuberculosis
Tubercle,
PULMONARY
MYCETOMA
AS A LATE COMPLICATION
(19711, 52, 123
OF TUBERCULOSIS
By J. MORRISON SMITH, V. H. SPRINGETT and H. E. THOMAS
from the Birmingham
Chest Clinic, 151 Great Charles Street, Birmingham B3 3HX.
SUMMARY The occurrence of pulmonary mycetoma up to 10 years after notification of pulmonary tuberculosis has been examined in patients first notified in the City of Birmingham in 1957 and 1958. Of 946 sputum-positive cases 316 were available for examination at the Clinic after 10 years. Only 1 definite case of mycetoma was found and out of 275 tests for precipitating antibody to Aspergillus Fumigatus this was the only positive result obtained. Another 222 patients were still under supervision at 2 years but were not available at 10 years. On review of available films and clinical notes none had definite evidence of mycetoma but 1 had been suspected of having this complication, the diagnosis not being confirmed before he left the city. The findings suggest that mycetomas are rare among patients still attending a chest clinic 10 years after notification of pulmonary tuberculosis.
L’apparition de my&tome pulmonaire dans les 10 annees suivant le dkpistage d’une tuberculose pulmonaire est CtudiCe chez des malades de Birmingham dont les premiers signes de tuberculose sont apparus en 1957 et 1958. Parmi les 946 sujets ayant eu une expectoration positive, 316 ont pu etre CxaminCs dans le service, 10 ans aprks. Un cas certain de my&tome, seulement, a &k trouvC, et parmi les 275 tests de prkcipitation des anticorps de l’aspergillus fumigatus, c’est le seul rksultat positif qui a CtC obtenu. Un groupe de 222 autres malades Ctait encore sous surveillance medicale apris 2 ans, mais plus aprks 10 ans. L’Ctude des radios et des renseignements cliniques disponibles n’a montrC aucun signe certain de mycttome. I1 y avait toutefois I cas suspect de cette complication mais le diagnostic n’a pas iti confirm6 avant qu’il ne quite Birmingham. Ces rksultats semblent montrer que les cas de my&tomes sont rares chez les malades ayant eu une tuberculose pulmonaire et Ctant encore sou? surveillance dans un service de pneumologie 10 ans aprt?s.
RESUMEN Se examinci la existencia de mycetomas pulmonares hasta 10 adios despues de la notificacibn de tuberculosis pulmonar en pacientes reciCn descubiertos en la ciudad de Birmingham en 1957 y 1958. Sobre 946 cases con esputo positivo, 316 estaban disponibles para el examen al cabo de 10s 10 adios. Sdlo se ha116 un case de mycetoma y sobre 275 tests para precipitinas de1 Aspergillus fumigatus, Cste fuC el tinico resultado positivo.
124
MORRISON
SMITH
AND
OTHERS
Otros 222 pacientes seguian siendo controlados a 10s 2 silos paro no estaban disponibles a 10s 10 adios. Al revisar las radiografias y 10s datos clinicos ninguno mostraba evidencia de mycetoma, aunque uno era sospechoso de tener esa complication; no se pudo confirmar el diagnostico. Estoa hallazgos sugieren que 10s mycetomas son raros entre 10s pacientes que siguen controlandose en 10s hospitales 10 adios despues de iniciar su tuberculosis pulmonar.
ZUSAMMENFASSUNG
Das Auftreten pulmonaler Mycetome bis zu 10 Jahren nach Diagnose der Lungentuberkulose ist bei Patienten aus Birmingham fur die Zugangsjahre 1957 und 1958 untersucht worden. Von 946 sputumpositiven Fallen konnten 316 nach 10 Jahren nachuntersucht werden. Nur 1 sicherer Fall von Mycetom ergab sich bei 275 Untersuchungen auf prazipitierende Antikijrper gegen Aspergillus fumigatus. Weitere 222 Patienten waren wohl nach 2, aber nicht mehr nach 10 Jahren in Uberwachung. Betrachtet man die vorhandenen Filme und iiberprtift die klinischen Befunde, so gab es keinen bewiesenen Fall von Mycetom. 1 Patient war auf das Vorhandensein dieser Komplikation verdachtig, aber die Diagnose konnte nicht vor seinem wegangaus Birmingham gesichert werden. Die Befunde sprechen dafiir, daB Mycetome unter Patienten, die 10 Jahre lang in einer Chest Clinic tiberwacht werden, selten anzutreffen sind. Introduction
The British Thoracic and Tuberculosis Association in 1968 published a study of aspergilloma in residual tuberculous cavities. In successfully treated tuberculous patients with persistent cavities of 2.5 cm. or more diameter drawn from chest clinics throughout England, Wales and Scotland 25 % had precipitating antibody to aspergillus in their serum and 11% had radiographic appearances consistent with a diagnosis of mycetoma. The maximum prevalence of aspergillus infection was in patients with persistent cavities of seven to 11 years duration. In a follow-up study published in 1970 it was reported that on resurvey 3 years later 15 % of the patients without precipitins at the time of the first survey had developed these antibodies and about half of these had evidence of mycetoma. Thus 34 % of the survivors had precipitins and 17 % had aspergillomas, while 3 % had probable aspergillomas with precipitins and 14 % had precipitins alone. The patients included in the BTTA study were, however, a selected group in whom the prevalence of aspergillus infection might well be different from that in an unselected group. In order to examine the frequency of this complication following the treatment of pulmonary tuberculosis without selection of specially susceptible subjects we undertook a follow-up study of patients first notified in Birmingham in 1957 and 1958. This group of patients had been included in a five-year assessment of the results of treatment of sputum-positive pulmonary tuberculosis by one of us (Thomas, 1965) and were easily identified for the purpose of this aspergillosis study. Methods The patients
There were 1,770 patients aged 15 years and over notified as suffering from pulmonary tuberculosis in the City of Birmingham between 1st January 1957 and 31st December 1958. Of these, 946 were reported at some time to have had tubercle bacilli isolated from their sputum. Two years after diagnosis 164 of these 946 patients had died. We excluded 61 patients who had had surgical treat-
PULMONARY
MYCETOMA
125
ment and were alive and we also excluded 60 Asiatics as we wished to avoid a special group who were unlikely to be representative of the country as a whole and in whom thelossfromsupervisionwas known to be high. Seventy-three patients had been transferred to other parts of the country or had been lost sight of. Thus after two years 358 patients had been excluded leaving 588 (62 % of the 946). Between 2 years and 10 years a further 222 patients died or were transferred elsewhere or failed to continue to attend the Clinic, leaving 366 (39% of the 946) whom we wished to study. These patients were asked to attend for a special examination, but 50 failed to do so; 316 were examined. Of the 946 sputum-positive patients 316 (33 %) had a radiographic examination at 10 years. Of these, 303 (32%) had intradermal tests using aspergillus fumigatus extract obtained from the Bencard Allergy Unit, 275 (29%) had blood examined for the presence of precipitating antibody against aspergilli and 159 (17 %) had sputum examined by culture for aspergillus species. Radiographs The films of each patient were read by one of the authors, not the physician under whose care the patient had been treated. The initial film before treatment was classified according to the number of zones of each lung affected and the diameter of the largest cavity in each lung. The chest radiograph taken nearest to 2 years from starting treatment was read in the same way and the rest of the films reviewed for further change. It was hoped that there would be enough cases to relate the radiographic appearances of mycetoma 10 years after diagnosis to the radiographic appearances at diagnosis and after 2 years treatment and also to the occurrence of positive precipitin tests, skin tests and sputum cultures. Skin tests The intradermal skin tests were read at lo-15 minutes and the wheal size measured. Each patient was asked to inspect the site of the test 6 hours later and to trace any wheal present with a ballpoint pen, apply a piece of Sellotape and stick the Sellotape with the tracing of the wheal on a card which could be posted back to the Clinic. Precipitin tests Patients, sera were tested for precipitating antibodies by the technique of double diffusion in agar gel (Ouchterlony, 1953). Precipitin lines were demonstrated by staining with Napthalene Black. Extracts of the following 6 fungi were used separately as antigens in each test:AspergiNus .fumigatus,jlavus, niger, nidulans, terreus; Allescheria boydii. Antigenic extracts were prepared by a method kindly supplied by Dr. I. G. Murray, Mycological Reference Laboratory, School of Hygiene, London, who also supplied the various fungal strains, and specific positive antisera against which the extracts were titrated. Any antigenic extract failing to produce a precipitin line at a dilution less than l/16 was discarded, the extraction being repeated on further fresh fungal cultures. The tests were carried out in the Department of Bacteriology at East Birmingham Hospital under the direction of Dr. F. A. J. Bridgewater. Results Radiographs Of the-316 patients with chest radiographs at 10 years, only 1 (0.3 %) had evidence of a mycetoma. Sixty-three (20 %) had cavities and in 27 (9 %) the largest cavity was 2 cm. or more in diameter. Precipitins Of the 275 patients tested only 1 (0.4%) had a positive precipitin test to Aspergillus Fumigatus. This patient was also the only one to have radiographic evidence of mycetoma. He was a man of 57 and there was no apparent cavity on the initial film, which showed only a lesion at the left apex. Nine years later tomography showed a cavity with a mycetoma. He had an immediate whealing reaction of 20 mm. diameter on skin testing with aspergillus extract but no late reaction. At 10 years he was free from symptoms. No aspergilli were found in the sputum. Of the 274 in whom the precipitin test was negative, 55 (20%) had radiographic evidence of cavrtatlon and 23 (8 ‘A) had cavities of 2 cm. or more diameter.
126
MORRISON
SMITH
AND
OTHERS
Thus, of 24 patients with cavities of 2 cm. or more diameter, 1 (4 %) had evidence of a mycetoma and 1 (4 %) a positive precipitin test. Skin Tests
Of 303 patients who had skin tests, 86 had a positive immediate reaction, the wheal being 5 mm. in diameter or more in 50. In only 1 of these 50 was there evidence of mycetoma or precipitins. In 81 patients a late skin reaction was recorded, the wheals being 5 mm. or more in diameter in 65 cases. In none of these 65 was there evidence of mycetoma or precipitins. Only 11 patients had both immediate and late skin reactions with wheals of 5 mm. or more. One of these had a history of wheezing while another had had haemoptysis. All these 11 had cavitation in the initial film but in only 1 case was it still evident at 10 years. Symptoms
The clinical notes of the 316 patients were searched for records of symptoms that might be associated with a mycetoma. Haemoptysis had occurred at some time in only 5 (2%); and 1 of these had a bronchial carcinoma. Wheezing was recorded in only 12 (4 %). Patients lost to observation between 2 and 10 years
There were 222 patients followed for 2 years who were not available for examination at 10 years. The chest radiographs and notes of 198 of these were reviewed. In only 1 case was there any radiographic change suggesting a mycetoma. The diagnosis was not confirmed before the patient left the city in 1965. Discussion
It is unfortunate that our follow-up study of sputum-positive patients after 10 years did not include a higher proportion of the patients originally notified. However, the results do suggest that only a very small proportion of patients still attending the same chest clinic 10 years after diagnosis of pulmonary tuberculosis will have a mycetoma. This does not conflict with the evidence of the British Thoracic and Tuberculosis Association’s study that in a group of surviving tuberculosis patients with large cavities mycetoma is common (11%) of those with cavities of 2.5 cm. or more diameter). In our small series of 24 patients with cavities of 2 cm. diameter or more, 1 (4%) had a mycetoma. The patients were under the care of the following physicians: Dr. D. E. P. Forbes, Dr. G. R. W. N. Luntz, Dr. H. J. T. Ross, Dr. J. Morrison Smith, Dr. V. H. Springett and Dr. H. E. Thomas. Follow-up examinations were carried out by Dr. G. R. W. N. Luntz, Dr. E. Shieff, Dr. J. Morrison Smith, Dr. V. H. Springett, Dr. H. E. Thomas and Dr. D. C. Waddy. We wish to thank Dr. F. A. J. Bridgwater, Consultant Bacteriologist to East Birmingham Hospital for carrying out the tests for precipitating antibody, Mrs. J. Hoskins for clerical assistance and the Birmingham Regional Hospital Board for financial help. REFERENCES BRITISHTUBERCULOSIS ASSOCIATION (1968). Aspergillus in persistent lung cavities after tuberculosis. Tubercle,49,l. BRITISHTHORACICAND TUBERCULOSIS ASSOCIATION (1970). Aspergilloma and residual tuberculous cavities - the results of a survey. Tuber&e, 51,227. OUCHTERLONY,0. (1953). Antigen-antibody reactions in gels. Acta Pathologica et Microbiologica Scandinavica, 32,231.
THOMAS,H. E. (1965). Five-year assessment of sputum positive pulmonary 1957-58. Tubercle, 46,352.
tuberculosis notified in Birmingham
in
PULMONARY
MYCETOMA
AS A LATE COMPLICATION
(19711, 52, 123
OF TUBERCULOSIS
By J. MORRISON SMITH, V. H. SPRINGETT and H. E. THOMAS
from the Birmingham
Chest Clinic, 151 Great Charles Street, Birmingham B3 3HX.
SUMMARY The occurrence of pulmonary mycetoma up to 10 years after notification of pulmonary tuberculosis has been examined in patients first notified in the City of Birmingham in 1957 and 1958. Of 946 sputum-positive cases 316 were available for examination at the Clinic after 10 years. Only 1 definite case of mycetoma was found and out of 275 tests for precipitating antibody to Aspergillus Fumigatus this was the only positive result obtained. Another 222 patients were still under supervision at 2 years but were not available at 10 years. On review of available films and clinical notes none had definite evidence of mycetoma but 1 had been suspected of having this complication, the diagnosis not being confirmed before he left the city. The findings suggest that mycetomas are rare among patients still attending a chest clinic 10 years after notification of pulmonary tuberculosis.
L’apparition de my&tome pulmonaire dans les 10 annees suivant le dkpistage d’une tuberculose pulmonaire est CtudiCe chez des malades de Birmingham dont les premiers signes de tuberculose sont apparus en 1957 et 1958. Parmi les 946 sujets ayant eu une expectoration positive, 316 ont pu etre CxaminCs dans le service, 10 ans aprks. Un cas certain de my&tome, seulement, a &k trouvC, et parmi les 275 tests de prkcipitation des anticorps de l’aspergillus fumigatus, c’est le seul rksultat positif qui a CtC obtenu. Un groupe de 222 autres malades Ctait encore sous surveillance medicale apris 2 ans, mais plus aprks 10 ans. L’Ctude des radios et des renseignements cliniques disponibles n’a montrC aucun signe certain de mycttome. I1 y avait toutefois I cas suspect de cette complication mais le diagnostic n’a pas iti confirm6 avant qu’il ne quite Birmingham. Ces rksultats semblent montrer que les cas de my&tomes sont rares chez les malades ayant eu une tuberculose pulmonaire et Ctant encore sou? surveillance dans un service de pneumologie 10 ans aprt?s.
RESUMEN Se examinci la existencia de mycetomas pulmonares hasta 10 adios despues de la notificacibn de tuberculosis pulmonar en pacientes reciCn descubiertos en la ciudad de Birmingham en 1957 y 1958. Sobre 946 cases con esputo positivo, 316 estaban disponibles para el examen al cabo de 10s 10 adios. Sdlo se ha116 un case de mycetoma y sobre 275 tests para precipitinas de1 Aspergillus fumigatus, Cste fuC el tinico resultado positivo.
124
MORRISON
SMITH
AND
OTHERS
Otros 222 pacientes seguian siendo controlados a 10s 2 silos paro no estaban disponibles a 10s 10 adios. Al revisar las radiografias y 10s datos clinicos ninguno mostraba evidencia de mycetoma, aunque uno era sospechoso de tener esa complication; no se pudo confirmar el diagnostico. Estoa hallazgos sugieren que 10s mycetomas son raros entre 10s pacientes que siguen controlandose en 10s hospitales 10 adios despues de iniciar su tuberculosis pulmonar.
ZUSAMMENFASSUNG
Das Auftreten pulmonaler Mycetome bis zu 10 Jahren nach Diagnose der Lungentuberkulose ist bei Patienten aus Birmingham fur die Zugangsjahre 1957 und 1958 untersucht worden. Von 946 sputumpositiven Fallen konnten 316 nach 10 Jahren nachuntersucht werden. Nur 1 sicherer Fall von Mycetom ergab sich bei 275 Untersuchungen auf prazipitierende Antikijrper gegen Aspergillus fumigatus. Weitere 222 Patienten waren wohl nach 2, aber nicht mehr nach 10 Jahren in Uberwachung. Betrachtet man die vorhandenen Filme und iiberprtift die klinischen Befunde, so gab es keinen bewiesenen Fall von Mycetom. 1 Patient war auf das Vorhandensein dieser Komplikation verdachtig, aber die Diagnose konnte nicht vor seinem wegangaus Birmingham gesichert werden. Die Befunde sprechen dafiir, daB Mycetome unter Patienten, die 10 Jahre lang in einer Chest Clinic tiberwacht werden, selten anzutreffen sind. Introduction
The British Thoracic and Tuberculosis Association in 1968 published a study of aspergilloma in residual tuberculous cavities. In successfully treated tuberculous patients with persistent cavities of 2.5 cm. or more diameter drawn from chest clinics throughout England, Wales and Scotland 25 % had precipitating antibody to aspergillus in their serum and 11% had radiographic appearances consistent with a diagnosis of mycetoma. The maximum prevalence of aspergillus infection was in patients with persistent cavities of seven to 11 years duration. In a follow-up study published in 1970 it was reported that on resurvey 3 years later 15 % of the patients without precipitins at the time of the first survey had developed these antibodies and about half of these had evidence of mycetoma. Thus 34 % of the survivors had precipitins and 17 % had aspergillomas, while 3 % had probable aspergillomas with precipitins and 14 % had precipitins alone. The patients included in the BTTA study were, however, a selected group in whom the prevalence of aspergillus infection might well be different from that in an unselected group. In order to examine the frequency of this complication following the treatment of pulmonary tuberculosis without selection of specially susceptible subjects we undertook a follow-up study of patients first notified in Birmingham in 1957 and 1958. This group of patients had been included in a five-year assessment of the results of treatment of sputum-positive pulmonary tuberculosis by one of us (Thomas, 1965) and were easily identified for the purpose of this aspergillosis study. Methods The patients
There were 1,770 patients aged 15 years and over notified as suffering from pulmonary tuberculosis in the City of Birmingham between 1st January 1957 and 31st December 1958. Of these, 946 were reported at some time to have had tubercle bacilli isolated from their sputum. Two years after diagnosis 164 of these 946 patients had died. We excluded 61 patients who had had surgical treat-
PULMONARY
MYCETOMA
125
ment and were alive and we also excluded 60 Asiatics as we wished to avoid a special group who were unlikely to be representative of the country as a whole and in whom thelossfromsupervisionwas known to be high. Seventy-three patients had been transferred to other parts of the country or had been lost sight of. Thus after two years 358 patients had been excluded leaving 588 (62 % of the 946). Between 2 years and 10 years a further 222 patients died or were transferred elsewhere or failed to continue to attend the Clinic, leaving 366 (39% of the 946) whom we wished to study. These patients were asked to attend for a special examination, but 50 failed to do so; 316 were examined. Of the 946 sputum-positive patients 316 (33 %) had a radiographic examination at 10 years. Of these, 303 (32%) had intradermal tests using aspergillus fumigatus extract obtained from the Bencard Allergy Unit, 275 (29%) had blood examined for the presence of precipitating antibody against aspergilli and 159 (17 %) had sputum examined by culture for aspergillus species. Radiographs The films of each patient were read by one of the authors, not the physician under whose care the patient had been treated. The initial film before treatment was classified according to the number of zones of each lung affected and the diameter of the largest cavity in each lung. The chest radiograph taken nearest to 2 years from starting treatment was read in the same way and the rest of the films reviewed for further change. It was hoped that there would be enough cases to relate the radiographic appearances of mycetoma 10 years after diagnosis to the radiographic appearances at diagnosis and after 2 years treatment and also to the occurrence of positive precipitin tests, skin tests and sputum cultures. Skin tests The intradermal skin tests were read at lo-15 minutes and the wheal size measured. Each patient was asked to inspect the site of the test 6 hours later and to trace any wheal present with a ballpoint pen, apply a piece of Sellotape and stick the Sellotape with the tracing of the wheal on a card which could be posted back to the Clinic. Precipitin tests Patients, sera were tested for precipitating antibodies by the technique of double diffusion in agar gel (Ouchterlony, 1953). Precipitin lines were demonstrated by staining with Napthalene Black. Extracts of the following 6 fungi were used separately as antigens in each test:AspergiNus .fumigatus,jlavus, niger, nidulans, terreus; Allescheria boydii. Antigenic extracts were prepared by a method kindly supplied by Dr. I. G. Murray, Mycological Reference Laboratory, School of Hygiene, London, who also supplied the various fungal strains, and specific positive antisera against which the extracts were titrated. Any antigenic extract failing to produce a precipitin line at a dilution less than l/16 was discarded, the extraction being repeated on further fresh fungal cultures. The tests were carried out in the Department of Bacteriology at East Birmingham Hospital under the direction of Dr. F. A. J. Bridgewater. Results Radiographs Of the-316 patients with chest radiographs at 10 years, only 1 (0.3 %) had evidence of a mycetoma. Sixty-three (20 %) had cavities and in 27 (9 %) the largest cavity was 2 cm. or more in diameter. Precipitins Of the 275 patients tested only 1 (0.4%) had a positive precipitin test to Aspergillus Fumigatus. This patient was also the only one to have radiographic evidence of mycetoma. He was a man of 57 and there was no apparent cavity on the initial film, which showed only a lesion at the left apex. Nine years later tomography showed a cavity with a mycetoma. He had an immediate whealing reaction of 20 mm. diameter on skin testing with aspergillus extract but no late reaction. At 10 years he was free from symptoms. No aspergilli were found in the sputum. Of the 274 in whom the precipitin test was negative, 55 (20%) had radiographic evidence of cavrtatlon and 23 (8 ‘A) had cavities of 2 cm. or more diameter.
126
MORRISON
SMITH
AND
OTHERS
Thus, of 24 patients with cavities of 2 cm. or more diameter, 1 (4 %) had evidence of a mycetoma and 1 (4 %) a positive precipitin test. Skin Tests
Of 303 patients who had skin tests, 86 had a positive immediate reaction, the wheal being 5 mm. in diameter or more in 50. In only 1 of these 50 was there evidence of mycetoma or precipitins. In 81 patients a late skin reaction was recorded, the wheals being 5 mm. or more in diameter in 65 cases. In none of these 65 was there evidence of mycetoma or precipitins. Only 11 patients had both immediate and late skin reactions with wheals of 5 mm. or more. One of these had a history of wheezing while another had had haemoptysis. All these 11 had cavitation in the initial film but in only 1 case was it still evident at 10 years. Symptoms
The clinical notes of the 316 patients were searched for records of symptoms that might be associated with a mycetoma. Haemoptysis had occurred at some time in only 5 (2%); and 1 of these had a bronchial carcinoma. Wheezing was recorded in only 12 (4 %). Patients lost to observation between 2 and 10 years
There were 222 patients followed for 2 years who were not available for examination at 10 years. The chest radiographs and notes of 198 of these were reviewed. In only 1 case was there any radiographic change suggesting a mycetoma. The diagnosis was not confirmed before the patient left the city in 1965. Discussion
It is unfortunate that our follow-up study of sputum-positive patients after 10 years did not include a higher proportion of the patients originally notified. However, the results do suggest that only a very small proportion of patients still attending the same chest clinic 10 years after diagnosis of pulmonary tuberculosis will have a mycetoma. This does not conflict with the evidence of the British Thoracic and Tuberculosis Association’s study that in a group of surviving tuberculosis patients with large cavities mycetoma is common (11%) of those with cavities of 2.5 cm. or more diameter). In our small series of 24 patients with cavities of 2 cm. diameter or more, 1 (4%) had a mycetoma. The patients were under the care of the following physicians: Dr. D. E. P. Forbes, Dr. G. R. W. N. Luntz, Dr. H. J. T. Ross, Dr. J. Morrison Smith, Dr. V. H. Springett and Dr. H. E. Thomas. Follow-up examinations were carried out by Dr. G. R. W. N. Luntz, Dr. E. Shieff, Dr. J. Morrison Smith, Dr. V. H. Springett, Dr. H. E. Thomas and Dr. D. C. Waddy. We wish to thank Dr. F. A. J. Bridgwater, Consultant Bacteriologist to East Birmingham Hospital for carrying out the tests for precipitating antibody, Mrs. J. Hoskins for clerical assistance and the Birmingham Regional Hospital Board for financial help. REFERENCES BRITISHTUBERCULOSIS ASSOCIATION (1968). Aspergillus in persistent lung cavities after tuberculosis. Tubercle,49,l. BRITISHTHORACICAND TUBERCULOSIS ASSOCIATION (1970). Aspergilloma and residual tuberculous cavities - the results of a survey. Tuber&e, 51,227. OUCHTERLONY,0. (1953). Antigen-antibody reactions in gels. Acta Pathologica et Microbiologica Scandinavica, 32,231.
THOMAS,H. E. (1965). Five-year assessment of sputum positive pulmonary 1957-58. Tubercle, 46,352.
tuberculosis notified in Birmingham
in