- Email: [email protected]
Smoking as risk factor of tuberculosis in children and youth
68
Tubercle and Lung Disease: Supplement
tests used had 100 % specificity. Mycobacterium bovis was always isolated from tuberculous lesions and studying DNA by RFLP, it could be observed that caprine isolates were different from field strains of M. bovis isolated from cattle, M. bovis and M. tuberculosis. 247 ACTIVE PULMONARY
TUBERCULOSIS IN DIABETIC AND NONDIABETIC PATIENTS
Aktogu, S., Qrak, Tiirkiye
K.; izmir Hospital of Chest Diseases, 35110,
Several studies have suggested that active pulmonary tuberculosis in diabetics tends to occur predominantly at the lower lung fields. In this study 102 diabetic and 102 nondiabetic patients with active pulmonary tuberculosis were studied in order to match according to sex, age, hepatotoxicity, primer drug resistance radiologic appearance and especially lower lung field tuberculosis (LLFT). When both groups were matched according to sex, hepatotoxicity, primer drug resistance and radiologic appearance, the difference was not significant. The mean age was 52.0 * 11.5 years in diabetics and 31.4 +- 13.7 years in nondiabetics. 64 of 102 diabetics and 13 of 102 nondiabetics were older than 50 years (p < 0,Ol). The pure LLFT was found in 16 (15 %) diabetics and in 12 (11%) nondiabetics. When all patients were considered, it was found that 22 female and 6 male patients had pure LLFT (p < 0.05). Finally, there was a significant interaction between sex and pure lower lung field tuberculosis and although pure LLFT in diabetics had higher frequency than that of nondiabetics, this difference was not significant (p > 0.05). 248 THE ANTIMYCOBACTERIAL
OF GANGAMICIN,
ACTIVITY A POTENTIAL DRUG
Pattisapu R. J. Gangadharam; Mycobacteriology Univ of Illinois at Chicago, Chicago, IL 60612
Research
Lab,
Dioscovery and development of powerful drugs active against Mycobacterium tuberculosis (M. tb), particularly those organisms resistant to available drugs (MDR) and against Mycobacterium avium complex (MAC) an important opportunistic pathogen in AIDS are urgently needed. Besides random screening of thousands of potential compounds, we are also making many innovative approaches. As an outcome of one such approach of testing dual analogues of vitamin K types of compounds which are present in the cell *all of mycobacteria and ubiquinone (coenzyme Q1o) which is known to stimulate mycobacterial growth, we discovered the powerful activity of 6-cycle octylamino-5,8 quinoline quinone (CQQ), later patented by the National Jewish Center for Immunology and Respiratory Medicine, Denver, CO, USA as Gangamicin (GM) (U.S. patent no. 4,963,563). In vitro its M.I.C. is between 0.1 and 2.0 Fg/ml for M. tb, including those resistant to isoniazid and rifampin and between 2.0 and 8.0 @ml against MAC. At concentration of 1.0 to 2.0 @ml, it inhibited the intracellular M. tb including drug resistant strains and MAC in mouse peritoneal and human monocyte derived macrophages and J774A macrophage cell line. In experimental chemotherapy studies, using doses of 40 to 80 mg/kg given orally or subcutaneously (S.C.) in C5,B1/6 and beige mice models for M. tb and MAC respectively, it has demonstrated high activity both in preventing mortality and in reduction of CFU counts from
spleen and lungs. In general, its activity is more pronounced in spleen and than in lungs, by S.C. than by oral treatment and more against M. tb than MAC. Of more significance is its similar activity against infection with drug resistant M. tb where it exhibited equal activity as with infection with susceptible strains. Besides the M. tb and MAC, it is highly active against M. kansasii and M. leprae. The drug has been found to be non toxic to several animal species. All these encouraging experimental findings warrant strong hopes for the chemotherapeutic potential of this drug against M. tb, drug resistant M. tb and MAC. 249 MASS X-RAY SCREENING FOR HOSTELS
AND HOMES OF THE ELDERLY IN A RELATIVELY HIGH PREVALENCE URBAN ENVIRONMENT Al Jarad, N., Rubens, M. B., Empey, D. W.; The East London Tuberculosis Centre, London Chest Hospital, Bonner Road, London E2 9JX
We have assessed the value of mass X-ray screening in hostels and homes for the elderly in London Borough of Tower Hamlets (East London). The notification rate in this area in 55-60 per 100,000 population (6-8 % of the whole notified cases in the UK). The mobile X-ray visited each hostel or home on an annual basis taking conventional size chest radiographs for residents and members of staff. These were read and reported on by an independent consultant radiologist at London Chest Hospital. Persons with abnormal chest radiograph suggesting tuberculosis, cancer or any other condition which may require further investigation were invited to a chest clinic for further assessment. Fourteen care homes were screened. A total of 936 radiographs were taken (636 for residents and 300 for members of staff). Abnormalities reported were as follows: old fractured ribs which required any follow up, 77 (8 %), old tuberculosis which did not require any treatment 57 (6 %), emphysema 18 (2 %), abnormalities related to the cardiovascular system 10 (1%) lung cancer 1 (0.1%). Total number of cases were considered to be suitable for a followup in the chest clinic was 45 (4.8%). No cases of active tuberculosis were detected by the chest radiograph or after investigation and follow-up in the clinic. Furthermore three cases of tuberculosis from one home of the elderly were notified in residents between two visits by the X-ray screening staff. We conclude that the mass X-ray screening is an unhelpful method of active case finding of tuberculosis in hostels and homes for the elderly. The method is labour intensive, time consuming and expensive. Alternative methods for active case finding in these institutions are discussed.
250 SMOKING AS RISK FACTOR OF TUBERCULOSIS IN CHILDREN AND YOUTH Altet, N., Alcaide, .I., Lozano, P., Plans, P., Parron, Salleras, Ll.; Centre Prevencid Control Tuberculosis. Amat, 8. 08001 Barcelona, Spain The
I. and Torres
aim of this Case-Control study is to investigate the association between smoking and the development of respiratory Tuberculosis in household contacts of new cases of pulmonary bacillary tuberculosis diagnosed in the Tuberculosis Prevention Center of Barcelona.
69
Tubercle and Lung Disease: Supplement Cases are the individuals diagnosed of active respiratory Tuberculosis (Category 3 of A.T.S.). Controls are the individuals infected by the My. Tuberculosis without clinical, radiological and/or bacteriological evidence of Tuberculosis (Category 2 of A.T.S.). All them were selected at random in the epidemiological investigation of a source case.
The tuberculosis incidence decline in the developed countries has led to a decreased vigilance and awareness with regard to this disease in health workers.
The results show that the Passive Smoking in children is a risk factor to develop active tuberculosis when the child has been newly infected (Odds Ratio: 5.7; I.C. at 95 % : 4.15/8.19; p < 0.001). And also smoking is a risk factor in the youth (15-25 years age): Odds Ratio: 3.25; C.I. at 95%: 1.X2/5.8; p < 0.025.
In Italy the BCG vaccination in Hospital workers is prescribed, despite their questionable efficiency. The Italian scientific organisations (AIPO) has recently suggested a guideline for the protection of health workers. The suggested strategy is, a part primary prevention, an annual tuberculin screening test followed by IPT for converters.
251 DAILY AND TWICE-WEEKLY ADMINISTERED SHORT-COURSE ANTI-TB TREATMENT WITH RIFAMPICIN +ISONIAZID FIXED COMBINATION: 10 YEARS OF FOLLOW-UP Besozzi. Mare/k,
G., Codecasa, L. R., Mantellini, V. le Zara 81, 20159 Milano, Italy
P. V.;
lstituto
Villa
In the period 1981-1982 we started a study in order to compare the effectiveness and tolerability of daily (D) and twice-weekly (TW) short-course therapy with tablets of fixed combination of Rifampicin 300 mg + Isoniazid 150 mg. In this paper we report the results of the study after IO years of follow-up. We selected 108 patients (55 M and 53 F, mean age 32.6) with bacteriologically-confirmed pulmonary TB of comparable severity. Both treatment regimens lasted 6 months and were randomized as follows: D therapy was administered to 55 pts (2 tablets in the morning), while 53 received TW treatment with 3 tablets in the morning. Of the original survey of 108 pts., 10 were ruled out: being Y not strictly compliant and 1 because sputum culture resulted positive for M. kansasii. All patients were visisted monthly, with at least sputum examination, blood tests, and a chest X-ray. Of the 98 pts. who concluded successfully the treatment, 49 received D therapy and 49 TW therapy. These two groups were compared for sputum negativization time after starting the treatment, tolerance to treatment and incidence of relapses after a follow up of 10 years. In both groups sputum became negative in all patients within 2 months, and no significant difference of tolerabilty were reported (mild nausea and/or vomit were reported in 3149 pts. who received TW therapy and in 5149 who received D therapy). Toxicity, defined as values of AST/ALT increased by at least twice time the basals, was absent in all pts. After 10 years, 77 pts. (78.6 %) were still in control at our institute. Of them, 37 received D and 40 TW therapy, and in both groups no relapses were reported. Of the remaining 21 pts., 15 had been followed for 3 to 5 years with no sign of relapse, while 6 had been lost shortly after the conclusion of the study. In conclusion, the two considered therapeutic regimens were equally effective and tolerable demonstrating that, provided a strict compliance by the patients, short course treatment, administered daily or twiceweekly, is an appropriate antitubercular tool. 252 TUBERCULIN SURVEY AMONG HOSPITAL WORKERS IN TURIN (ITALY) Bugiani, M., Cavallero, M., Piccioni, P., Carosso, A., Arossa, W. ; (Dispensario di Igiene Sociale CJSL 7. Lungo Dora Savona 26, Turin. Italy); Luccoli, L.. Coscia G. C.; (S. Giovanni Battista Hospital); DalConte. I. 1 Salassa, B.; (Amedeo di Savoia Hospital): Silvuplana. P.; S. Luigi Hospital
Because the resurgence of tuberculosis in all developed particularly in HIV positive patients, an countries, increased risk of nosocomial transmission, involving health workers, has been also detected.
This paper reports the result of a extensive tuberculin survey among Hospital workers in Turin (years 1992-1993) with different tuberculosis infection hazards. The distribution of tuberculin positivity (PPD Sclavo 5 UI > = IO mm) was studied, with the aim to identificate high hazard jobs. In high exposed groups the sex/age corrected rate of reactors was 5 folds the observed in a sample of general population. In low exposed groups the rate was significantly lower than in general population.
253 UPDATE OF THE INFECTION AND TUBERCULOSIS DISEASE IN SPAIN 1988-1992 Carninero, .I. A.; “Tuberculosis and Respiratory Infections” (TRI) Scientific Area. Spanish Society of Pneumology and Thoracic Surgery. Balmes 58, 2”. 2’. 08007 Barcelona, Spuin
Spain is one of the few developed countries that has no trustworthy official data about tuberculosis (TB). The declaration of new cases per year is about 20/100,000 inhabitants, although we believe that it is actually higher. That’s why, the TRI Scientific Area has wanted, since it was created in 1988, to know the real situation of TB in Spain. For this reason, since 1988, the TRI Area has sent every year 2 models of questionnaires, the first to the health council of the 17 Autonomic Regions of the country, and the second to 60 doctors of different regions of Spain who were well know workers in TB. Concerning the prevalence of tuberculosis infection in 6 year old children, in the period 1988-1992 we have obtained data from 154,686 mantoux (56.395 in 1988, 14,757 in 1989, 23,657 in 1990, 30,552 in 1991 and 29,326 in 1992) corresponding to a representative sample of 25 milion (62,5 % of Spain) inhabitants. For 14 year old children we have obtained data from 145,553 mantoux (36,386 in 1988, 25,492 in 1989, 22,492 in 1990, 33,070 in 1991 and 28,113 in 1992). The prevalence of infection was: 1YXX PREVAL. (%)
( 6 Year { 14 Year
I ‘%, 3.0 %
lY!iV
I’wo
, ‘$‘”
O.Y.i% 2.5 “4, 2.X%
IYYI
1992
O.YS% 3.1 %
0.9% 3.1 %
Concerning of new cases of tuberculosis disease, we have obtained data of 28 milions inhabitants (70 % of the whole Spanish population). The incidence, in cases per 100,OOtl inhabitants, was: INCIDENCE Total (Smear f)
1988
19x9
1990
I’)91
I’)92
36
32.8
34.7 (17.6)
35.x (I’))
40 (21.2)
Tubercle and Lung Disease: Supplement
tests used had 100 % specificity. Mycobacterium bovis was always isolated from tuberculous lesions and studying DNA by RFLP, it could be observed that caprine isolates were different from field strains of M. bovis isolated from cattle, M. bovis and M. tuberculosis. 247 ACTIVE PULMONARY
TUBERCULOSIS IN DIABETIC AND NONDIABETIC PATIENTS
Aktogu, S., Qrak, Tiirkiye
K.; izmir Hospital of Chest Diseases, 35110,
Several studies have suggested that active pulmonary tuberculosis in diabetics tends to occur predominantly at the lower lung fields. In this study 102 diabetic and 102 nondiabetic patients with active pulmonary tuberculosis were studied in order to match according to sex, age, hepatotoxicity, primer drug resistance radiologic appearance and especially lower lung field tuberculosis (LLFT). When both groups were matched according to sex, hepatotoxicity, primer drug resistance and radiologic appearance, the difference was not significant. The mean age was 52.0 * 11.5 years in diabetics and 31.4 +- 13.7 years in nondiabetics. 64 of 102 diabetics and 13 of 102 nondiabetics were older than 50 years (p < 0,Ol). The pure LLFT was found in 16 (15 %) diabetics and in 12 (11%) nondiabetics. When all patients were considered, it was found that 22 female and 6 male patients had pure LLFT (p < 0.05). Finally, there was a significant interaction between sex and pure lower lung field tuberculosis and although pure LLFT in diabetics had higher frequency than that of nondiabetics, this difference was not significant (p > 0.05). 248 THE ANTIMYCOBACTERIAL
OF GANGAMICIN,
ACTIVITY A POTENTIAL DRUG
Pattisapu R. J. Gangadharam; Mycobacteriology Univ of Illinois at Chicago, Chicago, IL 60612
Research
Lab,
Dioscovery and development of powerful drugs active against Mycobacterium tuberculosis (M. tb), particularly those organisms resistant to available drugs (MDR) and against Mycobacterium avium complex (MAC) an important opportunistic pathogen in AIDS are urgently needed. Besides random screening of thousands of potential compounds, we are also making many innovative approaches. As an outcome of one such approach of testing dual analogues of vitamin K types of compounds which are present in the cell *all of mycobacteria and ubiquinone (coenzyme Q1o) which is known to stimulate mycobacterial growth, we discovered the powerful activity of 6-cycle octylamino-5,8 quinoline quinone (CQQ), later patented by the National Jewish Center for Immunology and Respiratory Medicine, Denver, CO, USA as Gangamicin (GM) (U.S. patent no. 4,963,563). In vitro its M.I.C. is between 0.1 and 2.0 Fg/ml for M. tb, including those resistant to isoniazid and rifampin and between 2.0 and 8.0 @ml against MAC. At concentration of 1.0 to 2.0 @ml, it inhibited the intracellular M. tb including drug resistant strains and MAC in mouse peritoneal and human monocyte derived macrophages and J774A macrophage cell line. In experimental chemotherapy studies, using doses of 40 to 80 mg/kg given orally or subcutaneously (S.C.) in C5,B1/6 and beige mice models for M. tb and MAC respectively, it has demonstrated high activity both in preventing mortality and in reduction of CFU counts from
spleen and lungs. In general, its activity is more pronounced in spleen and than in lungs, by S.C. than by oral treatment and more against M. tb than MAC. Of more significance is its similar activity against infection with drug resistant M. tb where it exhibited equal activity as with infection with susceptible strains. Besides the M. tb and MAC, it is highly active against M. kansasii and M. leprae. The drug has been found to be non toxic to several animal species. All these encouraging experimental findings warrant strong hopes for the chemotherapeutic potential of this drug against M. tb, drug resistant M. tb and MAC. 249 MASS X-RAY SCREENING FOR HOSTELS
AND HOMES OF THE ELDERLY IN A RELATIVELY HIGH PREVALENCE URBAN ENVIRONMENT Al Jarad, N., Rubens, M. B., Empey, D. W.; The East London Tuberculosis Centre, London Chest Hospital, Bonner Road, London E2 9JX
We have assessed the value of mass X-ray screening in hostels and homes for the elderly in London Borough of Tower Hamlets (East London). The notification rate in this area in 55-60 per 100,000 population (6-8 % of the whole notified cases in the UK). The mobile X-ray visited each hostel or home on an annual basis taking conventional size chest radiographs for residents and members of staff. These were read and reported on by an independent consultant radiologist at London Chest Hospital. Persons with abnormal chest radiograph suggesting tuberculosis, cancer or any other condition which may require further investigation were invited to a chest clinic for further assessment. Fourteen care homes were screened. A total of 936 radiographs were taken (636 for residents and 300 for members of staff). Abnormalities reported were as follows: old fractured ribs which required any follow up, 77 (8 %), old tuberculosis which did not require any treatment 57 (6 %), emphysema 18 (2 %), abnormalities related to the cardiovascular system 10 (1%) lung cancer 1 (0.1%). Total number of cases were considered to be suitable for a followup in the chest clinic was 45 (4.8%). No cases of active tuberculosis were detected by the chest radiograph or after investigation and follow-up in the clinic. Furthermore three cases of tuberculosis from one home of the elderly were notified in residents between two visits by the X-ray screening staff. We conclude that the mass X-ray screening is an unhelpful method of active case finding of tuberculosis in hostels and homes for the elderly. The method is labour intensive, time consuming and expensive. Alternative methods for active case finding in these institutions are discussed.
250 SMOKING AS RISK FACTOR OF TUBERCULOSIS IN CHILDREN AND YOUTH Altet, N., Alcaide, .I., Lozano, P., Plans, P., Parron, Salleras, Ll.; Centre Prevencid Control Tuberculosis. Amat, 8. 08001 Barcelona, Spain The
I. and Torres
aim of this Case-Control study is to investigate the association between smoking and the development of respiratory Tuberculosis in household contacts of new cases of pulmonary bacillary tuberculosis diagnosed in the Tuberculosis Prevention Center of Barcelona.
69
Tubercle and Lung Disease: Supplement Cases are the individuals diagnosed of active respiratory Tuberculosis (Category 3 of A.T.S.). Controls are the individuals infected by the My. Tuberculosis without clinical, radiological and/or bacteriological evidence of Tuberculosis (Category 2 of A.T.S.). All them were selected at random in the epidemiological investigation of a source case.
The tuberculosis incidence decline in the developed countries has led to a decreased vigilance and awareness with regard to this disease in health workers.
The results show that the Passive Smoking in children is a risk factor to develop active tuberculosis when the child has been newly infected (Odds Ratio: 5.7; I.C. at 95 % : 4.15/8.19; p < 0.001). And also smoking is a risk factor in the youth (15-25 years age): Odds Ratio: 3.25; C.I. at 95%: 1.X2/5.8; p < 0.025.
In Italy the BCG vaccination in Hospital workers is prescribed, despite their questionable efficiency. The Italian scientific organisations (AIPO) has recently suggested a guideline for the protection of health workers. The suggested strategy is, a part primary prevention, an annual tuberculin screening test followed by IPT for converters.
251 DAILY AND TWICE-WEEKLY ADMINISTERED SHORT-COURSE ANTI-TB TREATMENT WITH RIFAMPICIN +ISONIAZID FIXED COMBINATION: 10 YEARS OF FOLLOW-UP Besozzi. Mare/k,
G., Codecasa, L. R., Mantellini, V. le Zara 81, 20159 Milano, Italy
P. V.;
lstituto
Villa
In the period 1981-1982 we started a study in order to compare the effectiveness and tolerability of daily (D) and twice-weekly (TW) short-course therapy with tablets of fixed combination of Rifampicin 300 mg + Isoniazid 150 mg. In this paper we report the results of the study after IO years of follow-up. We selected 108 patients (55 M and 53 F, mean age 32.6) with bacteriologically-confirmed pulmonary TB of comparable severity. Both treatment regimens lasted 6 months and were randomized as follows: D therapy was administered to 55 pts (2 tablets in the morning), while 53 received TW treatment with 3 tablets in the morning. Of the original survey of 108 pts., 10 were ruled out: being Y not strictly compliant and 1 because sputum culture resulted positive for M. kansasii. All patients were visisted monthly, with at least sputum examination, blood tests, and a chest X-ray. Of the 98 pts. who concluded successfully the treatment, 49 received D therapy and 49 TW therapy. These two groups were compared for sputum negativization time after starting the treatment, tolerance to treatment and incidence of relapses after a follow up of 10 years. In both groups sputum became negative in all patients within 2 months, and no significant difference of tolerabilty were reported (mild nausea and/or vomit were reported in 3149 pts. who received TW therapy and in 5149 who received D therapy). Toxicity, defined as values of AST/ALT increased by at least twice time the basals, was absent in all pts. After 10 years, 77 pts. (78.6 %) were still in control at our institute. Of them, 37 received D and 40 TW therapy, and in both groups no relapses were reported. Of the remaining 21 pts., 15 had been followed for 3 to 5 years with no sign of relapse, while 6 had been lost shortly after the conclusion of the study. In conclusion, the two considered therapeutic regimens were equally effective and tolerable demonstrating that, provided a strict compliance by the patients, short course treatment, administered daily or twiceweekly, is an appropriate antitubercular tool. 252 TUBERCULIN SURVEY AMONG HOSPITAL WORKERS IN TURIN (ITALY) Bugiani, M., Cavallero, M., Piccioni, P., Carosso, A., Arossa, W. ; (Dispensario di Igiene Sociale CJSL 7. Lungo Dora Savona 26, Turin. Italy); Luccoli, L.. Coscia G. C.; (S. Giovanni Battista Hospital); DalConte. I. 1 Salassa, B.; (Amedeo di Savoia Hospital): Silvuplana. P.; S. Luigi Hospital
Because the resurgence of tuberculosis in all developed particularly in HIV positive patients, an countries, increased risk of nosocomial transmission, involving health workers, has been also detected.
This paper reports the result of a extensive tuberculin survey among Hospital workers in Turin (years 1992-1993) with different tuberculosis infection hazards. The distribution of tuberculin positivity (PPD Sclavo 5 UI > = IO mm) was studied, with the aim to identificate high hazard jobs. In high exposed groups the sex/age corrected rate of reactors was 5 folds the observed in a sample of general population. In low exposed groups the rate was significantly lower than in general population.
253 UPDATE OF THE INFECTION AND TUBERCULOSIS DISEASE IN SPAIN 1988-1992 Carninero, .I. A.; “Tuberculosis and Respiratory Infections” (TRI) Scientific Area. Spanish Society of Pneumology and Thoracic Surgery. Balmes 58, 2”. 2’. 08007 Barcelona, Spuin
Spain is one of the few developed countries that has no trustworthy official data about tuberculosis (TB). The declaration of new cases per year is about 20/100,000 inhabitants, although we believe that it is actually higher. That’s why, the TRI Scientific Area has wanted, since it was created in 1988, to know the real situation of TB in Spain. For this reason, since 1988, the TRI Area has sent every year 2 models of questionnaires, the first to the health council of the 17 Autonomic Regions of the country, and the second to 60 doctors of different regions of Spain who were well know workers in TB. Concerning the prevalence of tuberculosis infection in 6 year old children, in the period 1988-1992 we have obtained data from 154,686 mantoux (56.395 in 1988, 14,757 in 1989, 23,657 in 1990, 30,552 in 1991 and 29,326 in 1992) corresponding to a representative sample of 25 milion (62,5 % of Spain) inhabitants. For 14 year old children we have obtained data from 145,553 mantoux (36,386 in 1988, 25,492 in 1989, 22,492 in 1990, 33,070 in 1991 and 28,113 in 1992). The prevalence of infection was: 1YXX PREVAL. (%)
( 6 Year { 14 Year
I ‘%, 3.0 %
lY!iV
I’wo
, ‘$‘”
O.Y.i% 2.5 “4, 2.X%
IYYI
1992
O.YS% 3.1 %
0.9% 3.1 %
Concerning of new cases of tuberculosis disease, we have obtained data of 28 milions inhabitants (70 % of the whole Spanish population). The incidence, in cases per 100,OOtl inhabitants, was: INCIDENCE Total (Smear f)
1988
19x9
1990
I’)91
I’)92
36
32.8
34.7 (17.6)
35.x (I’))
40 (21.2)