Tuberculosis
and social class
193
On the information available it is not possible to determine whether the mortality gradient between the social classes is the result of a difference in attack rate or a difference in case fatality, but there are good reasons to suppose that both factors are important. It is salutary to be reminded that in a developed country like Britain, and presumably also in other developed countries, social circumstances still play an important part in determining tuberculosis mortality. References British
Thoracic and Tuberculosis Association (1971). A survey of tuberculosis mortality in England and Wales in 1968. Tubercle. 52,l. Campbell, H. In Recent Advances in Community Medicine. Edited by A. E. Bennett. Churchill Livingstone, 1978. p. 261. Registrar General. Occupational Mortality. The Registrar General’s decennial supplement for England and Wales. 1970-72. Series DS no. 1. London, 1978. HMSO.
Tuberculosis in renal transplant patients The principal cause of death after organ transplantation is infection, which is responsible for 40 % of all fatalities (Gurland et a/, 1973). The incidence of infection, either pulmonary or septicaemia, is greatest during the first 60 days after operation, a time when there is also a high risk of graft rejection (Hulme, 1975). A variety of micro-organisms may be involved : bacteria (gram negative), viruses (cytomegalovirus, herpes simplex and zoster), fungi (monilia and aspergdhs) and pneumocystis csrinii. Tuberculous infection is a rarity, but since renal transplant operations have been performed with increasing frequency several case reports have appeared. Thus in an American series of 400 renal transplant patients 3 cases of tuberculosis were found (Neff and Hudgel, 1973) and in a similar series from Cambridge, England 5 cases were reported (Coutts, Jegarajah and Stark, 1979). Increased suceptibility to infection is the result of treatment with immunosuppressive drugs, namely corticosteroids and azothioprine, which are given to suppress graft rejection. This renders the patient vulnerable to attack by common or opportunist micro-organisms, many of which are not pathogenic in ordinary circumstances. However, tuberculosis does not arise from invasion by tubercle bacilli from outside but by the breakdown of old, quiescent lesions in the lungs and elsewhere in the body. This explains why it occurs as a later complication than other infections. Thus in the 5 Cambridge patients the interval between transplant operation and diagnosis of tuberculosis was 8 months, 10 months, 3, 6, and 7 years respectively, while in another report of 4 such patients the interval was 3 months in 2 cases, 10 months in one and over 2 years in the fourth (Bell and Williams, 1978). Although it is widely assumed that treatment with corticosteroids predisposes to reactivation of quiescent tuberculous lesions, this has never been established by a controlled study (Lakshminarayan and Sahn, 1976). Indeed if there is such an effect it must be a relatively weak one, judging by the rarity of active tuberculous infection amongst steroid-dependent asthmatics (Schatz et a/, 1976). In transplant patients there may be other factors which undermine resistance to infection, such as the immuno-suppressive effect of renal failure. In immunologically deficient patients infection is liable to enter the bloodstream and become widely disseminated. Four of the 5 Cambridge patients had evidence of extra-pulmonary spread and the 2 who died were both found at autopsy to have widely disseminated tuberculosis. In this type of patient diagnosis can present special problems because the normal clinical manifestations of infection may be absent and tuberculin skin sensitivity is depressed. If tubercle bacilli are not found in the sputum the only certain method of confirming the diagnosis, and of distinguishing it from other causes of pulmonary infection, is by needle aspiration or biopsy of the lung (Al Batata, 1977).
194
Tuberculosis
in renal transplant
patients
The selection of anti-tuberculosis drugs for treatment depends on the renal function of the transplant patient. In the presence of renal failure the safest combination is rifampicin and isoniazid. Rifampicin is largely excreted in the bile and even in severe renal failure normal doses can be given without producing toxic blood levels. lsoniazid is subject to acetylation in the liver and for slow acetylators a reduction of dose may be necessary. If the serum creatinine concentration is less than 1060 umol/l the full dose can safely be given, but if it exceeds this level the dose should be lowered, although it is rarely necessary to reduce it to below 200 mg daily (Bowersox et a/, 1973). The optimum duration of treatment is unknown, but to prevent relapse it would seem prudent to continue chemotherapy for at least 2 or 3 years. In one reported case (Neff and Hudgel, 1973) a renal transplant recipient developed miliary tuberculosis and was treated with chemotherapy for 20 months, followed by daily isoniazid. Because of graft rejection a second transplantation was done and this was followed by a relapse of tuberculosis with isoniazid-resistant organisms. The first treatment regimen, however, did not include rifampicin. The reported results of treatment have been variable. Some patients have recovered fully following anti-tuberculosis chemotherapy (Lakshiminarayan and Sahn, 1973; Bell and Williams, 1978), while others have died, in some cases having already received several months of treatment. Of such patient died from widely disseminated tuberculosis after 6 months of chemotherapy (Coutts, Jegarajah and Stark, 1979) and another died from generalized disease after 5 months (Stake and Flatmark, 1976). It is not surprising that deaths occur in these circumstances, for recovery from tuberculosis depends not solely on the effect of specific antibacterial drugs but also on an adequate immune response by the patient. References Al Batata, N. (1977). Pulmonary tuberculosis in a renal transplant recipient. Joumalof the American MedicalAssociation. 237,1465. Bell, T. J., 9 Williams, G. B. (1978). Successful treatment of tuberculosis in renal transplant recipients. Journal of the RoyalSociety of Medicine, 71,265. Bowersox, D. W., Winterbauer, R. H., Stewart, G. L., Ormer, B., Et Barron, E. (1973). lsoniazid dosage in patients with renal failure. New England Journal of Medicine, 289,84. Coutts, I. I., Jegaraja, S., 8 Stark, J. E. (1979). Tuberculosis in renal transplant recipients. British Jot/ma/ of Diseases of the Chest, 73,141. Gurland, H. J., Brunner, F. P., Delun, H., Harlen, H., Parsons, F. M., Et Scharer, K. (1973). Combined report on regular dialysis and transplantation in Europe. Proceedings of the European Dialysis and Transplant Association, X, 42. Hulme, B. In Recent Advances in Renal Disease. No. 1. Edited by N. F. Jones. Churchill Livingstone, 1975. p. 222. Lakshminarayan, S., 8 Sahn, S. A. (1973). Tuberculosis in a patient after renal transplantation. Tubercle, 54.72. Lakshminarayan, S., & Sahn, S. A. (1976). Tuberculosis after corticosteroid therapy. British Journal of Diseases of the Chest, 70.195. Neff, T. A., & Hudgel, D. W. (1973). Military tuberculosis in a renal transplant recipient. American Review of Respiratory Disease, 108.677. Schatz, M., Patterson, FL, Klauer, R., 8 Falk, J. (1976). Prevalence of tuberculosis and positive tuberculin skin tests in steroid-treated asthmatic populations. Anna/s of internal Medicine, 84,261. Stake, G., 8 Flatmark, A. (1976). Lung complications during immunosuppressive treatment in renal transplant recipients. Scandinavian Journalof Respiratory Disease, 87,51.
and social class
193
On the information available it is not possible to determine whether the mortality gradient between the social classes is the result of a difference in attack rate or a difference in case fatality, but there are good reasons to suppose that both factors are important. It is salutary to be reminded that in a developed country like Britain, and presumably also in other developed countries, social circumstances still play an important part in determining tuberculosis mortality. References British
Thoracic and Tuberculosis Association (1971). A survey of tuberculosis mortality in England and Wales in 1968. Tubercle. 52,l. Campbell, H. In Recent Advances in Community Medicine. Edited by A. E. Bennett. Churchill Livingstone, 1978. p. 261. Registrar General. Occupational Mortality. The Registrar General’s decennial supplement for England and Wales. 1970-72. Series DS no. 1. London, 1978. HMSO.
Tuberculosis in renal transplant patients The principal cause of death after organ transplantation is infection, which is responsible for 40 % of all fatalities (Gurland et a/, 1973). The incidence of infection, either pulmonary or septicaemia, is greatest during the first 60 days after operation, a time when there is also a high risk of graft rejection (Hulme, 1975). A variety of micro-organisms may be involved : bacteria (gram negative), viruses (cytomegalovirus, herpes simplex and zoster), fungi (monilia and aspergdhs) and pneumocystis csrinii. Tuberculous infection is a rarity, but since renal transplant operations have been performed with increasing frequency several case reports have appeared. Thus in an American series of 400 renal transplant patients 3 cases of tuberculosis were found (Neff and Hudgel, 1973) and in a similar series from Cambridge, England 5 cases were reported (Coutts, Jegarajah and Stark, 1979). Increased suceptibility to infection is the result of treatment with immunosuppressive drugs, namely corticosteroids and azothioprine, which are given to suppress graft rejection. This renders the patient vulnerable to attack by common or opportunist micro-organisms, many of which are not pathogenic in ordinary circumstances. However, tuberculosis does not arise from invasion by tubercle bacilli from outside but by the breakdown of old, quiescent lesions in the lungs and elsewhere in the body. This explains why it occurs as a later complication than other infections. Thus in the 5 Cambridge patients the interval between transplant operation and diagnosis of tuberculosis was 8 months, 10 months, 3, 6, and 7 years respectively, while in another report of 4 such patients the interval was 3 months in 2 cases, 10 months in one and over 2 years in the fourth (Bell and Williams, 1978). Although it is widely assumed that treatment with corticosteroids predisposes to reactivation of quiescent tuberculous lesions, this has never been established by a controlled study (Lakshminarayan and Sahn, 1976). Indeed if there is such an effect it must be a relatively weak one, judging by the rarity of active tuberculous infection amongst steroid-dependent asthmatics (Schatz et a/, 1976). In transplant patients there may be other factors which undermine resistance to infection, such as the immuno-suppressive effect of renal failure. In immunologically deficient patients infection is liable to enter the bloodstream and become widely disseminated. Four of the 5 Cambridge patients had evidence of extra-pulmonary spread and the 2 who died were both found at autopsy to have widely disseminated tuberculosis. In this type of patient diagnosis can present special problems because the normal clinical manifestations of infection may be absent and tuberculin skin sensitivity is depressed. If tubercle bacilli are not found in the sputum the only certain method of confirming the diagnosis, and of distinguishing it from other causes of pulmonary infection, is by needle aspiration or biopsy of the lung (Al Batata, 1977).
194
Tuberculosis
in renal transplant
patients
The selection of anti-tuberculosis drugs for treatment depends on the renal function of the transplant patient. In the presence of renal failure the safest combination is rifampicin and isoniazid. Rifampicin is largely excreted in the bile and even in severe renal failure normal doses can be given without producing toxic blood levels. lsoniazid is subject to acetylation in the liver and for slow acetylators a reduction of dose may be necessary. If the serum creatinine concentration is less than 1060 umol/l the full dose can safely be given, but if it exceeds this level the dose should be lowered, although it is rarely necessary to reduce it to below 200 mg daily (Bowersox et a/, 1973). The optimum duration of treatment is unknown, but to prevent relapse it would seem prudent to continue chemotherapy for at least 2 or 3 years. In one reported case (Neff and Hudgel, 1973) a renal transplant recipient developed miliary tuberculosis and was treated with chemotherapy for 20 months, followed by daily isoniazid. Because of graft rejection a second transplantation was done and this was followed by a relapse of tuberculosis with isoniazid-resistant organisms. The first treatment regimen, however, did not include rifampicin. The reported results of treatment have been variable. Some patients have recovered fully following anti-tuberculosis chemotherapy (Lakshiminarayan and Sahn, 1973; Bell and Williams, 1978), while others have died, in some cases having already received several months of treatment. Of such patient died from widely disseminated tuberculosis after 6 months of chemotherapy (Coutts, Jegarajah and Stark, 1979) and another died from generalized disease after 5 months (Stake and Flatmark, 1976). It is not surprising that deaths occur in these circumstances, for recovery from tuberculosis depends not solely on the effect of specific antibacterial drugs but also on an adequate immune response by the patient. References Al Batata, N. (1977). Pulmonary tuberculosis in a renal transplant recipient. Joumalof the American MedicalAssociation. 237,1465. Bell, T. J., 9 Williams, G. B. (1978). Successful treatment of tuberculosis in renal transplant recipients. Journal of the RoyalSociety of Medicine, 71,265. Bowersox, D. W., Winterbauer, R. H., Stewart, G. L., Ormer, B., Et Barron, E. (1973). lsoniazid dosage in patients with renal failure. New England Journal of Medicine, 289,84. Coutts, I. I., Jegaraja, S., 8 Stark, J. E. (1979). Tuberculosis in renal transplant recipients. British Jot/ma/ of Diseases of the Chest, 73,141. Gurland, H. J., Brunner, F. P., Delun, H., Harlen, H., Parsons, F. M., Et Scharer, K. (1973). Combined report on regular dialysis and transplantation in Europe. Proceedings of the European Dialysis and Transplant Association, X, 42. Hulme, B. In Recent Advances in Renal Disease. No. 1. Edited by N. F. Jones. Churchill Livingstone, 1975. p. 222. Lakshminarayan, S., 8 Sahn, S. A. (1973). Tuberculosis in a patient after renal transplantation. Tubercle, 54.72. Lakshminarayan, S., & Sahn, S. A. (1976). Tuberculosis after corticosteroid therapy. British Journal of Diseases of the Chest, 70.195. Neff, T. A., & Hudgel, D. W. (1973). Military tuberculosis in a renal transplant recipient. American Review of Respiratory Disease, 108.677. Schatz, M., Patterson, FL, Klauer, R., 8 Falk, J. (1976). Prevalence of tuberculosis and positive tuberculin skin tests in steroid-treated asthmatic populations. Anna/s of internal Medicine, 84,261. Stake, G., 8 Flatmark, A. (1976). Lung complications during immunosuppressive treatment in renal transplant recipients. Scandinavian Journalof Respiratory Disease, 87,51.
