- Email: [email protected]
Tuberculosis Transmitted Through Transplantation
251
Case Reports valve but a Teflon patch; second, the ventricular aneurysm was located beneath the floor of the left ventricle and had gone completely unnoticed upon cardiac ultrasound examination. In our observation, the gallium-67 scan allowed us to identify the source of infection. By identifying an area of hyperfixation under the xyphisternum, it enabled us to target the investigations leading to the diagnosis of a ventricular aneurysm, and thus to conduct CT scan and NMR imaging. Although confirmation of infection of the Teflon patch could not be obtained, this was the most likely diagnosis. Identification of a focus of infection with the aid of a gallium-67 scan has already been reported for patients with PUO.7 Its diagnostic importance in infectious endocarditis has also been shown.8 Gallium-67 scanning is mainly relevant in unusual situations. Venezio et al. report the case of an infected intraventricular thrombus suspected upon galium-67 scanning.9 Rosenbaum et al. report the first case of an infected pacemaker identified through gallium-67 scanning while cardiac ultrasound examination had shown no vegetations.10 Gallium-67 scanning can prove a valuable test for the diagnosis of infectious endocarditis especially when traditional investigations are inconclusive.
References 1. Brook I, Frazier EH. Infections caused by Propionibacterium species. Rev Infect Dis 1991; 13: 819–822.
2. Jakab E, Zbinden R, Gubler J, Ruef C, von Graevenitz A, Krause M. Severe infections caused by Propionibacterium acnes: an underestimated pathogen in late postoperative infections. Yale J Biol Med 1997; 69: 477–482. 3. Huynh TT, Walling AD, Miller MA, Leung TK, Leclerc Y. Propionibacterium acnes endocarditis. Can J Cardiol 1995; 11: 785–787. 4. Durupt S, Boiteux A, Ballet-Mechain M, Chaumentin G, Tremeau G, Roure C, Peyramond D. Endocardites infectieuses à Propionibacterium acnes. Presse Méd 1998; 27: 1839–1841. 5. Günthard H, Hany A, Turina M, Wüst J. Propionibacterium acnes as a cause of aggressive aortic valve endocarditis and importance of tissue grinding: case report and review. J Clin Microbiol 1994; 32: 3043–3045. 6. Daniel WG, Mugge A, Grote J et al. Comparison of transthoracic and transoesophageal echography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol 1993; 71: 210–215. 7. Mouratidis B, Lomas F. The role of gallium-67 scanning in febrile patients. Australas Radiol 1994; 38: 193–195. 8. Spies SM, Meyers SN, Barresi V, Grais IM, DeBoer A. A case of myocardial abscess evaluated by radionuclitde tecgniques: case report. J Nucl Med 1977; 18: 1089–1090. 9. Venezio FR, Thompson JE, Sullivan H, Subramanian R. Infection of a ventricular aneurysm and cardiac mural thrombus: survival after surgical resection. Am J Med 1884; 77: 551–554. 10. Rosembaum GS, Calubiran O, Cunha BA. Haemophilus parainfluenzae bacteremia associated with a pacemaker wire localized by gallium scan. Heart Lung 1990; 19: 271–273.
doi:10.1053/jinf.2000.0879, available online at http://www.idealibrary.com on
Tuberculosis Transmitted Through Transplantation J. C. Graham*1, A. M. Kearns2, J. G. Magee2, M. F. A. El-Sheikh3, M. Hudson3, D. Manas3, F. K. Gould1, K. E. Orr1 and R. Freeman2 1
Microbiology Department and 3Liver Unit, Freeman Hospital, High Heaton and 2Public Health Laboratory, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, U.K.
Tuberculosis in solid organ transplant recipients is associated with relatively high morbidity and mortality and is often extra-pulmonary. Reactivation of dormant infection is the usual mode of acquisition with donor and nosocomial transmission occurring infrequently. We report two cases of probable donor transmitted extra-pulmonary infection where both isolates of Mycobacterium tuberculosis proved to be indistinguishable using hemi-nested inverse PCR of the IS6110 region. © 2001 The British Infection Society
Introduction Tuberculosis is a serious hazard in transplant patients and despite modern chemotherapy mortality rates of 25–40% are * Please address all correspondence to: J. C. Graham, Microbiology Department, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, U.K. Fax: 0191-223-1224; E-mail: [email protected] Accepted for publication 6 July 2001.
still reported.1 This in part is due to diagnostic delay as infection is often extrapulmonary. Moreover, anti-tuberculous therapy interacts with immunosuppressive drugs, reducing serum levels and potentially causing organ rejection if doses are not readjusted. Although reactivation of dormant tuberculosis is the usual mode of acquisition, donor transmission does occur and in a recent review was the proposed source in 4% (nine) of 243 patients.1 We describe two further cases of extrapulmonary tuberculosis in recipients from a single donor. © 2001 The British Infection Society
252
Case Reports
Case Reports Case 1 A 44-year-old former postman with end-stage renal failure secondary to hypertension underwent cadaveric renal transplantation. He had delayed graft function and a renal biopsy on day 8 that showed mild cellular rejection necessitating augmentation with methylprednisolone. He had two episodes of CMV infection (the donor was a known CMV mismatch) that were treated with intravenous ganciclovir. Following the first episode of rejection the kidney functioned well but later it slowly deteriorated and at 14 months posttransplant a renal biopsy showed a granulomatous nephritis. Stains for acid-fast bacilli at that time were negative. Renal granulomas following transplantation are usually due to recrudescence of an underlying granulomatous disorder, it may also be due to drug allergy and a variety of infections. His immunosuppressive therapy was changed from azathioprine to mycophenolate mofetil but his renal function continued to deteriorate. A further biopsy revealed extensive granulomata with focal necrosis and acid fast bacilli. Mycobacterium tuberculosis was isolated from early morning urine samples. There was no personal or contact history of tuberculosis and his chest X-ray was normal. Despite 9 months of standard antituberculous therapy (treatment was prolonged due to concerns over ongoing infection within the kidney), his graft function continued to decline and he underwent a graft nephrectomy. Histology of the explanted kidney confirmed the diagnosis.
nine discrete bands were obtained. Using previously published criteria IS6110 fingerprints giving .6 identical bands are more predictive of clonality and such isolates can be considered matched.2 The third recipient who received a kidney from the same donor remains asymptomatic and early morning urine samples have failed to grow M. tuberculosis. Given the clear history of exposure and the risk that tuberculosis may present at an extrapulmonary site it was decided to commence her on isoniazid prophylaxis. The donor was a 69-year-old lady who died following an intra-cranial haemorrhage. No post mortem was performed and on review her chest X-ray was unremarkable. There was no past medical history of tuberculosis. Although both cases were transplanted at the same institution different surgical teams were involved and follow up was in separate hospitals. There was no social contact between the two patients. Despite the lack of conclusive data from post mortem material, it seems likely that the donor was the source. This is supported by the results of molecular typing.
Discussion It is interesting to speculate why the third patient has not developed clinical evidence of infection; we could not find any published data specifically assessing genetic risk factors for tuberculosis in transplant recipients as clearly these are important in the general population.3 The median onset to disease is 11.5 months and one would expect the majority of donor
Case 2 A 61-year-old woman underwent orthotopic liver transplantation for non alcoholic steatohepatitis (NASH) related cirrhosis. This was presumed secondary to ileo-jejunal bypass surgery for obesity performed many years earlier. Apart from an episode of rejection on day 9 her post-operative course was uneventful and she was discharged home. Twelve months following transplantation her right foot became swollen and tender. She was commenced on flucloxacillin but did not respond so further investigations were initiated. Ultrasound excluded a deep vein thrombosis. An isotope bone scan revealed a significantly raised uptake in the right mid foot (Fig. 1) and MRI scan revealed bone marrow and soft tissue oedema around the Lisfranc joint. In view of the radiological pattern suggesting chronic infection a bone biopsy was performed but on histology only non-specific osteoporotic changes were seen. The specimen was not cultured for mycobacteria but stains for acid fast bacilli were negative. The patient continued to have pain and discharge from the foot which was treated symptomatically. Four months later the first case came to our attention; because this patient had received a liver from the same donor the diagnosis of tuberculosis was therefore considered. A further bone biopsy was performed and, on this occasion, histological examination revealed a granulomatous osteomyelitis and acid fast bacilli were seen. This tissue was cultured and grew Mycobacterium tuberculosis. Again there was no history of previous tuberculosis and chest X-ray was normal. The isolate was fully sensitive and she was treated with a 6-month course of standard anti-tuberculous chemotherapy. Both isolates were indistinguishable using hemi-nested inverse polymerase chain reaction (PCR) (HIP) which targets the insertion sequence IS6110 (Fig. 2). Identical banding profiles comprising
Figure 1. (Case 2).
Bone scan showing increased uptake in right mid foot
253
Case Reports
Figure 2. Lane M, molecular size marker (⌽⌾ 174 RF DNA/ Hae III fragments); Lanes 1 and 2, IS6110 hemi-nested inverse polymerase chain reaction (PCR) of isolates from cases 1 and 2; Lane 3, control strain.
acquired infection to present around this time as late cases are presumably due to a mixture of late reactivation and acquisition post transplant. Certainly patients with a history of exposure to tuberculosis (positive skin test or radiological evidence of old tuberculosis) have a trend to develop TB early.1 Predictors of early onset tuberculosis include non-renal transplantation, early (:6 months) allograft rejection and type of immunosuppression. With current immunosuppressive regimens, the risk of hepatotoxicity in renal transplant patients is low and no different from normal individuals.4 The hepatic allograft however is more sensitive to first line anti-tuberculous agents, use of these drugs has to be weighed up against the diagnostic problems that will arise if liver function deteriorates. For treatment of such individuals it may be necessary to use second-line drugs such as ofloxacin.5 Where prophylaxis is indicated and isoniazid is felt to be unsuitable because of the risk of toxicity, surveillance cultures may be used.6 Case series and reports suggest that isoniazid is
effective for high-risk transplant patients but no controlled trial data is available.1 Both of these cases presented diagnostic difficulty due to the extrapulmonary location of their disease. Localization of infection to the transplanted organ and lack of previous history or contact with TB raised our suspicion of donor transmitted infection in Case 1. Renal allograft involvement is usually seen as part of a disseminated infection which was not evident in this patient.1 In the transplant population tuberculosis usually presents as either pulmonary or disseminated infection with use of OKT3 or anti T-cell antibodies being a risk factor for the latter.1 Histological evidence of renal involvement is documented in about 11% of kidney transplants but hepatic granulomas with or without acid-fast bacilli were found in 13 out of 27 liver transplant recipients.1 It should be remembered that a wide variety of conditions may cause granulomas in these patients.7 Although a low grade infection was suspected in Case 2, the initial negative biopsy result caused a delay in the diagnosis being made. If histological results differ from the radiological and clinical findings, a repeat biopsy should always be considered. Both patients have been successfully treated for their tuberculosis although not without loss of the renal graft in case 1 and significant morbidity in Case 2. Tuberculosis represents a significant hazard to solid organ transplant recipients but it may not always be considered due to its variable presentation. It is therefore important to consider early diagnostic investigations and to maintain a low threshold for mycobacterial culture in clinical samples. A number of methods have been employed to type M. tuberculosis. Although IS6110 ampliprinting can be poorly reproducible between batches, the hemi-nested technique used in this report has been shown to be adequate for strain comparison.8 When epidemiological testing is required on a larger scale then greater discrimination is required and IS6110 restriction fragment length polymorphism or a mixed-linker PCR are the methods of choice.9 At present we must still rely on clinical history alone to prevent cases of donor transmitted mycobacterial infection but with the advent of better molecular or serological tests it may be possible to identify those who would benefit most from prophylactic therapy. Macroscopic assessment does not preclude the presence of M. tuberculosis as it may persist intracellularly even in histologically normal tissue,10 fortunately in the U.K. few donors will be harbouring latent infection. Clinical cases represent a cross infection hazard on transplant unit and this could be averted by such pre-emptive therapy.
References 1 Singh N, Paterson DL. Mycobacterium tuberculosis infection in solidorgan transplant recipients: impact and implication for management. Clin Infect Dis 1998; 27: 1266–1277. 2 Braden CR, Templeton GL, Cave MD et al. Interpretation of restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from a state with a large rural population. J Infect Dis 1997; 175: 1446–1452. 3 Newport M, Levin M. Genetic susceptibility to tuberculosis. J Infect 1999; 39: 117–121. 4 Antony SJ, Ynares C, Dummer JS. Isoniazid hepatotoxicity in renal transplant recipients. Clin Transplant 1997; 11: 34. 5 Meyers BR, Papanicolaou GA, Sheiner P, Emre S, Miller C. Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens. Transplantation 2000; 69: 64–69.
254
Case Reports
6 Torre-Cisneros J, De la Mata M, Rufian S et al. Importance of surveillance mycobacterial cultures after liver transplantation. Transplantation 1995; 60: 1054–1055. 7 Ferrell LD, Lee R, Brixko C et al. Hepatic granulomas following liver transplantation. Transplantation 1995; 60: 926–933. 8 Kearns AM, Barratt A, Marshall C et al. Epidemiology and molecular typing of an outbreak of tuberculosis in a hostel for homeless men. J Clin Pathol 2000; 53: 122–124.
9 Kremer K, van Soolingen D, Frothingham R et al. Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: Interlaboratory study of discriminatory power and reproducibility. J Clin Microbiol 1999; 37: 2607–2618. 10 Hernández-Pando R, Jeyanathan M, Mengistu G et al. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 2000; 356: 2133–2138.
Case Reports valve but a Teflon patch; second, the ventricular aneurysm was located beneath the floor of the left ventricle and had gone completely unnoticed upon cardiac ultrasound examination. In our observation, the gallium-67 scan allowed us to identify the source of infection. By identifying an area of hyperfixation under the xyphisternum, it enabled us to target the investigations leading to the diagnosis of a ventricular aneurysm, and thus to conduct CT scan and NMR imaging. Although confirmation of infection of the Teflon patch could not be obtained, this was the most likely diagnosis. Identification of a focus of infection with the aid of a gallium-67 scan has already been reported for patients with PUO.7 Its diagnostic importance in infectious endocarditis has also been shown.8 Gallium-67 scanning is mainly relevant in unusual situations. Venezio et al. report the case of an infected intraventricular thrombus suspected upon galium-67 scanning.9 Rosenbaum et al. report the first case of an infected pacemaker identified through gallium-67 scanning while cardiac ultrasound examination had shown no vegetations.10 Gallium-67 scanning can prove a valuable test for the diagnosis of infectious endocarditis especially when traditional investigations are inconclusive.
References 1. Brook I, Frazier EH. Infections caused by Propionibacterium species. Rev Infect Dis 1991; 13: 819–822.
2. Jakab E, Zbinden R, Gubler J, Ruef C, von Graevenitz A, Krause M. Severe infections caused by Propionibacterium acnes: an underestimated pathogen in late postoperative infections. Yale J Biol Med 1997; 69: 477–482. 3. Huynh TT, Walling AD, Miller MA, Leung TK, Leclerc Y. Propionibacterium acnes endocarditis. Can J Cardiol 1995; 11: 785–787. 4. Durupt S, Boiteux A, Ballet-Mechain M, Chaumentin G, Tremeau G, Roure C, Peyramond D. Endocardites infectieuses à Propionibacterium acnes. Presse Méd 1998; 27: 1839–1841. 5. Günthard H, Hany A, Turina M, Wüst J. Propionibacterium acnes as a cause of aggressive aortic valve endocarditis and importance of tissue grinding: case report and review. J Clin Microbiol 1994; 32: 3043–3045. 6. Daniel WG, Mugge A, Grote J et al. Comparison of transthoracic and transoesophageal echography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol 1993; 71: 210–215. 7. Mouratidis B, Lomas F. The role of gallium-67 scanning in febrile patients. Australas Radiol 1994; 38: 193–195. 8. Spies SM, Meyers SN, Barresi V, Grais IM, DeBoer A. A case of myocardial abscess evaluated by radionuclitde tecgniques: case report. J Nucl Med 1977; 18: 1089–1090. 9. Venezio FR, Thompson JE, Sullivan H, Subramanian R. Infection of a ventricular aneurysm and cardiac mural thrombus: survival after surgical resection. Am J Med 1884; 77: 551–554. 10. Rosembaum GS, Calubiran O, Cunha BA. Haemophilus parainfluenzae bacteremia associated with a pacemaker wire localized by gallium scan. Heart Lung 1990; 19: 271–273.
doi:10.1053/jinf.2000.0879, available online at http://www.idealibrary.com on
Tuberculosis Transmitted Through Transplantation J. C. Graham*1, A. M. Kearns2, J. G. Magee2, M. F. A. El-Sheikh3, M. Hudson3, D. Manas3, F. K. Gould1, K. E. Orr1 and R. Freeman2 1
Microbiology Department and 3Liver Unit, Freeman Hospital, High Heaton and 2Public Health Laboratory, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, U.K.
Tuberculosis in solid organ transplant recipients is associated with relatively high morbidity and mortality and is often extra-pulmonary. Reactivation of dormant infection is the usual mode of acquisition with donor and nosocomial transmission occurring infrequently. We report two cases of probable donor transmitted extra-pulmonary infection where both isolates of Mycobacterium tuberculosis proved to be indistinguishable using hemi-nested inverse PCR of the IS6110 region. © 2001 The British Infection Society
Introduction Tuberculosis is a serious hazard in transplant patients and despite modern chemotherapy mortality rates of 25–40% are * Please address all correspondence to: J. C. Graham, Microbiology Department, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, U.K. Fax: 0191-223-1224; E-mail: [email protected] Accepted for publication 6 July 2001.
still reported.1 This in part is due to diagnostic delay as infection is often extrapulmonary. Moreover, anti-tuberculous therapy interacts with immunosuppressive drugs, reducing serum levels and potentially causing organ rejection if doses are not readjusted. Although reactivation of dormant tuberculosis is the usual mode of acquisition, donor transmission does occur and in a recent review was the proposed source in 4% (nine) of 243 patients.1 We describe two further cases of extrapulmonary tuberculosis in recipients from a single donor. © 2001 The British Infection Society
252
Case Reports
Case Reports Case 1 A 44-year-old former postman with end-stage renal failure secondary to hypertension underwent cadaveric renal transplantation. He had delayed graft function and a renal biopsy on day 8 that showed mild cellular rejection necessitating augmentation with methylprednisolone. He had two episodes of CMV infection (the donor was a known CMV mismatch) that were treated with intravenous ganciclovir. Following the first episode of rejection the kidney functioned well but later it slowly deteriorated and at 14 months posttransplant a renal biopsy showed a granulomatous nephritis. Stains for acid-fast bacilli at that time were negative. Renal granulomas following transplantation are usually due to recrudescence of an underlying granulomatous disorder, it may also be due to drug allergy and a variety of infections. His immunosuppressive therapy was changed from azathioprine to mycophenolate mofetil but his renal function continued to deteriorate. A further biopsy revealed extensive granulomata with focal necrosis and acid fast bacilli. Mycobacterium tuberculosis was isolated from early morning urine samples. There was no personal or contact history of tuberculosis and his chest X-ray was normal. Despite 9 months of standard antituberculous therapy (treatment was prolonged due to concerns over ongoing infection within the kidney), his graft function continued to decline and he underwent a graft nephrectomy. Histology of the explanted kidney confirmed the diagnosis.
nine discrete bands were obtained. Using previously published criteria IS6110 fingerprints giving .6 identical bands are more predictive of clonality and such isolates can be considered matched.2 The third recipient who received a kidney from the same donor remains asymptomatic and early morning urine samples have failed to grow M. tuberculosis. Given the clear history of exposure and the risk that tuberculosis may present at an extrapulmonary site it was decided to commence her on isoniazid prophylaxis. The donor was a 69-year-old lady who died following an intra-cranial haemorrhage. No post mortem was performed and on review her chest X-ray was unremarkable. There was no past medical history of tuberculosis. Although both cases were transplanted at the same institution different surgical teams were involved and follow up was in separate hospitals. There was no social contact between the two patients. Despite the lack of conclusive data from post mortem material, it seems likely that the donor was the source. This is supported by the results of molecular typing.
Discussion It is interesting to speculate why the third patient has not developed clinical evidence of infection; we could not find any published data specifically assessing genetic risk factors for tuberculosis in transplant recipients as clearly these are important in the general population.3 The median onset to disease is 11.5 months and one would expect the majority of donor
Case 2 A 61-year-old woman underwent orthotopic liver transplantation for non alcoholic steatohepatitis (NASH) related cirrhosis. This was presumed secondary to ileo-jejunal bypass surgery for obesity performed many years earlier. Apart from an episode of rejection on day 9 her post-operative course was uneventful and she was discharged home. Twelve months following transplantation her right foot became swollen and tender. She was commenced on flucloxacillin but did not respond so further investigations were initiated. Ultrasound excluded a deep vein thrombosis. An isotope bone scan revealed a significantly raised uptake in the right mid foot (Fig. 1) and MRI scan revealed bone marrow and soft tissue oedema around the Lisfranc joint. In view of the radiological pattern suggesting chronic infection a bone biopsy was performed but on histology only non-specific osteoporotic changes were seen. The specimen was not cultured for mycobacteria but stains for acid fast bacilli were negative. The patient continued to have pain and discharge from the foot which was treated symptomatically. Four months later the first case came to our attention; because this patient had received a liver from the same donor the diagnosis of tuberculosis was therefore considered. A further bone biopsy was performed and, on this occasion, histological examination revealed a granulomatous osteomyelitis and acid fast bacilli were seen. This tissue was cultured and grew Mycobacterium tuberculosis. Again there was no history of previous tuberculosis and chest X-ray was normal. The isolate was fully sensitive and she was treated with a 6-month course of standard anti-tuberculous chemotherapy. Both isolates were indistinguishable using hemi-nested inverse polymerase chain reaction (PCR) (HIP) which targets the insertion sequence IS6110 (Fig. 2). Identical banding profiles comprising
Figure 1. (Case 2).
Bone scan showing increased uptake in right mid foot
253
Case Reports
Figure 2. Lane M, molecular size marker (⌽⌾ 174 RF DNA/ Hae III fragments); Lanes 1 and 2, IS6110 hemi-nested inverse polymerase chain reaction (PCR) of isolates from cases 1 and 2; Lane 3, control strain.
acquired infection to present around this time as late cases are presumably due to a mixture of late reactivation and acquisition post transplant. Certainly patients with a history of exposure to tuberculosis (positive skin test or radiological evidence of old tuberculosis) have a trend to develop TB early.1 Predictors of early onset tuberculosis include non-renal transplantation, early (:6 months) allograft rejection and type of immunosuppression. With current immunosuppressive regimens, the risk of hepatotoxicity in renal transplant patients is low and no different from normal individuals.4 The hepatic allograft however is more sensitive to first line anti-tuberculous agents, use of these drugs has to be weighed up against the diagnostic problems that will arise if liver function deteriorates. For treatment of such individuals it may be necessary to use second-line drugs such as ofloxacin.5 Where prophylaxis is indicated and isoniazid is felt to be unsuitable because of the risk of toxicity, surveillance cultures may be used.6 Case series and reports suggest that isoniazid is
effective for high-risk transplant patients but no controlled trial data is available.1 Both of these cases presented diagnostic difficulty due to the extrapulmonary location of their disease. Localization of infection to the transplanted organ and lack of previous history or contact with TB raised our suspicion of donor transmitted infection in Case 1. Renal allograft involvement is usually seen as part of a disseminated infection which was not evident in this patient.1 In the transplant population tuberculosis usually presents as either pulmonary or disseminated infection with use of OKT3 or anti T-cell antibodies being a risk factor for the latter.1 Histological evidence of renal involvement is documented in about 11% of kidney transplants but hepatic granulomas with or without acid-fast bacilli were found in 13 out of 27 liver transplant recipients.1 It should be remembered that a wide variety of conditions may cause granulomas in these patients.7 Although a low grade infection was suspected in Case 2, the initial negative biopsy result caused a delay in the diagnosis being made. If histological results differ from the radiological and clinical findings, a repeat biopsy should always be considered. Both patients have been successfully treated for their tuberculosis although not without loss of the renal graft in case 1 and significant morbidity in Case 2. Tuberculosis represents a significant hazard to solid organ transplant recipients but it may not always be considered due to its variable presentation. It is therefore important to consider early diagnostic investigations and to maintain a low threshold for mycobacterial culture in clinical samples. A number of methods have been employed to type M. tuberculosis. Although IS6110 ampliprinting can be poorly reproducible between batches, the hemi-nested technique used in this report has been shown to be adequate for strain comparison.8 When epidemiological testing is required on a larger scale then greater discrimination is required and IS6110 restriction fragment length polymorphism or a mixed-linker PCR are the methods of choice.9 At present we must still rely on clinical history alone to prevent cases of donor transmitted mycobacterial infection but with the advent of better molecular or serological tests it may be possible to identify those who would benefit most from prophylactic therapy. Macroscopic assessment does not preclude the presence of M. tuberculosis as it may persist intracellularly even in histologically normal tissue,10 fortunately in the U.K. few donors will be harbouring latent infection. Clinical cases represent a cross infection hazard on transplant unit and this could be averted by such pre-emptive therapy.
References 1 Singh N, Paterson DL. Mycobacterium tuberculosis infection in solidorgan transplant recipients: impact and implication for management. Clin Infect Dis 1998; 27: 1266–1277. 2 Braden CR, Templeton GL, Cave MD et al. Interpretation of restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from a state with a large rural population. J Infect Dis 1997; 175: 1446–1452. 3 Newport M, Levin M. Genetic susceptibility to tuberculosis. J Infect 1999; 39: 117–121. 4 Antony SJ, Ynares C, Dummer JS. Isoniazid hepatotoxicity in renal transplant recipients. Clin Transplant 1997; 11: 34. 5 Meyers BR, Papanicolaou GA, Sheiner P, Emre S, Miller C. Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens. Transplantation 2000; 69: 64–69.
254
Case Reports
6 Torre-Cisneros J, De la Mata M, Rufian S et al. Importance of surveillance mycobacterial cultures after liver transplantation. Transplantation 1995; 60: 1054–1055. 7 Ferrell LD, Lee R, Brixko C et al. Hepatic granulomas following liver transplantation. Transplantation 1995; 60: 926–933. 8 Kearns AM, Barratt A, Marshall C et al. Epidemiology and molecular typing of an outbreak of tuberculosis in a hostel for homeless men. J Clin Pathol 2000; 53: 122–124.
9 Kremer K, van Soolingen D, Frothingham R et al. Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: Interlaboratory study of discriminatory power and reproducibility. J Clin Microbiol 1999; 37: 2607–2618. 10 Hernández-Pando R, Jeyanathan M, Mengistu G et al. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 2000; 356: 2133–2138.