Prevalence and manifestations of tuberculosis in renal transplant recipients: a single-center experience in Thailand

This retrospective review presented the prevalence and manifestations of tuberculosis among renal transplant recipients in our center between 1987 and mid 2007. The prevalence of tuberculosis was 5/151 (3.3%) recipients with a median age of 49 years (range = 38-55). The median time of diagnosis after transplantation was 23 months (range = 1-47). All five patients had pulmonary tuberculosis. None developed extrapulmonary infection. Presenting symptoms were fever (60%), productive cough (80%), weight loss (40%), and hemoptysis (20%). One patient had non-parathyroid-related hypercalcemia. Cyclosporine dosage needed to be increased in all patients. Two subjects who experienced side effects of hepatitis and/or jaundice from rifampicin were switched to second-line drugs. Infection with Mycobacterial tuberculosis is a not uncommon problem in renal transplant recipients especially in endemic areas. Tuberculosis must be excluded for immunosuppressed patients with clinical or radiological suspicion.     

Mycobacterium tuberculosis infection in renal transplant recipients

Mycobacterium tuberculosis (TB) infection is more common among renal allograft recipients compared with the general population due to immunosuppression. The epidemiological risk in a country is an important determinant of transplant TB after transplantation. We retrospectively analyzed 283 renal transplant recipients who underwent renal transplantation between 1990 and 2004. We evaluated the incidence, patient and disease characteristics, prognosis, and outcome of TB infection. Tuberculosis developed in 10 (seven men and three women of mean age of 41+/-9 years) among 283 patients (3.1%). All patients were culture-positive for M tuberculosis. Although pulmonary TB was the most common presentation in the general population, 50% of patients in the study group developed extrapulmonary TB. The mean elapsed time from renal transplantation was 38 months. Three patients (1%) developed TB in the first year after transplantation. All patients were treated with a quartet of anti-TB therapy. One patient developed isoniazid-related reversible hepatotoxicity. No acute allograft rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary TB died due to dissemination of the disease. In conclusion, extrapulmonary presentations of TB are more common among renal transplant recipients with the increased risk of mortality.     

Tuberculosis in Renal Transplant Recipients: A Brazilian Center Registry

Renal transplant recipients receiving immunosuppression show an increased risk for developing opportunistic infections, such as tuberculosis (TB). TB represents the major cause of morbidity and mortality in the world, mainly in underdeveloped countries. The aim of this study was to analyze the incidence of TB and its presentation among renal transplant recipients over 20 years.

Patients and Methods

This retrospective analysis included medical records of renal transplant recipients from January 1984 to April 2007.

Results

Among 1342 renal transplant recipients, 31 received treatment for TB due to clinical disease (n = 23) or prophylaxis (n = 8). The overall incidence of TB was 1.71%, which was diagnosed at 53 ± 49 months posttransplantation. The indications for TB prophylaxis were a previous history of TB (n = 6) or direct contact with a TB carrier (n = 1). The most common clinical presentation was extrapulmonary (n = 13). The classical treatment was effective in 16 cases. However, 7 cases of resistant TB required ethambutol added to therapy. Adverse events of treatment included liver toxicity (n = 1) and peripheral neuropathy (n = 1). Three patients died due to TB-related complications. Graft loss was observed in 3 patients after cessation of TB treatment. None of the patients on prophylaxis developed clinical disease.

Conclusions

TB incidence was significantly greater among renal transplant recipients compared with the local population, with a higher incidence of extrapulmonary disease. TB prophylaxis in selected cases was effective, avoiding new infections.     

A renal transplant recipient with pulmonary tuberculosis and visceral leishmaniasis: review of superimposed infections and therapy approaches

Visceral leishmaniasis (VL) is an acute or subacute disease that is almost invariably fatal if untreated. It is a rare disease in renal transplant recipients and frequently reported together with other infectious agents. A 39-year-old renal transplant patient was admitted to hospital for elective coronary surgery. In the post-operative period, he developed spiking fever and non-productive cough and his general condition deteriorated. While he was taking medication for non-specific pneumonia, a cavitary lesion occurred in his lung, and he had the diagnosis of pulmonary tuberculosis and antituberculous treatment was started. Despite treatment, his fever continued. As the patient developed pancytopenia and splenomegaly, a bone marrow aspiration was done. Evaluation of bone marrow aspirate indicated Leishmania parasites. He was successfully treated with a more intensive liposomal amphotericin (L-AmB). Complete cure was achieved during follow-up period of 10 months without clinical relapse. In the existence of fever and long-standing pancytopenia, VL should be suspected although the patient had another proved infection and did not live or visit an endemic area. L-AmB usage can be safely preferred for treatment of selected renal transplant recipients with VL as first-line therapy.     

Laryngeal tuberculosis in renal transplant recipients.

BACKGROUND: Tuberculosis is the most common non-pyogenic infection encountered among renal transplant recipients in India. Although the lung is the most common site of involvement, a number of extrapulmonary organs can be involved. There is often a delay in diagnosis and institution of effective chemotherapy when there is an unusual site of involvement. METHODS AND RESULTS: We report two renal transplant recipients with laryngeal tuberculosis who presented with prolonged hoarseness of voice and painful dysphagia. Acid-fast bacilli were demonstrated on laryngeal biopsy and smear. Fever and pulmonary involvement were seen in only one patient. This is the first report of laryngeal tuberculosis in renal transplant recipients. CONCLUSIONS: Laryngeal tuberculosis should be suspected in renal transplant recipients who develop hoarseness of voice and odynophagia. Demonstration of acid-fast bacilli on biopsy or smear obtained by direct laryngoscopy helps in determining the diagnosis.     

Miliary tuberculosis in a Caucasian male transplant recipient and the role of intravenous immunoglobulin as an immunosuppressive sparing agent

Opportunistic infections are a common and anticipated accompaniment of transplantation, but are generally somewhat predictable in their timing and epidemiology. The authors report here a case of miliary tuberculosis occurring within 3 weeks of transplantation, in a patient not expected to be significantly at risk, and with a normal chest X-ray at the time of transplantation. A 25-year-old Caucasian male dialysis patient who received two paediatric kidneys as an en bloc renal transplant developed fever 3 weeks following transplantation; this eventually proved to be miliary tuberculosis. As well as antituberculous therapy and a significant reduction in the patient's conventional immunosuppression, intravenous immunoglobulin was used as anti-rejection prophylaxis. The case highlights the immunosuppressed status of dialysis patients prior to transplantation and the need for broad differential diagnosis in transplant recipients even in the absence of recognized epidemiological factors. The case also emphasizes the role of intravenous immunoglobulin as an anti-rejection therapy that does not add to the patient's immunosuppressive burden.     

A Case Report of Lumbar Abscess in a Transplant Recipient: Is It Always What It Seems?

The percentage of solid organ transplant recipients who develop extrapulmonary or disseminated tuberculosis (TB) is higher than the general population. In countries where the disease is endemic, TB should always be considered a diagnostic possibility, and extrapulmonary disease should also be considered. We present the case of a kidney transplant patient who initially presented for an abscess in the left dorsolateral region and was ultimately diagnosed with pulmonary and extrapulmonary TB. With the initiation of antibacillary treatment, a drug interaction with immunosuppressants was verified, and rifampicin was maintained at a minimum dose with other antibacillary drugs at full dose, subsequently showing an improvement in the clinical picture. The adverse effects of TB treatment present great difficulty owing to the interactions of antibacillary drugs with immunosuppressants. Most patients with conventional treatment can be cured, so prompt diagnosis and treatment are important.     

Visceral leishmaniasis in renal transplant recipients: clinical aspects, diagnostic problems, and response to treatment

Visceral leishmaniasis (VL) is a parasitic infection that uncommonly affects renal transplantation recipients, even in endemic areas. It may be associated with other infections, or masked by these, and may present subclinically and/or atypically for extended periods. The evolution may be particularly severe and diagnosis is often delayed. If not adequately diagnosed and treated, VL can be fatal and so should be suspected in renal transplantation recipients presenting unexplained fever, splenomegaly, and pancytopenia. The authors report 8 cases of VL out of a total of 800 renal transplant recipients from two transplant hospitals centers in Brazil. The clinical, diagnostic, and therapeutic features are reviewed.     

Nocardiosis in tropical renal transplant recipients

BACKGROUND: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported. METHODS: An evaluation of nocardiosis for 30 yr in one of the large transplant centres in South Asian region. RESULTS: Of the 1968 patients who received primary renal allografts at Christian Medical College & Hospital, 27 patients developed nocardiosis over 30 yr. Early nocardiosis (2 yr). Seventeen patients (63%) had two or more associated post-transplant infections, of whom 10 had tuberculosis. Mortality in these patients was associated with chronic liver disease. CONCLUSIONS: Nocardiosis manifests earlier (<2 yr) in CsA treated patients who have chronic liver disease. Among renal transplant recipients of the tropics nocardiosis is a marker of a high susceptibility to tuberculosis and other infections, the association with tuberculosis is stronger in those developing early nocardiosis (<2 yr). Chronic liver disease is a risk factor for death in patients with nocardiosis especially when associated with tuberculosis. This report constitutes the largest single centre experience among renal transplant recipients.     

Prevalence of previous hepatitis A virus infection in renal transplant patients with hepatitis C: evidence of persistent anti-hepatitis A virus immune response

Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney transplant recipients are scarce. There is little information concerning natural immunity acquired after acute HAV infection. In most renal transplant recipients, anti-HAV antibodies are not detectable after vaccination; it is reasonable to suppose that immunosuppressive therapy interferes with the immunity. The objective of this study was to evaluate, in an endemic area, the prevalence of anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in 40 HCV-positive renal transplant recipients. This group showed a 90% prevalence of previous HAV infection. These findings suggest that in an endemic area, the prevalence of previous HAV infection is high, even among immunosuppressed patients. HAV antibodies acquired after natural infection are detectable even after the onset of immunosuppressive therapy. These data should be considered when renal transplant recipients are considered for HAV vaccination. Prevaccination screening of renal transplant recipients must follow the same guidelines as those for immunocompetent subjects.     

肾移植受者肺外结核的发病及诊治特点分析

目的 探讨肾移植患者术后肺外结核的发病及诊治特点. 方法 1991年1月至2007年4月行肾移植手术2333例,术后发现结核病37例,经病理学和(或)影像学检查确诊肺外结核者19例(51%).其中累及移植肾5例、脑膜4例、胸膜4例、淋巴结3例、软组织2例,喉、肝、胸椎、肠道各1例,同时有2个肺外部位受累者3例.发病高峰期为术后1年(53%).治疗方案主要采用异烟肼、利福平、乙胺丁醇和吡嗪酰胺组合,疗程6～25个月. 结果 14例经抗结核治疗痊愈,随访1～161个月,患者均存活且无复发;5例患者治疗无效,继发多脏器功能衰竭死亡(26%).抗结核治疗中发生急性排斥反应8例(42%),肝功能损害4例(21%). 结论肾移植患者术后肺外结核发生率、病死率较高,应引起临床足够重视,使用抗结核药物时应注意兼顾抗结核与抗排斥反应2方面.     

Mycobacterial infections in marrow transplant patients

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.     

“Triple infections” (fungal,bacterial and viral) in immunosuppressed renal transplant recipients

In a period of 5 years, 8 out of 77 renal transplant patients showed simultaneous fungal, bacterial and viral infections. Candida albicans was found in all cases. The most severe bacterial complications were infections with Klebsiella, Pseudomonas and Staphylococcus aureus. Cytomegalovirus, persistent HBsAg positive hepatitis, herpes zoster, and herpes simplex infections were also found. Seven patients died of bacterial superinfection and miliary tuberculosis. The data presented show that "triple infections" are associated with high mortality and that miliary tuberculosis occurred frequently in immunosuppressed renal transplant recipients.     

Leishmaniasis in solid organ and hematopoietic stem cell transplant recipients

Leishmaniasis occurs in <1% of solid organ and hematopoietic stem cell transplant recipients in endemic countries in which transplants are performed. Visceral leishmaniasis (VL) makes up the bulk of reported cases. The onset generally occurs months after transplantation and the mode of acquisition is often impossible to determine, but de novo vector‐borne infection and reactivation of inapparent infection are thought to be the principal means. The potential role of clinically inapparent donor infection is uncertain and screening is not currently recommended, nor is it recommended for recipients from endemic areas, some of whom may have detectable circulating protozoan nucleic acid. While transplant recipients with VL often present with the non‐specific findings of fever and cytopenia, the additional presence of hepatosplenomegaly in patients from endemic areas should lead to a directed diagnostic evaluation with bone marrow examination and PCR testing of marrow and peripheral blood having a high yield. Management may often be complicated by the presence of concomitant infections. A lipid formulation of amphotericin B is the preferred treatment, especially for VL, but the relapse rate in transplant recipients is approximately 25%. PCR monitoring of blood for either secondary prophylaxis or preemptive therapy requires further study.     

Management of chronic viral hepatitis before and after renal transplantation

Hepatitis C virus (HCV) infection is present in 2-50% of renal transplant recipients and patients receiving hemodialysis. Renal transplantation confers an overall survival benefit in HCV positive (HCV+) hemodialysis patients, with similar 5-year patient and graft survival to those without HCV infection. However, longer-term studies have reported increased liver-related mortality in HCV-infected recipients. Unfortunately, attempts to eradicate HCV infection before transplant have been disappointing. Interferon is poorly tolerated in-patients with end-stage renal disease and ribavirin is contraindicated because reduced renal clearance results in severe hemolysis. Antiviral therapy following renal transplantation is also poorly tolerated, because of interferon-induced rejection and graft loss. Although the prevalence of hepatitis B virus (HBV) infection has declined in hemodialysis patients and renal transplant recipients since the introduction of routine vaccination and other infection control measures, it remains high within countries with endemic HBV infection (especially Asia-Pacific and Africa). Renal transplantation is associated with reduced survival in HBsAg+ hemodialysis patients. Unlike interferon, lamivudine is a safe and effective antiviral HBV treatment both before and after renal transplantation. Lamivudine therapy commenced at transplantation should prevent early posttransplant reactivation and subsequent progression to cirrhosis and late liver failure. This preemptive therapy should also eradicate early liver failure from fibrosing cholestatic hepatitis. Because cessation of treatment may lead to severe lamivudine-withdrawal hepatitis, most patients require long-term therapy. The development of lamivudine-resistance will be accelerated by immunosuppression and may result in severe hepatitis flares with decompensation. Regular monitoring with liver function tests and HBV DNA measurements should enable early detection and rescue with adefovir. Chronic HCV and HBV infections are important causes of morbidity and mortality in renal transplant recipients. The best predictor for liver mortality is advanced liver disease at the time of transplant, and liver biopsy should be considered in all potential HBsAg+ or HCV+ renal transplant candidates without clinical or radiologic evidence of cirrhosis. Established cirrhosis with active viral infection should be considered a relative contraindication to isolated renal transplantation.     

Laryngeal tuberculosis in renal allograft patients

Laryngeal tuberculosis, although the most common granulomatous disease of the larynx, is a rare form of extrapulmonary tuberculosis, never reported in immunosuppressed allograft recipients. We present two cases of laryngeal tuberculosis in renal transplant patients and a review of the literature. Two women, a 29-year-old and a 60-year-old, each more than 9 years after their cadaveric renal allograft, presented with a 2-week febrile illness with hoarseness and dysphagia, and both were found to have laryngeal tuberculosis by direct laryngoscopy. Although both radiographs were unremarkable, both patients had sputum positive for acid-fast bacilli that subsequently grew Mycobacterium tuberculosis. Clinical response promptly followed institution of isoniazid, rifampicin, and pyrazinamide in each case, although both required threefold increases in daily cyclosporin A dosage to maintain therapeutic levels.     

Human Ehrlichiosis in Transplant Recipients

To characterize the impact of immunosuppression on human ehrlichiosis, we reviewed cases of ehrlichiosis occurring in transplant recipients and immunocompetent patients at three hospitals in Nashville, Tennessee. Between 1998 and 2006, 15 transplant patients were identified as having ehrlichiosis, diagnosed either by whole blood polymerase chain reaction (PCR) (n = 14) or serology (n = 1). They were compared with 43 immunocompetent patients diagnosed by whole blood PCR. We retrospectively collected demographic and clinical information. The species of Ehrlichia (E. ewingii or E. chaffeensis) was determined for patients diagnosed by PCR. The 15 transplant recipients with ehrlichiosis included 7 kidney recipients, 6 heart recipients, 1 liver recipient and 1 lung recipient. Transplant recipients had more infections with E. ewingii than immunocompetent patients (23% vs. 5%, p = 0.08). Transplant recipients experienced less rash (0% vs. 36%, p = 0.006) and presented with significantly lower hepatic enzymes, but more leukopenia and renal dysfunction than immunocompetent patients. Doxycycline therapy was started within 48 h of presentation in 73% of transplant recipients and 78% of immunocompetent patients (p = 0.7). No patient died in either group. Ehrlichia infections can occur in transplant recipients who live in an endemic area. With prompt treatment, the infected transplant recipients in our study had similar, favorable outcomes compared to immunocompetent patients.     

Fatal intestinal tubercolosis in a uremic patient with a renal transplant

We report the case of a 52 year-old woman who was re-admitted to regular hemodialysis treatment because of chronic rejection of a renal transplant. She had received her mother's kidney 17 years before and had been treated for a long time with steroids, cyclosporin and azathioprine. In the last two months, fever had occurred, and persisted with the start of hemodialysis. She was admitted to our nephrology unit. Clinical, laboratory, radiological and endoscopic investigations did not lead to a precise diagnosis and broad-spectrum antimicrobial therapy failed. Some days later, a clear clinical picture of acute abdomen arose and at laparatomy a perforated jejunal ulcer was found. Histological investigation revealed caseous necrosis around the ulcer. Ziehl-Neelsen (ZN) stain showed a number of acid-fast resistant bacilli. Polymerase chain reaction (PCR) confirmed the presence of Mycobacterium tuberculosis. Specific therapy was started, but nevertheless the patient died a few days later, of septic shock. Our case shows that tuberculosis continues to be a significant, severe clinical problem in transplant recipients and is in fact still an important cause of death in these patients. The possibility of tuberculosis must be taken into account when a transplant patient shows fever and severe abdominal trouble with no clear evidence of another infection.     

Mycobacterial infection after liver transplantation

Tuberculosis occurred in 5 (1.2%) of 462 liver transplant recipients. De novo infection was assumed in 4 patients and a recurrent infection in 1. The clinical courses varied, from asymptomatic open lung tuberculosis to disseminated disease with cerebral tuberculoma and convulsions. Four patients survived with anti-tuberculous triple-drug therapy. Very few cases of tuberculosis after liver transplantation have been reported (4 patients in the medical literature and 5 patients in this paper). However, the incidence, course of infection, and outcome seem to be similar to those of tuberculosis in renal transplant recipients, approximately 150 cases of which are known.     

A case of fungal sepsis due to aspergillus spondylitis followed by cytomegalovirus infection in a renal transplant recipient

Although advances in immunosuppressive therapy have led to increased survival of renal transplant recipients, there are greater risks of developing infectious complications. Because of its rarity and the lack of medical awareness, aspergillus spondylitis is often misdiagnosed as tuberculous spondylitis, especially in its early stages. We report a case of aspergillus spondylitis in a renal transplant followed by cytomegalovirus (CMV) retinitis. CASE: A 59-year-old woman was admitted due to general weakness and abdominal discomfort. She had undergone renal transplantation 3 years previously. One month before admission, she was diagnosed with CMV retinitis and treated with IV ganciclovir. On admission, she suffered from lower abdominal pain. Colonoscopy revealed multiple circular or patchy ulcers with surrounding severe mucosal edema in the sigmoid colon findings consistent with intestinal tuberculosis. On hospital day 30, she complained of lower extremity paresthesia and weakness. An MRI of the spine revealed a well-demarcated paraspinal mass around the L2-4 body; tuberculous spondylitis was initially considered. But despite antituberculosis medication, the patient progressed to spastic paraparesis and sensory changes in both lower legs, requiring urgent surgical decompression. At hospital day 60, she suffered persistent fever and developed thrombocytopenia. Wound discharge continued and paraparesis became denser. A CT of the spine showed progression of the paraspinal abscess from the L2 body to the iliac crest. CT-guided psoas muscle drainage was performed. Fungal culture showed Aspergillus species. Despite antifungal therapy, the patient died after a prolonged hospital stay due to fungal sepsis and septic shock from aspergillosis.