Tuberculosis in renal transplant recipients

Tuberculosis (TB) is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post-transplantation period. A retrospective study of all renal transplantation patients from 1989 to date was conducted. This study tried to examine the prevalence, course, and outcome of TB in renal transplant recipients. A comparison with the occurrence of TB in other modalities of renal replacement therapy was also made. We also discussed the treatment protocols for TB in this group of patients. No difference in the prevalence, age, or male/female ratio of TB was seen among the 3 modes of renal replacement therapy. TB of the lung was the more favored site of infection in patients on hemodialysis (77.3%), when compared with those on CAPD (30%) and renal transplant recipients (33.3%). In renal transplant recipients, no deaths occurred due to TB. In 7 patients there was co-infection with cytomegalovirus and in 3 patients there was Aspergillus lung infection.     

Fungal pneumonias in transplant recipients

Fungi are ubiquitous in the environment. Opportunistic fungal pneumonias in the immunocompromised host continue to increase most commonly due to Aspergillus sp. Affected patients are usually hematopoietic stem cell and lung transplant recipients. Clinical presentation is protean, and the diagnosis is challenging. Culture of respiratory specimens has limited utility. The detection of circulating fungal antigens and DNA seems promising, but more studies are needed. Value of prophylactic strategies or preemptive therapy remains contentious. New antifungal drugs for managing invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles.     

Infections in liver transplant recipients

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications.In this article,we review the contemporary state of infectious complications during the post-operative period,with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.Bacteria,and less commonly Candida infections,remain the predominant pathogens during the immediate post-operative period,especially during the first month,and infections caused by drugresistant strains are emerging.Infections caused by cytomegalovirus and Aspergillus sp.present clinically during the"opportunistic"period characterized by intense immunosuppression.As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed,one potential adverse effect is an increase in certain infections.Hence,it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk,local antimicrobial resistance patterns,and surveillance.A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.     

Lipids in liver transplant recipients

Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.     

Strongyloides infections in transplant recipients

Solid organ transplant recipients can experience serious disease and death from infection due to the parasitic roundworm Strongyloides stercoralis. This parasite lives in soil contaminated with human feces. Domestic dogs and cats may be another reservoir. Larvae can penetrate the skin, are carried hematogenously to the lungs, migrate up the bronchial tree, and then can be passed to the upper small intestine. Autoinfection occurs in the setting of immunosuppression when invasive larvae penetrate the gut wall and cause disseminated infection. Polymicrobial sepsis is sometimes seen due to enteric organisms adhering to the parasite. Transplant recipients are at highest risk during the first 3 months posttransplant. Many organ systems may be affected. Pulmonary symptoms include cough, wheezing, sputum production, dyspnea, hemoptysis, tachypneas, and pleuritic pain. Hyperinfection, an augmentation of the normal skin-lung-intestine life cycle, occurs in roughly two-thirds of infected transplant recipients, with dissemination in the remainder. Diagnosis is made primarily by examination of the stool or intestinal secretions for ova and parasites. Occasionally, parasites are noted in the sputum. New serologic tests show promise. The parasite may remain in the host for over 25 years before immunosuppression causes either dissemination or hyperinfection. Thiabendazole given for 3 to 7 days is the treatment of choice for organ transplant recipients. Repeat courses may be needed to eradicate infection.     

Fungal pneumonia in transplant recipients

Fungal pneumonia is an infrequent but devastating complication of solid organ transplantation. The suspicion of fungal pulmonary infections caused by the dimorphic fungi is based on particular knowledge about the recipient's past or present residence in an endemic area. Some fungi, such as Cryptococcus neoformans, Candida sp and Mucor sp are associated with concomitant diabetes mellitus. The level of immunosuppressive therapy is also a major predisposing factor. For some fungi, such as Coccidioides immitis and C neoformans, serologic tests may assist in diagnosis. For aspergillus, Candida sp and Mucor sp culture evidence is not sufficient to determine pulmonary involvement since these fungi may be nonpathogenic saprophytes. Histopathologic proof is required. In patients with abnormal host defenses, treatment of fungal pneumonia is complex. In solid organ transplant recipients it is made more difficult by drug interactions with cyclosporine. Amphotericin B exhibits synergistic nephrotoxicity with cyclosporine and ketoconazole competes with cyclosporine for hepatic metabolism in an unpredictable manner that may result in increased cyclosporine toxicity.     

Immunisations in solid-organ transplant recipients

Solid-organ transplant recipients are at increased risk of various infectious diseases, some of which are vaccine preventable mmunisations are among the most efficient interventions available. Solid-organ tranplant recipients would greatly benefit from effective immunisations, provided the recommendations are based on a careful risk-benefit analysis in which the effectiveness of the vaccine is weighed against possible adverse reactions, including graft rejection. In this review, we summarise the data from studies on relevant immunisations in solid-organ transplant recipients. The major issues are the immunogenicity and safety of immunisations, the factors associated with poor immune response, and recommendations for immunisation schemes.     

Hyperhomocysteinaemia in heart transplant recipients

The aim of this study was to determine the prevalence of hyperhomocysteinaemiain cardiac transplant recipients, Three groups of subjects werestudied: 27 heart transplant recipients, 14 to 63 months (mean=36.5)after transplantation; 10 patients with moderate chronic renalinsufficiency without clinical evidence of vascular disease;17 apparently healthy individuals. Twenty-five out of 27 transplantedpatients had a coronaroangiography within 6 months of homocysteinemeasurement. Plasma homocysteine was measured both while thesubject was fasting (tO) and 6 h after administration of 0.1g. kg^–1 of methionine (t6). Hyperhomocysteinaemia waspresent in 14127 fasting transplanted patients and after methionineloading. Mean plasma levels of homocysteine at tO were higher(P=0.03) in transplanted heart recipients (15.4 ± 7µmol.l^–1 than in the renal patients (9.9±5µmol.l^–1) despite similar mean plasma creatinin. In eight transplantedpatients with angiographic coronary abnormalities of the cardiacgraft, homocysteinaemia was at tO 17.1 ±9 µmol.l^–1 and at t6 47.8 ±25 µmol. l^–1. In17 transplanted patients with angiographically normal coronaryarteries, plasma homocysteine levels were at tO, 13.2 ±4µmol.l^–1 and at t6, 46.8±25µmol. l^–1. We conclude that hyperhomocysteinaemia is common in transplantedheart recipients, and partly related to renal insufficiency.No correlation was found between hyperhomocysteinaemia and angiographicevidence of coronary atherosclerosis of the graft, but the populationof the study was possibly too small to establish this correlation.     

Tuberculosis in renal transplant recipients

Tuberculosis (TB) has been described in kidney transplant recipients as an infection with predominantly pulmonary involvement. We report the impact of TB in kidney transplantation. Clinical records of adult kidney recipients, transplanted between 1 January 1986 and 31 December 1995 were analyzed for sex, age, graft origin, immunosuppressive therapy, TB sites, diagnostic methods and concomitant infections. Annual incidence, mean time of onset, relation to rejection treatment, tuberculin skin test (PPD) and outcome were analyzed. Patients with a history of TB or graft loss in the first month were excluded. TB was diagnosed in 14 of 384 (3.64%). Mean age at transplantation was 35 years. Twelve of these received the graft from a living donor. All had triple immunosuppression with cyclosporine. Ten had pulmonary TB, three extrapulmonary infection and one disseminated disease. In 13 cases an invasive diagnostic procedure was performed. Mycobacterium tuberculosis cultures were positive in all cases; microscopy revealed acid-fast bacilli (AFB) in 6, and adenosine deaminase was elevated in CSF and pleural effusion in 2. Annual incidence varied from 0% to 3.1%. At the time of TB presentation 8 patients had other concomitant infections (cytomegalovirus, nocardia, Pneumocystis carinii, disseminated herpes simplex virus). Median time of onset was 13 months. Diagnostic results became available post-mortem in 2 cases, and one had TB in a failing allograft. TB was treated with 4 drugs including rifampin in 10 patients. Cyclosporine was discontinued in one, lowered in one and increased in 8. During treatment 5 patients had rejection episodes. At 1 year, graft survival was 72.7% and patient survival 90.9%. TB was more prevalent when recipient and donor were both PPD positive. In summary: although TB is a growing threat in the transplant setting, early and aggressive diagnosis with meticulous monitoring of immunosuppression allows a successful outcome for both patient and graft. Optimal prophylaxis guidelines have yet to be completely defined.     

Legionellosis in heart transplant recipients

Summary We report on 20 cases of Legionnaires' Disease (LD) in heart transplant recipients during a two-year study. The overall frequency in this setting amounts thus to 17% (20/115). In contrast, the frequency of legionellosis in postoperative cardiac patients without immunosuppression was only 4.7% (4/84). Legionellosis was diagnosed by culture and/or antibody detection in ten (20) as well as by the detection of urinary antigens in all 20 patients. Only nine (20) patients developed pneumonia, whereas five patients presented with nodular infiltrates. The remaining six patients had moderate fever with no signs of lung infection. In contrast to the majority of patients with other underlying diseases, antigen shedding lasted for long periods in most transplant patients. In high risk patients the application of conventional diagnostic methods together with regular urinary antigen testings (i. e. twice a week) may be advantageous for the early diagnosis of Legionella infection.

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Legionärskrankheit bei Herztransplantierten

Zusammenfassung Wir berichten über 20 Erkrankungen von Legionärskrankheit bei Herztransplantierten während einer Zweijahresstudie. Die Erkrankungshäufigkeit betrug in dieser Patientengruppe 17% (20/115). Im Gegensatz dazu konnte bei herzoperierten Patienten ohne immunsuppressive Therapie nur eine Erkrankungshäufigkeit von 4,7% (4/84) festgestellt werden. Die Diagnose der Legionellose konnte kulturell und/oder durch Antikörpernachweis bei zehn (20) Patienten sowie durch Antigennachweis im Urin bei allen 20 Patienten gestellt werden. Nur neun von 20 Patienten erkrankten an einer Pneumonie, während fünf Patienten pulmonale Rundherde entwickelten. Die verbleibenden sechs Patienten zeigten Fieber ohne Hinweis auf eine Lungenbeteiligung. Im Gegensatz zur Mehrzahl der Legionellosepatienten mit anderen Grundkrankheiten, war die Antigenausscheidung bei den meisten Transplantationspatienten verlängert. Bei Risikopatienten kann eine regelmäßige (zweimal wöchentlich) Urinantigentestung — neben der konventionellen Legionellen-Diagnostik — für die Früherkennung der Legionellose von Vorteil sein.

     

Cytomegalovirus pneumonia in transplant recipients

The incidence of cytomegalovirus CMV pneumonia has been reduced by routine antiviral prophylaxis in susceptible populations. Many of the complications of this infection are caused by indirect effects of the virus, including acute and chronic graft rejection, graft-versus-host disease, and superinfection by other viruses, bacteria and fungi. Distinction must be made between viral secretion and invasion. Invasive procedures are often required for the optimal management of such infections. The use of sensitive and quantitative assays have greatly improved the outcomes of CMV infection.     

Vaccines for transplant recipients

Immune dysregulation and immunosuppression regimens impact on the ability of transplant recipients to respond to immunizations. The distinct challenges of immunizations to benefit stem cell transplant recipients and solid organ transplant recipients are discussed separately. Recommended vaccines for stem cell transplant recipients and solid organ transplant candidates are suggested. New approaches to consider to enhance immune responses of transplant recipients are discussed.