Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy.

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease-specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at-risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Epstein-Barr virus infection and posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV) is an important pathogen in recipients of solid organ transplants (SOT). Infection with EBV manifests as a spectrum of diseases/malignancies ranging from asymptomatic viremia through infectious mononucleosis to posttransplant lymphoproliferative disorder (PTLD). EBV disease and its associated PTLD is more frequently seen when primary EBV infection occurs after transplant, a common scenario in pediatric SOT recipients. Intensity of immunosuppressive therapies also influences the risk for PTLD. The use of EBV viral load monitoring facilitates the diagnosis and management of EBV/PTLD as well as being used to inform preemptive therapy with reduction of immunosuppression, the most effective intervention for prevention of and treatment for PTLD. Other therapies, including the rituximab (anti-CD20 monoclonal antibody) and traditional chemotherapy, are also useful in the treatment of established PTLD. The future development of standards for management based on EBV viral load and routine monitoring of EBV-specific CTL responses promise further improvement in outcomes with EBV and PTLD.

Influenza vaccination in the organ transplant recipient: review and summary recommendations.

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Guidance on novel influenza A/H1N1 in solid organ transplant recipients.

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.

Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children.

Increased use of serial EBV-PCR monitoring after pediatric transplantation has led to the identification of asymptomatic patients who carry very high viral loads over prolonged periods. The significance of this high-load state is unknown. We speculated that this state may identify patients at high risk for development of late PTLD/lymphoma. We reviewed data on 71 pediatric heart recipients who had serial viral load monitoring since 1997. Chronic high-load state was defined as the presence of >16,000 genome copies/mL whole blood on > or =50% of samples over at least 6 months. Among 20 high-load carriers (eight following prior PTLD, seven with prior symptomatic EBV infection, five without previous EBV disease), 9 (45%) developed late-onset PTLD 2.5-8.4 years posttransplant (including with four Burkitt's lymphoma). Among 51 controls with low (n = 39) or absent (n = 12) loads, only 2 (4%; p < 0.001 absent/low vs. high load) developed late PTLD/lymphoma. By multivariable analysis, high-load carrier state (OR = 12.4, 95% CI 2.1-74.4) and prior history of PTLD (OR = 10.7, 95% CI 1.9-60.6) independently predicted late PTLD. A chronic high EBV-load state is not benign and is a predictor of de novo or recurrent PTLD.

CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients.

A randomized controlled trial of CMV-IVIG (cytomegalovirus-intravenous immunoglobulin) for prevention of Epstein Barr virus (EBV) posttransplant lymphoproliferative disease (PTLD) in pediatric liver transplantation (PLTx) recipients was begun in Pittsburgh and subsequently expanded to four additional sites. Protocol EB viral loads were obtained in a blinded fashion; additional loads could be obtained for clinical indications. Patients were followed for 2 years post-LTx. Eighty-two evaluable patients (39 CMV-IVIG, 43 placebo) developed 18 episodes of EBV disease (7 CMV-IVIG, 11 placebo) including nine cases of PTLD (three CMV-IVIG, six placebo). No significant differences were seen in the adjusted 2-year EBV disease-free rate (CMV-IVIG 79%, placebo 71%) and PTLD-free rate (CMV-IVIG 91%, placebo 84%) between treatment and placebo groups at 2 years (p > 0.20). The absence of significant effect of CMV-IVIG may be explained by a lack of efficacy of the drug or limitations of sample size.

Nonhuman primate herpesviruses: importance for xenotransplantation.

Herpesviruses are found throughout the animal kingdom. Members of this family share properties including a highly orchestrated system of transcription, destruction of the host cell by active viral replication and an ability to persist in the host in a latent form. Human herpesviruses have all been implicated in causing substantial disease after allotransplantation. Often transmission of these viruses has been through the donor organ or blood products. Analogous species of herpesviruses exist in nonhuman primates. Accordingly, concern regarding the risk of their transmission and disease exists with xenotransplant procedures. This chapter reviews herpesviruses of nonhuman primates and their potential implication for causing disease after xenotransplantation.

Detection of infectious baboon cytomegalovirus after baboon-to-human liver xenotransplantation.

Xenotransplantation is considered to be a solution for the human donor shortage. However, there is a potential risk of transmitting animal infections from the transplanted organ. The known transmissibility and clinical significance of human cytomegalovirus (HCMV) infection after allotransplantation led us to evaluate whether baboon cytomegalovirus (BCMV) transmission could occur after a baboon-to-human liver xenotransplant. We examined serial blood samples from a baboon liver recipient and isolated replication-competent CMV-like agents on days 29, 36, and 42 after xenotransplantation. BCMV and HCMV DNAs were detected in the day 29 isolate, while only HCMV DNA was detected in the other isolates. This is the first report of detecting a replication-competent virus from a source animal after xenotransplantation and is a concern with regard to potential zoonotic transmission to others.

The management of Epstein-Barr virus associated post-transplant lymphoproliferative disorders in pediatric solid-organ transplant recipients.

Despite a growing understanding of the pathogenesis and spectrum of Epstein-Barr virus (EBV) and EBV-associated post-transplant lymphoproliferative disease (PTLD) in organ transplant recipients, the optimal management of this complication remains controversial. The absence of comparative data evaluating potential therapeutic strategies explains the lack of uniformly accepted guidelines for the management of PTLD. The purpose of this review is to provide an overview of potential therapies and offer a set of guidelines for the management of EBV-associated PTLD in children.

Non-aspergillus allergic bronchopulmonary mycosis in a pediatric patient with cystic fibrosis.

This article describes a child with cystic fibrosis (CF) and allergic bronchopulmonary mycosis caused by Tricosporon beigelii. An 11-year-old boy with CF failed to respond to conventional treatment for a pulmonary exacerbation. Bronchial washings contained copious budding yeast forms, subsequently identified as T beigelii. Total serum immunoglobulin E was elevated and precipitating antibodies to T beigelii were positive. Together these findings support the diagnosis of allergic bronchopulmonary mycosis. The patient improved with antifungal therapy and systemic glucocorticoid therapy. The pathologic potential of yeast in the airways of patients with CF is unclear. The diagnosis of non-Aspergillus allergic bronchopulmonary mycosis requires a high degree of suspicion and has potentially important implications for the management of patients with CF.

Amplification of simian retroviral sequences from human recipients of baboon liver transplants.

Investigations into the use of baboons as organ donors for human transplant recipients, a procedure called xenotransplantation, have raised the specter of transmitting baboon viruses to humans and possibly establishing new human infectious diseases. Retrospective analysis of tissues from two human transplant recipients with end-stage hepatic disease who died 70 and 27 days after the transplantation of baboon livers revealed the presence of two simian retroviruses of baboon origin, simian foamy virus (SFV) and baboon endogenous virus (BaEV), in multiple tissue compartments. The presence of baboon mitochondrial DNA was also detected in these same tissues, suggesting that xenogeneic "passenger leukocytes" harboring latent or active viral infections had migrated from the xenografts to distant sites within the human recipients. The persistence of SFV and BaEV in human recipients throughout the posttransplant period underscores the potential infectious risks associated with xenotransplantation.

Xenotransplant-associated infections.

Xenotransplantation is considered increasingly as a solution to the current shortage of human organs for allotransplantation. In addition, it is being investigated as a treatment for a number of other diseases such as Parkinson's disease, diabetes mellitus, and acquired immunodeficiency disease. The potential risk of novel zoonotic infections is a concern associated with these procedures. Accordingly, the role of animal microbial agents must be critically examined. This review examines the concerns and proposed mechanisms for xenogeneic infections and details what is known and what still needs to be learned as the field of xenotransplantation progresses. Emphasis is placed on microbial agents of baboons and swine because they are currently the most common species considered as donor sources for xenotransplantation.

Distinguishing baboon cytomegalovirus from human cytomegalovirus: importance for xenotransplantation.

The severe shortage of human organs for transplantation is the driving force behind xenotransplant research. Nonhuman primates, particularly baboons, are potential sources of organs and tissues. Human cytomegalovirus (HCMV) is the most common donor-associated infection after allotransplantation. Baboon cytomegalovirus (BCMV) is endemic in baboon populations and therefore is a potential cause of donor-associated disease after xenotransplantation. Accordingly, the ability for BCMV to grow in human cells was determined and a sensitive method to distinguish BCMV from HCMV was developed. Human fibroblasts were permissive for BCMV, isolates exhibited cytopathology characteristic of HCMV, and herpesvirus-like virions were observed by electron microscopy. BCMV and HCMV could be distinguished by restriction fragment length polymorphism patterns and by polymerase chain reaction with primers targeting the BCMV major immediate-early gene promoter. These methods can be used to evaluate BCMV pathogenicity in laboratory and clinical xenotransplant trials.