Transplant Infections

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The year 2003 marked not only the 50th anniversary of the discovery of the structure of DNA but also the 50th anniversary of the first description of invasive aspergillosis as an opportunistic infection. The publication of this report by Rankin in the British Medical Journal (1953;1:918-919.) ushered in a new era in the study of infectious diseases, that of the immunocompromised patient and opportunistic infections. A year later, syngeneic renal transplantation was achieved, with long-term survival, and bone marrow transplantation was first attempted in 1957. Thus began a new subspecialty -- transplantation medicine. The frequency and severity of numerous infections in the era before the common use of cyclosporine were such that transplantation was extremely risky, except in identical twins. The introduction of cyclosporine in 1980 and less-intensive immunosuppression abrogated the majority of these risks, and the modern era of transplantation was born. Approximately 500,000 transplantation procedures are undertaken each year around the world; slightly more than 50 percent are renal transplantations. (Figure) The diversity and complexity of the problems with infection inherent in transplant recipients are discussed in detail by the multiple authors of this excellent book. The editors of Transplant Infections have assembled a remarkable, international group of experts who describe the issues related to infection in solid-organ transplantation, hematopoietic stem-cell transplantation, and xenotransplantation. Epidemiology, clinical presentation, diagnostic approach, and therapy are addressed for each clinical syndrome and pathogen in each setting. This format can be duplicative; however, it is also important because the approach to management differs somewhat among types of transplantation. In some circumstances, surgical approaches are required, and these are also described in a scholarly but not overly technical way. The issues involved in reoperation are only touched on. Although several pediatric specialists have contributed to the book, no chapter is devoted solely to children. The practice of high-quality transplantation medicine is most certainly a multidisciplinary effort requiring a broad range of skills and knowledge. This book illustrates that requirement. The book uses the concepts of the "net state of immunosuppression" and its cousin, the "net state of tolerance," but perhaps because immune function is dynamic and difficult to measure with simple tests, there is little discussion of a practical means of assessing either, leaving the reader unsatisfied. The severity of complications is the chief reason why more allogeneic stem-cell transplantation procedures are not undertaken; better regimens for immunosuppression are required. Novel approaches, such as "mini transplantation," appear to avoid many of the early complications but may cause more trouble later. One of the challenges for the editors of this book was how to discuss the potential for infection after use of new biologic agents that may be used to treat rejection. Another was the recent introduction of two new antifungal agents -- caspofungin and voriconazole. There has been very little use of caspofungin in the context of transplantation because of a possible interaction with cyclosporine, and that cloud of uncertainty had not been lifted by the time this book went to press. With regard to voriconazole, a large randomized study of invasive aspergillosis confirmed its superiority to amphotericin B, but few solid-organ transplant recipients were included in the trial. There is limited experience in the use of voriconazole along with cyclosporine and tacrolimus (a combination of sirolimus and voriconazole is contraindicated). These ongoing issues meant it was difficult for the authors to be clear about the part these drugs may play in the management of transplant recipients who have fungal infections. None of the authors systematically address the issue of infections that can occur many years after transplantation. Anatomical abnormalities, aging organs, and long-standing rejection problems often transpire together to produce complex clinical situations. Examples include recurrent diverticulitis, lung abscesses, and recurrent cytomegalovirus disease in the context of chronic graft-versus-host disease. However, the principles of and management approaches to these problems are described in the book. Overall, this book is a hugely valuable resource to those who manage patients who are undergoing transplantation. David W. Denning, M.B., B.S.
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