Increasingly potent immunosuppressive agents have dramatically reduced the incidence of rejection of transplanted organs while increasing susceptibility to opportunistic infections and cancer. This ...article reviews general concepts for the management of transplantation-associated infections and discusses recent advances and challenges.
Increasingly potent immunosuppressive agents have increased susceptibility to opportunistic infections. This article reviews general concepts for the management of transplantation-associated infections and discusses recent advances and challenges.
Increasingly potent immunosuppressive agents have dramatically reduced the incidence of rejection of transplanted organs while increasing patients' susceptibility to opportunistic infections and cancer.
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At the same time, patterns of opportunistic infections after transplantation have been altered by routine antimicrobial prophylaxis for
Pneumocystis carinii
(also called
P. jirovecii
) and cytomegalovirus. These patterns have also been altered by the emergence of new clinical syndromes (e.g., polyomavirus type BK nephropathy) and by infections due to organisms with antimicrobial resistance. New quantitative molecular and antigen-based microbiologic assays detect previously unrecognized transplantation-associated pathogens such as lymphocytic choriomeningitis virus. These assays are used in . . .
Hurdles exist to clinical xenotransplantation including potential infectious transmission from nonhuman species to xenograft recipients. In anticipation of clinical trials of xenotransplantation, the ...associated infectious risks have been investigated. Swine and immunocompromised humans share some potential pathogens. Swine herpesviruses including porcine cytomegalovirus (PCMV) and porcine lymphotropic herpesvirus (PLHV) are largely species‐specific and do not, generally, infect human cells. Human cellular receptors exist for porcine endogenous retrovirus (PERV), which infects certain human‐derived cell lines in vitro. PERV‐inactivated pigs have been produced recently. Human infection due to PERV has not been described. A screening paradigm can be applied to exclude potential human pathogens from “designated pathogen free” breeding colonies. Various microbiological assays have been developed for screening and diagnosis including antibody‐based tests and qualitative and quantitative molecular assays for viruses. Additional assays may be required to diagnose pig‐specific organisms in human xenograft recipients. Significant progress has been made in the evaluation of the potential infectious risks of clinical xenotransplantation. Infectious risk would be amplified by intensive immunosuppression. The available data suggest that risks of xenotransplant‐associated recipient infection are manageable and that clinical trials can be performed safely. Possible infectious risks of xenotransplantation to the community at large are undefined but merit consideration.
Fishman reviews approaches for the mitigation of infectious risk associated with clinical xenotransplantation from swine, including meticulous screening of source animals and minimization of exogenous immunosuppression.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal ...infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim‐sulfamethoxazole (TMP‐SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO2 < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β‐d‐glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP‐SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6‐12 months post–transplant, preferably with TMP‐SMX.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Identifying pathogens using traditional culture systems for bacteria and fungi, even when supplemented by use of organism-specific protein or molecular diagnostics, is limited by requiring comparison ...with known human pathogens stored in datasets. Among the challenges of NGS have been costs (although they have been decreasing), detection of sequences of unknown clinical significance, and gaps in databank records for many viral and other species for comparison with detected sequences, notably among nonhuman species. ...new zoonotic exposures or recombinant species may be unrecognized or masked by any of numerous unknown nucleic acids. Dr. Fishman is professor of medicine at Harvard Medical School, director of the Transplant Infectious Diseases and Compromised Host Program at Massachusetts General Hospital (MGH), and associate director of the MGH Transplant Center.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The “net state of ...immune suppression” is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual’s ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.
Worldwide collaboration will be required to define viral pathogenesis, correlates of immunity, and biomarkers for progressive infection to optimize clinical care and to interrupt pandemic spread of ...SARS‐CoV‐2.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Xenotransplantation is a potential solution to the shortage of transplantable human organs. The author discusses the benefits and infectious risks of xenotransplantation and possible protocols for ...future use.
Pneumocystis jiroveci Fishman, Jay A
Seminars in respiratory and critical care medicine,
02/2020, Volume:
41, Issue:
1
Journal Article
Peer reviewed
remains an important fungal pathogen in a broad range of immunocompromised hosts. The natural reservoir of infection remains unknown.
Pneumonia (PJP) develops via airborne transmission or ...reactivation of inadequately treated infection. Nosocomial clusters of infection have been described among immunocompromised hosts. Subclinical infection or colonization may occur. Pneumocystis pneumonia occurs most often within 6 months of organ transplantation and with intensified or prolonged immunosuppression, notably with corticosteroids. Infection is also common during neutropenia and low-lymphocyte counts, with hypogammaglobulinemia, and following cytomegalovirus (CMV) infection. The clinical presentation generally includes fever, dyspnea with hypoxemia, and nonproductive cough. Chest radiographic patterns are best visualized by computed tomography (CT) scan with diffuse interstitial processes. Laboratory examination reveals hypoxemia, elevated serum lactic dehydrogenase levels, and elevated serum (1→3) β-D-glucan assays. Specific diagnosis is achieved using respiratory specimens with direct immunofluorescent staining; invasive procedures may be required and are important to avoid unnecessary therapies. Quantitative nucleic acid amplification is a useful adjunct to diagnosis but may be overly sensitive. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early in the clinical course; aggressive reductions in immunosuppression may provoke immune reconstitution syndromes. Pneumocystis pneumonia (PJP) prophylaxis is recommended and effective for immunocompromised individuals in the most commonly affected risk groups.
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