Infections in Solid-Organ Xenotransplantation: A Scoping Review

Résumé fourni par la source

Background Solid-organ xenotransplantation from genetically modified pigs has emerged as a potential strategy to address the persistent shortage of human organs. Advances in genetic engineering, immunosuppression, organ preservation, and perioperative care have enabled progression from pig-to-non-human-primate models to experimental solid organ xenotransplantation in human recipients [1], [2]. Infectious risk remains a major barrier to broader clinical implementation. Xenograft recipients may develop conventional opportunistic and healthcare-associated infections related to surgery, intensive care, invasive devices, and profound immunosuppression. In addition, microorganisms carried by the donor pig may be transmitted through the graft, including recognized zoonotic agents, porcine-specific pathogens, endogenous retroviruses, and previously unrecognized organisms [3], [4]. The clinical significance of porcine microorganisms is variable. Some may cause systemic infection, whereas others may replicate mainly within the graft and contribute to inflammation, graft dysfunction, or graft loss. Porcine cytomegalovirus, more accurately termed porcine roseolovirus, is the best-described example and has been associated with reduced xenograft survival in preclinical models and detected after the first pig-to-human heart xenotransplantation [1], [5]. Interpretation of microbiological findings is challenging because detection of microbial nucleic acids does not necessarily establish replication, tissue invasion, donor-to-recipient transmission, or clinical disease. Reliable assessment may require serial sampling, analysis of pre-transplant specimens, tissue-based diagnostics, and genomic comparison between microorganisms detected in the donor, graft, and recipient [4], [5]. Several narrative reviews and expert recommendations have addressed infectious hazards, donor screening and recipient surveillance in xenotransplantation [5], [6], [7]. However, the primary evidence remains fragmented across different organs, recipient species, study designs, diagnostic methods, and definitions of infection. A scoping review is therefore needed to systematically map infectious events reported in solid-organ xenotransplantation, distinguish observed events from theoretical risks, and identify gaps in prevention, diagnosis, surveillance, and reporting. Aims Primary Aim To systematically map the infectious and microbiological events reported in preclinical and clinical pig-to-primate solid-organ xenotransplantation. Secondary Aims The review will aim to: 1. identify the microorganisms detected in donor pigs, xenografts, and recipients; 2. distinguish donor-derived infections from recipient-derived reactivations, opportunistic infections, and healthcare-associated infections; 3. classify infectious events according to the strength of evidence supporting donor-to-recipient transmission; 4. describe the diagnostic methods used to detect and investigate infectious events; 5. summarize donor-screening, antimicrobial-prophylaxis, and recipient-surveillance strategies; 6. describe the management and clinical outcomes of reported infections; 7. assess the association between infectious events and xenograft dysfunction, graft loss, or recipient mortality; 8. identify gaps in current evidence, definitions, surveillance practices, and reporting standards. Primary review question What infectious and microbiological events have been reported in preclinical and clinical pig-to-primate solid-organ xenotransplantation, and how were they prevented, detected, classified, managed, and associated with recipient and xenograft outcomes? Secondary review questions The review will also address the following questions: - Which porcine microorganisms have been detected in donor pigs, transplanted organs, or recipients? - Which microorganisms have been associated with confirmed or probable donor-derived transmission? - Which infectious events were confined to the xenograft, and which resulted in systemic recipient infection? - Which conventional human opportunistic or healthcare-associated infections have been reported? - Which diagnostic techniques have been applied, and how have positive findings been interpreted? - What prophylactic and therapeutic interventions have been administered? - What were the consequences for xenograft function, xenograft survival, and recipient survival? PCC framework Population The review will include: - living human recipients of porcine solid-organ xenografts; - human decedents or brain-dead individuals who received porcine organs in experimental xenotransplantation studies; - non-human primates that received vascularized solid organs from porcine donors; - porcine donors when microbiological findings are directly linked to an included xenotransplantation procedure. Concept The central concept will be infectious and microbiological events associated with solid-organ xenotransplantation, including: - confirmed or probable donor-derived infections; - potential xenozoonotic transmission; - detection or replication of porcine microorganisms; - graft-restricted microbial replication; - reactivation of latent human infections; - opportunistic infections; - healthcare-associated infections; - surgical-site infections; - device-associated infections; - microbiologically relevant colonization or contamination; - donor microbiological screening; - antimicrobial prophylaxis; - recipient microbiological surveillance, - infection diagnosis, treatment, and outcomes. Context The review will consider preclinical and clinical transplantation of vascularized solid organs from pigs to non-human primates or humans, including: kidney/heart/liver/lung xenotransplantation and other vascularized porcine solid organs, should eligible studies be identified. Studies involving isolated cells, cellular products, islets, corneas, skin, bone, heart valves, bioengineered tissues, or non-vascularized tissues will not be included. Eligibility criteria Inclusion criteria The review will include original studies that: - report at least one pig-to-non-human-primate or pig-to-human solid-organ xenotransplantation procedure; - involve a vascularized porcine organ; - report microbiological screening, microbial detection, infection, transmission, prophylaxis, surveillance, treatment, or infection-related outcomes; - describe clinical, pathological, molecular, serological, microbiological, or genomic evidence relevant to an infectious event; - provide data from living human recipients, human decedent models, or non-human-primate recipients; - report donor-pig microbiological findings that can be linked directly to a transplanted organ or recipient; - are published as full original research articles, case reports, case series, cohort studies, experimental studies, or diagnostic investigations. Exclusion criteria The review will exclude: - studies of xenogeneic cells, pancreatic islets, tissues, skin, corneas, heart valves, bone, or tissue-engineered products; - non-vascularized xenotransplantation procedures; - studies using donor species other than pigs; - purely in vitro studies without a direct link to an in vivo solid-organ xenotransplantation procedure; - studies of infectious diseases in conventional pig farms without a direct connection to xenotransplantation donor programs or procedures; - studies addressing only immunology, rejection, coagulation, or surgical outcomes without microbiological or infectious-disease data; - publications discussing exclusively theoretical infectious risks without reporting original data. Relevant reviews, position papers, regulatory documents, and guidelines may be used to identify additional primary studies and to contextualize the findings but will not be included in the main evidence map. Methods The review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews [8] and reported according to the Preferred Reporting Items for Systema

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.