Title : Opportunistic central nervous system infections and transplant rejection in solid organ transplant recipients: A scoping review
Abstract:
Background: Opportunistic central nervous system (CNS) infections are uncommon but devastating complications of solid organ transplantation (SOT). Although individual pathogens are relatively rare, CNS infections collectively account for up to 10% of transplant-associated complications and carry disproportionate morbidity and mortality. Management is further complicated by atypical clinical presentations in immunosuppressed hosts and the absence of standardized guidelines for balancing antimicrobial therapy with immunosuppression reduction. While prior studies have focused on short-term neurological outcomes following CNS infection, the impact of immunosuppressive modulation on graft rejection and longer-term outcomes remains poorly characterized.
Objective: To map the existing literature describing transplant rejection in the setting of opportunistic CNS infections among SOT recipients, with emphasis on pathogen profiles, immunosuppressive management strategies, and clinical outcomes.
Methods: A scoping review was conducted in accordance with the Arksey and O’Malley framework, refined by the Joanna Briggs Institute, and is reported in accordance with the PRISMA Extension for Scoping Reviews (Figure 1). MEDLINE (PubMed), EMBASE, and Scopus were searched from inception through October 2025. Eligible studies included human experimental and observational designs (randomized trials, cohort studies, case series, case reports, and reviews) describing both CNS opportunistic infection and transplant rejection in SOT recipients of any age. Two reviewers independently screened studies and extracted data using a standardized form. Findings were synthesized narratively using the Population–Concept–Context framework.
Results: Of 1,008 records identified, 26 studies met inclusion criteria. Across cohort and case–control studies of opportunistic CNS infections in SOT recipients, infection and rejection were closely linked temporally and therapeutically. CNS infections often occurred years after transplantation, frequently following intensified immunosuppression for rejection. In large toxoplasmosis series, 35–70% of patients had prior rejection treated with high-dose corticosteroids, with diagnoses often delayed months to years; mortality remained high, particularly with delayed recognition. Immunosuppressive regimens—including calcineurin inhibitors, antimetabolites, and corticosteroids—were consistently associated with pathogen-specific CNS infections. High calcineurin inhibitor levels and recent corticosteroid exposure were independent risk factors. Reduction of immunosuppression during infection management was followed by acute rejection in approximately 25–35% of patients within one year. Neurologic outcomes ranged from full recovery to permanent neurologic injury and graft dysfunction, with diagnostic delays common due to overlapping features of rejection and infection.
Conclusions: The literature describing transplant rejection in the context of opportunistic CNS infections is limited and heterogeneous. Significant gaps exist regarding standardized immunosuppressive management, and long-term graft and neurological outcomes. These findings highlight the need for prospective studies and consensus-based guidance to optimize outcomes in this high-risk population.
