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Purpose of Review This article reviews current epidemiologic trends, clinical presentations, and diagnostic strategies for central nervous system (CNS) infections in human immunodeficiency virus-negative (HIV) patients immunocompromised by their underlying disease or by receipt of immunosuppressive or immunomodulating therapies. Three patient groups are considered: (1) cancer patients; (2) hematopoietic or solid organ transplantation recipients; and (3) patients with autoimmune or inflammatory conditions requiring therapies that alter the host immune response. Recent Findings Clinical presentations, associated neuroimaging, and cerebrospinal fluid (CSF) abnormalities differ between immunocompromised and immunocompetent patients. Infections can trigger the emergence of neurotropic antibodies or inflammatory conditions due to treatment with cancer immunotherapies. Unbiased metagenomic assays to identify obscure pathogens help clinicians navigate the increasing range of conditions affecting the growing population of patients with altered immunity. Summary Awareness of clinical presentations and disease and drug-specific risks is important for early diagnosis and intervention in these often life-threatening infections and their noninfectious mimes.

PMID: 34037866 PMCID: PMC8150146