Cryptococcal Immune Reconstitution Inflammatory Syndrome: a Paradoxical Response to a Complex Organism

AbstractPurpose of reviewTo describe the host-pathogen factors that impact the management of cryptococcal meningitis (CM) in immunosuppressed patients that lead to the development of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS).Recent findingsThe pre-screening of HIV-infected patients in resource-poor countries with the lateral flow cryptococcal antigen assay could prevent C-IRIS. Delaying ART by 4  weeks is associated with improved survival and recommended by guidelines; this approach remains controversial in wealthier areas as there is limited data. A 5-flucytosine-based combination regimen and avoidance of corticosteroids on initial treatment improve cryptococcus clearance from cerebrospin al fluid. New monoclonal antibodies and kinase inhibitors that alter the immune system, such as ibrutinib and ruxolitinib, have been associated with cryptococcosis.SummaryIt is important to recognize that restoration of the immune system, regardless of the host, can lead to C-IRIS. Prevention of C-IRIS by pre-screening patients, delaying antiretroviral therapy, and using a 5-flucytosine backbone regimen are important in the management of meningitis. C-IRIS management requires the exclusion of therapeutic failure or antifungal resistance. Further research is needed on whether delaying antiretroviral therapy by 4  weeks is necessary in wealthier countries to improve C-IRIS outcomes, and whether C-IRIS can be seen with new immunologic agents.
Source: Current Treatment Options in Infectious Diseases - Category: Infectious Diseases Source Type: research

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Abstract Cryptococcosis is a severe fungal disease causing 220,000 cases of cryptococcal meningitis yearly. The etiological agents of cryptococcosis are taxonomically grouped into at least two species complexes belonging to the genus Cryptococcus. All of these yeasts are environmentally ubiquitous fungi (often found in soil, leaves and decaying wood, tree hollows, and associated with bird feces especially pigeon guano). Infection in a range of animals including humans begins following inhalation of spores or aerosolized yeasts. Recent advances provide fundamental insights into the factors from both the pathogen an...
Source: Advances in Genetics - Category: Genetics & Stem Cells Authors: Tags: Adv Genet Source Type: research
AbstractPurpose of ReviewEvaluate the epidemiology, risk factors, pathophysiology, and clinical outcomes of cryptococcal infections in patients with advanced liver disease or liver transplantation.Recent FindingsCryptococcal infections in patients with advanced liver disease (ALD) are uncommon but associated with high mortality. Less than 10% of patients in a prospective study of non-HIV-infected cryptococcal meningitis patients had ALD. Significantly, fever was uncommon, resulting in delays in diagnosis. Modalities for diagnosing cryptococcal infections include the rapid lateral flow cryptococcal antigen (CrAg) assay from...
Source: Current Fungal Infection Reports - Category: Infectious Diseases Source Type: research
In this study, we investigated the role of IL-25, one of the type 2-inducing cytokines produced by epithelial cells, in contributing to the pathogenesis of cryptococcosis. We found that pulmonary but not systemic infection with a high-virulence strain of C. neoformans significantly induced pulmonary IL-25 expression in the lungs but not brains. In response to pulmonary infection, mice deficient in the surface IL-17 receptor B, a component of the IL-25R, exhibited improved survival with a decreased brain fungal burden. The absence of IL-25R signaling diminished the type 2 and enhanced the type 1 immune response that directe...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research
Disseminated cryptococcosis is a well-characterized complication in immunocompromised patients with cryptococcal pneumonia or meningitis; however, isolated cryptococcal osteomyelitis is a rare entity that occu...
Source: BMC Infectious Diseases - Category: Infectious Diseases Authors: Tags: Case report Source Type: research
We would like to make some comments on the interesting article by Yokose et al describing a case of cryptococcal meningitis presenting with lower leg cellulitis in a recipient of a kidney transplant.1 The authors state that their case “highlights a good example of an anchoring bias,” but, in our opinion, it could be better defined as an example of overlooked and delayed diagnosis of cryptococcosis for the following reasons: 1) the patient was an immunocompromised host (a solid organ transplant [SOT] recipient receiving immuno suppressive treatment), and the failure of empiric antibiotic treatment should have su...
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Letter Source Type: research
Abstract Clinical worsening or new manifestation of cryptococcal disease following initiation of anti-retroviral therapy (ART) in an HIV patient is a hallmark of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS). However, it can be difficult to distinguish IRIS from worsening or new infection. Here, we present a case of severe C-IRIS involving multiple cerebellar, spinal, and intradural abscesses and spinal arachnoiditis 7 months after ART initiation in an AIDS patient with uncertain prior ART compliance. He had multiple prior episodes of cryptococcal meningitis with complications necessitating ven...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
Background: The prevalence of different underlying cryptococcal diseases in human immunodeficiency virus (HIV)-infected patients screened positive for cryptococcal antigenemia and the association between cryptococcal diseases and serum cryptococcal antigen (CrAg) titers were understudied.Methods: HIV-infected patients with CD4
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
ConclusionsCryptococcosis develops in various organs. Typical radiological manifestation accompanied with positive serum CrAg provides helpful clues for the diagnosis. Lumbar puncture is a critical diagnostic method to distinguish CM. The accumulated dose of GC is associated with cryptococcosis in patients with CTD.Key Points•Pulmonary cryptococcosis is suspected if pulmonary nodules adjacent to the pleura are present, with serum CrAg positive.•Cryptococcal meningitis has insidious onset and the diagnosis mainly depends on lumber puncture.•Cryptococcal sepsis is not rare and needs timely blood culture in suspected patients.
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Conclusions and significanceFluconazole MIC50 and MIC90 values were two-fold higher in 2017 compared to 2007 –2008. Although there are no breakpoints, higher fluconazole doses may be required to maintain efficacy of standard treatment regimens for cryptococcal meningitis.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Early cryptococcal disease can be detected via circulating antigen in blood before fulminant meningitis develops, when early antifungal therapy improves survival. Two semiquantitative cryptococcal antigen (CrAg) lateral flow assays (LFAs) have been developed, but their diagnostic performance has not been defined. Cryopreserved serum samples from HIV-infected Ugandans obtained as part of a prospective CrAg-screening cohort were tested in duplicate for CrAg by the CrAgSQ (IMMY) and CryptoPS (Biosynex) lateral flow assays. Case-controlled diagnostic performance was measured using the FDA-approved CrAg LFA (IMMY) as a referenc...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Mycology Source Type: research
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