ABSTRACT
Objectives: We describe the clinical, mycological, immunological, and genetic characteristics of six HIV-negative patients presenting with invasive cryptococcosis. Methods: Patients with cryptococcosis without any of the classical risk factors, such as HIV infection, followed at Cayenne Hospital, were prospectively included. An immunologic and genetic assessment was performed. Results: Five male patients and one female patient, 5 adults and one child, were investigated. All presented a neuromeningeal localization. Cryptococcus neoformans var. gattii and C. neoformans var. grubii were isolated in two and three patients, respectively, whereas one patient could not be investigated. Overall, we did not observe any global leukocyte defect. Two patients were found with high levels of circulating autoantibodies against Granulocyte macrophage-colony stimulating factor (GM-CSF), and none had detectable levels of autoantibodies against Interferon gamma (IFN-γ) Sequencing of STAT1 exons and flanking regions performed for four patients was wild type. Conclusion: To better understand cryptococcosis in patients with cryptococcosis but otherwise healthy, further explorations are needed with repeated immune checkups and strain virulence studies.
Subject(s)
Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , HIV Infections , Adult , Autoantibodies , Child , Cryptococcus gattii/genetics , Cryptococcus neoformans/genetics , Female , French Guiana , HIV Infections/complications , Humans , MaleABSTRACT
Cryptococcosis diagnosis has been recently improved by the use of rapid cryptococcal antigen testing with lateral flow assays, which have proved sensitive and specific. Using "test and treat" screening strategies for cryptococcal disease with these tests has been showed effective in reducing cryptococcal meningitis (CM) in HIV-infected patients. Recommended induction, consolidation, and maintenance therapeutic strategy for CM is widely unavailable and/or expensive in low and middle-income settings. New therapeutic strategies, mostly using reduced duration, have recently shown acceptable outcome or are currently tested. Diagnostic and therapeutic guidelines for cryptococcal disease in limited resources countries are undergoing a paradigmatic shift.
Subject(s)
Cryptococcosis/diagnosis , Cryptococcosis/drug therapy , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Antifungal Agents/administration & dosage , Drug Therapy, Combination , Humans , Immunologic Tests , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapyABSTRACT
Cryptococcosis diagnosis has been recently improved by the use of rapid cryptococcal antigen testing with lateral flow assays, which have proved sensitive and specific. Using "test and treat" screening strategies for cryptococcal disease with these tests has been showed effective in reducing cryptococcal meningitis (CM) in HIV-infected patients. Recommended induction, consolidation, and maintenance therapeutic strategy for CM is widely unavailable and/or expensive in low and middle-income settings. New therapeutic strategies, mostly using reduced duration, have recently shown acceptable outcome or are currently tested. Diagnostic and therapeutic guidelines for cryptococcal disease in limited resources countries are undergoing a paradigmatic shift.
Subject(s)
Humans , Meningitis, Cryptococcal/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Cryptococcosis/drug therapy , Immunologic Tests , Drug Therapy, CombinationABSTRACT
Compared to the incidence in adults, cryptococcosis is rare among children. We report a case of neurocryptococcosis due to Cryptococcus gattii in a five-year-old girl without identified risk factors living in French Guiana. Neurological surgery in combination with long-term antifungal treatment with amphotericin B and 5-flucytosine successfully resolved the cryptococcal infection. Subsequent molecular characterization of the Cryptococcus isolate revealed that the infection was caused by a C. gattii genotype AFLP6B/VGIIb strain.
Subject(s)
Central Nervous System Fungal Infections/therapy , Cryptococcosis/therapy , Cryptococcus gattii , Child, Preschool , Female , French Guiana , Humans , Remission InductionABSTRACT
BACKGROUND: Patients with candidemia frequently have a central venous catheter (CVC) in place, and its early removal is considered the standard of care. METHODS: We performed a subgroup analysis of 2 phase III, multicenter, double-blind, randomized, controlled trials of candidemia to examine the effects of early CVC removal (within 24 or 48 h after treatment initiation) on the outcomes of 842 patients with candidemia. Inclusion criteria were candidemia, age >16 years, CVC at diagnosis, and receipt of 1 dose of the study drug. Six outcomes were evaluated: treatment success, rates of persistent and recurrent candidemia, time to mycological eradication, and survival at 28 and 42 days. Univariate and multivariate analyses were performed, controlling for potential confounders. RESULTS: In univariate analysis, early CVC removal did not improve time to mycological eradication or rates of persistent or recurrent candidemia but was associated with better treatment success and survival. These benefits were lost in multivariate analysis, which failed to show any beneficial effect of early CVC removal on all 6 outcomes and identified Acute Physiology and Chronic Health Evaluation II score, older age, and persistent neutropenia as the most significant variables. Our findings were consistent across all outcomes and time points (removal within 24 or 48 h and survival at 28 and 42 days). The median time to eradication of candidemia was similar between the 2 study groups. CONCLUSIONS: In this cohort of 842 adults with candidemia followed up prospectively, early CVC removal was not associated with any clinical benefit. These findings suggest an evidence-based re-evaluation of current treatment recommendations.