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The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species. [ABSTRACT FROM AUTHOR]

The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species.

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Background: The incidence of ocular complications in HIV-infected patients varies from 42% to 75% and some of these complications may lead to blindness. Here we report a rare case of retroviral disease with cytomegalovirus (CMV) retinitis in one eye and papillitis secondary to cryptococcus meningitis in the other eye. Case Report: A 14 year old Malay girl who was diagnosed with AIDS since birth through vertical transmission presented with fever, headache, seizure and chronic poor vision in the right eye for about 8 months duration. She was on antiretroviral therapy (HAART). Visual acuity in the right eye was only perception to light and in the left eye was 6/9. Both anterior segments were unremarkable. Fundoscopy of the right eye showed generalised shallow retinal detachment and left swollen hyperaemic disc. Computed tomography (CT) scan of the brain was normal. Lumbar puncture opening pressure was normal as well. A diagnosis of retroviral disease with cryptococcal meningitis, right advanced CMV retinitis and left papillitis was made. Patient was treated with HAART regime, ganciclovir, amphotericin B, flucytosine and fluconazole. The papillitis responded well to treatment. However, the CMV retinitis persisted. Conclusion: In conclusion, AIDS patients are susceptible to multiple opportunistic infection that may co-exist with different severity in either eye. Prompt diagnosis and early medical intervention may preserve vision and improve life expectancy. [ABSTRACT FROM AUTHOR]

Abstract Background Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature. Case presentation We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis. Conclusion Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.

Objective To investigate the effect of continuous drainage of cerebrospinal fluid combined with intrathecal amphotericin B in the treatment of cryptococcal meningitis. Methods Twenty-three patients with cryptococcal meningitis were selected.among them，12 cases of cryptococcal meningitis were treated with intravenous and oral antifungal therapy，combined with continuous drainage of cerebrospinal fluid and intrathecal amphotericin B for 8 weeks. 11 cases were used as the control group，only intravenous and oral antifungal treatment, clinical manifestations，brain pressure，cerebrospinal fluid biochemical indicators and pathogen detection，imaging and other changes before and after the phase contrast treatment. Results The total effective rate of the control group and the treatment group were 54.4%and 83.3%，respectively. The treatment group was higher than the control group （P < 0.05） . After 3 days of treatment，the brain pressure of the treatment group decreased significantly. The brain pressure after treatment for 3 days，1，4，and 8 weeks was statistically significant（P < 0.05） . After 8 weeks of treatment，the cerebrospinal fluid indexes were all significant. The normal level was restored, and the protein，sugar and cell number of cerebrospinal fluid were significantly different fromthose before treatment（P < 0.05）. There was no abnormal performance when the average dose of intrathecal amphotericin B was（0.33±0.16） mg. After the ultra-average dose，low back pain，numbness of both lower extremities，and difficulty in urinating were observed. Conclusions Intrathecal injection of appropriate amphotericin B is safe and effective in the treatment of cryptococcal meningitis. It can relieve intracranial hypertension quickly. Cerebrospinal fluid replacement can reduce pathogens， their metabolites and inflammatory factors in cerebrospinal fluid，purify cerebrospinal fluid; intrathecal injection Amphotericin B can increase the concentration of intracranial drugs，reduce the dose of intravenous administration and reduce the side effects of drugs，and can effectively improve the antifungal effect. [ABSTRACT FROM AUTHOR]

Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low-middle income countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients who develop cryptococcomas often have worse outcomes when compared to patients with cryptococcosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a Ugandan patient with AIDS, and review the diagnosis and management with special focus on difficulties encountered in low or middle-income countries.

Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS).

Cryptococcal meningitis is a central nervous system infection cause by Cryptococcus neoformans. Although Cryptococcus is found in bird droppings, it has never been reported for those ranchers involved in the niche swiftlet ranching industry despite having close proximity with the bird droppings. We present here a case of a 41-year-old healthy swiftlet rancher who presents with a history of prolonged fever, headache and altered behaviour of a month duration. Cerebral spinal fluid analysis revealed the presence of Cryptococcus. He was treated with intravenous amphotericin B and flucytosine and discharged well with fluconazole consolidation therapy for 8 weeks, followed by maintenance therapy for 1 year. We believe this is the first reported case of Cryptococcal meningitis (CM) occurring in an immunocompetent swiftlet rancher. This case should highlight the needs to wear a proper personal protective equipment inside a swiftlet ranch due to the constant exposure to the potential cryptococcal-rich environment. A high index of suspicion, careful history taking and physical examination focusing on neurologic assessment is key to early diagnosis and timely management of CM. [ABSTRACT FROM AUTHOR]

Résumé La cryptococcose est une affection fongique cosmopolite grave, due à une levure encapsulée Cryptococcus neoformans . C’est la mycose systémique la plus fréquente au cours de l’infection à VIH. Cette levure est présente dans l’environnement et sa porte d’entrée principale dans l’organisme est la voie respiratoire. Sa gravité est liée à son tropisme pour le système nerveux central. Elle affecte généralement les sujets ayant un déficit de l’immunité cellulaire sévère et en particulier, les patients vivant avec le VIH. Le diagnostic de la cryptococcose neuroméningée repose sur la mise en évidence de levures capsulées à l’examen microscopique du liquide céphalorachidien, sur la détection de l’antigène polysaccharidique capsulaire dans le sérum ou le liquide céphalorachidien, mais surtout sur la culture. Un bilan d’extension est toujours indispensable. Le pronostic est sévère. Le contrôle de l’hypertension intracrânienne est un élément majeur du pronostic. Summary Cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast Cryptococcus neoformans . This is the systemic fungal infection the most common in HIV infection. This yeast is present in the environment and its main entrance in the body is the respiratory tract. Its gravity is linked to its tropism for the central nervous system. It generally affects subjects with severe deficit of cellular immunity and in particular, patients living with HIV. The diagnosis of neuromeningeal cryptococcosis is based on the detection of encapsulated yeasts at microscopic examination of cerebrospinal fluid, the detection of capsular polysaccharide antigen in serum or cerebrospinal fluid, but especially on the culture. A staging is always essential. The prognosis is severe. The control of intracranial hypertension is a major element of prognosis. [ABSTRACT FROM AUTHOR]

Few estimates of fungal disease frequency have been attempted in the Middle East. We have estimated the burden of fungal infections in Qatar. The aim of the study was to compute and determine the burden of serious fungal infections, in an attempt to estimate fungal disease frequency, which has not previously been attempted in this country. Disease statistics were collected from the Microbiology laboratory database and from 2011 WHO statistics. The data are expressed per 100 000 populations. The reported cases of candidaemia rose to 288 with an estimated rate of 15.4/100 000. A real increase in the burden of candidaemia was found over that previously reported (12.9/100 000) for the years 2004-2009. Candida peritonitis was estimated in 8.02 cases/100 000 population. Recurrent (≥4 year−1) vaginal infections affect at least 32 782 women with a rate of 3506/100 000 inhabitants. Severe asthma with fungal sensitisation affected 1486 people, allergic bronchopulmonary aspergillosis 1126 people and chronic pulmonary aspergillosis 176 people. Rhinosinusitis, mucormycosis and Fusarium infection occurred at rates of 2.31, 1.23, 1.86 cases/100 000 respectively. The estimated rate of invasive aspergillosis was very low (0.6/100 000). Low rates of Cryptococcus meningitis and Pneumocystis pneumonia are attributable to low HIV infection rates. In conclusion, fungal infections are increasingly reported, especially candidaemia. Surveillance and guidelines are needed to optimise care and management of common fungal infections. In addition, a fungal registry system needs development for surveillance. [ABSTRACT FROM AUTHOR]

The pathogenesis of increased blood-brain barrier permeability during Cryptococcus meningitis is still largely unknown. Interleukin (IL-6) is a multifunctional cytokine, and numerous studies have shown that IL-6 influences the integrity of the blood-brain barrier. In this study we investigated the role of IL-6 in Cryptococcus meningitis. First, wild-type or IL-6 mice were injected with Cryptococcus neoformans ( C. neoformans) and the survival time in both groups was recorded. Second, the number of fungi was measured in the brains of IL-6 wild-type mice. Finally, the blood-brain barrier permeability index was detected in infected IL-6 mice treated with recombinant human IL-6. The blood-brain barrier permeability index was measured in infected wild-type mice treated with anti-IL-6 antibodies as well. The survival of IL-6 mice injected with C. neoformans was significantly lower than that of identically challenged wild-type mice. The infected IL-6 mice had significantly larger brain fungal burdens than wild-type mice. Furthermore, increased blood-brain barrier index was found in infected IL-6 mice when compared with that in infected control mice. Similar results were obtained when mice challenged with C. neoformans were treated systemically with neutralizing anti-IL-6 antibodies, resulting in an elevation of vascular permeability. Our data revealed that IL-6 reduced the blood-brain barrier permeability during Cryptococcus meningitis, and it might provide an explanation for the significantly lower survival of infected IL-6 mice. [ABSTRACT FROM AUTHOR]

Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low-middle income countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients who develop cryptococcomas often have worse outcomes when compared to patients with cryptococcosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a Ugandan patient with AIDS, and review the diagnosis and management with special focus on difficulties encountered in low or middle-income countries. [ABSTRACT FROM AUTHOR]

Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS). [ABSTRACT FROM AUTHOR]

Twenty adult cases of cryptococcus meningitis and their cranial CT scan findings were reviewed. Ten patients had abnormal CT scans. The findings were hydrocephalus, gyral enhancement, focal nodules, decreased attenuation in the white matter, and patchy increased uptake of contrast. The CT scan appearance often failed to correspond with symptoms. None of the appearances was specific to the cryptococcal infection. Fourteen patients developed papilloedema during the course of the illness. The majority of the patients who developed papilloedema did not have demonstrable hydrocephalus. [ABSTRACT FROM AUTHOR]

Cryptococcus meningitis is a potentially lethal disease, and cerebrospinal fluid cytology is crucial in establishing diagnosis. We report a novel and interesting morphological sign of Cryptococcus neoformansin CSF cytology resembling the logo of Mercedes-Benz. The sign is highly suggestive of Cryptococcus infection and is a strong indicator for more specific tests and timely treatment. [ABSTRACT FROM AUTHOR]

We report two patients with cryptococcal meningitis and combined immunodeficiency with unusual magnetic resonance imaging findings of gadolinium-enhancing white matter lesions, quite different from cryptococcomas and seen prior to anti-fungal treatment. The lesions resembled demyelinating plaques and resolved. In one patient, biopsy of the lesion revealed cryptococci, non-specific inflammatory changes and occasional small perivascular lymphocyte collections, but not demyelination. Leukoencephalopathy, previously rarely observed in Cryptococcal meningitis, was thought to be the sequelae of amphotericin toxicity. Our cases demonstrate cryptococcal meningitis may present with leukoencephalopathy, possibly as an immune response to the organism. [ABSTRACT FROM AUTHOR]

Background: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature., Case Presentation: We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis., Conclusion: Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.

Cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast Cryptococcus neoformans. This is the systemic fungal infection the most common in HIV infection. This yeast is present in the environment and its main entrance in the body is the respiratory tract. Its gravity is linked to its tropism for the central nervous system. It generally affects subjects with severe deficit of cellular immunity and in particular, patients living with HIV. The diagnosis of neuromeningeal cryptococcosis is based on the detection of encapsulated yeasts at microscopic examination of cerebrospinal fluid, the detection of capsular polysaccharide antigen in serum or cerebrospinal fluid, but especially on the culture. A staging is always essential. The prognosis is severe. The control of intracranial hypertension is a major element of prognosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: To determine the role of serine protease in the disruption of the blood-brain barrier (BBB) during Cryptococcus neoformans meningitis., Methods: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to determine the production of serine protease by different strains of C. neoformans. BBB permeability in immunosuppressed rats inoculated with C. neoformans or C. neoformans plus aprotinin was examined via Evans blue staining. In vitro BBB permeability (transwell passage of horseradish peroxidase) was determined in human brain microvascular endothelial cells (BMECs) cultured with serine protease or serine protease plus aprotinin. Electron microscopy of rat brain tissue was used to visualise C. neoformans infection., Results: Serine protease mRNA and protein were detected in all C. neoformans serotypes. C. neoformans infection increased BBB permeability in vivo, but this effect was ameliorated by aprotinin. Treatment of BMECs with serine protease increased permeability in vitro. This effect was reversed by aprotinin., Conclusion: Serine protease secreted by C. neoformans leads to BBB disruption during Cryptococcus meningitis. Serine protease may be a novel treatment target for Cryptococcus meningitis.

Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances.