Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS

Introduction. Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. Objectives. To analyze the clinical characteristics and evolution of people living with HIV/ AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). Materials and methods. This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. Results. We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). Conclusions. No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Introducción. Las infecciones fúngicas en pacientes con COVID-19 fue uno de los temas más debatidos durante la pandemia. Objetivo. Analizar las características clínicas y la evolución de personas con VIH/SIDA que presentaron la asociación de criptococosis meníngea y COVID-19 (grupo A), y compararlas con aquellas personas con VIH/SIDA que padecieron criptococosis meníngea, pero sin infección de COVID-19 (grupo B). Materiales y métodos. Se realizó un estudio analítico y retrospectivo en el que se revisaron las historias clínicas de pacientes que padecieron criptococosis meníngea entre abril de 2020 y mayo de 2021. Resultados. Se estudiaron 65 pacientes con HIV/SIDA y con criptococosis, diagnosticados entre abril de 2020 y mayo de 2021 (63 habían desarrollado sida y 2 eran negativos para VIH). De estos, 15 de los pacientes con sida padecían criptococosis y COVID-19, y 14 presentaban meningitis (grupo A), mientras que 28 pacientes padecieron criptococosis meníngea, pero no tuvieron COVID-19 (grupo B). Conclusiones. No se observaron diferencias estadísticamente significativas, entre los dos grupos, respecto a la hipertensión intracraneal, la presencia de antígenos de criptoccoco en líquido cefalorraquídeo, el deterioro del sensorio o la mortalidad. La detección de antígenos de Cryptococcus en suero por ensayo de flujo lateral fue efectiva para diagnosticar rápidamente criptococosis en personas con VIH/sida y con infección de COVID-19. Se observó que los pacientes de ambos grupos consultaron tarde por criptococosis en comparación con los casos prepandémicos de esta infección.

Clinical characteristics of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor autoantibodies / 中华传染病杂志

Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review / Abordagem diagnóstica e terapêutica da meningite crônica no Brasil: uma revisão narrativa

Abstract Background Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce. Objective To critically review the literature on CM and propose a rational approach in the Brazilian scenario. Methods Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil. Results In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data. Conclusion We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.

Resumo Antecedentes A meningite crônica (MC) é caracterizada por sintomas neurológicos associados à evidência de pleiocitose do líquido cefalorraquidiano por > 4 semanas. Os estudos sobre o manejo da MC no Brasil são escassos. Objetivo Rever criticamente a literatura sobre MC e propor uma abordagem racional no cenário brasileiro. Métodos Revisão da literatura narrativa discutindo a epidemiologia, avaliação clínica, testes diagnósticos básicos e avançados, além da terapia empírica e direcionada para as causas mais relevantes do MC. A presente revisão foi contextualizada com a experiência local dos autores. Além disso, propomos um algoritmo para o manejo da MC no Brasil. Resultados No Brasil, a tuberculose e a criptococose são endêmicas e devem ser sempre consideradas em pacientes com MC. Além destas doenças, a neurossífilis e outras condições endêmicas devem ser incluídas no diagnóstico diferencial, incluindo: neurocisticercose, síndrome de Baggio-Yoshinari e micoses endêmicas. Após etiologias infecciosas, devem ser consideradas a carcinomatose meningeal e doenças autoimunes sistêmicas. Métodos diagnósticos devem ser utilizados com base na disponibilidade, nos dados clínicos e nos dados epidemiológicos. Conclusão Propomos uma abordagem racional para a MC no Brasil, considerando o cenário epidemiológico, sistematizando a investigação etiológica e avaliando o uso oportuno de terapias empíricas.

Cryptococcal Meningitis Disguised As A Stroke: A Case Report

@#We present a case of cryptococcal meningitis initially misdiagnosed as stroke. Our patient is a young man on longterm corticosteroid due to gouty arthritis, who presented with acute onset of left-sided body weakness. Computed tomography of the brain revealed multifocal chronic lacunar infarcts with acute communicating hydrocephalus and cerebrospinal fluid culture isolated Cryptococcus neoformans. He was subsequently treated with amphotericin B and fluconazole but passed away due to multiorgan failure. This case report highlights the importance of considering chronic meningitis as a differential diagnosis when encountering stroke in young and immunocompromised patients.

Criptococosis meníngea en un paciente con linfopenia T-CD4+ idiopática / Cryptococcal meningitis in a patient with idiopathic CD4+ T lymphopenia

RESUMEN La infección por el virus de la inmunodeficiencia humana es el factor de riesgo principal para desarrollar criptococosis meníngea; sin embargo, existe una entidad poco conocida, la linfopenia T-CD4+ idiopática, que genera un inexplicable déficit de células T-CD4+ circulantes predisponiendo a variadas complicaciones, entre ellas la infección por gérmenes oportunistas. Presentamos el caso de un paciente con criptococosis meníngea secundaria a una linfopenia T-CD4+ idiopática, que a nuestro conocimiento es el primer caso reportado en el Perú. Esta enfermedad debería considerarse en pacientes negativos para el virus de inmunodeficiencia humana, que cursen con infecciones infrecuentes del sistema nervioso central, ya que la evolución, manejo y pronóstico podrían ser distintos en pacientes con esta condición.

ABSTRACT Infection with the human immunodeficiency virus (HIV) is the main risk factor for developing cryptococcal meningitis. However, there is a poorly known entity, idiopathic CD4+ T-cell lymphopenia, which leads to an unexplainable CD4+ circulating T-cell deficit, predisposing patients to many complications, including infections caused by opportunistic microorganisms. We present the case of a patient with cryptococcal meningitis secondary to idiopathic T-CD4+ lymphopenia, which, as far as we know, is the very first case of its kind reported in Peru. This entity should be considered in patients negative for HIV infection developing non-common infections of the central nervous system, since outcome, management, and prognosis may be different in patients with this condition.

Postinfectious inflammatory response syndrome in patients with cryptococcal meningitis / 中华神经科杂志

Cryptococcal meningitis is a common fungal meningitis that may present with an abnormal immune response during effective antifungal therapy and is called immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-infected patients. Similar phenomenon can also be seen in non-HIV patients with normal immune function in the past. Paradoxical clinical and/or imaging deterioration occurs due to strong immune response during treatment, which is called post-infectious inflammatory response syndrome. At present, it has not attracted attention. This complication is an important cause of poor prognosis in non-HIV patients. Early identification and treatment of post-infectious inflammatory response syndrome is of great significance. This article will review its possible pathogenesis, clinical manifestations, imaging characteristics, risk prediction, diagnosis, treatment and prognosis.

Clinical characteristics of 81 cases with acquired immunodeficiency syndrome complicated with cryptococcal meningitis / 中华传染病杂志

Objective@#To investigate the clinical features and prognosis factors of acquired immunodeficiency syndrome (AIDS) patients complicated with cryptococcal meningitis (CM).@*Methods@#Retrospective analyses were performed on clinical features, laboratory data, treatment status and related prognosis factors in 81 AIDS patients with CM admitted to the Department of Infectious Diseases, Beijing You′an Hospital, Capital Medical University from January 2010 to December 2017. The t test, rank sum test and χ2 test were employed to analyze the data.@*Results@#Of the 81 AIDS patients with CM, 71 cases were infected with human immunodeficiency virus (HIV) by sexual transmission (87.7%). The most common clinical symptoms were fever in 60 (74.1%), headache in 72 (88.9%), and nausea and vomiting in 56 (69.1%). Cerebrospinal fluid (CSF) examination results show that 60 cases (74.1%) had elevated opening pressure, the white blood cell count was 17.0 (6.0, 44.5)×106/L, monocyte count was 9.0 (3.0, 29.5)×106/L, the level of chloride was (117.26±5.61) mmol/L, of glucose was 2.89 (2.05, 3.41) mmol/L, of protein was 0.32 (0.21, 0.65) g/L, ink staining positive rate was 84.0% (68/81), fungal culture positive rate was 59.3% (48/81). The positive rate of serum cryptococcal antigen was 96.3% (78/81), and CSF cryptococcal antigen positive rate was 93.8% (76/81). The clinical efficacies were not significant different among different treatment regimens (χ2=1.479, P=0.533). After treatment, 60 patients survived and 21 died, with an overall mortality rate of 25.9%. Univariate analysis showed that consciousness disorder and CSF opening pressure were significantly higher in the death group than those in the survival group (χ2=22.365, t=0.317, respectively, both P<0.05), while serum albumin (Alb) and CD4+ T lymphocyte counts were significantly lower in the death group than those in the survival group (t=7.975, Z=-3.073, respectively, both P<0.05). Multivariate logistic regression analysis showed that consciousness disorder and Alb were independent factors influencing the clinical outcome of AIDS patients with CM. Consciousness disorder was related with poor outcome (odd ratio (OR)=26.704, P=0.011, 95% confidence interval (CI) 2.115-337.247), and higher Alb was related with good outcome (OR=0.671, P=0.005, 95%CI 0.507-0.888). The area under the receiver operating characteristic curve of serum Alb for predicting poor outcomes of AIDS patients with CM was 0.932 (95% CI 0.859-0.998, P<0.01). By using 31.7 g/L as cut-off value, the sensitivity was 95% and the specificity was 81% for predicting poor outcome.@*Conclusions@#AIDS complicated with CM has a high mortality rate, and its clinical features are lack of specificity. Consciousness disorder and Alb are independent prognosis factors.

Efficacy and safety of high-dose fluconazole in the initial treatment of non-human immunodeficiency virus-related cryptococcal meningitis / 中华传染病杂志

Objective@#To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis (CM) in non-human immunodeficiency virus (HIV)-related patients.@*Methods@#Twenty-five non-HIV-infected patients with CM from June 2015 to September 2018 in Huashan Hospital, Fudan University, who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal (600-800 mg/d) regimens were recorded, clinical responses and drug-related adverse events were evaluated. Mann-Whitney test and Fisher′s exact probabilities test were applied to compare variables between groups.@*Results@#Of the 25 patients enrolled in this study, 15 had predisposing factors. Headache (25 cases), fever (21 cases), vomiting (13 cases) and neck stiffness (13 cases) were common manifestations. Abnormalities of cranial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy, and six patients were treated with high-dose fluconazole alone. The course of initial regimens with high-dose fluconazole was 42 (29, 120) days. At the end of initial therapy, partial response in 20 patients, stable response in three patients and death in two patients were observed, and the overall effective rate was 80%(20/25). In treatment failure group of initial treatment, the proportion of patients with baseline cerebrospinal fluid opening pressure over 300 mmH2O (1 mmH2O=0.009 8 kPa) and with altered mental status were both significantly higher compared with those in treatment success group. Fluconazole related adverse drug events were observed including elevated transaminases (one case), gastrointestinal symptoms combined with hypokalemia (two cases), and systemic rash (three cases). Except for three patients with rash reduced the dosage of fluconazole, no other patients were given dosage adjustment.@*Conclusion@#High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.

Clinical characteristics of 81 cases with acquired immunodeficiency syndrome complicated with cryptococcal meningitis / 中华传染病杂志

Objective To investigate the clinical features and prognosis factors of acquired immunodeficiency syndrome(AIDS)patients complicated with cryptococcal meningitis(CM).Methods Retrospective analyses were performed on clinical features,laboratory data,treatment status and related prognosis factors in 8 1 AIDS patients with CM admitted to the Department of Infectious Diseases,Beijing You'an Hospital,Capital Medical University from January 2010 to December 2017.The t test,rank sum test and x2 test were employed to analyze the data.Results of the 81 AIDS patients with CM,71 cases were infected with human immunodeficiency virus(HIV)by sexual transmission(87.7％).The most common clinical symptoms were fever in 60(74.1％),headache in 72(88.9％),and nausea and vomiting in 56(69.1％),Cerebrospinal fluid(CSF)examination results show that 60 cases(74.1％)had elevated opening pressure,the white blood cell count was 17.0(6.0,44.5)×106/L,monocyte count was 9.0(3.0,29.5)×106/L,the level of chloride was(117.26±5.61)mmol/L,of glucose was 2.89(2.05,3.41)mmol/L,of protein was 0.32(0.21,0.65)g/L,ink staining positive rate was 84.0％(68/81),fungal culture positive rate was 59.3％(48/81).The positive rate of serum cryptococcal antigen was 96.3％(78/81),and CSF cryptococcal antigen positive rate was 93.8％(76/81).The clinical efficacies were not significant different among different treatment regimens(x2=1.479,P=0.533).After treatment,60 patients survived and 21 died,with an overall mortality rate of 25.9％.Univariate analysis showed that consciousness disorder and CSF opening pressure were significantly higher in the death group than those in the survival group(x2=22.365,t=0.317,respectively,both P＜0.05),while serum albumin(Alb)and CD4+T lymphocyte counts were significantly lower in the death group than those in the survival group(t=7.975,Z=-3.073,respectively,both P＜0.05).Multivariate logistic regression analysis showed that consciousness disorder and Alb were independent factors influencing the clinical outcome of AIDS patients with CM.Consciousness disorder was related with poor outcome(odd ratio(OR)=26.704,P=0.011,95％confidence interval(CI)2.115-337.247),and higher Alb was related with good outcome(OR=0.671,P=0.005,95％CI0.507-0.888).The area under the receiver operating characteristic curve of serum Alb for predicting poor outcomes of AIDS patients with CM was 0.932(95％CI0.859-0.998,P＜0.01).By using 31.7 g/L as cut-off value,the sensitivity was 95％and the specificity was 8 1％for predicting poor outcome.Conclusions AIDS complicated with CM has a high mortality rate,and its clinical features are lack of specificity.Consciousness disorder and Alb are independent prognosis factors.

Efficacy and safety of high-dose fluconazole in the initial treatment of non-human immunodeficiency virus-related cryptococcal meningitis / 中华传染病杂志

Objective To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis(CM)in non-human immunodeficiency virus(HIV)-related patients.Methods Twenty-five non-HIV-infected patients with CM from June 2015 to September 20 18 in Huashan Hospital,Fudan University,who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal(600-800 mg/d)regimens were recorded,clinical responses and drug-related adverse events were evaluated.Mann-Whitney test and Fisher's exact probabilities test were applied to compare variables between groups.Results of the 25 patients enrolled in this study,15 had predisposing factors.Headache(25 cases),fever(21 cases),vomiting(13 cases)and neck stiffness(13 cases)were common manifestations.Abnormalities of cranial computed tomography(CT)scan and/or magnetic resonance imaging(MRI)were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy,and six patients were treated with high-dose fluconazole alone.The course of initial regimens with high-dose fuconazole was 42(29,120)days.At the end of initial therapy,partial response in 20 patients,stable response in three patients and death in two patients were observed,and the overall effective rate was 80％(20/25).In treatment failure group of initial treatment,the proportion of patients with baseline cerebrospinal fuid opening pressure over 300 mmH2 O(1 mmH2O=0.009 8 kPa)and with altered mental status were both significantly higher compared with those in treatment Success group.Fluconazole related adverse drug events were observed including elevated transaminases(one case),gastrointestinal symptoms combined with hypokalemia(two cases),and systemic rash(three cases).Except for three patients with rash reduced the dosage of fluconazole.no other patients were given dosage adjustment.Conclusion High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.

Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune: reporte de un caso / Cerebral cryptococcosis and immune reconstitution inflammatory syndrome: case report

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 μg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 μg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation

ABSTRACT CONTEXT: Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. Case Report: A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. CONCLUSIONS: Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

Expert consensus on the diagnosis and treatment of cryptococcal meningitis / 中华内科杂志

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Neurocriptococose por Cryptococcus gattii resistente a fluconazol em imunocompetente / Fluconazole-resistant neurocryptococcosis caused by Cryptococcus gattii in immunocompetent individuals: case report

A criptococose é uma doença fúngica sistêmica causada por Cryptococcus neoformans, que acomete principalmente indivíduos imunocomprometidos, podendo eventualmente acometer imunocompetentes. Existem duas variedades da espécie (neoformans e gattii), com características diferentes, mas clinicamente semelhantes, sendo possível sua distinção apenas por do teste de identificação da espécie. O tratamento preconizado é constituído por anfotericina B e fluconazol endovenosos, com duração de meses, existindo pouco relato na literatura sobre resistência à terapêutica habitual ou tratamento alternativo. Neste trabalho, é relatado um caso de neurocriptococose por C. gattii resistente a fluconazol em imunocompetente, no qual foi realizada anfotericina B endovenosa associada a intratecal sem sucesso, evoluindo o paciente a óbito por provável complicações da hidrocefalia obstrutiva.(AU)

Cryptococcosis is a systemic fungal disease caused by Cryptococcus neoformans, which primarily affects immunocompromised individuals, but may occasionally affect immunocompetent individuals. There are two varieties of the species, with different, but clinically similar characteristics, with their distinction being possible only through the species identification test. The recommended treatment consists of intravenous amphotericin B and fluconazole, for some months. There are few reports in the literature on resistance to standard therapy, or an alternative treatment. In this study, we describe a case of fluconazole-resistant neurocryptococcosis by Cryptococcus gattii in immunocompetent individuals, who unsuccessfully received intravenous and intrathecal amphotericin B , with the patient progressing to death from probable complications of obstructive hydrocephalus.(AU)

Meningoencefalitis por Cryptococcus. Presentación de un caso / Meningoencephalitis by Cryptococcus. Case presentation

El Cryptococcus neoformans es un hongo levaduriforme capsulado, con marcado neurotropismo; es el agente causal de la criptococosis, infección micótica profunda, de curso subagudo o crónico, considerada como oportunista. La meningitis criptocócica presenta características clínicas distintivas. La mayoría de las veces se adquiere fuera del hospital y se desarrolla subagudamente. Si no se trata oportunamente puede ser fatal en algunas semanas. Por tales razones se decidió la publicación del caso de una paciente femenina, de 60 años de edad que fue traída al Hospital Gustavo Aldereguía, de Cienfuegos, con cefalea y toma de la conciencia. Al interrogatorio se recogió el antecedente de sufrir por cefalea sin causa aparente desde hacía un tiempo atrás. Fue ingresada en el Servicio de Cuidados Intensivos con toma de la conciencia. Se realizaron varios exámenes complementarios, entre ellos, estudios microbiológicos del líquido cefalorraquídeo y toma de muestras de hemocultivos, según las normas establecidas, donde se aisló Cryptococcus neoformans. Lamentablemente, al ser diagnosticada tiempo después de adquirir la infección, esta paciente falleció.

Cryptococcus neoformans is a yeast-capped fungus, with marked neurotropism; it is the causal agent of cryptococcosis, deep fungal infection, of sub-acute or chronic course, considered as opportunistic. Cryptococcal meningitis presents distinctive clinical characteristics. In most cases it is acquired out of the hospital and develops sub acutely. If it is not treated it can be fatal in a few weeks. For these reasons it was decided the publication of this case of a 60 year old female patient who was brought to the Gustavo Aldereguía Hospital in Cienfuegos, with headache and loss of consciousness. On questioning there was information of a personal antecedent of headaches without apparent cause for some time ago. She was admitted conscious at the ICU. Some tests were performed, among them, microbiological study of cerebrospinal fluid and blood culture samples were taken , according to the standards established , were Cryptococcus neoformans was isolated. Unfortunately after having been diagnosed the patient died.

Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms

Abstract Cryptococcosis is a fungal infection caused by Cryptococcus neoformans that tends to affect immunocompromised individuals. The fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. Later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. In addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of systemic involvement. The clinical presentation of cutaneous forms typically vary according to the infection mode. We report an unusual case of disseminated cryptococcosis in an immunocompetent patient with cutaneous lesions similar to those caused by primary inoculation. This clinical picture leads us to question the definition of primary cutaneous cryptococcosis established in the literature.

Abordagem cirúrgica de lesão granulomatosa criptocócica cerebral (criptococoma) em paciente imunocompetente / Surgical Approach to an Immunocompetent Patient's Cerebral Granulomatosis (cryptococcoma)

Acriptococose é a principalmicosequeatingeosistemanervosocentral, sendode distribuição mundial, mais prevalente em países em desenvolvimento. Atualmente, são descritas duas subespécies: Cryptococcus neoformans neoformans, associado à imunossupressão, e Cryptococcus neoformans gattii, em pacientes imunocompetentes. A criptococose do sistema nervoso central parenquimatosa em sua forma granulomatosa, ou criptococoma, é extremamente rara, sendo mais frequente a forma meningítica ou meningoencefalítica. Relatamos o caso de um paciente de 35 anos, não portador da síndrome de imunodeficiência adquirida e imunocompetente, com manifestações clínicas iniciais de cefaleia crônica, hemiparesia progressiva, confusão mental aguda e primeiro episódio de crise convulsiva tônico-clônica generalizada. Hipóteses diagnósticas préoperatórias de neoplasia maligna ou abscesso cerebral. Realizado procedimento cirúrgico, remoção completa da lesão maior, diminuindo o efeito de massa. A lesão foi diagnosticada, através de exame anatomopatológico, como criptococoma, o que torna o caso extremamente raro pelo tamanho da lesão e por ser o paciente imunocompetente. Houve melhora completa do déficit neurológico. O paciente encontra-se em seguimento clínico e tratamento medicamentoso com anfotericina-B.

Cryptococcosis is the main mycosis affecting the central nervous system, with worldwide distribution and higher prevalence in developing countries. Currently, two subspecies are described: Cryptococcus neoformans neoformans (associated with immunosuppression) and Cryptococcus neoformans gattii (in immunocompetent patients). Cryptococcosis of the central nervous system as a parenchymal granuloma or cryptococcoma is extremely rare, contrasting to themuchmore frequentmeningitic form. We report a 35 year-old immunocompetent patient with chronic headache, progressive hemiparesis, acute confusion and first episode of tonic-clonic seizures. Preoperative diagnostic hypotheses were malignancy or abscess. A large mass (5.5 cm) was surgically removed from the right parietal lobe relieving the mass effect. This was later diagnosed by pathological examination as cryptococcoma, an extremely rare case in view of lesion size and its occurrence in an immunocompetent subject. The patient evolved with complete resolution of the neurological deficit and is on amphotericin-B treatment.

Cryptococcal Meningoencephalitis in a Systemic Lupus Erythematosus Patient without Immunosuppressants / 대한내과학회지

Cryptococcosis is an opportunistic infection that generally occurs in patients with cell-mediated immune dysfunction and involves the central nervous system. Infection is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients because of its innate immune dysfunction along with the administration of steroids and immunosuppressants. However, central nervous system cryptococcosis has rarely been reported in SLE patients. A timely diagnosis is critical because of its significant mortality and morbidity. Most cases of cryptococcal meningitis in SLE patients have been reported in those treated with steroids or immunosuppressants. We report on a SLE patient not on medication, who was diagnosed with cryptococcal meningoencephalitis.

Meningite criptocócica fatal em paciente com lúpus eritematoso sistêmico juvenil / Fatal cryptococcal meningitis in a juvenile lupus erythematosus patient

Cryptococose é uma infecção fúngica causada pelo Cryptococcus neoformans, geralmente associada com imunodeficiências e drogas imunossupressoras, e foi raramente descrita em pacientes com lúpus eritematoso sistêmico (LES), particularmente em LES juvenil (LESJ). De janeiro de 1983 a Junho de 2011, 5,604 pacientes foram seguidos em nosso Hospital Universitário e 283 (5%) casos preencheram critérios de classificação diagnóstica do Colégio Americano de Reumatologia para LESJ. Apenas um (0.35%) destes apresentou meningite criptocócica. Esta paciente teve diagnostico de lúpus aos 10 anos de idade. Aos 15 anos, ela apresentou cefaleia, náuseas e vômitos durante 5 dias, sem febre, após viagem a região de cavernas. Neste momento, ela estava em uso de prednisona 10 mg/dia, azatioprina e hidroxicloroquina. Foi realizada punção lombar e a tintura da Índia foi positiva para cryptococo, a cultura do liquido cerebroespinhal também foi positiva para Cryptococcus neoformans e a pesquisa de antígeno cryptocócico sérico foi positiva em título de 1:280. Azatioprina foi suspensa e anfotericina B liposomal (3 mg/Kg/dia) foi iniciada. No entanto, quatro dias após ela desenvolveu amaurose e coma. A tomografia computadorizada de crânio demonstrou áreas isquêmicas e nódulos sugestivos de infecção fúngica. Após quatro dias, ela desenvolveu sepse grave e vancomicina e meropenem foram iniciados, entretanto foi a óbito devido choque séptico. Portanto, meningite cryptocócica foi uma rara e grave infecção oportunista em uma população de lúpus juvenil. Este estudo reforça a importância do diagnóstico precoce e da pronta introdução de agentes antifúngicos, principalmente em pacientes com história de contato com excrementos de pássaros.

Cryptococcosis is a fungal infection caused by Cryptococcus neoformans, generally associated with immunodeficiency and immunosuppressive agents, and it is rarely reported in systemic lupus erythematosus (SLE), particularly in juvenile SLE (JSLE). From January 1983 to June 2011, 5,604 patients were followed at our University Hospital and 283 (5%) of them met the American College of Rheumatology (ACR) classification criteria for SLE. Only one (0.35%) of our JSLE patients had cryptococcal meningitis and is described in this report. A 10-year old girl was diagnosed with JSLE. By the age of 15 years, she presented persistent headaches, nausea and vomiting for a 5 day period without fever, after a cave-exploring trip. At that moment, she was under 10 mg/day of prednisone, azathioprine and hydroxychloroquine. A lumbar puncture was performed and India ink preparation was positive for cryptococcosis, cerebrospinal fluid culture yielded Cryptococcus neoformans and serum cryptococcal antigen titer was 1:128. Azathioprine was suspended, and liposomal amphotericin B was introduced. Despite of treatment, after four days she developed amaurosis and fell into a coma. A computer tomography of the brain showed diffuse ischemic areas and nodules suggesting fungal infection. Four days later, she developed severe sepsis and vancomycin and meropenem were prescribed, nevertheless she died due to septic shock. In conclusion, cryptococcal meningitis is a rare and severe opportunistic infection in juvenile lupus population. This study reinforces the importance of an early diagnosis and prompt introduction of antifungal agents, especially in patients with history of contact with bird droppings.

Meta-analysis of flucytosine or fluconazole plus amphotericin B for the treatment of acquired immunodeficiency syndrome-associated cryptococcal meningitis / 中华传染病杂志

Objective To evaluate the survival benefit of amphotericin B (AmB) plus flucytosine or fluconazole for treatment of patients with acquired immunodeficiency syndrome (AIDS)-associated cryptococcal meningitis.Methods The following database were searched from the beginning to October 2013,including Cochrane library,PubMed,OVID,Embase,Wanfang Date,CNKI and Chinese Biomedical Database,and the references of eligible studies were manually screened.Reference lists of relevant articles were screened according to selection and extraction criteria.Meta-analysis was performed using RevMan 5.2.Results Four prospective controlled studies with a total of 399 patients with cryptococcal meningitis were identified,including 386 patients with AIDS-associated cryptococcal meningitis and 13 human immunodeficiency virus (HIV)-negative patients.Two hundred and twentyseven patients were treated with AmB and flucytosine combination therapy,including 217 patients with AIDS-associated cryptococcal meningitis and 10 HIV-negative patients.One hundred and seventy-two patients were treated with AmB and fluconazole combination therapy,including 169 patients with AIDS-associated cryptococcal meningitis and 3 HIV-negative patients.The Meta-analysis revealed that the mortality rate in AmB plus flucytosine combination therapy group was 6.6％ (95％ CI:18.5％-31.6 ％) at two weeks point,which was significantly lower than that in AmB plus fluconazole combination group (19.7％,95％CI:-23.6％-62.9％; OR=0.51,95％CI:0.27-0.93,P＜0.05).But at 10 weeks point,the mortality rate in flucytosine combination group was 12.9％ (95％oo CI:-22.2％-48.0％),which was lower than that in fluconazole combination group (31.4％,95％ CI:-23.1％-85.9 ％).However,there was no statistically significant difference between these two groups at 10 weeks point (OR=0.70,95％CI:0.44-1.13,P=0.15).Conclusion Administration of AmB plus flucytosine at early stage can reduce the mortality rate in patients with AIDS-associated cryptococcal meningitis.