Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS / Criptococosis meníngea e infección por SARS-CoV-2 en personas con VIH/SIDA

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.

Research progress of Cryptococcus gattii meningitis with different immune status / 中华神经科杂志

Cryptococcus gattii is a kind of Cryptococcus that infects the lungs and central nervous system through the inhalation of infectious particles such as spores or Cryptococcus yeast cells. The development of clinical disease of Cryptococcus gattii may be determined by the sex, immunity and genetics of the host factors, in which immune system factors play an important role in host injury. Their defects will have serious clinical consequences. Cryptococcus gattii mainly infects the population with normal immune, and the infection of immunosuppressed population is rare. The infection mechanism, molecular types, clinical characteristics, treatment and prognosis of Cryptococcus gattii meningitis were different between the two populations. This article reviews the main differences in different immune status with Cryptococcus gattii meningitis.

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.

Cutaneous Naganishia albida (Cryptococcus albidus) infection: a case report and literature review

ABSTRACT Naganishia albida (Cryptococcus albidus) is considered saprophytic fungi, and is rarely reported as a human pathogen. Cutaneous infections caused by non-neoformans cryptococcus are rare. We describe a case of an immunocompetent older male with cutaneous cryptococcosis caused by Naganishia albida following skin trauma, and conduct a literature review in PubMed, Lilacs, and Embase. Only six previous similar reports were found. The seven cases (including ours) were widely distributed geographically (Brazil, the US, the UK, Hungary, South Korea, and Iran), all males, and their ages varied, ranging from 14 to 86 years. Four individuals had underlying skin diseases (Sezary Syndrome, psoriasis, and skin rash without etiology) plus potentially immunosuppressive underlying conditions (diabetes mellitus, kidney transplantation, and the use of etanercept, adalimumab, and methylprednisolone). Cutaneous presentation was polymorphic, with lesions characterized as warts, ulcers, plaques, and even macules. Two patients presented disseminated disease. Serum cryptococcal antigen was negative in six patients, and diagnosis was made by fungal culture in all. There is a lack of data on optimal antifungal treatment and outcomes.

Perfil etiológico de las meningitis adquiridas en la comunidad en pacientes adultos en el Complejo Asistencial Sótero del Río, Santiago 2011-2017 / Community acquired meningitis in Santiago, Chile, 2011-2017

INTRODUCCIÓN: En Chile existe poca información sobre los microorganismos causantes de meningitis adquirida en la comunidad (MAC), la que es relevante a la hora de escoger el esquema antimicrobiano empírico. OBJETIVO: Describir la microbiología de MAC en pacientes mayores de 15 años atendidos en un hospital público de Santiago (Chile). METODOLOGÍA: Revisión de cultivos de líquido cefalorraquídeo positivos durante 2011-2017. Se recolectó la información clínica de los pacientes incluidos. Se excluyeron cultivos considerados como contaminación y las meningitis post-quirúrgicas. RESULTADOS: Se identificaron 20 episodios de meningitis bacteriana aguda (MBA) y seis episodios de meningitis criptocócica (MC) entre 2.720 cultivos. Los microorganismos causantes de MBA fueron: Streptococcus pneumoniae (50%), Listeria monocytogenes (25%) y otros cinco agentes (25%). Todos los pacientes con infección por L. monocytogenes presentaban alguna comorbilidad significativa. Cuatro de cinco casos de MC presentaban infección por VIH. CONCLUSIÓN: Streptococcus pneumoniae fue el microorganismo más frecuente de las MAC en esta serie, seguido por L. monocytogenes. Las recomendaciones actuales de esquemas empíricos de MAC consideran adecuadamente la cobertura de S. pneumoniae en todos los pacientes y de L. monocytogenes solo ante factores de riesgo. Además, es relevante considerar MC en casos en pacientes inmunocomprometidos.

BACKGROUND: In Chile, there is scarce information on the frequency of the causative microorganisms of community-acquired meningitis (CAM), which is relevant for the choice of empiric treatment. AIM: To describe the microbiology of CAM in patients over 15 years treated at a public hospital in Santiago (Chile). METHODS: Retrospective review of positive cerebrospinal fluid cultures during 2011-2017. Clinical information of the included patients was collected. Cultures considered as contamination and cases of post-surgical meningitis were excluded. RESULTS: We identified 20 episodes of bacterial meningitis (BM) and six episodes of cryptococcal meningitis (CM) in 2720 cultures. The microorganisms identified in BM cases were Streptococcus pneumoniae (50%), Listeria monocytogenes (25%) and five other agents (25%). All patients with L. monocytogenes infection had at least one well-known risk factor for this infection. Four of the five cases of CM had HIV infection. CONCLUSION: Streptococcus pneumoniae was the most frequent causative microorganism of CAM in this series, followed by L. monocytogenes. Current recommendations for empiric CAM regimens adequately consider coverage for S. pneumoniae in all patients and for L. monocytogenes only in those with risk factors. Furthermore, it is relevant to consider CM in cases involving immunocompromised patients.

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.

Criptococosis meníngea y pulmonar en paciente inmunocompetente

RESUMEN Presentamos el caso de un varón de 23 años, sin patologías conocidas, agricultor, procedente de la zona rural. Presenta un cuadro de 1 mes de evolución cefalea, náuseas y vómitos, además de alteración de la conciencia caracterizada por confusión. La tomografía de cráneo no muestra anomalías y la punción lumbar es compatible con meningitis, con tinta china positiva visualizándose Cryptococcus sp. Se inicia tratamiento con anfotericina B y fluconazol. Posteriormente retorna informe final de cultivo: Cryptococcus gatii. Se realizan estudios para descartar infecciones virósicas que retornan negativos. En su internación presenta neumonía nosocomial y por empeoramiento progresivo del estado de conciencia y la clínica respiratoria pasa a cuidados intensivos donde se mantuvo internado durante 21 días. En su estadía se confirmó además la presencia de C. gattii en lavado bronquioalveolar. Presentó falla multiorgánica y óbito. Es el primer caso de criptococosis en paciente inmunocompetente descrito en nuestro centro.

ABSTRACT We present the case of a 23-year-old male, with no known pathologies, a farmer, from a rural area. He presented a 1-month history of headache, nausea and vomiting, in addition to altered consciousness characterized by confusion. The skull tomography does not show abnormalities and the lumbar puncture is compatible with meningitis, with positive Chinese ink showing Cryptococcus sp. Treatment with amphotericin B and fluconazole is started. Later, the final culture report returns: Cryptococcus gatii. Studies are carried out to rule out viral infections that return negative. During his hospitalization, he presents nosocomial pneumonia and due to the progressive worsening of his state of consciousness and the respiratory symptoms goes to intensive care where he is hospitalized for 21 days. During his stay, the presence of C. gattii is also confirmed in bronchioalveolar lavage. He presents multiple organ failure and death. This is the first case of cryptococcosis in an immunocompetent patient described in our center.

Clinical analysis of cryptococcosis neoformans infection in patients with connective tissue disease / 中华风湿病学杂志

Objective:To improve the level of clinical diagnosis and treatment by analyzing the clinical features and relevant factors of cryptococcosis neoformans in patients with connective tissue disease(CTD).Methods:Twelve patients with CTD and cryptococcosis neoformans infection in Peking University People's Hospital from January 2010 to April 2021 were retrospectively enrolled. Clinical and laboratory data, treatment and outcome were collected and analyzed. Independent sample t-test or Rank-sum test was used. Results:The age of the patients ranged from 18 to 85 years old(mean 51 years old), all of whom were female. None of them were exposed to pigeons and their feces. Of the 12 patients, 3 patients suffered from rheumatoid arthritis, 7 patients had systemic lupus erythematosus, 1 patient was diagnosed with primary Sj?gren 's syndrome, and 1 patient was diagnosed as undifferentiated connective tissue disease. Four cases were cryptococcal meningitis, 8 were pulmonary cryptococcosis. None of the 12 patients had immunodeficiency virus infection. All 12 patients were given glucocorticoid alone or combined with immunosuppressive or biological agents. All were detected with positive cryptococcus neoformans antigen in serum; 6 got lumbar puncture, 2 cases were positive for ink stain, cerebrospinal fluid (CSF) culture were positive in 2, in whom 3 had high intracranial pressure, in which the highest one was more than 600 mmH 2O (1 mmH 2O=0.009 8 kPa); 7 cases underwent lung biopsy. Among these patients, all were positive for cryptococcosis neoformans in lung tissue pathological examination; 6 had the number of peripheral lymphocytes less than 1.0×10 9/L, and 2 were detected for the number of CD4 + T cell, which was significantly decreased. As for the initial anti-fungal drug therapy, all cases were treated with fluconazole intravenously; 2 were treated with combined amphotericin, 1 was treated with combined fluorocytosine, 1 was treated with amphotericin and fluorocytosine. Then oral flu-conazole was prescribed as sequential therapy. The whole treatmentcourse ranged from 4 to 21 months. Eleven patients were cured, and 1 was relieved. Conclusion:Patients with connective tissue disease complicated with cryptococcus neoformans infection have atypical clinical symptoms. Treatment with immunosuppressive drugs and glucocorticoids are related causes. Patients with decreased peripheral blood lymphocytes, especially CD4 + T cell, are more susceptible to infection. Early diagnosis and timely treatment are the key to improve the prognosis and cure of the disease.

Clinical efficacy of ventriculo-peritoneal shunt in the treatment of acquired immunodeficiency syndrome complicated with cryptococcal neoformans meningitis / 中华传染病杂志

Objective:To investigate the clinical efficacy of ventriculo-peritoneal shunt (VPS) in acquired immunodeficiency syndrome (AIDS) patients with cryptococcal neoformans meningitis (CNM).Methods:Patients with AIDS and CNM who were hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2015 to June 2020 were included and divided into VPS group and conventional treatment group.The data including symptoms and signs of meningitis, cerebrospinal fluid (CSF) pressure, CSF routine examination, ink staining, Cryptococcus culture and Cryptococcus culture negative time were obtained, and the clinical efficacy compared between the two groups after six and 48 weeks of treatment.Two independent samples t test or chi-square test was used for statistical analysis. Results:Among 66 AIDS patients with CNM, 26 cases in VPS group were (35.7±11.9) years, and 11 cases (42.3%) had CSF pressure> 330 mmH 2O (1 mmH 2O=0.009 8 kPa) at admission, 25 cases (96.2%) were positive for ink staining, and 20 cases (76.9%) had positive culture of Cryptococcus neoformans in CSF. There were 40 cases in the conventional treatment group with age of (38.9±12.9) years, 15 cases (37.5%) had CSF pressure>330 mmH 2O, 32 cases (80.0%) were positive for ink staining, and 31 cases (77.5%) were positive for culture of Cryptococcus neoformans in CSF. There were no significant differences of age, the proportion of patients with CSF pressure>330 mmH 2O, positive rate of ink staining, positive rate of Cryptococcus culture between the two groups ( t=-1.02, χ2=0.15, 3.49 and 0.00, respectively; all P>0.050). All patients were administrated with antifungal treatment, decreasing CSF pressure treatment, nutritional support and symptomatic treatment after admission. VPS was performed in patients with poor responses after medical conservative treatment in VPS group. At week six of treatment, the recovery rate of CSF pressure in VPS group was 57.7%(15/26), and the partial remission rate was 73.1%(19/26), which were both higher than those in conventional treatment group (31.0%(9/29) and 47.5%(19/40), respectively). The differences were both statistically significant ( χ2=3.96 and 4.22, respectively, both P<0.050). At week 48 of treatment, the recovery rate of CSF pressure in VPS group was 92.3%(24/26), the negative rate of Cryptococcus culture in CSF was 100.0%(20/20), and the complete remission rate was 46.2%(12/26), which were all higher than those in conventional treatment group (37.9%(11/29), 67.7%(21/31) and 20.0%(8/40), respectively). The differences were all statistically significant ( χ2=17.52, 8.03 and 5.10, respectively, all P<0.050). In VPS group, 22 cases were complete or partial remission, four cases were ineffective, and no death occurred, while there were 23 cases of complete or partial remission, 12 cases of ineffective and five cases of death in the conventional treatment group. The proportion of ineffective or death in the VPS group was 15.4%(4/26), which was lower than 42.5%(17/40) in the conventional treatment group. The difference was statistically significant ( χ2=5.34, P=0.021). Conclusions:VPS in AIDS patients with CNM could significantly improve the treatment outcomes, and reduce the rates of treatment failure and mortality.

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.

Co-infection with cryptococcal meningitis and Japanese encephalitis in an immunocompetent patient: A case report

@#Cryptococcal meningitis is a severe infection in both immunocompetent and immunosuppressed hosts. This report is an unusual case of co-infection with cryptococcal meningitis and Japanese encephalitis in a seronegative human immunodeficiency virus patient. A 51-year-old human immunodeficiency virus-negative patient presented with high-grade fever, nausea, vomiting, and later on, behavioral changes. A lumbar puncture was performed and cerebrospinal fluid revealed the presence of Cryptococcus and Japanese encephalitis virus. Treatment commenced with intravenous amphotericin B and flucytosine. Her condition initially improved but later on deteriorated due to bacteremia (MRSA-mecA gene positive) and septic shock which resulted in the patient’s demise. The occurrence of this co-infection in the absence of HIV infection is rare and there was no documented case up to this date.

Características clínicas de la criptococosis cerebral en pacientes infectados por el VIH: Hospital Nacional de Paraguay años 2012 a 2020 / Clinical characteristics of cerebral cryptococcosis in HIV-infected patients: Hospital Nacional de Paraguay years 2012 to 2020

RESUMEN Introducción: el cuadro clínico de la infección por el VIH refleja la inmunodeficiencia progresiva desde fases iniciales a veces asintomáticas hasta las finales cuando clínicamente corresponde a estadios más avanzados de inmunosupresión, con linfocitos T CD4 < 100cel /µL, el síndrome de inmunodeficiencia adquirida, en el que ya aparecen las enfermedades definitorias, una de ellas la criptococosis cerebral. Objetivos: describir las características clínicas de la criptococosis cerebral en pacientes infectados por el VIH internados en el servicio de Clínica Médica del Hospital Nacional ­ Itauguá, Paraguay de 2012 a 2020. Metodología: se realizó un estudio observacional descriptivo, retrospectivo de corte transversal, en pacientes de ambos sexos mayores de 18 años. Resultados: se estudiaron 35 pacientes, 69 % fueron varones, con mediana de edad 43 años. El 100 % se hallaba sin tratamiento antirretroviral al ingreso, 74 % no se conocían infectados por el VIH y el 26 % no tenía adherencia al tratamiento. El cuadro evolutivo en promedio fue de 20 días (2 a 90 días), el 91 % de los síntomas al ingreso fueron neurológicos, siendo el predominante la cefalea, que se presentó en forma aislada en el 28 % y el resto con otro síntoma neurológico. La carga viral promedio fue 867.464 copias/mL, la mediana del nivel CD4 34 cél/mm3 y el 100 % < 150 cél/mm3. El promedio de los hallazgos del líquido cefalorraquídeo fueron glucorraquia 37 mg/dl, proteinorraquia 174 mg/dl, la celularidad 46 % ≤ 6 cél/µl, 98 % con predominio mononuclear. Todos fueron tratados con anfotericina B y de mantenimiento con fluconazol. La mediana de los días de internación fue 30 días y la mortalidad de 26 %, siendo los factores de mal pronóstico: consulta tardía, no conocidos infectados por VIH y mayor carga viral. Conclusiones: se pudo evidenciar mayoría de los casos en pacientes varones, adultos jóvenes, en estadio sida, 100 % sin tratamiento en antirretrovirales y como factores de mal pronóstico la consulta tardía y la alta carga viral. Es válida la sospecha de concomitancia criptococosis meníngea-VIH, en pacientes con cefalea crónica aun en pacientes no conocidos infectados con VIH.

ABSTRACT Introduction: the clinical picture of HIV infection reflects the progressive immunodeficiency from the initial phases, sometimes asymptomatic to the final, when clinically it corresponds to more advanced stages of immunosuppression, with CD4 T lymphocytes <100cells / µL, the acquired immunodeficiency syndrome, in the one that already appears the defining diseases, one of them the cerebral cryptococcosis. Objectives: to describe the clinical characteristics of cerebral cryptococcosis in HIV-infected patients admitted to the Medical Clinic Service of the Hospital Nacional - Itauguá, Paraguay from 2012 to 2020. Methodology: a descriptive, retrospective, cross-sectional observational study was carried out in patients of both sexes older than 18 years. Results: 35 patients were studied, 69 % were male, with a median age of 43 years. 100 % were without antiretroviral treatment upon admission, 74 % were not known to be infected with HIV, and 26 % had no adherence to treatment. The evolutionary picture on average was 20 days (2 to 90 days), 91 % of the symptoms on admission were neurological, the predominant being headache, which occurred in isolation in 28% and the rest with another neurological symptom . The mean viral load was 867,464 copies / mL, the median CD4 level was 34 cells / mm3 and 100 % <150 cells / mm3. The mean cerebrospinal fluid findings were glucorrhachia 37 mg / dl, protein sprain 174 mg / dl, cellularity 46 % ≤ 6 cells / µl, 98% predominantly mononuclear. All were treated with amphotericin B and maintenance with fluconazole. The median number of days of hospitalization was 30 days and mortality was 26 %, with poor prognosis factors being: late consultation, unknown HIV-infected patients, and higher viral load. Conclusions: most of the cases could be evidenced in male patients, young adults, in the AIDS stage, 100 % without antiretroviral treatment, and late consultation and high viral load as poor prognostic factors. The suspicion of meningeal cryptococcosis-HIV concomitance is valid in patients with chronic headache even in unknown patients infected with HIV.

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 analysis of 42 elderly patients with pulmonary cryptococcosis / 中华老年医学杂志

Objective:To analyze the clinical features, imaging characteristics, diagnosis and treatment of elderly patients with pulmonary cryptococcosis, and to propose considerations for the early diagnosis and treatment of pulmonary cryptococcosis.Methods:Clinical data of 42 elderly patients with pulmonary cryptococcosis diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to September 2020 were retrospectively analyzed.Differences in clinical data were compared between immunocompromised patients and immunocompetent patients by using the SPSS software.Results:The mean age of patients of with pulmonary cryptococcosis was(66.0±5.3)years.Of the cases, 27 were immunocompromised, with common underlying diseases such as autoimmune rheumatic disorders, tumors and chronic kidney disease.Main clinical manifestations were cough, sputum expectoration, fever and chest tightness.Twenty-two cases showed nodules on chest CT scans, most of which contained multiple nodules.Twenty-four cases showed unilateral lesions, mainly in the lower lobe.There was no significant difference in clinical manifestations, lesion types or location distribution between the immunocompromised and immunocompetent groups( P>0.05), while the incidence of air bronchograms was higher in the immunocompetent group than in the immunocompromised group( P<0.05). Seventeen cases were diagnosed by histopathology, and the clinical diagnosis of 25 cases was confirmed by the positive detection of capsular polysaccharide antigens.Nine cases were treated surgically, 1 case underwent clinical observation postoperatively, and 8 cases were treated with fluconazole after surgery.Thirty-three cases were treated with antifungal therapy, 6 of whom were treated with a combination of drugs.Eight cases were lost to follow-up, 29 were cured or improved, 2 progressed, and 3 died. Conclusions:Pulmonary cryptococcosis in the elderly is more common in immunocompromised patients, with atypical clinical symptoms and a high rate of misdiagnosis.Cryptococcal capsular polysaccharide antigen testing is helpful for early diagnosis, and treatment plans need to be chosen and adjusted according to the patient's immune status and specific conditions.

A case of HIV negative cryptococcal meningitis with antiphospholipid syndrome / 中南大学学报(医学版)

Cryptococcal meningitis has become the largest cause for the death of infectious diseases in the central nervous system infectious disease worldwide. Most patients with cryptococcal meningitis have AIDS, autoimmune diseases, hematologic malignancies, and some other relevant diseases. It is mainly caused by infection with

Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil

Abstract INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Production of a latex agglutination reagent for the rapid diagnosis of cryptococcal meningitis / Producción de un reactivo de látex para el diagnóstico rápido de criptococosismeníngea

Abstract Cryptococcosis is a fungal disease affecting more than one million people per yearworldwide. Its main etiological agents are Cryptococcus neoformans species complex and Cryp-tococcus gattii species complex. Cryptococcal meningitis (CM) is considered an AIDS-definingcondition. Rapid diagnosis by cryptococcal antigen assays, either the latex agglutination test(LA) or the lateral flow assay, is key to decreasing mortality due to cryptococcal disease. Theaim of the study was to develop a latex agglutination reagent (LA-ANLIS) for the rapid and reliable diagnosis of cryptococcosis in Argentina. This reagent will be produced in order to supplythe NMLN (National Mycology Laboratory Network). The evaluation of LA-ANLIS performanceand its comparison with the Cryptococcus Antigen Latex Agglutination Test System (LA-IMMY)(Immuno-Mycologics, Inc., USA) were conducted in 94 samples of cerebrospinal fluid. LA-ANLISand LA-IMMY compared exhibited 100% positive agreement and 97% negative agreement. LA-ANLIS showed 94% sensitivity and 97% specificity with the positive and negative predictivevalues of 94% and 97%, respectively. The LA-ANLIS is a reliable, reproducible and cost-effectivereagent, especially useful in countries where the commercial kit is not generally available andmust be obtained at a high cost. National production of reagents is the best choice for a reliableaccess to the rapid diagnosis of CM in Argentina.

Resumen La criptococosis es una enfermedad fúngica que afecta a más de un millón de personas por año en todo el mundo. Los principales agentes etiológicos pertenecen a los complejos de especies Cryptococcus neoformans y Cryptococcus gattii. La criptococosis meníngea (CM) se considera una enfermedad marcadora de sida. El diagnóstico rápido de esta enfermedad a través de la detección del antígeno de Cryptococcus, ya sea por aglutinación en partículas de látex o por inmunocromatografía, es clave para disminuir la mortalidad. El objetivo del presente estudio fue desarrollar un reactivo de aglutinación en partículas de látex para el diagnóstico rápido y certero de la CM en Argentina. Este reactivo (denominado en adelante LA-ANLIS) será producido para abastecer a la Red Nacional de Laboratorios de Micología. Se evaluó el desempeno del reactivo LA-ANLIS, y se realizó una comparación con el reactivo comercial Immuno-Mycologics, Inc. (en adelante, LA-IMMY) utilizando 94 muestras de líquido cefalorraquídeo. Hubo un 100% de acuerdo positivo y un 97% de acuerdo negativo entre los resultados obtenidos con los reactivos LA-ANLIS y LA-IMMY. El reactivo LA-ANLIS mostró una sensibilidad del 94% y una especificidad del 97%; los valores predictivos positivo y negativo fueron del 94 y del 97%, respectivamente. Se concluye que el LA-ANLIS es un reactivo confiable y rentable, que arroja resultados reproducibles, por lo que es especialmente útil en países donde los reactivos comerciales generalmente no están disponibles o sus costos son elevados. La producción nacional de reactivos es la mejor opción para asegurar el acceso de todos los hospitales al diagnóstico rápido de la CM en Argentina.

Achados Epidemiológicos de Neurocriptococose em Pacientes Imunocompetentes: Relato de Casos de um Hospital Público de Joinville, Brasil / Epidemiological Findings of Neurocriptococcosis in Immunocompetent Patients: Case Reports from a Public Hospital in Joinville, Brazil / Hallazgos epidemiológicos de la neurocriptococosis en pacientes inmunocompetentes: relato de casos de un hospital público en Joinville, Brasil

Justificativa e Objetivos: Neurocriptococose é uma doença fúngica que acomete principalmente pacientes imunocomprometidos. Casos em pacientes imunocompetentes têm sido descritos em alguns relatos de casos; no entanto, por não ser uma doença de notificação compulsória no Brasil até 2020, ainda pouco se sabe sobre sua epidemiologia no sul do país. O presente estudo teve como objetivo descrever aspectos epidemiológicos relacionados à doença em pacientes supostamente imunocompetentes. Métodos: Estudo retrospectivo, observacional, baseado em uma série de casos atendidos entre 2018 e 2019, em um hospital público de Joinville, Santa Catarina, Brasil. Pacientes com diagnóstico clínico confirmado pela presença do fungo do gênero Cryptococcus spp. no líquido cefalorraquidiano pelo método tinta da China foram avaliados quanto aos aspectos clínicos, tratamento e complicações durante o período de internação. Resultados: Houve dois pacientes em 2018 e seis pacientes em 2019 com diagnóstico confirmado. Todos sem fatores aparentes para imunocomprometimento e sem fator de risco ambiental evidente. A maioria eram homens com média de idade de 39 anos. Febre e confusão mental foram os achados mais comuns na apresentação. A variante C. neoformans foi encontrada em 75% dos casos. Todos receberam Anfotericina B, no mínimo, durante 13 dias, associado ou não a Fluconazol. Seis pacientes apresentaram nefrotoxicidade pela Anfotericina B, dois evoluíram para óbito intra-hospitalar e dois permaneceram com sequelas neurológicas. Conclusão: A mortalidade e as complicações relacionadas ao tratamento da neurocriptococose em pessoas imunocompetentes foram altas na amostra estudada. A recente inclusão da doença como uma patologia de notificação compulsória poderá aprimorar dados epidemiológicos para o melhor entendimento e a prevenção dessa doença.(AU)

Background and Objectives: Neurocryptococcosis is a fungal disease that affects mainly immunocompromised patients. Cases in immunocompetent patients have been described in some case reports. However, as its reporting was not mandatory in Brazil until 2020, little is known about its epidemiology in the South Region of the country. The present study had the objective of describing epidemiological aspects related to the disease in presumably immunocompetent patients. Methods: A retrospective and observational study was developed, based on cases of patients who received care in a public hospital in Joinville, Santa Catarina, Brazil, between 2018 and 2019. Patients with a clinical diagnosis confirmed by the presence of the fungus Cryptococcus spp. in cerebrospinal fluid by means of the Chinese ink staining were evaluated regarding clinical aspects, treatment, and complications during hospitalization. Results: The diagnosis of the disease was confirmed for two patients in 2018 and six patients in 2019. All of them showed no apparent factors for immunodeficiency and no evident environmental risk factors. Most were men with an average age of 39 years. Fever and mental confusion were the most common symptoms at admission. The variant C. neoformans was found in 75% of the cases. All patients received amphotericin B for at least 13 days with or without combined fluconazole. Six patients had nephrotoxicity due to amphotericin B, two evolved to in-hospital death, and two had neurological sequelae. Conclusion: Mortality and complications related to the treatment of neurocryptococcosis in immunocompetent people showed high rates in the studied sample. The recent inclusion of this disease as a mandatory reporting pathology can improve epidemiological data, which will be used to achieve better understanding and prevention of this problem.(AU)

Justificación y Objetivos: La neurocriptococosis es una enfermedad fúngica que afecta especialmente a pacientes inmunocomprometidos. Fueron citados casos en pacientes inmunocompetentes en algunos relatos. Por no considerársela de notificación obligatoria en Brasil hasta 2020, poco se sabe aún sobre su epidemiología en el sur del país. El estudio objetivó describir aspectos epidemiológicos relativos a la enfermedad en pacientes supuestamente inmunocompetentes. Métodos: Estudio retrospectivo, observacional, en base a una serie de casos atendidos entre 2018 y 2019 en un hospital público de Joinville, Santa Catarina. Pacientes con diagnóstico clínico confirmado por presencia de Cryptococcus spp., utilizándose el método de tinta china en líquido cefalorraquídeo fueron evaluados respecto de aspectos clínicos, tratamiento y complicaciones durante su internación. Resultados: Hubo 2 pacientes en 2018 y 6 en 2019 con diagnóstico confirmado, todos sin factores aparentes de inmunocompromiso y sin factor de riesgo ambiental evidente. Mayoría de hombre, media etaria de 39 años. Fueron hallazgos comunes en su presentación la fiebre y confusión mental. La variante C. neoformans fue hallada en 75% de los casos. Todos recibieron anfotericina B como mínimo durante 13 días, en asociación o no con fluconazol. Seis pacientes presentaron nefrotoxicidad por anfotericina B, dos sufrieron fallecimiento intrahospitalario, y dos resultaron con secuelas neurológicas. Conclusión: La mortalidad y las complicaciones relativas al tratamiento de la neurocriptococosis en inmunocompetentes fueron altas en la muestra estudiada. La inclusión de la enfermedad como patología de notificación obligatoria podrá mejorar los datos epidemiológicos para entender mejor y prevenir la enfermedad.(AU)

Cryptococcal Antigenemia in HIV-Infected Patients with CD4+ T-cell Count ≤ 200 cells/μl: A study from a tertiary care hospital

Introduction: Cryptococcal meningitis is one of the leadingopportunistic infections associated with high mortality. Thepresent study was carried out to determine the prevalence ofcryptococcal antigenemia in HIV-infected patients with CD4+T-cell count ≤ 200 cells/μl.Material and methods: A cross-sectional study includinga total of 100 blood samples of HIV-infected patients withCD4+ T-cell count ≤ 200 cells/μl was carried out in a tertiarycare hospital. The Cryptococcal Antigen Latex AgglutinationTest was performed on serum separated from blood samplesincluded in the study group. A positive cryptococcalantigenemia was diagnosed by positive latex agglutinationtest of cryptococcal polysaccharide antigen in serum. BMI ofall patients included in the study group was calculated andWHO clinical staging of all patients was noted.Results: Three cases out of 100 were positive for cryptococcalantigenemia. The positive cases showed correlation with lowBMI and WHO Clinical stage II and III of HIV disease. Inthe present study, 33.33% and 66.67% of positive cases hadCD4+ T-cell count within the range of 0-100cells/μl and101-200cells/μl respectively.Conclusion: It is important to implement routine screeningfor cryptococcal antigen among HIV-infected cases withCD4+ T-cell count ≤ 200 cells/μl for early detection ofcryptococcal antigenemia. It will help in identifying the riskof subsequent cryptococcal meningitis and initiation of preemptive antifungal treatment.