Criptococosis meníngea: características y desenlace clínico en un hospital de tercer nivel de Bogotá, Colombia / Meningeal cryptococcosis: characteristics and clinical outcome in a tertiary care hospital in Bogotá, Colombia

Introducción: La criptococosis meníngea es una infección oportunista universal que presenta factores pronósticos variables, especialmente en pacientes inmunosuprimidos. Objetivo: Identificar variables clínicas y paraclínicas asociadas con el desenlace, al final de la hospitalización, en pacientes con criptococosis meníngea atendidos en un hospital de tercer nivel en Bogotá, Colombia. Materiales y métodos: Estudio observacional descriptivo. La información se obtuvo por medio de registros de historias clínicas de pacientes con diagnóstico confirmado de criptococosis meníngea durante el periodo 2016-2021. Resultados: Se analizaron 54 casos, el 85,2 % de ellos de sexo masculino, con una mediana de edad de 38 años. El síntoma principal fue cefalea (74,1 %), con un promedio de duración de 30 días antes del ingreso. El 83,3 % tenía diagnóstico de VIH, con niveles de CD4 por debajo de 50 células/mm3 y recuentos elevados de carga viral. El líquido cefalorraquídeo mostró en más del 50 % hipertensión intracraneal, pleocitosis de predominio linfocitario, hiperproteinorraquia e hipoglucorraquia. El tipo de patógeno aislado más frecuente fue C. neoformans var neoformans. Las variables más prevalentes en el grupo de pacientes que fallecieron fueron la presencia de pleocitosis en LCR (p = 0,025), cultivo para hongo positivo (p = 0,02) y aislamiento C. neoformans var neoformans (p = 0,03). Discusión: La criptococosis meníngea es una patología frecuente en hombres en la cuarta década de la vida y con infección por VIH, sin embargo, los factores relacionados con la mortalidad parecen variar dependiendo de la localización geográfica. Conclusión: En nuestro estudio los factores más prevalentes fueron la presencia de pleocitosis en LCR, cultivo positivo, aislamiento de C. neoformans var neoformans.

Introduction: Meningeal cryptococcosis is a universal opportunistic infection that presents variable prognostic factors, especially in immunosuppressed patients. Objective: To identify clinical and paraclinical variables associated with the outcome at the end of hospitalization in patients with meningeal cryptococcosis treated at a tertiary care hospital in Bogotá, Colombia. Materials and methods: Descriptive observational study. The information was obtained through records of medical records of patients with a confirmed diagnosis of meningeal cryptococcosis during the period 2016-2021. Results: 54 cases were analyzed. 85,2 % men, with a median age of 38 years. The main symptom was headache (74,1 %), with an average duration of 30 days prior to admission. 83,3 % had a diagnosis of HIV, with CD4 levels below 50 cell/mm3 and high viral load counts. The cerebrospinal fluid showed in more than 50 % intracranial hypertension, pleocytosis of lymphocyte predominance, hyperprotein- orrhachia and hypoglycorrhachia. The most frequent type of pathogen isolated was C. neoformans var neoformans. And the most prevalent variables in the group of patients who died were the presence of pleocytosis in CSF (p = 0,025), culture for positive fungus (p = 0,02) and isolation of C. neoformans var neoformans (p = 0,03). Discussion: Meningeal cryptococcosis is a frequent pathology in men, in the fourth decade of life and with HIV infection, however, the factors related to mortality seem to vary depending on the geographical location. Conclusion: In our study, the most prevalent factors were the presence of pleocytosis in CSF, positive culture, isolation of C. neoformans var neoformans.

Searching for new antifungals for the treatment of cryptococcosis

ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

Retrospective analysis of 77 pathologically confirmed cases of pulmonary mycosis in a hospital in the south Sichuan Basin, 2014-2021 / 中国热带医学

@#Abstract: Objective To observe the etiological distribution, basic information, clinical characteristics, imaging and pathological features, treatment regimens, and prognosis of pathologically confirmed cases of pulmonary mycosis, aiming to improve the diagnosis and treatment level of pulmonary mycosis. Methods The clinical, imaging and pathological data of patients with pulmonary mycosis diagnosed by pathological biopsy in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2021 were retrospectively analyzed. Results There were 77 cases of pulmonary mycosis who were diagnosed by pathology, and of these patients, 42 cases (54.54%) suffered from pulmonary aspergillosis, 34 cases (44.16%) suffered from pulmonary cryptococcosis, and 1 case (1.30%) suffered from pulmonary mucormycosis. Among the 77 patients, there were 38 male and 39 female patients, with an age range of 25 to 68 years old (mean age 51.13±10.32 years old). The common respiratory symptoms on admission included cough (33 cases, 42.86%), hemoptysis (24 cases, 31.17%), expectoration (22 cases, 28.57%) and chest pain (13 cases, 16.88%). Chest imaging features mainly included pulmonary nodules (37 cases, 48.05%), cavity (14 cases, 18.18%) and air crescent sign (10 cases, 12.99%). In this study, the main treatment measures for pulmonary mycosis were surgical resection (47 cases, 61.04%) and antifungal therapy combined with surgical resection (19 cases, 24.68%). After active treatments, most of these patients (72/77, 93.51%) discharged with better condition. Conclusions Pulmonary aspergillosis and pulmonary cryptococcosis are common pulmonary mycosis diagnosed by pathology. The main respiratory symptoms on admission are cough, expectoration and hemoptysis. Pulmonary nodules are the most common imaging features, and "air crescent sign" can be seen in some patients with pulmonary aspergillosis. Most pulmonary mycosis can have good treatment outcomes. Combining fungal histopathological characteristics and fungal special staining such as Periodic Acid-Schiff (PAS) staining and Gomori methenamine silver (GMS) staining can identify most pathogenic fungi into genera, which has important clinical significance for the timely diagnosis and treatment of pulmonary mycosis

Perfiles de expresión de los genes ERG11, MDR1 y AFR1 en Cryptococcus neoformans var. grubii aislados de pacientes con HIV / Gene expression profiles of ERG11, MDR1 y AFR1 in Cryptococcus neoformans var. grubbi isolated from HIV patients

Introducción. El fluconazol es el antifúngico más utilizado para la prevención y el tratamiento de infecciones causadas por el género Cryptococcus, agente etiológico de la criptococosis. La resistencia al fluconazol en los aislamientos de Cryptoccocus neoformans puede hacer fracasar el tratamiento y generar recaídas de la infección. Objetivo. Evaluar los perfiles de expresión de los genes AFR1, MDR1 y ERG11 en aislamientos clínicos de C. neoformans var. grubii, durante la respuesta in vitro a la inducción con fluconazol. Materiales y métodos. Se estudiaron 14 aislamientos de C. neoformans var. grubii provenientes de pacientes con HIV, de los cuales 6 eran sensibles al fluconaol y 8 presentaban sensibilidad disminuida. Los niveles de expresión de los genes ERG11, AFR1 y MDR1 se determinaron mediante PCR en tiempo real. Resultados. Los aislamientos resistentes al fluconazol mostraron sobreexpresión de los genes AFR1 y MDR1, mientras que la expresión de los fenotipos de resistencia evaluados se mantuvo homogénea en ERG11, en todos los aislamientos de C. neoformans var. grubii. Conclusiones. La sobreexpresión de los genes AFR1 y MDR1 que codifican las bombas de eflujo, contribuye a la resistencia al fluconazol en los aislamientos estudiados. Sin embargo, los patrones de resistencia que se registran en este hongo, sumado a los casos de recaídas en pacientes con HIV, no pueden atribuirse únicamente a los casos de resistencia por exposición al fármaco. Otros mecanismos podrían también estar involucrados en este fenómeno, como la resistencia emergente (resistencia mediante otros genes ERG) y la heterorresistencia, los cuales deben ser estudiados en estos aislamientos.

Introduction: Fluconazole is the most used antifungal drug for prevention and treatment of Cryptococcus spp. infections, the etiological agent of cryptococcosis. Resistance to fluconazole among Cryptococcus neoformans isolates can lead to treatment failure and generate relapses. Objective: To evaluate the expression profles of the AFR1, MDR1 and ERG11 genes in C. neoformans var. grubii clinical isolates during the in vitro response to fluconazole induction. Materials and methods: Fourteen C. neoformans var. grubii isolates recovered from HIV patients were studied, in which 6 showed sensitivities to fluconazole and 8 decreased sensitivity. The expression levels of ERG11, AFR1 and MDR1 genes were determined by real-time PCR from extracted mRNA. Results: AFR1 and MDR1 genes from C. neoformans var. grubii were overexpressed in fluconazole resistant isolates, whereas ERG11 maintains homogeneous expression in all the evaluated resistance phenotypes of C. neoformans var. grubii isolates. Conclusions: The overexpression of AFR1 and MDR1 genes, which codify for efflux pumps, contributes to fluconazole resistance in the studied isolates. However, the resistance patterns in this fungus and the relapse cases in HIV patients cannot be attributed solely to the exposure to the drug. Heteroresistance and the emerging resistance (resistance through other ERG genes), might be other mechanisms involved in this phenomenon, which must be studied in these isolations.

PNEUMOCYSTIS JIROVECII AND CRYPTOCOCCUS NEOFORMANS CO- INFECTION IN AN HIV-INFECTED PATIENT : A CASE REPORT

Opportunistic fungal infections have a high morality rate, occurring most often in immunocompromised subjects. We report the case of a 19-year-old girl who presented with progressively worsening dyspnea, hypoxemia requiring oxygen supplementation with bilateral pulmonary cystic lesions, treated with antibiotics for a presumptive diagnosis of pneumonia. The patient did not improve clinically. A diagnostic bronchoscopy was performed, which revealed ?ndings consistent with pulmonary pneumocystis. The patient tested positive for HIV, and had a positive cryptococcal antigenemia. She was put on treatment adapted to each fungal infection with a favorable evolution.

Micosis diseminadas en pacientes con SIDA en un hospital de referencia

RESUMEN Introducción: las micosis diseminadas siguen aumentando su incidencia en pacientes inmunodeprimidos originando elevadas tasas de morbimortalidad. Los factores de riesgo más importantes asociados al desarrollo de infecciones oportunistas en pacientes infectados con el VIH son recuentos bajos de linfocitos T CD4+ y falta de adherencia al tratamiento con antirretrovirales. Objetivo: describir las características clínicas de las micosis diseminadas en pacientes con SIDA internados en el Departamento de Medicina Interna del Hospital Nacional, Itauguá, Paraguay, desde 2016 al 2018. Materiales y métodos: estudio observacional descriptivo prospectivo y retrospectivo de corte transverso. Se incluyeron a todos los varones y mujeres mayores de 18 años con SIDA diagnosticados con micosis diseminada. La investigación fue aprobada por el Comité de Ética de la Facultad de Medicina de la Universidad Nacional de Itapúa, Paraguay. Resultados: Se incluyeron 80 pacientes de los cuales 52 fueron varones con una edad media de 40 años ±10 años. La micosis más frecuente fue la candidiasis diseminada en 39 pacientes (49,5%), seguida por la criptococosis en 19 pacientes (23%). Del total de los pacientes, 69 (87%) tenían recuentos de CD4+ 100.000 copias y 41 sujetos (51%) habían abandonado el tratamiento antirretroviral. Los órganos más afectados fueron el tubo digestivo y aparato respiratorio. La mortalidad se observó en 17 casos (21%). Entre éstos, 11 (63%) sujetos presentaron falla renal y 9 (55%) estaban caquécticos. Conclusión: se encontró predominio de sexo masculino con una edad media de 40 años. La mayoría de los pacientes tenían carga viral elevada y recuento de CD4+ bajos. La micosis más frecuente fue la candidiasis. Uno de cada cuatro pacientes presentó criptococosis, con mayor frecuencia a nivel meníngeo. La mortalidad por micosis diseminada fue 21%.

ABSTRACT Introduction: Disseminated mycoses continue to increase their incidence in immunosuppressed patients, causing high rates of morbidity and mortality. The most important risk factors associated with the development of opportunistic infections in HIV-infected patients are low CD4+ T lymphocyte counts and lack of adherence to antiretroviral treatment. Objective: To describe the clinical characteristics of disseminated mycoses in patients with AIDS admitted to the Department of Internal Medicine of the Hospital Nacional of Itauguá, Paraguay from 2016 to 2018. Materials and methods: Prospective and retrospective descriptive cross-sectional observational study. All men and women older than 18 years with AIDS and diagnosed with disseminated mycosis were included. The research was approved by the Ethics Committee of the Faculty of Medicine of the National University of Itapúa, Paraguay. Results: Eighty patients were included, of which 52 were men with a mean age of 40 years ±10 years. The most frequent mycosis was disseminated candidiasis in 39 patients (49.5%), followed by cryptococcosis in 19 patients (23%). Of the total number of patients, 69 (87%) had CD4+ counts 100,000 copies, and 41 subjects (51%) had discontinued antiretroviral treatment. The most affected organs were the digestive tract and the respiratory system. Mortality was observed in 17 cases (21%) and among these, 11 (63%) subjects had renal failure and 9 (55%) were cachectic. Conclusion: Male predominance was found with a mean age of 40 years. Most of the patients had high viral load and low CD4+ counts. The most frequent mycosis was candidiasis. One in four patients presented cryptococcosis, most frequently at meningeal level. Mortality due to disseminated mycosis was 21%.

Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo / Disseminated cryptococcosis by biological therapy: We must manage the risk

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.

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.

Criptococosis diseminada en paciente inmunocompetente imitando un cáncer de pulmón metastásico / Disseminated cryptococcosis in an immunocompetent patient imitating metastatic lung cancer

El cáncer de pulmón es la principal causa de muerte en el mundo por cáncer, y en Colombia es la segunda. Su pronóstico es pobre cuando se ha documentado enfermedad metastásica en el sistema nervioso central. El diagnóstico se basa en el resultado definitivo de patología. Aunque los hallazgos imagenológicos pueden ser muy sugestivos de malignidad, hay reportes de otras enfermedades que pueden imitar cáncer, tales como infecciones o tumores benignos, los cuales pueden llevar a adoptar conductas terapéuticas inapropiadas. Las infecciones fúngicas como las producidas por Criptococcus neoformans, son capaces de generar lesiones que pueden imitar neoplasias. El objetivo de esta publicación es reportar el caso de un hombre a quien inicialmente se le sospechó un carcinoma pulmonar metastásico al sistema nervioso central, y finalmente se le diagnosticó una criptococosis diseminada posterior a su fallecimiento

Lung cancer is the leading cause of death from cancer in the world and the second in Colombia, its prognosis is bad when the diagnosis of metastatic disease in the central nervous system is documented. The diagnosis is based on the definitive pathologic result. Although the imaging findings can be highly suggestive of malignancy, there are reports of other conditions that can mimic lung cancer, such as infections or benign tumors, which can lead to inappropriate treatment. Fungal infections such as those caused by Criptococcus neoformans are capable of generating lesions that can mimic neoplasms. The objective of this article is to report the case of a man who was initially diagnosed with metastatic lung carcinoma to the central nervous system, and was finally diagnosed with disseminated cryptococcosis after his death

Disseminated cryptococcosis caused by Cryptococcus neoformans a case report and review / 中国热带医学

@#Abstract: To analyze the clinical, therapeutic and laboratory characteristics of disseminated cryptococcosis caused by Cryptococcus neoformans invading the blood stream in patient with liver cirrhosis and splenectomy. A 30-year-old male underwent splenectomy plus pericardial devascularization due to "splenomegaly and hypersplenism" in March in 2016. The patient had intermittent fever after operation for many times, and successively accompanied with back pain, left lower limb abscess and right hip pain. The highest body temperature was 39 ℃. CT and MRI revealed the lung lesion and multiple bone destruction. During that period, the effect of antibiotics was not good. On April 19th, 2017, Gram's stain, India ink stain, API 32C, Vitek 2 Compact, ribosomal ITS and IGS sequence analysis were performed to identify the strain isolated from the pus and blood stream. The serum of the patient was detected for cryptococcal antigen. Antifungal susceptibility test was used to determine drug sensitivity and minimum inhibitory concentration (MIC). The Cryptococcus neoformans isolated from fresh pus specimen showed a prominent, thick capsule after India ink stain. The colonies isolated from pus and blood stream were identified Cryptococcus neoformans using API 32C, Vitek 2 Compact, and sequence analysis of rDNA ITS and IGS. Cryptococcal capsule antigen was positive. The minimal inhibitory concentrations of 5-Flucytosine, amphotericin B, fluconazole, itriconazole, voriconazole against the isolate were <4 μg/mL, <0.5 μg/mL, 4 μg/mL, ≤0.25 μg/mL, 0.125 μg/mL respectively. The patient was initially treated with intravenous amphotericin B and flucytosine. After anti-Cryptococcus treatment for two months, the patient clinically improved, and the lesions were reduced on a follow-up CT scan. The patient made a full functional recovery after treatment for six months. Cryptococcosis has hidden onset, atypical clinical symptoms and lack of specificity. Blood stream is the main channel for Cryptococcus to spread and involve many organs of the whole body, including skin, bone and so on. Therefore, early use of blood culture to monitor blood flow dissemination, actively removing the primary focus and cutting off the infection route in time and carrying out effective anti-Cryptococcus treatment are conducive to the patient's early recovery.

Clinical manifestations of pulmonary cryptococcosis: an analysis of 113 cases / 中华全科医师杂志

Objective:To analysis of clinical and imaging characteristics of pulmonary cryptococcosis.Methods:The clinical and imaging characteristics of 113 patients with pulmonary cryptococcosis who were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to March 2019, were retrospectively analyzed.Results:Among 113 patients, 74 cases (65.5%) were males, and 71 cases (62.8%) were at a age of 40-60 years. The imaging manifestations showed a nodular-infiltrating patchy mixed type ( n=44,38.9%), accompanied by halo sign ( n=48, 42.5%) and bronchial air sign ( n=48, 42.5%). All patients were treated with fluconazole and the follow-up at 3 months after discharge showed their conditions were all improved. Subgroup analysis showed that patients with complications had older average age [(54.28±10.64)y vs. (46.52±12.12)y, t=-5.05, P<0.001], longer hospital stay [(10.42±6.11)d vs. (7.09±5.63)d, t=-4.28, P=0.007], lower white blood cell count [(6.02±2.16)×10 9/L vs. (6.96±2.29)×10 9/L, t=2.44, P=0.027]. The symptomatic group had fewer male patients [56.2% (45/80) vs. 87.9% (29/33), χ 2=19.54, P<0.001], and imaging was more likely to show infiltrative patchy [32.5%(26/80) vs. 9.1%(3/33), χ 2=18.25, P=0.031]. There was no significant difference in clinical and imaging manifestations between antigen positive group and antigen negative group(all P>0.05). Conclusions:Most of the patients with pulmonary cryptococcosis are middle-aged men, and have nodular-infiltrating patchy mixed type in imaging; the complications would prolong the length of hospital stay.

Primary cutaneous cryptococcosis: the importance of early diagnosis

Abstract The species of the Cryptococcus neoformans complex show different epidemiological patterns in the infection of immunosuppressed or immunocompetent individuals, and a common tropism peculiarity for the central nervous system. Primary cutaneous cryptococcosis is a rare clinical entity, with manifestations that are initially restricted to the skin through fungal inoculation, and the absence of systemic disease. The authors report in the present study the case of a 61-year-old immunocompetent man, with a rapidly evolving mucoid tumor on abrasions in contact with bird droppings on the forearm. The early identification of the polymorphic skin manifestations and treatment are crucial for the favorable prognosis of the infection, which can be life-threatening.

Criptococosis meníngea / Meningeal cryptococcosis

RESUMEN La criptococosis es una enfermedad producida por levaduras encapsuladas que se adquiere por la inhalación de propágulos infectantes de Cryptoccoccus, principalmente por la C. neoformnas y en menor frecuencia por la C. gatti. La distribución de este hongo es global, pero se encuentra de manera habitual en excretas de aves como las palomas. El principal compromiso en las personas es a nivel de los pulmones, del cerebro o de forma diseminada. La criptococosis en el sistema nervioso central (SNQ se presenta con meningoencefalitis, rara vez en forma de lesiones localizadas granulomatosas conocidas como criptococoma. Esta micosis es una causa frecuente de meningitis que se encuentra, especialmente, en los pacientes con VIH/SIDA. Las manifestaciones clínicas de esta enfermedad en el SNC son: cefalea, alteración del estado mental, fiebre, náuseas, vómito, deterioro visual, parálisis del sexto nervio craneal y signos de irritación meníngea, entre otras. El diagnóstico se realiza por medio de cultivo, microscopía del líquido cefalorraquídeo (LCR) o detección del antígeno de criptococo. El tratamiento de la meningitis por criptococo se divide en tres fases: inducción, consolidación y mantenimiento. Los pilares del tratamiento son la anfotericina B, la flucitosina y el fluconazol.

SUMMARY Cryptococcosis is a disease produced by encapsulated yeast that is acquired by inhalation of infecting Cryp-tococcus propagules, mainly by C. neoformnas and less frequently by C gatti. The distribution of this fungus is global, but it is commonly found in the excreta of birds such as pigeons. The main commitment in people is at the level of the lungs, the brain or in a disseminated way. Cryptococcosis in the central nervous system (CNS) presents with meningoencephalitis, rarely as localized granulomatous lesions known as cryptococcoma. This mycosis is a frequent cause of meningitis especially found in patients with HIV / AIDS. The clinical manifestations of cryptococcosis in the CNS are: headache, altered mental status, fever, nausea, vomiting, visual impairment, sixth cranial nerve palsy, and signs of meningeal irritation, among others. Diagnosis is made by culture, cerebrospinal fluid (CSF) microscopy, or by detection of cryptococcal antigen. The treatment of cryptococcal meningitis is divided into three phases: induction, consolidation, and maintenance. The mainstays of treatment are amphotericin B, flucytosine, and fluconazole.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Trends and patterns of mortality arising from fungal infections in Brazil in a period of 11 years / Tendências e padrões de mortalidade em decorrência de infecções fúngicas no Brasil, em um período de 11 anos

Objective: To investigate the mortality attributed to fungal infections, in Brazil between 2003 and 2013. Methods: This ecological study relied on official data collected from the Sistema de Informação Sobre Mortalidade ­ Mortality Information System database. The mycoses were identified by the 10th revision of the International Classification of Diseases, which included categories B35­B49 in its first chapter. Results: Overall, 11,991,935 deaths were reported in the aforementioned period. The deaths of 4,192 individuals were primarily attributed to mycoses. High annual mortality rates were observed in all Brazilian regions, except in the Northeast. The main recorded mycoses were paracoccidioidomycosis (35.6%) and cryptococcosis (24.1%). There was a downward trend in the number of deaths due to paracoccidioidomycosis. In addition, 10,925 death certificates listed mycoses as an associated cause of death. Cryptococcosis (89.7%) and histoplasmosis (89.4%) were the most common mycoses associated with deaths in HIV patients. Conclusions: There was a downward trend in the number of deaths stemming from invasive fungal infections. However, opportunistic mycoses follow been a significant cause of death, especially in HIV patients.

Objetivo: Investigar a mortalidade atribuída para as infecções fúngicas, no Brasil, entre 2003 e 2013. Métodos: Trata-se de um estudo ecológico, em que os dados foram obtidos do Sistema de Informação sobre Mortalidade (SIM), disponíveis na plataforma do DATASUS. As micoses foram identificadas por meio da 10ª revisão da Classificação Internacional de Doenças (CID-10), a qual incluiu as categorias B35-B49 no primeiro capítulo da CID-10. Resultados: No total, 11.991.935 óbitos foram notificados no período do estudo. Os óbitos de 4,192 indivíduos foram atribuídos às micoses. Foram observadas elevadas taxas de mortalidade em todas as regiões brasileiras, com exceção do Nordeste. As principais micoses registradas foram paracoccidioidomicose (35,6%) e criptococose (24,1%). Houve uma tendência na redução do número de óbitos em relação à paracoccidioidomicose. Além disso, em 10.925 declarações de óbitos informavam que as micoses foram causas associadas ao óbito. Criptococose (89,7%) e Histoplasmose (89,4%) foram as micoses mais comumente associadas ao óbito, principalmente em pacientes HIV positivos. Conclusões: Houve uma tendencia na diminuição dos óbitos por infecções fúngicas invasivas. Entretanto, micoses oportunistas continuam sendo importantes causas de morte, especialmente em indivíduos HIV positivos.

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.

The therapeutics and management of cryptococcus-related immune reconstitution inflammatory syndrome in AIDS patients / 中华临床感染病杂志

Acquired immune deficiency syndrome (AIDS) can cause various opportunistic infections clinically due to severe defects in the body’s cellular immune function. Cryptococcosis is a common serious opportunistic infection in AIDS patients. With the promotion and popularization of high activity antiretroviral therapy (HAART) programs worldwide, the mortality rate of AIDS-related cryptococcosis has been significantly decreased. After initiating antiviral therapy, some patients experienced recurrence and aggravation of clinical symptoms during anti-cryptococcal treatment. The body has an inflammatory response to the excessive immune regulation of cryptococcal antigens, which is called cryptococcus-related immune reconstitution inflammatory syndrome (C-IRIS). C-IRIS seriously affects the quality of life and prognosis of patients. This article reviews the clinical features, pathogenesis and the latest treatment and management strategies of C-IRIS in AIDS patients.

Criptococosis pulmonar en un paciente con colitis ulcerativa tratado con prednisolona y azatioprina / Pulmonary cryptococcosis in a patient with ulcerative colitis treated with prednisolone and azathioprine

Resumen La enfermedad inflamatoria intestinal comprende la enfermedad de Crohn (EC) y la colitis ulcerativa (CU). Esta última es una patología crónica caracterizada por una inflamación difusa de la mucosa colónica, que afecta el recto y se extiende de forma proximal. Su curso clínico es intermitente, con exacerbaciones y remisiones. Su tratamiento, por lo general, es farmacológico, con corticoides, inmunomoduladores e inhibidor del factor de necrosis tumoral (anti tumor necrosis factor, TNF), los cuales causan un estado de inmunosupresión en el paciente, que puede asociarse en algunos casos a infecciones oportunistas. En la literatura se describe la aparición de la criptococosis pulmonar en pacientes con infección por el virus de inmunodeficiencia humana (VIH). En otros casos se asocia al tratamiento farmacológico de pacientes con EC, así como con otras infecciones oportunistas, tales como la tuberculosis y el herpes. Presentamos uno de los primeros casos de criptococosis pulmonar en un paciente con diagnóstico de colitis ulcerativa, quien recibió tratamiento escalonado con salicilatos, inmunomoduladores y terapia biológica. La infección fue documentada clínica, radiológica e histológicamente. El paciente recibió el tratamiento adecuado y presentó una evolución satisfactoria.

Abstract Inflammatory bowel disease comprises Crohn's disease (CD) and ulcerative colitis (UC), the latter being a chronic disease characterized by diffuse inflammation of the colonic mucosa that affects the rectum and extends proximally. Its clinical course is intermittent with exacerbations and remissions and its treatment is generally pharmacological, with steroids, immunomodulators, and anti-tumor necrosis factor inhibitors (TNF), which cause the patient to be in a state of immunosuppression associated, in some cases, with opportunistic infections. The literature describes the occurrence of pulmonary cryptococcosis in patients with human immunodeficiency virus (HIV) infection, in cases associated with drug treatment of patients with CD, as well as with other opportunistic infections such as tuberculosis and herpes. This is one of the first cases of pulmonary cryptococcosis reported in a patient diagnosed with ulcerative colitis, who received step therapy with salicylates, immunomodulators, and biological therapy. The infection was documented clinically, radiologically, and histologically. The patient received the appropriate treatment and had a satisfactory evolution.

Frequency and geographical distribution of genotypes and mating types of Cryptococcus neoformans and Cryptococcus gattii species complexes in Argentina / Frecuencia y distribución geográfica de genotipos y tipos sexuales de los complejos de especies Cryptococcus neoformans y Cryptococcus gattii en Argentina

Abstract The aim of this work was to know the frequency and geographical distribution of genotypes and mating types of Cryptococcus neoformans and Cryptococcus gattii species complexes isolated from human infections in Argentina during the period from April 2009 to April 2011. A multicenter study was conducted, in which 372 isolates were obtained from 61 laboratories throughout the country. Of those, 98.8% of the isolates belonged to the C. neoformans species complex and 1.1% to the C. gattii species complex. Genotype VNI (MATa) was the most frequently isolated (n = 326, 87.6%), followed by VNII (MATa) (n = 22, 5.9%), the recently described VNII-VNIV (aADa) hybrid (n = 14, 3.8%), VNIV (MATa) (n=4, 1.1%), VNIII (aADa) hybrid (n = 1, 0.3%), and VNIII (aADa) hybrid (n = 1, 0.3%). The Argentine Central region showed the greatest number of cases and genotype diversity. Interestingly, a relative high frequency was observed in genotype VNII (MATa) in the Cuyo, Northeast and Northwest regions and, also in VNII-VNIV (aADa) hybrids in the Northwest region. C. gattii species complex was isolated at a low rate; 3 VGI (MATa) and 1 VGII (MATa) isolates were obtained from the Northwest and Central regions. In conclusion, this study shows that genotype frequencies seem to vary among regions in Argentina and reveals a relatively high frequency of rare hybrids in the Northwest region. Further regional clinical and environmental studies may help to elucidate if those varia-tions in frequencies are associated with the existence of regional ecological niches or any other regional factors.

Resumen El objetivo de! trabajo fue conocer la frecuencia y la distribución geográfica de genotipos y tipos sexuales de aislados pertenecientes a los complejos de especies Cryptococcus neoformansy Cryptococcus gattii obtenidos de infecciones humanas en Argentina. Entre abril de 2009 y abril de 2011 se realizó un estudio multicéntrico del que se obtuvieron 372 aislados de 61 laboratorios de diferentes zonas del país. El 98,8% de los aislados pertenecieron al complejo C. neoformansy el 1,1% al complejo C. gattii. El genotipo VNI (MATa) fue el más frecuente (n = 326; 87,6%), le siguieron VNII (MATa) (n = 22; 5,9%), el híbrido VNII-VNIV (aADa) (n = 14; 3,8%), VNIV (MATa) (n =4; 1,1%) y los híbridos VNIII (aADa) (n = 1; 0,3%) y VNIII (aADa) (n = 1; 0,3%). La región Centro mostró el mayor número de casos y la mayor diversidad de genotipos. Cabe destacar que el genotipo VNII (MATa) tuvo una frecuencia relativamente alta en las regiones de Cuyo, Noreste y Noroeste. En esta última región, también fue alta la frecuencia del híbrido VNII-VNIV (aADa). La frecuencia de aislamiento de miembros del complejo C. gattii fue baja: se obtuvieron 3 aislados VGI (MATa) y 1 VGII (MATa) de las regiones Centro y Noroeste. En conclusión, este estudio muestra que las frecuencias de genotipos varían entre las distintas regiones de Argentina y señala la presencia de híbridos poco comunes en una frecuencia relativamente alta dentro de la región Noroeste. Contar con mayor número de estudios clínicos y ambientales regionales podría ayudar a elucidar si tales variaciones están asociadas a la existencia de nichos ecológicos particulares o a algún otro factor regional.