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

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

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

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

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

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.

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.

Recomendaciones para el diagnóstico y tratamiento de la infección por Cryptococcus spp

Las infecciones por levaduras del género Cryptococcus pueden causar un abanico amplio de manifestaciones clínicas, dependiendo de si se trata de una infección invasora o no. Los pacientes susceptibles, especialmente de las formas invasoras, comparten el compromiso de la inmunidad celular, ya sea por afecciones primarias o secundarias. El grupo más estudiado es el de personas que viven con VIH. La mortalidad es alta, especialmente en entornos de recursos reducidos. El esquema de tratamiento es en fases, inicialmente combinado, para luego continuar con monoterapia por un periodo prolongado, dependiendo de la duración del factor de riesgo subyacente. Hacemos una revisión de la evidencia y recomendaciones actualizadas.

Infection by yeast of the Cryptococcus genus can cause a wide range of clinical manifestations, depending on whether it is an invasive infection or not. Susceptible patients, especially those with invasive forms, share the compromise of cellular immunity, either due to primary or secondary conditions. The most studied group is that of people living with HIV. Mortality is high, especially in resource-poor settings. The treatment scheme is in phases, initially combined, to then continue with monotherapy for a prolonged period, depending on the duration of the underlying risk factor. We review the evidence and update recommendations.

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.

Características clínicas, métodos diagnósticos y evolución de la criptococosis extrameníngea en personas viviendo con VIH / Clinical features, diagnosis methods and evolution in non meningeal cryptococcosis in people living with VIH

La criptococosis es una micosis grave que se manifiesta, en el 90% de los casos, como una meningoencefalitis, especialmente en las personas con VIH. El objetivo de este estudio es describir los casos de criptococosis extrameníngea en personas viviendo con VIH y conocer cuántas de estas padecen compromiso meníngeo concomitante. Además, determinar la relación con el título de antígeno polisacárido capsular de Cryptococcus en suero. Se realizó un estudio retrospectivo, observacional y analítico. Se incluyeron personas viviendo con VIH cuyo diagnóstico inicial de criptococosis se había realizado a partir de muestras extrameníngeas en el período comprendido entre 2012 y 2019. Los pacientes se dividieron en dos grupos. Grupo 1, pacientes sin compromiso meníngeo; Grupo 2, aquellos que finalmente tenían compromiso del SNC. De un total de 531 criptococosis registradas en ese período, se incluyeron 113 pacientes (21%), de los cuales en 58 se comprobó el compromiso meníngeo. No se observaron diferencias significativas en cuanto a la mortalidad entre ambos grupos.Ninguno de los pacientes con antigenemia por LFA (antígeno capsular en suero por inmunocromatografía) positiva, pero con antigenemia por aglutinación de partículas de látex (AL) negativa, tuvo compromiso meníngeo. Se observó que títulos de antígeno para Cryptococcus en suero por AL mayor o igual a 1/100 se correlacionaron con un aumento de 30 veces en la posibilidad de padecer meningitis. En todos los casos se debe descartar el compromiso del SNC. La AL sigue siendo una prueba útil y complementaria, debido a que en los casos con AL negativa no se observó compromiso meníngeo

Cryptococcosis is a serious mycosis that manifests itself, in 90% of cases, as meningoencephalitis, especially in AIDS patients. The objective of this study is to describe the extra-meningeal cases of cryptococcosis in people living with HIV and to know how many of them suffer from concomitant meningeal involvement. Also, to determine its relationship with the Cryptococcus capsular polysaccharide antigen titer in serum.A retrospective, observational and analytical study was carried out. HIV-positive patients whose initial diagnosis had been made from extrameningeal samples in the period between 2012 and 2019 were included. The patients were divided into 2 groups. Group 1: patients without meningeal involvement; group 2: those who finally had CNS involvement.Of a total of 531 cryptococcosis registered in this period, 113 patients (21%) were included, of whom meningeal involvement was confirmed in 58. No significant differences were observed in terms of mortality in both groups.None of the patients with positive LFA antigenemia (Capsular antigen detection by lateral Flow assay) but negative latex particle agglutination (LA) antigenemia had meningeal involvement. LFA was found to be highly sensitive and allows early diagnosis, but it does not replace other diagnostic procedures.Serum Cryptococcus antigen titers for by LA greater than or equal to 1/100 were found to correlate with a 30-fold increase in the likelihood of meningitis.In all cases, CNS involvement must be ruled out. LA continues to be a useful and complementary test, because in cases with negative LA, no meningeal involvement was observed

Budding yeast in a child with acute leukemia: Nothing CRYPT(O)IC about it

A 13-year-old girl child with B-cell precursor acute lymphoblastic leukemia presented with complaints of fever, fatigue and left-sided iliac mass of 20 days duration. Preliminary blood culture from the peripherally inserted central catheter (PICC) demonstrated the presence of budding yeast cells. This is a rare form of “Disseminated cryptococcosis”. Budding yeast cells emphasizes the significance of various differentials of yeast in positive blood cultures bottles, as identifying Cryptococcus from gram stain can be complicated. This manuscript also highlights the presence of crystalloid geometric appearance like “Buckminsterfullerene”, which is derived from the mucopolysaccharide capsule in Cryptococcus. These structures are rarely observed, and in this case, are exceptionally remarkable.

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.

Aislamiento de Cryptococcus neoformans en excrementos de paloma de Castilla (Columba livia) provenientes de lugares públicos de El Salvador / Isolation of Cryptococcus neoformans from droppings of the Feral Pigeon (Columba livia) found in public places in El Salvador

Resumen Objetivo: El objetivo de este estudio fue aislar levaduras pertenecientes al complejo de especies Cryptococcus neoformans de los excrementos de paloma de Castilla (Columba livia) recolectados de plazas y parques públicos de El Salvador. Métodos: Las muestras se sembraron en medios de cultivos convencionales y a las colonias confirmadas se les efectuó una tipificación mediante la técnica de restricción enzimática del gen URA5. Resultados: De un total de 66 muestras analizadas, tres estaban positivas por levaduras pertenecientes al complejo de especies Cryptococcus neoformans. El estudio molecular agrupó los aislamientos en los tipos moleculares VNI y VNII; ambos corresponden a la especie Cryptococcus neoformans sensu stricto. Conclusión: En los sitios estudiados, la presencia de esta levadura es muy reducida, probablemente debido a factores ambientales. Se presenta el primer reporte de Cryptococcus neoformans sensu stricto, genotipos VNI y VNII en El Salvador, esta especie es de relevancia en salud pública por el ser el responsable de más del 90% de los casos de criptococosis a nivel mundial.

Abstract Aim: The objective of this study was to isolate yeast that belonged to the Cryptococcus neoformans species complex from the feces of the Feral Pigeon (Columba livia), from public places in El Salvador. Methods: Samples were seeded in conventional culture media and confirmed colonies were typed using the enzyme restriction technique of the URA5 gene. Results: Of a total of 66 samples analyzed, three were positive for yeasts that belonged to the Cryptococcus neoformans species complex. The molecular study grouped the isolates in the molecular types VNI and VNII; both belonging to the species Cryptococcus neoformans sensu stricto. Conclusions: In the studied sites the presence of this yeast is very low, probably due to environmental factors. We present the first report of Cryptococcus neoformans sensu stricto genotypes VNI and VNII in El Salvador. This specie is relevant in public health for being responsible for more than 90% of cases of cryptococcosis worldwide.

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.

A case of AIDS complicated with Pneumocystis jirovecii pneumonia and disseminated infection of Talaromyces marneffei and Cryptococcus neoformans / 中国热带医学

@#Abstract: AIDS combined with Pneumocystis jirovecii pneumonia (PJP) and disseminated infections of Talaromyces marneffei and Cryptococcus neoformans are rare. This paper summarizes and analyzes the diagnosis and treatment of an AIDS patient with multiple fungal infections for reference. A 79-year-old male patient was admitted to the hospital with "stool habit change for more than 20 days". The white blood cell count was 4.57×109/L, the percentage of neutrophils was 81.8%, the absolute count of CD4+ lymphocytes was 6/μL, and the CD4/CD8 ratio was 0.17. HIV antibody positive was confirmed by CDC. The cerebrospinal fluid and alveolar lavage fluid were positive for Cryptococcus neoformans capsular antigen, and Pneumocystis jirovecii was found by the bronchoalveolar lavage fluid stained with hexamine silver. The cerebrospinal fluid culture was positive for Cryptococcus neoformans, and the blood culture was positive for Cryptococcus neoformans and Talaromyces marneffei. CT showed that bronchovascular bundles in both lungs were more thick, patchy and cable-like high-density shadows were seen in both lungs, and the edges were blurred. Nodular and cable-like high-density shadows were seen in the posterior apical segment of the left upper lobe, with clear margins. Infection of both lungs was considered, and secondary pulmonary tuberculosis occurred in the left upper lobe. After admission, the patient was treated with various anti-bacterial and fungal drugs due to recurrent fever, but the effect was not effective. The fever symptoms of the patient could not be significantly improved, and his condition continued to worsen, and he eventually died. The patient with AIDS complicated with bacterial and fungal infection, especially PJP infection in serious condifiton and has a poor prognosis for rapid development, so clinical attention should be paid to. 

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.

Cryptococcus neoformans meningoencephalitis / 中华神经科杂志

Cryptococcal meningitis is a central nervous system infection caused by cryptococcal invasion of meninges and (or) brain parenchyma. It is characterized by severe intracranial hypertension and brain parenchyma damage. This opportunistic infection commonly occurs among HIV infected individuals, organ transplant recipients, and other immunosuppressive situations, and otherwise immunologically normal hosts. The global burden of human immunodeficiency virus/acquired immunodeficiency syndrome has declined over the years, but cryptococcal meningitis still has a high morbidity and mortality. The risk groups, clinical presentation, imaging characteristics, diagnostic criteria and therapeutic issues were reviewed in this article.

Hemolymph of triatomines presents fungistatic activity against Cryptococcus neoformans and improves macrophage function through MCP-I/TNF-α increase

Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.(AU)

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

Prevention and treatment of fungal infection after solid organ transplantation / 器官移植

Over nearly 70-year development, organ transplantation has become an effective treatment for multiple end-stage diseases. However, postoperative administration of immunosuppressants should be given for the recipients, which leads to low immune function and high incidence rate of infection, including viral, bacterial and fungal infections. Among them, the occurrence of fungal infection is hidden, and it is difficult to deliver prompt diagnosis. Candida, Aspergillus, Cryptococcus and Pneumocystis infection are common fungal infections in solid organ transplantation. High-risk factors of fungal infection after solid organ transplantation should be identified and prevented in advance, and prompt diagnosis and treatment should be carried out by combining the results of (1, 3)-β-D-glucan assay (fungal G-test), imaging examination and related body fluid culture. These interventions are of clinical significance to reduce the incidence of fungal infection and fatality after solid organ transplantation. In this article, common fungal infections after organ transplantation were reviewed, aiming to provide reference for the prevention and treatment of fungal infections after organ transplantation.

Coinfección por Cryptococcus neoformans en paciente trasplantado renal con COVID-19 / Cryptococcus neoformans co-infection in a kidney transplant patient with COVID-19

Resumen La infección por el síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), causante de la enfermedad COVID-19, representa una de las emergencias sanitarias más deletéreas de las últimas dos décadas; de la que aún existen innumerables incógnitas acerca del curso y manejo de presentaciones atípicas. Por lo anterior, resulta importante publicar casos clínicos de interés en población especial como lo son los pacientes receptores de trasplante renal, quienes pueden tener un mayor riesgo de contraer la enfermedad dado su estado de inmunosupresión, así como por el contacto frecuente con el sistema de atención médica. La coinfección con otros virus respiratorios no es infrecuente en población trasplantada con COVID-19, y la asociación con gérmenes oportunistas como Micobacterias, Citomegalovirus, Pneumocystis jirovecii y hongos, tal como el Cryptococcus neoformans es desconocida, pero es posible que dicha asociación pudiese empeorar la severidad del compromiso sistémico y pulmonar. Se presenta el caso de un hombre de 45 años, con antecedentes de trasplante renal de donante cadavérico, que ingresó al servicio de urgencias del Hospital de San José; el presentó síndrome de dificultad respiratoria aguda (SDRA) y falla ventilatoria por infección por SARS-CoV-2. Además, se confirmó infección sistémica por Cryptococcus neoformans sin compromiso del sistema nervioso central. Se inició manejo con ventilación mecánica invasiva, glucocorticoide, anfotericina B liposomal; fallece a los 12 días de su ingreso.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease COVID-19, represents one of the most deleterious health emergencies of the last two decades; of which there are still innumerable unknowns about the course and handling of atypical presentations. Therefore, it is important to publish clinical cases of interest in a special population, such as kidney transplant recipients, who may have a greater risk of contracting the disease due to their immunosuppression and frequent contact with the medical care system. Co-infection with other respiratory viruses is not uncommon in the transplanted population with COVID-19, and the association with opportunistic germs such as Mycobacteria, Cytomegalovirus, Pneumocystis jirovecii and fungi, such as Cryptococcus neoformans, is unknown, yet it is possible that this association could worsen the severity of the systemic and pulmonary involvement. We present the case of a 45-year-old deceased-donor kidney transplant recipient man who was admitted to the emergency service; he presented acute respiratory difficulty syndrome (ARDS) and ventilatory failure due to infection by SARS-CoV-2. It was also confirmed that he had systemic infection by Cryptococcus neoformans without compromise of the central nervous system. It was necessary to use invasive mechanical ventilation, glucocorticoid, liposomal amphotericin B; he died 12 days after admission.

Prevalencia y susceptibilidad de Cryptococcus neoformans aislados del suelo y excretas de palomas en la ciudad de Maceió ­ AL, Brasil / Prevalência e suscetibilidade de Cryptococcus neoformans isolados do solo e de excretas de pombos na cidade de Maceió ­ AL, Brasil

Introducción: Cryptococcus neoformans es una levadura encapsulada, que se encuentra en fuentes ambientales, incluyendo excrementos de palomas. Tiene una gran relevancia clínica porque es el agente etiológico de la criptococosis, considerada una causa importante de mortalidad en personas inmunocomprometidas en todo el mundo. Objetivo: determinar la prevalencia y susceptibilidad de C. neoformans aislados del suelo y excremento de palomas en la ciudad de Maceió ­ Alagoas, Brasil. Metodología: Se recolectaron 150 muestras (50 de excretas secas, 50 de excretas frescas y 50 del suelo) y cultivaron en Agar Dextrosa Sabouraud. Las colonias aisladas sugestivas de C. neoformans se sometieron a identificación y caracterización mediante análisis morfológicos, actividad de la enzima fenol-oxidasa, sensibilidad a la cicloheximida, desarrollo a 37°C, hidrólisis de urea, asimilación de carbono y nitrógeno y fenotipificación en medio canavanina-glicina-azul de bromotimol. La prueba de susceptibilidad antifúngica se realizó utilizando la técnica de difusión en agar. Resultados: se obtuvieron 36 (24%) muestras positivas para C. neoformans, de las cuales 33 fueron de excretas secas y 3 del suelo cercano al excremento. El perfil de susceptibilidad fue de 100.0% para anfotericina B y 87.4% para ketoconazol, no obstante, hubo un alto porcentaje de resistencia a fluconazol (91.5%) e itraconazol (80.0%). Conclusión: estos hallazgos confirman que las excretas de palomas secas son reservorios de C. neoformans en el medio ambiente, caracterizando un problema de salud única. Además, la anfotericina B exhibió una alta actividad in vitro, representando buena alternativa en el tratamiento de la criptococosis.

Introdução: Cryptococcus neoformans é um fungo leveduriforme encapsulado, encontrado em fontes ambientais, incluindo excretas de pombos. Apresenta grande relevância clínica por ser agente etiológico da criptococose, considerada importante causa de mortalidade em indivíduos imunocomprometidos em todo o mundo. Objetivo: determinar a prevalência e suscetibilidade de C. neoformans isolados do solo e de excretas de pombos na cidade de Maceió, Alagoas. Metodologia: foram coletadas 150 amostras (50 de excretas secas, 50 de excretas frescas e 50 do solo) e cultivadas em Ágar Sabouraud Dextrose. As colônias isoladas sugestivas de C. neoformans foram submetidas à identificação e caracterização por meio de análises morfológicas, atividade da enzima fenoloxidase, sensibilidade à cicloheximida, termotolerância à 37ºC, hidrólise da ureia, assimilação de carbono e nitrogênio e quimiotipagem em ágar L-canavanina-glicina-azul de bromotimol. O teste de suscetibilidade antifúngica foi realizado por meio da técnica de difusão em ágar. Resultados: foram obtidas 36 (24%) amostras positivas para C. neoformans, das quais 33 (91,6%) foram provenientes de excretas secas e 3 (8,3%) do solo próximo a excrementos. O perfil de suscetibilidade foi de 100,0% para a anfotericina B e 87,4% para o cetoconazol, não obstante, verificou-se alto percentual de resistência ao fluconazol (91,8%) e itraconazol (80%). Conclusão: estes achados confirmam que excretas de pombos secas são reservatórios de C. neoformans no ambiente, caracterizando um problema de saúde única. Além disso, a anfotericina B apresentou elevada atividade, in vitro, representando boa alternativa no tratamento da criptococose.

A rare cause of headache and fever in a healthy woman / Una rara causa de cefalea y fiebre en una mujer sana

Abstract Cryptococcocis is a fungal infection that primarily affects immunocompromised hosts; disseminated infection is uncommon in immunocompetent patients. We describe a case of a previously healthy woman without risk factors, who was admitted to the emergency department with headache, fever and altered mental status. As a result, a cryptococcal disseminated infection was diagnosed.

Resumen La criptococosis es una infección por hongos que afecta principalmente a huéspedes inmunodeprimidos; la infección diseminada es infrecuente en pacientes inmunocompetentes. Reportamos el caso de una mujer previamente sana, sin factores de riesgo, ingresada a urgencias por cefalea, fiebre y alteración del estado mental quien posteriormente fue diagnosticada con criptococosis diseminada.