Etiología, clínica y evolución de infecciones fúngicas invasoras en pacientes con neoplasias hematológicas en un hospital universitario de Argentina

Introducción: Las infecciones fúngicas invasoras (IFI) en pacientes con neoplasias hematológicas (NH) representan un desafío diagnóstico y terapéutico. Objetivos: Describir la etiología, características clínicas, diagnóstico y evolución de los episodios de IFI probadas y probables en pacientes con NH y trasplante de progenitores hematopoyéticos (TPH). Pacientes y Métodos: Estudio descriptivo, retrospectivo y de cohorte que incluyó IFI probadas y probables en pacientes adultos con NH y TPH. Se realizó seguimiento hasta el día 90. Resultados: Se incluyeron 80 episodios de IFI: 49% probadas y 51% probables, 67,5% por hongos filamentosos (HF), 30% por hongos levaduriformes (HL) y 2,5% por hongos dimorfos. Los tipos de IFI más frecuentes fueron aspergilosis invasoras pulmonares (AP) y candidiasis invasoras (CI), en su mayoría por Candida spp. no albicans. Todos los casos de AP se diagnosticaron por detección de galactomanano en sangre y/o lavado broncoalveolar, y solamente 22,2% presentaban nódulos con halo en la tomografía computada (TC) de tórax, siendo los infiltrados inespecíficos los hallazgos más frecuentes. Tuvieron coinfección bacteriana y viral el 30 y 17,5%, respectivamente. El 50% fueron IFI de brecha, y la mortalidad global y mortalidad relacionada a la IFI fue 51 y 24%, respectivamente. Conclusión: Los HF fueron la principal causa de IFI, con una gran proporción de IFI de brecha, y presentaron elevada mortalidad. Para el diagnóstico, resulta importante la utilización de biomarcadores y jerarquizar cualquier imagen patológica en la TC.

Background: Invasive fungal infections (IFI) in patients with hematological malignancies (HM) represent a diagnostic and therapeutic challenge. Aim: To describe the etiology, clinical characteristics, diagnosis and evolution of proven and probable IFI episodes in patients with HM and hematopoietic stem cell transplantation (HSCT). Methods: Retrospective, descriptive, cohort study performed in adult patients with HM and HSCT, who developed proven and probable IFI. Follow-up was carried out until day 90. Results: A total of 80 IFI episodes were included: 49% proven and 51% probable, 67,5% due to mold (M), 30% to yeast-like fungi (Y) and 2,5% to dimorphic fungi. The most frequent causes were probable pulmonary aspergillosis (PA) and invasive candidiasis (IC), mainly due to non-albicans Candida species. PA were all diagnosed by detection of galactomannan (GM) in blood and bronchoalveolar lavage, and only 22,2% presented halo sign on chest CT. Bacterial and viral coinfections were reported in 30% and 17,5% respectively. Breakthrough IFI occurred in 50%, and global and IFI-related mortality were 51% and 24% respectively. Conclusion: Mold was the main cause of IFI, with a large proportion of breakthrough IFI, presenting high mortality. The use of biomarkers and the classification of any pathological image on CT contribute to the diagnosis.

Infección por Aspergillus flavus y Rhizopus oryzae complex en paciente con diabetes mellitus / Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus

La sinusitis micótica es una condición patológica que puede presentarse en pacientes con diabetes mellitus y estar asociada a una crisis hiperglucémica. Es una entidad agresiva con complicaciones locales que incluyen afectación de la órbita y el sistema nervioso central, y compromiso vascular. A pesar del tratamiento quirúrgico y antimicótico, la mortalidad es de hasta el 75 %. Se describe el caso de una paciente con diagnóstico de cetoacidosis diabética y signos de oftalmoplejía unilateral que llevaron al estudio con resonancia magnética del sistema nervioso central; se encontraron signos de sinusitis, meningitis y cerebritis. Los estudios microbiológicos iniciales fueron negativos, y los biomarcadores galactomanano sérico y el antígeno de Cryptococcus también fueron negativos. Tras el manejo quirúrgico, se llegó a la identificación de Aspergillus flavus y Rhizopus spp. en el tejido de los senos paranasales. La paciente recibió tratamiento con posaconazol y, tras dos meses de seguimiento, había presentado mejoría clínica. La infección fúngica dual y la infección por A. flavus son entidades poco frecuentes y de relevancia clínica, sin casos presentados previamente en nuestro país por lo que este corresponde a un caso de interés clínico.

Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.

Efficacy analysis of subcutaneous injection of granulocyte-macrophage colony-stimulating factor for prevention of invasive fungal disease in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Infecciones fúngicas invasivas en niños hospitalizados en un centro de referencia de Uruguay / Invasive fungal infections in children hospitalized at a pediatric reference hospital in Uruguay / Infecções fúngicas invasivas em crianças internadas em um centro hospitalar de referência no Uruguai

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.

Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.

Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.

"Star of Bethlehem sign" in the analysis of the evolution of brain lesions during and after treatment for neuroparacoccidioidomycosis / "Sinal da Estrela de Belém" na análise evolutiva das lesões durante e após o tratamento em pacientes com neuroparacoccidioidomicose

Abstract Objective: To describe the clinical and radiological evolution of lesions during and after treatment in patients diagnosed with neuroparacoccidioidomycosis (NPCM). Materials and Methods: This was a retrospective study of the medical records, computed tomography scans, and magnetic resonance imaging (MRI) scans of patients with NPCM treated between September 2013 and January 2022. Results: Of 36 cases of NPCM, eight were included in the study. One patient presented only with pachymeningeal and skull involvement, and seven presented with pseudotumors in the brain. Collectively, the eight patients presented with 52 lesions, of which 46 (88.5%) were supratentorial. There were 32 lesions with a diameter ≤ 1.2 cm, of which 27 (84.4%) disappeared during the treatment. In three cases, there were lesions > 1.2 cm that showed a characteristic pattern of evolution on MRI: an eccentric gadolinium contrast-enhanced nodule, with a subsequent decreased in the size and degree of contrast enhancement of the lesions. Conclusion: In NPCM, supratentorial lesions seem to predominate. Lesions ≤ 1.2 cm tend to disappear completely during treatment. Lesions > 1.2 cm tend to present with a similar pattern, designated the "Star of Bethlehem sign", throughout treatment.

Resumo Objetivo: Descrever a evolução clínica e radiológica das lesões durante e após o tratamento de pacientes diagnosticados com neuroparacoccidioidomicose (NPCM). Materiais e Métodos: Revisamos os prontuários médicos, estudos de tomografia computadorizada e ressonância magnética (RM) de pacientes com NPCM de nossa instituição, no período de setembro de 2013 a janeiro de 2022. Resultados: Dos 36 casos de NPCM, oito foram incluídos no presente estudo. Um caso apresentava apenas envolvimento paquimeníngeo e ósseo craniano e sete casos apresentavam lesões encefálicas pseudotumorais, totalizando 52 lesões, sendo 46 (88,5%) supratentoriais. Dentre 32 lesões com diâmetro ≤ 1,2 cm, 27 (84,4%) apresentaram resolução completa durante o tratamento. Três casos apresentaram padrão semelhante de evolução da lesão na RM em lesões > 1,2 cm, caracterizado pelo aparecimento de nódulo excêntrico com impregnação pelo gadolínio, seguido de redução das dimensões e do realce nodular pelo contraste nos estudos subsequentes. Conclusão: A NPCM apresenta-se predominantemente com lesões supratentoriais. Lesões ≤ 1,2 cm tendem a desaparecer completamente durante o tratamento. Lesões > 1,2 cm tendem a apresentar um padrão de imagem de RM característico ao longo do tratamento, descrito como o "sinal da Estrela de Belém".

Mucurmicosis rinocerebral en un paciente con diabetes descompensada

La mucormicosis es una infección con una alta mortalidad, el pronóstico está en relación con el diagnóstico precoz, el tratamiento quirúrgico y antimicótico. Se presenta un varón de 65 años de edad, hipertenso conocido, tratado con losartan, ingresa con una historia de 15 días de evolución con astenia, anorexia, pérdida de peso y cefalea holocraneana, y ptosis palpebral de una semana de evolución. Al examen físico se constata una protrusión ocular y parálisis del tercer par del ojo derecho. Presentó hiperglicemia que fue revertida con insulina. La resonancia magnética de órbita y senos paranasales mostró un engrosamiento del nervio óptico derecho, ocupación de los senos paranasales. El paciente fue sometido a un tratamiento quirúrgico de la lesión retrocular, la biopsia de la lesión mostró al examen directo hifas hialinas compatible con mucorales. Se inició tratamiento con amfotericina B.

Mucormycosis is an infection with high mortality, the prognosis is related to early diagnosis, surgical and antifungal treatment. We present a 65-year-old male, known hypertensive, under treatment with losartan, admitted with a 15-day history of asthenia, anorexia, weight loss and holocranial headache, and palpebral ptosis of one week's evolution. Physical examination revealed ocular protrusion and paralysis of the third pair of the right eye. The patient presented hyperglycemia that was reversed with insulin. Magnetic resonance imaging of the orbit and paranasal sinuses showed thickening of the right optic nerve, occupation of the paranasal sinuses. The patient underwent surgical treatment of the retrocular lesion, biopsy of the lesion showed hyaline hyphae compatible with mucorales on direct examination. Treatment with amphotericin B was started.

Paraccoicidiomicosis, reflexión de una micosis diseminada: reporte de caso

Introducción: La paracoccidioidomicosis, es una micosis endémica en diferentes países de latinoamérica, incluyendo zonas de Colombia, con manifestación clínica muy variada ya que es considerada una enfermedad que puede ser crónica y sistémica. Objetivos: Exponer la importancia del examen clínico-estomatológico en la detección de diferentes entidades en sistema estomatognático, y el manejo multidisciplinario de paracoccidioidomicosis oral y sistémica. Caso clínico: paciente masculino en sexta década de vida, el cual presenta glosalgia y dolor de región ocular. Clínicamente presenta lesión de tipo granulomatoso en bordes laterales de lengua con evolución de hace 1 año aproximadamente, el resultado de la biopsia es paracoccidioidomicosis, se inicia manejo multidisciplinario con medicamentos intravenosos y orales, luego de 10 meses presenta resolución de este. Conclusiones: un buen interrogatorio, análisis de cuadro clínico y exámenes complementarios, son claves para un diagnóstico temprano y tratamiento oportuno, preservando la vida del paciente, especialmente en infecciones oportunistas como la paracoccidioidomicosis.

Introdução: A paracoccidioidomicose é uma micose endêmica em diferentes países da América Latina, incluindo áreas da Colômbia, com manifestação clínica muito variada por ser considerada uma doença que pode ser crônica e sistêmica. Objetivos: Expor a importância do exame clínico-estomatológico na detecção de diferentes entidades do sistema estomatognático e no manejo multidisciplinar da paracoccidioidomicose oral e sistêmica. Caso clínico: paciente do sexo masculino na sexta década de vida, que apresentava glossalgia e dor na região ocular. Clinicamente apresenta lesão tipo granulomatosa nas bordas laterais da língua com evolução de aproximadamente 1 ano, resultado da biópsia é paracoccidioidomicose, inicia-se manejo multidisciplinar com medicações endovenosas e orais, após 10 meses resolve. Conclusões: um bom questionamento, análise do quadro clínico e exames complementares são fundamentais para o diagnóstico precoce e tratamento oportuno, preservando a vida do paciente, principalmente nas infecções oportunistas como a paracoccidioidomicose.

Introduction: Paracoccidioidomycosis is an endemic mycosis in different Latin American countries, including areas of Colombia, with a very varied clinical manifestation since it is considered a disease that can be chronic and systemic. Objectives: To expose the importance of the clinical-stomatological examination in the detection of different entities in the stomatognathic system, and the multidisciplinary management of oral and systemic paracoccidioidomycosis. Clinical case: male patient in the sixth decade of life, who presented glossalgia and pain in the ocular region. Clinically, it presents a granulomatous-type lesion on the lateral edges of the tongue with evolution of approximately 1 year ago, the result of the biopsy is paracoccidioidomycosis, multidisciplinary management is started with intravenous and oral medications, after 10 months it resolves. Conclusions: a good questioning, analysis of the clinical picture and complementary tests are key to early diagnosis and timely treatment, preserving the patient's life, especially in opportunistic infections such as paracoccidioidomycosis.

Reporte de dos casos de neuro-paracoccidiomicosis / Report of two cases of neuro-paracoccidiomycosis

La paracoccidiodomicosis es la micosis sistémica más frecuente en América Latina. La afectación del sistema nervioso central (SNC) está descrita en un 10-27%. El objetivo es presentar dos pacientes del sexo masculino con neuroparacoccidiodomicosis internados en el Departamento de Medicina Interna del Hospital Nacional, uno en el año 2017 y el otro en el 2021. Ambos pacientes presentaron síntomas neurológicos con mejoría de las lesiones con anfotericina B. Los granulomas cerebrales de PCM pueden tener comportamiento pseudotumoral. La regresión de las lesiones fue completa con anfotericina B y trimetoprin sulfametoxasol en el primer caso y anfotericina B e itraconazol en el segundo caso.

Paracoccidioidomycosis is the most common systemic mycosis in Latin America. Central nervous system (CNS) involvement is described in 10-27%. The objective is to present two male patients with neuroparacoccidioidomycosis admitted to the Department of Internal Medicine of the National Hospital, one in 2017 and the other in 2021. Both patients presented neurological symptoms with improvement of the lesions with amphotericin B. The granulomas brain cells of PCM may have pseudotumor behavior. Regression of the lesions was complete with amphotericin B and trimethoprim sulfamethoxazole in the first case and amphotericin B and itraconazole in the second case.

Una experiencia de siete años en el laboratorio de Micología del Hospital de Pediatría Juan P. Garrahan / A seven-year experience in the Mycology Laboratory of Hospital de Pediatría Juan P. Garrahan

En noviembre del año 2015 nos incorporamos al Laboratorio de Micología del Servicio de Microbiología del Hospital Garrahan. En este breve resumen queremos compartir los avances logrados a través de nuestra experiencia durante siete años de trabajo profesional. Debido a los diagnósticos realizados y su complejidad, consideramos que el Hospital Garrahan, sus pacientes y la comunidad toda necesitan contar con un laboratorio de Micología que responda a sus necesidades. Creemos haber iniciado un camino que esperamos continúe y culmine con la creación de la Unidad de Micología (AU)

In November 2015 we joined the Mycology Laboratory of the Microbiology Service of the Hospital Garrahan. In this brief summary we want to share the advances achieved through our experience during seven years of professional work. Due to the diagnosis made and their complexity, we believe that the Hospital Garrahan, its patients and the entire community, need to have a Mycology laboratory that responds to their requirements. We believe we have started a path that we hope will continue and culminate with the creation of the Mycology Unit (AU)

Características de la infección fúngica invasiva en los pacientes críticos de la altitud con shock séptico

Introducción: En UCI, 19% tienen hongos, 23% desarrollan shock séptico. Cándida albicans el más frecuente. Antimicótico más utilizado es fluconazol. Objetivos: En residentes de la altitud con shock séptico (SS) describiremos: Características, evolución y sensibilidad de la infección fúngica invasiva (IFI) y los contrastaremos con los publicados a nivel del mar. El estudio: Retrospectivo y transversal. Analizamos hemocultivos de adultos con SS y IFIs en una UCI a 3,250 metros de altitud, durante 7 años. Hallazgos: 123 muestras. Las IFIs aumentaron 3.6 para candida albicans. Mujeres con 74 años fue frecuente. BGN representaron 52.88%, BGP 37.9% y hongos 9.22%. Cándida albicans 79.67% con sensibilidad mayor al 90% para Voriconazol, Anfotericina B y Fluconazol. Conclusiones: IFIs con SS fueron causadas por cándida albicans, IFIs aumentaron, existe adecuada sensibilidad a los antimicóticos En la altitud existe mayor frecuencia del sexo femenino, mayor promedio de edad y una buena sensibilidad al fluconazol.

Introduction: In the ICU, 19% have fungi, 23% develop septic shock. Candida albicans the most frequent. The most commonly used antifungal is fluconazole. Objectives: In high altitude residents with septic shock (SS) we will describe: Characteristics, evolution and sensitivity of invasive fungal infection (IFI) and we will contrast them with those published at sea level. The study: Retrospective and transversal. We analyzed blood cultures of adults with SS and IFIs in an ICU at 3,250 meters of altitude, for 7 years. Findings: 123 samples. The IFIs increased 3.6 for candida albicans. Women with 74 years was frequent. BGN represented 52.88%, BGP 37.9% and fungi 9.22%. Candida albicans 79.67% with sensitivity greater than 90% for Voriconazole, Amphotericin B and Fluconazole. Conclusions: IFIs with SS were caused by candida albicans, IFIs increased, there is adequate sensitivity to antifungals. At high altitudes there is a higher frequency of females, higher average age, and good sensitivity to fluconazole.

Afectación esofágica y pulmonar por paracoccidioidomicosis en paciente inmunocompetente: reporte de caso / Esophageal and Pulmonary Involvement Caused by Paracoccidioidomycosis in Immunocompromised Patient: Case Report

Resumen La paracoccidioidomicosis es una infección fúngica endémica de América del Sur, que afecta predominantemente a los hombres y, según su campo laboral, granjeros y agricultores. Es ocasionada por la aspiración del hongo en su forma micelar y debuta en tres formas de presentación: aguda, subaguda y crónica; esta última es más frecuente en adultos, cuyo tratamiento dependerá de los azoles, anfotericina B y sulfonamidas. El presente caso trata de un hombre de 57 años, colombiano, agricultor, sin antecedentes patológicos, quien presentaba dos meses de disfagia para sólidos que progresó a líquidos, sialorrea y pérdida de peso, a quien se le realizó endoscopia de vías digestivas altas y se observaron lesiones blanquecinas, por lo cual se realizó una biopsia que evidenció levaduras en múltiple gemación compatibles con paracoccidioidomicosis; a su vez, se observó en una tomografía de tórax compromiso parenquimatoso intersticial generalizado; posteriormente, recibió tratamiento con itraconazol, con el que mostró mejoría y resolución del cuadro clínico. En vista de que América del Sur es endémica de la patología descrita y puede presentarse de forma diseminada en inmunocompetentes, se debe tener en cuenta en aquellos pacientes que poseen factores de riesgo, sintomatología y hallazgos en estudios de extensión sugestivos de dicha enfermedad, dado el gran espectro de presentación de la infección, para así dar tratamiento oportuno y dirigido.

Abstract Paracoccidioidomycosis (PCM) is a fungal infection endemic to South America. It predominantly affects men, depending on their work field: farmers and agriculturists. Paracoccidioidomycosis is caused by the aspiration of the fungus in its micellar form and manifests in three conditions: acute, subacute, and chronic; the latter is more frequent in adults, whose treatment will depend on azoles, amphotericin B, and sulfonamides. This case concerns a 57-year-old Colombian man, a farmer with no pathological history who showed dysphagia for solids that progressed to liquids, sialorrhea, and weight loss for two months. He underwent upper GI endoscopy, and whitish lesions were observed; thus, he was biopsied, displaying yeasts in multiple gemmations compatible with paracoccidioidomycosis. In turn, a chest CT scan showed generalized interstitial parenchymal involvement. Subsequently, he was treated with itraconazole, showing improvement and resolution in his clinical picture. Since the pathology described is endemic in South America and can be disseminated in immunocompromised patients. Given the broad infection spectrum, consideration should be given to patients with risk factors, symptomatology, and findings in extension studies suggesting this disease to provide timely and specific treatment.

Infección fúngica invasiva por Saprochaete capitata en un niño con aplasia medular / Invasive fungal infection by Saprochaete capitata in a child with bone marrow aplasia

RESUMEN Saprochaete capitata es una causa rara de infección fúngica invasiva en pacientes inmunocomprometidos con alta mortalidad y resistencia antifúngica. Presentamos el caso de un niño de cinco años con diagnóstico de aplasia medular, sometido a trasplante de progenitores hematopoyéticos (TPH), que cursó con neutropenia febril persistente, dolor abdominal intenso, aparición de lesiones maculopapulares en piel y deterioro de la función renal. Se identificó la presencia de S. capitata, en hemocultivos transcatéter venoso central. Esta infección fúngica invasiva resulta ser rara, pero emergente y potencialmente mortal, en pacientes con neutropenia febril persistente y uso prolongado de dispositivos invasivos intravasculares como catéter venoso central.

ABSTRACT Saprochaete capitata is a rare cause of invasive fungal infection in immunocompromised patients with high mortality and antifungal resistance. We present the case of a 5-year-old boy with bone marrow aplasia, who underwent hematopoietic stem cell transplantation (HSCT) and presented persistent febrile neutropenia, abdominal pain, appearance of maculopapular lesions on the skin, and impaired renal function. The presence of S. capitata was identified by blood culture from a central venous catheter. This invasive fungal infection is rare but emergent and life-threatening, especially in immunocompromised patients with persistent febrile neutropenia and prolonged use of invasive devices such as central venous catheters.

Consensus on diagnosis and treatment of invasive fungal infection in patients with severe liver disease / 临床肝胆病杂志

The prognosis of severe liver disease combined with invasive fungal infection (IFI) is poor, and the clinical manifestations are often atypical. Moreover, most of the antifungal drugs are metabolized in the liver, with severe toxicities and side effects, making clinical diagnosis and treatment difficult. The Professional Committee for Hepatology, the Chinese Research Hospital Association and the Hepatology Branch of China Medical Association organized relevant experts to formulate an expert consensus based on the characteristics of patients with severe liver disease combined with IFI, in order to provide reference for medical personnel in making decisions on the diagnosis and treatment.

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.

Candidemia en Colombia / Candidemia in Colombia

En Colombia, especialmente en las unidades de cuidados intensivos, la candidemia es una causa frecuente de infección del torrente sanguíneo y representa el 88 % de las infecciones fúngicas en pacientes hospitalizados, con una mortalidad entre 36 y 78 %. Su incidencia en Colombia es mayor a la reportada en los países desarrollados e, incluso, en otros países de Latinoamérica. Para su manejo deben considerarse los factores de riesgo del paciente, luego valorar las características clínicas y, finalmente, hacer los estudios microbiológicos y, si es necesario, pruebas moleculares. En general, las guías estadounidenses, latinoamericanas y europeas recomiendan las equinocandinas como el tratamiento de primera línea de la candidemia y difieren en el uso de fluconazol dependiendo de la 'evidencia', la gravedad de la enfermedad, la exposición previa a los azoles y la prevalencia de Candida no albicans. Dada su gran incidencia en nuestro país, asociada con una elevada mortalidad, esta infección debe buscarse sistemáticamente en pacientes con factores de riesgo, con el fin de iniciar oportunamente el tratamiento antifúngico.

In Colombia, especially in intensive care units, candidemia is a frequent cause of infection, accounting for 88% of fungal infections in hospitalized patients, with mortality ranging from 36% to 78%. Its incidence in Colombia is higher than that reported in developed countries and even higher than in other Latin American countries. First, the patient's risk factors should be considered, and then clinical characteristics should be assessed. Finally, microbiological studies are recommended and if the evidence supports its use, molecular testing. In general, American, Latin American, and European guides place the echinocandins as the first-line treatment for candidemia and differ in the use of fluconazole based on evidence, disease severity, previous exposure to azoles, and prevalence of Candida non-albicans. Taking into account the high incidence of this disease in our setting, it should be looked for in patients with risk factors to start a prompt empirical anti-fungal treatment.

Advances in the study of T cell immunity in invasive fungal infections secondary to sepsis / 上海交通大学学报（医学版）

Invasive fungal infections (IFI) has high morbidity and mortality. It is more common in hospital infections, and especially in sepsis, the risk of secondary IFI is increased. Immunosuppression of sepsis may affect immune function of T cells, and various T cells subsets have different effects on various fungal pathogens of IFI. The review discusses the pathophysiological processes, mechanism and therapeutic methods of T cell immunity in IFI secondary to sepsis, in order to summarize the role of T cells in IFI secondary to sepsis and introduce the new immunotherapy.

Clinical analysis of 49 cases with invasive fungal infections in pediatric intensive care unit / 中国小儿急救医学

Objective To investigate the clinical characteristics of invasive fungal infections(IFI) in PICU and analyze the risk factors for diagnosis and treatment earlier.Methods The clinical data of patients with IFI hospitalized in PICU from January 2013 to December 2017 were retrospectively studied.Results There were 179 cases of patients with positive fungal cultures,of which 49 cases were IFI.There were 23 males and 26 females,the mean age was (3.87 ± 2.42) years.A total of 47 cases had underlying diseases.In positive specimen,there were 36 cases of bronchoalveolar lavage fluid or sputum cultures,14 cases of blood cultures,7 cases of urinary cultures,3 cases of thoracic/ascites cultures,2 cases of bone marrow cultures,and 1 case of cerebrospinal fluid culture.There were 12 cases who had at least two sites infection at the same time.A total of 53 strains of fungal pathogens were cultivated,among which 45 cases were candida,5 cases were aspergillus,and 3 cases were penicillium marneffei,and 4 cases had two fungal infections.The presence of underlying diseases,blood transfusions,use of antibiotics/glucocorticoids/immunosuppressors,invasive procedures,and long hospital stays were risk factors (all P ＜ 0.05).Drug susceptibility analysis showed that all strains were sensitive to antifungal drugs of amphotericin B/liposomes,azoles and echinocandins,except 1 case of Candida utilis,1 case of Saccharomyces cerevisiae and 1 case of Candida lusitaniae.There were 26 patients only treated with one antifungal drug and 23 had combined drugs.All patients had fever.Eleven patients developed multiple organ dysfunction syndrome and 6 died.Conclusion There are no specific clinical manifestations for children with IFI and with critical condition and high mortality.Candida is the most common fungal infection.The lung is the most common part of infection.The children of IFI with risk factors such as underlying diseases,blood transfusions,use of antibiotics/glucocorticoids/immunosuppressors,invasive procedures and long hospital stays,should be identified in combination with laboratory examination and use antifungal drugs rationally as early as possible.

Biologia Molecular como ferramenta de detecção fúngica no sangue: auxílio diagnóstico e redução de gastos / Molecular Biology as a tool for fungal detection on blood: diagnostic aid and cost reduction

Introdução: Os avanços médicos das últimas décadas contribuíram para aumentar a sobrevida de pacientes críticos e com a resposta imune comprometida. Consequentemente, a população em risco de adquirir infecções de origem fúngica também cresceu. Com altas taxas de morbidade e mortalidade, o difícil diagnóstico deste tipo de infecção, em conjunto com terapias ineficazes, gera elevados custos e sobrecarga ao sistema de saúde. Objetivos: Padronizar um método molecular de detecção fúngica diretamente do sangue e avaliar esta técnica comparativamente com a atualmente considerada padrão-ouro (hemocultura), associando aspectos clínicos, tempo de realização das técnicas e os custos envolvidos. Casuística e Métodos:Neste sentido, 94 pacientes com suspeita de infecção de corrente sanguínea foram submetidos a uma técnica de nestedPCR para detecção de DNA fúngico. Resultados: A técnica molecular foi positiva em 48,9% das amostras, enquanto que a hemocultura foi positiva em apenas 13,0% dos casos. Esses resultados demonstram uma alta sensibilidade do nested PCR e com um valor preditivo negativo de 100% em pacientes com suspeita clínica de infecção fúngica sistêmica e em situações de risco. O tempo de realização do método e os custos associados a ele, em comparação à hemocultura, também demonstraram seu potencial para uso clínico. Conclusões: Em comparação com a hemocultura, o método padronizado de nestedPCR constitui um teste rápido e economicamente viável capaz de descartar uma infecção sistêmica provocada por fungo, podendo facilitar o diagnóstico e evitar terapias ineficientes e caras, diminuir o tempo de internação e os impactos econômicos gerados por esse tipo de infecção.

Introduction: Medical advances in the past decades have contributed to the increase of survival of critically ill patients and the ones with impaired immune response. Consequently, the population at risk of acquiring a fungal infection also has increased. This type of infection generates expensive costs and heavy burden to the Health system. It also brings high morbidity and mortality rates, difficulty in diagnosing, and ineffective therapies. Objectives: Standardize a molecular method of fungal detection directly from blood and compare this technique with the blood culture, which is currently considered the gold standard. It associates clinical aspects, time, and costs involved. Patients and Methods: In this sense, 94 patients with suspected bloodstream infection were submitted to the technique of nested PCR for detection of fungal DNA. Results: The molecular technique was positive in 48.9% of the samples, while the blood culture was positive in only 13% of the cases. These results demonstrate high sensibility of the nested PCR and negative predictive value of 100%. The performing time and the costs associated with the method also demonstrated its value for clinical use. Conclusions: Therefore, the nested PCR is a quick and economically viable test, capable of ruling out a systemic infection caused by fungus, being able to facilitate the diagnosis, avoid inefficient and expensive therapies, and decrease the length of hospital stay, reducing the burden caused by this type of infection.

Tomographic assessment of thoracic fungal diseases: a pattern and signs approach / Avaliação tomográfica das doenças fúngicas no tórax: abordagem por padrões e sinais

Abstract Pulmonary fungal infections, which can be opportunistic or endemic, lead to considerable morbidity and mortality. Such infections have multiple clinical presentations and imaging patterns, overlapping with those of various other diseases, complicating the diagnostic approach. Given the immensity of Brazil, knowledge of the epidemiological context of pulmonary fungal infections in the various regions of the country is paramount when considering their differential diagnoses. In addition, defining the patient immunological status will facilitate the identification of opportunistic infections, such as those occurring in patients with AIDS or febrile neutropenia. Histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis usually affect immunocompetent patients, whereas aspergillosis, candidiasis, cryptococcosis, and pneumocystosis tend to affect those who are immunocompromised. Ground-glass opacities, nodules, consolidations, a miliary pattern, cavitary lesions, the halo sign/reversed halo sign, and bronchiectasis are typical imaging patterns in the lungs and will be described individually, as will less common lesions such as pleural effusion, mediastinal lesions, pleural effusion, and chest wall involvement. Interpreting such tomographic patterns/signs on computed tomography scans together with the patient immunological status and epidemiological context can facilitate the differential diagnosis by narrowing the options.

Resumo Pneumopatias fúngicas proporcionam considerável morbidade e mortalidade, podendo ser oportunistas ou endêmicas. De maneira geral, as apresentações clínicas e padrões de imagem são múltiplos e superponíveis a várias doenças, dificultando a abordagem diagnóstica. Tendo em conta a amplitude do território nacional, o conhecimento da realidade epidemiológica dessas doenças em cada região é fundamental para a consideração delas no diagnóstico diferencial. A definição do estado imunológico irá, ainda, definir a possibilidade de doenças fúngicas oportunistas, por exemplo, na síndrome da imunodeficiência adquirida ou em situações de neutropenia febril. Em geral, histoplasmose, coccidioidomicose e paracoccidioidomicose comprometem indivíduos imunocompetentes, e aspergilose, candidíase, criptococose e pneumocistose comprometem indivíduos imunodeprimidos. Vidro fosco, nódulos, consolidações, micronódulos de disseminação miliar, lesões escavadas, sinal do halo/halo invertido e bronquiectasias são padrões tomográficos frequentes no acometimento pulmonar e serão abordados individualmente, além de apresentações menos frequentes, como lesões mediastinais, derrame pleural e acometimento da parede torácica. A interpretação desses padrões/sinais tomográficos básicos associados a dados epidemiológicos e estado imunológico do paciente pode ser útil, contribuindo para o estreitamento das opções diagnósticas.

Disseminated mycosis in a patient with yellow fever

Disseminated mycosis (DM)­with cardiac involvement and shock­is an unexpected and severe opportunistic infection in patients with yellow fever. DM can mimic bacterial sepsis and should be considered in the differential diagnosis of causes of systemic inflammatory response syndrome in this group of patients, especially in areas where an outbreak of yellow fever is ongoing. We report the case of a 53-year-old male patient who presented to the emergency department with fever, myalgia, headache, and low back pain. The laboratory investigation revealed a positive molecular test for yellow fever, hepatic injury, and renal failure. During hospitalization, the patient developed hepatic encephalopathy, ascending leukocytosis, and ascites, with signs consistent with peritonitis. On the 11th day of hospitalization, the patient developed atrioventricular block, shock and died. At autopsy, angioinvasive mycosis was evidenced mainly in the heart, lungs, kidneys, and adrenals.