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.

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

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.

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

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

First case report of cryptococcosis due to Cryptococcus decagattii in a pediatric patient in Argentina

Abstract We report the first case of cryptococcosis due to Cryptococcus decagattii in an immunocompetent pediatric patient from an indigenous community in Argentina with a successful outcome. Two isolates (blood, cerebrospinal fluid) were genotyped by restriction fragment length polymorphism of the orotidine monophosphate pyrophosphorylase (URA5) gene as VGIV and identified by multi-locus sequence typing as C. decagattii. Matrix-assisted laser desorption/ionization time of flight mass spectrometry identification indicated genotype VGIII. The minimum inhibitory concentration of amphotericin B, fluconazole, itraconazole, and voriconazole was determined (cerebrospinal fluid: 0.25, 16, 0.12, and 0.12, blood: 0.25, 4, 0.12, and 0.06, respectively, all in mg/L).

Nódulo pulmonar solitario por Cryptococcus en paciente HIV positivo. Reporte de un caso / Solitary pulmonary nodule by c ryptoc oc cus in HIV pos itiv e patient. Case repor

Se presenta el caso de un paciente masculino VIH positivo con historia de cefalea y rigidez nucal. Dada su condición clínica el paciente es hospitalizado en sala. La radiografía de tórax es normal y se realiza tomografía de tórax de alta resolución debido a la historia clínica de VIH encontrándose un nódulo pulmonar solitario en el pulmón derecho con márgenes irregulares al cual se realiza biopsia dirigida por tomografía resultando un diagnóstico de micosis pulmonar.

A case of a positive VHI male patient with a history of headache and nuchal stiffness is reported. Gi­ven his clinical condition, the patient is hospitalized in the emergency room. The chest x­ray is nor­mal and a high­resolution chest tomography is performed due to the clinical history of HIV, finding a solitary pulmonary nodule in the right lung with irregular margins to which a biopsy directed by tomo­graphy is performed, resulting in a diagnosis of pulmonary mycosis.

Criptococcosis en el Hospital Carlos Van Buren de Valparaíso: una serie de casos / Cryptococcosis in Hospital Carlos Van Buren, Valparaiso: a clinical serie

Resumen Introducción: La criptococcosis es una infección micótica oportunista grave, Cryptococcus neoformans es la principal especie de importancia médica, pudiendo manifestarse como meningitis, neumonía o criptococcemia. Objetivo: Caracterizar a los pacientes con infección por Cryptococcus sp. entre el 01/01/13 y 30/06/16, en el HCVB. Materiales y Métodos: Se identificaron los cultivos con desarrollo de Cryptococcus sp., y a partir de éstos se obtuvo los registros de los pacientes, los que fueron analizados por dos revisores independientes. Resultados: Se recopiló la información de 13 pacientes, que presentaron 15 casos de infección por C. neoformans. De los 13 pacientes, 11 (84,6%) eran de sexo masculino, con una mediana de edad de 35 años. 11 pacientes (84,6%) padecían infección por VIH, uno (7,7%) tenía el antecedente de leucemia linfática crónica, y uno (7,7%) de etilismo crónico. De los 15 casos, nueve (60%) presentaron infección meníngea; cinco (33,3%) presentaron criptococcemia sin compromiso del LCR; y uno (6,6%) presentó infección pulmonar. De los 13 pacientes, ocho (53,3%) se encontraban fallecidos al año de seguimiento. Conclusiones: La infección por Cryptococcus sp. es una patología que debe ser sospechada en pacientes con inmunodeficiencia de predominio celular. La infección meníngea fue la forma más frecuente de presentación. Persiste presentando una elevada mortalidad.

Background: Cryptococcosis is a severe opportunistic mycotic infection, caused mainly by Cryptococcus neoformans. It can present as meningitis, pneumonia or cryptococcemia. Aim: To characterize patients with Cryptococcus infection between January 1°, 2013 and June 30, 2016, in Hospital Carlos van Buren, Valparaíso, Chile. Methods: We identified retrospectively those cultures with Cryptococcus sp. growth, and then obtained their clinical files which were analyzed by two independent reviewers. Results: We were able to obtain data from 13 of 15 patients who presented with Cryptococcus neoformans infection. Out of all, 11 (84.6%) were males, with a median age of 35 years old. 11 (84,6%) were HIV positive, 1 (7,7%) had chronic lymphocytic leukemia, and 1 (7,7%) refered alcohol abuse. Out of the 15 episodes, 9 (60%) had meningeal infection; 5 (33.3%) were cryptococcemia without meningeal involvement and 1 (6.6%) presented as a pulmonary infection. Eight patients were deceased at one year follow up. Conclusions: Cryptococcus sp. infection must be suspected in patients with cellular immunodeficiencies. Meningeal involvement is the most frequent form of clinical presentation. It still has a high mortality rate.

Diagnóstico de Cryptococcus neoformans mediante la PCR- RFLP en el líquido cefalorraquídeo (LCR) en pacientes hospitalizados en el sur de Brasil / Cryptococcus neoformans diagnosis using PCR-RFLP on cerebrospinal fluid (CSF) of hospitalized patients in southern Brazil

Introducción: Cryptococcus neoformans es un hongo levaduriforme encapsulado, de distribución mundial, principalmente en regiones tropicales, causando infecciones en individuos inmunocomprometidos, sobre todo en los infectados con el virus de la inmunodeficiencia humana (HIV). La capacidad de infección de este hongo es variable, pudiendo citar la facultativa patogenicidad, cápsula con actividad fagocitaria y producción de melanina como antioxidante. El objetivo de este trabajo fue evaluar el uso de la PCR/ RFLP para la detección e identificación de C. neoformans directamente del líquido cefalorraquídeo (LCR) de pacientes ingresados en un hospital público de la ciudad de Lages, Estado de Santa Catarina, sur de Brasil, comparando el resultado con la tinción específica para el hongo y el crecimiento en medio de cultivo. Métodos: Las muestras fueran directamente teñidas con tinta china para observar la cápsula, bien como después sembladas en medio de cultivo (agar dextrosa Sabouraud y agar de Níger) para crecimiento fúngico; también se hizo la extracción del ADN con fenol-cloroformo. La técnica fue utilizada para amplificación del gen URA5 mediante reacción en cadena de la polimerasa (PCR) y después con las enzimas de restricción HhaI y Sau96I para genotipaje mediante la PCR-RFLP. Resultados: En dos muestras fueran aislados C. neoformans con la tinción china y amplificados en la PCR, en las cuales fueran identificados como var. grubii. Conclusión: El serotipo A var. grubii es lo más aislado en la criptococosis humana, principalmente en pacientes HIV, pero se desconoce la preferencia de este serotipo por este grupo de enfermos. (AU)

Introduction: Cryptococcus neoformans is an encapsulated yeast with worldwide circulation, predominantly in tropical regions, causing infections in immunocompromised individuals, particularly those infected with human immunodeficiency virus (HIV). The virulence of this fungus is variable, and it should be mentioned the facultative pathogenicity, capsule with anti-phagocytic activity, and antioxidant melanin production. The aim of this study was to evaluate the use of polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP) for detection and identification of C. neoformans directly from the cerebrospinal fluid (CSF) of patients admitted to a public hospital with suspected meningitis and/or meningoencephalitis in the city of Lages, Santa Catarina, southern Brazil. Results were compared using Chinese ink and growth media. Methods: The samples were submitted to direct examination with Chinese ink for capsule observation, then to growth on culture media (Sabouraud Agar and Niger), with subsequent DNA extraction with phenol-chloroform. PCR was the technique used for amplification of URA5 gene, and then restriction enzymes HhaI and Sau96I were used for genotyping by PCR-RFLP. Results: In two samples, C. neoformans were isolated by Chinese ink and amplified by PCR. They were identified as serotype var. grubii. Conclusion: C. neoformans var. grubii is the most commonly isolated in human cryptococcosis, mainly in HIV patients. However, the preference of this serotype for this group of patients is unknown. (AU)

Identification of Cryptococcus neoformans by MALDI-TOF mass spectrometry in blood culture

This is a report of isolation of Cryptococcus neoformans from blood culture. Identification was conducted by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The relevance of this report is related to the site affected, the severity of the infection, and the importance of correct and rapid identification of the causative pathogen for a successful treatment and for reducing the risk of morbidity and mortality. (AU)

Cryptococcal cerebellitis in no-VIH patient / Cerebelitis criptococócica en paciente VIH negativo

Abstract Introduction: Cryptococcosis is an opportunistic fungal infection whose etiology is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised patients mainly. Meningeal infection is one of the most common presentations, but cerebellar affection is rare. Case Description: Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status. Clinical findings and diagnostic methods: Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. Treatment: Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died. Clinical Relevance: The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst.

Resumen Introducción: La Criptococosis es una infección micótica oportunista cuya etiología es el complejo Cryptococcus neofromans/C. gattii, el cual principalmente afecta pacientes inmunocomprometidos. La afección meníngea es una de las formas más frecuentes pero el compromiso cerebeloso es raro. Descripción del Caso: Paciente masculino de 65 años, procedente de un área rural con exposición crónica a aves de corral, sin antecedentes patológicos, con cuadro clínico inicial consistente en cefalea crónica, fiebre, convulsiones y alteración del estado mental. Hallazgos clínicos y métodos diagnósticos: Al principio sin signos de hipertensión intracraneana ni meníngeos y examen neurológico normal, con posterior desarrollo de ataxia, disdiadococinesia y dismetría. Se diagnosticó Cerebelitis Criptocococica con ayuda de repetidos estudios de LCR y resonancia magnética nuclear. Tratamiento: Se inició terapia antifúngica con Anfotericina B y Fluconazol, con respuesta tórpida y el paciente fallece. Relevancia clínica: La Cerebelitis Criptocococica es una presentación clínica infrecuente que requiere sospecha clínica y recursos diagnósticos para definir el tratamiento de forma temprana. La inmunosupresión no es requisito para padecer esta infección.

Fatal Cryptococcus gattii genotype VGI infection in an HIV-positive patient in Barranquilla, Colombia

ABSTRACT Cryptococcosis is a major invasive fungal disease related worldwide with the AIDS population. New reports of HIV/AIDS cases to the national public health surveillance system (SIVIGILA) in Colombia have shown that there is a growing community at risk of contracting cryptococcosis throughout the country who do not have access to ART. Even though the most prevalent species Cryptococcus neoformans is mainly associated with the HIV population, we report a fatal case of cryptococcosis in an AIDS patient in Barranquilla, associated with Cryptococcus gattii VGI, isolated from blood culture.

Cryptococcus laurentii fungaemia in a cervical cancer patient

ABSTRACT Infections caused by emerging Cryptococcus non-neoformans species are being reported with increasingly frequency. Here, we present a case of fungaemia byCryptococcus laurentii in a woman receiving aggressive immunosuppressive therapy for cervical neoplasia. Three venous blood samples were aseptically collected on consecutive days and C. laurentiiwas isolated and identified through phenotypic and molecular methods. After central venous catheter removal and appropriate antifungal therapy, the patient showed significant improvement and blood culture became negative. Thus, patients following immunosuppressive therapies and using invasive medical devices are at risk of C. laurentii blood infections.

Validation and clinical application of a molecular method for the identification of Cryptococcus neoformans/Cryptococcus gattii complex DNA in human clinical specimens

ABSTRACT The diagnosis of cryptococcosis is usually performed based on cultures of tissue or body fluids and isolation of the fungus, but this method may require several days. Direct microscopic examination, although rapid, is relatively insensitive. Biochemical and immunodiagnostic rapid tests are also used. However, all of these methods have limitations that may hinder final diagnosis. The increasing incidence of fungal infections has focused attention on tools for rapid and accurate diagnosis using molecular biological techniques. Currently, PCR-based methods, particularly nested, multiplex and real-time PCR, provide both high sensitivity and specificity. In the present study, we evaluated a nested PCR targeting the gene encoding the ITS-1 and ITS-2 regions of rDNA in samples from a cohort of patients diagnosed with cryptococcosis. The results showed that in our hands, this Cryptococcus nested PCR assay has 100% specificity and 100% sensitivity and was able to detect until 2 femtograms of Cryptococcus DNA.

Mortalidade por criptococose no Brasil (2000 a 2012) / Mortality from cryptococcosis in Brazil (2000 to 2012)

A criptococose é uma micose sistêmica cosmopolita negligenciada e predominantemente oportunista. Quando associada à AIDS, apresenta-se como a primeira infecção oportunista em 4,4 por cento dos casos diagnosticados no Brasil e geralmente é causada pela espécie Cryptococcus neoformans sendo estimados 1.000.000 de casos anuais e 250.000 óbitos relacionados. Não é agravo de notificação compulsória no país e seu diagnóstico é tardio, acompanhado de alta letalidade (45 a 65 por cento), constituindo importante problema de saúde pública. O presente estudo objetivou caracterizar a situação da mortalidade por criptococose no Brasil no período de 2000 a 2012. Trata-se de um estudo descritivo baseado em dados secundários obtidos do Departamento de Informática do Sistema Único de Saúde (DATASUS) e do Instituto Brasileiro de Geografia e Estatística (IBGE). Foram analisados 5755 registros de óbitos nos quais a criptococose foi relacionada como um dos estados mórbidos que contribuíram para o desfecho, sendo 1121 (19,5 por cento)registrados como causa básica da morte e 4634 (80,5 por cento) associados à AIDS e outras causas de imunodepressão. A taxa de mortalidade no Brasil, segundo causa básica foi de 0,47/milhão de habitantes e, por total de menções, foi de 2,41/milhão de habitantes. A razão de menções como causa básica, isto é, a freqüência com que a criptococose esteve presente como um dos agravos contribuintes para o desfecho do óbito, em comparação ao registro da micose como causa básica da morte,evidenciou um incremento de 400%. (...) Este estudo é relevante ao dar maior visibilidade à situação da mortalidade por criptococose no país, particularmente sua associação com a AIDS, e pode subsidiar a criação e a intensificação de programas de controle e vigilância da doença nas regiões mais carentes...

Cryptococcosis is a systemic mycosis neglected cosmopolitan and predominantly opportunistic. When associated with AIDS, is presented as the first opportunistici nfection in 4.4 percent of cases diagnosed in Brazil and is usually caused by Cryptococcus neoformans species being estimated 1,000,000 cases per year and 250,000 related deaths. Not interlocutory mandatory reporting in the country and its diagnosis isdelayed, accompanied by high mortality (45-65 percent), representing an important publichealth problem. This study aimed to characterize the situation of mortality from cryptococcosis in Brazil from 2000 to 2012. This is a descriptive study based on secondary data obtained from the Department of the Unified Health System (DATASUS) and the Brazilian Institute of Geography and Statistics (IBGE). Were analyzed 5755 records of deaths in which cryptococcosis was listed as one of the morbid conditions that contributed to the outcome, and 1121 (19.5 percent) recorded as the underlying cause of death and 4634 (80.5 percent) associated with AIDS and other causes of immunosuppression. The mortality rate in Brazil as primary cause was 0.47/millionin habitants, and total mentions, was 2.41/million inhabitants. The reason of mentionsas the underlying cause, namely, the frequency with which cryptococcosis waspresent as a taxpayer grievance for the outcome of death, compared to the record of ringworm as underlying cause of death, showed an increase of 400 percent. (...) This study is relevant to give greater visibility to the situation of mortality from cryptococcosis in the country, particularly its association with AIDS, and can support the creation and intensification of control programs and surveillance of the disease in the poorest regions...

Cryptococcosis in Colombian children and literature review

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.

Características histomorfológicas e histoquímicas determinantes no diagnóstico da criptococose em animais de companhia / Determining histomorphological and histochemical characteristics in the diagnosis of cryptococosis in companion animals

Seven cases of cryptococosis (six cats and one dog) were studied to establish the determining histomorphological and histochemical characteristics in the histopathological diagnosis of this condition. Additional data related to the epidemiology, clinical aspects, sites of the lesions, and gross findings were obtained from the necropsy and biopsy protocols. Histologically, yeasts were observed inside macrophages or free in the parenchyma, associated with scarse to severe lymphohistioplasmacytic inflammatory reaction. In the hematoxylin-eosin (HE) sections, the yeasts were round, with a central cell containing a nucleus, surrounded by a clear halo (usually non-stained capsule). The techniques of periodic Schiff acid (PAS), Groccot (GMS), and Fontana-Masson (FM) were utilized and demonstrated the wall of the yeast cells. The FM stain showed the melanin present in these cells. The Alcian blue and Mayer's mucicarmin stains showed mainly the yeast polysaccharide capsule. The diameter of the cells ranged from 1.67 to 10.00µm and the full diameter of the encapsulated yeasts varied between 4.17 e 34.16µm. Yeast buddings were better observed through the PAS stain and were narrow based, simple or multiple, mainly in the opposite poles of the cells or forming chains. The definitive diagnosis of cryptococosis was established through the histopathological exam, based on the specific morphology of the agent (encapsulated yeast) and on histochemical proprieties, mostly in the cases without fungal culture.

Sete casos de criptococose (seis gatos e um cão) foram estudados para estabelecer as características histomorfológicas e histoquímicas determinantes no diagnóstico histopatológico dessa condição. Os dados complementares relacionados à epidemiologia, aos aspectos clínicos, à localização das lesões e às alterações macroscópicas foram obtidos dos protocolos de necropsias e biópsias. Na histologia, as leveduras foram observadas no interior de macrófagos ou livres no parênquima, associadas à reação inflamatória linfo-histioplasmocítica que variou de escassa a acentuada. Pela técnica de hematoxilina-eosina (HE) as leveduras eram arredondadas, com célula central contendo um núcleo, circundada por um halo claro (cápsula geralmente não corada). As técnicas histoquímicas do ácido periódico de Schiff (PAS), Grocott e Fontana-Masson (FM) foram utilizadas e evidenciaram a parede das células das leveduras. Pelo FM observou-se a melanina presente nessas células. As técnicas do azul Alciano e da mucicarmina de Mayer evidenciaram principalmente a cápsula polissacarídica das leveduras. O diâmetro das células das leveduras variou de 1,67 a 10,00µm e o diâmetro total das leveduras encapsuladas variou entre 4,17 e 34,16µm. Os brotamentos foram melhor visualizados através do PAS e ocorreram em base estreita, de forma única ou múltipla, principalmente em polos opostos das células das leveduras ou formando uma cadeia. O diagnóstico definitivo de criptococose foi estabelecido através do exame histopatológico, baseando-se na morfologia característica do agente (levedura encapsulada) e em suas propriedades tintoriais (histoquímicas), principalmente nos casos em que a cultura micológica não foi realizada.

Ocorrência de micoses e pitiose em animais domésticos: 230 casos / Occurrence of mycoses and pythiosis in domestic animals: 230 cases

A retrospective study was performed to determine the main mycoses and oomycosis that affected domestic animals diagnosed in the Laboratório de Patologia Veterinária (LPV) of the Universidade Federal de Santa Maria (UFSM). A total of 29,686 exams (9,487 necropsy reports and 20,199 biopsy reports) performed between January 1990 and December 2012 were analyzed. Two hundred and thirty cases (78% of mycoses and 22% of pythiosis) were found. Data about epidemiology, clinical signs, gross and histologic lesions were obtained from the reports. In two cases the fungi observed were not identified. The main diseases observed, in descending order of prevalence, were: pythiosis, candidiasis, aspergillosis, zygomycosis, dermatophytosis, mallasseziosis, cryptococcosis, megabacteriosis, and sporothrichosis. Others diseases with only one cases each were histoplasmosis and pneumocystosis. Pythiosis affected mainly horses and the mycosis affected mainly companion animals (dogs and cats).

Para determinar as principais micoses e oomicoses que acometeram animais domésticos na área de abrangência do Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM), foi realizado um estudo retrospectivo em 9.487 protocolos de necropsias e 20.199 exames histopatológicos (totalizando 29.686 casos), realizados no LPV-UFSM, entre janeiro de 1990 e dezembro de 2012. Do total de protocolos analisados, 230 apresentaram micoses ou pitiose (oomicose), sendo 179 casos (78%) de micoses e 51 casos (22%) de pitiose. Os protocolos foram revisados para determinar os principais achados referentes à epidemiologia, sinais clínicos e às alterações macroscópicas e microscópicas. Em dois casos (0,8%) não foi possível determinar o gênero ou o grupo do fungo observado. As principais doenças diagnosticadas, em ordem decrescente de prevalência, foram: pitiose, candidíase, aspergilose, zigomicose, dermatofitose, malasseziose, criptococose, megabacteriose e esporotricose. Outras doenças diagnosticadas numa única ocorrência cada foram histoplasmose e pneumocistose. Os equinos foram os mais acometidos pela pitiose e os animais de companhia (cães e gatos) foram os mais acometidos pelas micoses.

Importance of the association of molecular and immunological diagnosis in immunocompetent patient with Histoplasma capsulatum and Cryptoccocus neoformans infection: a case report

This case reports an immunocompetent 29-year-old woman with suspected pneumonia, suggestive of fungal infection. Immunoblotting analysis reactivity againstHistoplasma capsulatum and Paracoccidioides brasiliensis were observed. Nested-PCR in blood employing species-specific primers was positive for H. capsulatum andCryptococcus neoformans. The evaluation of paucisymptomatic patients with positive results for H. capsulatum and C. neoformans could be relevant for the prevention as well as the possible evaluation of the reactivated quiescent foci. In conclusion, the associated methodology may have contributed to the monitoring endogenous reactivation of these diseases.(AU)

Criptococosis e histoplasmosis diseminadas y simultáneas como primera manifestación de SIDA / Disseminated and simultaneous histoplasmosis and cryptococcosis as a first clinical manifestation of AIDS

La histoplasmosis y la criptococosis son dos de las enfermedades fúngicas de mayor prevalenciaen pacientes con enfermedad HIV/SIDA avanzada y recuentos de linfocitos T CD4 + menores de100 cel/uL. Ambas continúan siendo una importante causa de mortalidad y morbilidad en aquellossujetos que no reciben tratamiento antirretroviral. La reactivación simultánea de ambos patógenoses una eventualidad infrecuente, que ha sido pocas veces publicada en la literatura médica yafecta especialmente a pacientes con marcado deterioro de la inmunidad mediada por células. Sepresenta un paciente con reactivación simultánea de la infección por Cryptococcus neoformanse Histoplasma capsulatum en el contexto de enfermedad HIV/SIDA avanzada y se efectúa unarevisión de la literatura sobre el tema.

Histoplasmosis and cryptococcosis are two of the most frequent fungal opportunistic infectionsin patients with advanced HIV/AIDS disease and CD4 T-cell counts below 100 cell/µL. Also,these mycoses are an important cause of morbimortality in those patients without antiretroviraltherapy. Simultaneous reactivation of disseminated infections due to Histoplasma capsulatum andCryptococcus neoformans have rarely been described in the literature, involving especially those patients with severe impairment of cellular immunity. Here we present a patient with advancedHIV/AIDS disease who developed a simultaneous reactivation of disseminated infections due to H.capsulatum and C. neoformans infections and we review the previously reported cases publishedin the medical literature.