Paracoccidoidomicosis: Reporte de 4 casos

La paracoccidioidomicosis (PCM) es una infección causada por hongos patógenos humanos del género Paracoccidioides. Es una micosis sistémica que puede afectar cualquier órgano. Se describen con este reporte cuatro casos de paracoccidioidomicosis con diferentes presentaciones clínicas, tiempo de evolución, con afectación mucocutánea, pulmonar, glándulas suprarrenales, sistema nervioso entre otros, principalmente en adultos varones de diferentes edades y profesiones, tanto inmunosuprimidos como inmunocompetentes, teniendo en común el contacto con el suelo. Se demuestra de esta manera la importancia de considerar esta patología ante una sospecha clínica de micosis sistémica para así realizar una confirmación temprana y tratamiento oportuno ya que presenta buena respuesta terapéutica antimicótica y mejoría clínica.

Paracoccidioidomycosis (PCM) is an infection caused by human pathogenic fungi of the genus Paracoccidioides. This report describes: 4 cases of paracoccidioidomycosis diagnosed with different clinical presentations, different times of evolution, with mucocutaneous, pulmonary, adrenal gland, and nervous system involvement, among others, mainly in male adults of different ages and professions, both immunosuppressed and immunocompetent, having in common contact with the ground. In this way, PCM is a systemic mycosis that can affect any organ and therefore the importance of considering this pathology when a diagnostic suspicion of systemic mycosis is presented in order to make an early diagnosis and timely treatment since it presents a good therapeutic response, antifungal and clinical improvement.

Diagnóstico micológico de paracoccidioidomicosis en un hospital de área no endémica: metodología clásica y molecular

Introducción. La paracoccidioidomicosis es una micosis sistémica y endémica en Latinoamérica. El cambio climático y el movimiento migratorio del huésped enfatizan la necesidad de optimizar el diagnóstico de esta infección. Objetivo. Evaluar la implementación de la detección de ADN de Paracoccidioides spp. al diagnóstico micológico de pacientes con sospecha de paracoccidioidomicosis. Materiales y métodos. Estudio retrospectivo con datos de laboratorio de pacientes con sospecha de paracoccidioidomicosis en un hospital de área no endémica. Resultados. Se analizaron los resultados de las muestras de 19 pacientes con sospecha clínica de paracoccidioidomicosis. El 90 % de los pacientes había nacido o visitado un área endémica de esta micosis en Latinoamérica. En 14 pacientes varones adultos se confirmó paracoccidioidomicosis por diagnóstico convencional. El examen directo fue positivo en 12 pacientes con enfermedad comprobada y en 4 de ellos se obtuvo crecimiento del hongo. Se detectaron anticuerpos contra Paracoccidioides spp. en ocho pacientes con la enfermedad. Se realizó PCR anidada con muestras de 14 pacientes para detectar ADN de Paracoccidioides spp. En 9 de los 10 pacientes con diagnóstico convencional de paracoccidioidomicosis se obtuvo una prueba de PCR positiva. Conclusiones. La implementación de técnicas moleculares para detectar ADN de Paracoccidioides spp. complementa el diagnóstico convencional de paracoccidioidomicosis y permite instaurar el tratamiento antifúngico, sobre todo en los casos clínicos donde no se observa la presencia del hongo en las muestras clínicas. La migración actual de poblaciones humanas dificulta el diagnóstico de paracoccidioidiomicosis y otras infecciones endémicas, por lo que se requiere optimizar el diagnostico micológico en los laboratorios clínicos para tratar pacientes con este tipo micosis desatendida.

Introduction. Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis. Objective. To evaluate the implementation of Paracoccidioides spp. DNA detection in the mycological diagnosis of patients with suspected paracoccidioidomycosis. Materials and methods. It is a retrospective study with laboratory data from patients with clinical suspicion of paracoccidioidomycosis, who consulted a university hospital from a non-endemic area. Results. We analyzed the laboratory results of samples from 19 patients with suspected paracoccidioidomycosis. Seventeen out of 19 patients were born in or had visited an endemic area in Latin America. Fourteen adult male patients were confirmed to have paracoccidioidomycosis by conventional diagnosis: the direct examination was positive in 12 samples while fungal growth was found only in 4. Anti-Paracoccidioides spp. antibodies were detected in 10 patients, 8 of them with proven paracoccidioidomycosis. Nested PCR for Paracoccidioides spp. detection was performed on clinical samples from 14 patients, and positive results were obtained for 9 out of 10 patients with the conventional diagnosis of paracoccidioidomycosis. Conclusions. The incorporation of molecular techniques to detect Paracoccidioides spp. DNA complements the conventional diagnosis of paracoccidioidomycosis. This tool allows the prescription of antifungal treatment in those cases where the fungus is not observed in the clinical samples. Current human migrations difficult the mycological diagnosis of paracoccidioidomycosis and other fungal infections. For this reason, it is necessary to improve mycological diagnosis in clinical laboratories to adequately treat patients with this neglected mycosis.

Fast and cost-effective protocol to produce Paracoccidioides spp. antigens

Introduction. The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility. Objective. To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis. Materials and methods. The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after 5, 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors. Results. Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time. Conclusion. The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.

Introducción. Los métodos existentes para la producción de los antígenos de Paracoccidioides spp. son problemáticos en su estandarización, especificidad, estabilidad, repetibilidad y reproducibilidad. Objetivo. Optimizar la metodología para la producción de antígenos de Paracoccidioides spp. y evaluar su aplicabilidad en el inmunodiagnóstico de la paracoccidioidomicosis. Materiales y métodos. Los antígenos se obtuvieron de aislamientos de P. lutzii (01, 66 y 8334), P. brasiliensis sensu stricto (113) y P. restripiensis (B-339). Estos hongos se cultivaron a 36 °C ± 1 °C en agar Fava-Netto modificado, según Freitas et al. (2018). Los antígenos de P. lutzii se obtuvieron a los 5, 10 y 20 días de cultivo y los antígenos de P. brasiliensis y P. restripiensis se obtuvieron a los 10 días. Los antígenos se evaluaron in natura, concentrados 10 y 20 veces. La capacidad antigénica se evaluó mediante un ensayo de inmunodifusión doble con muestras de suero de pacientes con paracoccidioidomicosis, histoplasmosis, aspergilosis y donantes de sangre aleatorios. Resultados. Se observó reacción cruzada con Paracoccidioides spp. cuando se evaluaron los antígenos de P. brasiliensis, P. restrepiensis y P. lutzii frente a los anticuerpos policlonales contra P. lutzii y P. brasiliensis, respectivamente. No hubo reactividad cruzada con los anticuerpos policlonales contra Histoplasma capsulatum y Aspergillus fumigatus, ni contra los donantes de sangre aleatorios. El protocolo propuesto permitió la producción estable, repetible y reproducible de antígenos dirigidos de un género específico (Paracoccidiodes) en un tiempo corto de cultivo y a un menor costo. Conclusión. El protocolo propuesto permitió obtener antígenos específicos de un género, que pueden ser desarrollados y reproducidos en todos los laboratorios de Antígenos de Paracoccidioides spp.: protocolo rápido Brasil y Surámerica donde la paracoccidioidomicosis es una enfermedad endémica y desatendida. Estos antígenos pueden contribuir al diagnóstico precoz de la infección, independientemente de la especie.

Hiperplasia pseudoepiteliomatosa: carcinoma escamocelular versus paracoccidioidomicosis oral, un caso con mirada dermatológica / Pseudoepitheliomatous hyperplasia: Squamous cell carcinoma versus oral paracoccidioidomycosis, a case from a dermatological perspective

La paracoccidioidomicosis es una micosis sistémica endémica en Latinoamérica. La presentación más frecuente compromete crónicamente los pulmones, la piel y las mucosas. Al inicio, este paciente presentó, por varios años, una lesión única en la mucosa oral que, en ausencia de otros síntomas, se relacionó con una neoplasia maligna, específicamente con un carcinoma escamocelular. La diferenciación entre los dos diagnósticos se hace mediante un examen directo, un estudio histopatológico y cultivos iniciales y subsecuentes. Sin embargo, tales estudios no fueron concluyentes. Después de varias consultas y pruebas, con los resultados del examen directo, la inmunodifusión y la PCR en tiempo real se confirmó el diagnóstico de paracoccidioidomicosis crónica multifocal. Este caso alerta sobre la ausencia de sospecha clínica de micosis endémicas, dada la presencia de lesiones mucocutaneas que pueden ser producidas por hongos como Paracoccidioides spp, y la importancia de considerarlas entre los diagnósticos diferenciales.

Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. The most frequent form involves a chronic compromise of the lungs, skin, and mucosa. The patient started with a single oral lesion that lasted for several years. The absence of other symptoms pointed out a possible malignant neoplasm, specifically a squamous cell carcinoma. Differentiation between both diagnoses-fungal infection and carcinoma-depends on the results of the direct examination, the histopathological study, and the initial and subsequent cultures. However, in this case, those findings were not conclusive. The coexistence of both diagnoses is frequent and increases the diagnostic challenge. After several consultations and tests, direct examination, immunodiffusion and real-time PCR findings the multifocal chronic paracoccidioidomycosis diagnosis was confirmed. This case warns about a systematical absence of clinical suspicion of endemic mycoses before the appereance of mucocutaneous lesions, which can be produced by fungi like Paracoccidioides spp, and the importance of considering those mycoses among the differential diagnoses.

Peritonitis caused by paracoccidioides spp. in a patient on continuous ambulatory peritoneal dialysis - A case report

ABSTRACT Paracoccidioidomycosis is a systemic mycosis found mainly in South America and is the most prevalent endemic and systemic mycosis in Brazil. The purpose of this paper was to report the case of a male patient who developed peritonitis caused by Paracoccidioides spp. Fortyeight-year-old, male patient, with type I Diabetes mellitus and chronic kidney disease who was undergoing a Continuous Ambulatory Peritoneal Dialysis (CAPD) program. After eighteen months of peritoneal dialysis, the patient developed turbidity of the peritoneal fluid and was diagnosed with peritonitis. Direct mycological examination of the peritoneal fluid revealed yeasts with morphology suggestive of Paracoccidioides spp. The patient was treated with sulfamethoxazole-trimethoprim (1,600 mg/320 mg dose/day) for 61 days, but he died because a bacterial septic shock. The diagnosis of opportunistic PCM peritonitis was later confirmed by autopsy and Paracoccidioides spp. isolation. This is the first reported case of a patient on CAPD who experienced complications due peritonitis caused by opportunistic PCM.

Chronic disseminated paracoccidioidomycosis: the first case reported in China / 中华皮肤科杂志

To report the first case of chronic disseminated paracoccidioidomycosis in China. A 49-year-old male patient presented with papules and nodules of the skin for 1 year, and papules and ulcers on the oral mucosa for 2 months. Skin examination showed the edema of the left foot, multiple crusting ulcers on the sole of the left foot, ulcers with a granular base in the interdigital regions between the third and fourth toes as well as fourth and fifth toes of the left foot, accompanied by punctate hemorrhage and exudation; there were multiple papules, nodules, and plaques on the dorsum and medial side of the left foot and the left knee, with ulcers and crusts in the center; 2 papules were observed on the left wrist, and 1 papule on the left upper lip with a crusted surface; red plaques with ulcers and punctate hemorrhage were observed on the gingival mucosa, buccal mucosa, labial mucosa, and palate, and the lesions mainly occurred on the left side. Ultrasonography of superficial lymph nodes showed bilateral cervical and supraclavicular lymph node enlargement, which was more obvious on the left side. Computed tomography of the chest and abdomen showed diffuse miliary nodular shadows, and cordlike, cloudy flocculent and nodular high-density shadows in both lungs, as well as obvious thickening of the left adrenal gland in the abdomen. Yeast cells were observed by immunofluorescent staining of biopsy tissues from the oral mucosa and left lower limb. Histopathological examination of biopsy tissues from the oral mucosa and left lower limb showed granulomatous inflammation, and refractive double-membrane yeast cells could be observed inside or outside the multinucleated giant cells, without or with a single bud or multiple buds; periodic acid-Schiff staining and hexamine silver staining of the above biopsy tissues were positive. Fungal culture of the left lower limb lesion in Sabouraud dextrose agar medium at 25℃ and 37℃ both yielded fungal hyphae. Metagenomics sequencing of the oral mucosal tissue and alveolar lavage fluid indicated the infection with Paracoccidioides brasiliensis. The diagnosis of chronic disseminated paracoccidioidomycosis was confirmed. After 1-month oral treatment with itraconazole capsules at a dose of 400 mg/d, the lesions on the skin and oral mucosa markedly improved, and computed tomography imaging of the lung and left adrenal gland also showed obvious improvement. The dose of itraconazole was reduced to 200 mg/d after 3 months. The patient′s condition further improved during a 10-month follow-up.

A scoping study of pulmonary paracoccidioidomycosis: severity classification based on radiographic and tomographic evaluation

The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one of the most frequently affected organs. Although they have been the subject of many studies with different approaches, the severity classification of the pulmonary involvement, using imaging procedures, has not been carried out yet. This study aimed to classify the active and the residual pulmonary damage using radiographic and tomographic evaluations, according to the area involved and types of lesions.

Multifocal Pseudotumorous Form of Neuroparacoccidioidomycosis in an Immunocompetent Patient: A Clinicopathological Review Based on a Case Report

Neuroparacoccidiodimycosis (NPDM) is an uncommon granulomatous disease, which more frequently affects immunocompromised male patients over 30 years of age in the course of chronic lung disease. Paracoccidioides brasiliensis (PB) is an endemic fungus in Brazil, and grows as thick-walled yeast (with round to oval bodies) measuring 10 µm to 60 µm in diameter. Neuroparacoccidiodimycosi may develop many years after transmission and/or primary lung involvement. The authors describe a case of NPDM affecting a male patient, 52 years of age, farmer, heavy smoker, with clinical complaint of headache, asthenia, seizures, and prostration in the previous nine months. Upon physical examination, the patient presented regular general condition, without other relevant physical alterations. Computed tomography (CT) showed multiple bilateral pulmonary nodules associated to enlargement of the mediastinal lymph node. Magnetic resonance imaging (MRI) and CTscans of the central nervous system showed six heterogeneous nodular lesions compromising the frontal and parietal lobes, the largest one measuring 3.8 3.2 3.2 cm. The hypothesis of a neoplastic process compromising the lung and brain was considered. A biopsy of the mediastinal lymph node showed epithelioid granulomas, which exhibited round, thin-walled fungal structures in Grocott silver stain. The stereotactic biopsy of the frontal lesion was constituted by necrotic tissue admixed with some round to oval, thin-walled fungi measuring 10 µm to 60 µm, compatible with PB (identified on Grocott silver stain/confirmed in culture). The diagnosis of NPDM was then established. The employed therapeutic regimen was intravenous amphotericin B, itraconazole, and sulfamethoxazole-trimetropin. After ninety days of clinical follow-up, no episodes of seizures/neurological deficits were identified, and a marked decrease in the number and size of the lung and brain lesions were found.

Acute/subacute paracoccidioidomycosis with associated eosinophilia

Paracoccidioidomycosis is an endemic mycosis whose initial diagnosis may be difficult, as it shares the clinical characteristics of granulomatous and neoplastic diseases. Although its chronic form is the most frequent, we present the case of a young patient with an acute/ subacute presentation with lymphadenopathy, peripheral eosinophilia and a false-positive hepatitis C serology. The diagnosis was confirmed by histopathology and tissue culture, and he was treated with amphotericin B due to clinical deterioration secondary to progression of systemic involvement. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1921).

La paracoccidiodomicosis es una micosis endémica cuyo diagnóstico inicial puede ser difícil al compartir características clínicas de enfermedades granulomatosas y neoplásicas. Aunque su forma más frecuente es la crónica presentamos el caso de un paciente joven con un cuadro agudo/subagudo con linfadenopatías, eosinofilia periférica y una serología para hepatitis C falsamente positiva. El diagnóstico fue confirmado por histopatología y cultivo de tejidos y se dio manejo con anfotericina B ante el deterioro clínico por progresión del compromiso sistémico.

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

BACKGROUND Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in Latin America that is caused by thermodimorphic fungal species of the Paracoccidioides genus. OBJECTIVES In this study, we used quantitative polymerase chain reaction (qPCR) to investigate the expression of genes related to the virulence of Paracoccidioides brasiliensis (Pb18) and P. lutzii (Pb01) strains in their mycelial (M) and yeast (Y) forms after contact with alveolar macrophages (AMJ2-C11 cell line) and fibroblasts (MRC-5 cell line). METHODS The selected genes were those coding for 43 kDa glycoprotein (gp43), enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 14-3-3 protein (30 kDa), phospholipase, and aspartyl protease. FINDINGS In the Pb18 M form, the aspartyl protease gene showed the highest expression among all genes tested, both before and after infection of host cells. In the Pb18 Y form after macrophage infection, the 14-3-3 gene showed the highest expression among all genes tested, followed by the phospholipase and gp43 genes, and their expression was 50-fold, 10-fold, and 6-fold higher, respectively, than that in the M form. After fibroblast infection with the Pb18 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 25-fold, 10-fold, and 10-fold higher, respectively, than that in the M form. Enolase and aspartyl protease genes were expressed upon infection of both cell lines. After macrophage infection with the Pb01 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 18-fold, 12.5-fold, and 6-fold higher, respectively, than that in the M form. MAIN CONCLUSIONS In conclusion, the data show that the expression of the genes analysed may be upregulated upon fungus-host interaction. Therefore, these genes may be involved in the pathogenesis of paracoccidioidomycosis.

Serological diagnosis of paracoccidioidomycosis using a Paracoccidioides spp. comercial antigen and the counterimmunoelectrophoresis method

ABSTRACT Purpose: In-house Paracoccidioides spp. antigens are commonly used in the serological diagnosis of paracoccidioidomycosis (PCM). The sensitivity and specificity of a commercial Paracoccidioides spp. antigen was assessed for PCM serological testing. Method: Counterimmunoelectrophoresis and double immunodiffusion were used to evaluate the Paracoccidioides ID Antigen reagent in sera from PCM cases and patients with other diseases. Results: All active PCM sera (n=24) were reactive using counterimmunoelectrophoresis (sensitivity = 100%), including 11 cases of infection by P. brasiliensis sensu stricto and one by P. americana. Fifteen (88%) out of 17 sera from patients on treatment or cured were reactive, including one case of P. lutzii infection. One to three bands of antigen-antibody precipitate were observed on the agarose gel, with a predominance of two to three bands in the test with untreated PCM sera or at the beginning of antifungal therapy. All sera from patients with histoplasmosis (n=7), aspergillosis (n=5), and other diseases (n=27) tested negative (specificity = 100%). The overall sensitivity and specificity using the commercial antigen and double diffusion test were 75% and 100%, respectively. Conclusion: The commercial antigen performed satisfactorily and may contribute to the dissemination of the use of serological tests for the PCM diagnosis.

Epidemiology of paracoccidioidomycosis in Venezuela: a retrospective study from 1954 to 2019

BACKGROUND Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Etiological agents are Paracoccidioides species that diverge phylogenetically throughout South America. OBJECTIVES This study aimed to document the epidemiology of PCM in Venezuela. METHODS We have performed a retrospective cross-sectional descriptive study in 31,081 clinical records of patients from two reference centres during 65 years (1954-2019). FINDINGS PCM diagnosis was confirmed in 745 patients. Chronic PCM was the most prevalent form (90.06% cases); 80.67% were male and the most affected age range was 41-60. Farming and construction were the most prevalent occupation and Miranda State had a higher prevalence. Lung and skin were the most affected organs, followed by oral manifestations. Direct examination, culture and serology showed a high sensibility, and no statistical difference was observed among the diagnostic tools. Out of 17 Paracoccidioides isolates genotyped from Venezuela, one was typed as Paracoccidioides americana and 16 as Paracoccidioides venezuelensis. MAIN CONCLUSIONS Clinical manifestations observed, information about the epidemiology and molecular profile is essential not only for diagnosis but also for understanding therapeutic responses to mycotic drugs and prognosis. Therefore, it is necessary to sequence all positive isolated strains in order to confirm the dominance of P. venezuelensis in Venezuela.

Intestinal Paracoccidioidomycosis: Case report and systematic review

ABSTRACT Background: Paracoccidioidomycosis is a systemic mycosis considered endemic and limited to Latin America with the majority of registered cases originating from Brazil. The purpose of this paper was to report a case of a female patient with paracoccidioidomycosis mimicking inflammatory bowel disease and to systematically review available cases of the intestinal presentation of this infectious disease. Case report: Female patient, 32-years old, previously asymptomatic, presenting with acute pain in the lower right abdomen, associated with signs of peritoneal irritation and abdominal distension. Urgent surgery was performed, which identified a severe suppurative perforated ileitis. The anatomopathological study revealed fungal structures shaped as a ship's pilot wheel in Grocott-Gomori's staining, suggestive of Paracoccidioides spp. Methods: Studies were retrieved based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), Embase, and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. Simple descriptive analysis was used to summarize the results. Results: Our search strategy retrieved 581 references. In the final analysis, 34 references were included, with a total of 46 case reports. The most common clinical finding was abdominal pain and weight loss present in 31 (67.3%) patients. Most patients were treated with itraconazole (41.3%) and amphotericin B (36.9%). All-cause mortality was 12.8%. Conclusions: Paracoccidioidomycosis should be suspected in endemics areas, specially as a differential diagnosis for inflammatory bowel disease. Endoscopic tests and biopsy are useful for diagnosis and treatment with antifungal drugs seem to be the first treatment option to achieve a significant success rate.

Úlcera lingual asociada a paracoccidiodomicosis pulmonar / Lingual ulcer as a manifestation of systemic paracoccidioidomycosis: case report

Resumen La paracoccidioidomicosis (PCM) es una enfermedad fúngica sistémica que puede invadir cualquier órgano. Es de alta mortalidad si no es diagnosticado oportunamente. Presentamos el caso de un varón de ocupación agricultor, con antecedente de diabetes mellitus, que desarrolló inicialmente una úlcera lingual y posteriormente, una neumonía y shock séptico, sin respuesta al tratamiento antituberculoso y antibacteriano. El frotis de la secreción bronquial permitió evidenciar las levaduras en gemación múltiple, compatible con una PCM. Tuvo una respuesta satisfactoria a la administración de anfotericina B deoxicolato.

Abstract Paracoccidioidomycosis is a fungal disease of systemic involvement that can invade any organ and is of high mortality if it is not diagnosed in a timely manner. We present the case of a farmer male with a history of diabetes mellitus, who previously develops lingual ulcers and subsequently presents severe lung disease associated with septic shock, without response to antituberculous and antibacterial treatment. The bronchial secretion smear shows evidence of yeasts in multiple budding, compatible with Paracoccidioidomycosis. The patient had a satisfactory recovery to the administration of amphotericin B deoxycholate.

Paracoccidioides brasiliensis habitat: far beyond armadillo burrows?

Paracoccidioides spp. isolation from environmental samples is rare and hardly reproducible. Molecular techniques have facilitated the fungal detection. However, it can be still difficult. Some strategies to enhance the capacity of DNA detection have been adopted, including the analysis of soil samples belonging to the habitat of animals from which Paracoccidioides spp. have already been isolated, notably armadillo burrows. To date, the detection of Paracoccidioides spp. has not yet been reported from outbreak hotspots. Clusters and outbreaks of acute paracoccidioidomycosis (PCM), usually a more severe clinical form, have currently occurred in urban areas being associated to climate changes, deforestation, and great constructions. These occurrences potentially signalise the fungus' environmental niche, a riddle not yet solved. The authors performed an environmental investigation in a deeply disturbed area, after a highway construction in Rio de Janeiro, Brazil, where a recent outbreak of acute PCM occurred. Specific DNA sequences of Paracoccidioides brasiliensis were detected in shallow soil samples around the highway, reinforcing the association between the road construction and this PCM outbreak.

Molecular detection of Paracoccidioides in soil from an urban area of southern Brazil

Abstract INTRODUCTION: Previous studies that detected Paracoccidioides spp. DNA in soil taken from rural areas have shown this to be a valuable tool for ecological and epidemiological studies. This study reports the detection of Paracoccidioides spp. DNA in soil samples from an urban area of southern Brazil. METHODS: Sixteen soil samples were submitted to nested-PCR and the amplicons of a representative number of positive samples were sequenced. RESULTS: Paracoccidioides spp. DNA was found in 44% of samples. Four DNA amplicons were sequenced, showing 100% homology with P. brasiliensis. CONCLUSIONS: The southern Brazilian urban population is commonly exposed to the Paracoccidioides fungus.

Perfil sorológico dos pacientes com suspeita clínica de paracoccidiodomicose avaliados pelo Instituto Adolfo Lutz no ano de 2016 / Serological profile of patients with clinical suspicion of paracoccidiodomycosis evaluated by Instituto Adolfo Lutz in 2016

Oitenta porcento dos casos de paracoccidioidomicose (PMC) ocorrem no Brasil. As regiões brasileiras com maior número de casos são: sul, sudeste e centro-oeste, sendo emergente no norte e nordeste. A imunodifusão dupla em gel de agarose assume grande importância no diagnóstico, por permitir o monitoramento da doença e por oferecer subsídios para levantamentos soroepidemiológicos. O objetivo deste trabalho foi de avaliar e caracterizar os pacientes atendidos no Laboratório de Imunodiagnóstico das Micoses do Instituto Adolfo Lutz de São Paulo, em 2016. Trata-se de um estudo retrospectivo realizado utilizando-se dados secundários e avaliando-se as seguintes informações: idade, sexo, procedência do pedido médico, resultado e histórico sorológico dos pacientes. Dos 1.408 pacientes, 12,8% apresentaram reatividade sorológica para Paracoccidioides brasiliensis. Destes, 42,5% não possuiam histórico sorológico, sendo considerados como casos novos da doença. A classificação dos pacientes reagentes por gênero demonstrou que 83,4% eram do sexo masculino, com razão de masculinidade de 5:1. A faixa etária variou de um (1) a 92 anos, e aproximadamente 40% dos pacientes eram da faixa etária de 41 a 60 anos. Este estudo demonstra e reforça a importância da implementação dos estudos soroepidemiológicos como ferramenta auxiliar para nortear as ações de vigilância e políticas em saúde na PCM. (AU)

Eighty percent of paracoccidioidomycosis (PMC) cases occur in Brazil. The highest numbers occur in south, southeast and center-west region, being emergent in the north and northeast areas. The double immunodiffusion in agarose gel is valuable for its diagnosis, as it allows the monitoring of the disease and offers subsidies for the seroepidemiological surveys. This study evaluated and characterized the patients attended in 2016 at the Mycoses Immunodiagnosis Laboratory of Adolfo Lutz Institute of São Paulo. This retrospective study, based on the secondary data, evaluated the information: age, sex, medical request origin, result and serological history of the patients. Of 1,408 patients, 12.8% presented positive serological reactivity for Paracoccidioides brasiliensis. Of them, 42.5% had no serological history and they were considered as new cases. The classification of reactive patients by gender showed that 83.4% were males, being the masculinity ratio of 5:1. The age range was one (1) to 92 years old, and ±40% of the patients were of age ranging from 41-60 years old. This study reinforces the importance of the implementation of the seroepidemiological studies as to guide the surveillance actions and the public health politics in PCM. (AU)

Perfil sorológico dos pacientes com suspeita clínica de paracoccidiodomicose avaliados pelo Instituto Adolfo Lutz no ano de 2016 / Serological profile of patients with clinical suspicion of paracoccidiodomycosis evaluated by Instituto Adolfo Lutz in 2016

Oitenta porcento dos casos de paracoccidioidomicose (PMC) ocorrem no Brasil. As regiões brasileiras com maior número de casos são: sul, sudeste e centro-oeste, sendo emergente no norte e nordeste. A imunodifusão dupla em gel de agarose assume grande importância no diagnóstico, por permitir o monitoramento da doença e por oferecer subsídios para levantamentos soroepidemiológicos. O objetivo deste trabalho foi de avaliar e caracterizar os pacientes atendidos no Laboratório de Imunodiagnóstico das Micoses do Instituto Adolfo Lutz de São Paulo, em 2016. Trata-se de um estudo retrospectivo realizado utilizando-se dados secundários e avaliando-se as seguintes informações: idade, sexo, procedência do pedido médico, resultado e histórico sorológico dos pacientes. Dos 1.408 pacientes, 12,8% apresentaram reatividade sorológica para Paracoccidioides brasiliensis. Destes, 42,5% não possuiam histórico sorológico, sendo considerados como casos novos da doença. A classificação dos pacientes reagentes por gênero demonstrou que 83,4% eram do sexo masculino, com razão de masculinidade de 5:1. A faixa etária variou de um (1) a 92 anos, e aproximadamente 40% dos pacientes eram da faixa etária de 41 a 60 anos. Este estudo demonstra e reforça a importância da implementação dos estudos soroepidemiológicos como ferramenta auxiliar para nortear as ações de vigilância e políticas em saúde na PCM.

Eighty percent of paracoccidioidomycosis (PMC) cases occur in Brazil. The highest numbers occur in south, southeast and center-west region, being emergent in the north and northeast areas. The double immunodiffusion in agarose gel is valuable for its diagnosis, as it allows the monitoring of the disease and offers subsidies for the seroepidemiological surveys. This study evaluated and characterized the patients attended in 2016 at the Mycoses Immunodiagnosis Laboratory of Adolfo Lutz Institute of São Paulo. This retrospective study, based on the secondary data, evaluated the information: age, sex, medical request origin, result and serological history of the patients. Of 1,408 patients, 12.8% presented positive serological reactivity for Paracoccidioides brasiliensis. Of them, 42.5% had no serological history and they were considered as new cases. The classification of reactive patients by gender showed that 83.4% were males, being the masculinity ratio of 5:1. The age range was one (1) to 92 years old, and ±40% of the patients were of age ranging from 41-60 years old. This study reinforces the importance of the implementation of the seroepidemiological studies as to guide the surveillance actions and the public health politics in PCM.

Diagnóstico de la paracoccidioidomicosis / Diagnosis of paracoccidioidomycosis

La paracoccidioidomicosis es una micosis sistemática, endémica de amplias regiones de América Latina, causada por un hongo termodimorfo, Paracoccidioides brasiliensis. Afecta de manera predominante a individuos de mediana edad y sexo masculino, en particular aquellos que cumplen tareas rurales. la infección se adquiere por vía inhalatoria, y puede diseminarse por vía hemática a diversos órganos y tejidos. La enfermedad puede evolucionar en forma aguda, subaguda o crónica. El diagnóstico presuntivo de la paracoccidioidomicosis se sustenta en los antecedentes epidemiológicos del paciente y en las manifestaciones clínicas. El diagnóstico etiológico clásico consiste en la visualización, el aislamiento y la identificación del agente causal, o bien el empleo de pruebas serológicas para determinar la presencia de anticuerpos específicos en sangre. Se presentan tres casos de paracoccidioidomicosis en pacientes varones, dos con formas agudas de la enfermedad y el restante con una forma crónica. En todos los casos, el diagnóstico se efectuó por los hallazgos de la microscopia, los cultivos y las pruebas serológicas

Paracoccidioidomycosis is a systemic mycosis, endemic to large regions of Latin America, caused by a thermodimorphic fungus, Paracoccidioides brasiliensis. It predominantly affects middle-aged and male individuals, particularly those who perform rural tasks. The infection is acquired by inhalation, and it can spread by blod to various organs and tissues. The disease can evolve in acute, subacute or chronic form. The presumptive diagnosis of paracoccidiodomycosis is based on the patient's epidemiological history and clinical manifestations. The classic etiological diagnosis consists of visualization, isolation and identification of the causative agent, or the use of serological tests to determine the presence of specific antibodies in the blood. There are threee cases of paracoccidioidomycosis in male patients, two with acute forms of the disease and the remaining with a chronic form. In all cases, the diagnosis was made by the findings of microscopy, cultures and serological tests

Metanálisis de pruebas inmunológicas para el diagnóstico de la infección por Paracoccidioides, 1972-2017 / Meta-analysis of immunological tests for the diagnosis of Paracoccidioides infection, 1972-2017

Objetivo: Evaluar la validez diagnóstica de las pruebas inmunológicas en la infección por Paracoccidioides, a partir de un metaanálisis de la literatura publicada entre 1972-2017. Métodos: Se realizó un metanálisis según las fases de identificación, tamización, elección e inclusión descritas en la guía PRISMA. Se evaluó la calidad metodológica con la guía QUADAS y se garantizó la reproducibilidad en la selección de estudios y extracción de la información. Se estimó la sensibilidad, especificidad, razones de verosimilitud, OR diagnóstica y área bajo la curva ROC usando Meta-DiSc. Resultados: Se identificaron 21 estudios que evaluaron 32 pruebas diagnósticas con una población de 1.404 individuos sanos, 2.415 con otras infecciones y 2.337 con Paracoccidioides. La mayoría de pacientes son de Brasil y Colombia. Las pruebas analizadas incluyen inmunodifusión, western blot, ELISA, aglutinación en látex. Las pruebas presentaron una sensibilidad y especificidad superior al 90%, razón de verosimilitud positiva y negativa de 24,7 y 0,08 respectivamente. La OR diagnóstica fue 495,9 y el área bajo la curva de 0,99. En la meta-regresión por tipo de antígeno se encontró que las mezclas de antígenos y el gp43 presentaron resultados satisfactorios en todos los parámetros; por su parte, los que utilizaron el antígeno p27 no presentaron resultados aceptables en ninguno de los parámetros. Conclusión: La elevada validez diagnóstica hallada en las pruebas serológicas que utilizan mezclas de antígenos o gp43 purificada evidencia la pertinencia de su uso en clínica y en programas de tamización.

Objective: To evaluate the diagnostic validity of the immunological tests in Paracoccidioides infection, from a meta-analysis of the literature published between 1970-2017. Methods: Meta-analysis according to the identification, screening, eligibility and inclusion phases of PRISMA. The methodological quality was evaluated with the QUADAS guide and the reproducibility in the selection of studies and extraction of the information was guaranteed. Sensitivity, specificity, likelihood ratios, diagnostic OR and area under the ROC curve were estimated using Meta-DiSc. Results: We identified 21 studies that evaluated 32 diagnostic tests with a population of 1404 healthy individuals, 2415 with other infections and 2337 with Paracoccidioides. The majority of patients are from Brazil and Colombia. The tests analyzed include immunodiffusion, western blot, ELISA, latex agglutination. The tests presented a sensitivity and specificity higher than 90%, positive and negative likelihood ratio of 24,7 and 0,08 respectively. The diagnostic OR was 495,9 and the area under the curve was 0,99. In the meta-regression by type of antigen it was found that mixtures of antigens and gp43 showed satisfactory results in all parameters; those who used the p27 antigen did not present acceptable results in any of the parameters. Conclusion: The diagnostic validity of the serological tests using mixtures of antigens or purifed gp43 is clinically similar, for the other antigens the validity was scarce.