RESUMO
O gênero Aspergillus compreende espécies de fungos saprotróficos, globalmente distribuídos, sendo os Aspergillus seção Fumigati conhecidos por causarem doença em humanos e animais imunocomprometidos. Os sinais clínicos dependem do sistema acometido, podendo apresentar febre branda, cólicas intensas, pneumonias, micose de bolsa gutural, e, ocasionalmente, lesões no sistema nervoso central. O presente trabalho objetiva relatar os sinais clínicos, os achados de necropsia e a histologia de um caso de aspergilose sistêmica em um potro de oito meses de idade. O animal apresentava refluxo enterogástrico, peristaltismo aumentado, fezes pastosas, dor abdominal e desidratação intensa. O quadro clínico evoluiu para óbito e o cadáver foi encaminhado para a necropsia. Macroscopicamente, havia sufusões e equimoses na serosa do trato gastrointestinal e ulcerações na mucosa do intestino delgado. No pulmão, havia nódulos multifocais, esbranquiçados e firmes que, ao corte, apresentavam-se císticos, com revestimento interno vinhoso e friável. O coração exibia áreas esbranquiçadas multifocais no miocárdio e os rins continham nódulos avermelhados nas regiões cortical e medular. No encéfalo, havia áreas multifocais amareladas e hemorrágicas com bordos avermelhados. Microscopicamente, observaram-se áreas multifocais de necrose com infiltrado inflamatório granulomatoso no intestino, pulmão, encéfalo, miocárdio e nos rins. Hifas fúngicas intralesionais e intravasculares foram observadas no encéfalo e no pulmão. Estruturas de fenótipo compatível com Aspergillus fumigatus foram observadas na cultura fúngica. Amostras encaminhadas para virologia apresentaram-se positivas para Herpesvírus Equino (HVE) tipo 1 e 4. O diagnóstico de aspergilose sistêmica foi determinado pelo histórico clínico, imunossupressão, achados macroscópicos, histológicos, isolamento do fungo e à infecção concomitante por HVE.
The Aspergillus genus comprises globally distributed species of saprotrophic fungi, with the Aspergillus section Fumigatus known to cause diseases in humans and immunocompromised animals. Clinical signs depend on the affected system, exhibiting mild fever, severe colic, pneumonia, guttural bag mycosis and occasionally lesions in the central nervous system. The present work aims to report the clinical signs, necropsy findings and histology of a case of systemic aspergillosis in an eight-months-old foal. The animal had enterogastric reflux, increased peristalsis, pasty feces, abdominal pain and severe dehydration. The condition evolved to death and the cadaver was sent for necropsy. Macroscopically, there were suffusions and ecchymosis in the serosa of the gastrointestinal tract and ulcerations in the mucosa of the small intestines. In the lung, there were multifocal, whitish and firm nodules that were cystic when cut with a friable winey internal lining. The heart had whitish multifocal areas in the myocardium and the kidneys contained reddish nodules in the cortical and medullary regions. In the brain there were yellowish and hemorrhagic multifocal areas with reddish borders. Microscopically, multifocal areas of necrosis with granulomatous inflammatory infiltrate were observed in the intestine, lung, brain, myocardium and kidneys. Intralesional and intravascular fungal were observed in the brain and lung. Structures with phenotype compatible with Aspergillus fumigatus were observed in the fungal culture. In virology, samples were positive for equine herpesvirus (HVE) types 1 and 4. The diagnosis of systemic aspergillosis was determined due to the clinical history, immunosuppression, macroscopic and histological findings, fungal isolation and concomitant HVE infection.
Assuntos
Masculino , Animais , Aspergilose/complicações , Aspergilose/diagnóstico , Aspergilose/sangue , Aspergilose/veterináriaRESUMO
O gênero Aspergillus compreende espécies de fungos saprotróficos, globalmente distribuídos, sendo os Aspergillus seção Fumigati conhecidos por causarem doença em humanos e animais imunocomprometidos. Os sinais clínicos dependem do sistema acometido, podendo apresentar febre branda, cólicas intensas, pneumonias, micose de bolsa gutural, e, ocasionalmente, lesões no sistema nervoso central. O presente trabalho objetiva relatar os sinais clínicos, os achados de necropsia e a histologia de um caso de aspergilose sistêmica em um potro de oito meses de idade. O animal apresentava refluxo enterogástrico, peristaltismo aumentado, fezes pastosas, dor abdominal e desidratação intensa. O quadro clínico evoluiu para óbito e o cadáver foi encaminhado para a necropsia. Macroscopicamente, havia sufusões e equimoses na serosa do trato gastrointestinal e ulcerações na mucosa do intestino delgado. No pulmão, havia nódulos multifocais, esbranquiçados e firmes que, ao corte, apresentavam-se císticos, com revestimento interno vinhoso e friável. O coração exibia áreas esbranquiçadas multifocais no miocárdio e os rins continham nódulos avermelhados nas regiões cortical e medular. No encéfalo, havia áreas multifocais amareladas e hemorrágicas com bordos avermelhados. Microscopicamente, observaram-se áreas multifocais de necrose com infiltrado inflamatório granulomatoso no intestino, pulmão, encéfalo, miocárdio e nos rins. Hifas fúngicas intralesionais e intravasculares foram observadas no encéfalo e no pulmão. Estruturas de fenótipo compatível com Aspergillus fumigatus foram observadas na cultura fúngica. Amostras encaminhadas para virologia apresentaram-se positivas para Herpesvírus Equino (HVE) tipo 1 e 4. O diagnóstico de aspergilose sistêmica foi determinado pelo histórico clínico, imunossupressão, achados macroscópicos, histológicos, isolamento do fungo e à infecção concomitante por HVE.(AU)
The Aspergillus genus comprises globally distributed species of saprotrophic fungi, with the Aspergillus section Fumigatus known to cause diseases in humans and immunocompromised animals. Clinical signs depend on the affected system, exhibiting mild fever, severe colic, pneumonia, guttural bag mycosis and occasionally lesions in the central nervous system. The present work aims to report the clinical signs, necropsy findings and histology of a case of systemic aspergillosis in an eight-months-old foal. The animal had enterogastric reflux, increased peristalsis, pasty feces, abdominal pain and severe dehydration. The condition evolved to death and the cadaver was sent for necropsy. Macroscopically, there were suffusions and ecchymosis in the serosa of the gastrointestinal tract and ulcerations in the mucosa of the small intestines. In the lung, there were multifocal, whitish and firm nodules that were cystic when cut with a friable winey internal lining. The heart had whitish multifocal areas in the myocardium and the kidneys contained reddish nodules in the cortical and medullary regions. In the brain there were yellowish and hemorrhagic multifocal areas with reddish borders. Microscopically, multifocal areas of necrosis with granulomatous inflammatory infiltrate were observed in the intestine, lung, brain, myocardium and kidneys. Intralesional and intravascular fungal were observed in the brain and lung. Structures with phenotype compatible with Aspergillus fumigatus were observed in the fungal culture. In virology, samples were positive for equine herpesvirus (HVE) types 1 and 4. The diagnosis of systemic aspergillosis was determined due to the clinical history, immunosuppression, macroscopic and histological findings, fungal isolation and concomitant HVE infection.(AU)
Assuntos
Animais , Masculino , Aspergilose/sangue , Aspergilose/complicações , Aspergilose/diagnóstico , Aspergilose/veterináriaRESUMO
OBJECTIVES: To compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF). METHODS: We retrospectively reviewed the charts of 36 patients with IA and 26 with IF diagnosed between 2006 and 2017 in haematologic patients, and compared baseline characteristics, coexisting exposures, clinical manifestations, treatment, and the outcome. RESULTS: Fever was more frequent in IF (96.2% vs. 63.9%, p 0.003), whereas pneumonia (88.9% vs. 50.0%, p 0.001) and sinusitis (63.9% vs. 38.5%, p 0.048) were more frequent in IA. Skin lesions and positive blood cultures occurred exclusively in patients with IF. Among patients with pneumonia, the halo sign was more frequent in IA (62.5% vs. 23.1%, p 0.02). Serum galactomannan was positive in 88.6% of patients with IA and in 73.3% with IF (p 0.18), with no differences in the median number of positive tests and galactomannan values. Positive serum galactomannan plus lung infiltrates was the predominant clinical presentation in IA and occurred in four of 13 patients with IF and lung involvement. The 30-day survival was 77.7% in IA and 46.1% in IF (p 0.01). CONCLUSIONS: IA and IF share the same epidemiologic scenario but different clinical presentations in the majority of cases, with disease in the airways in IA, and fever, metastatic skin lesions, and positive blood cultures in IF. However, a substantial proportion of patients with IF present with a clinical picture similar to IA, with fever, lung infiltrates, and positive serum galactomannan.
Assuntos
Aspergilose/epidemiologia , Fusariose/epidemiologia , Infecções Fúngicas Invasivas/epidemiologia , Adulto , Idoso , Aspergilose/sangue , Feminino , Febre/sangue , Febre/epidemiologia , Fusariose/sangue , Galactose/análogos & derivados , Humanos , Infecções Fúngicas Invasivas/sangue , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Pneumonia/sangue , Pneumonia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
ABSTRACT Introduction: Invasive aspergillosis is a condition associated with a high mortality rate mostly due to difficulties in performing an early diagnosis. In recent years, galactomannan detection has markedly improved the diagnosis of invasive aspergillosis, but very little is known on how physicians deal with this test in clinical practice. Methods: This cross-sectional study aimed to analyze the indications for the use of serum galactomannan in a large Brazilian hospital, between 2015 and 2016. No specific protocol was in place for GM request. We reviewed the medical records of adult (>18 years-old) patients who were tested for galactomannan due to one the following indications: screening, diagnosis, or treatment follow-up. Additional variables included demographic data, underlying diseases, presence of neutropenia, and use of previous antifungal (anti-Aspergillus) drugs. Results: The mean age of the patients was 51 years-old (sd ± 15.8), and 63.3% of patients were male. Patients with hematological malignancies accounted for 60.1% of the cases, mostly acute myeloid leukemia (19.6%). Galactomannan testing was positive in 12.2% of patients, including 1.6% of occasions in which the test was used for screening purposes, 13.2% for diagnosis, and 32.4% during follow-up. Median time for chest imaging request was two days before GM testing. Previous antifungal therapy was reported for 35.1% of patients, mostly amphotericin B (57.1%). Conclusion: The correct use of galactomannan testing is essential for an early diagnosis of invasive aspergillosis, which may improve the prognosis of the disease. We demonstrated that clinicians usually ask for galactomannan tests to confirm imaging findings in patients who frequently were on antifungal drugs, something that could be improved by medical education. We observed a low frequency of galactomannan use for preemptive antifungal therapy (25.7%), which is worrying considering the well-known beneficial use of GM testing in this scenario.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Aspergilose/diagnóstico , Aspergilose/sangue , Mananas/sangue , Aspergilose/tratamento farmacológico , Valores de Referência , Estudos Transversais , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Diagnóstico Precoce , Antifúngicos/uso terapêuticoRESUMO
INTRODUCTION: Invasive aspergillosis is a condition associated with a high mortality rate mostly due to difficulties in performing an early diagnosis. In recent years, galactomannan detection has markedly improved the diagnosis of invasive aspergillosis, but very little is known on how physicians deal with this test in clinical practice. METHODS: This cross-sectional study aimed to analyze the indications for the use of serum galactomannan in a large Brazilian hospital, between 2015 and 2016. No specific protocol was in place for GM request. We reviewed the medical records of adult (>18 years-old) patients who were tested for galactomannan due to one the following indications: screening, diagnosis, or treatment follow-up. Additional variables included demographic data, underlying diseases, presence of neutropenia, and use of previous antifungal (anti-Aspergillus) drugs. RESULTS: The mean age of the patients was 51 years-old (sd±15.8), and 63.3% of patients were male. Patients with hematological malignancies accounted for 60.1% of the cases, mostly acute myeloid leukemia (19.6%). Galactomannan testing was positive in 12.2% of patients, including 1.6% of occasions in which the test was used for screening purposes, 13.2% for diagnosis, and 32.4% during follow-up. Median time for chest imaging request was two days before GM testing. Previous antifungal therapy was reported for 35.1% of patients, mostly amphotericin B (57.1%). CONCLUSION: The correct use of galactomannan testing is essential for an early diagnosis of invasive aspergillosis, which may improve the prognosis of the disease. We demonstrated that clinicians usually ask for galactomannan tests to confirm imaging findings in patients who frequently were on antifungal drugs, something that could be improved by medical education. We observed a low frequency of galactomannan use for preemptive antifungal therapy (25.7%), which is worrying considering the well-known beneficial use of GM testing in this scenario.
Assuntos
Aspergilose/sangue , Aspergilose/diagnóstico , Mananas/sangue , Adulto , Idoso , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Estudos Transversais , Diagnóstico Precoce , Feminino , Galactose/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não ParamétricasRESUMO
BACKGROUND: A 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus. MATERIALS AND METHODS: Specimens were collected for microscopy examination and culture. The isolate was identified by morphological and molecular criteria. Susceptibility testing was performed using CLSI methods. CYP51A gene was PCR amplified and sequenced. RESULTS: An Aspergillus fumigatus strain resistant to itraconazole (MIC>8µg/ml) was isolated. The isolate was susceptible to amphotericin B, posaconazole, voriconazole and caspofungin. CYP51A sequencing showed two mutations leading on the G54E substitution. The patient received natamycin as treatment. CONCLUSIONS: This is the first report in South America of a clinical A. fumigatus strain carrying the substitution G54E at Cyp51Ap associated with itraconazole resistance. Considering the patient was azole-naive, this resistant isolate may have been acquired from the environment.
Assuntos
Aspergilose/sangue , Aspergillus fumigatus/efeitos dos fármacos , Farmacorresistência Fúngica , Infecções Oculares Fúngicas/microbiologia , Itraconazol/farmacologia , Ceratite/microbiologia , Adulto , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/genética , Infecções Oculares Fúngicas/tratamento farmacológico , Proteínas Fúngicas/genética , Humanos , Itraconazol/uso terapêutico , Ceratite/tratamento farmacológico , Masculino , Mutação , América do SulRESUMO
Invasive aspergillosis (IA) is associated with a high morbidity and mortality. Since Aspergillus species are usually not cultured in these patients, presumptive diagnosis of IA is more commonly based on galactomannan (GM) detection. Several factors are known to cause false-positive results in the GM test, but little is known on the influence of pre-analytical variables interfering on the test. Here we studied the influence of temperature and sample storage duration in GM results, using samples known to be negative and positive (spiked) for GM. We also evaluated the effect of hemolysis and hyperbilirubinemia on GM optical indexes. We found no influence of storage time (up to 96 h) and temperatures (refrigerated vs. RT) on GM results. However, bilirubin (P = .022) and haemoglobin (P = .003) content influenced GM readings in samples known for being GM positive and negative at baseline, respectively. We conclude that the Platelia GM test does not suffer major influence of pre-analytical variables such as storage conditions, and low levels of hemolysis and hyperbilirubinemia. Nonetheless, massive haemolysis seems to interfere with GM readings in GM-negative samples, and high levels of bilirubin can affect GM readings in samples that are positive for GM at baseline. These findings may facilitate logistics and the implementation of standard operational procedures in clinical laboratories.
Assuntos
Aspergilose/sangue , Aspergilose/diagnóstico , Bilirrubina/sangue , Análise Química do Sangue/normas , Hemoglobinas , Mananas/sangue , Manejo de Espécimes/normas , Adulto , Reações Falso-Positivas , Feminino , Galactose/análogos & derivados , Humanos , Masculino , Temperatura , Fatores de Tempo , Adulto JovemRESUMO
Increase in the incidence of invasive aspergillosis has represented a difficult problem for management of patients with this infection due to its high rate of mortality, limited knowledge concerning its diagnosis, and therapeutic practice. The difficulty in management of patients with aspergillosis initiates with detection of the fungus in the specimens of immunosuppressed patients infected with Aspergillus fumigatus; in addition, difficulty exists in terms of the development of resistance to antifungals as a consequence of their indiscriminate use in prophylactic and therapeutic practice and to ignorance concerning the epidemiological data of aspergillosis. With the aim of resolving these problems, molecular markers is employed at present with specific and accurate results. However, in Mexico, the use of molecular markers has not yet been implemented in the routine of intrahospital laboratories; despite the fact that these molecular markers has been widely referred in the literature, it is necessary for it to validated and standardized to ensure that the results obtained in any laboratory would be reliable and comparable. In the present review, we present an update on the usefulness of molecular markers in accurate identification of A. fumigatus, detection of resistance to antifugal triazoles, and epidemiological studies for establishing the necessary measures for prevention and control of aspergillosis.
El incremento en la incidencia de la aspergilosis invasora representa un grave problema para el tratamiento de pacientes con esta micosis, debido a su elevada tasa de mortalidad por deficiencias diagnósticas y terapéuticas. Éstas se han atribuido a la dificultad para detectar Aspergillus fumigatus, principal agente etiológico de esta micosis, en las muestras biológicas de pacientes inmunosuprimidos, que son los principales afectados por el hongo; además por la resistencia a los antifúngicos como consecuencia del uso incontrolado de éstos, a nivel profiláctico y terapéutico, y el desconocimiento de aspectos epidemiológicos de la aspergilosis. En la actualidad, para superar estas limitaciones se han empleado marcadores moleculares. En México su uso aún no está implementado en la rutina de los laboratorios intrahospitalarios, porque a pesar de que se han reportado ampliamente en la bibliografía, hace falta validarlos y estandarizarlos para asegurar que los resultados que se obtengan en cualquier laboratorio sean confiables y comparables. En este trabajo se presenta una revisión actualizada de la utilidad de los marcadores moleculares en la identificación certera de A. fumigatus en la detección de resistencia a los antifúngicos triazólicos y en estudios epidemiológicos para establecer las medidas necesarias en la prevención y control de la aspergilosis.
Assuntos
Aspergilose/sangue , DNA Fúngico/sangue , Fungemia/sangue , Técnicas de Diagnóstico Molecular/métodos , Animais , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/imunologia , Monitoramento de Medicamentos , Farmacorresistência Fúngica Múltipla/genética , Fungemia/diagnóstico , Fungemia/tratamento farmacológico , Amplificação de Genes , Genes Fúngicos , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , México/epidemiologia , Camundongos , Técnicas de Tipagem Micológica , Neoplasias/complicações , Neoplasias/imunologia , Infecções Oportunistas/sangue , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológicoRESUMO
Invasive aspergillosis is a leading cause of morbidity and mortality in immunocompromised patients, particularly in individuals with haematological malignancy and in haematopoietic stem cell transplant recipients. Nowadays, the galactomannan (GM) assay has been widely used as an indication of invasive aspergillosis, even though the test is known to generate false-positive results. The aim of this study was to compare the performance of GM and real-time PCR (qPCR) to detected Aspergillus in blood samples obtained from high-risk haematological patients. Haematological patients were screened twice weekly with GM testing, which was performed by the Platelia ELISA kit. An additional sample of whole blood (4 ml) was obtained for the purpose of qPCR testing. Sixty-four samples from 12 patients with haematopoietic stem cell transplant or haematological malignancy were studied. The overall accordance between GM and qPCR tests was 96.9 % (62 samples). Only two samples showed contradictory results, with positive GM test and negative real-time PCR results. Based on the high concordance between GM and qPCR in terms of negative results, the main utility of qPCR could be in the confirmation of positive results seen with GM testing.
Assuntos
Aspergilose/diagnóstico , Aspergillus/genética , DNA Fúngico/genética , Adulto , Aspergilose/sangue , Aspergillus/isolamento & purificação , DNA Fúngico/análise , Reações Falso-Positivas , Feminino , Galactose/análogos & derivados , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Mananas/análise , Programas de Rastreamento , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
This investigation determined the presence and prevalence of the zoonotic agents Leptospira interrogans, Trypanosoma cruzi, and Aspergillus spp. in the stray dog population (a total of 224 stray dogs) in an urban area of Southern Mexico. Blood serum samples were taken from all dogs, and root hair samples were taken from dogs with skin lesions and partial alopecia. IgG antibodies for L. interrogans from 10 serovars were detected using the microscopic agglutination test. Immunofluorescence antibody test and Western blot assay were used for serologic diagnosis of T. cruzi. The Sabouraud medium was used to isolate Aspergillus spp. Prevalence of L. interrogans was 4.9%, which was determined by identifying only serovars Pyrogenes, which accounted for 3.6%, and Tarassovi, which constituted 1.3%, with titers from 1:100 to 1:800. Additionally, T. cruzi antibodies were detected in 4.5% of the dogs. Skin lesions were found in 43% of the dogs (98/224), and 35 cultures were positive for Aspergillus spp. (35.7%, p < 0.05, 95% confidence interval 2.45-3.67), identified as A. niger (82.8%), A. flavus (14.3%), and A. terreus (2.9%). This study demonstrates the presence of certain zoonotic agents (bacteria, protozoa, and fungi) in stray dogs living within the studied area. Dogs play an important role in the transmission of diseases that are potentially harmful to humans. Although the prevalence of canine leptospirosis and trypanosomiasis is not high in Southern Mexico compared with other tropical regions of Mexico, the presence of these zoonotic agents in the stray dog population demonstrates that the stray dog population in this region is a significant reservoir and potential source of infection in humans. Special care should be taken when handling stray dogs that exhibit skin lesions with partial alopecia, since a pathological Aspergillus sp. fungus may be present.