Cerebrospinal fluid: a target of some fungi and an overview

Meningitis is a potentially life-threatening infection characterised by the inflammation of the leptomeningeal membranes. The estimated annual prevalence of 8.7 million cases globally and the disease is caused by many different viral, bacterial, and fungal pathogens. Although several genera of fungi are capable of causing infections in the central nervous system (CNS), the most significant number of registered cases have, as causal agents, yeasts of the genus Cryptococcus. The relevance of cryptococcal meningitis has changed in the last decades, mainly due to the increase in the number of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and medications that impair the immune responses. In this context, coronavirus disease 19 (COVID-19) has also emerged as a risk factor for invasive fungal infections (IFI), including fungal meningitis (FM), due to severe COVID-19 disease is associated with increased pro-inflammatory cytokines, interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha, reduced CD4-interferon-gamma expression, CD4 and CD8 T cells. The gold standard technique for fungal identification is isolating fungi in the culture of the biological material, including cerebrospinal fluid (CSF). However, this methodology has as its main disadvantage the slow or null growth of some fungal species in culture, which makes it difficult to finalise the diagnosis. In conclusions, this article, in the first place, point that it is necessary to accurately identify the etiological agent in order to assist in the choice of the therapeutic regimen for the patients, including the implementation of actions that promote the reduction of the incidence, lethality, and fungal morbidity, which includes what is healthy in the CNS.

Adverse drug events and the associated factors in patients with chronic Chagas disease

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Feline sporotrichosis: associations between clinical-epidemiological profiles and phenotypic-genotypic characteristics of the etiological agents in the Rio de Janeiro epizootic area

BACKGROUND Sporotrichosis is caused by species of the genus Sporothrix. From 1998 to 2015, 4,703 cats were diagnosed at the Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. Even after the description of the Sporothrix species, the characterisation of feline isolates is not performed routinely. OBJECTIVES To characterise the clinical isolates from cats at the species level and correlate them with the clinical and epidemiological characteristics of the cats. METHODS Forty seven Sporothrix spp. isolates from cats assisted at Fiocruz from 2010 to 2011 were included. Medical records were consulted to obtain the clinical and epidemiological data. The isolates were identified through their morphological and physiological characteristics. T3B polymerase chain reaction (PCR) fingerprinting was used for molecular identification of the species. FINDINGS In phenotypic tests, 34 isolates were characterised as S. brasiliensis, one as S. schenckii and 12 as Sporothrix spp. PCR identified all isolates as S. brasiliensis. MAIN CONCLUSIONS S. brasiliensis is the only etiological agent of feline sporotrichosis in Rio de Janeiro to date. None association was found between the isolates and the clinical and epidemiological data. In addition, we strongly recommend the use of molecular techniques for the identification of isolates of Sporothrix spp.

In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis

Abstract Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312 µg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.

Análise filogenética e implementação de ferramentas moleculares na identificação de isolados do complexo Sporothrix spp / Phylogenetic Analysis and implementation of molecular tools in identification of isolates of Sporothrix spp complex

A esporotricose, micose subcutânea causada pelo complexo Sporothrix schenckii, é cosmopolita e a mais frequente na América Latina. Nos últimos anos tem aumentado significativamente o número de casos no Brasil, com destaque para o aumento no estado do Rio de Janeiro. Atualmente, quatro novas espécies dentro do gênero Sporothrix têm sido consideradas, sendo essas: Sporothrix brasiliensis, Sporothrix globosa, Sporothrix mexicana e Sporothrix luriei, as quais são altamente associadas às duas espécies já existentes S. schenckii e S. albicans, sendo a última recentemente renomeada com o S. pallida . A caracterização destas espécies foi realizada por meio da utilização de provas fenotípicas: morfologia de conídios, teste de crescimento à 30ºC e 37ºC , teste de termotolerância, auxonograma e sequenciamento parcial do gene da calmodulina . O princ ipal objetivo deste estudo foi a caracterização de espécies do complexo Sporothrix por meio de taxonomia molecular através do desenvolvimento de metodologia baseada em ácidos nucléicos para a identificação das espécies e a determinação do perfil proteômico do complexo Sporothrix , utilizando metodologia baseada em espectrometria de massa em célula intacta (MALDI - TOF ICMS). No presente trabalho foi realizada a identificação em nível de espécie de isolados clínicos e ambientais oriundos da epidemia de esporotricose no Rio de Janeiro, de um surto zoonótico familiar no estado do Espírito Santo e dois isolados clínicos oriundos de Portugal. Por meio da identificação por taxonomia polifásica de 246 isolados clínicos e um ambiental obtidos da endemia de esporotricose no Estado do Rio de Janeiro foi demonstrado que esta abordagem é fundamental para a identificação das espécies do complexo Sporothrix...

A identificação em nível de espécies de cepas do complexo Sporothrix spp. provenientes de diferentes regiões geográficas, demonstrou S. globosa e S. mexicana circulando em Portugal, sugerindo que a esporotricose seja subdiagnosticada naquele país, e que esta micose poderia ser considerada emergente no sul da Europa. Também descrevemos o primeiro surto causado por S. brasiliensis fora da zona endêmica do Rio de Janeiro. Para a identificação das espécies de Sporothrix descrevemos uma PCR fingerprinting utilizando o primer universal T3B, o qual distinguiu com sucesso as espécies S. brasiliensis, S. globosa, S. mexicana, e S. schenckii. Essa metodologia gerou padrões de bandas distintos, permitindo a correta identificação de todos os 35 isolados clínicos estudados apresentando 100 por cento de concordância com o sequenciamento parcial do gene da calmoduli na , sendo uma técnica rápida e de fácil execução. A padronização da metodologia do MALDI - TOF ICMS, possibilitou a determinação de perfis proteômicos distintos entre as espécies do complexo Sporothrix , demostrando a aplicabilidade desta técnica na diferenciação das espécies. A caracterização de espécies do complexo Sporothrix em nosso estudo foi a maior reportada na literatura especializada até o presente. Concluimos que a taxonomia polifásica é fundamental para diferenciação das espécies de Sporothrix, podendo ser realizada com as técnicas de T3B Fingerprinting e MALDI - TOF ICMS, tendo importância na epidemiologia e clínica da esporotricose...

Possível relação entre estresse ocupacional e síndrome metabólica / Relationship between job stress and the metabolic syndrome

O crescente número de casos de síndrome metabólica está relacionado àa mudanças no estilo de vida e no padrão alimentar das populações e, possivelmente, às situações de estresse cotidiano. O objetivo do presente estudo é investigar a possível relação entre estresse ocupacional e síndrome metabólica. Em estudo transversal foram avaliados 94 indivíduos: 51 agentes penitenciários (Grupo 1) e 43 funcionários da administração pública, que constituíram o grupo controle (grupo 2), submetidos a exame físico, avaliação laboratorial (dosagens de glicose, colesterol total, colesterol HDL, triglicérides e ácido úrico) além da aplicação de questionário para avaliação do grau de estresse no trabalho. O diagnóstico de síndrome metabólica se baseou nos critérios do National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATPIII). Foi encontrada maior prevalência de obesidade abdominal, hipertensão arterial, hipertrigliceridemia e baixos níveis de colesterol HDL entre os agentes penitenciários, quando comparados ao grupo controle (p<0,05). O diagnóstico de síndrome metabólica foi realizado em 11 (26,2%) indivíduos do grupo 1 e em doi2 indivíduos (5,7%) do grupo 2 (p<0,05). A razão de prevalência do estresse ocupacional para o grupo 1, em relação ao grupo 2 foi de 3,909 (IC de 95%: 0,88 a 17,4, p=0,048). A frequência de síndrome metabólica foi mais elevada entre os indivíduos submetidos à maior demanda psicológica no exercício da profissão sendo provável a relação entre essa entidade clínica e o estresse ocupacional.

The increasing number in the cases of metabolic syndrome is related to changes in the life style and food patterns of the populations and, possibly, to daily stress circumstances. The aim of the present study is to investigate the relationship between work stress and the metabolic syndrome. In a transversal study 94 individuals were evaluated: 51 prison guards (group 1) and 43 civil employees as the control group (group 2), who were submitted to physical examination, laboratory evaluation (fasting plasma glucose, total cholesterol, HDL cholesterol, triglycerides, and uric acid) in addition to a questionnaire to evaluate the level of stress at work. The diagnosis of metabolic syndrome was based on the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATPIII) criteria. Prison guards showed greater prevalence of abdominal obesity, hypertension, high triglycerides and low HDL-cholesterol levels when compared to control group (p<0.05). The metabolic syndrome diagnosis was accomplished in 11 (26.2%) individuals, in group 1 and 2 (5.7%) in group 2 (p<0.05). The prevalence ratio of work stress of group 1 vs group 2 was 3.91 (95% CI: 0.88 to 17.4, p=0.048). The metabolic syndrome prevalence was higher among individuals who were submitted to greater psychological demand in the job, and the relationship between this clinical entity and work stress is probable.

Identificação e análise filogenética de espécies do gênero Sporothrix isoladas em área endêmica de esporotricose no Estado do Rio de Janeiro / Identification and phylogenetic analysis of species of the Genus Sporothrix from endemic are of sporothrichosis in the Rio de Janeiro State

A esporotricose, micose subcutânea causada pelo complexo Sporothrix schenckii, é cosmopolita e a mais freqüente na América Latina. Nos últimos anos tem aumentado significativamente o número de casos no Brasil, com destaque para o aumento no Estado do Rio de Janeiro na última década. Recentemente, foram consideradas quatro novas espécies dentro do gênero Sporothrix, sendo essas: Sporothrix brasiliensis, S. globosa, S. mexicana e S. luriei. Entretanto somente 25 isolados de área endêmica no Rio de Janeiro foram incluídos nos estudos prévios. A caracterização destas foi realizada por meio da utilização de provas fenotípicas: morfologia de conídios, teste de crescimento à 30ºC, teste de termotolerância e auxonograma. No presente trabalho realizamos a caracterização de 248 isolados oriundos de pacientes atendidos no ambulatório de Dermatologia do IPEC, os quais tiveram diagnóstico de esporotricose durante a epidemia de esporotricose, no período de 1998 e 2008. De acordo com as características fenotípicas, 206 isolados (83,1 porcento) foram caracterizados como S. brasiliensis, um isolado (0,4 porcento) como S. mexicana, 15 (6,0 porcento) como S. schenckii e em 26 isolados (10,5 porcento) não foi possível realizar a caracterização da espécie sendo classificadas como Sporothrix sppDentre esse isolados foi realizada a análise molecular de 8 (31 porcento) isolados que apresentaram resultados inconclusivos nos estudos fenotípicos através do sequenciamento de um locus do gene calmodulina possibilitou a formação de um grande grupo constituído por 7 isolados todos caracterizados genotipicamente como pertencentes à espécie S. brasiliensis. A análise em nível de genótipo deve ser utilizada como ferramenta complementar na identificação de espécies do complexo Sporothrix. A correlação entre dados moleculares e características fenotípicas é fundamental na identificação de espécies complexo Sporothrix, possibilitando a implementação da taxonomia polifásica.

Sporothrix schenckii is the species responsible for sporotrichosis, an important subcutaneous mycosis with a worldwide distribution, and very frequent in Latin America, and it has been reported as endemic in Rio de Janeiro, Brazil. Recent molecular studies have demonstrated that this species constitutes a complex of numerous phylogenetic species, which were phenotipically characterized using different culture media, growth rates at different temperatures, and nutritional tests as well comparison calmodulin genes and it was proposed four new species Sporothrix brasiliensis, Sporothrix globosa, Sporothrix mexicana and Sporothrix luriei. And just 25 isolates from the endemic occurring in Rio de Janeiro were included in this previous study. We have studied a total of 248 Sporothrix isolates from this endemic obtained during the period of 1998 and 2008. The phenotypic characterization was based on the morphology of conidia, growth rates at 30ºC and 37 ºC, ability to grow at 37 ºC, and auxonographic method. According to the key features for species differentiation, 206 isolates (83.1 percent) were characterized as S. brasiliensis, one as S. mexicana (0.4 percent), 15 (6.0 percent) as S. schenckii and in 26 isolates (10.5 percent) the species was not differentiated being classified as Sporothrix spp. Among 8 (31 percent) of these unidentified isolates, molecular methodology, by sequence analysis of on protein coding locus (calmodulin) was performed, revealing the presence of one major clade, grouping 7 of these isolates with S. brasiliensis, representing this phylogenetic species. The analysis in genotype level should be used as complemental tool in the identification of species of the Sporothrix complex. The correlation among molecular data and phenotipe is fundamental in the identification of species Sporothrix complex, making possible the implementation of the polyphasic taxonomy.