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1.
Mem. Inst. Oswaldo Cruz ; 116: e210207, 2021. tab, graf
Article in English | LILACS | ID: biblio-1346578

ABSTRACT

BACKGROUND Treatment of mycoses is often ineffective, usually prolonged, and has some side effects. These facts highlight the importance of discovering new molecules to treat fungal infections. OBJECTIVES To search the Medicines for Malaria Venture COVID Box for drugs with antifungal activity. METHODS Fourteen human pathogenic fungi were tested against the 160 drugs of this collection at 1.0 µM concentration. We evaluated the ability of the drugs to impair fungal growth, their fungicidal nature, and morphological changes caused to cells. FINDINGS Thirty-four molecules (21.25%) presented antifungal activity. Seven are antifungal drugs and one is the agricultural fungicide cycloheximide. The other drugs with antifungal activity included antibiotics (n = 3), antimalarials (n = 4), antivirals (n = 2), antiparasitcs (n = 3), antitumor agents (n = 5), nervous system agents (n = 3), immunosuppressants (n = 3), antivomiting (n = 1), antiasthmatic (n = 1), and a genetic disorder agent (n = 1). Several of these drugs inhibited Histoplasma capsulatum and Paracoccidioides brasiliensis growth (15 and 20, respectively), while Fusarium solani was not affected by the drugs tested. Most drugs were fungistatic, but niclosamide presented fungicidal activity against the three dimorphic fungi tested. Cyclosporine affected morphology of Cryptococcus neoformans. MAIN CONCLUSIONS These drugs represent new alternatives to the development of more accessible and effective therapies to treat human fungal infections.


Subject(s)
Humans , Pharmaceutical Preparations , Cryptococcus neoformans , COVID-19 , Malaria/drug therapy , Microbial Sensitivity Tests , Drug Repositioning , SARS-CoV-2 , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology
2.
Mem. Inst. Oswaldo Cruz ; 115: e200208, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1135227

ABSTRACT

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.


Subject(s)
Animals , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/microbiology , Armadillos , DNA, Fungal/genetics , Paracoccidioides/growth & development , Paracoccidioides/genetics , Soil Microbiology , Brazil , Base Sequence , Sequence Analysis, DNA , Ecosystem
3.
Mem. Inst. Oswaldo Cruz ; 113(3): 167-172, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-894906

ABSTRACT

BACKGROUND Paracoccidioidomycosis (PCM) is one of the most important systemic mycoses in Latin America and the leading fungal cause of mortality in non-immunosuppressed individuals in Brazil. However, HIV/PCM co-infection can increase the clinical severity in these co-infected patients. This co-infection is rarely reported in the literature mainly because of the different epidemiological profiles of these infections. Furthermore, PCM is a neglected and non-notifiable disease, which may underestimate the real importance of this disease. The advent of molecular studies on the species of the genus Paracoccidioides has expanded the knowledge regarding the severity and the clinical spectrum in PCM. In this context, the development of studies to describe the association of the Paracoccidioides phylogenetic cryptic species in vulnerable populations, such as HIV-infected patients, appears relevant. OBJECTIVE To describe the clinical, epidemiological, therapeutic and prognostic aspects in HIV/PCM co-infected patients, along with the molecular identification of the Paracoccidioides species involved in these cases. METHODS The investigators performed a molecular and clinical retrospective study involving HIV/PCM co-infected patients, from a reference centre for PCM care in the endemic area of Rio de Janeiro, Brazil, from 1998 to 2015. Molecular identification of the fungal strains was done by amplification of partial sequences of arf and gp43 genes. FINDINGS Of 89 patients diagnosed with PCM by fungal isolation in the culture, a viable isolate was recovered for molecular analysis from 44 patients. Of these 44 patients, 28 (63.6%) had their serum samples submitted for enzyme immunoassay tests for screening of HIV antibodies, and 5 (17.9%) had a positive result. All cases were considered severe, with a variable clinical presentation, including mixed, acute/subacute clinical forms and a high rate of complications, requiring combination therapy. Paracoccidioides brasiliensis S1 was the species identified in all cases. CONCLUSIONS HIV/PCM co-infection can change the natural history of this fungal disease. The authors reinforce the need to include HIV screening diagnostic tests routinely for patients with PCM.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/drug therapy , Socioeconomic Factors , Severity of Illness Index
4.
Mem. Inst. Oswaldo Cruz ; 113(3): 185-196, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-894908

ABSTRACT

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.


Subject(s)
Sporothrix/classification , Cat Diseases/microbiology , Cat Diseases/epidemiology , Sporothrix/genetics , Brazil/epidemiology , DNA Fingerprinting
5.
Rev. Soc. Bras. Med. Trop ; 51(1): 111-114, Jan.-Feb. 2018. graf
Article in English | LILACS | ID: biblio-897041

ABSTRACT

Abstract The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process. Together with P. lutzii, P. brasiliensis appears to be involved in severe cases of PCM.


Subject(s)
Humans , Male , Young Adult , Paracoccidioides/genetics , Paracoccidioidomycosis/complications , Paracoccidioidomycosis/diagnosis , Phylogeny , Shock, Septic/microbiology , Severity of Illness Index , Fatal Outcome , Immunocompetence
6.
Mem. Inst. Oswaldo Cruz ; 112(5): 376-381, May 2017. tab, graf
Article in English | LILACS | ID: biblio-841795

ABSTRACT

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.


Subject(s)
Humans , Animals , Cats , Sporothrix/drug effects , Triazoles/pharmacology , Amphotericin B/pharmacology , Itraconazole/pharmacology , Ketoconazole/pharmacology , Antifungal Agents/pharmacology , Naphthalenes/pharmacology , Drug Resistance , Cats , Anti-Infective Agents
7.
Braz. j. infect. dis ; 20(6): 637-640, Nov.-Dec. 2016. graf
Article in English | LILACS | ID: biblio-828171

ABSTRACT

ABSTRACT Angionvasive mucormycosis is an emerging fungal disease known to affect mainly diabetics or subjects with profound neutropenia. Infection usually occurs through the inhalation route, but cutaneous inoculation may occur after trauma or burns. However, mucormycosis remains unusual in HIV infection. We report a fatal case of cutaneous mucormycosis due to Rhizopus arrhizus involving the scalp following herpes zoster infection. The patient was a 42-year-old man with advanced AIDS failing on salvage antiretroviral therapy. The fungus was diagnosed on the basis of histopathology and culture. Our case emphasizes the need to consider mucormycosis in the differential diagnosis of necrotic cutaneous lesions in patients with late-stage HIV disease.


Subject(s)
Humans , Male , Adult , Rhizopus/isolation & purification , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Mucormycosis/diagnosis , Mucormycosis/drug therapy
8.
Mem. Inst. Oswaldo Cruz ; 111(1): 51-58, Jan. 2016. tab, graf
Article in English | LILACS | ID: lil-771081

ABSTRACT

This study evaluated the antifungal susceptibility profile and the production of potential virulence attributes in a clinical strain of Candida nivariensis for the first time in Brazil, as identified by sequencing the internal transcribed spacer (ITS)1-5.8S-ITS2 region and D1/D2 domains of the 28S of the rDNA. For comparative purposes, tests were also performed with reference strains. All strains presented low planktonic minimal inhibitory concentrations (PMICs) to amphotericin B (AMB), caspofungin (CAS), and voriconazole. However, our strain showed elevated planktonic MICs to posaconazole (POS) and itraconazole, in addition to fluconazole resistance. Adherence to inert surfaces was conducted onto glass and polystyrene. The biofilm formation and antifungal susceptibility on biofilm-growing cells were evaluated by crystal violet staining and a XTT reduction assay. All fungal strains were able to bind both tested surfaces and form biofilm, with a binding preference to polystyrene (p < 0.001). AMB promoted significant reductions (≈50%) in biofilm production by our C. nivariensis strain using both methodologies. This reduction was also observed for CAS and POS, but only in the XTT assay. All strains were excellent protease producers and moderate phytase producers, but lipases were not detected. This study reinforces the pathogenic potential of C. nivariensis and its possible resistance profile to the azolic drugs generally used for candidiasis management.


Subject(s)
Humans , Antifungal Agents/pharmacology , Candida/drug effects , Candidiasis/microbiology , Brazil , Biofilms/drug effects , Candida/classification , Candida/isolation & purification , Candida/pathogenicity , Microbial Sensitivity Tests , Phenotype , Virulence
9.
Mem. Inst. Oswaldo Cruz ; 104(5): 769-774, Aug. 2009. ilus, tab
Article in English | LILACS | ID: lil-528088

ABSTRACT

An epidemic of sporotrichosis, a subcutaneous mycosis caused by the fungus Sporothrix schenckii, is ongoing in Rio de Janeiro, Brazil, in which cases of human infection are related to exposure to cats. In an attempt to demonstrate the zoonotic character of this epidemic using molecular methodology, we characterised by DNA-based typing methods 19 human and 25 animal S. schenckii isolates from the epidemic, as well as two control strains. To analyse the isolates, the random amplified polymorphic DNA (RAPD) technique was performed using three different primers, together with DNA fingerprinting using the minisatellite derived from the wild-type phage M13 core-sequence. The analyses generated amplicons with considerable polymorphism. Although isolates exhibited high levels of genetic relatedness, they could be clustered into 5-10 genotypes. The RAPD profiles of epidemic S. schenckii isolates could be distinguished from that of the United States isolate, displaying 20 percent similarity to each primer and 60 percent when amplified with the M13 primer. DNA fingerprinting of S. schenckii isolated from the nails (42.8 percent) and the oral cavities (66 percent) of cats were identical to related human samples, suggesting that there is a common infection source for animals and humans in this epidemic. It is clear that cats act as a vehicle for dissemination of S. schenckii.


Subject(s)
Animals , Cats , Humans , Cat Diseases/microbiology , Disease Outbreaks , Sporothrix/isolation & purification , Sporotrichosis/microbiology , Brazil/epidemiology , Cat Diseases/diagnosis , Cat Diseases/epidemiology , DNA Fingerprinting , DNA, Fungal , Mycological Typing Techniques , Polymorphism, Genetic , Random Amplified Polymorphic DNA Technique , Sporothrix/genetics , Sporotrichosis/diagnosis , Sporotrichosis/epidemiology , Sporotrichosis/veterinary
10.
Rev. Inst. Med. Trop. Säo Paulo ; 48(2): 113-116, Mar,-Apr. 2006. ilus
Article in English | LILACS | ID: lil-426807

ABSTRACT

Reportamos um caso raro de histoplasmose crônica disseminada com diversas lesões ulceradas na cavidade oral de um paciente alcoólatra, sem o vírus da imunodeficiência humana, com nenhum outro sinal detectável ou sintomas de doença sistêmica ou manifestações extra-orais. Análise histopatológica revelou processo inflamatório crônico com granulomas contendo organismos fúngicos. O isolamento do Histoplasma capsulatum forneceu o diagnóstico definitivo. Tratamento com itraconazol resultou numa remissão completa das lesões orais. De acordo com nosso conhecimento, este é o segundo caso reportado de histoplasmose oral em um paciente HIV negativo descrito no Brasil.


Subject(s)
Humans , Male , Middle Aged , Histoplasma/isolation & purification , Histoplasmosis/diagnosis , Mouth Diseases/microbiology , Antifungal Agents/therapeutic use , Chronic Disease , Histoplasmosis/drug therapy , Itraconazole/therapeutic use , Mouth Diseases/diagnosis , Mouth Diseases/drug therapy
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