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1.
Infectio ; 25(3): 159-162, jul.-set. 2021. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1250086

ABSTRACT

Resumen La criptococosis meníngea presenta alta mortalidad mundial, especialmente en población VIH/sida. La OMS recomienda detectar el antígeno capsular de Crypto coccus como estrategia para un diagnóstico temprano y poder minimizar complicaciones. Objetivo: realizar antigenemia temprana de Cryptococcus mediante in munocromatografía/ensayo de flujo lateral en pacientes asintomáticos VIH+. Material y método: estudio descriptivo observacional; entre julio-2016 y mayo-2019 se procesaron mediante ensayo de flujo lateral, muestras de suero de 169 pacientes asintomáticos VIH+, con CD4 ≤120 cel/μL en Barranquilla, Colombia. Ante resultado positivo, se indicó profilaxis con fluconazol; se hizo seguimiento a todos los casos. Resultados: la antigenemia fue positiva en cinco pacientes (2,96%); uno falleció, cuatro recibieron profilaxis y la prueba se negativizó en dos. Los pacientes con resultado negativo inicial no desarrollaron durante el estudio sinto matología compatible con esta micosis. Discusión: el ensayo de flujo lateral de Cryptococcus está recomendado para el diagnóstico temprano de la criptococosis en población VIH/sida. Conclusión: detectar tempranamente el antígeno circulante de Cryptococcus mediante ensayo de flujo lateral en pacientes asintomáticos VIH+, permitió instaurar profilaxis oportuna, hacer seguimiento y control para reducir la mortalidad asociada con la criptococosis meníngea.


Abstract Meningeal cryptococcosis presents high levels of global mortality, especially in the HIV/AIDS population. The WHO recommends detecting the capsular antigen as an important strategy for early diagnosis and be able to minimize complications. Objective: Perform early cryptococcal antigenemia by immunochromatographic/ lateral flow assay in asymptomatic HIV+ patients. Material and method: descriptive observational study; between July-2016 and May-2019, serum samples from 169 asymptomatic HIV+ patients with CD4 ≤120 cells/μL were processed by lateral flow assay in Barranquilla, Colombia. Given a positive result, prophylaxis with fluconazole was indicated; all cases were followed up. Results: antigenemia was positive in five (2.96%) patients; one died; four received prophylaxis, and the test turned negative in two. The patients with an initial negative result, did not developed symptoms compatible with this mycosis during the study period. Discussion: lateral flow assay for Cryptococcus is recommended for the early diagnosis of cryptococcosis in the HIV/AIDS population. Conclusion: early detection of circulating Cryptococcus antigen by lateral flow assay in HIV+ patients allowed the establishment of timely prophylaxis, follow-up, and control to reduce mortality associated with meningeal cryptococcosis.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Acquired Immunodeficiency Syndrome , Cryptococcosis , CD4 Antigens , HIV , Aftercare , Cryptococcus , Meningitis
2.
Infectio ; 25(1): 49-54, ene.-mar. 2021. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1154402

ABSTRACT

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.


Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.


Subject(s)
Humans , Male , Adult , Cryptococcosis , T-Lymphocytes , HIV Infections , HIV , Immunosuppression , Cryptococcus , Herpes Zoster , Lymphopenia
3.
REVISA (Online) ; 9(4): 823-833, 2020.
Article in Portuguese | LILACS | ID: biblio-1146145

ABSTRACT

Objetivo: Investigar a presença de fungos patogênicos isolados a partir de amostras de fezes de pombos, em locais de atenção a pacientes imunocomprometidos no DF. Método: As amostras foram coletadas em hospitais onde se oferta atendimento a pacientes HIV/AIDS e que tenha uma presença massiva de pombos. Colônias de leveduras foram previamente selecionados em meio Ágar Sabouraud Dextrose acrescido de cloranfenicol, seguindo-se com análise microscópica das estruturas leveduriformes. Colônias de leveduras com suspeita de pertencerem ao gênero Candida spp. ou Cryptococcus sp., foram inoculadas no meio Ágar Cromogênico para identificação das espécies de Candida e em meio Ágar quimicamente definido para indução dos fenótipos de virulência característicos de Cryptococcus sp. Resultados: 100% das amostras analisadas apresentaram crescimento de leveduras do gênero Candida spp. e Rhodotorula sp. No meio Ágar Cromogênico foram identificadas nas amostras C. krusei em 75%; C. tropicalis em 50% e C. glabrata em 15%. Em 15% das amostras foi identificado leveduras do gênero Cryptococcus sp. Conclusão: Dados deste estudo sugerem que fezes de pombo podem estar dispersando leveduras patogênicas e contribuindo com a incidência de infecções fúngicas no DF.


Objective: To investigate the presence of pathogenic fungi isolated from pigeon stool samples, in places of care for immunocompromised patients in the Federal District. Method: The samples were collected in hospitals where care is offered to HIV / AIDS patients and which has a massive presence of pigeons. Yeast colonies were previously selected on Sabouraud Dextrose Agar plus chloramphenicol, followed by microscopic analysis of the yeast structures. Yeast colonies suspected of belonging to the genus Candida spp. or Cryptococcus sp., were inoculated in the Chromogenic Agar medium to identify Candida species and in chemically defined Agar medium to induce the virulence phenotypes characteristic of Cryptococcus sp. Results: 100% of the analyzed samples showed growth of yeasts of the genus Candida spp. and Rhodotorula sp. In the chromogenic agar medium, 75% were identified in C. krusei samples; C. tropicalis in 50% and C. glabrata in 15%. In 15% of the samples, yeasts of the genus Cryptococcus sp. Conclusion: Data from this study suggest that pigeon feces may be dispersing pathogenic yeasts and contributing to the incidence of fungal infections in DF


Objetivo: Investigar la presencia de hongos patógenos aislados de muestras de heces de palomas, en los lugares de atención a pacientes inmunodeprimidos del Distrito Federal. Método: Las muestras se recolectaron en hospitales donde se brinda atención a pacientes con VIH / SIDA y que tiene una presencia masiva de palomas. Las colonias de levadura se seleccionaron previamente en Sabouraud Dextrose Agar más cloranfenicol, seguido de un análisis microscópico de las estructuras de la levadura. Las colonias de levaduras sospechosas de pertenecer al género Candida spp. o Cryptococcus sp., se inocularon en medio de agar cromogénico para identificar especies de Candida y en medio de agar químicamente definido para inducir los fenotipos de virulencia característicos de Cryptococcus sp. Resultados: el 100% de las muestras analizadas presentó crecimiento de levaduras del género Candida spp. y Rhodotorula sp. En el medio agar cromogénico, el 75% se identificó en muestras de C. krusei; C. tropicalis en 50% y C. glabrata en 15%. En el 15% de las muestras, levaduras del género Cryptococcus sp. Conclusión: Los datos de este estudio sugieren que las heces de las palomas pueden estar dispersando levaduras patógenas y contribuyendo a la incidencia de infecciones fúngicas en el DF.


Subject(s)
Humans , Animals , Columbidae/microbiology , Rhodotorula/isolation & purification , Candida/isolation & purification , Cryptococcus/isolation & purification , Feces/microbiology , Hospitals , Mycoses/transmission
4.
Chinese Medical Journal ; (24): 2859-2866, 2020.
Article in English | WPRIM | ID: wpr-877942

ABSTRACT

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.


Subject(s)
AIDS-Related Opportunistic Infections , CD4 Lymphocyte Count , China , Cryptococcosis/epidemiology , Cryptococcus , HIV Infections/complications , Humans , Meningitis, Cryptococcal
5.
Braz. j. infect. dis ; 23(6): 451-461, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1089312

ABSTRACT

ABSTRACT Background: Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients. Aim: To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans. Methods: Retrieval of studies was 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), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually. Results: The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection. Conclusion: P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.


Subject(s)
Humans , Female , Aged , Stomach Neoplasms/diagnostic imaging , Catheter-Related Infections/diagnostic imaging , Stomach Neoplasms/microbiology , Stomach Neoplasms/therapy , Biopsy , Vancomycin/therapeutic use , Tomography, X-Ray Computed , Fluconazole/therapeutic use , Amphotericin B/therapeutic use , Bacteremia/microbiology , Cryptococcus/isolation & purification , Catheter-Related Infections/etiology , Catheter-Related Infections/microbiology , Catheter-Related Infections/drug therapy , Piperacillin, Tazobactam Drug Combination/therapeutic use , Anti-Bacterial Agents/therapeutic use
6.
Rev. chil. infectol ; 36(5): 656-662, oct. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058092

ABSTRACT

Resumen La criptococosis es una micosis sistémica producida por un hongo levaduriforme encapsulado denominado Cryptococcus neoformans. Es una enfermedad universal, que ocurre con mayor frecuencia en pacientes inmunocomprometidos, manifestándose principalmente como una enfermedad diseminada con compromiso meníngeo o pulmonar. Sin embargo, la osteomielitis ocurre solo en 5-10% de los casos, siendo el compromiso vertebral el más frecuente. Presentamos un caso de criptococosis vertebral aislada y una búsqueda bibliográfica sobre el tema. Se recomienda realizar una terapia antifúngica de inducción intravenosa y continuar con una fase de consolidación, vía oral, de duración variable. La indicación quirúrgica se considera en lesiones que comprometen la estabilidad vertebral y aquellas que presentan un compromiso neurológico, producen deformidad y para reducir el inóculo infeccioso.


Cryptococcosis is an infectious disease caused by a ubiquitous encapsulated yeast called Cryptococcus neoformans, it is usually associated with immunosuppressed patients. Osteomyelitis occurs in 5-10%, the spine involvement is one of the most reported. The purpose of this work is to present a case of isolated vertebral cryptococcosis and detail the results of a literature review. The treatment protocol is not yet established but it is recommended to start with aggressive intravenous therapy and continue with a suppressive treatment orally during a variable time. Surgical indication is considered in lesions that affect the spinal stability, deformity or neurological compromise and for local infectious control.


Subject(s)
Humans , Male , Aged , Osteomyelitis/microbiology , Osteomyelitis/pathology , Spinal Diseases/microbiology , Spinal Diseases/pathology , Cryptococcosis/pathology , Osteomyelitis/diagnostic imaging , Spinal Diseases/diagnostic imaging , Biopsy , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Cryptococcosis/diagnostic imaging , Cryptococcus/isolation & purification
7.
Mem. Inst. Oswaldo Cruz ; 114: e180391, 2019. tab, graf
Article in English | LILACS | ID: biblio-984762

ABSTRACT

BACKGROUND Cryptococcosis is one of the most devastating fungal infections in humans. Despite the disease's clinical importance, current therapy is based on limited antifungals that are either toxic, inefficient, unavailable worldwide, or that quickly lead to resistance. OBJECTIVES The goal of this study was to provide insight into the future of cryptococcosis treatment by describing the patent scenario in this field. METHODS We identified and analysed patent documents revealing compounds with anti-cryptococcal activity supported by experimental evidence. FINDINGS Patenting in this field has been historically low, with an overall tendency of increase since 2012. Most applications are single filings, suggesting that they do not encompass strategic inventions requiring broad protection. Research and development essentially took place in China and the United States, which also represent the main countries of protection. Both academic and corporate institutions contributed to patenting in this field. Universities are the leading actors, with the highest patent family counts. CONCLUSION The low number of patents in this field indicates that efforts to mitigate the unmet needs for cryptococcosis treatment remain insufficient. Without investment to drive research and innovation, patients will likely continue to face inadequate assistance. Given the current scenario characterised by poor funding and low interest for technological development, drug repurposing may be the best alternative for cryptococcosis treatment.


Subject(s)
Humans , Meningitis, Cryptococcal/therapy , Cryptococcosis , Cryptococcus , /organization & administration
8.
Rev. Soc. Bras. Med. Trop ; 52: e20180419, 2019. graf
Article in English | LILACS | ID: biblio-990432

ABSTRACT

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


Subject(s)
Humans , Female , Child , Cryptococcosis/microbiology , Cryptococcus/genetics , Argentina , Cryptococcosis/diagnosis , Cryptococcus/isolation & purification , Cryptococcus/classification , Multilocus Sequence Typing , Genotype
9.
Korean Journal of Medicine ; : 383-386, 2019.
Article in Korean | WPRIM | ID: wpr-759942

ABSTRACT

Ventriculoperitoneal (VP) shunt insertion is the standard treatment for hydrocephalus; shunt-associated infection is the most common complication after surgery. However, fungal infections are unusual. We present a case of cryptococcal meningitis complicated by a brain abscess and an infected intra-abdominal pseudocyst that developed 14 weeks after VP shunt insertion to treat hydrocephalus in a 74-year-old patient. Cryptococcal central nervous system (CNS) infection has a high mortality rate; however, diagnosis is challenging. Therefore, prompt diagnosis and treatment are required when a cryptococcal CNS infection is suspected in patients with VP shunts.


Subject(s)
Aged , Brain Abscess , Brain , Central Nervous System , Cryptococcus , Diagnosis , Humans , Hydrocephalus , Meningitis, Cryptococcal , Mortality , Ventriculoperitoneal Shunt
10.
Mycobiology ; : 242-249, 2019.
Article in English | WPRIM | ID: wpr-760535

ABSTRACT

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.


Subject(s)
Anti-Infective Agents , Betaine , Cell Membrane , Cryptococcus , Cryptococcus neoformans , Dandruff , Ergosterol , Fungi , Gene Deletion , Genetic Testing , Genomics , Humans , Malassezia , Methods , Skin , Transcriptome
11.
S. Afr. fam. pract. (2004, Online) ; 61(4): 159-164, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1270107

ABSTRACT

Background: South Africa has 7.06 million people who are HIV-positive, with those having a low CD4 count being susceptible to cryptococcal meningitis (CCM), which has an estimated mortality of 30­50%. This study aimed to establish the outcome of patients admitted with CCM to a regional hospital in Durban between June 2015 and May 2016, and the extent to which the National Department of Health (NDoH) protocol was adhered to in managing their condition. Method: This retrospective observational descriptive study reviewed the records of patients ≥ 12 years old admitted with CCM between June 2015 and May 2016, from which their demographic and medical data were extracted.Results: Seventy-six complete records were found of which 49 were men and 27 were women. The average CD4 count was 55.9 cells/mm3, 85.5% were treated with intravenous amphotericin B and high-dose oral fluconazole, 6.7% received only amphotericin B and 5.2% received only fluconazole. There was an in-hospital mortality of 31.6%, and the NDoH protocol was adhered to in 72.4% (55/76) of patients. There was, however, no significant difference in outcome between those who were and were not managed as per the protocol (p = 0.177).Discussion and conclusion: In-hospital mortality for CCM continues to be significant despite high rates of adherence to the NDoH protocol in the majority of patients. For this to be addressed, early diagnosis of HIV and initiation of ART to prevent the profound immunosuppression is essential


Subject(s)
Cryptococcus , Meningitis , South Africa
12.
São Paulo; s.n; 2019. 168 p.
Thesis in Portuguese | LILACS | ID: biblio-1005470

ABSTRACT

Introdução: A meningite criptocócica causa elevada mortalidade, sobretudo em pacientes acometidos de alguma condição imunossupressora. O objetivo deste estudo foi identificar fenômenos de baixa suscetibilidade a antifúngicos e outros preditores clínicos que possam explicar falha terapêutica e recidiva da neurocriptococose Metodologia: Foram avaliados 96 casos com coleta de dados clínicos epidemiológicos e laboratoriais. Os isolados foram identificados quanto a genótipo molecular, suscetibilidade de anfotericina B (AMB) e fluconazol (FCZ) pela determinação da concentração inibitória mínima (Minimal Inhibitory Concentration, MIC), nível de heteroresistência ao FCZ (NHF) e determinação do tempo de morte frente AMB (Time-Kill, TK). Foram selecionados isolados heterorresistentes para análise quantitativa de DNA por PCR em tempo Real, expressão de bombas de efluxo por citometria de fluxo e isolados tolerantes a AMB para estudo de resistência ao estresse oxidativo. Foi realizada análise univariável e múltipla usando regressão logística para identificar preditores de óbito hospitalar e de um desfecho composto definido pelo óbito, encaminhamento para unidade de terapia intensiva ou recidiva 6 meses após alta hospitalar. Resultados: A maioria dos pacientes eram imunodeprimidos, com CD4 de 2 a 722 cel./mm3 e 96,7% eram portadores do HIV. Foram identificados 93 isolados de C. neoformans, sendo 76 do genótipo VNI e 17 VNII e 3 C. gattii, todos VGII. MIC de AMB variou de 0,012 a 0,94 mg/L e MIC de FCZ estiverem entre 0,12 e 64 mg/L. Resistência a FCZ (MIC>16mg/L) foi maior em VNI do que em VNII (p=0,03). Dentre os isolados VNI, 64,5% sofreu atividade fungicida até as 24h (TK24) de exposição à AMB e 6 cepas VNI não sofreram ação fungicida (TK>72). A maioria dos isolados VNII (64,7%) apresentou TK24. Os 3 isolados VGII sofreram atividade fungicida a partir de TK24. A maioria dos isolados VNI, VNII e todos os isolados VGII apresentaram alto NHF (>32mg/L). Diferença no NHF de acordo com os genótipos foi observada (p=0,005). No modelo múltiplo, as variáveis associadas significativamente ao óbito foram: idade em anos (OR=1,08;IC95%=1,02-1,15), contagem de leveduras no líquido cefalorraquidiano em logaritmo (LCR) (OR=1,66;IC95%=1,21-2,28) e uma variável composta por hipertensão arterial sistêmica ou diagnóstico de edema cerebral ou dilatação ventricular por tomografia (OR=35,68;IC95%=4,97-256,31). Para o desfecho composto, as variáveis associadas foram: contagem de leveduras do 1D em logaritmo (OR=1,50; IC95%=;1,20-1,86; p=<0,001), cultura de sangue positiva para Cryptococcus spp. (OR=3,30; IC95%=0,86-12,59; p=0,08) e descrição de neurotoxoplasmose (OR=18,62; IC95%=1,85-187,5; p=0,01). As associações foram consistentes em modelos de sobrevida. Conclusão: Foi possível descrever genótipos mais frequentes e identificar fatores genéticos, como aumento da expressão de genes e bombas de efluxo, relacionados à resistência aos fármacos. Nenhum dos testes de suscetibilidade esteve associado com os desfechos. Variáveis obtidas nos primeiros dias de internação mostraram utilidade para predizer o prognóstico em pacientes com meningite criptocóccica. Estes preditores podem ajudar a identificar os casos com maior potencial de óbito e que necessitam da otimização dos recursos terapêuticos.


Background: Cryptococcal meningitis causes high mortality in immunocompromised patients. The objective of this study was to identify the phenomena of low susceptibility to antifungal and other clinical predictors that may explain therapeutic failure and relapse of neurocryptococcosis Methodology: It was analyzed 96 cases with clinical and epidemiological data. The respective isolates were identified for genotype, susceptibility profile by Minimal Inhibitory Concentration (MIC), FCZ heteroresistance level (NHF), and time to death determination against 1 mg / L BMA (Time-Kill, TK). We isolated heteroresistant DNA expression analysis by real-time PCR, expression of efflux pumps by flow cytometry and, some isolates tolerant to AMB were selected to study resistance to oxidative stress. Univariable and multiple analyses using logistic regression were performed to identify predictors of in-hospital mortality and a composed outcome defined by death, referral to the intensive care unit and relapse 6 months after hospital discharge. Results: Most of the patients were immunocompromised, with CD4 range from 2 to 722 cells/mm3 and 96.7% patients HIV-positive. It was analyzed 93 strains of Cryptococcus neoformans of which 76 were genotype VNI and 17 were VNII and 3 were C. gattii, all were VGII. AMB MIC ranged from 0.012 to 0.94 mg/L and FCZ MIC were between 0.12 and 64 mg/L. Resistance to FCZ (MIC>16mg/L) was higher to VNI than VNII (p=0.03). Among the VNI strains, 64.5% had fungicidal activity up to 24h (TK24) of exposure to AMB and 6 VNI did not present this activity until 72h (TK> 72). Most VNII strains (64.7%) had TK24. The 3 VGII strains presented fungicidal activity from TK24. According to the MIC, all strains were susceptible to AMB. The majority of VNI strains (93.4%) and VNII (76.5%) and 3 VGII strains showed high NHF (>32mg/L) and it was observed statistical difference according to the genotypes VNI and VNII (p=0.005). At the multiple analysis, the variables significantly associated with the death were the age in years (OR=1.08,95%CI=1.02-1.15), the cerebrospinal fluid (CSF) yeasts count-log (OR=1.66,95%CI=1.21-2.28), and a variable composed of systemic arterial hypertension or diagnosis of cerebral edema or ventricular dilatation by tomography (OR=35.68,95%CI=4.97-256.31). At the composed outcome, the variables associated were: CSF yeasts count-log (OR=1,50; IC95%=;1,20-1,86; p=<0,001), positive blood culture for Cryptococcus spp. (OR=3,30; IC95%=0,86-12,59; p=0,08) and neurotoxoplasmosis (OR=18,62; IC95%=1,85-187,5; p=0,01). The associations were consistent at survival models. Conclusion: It was possible to describe more frequent genotypes and to identify genetic factors, such as increased gene expression and efflux pumps, related to drug resistance. The antifungal susceptibilities were not associated with the outcomes. were not associated with outcomes. Variables available in the first days of hospitalization showed utility to predict the prognosis in patients with cryptococcal meningitis. These predictors can help to identify the cases with higher potential of death and that require the optimization of the therapeutic resources.


Subject(s)
Meningitis, Fungal , Cryptococcosis , Cryptococcus/immunology , Antibodies, Fungal , Prognosis , Recurrence
13.
Rev. bras. anal. clin ; 50(3): 233-236, dez.16, 2018. tab
Article in Portuguese | LILACS | ID: biblio-969447

ABSTRACT

Objetivo: Este estudo objetivou a pesquisa de Cryptococcus spp. em locais públicos de Goiânia-GO onde há grande fluxo de pessoas. Métodos: Sessenta amostras foram coletadas com swabs umedecidos em NaCl 0,85%, inoculadas em tubos com ágar Sabouraud e incubadas à temperatura ambiente, sendo as leituras das culturas realizadas com 24 horas, 48 horas e 72 horas. Após análise macroscópica, as colônias de leveduras foram submetidas à coloração de Gram e à coloração com tinta nanquim, para análise microscópica. Resultados: Cryptococcus spp. foi identificado em seis (10,0%) das sessenta amostras analisadas, sendo encontrado em 100,0% dos espaços públicos pesquisados. Conclusão: Os pombos representam importantes reservatórios deste fungo na natureza, atuando como disseminadores. Assim, ressalta-se a necessidade do controle dessas aves, bem como a conscientização da população sobre os riscos da proliferação desses animais nos centros urbanos.


Subject(s)
Columbidae , Cryptococcosis , Cryptococcus , Guano australis , Public Health
14.
Braz. j. infect. dis ; 22(1): 11-15, Jan.-feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-951617

ABSTRACT

ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.


Subject(s)
Humans , Adult , Middle Aged , Fluconazole/cerebrospinal fluid , Fluconazole/blood , Cryptococcosis/drug therapy , Antifungal Agents/cerebrospinal fluid , Antifungal Agents/blood , Reference Values , Candidiasis/cerebrospinal fluid , Candidiasis/drug therapy , Candidiasis/blood , Microbial Sensitivity Tests , Fluconazole/administration & dosage , Chromatography, High Pressure Liquid , Treatment Outcome , AIDS-Related Opportunistic Infections/drug therapy , Statistics, Nonparametric , Cryptococcosis/cerebrospinal fluid , Cryptococcosis/blood , Cryptococcus/isolation & purification , Cryptococcus/drug effects , Dose-Response Relationship, Drug , Histoplasmosis/cerebrospinal fluid , Histoplasmosis/drug therapy , Histoplasmosis/blood , Antifungal Agents/administration & dosage
16.
Mycobiology ; : 114-121, 2018.
Article in English | WPRIM | ID: wpr-729789

ABSTRACT

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.


Subject(s)
Autophagy , Cell Wall , Cryptococcus neoformans , Cryptococcus , Endoplasmic Reticulum Stress , Fluconazole , GTP Phosphohydrolases , Guanine Nucleotide Exchange Factors , Humans , Hypersensitivity , Inhalation , Insecta , Saccharomyces cerevisiae , Vacuoles , Virulence
17.
São Paulo; s.n; s.n; 2017. 168 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1361543

ABSTRACT

Fungos no ambiente podem ser patogênicos ou oportunistas, dependendo da imunidade do hospedeiro. Existem várias espécies de fungos, por exemplo, Cândida albicans, Cryptococcus e Aspergillus. A primeira espécie fúngica pode ser tratada com o antifúngico fluconazol, que é um composto que contém anéis heterocíclicos 1,2,4-triazólicos. Além disso, existem cepas de fungos que são resistentes à terapia com fluconazol, que é o caso das Cândida krusei, Cândida tropicalis; entre outras. A busca por novos tratamentos envolve o desenvolvimento de novas moléculas sintéticas. Neste trabalho, sintetizamos uma biblioteca de compostos oxazolínicos e seus derivados 1,2,3-triazólicos. A atividade microbiológica foi avaliada contra 10 tipos de Cândida, 2 tipos de Cryptococcus e 2 tipos de Aspergillus. Além disso, foram feitos os testes de hemólise, citotoxicidade, combinações de drogas e permeabilidade de membrana. Os resultados sugerem um alto potencial terapêutico dos compostos e os propomos como potenciais novos antifúngicos


ungi in the environment may be pathogenic or opportunistic depending on the immune status of the host. There are several species of fungi, for example, Candida albicans, Cryptococcus and Aspergillus. The first fungal species can be treated with the antifungal fluconazole, which is a compound containing 1,2,4-triazole heterocyclic rings. In addition, there are strains of fungi that are resistant to fluconazole therapy, which is the case of Candida krusei, Candida tropicalis; among others. The search for new treatments involves the development of new synthetic molecules. In this work, we synthesized a library of oxazoline compounds and their 1,2,3-triazole derivatives. Microbiological activity was evaluated against 10 types of Candida, 2 types of Cryptococcus and 2 types of Aspergillus. In addition, hemolysis, cytotoxicity, drug combinations and membrane permeability were performed. The results suggest the high therapeutic potential of the compounds and we propose them as potential new antifungals


Subject(s)
Triazoles/analysis , Pharmaceutical Preparations , Drug Combinations , Fungi/drug effects , Antifungal Agents/pharmacology , Aspergillus/isolation & purification , Biological Products , Candida albicans/isolation & purification , Fluconazole/administration & dosage , Cryptococcus/isolation & purification , Growth and Development/drug effects
18.
São Paulo; s.n; 2017. 128 p. ilus, graf, tab.
Thesis in Portuguese | SES-SP, LILACS, SES-SP, SESSP-CTDPROD, SES-SP, SESSP-ACVSES, SESSP-TESESESSP, SES-SP | ID: biblio-972088

ABSTRACT

Criptococose é uma micose com alta morbidade e mortalidade. Oestabelecimento e progressão da doença envolve uma interação complexaentre o fungo e células hospedeiras. Este estudo teve o objetivo de buscarnovos modelos alternativos (larvas de insetos) para criptococose, selecionarcepas do complexo Cryptococcus neoformans/Cryptococcus gattii portriagem em cultura celular pela produção de óxido nítrico, IL-8 e pelacitotoxidade, determinar a suscetibilidade de duas linhagens murinas (A/Sn eBALB/c) à infecção e analisar no modelo mais suscetível a virulência (cargafúngica, sobrevida e histopatológico) e a resposta imunológica porrecrutamento de células T (CD3+, CD4+ e CD8+), células B, granulócitos emacrófagos, ou por produção de citocinas Th1 (IFN-γ, TNF-α, IL-2, IL-6) eTh2 (IL-4 e IL-10). Os modelos invertebrados estudados foram Apis melliferae Zophobas morio em fase larval. As larvas foram inoculadas com cepapadrão de C. neoformans e sobrevivência foi registrada, diariamente. Larvasforam eutanasiadas periodicamente e colônias foram analisadas pela técnicaPCR fingerprinting com primer M13, para determinação molecular desimilaridade. A linhagem murina mais sucetível foi BALB/c, para estudo emcepas produtoras de células titans foram selecionados três isoladosresultantes de alta secreção de IL-8, e inoculados para quantificação decarga fúngica e histopatológico aos 14 e 21 dias. Para estudo em cepatolerante a AmB foram selecionadas subpopulações tolerantes das cepasH99 e R265, e inoculadas em BALB/c, para produção de citocinas Th1 e Th2e virulência aos 7, 14 e 21 dias. Larvas de Apis mellifera foram suscetíveis ainfecção por C. neoformans, diferentemente, larvas de Zophobas morioapresentaram desenvolvimento biológico normal e 100% de sobrevida até ofinal do experimento...


Cryptococcosis, a life-threatening fungal disease. Establishment andprogression of disease involves a complex interplay between the fungus anda diverse range of host cell types. The aim this study was to evaluate strainsof the complex species C. neoformans/C. gattii in murine model and in 2 newalternative model invertebrate. In first step, We evaluated the virulence of theCryptococcus spp. strains at screening in cell culture human and murine, therelease of the inflammatory cytokine IL-8 and host cell damage were adoptedfor analyze the activation of the cell line. To study strains produce titans cells,we select 2 clinical isolates and strain type H99 resulting high release of IL-8to inoculated BALB/c mice aiming to analyze titan cell production andimmune responses of T-cells (CD3+, CD4+ and CD8+), B-cells, granulocytesand macrophages. We quantified the cryptococcal burden (CFUs/mL) in thelungs and brains at 14 and 21 days. To study tolerant strain to amphotericinB we select 2 strains strain type H99 and IAL 3238, inoculated in two murineBALB/c and A/Sn, the progression of cryptococcosis was assessed byquantification of fungal burden and histopathology analysis after 7, 14 and 21days. The invertebrate models studied were Apis mellifera and Zophobasmorio in larval stage. The larvae were inoculate with strain type of C.neoformans and survival was recorde daily for up to 96 hours to Apismellifera and Zophobas morio to adulthood. Larvae were euthanizeperiodically and colonies were analyze by polymerase chain reaction (PCR)fingerprinting with M13 primer for molecular determination of similarity.Larvae of Apis mellifera were susceptible to infection with C. neoformans, bycontrast, larvae Zophobas morio had normal biological development and100% survival to the end of the experiment...


Subject(s)
Humans , Cryptococcus , Cytokines , Fluconazole , Virulence
19.
Infection and Chemotherapy ; : 142-145, 2017.
Article in English | WPRIM | ID: wpr-105542

ABSTRACT

Cryptococcus spp. other than Cryptococcus neoformans or Cryptococcus gattii were previously considered saprophytes and thought to be non-pathogenic to humans. However, opportunistic infections associated with non-neoformans and non-gattii species, such as Cryptococcus laurentii and Cryptococcus albidus, have increased over the past four decades. We experienced a case of cryptococcosis caused by non-neoformans and non-gattii spp. in a 47-year-old female with refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. The patient underwent salvage chemotherapy with fluconazole prophylaxis and subsequently developed neutropenic fever with multiple erythematous umbilicated papules. A skin biopsy revealed fungal hyphae and repetitive blood cultures showed yeast microorganisms that were identified later as C. laurentii by Vitek-II®. Skin lesions and fever began to improve with conventional amphotericin B therapy. The treatment regimen was continued for 21 days until the disseminated cryptococcosis was completely controlled.


Subject(s)
Amphotericin B , Biopsy , Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , Cryptococcus , Drug Therapy , Female , Fever , Fluconazole , Hematopoietic Stem Cell Transplantation , Humans , Hyphae , Leukemia, Myeloid, Acute , Middle Aged , Opportunistic Infections , Skin Manifestations , Skin , Yeasts
20.
Article in English | WPRIM | ID: wpr-110375

ABSTRACT

BACKGROUND: Histoplasmosis (HP) is diagnosed by visualizing intracellular microorganisms in biopsy and/or culture. Periodic-acid Schiff (PAS) and Gomori methenamine silver (GMS) staining methods are routinely used for identification. The acid-fast property of Histoplasma was identified decades ago, but acid-fast staining has not been practiced in current surgical pathology. Awareness of the acid-fast property of Histoplasma, which is due to mycolic acid in the cell wall, is important in distinguishing Histoplasma from other infective microorganisms. Here, we examined acid-fastness in previously diagnosed cases of Histoplasma using the Ziehl-Neelsen (ZN) stain and correlated those findings with other known fungal stains. METHODS: All cases diagnosed as HP were retrieved and reviewed along with ZN staining and other fungal stains. We also stained cases diagnosed with Cryptococcus and Leishmania as controls for comparison. RESULTS: A total of 54 patients ranging in age from 11 to 69 years were examined. The most common sites of infection were the skin, adrenal tissue, and respiratory tract. Of the total 43 tissue samples, 20 (46.5%) stained positive with the ZN stain. In viable cases, a significant proportion of microorganisms were positive while necrotic cases showed only rare ZN-positive yeasts. In comparison to PAS and GMS stains, there was a low burden of ZN-positive yeasts. Cryptococcus showed characteristic ZN staining and all cases of Leishmania were negative. CONCLUSIONS: Although the morphology of fungal organisms is the foundation of identification, surgical pathologists should be aware of the acid-fast property of fungi, particularly when there is the potential for confusion with other infective organisms.


Subject(s)
Biopsy , Cell Wall , Coloring Agents , Cryptococcus , Fungi , Histoplasma , Histoplasmosis , Humans , Leishmania , Methenamine , Mycolic Acids , Pathology, Surgical , Respiratory System , Skin , Yeasts
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