Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-31405852

RESUMO

We report the cases of a 39-year-old woman with chronic lymphocytic leukemia and a 21-year-old man with chronic granulomatous disease treated for cerebral aspergillosis. The patients required radical surgery for infection progression despite adequate isavuconazole plasma concentration or neurological complication. We thus decided to measure the brain isavuconazole concentration. These results suggest that the concentrations of isavuconazole obtained in the infected brain tissue clearly differ from those obtained in the normal brain tissue and the cerebrospinal fluid.

2.
Med Mycol ; 57(Supplement_2): S94-S103, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816963

RESUMO

Invasive aspergillosis (IA) incidence is increasing in several countries like France, and numerous cases are indeed missed and still only diagnosed at autopsy as evidenced by recently published data. Such missed diagnoses are obviously encountered when appropriate diagnostic tools are not available especially in low resource areas or when biologists have not been trained enough in medical mycology (i.e., microscopic examination and culture in most of those areas). Besides logistical issues, which are indeed critical, IA may not be recognized because clinicians failed to consider that risk factors are evolving with the IA burden now observed among patients with chronic lymphoid malignancies or receiving new biotherapies, with diabetes mellitus or liver cirrhosis and/or acute alcoholic hepatitis, with patients from the intensive care unit (ICU) and among patients with some predisposing primary immune deficiencies now reaching the adult's age. This is also the case for human immunodeficiency virus (HIV)-infected patients who failed to meet the classical definitions of IA. From the radiology perspective, new entities of IA have also emerged which absolutely need to be recognized especially bronchial-based-IA among allogeneic stem cell transplant recipients. Finally, from the laboratory side, contribution and limits of indirect blood biomarkers should be integrated to the clinical life in order not to miss IA cases. To conclude, several diagnostic tools should be combined and a constant dialog between laboratory and clinics is crucial to appropriately diagnose IA.


Assuntos
Testes Diagnósticos de Rotina/métodos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/epidemiologia , França/epidemiologia , Humanos , Incidência , Fatores de Risco
3.
J Allergy Clin Immunol Pract ; 7(6): 1986-1995.e3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30878710

RESUMO

BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.

4.
MBio ; 10(1)2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755510

RESUMO

Fungal cell wall mannans are complex carbohydrate polysaccharides with different structures in yeasts and molds. In contrast to yeasts, their biosynthetic pathway has been poorly investigated in filamentous fungi. In Aspergillus fumigatus, the major mannan structure is a galactomannan that is cross-linked to the ß-1,3-glucan-chitin cell wall core. This polymer is composed of a linear mannan with a repeating unit composed of four α1,6-linked and α1,2-linked mannoses with side chains of galactofuran. Despite its use as a biomarker to diagnose invasive aspergillosis, its biosynthesis and biological function were unknown. Here, we have investigated the function of three members of the Ktr (also named Kre2/Mnt1) family (Ktr1, Ktr4, and Ktr7) in A. fumigatus and show that two of them are required for the biosynthesis of galactomannan. In particular, we describe a newly discovered form of α-1,2-mannosyltransferase activity encoded by the KTR4 gene. Biochemical analyses showed that deletion of the KTR4 gene or the KTR7 gene leads to the absence of cell wall galactomannan. In comparison to parental strains, the Δktr4 and Δktr7 mutants showed a severe growth phenotype with defects in polarized growth and in conidiation, marked alteration of the conidial viability, and reduced virulence in a mouse model of invasive aspergillosis. In yeast, the KTR proteins are involved in protein 0- and N-glycosylation. This study provided another confirmation that orthologous genes can code for proteins that have very different biological functions in yeasts and filamentous fungi. Moreover, in A. fumigatus, cell wall mannans are as important structurally as ß-glucans and chitin.IMPORTANCE The fungal cell wall is a complex and dynamic entity essential for the development of fungi. It allows fungal pathogens to survive environmental challenge posed by nutrient stress and host defenses, and it also is central to polarized growth. The cell wall is mainly composed of polysaccharides organized in a three-dimensional network. Aspergillus fumigatus produces a cell wall galactomannan whose biosynthetic pathway and biological functions remain poorly defined. Here, we described two new mannosyltransferases essential to the synthesis of the cell wall galactomannan. Their absence leads to a growth defect with misregulation of polarization and altered conidiation, with conidia which are bigger and more permeable than the conidia of the parental strain. This study showed that in spite of its low concentration in the cell wall, this polysaccharide is absolutely required for cell wall stability, for apical growth, and for the full virulence of A. fumigatus.


Assuntos
Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/crescimento & desenvolvimento , Parede Celular/metabolismo , Mananas/biossíntese , Manosiltransferases/metabolismo , Animais , Aspergillus fumigatus/metabolismo , Modelos Animais de Doenças , Deleção de Genes , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/patologia , Manosiltransferases/genética , Camundongos , Viabilidade Microbiana , Esporos Fúngicos/crescimento & desenvolvimento , Virulência
6.
Artigo em Inglês | MEDLINE | ID: mdl-29967027

RESUMO

Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.

7.
Am J Trop Med Hyg ; 96(5): 1205-1214, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28500816

RESUMO

AbstractThe serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In total, 217 patients were included in the study (111 malaria patients and 106 symptomatic controls, defined as malaria-negative febrile patients). Serum lipid levels (mmol/L) were significantly lower in malaria patients compared with those with other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94] versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] = 0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No significant differences were found for apolipoprotein A1, apolipoprotein B, and lipoprotein(a). Cholesterol levels increased toward reference values on day 28 (TC = 3.26-3.98, P < 0.001; HDL-C = 0.43-0.96, P < 0.001; LDL-C = 2.05-2.60, P < 0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day 28; P = 0.130). Lipid profile changes were not correlated with parasitemia or Plasmodium falciparum histidine-rich protein 2 levels. This study confirms characteristic temporary lipid profile changes in malaria. Lipid profile changes demonstrated a good accuracy to discriminate between malaria and other febrile diseases (area under the curve = 0.80 (95% confidence interval = 0.742-0.863, P < 0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid profile changes in malaria. Further studies to elucidate the precise pathways may lead to improved understanding of the underlying pathophysiology.


Assuntos
Febre/diagnóstico , Malária Falciparum/diagnóstico , Parasitemia/diagnóstico , Adulto , Antígenos de Protozoários/sangue , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Febre/sangue , Gabão , Humanos , Metabolismo dos Lipídeos , Lipoproteína(a)/sangue , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Masculino , Parasitemia/sangue , Parasitemia/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas de Protozoários/sangue , Curva ROC , Triglicerídeos/sangue
9.
RMD Open ; 3(2): e000555, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29435362

RESUMO

Background: The efficacy of antitumour necrosis factor alpha (anti-TNF-α) treatment is well recognised in rheumatoid arthritis (RA) but remains controversial in systemic lupus erythematosus (SLE). Therefore, the role of anti-TNF-α treatment in 'Rhupus', a disease sharing features of RA and SLE, is still debated. Objective: To evaluate the efficacy and tolerance of anti-TNF-α in patients with rhupus. Methods: Fifteen patients with rhupus with Disease Activity Score 28 (DAS 28) >3.2 despite conventional disease-modifying anti-rheumatic drugs were included in an open-label study. Patients were monitored at months (M) 3, 6, 12, 24 and 60 with SLE Disease Activity Index (SLEDAI) and DAS 28. Statistical analyses were performed using Bayesian methods and Prob >97.5% was considered significant. Results: Twelve patients were treated with etanercept for a median duration of 62.5 (range: 6-112) months and three patients by adalimumab during 36.0 (range: 4-52) months. At baseline, median DAS 28 and SLEDAI were 5.94 (4.83-8.09) and 6 (4-8), respectively. DAS 28 and SLEDAI decreased significantly after 3 months, respectively, to 3.70 (1.80-6.42) and 4 (0-6) (Prob >99.9%, for both). These changes persisted at M6, M12, M24 and M60 (Prob >99.9%, for all). Median prednisone dose decreased significantly from 15 (5-35) mg/day to 5 (0-20) mg/day after 6 months and over the follow-up (Prob >99.9%, for all). Tolerance was acceptable, with a severe infection rate of 3.0 per 100 patient-years. Conclusion: This pilot study suggests that anti-TNF-α is effective in patients with rhupus with refractive arthritis and has an acceptable safety profile.

10.
Semin Respir Crit Care Med ; 36(5): 692-705, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26398536

RESUMO

Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Pneumopatias Fúngicas/diagnóstico , Mucorales/genética , Mucormicose/diagnóstico , Mucormicose/terapia , Terapia Combinada , Desbridamento/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumopatias Fúngicas/terapia , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA