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1.
Med Mycol ; 62(3)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38389256

RESUMEN

Previous molecular studies have shown that Candida africana corresponds to the clade 13 of Candia albicans. It has been mostly involved in vulvovaginal candidiasis worldwide but few data exist in South America. The aim of our study was to investigate the prevalence of C. africana in women living in French Guiana. For this, we first set up a fluorescent-intercalating-dye-real time Polymerase Chain Reaction (PCR) targeting the hyphal wall protein 1 gene. The test was applied to 212 C. albicans isolates collected from May to August 2019 from vaginal swabs, allowing the identification of six women harboring C. africana (eight isolates). The in vitro susceptibility of these eight isolates to six antifungal drugs was also evaluated. No demographics or clinical-specific features could be demonstrated. Genetic diversity of those isolates was analyzed through multilocus sequence typing and showed that diploid sequence type 182 was predominant (n = 6) and allowed the report of a new diploid sequence type.


Candida africana, the clade 13 of C. albicans, is characterized by specific genetic and phenotypic traits. Using a new molecular technique, we report a high prevalence of C. africana in vaginal swabs from patients living in French Guiana. The worldwide predominant genotype was detected in all but one patient.


Asunto(s)
Candida , Candidiasis Vulvovaginal , Femenino , Humanos , Guyana Francesa/epidemiología , Epidemiología Molecular , Pruebas de Sensibilidad Microbiana/veterinaria , Candidiasis Vulvovaginal/epidemiología , Candidiasis Vulvovaginal/microbiología , Candidiasis Vulvovaginal/veterinaria , Vagina/microbiología , Antifúngicos , Candida albicans
2.
J Allergy Clin Immunol ; 152(3): 748-759.e3, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37169153

RESUMEN

BACKGROUND: Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown. OBJECTIVES: Our goal was to study the impact of IgA on gut mycobiota ecology. METHODS: The Fungi-Flow method was used to characterize fecal, systemic, and maternal IgA, IgM, and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HDs) (n = 34, 31, and 20, respectively) and to also compare gut mycobiota opsonization by secretory antibodies in HDs (n = 28) and patients with selective IgA deficiency (SIgAd) (n = 12). Stool mycobiota composition was determined by internal transcribed spacer gene sequencing in HDs (n = 23) and patients with SIgAd (n = 17). Circulating CD4+ T-cell cytokine secretion profiles were determined by intracellular staining. The impact of secretory IgA, purified from breast milk (n = 9), on Candidaalbicans growth and intestinal Caco-2 cell invasion was tested in vitro. RESULTS: Homeostatic IgA binds commensal fungi with a body fluid-selective pattern of recognition. In patients with SIgAd, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut Calbicans overgrowth nevertheless occurs in this condition but only in clinically symptomatic patients with decreased TH17/TH22 T-cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by Calbicans and therefore exert control on this pathobiont. CONCLUSION: IgA has a selective impact on Calbicans ecology to preserve fungal-host mutualism.


Asunto(s)
Candida albicans , Deficiencia de IgA , Femenino , Humanos , Células CACO-2 , Inmunoglobulina A , Inmunoglobulina A Secretora , Inmunoglobulina M
3.
Clin Infect Dis ; 77(5): 711-720, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37132362

RESUMEN

BACKGROUND: Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of ß1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients. METHODS: Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature. RESULTS: In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FI-CNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%‒90.2%] to 100% [95% CI: 51%‒100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%‒86.8%]. Bacterial neurologic infections were associated with several false positive results. CONCLUSIONS: Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS.


Asunto(s)
Criptococosis , beta-Glucanos , Humanos , Glucanos , Estudios Retrospectivos , Sensibilidad y Especificidad , Criptococosis/diagnóstico , Sistema Nervioso Central , Estudios Multicéntricos como Asunto
5.
Strahlenther Onkol ; 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37945929

RESUMEN

PURPOSE: Extranodal nasal-type NK/T-cell lymphoma (ENKTL) is very rare in western countries and few data are available regarding the prognosis and the outcome of patients treated for this disease. We aimed to evaluate the prognosis, the pattern and risk factors of disease failure after combined therapy and also performed a review of the literature. PATIENTS AND METHODS: We retrospectively analyzed 20 patients with (ENKTL) who underwent L­Asparaginase based chemotherapy followed by (chemo-) radiotherapy between 2010 and 2020 in our center. Data on clinical characteristics and irradiation were collected. Failure patterns were recorded as local (tumor site), regional (regional lymph nodes) or distant failure (metastasis and/or nonregional lymph nodes). RESULTS: During a median follow-up period of 46 months, disease failure was observed in 8 patients (40%). The 3­year progression-free survival (PFS) and overall survival (OS) rates were 62.5 and 83.0%, respectively. The failure patterns were local (n = 6, 30%), regional (n = 3, 15%) and distant (n = 4, 20%). Among patients with local failure, all failures occurred within the radiation fields (100%). Univariate analysis showed that bilateral regional lymph node involvement (p = 0.0002), initial circulating EBV viral load ≥ 3.5 log (p = 0.03) and no negativation of EBV PCR after induction CT (p = 0.0497) were independent predictors of PFS. CONCLUSION: Patients with bilateral lymph node involvement and/or high EBV viral load have a significant recurrence rate despite multimodal therapy. These results need to be confirmed by larger studies. Given the high rate of local recurrence within radiotherapy fields, the value of dose escalation should be considered. Patients at risk of relapse should be included in dedicated trials.

6.
BJU Int ; 132(1): 56-64, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36745012

RESUMEN

OBJECTIVE: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety. RESULTS: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%. CONCLUSION: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Anciano , Humanos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria/patología , Cistectomía , Fluorouracilo , Invasividad Neoplásica , Resultado del Tratamiento , Terapia Combinada
7.
World J Urol ; 41(11): 3249-3255, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37410102

RESUMEN

PURPOSE: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. PATIENT AND METHODS: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. RESULTS: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. CONCLUSION: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Vejiga Urinaria , Humanos , Vejiga Urinaria/patología , Cistectomía , Terapia Neoadyuvante , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Músculos , Invasividad Neoplásica/patología
8.
World J Urol ; 41(10): 2715-2722, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37555987

RESUMEN

PURPOSE: This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. METHODS: This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. RESULTS: Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. CONCLUSION: Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Anciano , Humanos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Cisplatino/uso terapéutico , Pronóstico , Terapia Neoadyuvante , Quimioterapia Adyuvante , Cistectomía , Músculos , Invasividad Neoplásica
9.
Med Mycol ; 61(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37076775

RESUMEN

The increase in terbinafine resistance worldwide due to Trichophyton indotineae underlies the need for surveillance networks, deploying easy to perform methods to correctly identify resistant isolates and thereby reduce their spread. In the present study, we evaluated the performances of the terbinafine containing agar method (TCAM). Different technical parameters, such as culture medium (RPMI agar [RPMIA] or Sabouraud dextrose agar [SDA]) and inoculum size, were evaluated. Our study showed that terbinafine susceptibility determined using the TCAM was reliable and independent of the inoculum or medium used. We then performed a multicenter, blinded study. 5 isolates of T. indotineae and 15 of genotype I or II of T. interdigitale, including 5 terbinafine-resistant isolates (4 T. indotineae and 1 T. interdigitale), were sent to eight clinical microbiology laboratories. Each laboratory analyzed the 20 isolates' terbinafine susceptibility by the TCAM using both culture media. TCAM allowed all participants to correctly determine the terbinafine susceptibility of analyzed isolates without prior training. All participants agreed that the dermatophyte tested, regardless of species or genotype, grew better on SDA than on RPMIA medium but accumulated fungal growth after 14 days eventually minimized the effect of this difference. In conclusion, TCAM is a reliable, easy to perform screening method for assessing terbinafine resistance. However, despite good performances, TCAM is a qualitative method and minimal inhibitory concentrations must be determined by the European Committee for Antimicrobial Susceptibility Testing standardized method to follow the evolution of terbinafine resistance levels.


The increase in terbinafine resistance worldwide due to Trichophyton indotineae underlies the need for surveillance networks. The terbinafine containing agar method is a reliable and easy-to-use tool in clinical microbiology laboratories. It can be used to rapidly screening resistant isolates, thereby reducing their spread.


Asunto(s)
Antifúngicos , Arthrodermataceae , Animales , Terbinafina/farmacología , Antifúngicos/farmacología , Agar , Reproducibilidad de los Resultados , Trichophyton , Pruebas de Sensibilidad Microbiana/veterinaria , Medios de Cultivo/farmacología , Farmacorresistencia Fúngica
10.
Emerg Infect Dis ; 28(1): 229-233, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34932456

RESUMEN

Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae harboring Phe397Leu and Leu393Ser substitutions in the squalene epoxidase enzyme was diagnosed in France. Analysis of internal transcribed spacer sequences revealed the wide spread of this species in Asia and Europe. Detection of T. indotineae in animals suggests their possible role as reservoirs.


Asunto(s)
Arthrodermataceae , Tiña , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica , Francia/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Terbinafina , Tiña/diagnóstico , Tiña/tratamiento farmacológico , Trichophyton/genética
11.
Med Mycol ; 60(4)2022 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-35188208

RESUMEN

PCR-based methods applied to various body fluids emerged in recent years as a promising approach for the diagnosis of mucormycosis. In this study, we set up and assess the value of a qPCR to detect a wide variety of Mucorales species in a single tube. A pair of degenerated primers targeting the rDNA operon was used in a qPCR utilizing an intercalating fluorescent dye. Analytical assessment, using a wide variety of both Mucorales strains (8 genera, 11 species) and non-Mucorales strains (9 genera, 14 species), showed 100% sensitivity and specificity rates with a limit of detection at 3 rDNA copy/qPCR reaction. Subsequently, 364 clinical specimens from 166 at-risk patients were prospectively tested with the assay. All the seven patients classified as proven/probable mucormycosis using the EORTC-MSG criteria had a positive qPCR as well as a patient with a proven uncharacterized invasive mold infection. In addition, three out of seven patients with possible mold invasive infections had at least one positive qPCR test. Sensitivity was calculated between 73.33 and 100% and specificity between 98.10 and 100%. The qPCR method proposed showed excellent performances and would be an important adjunctive tool for the difficult diagnosis of mucormycosis diagnosis. LAY ABSTRACT: qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.


Asunto(s)
Mucorales , Mucormicosis , Animales , Cartilla de ADN , ADN de Hongos/genética , Mucorales/genética , Mucormicosis/diagnóstico , Mucormicosis/veterinaria , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria
12.
Urol Int ; 106(9): 897-902, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34781287

RESUMEN

BACKGROUND: Local recurrence after radiation therapy for prostate cancer is a major clinical issue. Various local treatments are available with mitigated functional and oncological outcomes. The aim of the present study was to evaluate perioperative and oncological results of salvage cryotherapy (CT) as treatment of local recurrence of prostate cancer. METHODS: We retrospectively reviewed all patients treated with hemi-prostatic salvage CT for local recurrence of prostate cancer in 1 academic hospital between November 2011 and April 2019. Local recurrence was defined according to the Phoenix criteria (prostate-specific antigen [PSA] nadir + 2 ng/mL), associated with a prostatic MRI target lesion and confirmed by biopsy. Perioperative and functional complications were collected. Cox regression was conducted to assess factors associated with time to initiation of androgen deprivation therapy (ADT). Statistical analyses were conducted using R Studio. RESULTS: A total of 29 patients were treated with an average follow-up of 37.6 months. Median age at CT was 77 years. Median PSA before CT was 5.1 ng/mL (min-max: 2.74-18). 17.2% of patients displayed a high D'Amico risk group. Median hospital stay was 1.4 days. Four patients (13.8%) experienced postoperative acute urinary retention. Nineteen patients (65.5%) experienced late functional complications (3 erectile dysfunctions, 3 stress incontinence, and 13 urinary frequency). Fourteen patients displayed recurrence after salvage treatment (48.2%). Median time to introduction of ADT was 15.1 months. ADT-free survival at 1 and 2 years was, respectively, 74% and 61%. In multivariate analysis, ISUP score 4 and PSA nadir <1 ng/mL after CT were significantly associated with time to ADT initiation. CONCLUSIONS: Salvage focal CT may delay the use of ADT in locally recurrent prostate cancer after RT and offers an alternative for eligible patients. The technique was feasible with acceptable perioperative morbidity and acceptable midterm oncological outcome.


Asunto(s)
Neoplasias de la Próstata , Terapia Recuperativa , Antagonistas de Andrógenos/uso terapéutico , Crioterapia , Supervivencia sin Enfermedad , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Terapia Recuperativa/métodos , Resultado del Tratamiento
13.
Clin Infect Dis ; 72(8): 1379-1385, 2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-32155262

RESUMEN

BACKGROUND: Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. METHODS: Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. RESULTS: Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. CONCLUSIONS: Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.


Asunto(s)
Aspergilosis , Infecciones Fúngicas Invasoras , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergillus , Humanos , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , Estudios Retrospectivos
14.
Eur J Clin Microbiol Infect Dis ; 40(6): 1191-1198, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33411170

RESUMEN

In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.


Asunto(s)
Neumonía por Pneumocystis/complicaciones , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Enfermedad Aguda , Anciano , Femenino , Enfermedades Hematológicas/complicaciones , Humanos , Leucemia Linfoide/complicaciones , Masculino , Persona de Mediana Edad , Neumonía por Pneumocystis/diagnóstico , Estudios Prospectivos
15.
Mycoses ; 64(3): 309-315, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33245794

RESUMEN

BACKGROUND: Severe onychomycosis treatment in kidney transplant recipients (KTR) is challenging because of drug interactions and adverse events. Tacrolimus remains the antirejection treatment (ART) of choice in kidney transplantation but tolerance with systemic terbinafine for the management of severe onychomycosis has not been studied. OBJECTIVE: This study illustrates severe onychomycosis management in a kidney transplantation setting and investigates systemic terbinafine tolerance profile in KTR. PATIENTS/METHODS: We retrospective analysed clinical data of KTR with a confirmed diagnosis of severe onychomycosis. RESULTS: We retrieved a total of 29 KTR with severe onychomycosis needing an oral treatment to manage onychomycosis. In 55.1% (16/29) KTR, altered renal biological parameters or lack of guidelines to manage severe onychomycosis were the main reasons to deterring clinicians from prescribing oral treatments. 13 patients received an oral terbinafine treatment (9, 3 and 1 with a tacrolimus, cyclosporine and everolimus-based ART, respectively). Clinical and biological follow-up did not reveal severe drug interactions. ART blood levels showed significant variations in 2 patients without clinical consequences in renal graft. Two patients reported mild adverse events but after only one dose of terbinafine. Using an open-source image analysis program, clinical evolution of onychomycosis could be retrospectively quantified and followed up. CONCLUSIONS: The results presented here suggest that oral terbinafine can be proposed to treat severe onychomycosis with an acceptable tolerance profile in KTR with different ART such as tacrolimus and highlight the need of multicentric studies to establish guidelines for onychomycosis treatment in KTR.


Asunto(s)
Antifúngicos/uso terapéutico , Manejo de la Enfermedad , Tolerancia a Medicamentos , Trasplante de Riñón/efectos adversos , Onicomicosis/diagnóstico por imagen , Onicomicosis/tratamiento farmacológico , Terbinafina/uso terapéutico , Administración Oral , Adulto , Anciano , Antifúngicos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Terbinafina/administración & dosificación
16.
Parasitol Res ; 120(9): 3195-3202, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34341858

RESUMEN

Human cystic echinococcosis is a zoonosis due to the flat worm Echinococcus granulosus sensu lato. The disease remains a major public health problem in Northern Africa. Molecular typing enables a better understanding of the parasite circulation from animals to humans. In this study, we investigated the genotypic diversity of 46 Echinococcus granulosus isolates collected from humans in the western part of Algeria by the mean of partial sequences of 4 mitochondrial loci, namely cox1a, cox1b, nd3, and atp6. Nucleotide polymorphism ranges from 0.6 (nd3) to 2.7% (cox1a). Eight alleles had not been previously reported. Multilocus analysis showed that all the isolates were from the Echinococcus granulosus sensu stricto (G1 genotype). Nineteen different haplotypes made of the concatenation of 4 sequenced loci were observed, the most common type clustering 13 isolates (36.1%). Twelve of these haplotypes had never been described previously and fifteen (41.7%) haplotypes were represented by only one isolate. Using sequences from this study and others retrieved from the GenBank database, any clustering either according to the geographic origin within Algeria or according to the human or animal origin of the isolates could be demonstrated supporting that genotype G1 population genetics has been shaped by intensive animal breeding.


Asunto(s)
Equinococosis , Echinococcus granulosus , Argelia , Animales , Equinococosis/epidemiología , Equinococosis/veterinaria , Echinococcus granulosus/genética , Variación Genética , Genotipo , Haplotipos , Humanos , Zoonosis
17.
J Infect Dis ; 221(6): 1000-1005, 2020 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-31678998

RESUMEN

Human bronchial epithelial cells play a key role in airway immune homeostasis. We hypothesized that these sentinel cells can remember a previous contact with pathogen compounds and respond nonspecifically to reinfection, a phenomenon called innate immune memory. We demonstrated that their preexposure to Pseudomonas aeruginosa flagellin modify their inflammatory response to a second, nonrelated stimulus, including live pathogens or lipopolysaccharide. Using histone acetyltransferase and methyltransferase inhibitors, we showed that this phenomenon relied on epigenetic regulation. This report is a major breakthrough in the field of multimicrobial respiratory tract infections, wherein control of inflammatory exacerbations is a major therapeutic issue.


Asunto(s)
Memoria Inmunológica , Mucosa Respiratoria/citología , Epigénesis Genética , Células Epiteliales/inmunología , Flagelina/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Inflamación , Lipopolisacáridos , Prueba de Estudio Conceptual , Pseudomonas aeruginosa/inmunología , ARN Mensajero , Mucosa Respiratoria/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo
18.
J Clin Microbiol ; 58(2)2020 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-31801837

RESUMEN

PCR-based methods are a key tool for the diagnosis of toxoplasmosis in immunocompromised patients. Laboratory-developed protocols lack standardization. This study aimed to assess the performances of a commercial kit for the detection of Toxoplasma DNA in different specimens drawn from immunocompromised patients. This multicentric retrospective study included 227 DNA specimens (157 blood specimens, 22 bronchoalveolar fluid [BALF] specimens, 39 cerebrospinal fluid [CSF] specimens, and 9 miscellaneous specimens) collected between 2010 and 2015 from 126 immunocompromised patients. The specimens were selected based on previous laboratory-developed quantitative PCR (qPCR) analyses targeting either the rep529 element or the B1 gene, and the results were classified as positive, negative, and "negative of interest," where the latter was defined as representing either the last specimen with a negative result before a positive one or the first with a negative result following a positive result(s). All specimens were secondary tested using the Bio-Evolution Toxoplasma DNA assay targeting the T. gondii rep529 element. We found a 95.6% concordance rate for qualitative results obtained with laboratory-developed qPCR techniques and the commercial kit. The rate reached 99.3% in comparisons of rep529-based laboratory-developed PCR methods and the commercial kit. The quantifications obtained with the commercial kit and the rep529 laboratory-developed PCRs were in very good agreement. Sensitivity and specificity of the commercial kit were calculated at 98.8% and 100%, respectively. The Bio-Evolution Toxoplasma DNA assay appears to be a valuable method for the detection of Toxoplasma DNA in blood, BALF, and CSF specimens from immunocompromised patients.


Asunto(s)
ADN Protozoario/genética , Huésped Inmunocomprometido , Técnicas de Diagnóstico Molecular/normas , Juego de Reactivos para Diagnóstico/normas , Toxoplasma/genética , Toxoplasmosis/diagnóstico , Humanos , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Estudios Retrospectivos , Sensibilidad y Especificidad , Toxoplasmosis/sangre , Toxoplasmosis/líquido cefalorraquídeo
19.
Mycoses ; 63(6): 543-552, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32181941

RESUMEN

BACKGROUND: The Republic of Congo (RoC) is characterised by a high prevalence of tuberculosis and HIV/AIDS, which largely drive the epidemiology of serious fungal infections. OBJECTIVE: We aimed to estimate the current burden of serious fungal infections in RoC. MATERIAL AND METHODS: Using local, regional or global data and estimates of population and at-risk population groups, deterministic modelling was employed to estimate national incidence or prevalence of the most serious fungal infections. RESULTS: Our study revealed that about 5.4% of the Congolese population (283 450) suffer from serious fungal infections yearly. The incidence of cryptococcal meningitis, Pneumocystis jirovecii pneumonia and disseminated histoplasmosis in AIDS patients was estimated at 560, 830 and 120 cases per year. Oral and oesophageal candidiasis collectively affects 12 320 HIV-infected patients. Chronic pulmonary aspergillosis, 67% post-tuberculosis, probably has a prevalence of 3420. Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation) probably has a prevalence of 3640 and 4800, although some overlap due to disease definition is likely. The estimated prevalence of recurrent vulvovaginal candidiasis and tinea capitis is 85 440 and 178 400 respectively. Mostly related to agricultural activity, fungal keratitis affects an estimated 700 Congolese yearly. CONCLUSION: These data underline the urgent need for an intensified awareness towards Congolese physicians to fungal infections and for increased efforts to improve diagnosis and management of fungal infections in the RoC.


Asunto(s)
Micosis/epidemiología , Micosis/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Enfermedad Crónica/epidemiología , Congo/epidemiología , Costo de Enfermedad , Humanos , Incidencia , Prevalencia , Tuberculosis/complicaciones , Tuberculosis/epidemiología
20.
J Antimicrob Chemother ; 73(2): 280-286, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29126309

RESUMEN

Chronic pulmonary aspergillosis (CPA) is a severe fungal infection with a high morbidity and mortality, and is usually seen in immunocompetent patients with respiratory disorders. Clinical presentation is nonspecific and often overlaps with the symptoms and the radiological pattern caused by the underlying disease. Clinical management of CPA is further hampered by limited information about the epidemiology, disease dynamics, sensitivity and specificity of different mycological tests, mechanisms of antifungal resistance, efficient treatment and management strategies. In order to contribute to a better understanding and to improve CPA patient management and outcome, we established the Chronic Pulmonary Aspergillosis Network (CPAnet), a self-organized multinational research collaboration. Key research priorities, defined by using a modified Delphi process, include the establishment of a multinational web-based registry, the validation of different diagnostic tests, the establishment of a culture collection from samples of patients with proven CPA and the establishment of a consensus on a treatment outcome definition.


Asunto(s)
Investigación Biomédica/organización & administración , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Investigación , Enfermedad Crónica , Humanos , Enfermedades Desatendidas/epidemiología , Aspergilosis Pulmonar/epidemiología
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