Molecular epidemiology of Candida africana isolates collected from vagina swabs in French Guiana.

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.

Pulmonary Histoplasmosis in People Living with Human Immunodeficiency Virus in French Guiana: Clinical Epidemiology, Medical Imaging and Prognostic.

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care. METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded. RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%. CONCLUSION: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

Pulmonary cystic echinococcosis in a child.

This case report describes the presentation, diagnosis, and treatment of a 13-year-old boy with pulmonary cystic echinococcosis. The patient presented with low-volume hemoptysis, and lung imaging revealed a large cystic mass, as well as smaller pseudo-nodular lesions, suggesting a large intrathoracic hydatid cyst and ruptured cysts. The diagnosis was confirmed by a positive echinococcosis Western Blot assay, despite equivocal serology. The treatment consisted of surgical removal of the large cyst using thoracoscopy, along with a two-week course of albendazole and praziquantel, followed by albendazole alone for two years. Analysis of the cyst membrane revealed an Echinococcus granulosus protoscolex. The patient had a successful recovery.

ß-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of Non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature.

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.

Effect of Flagellin Pre-Exposure on the Inflammatory and Antifungal Response of Bronchial Epithelial Cells to Fungal Pathogens.

Bronchial epithelial cells (BEC) play a crucial role in innate immunity against inhaled fungi. Indeed, in response to microorganisms, BEC synthesize proinflammatory cytokines involved in the recruitment of neutrophils. We have recently shown that BEC exert antifungal activity against Aspergillus fumigatus by inhibiting filament growth. In the present study, we first analyzed the inflammatory and antifungal responses of BEC infected by several fungal species such as Aspergillus spp., Scedosporium apiospermum and Candida albicans, which are frequently isolated from the sputum of people with chronic pulmonary diseases. The airways of these patients, such as people with cystic fibrosis (pwCF), are mainly colonized by P. aeruginosa and secondary by fungal pathogens. We have previously demonstrated that BEC are capable of innate immune memory, allowing them to increase their inflammatory response against A. fumigatus following a previous contact with Pseudomonas aeruginosa flagellin. To identify the impact of bacteria exposure on BEC responses to other fungal infections, we extended the analysis of BEC innate immune memory to Aspergillus spp., Scedosporium apiospermum and Candida albicans infection. Our results show that BEC are able to recognize and respond to Aspergillus spp., S. apiospermum and C. albicans infection and that the modulation of BEC responses by pre-exposure to flagellin varies according to the fungal species encountered. Deepening our knowledge of the innate immune memory of BEC should open new therapeutic avenues to modulate the inflammatory response against polymicrobial infections observed in chronic pulmonary diseases such as CF.

Usefulness of ß-d-Glucan Assay for the First-Line Diagnosis of Pneumocystis Pneumonia and for Discriminating between Pneumocystis Colonization and Pneumocystis Pneumonia.

According to the immunodepression status, the diagnosis of Pneumocystis jirovecii pneumonia (PjP) may be difficult. Molecular methods appear very sensitive, but they lack specificity because Pj DNA can be detected in Pneumocystis-colonized patients. The aim of this study was to evaluate the value of a serum ß-d-Glucan (BDG) assay for the diagnosis of PjP in a large cohort of HIV-negative and HIV-positive patients, either as a first-line diagnostic test for PjP or as a tool to distinguish between colonization and PjP in cases of low fungal load. Data of Pj qPCR performed on bronchopulmonary specimens over a 3-year period were retrieved retrospectively. For each result, we searched for a BDG serum assay performed within ±5 days. Among the 69 episodes that occurred in HIV-positive patients and the 609 episodes that occurred in immunocompromised HIV-negative patients, we find an equivalent sensitivity of BDG assays compared with molecular methods to diagnose probable/proven PjP, in a first-line strategy. Furthermore, BDG assay can be used confidently to distinguish between infected and colonized patients using a 80 pg/mL cut-off. Finally, it is necessary to search for causes of false positivity to increase BDG assay performance. BDG assay represents a valuable adjunctive tool to distinguish between colonization and infection.

Antifungal combination therapy for invasive fungal infections in a paediatric oncology and haematology department: A retrospective analysis of practice.

BACKGROUND: Invasive fungal infections (IFI) are an important cause of morbidity and mortality in children with leukaemia. International guidelines recommend a monotherapy for most IFI. The use of antifungal combination therapy (ACT) has been reported, but clinical data supporting these combinations are scarce, particularly in paediatrics. OBJECTIVE: To describe, among patients treated in our department, the situations in which an ACT was used. RESULTS: Between January 2017 and December 2020, 239 patients (406 hospital stays) benefited from systemic antifungals. Among them, ACT was prescribed for 14 (5.9%) patients (13 leukaemia, 1 aplastic anaemia) corresponding to 16 (3.9%) hospital stays. IFI cases treated with ACT were mainly proven (n=9) or probable (n=4). Seven cases required admission to the intensive care unit. The most commonly used antifungal agents were liposomal amphotericin B (n=13), caspofungin (n=12) and voriconazole (n=9). In 13 cases, monotherapy was prescribed as first-line therapy and changed to an ACT for an uncontrolled infection. But in 3 cases, the ACT was started immediately. The response at 12 weeks after diagnosis of proven/probable IFI was successful in 12 cases (92.3%). The only IFI-related death was attributed to disseminated mucormycosis. ACT were generally well tolerated. In 4 cases, adverse events led to the discontinuation of the offending antifungal agent. CONCLUSION: This retrospective analysis of practices shows that the use of ACT in our paediatric haemato-oncology department is rare, and concerns the most severe cases and/or those not responding to the first line treatment. In most cases, ACT was efficient and well tolerated.

Diagnosis of mucormycosis using an intercalating dye-based quantitative PCR.

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.

"Pornography Addiction": Elements for Discussion of a Case Report.

Can Internet pornography use (IPU) lead to addiction? "Pornography addiction" is a highly controversial concept within the scientific community. In the absence of consensus, international classifications do not consider that the concept meets the criteria to be recognized as a distinct diagnostic entity. However, the term "pornography addiction" has now become common parlance and is therefore present in the discourse of patients seeking therapy to address what they perceive as problematic pornography consumption. Drawing on a brief case vignette, presenting the case of a man who views himself as a pornography addict, we offer a critical review of this concept. Different diagnostic hypotheses will be considered. Beyond the diagnostic process, we consider the issue of "perceived addiction" and its relationship with "moral incongruence." From a psychotherapeutic view, we suggest that patients who self-identify as "porn addicts" must be supported using a more comprehensive approach that goes beyond their symptomatic behavior or the manner in which they present or perceive themselves. The proposed therapy did not seek or require an end to the behavior. The therapy approach focused on exploring the patient's history in an attempt to understand the construction of his sexuality and morality. In the case analyzed, focusing on the source of moral incongruence led to the disappearance of IPU and all associated suffering.

Flagellin From Pseudomonas aeruginosa Modulates SARS-CoV-2 Infectivity in Cystic Fibrosis Airway Epithelial Cells by Increasing TMPRSS2 Expression.

In the coronavirus disease 2019 (COVID-19) health crisis, one major challenge is to identify the susceptibility factors of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in order to adapt the recommendations for populations, as well as to reduce the risk of COVID-19 development in the most vulnerable people, especially patients with chronic respiratory diseases such as cystic fibrosis (CF). Airway epithelial cells (AECs) play a critical role in the modulation of both immune responses and COVID-19 severity. SARS-CoV-2 infects the airway through the receptor angiotensin-converting enzyme 2, and a host protease, transmembrane serine protease 2 (TMPRSS2), plays a major role in SARS-CoV-2 infectivity. Here, we show that Pseudomonas aeruginosa increases TMPRSS2 expression, notably in primary AECs with deficiency of the ion channel CF transmembrane conductance regulator (CFTR). Further, we show that the main component of P. aeruginosa flagella, the protein flagellin, increases TMPRSS2 expression in primary AECs and Calu-3 cells, through activation of Toll-like receptor-5 and p38 MAPK. This increase is particularly seen in Calu-3 cells deficient for CFTR and is associated with an intracellular increased level of SARS-CoV-2 infection, however, with no effect on the amount of virus particles released. Considering the urgency of the COVID-19 health crisis, this result may be of clinical significance for CF patients, who are frequently infected with and colonized by P. aeruginosa during the course of CF and might develop COVID-19.

Bronchial Epithelial Cells on the Front Line to Fight Lung Infection-Causing Aspergillus fumigatus.

Aspergillus fumigatus is an environmental filamentous fungus that can be pathogenic for humans, wherein it is responsible for a large variety of clinical forms ranging from allergic diseases to life-threatening disseminated infections. The contamination occurs by inhalation of conidia present in the air, and the first encounter of this fungus in the human host is most likely with the bronchial epithelial cells. Although alveolar macrophages have been widely studied in the Aspergillus-lung interaction, increasing evidence suggests that bronchial epithelium plays a key role in responding to the fungus. This review focuses on the innate immune response of the bronchial epithelial cells against A. fumigatus, the predominant pathogenic species. We have also detailed the molecular interactants and the effects of the different modes of interaction between these cells and the fungus.

Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis.

The solute carrier family 6 member 14 (SLC6A14) protein imports and concentrates all neutral amino acids as well as the two cationic acids lysine and arginine into the cytoplasm of different cell types. Primarily described as involved in several cancer and colonic diseases physiopathological mechanisms, the SLC6A14 gene has been more recently identified as a genetic modifier of cystic fibrosis (CF) disease severity. It was indeed shown to have a pleiotropic effect, modulating meconium ileus occurrence, lung disease severity, and precocity of P. aeruginosa airway infection. The biological mechanisms explaining the impact of SLC6A14 on intestinal and lung phenotypes of CF patients are starting to be elucidated. This review focuses on SLC6A14 in lung and gastrointestinal physiology and physiopathology, especially its involvement in the pathophysiology of CF disease.

Respiratory Epithelial Cells Can Remember Infection: A Proof-of-Concept Study.

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.

Multicentric Evaluation of the Bio-Evolution Toxoplasma gondii Assay for the Detection of Toxoplasma DNA in Immunocompromised Patients.

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.

A Psychoanalytical Approach to Diogenes Syndrome.

This article is an attempt at a psychoanalytic understanding of Diogenes syndrome, or hoarding disorder syndrome, by way of a clinical case. This syndrome is characterized by a failure to attend to proper housing habits, including the hoarding of rubbish that may, in fact, create unsuitable, even dangerous, living conditions. The clinical case used suggests that Diogenes syndrome or hoarding disorder reflects or indicates an extreme form of obsessive neurosis involving libidinal regressions to anal fixations designed, paradoxically, to satisfy both a passion for dirty and for order. However, this pathological hoarding may also function to protect the subject against fears associated with meeting people, thereby avoiding any possible intimacy and promoting self-exclusion in an anti-object aim. Finally, the case under discussion helps us to understand the particular psychological aspects or relevance that the actual items and rubbish accumulated have in this syndrome.