bluuebunny/crossref_metadata_2025_split huggingface dataset:
S4.2d Efficacy of LD Bio Aspergillus ICT lateral flow assay for serodiagnosis of chronic pulmonary aspergillosis
Authors: Ray Animesh , Chowdhary Mohit , Sachdeva Janya , Singh Gagandeep , Xess Immaculata , Sinha Sanjeev , Vyas Surabhi , Dennings David W , Wig Naveet , Kabra Sunil Kumar 
Published: September 2022

Abstract

S4.2 Advances in diagnosis of invasive fungal infection, September 22, 2022, 10:30 AM – 12:00 PM

Background
The diagnosis of chronic pulmonary aspergillosis (CPA) relies on the detection of IgG Aspergillus antibody which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio in the setting of tuberculosis endemic countries and has compared it with that of IgG Aspergillus.

Objectives
This study aimed to evaluate the diagnostic performances of LDBio in CPA and compare it with the existing diagnostic algorithm utilizing ImmunoCAP IgG Aspergillus.

Methods
Serial patients presenting with respiratory symptoms (cough, hemoptysis, fever, etc) for &gt;4 weeks were screened for eligibility. Relevant investigations including respiratory secretions stain/culture, IgG Aspergillus, chest imaging, etc were done according to the existing algorithm. Serum of all patients was tested by LDBio and IgG Aspergillus (ImmunoCAP) and their diagnostic performances were compared.

Results
A total of 218 patients were screened and 174 patients were included in the study with ∼ 66.7% of patients having a past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) patients. The estimated sensitivity and specificity of LDBio was 67.6% [95% confidence interval (CI), 55.7%-78%] and 81% (95% CI, 71.9%-81%) respectively which increased to 73.3% (95% CI, 60.3%-83.9%), and 83.9% (95% CI, 71.7%-92.4%) respectively in patients with past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI, 71.8%-90.3%) and 82% (95% CI, 73.1-89%); 86.7% (95% CI, 75.4%-94.1%), and 80.4% (95% CI, 67.6%-89.8%) in the whole group and those with past history of tuberculosis respectively. The baseline characteristics and diagnostic accuracies are listed in Tables 1 and 2 respectively.

Conclusions
LDBio is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting.
S5.1b Antifungal r esistance
Authors: Seidel Danila 
Published: September 2022

Abstract

S5.1 Antifungal resistance, September 22, 2022, 3:00 PM - 4:30 PM
Resistance to clinical antimycotics in Aspergillus fumigatus has become an increasing threat in healthcare worldwide over the past two decades. Factors that contribute to this continuing trend are manifold, among others resistance emerge in environmental fungi through selection pressure due to fungicides widely used in agriculture and farming, resistant clones are diffused around the world through global travel and shipping routes, as well as prophylactic and long-term administration of antifungal agents in patients with chronic fungal disease creating selection pressure.

Physicians face particular challenges in their patients with invasive aspergillosis, with emerging resistance adding another layer of therapeutic complexity. We are beginning to gain an understanding of the clinical implications of the different patterns of resistance. First international studies have shown that resistance of A. fumigatus to clinical antifungal agents significantly hampers the successful treatment of patients.

This presentation aims to highlight the difficulties associated with antifungal resistance in A. fumigatus with a focus on hematological oncological patients.
S5.1d Mechanisms of azole antifungal resistance in clinical isolates of Candida tropicalis
Authors: Ghosh Anup , Paul Paul , Shaw Dipika , Joshi Himanshu , Singh Shreya , Chakrabarti Arunaloke , Rudramurthy Shivaprakash M , Kaur Harsimran 
Published: September 2022

Abstract

S5.1 Antifungal resistance, September 22, 2022, 3:00 PM - 4:30 PM

Objectives
In tropical countries, the azole resistance in Candida tropicalis is on the rise. There are limited studies available regarding the azole resistance mechanisms in C. tropicalis. This study was designed to understand the molecular mechanisms of azole resistance in C. tropicalis by using genetic and bioinformatics approaches.

Methods
A total of 32 azole-resistant (R) and 10 azole-susceptible (S) clinical isolates of C. tropicalis were included in this study. All the isolates were subjected to complete gene sequencing of azole target genes including ERG11 to analyze the mutations which could lead the azole resistance. Four fragments were amplified, sequenced, and aligned to get full-length ERG11 gene. Inducible expression analysis of 17 other genes potentially associated with azole resistance was also evaluated. Homology modeling and molecular docking analysis were performed to study the effect of amino acid alterations in mediating azole resistance.

Results
Of the 32 resistant isolates, 12 (37.5%) showed A395T and C461T mutations in the ERG11 gene. The mean overexpression of CDR1, CDR3, TAC1, ERG1, ERG2, ERG3, ERG11, UPC2, and MKC1 in resistant isolates without mutation (R-WTM) was significantly higher (P &lt;.05) than those with mutation (R-WM) and the sensitive isolates (3.2-11 vs. 0.2-2.5, and 0.3-2.2 folds, respectively). Although the R-WTM and R-WM had higher (P &lt;.05) CDR2 and MRR1 expression compared to S isolates, noticeable variation was not seen among the other genes. Protein homology modeling and molecular docking revealed that the mutations in the ERG11 gene were responsible for structural alteration and low binding efficiency between ERG11p and ligands. Isolates with ERG11 mutations also presented A220C in ERG1 and together T503C, G751A mutations in UPC2.

Conclusions
Nonsynonymous mutations in the ERG11 gene and coordinated overexpression of various genes including different transporters, ergosterol biosynthesis pathway, transcription factors, and stress-responsive genes are associated with azole resistance in clinical isolates of C. tropicalis.
S6.4c Primary cutaneous implantation coccidioidomycosis
Authors: Bonifaz Alexandro , Araiza Javier , Arce Martin 
Published: September 2022

Abstract

S6.4 One health approach for endemic mycoes in the Americas, September 22, 2022, 4:45 PM - 6:15 PM

Objective
To present a series of cases of primary cutaneous coccidioidomycosis, to highlight this mycosis that can start as cutaneous implantation, after trauma, and to emphasize the classification criteria.

Methods
A series of cases of primary cutaneous coccidioidomycosis will be presented, all of them confirmed by mycological studies, fresh examinations, stains, and cultures, as well as their molecular identification; also confirmed by histopathology.

Results
A series of 22 cases of primary cutaneous coccidioidomycosis is presented, 16 (72.8%) in men, 6 (27.2%) in women. With an average age of 35.2 years, with the lowest case in a 14-year-old child and the highest at 72 years. All from rural and endemic areas. A total of 11 (50%) with fieldwork and the rest due to various injuries. The etiological agent was isolated in all of them: Coccidiodes posadasii in 16 (72.8%), C. immits in 3 and one by Coccidiodes sp. 20 cases were managed with itraconazole, with an average of 8 months and two more with a cycle of amphotericin B and subsequent itraconazole. Clinical and mycological cure was obtained in all.

Discussion
Primary cutaneous coccidioidomycosis, is considered an implantation mycosis, similar to other endemic ones, it occurs between 2%-10% of cases. It begins after trauma that inoculates the fungus, such as a primary chancre. To confirm that it is a primary form, Wilson's criteria must be met: the presence of skin trauma, regional lymphadenopathy, no evidence of pulmonary involvement, positive intradermal reaction, and low antibody titers. It may present auto involution and in immunosuppressed patients, it can spread.

Conclusion
The initial cutaneous form of coccidioidomycosis is rare, usually seen in patients living in endemic areas, and usually present in patients with rural occupations. It has a variety of clinical forms, being confused with many diseases. Its diagnosis is simple, being the biopsy the most used, and it must be confirmed by mycological tests. It has a good prognosis and its main management is with itraconazole.
S6.5b Genomics and metagenomics of Madurella mycetomatis
Authors: Litvintseva Anastasia , Bakhiet Sahar , Gade Lalitha , Bagal Ujwal , Wagner Darlene , Siddig Emmanuel Edwar , Mhmoud Najwa Adam , Fahal Ahmed 
Published: September 2022

Abstract

S6.5 Efforts of improving the management of mycetoma: working towards the 2030 goals, September 22, 2022, 4:45 PM - 6:15 PM

Mycetoma is a debilitating disease recognized as a neglected tropical disease by the World Health Organization. The etiology of mycetoma is poorly understood; ∼ 60% of cases are caused by fungi and the rest are bacterial, although this varies by region. The pathogenic fungus, Madurella mycetomatis, is most frequently identified in mycetoma cases. Here, we present a high-quality genome assembly of M. mycetomatis and the results of the whole genome sequence analysis of 25 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. Shotgun metagenomic analysis of DNA from mycetoma grains confirmed that M. mycetomatis was the predominant causative agent of eumycetoma Sudan; however, 10% of grains also contained bacterial reads suggestive of secondary infections. A thorough understanding of the genetic structure and diversity of fungi causing mycetoma is essential for the development of new diagnostic methods and for identifying potential drug targets.
S6.5c MycetOS: identifying drugs which can penetrate the mycetoma grain
Authors: Van de Sande Wendy 
Published: September 2022

Abstract

S6.5 Efforts of improving the management of mycetoma: working towards the 2030 goals, September 22, 2022, 4:45 PM - 6:15 PM
Mycetoma is a neglected tropical disease characterized by large subcutaneous swellings and the formation of grains. Madurella mycetomatis is the most common causative agent. Currently, mycetoma is treated with a combination of itraconazole therapy and surgery with low success rates, resulting often in amputation and social sigma. To improve the current therapeutic success rates a novel drug is needed. Due to the lack of interest in the pharmaceutical industry, an open-source drug discovery program for mycetoma was established called MycetOS.

In total 1360 compounds were screened for in vitro activity against M. mycetomatis, and many more are currently being screened. Compounds that were able to inhibit growth at 100 μm, 25 μm, and had an IC50 &lt;8 μm were selected for studying the in vivo efficacy in an M. mycetomatis grain model in the invertebrate Galleria mellonella.

Out of the 1360 compounds screened against M. mycetomatis, 302 were able to inhibit growth at 100 μm, and 23 of those met all criteria to be screened in vivo. Of these 23, nine did prolong larval survival. These included 3/7 azoles tested, olorofim, fenbendazole, MMV006357, MMV022478, MMV675968, and MMV1782387. Based on these results, 6 compound series were selected for further studying, these included the fenarimols (series 1), the aminothiazoles (series 2), the phenotiazines (series 3), dihydrofolate reductase inhibitors (series 4), benzimidazoles (series 5) and the ketoximines (series 6). For series 1 in total 185 additional compounds were screened. By analyzing the in vitro activity and in vivo efficacy in relation to the chemical properties of the molecules it appears that the LogD value of a compound was important for penetrating into the mycetoma grain.

In conclusion, using an open source drug discovery approach for mycetoma we were able to identify novel lead compounds. Some of these compounds were highly active against M. mycetomatis only (fenarimols, aminothiazoles, phenotiazines, and ketoximines), while other compounds such as the benzimidazoles also were active against other causative agents as well. Screening more analogs of identified compounds allowed us also to identify chemical properties which are favorable for grain penetration in vivo. This will allow us to chemically design more active compounds for this difficult to treat infection.
S6.5d Molecular identification of mycetoma causative agents from patients in ahospital setting in Senegal
Authors: Sow Doudou , Deh Aminata , Minlékib Carole Pab , Ndiaye Maodo , Manga Isaac , Lelo Souleye , Fall Cheikh Bintou , Sylla Khadime , Ndiaye Magatte , Tine Roger , Dieng Thérèse , Faye Babacar 
Published: September 2022

Abstract

S6.5 Efforts of improving the management of mycetoma: working towards the 2030 goals, September 22, 2022, 4:45 PM - 6:15 PM

Background
Mycetoma is a chronic granulomatous inflammatory disease that is caused either by bacteria or fungi. The diagnosis of species is important to guide the therapeutic management of patients particularly for white and yellow grains. However, the identification of the causative agents using mycological and histological techniques is a real problem in our countries. This study aims to identify etiologic agents using molecular techniques in Senegal.

Methods
A prospective study was carried out to compare mycological and histological techniques with molecular methods in patients attending hospital settings. Biopsy specimens and/or grains obtained from these patients were examined by PCR targeting the ITS (fungal agents) and 16S (actinomycosis agents) genes. Sequencing with the SANGER method allowed us to identify the species.

Results
Preliminary results were obtained from 30 patients. The grains collected were black (38%), red (4.7%), white (47.6%), and yellow (9.5%). Discriminative PCR ITS vs 16S identified 5 actinomycosis agents including white and yellow grains and 1 fungal agent. The fungal agent was identified after sequencing as Microsporum langeronii.

Conclusion
The preliminary results of this study show the importance of discriminative PCR to guide the therapeutic choice of clinicians. Its widespread use could improve the detection and management of mycetoma cases in Senegal.
S7.2d Divergent EGFR/MAPK-mediated immune responses to clinical Candida pathogens in vulvovaginal candidiasis
Authors: Zhang Jingyun , Peng Jingwen , Li Dongmei , Mei Huan , Yu Yu , Li Xiaofang , She Xiaodong , Liu Weida 
Published: September 2022

Abstract

S7.2 More than just candidemia: clinical aspects, diagnosis and treatment, and pathogenesis of deep-seated candidiasis, September 23, 2022, 10:30 AM - 12:00 PM

Objectives
Vulvovaginal candidiasis (VVC) is characterized by symptomatic inflammatory responses in the vagina caused by Candida albicans and non-albicans Candida (NAC) species. The epidermal growth factor receptor (EGFR) -mitogen-activated protein kinase (MAPK) signaling pathway has been linked to immune responses of oral epithelial cells upon C. albicans exposure, but whether this pathway plays a similar response in vaginal epithelial cells is not determined.

Methods
The activation of EGFR and MAPK signaling pathways in vaginal epithelial cells infected with C. albicans was determined by RNA sequencing and Western blot. The relationship between EGFR and MAPK signaling was verified via inhibition of EGFR and construction of EGFR-overexpressing cells. Enzyme-linked immunosorbent assay (ELISA) and Real Time Cellular Analysis (RTCA) techniques were used to detect the effect of EGFR-MAPK signaling pathway on regulating the secretion of inflammatory cytokines and cell damage induced by C. albicans. The mouse model of VVC infected by C. albicans was constructed, and the role of EGFR signaling pathway in regulating fungal burden, vaginal inflammation, and epithelial damage was determined by Periodic Acid-Schiff stain and immunofluorescence.

Results
We observed that phosphorylation of EGFR and p38 was continuously activated in vaginal epithelial cells by C. albicans strain SC5314. The response is not in a biphasic manner that is critical for oral epithelial cells to discriminate the morphology of C. albicans. When compared with SC5314, a highly azole-resistant C. albicans isolate 1052 can induce a stronger phosphorylated signal of EGFR and p38, while clinically-isolated NAC strains including C. tropicalis, C. glabrata, C. parapsilosis, and C. auris triggered higher levels of phosphorylated ERK1/2 and c-Fos than C. albicans. Consistently, inhibition of EGFR significantly reduced inflammatory response and epithelial damage induced by C. albicans in vitro and in vivo, while inhibition of p38 led to great loss of epithelial damage triggered by both C. albicans and NAC species.

Conclusion
These results confirm the importance of the EGFR-MAPK signaling in VVC pathogenesis and highlight the remarkable immunogenic differences between C. albicans and NAC species in host-microbe interactions.
S8.2a Trends in epidemiology of pediatric Candida infections
Authors: Roilides Emmanuel 
Published: September 2022

Abstract

S8.2 What is new in pediatric mycology?, September 23, 2022, 3:00 PM - 4:30 PM

Invasive Candida infections are a cause of increased morbidity and excessive mortality in immunocompromised and critically ill patients including premature neonates. In the pediatric setting, they are more frequent in the neonatal intensive care unit (ICU), in the pediatric ICU, and in the pediatric oncology/hematology departments. Its frequency in other pediatric departments, such as gastroenterology, surgery, and nephrology is less of a problem. Candida albicans remains the most frequent Candida species, whereas other non-albicans Candida spp. are less frequent. Candida parapsilosis is second in frequency, but in certain pediatric settings and countries, it may be first. While C. albicans is almost entirely susceptible to azoles, C. parapsilosis has started to manifest increasing resistance to fluconazole and this is of concern. However, due to improved infection control and prevention measures and to use of fluconazole prophylaxis in a number of neonatal ICUs, its incidence has been shown to decrease in a multi-state study conducted by the Centers of Disease Control and Prevention in the United States. Another large multinational study that was conducted in many European countries showed no changes in epidemiology over a number of years, and more non-albicans Candida, particularly C. parapsilosis, in South Europe. The epidemiology of Candida in pediatric ICU has been less studied. Similar epidemiology and risk factors exist in PICU as in neonates. Abdominal surgery and multi-site colonization with Candida of patients are risk factors for developing invasive Candida infections, mainly candidemia. In the patients with hematological malignancies, antifungal prophylaxis for mold infections is also active against Candida, therefore, the incidence of invasive candidiasis is relatively low. However, non-Candida albicans species with reduced susceptibility to azoles, such as C. glabrata, are found more frequently. In pediatric patients with solid organ transplantation, invasive candidiasis is the most frequent fungal infection, mainly in those with liver transplantation. Candida causes infection in the first weeks after transplantation earlier than other fungal infections.
S8.3b How fungal cell wall glycans modulate the activation of platelets ?
Authors: Jawhara Samir 
Published: September 2022

Abstract

S8.3 How the fungal cell wall glycan can modulate the immune response?, September 23, 2022, 3:00 PM - 4:30 PM

Platelets are the first circulating blood cells that interact and adhere to vascular lesions. They play an important role in vascular repair and maintenance of blood homeostasis. Platelets are involved in the immune defense of the host against many infections caused by bacteria, viruses, and fungi. Following infection, these microorganisms can alter platelet function leading to platelet activation. During fungal infection, β-glucans, mannan, and chitin, are critical components of Candida albicans, an opportunistic pathogenic yeast of humans. These fungal glycans play an important role in the modulation of the host response. They are released into the bloodstream and can be detected up to 10 days before the onset of clinical signs of invasive candidiasis. However, their role in the modulation of platelet activities is unknown. In our studies, we observed that β -glucans and chitin decrease platelet activation and modulate the production of inflammatory mediators, mediated by TLR4 or TLR8 respectively. These glycans also reduce platelet adherence to C. albicans and to polynuclear neutrophils, suggesting a process by which C. albicans can escape from cells of innate immunity by releasing cell wall polysaccharides into the close environment or the blood circulation. This study provides evidence that fungal glycans play a role in the modulation of the immune response and how C. albicans can escape from the innate immune response.
S8.3c Cell wall glycans as targets for the development of new antifungals
Authors: Aimanianda Vishukumar , Wong Sarah Sze Wah , Delliere Sarah , Schiefermeier-Mach Natalia , Lechner Lukas , Perkhofer Susanne , Bomme Perrine , Fontaine Thierry , Schlosser Anders , Sorensen Grith , Madan Taruna , Kishore Uday 
Published: September 2022

Abstract

S8.3 How the fungal cell wall glycan can modulate the immune response?, September 23, 2022, 3:00 PM - 4:30 PM

Being an extracellular organelle, the cell wall plays a crucial role in fungal life, by protecting fungal cells from a hostile environments and providing cells with mechanical strength. Exploiting the essentiality of this cell wall, available antifungal drugs target cell wall biosynthesis directly or by altering the fungal cell membrane. However, the emergence of resistance to antifungal drugs, new at risk-cohorts, and drug-drug interaction issue with antifungals demand new/alternative therapeutic strategy. In this regard, we have identified that surfactant protein-D (SP-D; a host humoral immune component) has growth inhibitory activity on Aspergillus fumigatus, a ubiquitous airborne opportunistic pathogen. SP-D, a soluble pattern recognition receptor of the collection family, targets galactosaminogalactan and galactomannan, the cell wall glycans of A. fumigatus hyphae, as the ligands. Hyphae grown in presence of SP-D show a significant decrease in the growth and are hyperbranched compared to control hyphae. SP-D treatment alters surface exposure of hyphal cell wall polysaccharides, thereby modifying hyphal immunoreactivity. SP-D pre-treatment increases the efficacy of the echinocandin and azole classes of antifungals against A. fumigatus. Interestingly, SP-D show hyphal growth inhibitory activity against multi-/pan-azole-resistant isolates of A. fumigatus. Overall, SP-D seems to target A. fumigatus cell wall glycans to execute its fungistatic activity. We are currently investigating the exact mechanism of anti-A. fumigatus activity associated with SP-D.