Universal azole prophylaxis for prevention of coccidioidomycosis among lung transplant recipients transferring care to a center within a highly endemic region.

BACKGROUND: Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown. METHODS: Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post-transplant follow-up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions. RESULTS: Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work-up for suspected infection during hospitalization. After a median follow-up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post-transplant and >2 years post-transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications. CONCLUSION: Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region.

Evaluation of Turnaround Times for Antigen Testing in Hospitalized Patients With Histoplasmosis and Blastomycosis.

Review of histoplasmosis and blastomycosis antigen testing for 39 patients hospitalized with these diseases found that there were significantly longer turnaround times between the time of specimen collection and receipt of positive test results among those patients who had worse outcomes.

Fungal coinfection/superinfection in COVID-19 patients in a tertiary hospital in Mexico / Coinfección o sobreinfección fúngica en pacientes con COVID-19 en un hospital de tercer nivel en México

Introduction: Data on the prevalence of fungal coinfections/superinfections in patients with COVID-19 are limited. Objective: To describe the prevalence of fungal coinfections/superinfections in patients with COVID-19, as well as risk factors and demographic, clinical, and microbiological characteristics. Material and methods: We included patients with a confirmed COVID-19 diagnosis and a confirmed fungal infection hospitalized in the ICU from March 2020 to December 2021. We collected data on age, sex, comorbidities, hospital length of stay (days), laboratory (ferritin) and microbiological results, treatment for COVID-19, antifungal therapy, and outcomes obtained from the clinical records. Results: Only 11 out of 740 patients met the inclusion criteria. The coinfection rate was 0.3% and the superinfection was 1.2%. The most affected population was male adults. The coinfections/superinfections diagnosed were candiduria and candidemia, caused by Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae, and Kluyveromyces marxianus (C. kefyr). In addition, tracheobronchitis due to Aspergillus fumigatus was found. The most used antifungals were fluconazole and caspofungin. The lethality in patients with fungal coinfections was 50% and superinfections, 22%. The length of hospital stay was 11-65 days. Eight patients required mechanical ventilation and six received corticosteroids. The main comorbidity was diabetes mellitus (81.8%). Conclusions: The rate of fungal coinfections/superinfections in COVID-19 patients was low, but the lethality found urges for routine fungal screening in patients with severe COVID-19 to timely detect fungal infections that may further compromise the patient's life.

Introducción: Los datos sobre la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19 son limitados. Objetivo: Describir la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19, así como los factores de riesgo y las características demográficas, clínicas y microbiológicas. Material y métodos: Se incluyeron pacientes con diagnóstico confirmado de COVID-19, hospitalizados en la unidad de cuidados intensivos y con infección fúngica confirmada entre marzo del 2020 y diciembre del 2021. Del expediente clínico se obtuvieron datos sobre edad, sexo, comorbilidades, días de estancia hospitalaria, resultados de laboratorio (ferritina) y microbiológicos, tratamiento contra COVID-19, terapia antifúngica y desenlace. Resultados: Once de 740 pacientes cumplieron con los criterios de inclusión. La tasa de coinfección fue del 0,3 % y la de sobreinfección fue del 1,2 %. La población más afectada fue la de hombres adultos. Las coinfecciones o sobreinfecciones diagnosticadas fueron candiduria y candidemia, causadas por Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae y Kluyveromyces marxianus (C. kefyr). Además, se encontró una traqueobronquitis por Aspergillus fumigatus. Los antifúngicos más administrados fueron fluconazol y caspofungina. La letalidad en pacientes con coinfecciones fue del 50 % y con sobreinfecciones fúngicas, del 22 %. El tiempo de estancia intrahospitalaria fue de 11 a 65 días. Ocho de los pacientes requirieron asistencia respiratoria mecánica y seis recibieron corticoides. La principal comorbilidad fue diabetes mellitus (81,8 %). Conclusiones: La tasa de coinfecciones o sobreinfecciones por hongos en pacientes con COVID-19 fue baja, pero la letalidad de estas requiere, con urgencia, la realización de pruebas de rutina para detectar hongos en pacientes con COVID-19 grave para diagnosticar oportunamente infecciones fúngicas que puedan comprometer aún más la vida del paciente.

Tinea Nigra: Clinical and Diagnostic Guidance.

Tinea nigra is a rare superficial fungal infection characterized by asymptomatic, unilateral, well-defined brown to black macules predominantly affecting the palms and soles. Diagnosis is often challenging due to its rarity and resemblance to other pigmented lesions. This report presents a clinical case, a diagnostic algorithm, and treatment recommendations, emphasizing the role of thorough examination and questioning. We describe the case of a 64-year-old woman of Amerindian (Maya) heritage from Yucatan, Mexico, who presented with a three-month history of a slowly growing dark spot on her left palm. The lesion was asymptomatic, non-scaling, and non-palpable. Palmar skin scrapings, prepared with KOH, revealed pigmented yeast and hyphae, leading to a diagnosis of tinea nigra. Following treatment with topical ketoconazole, the patient's lesions completely resolved at the one-month follow-up. The cultivation of scales confirmed the presence of Hortaea werneckii. Our findings highlight the importance of considering tinea nigra in the differential diagnosis of pigmented lesions on acral surfaces. We propose a diagnostic algorithm to aid healthcare professionals in recognizing this uncommon condition and recommend treatment protocols that effectively resolve the infection within two weeks. This case underscores the necessity for increased awareness and accurate diagnosis of tinea nigra, particularly in non-endemic regions.

An Unlikely Case of Blastomycosis in an Elderly Female: A Diagnostic Challenge in a Non-endemic Region.

Blastomyces dermatitidis is a fungus typically found in the soil of endemic regions such as the Midwest, concentrating in areas like Ohio, Mississippi, and the Great Lakes area. The systemic infection caused by inhaling Blastomyces dermatitidis is known as blastomycosis. The frequency of blastomycosis in non-endemic regions is increasing for a variety of speculated reasons, such as higher rates of immunosuppressed individuals and possible climate. Due to clinician unfamiliarity, misdiagnosis of blastomycosis is common, which potentiates worsening systemic infections. This study shows the clinical course of a patient with blastomycosis in a non-endemic region, highlighting the need for education for clinicians in non-endemic areas. A 72-year-old female with a history of chronic obstructive pulmonary disease (COPD), coronary artery disease, a 47-year smoking history, and hypertension presented for outpatient management of COPD. CT three months prior to presentation showed nodular opacities in the lungs. A bronchoscopy was performed and revealed negative findings for malignancy or infection; the patient developed worsening symptoms leading to hospitalization. Subsequent testing revealed Blastomyces dermatitidis. She was promptly treated with a six to 12-month course of itraconazole with close follow-up. The study highlights the need not to rule out causes of infection based on location. Blastomycosis can resemble community-acquired pneumonia. Making the correct diagnosis is paramount, as delays can result in morbidity. Fungal cultures may be the gold standard, but due to the long culture time, there need to be other diagnostic tests like urine antigen testing. This study highlights the need to increase awareness of clinicians who experience blastomycosis patients in a non-endemic region.

Skin mycosis distribution, and burden of visits over a decade in Colombia: ecological study.

Objectives: To describe the sociodemographic distribution of dermatomycosis and the visits burden over a 10-year period of care. Methods: An ecological study was conducted using data on visits and people treated in the Colombian Health System during 2010-2019 using the International Classification of Diseases, Tenth Revision codes (ICD-10). Departments and geopolitical regions were the units of analysis, and visit burden was reported as frequency, intensity (visits per person), and rate of dermatomycosis visits (per 10,000 visits; 95% confidence interval). Results: A total of 4,570,593 visits were analyzed. The most used ICD-10 codes were B369 (superficial mycosis, unspecified), B360 (pityriasis versicolor), B354 (Tinea corporis), B359 (dermatophytosis), and B351 (Tinea unguium) (56.5%), with visits primarily involving the adult population (27-59 years; 32.2%), women (43.4%), and urban populations (57.3%). Amazonas department had the highest rate of visits (2.36 per 10,000), while Nariño had the highest intensity of visits (1.94 visits per person). Caribbean region had the highest rate of visits (17.0 per 10,000 visits; 17.0-17.0), followed by the Amazon region (16.3 per 10,000 visits; 16.2-16.4). Conclusions: The annual visits burden of dermatomycosis in Colombia is high and concentrated in susceptible geographic areas, possibly due to socio-environmental factors. This health problem is overshadowed by chronic diseases and trauma but is often recurrent, and chronic, and induces out-of-pocket costs for treatment.

Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review.

INTRODUCTION: Intracranial fungal infections' (IcFIs) varying clinical manifestations lead to difficulties in diagnosis and treatment. African populations are disproportionately affected by the high burden of the disease. There is a lack of clarity as to the diagnostic and treatment modalities employed across the continent. In this review, we aim to detail the management, and outcome of IcFIs across Africa. METHODS: This scoping review was conducted using the Arksey and O'Malley framework. MEDLINE, EMBASE, Cochrane Library, African Index Medicus, and African Journals Online were searched for relevant articles from database inception to August 10th, 2021. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews guidelines were used to report the findings of the review. RESULTS: Of the 5,779 records identified, 131 articles were included. The mean age was 35.6 years, and the majority (56.4%) were males. The majority (n = 8,433/8,693, 97.0%) of IcFIs presented as a meningitis, the most common communicable predisposing factor of IcFIs was HIV/AIDS (n = 7,815/8,693, 89.9%), and the most common non-communicable risk factor was diabetes mellitus (n = 32/8,693, 0.4%). Cryptococcus species was the most common (n = 8,428/8,693, 97.0%) causative organism. The most commonly used diagnostic modality was cerebrospinal (CSF) cultures (n = 4,390/6,830, 64.3%) for diffuse IcFIs, and MRI imaging (n = 12/30, 40%) for focal IcFIs. The most common treatment modality was medical management with antifungals only (n = 4,481/8,693, 51.6%). The most commonly used antifungal agent in paediatric, and adult patients was amphotericin B and fluconazole dual therapy (51.5% vs 44.9%). The overall mortality rate was high (n = 3,475/7,493, 46.3%), and similar for both adult and paediatric patients (47.8% vs 42.1%). CONCLUSION: Most IcFIs occurred in immunosuppressed individuals, and despite the new diagnostic techniques, CSF culture was mostly used in Africa. Antifungals regimens used was similar between children and adults. The outcome of IcFIs in Africa was poor for both paediatric and adult patients.

Epidemiological overview of mucocutaneous fungal infections in Munich.

BACKGROUND AND OBJECTIVES: Knowledge about the current spectrum of dermatomycoses is important for diagnosis and therapy. PATIENTS AND METHODS: A retrospective, monocentric analysis of mucocutaneous fungal infections diagnosed at a large European academic dermatology department in Munich was conducted; 87,229 samples from 48,916 patients from January 1, 2011, to August 30, 2020, were included. RESULTS: Fungi were detected in 11,513 samples from 48,916 (23.54%), and 36 different species were identified. Candida (C.) albicans was the most common pathogen (5,055 detections; 43.91% of all positive samples), followed by Trichophyton (T.) rubrum (3,076 detections; 26.72% of all positive samples) and Candida parapsilosis (923 detections; 8.02% of all positive samples). Rare pathogens such as Trichophyton raubitschekii were also detected. Coinfections with multiple species were detected in 44 cases. CONCLUSIONS: Even though C. albicans, T. rubrum, and C. parapsilosis were confirmed as the most common pathogens, rare pathogens should also be considered in clinical practice. The predominant spectrum of fungi differed from that reported in other countries. Furthermore, a difference in the pathogen spectrum could be observed depending on the age group and body site.

Antifungal resistance in dermatophytes - review of the epidemiology, diagnostic challenges and treatment strategies for managing Trichophyton indotineae infections.

INTRODUCTION: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. AREAS COVERED: A literature search was conducted in May 2024. T.indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting.As a newly identified dermatophyte species closely related to the T. mentagrophytes complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for T. indotineae. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. EXPERT OPINION: When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles.

Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 20­25% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development.While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as Trichophyton indotineae. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for T. indotineae. Currently, most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays.Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of T. indotineae infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered.

Disseminated paracoccidioidomycosis in a captive western black-handed tamarin (Saguinus niger).

Paracoccidioidomycosis (PCM) is an endemic fungal disease that occurs in Latin America and primarily affects humans. The disease has been rarely documented in non-human primates. This report details a disseminated and fatal case of PCM caused by Paracoccidioides brasiliensis in a western black-handed tamarin (Saguinus niger) under human care. Histopathological examination revealed extensive pyogranulomatous inflammation in the lungs, spleen, liver, lymph nodes, kidneys, epididymis, right testicle, heart, adrenal gland and intestines, associated with characteristic yeast forms consistent with Paracoccidioides spp and confirmed by immunohistochemistry. Molecular analysis indicated a high nucleotide similarity with P. brasiliensis sequences for both the 18S rRNA and gp43 genes. This naturally occurring infection highlights the susceptibility of these animals to PCM and their role in ecoepidemiology warrants further investigation.

Clinical Mycology Today: Emerging Challenges and Opportunities.

The Mycoses Study Group Education and Research Consortium is a collective of clinicians, researchers, and educators with the common goal to advance awareness, diagnosis, and management of invasive fungal diseases. Clinical Mycology Today, the Mycoses Study Group Education and Research Consortium's biennial meeting, is dedicated to discussing the most pressing contemporary issues facing the field of clinical mycology, promoting clinical, translational, and basic science collaborations, and mentoring the next generation of clinical mycologists. Here, we review the current opportunities and challenges facing the field of mycology that arose from discussions at the 2022 meeting, with emphasis on novel host risk factors, emerging resistant fungal pathogens, the evolving antifungal pipeline, and critical issues affecting the advancement of mycology research.

Epidemiology of Invasive Fungal Diseases: A 10-Year Experience in a Tertiary Pediatric Hematology-Oncology Department in Greece.

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology-Oncology Department of the University General Hospital of Heraklion for 2013-2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment.

Causal relationship between type 1 diabetes mellitus and mycoses: a Mendelian randomization study.

Background: Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses. Methods: Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy. Results: Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis. Conclusion: This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

Chromoblastomycosis caused by Alternaria infectoria, concurrent with myiasis, in a recipient of a kidney transplant: a compelling case report.

Neglected tropical diseases (NTDs) pose a significant threat to the health of millions of people worldwide, particularly in impoverished populations in tropical and subtropical regions. The World Health Organization (WHO) considers certain fungal infections, such as chromoblastomycosis, as NTDs. Chromoblastomycosis is a chronic fungal infection affecting the skin and subcutaneous tissue, primarily found in tropical and subtropical regions of Latin America, Africa, and Asia. This case report presents a 46-year-old female patient with chromoblastomycosis who had a history of renal transplantation and was receiving immunosuppressive therapy. The patient exhibited dark, verrucous, and ulcerative lesions on the legs, and the diagnosis was confirmed through the microscopic examination of skin scrapings by observing medlar bodies. Two sequential fungal tissue cultures and ITS sequencing verified the presence of Alternaria infectoria, not formerly described in chromoblastomycosis. Moreover, observation of fly larvae in the lesions verified the diagnosis of myiasis. Treatment with voriconazole and terbinafine resulted in complete resolution of the lesions after 5 months. This case emphasizes the importance of considering chromoblastomycosis in individuals with occupational exposure in tropical areas, as well as the challenges associated with its diagnosis, coinfections, and treatment.

Dermatologic Fungal Neglected Tropical Diseases-Part I. Epidemiology and Clinical Features.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

[Fatal case of rhinocerebral mucormycosis on the background of type II diabetes mellitus]. / Letal'nyi sluchai rinotserebral'nogo mukormikoza na fone sakharnogo diabeta 2-go tipa.

Mucormycosis is a disease caused by fungi of the Mucorales family, widespread in the environment, with pronounced angiotropism and the ability to angioinvasion, leading to thrombosis with surrounding necrosis. The main triggers for the development of mucormycosis are: immunodeficiency states, use of glucocorticosteroid drugs, decompensation of diabetes mellitus, concomitant diseases, age > 65 years. We present a clinical case of rhinocerebral mucormycosis in a 79-year-old patient against the background of uncontrolled type 2 diabetes mellitus with ketoacidosis, a condition after previous glucocorticosteroid therapy for COVID-19 (according to the severity of the disease). After suffering a new coronavirus infection caused by the SARS-CoV-2 virus, she was admitted to the hospital with complaints characteristic of mucormycosis. On the 5th day of hospital stay, the patient's condition worsened significantly, despite the correction of the therapy, and on the 12th day the patient died. According to the results of the autopsy, it was established that the rhinocerebral mucormycosis was complicated by thrombosis of the anterior and posterior left cerebral arteries with subsequent infarctions in the frontal lobe and parieto-occipital region of the brain left hemisphere, cerebral edema, which was the immediate cause of death.

The Antifungal Potential of Niclosamide and Structurally Related Salicylanilides.

Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure-activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024.

Dermatologic Fungal Neglected Tropical Diseases-Part II. Management and Morbidity.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

Development and Clinical Evaluation of a CRISPR/Cas12a-Based Nucleic Acid Detection Platform for the Diagnosis of Keratomycoses.

Objective: The objective of this study was to develop a rapid and accurate clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-based molecular diagnostic assay (Rapid Identification of Mycoses using CRISPR, RID-MyC assay) to detect fungal nucleic acids and to compare it with existing conventional mycologic methods for the diagnosis of fungal keratitis (FK). Design: This study was structured as a development and validation study focusing on the creation and assessment of the RID-MyC assay as a novel diagnostic modality for FK. Subjects: Participants comprised 142 individuals presenting with suspected microbial keratitis at 3 tertiary care institutions in South India. Methods: The RID-MyC assay utilized recombinase polymerase amplification targeting the 18S ribosomal RNA gene for isothermal amplification, followed by a CRISPR/Cas12a reaction. This was benchmarked against microscopy, culture, and polymerase chain reaction for the diagnosis of FK. Main Outcome Measures: The primary outcome measures focused on the analytical sensitivity and specificity of the RID-MyC assay in detecting fungal nucleic acids. Secondary outcomes measured the assay's diagnostic sensitivity and specificity for FK, including its concordance with conventional diagnostic methods. Results: The RID-MyC assay exhibited a detection limit ranging from 13.3 to 16.6 genomic copies across 4 common fungal species. In patients with microbial keratitis, the RID-MyC assay showed substantial agreement with microscopy (kappa = 0.714) and fair agreement with culture (kappa = 0.399). The assay demonstrated a sensitivity of 93.27% (95% confidence interval [CI], 86.62%-97.25%) and a specificity of 89.47% (95% CI, 66.86%-98.70%) for FK diagnosis, with a median diagnostic time of 50 minutes (range, 35-124 minutes). Conclusions: The RID-MyC assay, utilizing CRISPR-Cas12a technology, offers high diagnostic accuracy for FK. Its potential for point-of-care use could expedite and enhance the precision of fungal diagnostics, presenting a promising solution to current diagnostic challenges. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Challenges to Implementing a Vaccine for Coccidioidomycosis.

A vaccine for coccidioidomycosis is likely to undergo trials in the near future. In this paper, we raise 4 questions that should be answered before its use and offer our solutions to these questions. These include defining the goals of vaccination, determining who should be vaccinated, how to measure vaccine immunity and protection, and how to address vaccine hesitancy and denial.