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Clinical and Experimental Allergy :... Jul 2023Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by immune-mediated reactions mounted against Aspergillus fumigatus. The disorder most commonly... (Review)
Review
Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by immune-mediated reactions mounted against Aspergillus fumigatus. The disorder most commonly complicates the course of patients with asthma and cystic fibrosis. From its first description in 1952, significant advances have been made in understanding the pathogenesis and the diagnosis and treatment of ABPA. In the last two decades, most research on ABPA has been published from India. The prevalence and clinical presentation may differ in India from that reported elsewhere. Herein, we review the epidemiology, clinical and radiological characteristics, and distinctive features of ABPA in the Indian subcontinent. To support the review, we surveyed pulmonologists nationwide to understand the challenges in diagnosing and managing ABPA. The survey has yielded valuable insights into the practices associated with the diagnosis and management of ABPA in India.
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Asthma; Aspergillus fumigatus; Cystic Fibrosis; India
PubMed: 37062874
DOI: 10.1111/cea.14319 -
Advanced Drug Delivery Reviews Jul 2023The growing occurrence of invasive fungal infections and the mounting rates of drug resistance constitute a significant menace to human health. Antifungal drug... (Review)
Review
The growing occurrence of invasive fungal infections and the mounting rates of drug resistance constitute a significant menace to human health. Antifungal drug combinations have garnered substantial interest for their potential to improve therapeutic efficacy, reduce drug doses, reverse, or ameliorate drug resistance. A thorough understanding of the molecular mechanisms underlying antifungal drug resistance and drug combination is key to developing new drug combinations. Here we discuss the mechanisms of antifungal drug resistance and elucidate how to discover potent drug combinations to surmount resistance. We also examine the challenges encountered in developing such combinations and discuss prospects, including advanced drug delivery strategies.
Topics: Humans; Antifungal Agents; Mycoses; Drug Combinations; Drug Resistance, Fungal
PubMed: 37211279
DOI: 10.1016/j.addr.2023.114874 -
Nature Communications Sep 2023The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways. While much is known about the role played by downstream...
The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways. While much is known about the role played by downstream metabolites of each pathways in intestinal homeostasis, their role in lung immune homeostasis is underappreciated. Here we have examined the role played by the Trp hydroxylase/5-hydroxytryptamine (5-HT) pathway in calibrating host and microbial Trp metabolism during Aspergillus fumigatus pneumonia. We found that 5-HT produced by mast cells essentially contributed to pathogen clearance and immune homeostasis in infection by promoting the host protective indoleamine-2,3-dioxygenase 1/kynurenine pathway and limiting the microbial activation of the indole/aryl hydrocarbon receptor pathway. This occurred via regulation of lung and intestinal microbiota and signaling pathways. 5-HT was deficient in the sputa of patients with Cystic fibrosis, while 5-HT supplementation restored the dysregulated Trp partitioning in murine disease. These findings suggest that 5-HT, by bridging host-microbiota Trp partitioning, may have clinical effects beyond its mood regulatory function in respiratory pathologies with an inflammatory component.
Topics: Humans; Animals; Mice; Tryptophan; Serotonin; Pneumonia; Mycoses; Microbiota; Aspergillosis; Influenza, Human
PubMed: 37717018
DOI: 10.1038/s41467-023-41536-8 -
Current Opinion in Microbiology Dec 2023Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised.... (Review)
Review
Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.
Topics: Humans; Antifungal Agents; Mycoses; Histoplasmosis; Coccidioidomycosis; Cryptococcosis; Central Nervous System Infections
PubMed: 37898052
DOI: 10.1016/j.mib.2023.102397 -
Infectious Disease Clinics of North... Sep 2023Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular... (Review)
Review
Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B).
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections; Drug Resistance, Fungal
PubMed: 37532392
DOI: 10.1016/j.idc.2023.05.001 -
Philosophical Transactions of the Royal... Jul 2023Animal defences against infection involve two distinct but complementary mechanisms: tolerance and resistance. Tolerance measures the animal's ability to limit... (Review)
Review
Animal defences against infection involve two distinct but complementary mechanisms: tolerance and resistance. Tolerance measures the animal's ability to limit detrimental effects from a given infection, whereas resistance is the ability to limit the intensity of that infection. Tolerance is a valuable defence for highly prevalent, persistent or endemic infections where mitigation strategies based on traditional resistance mechanisms are less effective or evolutionarily stable. Selective breeding of amphibians for enhanced tolerance to spp has been suggested as a strategy for mitigating the impacts of the fungal disease, chytridiomycosis. Here, we define infection tolerance and resistance in the context of chytridiomycosis, present evidence for variation in tolerance to chytridiomycosis, and explore epidemiological, ecological and evolutionary implications of tolerance to chytridiomycosis. We found that exposure risk and environmental moderation of infection burdens are major confounders of resistance and tolerance, chytridiomycosis is primarily characterized by variation in constitutive rather than adaptive resistance, tolerance is epidemiologically important in driving pathogen spread and maintenance, heterogeneity of tolerance leads to ecological trade-offs, and natural selection for resistance and tolerance is likely to be dilute. Improving our understanding of infection tolerance broadens our capacity for mitigating the ongoing impacts of emerging infectious diseases such as chytridiomycosis. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.
Topics: Animals; Mycoses; Amphibians; Biological Evolution; Communicable Diseases, Emerging; Immune Tolerance
PubMed: 37305912
DOI: 10.1098/rstb.2022.0133 -
Expert Review of Molecular Diagnostics Mar 2024Over the last years, severe respiratory viral infections, particularly those caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the influenza... (Review)
Review
INTRODUCTION
Over the last years, severe respiratory viral infections, particularly those caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the influenza virus, have emerged as risk factor for viral-associated pulmonary aspergillosis (VAPA) among critically ill patients. Delays in diagnosis of VAPA are associated with increased mortality. Point-of-care-tests may play an important role in earlier diagnosis of VAPA and thus improve patient outcomes.
AREAS COVERED
The following review will give an update on point-of-care tests for VAPA, analyzing performances in respiratory and blood specimens.
EXPERT OPINION
Point-of-care tests have emerged, and particularly the IMMY Aspergillus galactomannan lateral flow assay (LFA) shows performances comparable to the galactomannan ELISA for diagnosis of VAPA. Notably, nearly all evaluations of POC tests for VAPA have been performed in COVID-19 patients, with very limited data in influenza patients. For early diagnosis of COVID associated pulmonary aspergillosis (CAPA), the LFA has shown promising performances in respiratory samples, particularly in bronchoalveolar lavage fluid, and may thereby help in improving patient outcomes. In contrast, serum LFA testing may not be useful for early diagnosis of disease, except in cases with invasive tracheobronchial aspergillosis.
Topics: Humans; Invasive Pulmonary Aspergillosis; Pulmonary Aspergillosis; Aspergillus; Point-of-Care Testing; COVID-19; SARS-CoV-2; Aspergillosis
PubMed: 37688631
DOI: 10.1080/14737159.2023.2257597 -
Dermatitis : Contact, Atopic,... 2024Prayer rituals are an integral part of the daily lives of Muslims worldwide. This comprehensive review aims to explore the common dermatoses associated with prayer among... (Review)
Review
Prayer rituals are an integral part of the daily lives of Muslims worldwide. This comprehensive review aims to explore the common dermatoses associated with prayer among Muslims and provide insights for dermatologists to facilitate accurate diagnosis and reduce unnecessary investigations. A systematic literature search returned 367 published articles, of which 21 met the inclusion criteria. Friction-induced dermatitis was the most frequently reported dermatosis, primarily affecting the forehead, knees, dorsum of the feet, and lateral malleoli. Friction-related marks often present as hyperpigmented lichenified plaques, and are more common in elderly individuals and males. Cases of contact dermatitis and fungal infections were also reported. Allergic contact dermatitis was linked to perfume application before Friday prayers, whereas fungal infections were attributed to increased water retention between toe webs, possibly related to communal ablution and prayer areas. Awareness of these prayer-related dermatoses enables dermatologists to provide holistic care for diverse populations and targeting specific interventions with respect for patients' religious beliefs. For example, Muslim patients with symptomatic frictional dermatoses may benefit from use of padded prayer rugs, especially diabetic patients whose lesions carry an increased risk of progressing to neuropathic ulcers.
Topics: Male; Humans; Aged; Islam; Skin; Hyperpigmentation; Dermatitis, Allergic Contact; Mycoses
PubMed: 37651213
DOI: 10.1089/derm.2023.0191 -
Clinical Medicine (London, England) Jan 2024While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to... (Review)
Review
While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to considerable delay to appropriate treatment. Clinical suspicion must be present for respiratory disease, particularly in the immunocompromised or in those not responding to empiric treatment approaches, and an extended travel history should be obtained. This article summarises the epidemiology of PEM, key clinical features, diagnostic strategies and management.
Topics: Humans; Immunocompromised Host; Mycoses; Lung Diseases, Fungal
PubMed: 38382182
DOI: 10.1016/j.clinme.2024.100014 -
Seminars in Respiratory and Critical... Feb 2024Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of The broad spectrum of... (Review)
Review
Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of The broad spectrum of pathological manifestations associated with pulmonary aspergillosis necessitates a differentiation of commensalism from saprophytic colonization, hypersensitivity reactions, and true invasive infections, which highlights the importance of histopathology as a gold standard in a diagnostic setting. For the past decades, changes in terminology and contradicting contributions from different diagnostic disciplines have made the classification of pulmonary aspergillosis rather confusing. This review offers a categorization of aspergillosis lesions based on what can be histopathologically identified and distinguished, differentiating between acute invasive infection and forms of subacute, chronic, and allergic diseases and coinfections, and summarizes important manifestations of lesions associated with the different forms of pulmonary aspergillosis.
Topics: Humans; Pulmonary Aspergillosis; Aspergillosis; Aspergillus
PubMed: 38266999
DOI: 10.1055/s-0043-1776757