Invasive fungal disease in the immunocompromised host: changing epidemiology, new antifungal therapies and management challenges.

BACKGROUND: Invasive fungal disease (IFD) causes morbidity and mortality in immunocompromised hosts (ICH). Based on increasing recognition of the impact of IFD on human disease, a recent WHO priority list identified key areas of need. OBJECTIVES: This review examines changes in epidemiology of IFD, in particular emergence of antifungal resistant pathogens and current availability of rapid diagnostic tests and antifungal treatment options. SOURCES: Literature between 2000 and January 2024 regarding fungal epidemiology, diagnostic test, antifungal resistance, emerging fungal pathogens and novel antifungal agents in both adult and pediatric immunocompromised hosts (ICH) was reviewed. CONTENT: We describe the changing epidemiology and continued burden and mortality of IFD in ICH. Further we discuss the emergence of antifungal resistant organisms driven by new immunosuppressed populations, climate change and antifungal exposure in the individual and environment. We highlight novel antifungal agents and how they will address current unmet needs. IMPLICATIONS: The changing epidemiology and increased population at risk for IFD, lack of recognition of or quantification of risks for IFD with new therapies, current gaps in the availability of rapid diagnostic tests and the imminent availability of novel antifungals with distinct spectra of activity argue for improved availability of and access to rapid diagnostics, antifungal stewardship programs and global of access to antifungal agents.

Utilizing High-Resolution Imaging and Artificial Intelligence for Accurate Leaf Wetness Detection for the Strawberry Advisory System (SAS).

In strawberry cultivation, precise disease management is crucial for maximizing yields and reducing unnecessary fungicide use. Traditional methods for measuring leaf wetness duration (LWD), a critical factor in assessing the risk of fungal diseases such as botrytis fruit rot and anthracnose, have been reliant on sensors with known limitations in accuracy and reliability and difficulties with calibrating. To overcome these limitations, this study introduced an innovative algorithm for leaf wetness detection systems employing high-resolution imaging and deep learning technologies, including convolutional neural networks (CNNs). Implemented at the University of Florida's Plant Science Research and Education Unit (PSREU) in Citra, FL, USA, and expanded to three additional locations across Florida, USA, the system captured and analyzed images of a reference plate to accurately determine the wetness and, consequently, the LWD. The comparison of system outputs with manual observations across diverse environmental conditions demonstrated the enhanced accuracy and reliability of the artificial intelligence-driven approach. By integrating this system into the Strawberry Advisory System (SAS), this study provided an efficient solution to improve disease risk assessment and fungicide application strategies, promising significant economic benefits and sustainability advances in strawberry production.

Fungicide-Loaded Liposomes for the Treatment of Fungal Diseases in Agriculture: An Assessment of Botrytis cinerea.

In this work, liposomes loaded with the fungicide, Fludioxonil (FLUD), for the containment of fungal diseases in agriculture were developed. Three types of vesicles with different compositions were compared: (I) plain vesicles, composed of soy phosphatidylcholine and cholesterol; (II) PEG-coated vesicles, with an additional polyethylene glycol coating; and (III) cationic vesicles, containing didodecyldimethylammonium bromide. Nanometric-sized vesicles were obtained both by the micelle-to-vesicle transition method and by the extrusion technique, and encapsulation efficiency, drug loading content, and Zeta potential were determined for all the samples. The extruded and PEGylated liposomes were the most stable over time and together with the cationic ones showed a significant prolonged FLUD release capacity. The liposomes' biological activity was evaluated on conidial germination, germ tube elongation and colony radial growth of the ascomycete Botrytis cinerea, a phytopathogenic fungus affecting worldwide many important agricultural crops in the field as well as in the postharvest phase. The extruded and PEGylated liposomes showed greater effectiveness in inhibiting germ tube elongation and colony radial growth of the fungal pathogen, even at 0.01 µg·mL-1, the lowest concentration assessed.

Farmers' perceptions and management of citrus fungal diseases in Benin.

Background and aim: Citrus production represents an important activity for the national economy and a source of income for farmers in Benin. However, fungal diseases are a major constraint to production intensification. The aim of this study is to assess farmers' perceptions on citrus fungal diseases in production areas in Benin. Methods: A survey was conducted among 417 farmers between July and December 2021 in four major citrus-producing agro-ecological zones (zones V, VI, VII and VIII) to collect their perceptions, knowledge and management practices of citrus fungal diseases. Results: Farmers reported that fungal diseases are one of the main constraints to citrus production, including black spot, anthracnose, brown rot, sooty mold and fruit rot. Among them, black spot disease is the most severe, causing damage to production. According to farmers, symptoms appear on fruit after fruit set, with a very remarkable presence and high incidence at maturity. Although farmers are most of times aware of the damage caused by fungal diseases with adverse consequences on their income, they have a poor knowledge of appropriate phytosanitary products to manage these diseases. Indeed, the majority of farmers (>60 %) use chemical insecticides, which they reported to be ineffective against citrus fungal diseases. Although chemical insecticides are their only recourse, almost 40 % use nothing to control these diseases. Farmers stated that climatic variability is a factor favoring the development of diseases, leading to reduced production. Conclusions: Among the several citrus fungal diseases, black spot is perceived as the most damaging, causing greater yield losses under favorable conditions, coupled with an almost total absence of appropriate control methods. This study contributes to the reorganization of the citrus industry and to decision-making on capacity building for farmers in terms of orchard pest protection, in order to guarantee better production of marketable and exportable fruit.

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.

Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans.

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.

Optimizing Antifungal Treatment Strategies to Prevent Invasive Pulmonary Aspergillosis Infection-Related Deaths in Intensive Care Unit Patients: The Need for Standardization of Research Definitions.

The clinical spectrum of invasive pulmonary aspergillosis (IPA) has expanded in recent decades. A large group of patients admitted to intensive care units (ICU) is indeed susceptible to the development of IPA. Although timely diagnosis and antifungal therapy of IPA in this expanding population is crucial to prevent IPA-related deaths, the magnitude of the favorable prognostic impact of antifungal therapy is difficult to measure precisely. In our opinion, the development of standardized research definitions could have favorable implications for further improving our ability both to measure the favorable effect of antifungal treatment and to prevent IPA-related death in ICU patients.

Meeting the Therapeutic Challenges of Emergent and Rare Invasive Fungal Diseases Through Novel Clinical Trial Designs.

Treatments for emerging and rare invasive fungal diseases (IFDs) represent a critical unmet medical need. For IFDs that occur less frequently than invasive aspergillosis, such as mucormycosis, hyalohyphomycosis, and phaeohyphomycosis, randomized controlled clinical trials are impractical and unlikely to meet urgent public health needs. Understanding regulatory approaches for approval of drugs for rare cancers and rare metabolic diseases could help meet the challenges of studying drugs for rare IFDs. A single-arm, controlled clinical trial with a high-quality external control(s), with confirmatory evidence from nonclinical studies, including pharmacokinetic/pharmacodynamic data in predictive animal models of the disease may support findings of effectiveness of new drugs and biologics. Control populations may include historical controls from published literature, patient registries, and/or contemporaneous external control groups. Continuous engagement among clinicians, industrial sponsors, and regulatory agencies to develop consensus on trial design and innovative development pathways for emergent and rare invasive fungal diseases is important.

Validation and identification of promising gene specific markers governing foliar disease resistance in groundnut (Arachis hypogaea L.).

BACKGROUND: Groundnut is vulnerable to the major foliar fungal disease viz., late leaf spot (LLS) and rust in kharif season, which results in severe yield losses. Until now, LLS and rust resistance linked markers were developed based on GPBD 4 as a major donor source and were validated in its derivatives only, which restricted their use in marker assisted selection (MAS) involving other donors. METHODS AND RESULTS: The current study focused to validate LLS and rust resistance linked markers employing advanced breeding lines of F6 generation, derived from nine different crosses involving nine diverse parents, to identify potential markers for marker-assisted breeding of LLS and rust resistance in groundnut. Out of 28-trait linked markers used for validation, 8 were polymorphic (28.57%). Marker-trait association (MTA) and Single Marker Analysis (SMA) revealed that the SSR marker pPGPseq5D05 is significantly associated with both LLS (15.8% PVE) and rust (17.5% PVE) resistance, whereas, the marker IPAHM103 is tightly linked with rust resistance (26.8% PVE) alone. In silico analysis revealed that the marker gene for IPAHM103 is a zinc finger protein and the marker gene for pPGPseq5D05 is an ADP-ribosylation factor GTPase-activating protein. Both these protein products impart resistance or tolerance to biotic stress in crop plants. Two other markers namely, GMLQ975 and pPGPseq13A10 were also found to be associated with LLS resistance explaining MTA up to 60%. CONCLUSION: These gene specific markers will enable us to screen more number of germplasm lines or newly developed lines in MAS schemes for LLS and rust resistance using a wide range of resistant sources.

Endophytic Fungi Inoculation Reduces Ramulosis Severity in Gossypium hirsutum Plants.

Biotic stress in cotton plants caused by the phytopathogenic fungus Colletotrichum gossypii var. cephalosporioides triggers symptoms of ramulosis, a disease characterized by necrotic spots on young leaves, followed by death of the affected branch's apical meristem, plant growth paralysis, and stimulation of lateral bud production. Severe cases of ramulosis can cause up to 85% yield losses in cotton plantations. Currently, this disease is controlled exclusively by using fungicides. However, few studies have focused on biological alternatives for mitigating the effects of contamination by C. gossypii var. cephalosporioides on cotton plants. Thus, the hypothesis raised is that endophytic fungi isolated from an Arecaceae species (Butia purpurascens), endemic to the Cerrado biome, have the potential to reduce physiological damage caused by ramulosis, decreasing its severity in these plants. This hypothesis was tested using plants grown from seeds contaminated with the pathogen and inoculated with strains of Gibberella moniliformis (BP10EF), Hamigera insecticola (BP33EF), Codinaeopsis sp. (BP328EF), G. moniliformis (BP335EF), and Aspergillus sp. (BP340EF). C. gossypii var. cephalosporioides is a leaf pathogen; thus, the evaluations were focused on leaf parameters: gas exchange, chlorophyll a fluorescence, and oxidative metabolism. The hypothesis that inoculation with endophytic strains can mitigate physiological and photochemical damage caused by ramulosis in cotton was confirmed, as the fungi improved plant growth and stomatal index and density, increased net photosynthetic rate (A) and carboxylation efficiency (A/Ci), and decreased photochemical stress (ABS/RC and DI0/RC) and oxidative stress by reducing enzyme activity (CAT, SOD, and APX) and the synthesis of malondialdehyde (MDA). Control plants developed leaves with a low adaxial stomatal index and density to reduce colonization of leaf tissues by C. gossypii var. cephalosporioides due to the absence of fungal antagonism. The Codinaeopsis sp. strain BP328EF can efficiently inhibit C. gossypii var. cephalosporioides in vitro (81.11% relative inhibition), improve gas exchange parameters, reduce photochemical stress of chlorophyll-a, and decrease lipid peroxidation in attacked leaves. Thus, BP328EF should be further evaluated for its potential effect as a biological alternative for enhancing the resistance of G. hirsutum plants and minimizing yield losses caused by C. gossypii var. cephalosporioides.

Cerebral Infectious Opportunistic Lesions in a Patient with Acute Myeloid Leukaemia: The Challenge of Diagnosis and Clinical Management.

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.

Unveiling the menace: a thorough review of potential pandemic fungal disease.

Fungal diseases have emerged as a significant global health threat, with the potential to cause widespread outbreaks and significant morbidity and mortality. Anticipating future pandemic fungal diseases is essential for effective preparedness and response strategies. This comprehensive literature review aims to provide a comprehensive analysis of the existing research on this topic. Through an extensive examination of scholarly articles, this review identifies potential fungal pathogens that have the potential to become pandemics in the future. It explores the factors contributing to the emergence and spread of these fungal diseases, including climate change, globalization, and antimicrobial resistance. The review also discusses the challenges in diagnosing and treating these diseases, including limited access to diagnostic tools and antifungal therapies. Furthermore, it examines the strategies and interventions that can be employed to mitigate the impact of future pandemic fungal diseases, such as improved surveillance systems, public health education, and research advancements. The findings of this literature review contribute to our understanding of the potential risks posed by fungal diseases and provide valuable insights for public health professionals and policymakers in effectively preparing for and responding to future pandemic outbreaks. Overall, this review emphasizes the importance of proactive measures and collaborative efforts to anticipate and mitigate the impact of future pandemic fungal diseases.

Inherited CARD9 Deficiency Due to a Founder Effect in East Asia.

Autosomal recessive CARD9 deficiency can underly deep and superficial fungal diseases. We identified two Japanese patients, suffering from superficial and invasive Candida albicans diseases, carrying biallelic variants of CARD9. Both patients, in addition to another Japanese and two Korean patients who were previously reported, carried the c.820dup CARD9 variant, either in the homozygous (two patients) or heterozygous (three patients) state. The other CARD9 alleles were c.104G > A, c.1534C > T and c.1558del. The c.820dup CARD9 variant has thus been reported, in the homozygous or heterozygous state, in patients originating from China, Japan, or South Korea. The Japanese, Korean, and Chinese patients share a 10 Kb haplotype encompassing the c.820dup CARD9 variant. This variant thus originates from a common ancestor, estimated to have lived less than 4,000 years ago. While phaeohyphomycosis caused by Phialophora spp. was common in the Chinese patients, none of the five patients in our study displayed Phialophora spp.-induced disease. This difference between Chinese and our patients probably results from environmental factors. (161/250).

Resurgence of wheat stem rust infections in western Europe: causes and how to curtail them.

Ten years ago, (black) stem rust - the most damaging of wheat (Triticum aestivum) rusts - re-emerged in western Europe. Disease incidences have since increased in scale and frequency. Here, we investigated the likely underlying causes and used those to propose urgently needed mitigating actions. We report that the first large-scale UK outbreak of the wheat stem rust fungus, Puccinia graminis f. sp. tritici (Pgt), in 2022 may have been caused by timely arrival of airborne urediniospores from southwest Europe. The drive towards later-maturing wheat varieties in the UK may be exacerbating Pgt incidences, which could have disastrous consequences. Indeed, infection assays showed that two UK Pgt isolates from 2022 could infect over 96% of current UK wheat varieties. We determined that the temperature response data in current disease risk simulation models are outdated. Analysis of germination rates for three current UK Pgt isolates showed substantial variation in temperature response functions, suggesting that the accuracy of disease risk simulations would be substantially enhanced by incorporating data from prevailing Pgt isolates. As Pgt incidences continue to accelerate in western Europe, we advocate for urgent action to curtail Pgt losses and help safeguard future wheat production across the region.

Marine-Derived Metabolites Act as Promising Antifungal Agents.

The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, and echinocandins, face increasing resistance from pathogenic fungi. Therefore, there is a pressing need for the development of novel antifungal drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures and pharmacological activities. While numerous compounds exhibiting promising antifungal activity have been identified, a comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we have compiled a summary of antifungal compounds derived from marine organisms, highlighting their diverse mechanisms of action targeting various fungal cellular components, including the cell wall, cell membrane, mitochondria, chromosomes, drug efflux pumps, and several biological processes, including vesicular trafficking and the growth of hyphae and biofilms. This review is helpful for the subsequent development of antifungal drugs due to its summary of the antifungal mechanisms of secondary metabolites from marine organisms.

Antifungal Properties of Bio-AgNPs against D. pinodes and F. avenaceum Infection of Pea (Pisum sativum L.) Seedlings.

Ascochyta blight and Fusarium root rot are the most serious fungal diseases of pea, caused by D. pinodes and F. avenaceum, respectively. Due to the lack of fully resistant cultivars, we proposed the use of biologically synthesized silver nanoparticles (bio-AgNPs) as a novel protecting agent. In this study, we evaluated the antifungal properties and effectiveness of bio-AgNPs, in in vitro (poisoned food technique; resazurin assay) and in vivo (seedlings infection) experiments, against D. pinodes and F. avenaceum. Moreover, the effects of diseases on changes in the seedlings' metabolic profiles were analyzed. The MIC for spores of both fungi was 125 mg/L, and bio-AgNPs at 200 mg/L most effectively inhibited the mycelium growth of D. pinodes and F. avenaceum (by 45 and 26%, respectively, measured on the 14th day of incubation). The treatment of seedlings with bio-AgNPs or fungicides before inoculation prevented the development of infection. Bio-AgNPs at concentrations of 200 mg/L for D. pinodes and 100 mg/L for F. avenaceum effectively inhibited infections' spread. The comparison of changes in polar metabolites' profiles revealed disturbances in carbon and nitrogen metabolism in pea seedlings by both pathogenic fungi. The involvement of bio-AgNPs in the mobilization of plant metabolism in response to fungal infection is also discussed.

Integrated Management of Pathogens and Microbes in Cannabis sativa L. (Cannabis) under Greenhouse Conditions.

The increased cultivation of high THC-containing Cannabis sativa L. (cannabis), particularly in greenhouses, has resulted in a greater incidence of diseases and molds that can negatively affect the growth and quality of the crop. Among them, the most important diseases are root rots (Fusarium and Pythium spp.), bud rot (Botrytis cinerea), powdery mildew (Golovinomyces ambrosiae), cannabis stunt disease (caused by hop latent viroid), and a range of microbes that reduce post-harvest quality. An integrated management approach to reduce the impact of these diseases/microbes requires combining different approaches that target the reproduction, spread, and survival of the associated pathogens, many of which can occur on the same plant simultaneously. These approaches will be discussed in the context of developing an integrated plan to manage the important pathogens of greenhouse-grown cannabis at different stages of plant development. These stages include the maintenance of stock plants, propagation through cuttings, vegetative growth of plants, and flowering. The cultivation of cannabis genotypes with tolerance or resistance to various pathogens is a very important approach, as well as the maintenance of pathogen-free stock plants. When combined with cultural approaches (sanitation, management of irrigation, and monitoring for diseases) and environmental approaches (greenhouse climate modification), a significant reduction in pathogen development and spread can be achieved. The use of preventive applications of microbial biological control agents and reduced-risk biorational products can also reduce disease development at all stages of production in jurisdictions where they are registered for use. The combined use of promising strategies for integrated disease management in cannabis plants during greenhouse production will be reviewed. Future areas for research are identified.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Itraconazole in human medicine and veterinary practice.

Diagnosis and management of fungal infections are challenging in both animals and humans, especially in immunologically weakened hosts. Due to its broad spectrum and safety profile when compared to other antifungals, itraconazole (ITZ) has been widely used in the treatment and prophylaxis of fungal infections, both in human and veterinary medicine. The dose and duration of management depend on factors such as the type of fungal pathogen, the site of infection, sensitivity to ITZ, chronic stages of the disease, the health status of the hosts, pharmacological interactions with other medications and the therapeutic protocol used. In veterinary practice, ITZ doses generally vary between 3 mg/kg and 50 mg/kg, once or twice a day. In humans, doses usually vary between 100 and 400 mg/day. As human and veterinary fungal infections are increasingly associated, and ITZ is one of the main medications used, this review addresses relevant aspects related to the use of this drug in both clinics, including case reports and different clinical aspects available in the literature.

Fungal Species Causing Canker and Wilt of Ficus carica and Evidence of Their Association by Bark Beetles in Italy.

Field surveys conducted during 2021 and 2022 in Western Sicily, Italy, revealed the presence of common fig trees severely affected by trunk and crown root canker and bark cracking. Moreover, in conjunction with the symptomatic tissues, the same surveyed plants showed the presence of bark beetle holes and internal wood galleries. The predominant beetle Criphalus dilutus was previously reported attacking figs in Sicily. Phylogenetic analyses based on multilocus DNA data showed the presence of different fungal taxa associated with disease symptoms, including Botryosphaeria dothidea, Ceratocystis ficicola, Diaporthe foeniculina, Neocosmospora bostrycoides, N. perseae, and Neofusicoccum luteum. Pathogenicity tests conducted on potted fig plants showed that all the species were pathogenic to fig, with C. ficicola and Neocosmospora spp. as the most aggressive fungal species. Moreover, isolations conducted from the bodies of emerging adult insects recovered from disease samples confirmed the presence of C. ficicola and Neocosmospora spp., suggesting the potential involvement of C. dilutus in their dissemination.