Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Identification of locally isolated entomopathogenic Fusarium species from the soil of Changa Manga Forest, Pakistan and evaluation of their larvicidal efficacy against Aedes aegypti / Identificação de espécies de Fusarium entomopatogênicas localmente isoladas do solo da Floresta de Changa Manga, Paquistão e avaliação de sua eficácia larvicida contra Aedes aegypti

Dengue fever vectored by the mosquito Aedes aegypti is one of the most rapidly spreading insect-borne diseases. Current reliance of dengue vector control is mostly on chemical insecticides. Growing insecticide resistance in the primary mosquito vector, Aedes aegypti, limits the effectiveness of vector control through chemical insecticides. These chemical insecticides also have negative environmental impacts on animals, plants and human health. Myco-biocontrol agents are naturally occurring organisms and are found to be less damaging to the environment as compared to chemical insecticides. In the present study, entomopathogenic potential of local strains of fungi isolated from soil was assessed for the control of dengue vector. Local fungal isolates presents better alternative to introducing a foreign biocontrol strain, as they may be better adapted to environmental conditions of the area to survive and may have more entomopathogenic efficacy against target organism. Larvicidal efficacy of Fusarium equiseti and Fusarium proliferatum was evaluated against Aedes aegypti. Local strains of F. equiseti (MK371718) and F. proliferatum (MK371715) were isolated from the soil of Changa Manga Forest, Pakistan by using insect bait method. Larvicidal activity of two Fusarium spp. was tested against forth instar larvae of A. aegypti in the laboratory, using concentrations 105, 106, 107 and 108 conidia /ml. LC50 values for F. equiseti after 24h, 48h, 72h and 96h of exposure were recorded as 3.8x108, 2.9x107, 2.0x107, and 7.1x106 conidia /ml respectively while LC50 values for F. proliferatum were recorded as 1.21x108, 9.6x107, 4.2x107, 2.6x107 conidia /ml respectively after 24h, 48h, 72h and 96h of exposure. The results indicate that among two fungal strains F. equiseti was found to be more effective in terms of its larvicidal activity than F. proliferatum against larvae of A. aegypti.

A dengue transmitida pelo mosquito Aedes aegypti é uma das doenças transmitidas por insetos de propagação mais rápida. A dependência atual do controle do vetor da dengue é principalmente de inseticidas químicos. O aumento da resistência a inseticidas no principal vetor do mosquito, Aedes aegypti, limita a eficácia do controle do vetor por meio de inseticidas químicos. Esses inseticidas químicos também têm impactos ambientais negativos sobre os animais, plantas e saúde humana. Os agentes de micobiocontrole são organismos que ocorrem naturalmente e são menos prejudiciais ao meio ambiente em comparação com os inseticidas químicos. No presente estudo, avaliou se o potencial entomopatogênico de cepas locais de fungos isolados do solo para o controle do vetor da dengue. Isolados de fungos locais apresentam melhor alternativa para a introdução de uma cepa de biocontrole estrangeira, pois podem ser mais bem adaptados às condições ambientais da área para sobreviver e podem ter maior eficácia entomopatogênica contra o organismo-alvo. A eficácia larvicida de Fusarium equiseti e Fusarium proliferatum foi avaliada contra Aedes aegypti. Cepas locais de F. equiseti (MK371718) e F. proliferatum (MK371715) foram isoladas do solo de Changa Manga Forest, Paquistão, usando o método de isca para insetos. Atividade larvicida de dois Fusarium spp. foi testado contra larvas de quarto ínstar de A. aegypti em laboratório, nas concentrações 105, 106, 107 e 108 conídios / ml. Os valores de LC50 para F. equiseti após 24 h, 48 h, 72 h e 96 h de exposição foram registrados como 3,8x 108, 2,9x107, 2,0x107 e 7,1x106 conídios / ml, respectivamente, enquanto os valores de LC50 para F. proliferatum foram registrados como 1,21x108, 9,6 x107, 4,2x107, 2,6x107 conídios / ml, respectivamente, após 24 h, 48 h, 72 h e 96 h de exposição. Os resultados indicam que entre duas cepas de fungos F. equiseti se mostrou mais eficaz em termos de atividade [...].

Results From the German Fungal Keratitis Registry: Significant Differences Between Cases With and Without a History of Contact Lens Use.

PURPOSE: Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome. METHODS: Data from 173 cases reported in the German FK registry until August 2019 were evaluated regarding CL behavior, other ophthalmological and general risk factors, age, sex, identified pathogens, conservative and surgical therapy, visual acuity, and findings at admission and follow-up. RESULTS: One hundred seventy-four eyes from 173 patients between 2000 and 2019 were included [64.4% women, median age 54 (39; 72) years]; 49.7% wore CL, of which 81.3% were soft CL, and 50.3% had no history of contact lens use (NCL). CL users were significantly more often women and otherwise healthy (CL: 80.2% vs. NCL: 48.9%; P < 0.0001). The spectrum of pathogens among CL users showed a significantly higher proportion of infections with filamentous pathogens, in particular Fusarium sp. (total filament: CL 69.8% vs. NCL 27.3%; P = 0.0001; Fusarium sp.: CL 50.0% vs. NCL 14.8%; P < 0.0001). Overall, 54.6% required keratoplasty and 8.6% enucleation. CONCLUSIONS: CLS are the most important risk factor for FK in Germany. With CLs, typically, the infection is caused by molds, and patients are comparably younger and otherwise healthy. Often, extensive surgery is needed. To evaluate changes in the pathogen and resistance spectrum and to further monitor possible CL-related risk factors, a consistent collection of data remains paramount.

fuPCR as diagnostic method for the detection of rare fungal pathogens, such as Trichosporon, Cryptococcus and Fusarium.

Fungal respiratory tract colonization is a common finding in patients with hematologic neoplasms due to immunosuppression inherent in the diseases and exacerbated by therapy. This greatly increases the risk of fungal infections of the lungs, which is associated with significant mortality. Therefore, reliable diagnostic methods with rapidly available results are needed to administer adequate antifungal therapy. We have established an improved method for fungal DNA extraction and amplification that allows simultaneous detection of fungal families based on a set of multiplexed real-time PCR reactions (fuPCR). We analyzed respiratory rinses and blood of 94 patients with hematological systemic diseases by fuPCR and compared it with the results of culture and serological diagnostic methods. 40 healthy subjects served as controls. Regarding Candida species, the highest prevalence resulted from microbiological culture of respiratory rinses and from detection of antibodies in blood serum in patients (61 and 47%, respectively) and in the control group (29 and 51%, respectively). Detection of other pathogenic yeasts, such as Cryptococcus and Trichosporon, and molds, such as Fusarium, was only possible in patients by fuPCR from both respiratory rinses and whole blood and serum. These fungal species were found statistically significantly more frequent in respiratory rinses collected from patients after myeloablative therapy for stem cell transplantation compared to samples collected before treatment (P < 0.05i). The results show that fuPCR is a valuable complement to culturing and its inclusion in routine mycological diagnostics might be helpful for early detection of pathophysiologically relevant respiratory colonization for patients with hematologic neoplasms.

We validated a set of PCR reactions (fuPCR) for use in routine diagnostic. In contrast to culture and serological methods, only by fuPCR pathogenic yeasts (Cryptococcus and Trichosporon) and molds (Aspergillus and Fusarium) were detected in respiratory rinses and blood of hematological patients.

A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation.

A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia.

Fungal keratitis management in a referral cornea center in Brazil / Manejo de ceratites fúngicas em centro de referência no Brasil

Abstract Purpose: To report etiological diagnosis, predisposing risk factors, therapeutic strategies and visual outcome of patients treated at the Department of Ophthalmology of Federal University of São Paulo. Methods: This is a retrospective, descriptive, and observational study from medical and laboratory records of the Department of Ophthalmology of Federal University of São Paulo, including all patients with culture proven fungal keratitis in 5 years, from October 2012 through October 2017. Results: There were 2260 fungi microbiologic test requests. Of these, 140 samples had positive cultures for fungi and sixty-six patients were followed at our clinic. Forty-five patients (68.2%) were men, and the mean age was 48.06 (±17.39) years. Fusarium spp. was the most frequently isolated fungus (32 cases; 48.5%), followed by Candida parapsilosis (12 cases; 18.2%). Thirty-four patients (51.5%) underwent intracameral injection of amphotericin B (5 µg per 0.1 ml). In 11 patients (32.3%), infection was eradicated after intracameral amphotericin B associated to topical antifungal treatment and, in 23 patients (67.7%), therapeutic keratoplasty was needed. No complication related to intracameral amphotericin B injection was observed in this series. Forty-three patients (65.1%) ended up with therapeutic keratoplasty. Three patients (4.5%) evolved to evisceration or enucleation. At the last follow-up visit, 53 patients (80.3%) had visual acuity worse than 20/200. Conclusion: Despite current antifungals drugs and distinct administration strategies, fungal keratitis remains challenging. Delayed antifungal therapy may explain poor clinical outcomes. Intracameral amphotericin B associated to topical antfungal treatment seems to be a safe and helpful alternative for non-responsive fungal keratitis. But it is important to formulate other treatment strategies, hence to improve patients' outcomes, since most patients ended-up with significant visual impairment even after current treatment.

Resumo Objetivo: Descrever diagnósticos etiológicos, fatores de risco, estratégias terapêuticas e resultados visuais de pacientes com ceratite fúngica tratados no Departamento de Oftalmologia da Universidade Federal de São Paulo. Métodos: Trata-se de um estudo retrospectivo, descritivo e observacional, a partir da análise de prontuários médicos e laboratoriais do Departamento de Oftalmologia da Universidade Federal de São Paulo, incluindo todos os pacientes com ceratite fúngica comprovada por cultura no período de outubro de 2012 a outubro de 2017. Resultados: Foram realizadas 2260 solicitações de testes microbiológicos. Destas, 140 amostras apresentaram culturas positivas para fungos, e 66 pacientes foram acompanhados em nosso serviço. Quarenta e cinco pacientes (68,2%) eram do sexo masculino, e a média de idade foi de 48,06 (± 17,39) anos. Fusarium spp. foi o fungo mais freqüentemente isolado (32 casos; 48,5%), seguido por Candida parapsilosis (12 casos; 18,2%). Trinta e quatro pacientes (51,5%) foram submetidos à injeção intracameral de anfotericina B (5 µg por 0,1 ml). Destes, 11 pacientes (32,3%) tiveram a infecção erradicada. Nos outros 23 pacientes (67,7%), o transplante terapêutico foi necessário. Nenhuma complicação relacionada à injeção intracameral de anfotericina B foi observada neste estudo. No total, 43 pacientes (65,1%) evoluíram para transplante terapêutico, e 3 pacientes (4,5%) foram submetidos à evisceração ou enucleação. Cinquenta e três pacientes (80,3%) apresentaram acuidade visual final pior que 20/200. Conclusões: Apesar dos diversos medicamentos antifúngicos atuais e vias de administração, o tratamento das ceratites fúngicas permanece desafiador. O atraso no início do tratamento adequado pode justificar o desfecho clínico desfavorável de grande parte dos pacientes. A injeção intracameral de anfotericina B mostrou-se uma alternativa terapêutica segura para ceratites fúngicas refratárias. Mas outras estratégias de tratamento devem ser formuladas, visando melhorar os resultados visuais dos pacientes.

Fusarium infection alters the m6A-modified transcript landscape in the cornea.

N6-methyladenosine (m6A) is the most common post-transcriptional modification of RNA in eukaryotes that regulates the post-transcriptional expression level of genes without changing the base sequence. The role of m6A in fungal keratitis has not yet been elucidated. Here, we aimed to identify m6A modification changes and their potential roles in fungal keratitis. The murine model of fungal keratitis was established by inoculating mice with Fusarium solani (F. solani). The overall m6A level was detected via an m6A RNA methylation assay kit. The expression levels of key m6A modification-related genes were estimated by quantitative real-time polymerase chain reaction (PCR). The expression and localization of METTL (methyltransferase like)3, the key component of the m6A methyltransferase complex, was determined by immunostaining and Western blotting (WB). Immunoprecipitation methylation microarray was used to describe the changes in m6A modification in F. solani-infected corneal tissue. The overall m6A level in corneal tissue on the 5th day in the F. solani-treated group was upregulated compared with that in the control group. The demethylase levels were unaltered, but the level of the methylase METTL3 was increased significantly after fungal infection. Additionally, differences were found in m6A modifications in 1137 mRNAs, of which 780 were hypermethylated and 357 were hypomethylated. To the best of our knowledge, the present work is the first investigation on the m6A modification profiles in experimental fungal keratitis, and it may provide a potential therapeutic target.

Breakthrough invasive fungal infections: Who is at risk?

The epidemiology of invasive fungal infections (IFIs) in immunocompromised individuals has changed over the last few decades, partially due to the increased use of antifungal agents to prevent IFIs. Although this strategy has resulted in an overall reduction in IFIs, a subset of patients develop breakthrough IFIs with substantial morbidity and mortality in this population. Here, we review the most significant risk factors for breakthrough IFIs in haematology patients, solid organ transplant recipients, and patients in the intensive care unit, focusing particularly on host factors, and highlight areas that require future investigation.

A Rare Case of Fungal Burn Wound Infection Caused by Fusarium solani in Vietnam.

A patient with extensive burn injuries was admitted to the National Hospital of Burns in Hanoi, Vietnam, and diagnosed with fungal wound infection by histological examination of skin biopsy samples. Fusarium solani was isolated and identified by analysis of its morphological features and the sequence of the internal transcribed spacer region. The isolation showed in vitro resistant to fluconazole, voriconazole, itraconazole, amphotericin B, and caspofungin. Invasive fusariosis is difficult to treat due to its angioinvasive property and its lacking amenability to treatment with antifungal drugs. This infection is rare and has not been reported so far in Vietnam.

Pearl millet populations characterized by Fusarium prevalence, morphological traits, phenolic content, and antioxidant potential.

BACKGROUND: Pearl millet (Pennisetum glaucum L.) has become increasingly attractive due to its health benefits. It is grown as food for human consumption and fodder for livestock in Africa and Asia. This study focused on five pearl millet populations from different agro-ecological zones from Tunisia, and on characterization by morphological traits, total phenolic and flavonoid content, antioxidant activity, and occurrence of Fusarium. RESULTS: Analysis of variance revealed highly significant differences between populations for the quantitative traits. The highest grain weights occurred in the pearl millet cultivated in Zaafrana and Gergis of Tunisia. Early flowering and early maturing populations cultivated in the center (Zaafrana, Rejiche) and south (Gergis) of Tunisia tended to have a higher grain yield. The Zaafrana population showed the highest value of green fodder potentiel (number and weight of leaves/cultivar and the weight of tillers and total plant/cultivar) followed by Gergis and Rejiche. The Kelibia population showed the highest total phenolic and flavonoid content. Rejiche exhibited the greatest antioxidant activity. Trans-cinnamic, protocatechuic, and hydroxybenzoic acids were the major phenolic compounds in all the extracts. Three Fusarium species were identified in Tunisian pearl millet populations based on morphologic and molecular characterization. Fusarium graminearum and Fusarium culmorum occurred most frequently. The average incidence of the three Fusarium species was relatively low (<5%) in all populations. The lowest infection rate (0.1%) was recorded in the samples from Zaafrana. CONCLUSION: Chemometric analysis confirmed the usefulness of the above traits for discrimination of pearl millet populations, where a considerable variation according to geographical origin and bioclimatic conditions was observed. © 2020 Society of Chemical Industry.

Non-Aspergillus invasive mould infections in patients treated with ibrutinib.

BACKGROUND: Invasive mould infections (IMIs) are very rare in patients with lymphoid malignancies. However, IMIs, mostly due to Aspergillus species, have been increasingly reported in such patients receiving ibrutinib (IBR). There is paucity of information regarding non-Aspergillus invasive mould infections (NAIMIs) in this setting, OBJECTIVES: To review our recent experience and the published literature on the topic. PATIENTS/METHODS: We present a case of invasive sinusitis caused by Fusarium in a patient with refractory chronic lymphocytic leukaemia (CLL) who was treated with IBR and review the 12 published cases of NAIMIs during IBR. RESULTS: Nearly all cases of NAIMIs in the setting of IBR use were encountered in patients with CLL. Mixed fungal infections, brain involvement and late-onset infections were common. CONCLUSIONS: Although rare, NAIMIs should be considered in patients who receive IBR.

[A clinical analysis of 1 414 cases of fungal keratitis].

Objective: To discuss clinical features and treatments of fungal keratitis, and to provide statistical data for clinical therapy and increase the therapeutic effects. Methods: This is a retrospective case series study. An analysis was performed by collecting patients' demography features, risk factors, onset time, lab results, clinical features and treatment from 1 414 cases of fungal keratitis from January 2006 to October 2016 in Qingdao Eye Hospital, Shandong Eye Institute. Results: In the 1 414 cases (1 414 patients), 1 174 patients (83.0%) came from different areas in Shandong Province, and the rest mainly from provinces on the north of Yangtze River. The age was 40 to 60 years in 874 cases (61.4%). The onset time was often in autumn and winter. The average duration between the onset and treatment was 1 to 74 days; 942 patients (67.1%) visited our hospital in 8-30 days after the appearance of the symptoms. Corneal trauma was the most common risk factor, especially injury by plants (367 cases, 26.4%). The positive rate of direct microscopic examination of potassium hydroxide wet mounts was 96.4%. The positive rate of confocal microscopy was 89.8%. Fungi were detected in corneal ulcer scrapings and (or) diseased corneal tissues obtained during surgery from 973 patients (68.8%). Most of the fungi were Fusarium (595 cases, 61.1%), followed by Alternaria (184 cases, 18.9%) and Aspergillus (119 cases, 12.2%). There were 603 cases (42.7%) of superficial and middle stromal infiltration, 614 cases (43.4%) of deep stromal infiltration and 197 cases (13.9%) of full-thickness corneal infiltration. Diameters of the corneal ulcer lesion were mostly between 4 and 6 mm (725 cases, 51.6%), followed by<3 mm (372 cases, 26.4%) and>6 mm (302 cases, 22.0%). Hypopyon was combined in 498 cases (35.2%), corneal perforation in 34 cases (2.4%), and endophthalmitis in 58 cases (4.1%). Surgery was performed in 1 198 cases (84.8%), including penetrating keratoplasty in 416 cases (29.4%), lamellar keratoplasty in 199 cases (14.1%), and corneal ulcer debridement in 532 cases (37.6%), with an effective rate of 98.1% (408 cases), 97.0% (193 cases) and 92.8% (494 cases), respectively. Two hundred and fifteen cases (15.2%) were treated with medical therapy alone, of which 147 cases (68.4%) were cured. Fifty-six patients (3.9%) finally lost their eye balls, including 54 cases of evisceration and 2 cases of ophthalmectomy. Conclusions: Fusarium is the main causative agent of fungal keratitis in Shandong Province. Direct microscopic examination of potassium hydroxide wet mounts is a simple, rapid and effective test method. Early diagnosis can be made if the result of corneal ulcer scraping examination is positive. Antifungal drug treatments can be done in early onset time. If the drug efficacy is poor or the patient's condition gets worse, immediate surgery is the key to controlling fungal keratitis. (Chin J Ophthalmol, 2020, 56:286-293).

Construction of Raman spectroscopic fingerprints for the detection of Fusarium wilt of banana in Taiwan.

Banana (Musa sp.) is cultivated worldwide and is one of the most popular fruits. The soil-borne fungal disease Fusarium wilt of banana (FWB), commonly known as Panama disease, is caused by Fusarium oxysporum f. sp. cubense (Foc) and is a highly lethal vascular fungal disease in banana plants. Raman spectroscopy, an emerging laser-based technology based on Raman scattering, has been used for the qualitative characterization of biological tissues such as foodborne pathogens, cancer cells, and melamine. In this study, we describe a Raman spectroscopic technique that could potentially be used as a method for diagnosing FWB. To that end, the Raman fingerprints of Foc (including mycelia and conidia) and Foc-infected banana pseudostems with varying levels of symptoms were determined. Our results showed that eight, eleven, and eleven characteristic surface-enhanced Raman spectroscopy peaks were observed in the mycelia, microconidia, and macroconidia of Foc, respectively. In addition, we constructed the Raman spectroscopic fingerprints of banana pseudostem samples with varying levels of symptoms in order to be able to differentiate Foc-infected bananas from healthy bananas. The rate at which FWB was detected in asymptomatic Foc-infected samples by using the spectral method was 76.2%, which was comparable to the rates previously reported for other FWB detection methods based on real-time PCR assays, suggesting that the spectral method described herein could potentially serve as an alternative tool for detecting FWB in fields. As such, we hope that the developed spectral method will open up new possibilities for the on-site diagnosis of FWB.

Clinical Spectrum, Diagnosis and Outcome of Rare Fungal Infections in Patients with Hematological Malignancies: Experience of 15-Year Period from a Single Tertiary Medical Center.

BACKGROUND: Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI). METHODS: We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center. RESULTS: Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis. CONCLUSIONS: Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.