Fungal Mycosis Research Articles

Chronicles of A.I. Pospelov Moscow Society of Dermatovenerologists and Cosmetologists (MSDС was founded on October 4, 1891) Bulletin of the MSDС № 1157

On April 16th we held our last meeting of A.I. Pospelov Moscow Society of Dermatologists and Cosmetologists in person. There were 102 participants and 5 applicants. Our agenda included two clinical cases: the first one was a clinical case of fulminant acne (Miderm Clinic); the second one was about gangrenous pyoderma as a possible marker or paraneoplasia in intestinal oncological diseases (Sechenov University). We present clinical cases of patients with fulminant acne and periorbital oedema in the first report, and ascending colon tumour and T3N0M0 rectal cancer in the second report. Three reports were presented in the scientific part of the meeting: the effectiveness of therapy for severe psoriasis (Sechenov University), the effectiveness of Janus kinase inhibitors in atopic dermatitis (Sechenov University), the molecular genetic aspects of the fungal mycosis pathogenesis (State Scientific Center of Dermatovenerology and Cosmetology). The authors presented the results of their own clinical studies of the effectiveness of therapy of diseases, including in the report on molecular-genetic aspects of the pathogenesis of mycosis fungoides the author assessed the changes in the expression levels of genes of the JAK-STAT signalling pathway and transcription factors both in visually unaffected skin and in the focus of clinically detectable lesions.

Insect fungal pathogens secrete a cell wall-associated glucanase that acts to help avoid recognition by the host immune system.

Fungal insect pathogens have evolved diverse mechanisms to evade host immune recognition and defense responses. However, identification of fungal factors involved in host immune evasion during cuticular penetration and subsequent hemocoel colonization remains limited. Here, we report that the entomopathogenic fungus Beauveria bassiana expresses an endo-β-1,3-glucanase (BbEng1) that functions in helping cells evade insect immune recognition/ responses. BbEng1 was specifically expressed during infection, in response to host cuticle and hemolymph, and in the presence of osmotic or oxidative stress. BbEng1 was localized to the fungal cell surface/ cell wall, where it acts to remodel the cell wall pathogen associated molecular patterns (PAMPs) that can trigger host defenses, thus facilitating fungal cell evasion of host immune defenses. BbEng1 was secreted where it could bind to fungal cells. Cell wall β-1,3-glucan levels were unchanged in ΔBbEng1 cells derived from in vitro growth media, but was elevated in hyphal bodies, whereas glucan levels were reduced in most cell types derived from the BbEng1 overexpressing strain (BbEng1OE). The BbEng1OE strain proliferated more rapidly in the host hemocoel and displayed higher virulence as compared to the wild type parent. Overexpression of their respective Eng1 homologs or of BbEng1 in the insect fungal pathogens, Metarhizium robertsii and M. acridum also resulted in increased virulence. Our data support a mechanism by which BbEng1 helps the fungal pathogen to evade host immune surveillance by decreasing cell wall glucan PAMPs, promoting successful fungal mycosis.

Effect of nurse-led intervention on knowledge and preventive behavior of diabetic pregnant women regarding COVID-19 associated mucromycosis infection in mid-delta region of Egypt

BackgroundBlack fungus (mycoses) is an opportunistic invasive infection that predominantly occurred among immunosuppressed persons. It has been recently detected in COVID-19 patients. The pregnant diabetic woman is susceptible to such infections and needs recognition for protection. This study aimed to evaluate the effect of the nurse-led intervention on the knowledge and preventive practice of diabetic pregnant women regarding fungal mycosis during the COVID-19 pandemic.MethodThis quasi-experimental study was conducted at maternal health care centers in Shebin El-Kom, Menoufia Governorate, Egypt. The study recruited 73 diabetic pregnant women through a systematic random sampling of pregnant women attending the maternity clinic during the period of the study. A structured interview questionnaire was used to measure their knowledge regarding Mucormycosis and COVID-19 manifestations. The preventive practices were assessed through an observational checklist of hygienic practice, insulin administration, and blood glucose monitoring for the prevention of Mucormycosis infection.ResultsThe study revealed a statistically significant increment in the participants’ knowledge, preventive practice, personal hygiene, and diabetes self-care scores (9.56 ± 1.75 ,3.6 ± 1.18, 3.18 ± 1.29 post-intervention) comparable to (6.19 ± 1.66, 1.97 ± 1.35, 0.89 ± 1.38 pre-intervention) respectively. There was a significant improvement in the overall COVID-19 protective score against Mucormycosis (from 2.66 ± 1.74 to 4.53 ± 1.43).ConclusionNursing educational sessions had a positive effect on pregnant women’s awareness and preventive behavior. Hence, it is recommended to integrate nurse-led intervention targeting the preventive practice against COVID-19-associated Mucormycosis infection (CAM) as routine services for diabetic pregnant women during antenatal care.

SPOROTRICHOSIS IN CHILDREN: A FORGOTTEN ENTITY

Sporotrichosis is regarded as the most common subcutaneous fungal mycosis, which occurs following traumatic inoculation of Sporothrix schenckii complex. Albeit rare, sporotrichosis, also known as 'rose gardener's disease', has been reported to involve children whereby active or passive transmission through a vector such as domestic animals has been identified as the main culprit. Herein, we report sporotrichosis in a pair of siblings who presented to the outpatient Otorhinolaryngology clinic in University Malaya Medical Centre with a lower lips skin lesion and submental swelling after kissing their domestic cat. Sporotrichosis was diagnosed following the fungal culture of the skin scrapings of the lower lip’s pustular lesions. Prompt treatment with oral itraconazole (8 mg/kg/day) for six weeks showed the resolution of symptoms. We highlight the pathophysiology of zoonotic sporotrichosis and the mode of management of this entity. Additionally, the management of sporotrichosis should include the veterinarian's assessment of the infected animal.

Potential of a combination of entomopathogenic fungal strains and a non-ionic surfactant to control the fall armyworm (Spodoptera frugiperda)

• Two entomopathogenic fungi isolates were isolated for controlling fall armyworm. • Mp -NCHU-124 and Bb -NCHU-157 showed dose-dependent effects on the FAW. • The Silwet L-77 rapidly killed FAW and tested for the EPF compatibility. • Combination with Silwet L-77 and EPF increased the mortality of FAW, reduced LT 50. • Combination with Silwet L-77 and EPF increased fungal mycosis of FAW. The fall armyworm, Spodoptera frugiperda , is an emerging invasive pest in Taiwan that feeds on a wide range of crops and causes serious damage. Herein, an entomopathogenic fungal library (EFLib) was constructed to identify potential microbes to control FAW. Twenty-eight indigenous entomopathogenic fungi (EPF) were isolated and investigated for their potential pathogenicity, with Metarhizium pinghaense ( Mp -NCHU-124) and Beauveria bassiana ( Bb -NCHU-157) exerting dose-dependent effects on the 4 th instar FAW larvae. The non-ionic surfactant Silwet L-77 rapidly killed FAW larvae after spraying at a concentration of 300 mg/kg and the toxic effect of Silwet L-77 on FAW larvae was dose-dependent. When the EPF isolates (10 6 conidia/mL) were applied to FAW larvae in combination with the non-ionic surfactant Silwet L-77 (30–90 mg/kg), the mortality rate dramatically increased and the LT 50 reduced, with increased fungal mycosis ( Mp -NCHU-124: 38% to 72% and Bb -NCHU-157: 20 to 62%), indicating the high compatibility of EPF with the non-ionic surfactant. Thus, the Silwet L-77+EPF combined formulation has potential for practical field application for FAW pest control and sustainable agriculture in the future.

Evaluation of the Potential Entomopathogenic Fungi Purpureocillium lilacinum and Fusarium verticillioides for Biological Control of Forcipomyia taiwana (Shiraki).

Forcipomyia taiwana (Diptera: Ceratopogonidae) is a nuisance blood-sucking pest to humans in Taiwan. An F. taiwana bite causes itching and redness and usually causes serious harassment to human outdoor activity. In terms of F. taiwana control, chemical pesticides are ineffective. Therefore, other efforts are needed. Fungal mycosis in the larvae, pupae, and emerging F. taiwana adults was found during the rearing of F. taiwana. In this study, six fungal isolates were isolated from infected cadavers and subjected to molecular identification. In addition, their biocontrol potential was evaluated against different life stages of F. taiwana. Based on the pathogenicity screening, two fungal isolates, NCHU-NPUST-175 and -178, which caused higher mortality on the fourth instar larvae of F. taiwana, were selected for virulence tests against different life stages of F. taiwana larvae. The results of the phylogenetic analysis indicated that the NCHU-NPUST-175 and -178 belonged to Purpureocillium lilacinum and Fusarium verticillioides, respectively. Bioassay against different life stages of F. taiwana with different spore concentrations (5 × 105 to 5 × 107 conidia/mL) revealed a dose-dependent effect on larvae for both fungal isolates, while only 38% and 50% mortality was found in highest concentration (5 × 107 conidia/mL) at fourth instar larvae by Pl-NCHU-NPUST-175 and Fv-NCHU-NPUST-178, respectively. Moreover, reductions in egg-hatching rate and adult emergence rate were found, when the last stage of F. taiwana was inoculated with both fungal isolates, indicating the ovicidal potential and the impact of entomopathogenic fungi on the development of F. taiwana. In conclusion, Pl-NCHU-NPUST-175 and Fv-NCHU-NPUST-178 showed larvicidal activity, ovicidal activity, and impact on adult emergence on F. taiwana.

MicroRNA as a diagnostic marker in cutaneous T-cell lymphomas

BACKGROUND: In recent years, thanks to the development of methods of molecular genetic analysis, microRNA has become one of the promising markers for the diagnosis of many human diseases.
 AIMS: to study microRNA as a new method for the diagnosis of fungal mycosis.
 MATERIALS AND METHODS: The study included 30 patients with histologically confirmed diagnosis of T-cell lymphomas of the skin, 25 were diagnosed with fungal mycosis, 5 ― Cesari syndrome. The control group consisted of 10 patients with benign lymphoproliferative dermatoses. The patients underwent the determination of microRNA 223, 16, 326, 663, 423, 711 in blood plasma. MicroRNA was also detected in plasma in patients with T-cell lymphomas of the skin at early and late stages.
 RESULTS: Statistically significant difference of 223, 16, 326, 711 microRNAs in blood plasma was revealed in patients with fungal mycosis, compared with patients with benign lymphoproliferative dermatoses. Statistically significant difference of 663 microRNA in blood plasma was revealed in patients with T-cell lymphomas of the skin at early and late stages. A statistically significant difference of 223, 711 microRNAs in blood plasma was revealed in patients with fungal mycosis at an early stage compared with patients with benign lymphoproliferative dermatoses.
 CONCLUSION: The determination of microRNA 223, 16, 326, 711 in blood plasma can be used for early diagnosis of T-cell lymphomas of the skin.

Diatomaceous earth low-lethal dose effects on the fitness of entomopathogenic fungus, Beauveria bassiana, against two coleopteran stored product pests

Efficacy of different doses of the Beauveria bassiana-IRAN441C alone (66,125, 250, 500, 1000 mg conidia. Kg−1 grains) and combined with a low-lethal dose (LD25) of diatomaceous earth (DE) SilicoSec® as lethal agents were assessed against the adults of Callosobruchus maculatus (F.) (Chrysomelidae) on mung, and cowpeas, and Oryzaephilus surinamensis (L.) (Silvanidae) on wheat and barley seeds. In both species, mortality reached 60–73% in B. bassiana alone and 83–100% in fungus combined with the DE at the highest dose. A synergistic effect between B. bassiana conidia and the DE was confirmed. The DE low-lethal dose alters fungal mycosis and sporogenesis (conidia mL−1) rates in the infected cadavers. The adult populations of both species were suppressed desirably despite a decrease in the number of cadaver-derived mycosis and their spore production at the highest combination doses (1000 mg kg−1+ LD25 of DE). Seed type had no significant effect on mycosis and sporogenesis on both insects in several combination doses. The cadaver-derived aerial conidia germination rate was increased in the presence of DE low-lethal dose, but it declined by increasing the fungal dose. Type of commodity failed to affect the germination rate of O. surinamensis-derived conidia; however, the mung bean intensified this case for another insect. In both beetles, offspring's emergence was suppressed dose-dependently seven weeks after removing exposed parents to the lethal agents as well it was more in doses mixed with DE. The most significant reduction in progeny production of treated C. maculatus occurred on cowpeas and that of treated O. surinamensis on wheat seeds. Our findings demonstrate that DE's low-lethal dose enhances the virulence of B. bassiana in the various mixtures synergistically, and co-applications of the two substances were feasible. As well, the lethal agents' adverse effects were found to carry over onto both species' offspring during two-month storage time.

Nonspecific skin lesions in malignant lymphomas

Objective: Clinical characteristics of the peculiarities of non-specific skin lesions with patients having malignant lymphomas (ML).Methods: 130 patients having malignant lymphomas were observed, 50 patients – having Hodgkin’s lymphomas, 38 patients - B-cell lymphomas and 42 patients – T-cell lymphomas.Results: Six main types of nonspecific lesions are defined among patients having malignant lymphomas: 1) skin lesions of auto toxic genesis, 2) skin lesions determined with vascular pathology, 3) skin lesions due to hemolysis and hemostatic disorders, 4) skin lesions of those having cryoglobulinemia/cryofibrinogenemia, 5) skin lesions due to metabolic disorder, 6) infectious diseases.Conclusions: Lesions of auto toxic genesis and infectious diseases prevail among nonspecific skin changes when having malignant lymphomas. Patients having Hodgkin’s lymphomas experience dermal itching more often. Among B-cell lymphomas skin lesions are more pathognomonic for chronic lymphocytic leukemia, among T-cell lymphomas – for fungal mycosis. Nonspecific skin lesions, having arisen before typical clinical picture of malignant lymphomas allow to suspect and diagnose the main illness on time. Disappearance of skin lesions against the background of specific therapy can bear evidence to the efficiency of the malignant lymphomas’ treatment.

Multiple primary cancer in Leser — Trelat syndrome (description of a clinical case)

The article provides information about one of the typical paraneoplastic syndromes — Leser — Trelat syndrome, a condition that develops jointly and sometimes precedes the appearance of a malignant visceral tumor. Brief clinical characteristics of Leser — Trelat syndrome are presented. Its predominant development in elderly and senile patients has been outlined, as well as its predominant association with malignant neoplasms of the gastrointestinal tract (47.7 %), lungs, mammary glands, prostate, kidneys, liver, T‑cell lymphomas (fungal mycosis, Sesari syndrome). Possible atypical relationships of Leser — Trelat syndrome with basalioma of the lower eyelid, skin melanoma are disclosed. Cases of fast (several months) and slow (years) formation of this paraneoplastic syndrome with a typical widespread nature of the lesion and a rare focal localization of keratomas are described. A clinical case with typical manifestations of dermatological paraneoplastic syndrome in the form of Leser — Trelat syndrome in a patient with multiple primary metachronous cancer is presented: right breast cancer (T2N0M0; ER‑, PR‑, HER2neu‑; 2017), right kidney cancer (T1N0M0; 24.02.2020), cancer of the rectum and sigmoid colon (T4N0M0; 22.07.2020). Pathological signs of malignant transformation of female genitals, peripheral lymph nodes were not found. Combined treatment (surgical intervention: resection of right kidney, combined resection of sigmoid colon, extirpation of uterus with appendages, polypectomy of colon in combination with a course of chemotherapy in a neoadjuvant mode) facilitated the resolution of seborrheic adenomas, which confirmed the paraneoplastic nature of Leser — Trelat syndrome.

Importance of Flow Cytometry in the Diagnosis of Sezary Syndrome in the State of Rio Grande Do Norte, Brazil

Introduction:Sézary Syndrome (SS) is a leukemic form of Fungal Mycosis (FM), a rare form of T-cell lymphoma, characterized by erythroderma, generalized lymphadenopathy and infiltration of neoplastic T cells (Sézary cells) with cerebriform nucleus on the skin, lymph nodes and peripheral blood, being observed predominantly in men and individuals over the age of 60 and black. In the diagnosis of SS / FM, at least one of the criteria must be observed: minimum absolute Sézary cells count of 1000/mm3, expansion of TCD4+ cells with a ratio CD4/CD8 >10, loss of at least one mature T cell antigens as CD2, CD3, CD5, CD7 and CD26 in associated with increased lymphocyte count with evidence of a clone of circulating TCD4 cells determined by flow cytometry (CF).Objective:To investigate MF/SS in patients diagnosed with cutaneous lymphoma by CF immunophenotyping. Methodology: Were investigated in samples of peripheral blood (SP) from 11 patients of both sexes with initial history of MF and confection of SS due to the presence of Sézary cells by cytomorphological analysis by CF constituted by a panel of conjugated monoclonal antibodies (AcMo) to fluorochromes and targeted to T lymphocytes: CD1a, CD2, CD3, CD5, CD7, subpopulation T-Helper (CD3+/CD4+) and T-cytotoxic (CD3+/CD8+), in addition to TCR a/b and TCR g/d; Natural Killer cells: CD16-56; B lymphocytes: CD19, CD20, CD21, CD22, CD23, IgM, IgG, IgD anti-kappa and anti-lambda, in addition to CD10, TdT, CD103, CD25, CD38 and CD138, CD45 and CD14. At the same time, a complete blood count with differential white blood cell count and investigation of clinical and demographic data such as age, sex and ethnicity/race were also performed. Results: Of the patients analyzed, 6/11 were male, the age group above 60 years and white individuals were also found in 6/11 patients. The blood count showed lymphocytosis in 9/11 patients with the presence of convoluted cells in all cases. The diagnosis of SS was confirmed by the presence of Sezary cells in PB counting above 1000/mm3, with an immunophenotype confirmed by the predominance of TCD4+ lymphocytes (CD4/CD8 ratio > 10.0), associated with the expression of CD5, CD2, TCR a/b, CD3 weakly expressed. CD7 was absent in 10/11 samples analyzed. Antigens related to B lymphocytes and NK cells were absent in neoplastic cells as well as CD10, TdT and CD1a.Conclusions:SS is a leukemic variant of FM, characterized by exfoliative erythroderma, associated with lymphadenopathy and leukemization of FM with the appearance of Sézary cells in PB. Because it is a rare and essential disease, an accurate diagnosis of these diseases is necessary, and FC is an important diagnostic confirmation tool for SS. Disclosures No relevant conflicts of interest to declare.

IBCL-338: The Incidence of Composite Lymphomas: One Center Experience (Russia)

Context: Composite lymphomas (CL) can occur simultaneously or sequentially and are of a particular interest in hematology. Objective: Approaches to the diagnosis and treatment of CL are complex with a full range of modern laboratory methods. Design: Analysis of cases of CL with histological and molecular features of these cases. Setting: Study setting can be used in hematological inpatient and outpatient departments. Patients: There were 37 cases of CL (M:F=2:1, median age 64 (38-83 years)). Interventions: All patients underwent a full range of diagnostic procedures, including histological, immunophenotypic, cytogenetic and molecular tests. Main outcomes measures: Study the combination types of CL. Results: Metachronous CL were observed in 17 cases; synchronous CL in 20 cases. Metachronous CL cases: the most common type of the second lymphoma was diffuse B-large cell lymphoma (DBLCL) with 58.8% and Hodgkin's lymphoma (HL) with 29.4%. In 30% of cases, DBLCL developed after HL therapy, and in 30% - after therapy of angioimmunoblastic lymphoma. The median time to development of the second lymphoproliferative disease (LD) was 6 years (range 7 mo - 40 yrs). Synchronous CL were observed in 55% of cases; the most common were the combination of chronic lymphocytic leukemia (CLL) with other LD, hairy cell leukemia (HCL) 54.5%, large granular lymphocytic leukemia, marginal zone lymphoma (MZL), follicular lymphoma, multiple myeloma, and fungal mycosis. Combination of HL with other LD was observed in 25% of cases (HL+MZL represent 60% of cases). It is not clear whether HL in this combination represents a clonal transformation from MZL cells or it is a secondary tumor that develops de novo after MZL treatment. Since common IGVH gene rearrangements and somatic mutation status could be detected for both types of cells; this may indicate that MZL and HL cell clones may originate from a single B–cell of the follicular germinal center. Conclusions: Careful examination is needed in atypical clinical course of lymphomas to exclude the second LD, including clonally related. CL are excellent models for studying the complex process of tumor cells evolution during the course of the disease. Treatment of CL is a non-trivial task and aims to control both diseases.

Comparing the results of invasive candidiasis prevention with anidulafungin vs. the lipid formulation of amphotericin B in high-risk patients in the early postoperative period after liver transplantation

Introduction. The development of invasive candidiasis leads to high mortality after liver transplantation. Choosing an effective prophylaxis is an important task.The study purpose was to compare the results of invasive candidiasis prevention with anidulafungin vs. the lipid formulation of amphotericin B in high-risk patients in the early postoperative period after liver transplantation. Material and methods. The study included 80 patients with risk factors for the development of invasive mycosis who underwent liver transplantation. Patients were divided into 2 groups. In the first group (n = 40), anidulafungin was prescribed for prophylaxis; in the 2nd group (n = 40), the lipid complex of amphotericin B was used.Results. The most common of Candida spp. isolated in the patients of our study, as expected, was Candida albicans accounting for 31.2%, significantly less than a half. Neither fungal infection breakthrough nor invasive mycosis development were reported in any patient. In group 2, renal replacement therapy was significantly more frequently used. In two cases, the amphotericin B lipid complex was canceled and the conversion to echinocandin was undertaken due to the occurrence of adverse events (chills and fever) associated, in our opinion, with the drug used. Conclusions. 1. Patients after liver transplantation with 2 or more risk factors have absolute indications to invasive mycosis prevention. 2. Anidulafungin and the lipid formulation of amphotericin B are effective for prophylaxis and prevention of fungal infection breakthrough. 3. Anidulafungin has an advantage in safety over the lipid formulation of amphotericin B.

Successful experience of combined immunochemotherapy at refractory course of primary cutaneous peripheral T-cell lymphoma, unspecified

Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of T-cell lymphoproliferative diseases that involve mainly the skin and are characterized by features of their diagnosis, clinical course and therapeutic approach. They include mainly fungal mycosis and CD30 + lymphoproliferative skin diseases (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) which account for >50% of CTCL and primary cutaneous peripheral T-cell lymphoma, unspecified/ /not otherwise specified (PTL NOS) which occurs extremely rare. Activation antigen CD30 is a cell membrane glycoprotein that belongs to tumor necrosis factor (TNF) superfamily. Tumor cells in primary skin CD30-positive skin lymphomas express CD30 in more than 75%; in other nosological units it also can be detected but to a lesser extent. Most patients with cutaneous CD30 + lymphoproliferative diseases have an indolent the disease course of the disease with a favorable prognosis. Refractory course occurs in approximately 30% patients, and in 8% of cases lymphoma results in deaths. Recently monoclonal antibodies have been included in clinical practice for the treatment of T-cell lymphomas, one of which is brentuximab vedotin, a CD30 monoclonal antibody conjugated to monomethyl auristatin E. This article provides the clinical case of a patient with a refractory form of PTL NOS.

PB1876 GENETIC MARKERS OF THE PRIMARY AND SECOND TUMORS RISK DEVELOPMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Background:Malignant tumors in patients with chronic lymphocytic leukemia (CLL) occur with equal frequency in both previously untreated patients and those receiving high‐dose therapy. This is due not only to the presence of CLL‐associated, but with drug‐induced immunodeficiency, and, probably, with modifications in the immune response genes.Aims:Identify the relationship of the several immune response genes mutational status with the development of primary and second tumors in patients with CLL.Methods:Surveyed 202 patients in the beginning of CLL at the age of 32 to 87 years (median‐63 years), 112 men (55.4%), 90 women (44.6%). Genotyping of 20 polymorphic regions of the 14 immune response genes (TLR2, TLR3, TLR4, TLR6, TLR9, IL1β, IL2, IL4, IL6, IL10, IL17A, CD14, TNFα, FCGR2A) in genomic DNA obtained from peripheral blood leukocytes was carried out by the PCR‐ASP. Intergenic interactions analysis was performed using the MDR program version 3.0.2, http://www.mybiosoftware.com/mdr‐2‐0‐multifactor‐dimensionality‐reduction.html.Results:Patients were divided into 3 groups. The first group consisted of 6 patients who had other malignancies before onset CLL. The appearance of CLL was preceded in 2 cases by the breast cancer and one: cancer of the testicle, ovary, skin and fungal mycosis from 36 to 252 months (median‐135.5 months). The second ‐ consisted of 190 CLL patients with no previous or second malignant tumors history. The third included 6 patients, who developed the second solid tumors in CLL remission after FCR treatment. Within 13‐94 months (median‐53.5 months) from the onset of CLL, they had skin cancer in 2 cases, colon cancer in 2 patients, melanoma and breast cancer in one case. In all selected groups, age and gender differences were not found. All possible combinations of the key immune response genes polymorphic variants were analyzed. It was found that the first group of patients is characterized by 2 statistically significant models: single‐ FCGR2A (A519C) (p = 0.0001) and two‐locus TLR4 (G896A)/FCGR2A (A519C) (p < 0.0001). Patients who had a second tumors after onset CLL also distinguished two models: single‐locus with the participation of the IL17A gene (G197A), p = 0.00006 and three‐locus model TLR6 (C745T)/TLR9 (A2848G)/IL1β (T511C) (p < 0.0001). It is very likely that the triggering factor for the second malignant tumors occurrence in these patients was high‐dose chemotherapy of CLL, which aggravated the existing CLL‐mediated immunodeficiency. As a result of the intergenic interactions evaluation, it was noted that in patients with a previous CLL cancer history, the risk factors for the development of primary tumors were 3 combined genotypes: FCGR2A‐519AA/TLR4‐896GG; FCGR2A‐519AA/TLR9‐2848AA/TLR4‐896GG; FCGR2A‐519AA/TLR9‐2848AG/TLR4‐896AG. For patients with CLL and second tumors detected in remission of leukemia, the most prognostically important were the combinations of genotypes: IL1β‐511CC/TLR9‐2848AA/TLR6‐745TT; IL1β‐511CC/TLR9‐2848AG/TLR6‐745TT; IL1β‐511TT/TLR9‐2848AG/TLR6‐745TT.Summary/Conclusion:Studies have confirmed the involvement of immune mechanisms in the carcinogenesis. Analysis of the polymorphic status genes FCGR2A, TLR6, TLR9 (A2848G), IL1β (T511C), IL17A, which are involved in the development and progression of various human tumors, will allow to select among patients with CLL a group with an increased risk of the development of previous and second malignant neoplasms.

Efficacy of Two Entomopathogenic Fungi, Metarhizium brunneum, Strain F52 Alone and Combined with Paranosema locustae against the Migratory Grasshopper, Melanoplus sanguinipes, under Laboratory and Greenhouse Conditions.

Grasshopper outbreaks cause significant damage to crops and grasslands in US. Chemical control is widely used to suppress these pests but it reduces environmental quality. Biological control of insect pests is an alternative way to reduce the use of chemical insecticides. In this context, two entomopathogenic fungi, Metarhizium brunneum strain F52 and Paranosema locustae were evaluated as control agents for the pest migratory grasshopper Melanoplus sanguinipes under laboratory and greenhouse conditions. Third-instar grasshoppers, reared in the laboratory, were exposed up to fourteen days to wheat bran treated with different concentrations of each of the fungi alone or the two pathogens combined. In the greenhouse, nymphs were placed individually in cages where they were able to increase their body temperatures by basking in the sun in an attempt to inhibit the fungal infection, and treated with each pathogen alone or in combination. Mortality was recorded daily and presence of fungal outgrowth in cadavers was confirmed by recording fungal mycosis for two weeks’ post-treatment (PT). For combination treatment, the nature of the pathogen interaction (synergistic, additive, or antagonistic effects) was also determined. In laboratory conditions, all treatments except P. locustae alone resulted in grasshopper mortality. The application of the pathogen combinations caused 75% and 77%, mortality for lower and higher concentrations, respectively than each of the pathogens alone. We infer a synergistic effect occurred between the two agents. In greenhouse conditions, the highest mortalities were recorded in combination fungal treatments with a M. brunneum dose (60% mortality) and with a combination of the two pathogens in which M. brunneum was applied at high rate (50%) two weeks after application. This latter combination also exhibited a synergistic effect. Exposure to the P. locustae treatment did not lead to mortality until day 14 PT. We infer that these pathogens are promising for developing a biopesticide formulation for rangeland pest grasshopper management.

Behavioral thermoregulation in Locusta migratoria manilensis (Orthoptera: Acrididae) in response to the entomopathogenic fungus, Beauveria bassiana.

Insects such as locusts and grasshoppers can reduce the effectiveness of pathogens and parasites by adopting different defense strategies. We investigated the behavioral thermopreference of Locusta migratoria manilensis (Meyen) (Orthoptera: Acrididae) induced by the fungus Beauveria bassiana, and the impact this behavior had on the fungal mycosis under laboratory conditions. By basking in higher temperature locations, infected nymphs elevated their thoracic temperature to 30–32.6 °C, which is higher than the optimum temperature (25°C) for B. bassiana conidial germination and hyphal development. A minimum thermoregulation period of 3 h/day increased survival of infected locusts by 43.34%. The therapeutic effect decreased when thermoregulation was delayed after initial infection. The fungus grew and overcame the locusts as soon as the thermoregulation was interrupted, indicating that thermoregulation helped the insects to cope with infection but did not completely rid them of the fungus. A significant enhancement in the number of haemocytes was observed in infected thermoregulating locusts, reaching levels that were even higher than those observed in the controls. In contrast, haemocyte concentration was severely reduced in infected insects that did not thermoregulate. In infected non-thermoregulating locusts, the reduction in haemocyte number was accompanied by an increase in fungal blastospore concentration that was obvious in the haemolymph by day four. In contrast, no circulating blastospores were found in the haemolymph of infected thermoregulating locusts three days post-inoculation. We also examined the phagocytic activity of infected insects in vivo by using fluorescein isothiocyanate (FITC)-labelled silica beads. The proportion of beads that was engulfed by haemocytes in infected, thermoregulating insects was similar to that in the controls throughout the experiment, whereas the rate of phagocytosis in infected, non-thermoregulating insects progressively decreased after infection. These findings demonstrated that behavioural thermoregulation can adversely affect B. bassiana mycosis in infected L. migratoria manilensis, thereby limiting the development of lethal entomopathogenic fungi in locusts. This is apparently accomplished through an increase in the levels of haemocytes, leading to greater phagocytic activity under certain environmental conditions.

Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient

Abstract Meningitis caused by fungal mycosis Cryptococcus neoformans is normally seen in immunocompromised hosts. However, immunocompetent patients are also susceptible to cryptococcal meningitis. In patients with an intact immune system, cryptococcal meningitis presents with the typical signs and symptoms of meningitis: fever, neck stiffness and headache. Our case report becomes unusual and interesting as here Cryptococcus neoformans is the cause of meningitis in a young immunocompetent male. This report also highlights the importance of culture and a need for thorough microbiological work up of CSF samples even in immunocompetent patients without any known risk factors. So care needs to be focussed on minimising sequelae and side effects of treatment and maximising functional recovery.

Potential of Tenebrio molitor (Coleoptera: Tenebrionidae) as a Bioassay Probe for Metarhizium brunneum (Hypocreales: Clavicipitaceae) Activity Against Ixodes scapularis (Acari: Ixodidae)

The yellow mealworm, Tenebrio molitor L., has been used to indicate qualitatively the presence of entomopathogenic fungi in the soil or as a model for evaluating stress and other factors on fungal activity. Although this beetle appears highly susceptible to many of these fungi, little quantitative information is available on the sensitivity of T. molitor to a specific fungus and, therefore, fungal presence or as an indicator for pathogenicity to other species. The purpose of this study was to establish the suitability of T. molitor larvae as a bioassay probe for Metarhizium brunneum for comparison against the blacklegged tick, Ixodes scapularis. Nine concentrations of M. brunneum strain F52 ranging from 1.0 x 10(1) to 8.4 x 10(8) conidial/ml were simultaneously tested against T. molitor larvae and I. scapularis adults. Larvae of yellow mealworm were less sensitive to M. brunneum than I. scapularis adults (LC50's 4.4 x 10(7) and 1.7 x 10(5) conidia/ml, respectively, 4-wk post-treatment). The greater sensitivity of I. scapularis to the fungus suggests that the detection of fungal mycosis in mealworms would indicate sufficient inoculum to be pathogenic to I. scapularis and make this insect a suitable probe for evaluation of the presence and activity of M. brunneum against the blacklegged tick in field applications.

Fungal Mycotic Vegetation In The Ascending Aorta

In most clinical scenarios, the appropriate diagnostic methodology and treatment plan can be determined in a timely manner. However, complex clinical cases with obscure etiology can be deceptive, and a multidisciplinary approach can help to clarify things. At the Methodist DeBakey Heart & Vascular Center, we encountered a huge progressive mass in the ascending aorta in a 50-year-old chronic hemodialysis patient after mechanical aortic valve replacement. In addition to initial image diagnosis and consultation workups, a transcranial Doppler (TCD) study identified continuous generation of microemboli that suggested the need for urgent surgical resection instead of conservative heparin IV therapy. Histopathology showed the huge friable mass to be hyphenated fungal mycosis (Aspergillus or Fusarium) and necrotic tissue surrounded by fresh thrombus. The postoperative course was uneventful, and the patient was discharged home.