Sample records for acute invasive fungal

  1. Secondary free-flap reconstruction following ablation for acute invasive fungal sinusitis.

    PubMed

    Allensworth, Jordan J; Troob, Scott H; Weaver, Tyler S; Gonzalez, Javier D; Petrisor, Daniel; Wax, Mark K

    2017-04-01

    Acute invasive fungal sinusitis (AIFS) is a frequently fatal infection for which extensive and debilitating surgical debridement is a mainstay of therapy. Resulting defects are often composite in nature, mandating free tissue-transfer reconstruction. Outcomes data for free flap reconstruction are limited. The purpose of this study was to examine surgical outcomes and survival in patients undergoing free flap transfer following invasive fungal sinusitis. Retrospective case series. Between 1995 and 2015, patients undergoing operative debridement for AIFS were identified. Surgical records were used to identify survivors of acute infection who subsequently underwent free flap reconstructive surgery. Patient demographics, cause of immune compromise, defect description, flap type, perioperative complications, indications for revision surgery, functional outcomes, and long-term survival were reviewed. Forty-four patients were treated for AIFS, of those, 30 (68%) survived acute infection. Ten patients underwent maxillectomy, six with orbital exenteration, and were designated candidates for reconstruction. Eight patients underwent reconstruction. Median time from debridement to reconstruction was 67.5 days. Flap types included latissimus dorsi, scapula, anterolateral thigh, rectus, radial forearm, and fibula. Median follow-up was 7.7 months. No perioperative complications were encountered, and all subjects remained disease-free, able to speak and eat normally without prosthetic supplementation. Seven patients (87%) are currently alive. Reconstruction of defects left by invasive fungal sinusitis using free-tissue transfer resulted in successful flap survival, with no disease recurrence for all defects and flap types reviewed. Survivors of AIFS are able to tolerate midface reconstruction, with favorable functional outcomes and survival rates. 4. Laryngoscope, 127:815-819, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Invasive fungal infections in pediatric oncology.

    PubMed

    Mor, Meirav; Gilad, Gil; Kornreich, Liora; Fisher, Salvador; Yaniv, Isaac; Levy, Itzhak

    2011-07-01

    Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population. The medical records of all children with malignancies diagnosed with an invasive fungal infection in 1998-2006 at a tertiary pediatric medical center were reviewed for demographic, clinical, and laboratory data. Invasive fungal infection was diagnosed according to the latest EORTC/MSG criteria. Of the 1,047 children hospitalized in the hematology/oncology department during the study period, 75 (7.2%) were diagnosed with a proven (n = 16, 21.3%), probable (n = 18, 24%), or possible (n= 41, 54.7%) invasive fungal infection. Fifteen (20%) had candidemia (non-albicans in 60%), and 60 (80%) had a mold infection (non-Aspergillus in 55%). Crude mortality was 21.7%. The most common underlying diseases were myeloid leukemia (n = 26, 34.7%) and acute lymphoblastic leukemia (n = 24, 32%). Compared to other malignancies, acute myeloid leukemia was significantly associated with the development of invasive fungal infections. Profound neutropenia and high treatment intensity were present in 89% and 73% of patients with IFI respectively. The current mortality rates of invasive fungal infection in children with cancer are lower than previously reported in children and adults. However, the proportion of non-albicans candidemia is increasing, and non-Aspergillus molds are emerging as important pathogens, which may have important implications for prophylaxis and empiric therapy. Improved prevention, early detection, and advanced treatment strategies are needed to improve the outcome. Copyright © 2011 Wiley-Liss, Inc.

  3. Ecthyma gangrenosum mimicking acute invasive fungal sinusitis in an immunocompromised patient.

    PubMed

    Hekiert, Adrianna M; Cohen, Michael B; Montone, Kathleen T; Palmer, James N; Govindaraj, Satish

    2010-06-01

    Ecthyma gangrenosum is a rare necrotizing cutaneous infection usually caused by Pseudomonas aeruginosa. We report a case of ecthyma gangrenosum presenting as a sinonasal eschar and mimicking acute invasive fungal sinusitis in an immunocompromised 39-year-old man with a hematologic malignancy. To the best of our knowledge, this represents the first case of ecthyma gangrenosum affecting the sinonasal mucosa to be reported in the literature.

  4. Acute invasive fungal rhinosinusitis: our experience with 18 cases.

    PubMed

    Bakhshaee, Mehdi; Bojdi, Amin; Allahyari, Abolghasem; Majidi, Mohammad Reza; Tavakol, Sherwin; Najafzadeh, Mohammad Javad; Asghari, Masoud

    2016-12-01

    Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive life threatening infection that is seen most commonly among immunocompromised patients. We present a case series of 18 patients clinically and histopathologically diagnosed with AIFRS with a mean follow-up of 9.11 ± 2.51 months (range 6-17). Demographic data, apparent symptoms and signs, underlying disorders, and outcomes are discussed. The mean age was 39.56 ± 20.66 years (range 2-75). The most common underlying diseases were diabetes mellitus (50 %) and leukemia (44.44 %). Mucosal biopsy confirmed fungal invasion of the nasal mucosa in all cases. The main fungi were Rhizopus oryzae (55.56 %), Absidia mucor (16.67 %), and Aspergillus fumigatus (27.78 %). Headache and facial pain (77.8 %), facial paresthesia (55.6 %), and ophthalmoplegia (33.3 %) were the most common symptoms and signs. Computed tomography and endoscopic findings showed various stages of sinonasal (100 %), pterygopalatine fossa (55.56 %), orbital (44.45 %), and cerebral (5.56 %) involvement. All patients underwent serial surgical debridement (3.78 ± 1.80 times; range 2-8) simultaneously with systemic antifungal therapy and proper management of the underlying disease. The most extreme case with brain involvement survived and recovered with no evidence of recurrent disease following treatment. All patients were considered cured after two endoscopic negative histopathologic evaluations. Three patients (16.67 %) died, one from uncontrolled leukemia and two due to renal failure. AIFRS is a potentially fatal condition, however, early diagnosis and management of the underlying disease accompanied with systemic antifungal and aggressive serial surgical intervention appears to be effective in reducing mortality in most patients.

  5. [Clinicopathologic study of invasive fungal rhinosinusitis caused by Aspergillus and Mucorales].

    PubMed

    He, Chun-yan; Piao, Ying-shi; Tian, Cheng; Li, Li-li; Liu, Hong-gang

    2012-10-01

    To compare the differences in clinicopathologic features of invasive fungal rhinosinusitis caused by Aspergillus and Mucorales, and to discuss the pathogenesis of tissue injury induced by these two kinds of fungi. The clinical and pathologic features of 19 patients with invasive fungal rhinosinusitis due to Aspergillus (group A) and 16 patients with invasive fungal rhinosinusitis due to Mucorales (group M) were retrospectively reviewed. HE, PAS and GMS stains were performed on all the paraffin-embedded tissues. The diagnosis was confirmed by histologic examination and microbiological culture results. Amongst the group A patients, the clinical course was acute in 4 cases and chronic in 15 cases. Thirteen cases had underlying predisposing conditions, including diabetes (number = 4), malignant tumor (number = 5), history of trauma (number = 1) and radical maxillary sinus surgery (number = 3). Follow-up information was available in 13 patients. Seven of them died, 4 due to fungal encephalopathy and 3 due to underlying diseases. Amongst the group M patients, the clinical course was acute in 14 cases and chronic in 2 cases. Fourteen cases had underlying predisposing conditions, including diabetes (number = 8), malignant tumor (number = 5) and history of wisdom tooth extraction (number = 1). Follow-up information was available in 14 patients. Four of them died of fungal encephalopathy. There was significant difference in clinical onset between the two groups (P = 0.01). There was however no difference in terms of underlying predisposing conditions and disease mortality. Histologically, the microorganisms in group A patients formed fungal masses and attached to the mucosal surface, resulting in necrotic bands (11/19). Epithelioid granulomas were conspicuous but multinucleated giant cells were relatively rare. Deep-seated necrosis, granulomatous inflammation against fungal organisms (3/19) and vasculitis with thrombosis (4/19) were not common. On the other hand, large areas

  6. How We Manage Invasive Fungal Disease in Acute Myeloid Leukemia Patients with Glucose 6 Dehydrogenase Deficiency

    PubMed Central

    Sanna, Marco; Caocci, Giovanni; La Nasa, Giorgio

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) represents a common human enzyme defect, particularly prevalent in the Mediterranean, African e Asian area, where malaria was or is still endemic. Recently, we identified G6PD deficiency as a risk factor for developing invasive fungal disease (IFD) and particularly Candida Sepsis in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML), suggesting that there is an urgent need for strategies to properly manage this kind of patients at high risk of invasive mycoses. Here we propose our algorithm for correct identification, prophylaxis, and treatment of IFD in patients with G6PD deficiency undergoing intensive chemotherapy for AML. PMID:28894556

  7. How We Manage Invasive Fungal Disease in Acute Myeloid Leukemia Patients with Glucose 6 Dehydrogenase Deficiency.

    PubMed

    Sanna, Marco; Caocci, Giovanni; La Nasa, Giorgio

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) represents a common human enzyme defect, particularly prevalent in the Mediterranean, African e Asian area, where malaria was or is still endemic. Recently, we identified G6PD deficiency as a risk factor for developing invasive fungal disease (IFD) and particularly Candida Sepsis in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML), suggesting that there is an urgent need for strategies to properly manage this kind of patients at high risk of invasive mycoses. Here we propose our algorithm for correct identification, prophylaxis, and treatment of IFD in patients with G6PD deficiency undergoing intensive chemotherapy for AML.

  8. Diagnosis of invasive fungal infections using real-time PCR assay in paediatric acute leukaemia induction.

    PubMed

    Mandhaniya, Sushil; Iqbal, Sobuhi; Sharawat, Surender Kumar; Xess, Immaculata; Bakhshi, Sameer

    2012-07-01

    Invasive fungal infections (IFI) lead to morbidity and mortality in neutropenic patients and in allogenic stem cell transplantation. Serum-based fungal detection assays have limitation of specificity or sensitivity. Studies on fungal DNA detection using real-time PCR in childhood leukaemia are lacking. The aim of this study was to develop sensitive and specific diagnostic tools for IFI in paediatric acute leukaemia patients using real-time PCR. Of 100 randomised paediatric acute leukaemia patients receiving antifungal prophylaxis with voriconazole/amphotericin B, single peripheral whole blood sample in EDTA was used for Pan-AC real-time PCR assay (detects nine Candida and six Aspergillus species) in patients who failed prophylaxis due to proven, probable, possible or suspected fungal infections. PCR results were retrospectively correlated with clinical profile. Real-time PCR test was positive in 18/29 (62%) patients who failed prophylaxis. The only patient with proven IFI (mucormycosis), real-time PCR assay was negative. Real-time PCR was positive in 2/4 (50%) patients with possible and 16/24 (66.6%) suspected IFI and 5/10 (50%) patients with pneumonia. By applying method A/B, sensitivity and positive predictive value could not be commented due to unproven Aspergillus or Candida infections; specificity and negative predictive values (NPV) were 41% and 100% respectively; by method C (included episodes of possible IFI as true positive), sensitivity, specificity, PPV and NPV were 50%, 36%, 11% and 81% respectively. In those with suspected IFI, 8/24 (33.3%) were PCR negative and unnecessarily received empirical antifungal therapy (EAFT). Real-time PCR is a practical, rapid, non-invasive screening test for excluding IFI in paediatric leukaemia. The high NPV makes real-time PCR a promising tool to use this prior to initiating EAFT in antibiotic-resistant febrile neutropenic patients; this would avoid toxicity, cost and hospitalisation for EAFT (Clinical

  9. Chronic Invasive Fungal Sinusitis Presenting as Inferior Altitudinal Visual Field Defect.

    PubMed

    Bansal, Reema; Takkar, Aastha; Lal, Vivek; Bal, Amanjit; Bansal, Sandeep

    2017-06-01

    A young male with acute blurring of vision (6/9) complained of an inferior altitudinal field defect in right eye. Clinical ophthalmological examination was normal. Magnetic resonance imaging (MRI) of the brain revealed the expansion and mucosal thickening of right posterior ethmoid and sphenoid sinuses and opacified right maxillary sinus. Surgical intervention (transethmoidal sphenoidotomy) and histopathological examination revealed chronic invasive granulomatous fungal sinusitis. Anti-fungal therapy led to resolution of visual complaints and restoration of visual field defects.

  10. Chapter 8: Invasive fungal rhinosinusitis.

    PubMed

    Duggal, Praveen; Wise, Sarah K

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  11. Chapter 8: Invasive fungal rhinosinusitis.

    PubMed

    Duggal, Praveen; Wise, Sarah K

    2013-05-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  12. Invasive fungal rhinosinusitis in adult patients: Our experience in diagnosis and management.

    PubMed

    Pagella, Fabio; De Bernardi, Francesca; Dalla Gasperina, Daniela; Pusateri, Alessandro; Matti, Elina; Avato, Irene; Cavanna, Caterina; Zappasodi, Patrizia; Bignami, Maurizio; Bernardini, Elena; Grossi, Paolo Antonio; Castelnuovo, Paolo

    2016-04-01

    This paper describes our experience in the management of acute and chronic invasive fungal rhinosinusitis (IFRS) in adults. Medical files of all patients aged >18 years treated in our institutions for IFRS from 2002 to 2013 were retrospectively reviewed. A total of 18 cases (10 acute and 8 chronic) were recorded. In acute form, haematological malignancies represented the principal comorbidity (100%), while in chronic form this was diabetes mellitus (87.5%). All patients received systemic antifungal agents. Endoscopic sinus surgery was performed in 16/18 patients (88.9%). Among patients with an acute IFRS, 4/10 died of fungal infection (40%), on the other side 2/8 patients with chronic IFRS died of the evolution of the mycosis (25%). Acute and chronic IFRS are different entities: in acute form, prognosis is poor, so therapy should be promptly performed, although host immune status and evolution of the haematological disease are key factors for the outcome. In chronic form, a wide surgical excision of the disease is recommended in order to obtain a complete removal of fungal infection. In both forms, early clinical findings are non-specific and ambiguous, so diagnosis depends on a high index of suspicion, taking into account predisposing factors. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  13. Invasive fungal infections in Colombian patients with systemic lupus erythematosus.

    PubMed

    Santamaría-Alza, Y; Sánchez-Bautista, J; Fajardo-Rivero, J F; Figueroa, C L

    2018-06-01

    Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P < 0.05). Conclusions We describe for the first time the prevalence of invasive fungal infection in a Colombian population with systemic lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality

  14. Responses of the soil fungal communities to the co-invasion of two invasive species with different cover classes.

    PubMed

    Wang, C; Zhou, J; Liu, J; Jiang, K; Xiao, H; Du, D

    2018-01-01

    Soil fungal communities play an important role in the successful invasion of non-native species. It is common for two or more invasive plant species to co-occur in invaded ecosystems. This study aimed to determine the effects of co-invasion of two invasive species (Erigeron annuus and Solidago canadensis) with different cover classes on soil fungal communities using high-throughput sequencing. Invasion of E. annuus and/or S. canadensis had positive effects on the sequence number, operational taxonomic unit (OTU) richness, Shannon diversity, abundance-based cover estimator (ACE index) and Chao1 index of soil fungal communities, but negative effects on the Simpson index. Thus, invasion of E. annuus and/or S. canadensis could increase diversity and richness of soil fungal communities but decrease dominance of some members of these communities, in part to facilitate plant further invasion, because high soil microbial diversity could increase soil functions and plant nutrient acquisition. Some soil fungal species grow well, whereas others tend to extinction after non-native plant invasion with increasing invasion degree and presumably time. The sequence number, OTU richness, Shannon diversity, ACE index and Chao1 index of soil fungal communities were higher under co-invasion of E. annuus and S. canadensis than under independent invasion of either individual species. The co-invasion of the two invasive species had a positive synergistic effect on diversity and abundance of soil fungal communities, partly to build a soil microenvironment to enhance competitiveness of the invaders. The changed diversity and community under co-invasion could modify resource availability and niche differentiation within the soil fungal communities, mediated by differences in leaf litter quality and quantity, which can support different fungal/microbial species in the soil. © 2017 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

  15. Epidemiology and treatment approaches in management of invasive fungal infections

    PubMed Central

    Kriengkauykiat, Jane; Ito, James I; Dadwal, Sanjeet S

    2011-01-01

    Over the past 20 years, the number of invasive fungal infections has continued to persist, due primarily to the increased numbers of patients subjected to severe immunosuppression. Despite the development of more active, less toxic antifungal agents and the standard use of antifungal prophylaxis, invasive fungal infections (especially invasive mold infections) continue to be a significant factor in hematopoietic cell and solid organ transplantation outcomes, resulting in high mortality rates. Since the use of fluconazole as standard prophylaxis in the hematopoietic cell transplantation setting, invasive candidiasis has come under control, but no mold-active antifungal agent (except for posaconazole in the setting of acute myelogenous leukemia and myelodysplastic syndrome) has been shown to improve the survival rate over fluconazole. With the advent of new azole and echinocandin agents, we have seen the emergence of more azole-resistant and echinocandin-resistant fungi. The recent increase in zygomycosis seen in the hematopoietic cell transplantation setting may be due to the increased use of voriconazole. This has implications for the empiric approach to pulmonary invasive mold infections when zygomycosis cannot be ruled out. It is imperative that an amphotericin B product, an antifungal that has never developed resistance in over 50 years, be initiated. The clinical presentations of invasive mold infections and invasive candidiasis can be nonspecific and the diagnostic tests insensitive, so a high index of suspicion and immediate initiation of empiric therapy is required. Unfortunately, our currently available serologic tests do not predict infection ahead of disease, and, therefore cannot be used to initiate “preemptive” therapy. Also, the Aspergillus galactomannan test gives a false negative result in patients receiving antimold prophylaxis, ie, virtually all of our patients with hematologic malignancy and hematopoietic cell transplant recipients. We may

  16. Invasive fungal infection following chemotherapy for acute myeloid leukaemia-Experience from a developing country.

    PubMed

    Korula, Anu; Abraham, Aby; Abubacker, Fouzia N; Viswabandya, Auro; Lakshmi, Kavitha M; Abraham, O C; Rupali, Priscilla; Varghese, George M; Michael, Joy S; Srivastava, Alok; Mathews, Vikram; George, Biju

    2017-10-01

    The incidence of invasive fungal infections (IFI) is believed to be higher in patients with acute myeloid leukaemia (AML) undergoing chemotherapy in non-HEPA-filtered rooms. The aim of this study is to review the incidence of IFI in a large cohort of patients with AML treated at a single centre in India. Two hundred and twenty-two patients with AML treated with either induction chemotherapy or salvage chemotherapy between 2008 and 2013 were studied retrospectively. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy, prophylactic strategies, engraftment (ANC>500), the presence of IFI and survival were collected. IFI was diagnosed in 86 patients (38.7%) with proven IFI in 12 (5.4%). Use of posaconazole prophylaxis (P=.001) was the only factor associated with reduced incidence of IFI. Survival in patients with proven IFI was lower than those without proven IFI, but not statistically significant (59.4% vs 78.5%; P=.139). There is a high incidence of IFI during induction chemotherapy for acute myeloid leukaemia in developing countries. Posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal yet cost-effective strategies for prevention and early diagnosis of IFI are required to improve survival in patients undergoing chemotherapy for AML. © 2017 Blackwell Verlag GmbH.

  17. Fungal Rhinosinusitis: Microbiological and Histopathological Perspective

    PubMed Central

    Singh, Ajay Kumar; Verma, Nitya; Khare, Vineeta; Ahamad, Abrar; Verma, Virendra; Agarwal, S.P

    2017-01-01

    Introduction On the basis of histopathology Fungal Rhinosinusitis (FRS) is categorized into non-invasive (allergic fungal rhinosinusitis, fungal ball) and invasive (acute invasive, chronic invasive and granulomatous invasive fungal sinusitis). This differentiation helps to decide the treatment. Role of latest molecular methods such as PCR and conventional methods such as KOH microscopy and culture also needs to be evaluated. Therefore, in this study we planned to categorise fungal rhinosinusitis on the basis of histopathology and compare it with other methods such as PCR, culture and KOH microscopy. Aim To analyse fungal rhinosinusitis cases by both histopathologically and microbiologically. Materials and Methods A total of 76 clinically suspected fungal rhinosinusitis cases were included in the study. The tissue of suspected cases were processed and examined by KOH microscopy, histopathologically, culture and PCR. Histopathological examination was done by PAS, GMS and H&E stain. Results FRS was diagnosed in 37 (48.68%) cases out of 76 clinically suspected cases of FRS. In which 17 (22.3%) cases were positive by direct microscopy, 21 (27.6%) by culture, 27 (35.5%) by PCR and 14 (18.42%) by histopathology. Approximately 14 cases of FRS were classified according to histopathology; 10 (71.3%) as non-invasive FRS. Out of these 10, 9 (64.2%) were classified as AFRS and 1 (7.14%) as fungal ball. Only 4 cases (28.5%) were diagnosed with invasive FRS. Out of these 4 cases, 2 (14.2%) were of chronic invasive fungal rhinosinusitis, 1 (7.14%) was of granulomatous invasive fungal rhinosinusitis and 1 (7.14%) was of acute fulminant invasive fungal rhinosinusitis. Allergic Fungal Rhinosinusitis (AFRS) is the most common type of FRS. Aspergillus flavus was found to be the most common fungi causing FRS. Conclusion Diagnosis should not be based on the single method. It should be done by both histopathological and microbiological methods, especially for those cases which are

  18. Invasive filamentous fungal infections associated with renal transplant tourism.

    PubMed

    Shoham, S; Hinestrosa, F; Moore, J; O'Donnell, S; Ruiz, M; Light, J

    2010-08-01

    'Transplant tourism,' the practice of traveling abroad to acquire an organ, has emerged as an issue in kidney transplantation. We treated a patient who developed invasive aspergillosis of the allograft vascular anastomosis after receiving a kidney transplant in Pakistan, prompting us to review the literature of invasive mycoses among commercial organ transplant recipients. We reviewed all published cases of infections in solid organ transplant recipients who bought their organs abroad and analyzed these reports for invasive fungal infections. Including the new case reported here, 19 cases of invasive fungal infections post commercial kidney transplant occurring in 17 patients were analyzed. Infecting organisms were Aspergillus species (12/19; 63%), Zygomycetes (5/19; 26%), and other fungi (2/19; 5%). Invasive mold infections were present at the transplanted graft in 6/17 patients (35%) with graft loss or death in 13/17 (76%) of patients and overall mortality (10/17) 59%. Invasive fungal infections, frequently originating at the graft site, have emerged as a devastating complication of commercial renal transplant and are associated with high rates of graft loss and death.

  19. A single ectomycorrhizal fungal species can enable a Pinus invasion.

    PubMed

    Hayward, Jeremy; Horton, Thomas R; Pauchard, Aníbal; Nuñnez, Martin A

    2015-05-01

    Like all obligately ectomycorrhizal plants, pines require ectomycorrhizal fungal symbionts to complete their life cycle. Pines introduced into regions far from their native range are typically incompatible with local ectomycorrhizal fungi, and, when they invade, coinvade with fungi from their native range. While the identities and distributions of coinvasive fungal symbionts of pine invasions are poorly known, communities that have been studied are notably depauperate. However, it is not yet clear whether any number of fungal coinvaders is able to support a Pinaceae invasion, or whether very depauperate communities are unable to invade. Here, we ask whether there is evidence for a minimum species richness of fungal symbionts necessary to support a pine/ectomycorrhizal fungus coinvasion. We sampled a Pinus contorta invasion front near Coyhaique, Chile, using molecular barcoding to identify ectomycorrhizal fungi. We report that the site has a total richness of four species, and that many invasive trees appear to be supported by only a single ectomycorrhizal fungus, Suillus luteus. We conclude that a single ectomycorrhizal (ECM) fungus can suffice to enable a pine invasion.

  20. Invasive fungal bezoar requiring partial cystectomy.

    PubMed

    Sundi, Debasish; Tseng, Kenneth; Mullins, Jeffrey K; Marr, Kieren A; Hyndman, Matthew Eric

    2012-02-01

    A 67-year-old man developed dysuria and position-dependent obstructive voiding symptoms after undergoing holmium laser ablation of the prostate (HOLAP) for benign prostatic hypertrophy. A large fungal (candidal) ball adherent to the bladder wall was removed by loop excision, but the bezoar recurred in 2 weeks despite systemic fluconazole and intravesical amphotericin B. A second attempt at endoscopic removal with ultrasonic lithotripsy, endoscopic graspers, and fulguration was also unsuccessful. The patient underwent open partial cystectomy to remove his invasive fungal bezoar. Convalescence was unremarkable. Urinalysis, culture, and follow-up cystoscopy after partial cystectomy demonstrated successful definitive treatment of the fungal ball. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Azole-based chemoprophylaxis of invasive fungal infections in paediatric patients with acute leukaemia: an internal audit.

    PubMed

    Yunus, Sara; Pieper, Stephanie; Kolve, Hedwig; Goletz, Grazyna; Jürgens, Heribert; Groll, Andreas H

    2014-03-01

    Children and adolescents with acute myeloid leukaemia (AML) and recurrent acute leukaemias (RALs) are at high risk of life-threatening invasive fungal infections (IFIs). We analysed implementation, safety and efficacy of a standard operating procedure for oral, azole-based, mould-active antifungal prophylaxis. Patients with AML and RALs aged ≥13 years received 200 mg of posaconazole three times daily and patients aged 2-12 years received 200 mg of voriconazole two times daily from the completion of chemotherapy until haematopoietic recovery. Algorithms for fever or focal findings in all patients with haematological malignancies included blood cultures, high-resolution CT and other appropriate imaging, serial serum galactomannan, invasive diagnostics and pre-emptive therapy with change in class if on antifungal medication. From 2006 to 2010, 40 patients (0.8-17 years; 21 males) with newly diagnosed AML (n = 31) or RAL (n = 9) were admitted, of whom 36 received a total of 149 courses of chemotherapy (reasons for exclusion: contraindications and early death ≤3 days). Azole prophylaxis was given in 87.2% (n = 130/149) of episodes. Pre-emptive antifungal therapy for pulmonary infiltrates was initiated in 5/36 (13.9%) patients or 6/130 (4.6%) episodes for a duration of 3-22 days. No proven or probable IFIs occurred. Adverse events (AEs) were common but mostly low grade and reversible. Three courses (2.3%) were discontinued due to AEs. In simultaneously admitted new patients with acute lymphatic leukaemia (ALL; n = 101) and paediatric lymphomas (n = 29) not receiving standard antifungal prophylaxis, proven/probable IFIs occurred in 4 patients with ALL (4.0%) and 7/130 patients (5.4%) received pre-emptive therapy. Azole-based, mould-active antifungal prophylaxis in high-risk paediatric patients with AML and RALs was satisfactorily implemented, well tolerated and effective. The low rate of IFIs in patients with ALL/lymphoma supports the lack of a general indication for

  2. Cervicofacial tissue infarction in patients with acute invasive fungal sinusitis: prevalence and characteristic MR imaging findings.

    PubMed

    Seo, Jungmin; Kim, Hyung-Jin; Chung, Seung-Kyu; Kim, Eunhee; Lee, Hanbee; Choi, Jin Wook; Cha, Ji Hoon; Kim, Hye Jung; Kim, Sung Tae

    2013-03-01

    Tissue infarction is known as one of the characteristic features of invasive fungal sinusitis (IFS). The purpose of this study was to investigate the prevalence and characteristic MR imaging findings of cervicofacial tissue infarction (CFTI) associated with acute IFS. We retrospectively reviewed MR images in 23 patients with histologically or microbiologically proven acute IFS. CFTI was defined as an area of lack of enhancement in and around the sinonasal tract on contrast-enhanced T1-weighted images. We divided CFTI into two groups, i.e., intrasinonasal and extrasinonasal. Particular attention was paid to the location of extrasinonasal CFTI and the signal intensity of CFTI on T1- and T2-weighted images. The presence of bone destruction on CT scans was also recorded. CFTI was found in 17 (74%) of 23 patients. All of these 17 patients had intrasinonasal CFTI, and 13 patients also had extrasinonasal CFTI. All 13 patients with extrasinonasal CFTI died of disease directly related to IFS. Various locations were involved in the 13 patients with extrasinonasal CFTI, including the orbit (n = 8), infratemporal fossa (n = 7), intracranial cavity (n = 3), and oral cavity and/or facial soft tissue (n = 4). Various signal intensities were noted at the area of CFTI on T1- and T2-weighted images. Bone destruction was found on CT scans in only 3 of 17 patients with CFTI. CFTI with preservation of the bony wall of the involved sinonasal tract may be a characteristic MR imaging finding of acute IFS. The mortality is very high once the lesion extends beyond the sinonasal tract.

  3. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

    PubMed

    Ghez, David; Calleja, Anne; Protin, Caroline; Baron, Marine; Ledoux, Marie-Pierre; Damaj, Gandhi; Dupont, Mathieu; Dreyfus, Brigitte; Ferrant, Emmanuelle; Herbaux, Charles; Laribi, Kamel; Le Calloch, Ronan; Malphettes, Marion; Paul, Franciane; Souchet, Laetitia; Truchan-Graczyk, Malgorzata; Delavigne, Karen; Dartigeas, Caroline; Ysebaert, Loïc

    2018-04-26

    Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present. © 2018 by The American Society of Hematology.

  4. Invasive fungal infections during the neonatal period: diagnosis, treatment and prophylaxis.

    PubMed

    Tezer, Hasan; Canpolat, Fuat Emre; Dilmen, Uğur

    2012-02-01

    The incidence of preterm births seems to be increased in many countries around the world, in parallel to the advances in neonatal medicine. However, this has resulted in longer hospital stays and more exposure to invasive interventions, both of which can lead to an increase in late-onset nosocomial infections in the newborn period. In addition to bacteria, fungi are thought to be an important cause of hospital infections. The present article reviews the diagnosis, treatment and prophylaxis of invasive fungal infections (IFIs) during the neonatal period. IFIs are associated with high morbidity and mortality in preterm neonates. The main risk factors are multiple antibiotics, central venous catheters, parenteral nutrition, immunodepression, very low birth weight, and fungal colonization. Successful management of IFIs relies on early recognition and rapid initiation of effective treatment. Invasive-fungal-infection-related morbidity and mortality is a major concern for most neonatal intensive care units worldwide. Incidence rates are increasing for preterm neonates. Preterm infants display clinical characteristics that make them prone to fungal infections, and there is a high frequency of neurodevelopmental sequelae in those who survive after neonatal fungal infections. Specific prevention - rather than treatment - should be the optimal strategy. Both fluconazole and nystatin prophylaxis reduce the incidence of IFI and fungal colonization in very preterm infants.

  5. Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

    PubMed Central

    Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

    2014-01-01

    SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

  6. Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in premature infants.

    PubMed

    Demirel, Gamze; Celik, Istemi Han; Erdeve, Omer; Saygan, Sibel; Dilmen, Ugur; Canpolat, Fuat Emre

    2013-10-01

    This study aims to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in very low birth weight infants. A prospective, randomized comparative study was conducted in preterm infants with a gestational age of ≤ 32 weeks and birth weight of ≤ 1,500 g. They were randomized into two groups, to receive S. boulardii or nystatin. Skin and stool cultures were performed for colonization and blood cultures for invasive infections, weekly. A total of 181 infants were enrolled (S. boulardii group, n = 91; nystatin group, n = 90). Fungal colonization of the skin (15.4 vs 18.9 %, p = 0.532) and the stool (32.2 vs 27 %, p = 0.441) were not different between the probiotic and nystatin groups. Two patients had Candida-positive blood culture in the nystatin group whereas none in the probiotic group. Feeding intolerance, clinical sepsis, and number of sepsis attacks were significantly lower in the probiotics group than in the nystatin group. Prophylactic S. boulardii supplementation is as effective as nystatin in reducing fungal colonization and invasive fungal infection, more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance.

  7. A novel model of invasive fungal rhinosinusitis in rats.

    PubMed

    Zhang, Fang; An, Yunfang; Li, Zeqing; Zhao, Changqing

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats. The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed. The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates. A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.

  8. A breath fungal secondary metabolite signature to diagnose invasive aspergillosis.

    PubMed

    Koo, Sophia; Thomas, Horatio R; Daniels, S David; Lynch, Robert C; Fortier, Sean M; Shea, Margaret M; Rearden, Preshious; Comolli, James C; Baden, Lindsey R; Marty, Francisco M

    2014-12-15

    Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America

  9. Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis.

    PubMed

    Papagiannopoulos, Peter; Lin, Diana Murro; Al-Khudari, Samer; Rajan, Kumar; Reddy, Swathi; Gattuso, Paulo; Tajudeen, Bobby; Batra, Pete S

    2017-05-01

    Acute invasive fungal rhinosinusitis (AIFRS) represents a fulminant, potentially fatal, disease process in immunocompromised patients. The diagnosis often rests on high index of clinical suspicion, with relative paucity of data on the diagnostic and therapeutic implications of intraoperative frozen sections. Retrospective review was performed for 18 cases undergoing endoscopic sinus surgery for AIFRS. Reliability of intraoperative frozen section diagnosis was evaluated for all patients using final pathology as the gold standard. A total of 66 frozen sections were performed. Diagnostic accuracy of frozen sections illustrated sensitivity of 72.7% (95% confidence interval [CI], 0.57 to 0.85), specificity of 100% (95% CI, 0.85 to 1.00), positive predictive value (PPV) of 100% (95% CI, 0.89 to 1.00), and negative predictive value (NPV) of 64.7% (95% CI, 0.46 to 0.80). There was no statistically significant difference in sensitivity of frozen sections in cases of Mucor and Aspergillus at 68.8%% and 76.2%, respectively (p = 0.61). This study represents the largest series assessing the diagnostic accuracy of frozen section analysis in AIFRS. Frozen section analysis is an effective tool for guiding intraoperative decision making in patients with AIFRS with a high PPV. A Low NPV underscores the importance of clinical suspicion and intraoperative decision making based on endoscopic findings when negative frozen section results are encountered. Further, frozen section analysis appears to be equally effective in detecting either Mucor or Aspergillus. © 2017 ARS-AAOA, LLC.

  10. [Iron and invasive fungal infection].

    PubMed

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  11. Soil fungal abundance and diversity: another victim of the invasive plant Centaurea maculosa.

    PubMed

    Broz, Amanda K; Manter, Daniel K; Vivanco, Jorge M

    2007-12-01

    Interactions between plants and soil microbes are important determinants of both above- and belowground community composition, and ultimately ecosystem function. As exotic plants continue to invade and modify native plant communities, there has been increasing interest in determining the influence of exotic invasives on native soil microbial communities. Here, using highly sensitive molecular techniques, we examine fungal abundance and diversity in the soil surrounding a particularly aggressive invasive plant species in North America, Centaurea maculosa Lam. In mixed stands, we show that this invasive weed can alter the native fungal community composition within its own rhizosphere and that of neighboring native plants. At higher densities, the effect of C. maculosa on native soil fungal communities was even greater. Our results demonstrate that this invasive weed can have significant effects not only on visible aboveground biodiversity but also on the native soil microbial community that extends beyond its rhizosphere.

  12. Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease in patients with acute myeloid leukemia.

    PubMed

    Sanna, Marco; Caocci, Giovanni; Ledda, Antonio; Orrù, Federica; Fozza, Claudio; Deias, Paola; Tidore, Gianni; Dore, Fausto; La Nasa, Giorgio

    2017-11-01

    Invasive fungal diseases (IFD) are still a leading cause of morbidity and mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate dehydrogenase is an enzyme that leads to the production of NADPH, required to destroy microorganisms in the respiratory burst reaction of white blood cells. We evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML patients undergoing intensive chemotherapy. In all, 28 patients harbored G6PD deficiency (G6PD-), whereas 80 were normal (G6PD +). Incidence of IFD was significantly higher in G6PD- patients compared to G6PD + patients (35.7% vs. 5%, p = .0002, OR = 10, 95% CI = 2.96-37.5). Higher risk of mold infections (17.9% vs. 5%, p = .048, OR = 4.1, 95% CI = 1.0-16.6) and Candida sepsis (17.9% vs. 0%, p = .0009, OR = 37.68, 95% CI =2.0-707.1) was observed in G6PD - patients. The evaluation of G6PD activity may help to identify AML patients at higher risk of IFD, allowing to design more intensive surveillance and therapeutic strategies.

  13. [Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2014-01-01

    The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. Copyright © 2014. Published by Elsevier Espana.

  14. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-11-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. Clinical characteristics and outcome of invasive fungal infections in pediatric acute myeloid leukemia patients in a medical center in Taiwan.

    PubMed

    Lin, Gu-Lung; Chang, Hsiu-Hao; Lu, Chun-Yi; Chen, Chung-Ming; Lu, Meng-Yao; Lee, Ping-Ing; Jou, Shiann-Tarng; Yang, Yung-Li; Huang, Li-Min; Chang, Luan-Yin

    2018-04-01

    Invasive fungal infection (IFI) causes significant morbidity and mortality in patients with hematological malignancies, especially those with acute myeloid leukemia (AML), recurrent acute leukemia, high-risk acute lymphoblastic leukemia, and after allogeneic hematopoietic stem cell transplantation. The study aimed to investigate the clinical characteristics and outcome of IFIs in pediatric AML patients in a medical center in Taiwan. We performed retrospective chart reviews. We enrolled pediatric AML patients who were admitted to National Taiwan University Hospital between January 2005 and December 2014. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group 2008 consensus criteria. In total, 78 patients were included for analysis. Twenty two episodes of IFIs were identified in 16 patients. The incidence for IFIs was 20.5% (16/78), and no specific trend of increase or decrease was observed through the study period (p=0.374). Candida species caused the majority (59.1%) of IFIs. Prolonged neutropenia and elevated alanine aminotransferase and creatinine values were factors associated with IFIs (p<0.001, p<0.001, and p=0.001, respectively). Patients with endotracheal intubation or inotropes usage had a higher probability of developing IFIs (p<0.001 and p=0.001, respectively). The overall mortality of IFIs was 53% (8/15) over 10 years, and patients with pulmonary aspergillosis had the highest mortality (80%). IFIs continue to pose significant morbidity and mortality in pediatric AML patients, and patients with other hematology-oncology cancers. Recognition of factors associated with IFIs may help us early identify IFIs and promptly initiate antifungal therapy. Copyright © 2017. Published by Elsevier B.V.

  16. The sensitivity and specificity of touch preparation for rapid diagnosis of invasive fungal sinusitis: A pilot study.

    PubMed

    Schuman, Theodore A; Nguyen, Josephine H; Yelverton, Joshua C; Almenara, Jorge A; Powers, Celeste N

    2018-01-01

    Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period. Thirteen patients had touch preparation of nasal specimens followed by routine histologic processing; 2 of these patients underwent two and 1 patient had three separate debridements, for a total of 17 touch preparations performed. The sensitivity and specificity of touch preparation were calculated by correlating the initial results with the presence of fungal invasion on final pathologic analysis. The sensitivity of touch preparation was 56% (95% confidence interval [CI]: 0.23 to 0.85), specificity was 100% (95% CI: 0.60 to 1.00), positive predictive value was 100% (95% CI: 0.46 to 1.00), and negative predictive value was 67% (95% CI: 0.35 to 0.89). This procedure may be a useful adjunct in situations requiring rapid diagnosis of invasive fungal sinusitis but should not be used as the sole criterion for determining the need for surgical intervention.

  17. Fungal Rhinosinusitis: A Retrospective Microbiologic and Pathologic Review of 400 Patients at a Single University Medical Center

    PubMed Central

    Montone, Kathleen T.; Livolsi, Virginia A.; Feldman, Michael D.; Palmer, James; Chiu, Alexander G.; Lanza, Donald C.; Kennedy, David W.; Loevner, Laurie A.; Nachamkin, Irving

    2012-01-01

    Fungal Rhinosinusitis (FRS) is a well known entity, but only in more recent times have the types of FRS been more fully defined. In this study, we evaluate the diagnosis of FRS in a single medical center. Cases were divided into 2 main categories, non-invasive and invasive. Non-invasive FRS included fungus ball (FB) and allergic fungal rhinosinusitis (AFRS). Invasive FRS included acute invasive fungal rhinosinusitis (AIFRS), chronic invasive fungal rhinosinusitis (CIFRS), and chronic invasive granulomatous fungal rhinosinusitis (CGFRS). Fungal culture data, if available was reviewed. 400 patients with FRS were identified. 87.25% were non-invasive (45% AFRS, 40% FB, and 2% combined AFRS and FB and 12.5% were invasive 11% AIFRS 1.2% CIFRS 0.5% CGFRS. One patient (0.25%) had combined FB/CGFRS. Aspergillus sp. or dematiaceous species were the most common fungi isolated in AFS while Aspergillus sp. was most common in FB and AIFRS. In our experience, most FRS is non-invasive. In our patient population, invasive FRS is rare with AIFRS representing >90% of cases. Culture data supports that a variety of fungal agents are responsible for FRS, but Aspergillus sp. appears to be one of the most common organisms in patients with FRS. PMID:22518160

  18. Clinical use of fungal PCR from deep tissue samples in the diagnosis of invasive fungal diseases: a retrospective observational study.

    PubMed

    Ala-Houhala, M; Koukila-Kähkölä, P; Antikainen, J; Valve, J; Kirveskari, J; Anttila, V-J

    2018-03-01

    To assess the clinical use of panfungal PCR for diagnosis of invasive fungal diseases (IFDs). We focused on the deep tissue samples. We first described the design of panfungal PCR, which is in clinical use at Helsinki University Hospital. Next we retrospectively evaluated the results of 307 fungal PCR tests performed from 2013 to 2015. Samples were taken from normally sterile tissues and fluids. The patient population was nonselected. We classified the likelihood of IFD according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG), comparing the fungal PCR results to the likelihood of IFD along with culture and microscopy results. There were 48 positive (16%) and 259 negative (84%) PCR results. The sensitivity and specificity of PCR for diagnosing IFDs were 60.5% and 91.7%, respectively, while the negative predictive value and positive predictive value were 93.4% and 54.2%, respectively. The concordance between the PCR and the culture results was 86% and 87% between PCR and microscopy, respectively. Of the 48 patients with positive PCR results, 23 had a proven or probable IFD. Fungal PCR can be useful for diagnosing IFDs in deep tissue samples. It is beneficial to combine fungal PCR with culture and microscopy. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Comparative Analysis of Amphotericin B Lipid Complex and Liposomal Amphotericin B Kinetics of Lung Accumulation and Fungal Clearance in a Murine Model of Acute Invasive Pulmonary Aspergillosis▿

    PubMed Central

    Lewis, Russell E.; Liao, Guangling; Hou, Jinggou; Chamilos, Georgios; Prince, Randall A.; Kontoyiannis, Dimitrios P.

    2007-01-01

    The reformulation of amphotericin B (AMB) into a lipid complex (AMB lipid complex [ABLC]) or liposomal carrier (liposomal AMB [L-AMB]) changes the rate and extent of drug distribution to the lung. The importance of pharmacokinetic differences among the various lipid AMB formulations in the treatment of invasive pulmonary aspergillosis (IPA) remains unknown. We compared the kinetics of AMB lung accumulation and fungal clearance of ABLC- and L-AMB-treated mice with acute IPA. BALB/c mice were immunosuppressed with cyclophosphamide and cortisone before intranasal inoculation with 1.5 × 106 Aspergillus fumigatus 293 conidia. ABLC or L-AMB was administered in daily intravenous doses (1, 5, or 10 mg/kg of body weight), starting 12 h after infection and continuing until day 5. At predetermined times (0, 24, 72, and 120 h), mice were euthanized, and lungs were harvested for determinations of lung fungal burdens (quantitative PCR) and total AMB lung tissue concentrations. Both ABLC and L-AMB were effective at reducing lung fungal burdens at doses of ≥5 mg/kg/day. Clearance of A. fumigatus during the first 24 h was associated with AMB tissue concentrations of >4 μg/g. At 5 mg/kg/day, ABLC produced a more rapid fungal clearance than did L-AMB, but at the end of therapy, fungal burden reductions were similar for both formulations and were not improved with higher dosages. These data suggest that ABLC delivers active AMB to the lung more rapidly than does L-AMB, resulting in faster Aspergillus clearance in an experimental model of IPA. However, pharmacodynamic differences between the two formulations were less apparent when mice were dosed at 10 mg/kg/day. PMID:17261624

  20. Transplant tourism and invasive fungal infection.

    PubMed

    Al Salmi, I; Metry, A M; Al Ismaili, F; Hola, A; Al Riyami, M; Khamis, F; Al-Abri, S

    2018-04-01

    Deceased and live-related renal transplants (RTXs) are approved procedures that are performed widely throughout the world. In certain regions, commercial RTX has become popular, driven by financial greed. This retrospective, descriptive study was performed at the Royal Hospital from 2013 to 2015. Data were collected from the national kidney transplant registry of Oman. All transplant cases retrieved were divided into two groups: live-related RTX performed in Oman and commercial-unrelated RTX performed abroad. These groups were then divided again into those with and without evidence of fungal infection, either in the wound or renal graft. A total of 198 RTX patients were identified, of whom 162 (81.8%) had undergone a commercial RTX that was done abroad. Invasive fungal infections (IFIs) were diagnosed in 8% of patients who had undergone a commercial RTX; of these patients, 76.9% underwent a nephrectomy and 23.1% continued with a functioning graft. None of the patients with RTXs performed at the Royal Hospital contracted an IFI. The most common fungal isolates were Aspergillus species (including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, and Aspergillus nigricans), followed by Zygomycetes. However, there was no evidence of fungal infection including Aspergillus outside the graft site. Computed tomography (CT) findings showed infarction of the graft, renal artery thrombosis, aneurysmal dilatation of the external iliac artery, fungal ball, or just the presence of a perigraft collection. Of the total patients with IFIs, 23.1% died due to septic shock and 53.8% were alive and on hemodialysis. The remaining 23.1% who did not undergo nephrectomy demonstrated acceptable graft function. This is the largest single-center study on commercial RTX reporting the highest number of patients with IFI acquired over a relatively short period of time. Aspergillus spp were the main culprit fungi, with no Candida spp being isolated. A high index of suspicion might

  1. Predicting Invasive Fungal Pathogens Using Invasive Pest Assemblages: Testing Model Predictions in a Virtual World

    PubMed Central

    Paini, Dean R.; Bianchi, Felix J. J. A.; Northfield, Tobin D.; De Barro, Paul J.

    2011-01-01

    Predicting future species invasions presents significant challenges to researchers and government agencies. Simply considering the vast number of potential species that could invade an area can be insurmountable. One method, recently suggested, which can analyse large datasets of invasive species simultaneously is that of a self organising map (SOM), a form of artificial neural network which can rank species by establishment likelihood. We used this method to analyse the worldwide distribution of 486 fungal pathogens and then validated the method by creating a virtual world of invasive species in which to test the SOM. This novel validation method allowed us to test SOM's ability to rank those species that can establish above those that can't. Overall, we found the SOM highly effective, having on average, a 96–98% success rate (depending on the virtual world parameters). We also found that regions with fewer species present (i.e. 1–10 species) were more difficult for the SOM to generate an accurately ranked list, with success rates varying from 100% correct down to 0% correct. However, we were able to combine the numbers of species present in a region with clustering patterns in the SOM, to further refine confidence in lists generated from these sparsely populated regions. We then used the results from the virtual world to determine confidences for lists generated from the fungal pathogen dataset. Specifically, for lists generated for Australia and its states and territories, the reliability scores were between 84–98%. We conclude that a SOM analysis is a reliable method for analysing a large dataset of potential invasive species and could be used by biosecurity agencies around the world resulting in a better overall assessment of invasion risk. PMID:22016773

  2. Predicting invasive fungal pathogens using invasive pest assemblages: testing model predictions in a virtual world.

    PubMed

    Paini, Dean R; Bianchi, Felix J J A; Northfield, Tobin D; De Barro, Paul J

    2011-01-01

    Predicting future species invasions presents significant challenges to researchers and government agencies. Simply considering the vast number of potential species that could invade an area can be insurmountable. One method, recently suggested, which can analyse large datasets of invasive species simultaneously is that of a self organising map (SOM), a form of artificial neural network which can rank species by establishment likelihood. We used this method to analyse the worldwide distribution of 486 fungal pathogens and then validated the method by creating a virtual world of invasive species in which to test the SOM. This novel validation method allowed us to test SOM's ability to rank those species that can establish above those that can't. Overall, we found the SOM highly effective, having on average, a 96-98% success rate (depending on the virtual world parameters). We also found that regions with fewer species present (i.e. 1-10 species) were more difficult for the SOM to generate an accurately ranked list, with success rates varying from 100% correct down to 0% correct. However, we were able to combine the numbers of species present in a region with clustering patterns in the SOM, to further refine confidence in lists generated from these sparsely populated regions. We then used the results from the virtual world to determine confidences for lists generated from the fungal pathogen dataset. Specifically, for lists generated for Australia and its states and territories, the reliability scores were between 84-98%. We conclude that a SOM analysis is a reliable method for analysing a large dataset of potential invasive species and could be used by biosecurity agencies around the world resulting in a better overall assessment of invasion risk.

  3. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review.

    PubMed

    Muskett, Hannah; Shahin, Jason; Eyres, Gavin; Harvey, Sheila; Rowan, Kathy; Harrison, David

    2011-01-01

    Over 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study. An internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining reliable estimates. This review

  4. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review

    PubMed Central

    2011-01-01

    Introduction Over 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study. Methods An internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Results Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining

  5. Breakthrough mucormycosis after voriconazole use in a case of invasive fungal rhinosinusitis due to Curvularia lunata.

    PubMed

    Gupta, Nitin; Kumar, Arvind; Singh, Gagandeep; Ratnakar, Gogineni; Vinod, Kutty Sharada; Wig, Naveet

    2017-01-01

    Invasive fungal rhinosinusitis (FRS) is a potentially fatal illness requiring early diagnosis and aggressive treatment with surgery and antifungals. We report a case of chronic FRS in a recently diagnosed diabetic individual due to Curvularia lunata. Imaging revealed extension into the right orbit and right basifrontal lobe. This was further complicated by development of nosocomial mucormycosis which was attributed to voriconazole therapy. The patient responded well to debridement and amphotericin B based therapy. To our knowledge, there are no reported cases of invasive FRS due to Curvularia lunata. Also, breakthrough mucormycosis on voriconazole therapy is rarely seen in non-malignancy, non-transplant settings. The possibility of rare fungal infections (community and nosocomial) should be entertained in developing settings where fungal spores are ubiquitous.

  6. Comparison of Non-Culture-Based Methods for Detection of Systemic Fungal Infections, with an Emphasis on Invasive Candida Infections

    PubMed Central

    White, P. Lewis; Archer, Alice E.; Barnes, Rosemary A.

    2005-01-01

    The accepted limitations associated with classic culture techniques for the diagnosis of invasive fungal infections have lead to the emergence of many non-culture-based methods. With superior sensitivities and quicker turnaround times, non-culture-based methods may aid the diagnosis of invasive fungal infections. In this review of the diagnostic service, we assessed the performances of two antigen detection techniques (enzyme-linked immunosorbent assay [ELISA] and latex agglutination) with a molecular method for the detection of invasive Candida infection and invasive aspergillosis. The specificities for all three assays were high (≥97%), although the Candida PCR method had enhanced sensitivity over both ELISA and latex agglutination with values of 95%, 75%, and 25%, respectively. However, calculating significant sensitivity values for the Aspergillus detection methods was not feasible due to a low number of proven/probable cases. Despite enhanced sensitivity, the PCR method failed to detect nucleic acid in a probable case of invasive Candida infection that was detected by ELISA. In conclusion, both PCR and ELISA techniques should be used in unison to aid the detection of invasive fungal infections. PMID:15872239

  7. Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

    PubMed Central

    Lee, Pamela P.; Lau, Yu-Lung

    2017-01-01

    The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and

  8. Active invasion of bacteria into living fungal cells

    PubMed Central

    Moebius, Nadine; Üzüm, Zerrin; Dijksterhuis, Jan; Lackner, Gerald; Hertweck, Christian

    2014-01-01

    The rice seedling blight fungus Rhizopus microsporus and its endosymbiont Burkholderia rhizoxinica form an unusual, highly specific alliance to produce the highly potent antimitotic phytotoxin rhizoxin. Yet, it has remained a riddle how bacteria invade the fungal cells. Genome mining for potential symbiosis factors and functional analyses revealed that a type 2 secretion system (T2SS) of the bacterial endosymbiont is required for the formation of the endosymbiosis. Comparative proteome analyses show that the T2SS releases chitinolytic enzymes (chitinase, chitosanase) and chitin-binding proteins. The genes responsible for chitinolytic proteins and T2SS components are highly expressed during infection. Through targeted gene knock-outs, sporulation assays and microscopic investigations we found that chitinase is essential for bacteria to enter hyphae. Unprecedented snapshots of the traceless bacterial intrusion were obtained using cryo-electron microscopy. Beyond unveiling the pivotal role of chitinolytic enzymes in the active invasion of a fungus by bacteria, these findings grant unprecedented insight into the fungal cell wall penetration and symbiosis formation. DOI: http://dx.doi.org/10.7554/eLife.03007.001 PMID:25182414

  9. [Mixed invasive fungal infection due to Rhizomucor pusillus and Aspergillus niger in an immunocompetent patient].

    PubMed

    Pozo-Laderas, Juan Carlos; Pontes-Moreno, Antonio; Robles-Arista, Juan Carlos; Bautista-Rodriguez, M Dolores; Candau-Alvarez, Alberto; Caro-Cuenca, Maria Teresa; Linares-Sicilia, María José

    2015-01-01

    Mucormycosis infections are rare in immunocompetent patients, and very few cases of mucormycosis associated with aspergillosis in non-haematological patients have been reported. A 17-year-old male, immunocompetent and without any previously known risk factors, was admitted to hospital due to a seizure episode 11 days after a motorcycle accident. He had a complicated clinical course as he had a mixed invasive fungal infection with pulmonary involvement due to Aspergillus niger and disseminated mucormycosis due to Rhizomucor pusillus (histopathological and microbiological diagnosis in several non-contiguous sites). He was treated with liposomal amphotericin B for 7 weeks (total cumulative dose >10 g) and required several surgical operations. The patient survived and was discharged from ICU after 5 months and multiple complications. Treatment with liposomal amphotericin B and aggressive surgical management achieved the eradication of a mixed invasive fungal infection. However, we emphasise the need to maintain a higher level of clinical suspicion and to perform microbiological techniques for early diagnosis of invasive fungal infections in non-immunocompromised patients, in order to prevent spread of the disease and the poor prognosis associated with it. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  10. Phylogenetics of a fungal invasion: origins and widespread dispersal of white-nose syndrome

    Treesearch

    Kevin P. Drees; Jeffrey M. Lorch; Sebastien J. Puechmaille; Katy L. Parise; Gudrun Wibbelt; Joseph R. Hoyt; Keping Sun; Ariunbold Jargalsaikhan; Munkhnast Dalannast; Jonathan M. Palmer; Daniel L. Lindner; A. Marm Kilpatrick; Talima Pearson; Paul S. Keim; David S. Blehert; Jeffrey T. Foster; Joseph Heitman

    2017-01-01

    Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans, a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has...

  11. [Risk factors of invasive fungal infections in patients admitted to non- hematological oncology department and pediatric intensive care unit].

    PubMed

    Zhao, Cheng-song; Zhao, Shun-ying; Liu, Gang; Xi-Wei, Xu

    2013-08-01

    To determine risk factors of invasive fungal infections (IFI) in patients admitted to non-hematological oncology department and pediatric intensive care unit (PICU), in order to improve diagnostic level of invasive fungal infections. We retrospectively assessed 85 hospitalized pediatric patients with invasive fungal infections in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2007 to Nov.2012. All the cases were either from non-hematological oncology department or the PICU.We reviewed risk factors of invasive fungal infections. Among 85 patients, 42 had invasive candida infection, 20 invasive aspergillus infection, 21 cryptococcus infection, 1 Histoplasma capsulatum infection and 1 Mucor mucedo infection.In the 42 patients with invasive candida infection, 5 were young infants, 3 had combined immunodeficiency, 1 cellular immunodeficiency, 25 secondary infection due to long term use of corticosteroids and/or combined use of more than 2 kinds of antibiotics with primary disease, 5 prior intestinal tract surgery or chronic diarrheal disease, 1 reflux gastritis.In the 20 patients with invasive aspergillosis infection, 10 patients had chronic granulomatous disease, 5 long term use of corticosteroids ≥ 1 month, 3 long term use of corticosteroids and combined use of more than 2 kinds of antibiotics, 2 had no apparent host factors.In the 21 patients with cryptococcus infection, 2 patients had used corticosteroids ≥ 1 month, 2 had immunodeficiency mainly for lack of antibodies, while others had no apparent host factors. The child with Mucor mucedo infection had diabetes mellitus. And the one with Histoplasma capsulatum infection had immunodeficiency. High risk factors for IFI in patients admitted to non-hematological oncology department and PICU are primary immunodeficiency disease and long term use of corticosteroids and/or long term combined use of more than 2 kinds of antibiotics. Besides, young infant is also a high risk factor for

  12. Invasive fungal infections after natural disasters.

    PubMed

    Benedict, Kaitlin; Park, Benjamin J

    2014-03-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed.

  13. Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?

    PubMed

    Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A

    2015-04-01

    Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.

  14. Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes.

    PubMed

    Dahlén, Torsten; Kalin, Mats; Cederlund, Kerstin; Nordlander, Anna; Björkholm, Magnus; Ljungman, Per; Blennow, Ola

    2016-02-01

    Posaconazole prophylaxis during induction chemotherapy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) has been shown to significantly decrease the incidence of invasive fungal disease (IFD) and increase overall survival in a trial setting, but only small real-life studies have been published. This was a retrospective cohort study including consecutive patients with AML/MDS treated with intensive induction chemotherapy; 176 patients received fluconazole prophylaxis 2008-2011 and 107 patients received posaconazole prophylaxis 2011-2013. Only proven and probable IFD according to the revised EORTC/MSG criteria were included in the analysis. The two cohorts were well matched without significant differences in patient characteristics. At day 100, patients receiving posaconazole had a significantly lower incidence of total IFD (0.9% vs. 10.8%, P < 0.01), invasive aspergillosis (0% vs. 5.7%, P = 0.02) and invasive candidiasis (0% vs. 4.0%, P < 0.05). There was no significant difference in overall survival, neither at day 100 (87% in the posaconazole group vs. 85% in the fluconazole group) nor at end of follow-up (78% vs. 77%). Posaconazole prophylaxis decreased the incidence of IFD but did not improve short-term overall survival. Improved treatment efficacy of manifest IFD is likely to explain the lack of survival benefit. © 2015 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

  15. Invasive Fungal Infections after Natural Disasters

    PubMed Central

    Benedict, Kaitlin

    2014-01-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed. PMID:24565446

  16. Diagnostic Imaging and Invasive Fungal Diseases in Children.

    PubMed

    Katragkou, Aspasia; Fisher, Brian T; Groll, Andreas H; Roilides, Emmanuel; Walsh, Thomas J

    2017-09-01

    Invasive fungal disease (IFD) is a life-threatening condition, especially in immunocompromised children. The role of diagnostic imaging in children at risk for an IFD is multifactorial, including initially detecting it, evaluating for dissemination of infection beyond the primary site of disease, monitoring the response to antifungal therapy, and assessing for potential relapse. The objective of this review was to synthesize the published literature relevant to the use of various imaging modalities for the diagnosis and management of IFD in children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Fungal endophytes from seeds of invasive, non-native Phragmites australis and their potential role in germination and seedling growth

    USGS Publications Warehouse

    Shearin, Zackery R. C.; Filipek, Matthew; Desai, Rushvi; Bickford, Wesley A.; Kowalski, Kurt P.; Clay, Keith

    2018-01-01

    Background and aimsWe characterized fungal endophytes of seeds of invasive, non-native Phragmites from three sites in the Great Lakes region to determine if fungal symbiosis could contribute to invasiveness through their effects on seed germination and seedling growth.MethodsField-collected seeds were surface sterilized and plated on agar to culture endophytes for ITS sequencing. Prevalence of specific endophytes from germinated and non-germinated seeds, and from seedlings, was compared.ResultsOne-third of 740 seeds yielded endophyte isolates. Fifteen taxa were identified with Alternaria sp. representing 54% of all isolates followed by Phoma sp. (21%) and Penicillium corylophilum (12%). Overall germination of seeds producing an isolate (36%) was significantly higher than seeds not producing an isolate (20%). Penicillium in particular was strongly associated with increased germination of seeds from one site. Sixty-three isolates and 11 taxa were also obtained from 30 seedlings where Phoma, Penicillium and Alternaria respectively were most prevalent. There was a significant effect of isolating an endophyte from the seed on seedling growth.ConclusionsThese results suggest that many endophyte taxa are transmitted in seeds and can increase seed germination and seedling growth of invasive Phragmites. The role of fungal endophytes in host establishment, growth and invasiveness in nature requires further research.

  18. Diagnostic value of (1 → 3)-β-D-glucan in bronchoalveolar lavage fluid for invasive fungal disease: A meta-analysis.

    PubMed

    Shi, Xin-Yu; Liu, Yao; Gu, Xian-Min; Hao, Sheng-Yu; Wang, Yu-Hong; Yan, Di; Jiang, Shu-Juang

    2016-08-01

    The serum (1 → 3)-β-D-glucan (BG) assay has been approved for diagnosing invasive fungal diseases (IFDs). However, the performance of (1 → 3)-β-D-glucan assay in bronchoalveolar lavage (BAL) fluid is various among studies. The present study aimed to assess the accuracy of (1 → 3)-β-D-glucan assay in bronchoalveolar lavage fluid for the diagnosis of invasive fungal diseases by means of meta-analysis and systematic review of relevant studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (OR) and a summary receiver-operating characteristic curve of BAL-BG for diagnosing invasive fungal diseases were pooled using meta-analysis. We also performed meta-regression analysis. A total of 838 patients (138 with proven or probable invasive fungal diseases), included in 6 studies, were analyzed. The pooled sensitivity, specificity, PLR, NLR and diagnostic odds ratio were 0.52 (95%CI, 0.38-0.53), 0.58 (95%CI, 0.55-0.61), 1.34 (95%CI, 1.08-1.66), 0.82 (95% CI, 0.63-1.07) and 1.71 (95%CI, 1.01-2.92) respectively. The area under the summary receiver operating characteristic curve, with 95% confidence intervals was 0.61 (95%CI, 0.67-0.55). The accuracy of (1 → 3)-β-D-glucan test in bronchoalveolar lavage fluid is marginal, so that the results should not be interpreted alone but can be used as a part of full assessment with clinical features, image findings and other laboratory results for the diagnosis of invasive fungal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. [Clinical analyses of the diagnosis and treatment of invasive fungal rhinosinusitis: report of 14 cases].

    PubMed

    Shi, G G; Shi, L; Zhang, Z Y; Wan, Y Z; Li, B; Yu, L; Zhang, E P; Ju, H S; He, M Q; Ji, H Z

    2016-08-07

    Through the retrospective analysis of the clinical data in 14 cases of invasive fungal rhinosinusitis (IFRS), the clinical characteristics, diagnosis and treatment of this disease were evaluated. Fourteen clinically confirmed cases of IFRS since January 2008 to October 2015 were evaluated.collected, the clinical features, diagnosis, treatment and prognosis were analyzed to obtain a more comprehensive understanding for clinical reference. Fourteen patients were confirmed by pathological examination as IFRS, including 9 cases of aspergillus, 4 cases of mucor, and 1 case of rhinocerebral zygomycosis; including 5 cases of acute IFRS, 9 cases of chronic IFRS. All patients were treated with endoscopic surgery and intravenous antifungal therapy. Nine cases of chronic IFRS (including 1 case of mucor, 7 cases of aspergillus and 1 case of rhinocerebral zygomycosis) were cured, but the vision loss, diplopia or blindness, hard palate perforation remained. Five cases of acute IFRS included 3 cases of mucor and 2 cases of aspergillus. Among the 3 cases of mucor, 2 cases were died and 1 case was cured. Among the 2 cases of aspergillus, 1 patient was cured and the other patient died of electrolyte disorder after discharge from hospital. Patients with IFRS usually have diabetes. After the active surgical cleaning of lesion tissue and the systematic antifungal treatment with adequate dosage, these patients would have a better result. IFRS caused by mucor is ofen dangerous.

  20. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases.

    PubMed

    Ruhnke, Markus; Schwartz, Stefan

    2016-12-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non- Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft- versus -host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay ( Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the 'traditional' empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  1. Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells.

    PubMed

    Kumaresan, Pappanaicken R; da Silva, Thiago Aparecido; Kontoyiannis, Dimitrios P

    2017-01-01

    Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in immunocompromised patients. Pattern-recognition receptors present on the surfaces of innate immune cells recognize fungal pathogens and activate the first line of defense against fungal infection. The second line of defense is the adaptive immune system which involves mainly CD4 + T cells, while CD8 + T cells also play a role. CD8 + T cell-based vaccines designed to prevent IFIs are currently being investigated in clinical trials, their use could play an especially important role in acquired immune deficiency syndrome patients. So far, none of the vaccines used to treat IFI have been approved by the FDA. Here, we review current and future antifungal immunotherapy strategies involving CD8 + T cells. We highlight recent advances in the use of T cells engineered using a Sleeping Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen receptor (CAR) T-cell therapy to treat patients with leukemia have shown very promising results. We hypothesized that CAR T cells could also be used to control IFI. Therefore, we designed a CAR that targets β-glucan, a sugar molecule found in most of the fungal cell walls, using the extracellular domain of Dectin-1, which binds to β-glucan. Mice treated with D-CAR + T cells displayed reductions in hyphal growth of Aspergillus compared to the untreated group. Patients suffering from IFIs due to primary immunodeficiency, secondary immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit from bioengineered CAR T cell therapy.

  2. Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

    PubMed Central

    Kumaresan, Pappanaicken R.; da Silva, Thiago Aparecido; Kontoyiannis, Dimitrios P.

    2018-01-01

    Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in immunocompromised patients. Pattern-recognition receptors present on the surfaces of innate immune cells recognize fungal pathogens and activate the first line of defense against fungal infection. The second line of defense is the adaptive immune system which involves mainly CD4+ T cells, while CD8+ T cells also play a role. CD8+ T cell-based vaccines designed to prevent IFIs are currently being investigated in clinical trials, their use could play an especially important role in acquired immune deficiency syndrome patients. So far, none of the vaccines used to treat IFI have been approved by the FDA. Here, we review current and future antifungal immunotherapy strategies involving CD8+ T cells. We highlight recent advances in the use of T cells engineered using a Sleeping Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen receptor (CAR) T-cell therapy to treat patients with leukemia have shown very promising results. We hypothesized that CAR T cells could also be used to control IFI. Therefore, we designed a CAR that targets β-glucan, a sugar molecule found in most of the fungal cell walls, using the extracellular domain of Dectin-1, which binds to β-glucan. Mice treated with D-CAR+ T cells displayed reductions in hyphal growth of Aspergillus compared to the untreated group. Patients suffering from IFIs due to primary immunodeficiency, secondary immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit from bioengineered CAR T cell therapy. PMID:29358941

  3. Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

    PubMed

    Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

    2011-09-01

    Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

  4. INVASIVE FUNGAL INFECTION AMONG FEBRILE PATIENTS WITH CHEMOTHERAPY-INDUCED NEUTROPENIA IN THAILAND.

    PubMed

    Phikulsod, Ployploen; Suwannawiboon, Bundarika; Chayakulkeeree, Methee

    2017-01-01

    Invasive fungal infections (IFI) can cause serious morbidity and mortality among febrile patients with chemotherapy-induced neutropenia (CIN). In order to evaluate the incidence, treatment outcome and factors associated with IFI in this patient population in Thailand, we retrospectively reviewed the medical record of patients admitted to Siriraj Hospital from January 2008 to June 2010. Criteria used to diagnosed IFI were those of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases/Mycoses Study Group (EORTC/MSG) consensus 2008 criteria. Three hundred ten episodes of chemotherapy-induced neutropenia occurred in 233 patients. IFI were found in 37 episodes (12%) and occurred only in patients who received chemotherapy for hematological malignancies. The incidence of IFI among patients with hematologic malignancies was 14%. Most commonly occurred in AML patients (17%). Patients who received aggressive induction chemotherapy regimens for AML had the highest incidence of IFI (20.5%). Of the 37 episodes, 12 were candidiasis, 5 were aspergillosis, 1 was zygomycosis, 1 was fusariosis, 10 were probable and 9 were possible IFI. The IFI-related mortality was 35%. The clinical factor associated with IFI was a temperature > 39 °C during febrile neutropenia. A higher mortality rate was seen in patients aged > 40 years and those with a serum albumin level < 3 g/dl.

  5. The burden of serious fungal diseases in Russia.

    PubMed

    Klimko, N; Kozlova, Y; Khostelidi, S; Shadrivova, O; Borzova, Y; Burygina, E; Vasilieva, N; Denning, D W

    2015-10-01

    The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082. © 2015 Blackwell Verlag GmbH.

  6. Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature.

    PubMed

    Benedict, Kaitlin; Chiller, Tom M; Mody, Rajal K

    2016-07-01

    Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration.

  7. [Significance of MUC5B antibody in differential diagnosis between Aspergillus species and Mucorales of fungal sinusitis].

    PubMed

    Piao, Ying-shi; Liu, Hong-gang; Liu, Xian-jun

    2008-04-01

    To differentiate between Aspergillus species and Mucorales of fungal sinusitis by immunohistochemistry. Formalin-fixed paraffin-embedded tissue blocks of 66 cases of fungal sinusitis were retrieved from the archival files of Department of Pathology of Beijing Tongren Hospital during the period from 2001 to 2006. The samples included 29 cases of fungal balls, 12 cases of allergic fungal sinusitis, 24 cases of chronic invasive fungal sinusitis and 1 case of acute invasive fungal sinusitis. The types of fungi were 44 Aspergillus species (31 cases of A. fumigatus, 7 cases of A. flavus and 6 cases of A. terreus) and 22 Mucorales (14 cases of Mucor species and 8 cases of Rhizopus species). Immunohistochemistry was performed with MUC2, MUC5AC and MUC5B antibodies. The results were compared with histochemical study for periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains. Immunohistochemical study for MUC5B showed that the positive rate of Aspergillus species was 90.9%, in contrast to 4.5% in Mucorales (P < 0.001). The expression of MUC2 and MUC5AC was completely negative, whereas PAS and GMS stains were positive in all cases. MUC5B antibody appears to be a useful immunohistochemical marker for identifying fungal types in tissue sections, especially in distinguishing between Aspergillus species and Mucorales in fungal sinusitis.

  8. Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature

    PubMed Central

    Benedict, Kaitlin; Chiller, Tom M.; Mody, Rajal K.

    2017-01-01

    Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration. PMID:27074753

  9. Clinical Utility of Fungal Screening Assays in Adults with Severe Burns

    DTIC Science & Technology

    2013-01-01

    available test, FungitellTM Glucan Assay for (1,3) b D glucan (BG) in serum (Associates of Cape Cod Inc., East Falmouth, MA), is a qualitative...considered a positive test in the United States and was used as a positive value in this study. A positive test is reported with a b D glucan concentration... Glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous

  10. [Invasive fungal infections in immunocompromised patients with focus on aspergillosis and its causative agents].

    PubMed

    Paloušová, Dita; Lengerová, Martina; Volfová, Pavlína; Bejdák, Petr; Kocmanová, Iva; Mayer, Jiří; Ráčil, Zdeněk

    2012-08-01

    Invasive fungal diseases (IFD) are a life-threatening infectious complications in immunocompromised patients and are associated with high rate of morbidity and mortality. The most common invasive mycosis in patients who underwent an allogeneic hematopoietic stem cell transplantation is invasive aspergilosis (IA), most frequently caused by the clinically dominant species Aspergillus fumigatus and, rarely, also by Aspergillus flavus, Aspergillus terreus and Aspergillus niger. In recent years, other related Aspergillus species were also reported to cause IFD, phenotypically similar to A. fumigatus and moreover, frequently exhibiting resistance towards various antifungals. For example, it is Aspergillus lentulus, Aspergillus viridinutans, Neosartoya fischeri, etc. Classical microbiological methods such as direct microscopy or culture are usually used for the identification of Aspergillus species. The application of PCR-based molecular techniques and monitoring of secondary metabolites production enable detection and identification of species, which are not distinguishable solely by their morphology. PCR methods are also useful for molecular strain typing of aspergilli and can reveal the genetic diversity of isolates.

  11. [Clinically documented fungal infections].

    PubMed

    Kakeya, Hiroshi; Kohno, Shigeru

    2008-12-01

    Proven fungal infections are diagnosed by histological/microbiological evidence of fungi at the site of infection and positive blood culture (fungemia). However, invasive diagnosing examinations are not always applied for all of immunocompromised patients. Clinically documented invasive fungal infections are diagnosed by typical radiological findings such as halo sign on chest CT plus positive serological/molecular evidence of fungi. Serological tests of Aspergillus galactomannan antigen and beta-glucan for aspergillosis and cryptococcal glucuronoxylomannan antigen for cryptococcosis are useful. Hence, none of reliable serological tests for zygomycosis are available so far. In this article, risk factors, sign and symptoms, and diagnostic methods for clinically documented cases of invasive aspergillosis, pulmonary cryptococcosis, and zygomycosis with diabates, are reviewed.

  12. Posaconazole vs fluconazole or itraconazole for prevention of invasive fungal diseases in patients with acute myeloid leukemia or myelodysplastic syndrome: a cost-effectiveness analysis in an Asian teaching hospital.

    PubMed

    Chan, Thomas S Y; Marcella, Stephen W; Gill, Harinder; Hwang, Yu-Yan; Kwong, Yok-Lam

    2016-01-01

    Posaconazole is superior to fluconazole/itraconazole in preventing invasive fungal diseases (IFDs) in neutropenic patients. Whether the higher cost of posaconazole is offset by decreases in IFDs in a given institute requires cost-effective analysis encompassing the spectrum of IFDs and socioeconomic factors specific to that geographic area. This study performed a cost-effective analysis of posaconazole prophylaxis for IFDs in an Asian teaching hospital, employing decision modeling and data of IFDs and medication costs specific to the institute, in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In the cost-effectiveness analysis, the higher cost of posaconazole was partially offset by a reduction in the cost of treating IFDs that were prevented, resulting in an incremental cost of 125,954 Hong Kong dollars/16,148 USD per IFD avoided. Over a lifetime horizon, assuming same case fatality rate of IFDs in both groups, use of posaconazole results in 0.07 discounted life years saved. This corresponds to an incremental cost of 116,023 HKD/14,875 USD per life year saved. This incremental cost per life year saved in posaconazole prophylaxis fulfilled the World Health Organization defined threshold for cost-effectiveness. Posaconazole prophylaxis was cost-effective in Hong Kong.

  13. Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods

    PubMed Central

    Enguita, Francisco J.; Costa, Marina C.; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José; Leitão, Ana Lúcia

    2016-01-01

    Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future design of more efficient therapeutic strategies. Simultaneous transcriptomic studies of pathogen and host by high-throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the intricate regulatory networks underlying the infectious process. This protocol is starting to be applied to the study of the interactions between fungal pathogens and their hosts. To date, our knowledge of the molecular basis of infection for fungal pathogens is still very limited, and the putative role of regulatory players such as non-coding RNAs or epigenetic factors remains elusive. The wider application of high-throughput transcriptomics in the near future will help to understand the fungal mechanisms for colonization and survival, as well as to characterize the molecular responses of the host cell against a fungal infection. PMID:29376924

  14. Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

    PubMed Central

    Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

    2015-01-01

    Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

  15. Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis.

    PubMed

    Kale, Shiv D; Ayubi, Tariq; Chung, Dawoon; Tubau-Juni, Nuria; Leber, Andrew; Dang, Ha X; Karyala, Saikumar; Hontecillas, Raquel; Lawrence, Christopher B; Cramer, Robert A; Bassaganya-Riera, Josep

    2017-12-06

    Incidences of invasive pulmonary aspergillosis, an infection caused predominantly by Aspergillus fumigatus, have increased due to the growing number of immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in the host to facilitate invasive disease, the distinct mechanisms that govern the host-pathogen interaction remain enigmatic, particularly in the context of distinct immune modulating therapies. To gain insights into these mechanisms, RNA-Seq technology was utilized to sequence RNA derived from lungs of 2 clinically relevant, but immunologically distinct murine models of IPA on days 2 and 3 post inoculation when infection is established and active disease present. Our findings identify notable differences in host gene expression between the chemotherapeutic and steroid models at the interface of immunity and metabolism. RT-qPCR verified model specific and nonspecific expression of 23 immune-associated genes. Deep sequencing facilitated identification of highly expressed fungal genes. We utilized sequence similarity and gene expression to categorize the A. fumigatus putative in vivo secretome. RT-qPCR suggests model specific gene expression for nine putative fungal secreted proteins. Our analysis identifies contrasting responses by the host and fungus from day 2 to 3 between the two models. These differences may help tailor the identification, development, and deployment of host- and/or fungal-targeted therapeutics.

  16. Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy.

    PubMed

    Mattiuzzi, Gloria N; Kantarjian, Hagop; Faderl, Stefan; Lim, JoAnn; Kontoyiannis, Dimitrios; Thomas, Deborah; Wierda, William; Raad, Isaam; Garcia-Manero, Guillermo; Zhou, Xian; Ferrajoli, Alexandra; Bekele, Nebiyou; Estey, Elihu

    2004-02-01

    The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy. Copyright 2003 American Cancer Society.

  17. [Antifungal therapy for infants, children and adolescents with suspected or documented invasive fungal infection].

    PubMed

    Odio, C M

    2010-04-01

    Fungal nosocomial infections have gradually and consistently increased since the 90s.This increasing threat is closely related with the growing number of people with immune system disorders and their survival. It is also related with the destruction of their physical barriers against infection due to the use of cytotoxic drugs or invasive procedures, such is the case of cancer patients and bone marrow and solid organ transplant patients. Increased survival of patients with congenital or acquired immunodeficiency, premature babies and patients with complex congenital malformations, especially in the gastrointestinal tract, also add up to this scenario. The occurrence of yeast and filamentous fungi infections, especially of the Candida species, has been on the rise. Azole agents overuse, especially fluconazole, for the treatment and prophylaxis of fungal infections has put selective pressure on Candida spp. which resulted in an increase of non-albican species such as C. krusei, C. glabrata and C. famata, among others, as well as their growing resistance to these antifungal agents.

  18. Phylogenetics of a Fungal Invasion: Origins and Widespread Dispersal of White-Nose Syndrome.

    PubMed

    Drees, Kevin P; Lorch, Jeffrey M; Puechmaille, Sebastien J; Parise, Katy L; Wibbelt, Gudrun; Hoyt, Joseph R; Sun, Keping; Jargalsaikhan, Ariunbold; Dalannast, Munkhnast; Palmer, Jonathan M; Lindner, Daniel L; Marm Kilpatrick, A; Pearson, Talima; Keim, Paul S; Blehert, David S; Foster, Jeffrey T

    2017-12-12

    Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans , a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has exhibited few genetic polymorphisms in previous studies, presenting challenges for both epizoological tracking of the spread of this fungus and for determining its evolutionary history. We used single nucleotide polymorphisms (SNPs) from whole-genome sequencing and microsatellites to construct high-resolution phylogenies of P. destructans Shallow genetic diversity and the lack of geographic structuring among North American isolates support a recent introduction followed by expansion via clonal reproduction across the epizootic zone. Moreover, the genetic relationships of isolates within North America suggest widespread mixing and long-distance movement of the fungus. Genetic diversity among isolates of P. destructans from Europe was substantially higher than in those from North America. However, genetic distance between the North American isolates and any given European isolate was similar to the distance between the individual European isolates. In contrast, the isolates we examined from Asia were highly divergent from both European and North American isolates. Although the definitive source for introduction of the North American population has not been conclusively identified, our data support the origin of the North American invasion by P. destructans from Europe rather than Asia. IMPORTANCE This phylogenetic study of the bat white-nose syndrome agent, P. destructans , uses genomics to elucidate evolutionary relationships among populations of the fungal pathogen to understand the epizoology of this biological invasion. We analyze hypervariable and abundant genetic characters (microsatellites and genomic SNPs

  19. Fungal colonization in soils with different management histories: modeling growth in three-dimensional pore volumes.

    PubMed

    Kravchenko, Alexandra; Falconer, Ruth E; Grinev, Dmitri; Otten, Wilfred

    2011-06-01

    Despite the importance of fungi in soil functioning they have received comparatively little attention, and our understanding of fungal interactions and communities is lacking. This study aims to combine a physiologically based model of fungal growth with digitized images of internal pore volume of samples of undisturbed soil from contrasting management practices to determine the effect of physical structure on fungal growth dynamics. We quantified pore geometries of the undisturbed-soil samples from two contrasting agricultural practices, conventionally plowed (chisel plow) (CT) and no till (NT), and from native-species vegetation land use on land that was taken out of production in 1989 (NS). Then we modeled invasion of a fungal species within the soil samples and evaluated the role of soil structure on the progress of fungal colonization of the soil pore space. The size of the studied pores was > or =110 microm. The dynamics of fungal invasion was quantified through parameters of a mathematical model fitted to the fungal invasion curves. Results indicated that NT had substantially lower porosity and connectivity than CT and NS soils. For example, the largest connected pore volume occupied 79% and 88% of pore space in CT and NS treatments, respectively, while it only occupied 45% in NT. Likewise, the proportion of pore space available to fungal colonization was much greater in NS and CT than in NT treatment, and the dynamics of the fungal invasion differed among the treatments. The relative rate of fungal invasion at the onset of simulation was higher in NT samples, while the invasion followed a more sigmoidal pattern with relatively slow invasion rates at the initial time steps in NS and CT samples. Simulations allowed us to elucidate the contribution of physical structure to the rates and magnitudes of fungal invasion processes. It appeared that fragmented pore space disadvantaged fungal invasion in soils under long-term no-till, while large connected pores in

  20. [Non-invasive mechanical ventilation in the treatment of acute heart failure].

    PubMed

    Alfonso Megido, Joaquín; González Franco, Alvaro

    2014-03-01

    When acute heart failure progresses and there is acute cardiogenic pulmonary edema, routine therapeutic measures should be accompanied by other measures that help to correct oxygenation of the patient. The final and most drastic step is mechanical ventilation. Non-invasive ventilation has been developed in the last few years as a method that attempts to improve oxygenation without the need for intubation, thus, in theory, reducing morbidity and mortality in these patients. The present article describes the controversies surrounding the results of this technique and discusses its indications. The article also discusses how to start non-invasive ventilation in patients with acute pulmonary edema from a practical point of view. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  1. Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients.

    PubMed

    Vinh, Daniel; Yim, Michael; Dutta, Ankhi; Jones, John K; Zhang, Wei; Sitton, Matthew

    2017-08-01

    To investigate outcomes of pediatric patients at a single institution with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact overall survival. All pediatric patients at a large tertiary children's hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015 were retrospectively reviewed. Demographics, underlying diseases, symptoms, antifungal therapy, absolute neutrophil count (ANC), surgical management,and outcomes were analyzed. Seventeen patients were identified with IFRS with an average age of 8.7 years and 53% male. Hematologic malignancy was the most common (n = 13) underlying disease. The most common presenting symptoms were fever (82%) and congestion (41%). 15 patients had severe neutropenia (Absolute Neutrophil Count (ANC) < 500) within 2 weeks prior to diagnosis. The average ANC at time of diagnosis was 1420 cells/uL. 16 patients were treated with serial nasal endoscopy and debridement, while 1 patient was treated with an open approach. 16 received combination antifungals while 1 was treated with amphotericin monotherapy. The most common genus cultured was Fusarium (n = 6). The average number of surgical interventions was 3.4, with the average interval between interventions 6.2 days. 13 of 17 (76%) were cleared of IFRS. Overall survival at 6 months was 41%. Pediatric IFRS is a life-threatening disease that requires a coordinated surgical and medical approach. Despite a relatively high local control rate, overall mortality remains disappointingly high, reflecting the disease's underlying pathogenesis - lack of host defense and risk of disseminated fungal infection. Further investigation is necessary to reveal optimal management with regards to antifungal therapy, surgery, and utility of labs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Risk Factors Associated with Invasive Fungal Infections in Combat Trauma

    PubMed Central

    Rodriguez, Carlos J.; Weintrob, Amy C.; Shah, Jinesh; Malone, Debra; Dunne, James R.; Weisbrod, Allison B.; Lloyd, Bradley A.; Warkentien, Tyler E.; Murray, Clinton K.; Wilkins, Kenneth; Shaikh, Faraz; Carson, M. Leigh; Aggarwal, Deepak

    2014-01-01

    Abstract Background: In recent years, invasive fungal infections (IFI) have complicated the clinical course of patients with combat-related injuries. Commonalities in injury patterns and characteristics among patients with IFI led to the development of a Joint Trauma System (JTS) clinical practice guideline (CPG) for IFI management. We performed a case-control study to confirm and further delineate risk factors associated with IFI development in combat casualties with the objective of generating data to refine the CPG and promote timelier initiation of treatment. Methods: Data were collected retrospectively for United States (U.S.) military personnel injured during deployment in Afghanistan from June 2009 through August 2011. Cases were identified as IFI based upon wound cultures with fungal growth and/or fungal elements seen on histology, in addition to the presence of recurrent wound necrosis. Controls were matched using date of injury (±3 mo) and injury severity score (±10). Risk factor parameters analyzed included injury circumstances, blood transfusion requirements, amputations after first operative intervention, and associated injuries. Data are expressed as multivariate odds ratios (OR; 95% confidence interval [CI]). Results: Seventy-six IFI cases were identified from 1,133 U.S. military personnel wounded in Afghanistan and matched to 150 controls. Parameters associated significantly with the development of IFI multivariate analysis were blast injuries (OR: 5.7; CI: 1.1–29.6), dismounted at time of injury (OR: 8.5; CI: 1.2–59.8); above the knee amputations (OR: 4.1; CI: 1.3-12.7), and large-volume packed red blood cell (PRBC; >20 U) transfusions within first 24 h (OR: 7.0; CI: 2.5-19.7). Conclusions: Our analysis indicates that dismounted blast injuries, resulting in above the knee amputations, and requirement of large volume PRBC transfusions are independent predictors of IFI development. These data confirm all the preliminary risk factors, except for

  3. British Thoracic Society Quality Standards for acute non-invasive ventilation in adults

    PubMed Central

    Davies, Michael; Allen, Martin; Bentley, Andrew; Bourke, Stephen C; Creagh-Brown, Ben; D’Oliveiro, Rachel; Glossop, Alastair; Gray, Alasdair; Jacobs, Phillip; Mahadeva, Ravi; Moses, Rachael; Setchfield, Ian

    2018-01-01

    Introduction The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for the provision of acute non-invasive ventilation in adults together with measurable markers of good practice. Methods Development of British Thoracic Society (BTS) Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. Results 6 quality statements have been developed, each describing a standard of care for the provision of acute non-invasive ventilation in the UK, together with measurable markers of good practice. Conclusion BTS Quality Standards for acute non-invasive ventilation in adults form a key part of the range of supporting materials that the Society produces to assist in the dissemination and implementation of guideline’s recommendations. PMID:29636979

  4. Challenges on non-invasive ventilation to treat acute respiratory failure in the elderly.

    PubMed

    Scala, Raffaele

    2016-11-15

    Acute respiratory failure is a frequent complication in elderly patients especially if suffering from chronic cardio-pulmonary diseases. Non-invasive mechanical ventilation constitutes a successful therapeutic tool in the elderly as, like in younger patients, it is able to prevent endotracheal intubation in a wide range of acute conditions; moreover, this ventilator technique is largely applied in the elderly in whom invasive mechanical ventilation is considered not appropriated. Furthermore, the integration of new technological devices, ethical issues and environment of treatment are still largely debated in the treatment of acute respiratory failure in the elderly.This review aims at reporting and critically analyzing the peculiarities in the management of acute respiratory failure in elderly people, the role of noninvasive mechanical ventilation, the potential advantages of applying alternative or integrated therapeutic tools (i.e. high-flow nasal cannula oxygen therapy, non-invasive and invasive cough assist devices and low-flow carbon-dioxide extracorporeal systems), drawbacks in physician's communication and "end of life" decisions. As several areas of this topic are not supported by evidence-based data, this report takes in account also "real-life" data as well as author's experience.The choice of the setting and of the timing of non-invasive mechanical ventilation in elderly people with advanced cardiopulmonary disease should be carefully evaluated together with the chance of using integrated or alternative supportive devices. Last but not least, economic and ethical issues may often challenges the behavior of the physicians towards elderly people who are hospitalized for acute respiratory failure at the end stage of their cardiopulmonary and neoplastic diseases.

  5. Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

    PubMed

    Fisher, Brian T; Robinson, Paula D; Lehrnbecher, Thomas; Steinbach, William J; Zaoutis, Theoklis E; Phillips, Bob; Sung, Lillian

    2017-05-26

    Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia.

    PubMed

    Vallipuram, Janaki; Dhalla, Sidika; Bell, Chaim M; Dresser, Linda; Han, Heekyung; Husain, Shahid; Minden, Mark D; Paul, Narinder S; So, Miranda; Steinberg, Marilyn; Vallipuram, Mayuran; Wong, Gary; Morris, Andrew M

    2017-04-01

    Chest computed tomography (CT) findings of nodules, ground glass opacities, and consolidations are often interpreted as representing invasive fungal infection in individuals with febrile neutropenia. We assessed whether these CT findings were present in asymptomatic individuals with acute myeloid leukemia (AML) at low risk of invasive fungal disease. A retrospective study of consecutive asymptomatic adult patients with newly diagnosed AML over a 2-year period was performed at a tertiary care oncology center. Radiology reports of baseline chest CTs were reviewed. Of 145 CT scans, the majority (88%) had pulmonary abnormalities. Many (70%) had one or both of unspecified opacities (52%) and nodules (49%). Ground glass opacities (18%) and consolidations (12%) occurred less frequently. Radiologists suggested pneumonia as a possible diagnosis in 32% (n = 47) of scans. Chest CT may result in over-diagnosis of invasive fungal disease in individuals with febrile neutropenia if interpreted without correlation to the patients' clinical status.

  7. Co-incidental Plasmodium Knowlesi and Mucormycosis infections presenting with acute kidney injury and lower gastrointestinal bleeding.

    PubMed

    Ramaswami, Arunachalam; Pisharam, Jayakrishnan K; Aung, Hla; Ghazala, Kafeel; Maboud, Khalil; Chong, Vui Heng; Tan, Jackson

    2013-01-01

    Plasmodium knowlesi is frequently reported in Southeast Asian countries and is now widely regarded as the fifth malarial parasite. Mucormycosis is a rare fungal infection that can occur in patients with a weakened immune system. We report a case of acute kidney injury secondary to Plasmodium knowlesi malaria infection and mucormycosis fungal infection. In addition, the patient also had lower gastrointestinal bleeding from invasive gastrointestinal mucormycosis. P. knowlesi infection was diagnosed by blood film and mucormycosis was diagnosed by histopathological examination of biopsy specimen of the colon. The patient recovered with antimalarial treatment (Quinine), antifungal treatment (Lipophilic Amphotericin), and supportive hemodialysis treatment. We hypothesize that P. knowlesi malarial infection can lower the immunologic threshold and predisposes vulnerable individuals to rare disseminated fungal infections. To the best of our knowledge, this is the first P. Knowlesi malaria-associated invasive fungal infection reported in the literature.

  8. High-Throughput Sequencing Reveals Drastic Changes in Fungal Communities in the Phyllosphere of Norway Spruce (Picea abies) Following Invasion of the Spruce Bud Scale (Physokermes piceae).

    PubMed

    Menkis, Audrius; Marčiulynas, Adas; Gedminas, Artūras; Lynikienė, Jūratė; Povilaitienė, Aistė

    2015-11-01

    The aim of this study was to assess the diversity and composition of fungal communities in damaged and undamaged shoots of Norway spruce (Picea abies) following recent invasion of the spruce bud scale (Physokermes piceae) in Lithuania. Sampling was done in July 2013 and included 50 random lateral shoots from ten random trees in each of five visually undamaged and five damaged 40-50-year-old pure stands of P. abies. DNA was isolated from 500 individual shoots, subjected to amplification of the internal transcribed spacer of fungal ribosomal DNA (ITS rDNA), barcoded and sequenced. Clustering of 149,426 high-quality sequences resulted in 1193 non-singleton contigs of which 1039 (87.1 %) were fungal. In total, there were 893 fungal taxa in damaged shoots and 608 taxa in undamaged shoots (p < 0.0001). Furthermore, 431 (41.5 %) fungal taxa were exclusively in damaged shoots, 146 (14.0 %) were exclusively in undamaged shoots, and 462 (44.5 %) were common to both types of samples. Correspondence analysis showed that study sites representing damaged and undamaged shoots were separated from each other, indicating that in these fungal communities, these were largely different and, therefore, heavily affected by P. piceae. In conclusion, the results demonstrated that invasive alien tree pests may have a profound effect on fungal mycobiota associated with the phyllosphere of P. abies, and therefore, in addition to their direct negative effect owing physical damage of the tissue, they may also indirectly determine health, sustainability and, ultimately, distribution of the forest tree species.

  9. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

    PubMed

    Pomares, Helena; Arnan, Montserrat; Sánchez-Ortega, Isabel; Sureda, Anna; Duarte, Rafael F

    2016-08-01

    The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis. © 2016 Blackwell Verlag GmbH.

  10. Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.

    PubMed

    King, Jill; Pana, Zoi-Dorothea; Lehrnbecher, Thomas; Steinbach, William J; Warris, Adilia

    2017-09-01

    Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.

  11. Hospital environment fungal contamination and aspergillosis risk in acute leukaemia patients in Sousse (Tunisia).

    PubMed

    Gheith, Soukeina; Ranque, Stéphane; Bannour, Wadiaa; Ben Youssef, Yosra; Khelif, Abderrahim; Ben Said, Moncef; Njah, Mansour; Saghrouni, Fatma

    2015-06-01

    Hospital environment is considered the main source of invasive aspergillosis (IA) in leukemic patients. This study aimed to describe Aspergillus colonisation in leukemic patients and their hospital environment and to test whether Aspergillus environmental contamination was associated with IA. For a 2-year period including 14-month renovation work, 91 acute leukaemia inpatients at the hematology department of University hospital in Sousse (Tunisia) were prospectively included. The incidence of probable IA (EORTC/MSG criteria) was 9.9%. Fifty-six Aspergillus were isolated from 53 (6.5%) of 811 sputa collected from 35 (38.5%) patients. Aspergillus spp. were isolated in 59.7% of 494 air samples and in 52.8% of 1579 surface samples taken in the patients' room. Aspergillus section Nigri (72.7%) was the most frequent. Aspergillus contamination peaked in autumn and winter on surface and in summer and autumn in air samples and was higher (P = 0.03) during the renovation work period. Multivariate analysis showed that for each Aspergillus section Nigri CFU airborne contamination IA risk increased by 1.05 (P = 0.04). In Tunisia, Aspergillus section Nigri and Flavi, but not Fumigati, are chiefly involved in IA. Our findings support swift implementation of airborne fungal contamination control measures in areas where immunocompromised patient are hospitalised. © 2015 Blackwell Verlag GmbH.

  12. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2013-02-01

    Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Seed bank survival of an invasive species, but not of two native species, declines with invasion.

    PubMed

    Orrock, John L; Christopher, Cory C; Dutra, Humberto P

    2012-04-01

    Soil-borne seed pathogens may play an important role in either hindering or facilitating the spread of invasive exotic plants. We examined whether the invasive shrub Lonicera maackii (Caprifoliaceae) affected fungi-mediated mortality of conspecific and native shrub seeds in a deciduous forest in eastern Missouri. Using a combination of L. maackii removal and fungicide treatments, we found no effect of L. maackii invasion on seed viability of the native Symphoricarpos orbiculatus (Caprifoliaceae) or Cornus drummondii (Cornaceae). In contrast, fungi were significant agents of L. maackii seed mortality in invaded habitats. Losses of L. maackii to soil fungi were also significant in invaded habitats where L. maackii had been removed, although the magnitude of the effect of fungi was lower, suggesting that changes in soil chemistry or microhabitat caused by L. maackii were responsible for affecting fungal seed pathogens. Our work suggests that apparent competition via soil pathogens is not an important factor contributing to impacts of L. maackii on native shrubs. Rather, we found that fungal seed pathogens have density-dependent effects on L. maackii seed survival. Therefore, while fungal pathogens may provide little biotic resistance to early invasion by L. maackii, our study illustrates that more work is needed to understand how changes in fungal pathogens during the course of an invasion contribute to the potential for restoration of invaded systems. More generally, our study suggests that increased rates of fungal pathogen attack may be realized by invasive plants, such as L. maackii, that change the chemical or physical environment of the habitats they invade.

  14. Race and invasive fungal infection in solid organ transplant recipients.

    PubMed

    Boehme, Amelia K; McGwin, Gerald; Andes, David R; Lyon, G Marshall; Chiller, Tom; Pappas, Peter G; Baddley, John W

    2014-01-01

    Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n = 1,214) and controls (n = 16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR = .97, 95% Cl 0.82-1.15, P = .7125), while participants who identified as other ethnicity were less likely to develop IFI (OR = .56, 95% Cl .41-.75, P < .001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95% CI 1.35-3.54, P = .002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients.

  15. Invasive fungal infections and antifungal therapies in solid organ transplant recipients.

    PubMed

    Gabardi, Steven; Kubiak, David W; Chandraker, Anil K; Tullius, Stefan G

    2007-12-01

    This manuscript will review the risk factors, prevalence, clinical presentation, and management of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients. Primary literature was obtained via MEDLINE (1966-April 2007) and EMBASE. Abstracts were obtained from scientific meetings or pharmaceutical manufacturers and included in the analysis. All studies and abstracts evaluating IFIs and/or antifungal therapies, with a primary focus on solid organ transplantation, were considered for inclusion. English-language literature was selected for inclusion, but was limited to those consisting of human subjects. Infectious complications following SOT are common. IFIs are associated with high morbidity and mortality rates in this patient population. Determining the best course of therapy is difficult due to the limited availability of data in SOT recipients. Well-designed clinical studies are infrequent and much of the available information is often based on case-reports or retrospective analyses. Transplant practitioners must remain aware of their therapeutic options and the advantages and disadvantages associated with the available treatment alternatives.

  16. Effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection

    PubMed Central

    Zhang, Yu; Gu, Fang; Wang, Fengxian; Zhang, Yuanda

    2016-01-01

    Objective: To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection. Methods: A total of 120 patients with burn-induced invasive fungal infection were randomly divided into an early enteral nutrition (EN) group and a parenteral nutrition (PN) group (n=60). The patients were given nutritional support intervention for 14 days, and the expression levels of serum transferrin, albumin, total protein, endotoxin, D-lactic acid and inflammatory cytokines were detected on the 1st, 7th and 14th days respectively. Results: As the treatment progressed, the levels of serum transferrin, albumin and total protein of the EN group were significantly higher than those of the PN group (P<0.05), while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower (P<0.05). After treatment, the expression levels of IL-6 and TNF-α were decreased in the EN group, which were significantly different from those of the PN group (P<0.05). During treatment, the incidence rates of complications such as abdominal distension, diarrhea, sepsis, nausea, vomiting and gastric retention were similar. The mean healing time of wound surface was 9.34±0.78 days in the EN group and 12.46±2.19 days in the PN group, i.e. such time of the former was significantly shorter than that of the latter (P<0.05). Conclusion: Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction, strengthen cellular immune function and promote wound healing, thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier. PMID:27375697

  17. An estimation of burden of serious fungal infections in France.

    PubMed

    Gangneux, J-P; Bougnoux, M-E; Hennequin, C; Godet, C; Chandenier, J; Denning, D W; Dupont, B

    2016-12-01

    An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Contrasting introduction scenarios among continents in the worldwide invasion of the banana fungal pathogen Mycosphaerella fijiensis.

    PubMed

    Robert, S; Ravigne, V; Zapater, M-F; Abadie, C; Carlier, J

    2012-03-01

    Reconstructing and characterizing introduction routes is a key step towards understanding the ecological and evolutionary factors underlying successful invasions and disease emergence. Here, we aimed to decipher scenarios of introduction and stochastic demographic events associated with the global spread of an emerging disease of bananas caused by the destructive fungal pathogen Mycosphaerella fijiensis. We analysed the worldwide population structure of this fungus using 21 microsatellites and 8 sequence-based markers on 735 individuals from 37 countries. Our analyses designated South-East Asia as the source of the global invasion and supported the location of the centre of origin of M. fijiensis within this area. We confirmed the occurrence of bottlenecks upon introduction into other continents followed by widespread founder events within continents. Furthermore, this study suggested contrasting introduction scenarios of the pathogen between the African and American continents. While potential signatures of admixture resulting from multiple introductions were detected in America, all the African samples examined seem to descend from a single successful founder event. In combination with historical information, our study reveals an original and unprecedented global scenario of invasion for this recently emerging disease caused by a wind-dispersed pathogen. © 2012 Blackwell Publishing Ltd.

  19. Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick

    PubMed Central

    de Groot, Piet W. J.; Bader, Oliver; de Boer, Albert D.; Weig, Michael

    2013-01-01

    Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenic Candida species, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases. PMID:23397570

  20. Estimating the Burden of Serious Fungal Infections in Uruguay

    PubMed Central

    Macedo-Viñas, Marina

    2018-01-01

    We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries, and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure (inhabitants): total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk (total cases per year): HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006; asthma in adults 223,431; cystic fibrosis in adults 48; tuberculosis 613; lung cancer 1400. Annual incidence estimations per 100,000: invasive aspergillosis, 22.4; candidemia, 16.4; Candida peritonitis, 3.7; Pneumocystis jirovecii pneumonia, 1.62; cryptococcosis, 0.75; severe asthma with fungal sensitization, 217; allergic bronchopulmonary aspergillosis, 165; recurrent Candida vaginitis, 6323; oral candidiasis, 74.5; and esophageal candidiasis, 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis, and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis, and warrant access to first line antifungals. PMID:29562641

  1. Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study.

    PubMed

    Hsu, L Y; Lee, D G; Yeh, S P; Bhurani, D; Khanh, B Q; Low, C Y; Norasetthada, L; Chan, T; Kwong, Y L; Vaid, A K; Alejandria, I; Mendoza, M; Chen, C Y; Johnson, A; Tan, T Y

    2015-06-01

    We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Performance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory

    PubMed Central

    Bernal-Martinez, L.; Castelli, M. V.; Rodriguez-Tudela, J. L.; Cuenca-Estrella, M.

    2014-01-01

    A retrospective analysis of real-time PCR (RT-PCR) results for 151 biopsy samples obtained from 132 patients with proven invasive fungal diseases was performed. PCR-based techniques proved to be fast and sensitive and enabled definitive diagnosis in all cases studied, with detection of a total of 28 fungal species. PMID:24574295

  3. [Invasive fungal infections in children with cancer, neutropenia and fever, in Chile].

    PubMed

    Lucero, Yalda; Brücher, Roberto; Alvarez, Ana María; Becker, Ana; Cofré, José; Enríquez, Nancy; Payá, Ernesto; Salgado, Carmen; Santolaya, María Elena; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Zubieta, Marcela; O'Ryan, Miguel

    2002-10-01

    Invasive fungal infections (IFI) cause prolonged hospitalizations and increase the possibility of death among patients with cancer and febrile neutropenia (FN). Up to 10% of febrile neutropenic episodes may be caused by IFI. To estimate the incidence of IFI among a large group of Chilean children with cancer and FN. Clinical and laboratory information was collected from a data base provided by the "Programa Infantil Nacional de Drogas Antineoplásicas" (PINDA) that included 445 FN episodes occurring in five hospitals in Santiago, Chile. This information was used to identify children that presented with signs and symptoms compatible with an IFI. According to predefined criteria based on a literature review, IFI episodes were categorized as "proven", "probable" or "possible". A total of 41/445 episodes (9.2%) were compatible with an IFI of which 4 (0.9%) were proven, 23 (5.2%) probable, and 14 (3.1%) possible. Hospitalization was longer (27 vs 8 days, p < .01), new infectious foci appeared with higher frequency (71 vs 38%, p < .01), and mortality was higher (10 vs 1.6%, p < .001) in children with IFI compatible episodes, when compared to children who did not have an IFI. The estimated incidence of IFI in Chilean children with cancer and FN ranged between 6-9% depending on the stringency of criteria selection used for classification. This estimate is similar to that reported by other studies. The low detection yield of clinically compatible IFI underscores the need of improved diagnosis of fungal infections in this population.

  4. Complications of hematopoietic stem transplantation: Fungal infections.

    PubMed

    Omrani, Ali S; Almaghrabi, Reem S

    2017-12-01

    Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients. The improved diagnostic performance of serum biomarkers such as galactomannan and β-D-glucan, as well as polymerase chain reaction assays has allowed the development of diagnostic-driven antifungal therapy strategies for high risk patients. Diagnostic-driven approaches have resulted in reduced unnecessary antifungal exposure, improved diagnosis of invasive fungal disease, and reduced costs without increased risk of mortality. The appropriateness of diagnostic-driven antifungal strategy for individual HSCT centers depends on the availability and turnaround times for diagnostics, multidisciplinary expertise, and the local epidemiology of invasive fungal infections. Echinocandins are the treatment of choice for invasive candidiasis in most HSCT recipients. Fluconazole may be used for the treatment of invasive candidiasis in hemodynamically stable patients with no prior azole exposure. The primary treatment of choice for invasive aspergillosis is voriconazole. Alternatives include isavuconazole and lipid formulations of amphotericin. Currently available evidence does not support routine primary combination antifungal therapy for invasive aspergillosis. However, combination salvage antifungal therapy may be considered in selected patients. Therapeutic drug monitoring is recommended for the majority of HSCT recipients on itraconazole, posaconazole, or voriconazole. Copyright © 2017

  5. Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.

    PubMed

    Barnes, Rosemary A; Stocking, Kate; Bowden, Sarah; Poynton, Matthew H; White, P Lewis

    2013-09-01

    The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

    PubMed Central

    Kuo, I fan; Ensom, Mary H H

    2009-01-01

    Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective: To determine the utility of therapeutic drug monitoring for voriconazole. Methods: A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole. Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug–drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug–drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25–2 mg/L and 4–6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions: Routine therapeutic drug monitoring of voriconazole is not recommended except in certain

  7. Outcomes with invasive vs conservative management of cardiogenic shock complicating acute myocardial infarction.

    PubMed

    Bangalore, Sripal; Gupta, Navdeep; Guo, Yu; Lala, Anuradha; Balsam, Leora; Roswell, Robert O; Reyentovich, Alex; Hochman, Judith S

    2015-06-01

    In the SHOCK trial, an invasive strategy of early revascularization was associated with a significant mortality benefit at 6 months when compared with initial stabilization in patients with cardiogenic shock complicating acute myocardial infarction. Our objectives were to evaluate the data on real-world practice and outcomes of invasive vs conservative management in patients with cardiogenic shock. We analyzed data from the Nationwide Inpatient Sample from 2002 to 2011 with primary discharge diagnosis of acute myocardial infarction and secondary diagnosis of cardiogenic shock. Propensity score matching was used to assemble a cohort of patients managed invasively (with cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery) vs conservatively with similar baseline characteristics. The primary outcome was in-hospital mortality. We identified 60,833 patients with cardiogenic shock, of which 20,644 patients (10,322 in each group) with similar propensity scores, including 11,004 elderly patients (≥75 years), were in the final analysis. Patients who underwent invasive management had 59% lower odds of in-hospital mortality (37.7% vs 59.7%; odds ratio [OR] 0.41; 95% confidence interval [CI], 0.39-0.43; P < .0001) when compared with those managed conservatively. This lower mortality was consistently seen across all tested subgroups; specifically in the elderly (≥75 years) (44.0% vs 63.6%; OR 0.45; 95% CI, 0.42-0.49; P < .0001) and those younger than 75 years (30.6% vs 55.1%; OR 0.36; 95% CI, 0.33-0.39; P < .0001), although the magnitude of risk reduction differed (Pinteraction < .0001). In this largest cohort of patients with cardiogenic shock complicating acute myocardial infarction, patients managed invasively had significantly lower mortality when compared with those managed conservatively, even in the elderly. Our results emphasize the need for aggressive management in this high-risk subgroup. Copyright © 2015 Elsevier

  8. Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

    PubMed

    Czurda, Stefan; Lion, Thomas

    2017-01-01

    Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

  9. Human Skin Fungal Diversity

    PubMed Central

    Findley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Schoenfeld, Deborah; Nomicos, Effie; Park, Morgan; Kong, Heidi H.; Segre, Julia A.

    2013-01-01

    Traditional culture-based methods have incompletely defined the etiology of common recalcitrant human fungal skin diseases including athlete’s foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms, while providing a home for diverse commensal microbiota1. Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders2,3,4. However, microbial diversity is not limited to bacteria; microorganisms such as fungi also play major roles in microbial community stability, human health and disease5. Genomic methodologies to identify fungal species and communities have been limited compared with tools available for bacteria6. Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes7. Here, we sequenced and analyzed fungal communities of 14 skin sites in 10 healthy adults. Eleven core body and arm sites were dominated by Malassezia fungi, with species-level classifications revealing greater topographical resolution between sites. By contrast, three foot sites, plantar heel, toenail, and toeweb, exhibited tremendous fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that skin physiologic attributes and topography differentially shape these two microbial communities. These results provide a framework for future investigation of interactions between pathogenic and commensal fungal and bacterial communities in maintaining human health and contributing to disease pathogenesis. PMID:23698366

  10. Early Complications and Outcomes in Combat Injury Related Invasive Fungal Wound Infections: A Case-Control Analysis

    PubMed Central

    Lewandowski, Louis R.; Weintrob, Amy C.; Tribble, David R.; Rodriguez, Carlos J.; Petfield, Joseph; Lloyd, Bradley A.; Murray, Clinton K.; Stinner, Daniel; Aggarwal, Deepak; Shaikh, Faraz; Potter, Benjamin K.

    2015-01-01

    Objective Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures prior to initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. Design Retrospective review and case-control analysis. Setting Military hospitals. Patients/Participants United States military personnel injured during combat operations (2009–2011). The IFI cases were identified based upon the presence of recurrent, necrotic extremity wounds with mold growth in culture and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. Intervention None. Main Outcome Measurements Amputation revision rate and loss of functional levels. Results Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (p<0.001). Additionally, significantly (p<0.001) higher number of operative procedures and longer duration to initial wound closure was associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% CI: 1.17, 2.01). The supplemental matching analysis found similar results. Conclusions Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. PMID:26360542

  11. [Favorable Outcome of Hepatosplenic Candidiasis in a Patient with Acute Leukemia].

    PubMed

    Čolović, Nataša; Arsenijević, Valentina Arsić; Suvajdžić, Nada; Djunić, Irena; Tomin, Dragica

    2015-01-01

    Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy "3+7" regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2 x 170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (FI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy.Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for"probable HSC" and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved.

  12. Serious fungal infections in Pakistan.

    PubMed

    Jabeen, K; Farooqi, J; Mirza, S; Denning, D; Zafar, A

    2017-06-01

    The true burden of fungal infection in Pakistan is unknown. High-risk populations for fungal infections [tuberculosis (TB), diabetes, chronic respiratory diseases, asthma, cancer, transplant and human immunodeficiency virus (HIV) infection] are numerous. Here, we estimate the burden of fungal infections to highlight their public health significance. Whole and at-risk population estimates were obtained from the WHO (TB), BREATHE study (COPD), UNAIDS (HIV), GLOBOCAN (cancer) and Heartfile (diabetes). Published data from Pakistan reporting fungal infections rates in general and specific populations were reviewed and used when applicable. Estimates were made for the whole population or specific populations at risk, as previously described in the LIFE methodology. Of the 184,500,000 people in Pakistan, an estimated 3,280,549 (1.78%) are affected by a serious fungal infection, omitting all cutaneous infection, oral candidiasis and allergic fungal sinusitis, which we could not estimate. Compared with other countries, the rates of candidaemia (21/100,000) and mucormycosis (14/100,000) are estimated to be very high, and are based on data from India. Chronic pulmonary aspergillosis rates are estimated to be high (39/100,000) because of the high TB burden. Invasive aspergillosis was estimated to be around 5.9/100,000. Fungal keratitis is also problematic in Pakistan, with an estimated rate of 44/100,000. Pakistan probably has a high rate of certain life- or sight-threatening fungal infections.

  13. [Nasal phaeohyphomycosis by Curvularia spicifera in pediatric patient with neutropenia and acute myeloid leukemia].

    PubMed

    Bay, Constanza; González, Tamara; Munoz, Gonzalo; Legarraga, Paulette; Vizcaya, Cecilia; Abarca, Katia

    2017-06-01

    There are very few reports of pediatric patients with infections by dematiaceous filamentous fungi. In this publication we report a case of invasive fungal infection of the nasal septum by Curvularia spicifera in a pediatric patient with acute myeloid leukemia. The patient presented with a painful scabby wound in the nasal vestibule. Culture and universal PCR were consistent with Curvularia spicifera. Early management with surgical debridement and bi-associated antifungal therapy achieved complete resolution of the lesions, with no evidence of dissemination and relapses. Clinical management of these fungal infections represents a challenge as the antifungal selection and duration of therapy is not yet well stablished.

  14. Phylogenetics of a fungal invasion: Origins and widespread dispersal of white-nose syndrome

    USGS Publications Warehouse

    Drees, Kevin P.; Lorch, Jeffrey M.; Puechmaille, Sebastein J.; Parise, Katy L.; Wibbelt, Gudrun; Hoyt, Joseph R.; Sun, Keping; Jargalsaikhan, Ariunbold; Dalannast, Munkhnast; Palmer, Jonathan M.; Linder, Daniel L.; Kilpatrick, Marm; Pearson, Talima; Keim, Paul S.; Blehert, David; Foster, Jeffrey T.

    2017-01-01

    Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans, a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has exhibited few genetic polymorphisms in previous studies, presenting challenges for both epizoological tracking of the spread of this fungus and for determining its evolutionary history. We used single nucleotide polymorphisms (SNPs) from whole-genome sequencing and microsatellites to construct high-resolution phylogenies of P. destructans. Shallow genetic diversity and the lack of geographic structuring among North American isolates support a recent introduction followed by expansion via clonal reproduction across the epizootic zone. Moreover, the genetic relationships of isolates within North America suggest widespread mixing and long-distance movement of the fungus. Genetic diversity among isolates of P. destructans from Europe was substantially higher than in those from North America. However, genetic distance between the North American isolates and any given European isolate was similar to the distance between the individual European isolates. In contrast, the isolates we examined from Asia were highly divergent from both European and North American isolates. Although the definitive source for introduction of the North American population has not been conclusively identified, our data support the origin of the North American invasion by P. destructans from Europe rather than Asia.

  15. Phylogenetics of a Fungal Invasion: Origins and Widespread Dispersal of White-Nose Syndrome

    PubMed Central

    Drees, Kevin P.; Lorch, Jeffrey M.; Puechmaille, Sebastien J.; Parise, Katy L.; Wibbelt, Gudrun; Hoyt, Joseph R.; Sun, Keping; Jargalsaikhan, Ariunbold; Dalannast, Munkhnast; Lindner, Daniel L.; Marm Kilpatrick, A.; Pearson, Talima; Blehert, David S.

    2017-01-01

    ABSTRACT Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans, a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has exhibited few genetic polymorphisms in previous studies, presenting challenges for both epizoological tracking of the spread of this fungus and for determining its evolutionary history. We used single nucleotide polymorphisms (SNPs) from whole-genome sequencing and microsatellites to construct high-resolution phylogenies of P. destructans. Shallow genetic diversity and the lack of geographic structuring among North American isolates support a recent introduction followed by expansion via clonal reproduction across the epizootic zone. Moreover, the genetic relationships of isolates within North America suggest widespread mixing and long-distance movement of the fungus. Genetic diversity among isolates of P. destructans from Europe was substantially higher than in those from North America. However, genetic distance between the North American isolates and any given European isolate was similar to the distance between the individual European isolates. In contrast, the isolates we examined from Asia were highly divergent from both European and North American isolates. Although the definitive source for introduction of the North American population has not been conclusively identified, our data support the origin of the North American invasion by P. destructans from Europe rather than Asia. PMID:29233897

  16. Plant hormones: a fungal point of view.

    PubMed

    Chanclud, Emilie; Morel, Jean-Benoit

    2016-10-01

    Most classical plant hormones are also produced by pathogenic and symbiotic fungi. The way in which these molecules favour the invasion of plant tissues and the development of fungi inside plant tissues is still largely unknown. In this review, we examine the different roles of such hormone production by pathogenic fungi. Converging evidence suggests that these fungal-derived molecules have potentially two modes of action: (i) they may perturb plant processes, either positively or negatively, to favour invasion and nutrient uptake; and (ii) they may also act as signals for the fungi themselves to engage appropriate developmental and physiological processes adapted to their environment. Indirect evidence suggests that abscisic acid, gibberellic acid and ethylene produced by fungi participate in pathogenicity. There is now evidence that auxin and cytokinins could be positive regulators required for virulence. Further research should establish whether or not fungal-derived hormones act like other fungal effectors. © 2016 The Authors. Molecular Plant Pathology Published by British Society for Plant Pathology and John Wiley & Sons Ltd.

  17. Fungal endophytes which invade insect galls: insect pathogens, benign saprophytes, or fungal inquilines?

    PubMed

    Wilson, Dennis

    1995-08-01

    Fungi are frequently found within insect galls. However, the origin of these fungi, whether they are acting as pathogens, saprophytes invading already dead galls, or fungal inquilines which invade the gall but kill the gall maker by indirect means, is rarely investigated. A pathogenic role for these fungi is usually inferred but never tested. I chose the following leaf-galling-insect/host-plant pairs (1) a cynipid which forms two-chambered galls on the veins of Oregon white oak, (2) a cynipid which forms single-chambered galls on California coast live oak, and (3) an aphid which forms galls on narrowleaf cottonwood leaves. All pairs were reported to have fungi associated with dead insects inside the gall. These fungi were cultured and identified. For the two cynipids, all fungi found inside the galls were also present in the leaves as fungal endophytes. The cottonwood leaves examined did not harbor fungal endophytes. For the cynipid on Oregon white oak, the fungal endophyte grows from the leaf into the gall and infects all gall tissue but does not directly kill the gall maker. The insect dies as a result of the gall tissue dying from fungal infection. Therefore, the fungus acts as an inquiline. Approximately 12.5% of these galls die as a result of invasion by the fungal endophyte.

  18. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

    PubMed

    Pappas, Peter G; Alexander, Barbara D; Andes, David R; Hadley, Susan; Kauffman, Carol A; Freifeld, Alison; Anaissie, Elias J; Brumble, Lisa M; Herwaldt, Loreen; Ito, James; Kontoyiannis, Dimitrios P; Lyon, G Marshall; Marr, Kieren A; Morrison, Vicki A; Park, Benjamin J; Patterson, Thomas F; Perl, Trish M; Oster, Robert A; Schuster, Mindy G; Walker, Randall; Walsh, Thomas J; Wannemuehler, Kathleen A; Chiller, Tom M

    2010-04-15

    Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

  19. Burden of serious fungal infections in the Czech Republic.

    PubMed

    Chrdle, Aleš; Mallátová, Nad'a; Vašáková, Martina; Haber, Jan; Denning, David W

    2015-10-01

    We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care. © 2015 Blackwell Verlag GmbH.

  20. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

    PubMed Central

    Carter, Shelly L.; Walsh, Thomas J.; Kurtzberg, Joanne; Small, Trudy N.; Baden, Lindsey R.; Gersten, Iris D.; Mendizabal, Adam M.; Leather, Helen L.; Confer, Dennis L.; Maziarz, Richard T.; Stadtmauer, Edward A.; Bolaños-Meade, Javier; Brown, Janice; DiPersio, John F.; Boeckh, Michael; Marr, Kieren A.

    2010-01-01

    Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803. PMID:20826719

  1. Defining Responses to Therapy and Study Outcomes in Clinical Trials of Invasive Fungal Diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria

    PubMed Central

    Segal, Brahm H.; Herbrecht, Raoul; Stevens, David A.; Ostrosky-Zeichner, Luis; Sobel, Jack; Viscoli, Claudio; Walsh, Thomas J.; Maertens, Johan; Patterson, Thomas F.; Perfect, John R.; Dupont, Bertrand; Wingard, John R.; Calandra, Thierry; Kauffman, Carol A.; Graybill, John R.; Baden, Lindsey R.; Pappas, Peter G.; Bennett, John E.; Kontoyiannis, Dimitrios P.; Cordonnier, Catherine; Viviani, Maria Anna; Bille, Jacques; Almyroudis, Nikolaos G.; Wheat, L. Joseph; Graninger, Wolfgang; Bow, Eric J.; Holland, Steven M.; Kullberg, Bart-Jan; Dismukes, William E.; De Pauw, Ben E.

    2009-01-01

    Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge. PMID:18637757

  2. Invasive fungal infections in endogenous Cushing's syndrome

    PubMed Central

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  3. Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

    PubMed

    Jaworski, Radoslaw; Haponiuk, Ireneusz; Irga-Jaworska, Ninela; Chojnicki, Maciej; Steffens, Mariusz; Paczkowski, Konrad; Zielinski, Jacek

    2016-09-01

    Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may

  4. Fungal endocarditis in paediatrics: a review of 192 cases (1971-2016).

    PubMed

    Ganesan, Vithiya; Ponnusamy, Shunmuga Sundaram; Sundaramurthy, Raja

    2017-10-01

    The aims of this article were to review the published literature on fungal endocarditis in children and to discuss the aetiology and diagnosis, with emphasis on non-invasive methods and various treatment regimes. We systematically reviewed published cases and case series of fungal endocarditis in children. We searched the literature, including PubMed and individual references for publications of original articles, single cases, or case series of paediatric fungal endocarditis, with the following keywords: "fungal endocarditis", "neonates", "infants", "child", and "cardiac vegetation". There have been 192 documented cases of fungal endocarditis in paediatrics. The highest number of cases was reported in infants (93/192, 48%) including 60 in neonates. Of the neonatal cases, 57 were premature with a median gestational age of 27 weeks and median birth weight of 860 g. Overall, 120 yeast - fungus that grows as a single cell - infections and 43 mould - fungus that grows in multicellular filaments, hyphae - infections were reported. With increasing age, there was an increased infection rate with moulds. All the yeast infections were detected by blood culture. In cases with mould infection, diagnosis was mainly established by culture or histology of emboli or infected valves after invasive surgical procedures. There have been a few recent cases of successful early diagnosis by non-invasive methods such as blood polymerase chain reaction (PCR) for moulds. The overall mortality for paediatric fungal endocarditis was 56.25%. The most important cause of death was cardiac complications due to heart failure. Among the various treatment regimens used, none of them was significantly associated with better outcome. Non-invasive methods such as PCR tests can be used to improve the chances of detecting and identifying the aetiological agent in a timely manner. Delays in the diagnosis of these infections may result in high mortality and morbidity. No significant difference was noted

  5. Surgical treatment of acute acromioclavicular joint dislocations: hook plate versus minimally invasive reconstruction.

    PubMed

    Metzlaff, S; Rosslenbroich, S; Forkel, P H; Schliemann, B; Arshad, H; Raschke, M; Petersen, W

    2016-06-01

    This study was performed to compare the clinical results of a minimally invasive technique for acute acromioclavicular (AC) joint dislocation repair with the traditional hook plate fixation. Forty-four patients with an acute (within 2 weeks after trauma) complete AC joint separation (35 male, nine female; median age 36.2 years, range 18-56) underwent surgical repair with either a minimally invasive AC joint repair or a conventional hook plate. Functional outcome was evaluated using the Constant-Murley Score (CMS), the TAFT score and the AC joint instability score (ACJI). Radiographic evaluation was performed with bilateral anterior-posterior (a.p.) stress and Alexander views. All patients were available after a median follow-up of 32 months (range 24-51). There were no significant differences in the mean CMS, Taft score and the ACJI between the two groups. The radiological assessment revealed no significant difference in the coracoclavicular distance. In both groups, a slight loss of reduction was observed. Periarticular ossification was seen in 11 patients of the minimally invasive AC joint repair and eight patients of the hook plate group but this did not affect the final outcome. Hook plates were removed after a median interval of 11.9 weeks (range 10-13). Good clinical results can be achieved with both minimally invasive AC joint repair and hook plate fixation. However, in the hook plate group a second operation is mandatory for plate removal. III.

  6. Sphingolipids as targets for treatment of fungal infections

    PubMed Central

    Rollin-Pinheiro, Rodrigo; Singh, Ashutosh; Barreto-Bergter, Eliana; Del Poeta, Maurizio

    2016-01-01

    Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids. PMID:27502288

  7. Tissue-Resident Macrophages in Fungal Infections.

    PubMed

    Xu, Shengjie; Shinohara, Mari L

    2017-01-01

    Invasive fungal infections result in high morbidity and mortality. Host organs targeted by fungal pathogens vary depending on the route of infection and fungal species encountered. Cryptococcus neoformans infects the respiratory tract and disseminates throughout the central nervous system. Candida albicans infects mucosal tissues and the skin, and systemic Candida infection in rodents has a tropism to the kidney. Aspergillus fumigatus reaches distal areas of the lung once inhaled by the host. Across different tissues in naïve hosts, tissue-resident macrophages (TRMs) are one of the most populous cells of the innate immune system. Although they function to maintain homeostasis in a tissue-specific manner during steady state, TRMs may function as the first line of defense against invading pathogens and may regulate host immune responses. Thus, in any organs, TRMs are uniquely positioned and specifically programmed to function. This article reviews the current understanding of the roles of TRMs during major fungal infections.

  8. Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

    PubMed Central

    López-Jiménez, Javier; Cornely, Oliver A.; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L. P. S.; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

    2014-01-01

    Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.) PMID:25049247

  9. Consensus guidelines for implementation of quality processes to prevent invasive fungal disease and enhanced surveillance measures during hospital building works, 2014.

    PubMed

    Chang, C C; Ananda-Rajah, M; Belcastro, A; McMullan, B; Reid, A; Dempsey, K; Athan, E; Cheng, A C; Slavin, M A

    2014-12-01

    Healthcare-associated fungal outbreaks impose a substantial economic burden on the health system and typically result in high patient morbidity and mortality, particularly in the immunocompromised host. As the population at risk of invasive fungal infection continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ preventative measures has become increasingly important. These guidelines outline the standard quality processes hospitals need to accommodate into everyday practice and at times of healthcare-associated outbreak, including the role of antifungal stewardship programmes and best practice environmental sampling. Specific recommendations are also provided to help guide the planning and implementation of quality processes and enhanced surveillance before, during and after high-risk activities, such as hospital building works. Areas in which information is still lacking and further research is required are also highlighted. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  10. Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis

    PubMed Central

    Calmettes, Claire; Gabriel, Frederic; Blanchard, Elodie; Servant, Vincent; Bouchet, Stéphane; Kabore, Nathanael; Forcade, Edouard; Leroyer, Camille; Bidet, Audrey; Latrabe, Valérie; Leguay, Thibaut; Vigouroux, Stephane; Tabrizi, Reza; Breilh, Dominique; Accoceberry, Isabelle; de Lara, Manuel Tunon; Pigneux, Arnaud; Milpied, Noel; Dumas, Pierre-Yves

    2018-01-01

    Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed. A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%. In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

  11. Evolution of acuteness in pathogen metapopulations: conflicts between “classical” and invasion-persistence trade-offs

    PubMed Central

    Shrestha, Sourya; Bjørnstad, Ottar N.; King, Aaron A.

    2014-01-01

    Classical life-history theory predicts that acute, immunizing pathogens should maximize between-host transmission. When such pathogens induce violent epidemic outbreaks, however, a pathogen’s short-term advantage at invasion may come at the expense of its ability to persist in the population over the long term. Here, we seek to understand how the classical and invasion-persistence trade-offs interact to shape pathogen life-history evolution as a function of the size and structure of the host population. We develop an individual-based infection model at three distinct levels of organization: within an individual host, among hosts within a local population, and among local populations within a metapopulation. We find a continuum of evolutionarily stable pathogen strategies. At one end of the spectrum—in large well-mixed populations—pathogens evolve to greater acuteness to maximize between-host transmission: the classical trade-off theory applies in this regime. At the other end of the spectrum—when the host population is broken into many small patches—selection favors less acute pathogens, which persist longer within a patch and thereby achieve enhanced between-patch transmission: the invasion-persistence tradeoff dominates in this regime. Between these extremes, we explore the effects of the size and structure of the host population in determining pathogen strategy. In general, pathogen strategies respond to evolutionary pressures arising at both scales. PMID:25214895

  12. Monitoring of clinical strains and environmental fungal aerocontamination to prevent invasive aspergillosis infections in hospital during large deconstruction work: a protocol study

    PubMed Central

    Loeffert, Sophie Tiphaine; Melloul, Elise; Dananché, Cédric; Hénaff, Laetitia; Bénet, Thomas; Cassier, Pierre; Dupont, Damien; Guillot, Jacques; Botterel, Françoise; Wallon, Martine; Gustin, Marie-Paule; Vanhems, Philippe

    2017-01-01

    Introduction Monitoring fungal aerocontamination is an essential measure to prevent severe invasive aspergillosis (IA) infections in hospitals. One central block among 32 blocks of Edouard Herriot Hospital (EHH) was entirely demolished in 2015, while care activities continued in surrounding blocks. The main objective was to undertake broad environmental monitoring and clinical surveillance of IA cases to document fungal dispersion during major deconstruction work and to assess clinical risk. Methods and analysis A daily environmental survey of fungal loads was conducted in eight wards located near the demolition site. Air was collected inside and outside selected wards by agar impact samplers. Daily spore concentrations were monitored continuously by volumetric samplers at a flow rate of 10 L.min-1. Daily temperature, wind direction and speed as well as relative humidity were recorded by the French meteorological station Meteociel. Aspergillus fumigatus strains stored will be genotyped by multiple-locus, variable-number, tandem-repeat analysis. Antifungal susceptibility will be assessed by E-test strips on Roswell Park Memorial Institute medium supplemented with agar. Ascertaining the adequacy of current environmental monitoring techniques in hospital is of growing importance, considering the rising impact of fungal infections and of curative antifungal costs. The present study could improve the daily management of IA risk during major deconstruction work and generate new data to ameliorate and redefine current guidelines. Ethics and dissemination This study was approved by the clinical research and ethics committees of EHH. PMID:29175886

  13. Invasive strategy and frailty in very elderly patients with acute coronary syndromes.

    PubMed

    Llaó, Isaac; Ariza-Solé, Albert; Sanchis, Juan; Alegre, Oriol; López-Palop, Ramon; Formiga, Francesc; Marín, Francisco; Vidán, María T; Martínez-Sellés, Manuel; Sionis, Alessandro; Vives-Borrás, Miguel; Gómez-Hospital, Joan Antoni; Gómez-Lara, Josep; Roura, Gerard; Díez-Villanueva, Pablo; Núñez-Gil, Iván; Maristany, Jaume; Asmarats, Lluis; Bueno, Héctor; Abu-Assi, Emad; Cequier, Àngel

    2018-04-03

    Current guidelines recommend an early invasive strategy in patients with non-ST segment elevation acute coronary syndromes (NSTEACS). The role of an invasive strategy in frail elderly patients remains controversial. The LONGEVO-SCA registry included unselected NSTEACS patients aged ≥80 years. A geriatric assessment was performed during hospitalization, including frailty. We evaluated the impact of an invasive strategy during the admission on the incidence of cardiac death, reinfarction or new revascularisation at 6-months. From 531 patients included, 145 (27.3%) were frail. Mean age was 84.3 years. Most patients underwent an invasive strategy (407/531, 76.6%). Patients undergoing an invasive strategy were younger and had lower proportion of frailty (23.3% vs 40.3%, p<0.001). The incidence of cardiac events was more common in patients managed conservatively, after adjusting for confounding factors (sub-Hazard ratio (sHR) 2.32, 95% confidence interval (CI) 1.26-4.29, p=0.007). This association remained significant in non-frail patients (sHR 3.85, 95% CI 2.13-6.95, p=0.001), but was not significant in patients with established frailty criteria (sHR 1.40, 95% CI 0.72-2.75, p=0.325). The interaction invasive strategy-frailty was significant (p=0.032) Conclusions: An invasive strategy was independently associated with better outcomes in very elderly patients with NSTEACS. This association was different according to frailty status.

  14. Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil.

    PubMed

    de Oliveira, Renata Buccheri; Atobe, Jane Harumi; Souza, Simone Aparecida; de Castro Lima Santos, Daniel Wagner

    2014-08-01

    Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20-25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.

  15. Dermatophyte-host relationship of a murine model of experimental invasive dermatophytosis.

    PubMed

    Venturini, James; Alvares, Anuska Marcelino; Camargo, Marcela Rodrigues de; Marchetti, Camila Martins; Fraga-Silva, Thais Fernanda de Campos; Luchini, Ana Carolina; Arruda, Maria Sueli Parreira de

    2012-11-01

    Recognizing the invasive potential of the dermatophytes and understanding the mechanisms involved in this process will help with disease diagnosis and with developing an appropriate treatment plan. In this report, we present the histopathological, microbiological and immunological features of a model of invasive dermatophytosis that is induced by subcutaneous infection of Trichophyton mentagrophytes in healthy adult Swiss mice. Using this model, we observed that the fungus rapidly spreads to the popliteal lymph nodes, spleen, liver and kidneys. Similar to the human disease, the lymph nodes were the most severely affected sites. The fungal infection evoked acute inflammation followed by a granulomatous reaction in the mice, which is similar to what is observed in patients. The mice were able to mount a Th1-polarized immune response and displayed IL-10-mediated immune regulation. We believe that the model described here will provide valuable information regarding the dermatophyte-host relationship and will yield new perspective for a better understanding of the immunological and pathological aspects of invasive dermatophytosis. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study.

    PubMed

    Wallentin, Lars; Lindhagen, Lars; Ärnström, Elisabet; Husted, Steen; Janzon, Magnus; Johnsen, Søren Paaske; Kontny, Frederic; Kempf, Tibor; Levin, Lars-Åke; Lindahl, Bertil; Stridsberg, Mats; Ståhle, Elisabeth; Venge, Per; Wollert, Kai C; Swahn, Eva; Lagerqvist, Bo

    2016-10-15

    The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up. The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p=0·0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p interaction =0·0182), patients with elevated troponin T (778 days, 357-1165; p interaction =0·0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p interaction =0·0210). The difference was mainly driven by postponement of new myocardial infarction

  17. Caspofungin in the treatment of invasive fungal infections.

    PubMed

    Keady, Simon; Thacker, Meera

    2006-02-01

    Caspofungin is a member of a new class of antifungals called Echinocandins and is the first to have marketing authorisation in the United Kingdom. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of caspofungin. The article also discusses the warnings and precautions associated with the use of this drug. Caspofungin is an effective treatment option in the management of fungal infections.

  18. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections.

    PubMed

    Denning, David W; Kibbler, Christopher C; Barnes, Rosemary A

    2003-04-01

    Outcomes for invasive fungal infections have greatly improved in the past decade, and several new antifungal drugs have been or will be licensed in the next few years. Early accurate diagnosis and appropriate treatment have major impact on survival. In a 1995 survey of laboratory practice in the UK for mycology, major disparities were seen, with many laboratories not undertaking even simple diagnostic procedures. Delays in processing and inadequate procedures for handling samples, incomplete or delayed reporting of results, or a combination of these, compromise the care of patients. In randomised trials of antifungal chemotherapy, optimum treatments and good alternatives for others have been defined for some infections. High-quality care requires a multidisciplinary approach to diagnosis and management. In this review, we propose microbiology, histopathology, radiology, and clinical auditing standards, with the evidence base for each reviewed. The standards are absolutes, and, therefore, provide a straightforward basis for improving services to patients if they are all implemented.

  19. Long-distance endosome trafficking drives fungal effector production during plant infection

    PubMed Central

    Bielska, Ewa; Higuchi, Yujiro; Schuster, Martin; Steinberg, Natascha; Kilaru, Sreedhar; Talbot, Nicholas J.; Steinberg, Gero

    2014-01-01

    To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo long-distance cell signalling to regulate effector production during infection is not known. Here we show that long-distance retrograde motility of early endosomes (EEs) is necessary to trigger transcription of effector-encoding genes during plant infection by the pathogenic fungus Ustilago maydis. We demonstrate that motor-dependent retrograde EE motility is necessary for regulation of effector production and secretion during host cell invasion. We further show that retrograde signalling involves the mitogen-activated kinase Crk1 that travels on EEs and participates in control of effector production. Fungal pathogens therefore undergo long-range signalling to orchestrate host invasion. PMID:25283249

  20. Long-distance endosome trafficking drives fungal effector production during plant infection.

    PubMed

    Bielska, Ewa; Higuchi, Yujiro; Schuster, Martin; Steinberg, Natascha; Kilaru, Sreedhar; Talbot, Nicholas J; Steinberg, Gero

    2014-10-06

    To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo long-distance cell signalling to regulate effector production during infection is not known. Here we show that long-distance retrograde motility of early endosomes (EEs) is necessary to trigger transcription of effector-encoding genes during plant infection by the pathogenic fungus Ustilago maydis. We demonstrate that motor-dependent retrograde EE motility is necessary for regulation of effector production and secretion during host cell invasion. We further show that retrograde signalling involves the mitogen-activated kinase Crk1 that travels on EEs and participates in control of effector production. Fungal pathogens therefore undergo long-range signalling to orchestrate host invasion.

  1. [Reflections on the use of non-invasive mechanical ventilation in acute respiratory failure].

    PubMed

    Scala, Raffaele

    2012-12-01

    Given its prevalence into the clinical practice, non-invasive ventilation (NIV) can be included among the cornerstones of medicine. Just think of the acute applications of NIV which are in constant expansion, from COPD exacerbation to severe de novo hypoxemia, from postoperative distress to extra-hospital use in acute pulmonary edema, from ongoing support of interventional procedures to delicate strategies for end of life in terminally ill oncologic and non-oncologic patients. The thought should be focused on how, by whom, where and to whom is delivered this mode of artificial ventilation to avoid the risk of trivialization and flattening.

  2. Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies

    PubMed Central

    Gamaletsou, Maria N.; Walsh, Thomas J.; Sipsas, Nikolaos V.

    2018-01-01

    Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better

  3. Early Invasive Strategy and In-Hospital Survival Among Diabetics With Non-ST-Elevation Acute Coronary Syndromes: A Contemporary National Insight.

    PubMed

    Mahmoud, Ahmed N; Elgendy, Islam Y; Mansoor, Hend; Wen, Xuerong; Mojadidi, Mohammad K; Bavry, Anthony A; Anderson, R David

    2017-03-18

    There are limited data on the merits of an early invasive strategy in diabetics with non-ST-elevation acute coronary syndrome, with unclear influence of this strategy on survival. The aim of this study was to evaluate the in-hospital survival of diabetics with non-ST-elevation acute coronary syndrome treated with an early invasive strategy compared with an initial conservative strategy. The National Inpatient Sample database, years 2012-2013, was queried for diabetics with a primary diagnosis of non-ST-elevation acute coronary syndrome defined as either non-ST-elevation myocardial infarction or unstable angina (unstable angina). An early invasive strategy was defined as coronary angiography±revascularization within 48 hours of admission. Propensity scores were used to assemble a cohort managed with either an early invasive or initial conservative strategy balanced on >50 baseline characteristics and hospital presentations. Incidence of in-hospital mortality was compared in both groups. In a cohort of 363 500 diabetics with non-ST-elevation acute coronary syndrome, 164 740 (45.3%) were treated with an early invasive strategy. Propensity scoring matched 21 681 diabetics in both arms. Incidence of in-hospital mortality was lower with an early invasive strategy in both the unadjusted (2.0% vs 4.8%; odds ratio [OR], 0.41; 95% CI, 0.39-0.42; P <0.0001) and propensity-matched models (2.2% vs 3.8%; OR, 0.57; 95% CI, 0.50-0.63; P <0.0001). The benefit was observed across various subgroups, except for patients with unstable angina ( P interaction =0.02). An early invasive strategy may be associated with a lower incidence of in-hospital mortality in patients with diabetes. The benefit of this strategy appears to be superior in patients presenting with non-ST-elevation myocardial infarction compared with unstable angina. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Severe plant invasions can increase mycorrhizal fungal abundance and diversity.

    PubMed

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-07-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)--but not cheatgrass (Bromus tectorum)--support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance.

  5. Severe plant invasions can increase mycorrhizal fungal abundance and diversity

    PubMed Central

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-01-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)—but not cheatgrass (Bromus tectorum)—support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance. PMID:23486251

  6. Burden of fungal infections in Algeria.

    PubMed

    Chekiri-Talbi, M; Denning, D W

    2017-06-01

    We report for the first time in Algeria and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the National Office of Statistics (Office National des Statistiques: ONS), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants, and probably at least 568,900 (1.41%) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems, as there are over 1 million adult asthmatics. Candidaemia is estimated in 2,020 people, invasive aspergillosis in 2,865 people, and intra-abdominal candidiasis in 303 people; these are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer including 1,500 in children), nor is COPD (an estimated 317,762 patients, of whom 20.3% are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.

  7. Acute upper thermal limits of three aquatic invasive invertebrates: hot water treatment to prevent upstream transport of invasive species.

    PubMed

    Beyer, Jessica; Moy, Philip; De Stasio, Bart

    2011-01-01

    Transport of aquatic invasive species (AIS) by boats traveling up rivers and streams is an important mechanism of secondary spread of AIS into watersheds. Because physical barriers to AIS movement also prevent navigation, alternate methods for preventing spread are necessary while allowing upstream navigation. One promising approach is to lift boats over physical barriers and then use hot water immersion to kill AIS attached to the hull, motor, or fishing gear. However, few data have been published on the acute upper thermal tolerance limits of potential invaders treated in this manner. To test the potential effectiveness of this approach for a planned boat lift on the Fox River of northeastern WI, USA, acute upper thermal limits were determined for three AIS, adult zebra mussels (Dreissena polymorpha), quagga mussels (Dreissena rostriformis bugensis), and spiny water fleas (Bythotrephes longimanus) from the local area employing temperatures from 32 to 54°C and immersion times from 1 to 20 min. Mortality was determined after immersion followed by a 20-min recovery period. Immersion at 43°C for at least 5 min was required to ensure 100% mortality for all three species, but due to variability in the response by Bythotrephes a 10 min immersion would be more reliable. Overall there were no significant differences between the three species in acute upper thermal limits. Heated water can be an efficient, environmentally sound, and cost effective method of controlling AIS potentially transferred by boats, and our results should have both specific and wide-ranging applications in the prevention of the spread of aquatic invasive species.

  8. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

    PubMed Central

    2012-01-01

    Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole) for the prevention of invasive fungal infections (IFI) and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML) or myelodysplastic syndromes (MDS). The perspective was that of the Spanish National Health Service (NHS). Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS), total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS) over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values) which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS) was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11), increased LYS (2.52 versus 2.43), and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928) per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy) compared with fluconazole or itraconazole in high-risk neutropenic patients. PMID:22471553

  9. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases.

    PubMed

    Schelenz, Silke; Barnes, Rosemary A; Barton, Richard C; Cleverley, Joanne R; Lucas, Sebastian B; Kibbler, Christopher C; Denning, David W

    2015-04-01

    Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. We therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically significant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, we provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, we consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Archaea and bacteria mediate the effects of native species root loss on fungi during plant invasion.

    PubMed

    Mamet, Steven D; Lamb, Eric G; Piper, Candace L; Winsley, Tristrom; Siciliano, Steven D

    2017-05-01

    Although invasive plants can drive ecosystem change, little is known about the directional nature of belowground interactions between invasive plants, native roots, bacteria, archaea and fungi. We used detailed bioinformatics and a recently developed root assay on soils collected in fescue grassland along a gradient of smooth brome (Bromus inermis Leyss) invasion to examine the links between smooth brome shoot litter and root, archaea, bacteria and fungal communities. We examined (1) aboveground versus belowground influences of smooth brome on soil microbial communities, (2) the importance of direct versus microbe-mediated impacts of plants on soil fungal communities, and (3) the web of roots, shoots, archaea, bacteria and fungi interactions across the A and B soil horizons in invaded and non-invaded sites. Archaea and bacteria influenced fungal composition, but not vice versa, as indicated by redundancy analyses. Co-inertia analyses suggested that bacterial-fungal variance was driven primarily by 12 bacterial operational taxonomic units (OTUs). Brome increased bacterial diversity via smooth brome litter in the A horizon and roots in the B horizon, which then reduced fungal diversity. Archaea increased abundance of several bacterial OTUs, and the key bacterial OTUs mediated changes in the fungi's response to invasion. Overall, native root diversity loss and bacterial mediation were more important drivers of fungal composition than were the direct effects of increases in smooth brome. Critically, native plant species displacement and root loss appeared to be the most important driver of fungal composition during invasion. This causal web likely gives rise to the plant-fungi feedbacks, which are an essential factor determining plant diversity in invaded grassland ecosystems.

  11. Archaea and bacteria mediate the effects of native species root loss on fungi during plant invasion

    PubMed Central

    Mamet, Steven D; Lamb, Eric G; Piper, Candace L; Winsley, Tristrom; Siciliano, Steven D

    2017-01-01

    Although invasive plants can drive ecosystem change, little is known about the directional nature of belowground interactions between invasive plants, native roots, bacteria, archaea and fungi. We used detailed bioinformatics and a recently developed root assay on soils collected in fescue grassland along a gradient of smooth brome (Bromus inermis Leyss) invasion to examine the links between smooth brome shoot litter and root, archaea, bacteria and fungal communities. We examined (1) aboveground versus belowground influences of smooth brome on soil microbial communities, (2) the importance of direct versus microbe-mediated impacts of plants on soil fungal communities, and (3) the web of roots, shoots, archaea, bacteria and fungi interactions across the A and B soil horizons in invaded and non-invaded sites. Archaea and bacteria influenced fungal composition, but not vice versa, as indicated by redundancy analyses. Co-inertia analyses suggested that bacterial–fungal variance was driven primarily by 12 bacterial operational taxonomic units (OTUs). Brome increased bacterial diversity via smooth brome litter in the A horizon and roots in the B horizon, which then reduced fungal diversity. Archaea increased abundance of several bacterial OTUs, and the key bacterial OTUs mediated changes in the fungi’s response to invasion. Overall, native root diversity loss and bacterial mediation were more important drivers of fungal composition than were the direct effects of increases in smooth brome. Critically, native plant species displacement and root loss appeared to be the most important driver of fungal composition during invasion. This causal web likely gives rise to the plant–fungi feedbacks, which are an essential factor determining plant diversity in invaded grassland ecosystems. PMID:28140393

  12. Serious fungal infections in Ecuador.

    PubMed

    Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M

    2017-06-01

    There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

  13. Spontaneous fungal peritonitis: a rare but severe complication of liver cirrhosis.

    PubMed

    Gravito-Soares, Marta; Gravito-Soares, Elisa; Lopes, Sandra; Ribeiro, Graça; Figueiredo, Pedro

    2017-09-01

    Spontaneous bacterial peritonitis is the most common infectious complication in cirrhosis. Spontaneous fungal peritonitis is rare and remains unknown. In this work, spontaneous fungal peritonitis as well as risk factors and prognosis are characterized. A retrospective case-control study of 253 consecutive admissions by peritonitis in cirrhotic patients was carried out between 2006 and 2015. Comparison of patients with spontaneous fungal peritonitis (cases) and spontaneous bacterial peritonitis with positive microbiologic ascitic fluid culture (controls) was performed. Variables such as sociodemographic and clinical features, cirrhosis etiology, liver dysfunction scores, ascitic and laboratory parameters, invasive procedures, and prognosis were evaluated. Of the 231 patients, eight (3.5%) developed spontaneous fungal peritonitis, 62.5% of cases being coinfected with bacteria. Candida spp. was isolated in 87.5% of cases, mainly Candida albicans (37.5%) and C. krusei (25.0%). Patients with spontaneous fungal peritonitis had higher ascitic fluid lactate dehydrogenase (288.4±266.6 vs. 161.0±179.5; P=0.011), blood leukocyte count (15187.5±5432.3 vs. 10969.8±6949.5; P=0.028), blood urea nitrogen (69.8±3.1 vs. 36.3±25.5; P=0.001), higher number of invasive procedures (colonoscopy: 25.0 vs. 0.8%, P=0.001; urinary catheterization: 87.5 vs. 49.6%, P=0.038; nasogastric intubation: 87.5 vs. 26.9%, P=0.001), and longer duration of hospital stay (30.0±32.9 vs. 18.9±17.0 days; P=0.031). No statistical difference was found between the two groups for Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-sodium, and Child-Pugh scores. Spontaneous fungal peritonitis was associated with a worse prognosis, particularly severe sepsis/septic shock (87.5 vs. 42.8%, P=0.023), admission in the gastroenterology intensive care unit (87.5 vs. 24.4%; P=0.001), and overall (62.5 vs. 31.9%; P=0.039) or 30-day mortality (50.0 vs. 24.4%; P=0.034), with a mean diagnosis

  14. Extrasinonasal infiltrative process associated with a sinonasal fungus ball: does it mean invasive fungal sinusitis?

    PubMed Central

    Kim, Yi-Kyung; Kim, Hyung-Jin; Kim, Hyo Yeol; Cha, Jihoon; Lee, Ji Young; Chung, Seung-Kyu; Dhong, Hun-Jong; Song, Mina; Kim, Sung Tae

    2016-01-01

    PURPOSE Invasive fungal sinusitis (IFS) has rarely been reported to develop from non-IFS. The purpose of this study was to disclose the nature of the extrasinonasal infiltrative process in the presence of a sinonasal fungus ball (FB). METHODS We retrospectively reviewed the medical records, computed tomography, magnetic resonance images of 13 patients with sinonasal FB and the extrasinonasal infiltrative process. Based on histology and clinical course, we divided the extrasinonasal infiltrative process into IFS and the nonfungal inflammatory/infectious process (NFIP). The images were analyzed with particular attention to the presence of cervicofacial tissue infarction (CFTI). RESULTS Of the 13 patients, IFS was confirmed in only one, while the remaining 12 were diagnosed to have presumed NFIP. One patient with IFS died shortly after diagnosis. In contrast, all 12 patients with presumed NFIP, except one, survived during a mean follow-up of 17 months. FB was located in the maxillary sinus (n=4), sphenoid sinus (n=8), and both sinuses (n=1). Bone defect was found in five patients, of whom four had a defect in the sphenoid sinus. Various sites were involved in the extrasinonasal infiltrative process, including the orbit (n=10), intracranial cavity (n=9), and soft tissues of the face and neck (n=7). CFTI was recognized only in one patient with IFS. CONCLUSION In most cases, the extrasinonasal infiltrative process in the presence of sinonasal FB did not seem to be caused by IFS but probably by NFIP. In our study, there were more cases of invasive changes with the sphenoid than with the maxillary FB. PMID:27283592

  15. Extrasinonasal infiltrative process associated with a sinonasal fungus ball: does it mean invasive fungal sinusitis?

    PubMed

    Kim, Yi Kyung; Kim, Hyung Jin; Kim, Hyo Yeol; Cha, Jihoon; Lee, Ji Young; Chung, Seung Kyu; Dhong, Hun Jong; Song, Mina; Kim, Sung Tae

    2016-01-01

    Invasive fungal sinusitis (IFS) has rarely been reported to develop from non-IFS. The purpose of this study was to disclose the nature of the extrasinonasal infiltrative process in the presence of a sinonasal fungus ball (FB). We retrospectively reviewed the medical records, computed tomography, magnetic resonance images of 13 patients with sinonasal FB and the extrasinonasal infiltrative process. Based on histology and clinical course, we divided the extrasinonasal infiltrative process into IFS and the nonfungal inflammatory/infectious process (NFIP). The images were analyzed with particular attention to the presence of cervicofacial tissue infarction (CFTI). Of the 13 patients, IFS was confirmed in only one, while the remaining 12 were diagnosed to have presumed NFIP. One patient with IFS died shortly after diagnosis. In contrast, all 12 patients with presumed NFIP, except one, survived during a mean follow-up of 17 months. FB was located in the maxillary sinus (n=4), sphenoid sinus (n=8), and both sinuses (n=1). Bone defect was found in five patients, of whom four had a defect in the sphenoid sinus. Various sites were involved in the extrasinonasal infiltrative process, including the orbit (n=10), intracranial cavity (n=9), and soft tissues of the face and neck (n=7). CFTI was recognized only in one patient with IFS. In most cases, the extrasinonasal infiltrative process in the presence of sinonasal FB did not seem to be caused by IFS but probably by NFIP. In our study, there were more cases of invasive changes with the sphenoid than with the maxillary FB.

  16. [Evolution of non-invasive ventilation in acute bronchiolitis].

    PubMed

    Toledo del Castillo, B; Fernández Lafever, S N; López Sanguos, C; Díaz-Chirón Sánchez, L; Sánchez da Silva, M; López-Herce Cid, J

    2015-08-01

    The aim of the study was to analyse the evolution, over a12-year period, of the use of non-invasive (NIV) and invasive ventilation (IV) in children admitted to a Paediatric Intensive Care Unit (PICU) due to acute bronchiolitis. A retrospective observational study was performed including all children who were admitted to the PICU requiring NIV or IV between 2001 and 2012. Demographic characteristics, ventilation assistance and clinical outcome were analysed. A comparison was made between the first six years and the last 6 years of the study. A total of 196 children were included; 30.1% of the subjects required IV and 93.3% required NIV. The median duration of IV was 9.5 days and NIV duration was 3 days. The median PICU length of stay was 7 days, and 2% of the patients died. The use of NIV increased from 79.4% in first period to 100% in the second period (P<.0001) and IV use decreased from 46% in first period to 22.6% in the last 6 years (P<.0001). Continuous positive airway pressure and nasopharyngeal tube were the most frequently used modality and interface, although the use of bi-level non-invasive ventilation (P<.001) and of nasal cannulas significantly increased (P<.0001) in the second period, and the PICU length of stay was shorter (P=.011). The increasing use of NIV in bronchiolitis in our PICU during the last 12 years was associated with a decrease in the use of IV and length of stay in the PICU. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  17. Invasive Aspergillosis with Disseminated Skin Involvement in a Patient with Acute Myeloid Leukemia: A Rare Case

    PubMed Central

    Mert, Duygu; Iskender, Gülşen; Duygu, Fazilet; Merdin, Alparslan; Dal Mehmet, Sinan; Dogan, Mehmet; Tekgündüz, Emre; Ertek, Mustafa; Altuntaş, Fevzi

    2017-01-01

    Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear. PMID:28626542

  18. [Allergic fungal rhinosinusitis caused by Curvularia sp.].

    PubMed

    Alvarez, Verónica C; Guelfand, Liliana; Pidone, Juan Carlos; Soloaga, Rolando; Ontivero, Paula; Margari, Alejandra; López Daneri, Gabriela

    2011-01-01

    Allergic fungal rhinosinusitis is a benign and non-invasive sinusal disease related to a hypersensitivity reaction to fungal antigens. This process can cause tissue edema with chronic inflammatory disturbances of the respiratory mucosa. We present the case of a 17 year-old immunocompetent male, with history of seasonal allergic rhinosinusitis, nasal polyps and previous surgery for mucocele of the frontal sinus. Sticky material was removed in the last surgery that revealed pigmented and septed filaments on direct examination, and yielded Curvularia on Sabouraud dextrose agar. After a course of amphotericin B, treatment was switched to itraconazole, with good tolerance and favorable clinical outcome. Copyright © 2011. Published by Elsevier Espana.

  19. Role of Neutrophils in Preventing and Resolving Acute Fungal Sinusitis▿ †

    PubMed Central

    Rodriguez, Tobias E.; Falkowski, Nicole R.; Harkema, Jack R.; Huffnagle, Gary B.

    2007-01-01

    Acute fungal sinusitis (AFS) is a devastating disease of the paranasal sinuses afflicting immunocompromised individuals. Knowledge about this disease is limited to clinical observations because there are no animal models in which to study the pathogenesis of the infection. Our goal was to develop a murine model of AFS and examine the role of neutrophils in host defense within the nasal cavity. Female C57BL/6 mice were depleted of neutrophils using anti-Gr-1 monoclonal antibody from day −1 to day 5 postinfection to initiate a transient neutropenia within the mice. At day 0, Aspergillus fumigatus conidia were administered intranasally. The untreated Aspergillus-exposed group had significant neutrophil recruitment by day 3, but by day 7 the leukocyte numbers had returned to unexposed levels. There was not a significant influx of mononuclear cells at either time point. In contrast, beginning at day 3 postinfection and continuing through day 7, anti-Gr-1-treated mice had increased cellular recruitment consisting of banded neutrophils at day 3 and mature neutrophils at day 7. Hyphal masses developed only in the anti-Gr-1-treated mice (25 to 36%) but only during the period of treatment. When the treatment was discontinued, hyphal masses could no longer be detected in the nasal cavities of these mice. In contrast, cyclophosphamide treatment did not induce neutropenia, and the nasal cavity remained free of hyphal masses. These studies demonstrate the feasibility of using this model to study AFS and implicate neutrophils in protection of the sinuses against acute Aspergillus infection and in clearance of established hyphal masses. PMID:17875637

  20. Activity of a Long-Acting Echinocandin (CD101) and Seven Comparator Antifungal Agents Tested against a Global Collection of Contemporary Invasive Fungal Isolates in the SENTRY 2014 Antifungal Surveillance Program.

    PubMed

    Pfaller, Michael A; Messer, Shawn A; Rhomberg, Paul R; Castanheira, Mariana

    2017-03-01

    The activity of CD101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the Clinical and Laboratory Standards Institute (CLSI) method. All Candida albicans ( n = 251), Candida tropicalis ( n = 51), Candida krusei ( n = 16), and Candida dubliniensis ( n = 11) isolates were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. Five C. glabrata isolates ( n = 100) displayed CD101 MIC values of 1 to 4 μg/ml, had elevated MICs of caspofungin (2 to >8 μg/ml), anidulafungin (2 to 4 μg/ml), and micafungin (2 to 4 μg/ml), and carried mutations on fks1 and fks2 Candida parapsilosis ( n = 92) and Candida orthopsilosis ( n = 10) displayed higher CD101 MIC values (ranges, 0.5 to 4 μg/ml and 0.12 to 2 μg/ml, respectively), and similar results were observed for the other echinocandins tested. Fluconazole resistance was noted among 11.0% of Candida glabrata isolates, 4.3% of C. parapsilosis isolates, and 2.0% of C. albicans and C. tropicalis isolates. The activity of CD101 against Aspergillus fumigatus ( n = 56) was similar to that of micafungin and 2-fold greater than that of caspofungin but less than that of anidulafungin. These isolates had wild-type susceptibility to itraconazole, voriconazole, and posaconazole. The echinocandins had limited activity against Cryptococcus neoformans ( n = 19). CD101 was as active as the other echinocandins against common fungal organisms recovered from patients with invasive fungal infections. The long half-life profile is very desirable for the prevention and treatment of serious fungal infections, especially in patients who can then be discharged from the hospital to complete antifungal therapy on an outpatient basis. Copyright © 2017 Pfaller et al.

  1. Histopathologic Diagnosis of Fungal Infections in the 21st Century

    PubMed Central

    Guarner, Jeannette; Brandt, Mary E.

    2011-01-01

    Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs. PMID:21482725

  2. [Early invasive strategy in diabetic patients with non-ST-segment elevation acute coronary syndromes].

    PubMed

    Baeza Román, Anna; Latour Pérez, Jaime; de Miguel Balsa, Eva; Pino Izquierdo, Karel; Coves Orts, Francisco Javier; García Ochando, Luis; de la Torre Fernández, Maria José

    2014-05-20

    In the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS), several studies have shown a reduction in mortality with the use of an invasive strategy in high-risk patients, including diabetic patients. Paradoxically, other studies have shown an under-utilization of this invasive strategy in these patients. The aim of this study is to determine the characteristics of patients managed conservatively and identify determinants of the use of invasive or conservative strategy. Retrospective cohort study conducted in diabetic patients with NSTE-ACS included in the ARIAM-SEMICYUC registry (n=531) in 2010 and 2011. We performed crude and adjusted unconditional logistic regression. We analyzed 531 diabetic patients, 264 (49.7%) of which received invasive strategy. Patients managed conservatively were a subgroup characterized by older age and cardiovascular comorbidity, increased risk of bleeding and the absence of high-risk electrocardiogram (ECG). In diabetic patients with NSTE-ACS, independent predictors associated with conservative strategy were low-risk ECG, initial Killip class>1, high risk of bleeding and pretreatment with clopidogrel. The fear of bleeding complications or advanced coronary lesions could be the cause of the underutilization of an invasive strategy in diabetic patients with NSTE-ACS. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. Papillary necrosis with invasive fungal infections: a case series of 29 patients

    PubMed Central

    Gupta, Krishan L.; Muthukumar, Thangamani; Joshi, Kusum; Chakrbarti, Arunaloke; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

    2013-01-01

    Background Renal papillary necrosis (RPN) is associated with a number of comorbid conditions. However, it has been rarely reported in patients with fungal infections of the kidney. Methods We analyzed medical records of our hospital for the last two decades and identified 29 patients with fungal infections and RPN. Results Among the 29 patients, there were 24 men and 5 women. The median (range) age at presentation was 31.2 years (2 days–73 years). Three patients (10%) were kidney transplant recipients. The remaining had varied co-existing medical conditions that included diabetes mellitus in 16 (55%) and septicemia in 4 (14%). Clinical features at presentation were fever and oliguric kidney failure in 17 patients and loin pain accompanied by passage of fleshy material per urethra in 11 (38%). Diagnosis was made ante-mortem in 17 (59%) patients. Twenty patients (69%) had infection limited to the kidneys, while in the rest, it was disseminated. Kidney involvement was bilateral in 17 patients (59%). Urinalysis showed pyuria in 23 (79%) and microhematuria in 8 (28%) patients. Fungal infections included candidiasis (69%), aspergillosis (21%) and zygomycosis (10%). Of the 17 patients in whom the diagnoses was made ante-mortem, 12 survived and 5 died. Overall mortality was observed in 48% of cases. Conclusions We herein report a series of patients with RPN associated with fungal infections of the kidney. Presentation varies from asymptomatic urinary tract infection to severe kidney failure with poor outcome. High index of suspicion is necessary to reduce the associated high mortality in these patients. PMID:27293566

  4. Miscellaneous fungal diseases

    USGS Publications Warehouse

    Friend, M.

    1999-01-01

    As for other types of disease, fungal infections probably are more common causes of disease in wild birds than is currently recognized. Also, the similarity in gross lesions produced by some fungi mask the detection of less common fungi as disease agents. Numerous types of disease-causing fungi in addition to Aspergillus fumigatus and Candida albicans have been isolated from birds; most isolations have been from poultry and wild birds being maintained in captivity. Enhanced disease surveillance that is often associated with privately owned birds and greater opportunity to detect disease in confined birds are reasons for these findings rather than any known differences in the occurrence of fungal diseases in free-ranging and captive birds. Many of the reported infections appear to have been opportunistic invasions by the fungi involved. The important points are that many fungi are capable of causing disease in birds but their collective impacts do not rival A. fumigatus as a single cause of disease in wild birds. Nevertheless, it is important to be aware of the diversity of pathogenic or disease causing fungi.

  5. Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre.

    PubMed

    Zicker, Michelle; Colombo, Arnaldo Lopes; Ferraz-Neto, Ben-Hur; Camargo, Luis Fernando Aranha

    2011-05-01

    Liver transplant seems to be an effective option to prolong survival in patients with end-stage liver disease, although it still can be followed by serious complications. Invasive fungal infections (ifi) are related to high rates of morbidity and mortality. The epidemiology of fungal infections in Brazilian liver transplant recipients is unknown. The aim of this observational and retrospective study was to determine the incidence and epidemiology of fungal infections in all patients who underwent liver transplantation at Albert Einstein Israeli Hospital between 2002-2007. A total of 596 liver transplants were performed in 540 patients. Overall, 77 fungal infections occurred in 68 (13%) patients. Among the 77 fungal infections, there were 40 IFI that occurred in 37 patients (7%). Candida and Aspergillus species were the most common etiologic agents. Candida species accounted for 82% of all fungal infections and for 67% of all IFI, while Aspergillus species accounted for 9% of all fungal infections and for 17% of all IFI. Non-albicans Candida species were the predominant Candida isolates. Invasive aspergillosis tended to occur earlier in the post-transplant period. These findings can contribute to improve antifungal prophylaxis and therapy practices in Brazilian centres.

  6. Economic evaluation of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infection in high-risk neutropenic patients in Sweden.

    PubMed

    Lundberg, Johan; Höglund, Martin; Björkholm, Magnus; Åkerborg, Örjan

    2014-07-01

    In patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole has been proven more effective in the prevention of invasive fungal infection (IFI) than fluconazole or itraconazole (standard azoles) The current analysis seeks to estimate the cost effectiveness of prophylactic posaconazole compared with standard azoles in AML or MDS patients with severe chemotherapy-induced neutropenia in Sweden. A decision-analytic model was used to estimate life expectancy, costs, and quality-adjusted life-years (QALYs). Efficacy data were derived from a phase III clinical trial. Life expectancy and quality of life data were collected from the literature. A modified Delphi method was used to gather expert opinion on resource use for an IFI. Unit costs were captured from hospital and pharmacy pricelists. A probabilistic sensitivity analysis (PSA) was used to investigate the impact of uncertainty in the model parameters on the cost-effectiveness results. The estimated mean direct cost per patient with posaconazole prophylaxis was 46,893 Swedish kronor (SEK) (€5,387) and SEK50,017 (€5,746) with standard azoles. Prophylaxis with posaconazole resulted in 0.075 QALYs gained compared with standard azoles. At a cost-effectiveness threshold of SEK500,000/QALY the PSA demonstrated a more than 95 % probability that posaconazole is cost effective versus standard azoles for the prevention of IFI in high-risk neutropenic patients in Sweden. Given the assumptions, methods, and data used, posaconazole is expected to be cost effective compared with standard azoles when used as antifungal prophylaxis in AML or MDS patients with chemotherapy-induced prolonged neutropenia in Sweden.

  7. Estimated burden of fungal infections in Germany.

    PubMed

    Ruhnke, Markus; Groll, Andreas H; Mayser, Peter; Ullmann, Andrew J; Mendling, Werner; Hof, Herbert; Denning, David W

    2015-10-01

    In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14 years) and 16% of population are ≥65 years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease. © 2015 Blackwell Verlag GmbH.

  8. Fungal infections in adult patients on extracorporeal life support.

    PubMed

    Cavayas, Yiorgos Alexandros; Yusuff, Hakeem; Porter, Richard

    2018-04-17

    Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO. We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture. Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001). Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007). In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival. The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population. Both were independently associated with a reduced survival. Aspergillus involvement was strongly associated with ECMO for respiratory support and influenza.

  9. Loss of functional diversity and network modularity in introduced plant–fungal symbioses

    PubMed Central

    Cooper, Jerry A.; Bufford, Jennifer L.; Hulme, Philip E.; Bates, Scott T.

    2017-01-01

    The introduction of alien plants into a new range can result in the loss of co-evolved symbiotic organisms, such as mycorrhizal fungi, that are essential for normal plant physiological functions. Prior studies of mycorrhizal associations in alien plants have tended to focus on individual plant species on a case-by-case basis. This approach limits broad scale understanding of functional shifts and changes in interaction network structure that may occur following introduction. Here we use two extensive datasets of plant–fungal interactions derived from fungal sporocarp observations and recorded plant hosts in two island archipelago nations: New Zealand (NZ) and the United Kingdom (UK). We found that the NZ dataset shows a lower functional diversity of fungal hyphal foraging strategies in mycorrhiza of alien when compared with native trees. Across species this resulted in fungal foraging strategies associated with alien trees being much more variable in functional composition compared with native trees, which had a strikingly similar functional composition. The UK data showed no functional difference in fungal associates of alien and native plant genera. Notwithstanding this, both the NZ and UK data showed a substantial difference in interaction network structure of alien trees compared with native trees. In both cases, fungal associates of native trees showed strong modularity, while fungal associates of alien trees generally integrated into a single large module. The results suggest a lower functional diversity (in one dataset) and a simplification of network structure (in both) as a result of introduction, potentially driven by either limited symbiont co-introductions or disruption of habitat as a driver of specificity due to nursery conditions, planting, or plant edaphic-niche expansion. Recognizing these shifts in function and network structure has important implications for plant invasions and facilitation of secondary invasions via shared mutualist

  10. Hyperthyroidism secondary to disseminated mucormycosis in a child with acute lymphoblastic leukemia: case report and a review of published reports.

    PubMed

    Irga, Ninela; Kosiak, Wojciech; Jaworski, Radoslaw; Komarnicka, Jolanta; Birkholz, Dorota

    2013-02-01

    Thyroiditis due to fungal infection is an extremely rare cause of hyperthyroidism. The most common etiological factor of thyroiditis is Aspergillus. Infections due to members of the Mucorales have been an increasing clinical problem in recent years, and the prognosis in generalized infections due to those fungi is usually very poor. No hyperthyroidism in a child with thyroiditis due to mucormycosis has been reported in the literature so far. We describe a clinical course of generalized mucormycosis with thyroid involvement in a 12-year-old girl treated for acute lymphoblastic leukemia. The child underwent a hyperthyroidism connected with thyroid involvement due to a fungal process. The diagnosis was based on the clinical signs, laboratory findings and typical ultrasound scan; however, later attempt to amplify the fungi DNA from the tissue block has failed. The child died because of multiorgan failure due to general fungal infection 49 days after the invasive fungal infection was diagnosed. The generalized mucormycosis is always connected with poor prognosis and the mortality is high.

  11. Five-year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study.

    PubMed

    Xiao, Meng; Sun, Zi-Yong; Kang, Mei; Guo, Da-Wen; Liao, Kang; Chen, Sharon C-A; Kong, Fanrong; Fan, Xin; Cheng, Jing-Wei; Hou, Xin; Zhou, Meng-Lan; Li, Ying; Yu, Shu-Ying; Huang, Jing-Jing; Wang, He; Xu, Ying-Chun

    2018-05-09

    Data on the epidemiology of invasive candidiasis (IC) and antifungal susceptibility of Candida isolates in China are still limited. Here we report surveillance for IC from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study. Sixty-five tertiary hospitals collected 8,829 Candida isolates from August 1, 2009 to July 31, 2014. Matrix-assisted laser desorption/ionization -time of flight mass spectrometry supplemented by rDNA sequencing was used to define species, and fluconazole and voriconazole susceptibilities determined by the Clinical and Laboratory Standards Institute disk diffusion method. A total of 32 Candida species were identified. C. albicans was the most common species (44.9%) followed by C. parapsilosis complex (20.0%), C. tropicalis (17.2%) and C. glabrata complex (10.8%), with other species comprising <3%. However, in candidemia, the proportion of cases caused by C. albicans was only 32.3%. C. albicans and C. parapsilosis complex isolates were susceptible to fluconazole and voriconazole (<6% resistance), while fluconazole- and azole cross-resistant rates were high in C. tropicalis (13.3% and 12.9%), C. glabrata complex (18.7% and 14%) and uncommon Candida species (44.1% and 10.3%) isolates. Moreover, from year 1 to 5 of the study, there was a significant increase in resistant rates amongst C. glabrata complex isolates to fluconazole (12.2% to 24.0%), and amongst C. tropicalis isolates to both fluconazole (5.7% to 21.0%) and voriconazole (5.7% to 21.4%) (all P<0.01). Geographic variations in causative species and susceptibilities were noted. Our findings indicated that antifungal resistance have become noteworthy in China, and enhanced surveillance is warranted. Copyright © 2018 American Society for Microbiology.

  12. An annotated bibliography of invasive tree pathogens Sirococcus clavigignenti-juglandacearum, Phytophthora alni, and Phytophthora quercina and a regulatory policy and management practices for invasive species

    Treesearch

    T.M. Seeland; M.E. Ostry; R. Venette; J. Juzwik

    2006-01-01

    Provides a database of selected literature pertaining to the prevention, early detection and rapid response, control and management, and rehabilitation and restoration related to three invasive fungal pathogens of forest trees. Literature addressing regulatory policy and management practices for invasive species is also included.

  13. Emerging IL-12 family cytokines in the fight against fungal infections.

    PubMed

    Thompson, Aiysha; Orr, Selinda J

    2018-05-21

    Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL-12p70, IL-23, IL-27 and IL-35) link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 and IL-23 have established roles during anti-fungal immunity, whereas emerging roles for IL-27 and IL-35 have recently been reported. Here, we discuss the IL-12 family, focusing on IL-27 and IL-35 during anti-fungal immune responses to pathogens such as Candida and Aspergillus. Copyright © 2018. Published by Elsevier Ltd.

  14. Multiple introductions of divergent genetic lineages in an invasive fungal pathogen, Cryphonectria parasitica, in France.

    PubMed

    Dutech, C; Fabreguettes, O; Capdevielle, X; Robin, C

    2010-08-01

    The occurrence of multiple introductions may be a crucial factor in the successful establishment of invasive species, but few studies focus on the introduction of fungal pathogens, despite their significant effect on invaded habitats. Although Cryphonectria parasitica, the chestnut blight fungus introduced in North America and Europe from Asia during the 20th century, caused dramatic changes in its new range, the history of its introduction is not well retraced in Europe. Using 10 microsatellite loci, we investigated the genetic diversity of 583 isolates in France, where several introductions have been hypothesized. Our analyses showed that the seven most frequent multilocus genotypes belonged to three genetic lineages, which had a different and geographically limited distribution. These results suggest that different introduction events occurred in France. Genetic recombination was low among these lineages, despite the presence of the two mating types in each chestnut stand analysed. The spatial distribution of lineages suggests that the history of introductions in France associated with the slow expansion of the disease has contributed to the low observed rate of recombination among the divergent lineages. However, we discuss the possibility that environmental conditions or viral interactions could locally reduce recombination among genotypes.

  15. PCR Followed by Electrospray Ionization Mass Spectrometry for Broad-Range Identification of Fungal Pathogens

    PubMed Central

    Massire, Christian; Buelow, Daelynn R.; Zhang, Sean X.; Lovari, Robert; Matthews, Heather E.; Toleno, Donna M.; Ranken, Raymond R.; Hall, Thomas A.; Metzgar, David; Sampath, Rangarajan; Blyn, Lawrence B.; Ecker, David J.; Gu, Zhengming; Walsh, Thomas J.

    2013-01-01

    Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Early and accurate identification of these pathogens is central to direct therapy and to improve overall outcome. PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was evaluated as a novel means for identification of fungal pathogens. Using a database grounded by 60 ATCC reference strains, a total of 394 clinical fungal isolates (264 molds and 130 yeasts) were analyzed by PCR/ESI-MS; results were compared to phenotypic identification, and discrepant results were sequence confirmed. PCR/ESI-MS identified 81.4% of molds to either the genus or species level, with concordance rates of 89.7% and 87.4%, respectively, to phenotypic identification. Likewise, PCR/ESI-MS was able to identify 98.4% of yeasts to either the genus or species level, agreeing with 100% of phenotypic results at both the genus and species level. PCR/ESI-MS performed best with Aspergillus and Candida isolates, generating species-level identification in 94.4% and 99.2% of isolates, respectively. PCR/ESI-MS is a promising new technology for broad-range detection and identification of medically important fungal pathogens that cause invasive mycoses. PMID:23303501

  16. The cost implications of an early versus delayed invasive strategy in Acute Coronary Syndromes: the TIMACS study.

    PubMed

    Bainey, Kevin R; Gafni, Amiram; Rao-Melacini, Purnima; Tong, Wesley; Steg, Philippe G; Faxon, David P; Lamy, Andre; Granger, Christopher B; Yusuf, Salim; Mehta, Shamir R

    2014-06-01

    The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial demonstrated that early invasive intervention (within 24 hours) was similar to a delayed approach (after 36 hours) overall but improved outcomes were seen in patients at high risk. However, the cost implications of an early versus delayed invasive strategy are unknown. A third-party perspective of direct cost was chosen and United States Medicare costs were calculated using average diagnosis related grouping (DRG) units. Direct medical costs included those of the index hospitalization (including clinical, procedural and hospital stay costs) as well as major adverse cardiac events during 6 months of follow-up. Sensitivity and sub-group analyses were performed. The average total cost per patient in the early intervention group was lower compared with the delayed intervention group (-$1170; 95% CI -$2542 to $202). From the bootstrap analysis (5000 replications), the early invasive approach was associated with both lower costs and better clinical outcomes regarding death/myocardial infarction (MI)/stroke in 95.1% of the cases (dominant strategy). In high-risk patients (GRACE score ≥141), the net reduction in cost was greatest (-$3720; 95% CI -$6270 to -$1170). Bootstrap analysis revealed 99.8% of cases were associated with both lower costs and better clinical outcomes (death/MI/stroke). We were unable to evaluate the effect of community care and investigations without hospitalization (office visits, non-invasive testing, etc). Medication costs were not captured. Indirect costs such as loss of productivity and family care were not included. An early invasive management strategy is as effective as a delayed approach and is likely to be less costly in most patients with acute coronary syndromes.

  17. [The burden of fungal infections in Algeria].

    PubMed

    Chekiri-Talbi, M; Denning, D W

    2017-06-01

    In Algeria, superficial mycoses are very commonly diagnosed. Deep fungal infections are less often observed. Few data from Algeria are found in the literature. We report for the first time the main causes of these diseases in our country and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the Service (Office) of the Statistics (ONES), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants and probably at least 568,900 (1.41 %) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems as there are over 1 million adult asthmatics. Candidaemia is estimated in 2020, invasive aspergillosis in 2865, intra-abdominal candidiasis in 303 people and are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer among including 1500 in children) and nor is COPD (an estimated 317,762 patients of whom 20.3 % are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

    PubMed Central

    Kovanda, Laura L.; Desai, Amit V.; Lu, Qiaoyang; Townsend, Robert W.; Akhtar, Shahzad; Bonate, Peter

    2016-01-01

    Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.) PMID:27185799

  19. Fungal prosthetic valve endocarditis with mycotic aneurysm: Case report.

    PubMed

    Brandão, Mariana; Almeida, Jorge; Ferraz, Rita; Santos, Lurdes; Pinho, Paulo; Casanova, Jorge

    2016-09-01

    Fungal prosthetic valve endocarditis is an extremely severe form of infective endocarditis, with poor prognosis and high mortality despite treatment. Candida albicans is the most common etiological agent for this rare but increasingly frequent condition. We present a case of fungal prosthetic valve endocarditis due to C. albicans following aortic and pulmonary valve replacement in a 38-year-old woman with a history of surgically corrected tetralogy of Fallot, prior infective endocarditis and acute renal failure with need for catheter-based hemodialysis. Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac surgery, in which the bioprostheses were replaced by homografts, providing greater resistance to recurrent infection. During hospitalization, a mycotic aneurysm was diagnosed following an episode of acute arterial ischemia, requiring two vascular surgical interventions. Despite the complications, the patient's outcome was good and she was discharged on suppressive antifungal therapy with oral fluconazole for at least a year. The reported case illustrates multiple risk factors for fungal endocarditis, as well as complications and predictors of poor prognosis, demonstrating its complexity. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. The role of non-invasive biomarkers in detecting acute respiratory effects of traffic-related air pollution.

    PubMed

    Scarpa, M C; Kulkarni, N; Maestrelli, P

    2014-09-01

    The role of non-invasive methods in the investigation of acute effects of traffic-related air pollution is not clearly established. We evaluated the usefulness of non-invasive biomarkers in detecting acute air pollution effects according to the age of participants, the disease status, their sensitivity compared with lung function tests and their specificity for a type of pollutant. Search terms lead to 535 titles, among them 128 had potentially relevant abstracts. Sixtynine full papers were reviewed, while 59 articles were excluded as they did not meet the selection criteria. Methods used to assess short-term effects of air pollution included analysis of nasal lavage (NAL) for the upper airways, and induced sputum (IS), exhaled breath condensate (EBC) and exhaled nitric oxide (FeNO) for central and lower airways. There is strong evidence that FeNO evaluation is useful independently from subject age, while IS analysis is suitable almost for adults. Biomarker changes are generally observed upon pollutant exposure irrespective of the disease status of the participants. None of the biomarkers identified are specific for a type of pollutant exposure. Based on experimental exposure studies, there is moderate evidence that IS analysis is more sensitive than lung function tests, whereas this is not the case for biomarkers obtained by NAL or EBC. Cells and some cytokines (IL-6, IL-8 and myeloperoxidase) have been measured both in the upper respiratory tract (NAL) and in the lower airways (IS). Overall, the response to traffic exposure seems different in the two compartments. In conclusion, this survey of current literature displays the complexity of this research field, highlights the significance of short-term studies on traffic pollution and gives important tips when planning studies to detect acute respiratory effects of air pollution in a non-invasive way. © 2014 John Wiley & Sons Ltd.

  1. Distance to invasive heart centre, performance of acute coronary angiography, and angioplasty and associated outcome in out-of-hospital cardiac arrest: a nationwide study.

    PubMed

    Tranberg, Tinne; Lippert, Freddy K; Christensen, Erika F; Stengaard, Carsten; Hjort, Jakob; Lassen, Jens Flensted; Petersen, Frants; Jensen, Jan Skov; Bäck, Caroline; Jensen, Lisette Okkels; Ravkilde, Jan; Bøtker, Hans Erik; Terkelsen, Christian Juhl

    2017-06-01

    To evaluate whether the distance from the site of event to an invasive heart centre, acute coronary angiography (CAG)/percutaneous coronary intervention (PCI) and hospital-level of care (invasive heart centre vs. local hospital) is associated with survival in out-of-hospital cardiac arrest (OHCA) patients. Nationwide historical follow-up study of 41 186 unselected OHCA patients, in whom resuscitation was attempted between 2001 and 2013, identified through the Danish Cardiac Arrest Registry. We observed an increase in the proportion of patients receiving bystander CPR (18% in 2001, 60% in 2013, P < 0.001), achieving return of spontaneous circulation (ROSC) (10% in 2001, 29% in 2013, P < 0.001) and being admitted directly to an invasive centre (26% in 2001, 45% in 2013, P < 0.001). Simultaneously, 30-day survival rose from 5% in 2001 to 12% in 2013, P < 0.001. Among patients achieving ROSC, a larger proportion underwent acute CAG/PCI (5% in 2001, 27% in 2013, P < 0.001). The proportion of patients undergoing acute CAG/PCI annually in each region was defined as the CAG/PCI index. The following variables were associated with lower mortality in multivariable analyses: direct admission to invasive heart centre (HR 0.91, 95% CI: 0.89-0.93), CAG/PCI index (HR 0.33, 95% CI: 0.25-0.45), population density above 2000 per square kilometre (HR 0.94, 95% CI: 0.89-0.98), bystander CPR (HR 0.97, 95% CI: 0.95-0.99) and witnessed OHCA (HR 0.87, 95% CI: 0.85-0.89), whereas distance to the nearest invasive centre was not associated with survival. Admission to an invasive heart centre and regional performance of acute CAG/PCI were associated with improved survival in OHCA patients, whereas distance to the invasive centre was not. These results support a centralized strategy for immediate post-resuscitation care in OHCA patients. © The Author 2017. Published on behalf of the European Society of Cardiology.

  2. Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

    PubMed

    Hazar, Volkan; Karasu, Gülsün Tezcan; Uygun, Vedat; Öztürk, Gülyüz; Kiliç, Suar Çaki; Küpesiz, Alphan; Daloglu, Hayriye; Aksoylar, Serap; Atay, Didem; Ince, Elif Ünal; Karakükçü, Musa; Özbek, Namik; Tayfun, Funda; Kansoy, Savas; Özyürek, Emel; Akçay, Arzu; Gürsel, Orhan; Haskologlu, Sule; Kaya, Zühre; Yilmaz, Sebnem; Tanyeli, Atila; Yesilipek, Akif

    2018-03-27

    Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

  3. Fungal discitis due to Aspergillus terreus in a patient with acute lymphoblastic leukemia.

    PubMed Central

    Park, K. U.; Lee, H. S.; Kim, C. J.; Kim, E. C.

    2000-01-01

    We report a case of Aspergillus terreus discitis which developed in a patient with acute lymphoblastic leukemia following induction chemotherapy. A. terreus was isolated from sputum, one month earlier, but the physician did not consider it significant at the time. Magnetic resonance imaging study showed the involvement of L3-4, L4-5 and L5-S1 intervertebral discs. Etiology was established by means of histology and culturing a surgical specimen of disc materials. Our patient survived after a surgical debridement and amphotericin B administration with a total dose of 2.0 g. Discitis caused by Aspergillus terreus is a very rare event. A. terreus is one of the invasive Aspergillus species. The pathogenetic mechanism is discussed and the literature is reviewed. PMID:11194199

  4. Fungal discitis due to Aspergillus terreus in a patient with acute lymphoblastic leukemia.

    PubMed

    Park, K U; Lee, H S; Kim, C J; Kim, E C

    2000-12-01

    We report a case of Aspergillus terreus discitis which developed in a patient with acute lymphoblastic leukemia following induction chemotherapy. A. terreus was isolated from sputum, one month earlier, but the physician did not consider it significant at the time. Magnetic resonance imaging study showed the involvement of L3-4, L4-5 and L5-S1 intervertebral discs. Etiology was established by means of histology and culturing a surgical specimen of disc materials. Our patient survived after a surgical debridement and amphotericin B administration with a total dose of 2.0 g. Discitis caused by Aspergillus terreus is a very rare event. A. terreus is one of the invasive Aspergillus species. The pathogenetic mechanism is discussed and the literature is reviewed.

  5. Fungal diversity and Aspergillus species in hospital environments.

    PubMed

    Martínez-Herrera, Erick Obed; Frías De-León, María Guadalupe; Duarte-Escalante, Esperanza; Calderón-Ezquerro, María Del Carmen; Jiménez-Martínez, María Del Carme; Acosta-Altamirano, Gustavo; Rivera-Becerril, Facundo; Toriello, Conchita; Reyes Montes, María Del Rocío

    2016-06-02

    Nosocomial invasive fungal infections, particularly aspergillosis, are an increasing problem in immunocompromised patients. The presented study evaluates fungal diversity and the presence of Aspergillus in air samples from two hospitals. Over the course of one year (rainy and dry seasons), the air was sampled from three areas in two hospitals (1 and 2) using a single-stage Andersen viable particle sampler (Thermo Scientific, Waltham, MA, USA). The fungi were identified by macro- and micromorphology, and the number of colony forming units (CFU)/m(3) air and their richness, abundance, and diversity were determined. Isolates Aspergillus genus were characterized by their thermotolerance. The CFU/m(3) air was similar at both hospitals during the two seasons, but different between the sampled areas. Results showed 10 fungal genera for hospital 1, and 8 for hospital 2. The most abundant were Penicillium, Cladosporium and Aspergillus. The thermotolerance test confirmed the identification of A. fumigatus section Fumigati. The highest growth rate was found in Aspergillus section Nigri. Determining the fungal diversity in the two hospitals was important because all the species have the potential to be pathogenic, especially the section Fumigati.

  6. Non-invasive detection of infection in acute pancreatic and acute necrotic collections with diffusion-weighted magnetic resonance imaging: preliminary findings.

    PubMed

    Islim, Filiz; Salik, Aysun Erbahceci; Bayramoglu, Sibel; Guven, Koray; Alis, Halil; Turhan, Ahmet Nuray

    2014-06-01

    The purpose of this study was to evaluate the contribution of diffusion-weighted magnetic resonance imaging (DW-MRI) to the detection of infection in acute pancreatitis-related collections. A total of 21 DW-MRI, and computed tomography (CT) were performed on 20 patients diagnosed as acute pancreatitis with acute peri-pancreatic fluid or necrotic collections. Collections were classified as infected or sterile according to the culture and follow-up results. Collections with gas bubbles on CT images were considered to be infected. Collections with peripheral bright signals on DW-MRI images were considered to be positive, whereas those without signals were considered to be negative. Apparent diffusion coefficient (ADC) values of the peripheral and central parts of the collections were measured. Student's t test was used to compare the means of ADC values of independent groups. Apart from one false positive result, the presence of infection was detected by DW-MRI with 95.2% accuracy. The sensitivity and accuracy of DW-MRI were higher than CT for the detection of infection. The ADC values in the central parts of the collections were significantly different between the infected and sterile groups. DW-MRI can be used as a non-invasive technique for the detection of infection in acute pancreatitis-associated collections.

  7. [Invasive yeast infections in neutropenic patients].

    PubMed

    Ruiz Camps, Isabel; Jarque, Isidro

    2016-01-01

    Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Deep Invasive Fungal Infection of the Hand in a Child Mimicking a Local Gigantism.

    PubMed

    Chatterjee, Anirban; Chatterjee, Shamita

    2018-04-01

    Subcutaneous and deep fungal infections in the hand are rare among children. These are usually found in immunocompromised adults or in persons engaged in soil handling activities, due to direct exposure, especially in the tropics. Delay in diagnosis is usual because pyogenic and other granulomatous infections are considered first. The authors present the case of a healthy, immunocompetent 2½-year-old child who presented with progressive swelling of the right hand mimicking a localized gigantism of the entire hand. Multiple operative drainage procedures done previously had failed to resolve the condition. A biopsy established the presence of fungal hyphae, thus confirming the diagnosis of deep fungal infection of the hand and guided proper therapeutic intervention. A strong index of suspicion needs to be maintained in cases not responding to conventional antibacterial therapy, and both microbiologic and histopathologic samples need to be obtained to establish the diagnosis.

  9. Thoracic spinal cord intramedullary aspergillus invasion and abscess.

    PubMed

    McCaslin, Addason F; Lall, Rishi R; Wong, Albert P; Lall, Rohan R; Sugrue, Patrick A; Koski, Tyler R

    2015-02-01

    Invasive central nervous system aspergillosis is a rare form of fungal infection that presents most commonly in immunocompromised individuals. There have been multiple previous reports of aspergillus vertebral osteomyelitis and spinal epidural aspergillus abscess; however to our knowledge there are no reports of intramedullary aspergillus infection. We present a 19-year-old woman with active acute lymphoblastic leukemia who presented with several weeks of fevers and bilateral lower extremity weakness. She was found to have an intramedullary aspergillus abscess at T12-L1 resulting from adjacent vertebral osteomyelitis and underwent surgical debridement with ultra-sound guided aspiration and aggressive intravenous voriconazole therapy. To our knowledge this is the first reported case of spinal aspergillosis invading the intramedullary cavity. Though rare, this entity should be included in the differential for immunocompromised patients presenting with fevers and neurologic deficit. Early recognition with aggressive neurosurgical intervention and antifungal therapy may improve outcomes in future cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Galactomannan, β-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

    PubMed

    Lehrnbecher, Thomas; Robinson, Paula D; Fisher, Brian T; Castagnola, Elio; Groll, Andreas H; Steinbach, William J; Zaoutis, Theoklis E; Negeri, Zelalem F; Beyene, Joseph; Phillips, Bob; Sung, Lillian

    2016-11-15

    We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. Toxicity assessment of chlorpyrifos-degrading fungal bio-composites and their environmental risks.

    PubMed

    Liu, Jie; Zhang, Xiaoying; Yang, Mengran; Hu, Meiying; Zhong, Guohua

    2018-02-01

    Bioremediation techniques coupling with functional microorganisms have emerged as the most promising approaches for in-situ elimination of pesticide residue. However, the environmental safety of bio-products based on microorganisms or engineered enzymes was rarely known. Here, we described the toxicity assessment of two previously fabricated fungal bio-composites which were used for the biodegradation of chlorpyrifos, to clarify their potential risks on the environment and non-target organisms. Firstly, the acute and chronic toxicity of prepared bio-composites were evaluated using mice and rabbits, indicating neither acute nor chronic effect was induced via short-term or continuous exposure. Then, the acute mortality on zebrafish was investigated, which implied the application of fungal bio-composites had no lethal risk on aquatic organisms. Meanwhile, the assessment on soil organic matters suggested that no threat was posed to soil quality. Finally, by monitoring, the germination of cabbage was not affected by the exposure to two bio-products. Therefore, the application of fungal bio-composites for chlorpyrifos elimination cannot induce toxic risk to the environment and non-target organisms, which insured the safety of these engineered bio-products for realistic management of pesticide residue, and provided new insights for further development of bioremediation techniques based on functional microorganisms.

  12. Serious fungal infections in the Philippines.

    PubMed

    Batac, M C R; Denning, D

    2017-06-01

    The Philippines is a low middle-income, tropical country in Southeast Asia. Infectious diseases remain the main causes of morbidity, including tuberculosis. AIDS/HIV prevalence is still low at <1%, but is rapidly increasing. Fungal disease surveillance has not been done, and its burden has never been estimated. This becomes more important as the population of immunocompromised patients increases, drawn from patients with AIDS, TB, malignancies, and autoimmune diseases requiring chronic steroid use. Using the methodology of the LIFE program ( www.LIFE-worldwide.org ), estimates were derived from data gathered from WHO, UNAIDS, Philippine Health Statistics 2011, Philippine Dermatological Society Health Information System database, HIV/AIDS and ART registry of the Philippines, epidemiological studies such as The TREAT Asia HIV Observational Database 2005, and personal communication. Aspergillosis and candidiasis were the top causes of fungal infections in the Philippines. Chronic pulmonary aspergillosis (CPA), drawn from the number of tuberculosis patients, affects 77,172 people. Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) frequencies, which were derived from the number of asthmatic patients, affect 121,113 and 159,869 respectively. Recurrent vulvovaginal candidiasis (RVVC) affects 1,481,899 women. Other estimates were cryptococcal meningitis 84, Pneumocystis pneumonia 391, oral candidiasis 3,467, esophageal candidiasis 1,522 (all in HIV-infected people), invasive aspergillosis (IA) 3,085, candidemia 1,968, candida peritonitis 246, mucormycosis 20, fungal keratitis 358, tinea capitis 846 and mycetoma 97 annually. A total of 1,852,137 (1.9% of population) are afflicted with a serious fungal infection. Epidemiological studies are needed to validate these estimates, facilitating appropriate medical care of patients and proper prioritization of limited resources.

  13. Fungal Disease Prevention in Seedlings of Rice (Oryza sativa) and Other Grasses by Growth-Promoting Seed-Associated Endophytic Bacteria from Invasive Phragmites australis

    PubMed Central

    Verma, Satish K.; Kingsley, Kathryn L.; Bergen, Marshall S.; White, James F.

    2018-01-01

    Non-cultivated plants carry microbial endophytes that may be used to enhance development and disease resistance of crop species where growth-promoting and protective microbes may have been lost. During seedling establishment, seedlings may be infected by several fungal pathogens that are seed or soil borne. Several species of Fusarium, Pythium and other water moulds cause seed rots during germination. Fusarium blights of seedlings are also very common and significantly affect seedling development. In the present study we screened nine endophytic bacteria isolated from the seeds of invasive Phragmites australis by inoculating onto rice, Bermuda grass (Cynodon dactylon), or annual bluegrass (Poa annua) seeds to evaluate plant growth promotion and protection from disease caused by Fusarium oxysporum. We found that three bacteria belonging to genus Pseudomonas spp. (SLB4-P. fluorescens, SLB6-Pseudomonas sp. and SY1-Pseudomonas sp.) promoted seedling development, including enhancement of root and shoot growth, and stimulation of root hair formation. These bacteria were also found to increase phosphate solubilization in in vitro experiments. Pseudomonas sp. (SY1) significantly protected grass seedlings from Fusarium infection. In co-culture experiments, strain SY1 strongly inhibited fungal pathogens with 85.71% growth inhibition of F. oxysporum, 86.33% growth inhibition of Curvularia sp. and 82.14% growth inhibition of Alternaria sp. Seedlings previously treated with bacteria were found much less infected by F. oxysporum in comparison to non-treated controls. On microscopic observation we found that bacteria appeared to degrade fungal mycelia actively. Metabolite products of strain SY1 in agar were also found to inhibit fungal growth on nutrient media. Pseudomonas sp. (SY1) was found to produce antifungal volatiles. Polymerase chain reaction (PCR) amplification using specific primers for pyrrolnitirin synthesis and HCN (hydrogen cyanide) production suggested presence of

  14. Fungal Disease Prevention in Seedlings of Rice (Oryza sativa) and Other Grasses by Growth-Promoting Seed-Associated Endophytic Bacteria from Invasive Phragmites australis.

    PubMed

    Verma, Satish K; Kingsley, Kathryn L; Bergen, Marshall S; Kowalski, Kurt P; White, James F

    2018-03-08

    Non-cultivated plants carry microbial endophytes that may be used to enhance development and disease resistance of crop species where growth-promoting and protective microbes may have been lost. During seedling establishment, seedlings may be infected by several fungal pathogens that are seed or soil borne. Several species of Fusarium , Pythium and other water moulds cause seed rots during germination. Fusarium blights of seedlings are also very common and significantly affect seedling development. In the present study we screened nine endophytic bacteria isolated from the seeds of invasive Phragmites australis by inoculating onto rice, Bermuda grass ( Cynodon dactylon ), or annual bluegrass ( Poa annua ) seeds to evaluate plant growth promotion and protection from disease caused by Fusarium oxysporum . We found that three bacteria belonging to genus Pseudomonas spp. (SLB4- P. fluorescens , SLB6- Pseudomonas sp. and SY1- Pseudomonas sp.) promoted seedling development, including enhancement of root and shoot growth, and stimulation of root hair formation. These bacteria were also found to increase phosphate solubilization in in vitro experiments. Pseudomonas sp. (SY1) significantly protected grass seedlings from Fusarium infection. In co-culture experiments, strain SY1 strongly inhibited fungal pathogens with 85.71% growth inhibition of F. oxysporum , 86.33% growth inhibition of Curvularia sp. and 82.14% growth inhibition of Alternaria sp. Seedlings previously treated with bacteria were found much less infected by F. oxysporum in comparison to non-treated controls. On microscopic observation we found that bacteria appeared to degrade fungal mycelia actively. Metabolite products of strain SY1 in agar were also found to inhibit fungal growth on nutrient media. Pseudomonas sp. (SY1) was found to produce antifungal volatiles. Polymerase chain reaction (PCR) amplification using specific primers for pyrrolnitirin synthesis and HCN (hydrogen cyanide) production suggested

  15. Estimated burden of fungal infections in Kenya.

    PubMed

    Guto, John Abuga; Bii, Christine C; Denning, David W

    2016-08-31

    Kenya is a developing country with a high rate of tuberculosis (TB) and a moderate HIV infection burden. No estimate of the burden of fungal diseases in Kenya is published. We used specific populations at risk and fungal infection frequencies from the literature to estimate national incidence or prevalence of serious fungal infections. Used sources were: 2010 WHO TB statistics, Kenya Acquired Immunodeficiency Syndrome (AIDS) Epidemic Update 2012, Kenya Facts and figures 2012, Kenya Demographic and Health Survey 2008-2009. Of Kenya's population of ~40 million, 43% are under 15 years old and approximately 594,660 Kenyan women get >4 episodes Candida vulvovaginitis annually (2,988/100,000). The HIV/AIDS population at risk of opportunistic infections (OI) is 480,000 and the OI estimates include 306,000 patients with oral thrush (768/100,000), 114,000 with oesophageal candidiasis (286/100,000), 11,900 with cryptococcal meningitis (29/100,000) and 17,000 patients with Pneumocystis pneumonia (42/100,000). Chronic pulmonary aspergillosis following TB has a prevalence of 10,848 cases (32/100,000). The adult asthma prevalence is 3.1% and assuming 2.5% have allergic bronchopulmonary aspergillosis then 17,696 (44/100,000) are affected.  Invasive aspergillosis, candidaemia and Candida peritonitis are probably uncommon. Tinea capitis infects 9.6% of children in Kenya, while fungal keratitis and otomycoses are difficult to estimate. At any one time, about 7% of the Kenyan population suffers from a significant fungal infection, with recurrent vaginitis and tinea capitis accounting for 82% of the infections. These estimates require further epidemiological studies for validation.

  16. Thigmo Responses: The Fungal Sense of Touch.

    PubMed

    Almeida, Mariana Cruz; Brand, Alexandra C

    2017-04-01

    The growth and development of most fungi take place on a two-dimensional surface or within a three-dimensional matrix. The fungal sense of touch is therefore critical for fungi in the interpretation of their environment and often signals the switch to a new developmental state. Contact sensing, or thigmo-based responses, include thigmo differentiation, such as the induction of invasion structures by plant pathogens in response to topography; thigmonasty, where contact with a motile prey rapidly triggers its capture; and thigmotropism, where the direction of hyphal growth is guided by physical features in the environment. Like plants and some bacteria, fungi grow as walled cells. Despite the well-demonstrated importance of thigmo responses in numerous stages of fungal growth and development, it is not known how fungal cells sense contact through the relatively rigid structure of the cell wall. However, while sensing mechanisms at the molecular level are not entirely understood, the downstream signaling pathways that are activated by contact sensing are being elucidated. In the majority of cases, the response to contact is complemented by chemical cues and both are required, either sequentially or simultaneously, to elicit normal developmental responses. The importance of a sense of touch in the lifestyles and development of diverse fungi is highlighted in this review, and the candidate molecular mechanisms that may be involved in fungal contact sensing are discussed.

  17. Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

    PubMed

    Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

    2015-06-01

    Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored. © 2015 John Wiley & Sons Ltd.

  18. Advances in the diagnosis and treatment of fungal infections of the CNS.

    PubMed

    Schwartz, Stefan; Kontoyiannis, Dimitrios P; Harrison, Thomas; Ruhnke, Markus

    2018-04-01

    Fungal infections of the CNS are challenging to treat and their optimal management requires knowledge of their epidemiology, host characteristics, diagnostic criteria, and therapeutic options. Aspergillus and Cryptococcus species predominate among fungal infections of the CNS. Most of these fungi are ubiquitous, but some have restricted geographical distribution. Fungal infections of the CNS usually originate from primary sites outside the CNS (eg, fungal pneumonia) or occur after inoculation (eg, invasive procedures). Most patients with these infections have immunodeficiencies, but immunocompetent individuals can also be infected through heavy exposure. The infecting fungi can be grouped into moulds, yeasts, and dimorphic fungi. Substantial progress has been made with new diagnostic approaches and the introduction of novel antifungal drugs, but fungal infections of the CNS are frequently lethal because of diagnostic delays, impaired drug penetration, resistance to antifungal treatments, and inadequate restoration of immune function. To improve outcomes, future research should advance diagnostic methods (eg, molecular detection and fungus identification), develop antifungal compounds with enhanced CNS-directed efficacy, and further investigate crucial host defence mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity.

    PubMed

    Sterkel, Alana K; Lorenzini, Jenna L; Fites, J Scott; Subramanian Vignesh, Kavitha; Sullivan, Thomas D; Wuthrich, Marcel; Brandhorst, Tristan; Hernandez-Santos, Nydiaris; Deepe, George S; Klein, Bruce S

    2016-03-09

    Systemic fungal infections trigger marked immune-regulatory disturbances, but the mechanisms are poorly understood. We report that the pathogenic yeast of Blastomyces dermatitidis elaborates dipeptidyl-peptidase IVA (DppIVA), a close mimic of the mammalian ectopeptidase CD26, which modulates critical aspects of hematopoiesis. We show that, like the mammalian enzyme, fungal DppIVA cleaved C-C chemokines and GM-CSF. Yeast producing DppIVA crippled the recruitment and differentiation of monocytes and prevented phagocyte activation and ROS production. Silencing fungal DppIVA gene expression curtailed virulence and restored recruitment of CCR2(+) monocytes, generation of TipDC, and phagocyte killing of yeast. Pharmacological blockade of DppIVA restored leukocyte effector functions and stemmed infection, while addition of recombinant DppIVA to gene-silenced yeast enabled them to evade leukocyte defense. Thus, fungal DppIVA mediates immune-regulatory disturbances that underlie invasive fungal disease. These findings reveal a form of molecular piracy by a broadly conserved aminopeptidase during disease pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  1. 10-Year Mortality Outcome of a Routine Invasive Strategy Versus a Selective Invasive Strategy in Non-ST-Segment Elevation Acute Coronary Syndrome: The British Heart Foundation RITA-3 Randomized Trial.

    PubMed

    Henderson, Robert A; Jarvis, Christopher; Clayton, Tim; Pocock, Stuart J; Fox, Keith A A

    2015-08-04

    The RITA-3 (Third Randomised Intervention Treatment of Angina) trial compared outcomes of a routine early invasive strategy (coronary arteriography and myocardial revascularization, as clinically indicated) to those of a selective invasive strategy (coronary arteriography for recurrent ischemia only) in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). At a median of 5 years' follow-up, the routine invasive strategy was associated with a 24% reduction in the odds of all-cause mortality. This study reports 10-year follow-up outcomes of the randomized cohort to determine the impact of a routine invasive strategy on longer-term mortality. We randomized 1,810 patients with NSTEACS to receive routine invasive or selective invasive strategies. All randomized patients had annual follow-up visits up to 5 years, and mortality was documented thereafter using data from the Office of National Statistics. Over 10 years, there were no differences in mortality between the 2 groups (all-cause deaths in 225 [25.1%] vs. 232 patients [25.4%]: p = 0.94; and cardiovascular deaths in 135 [15.1%] vs. 147 patients [16.1%]: p = 0.65 in the routine invasive and selective invasive groups, respectively). Multivariate analysis identified several independent predictors of 10-year mortality: age, previous myocardial infarction, heart failure, smoking status, diabetes, heart rate, and ST-segment depression. A modified post-discharge Global Registry of Acute Coronary Events (GRACE) score was used to calculate an individual risk score for each patient and to form low-risk, medium-risk, and high-risk groups. Risk of death within 10 years varied markedly from 14.4 % in the low-risk group to 56.2% in the high-risk group. This mortality trend did not depend on the assigned treatment strategy. The advantage of reduced mortality of routine early invasive strategy seen at 5 years was attenuated during later follow-up, with no evidence of a difference in outcome at 10 years

  2. CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

    PubMed Central

    Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

    2015-01-01

    Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9 -/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9 -/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

  3. Fungal decomposers of leaf litter from an invaded and native mountain forest of NW Argentina.

    PubMed

    Fernandez, Romina Daiana; Bulacio, Natalia; Álvarez, Analía; Pajot, Hipólito; Aragón, Roxana

    2017-09-01

    The impact of plant species invasions on the abundance, composition and activity of fungal decomposers of leaf litter is poorly understood. In this study, we isolated and compared the relative abundance of ligninocellulolytic fungi of leaf litter mixtures from a native forest and a forest invaded by Ligustrum lucidum in a lower mountain forest of Tucuman, Argentina. In addition, we evaluated the relationship between the relative abundance of ligninocellulolytic fungi and properties of the soil of both forest types. Finally, we identified lignin degrading fungi and characterized their polyphenol oxidase activities. The relative abundance of ligninocellulolytic fungi was higher in leaf litter mixtures from the native forest. The abundance of cellulolytic fungi was negatively related with soil pH while the abundance of ligninolytic fungi was positively related with soil humidity. We identified fifteen genera of ligninolytic fungi; four strains were isolated from both forest types, six strains only from the invaded forest and five strains were isolated only from the native forest. The results found in this study suggest that L. Lucidum invasion could alter the abundance and composition of fungal decomposers. Long-term studies that include an analysis of the nutritional quality of litter are needed, for a more complete overview of the influence of L. Lucidum invasion on fungal decomposers and on leaf litter decomposition.

  4. Rare fungal infectious agents: a lurking enemy

    PubMed Central

    Skiada, Anna; Pavleas, Ioannis; Drogari-Apiranthitou, Maria

    2017-01-01

    In the expanding population of immunocompromised patients and those treated in intensive care units, rare fungal infectious agents have emerged as important pathogens, causing invasive infections associated with high morbidity and mortality. These infections may present either as de novo or as breakthrough invasive infections in high-risk patients with hematologic malignancies receiving prophylactic or empirical antifungal therapy or in patients with central venous catheters. Diagnosis and treatment are challenging. Physicians should have a high index of suspicion because early diagnosis is of paramount importance. Conventional diagnostic methods such as cultures and histopathology are still essential, but rapid and more specific molecular techniques for both detection and identification of the infecting pathogens are being developed and hopefully will lead to early targeted treatment. The management of invasive fungal infections is multimodal. Reversal of risk factors, if feasible, should be attempted. Surgical debridement is recommended in localized mold infections. The efficacy of various antifungal drugs is not uniform. Amphotericin B is active against most yeasts, except Trichosporon, as well as against Mucorales, Fusarium, and some species of Paecilomyces and dimorphic fungi. The use of voriconazole is suggested for the treatment of trichosporonosis and scedosporiosis. Combination treatment, though recommended as salvage therapy in some infections, is controversial in most cases. Despite the use of available antifungals, mortality remains high. The optimization of molecular-based techniques, with expansion of reference libraries and the possibility for direct detection of resistance mechanisms, is awaited with great interest in the near future. Further research is necessary, however, in order to find the best ways to confront and destroy these lurking enemies. PMID:29152230

  5. Quantifying the associations between fungal endophytes and biocontrol-induced herbivory of invasive purple loosestrife (Lythrum salicaria L.).

    PubMed

    David, Aaron S; Quiram, Gina L; Sirota, Jennie I; Seabloom, Eric W

    2016-01-01

    Fungal endophytes are one of several groups of heterotrophic organisms that associate with living plants. The net effects of these groups of organisms on each other and ultimately on their host plants depend in part on how they facilitate or antagonize one another. In this study we quantified the associations between endophyte communities and herbivory induced by a biological control in the invasive Lythrum salicaria at various spatial scales using a culture-based approach. We found positive associations between herbivory damage and endophyte isolation frequency and richness at the site level and weak, positive associations at the leaf level. Herbivory damage was more strongly influenced by processes at the site level than were endophyte isolation frequency and community structure, which were influenced by processes at the plant and leaf levels. Furthermore, endophytic taxa found in low herbivory sites were nested subsets of those taxa found at high herbivory sites. Our findings suggest that endophyte communities of L. salicaria are associated with, and potentially facilitated by, biocontrol-induced herbivory. Quantifying the associations between heterotrophic groups ultimately may lead to a clearer understanding of their complex interactions with plants. © 2016 by The Mycological Society of America.

  6. Role of pathogen-associated molecular patterns (PAMPS) in immune responses to fungal infections.

    PubMed

    Taghavi, Mehdi; Khosravi, Alireza; Mortaz, Esmaeil; Nikaein, Donya; Athari, Seyyed Shamsadin

    2017-08-05

    Recent years have seen the rise of invasive fungal infections, which are mostly due to the increase in patients. Three major opportunistic fungal species in human are Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans that pose the biggest concern for these immunocompromised patients' mortality. The growing occurrence of opportunistic fungal infections has sparked the interest to understand defense mechanisms against pathogenic fungi. Toll-like receptors (TLRs), as a part of innate immune system, play an important role for recognizing the invading microorganisms and initiating sufficient immune responses. Recent studies have revealed an integrated role for TLR, signaling inactivating immune defense mechanisms against exact fungi. Among TLRs, TLR2 and TLR4 are the major participants in fungi recognition. The present paper highlights the role of TLR participants in fungal recognition as well as their mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Miconazole therapy for treatment of fungal infections in cancer patients.

    PubMed

    Jordan, W M; Bodey, G P; Rodriguez, V; Ketchel, S J; Henney, J

    1979-12-01

    The effectiveness of miconazole was evaluated in 37 documented fungal infections, 32 of which were major infections. All patients were receiving therapy for advanced malignancy, with 28 patients having acute leukemia. The overall cure rate was 41% and it was also 41% for major fungal infections. Nine of 22 patients with Candida albicans infections were cured, and 3 of 11 patients with Candida tropicalis infections were cured. A total of 183 patients who received miconazole for presumed or documented fungal infection were evaluated for toxicity. Nausea and vomiting and central nervous system toxicity were the most common side effects, occurring in 25 and 16% of the patients, respectively. Overall, the drug was tolerated well, with only four patients requiring the drug to be permanently discontinued because of toxicity.

  9. Invasive fungal infection caused by geotrichum capitatum in patients with acute lymphoblastic leukemia: a case study and literature review

    PubMed Central

    Gao, Guang-Xun; Tang, Hai-Long; Zhang, Xuan; Xin, Xiao-Li; Feng, Juan; Chen, Xie-Qun

    2015-01-01

    Geotrichum capitatum infection has a very low incidence rate with atypical clinical symptoms, making diagnosis difficult, and it has a poor prognosis. The incidence is even more rare in China. This paper reports the first case of infection caused by G. capitatum during bone marrow suppression after chemotherapy in a Chinese patient with acute lymphoblastic leukemia. In addition, it reports a systematic literature review of diagnosis and treatment. The patient with acute lymphoblastic leukemia was confirmed to be infected with G. capitatum, involving lung, liver and skin, through a blood culture test. Caspofungin, amphotericin B loposome, and a combination therapy of amphotericin B liposome and voriconazole were used in succession for treatment. Despite normal body temperature and a slight improvement of clinical symptoms with the combination therapy treatment, the patient died 40 days after chemotherapy due to heart and lung failure. PMID:26550401

  10. Estimation of the Burden of Serious Human Fungal Infections in Malaysia

    PubMed Central

    Velayuthan, Rukumani Devi; Samudi, Chandramathi; Lakhbeer Singh, Harvinder Kaur; Ng, Kee Peng

    2018-01-01

    Fungal infections (mycoses) are likely to occur more frequently as ever-increasingly sophisticated healthcare systems create greater risk factors. There is a paucity of systematic data on the incidence and prevalence of human fungal infections in Malaysia. We conducted a comprehensive study to estimate the burden of serious fungal infections in Malaysia. Our study showed that recurrent vaginal candidiasis (>4 episodes/year) was the most common of all cases with a diagnosis of candidiasis (n = 501,138). Oesophageal candidiasis (n = 5850) was most predominant among individuals with HIV infection. Candidemia incidence (n = 1533) was estimated in hospitalized individuals, some receiving treatment for cancer (n = 1073), and was detected also in individuals admitted to intensive care units (ICU) (n = 460). In adults with asthma, allergic bronchopulmonary aspergillosis (ABPA) was the second most common respiratory mycoses noticed (n = 30,062) along with severe asthma with fungal sensitization (n = 39,628). Invasive aspergillosis was estimated in 184 cases undergoing anti-cancer treatment and 834 ICU cases. Cryptococcal meningitis was diagnosed in 700 subjects with HIV/AIDS and Pneumocystis jirovecii pneumonitis (PCP) in 1286 subjects with underlying HIV disease. The present study indicates that at least 590,214 of the Malaysian population (1.93%) is affected by a serious fungal infection annually. This problem is serious enough to warrant the further epidemiological studies to estimate the burden of human fungal infections in Malaysia. PMID:29562712

  11. Burden of serious fungal infections in Ukraine.

    PubMed

    Osmanov, Ali; Denning, David W

    2015-10-01

    Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually. © 2015 Blackwell Verlag GmbH.

  12. Pathogen dynamics during invasion and establishment of white-nose syndrome explain mechanisms of host persistence.

    PubMed

    Frick, Winifred F; Cheng, Tina L; Langwig, Kate E; Hoyt, Joseph R; Janicki, Amanda F; Parise, Katy L; Foster, Jeffrey T; Kilpatrick, A Marm

    2017-03-01

    Disease dynamics during pathogen invasion and establishment determine the impacts of disease on host populations and determine the mechanisms of host persistence. Temporal progression of prevalence and infection intensity illustrate whether tolerance, resistance, reduced transmission, or demographic compensation allow initially declining populations to persist. We measured infection dynamics of the fungal pathogen Pseudogymnoascus destructans that causes white-nose syndrome in bats by estimating pathogen prevalence and load in seven bat species at 167 hibernacula over a decade as the pathogen invaded, became established, and some host populations stabilized. Fungal loads increased rapidly and prevalence rose to nearly 100% at most sites within 2 yr of invasion in six of seven species. Prevalence and loads did not decline over time despite huge reductions in colony sizes, likely due to an extensive environmental reservoir. However, there was substantial variation in fungal load among sites with persisting colonies, suggesting that both tolerance and resistance developed at different sites in the same species. In contrast, one species disappeared from hibernacula within 3 yr of pathogen invasion. Variable host responses to pathogen invasion require different management strategies to prevent disease-induced extinction and to facilitate evolution of tolerance or resistance in persisting populations. © 2016 by the Ecological Society of America.

  13. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

    PubMed

    Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

    2016-04-19

    Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

  14. A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.

    PubMed

    Doria, Cataldo; Bodzin, Adam S; Vaccino, Silvia; Daskalakis, Constantine; Krawitz, Steven; Ramirez, Carlo B

    2011-01-01

    This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high-risk patients. Post-transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re-transplantation; (ii) re-operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re-intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two-thirds male and three-quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment

  15. Fungal disease prevention in seedlings of rice (Oryza sativa) and other grasses by growth-promoting seed-associated endophytic bacteria from invasive Phragmites australis

    USGS Publications Warehouse

    Verma, Satish K.; Kingsley, Kathryn L.; Bergen, Marshall S.; Kowalski, Kurt P.; White, James F.

    2018-01-01

    Non-cultivated plants carry microbial endophytes that may be used to enhance development and disease resistance of crop species where growth-promoting and protective microbes may have been lost. During seedling establishment, seedlings may be infected by several fungal pathogens that are seed or soil borne. Several species of Fusarium, Pythium and other water moulds cause seed rots during germination. Fusariumblights of seedlings are also very common and significantly affect seedling development. In the present study we screened nine endophytic bacteria isolated from the seeds of invasive Phragmites australis by inoculating onto rice, Bermuda grass (Cynodon dactylon), or annual bluegrass (Poa annua) seeds to evaluate plant growth promotion and protection from disease caused by Fusarium oxysporum. We found that three bacteria belonging to genus Pseudomonas spp. (SLB4-P. fluorescens, SLB6-Pseudomonas sp. and SY1-Pseudomonassp.) promoted seedling development, including enhancement of root and shoot growth, and stimulation of root hair formation. These bacteria were also found to increase phosphate solubilization in in vitro experiments. Pseudomonas sp. (SY1) significantly protected grass seedlings from Fusarium infection. In co-culture experiments, strain SY1 strongly inhibited fungal pathogens with 85.71% growth inhibition of F. oxysporum, 86.33% growth inhibition of Curvularia sp. and 82.14% growth inhibition of Alternaria sp. Seedlings previously treated with bacteria were found much less infected by F. oxysporum in comparison to non-treated controls. On microscopic observation we found that bacteria appeared to degrade fungal mycelia actively. Metabolite products of strain SY1 in agar were also found to inhibit fungal growth on nutrient media. Pseudomonas sp. (SY1) was found to produce antifungal volatiles. Polymerase chain reaction (PCR) amplification using specific primers for pyrrolnitirin synthesis and HCN (hydrogen cyanide) production

  16. Multiple pancreaticoduodenal penetrating gunshot trauma evolving into acute necrotizing pancreatitis. A combined surgical and minimally invasive approach.

    PubMed

    Testini, Mario; Piccinni, Giuseppe; Pedote, Pasquale; Lissidini, Germana; Gurrado, Angela; Lardo, Domenica; Greco, Luigi; Marzaioli, Rinaldo

    2008-09-02

    Shotgun injuries are the cause of increasing surgical problems related to the proliferation of firearms. Gunshot pancreaticoduodenal traumas are unusual in urban trauma units. Their management remains complex because of the absence of standardized, universal guidelines for treatment and the high incidence of associated lesions of major vessels as well as of other gastrointestinal structures. Surgical treatment is still controversial, and the possibilities offered by the safe and effective mini-invasive techniques seem to open new, articulated perspectives for the treatment of pancreaticoduodenal injury complications. We present the case of a 27-year-old man with multiple penetrating gunshot trauma evolving into acute necrotizing pancreatitis, treated by combining a surgical with a mini-invasive approach. At admission, he presented a Glasgow Coma Score of 4 due to severe hemorrhagic shock. First, surgical hemostasis, duodenogastric resection, multiple intestinal resections, peripancreatic and thoracic drainage were carried out as emergency procedures. On the 12th postoperative day, the patient underwent re-surgery with toilette, external duodenal drainage with Foley tube and peripancreatic drainage repositioning as a result of a duodenal perforation due to acute necrotizing pancreatitis. Eight days later, following the accidental removal of the peripancreatic drains, a CT scan was done showing a considerable collection of fluid in the epiploon retrocavity. Percutaneous CT-guided drainage was performed by inserting an 8.5 Fr pigtail catheter, thus avoiding further re-operation. The patient was successfully discharged on the 80th postoperative day. The treatment of multiple pancreaticoduodenal penetrating gunshot traumas should focus on multidisciplinary surgical and minimally invasive treatment to optimize organ recovery.

  17. Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach.

    PubMed

    Mech, Franziska; Wilson, Duncan; Lehnert, Teresa; Hube, Bernhard; Thilo Figge, Marc

    2014-02-01

    Candida albicans is the most common opportunistic fungal pathogen of the human mucosal flora, frequently causing infections. The fungus is responsible for invasive infections in immunocompromised patients that can lead to sepsis. The yeast to hypha transition and invasion of host-tissue represent major determinants in the switch from benign colonizer to invasive pathogen. A comprehensive understanding of the infection process requires analyses at the quantitative level. Utilizing fluorescence microscopy with differential staining, we obtained images of C. albicans undergoing epithelial invasion during a time course of 6 h. An image-based systems biology approach, combining image analysis and mathematical modeling, was applied to quantify the kinetics of hyphae development, hyphal elongation, and epithelial invasion. The automated image analysis facilitates high-throughput screening and provided quantities that allow for the time-resolved characterization of the morphological and invasive state of fungal cells. The interpretation of these data was supported by two mathematical models, a kinetic growth model and a kinetic transition model, that were developed using differential equations. The kinetic growth model describes the increase in hyphal length and revealed that hyphae undergo mass invasion of epithelial cells following primary hypha formation. We also provide evidence that epithelial cells stimulate the production of secondary hyphae by C. albicans. Based on the kinetic transition model, the route of invasion was quantified in the state space of non-invasive and invasive fungal cells depending on their number of hyphae. This analysis revealed that the initiation of hyphae formation represents an ultimate commitment to invasive growth and suggests that in vivo, the yeast to hypha transition must be under exquisitely tight negative regulation to avoid the transition from commensal to pathogen invading the epithelium. © 2013 International Society for

  18. Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.

    PubMed

    Chamilos, Georgios; Lionakis, Michail S; Kontoyiannis, Dimitrios P

    2018-01-06

    Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. A Pilot Study of a Computerized Decision Support System to Detect Invasive Fungal Infection in Pediatric Hematology/Oncology Patients.

    PubMed

    Bartlett, Adam; Goeman, Emma; Vedi, Aditi; Mostaghim, Mona; Trahair, Toby; O'Brien, Tracey A; Palasanthiran, Pamela; McMullan, Brendan

    2015-11-01

    Computerized decision support systems (CDSSs) can provide indication-specific antimicrobial recommendations and approvals as part of hospital antimicrobial stewardship (AMS) programs. The aim of this study was to assess the performance of a CDSS for surveillance of invasive fungal infections (IFIs) in an inpatient hematology/oncology cohort. Between November 1, 2012, and October 31, 2013, pediatric hematology/oncology inpatients diagnosed with an IFI were identified through an audit of the CDSS and confirmed by medical record review. The results were compared to hospital diagnostic-related group (DRG) coding for IFI throughout the same period. A total of 83 patients were prescribed systemic antifungals according to the CDSS for the 12-month period. The CDSS correctly identified 19 patients with IFI on medical record review, compared with 10 patients identified by DRG coding, of whom 9 were confirmed to have IFI on medical record review. CDSS was superior to diagnostic coding in detecting IFI in an inpatient pediatric hematology/oncology cohort. The functionality of CDSS lends itself to inpatient infectious diseases surveillance but depends on prescriber adherence.

  20. Endoscope-assisted, minimally invasive evacuation of sub-acute/chronic epidural hematoma: Novelty or paradox of Theseus?

    PubMed

    Ansari, Ishtyaque; Futane, Sameer; Ansari, Ashfaque

    2016-08-01

    Sub-acute/chronic epidural hematoma (EDH) may present with nagging symptoms of headache, nausea, vomiting, lethargy, etc. We attempted to offer a minimally invasive, single burr hole, endoscope-assisted evacuation of EDHs instead of a conventional craniotomy. Seven patients with sub-acute/chronic EDH (six supratentorial and one infratentorial) presented to us 3 to 7 days after low-velocity road traffic accidents with complaints of headache and lethargy. The EDH volumes measured between 20 to 50 ml, and the patients were operated on using a single burr hole made through a small incision. We used 0-, 30- and 70-degree, angulated, rigid, high-definition endoscopes to identify and evacuate the organized clots in the extradural space. Flexible catheters were used for suction and irrigation. After achieving hemostasis, the dura was hitched back to the burr hole site. The wound was closed over a negative suction drain. All patients had prompt recovery from symptoms. Postoperative CT scans showed complete or near complete evacuation of the hematomas. The hospital stay and analgesic requirements were minimal. There was no infective complication or conversion to conventional open surgery. The average time for surgery was 77.8 min, and average blood loss was 328.5 ml. Endoscope-assisted evacuation of sub-acute/chronic EDH is a novel concept, which offers quick relief from symptoms in a minimally invasive fashion and a cosmetically acceptable way. None of the standard principles of surgery are hampered. It avoids extensive dissection of the temporalis or sub-occipital muscles. However, achieving hemostasis can be difficult. Further study and better equipment will validate the procedure.

  1. Non-invasive ventilation (NIV) as an aid to rehabilitation in acute respiratory disease.

    PubMed

    Dyer, Fran; Flude, Lizzie; Bazari, Farid; Jolley, Caroline; Englebretsen, Catherine; Lai, Dilys; Polkey, Michael I; Hopkinson, Nicholas S

    2011-12-16

    Non-invasive ventilation (NIV) can increase exercise tolerance, reduce exercise induced desaturation and improve the outcome of pulmonary rehabilitation in patients with chronic respiratory disease. It is not known whether it can be applied to increase exercise capacity in patients admitted with non-hypercapnic acute exacerbations of COPD (AECOPD). We investigated the acceptability and feasibility of using NIV for this purpose. On a single occasion, patients admitted with an acute exacerbation of chronic respiratory disease who were unable to cycle for five minutes at 20 watts attempted to cycle using NIV and their endurance time (T(lim)) was recorded. To determine feasibility of this approach in clinical practice patients admitted with AECOPD were screened for participation in a trial of regular NIV assisted rehabilitation during their hospital admission. In 12 patients tested on a single occasion NIV increased T(lim) from 184(65) seconds to 331(229) seconds (p = 0.04) and patients desaturated less (median difference = 3.5%, p = 0.029). In the second study, 60 patients were admitted to hospital during a three month period of whom only 18(30)% were eligible to participate and of these patients, only four (7%) consented to participate. NIV improves exercise tolerance in patients with acute exacerbations of chronic respiratory disease but the applicability of this approach in routine clinical practice may be limited. http://www.controlled-trials.com/ISRCTN35692743.

  2. Arbuscular and Ectomycorrhizal Fungi Associated with the Invasive Brazilian Pepper Tree (Schinus terebinthifolius) and Two Native Plants in South Florida

    PubMed Central

    Dawkins, Karim; Esiobu, Nwadiuto

    2017-01-01

    The potential role of soil fungi in the invasion of the Brazilian pepper tree (Schinus terebinthifolius—BP) in Florida is not known; although the low biotic resistance of Florida soils is often invoked to explain the prevalence of many invasive species. To gain an initial insight into BP's mycorrhizal associations, this study examined the rhizobiome of BP and two native plants (Hamelia patens and Bidens alba) across six locations. Arbuscular mycorrhizal fungi (AMF) associated with the roots of the target plants and bulk soil was characterized by spore morphotyping. Sequence analysis of metagenomic DNA from lateral roots/rhizosphere of BP (n = 52) and a native shrub H. patens (n = 37) on the same parcel yielded other fungal associates. Overall, the total population of AMF associated with BP was about two folds greater than that of the two native plants (p = 0.0001) growing on the same site. The dominant AMF under Schinus were members of the common Glomus and Rhizophagus spp. By contrast, the most prevalent AMF in the bulk soil and rhizosphere of the two Florida native plants, Acaulospora spp (29%) was sharply diminished (9%) under BP rhizosphere. Analysis of the ITS2 sequences also showed that Schinus rhizosphere had a high relative abundance of ectomycorrhizal fungi (76.5%) compared to the native H. patens (2.6%), with the species Lactifluus hygrophoroides (Basidiomycota) being the most prevalent at 61.5% (p < 0.05). Unlike the native plants where pathogenic fungi like Phyllosticta sp., Phoma sp., and Neofusicoccum andium were present (8.1% for H. patens), only one potentially pathogenic fungal taxon was detected (3.9%) under BP. The striking disparity in the relative abundance of AMF and other fungal types between BP and the native species is quite significant. Fungal symbionts could aide plant invasion via resource-use efficiency and other poorly defined mechanisms of protection from pathogens in their invaded range. This report exposes a potentially

  3. Imaging O2 changes induced in tomato roots by fungal pathogen

    NASA Astrophysics Data System (ADS)

    Rubol, S.; Turco, E.; Rodeghiero, M.; Bellin, A.

    2014-12-01

    In the last decade, planar optodes have demonstrated to be a useful non-invasive tool to monitor real time oxygen concentrations in a wide range of applications. However, only limited investigations have been carried out to explore the use of optodes in plant respiration studies. In particular, their use to study plant-pathogen interactions has been not deeply investigated. Here, we present for the first time an in vitro experimental setup capable to depict the dynamical effects of the fungal pathogen Fusarium oxysporum f.sp. lycopersici (Fol) on tomato roots by the use of a recently developed optical non-invasive optode oxygen sensor (Visisens, Presens, Germany). Fol is a soil-borne pathogen and the causal agent of wilt in tomato plants, a destructive worldwide disease. The interaction Fol-tomato is widely accepted as a model system in plant pathology. In this work, oxygen concentrations are monitored continuously in time and considered a proxy for root respiration and metabolic activity. The experimental procedure reveals three different dynamic stages: 1) a uniform oxygen consumption in tomato roots earlier before pathogen colonization, 2) a progressive decrease in the oxygen concentration indicating a high metabolic activity as soon as the roots were surrounded and colonized by the fungal mycelium, and 3) absence of root respiration, as a consequence of root death. Our results suggest the ability of the fungal mycelium to move preferentially towards and along the root as a consequence of the recognition event.

  4. Effectiveness of environmental control measures to decrease the risk of invasive aspergillosis in acute leukaemia patients during hospital building work.

    PubMed

    Combariza, J F; Toro, L F; Orozco, J J

    2017-08-01

    Invasive aspergillosis (IA) is a significant problem in acute leukaemia patients. Construction work near hospital wards caring for immunocompromised patients is one of the main risk factors for developing invasive pulmonary aspergillosis (IPA). To assess the impact of environmental control measures used during hospital construction for the prevention of IA in acute leukaemia patients. A retrospective cohort study was developed to evaluate the IA incidence in acute leukaemia patients with different environmental control measures employed during hospital construction. We used European Organisation for the Research and Treatment of Cancer (EORTC) criterial diagnosis parameters for definition of IA. A total of 175 episodes of inpatient care were evaluated, 62 of which did not have any environmental control measures (when an outbreak occurred), and 113 that were subject to environmental control measures directed to preventing IA. The study showed an IA incidence of 25.8% for the group without environmental control measures vs 12.4% for those who did receive environmental control measures (P=0.024). The relative risk for IA was 0.595 (95% confidence interval: 0.394-0.897) for the group with environmental control measures. The current study suggests that the implementation of environmental control measures during a hospital construction has a positive impact for prevention of IA in patients hospitalized with acute leukaemia. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  5. Role of non-invasive ventilation in difficult-to-wean children with acute neuromuscular disease.

    PubMed

    Reddy, V G; Nair, M P; Bataclan, F

    2004-05-01

    Weaning from mechanical ventilation in children could be time-consuming and on many occasions, leads to reintubation with its associate complications. We report two children with acute neuromuscular disease, in whom bi-level positive airway pressure (BiPAP) as a mode of non-invasive ventilation was successfully used to wean the child from ventilators and prevented the need for tracheostomy. Despite the limited number of studies published in the literature suggesting BiPAP as a mode of weaning from mechanical ventilation, the technique when applied correctly seems to be safe and effective in weaning and avoiding tracheostomy.

  6. Starvation and imidacloprid exposure influence immune response by Anoplophora glabripennis (Coleoptera: Cerambycidae) to a fungal pathogen

    USDA-ARS?s Scientific Manuscript database

    In several insect systems, fungal entomopathogens synergize with neonicotinoid insecticides which results in accelerated host death. Using the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), an invasive woodborer inadvertently introduced into North America and Europe, we investigate...

  7. Invasion dynamics of white-nose syndrome fungus, midwestern United States, 2012-2014.

    PubMed

    Langwig, Kate E; Hoyt, Joseph R; Parise, Katy L; Kath, Joe; Kirk, Dan; Frick, Winifred F; Foster, Jeffrey T; Kilpatrick, A Marm

    2015-06-01

    White-nose syndrome has devastated bat populations in eastern North America. In Midwestern United States, prevalence increased quickly in the first year of invasion (2012-13) but with low population declines. In the second year (2013-14), environmental contamination led to earlier infection and high population declines. Interventions must be implemented before or soon after fungal invasion to prevent population collapse.

  8. Recovery of calf muscle strength following acute achilles tendon rupture treatment: a comparison between minimally invasive surgery and conservative treatment.

    PubMed

    Metz, Roderik; van der Heijden, Geert J M G; Verleisdonk, Egbert-Jan M M; Tamminga, Rob; van der Werken, Christiaan

    2009-10-01

    The aim of this study was to measure the effect of treatment of acute Achilles tendon ruptures on calf muscle strength recovery. Eighty-three patients with acute Achilles tendon rupture were randomly allocated to either minimally invasive surgery with functional after-treatment or conservative treatment by functional bracing. Calf muscle strength using isokinetic testing was evaluated at 3 months and after 6 or more months posttreatment. To exclusively investigate the effect of treatment on outcome, the authors excluded patients with major complications from the analysis. In 31 of 39 patients in the surgical treatment group and 25 of 34 patients in the conservative treatment group, isokinetic strength tests were performed. In the analysis of differences in mean peak torque, no statistically significant differences were found between surgery and conservative treatment, except for plantar flexion strength at 90 degrees per second at the second measurement, favoring conservative treatment. After 8 to 10 months follow- up, loss of plantar flexion strength was still present in the injured leg in both treatment groups. In conclusion, isokinetic muscle strength testing did not detect a statistically significant difference between minimally invasive surgical treatment with functional after-treatment and conservative treatment by functional bracing of acute Achilles tendon ruptures.

  9. Successful management of a renal fungal ball in a pretermature neonate: A case report and review of literature

    PubMed Central

    Raghunath, B. V.; Gowrishankar, B. C.; Narendrababu, M.; Ramesh, S.

    2013-01-01

    Invasive fungal infection is common in the present day NICUs - generally manifesting as candiduria or candida sepsis. Fungal balls in the kidneys are very uncommon and most are amenable to higher antifungal agents. However, we had a child who did not respond to such measures and ultimately needed a surgical removal of the fungal ball in his kidney. We report this case along with a review of literature to highlight about this uncommon, but an important cause of persistent sepsis in pre-term infants and to review the treatment options including a surgical removal. PMID:24019645

  10. Non-invasive coronary angiography for patients with acute atypical chest pain discharged after negative screening including maximal negative treadmill stress test. A prospective study.

    PubMed

    Bonello, L; Armero, S; Jacquier, A; Com, O; Sarran, A; Sbragia, P; Panuel, M; Arques, S; Paganelli, F

    2009-05-01

    Among patients admitted in the emergency department for acute atypical chest pain those with an acute coronary syndrome (ACS) who are mistakenly discharged home have high mortality. A recent retrospective study has demonstrated that multislice computed tomography (MSCT) coronary angiography could improve triage of these patients. We aimed to prospectively confirm these data on patients with a negative screening including maximal treadmill stress. 30 patients discharged from the emergency department after negative screening for an ACS were included. All patients underwent MSCT angiography of the coronary artery. Patients with coronary atheroma on MSCT had an invasive coronary angiography to confirm these findings. Seven patients (23%) had obstructive coronary artery disease on MSCT. Invasive coronary angiography (ICA) confirmed the diagnosis in all patients. In patients with no previously known coronary artery disease admitted to the emergency department with atypical acute chest pain and discharged after negative screening, including maximal treadmill stress test, MSCT coronary angiography is useful for the diagnosis of obstructive coronary artery disease.

  11. Preinfarct Health Status and the Use of Early Invasive Versus Ischemia-Guided Management in Non-ST-Elevation Acute Coronary Syndrome.

    PubMed

    Qintar, Mohammed; Smolderen, Kim G; Chan, Paul S; Gosch, Kensey L; Jones, Philip G; Buchanan, Donna M; Girotra, Saket; Spertus, John A

    2017-10-01

    Early invasive management improves outcomes in non-ST-elevation myocardial infarction (NSTEMI). The association between preinfarct health status and the selecting patients for early invasive management is unknown. The Prospective Registry Evaluating outcomes after Myocardial Infarctions: Events and Recovery and Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status are consecutive US multicenter registries, in which the associations between preinfarct angina frequency and quality of life (both assessed by the Seattle Angina Questionnaire on admission) and the Global Registry of Acute Coronary Events (GRACE) risk score and referral to early invasive management (coronary angiography within 48 hours) were evaluated using Poisson regression, after adjusting for site, demographics, and clinical and psychosocial variables. Of 3,768 patients with NSTEMI, 2,182 (57.9%) patients were referred for early invasive treatment. Patients with excellent, good, or very good baseline angina-specific quality of life, respectively, were more likely to receive early angiography, even after adjustment, as compared with patients reporting poor baseline quality of life because of angina (62.1.0%, 60.9%, 59.6%, vs 51.2%; adjusted relative risk [RR] = 1.09, 95% confidence interval [CI] 1.04 to 1.16; RR = 1.13, 95% CI 1.01 to 1.27; RR 1.14, 95% CI 0.99 to 1.31, respectively). Finally, patients with a GRACE score in the highest risk decile (199.5 to <321.4) had significantly lower rates of early invasive treatment (42.7%) than patients in the lowest decile of risk (67.6%; adjusted RR for continuous GRACE score per SD [1 SD = 40 points], 0.96, 95% CI 0.92 to 0.99, p = 0.019). In conclusion, in this real-world NSTEMI cohort, patients with the highest mortality risk and worst health status were less likely to be referred for early invasive management. Further work is needed to understand the role of preinfarct health status

  12. Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial.

    PubMed

    Perfect, John R; Cornely, Oliver A; Heep, Markus; Ostrosky-Zeichner, Luis; Mullane, Kathleen M; Maher, Rochelle; Croos-Dabrera, Rodney; Lademacher, Christopher; Engelhardt, Marc; Chen, Caroline; Marty, Francisco M

    2018-03-23

    Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator. © 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.

  13. Serious fungal infections in Egypt.

    PubMed

    Zaki, S M; Denning, D W

    2017-06-01

    We aimed to estimate the burden of serious fungal infections in Egypt, currently unknown, based on the size of the populations at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports with clearcut denominators. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. The population of Egypt in 2011 was ∼82,500,000; 31% children, and 8% women >60 years of age. Amongst about 21.8 million women aged 15-50 years, recurrent vulvovaginal candidiasis (≥4 episodes/year) is estimated to occur in 1.3 million (3,169/100,000 females). Using a low international average rate of 5/100,000, we estimate 4,127 cases of candidaemia, and 619 patients with intra-abdominal candidiasis. Amongst the survivors of pulmonary tuberculosis (TB) in Egypt in 2012, 319 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 1,005 post-TB and a total prevalence estimate of 3,015 CPA patients in all. Asthma is common in Egypt, affecting 9.4% of adults, 5.35 million, and so ABPA and SAFS were estimated in around 162/100,000 and 214/100,000 respectively. Invasive aspergillosis is estimated to affect 495 patients following leukaemia therapy, there are an estimated 37 cases in renal and liver transplant recipients, and an estimated 132 patients develop IA in the context of lung cancer. Amongst 641,000 COPD admissions to hospital each year, 8,337 patients develop IA. The total HIV-infected population is small, with an estimated 6,500 patients, 2,500 not on antiretroviral therapy. Amongst HIV-infected patients, 38 (0.6%) cases of cryptococcal meningitis and 125 (1.9%) cases of Pneumocystis pneumonia are estimated each year. Fungal keratitis is common, with 28-55% (mean 40%) of corneal infections being fungal, an estimated total of 11,550 cases. The present study indicates

  14. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

    PubMed Central

    Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

    2016-01-01

    Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1–3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77–510) vs. 50 (30–125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68–0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe. PMID:26910891

  15. Time of non-invasive ventilation.

    PubMed

    Nava, Stefano; Navalesi, Paolo; Conti, Giorgio

    2006-03-01

    Non-invasive ventilation (NIV) is a safe, versatile and effective technique that can avert side effects and complications associated with endotracheal intubation. The success of NIV relies on several factors, including the type and severity of acute respiratory failure, the underlying disease, the location of treatment, and the experience of the team. The time factor is also important. NIV is primarily used to avert the need for endotracheal intubation in patients with early-stage acute respiratory failure and post-extubation respiratory failure. It can also be used as an alternative to invasive ventilation at a more advanced stage of acute respiratory failure or to facilitate the process of weaning from mechanical ventilation. NIV has been used to prevent development of acute respiratory failure or post-extubation respiratory failure. The number of days of NIV and hours of daily use differ, depending on the severity and course of the acute respiratory failure and the timing of application. In this review article, we analyse, compare and discuss the results of studies in which NIV was applied at various times during the evolution of acute respiratory failure.

  16. Repurposing antipsychotic drugs into antifungal agents: Synergistic combinations of azoles and bromperidol derivatives in the treatment of various fungal infections.

    PubMed

    Holbrook, Selina Y L; Garzan, Atefeh; Dennis, Emily K; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2017-10-20

    As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles. Exploring combination therapy that involves the current azoles and another drug has been shown to be a promising strategy. Haloperidol and its derivative, bromperidol, were originally discovered as antipsychotics. Herein, we synthesize and report a series of bromperidol derivatives and their synergistic antifungal interactions in combination with a variety of current azole antifungals against a wide panel of fungal pathogens. We further select two representative combinations and confirm the antifungal synergy by performing time-kill assays. Furthermore, we evaluate the ability of selected combinations to destroy fungal biofilm. Finally, we perform mammalian cytotoxicity assays with the representative combinations against three mammalian cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial.

    PubMed

    Hoedemaker, Niels P G; Damman, Peter; Woudstra, Pier; Hirsch, Alexander; Windhausen, Fons; Tijssen, Jan G P; de Winter, Robbert J

    2017-04-18

    The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years. The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T. The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization. Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001). In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of

  18. Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis

    PubMed Central

    García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-01-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens. PMID:25830627

  19. Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

    PubMed

    Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-04-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

  20. Automated in vivo identification of fungal infection on human scalp using optical coherence tomography and machine learning

    NASA Astrophysics Data System (ADS)

    Dubey, Kavita; Srivastava, Vishal; Singh Mehta, Dalip

    2018-04-01

    Early identification of fungal infection on the human scalp is crucial for avoiding hair loss. The diagnosis of fungal infection on the human scalp is based on a visual assessment by trained experts or doctors. Optical coherence tomography (OCT) has the ability to capture fungal infection information from the human scalp with a high resolution. In this study, we present a fully automated, non-contact, non-invasive optical method for rapid detection of fungal infections based on the extracted features from A-line and B-scan images of OCT. A multilevel ensemble machine model is designed to perform automated classification, which shows the superiority of our classifier to the best classifier based on the features extracted from OCT images. In this study, 60 samples (30 fungal, 30 normal) were imaged by OCT and eight features were extracted. The classification algorithm had an average sensitivity, specificity and accuracy of 92.30, 90.90 and 91.66%, respectively, for identifying fungal and normal human scalps. This remarkable classifying ability makes the proposed model readily applicable to classifying the human scalp.

  1. An integrated approach to evaluating alternative risk prediction strategies: a case study comparing alternative approaches for preventing invasive fungal disease.

    PubMed

    Sadique, Z; Grieve, R; Harrison, D A; Jit, M; Allen, E; Rowan, K M

    2013-12-01

    This article proposes an integrated approach to the development, validation, and evaluation of new risk prediction models illustrated with the Fungal Infection Risk Evaluation study, which developed risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD). Our decision-analytical model compared alternative strategies for preventing IFD at up to three clinical decision time points (critical care admission, after 24 hours, and end of day 3), followed with antifungal prophylaxis for those judged "high" risk versus "no formal risk assessment." We developed prognostic models to predict the risk of IFD before critical care unit discharge, with data from 35,455 admissions to 70 UK adult, critical care units, and validated the models externally. The decision model was populated with positive predictive values and negative predictive values from the best-fitting risk models. We projected lifetime cost-effectiveness and expected value of partial perfect information for groups of parameters. The risk prediction models performed well in internal and external validation. Risk assessment and prophylaxis at the end of day 3 was the most cost-effective strategy at the 2% and 1% risk threshold. Risk assessment at each time point was the most cost-effective strategy at a 0.5% risk threshold. Expected values of partial perfect information were high for positive predictive values or negative predictive values (£11 million-£13 million) and quality-adjusted life-years (£11 million). It is cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients. This integrated approach to developing and evaluating risk models is useful for informing clinical practice and future research investment. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Published by International Society for Pharmacoeconomics and Outcomes Research (ISPOR) All rights reserved.

  2. Comparison between open plating versus minimally invasive plate osteosynthesis for acute displaced clavicular shaft fractures.

    PubMed

    Sohn, Hoon-Sang; Kim, Won Ju; Shon, Min Soo

    2015-08-01

    Current literatures describe good clinical outcomes of acute displaced fracture of clavicle treated with minimally invasive plate osteosynthesis (MIPO). But, there are little comparative data of the outcomes between open plating and MIPO techniques. We compared the outcomes of open plating and MIPO for treatment of acute displaced clavicular shaft fractures. The author performed a retrospective review on a consecutive series of patients with clavicular shaft fracture who underwent open plating or MIPO. Fourteen patients were treated with open plating with interfragmentary screw fixation, and 19 were treated with the MIPO technique without exposing a fracture site itself. A superior plating method was applied to both groups. Patient demographics, clinical outcomes using Constant score and University of California Los Angeles (UCLA) shoulder score, operation time, union rate, complications, and radiographic evaluation were evaluated. There were no statistically significant differences in the demographic data, including patient's variables (age, gender, involved side, smoking, alcohol, and diabetic status) and fracture characteristics (trauma mechanism, distribution of fracture type, presence of polytrauma, and time from trauma to surgery) between the two groups. Mean operation time was 87.5 min in open plating and 77.2 min in MIPO (p=0.129). The mean time to union was 15.7 weeks in patients who underwent open plating and 16.8 weeks in patients who underwent MIPO (p=0.427). Although there was no significant difference, nonunion developed 1 case in MIPO while none was in open plating. Four patients in open plating had skin numbness (none in MIPO, p=0.024). There was no significant difference in the Constant score and UCLA score of the two surgical methods. This study showed that both open plating with interfragmentary screw fixation (Open plating) and minimally invasive plate osteosynthesis (MIPO) are equally effective and safe treatment methods for acute displaced

  3. Treatment of invasive fungal infections in high-risk haematological patients: what have we learnt in the past 10 years?

    PubMed

    Vallejo, Carlos; Vázquez, Lourdes; Cabrera Martín, José Rafael; Carreras, Enric; García Rodríguez, Julio; Ruiz Camps, Isabel; Fortún, Jesús; Mensa, Josep; Barberán, José

    2013-12-01

    Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.

  4. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

    PubMed

    Mellinghoff, Sibylle C; Panse, Jens; Alakel, Nael; Behre, Gerhard; Buchheidt, Dieter; Christopeit, Maximilian; Hasenkamp, Justin; Kiehl, Michael; Koldehoff, Michael; Krause, Stefan W; Lehners, Nicola; von Lilienfeld-Toal, Marie; Löhnert, Annika Y; Maschmeyer, Georg; Teschner, Daniel; Ullmann, Andrew J; Penack, Olaf; Ruhnke, Markus; Mayer, Karin; Ostermann, Helmut; Wolf, Hans-H; Cornely, Oliver A

    2018-02-01

    Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in

  5. Positive feedback between mycorrhizal fungi and plants influences plant invasion success and resistance to invasion.

    PubMed

    Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

    2010-08-24

    Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.

  6. Infrared spectroscopy detection of fungal infections and mycotoxins for food safety concerns

    USDA-ARS?s Scientific Manuscript database

    Mycotoxins, which are toxins produced by fungi, can pose great danger to human health with their acute and chronic effects when contaminated foods (grains, fruits, meat, or milk) are ingested. Fungal infections in food crops are extremely common and many developed countries have set standards to mon...

  7. Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities.

    PubMed

    Ho, Dora Y; Lin, Margaret; Schaenman, Joanna; Rosso, Fernando; Leung, Ann N C; Coutre, Steven E; Sista, Ramachandra R; Montoya, Jose G

    2011-01-01

    Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas. © 2009 Blackwell Verlag GmbH.

  8. [Quantitative assessment of fungal risk in the case of construction works in healthcare establishments: Proposed indicators for the determination of the impact of management precautions on the risk of fungal infection].

    PubMed

    Gangneux, J-P; Adjidé, C-C; Bernard, L; Botterel, F; Carel, A; Castel, O; Derouin, F; Hoarau, G; Labussière, H; Lafaurie, M; Millon, L; Pottecher, B; Thiebaut, A; Turco, M; Baron, R

    2012-03-01

    Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used. Copyright © 2012. Published by Elsevier SAS.

  9. Standard methods for fungal brood disease research

    PubMed Central

    Jensen, Annette Bruun; Aronstein, Kathrine; Flores, José Manuel; Vojvodic, Svjetlana; Palacio, María Alejandra; Spivak, Marla

    2013-01-01

    Summary Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. that are rarely observed, so the impact on colony health is not very well understood. A major concern with the presence of Aspergillus in honey bees is the production of airborne conidia, which can lead to allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, or even invasive aspergillosis in lung tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases. PMID:24198438

  10. How to reduce the incidence of contrast induced acute kidney injury after cardiac invasive procedures, a review and practical recommendations.

    PubMed

    de Bie, Mihály K; van Rees, Johannes B; Herzog, Charles A; Rabelink, Ton J; Schalij, Martin J; Jukema, J Wouter

    2011-07-01

    Contrast induced acute kidney injury is an important complication after cardiac (invasive) procedures and is associated with substantial morbidity and mortality. The aim of the current article is to provide a comprehensive overview of the current knowledge regarding contrast induced acute kidney injury. Current literature was reviewed and relevant articles were selected. Articles were identified through MEDLINE and Pubmed selecting articles, limited between 1980 and 2010. The pathophysiological process resulting in contrast induced acute kidney injury is not completely understood, nevertheless several mechanisms involved have been proposed. However, the risk factors for contrast induced acute kidney injury and its timing are well known, making it amenable for preventive strategies. In the past decade various preventive strategies have been investigated with different results. Currently, only adequate hydration, with saline, is uniformly accepted as a beneficial prophylactic strategy. Furthermore promising results have also been reported for several other prophylactic strategies. These results, however, need to be confirmed in future trials.

  11. Acute invasive pulmonary aspergillosis, shortly after occupational exposure to polluted muddy water, in a previously healthy subject

    PubMed Central

    Pilaniya, Vikas; Gera, Kamal; Gothi, Rajesh; Shah, Ashok

    2015-01-01

    Invasive pulmonary aspergillosis (IPA) predominantly occurs in severely neutropenic immunocompromised subjects. The occurrence of acute IPA after brief but massive exposure to Aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. The diagnosis was delayed in all six of the affected patients, five of whom died. We report the case of a 50-year-old HIV-negative male, a water pipeline maintenance worker, who presented with acute-onset dyspnea and fever one day after working for 2 h in a deep pit containing polluted, muddy water. Over a one-month period, his general condition deteriorated markedly, despite antibiotic therapy. Imaging showed bilateral diffuse nodules with cavitation, some of which were surrounded by ground-glass opacity suggestive of a halo sign (a hallmark of IPA). Cultures (of sputum/bronchial aspirate samples) and serology were positive for Aspergillus fumigatus. After being started on itraconazole, the patient improved. We conclude that massive exposure to Aspergillus conidia can lead to acute IPA in immunocompetent subjects. PMID:26578140

  12. The Burden of Fungal Diseases in Romania

    PubMed Central

    Moroti-Constantinescu, Valentina Ruxandra

    2018-01-01

    Objective: To estimate for the first time the burden of fungal infections in Romania. Methods: Data derived from the World Health Organization (WHO), National Institute of Statistics, Romanian public health agencies and non-profit health organizations, and published annual reports on local epidemiology were used in the present study. When no data were available, specific at-risk populations were used to calculate frequencies of serious fungal diseases, using previously published epidemiological parameters. All data refer to the year 2016. Results: The estimated number of serious fungal infections in Romanian population was 436,230 in 2016. Recurrent vulvovaginal candidiasis accounted for up to 80% of total cases (more than 350,000 women annually). Concerning HIV-related infections, among 14,349 infected persons, Pneumocystis pneumonia occurred in about 10% of late presenters (30 cases in 2016), while cryptococcal meningitis was rarely diagnosed (less than 20 cases). Annually, the total number of oesophageal candidiasis and oral thrush cases in HIV-positive patients may have been as high as 1229 and 3066, respectively. In immunocompromised and cancer patient populations, the annual incidence of candidaemia was 295, and at least 458 invasive aspergillosis cases and 4 mucormycosis cases occurred yearly. With 4966 critical care beds and approximately 200,000 abdominal surgeries performed, the estimated annual incidence of candidaemia and Candida peritonitis was 689 and 344, respectively. The annual incidence of pulmonary tuberculosis is still high in Romania (12,747 cases). Thus, the prevalence of post-TB chronic pulmonary aspergillosis is estimated to be 8.98/100,000 (1768 cases). The prevalence of chronic obstructive pulmonary disease (COPD) and asthma in adults is 6% and 6.5%, respectively. Therefore, allergic bronchopulmonary aspergillosis prevalence is estimated at 29,387 and severe asthma with fungal sensitisation at 38,731 cases annually. Conclusions: Not being

  13. The Burden of Fungal Diseases in Romania.

    PubMed

    Mareș, Mihai; Moroti-Constantinescu, Valentina Ruxandra; Denning, David W

    2018-03-01

    To estimate for the first time the burden of fungal infections in Romania. Data derived from the World Health Organization (WHO), National Institute of Statistics, Romanian public health agencies and non-profit health organizations, and published annual reports on local epidemiology were used in the present study. When no data were available, specific at-risk populations were used to calculate frequencies of serious fungal diseases, using previously published epidemiological parameters. All data refer to the year 2016. The estimated number of serious fungal infections in Romanian population was 436,230 in 2016. Recurrent vulvovaginal candidiasis accounted for up to 80% of total cases (more than 350,000 women annually). Concerning HIV-related infections, among 14,349 infected persons, Pneumocystis pneumonia occurred in about 10% of late presenters (30 cases in 2016), while cryptococcal meningitis was rarely diagnosed (less than 20 cases). Annually, the total number of oesophageal candidiasis and oral thrush cases in HIV-positive patients may have been as high as 1229 and 3066, respectively. In immunocompromised and cancer patient populations, the annual incidence of candidaemia was 295, and at least 458 invasive aspergillosis cases and 4 mucormycosis cases occurred yearly. With 4966 critical care beds and approximately 200,000 abdominal surgeries performed, the estimated annual incidence of candidaemia and Candida peritonitis was 689 and 344, respectively. The annual incidence of pulmonary tuberculosis is still high in Romania (12,747 cases). Thus, the prevalence of post-TB chronic pulmonary aspergillosis is estimated to be 8.98/100,000 (1768 cases). The prevalence of chronic obstructive pulmonary disease (COPD) and asthma in adults is 6% and 6.5%, respectively. Therefore, allergic bronchopulmonary aspergillosis prevalence is estimated at 29,387 and severe asthma with fungal sensitisation at 38,731 cases annually. Not being on the list of reportable diseases, the

  14. Emerging Fungal Threats to Plants and Animals Challenge Agriculture and Ecosystem Resilience.

    PubMed

    Fones, Helen N; Fisher, Matthew C; Gurr, Sarah J

    2017-03-01

    While fungi can make positive contributions to ecosystems and agro-ecosystems, for example, in mycorrhizal associations, they can also have devastating impacts as pathogens of plants and animals. In undisturbed ecosystems, most such negative interactions will be limited through the coevolution of fungi with their hosts. In this article, we explore what happens when pathogenic fungi spread beyond their natural ecological range and become invasive on naïve hosts in new ecosystems. We will see that such invasive pathogens have been problematic to humans and their domesticated plant and animal species throughout history, and we will discuss some of the most pressing fungal threats of today.

  15. Invasive mold infections: virulence and pathogenesis of mucorales.

    PubMed

    Morace, Giulia; Borghi, Elisa

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses.

  16. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2018-05-07

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  17. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

  18. Bacterial and fungal endophthalmitis in upper Egypt: related species and risk factors.

    PubMed

    Gharamah, A A; Moharram, A M; Ismail, M A; Al-Hussaini, A K

    2012-08-01

    To study risk factors, contributing factors of bacterial and fungal endophthalmitis in Upper Egypt, test the isolated species sensitive to some therapeutic agents, and to investigate the air-borne bacteria and fungi in opthalmology operating rooms. Thirty one cases of endophthalmitis were clinically diagnosed and microbiologically studied. Indoor air-borne bacteria and fungi inside four air-conditioned operating rooms in the Ophthalmology Department at Assiut University Hospitals were also investigated. The isolated microbes from endophthalmitis cases were tested for their ability to produce some extracellular enzymes including protease, lipase, urease, phosphatase and catalase. Also the ability of 5 fungal isolates from endophthalmitis origin to produce mycotoxins and their sensitivity to some therapeutic agents were studied. Results showed that bacteria and fungi were responsihle for infection in 10 and 6 cases of endophthalmitis, respectively and only 2 cases produced a mixture of bacteria and fungi. Trauma was the most prevalent risk factor of endophthalmitis where 58.1% of the 31 cases were due to trauma. In ophthalmology operating rooms, different bacterial and fungal species were isolated. 8 bacterial and 5 fungal isolates showed their ability to produce enzymes while only 3 fungal isolates were able to produce mycotoxins. Terbinafine showed the highest effect against most isolates in vitro. The ability of bacterial and fungal isolates to produce extracellular enzymes and mycotoxins may be aid in the invasion and destruction of eye tissues. Microbial contamination of operating rooms with air-borne bacteria and fungi in the present work may be a source of postoperative endophthalmitis.

  19. Soil Bacteria and Fungi Respond on Different Spatial Scales to Invasion by the Legume Lespedeza cuneata.

    PubMed

    Yannarell, Anthony C; Busby, Ryan R; Denight, Michael L; Gebhart, Dick L; Taylor, Steven J

    2011-01-01

    The spatial scale on which microbial communities respond to plant invasions may provide important clues as to the nature of potential invader-microbe interactions. Lespedeza cuneata (Dum. Cours.) G. Don is an invasive legume that may benefit from associations with mycorrhizal fungi; however, it has also been suggested that the plant is allelopathic and may alter the soil chemistry of invaded sites through secondary metabolites in its root exudates or litter. Thus, L. cuneata invasion may interact with soil microorganisms on a variety of scales. We investigated L. cuneata-related changes to soil bacterial and fungal communities at two spatial scales using multiple sites from across its invaded N. American range. Using whole-community DNA fingerprinting, we characterized microbial community variation at the scale of entire invaded sites and at the scale of individual plants. Based on permutational multivariate analysis of variance, soil bacterial communities in heavily invaded sites were significantly different from those of uninvaded sites, but bacteria did not show any evidence of responding at very local scales around individual plants. In contrast, soil fungi did not change significantly at the scale of entire sites, but there were significant differences between fungal communities of native versus exotic plants within particular sites. The differential scaling of bacterial and fungal responses indicates that L. cuneata interacts differently with soil bacteria and soil fungi, and these microorganisms may play very different roles in the invasion process of this plant.

  20. Perspectives on advance care planning among patients recently requiring non-invasive ventilation for acute respiratory failure: A qualitative study using thematic analysis.

    PubMed

    Smith, Tracy A; Disler, Rebecca T; Jenkins, Christine R; Ingham, Jane M; Davidson, Patricia M

    2017-06-01

    Patients requiring non-invasive ventilation for acute-on-chronic respiratory failure due to chronic obstructive pulmonary disease or heart failure exacerbations may have a poor prognosis underscoring the importance of advance care planning. We aimed to describe attitudes to, and experiences of, discussing the future among patients recently treated with non-invasive ventilation. Qualitative research using thematic analysis. Tertiary teaching hospital. Patients with acute hypercapnic respiratory failure requiring non-invasive ventilation. Individuals recently treated with non-invasive ventilation describe feeling the future is beyond their control and instead controlled by their illness. Participants often recognised their poor prognosis but avoided discussing some difficult topics. The majority preferred not to undergo cardiopulmonary resuscitation but most had not discussed this with healthcare professionals. When participants voiced concerns about their future health to family members, they were met with polarised responses. Some encountered willingness for further discussion, while others met deflection, deterring further conversation. An overarching narrative of 'Looking through my illness to an uncertain but concerning future' unites these themes. This study suggests opportunities and barriers for advance care planning in individuals with chronic disease. Patients' understanding of their prognosis and their attitudes to cardiopulmonary resuscitation suggests an opportunity for advance care planning. Structuring discussions around patients' preferences for care during future exacerbations may foster a sense of control over the future despite illness. The diversity of familial responses to patients' concerns about their future health has implications for advance care planning. These findings have the potential to improve care for patients with respiratory failure and suggest an important ongoing research agenda.

  1. An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States.

    PubMed

    Sung, Anita H; Marcella, Stephen W; Xie, Yang

    2015-05-01

    Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs. An existing model was used to assess the cost-effectiveness of posaconazole vs FLU/ITRA in the prevention of IFD among patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and chemotherapy-induced neutropenia. Drug efficacy, mortality related to IFD, and death from other causes were estimated for tablet formulations using data from a randomized clinical trial of oral suspensions based on bioequivalence. IFD treatment costs were updated using the average inflation rate over 8 years (2006-2014) and drug costs were based on 2014 Analysource data. Trial data show a lower IFD probability over 100 days of follow-up with posaconazole compared to standard azole therapy (0.05 vs 0.11). The treatment duration on posaconazole is 29 days compared to 24 days for FLU and 29 days for ITRA. The average cost of prophylaxis is higher in the posaconazole group compared to FLU/ITRA ($4673 vs $353); however, the costs associated with treating the IFD are lower in the posaconazole group compared to FLU/ITRA ($2205 vs $5303). The incremental cost effectiveness ratio of IFD avoided for posaconazole is $18,898 vs FLU/ITRA. In the current healthcare cost environment where both drug costs and overall IFD treatment costs have increased since 2007, posaconazole tablets are a cost-effective alternative to fluconazole or itraconazole in the prevention of IFD among neutropenic patients with AML and MDS in the US.

  2. Burden of serious fungal infections in Bangladesh.

    PubMed

    Gugnani, H C; Denning, D W; Rahim, R; Sadat, A; Belal, M; Mahbub, M S

    2017-06-01

    In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count <350 μL, Pneumocystis pneumonia and cryptococcal meningitis being rare. Superficial mycoses are very common with Trichophyton rubrum as the predominant etiological agent (80.6%). Numerous cases of mycotic keratitis have been reported from several parts of Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.

  3. Endophytic fungal communities of Bromus tectorum: Mutualisms, community assemblages and implications for invasion

    Treesearch

    Melissa A. Baynes

    2011-01-01

    Exotic plant invasions are of serious economic, social and ecological concern worldwide. Although many promising hypotheses have been posited in attempt to explain the mechanism(s) by which plant invaders are successful, there is no single explanation for all invasions and often no single explanation for the success of an individual species. Cheatgrass (Bromus tectorum...

  4. Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study.

    PubMed

    Koehler, Philipp; Hamprecht, Axel; Bader, Oliver; Bekeredjian-Ding, Isabelle; Buchheidt, Dieter; Doelken, Gottfried; Elias, Johannes; Haase, Gerhard; Hahn-Ast, Corinna; Karthaus, Meinolf; Kekulé, Alexander; Keller, Peter; Kiehl, Michael; Krause, Stefan W; Krämer, Carolin; Neumann, Silke; Rohde, Holger; La Rosée, Paul; Ruhnke, Markus; Schafhausen, Philippe; Schalk, Enrico; Schulz, Katrin; Schwartz, Stefan; Silling, Gerda; Staib, Peter; Ullmann, Andrew; Vergoulidou, Maria; Weber, Thomas; Cornely, Oliver A; Vehreschild, Maria J G T

    2017-02-01

    Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  5. Non-invasive ventilation in acute respiratory failure in children

    PubMed Central

    Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena

    2012-01-01

    The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO2 at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO2/FiO2 improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42–71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33–111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection. PMID:22802994

  6. Non-invasive ventilation in acute respiratory failure in children.

    PubMed

    Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena

    2012-04-02

    The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO(2) at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO(2)/FiO(2)) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO(2)/FiO(2) improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42-71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33-111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection.

  7. Fungal Endocarditis.

    PubMed

    Yuan, Shi-Min

    2016-01-01

    Fungal endocarditis is a rare and fatal condition. The Candida and Aspergillus species are the two most common etiologic fungi found responsible for fungal endocarditis. Fever and changing heart murmur are the most common clinical manifestations. Some patients may have a fever of unknown origin as the onset symptom. The diagnosis of fungal endocarditis is challenging, and diagnosis of prosthetic valve fungal endocarditis is extremely difficult. The optimum antifungal therapy still remains debatable. Treating Candida endocarditis can be difficult because the Candida species can form biofilms on native and prosthetic heart valves. Combined treatment appears superior to monotherapy. Combination of antifungal therapy and surgical debridement might bring about better prognosis.

  8. Translational Development and Application of (1→3)-β-d-Glucan for Diagnosis and Therapeutic Monitoring of Invasive Mycoses

    PubMed Central

    McCarthy, Matthew W.; Petraitiene, Ruta; Walsh, Thomas J.

    2017-01-01

    Early diagnosis and prompt initiation of appropriate antimicrobial therapy are crucial steps in the management of patients with invasive fungal infections. However, the diagnosis of invasive mycoses remains a major challenge in clinical practice, because presenting symptoms may be subtle and non-invasive diagnostic assays often lack sensitivity and specificity. Diagnosis is often expressed on a scale of probability (proven, probable and possible) based on a constellation of imaging findings, microbiological tools and histopathology, as there is no stand-alone assay for diagnosis. Recent data suggest that the carbohydrate biomarker (1→3)-β-d-glucan may be useful in both the diagnosis and therapeutic monitoring of invasive fungal infections due to some yeasts, molds, and dimorphic fungi. In this paper, we review recent advances in the use of (1→3)-β-d-glucan to monitor clinical response to antifungal therapy and explore how this assay may be used in the future. PMID:28538702

  9. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereasmore » miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.« less

  10. The impacts of invaders: basal and acute stress glucocorticoid profiles and immune function in native lizards threatened by invasive ants.

    PubMed

    Graham, Sean P; Freidenfelds, Nicole A; McCormick, Gail L; Langkilde, Tracy

    2012-05-01

    As anthropogenic stressors increase exponentially in the coming decades, native vertebrates will likely face increasing threats from these novel challenges. The success or failure of the primary physiological mediator of these stressors--the HPA axis--will likely involve numerous and chaotic outcomes. Among the most challenging of these new threats are invasive species. These have the capacity to simultaneously challenge the HPA axis and the immune system as they are often associated with, or the cause of, emerging infectious diseases, and energetic tradeoffs with the HPA response can have immunosuppressive effects. To determine the effects of invasive species on the vertebrate GC response to a novel stressor, and on immunity, we examined the effects of invasive fire ants on native lizards, comparing lizards from sites with long histories with fire ants to those outside the invasion zone. We demonstrated higher baseline and acute stress (captive restraint) CORT levels in lizards from within fire ant invaded areas; females are more strongly affected than males, suggesting context-specific effects of invasion. We found no effect of fire ant invasion on the immune parameters we measured (complement bacterial lysis and antibody hemagglutination) with the exception of ectoparasite infestation. Mites were far less prevalent on lizards within fire ant invaded sites, suggesting fire ants may actually benefit lizards in this regard. This study suggests that invasive species may impose physiological stress on native vertebrates, but that the consequences of this stress may be complicated and unpredictable. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Fungal Endocarditis

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Fungal endocarditis is a rare and fatal condition. The Candida and Aspergillus species are the two most common etiologic fungi found responsible for fungal endocarditis. Fever and changing heart murmur are the most common clinical manifestations. Some patients may have a fever of unknown origin as the onset symptom. The diagnosis of fungal endocarditis is challenging, and diagnosis of prosthetic valve fungal endocarditis is extremely difficult. The optimum antifungal therapy still remains debatable. Treating Candida endocarditis can be difficult because the Candida species can form biofilms on native and prosthetic heart valves. Combined treatment appears superior to monotherapy. Combination of antifungal therapy and surgical debridement might bring about better prognosis. PMID:27737409

  12. Fungal Genomics Program

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigoriev, Igor

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scalemore » genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.« less

  13. Diagnosis and management of fungal urinary tract infection.

    PubMed

    Kauffman, Carol A

    2014-03-01

    When the terms funguria or fungal urinary tract infection are used, most physicians are referring to candiduria and urinary tract infections due to Candida species. Other fungi, including yeasts and molds can involve the kidney during the course of disseminated infection, but rarely cause symptoms referable to the urinary tract. Candida species appear to be unique in their ability to both colonize and cause invasive disease in the urinary tract. This overview focuses only on candiduria and Candida urinary tract infection because they are common and many times present perplexing management issues. Published by Elsevier Inc.

  14. Potential involvement of Aspergillus flavus laccases in peanut invasion at low water potential

    USDA-ARS?s Scientific Manuscript database

    Aspergillus flavus (Link) accumulates aflatoxins in peanuts, mainly affecting immature kernels during drought. Peanut invasion by A. flavus induces synthesis of phytoalexins, mostly stilbenoids, as a plant defense mechanism. Fungal laccases are often related to pathogenicity, and among other subst...

  15. Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

    PubMed

    Decembrino, Nunzia; Zecca, Marco; Tortorano, Anna Maria; Mangione, Francesca; Lallitto, Fabiola; Introzzi, Francesca; Bergami, Elena; Marone, Piero; Tamarozzi, Francesca; Cavanna, Caterina

    2016-01-01

    We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

  16. Bacterial and fungal keratitis in Upper Egypt: In vitro screening of enzymes, toxins and antifungal activity

    PubMed Central

    Gharamah, Abdullah A; Moharram, Ahmed M; Ismail, Mady A; AL-Hussaini, Ashraf K

    2014-01-01

    Purpose: This work was conducted to study the ability of bacterial and fungal isolates from keratitis cases in Upper Egypt to produce enzymes, toxins, and to test the isolated fungal species sensitivity to some therapeutic agents. Materials and Methods: One hundred and fifteen patients clinically diagnosed to have microbial keratitis were investigated. From these cases, 37 bacterial isolates and 25 fungal isolates were screened for their ability to produce extra-cellular enzymes in solid media. In addition, the ability of fungal isolates to produce mycotoxins and their sensitivity to 4 antifungal agents were tested. Results: Protease, lipase, hemolysins, urease, phosphatase, and catalase were detected respectively in 48.65%, 37.84%, 59.46%, 43.24%, 67.57%, and 100% out of 37 bacterial isolates tested. Out of 25 fungal isolates tested during the present study, 80% were positive for protease, 84% for lipase and urease, 28% for blood hemolysis, and 100% for phosphatase and catalase enzymes. Thirteen fungal isolates were able to produce detectable amounts of 7 mycotoxins in culture medium (aflatoxins (B1, B2, G1, and G2), sterigmatocystin, fumagillin, diacetoxyscirpenol, zearalenone, T-2 toxin, and trichodermin). Among the antifungal agents tested in this study, terbinafine showed the highest effect against most isolates in vitro. Conclusion: In conclusion, the ability of bacterial and fungal isolates to produce extracellular enzymes and toxins may be aid in the invasion and destruction of eye tissues, which, in turn, lead to vision loss. PMID:24008795

  17. Emerging issues, challenges, and changing epidemiology of fungal disease outbreaks.

    PubMed

    Benedict, Kaitlin; Richardson, Malcolm; Vallabhaneni, Snigdha; Jackson, Brendan R; Chiller, Tom

    2017-12-01

    Several high-profile outbreaks have drawn attention to invasive fungal infections (IFIs) as an increasingly important public health problem. IFI outbreaks are caused by many different fungal pathogens and are associated with numerous settings and sources. In the community, IFI outbreaks often occur among people without predisposing medical conditions and are frequently precipitated by environmental disruption. Health-care-associated IFI outbreaks have been linked to suboptimal hospital environmental conditions, transmission via health-care workers' hands, contaminated medical products, and transplantation of infected organs. Outbreak investigations provide important insights into the epidemiology of IFIs, uncover risk factors for infection, and identify opportunities for preventing similar events in the future. Well recognised challenges with IFI outbreak recognition, response, and prevention include the need for improved rapid diagnostic methods, the absence of routine surveillance for most IFIs, adherence to infection control practices, and health-care provider awareness. Additionally, IFI outbreak investigations have revealed several emerging issues, including new populations at risk because of travel or relocation, occupation, or immunosuppression; fungal pathogens appearing in geographical areas in which they have not been previously recognised; and contaminated compounded medications. This report highlights notable IFI outbreaks in the past decade, with an emphasis on these emerging challenges in the USA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.

    PubMed

    Jobs, Alexander; Mehta, Shamir R; Montalescot, Gilles; Vicaut, Eric; Van't Hof, Arnoud W J; Badings, Erik A; Neumann, Franz-Josef; Kastrati, Adnan; Sciahbasi, Alessandro; Reuter, Paul-Georges; Lapostolle, Frédéric; Milosevic, Aleksandra; Stankovic, Goran; Milasinovic, Dejan; Vonthein, Reinhard; Desch, Steffen; Thiele, Holger

    2017-08-19

    A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality. We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988). We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive. An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Estimation of the incubation period of invasive aspergillosis by survival models in acute myeloid leukemia patients.

    PubMed

    Bénet, Thomas; Voirin, Nicolas; Nicolle, Marie-Christine; Picot, Stephane; Michallet, Mauricette; Vanhems, Philippe

    2013-02-01

    The duration of the incubation of invasive aspergillosis (IA) remains unknown. The objective of this investigation was to estimate the time interval between aplasia onset and that of IA symptoms in acute myeloid leukemia (AML) patients. A single-centre prospective survey (2004-2009) included all patients with AML and probable/proven IA. Parametric survival models were fitted to the distribution of the time intervals between aplasia onset and IA. Overall, 53 patients had IA after aplasia, with the median observed time interval between the two being 15 days. Based on log-normal distribution, the median estimated IA incubation period was 14.6 days (95% CI; 12.8-16.5 days).

  20. Fungal Eye Infections

    MedlinePlus

    ... fungal eye infections . Fungal eye infections are extremely rare, but they can be very serious. The most common way for someone to develop a fungal eye infection is as a result of an eye injury, particularly if the injury was caused by plant material such as a stick or a thorn. ...

  1. Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high-risk liver transplantation recipients: A propensity score analysis.

    PubMed

    Fortún, Jesús; Muriel, Alfonso; Martín-Dávila, Pilar; Montejo, Miguel; Len, Oscar; Torre-Cisneros, Julian; Carratalá, Jordi; Muñoz, Patricia; Fariñas, Carmen; Moreno, Asunción; Fresco, Gema; Goikoetxea, Josune; Gavaldá, Joan; Pozo, Juan Carlos; Bodro, Marta; Vena, Antonio; Casafont, Fernando; Cervera, Carlos; Silva, José Tiago; Aguado, José M

    2016-04-01

    Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high-risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR-LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005-2012), we analyzed 195 HR-LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001-0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR-LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR-LTRs, although bilirubin levels may be increased. © 2015 American

  2. Non-invasive detection of vulnerable coronary plaque

    PubMed Central

    Sharif, Faisal; Lohan, Derek G; Wijns, William

    2011-01-01

    Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and non-invasive imaging techniques have shown the potential to identify these high-risk plaques. Non-invasive imaging with magnetic resonance imaging, computed tomography and positron emission tomography holds the potential to differentiate between low- and high-risk plaques. There have been significant technological advances in non-invasive imaging modalities, and the aim is to achieve a diagnostic sensitivity for these technologies similar to that of the invasive modalities. Molecular imaging with the use of novel targeted nanoparticles may help in detecting high-risk plaques that will ultimately cause acute myocardial infarction. Moreover, nanoparticle-based imaging may even provide non-invasive treatments for these plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque nor have they been shown to definitively predict outcome. Further trials are needed to provide more information regarding the natural history of high-risk but non-flow-limiting plaque to establish patient specific targeted therapy and to refine plaque stabilizing strategies in the future. PMID:21860703

  3. Biological Invasion Influences the Outcome of Plant-Soil Feedback in the Invasive Plant Species from the Brazilian Semi-arid.

    PubMed

    de Souza, Tancredo Augusto Feitosa; de Andrade, Leonaldo Alves; Freitas, Helena; da Silva Sandim, Aline

    2017-05-30

    Plant-soil feedback is recognized as the mutual interaction between plants and soil microorganisms, but its role on the biological invasion of the Brazilian tropical seasonal dry forest by invasive plants still remains unclear. Here, we analyzed and compared the arbuscular mycorrhizal fungi (AMF) communities and soil characteristics from the root zone of invasive and native plants, and tested how these AMF communities affect the development of four invasive plant species (Cryptostegia madagascariensis, Parkinsonia aculeata, Prosopis juliflora, and Sesbania virgata). Our field sampling revealed that AMF diversity and frequency of the Order Diversisporales were positively correlated with the root zone of the native plants, whereas AMF dominance and frequency of the Order Glomerales were positively correlated with the root zone of invasive plants. We grew the invasive plants in soil inoculated with AMF species from the root zone of invasive (I changed ) and native (I unaltered ) plant species. We also performed a third treatment with sterilized soil inoculum (control). We examined the effects of these three AMF inoculums on plant dry biomass, root colonization, plant phosphorous concentration, and plant responsiveness to mycorrhizas. We found that I unaltered and I changed promoted the growth of all invasive plants and led to a higher plant dry biomass, mycorrhizal colonization, and P uptake than control, but I changed showed better results on these variables than I unaltered . For plant responsiveness to mycorrhizas and fungal inoculum effect on plant P concentration, we found positive feedback between changed-AMF community (I changed ) and three of the studied invasive plants: C. madagascariensis, P. aculeata, and S. virgata.

  4. The downregulation of miR-3173 in B-cell acute lymphoblastic leukaemia promotes cell invasion via PTK2.

    PubMed

    Tian, Lijun; Cao, Junhua; Ji, Qiang; Zhang, Chuanling; Qian, Tong; Song, Xianchuan; Huang, Baoshan; Tian, Xinyi

    2017-12-16

    MicroRNAs are important regulators of the pathogenesis of B-cell acute lymphoblastic leukaemia (B-ALL). In this study, we identified miR-3173 and its predicted target gene PTK2 were correspondingly differentially expressed in B-ALL patients. In B-ALL cell lines, CCK-8 proliferation assay revealed that miR-3173 could inhibit the cell proliferation. Moreover, transwell assay revealed that miR-3173 could also inhibit cell migration and invasion in B-ALL cell lines. Luciferase assays revealed that miR-3173 directly bound to the 3'untranslated region of PTK2, and western blotting showed that miR-3173 suppressed the expression of PTK2 at the protein level. Generally, this study indicates that miR-3173 negatively regulates PTK2 and inhibits proliferation and invasion of B-ALL cell lines. Thus, miR-3173 may represent a potential therapeutic molecule for B-ALL intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study.

    PubMed

    Harrison, D; Muskett, H; Harvey, S; Grieve, R; Shahin, J; Patel, K; Sadique, Z; Allen, E; Dybowski, R; Jit, M; Edgeworth, J; Kibbler, C; Barnes, R; Soni, N; Rowan, K

    2013-02-01

    There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. Ninety-six UK adult general critical care units. Consecutive admissions to participating critical care units. None. Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD

  6. Application of an oligonucleotide microarray-based nano-amplification technique for the detection of fungal pathogens.

    PubMed

    Lu, Weiping; Gu, Dayong; Chen, Xingyun; Xiong, Renping; Liu, Ping; Yang, Nan; Zhou, Yuanguo

    2010-10-01

    The traditional techniques for diagnosis of invasive fungal infections in the clinical microbiology laboratory need improvement. These techniques are prone to delay results due to their time-consuming process, or result in misidentification of the fungus due to low sensitivity or low specificity. The aim of this study was to develop a method for the rapid detection and identification of fungal pathogens. The internal transcribed spacer two fragments of fungal ribosomal DNA were amplified using a polymerase chain reaction for all samples. Next, the products were hybridized with the probes immobilized on the surface of a microarray. These species-specific probes were designed to detect nine different clinical pathogenic fungi including Candida albicans, Candida tropocalis, Candida glabrata, Candida parapsilosis, Candida krusei, Candida lusitaniae, Candida guilliermondii, Candida keyfr, and Cryptococcus neoformans. The hybridizing signals were enhanced with gold nanoparticles and silver deposition, and detected using a flatbed scanner or visually. Fifty-nine strains of fungal pathogens, including standard and clinically isolated strains, were correctly identified by this method. The sensitivity of the assay for Candida albicans was 10 cells/mL. Ten cultures from clinical specimens and 12 clinical samples spiked with fungi were also identified correctly. This technique offers a reliable alternative to conventional methods for the detection and identification of fungal pathogens. It has higher efficiency, specificity and sensitivity compared with other methods commonly used in the clinical laboratory.

  7. Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

    PubMed

    Herrera, Sabina; Husain, Shahid

    2018-05-21

    The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

  8. Fungal hemolysins

    PubMed Central

    Nayak, Ajay P.; Green, Brett J.; Beezhold, Donald H.

    2015-01-01

    Hemolysins are a class of proteins defined by their ability to lyse red cells but have been described to exhibit pleiotropic functions. These proteins have been extensively studied in bacteria and more recently in fungi. Within the last decade, a number of studies have characterized fungal hemolysins and revealed a fascinating yet diverse group of proteins. The purpose of this review is to provide a synopsis of the known fungal hemolysins with an emphasis on those belonging to the aegerolysin protein family. New insight and perspective into fungal hemolysins in biotechnology and health are additionally presented. PMID:22769586

  9. Long-term Outcomes of Regional Variations in Intensity of Invasive vs Medical Management of Medicare Patients With Acute Myocardial Infarction

    PubMed Central

    Stukel, Therese A.; Lucas, F. Lee; Wennberg, David E.

    2005-01-01

    Context The health and policy implications of the marked regional variations in intensity of invasive compared with medical management of patients with acute myocardial infarction (AMI) are unknown. Objectives To evaluate patient clinical characteristics associated with receiving more intensive treatment; and to assess whether AMI patients residing in regions with more intensive invasive treatment and management strategies have better long-term survival than those residing in regions with more intensive medical management strategies. Design, Setting, and Patients National cohort study of 158 831 elderly Medicare patients hospitalized with first episode of confirmed AMI in 1994–1995, followed up for 7 years (mean, 3.6 years), according to the intensity of invasive management (performance of cardiac catheterization within 30 days) and medical management (prescription of β-blockers to appropriate patients at discharge) in their region of residence. Baseline chart reviews were drawn from the Cooperative Cardiovascular Project and linked to Medicare health administrative data. Main Outcome Measure Long-term survival over 7 years of follow-up. Results Patient baseline AMI severity was similar across regions. In all regions, younger and healthier patients were more likely than older high-risk patients to receive invasive treatment and medical therapy. Regions with more invasive treatment practice styles had more cardiac catheterization laboratory capacity; patients in these regions were more likely to receive interventional treatment, regardless of age, clinical indication, or risk profile. The absolute unadjusted difference in 7-year survival between regions providing the highest rates of both invasive and medical management strategies and those providing the lowest rates of both was 6.2%. For both ST- and non–ST-segment elevation AMI patients, survival improved with regional intensity of both invasive and medical management. In areas with higher rates of medical

  10. Long-term outcomes of regional variations in intensity of invasive vs medical management of Medicare Patients with acute myocardial infarction.

    PubMed

    Stukel, Therese A; Lucas, F Lee; Wennberg, David E

    2005-03-16

    The health and policy implications of the marked regional variations in intensity of invasive compared with medical management of patients with acute myocardial infarction (AMI) are unknown. To evaluate patient clinical characteristics associated with receiving more intensive treatment; and to assess whether AMI patients residing in regions with more intensive invasive treatment and management strategies have better long-term survival than those residing in regions with more intensive medical management strategies. National cohort study of 158,831 elderly Medicare patients hospitalized with first episode of confirmed AMI in 1994-1995, followed up for 7 years (mean, 3.6 years), according to the intensity of invasive management (performance of cardiac catheterization within 30 days) and medical management (prescription of beta-blockers to appropriate patients at discharge) in their region of residence. Baseline chart reviews were drawn from the Cooperative Cardiovascular Project and linked to Medicare health administrative data. Long-term survival over 7 years of follow-up. Patient baseline AMI severity was similar across regions. In all regions, younger and healthier patients were more likely than older high-risk patients to receive invasive treatment and medical therapy. Regions with more invasive treatment practice styles had more cardiac catheterization laboratory capacity; patients in these regions were more likely to receive interventional treatment, regardless of age, clinical indication, or risk profile. The absolute unadjusted difference in 7-year survival between regions providing the highest rates of both invasive and medical management strategies and those providing the lowest rates of both was 6.2%. For both ST- and non-ST-segment elevation AMI patients, survival improved with regional intensity of both invasive and medical management. In areas with higher rates of medical management, there appeared to be little or no improvement in survival associated

  11. Outcomes of Minimally Invasive Temporary Right Ventricular Assist Device Support for Acute Right Ventricular Failure During Minimally Invasive Left Ventricular Assist Device Implantation.

    PubMed

    Schaefer, Andreas; Reichart, Daniel; Bernhardt, Alexander M; Kubik, Mathias; Barten, Markus J; Wagner, Florian M; Reichenspurner, Hermann; Philipp, Sebastian A; Deuse, Tobias

    Right ventricular failure (RVF) may still occur despite the benefits of minimally invasive left ventricular assist device (MI-LVAD) implantation. Our center strategy aims to avoid aggressive postoperative inotrope use by using mechanical support to facilitate right ventricle recovery and adaptation. We herein report first outcomes of patients with minimally invasive temporary right ventricular assist device (MI-t-RVAD) support for RVF during MI-LVAD implantation. Right ventricular failure was defined as requiring more than moderate inotopic support after weaning from cardiopulmonary bypass according to Interagency Registry for Mechanically Assisted Circulatory Support adverse event definitions. All patients requiring MI-t-RVAD support for RVF during MI-LVAD implantation between January, 2012 and April, 2016 were retrospectively reviewed. Clinical endpoints were death or unsuccessful RVAD weaning. Overall 10 patients (90% male, mean age 49.6 ± 14.8 years) underwent MI-t-RVAD implantation. Duration of MI-t-RVAD support was 16.2 ± 11.6 days. Right ventricular assist device weaning and subsequent uneventful awake device explantation was successful in all cases. The 30 day survival was 80%. Our results confirm safety and feasibility of MI-t-RVAD support for acute RVF in the setting of MI-LVAD implantation. The potential benefits of this strategy are more stable hemodynamics in the first postoperative days that usually are crucial for LVAD patients and reduced inotrope requirement.

  12. Experimental evidence of a pathogen invasion threshold

    PubMed Central

    Krkošek, Martin

    2018-01-01

    Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l−1) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models. PMID:29410876

  13. The microbiome-metabolome crosstalk in the pathogenesis of respiratory fungal diseases.

    PubMed

    Gonçalves, Samuel M; Lagrou, Katrien; Duarte-Oliveira, Cláudio; Maertens, Johan A; Cunha, Cristina; Carvalho, Agostinho

    2017-08-18

    Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and pathogen exposure. There is increasing evidence that the individual microbiome supervises the outcome of the host-fungus interaction by influencing mechanisms of immune regulation, inflammation, metabolism, and other physiological processes. Microbiome-mediated mechanisms of resistance allow therefore the control of fungal colonization, preventing the onset of overt disease, particularly in patients with underlying immune dysfunction. Here, we review this emerging area of research and discuss the contribution of the microbiota (and its dysbiosis), including its immunoregulatory properties and relationship with the metabolic activity of commensals, to respiratory fungal diseases. Finally, we highlight possible strategies aimed at decoding the microbiome-metabolome dialog and at its exploitation toward personalized medical interventions in patients at high risk of infection.

  14. (1→3)-β-D-Glucan Assay in Monitoring Response to Anti-Fungal Therapy in Fungal Endocarditis.

    PubMed

    Slim, Jihad; Saling, Christopher; Szabela, Maria; Brown, Melinda; Johnson, Tamara; Goldfarb, Irvin

    2017-03-01

    A case is reported of Candida glabrata infective endocarditis (IE) treated without surgical intervention. The study aim was to: (i) briefly discuss the outcomes of other documented cases of fungal IE managed medically with fluconazole; (ii) discuss the (1→3)-β-D-glucan assay and its previously studied role in the diagnosis of invasive fungal infections; and (iii) examine a possible application of the (1→3)-β-D-glucan assay to monitor response to antifungal treatment in patients with Candida endocarditis. The serum Fungitell assay was used to trend (1→3)-β-D-glucan in a patient with Candida endocarditis to determine treatment effectiveness with fluconazole, to provide an appropriate end date for antifungal therapy, and to survey infection suppression while off treatment. The (1→03)-β-D-glucan assay began trending downwards at 197 days into treatment with oral fluconazole. After 16 months of therapy, fluconazole was stopped due to transaminitis. (1→3)-β-Dglucan levels were checked six weeks after the discontinuation of treatment and were negative. The patient has now been off therapy for 21 weeks with no signs of clinical disease, and values remain negative. The present case indicates that a trending (1→3)-β-D-glucan assay may have valuable application in monitoring treatment response and infection suppression for Candida endocarditis.

  15. Plant Invasions Associated with Change in Root-Zone Microbial Community Structure and Diversity.

    PubMed

    Rodrigues, Richard R; Pineda, Rosana P; Barney, Jacob N; Nilsen, Erik T; Barrett, John E; Williams, Mark A

    2015-01-01

    The importance of plant-microbe associations for the invasion of plant species have not been often tested under field conditions. The research sought to determine patterns of change in microbial communities associated with the establishment of invasive plants with different taxonomic and phenetic traits. Three independent locations in Virginia, USA were selected. One site was invaded by a grass (Microstegium vimineum), another by a shrub (Rhamnus davurica), and the third by a tree (Ailanthus altissima). The native vegetation from these sites was used as reference. 16S rRNA and ITS regions were sequenced to study root-zone bacterial and fungal communities, respectively, in invaded and non-invaded samples and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Though root-zone microbial community structure initially differed across locations, plant invasion shifted communities in similar ways. Indicator species analysis revealed that Operational Taxonomic Units (OTUs) closely related to Proteobacteria, Acidobacteria, Actinobacteria, and Ascomycota increased in abundance due to plant invasions. The Hyphomonadaceae family in the Rhodobacterales order and ammonia-oxidizing Nitrospirae phylum showed greater relative abundance in the invaded root-zone soils. Hyphomicrobiaceae, another bacterial family within the phyla Proteobacteria increased as a result of plant invasion, but the effect associated most strongly with root-zones of M. vimineum and R. davurica. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed bacteria responsible for nitrogen cycling in soil increased in relative abundance in association with plant invasion. In agreement with phylogenetic and functional analyses, greater turnover of ammonium and nitrate was associated with plant invasion. Overall, bacterial and fungal communities changed congruently across plant invaders, and support the hypothesis that nitrogen

  16. Plant Invasions Associated with Change in Root-Zone Microbial Community Structure and Diversity

    PubMed Central

    Rodrigues, Richard R.; Pineda, Rosana P.; Barney, Jacob N.; Nilsen, Erik T.; Barrett, John E.; Williams, Mark A.

    2015-01-01

    The importance of plant-microbe associations for the invasion of plant species have not been often tested under field conditions. The research sought to determine patterns of change in microbial communities associated with the establishment of invasive plants with different taxonomic and phenetic traits. Three independent locations in Virginia, USA were selected. One site was invaded by a grass (Microstegium vimineum), another by a shrub (Rhamnus davurica), and the third by a tree (Ailanthus altissima). The native vegetation from these sites was used as reference. 16S rRNA and ITS regions were sequenced to study root-zone bacterial and fungal communities, respectively, in invaded and non-invaded samples and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Though root-zone microbial community structure initially differed across locations, plant invasion shifted communities in similar ways. Indicator species analysis revealed that Operational Taxonomic Units (OTUs) closely related to Proteobacteria, Acidobacteria, Actinobacteria, and Ascomycota increased in abundance due to plant invasions. The Hyphomonadaceae family in the Rhodobacterales order and ammonia-oxidizing Nitrospirae phylum showed greater relative abundance in the invaded root-zone soils. Hyphomicrobiaceae, another bacterial family within the phyla Proteobacteria increased as a result of plant invasion, but the effect associated most strongly with root-zones of M. vimineum and R. davurica. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed bacteria responsible for nitrogen cycling in soil increased in relative abundance in association with plant invasion. In agreement with phylogenetic and functional analyses, greater turnover of ammonium and nitrate was associated with plant invasion. Overall, bacterial and fungal communities changed congruently across plant invaders, and support the hypothesis that nitrogen

  17. Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

    PubMed

    Kidane, Yared H; Lawrence, Christopher; Murali, T M

    2013-10-07

    Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host's tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Our computational approaches and methodologies described here can now be applied to

  18. Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions

    PubMed Central

    2013-01-01

    Background Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host’s tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host’s tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. Results In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Conclusions Our computational approaches and methodologies

  19. Gene flow contributes to diversification of the major fungal pathogen Candida albicans.

    PubMed

    Ropars, Jeanne; Maufrais, Corinne; Diogo, Dorothée; Marcet-Houben, Marina; Perin, Aurélie; Sertour, Natacha; Mosca, Kevin; Permal, Emmanuelle; Laval, Guillaume; Bouchier, Christiane; Ma, Laurence; Schwartz, Katja; Voelz, Kerstin; May, Robin C; Poulain, Julie; Battail, Christophe; Wincker, Patrick; Borman, Andrew M; Chowdhary, Anuradha; Fan, Shangrong; Kim, Soo Hyun; Le Pape, Patrice; Romeo, Orazio; Shin, Jong Hee; Gabaldon, Toni; Sherlock, Gavin; Bougnoux, Marie-Elisabeth; d'Enfert, Christophe

    2018-06-08

    Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.

  20. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess.

    PubMed

    Grannan, Benjamin L; Yanamadala, Vijay; Venteicher, Andrew S; Walcott, Brian P; Barr, John C

    2014-10-01

    Mucormycosis is an invasive fungal infection associated with a high mortality. Cerebral mucor abscesses can result secondary to rhinocerebral or hematogenous spread. Amphotericin B, posaconazole, and aggressive surgical resection are the hallmarks of treatment. While amphotericin is typically administered intravenously, less is known about the use of intrathecal amphotericin B. We describe a 42-year-old man who developed a cerebellar mucor abscess after undergoing hematopoietic stem cell transplant for the treatment of myelodysplastic syndrome. In the post-operative period he was admitted to the neurocritical care unit and received liposomal amphotericin B intravenously and through an external ventricular drain. This patient demonstrates that utilization of an external ventricular drain for intrathecal antifungal therapy in the post-operative period may warrant further study in patients with difficult to treat intracranial fungal abscesses. Copyright © 2014. Published by Elsevier Ltd.

  1. Complex interactions among host pines and fungi vectored by an invasive bark beetle

    Treesearch

    Min Lu; Michael J. Wingfield; Nancy E. Gillette; Sylvia R. Mori; Jian-Hua Sun

    2010-01-01

    Recent studies have investigated the relationships between pairs or groups of exotic species to illustrate invasive mechanisms, but most have focused on interactions at a single trophic level.Here, we conducted pathogenicity tests, analyses of host volatiles and fungal growth tests to elucidate an intricate network of interactions between the host...

  2. Economic Comparison of an Empirical Versus Diagnostic-Driven Strategy for Treating Invasive Fungal Disease in Immunocompromised Patients.

    PubMed

    Barnes, Rosemary; Earnshaw, Stephanie; Herbrecht, Raoul; Morrissey, Orla; Slavin, Monica; Bow, Eric; McDade, Cheryl; Charbonneau, Claudie; Weinstein, David; Kantecki, Michal; Schlamm, Haran; Maertens, Johan

    2015-06-01

    Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective. An empirical strategy with conventional amphotericin B deoxycholate (C-AmB), liposomal amphotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling. Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000; empirical strategy, 125 of 1000), with similar survival rates. This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

    PubMed

    van Someren Gréve, Frank; Juffermans, Nicole P; Bos, Lieuwe D J; Binnekade, Jan M; Braber, Annemarije; Cremer, Olaf L; de Jonge, Evert; Molenkamp, Richard; Ong, David S Y; Rebers, Sjoerd P H; Spoelstra-de Man, Angelique M E; van der Sluijs, Koenraad F; Spronk, Peter E; Verheul, Kirsten D; de Waard, Monique C; de Wilde, Rob B P; Winters, Tineke; de Jong, Menno D; Schultz, Marcus J

    2018-01-01

    The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. Prospective observational study. Five ICUs in the Netherlands. Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. None. Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

  4. Use of (1→3)-β-D-Glucan for diagnosis and management of invasive mycoses in HIV-infected patients.

    PubMed

    Farhour, Zahra; Mehraj, Vikram; Chen, Jun; Ramendra, Rayoun; Lu, Hongzhou; Routy, Jean-Pierre

    2018-05-31

    People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualize and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)-β-D-Glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV-infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Molecular detection of fungal pathogens in clinical specimens by 18S rDNA high-throughput screening in comparison to ITS PCR and culture.

    PubMed

    Wagner, K; Springer, B; Pires, V P; Keller, P M

    2018-05-03

    The rising incidence of invasive fungal infections and the expanding spectrum of fungal pathogens makes early and accurate identification of the causative pathogen a daunting task. Diagnostics using molecular markers enable rapid identification of fungi, offer new insights into infectious disease dynamics, and open new possibilities for infectious disease control and prevention. We performed a retrospective study using clinical specimens (N = 233) from patients with suspected fungal infection previously subjected to culture and/or internal transcribed spacer (ITS) PCR. We used these specimens to evaluate a high-throughput screening method for fungal detection using automated DNA extraction (QIASymphony), fungal ribosomal small subunit (18S) rDNA RT-PCR and amplicon sequencing. Fungal sequences were compared with sequences from the curated, commercially available SmartGene IDNS database for pathogen identification. Concordance between 18S rDNA RT-PCR and culture results was 91%, and congruence between 18S rDNA RT-PCR and ITS PCR results was 94%. In addition, 18S rDNA RT-PCR and Sanger sequencing detected fungal pathogens in culture negative (N = 13) and ITS PCR negative specimens (N = 12) from patients with a clinically confirmed fungal infection. Our results support the use of the 18S rDNA RT-PCR diagnostic workflow for rapid and accurate identification of fungal pathogens in clinical specimens.

  6. Nationwide trends in use and timeliness of diagnostic coronary angiography in acute coronary syndromes from 2005 to 2011: Does distance to invasive heart centres matter?

    PubMed

    Hansen, Kim W; Sørensen, Rikke; Madsen, Mette; Madsen, Jan K; Jensen, Jan S; von Kappelgaard, Lene M; Mortensen, Poul E; Galatius, Søren

    2015-08-01

    To examine trends in the use of diagnostic coronary angiography according to distance from home to the nearest invasive heart centre following implementation of fast-track protocols and extensive pre-hospital triaging of acute coronary syndrome patients. We performed a register-based cohort study of all patients admitted to Danish hospitals with incident acute coronary syndrome in 2005-2011. Diagnostic coronary angiography within 60 days of admission was investigated according to distance tertiles (DTs) calculated as range from each patient's home to the nearest invasive heart centre (short DT: <22 km, medium DT: 22-65 km, long DT: >65 km). Cox proportional hazards models were applied.Among the 52,409 patients included, diagnostic coronary angiography was increasingly used during 2005-2011 (short DT: 76% to 81%; medium DT: 74% to 81%; long DT: 69% to 78%; all p-values for trend <0.001). Using the short DT as reference the adjusted hazard ratios for medium DT were 0.87 (0.84-0.89) for 2005-2007, 0.94 (0.90-0.98) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Corresponding figures for long DT were 0.74 (0.72-0.76) for 2005-2007, 0.87 (0.83-0.90) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Length of hospital stay, time to coronary angiography, and 60-day mortality decreased in all DT. This nationwide study found significant increases in diagnostic coronary angiography use over time in incident acute coronary syndrome patients with a relatively larger increase in patients residing farthest from an invasive heart centre. Additionally, selected quality of care measures improved in the entire cohort, suggesting a benefit of national clinical protocols. © The European Society of Cardiology 2014.

  7. Fungal Skin Infections

    MedlinePlus

    ... Skin Infections Overview of Fungal Skin Infections Candidiasis (Yeast Infection) Dermatophytid Reaction Intertrigo Tinea Versicolor Overview of ... breasts. Common fungal skin infections are caused by yeasts (such as Candida or Malassezia furfur ) or dermatophytes , ...

  8. The early response during the interaction of fungal phytopathogen and host plant.

    PubMed

    Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

    2017-05-01

    Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

  9. The early response during the interaction of fungal phytopathogen and host plant

    PubMed Central

    Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

    2017-01-01

    Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

  10. Plant phenolic compounds and oxidative stress: integrated signals in fungal-plant interactions.

    PubMed

    Shalaby, Samer; Horwitz, Benjamin A

    2015-08-01

    Upon invasion of a host, fungal pathogens are exposed to a variety of stresses. Plants release reactive oxygen species, and mount a variety of preformed and induced chemical defenses. Phenolic compounds are one example: they are ubiquitous in plants, and an invading pathogen encounters them already at the leaf surface, or for soil-borne pathogens, in the rhizosphere. Phenolic and related aromatic compounds show varying degrees of toxicity to cells. Some compounds are quite readily metabolized, and others less so. It was known already from classical studies that phenolic substrates induce the expression of the enzymes for their degradation. Recently, the ability to degrade phenolics was shown to be a virulence factor. Conversely, phenolic compounds can increase the effectiveness of antifungals. Phenolics are known antioxidants, yet they have been shown to elicit cellular responses that would usually be triggered to counter oxidant stress. Here, we review the evidence for a connection between the fungal response to phenolics as small-molecule signals, and the response to oxidants. The connections proposed here should enable genetic screens to identify specific fungal receptors for plant phenolics. Furthermore, understanding how the pathogen detects plant phenolic compounds as a stress signal may facilitate new antifungal strategies.

  11. Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

    PubMed Central

    Vipparti, Haritha

    2014-01-01

    The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy. PMID:24959447

  12. Metabolism in Fungal Pathogenesis

    PubMed Central

    Ene, Iuliana V.; Brunke, Sascha; Brown, Alistair J.P.; Hube, Bernhard

    2014-01-01

    Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. PMID:25190251

  13. Protection by fungal starters against growth and secondary metabolite production of fungal spoilers of cheese.

    PubMed

    Nielsen, M S; Frisvad, J C; Nielsen, P V

    1998-06-30

    The influence of fungal starter cultures on growth and secondary metabolite production of fungal contaminants associated with cheese was studied on laboratory media and Camembert cheese. Isolates of the species Penicillium nalgiovense, P. camemberti, P. roqueforti and Geotrichum candidum were used as fungal starters. The species P. commune, P. caseifulvum, P. verrucosum, P. discolor, P. solitum, P. coprophilum and Aspergillus versicolor were selected as contaminants. The fungal starters showed different competitive ability on laboratory media and Camembert cheese. The presence of the Penicillium species, especially P. nalgiovense, showed an inhibitory effect on the growth of the fungal contaminants on laboratory media. G. candidum caused a significant inhibition of the fungal contaminants on Camembert cheese. The results indicate that G. candidum plays an important role in competition with undesirable microorganisms in mould fermented cheeses. Among the starters, P. nalgiovense caused the largest reduction in secondary metabolite production of the fungal contaminants on the laboratory medium. On Camembert cheese no significant changes in metabolite production of the fungal contaminants was observed in the presence of the starters.

  14. Diversity of fungal endophytes in non-native Phragmites australis in the Great Lakes

    USGS Publications Warehouse

    Clay, Keith; Shearin, Zachery; Bourke, Kimberly; Bickford, Wesley A.; Kowalski, Kurt P.

    2016-01-01

    Plant–microbial interactions may play a key role in plant invasions. One common microbial interaction takes place between plants and fungal endophytes when fungi asymptomatically colonize host plant tissues. The objectives of this study were to isolate and sequence fungal endophytes colonizing non-native Phragmites australis in the Great Lakes region to evaluate variation in endophyte community composition among three host tissue types and three geographical regions. We collected entire ramets from multiple clones and populations, surface sterilized plant tissues, and plated replicate tissue samples from leaves, stems, and rhizomes on corn meal agar plates to culture and isolate fungal endophytes. Isolates were then subjected to Sanger sequencing of the ITS region of the nuclear ribosomal DNA. Sequences were compared to fungal databases to define operational taxonomic units (OTUs) that were analyzed statistically for community composition. In total, we obtained 173 endophyte isolates corresponding to 55 OTUs, 39 of which were isolated only a single time. The most common OTU corresponded most closely to Sarocladium strictum and comprised 25 % of all fungal isolates. More OTUs were found in stem tissues, but endophyte diversity was greatest in rhizome tissues. PERMANOVA analyses indicated significant differences in endophyte communities among tissue types, geographical regions, and the interaction between those factors, but no differences among individual ramets were detected. The functional role of the isolated endophytes is not yet known, but one genus isolated here (Stagonospora) has been reported to enhance Phragmites growth. Understanding the diversity and functions of Phragmites endophytes may provide targets for control measures based on disrupting host plant/endophyte interactions.

  15. Fungal Zinc Homeostasis - A Tug of War Between the Pathogen and Host.

    PubMed

    Walencik, Paulina K; Watly, Joanna; Rowinska-Zyrek, Magdalena

    2016-01-01

    In the last decade, drug resistant invasive mycoses have become significantly more common and new antifungal drugs and ways to specifically deliver them to the fungal cell are being looked for. One of the biggest obstacles in finding such comes from the fact that fungi share essential metabolic pathways with humans. One significant difference in the metabolism of those two cells that can be challenged when looking for possible selective therapeutics is the uptake of zinc, a nutrient crucial for the fungal survival and virulence. This work summarizes the recent advances in the biological inorganic chemistry of zinc metabolism in fungi. The regulation of zinc uptake, various types of its transmembrane transport, storage and the maintenance of intracellular zinc homeostasis is discussed in detail, with a special focus on the concept of a constant 'tug of war' over zinc between the fungus and its host, with the host trying to withhold essential Zn(II), and the fungus counteracting by producing high-affinity zinc binding molecules.

  16. Prospecting fungal parasites of the potato cyst nematode Globodera pallida using a rapid screening technique.

    PubMed

    Kooliyottil, Rinu; Dandurand, Louise-Marie; Knudsen, Guy R

    2017-05-01

    Seven filamentous fungal species were isolated from individual eggs of Globodera pallida cysts collected from infested fields in Shelley Idaho, USA and identified as Chaetomium globosum, Fusarium oxysporum, Fusarium solani, Fusarium tricinctum, Microdochium bolleyi, Purpureocillium lilacinum, and Plectosphaerella cucumerina. Their ability to reduce infection by G. pallida in planta were assessed in simple, reproducible micro-rhizosphere chambers (micro-ROCs). All fungi reduced G. pallida infection in potato, but greatest reduction was observed with C. globosum at an average reduction of 76%. Further non-destructive methods were developed to rapidly assess biological control potential of putative fungal strains by staining the infectious second stage juveniles of G. pallida with the live fluorescent stain PKH26. In comparisons between the standard, invasive acid fuchsin method and use of the live stain PKH26, no significant difference in infection level of G. pallida was observed whether roots were stained with PKH26 or acid fuchsin. For both methods, a similar reduction (77% for acid fuchsin, and 78% for PKH26 stain) in invasion of infectious stage of G. pallida was observed when potato plants were inoculated with C. globosum compared to non-inoculated potato. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Burden of serious fungal infections in Mexico.

    PubMed

    Corzo-León, D E; Armstrong-James, D; Denning, D W

    2015-10-01

    Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100,000) followed by allergic bronchopulmonary aspergillosis (60 per 100,000), chronic pulmonary aspergillosis (15.9 per 100,000), fungal keratitis (10.4 per 100,000), invasive candidiasis (8.6 per 100,000) and SFIs in HIV (8.2 per 100,000); coccidioidomycosis (7.6 per 100,000), IA (4.56 per 100,000). These correspond to 2,749,159 people affected in any year (2.45% of the population), probably >10,000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists. © 2015 Blackwell Verlag GmbH.

  18. Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis.

    PubMed

    Caffrey-Carr, Alayna K; Hilmer, Kimberly M; Kowalski, Caitlin H; Shepardson, Kelly M; Temple, Rachel M; Cramer, Robert A; Obar, Joshua J

    2017-01-01

    Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B 4 (LTB 4 ) are critical for leukocyte recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and in vivo LTB 4 production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to A. fumigatus .

  19. Acidic Mammalian Chitinase Negatively Affects Immune Responses during Acute and Chronic Aspergillus fumigatus Exposure.

    PubMed

    Garth, Jaleesa M; Mackel, Joseph J; Reeder, Kristen M; Blackburn, Jonathan P; Dunaway, Chad W; Yu, Zhihong; Matalon, Sadis; Fitz, Lori; Steele, Chad

    2018-07-01

    Chitin is a polysaccharide that provides structure and rigidity to the cell walls of fungi and insects. Mammals possess multiple chitinases, which function to degrade chitin, thereby supporting a role for chitinases in immune defense. However, chitin degradation has been implicated in the pathogenesis of asthma. Here, we determined the impact of acidic mammalian chitinase (AMCase) ( Chia ) deficiency on host defense during acute exposure to the fungal pathogen Aspergillus fumigatus as well as its contribution to A. fumigatus -associated allergic asthma. We demonstrate that chitin in the fungal cell wall was detected at low levels in A. fumigatus conidia, which emerged at the highest level during hyphal transition. In response to acute A. fumigatus challenge, Chia -/- mice unexpectedly demonstrated lower A. fumigatus lung burdens at 2 days postchallenge. The lower fungal burden correlated with decreased lung interleukin-33 (IL-33) levels yet increased IL-1β and prostaglandin E 2 (PGE 2 ) production, a phenotype that we reported previously to promote the induction of IL-17A and IL-22. During chronic A. fumigatus exposure, AMCase deficiency resulted in lower dynamic and airway lung resistance than in wild-type mice. Improved lung physiology correlated with attenuated levels of the proallergic chemokines CCL17 and CCL22. Surprisingly, examination of inflammatory responses during chronic exposure revealed attenuated IL-17A and IL-22 responses, but not type 2 responses, in the absence of AMCase. Collectively, these data suggest that AMCase functions as a negative regulator of immune responses during acute fungal exposure and is a contributor to fungal asthma severity, putatively via the induction of proinflammatory responses. Copyright © 2018 American Society for Microbiology.

  20. Spartina alterniflora invasion alters soil microbial community composition and microbial respiration following invasion chronosequence in a coastal wetland of China

    PubMed Central

    Yang, Wen; Jeelani, Nasreen; Leng, Xin; Cheng, Xiaoli; An, Shuqing

    2016-01-01

    The role of exotic plants in regulating soil microbial community structure and activity following invasion chronosequence remains unclear. We investigated soil microbial community structure and microbial respiration following Spartina alterniflora invasion in a chronosequence of 6-, 10-, 17-, and 20-year-old by comparing with bare flat in a coastal wetland of China. S. alterniflora invasion significantly increased soil moisture and salinity, the concentrations of soil water-soluble organic carbon and microbial biomass carbon (MBC), the quantities of total and various types of phospholipid fatty acids (PLFAs), the fungal:bacterial PLFAs ratio and cumulative microbial respiration compared with bare flat. The highest MBC, gram-negative bacterial and saturated straight-chain PLFAs were found in 10-year-old S. alterniflora soil, while the greatest total PLFAs, bacterial and gram-positive bacterial PLFAs were found in 10- and 17-year-old S. alterniflora soils. The monounsaturated:branched PLFAs ratio declined, and cumulative microbial respiration on a per-unit-PLFAs increased following S. alterniflora invasion in the chronosequence. Our results suggest that S. alterniflora invasion significantly increased the biomass of soil various microbial groups and microbial respiration compared to bare flat soil by increasing soil available substrate, and modifying soil physiochemical properties. Soil microbial community reached the most enriched condition in the 10-year-old S. alterniflora community. PMID:27241173

  1. A new horizon for the use of non-invasive ventilation in patients with acute respiratory distress syndrome.

    PubMed

    Carron, Michele

    2016-09-01

    Non-invasive ventilation (NIV) has assumed an important role in the management of acute respiratory failure (ARF). NIV, compared with standard medical therapy, improves survival and reduces complications in selected patients with ARF. NIV represents the first-line intervention for some forms of ARF, such as chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic pulmonary edema. The use of NIV is also well supported for immunocompromised patients who are at high risk for infectious complications from endotracheal intubation. Selection of appropriate patients is crucial for optimizing NIV success rates. Appropriate ventilator settings, a well-fitting and comfortable interface, and a team skilled and experienced in managing NIV are key components to its success. In a recent issue of the Journal of the American Medical Association , Patel et al . reported the results of their single-center trial of 83 patients with acute respiratory distress syndrome (ARDS) who were randomly assigned to NIV delivered via a helmet or face mask. Patients assigned to the helmet group exhibited a significantly lower intubation rate and were more likely to survive through 90 days. This perspective reviews the findings of this trial in the context of current clinical practice and in light of data from the literature focused on the potential reasons for success of NIV delivered through a helmet compared to face mask. The implications for early management of patients with ARDS are likewise discussed.

  2. Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

    PubMed Central

    Ullmann, A. J.; Cornely, O. A.; Burchardt, A.; Hachem, R.; Kontoyiannis, D. P.; Töpelt, K.; Courtney, R.; Wexler, D.; Krishna, G.; Martinho, M.; Corcoran, G.; Raad, I.

    2006-01-01

    The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure. PMID:16436724

  3. Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis

    PubMed Central

    Zhao, Ying Jiao; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

    2015-01-01

    Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care

  4. Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans.

    PubMed

    Gauthier, Gregory M; Keller, Nancy P

    2013-12-01

    The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. A Common Fungal Associate of the Spruce Bark Beetle Metabolizes the Stilbene Defenses of Norway Spruce1[C][W][OA

    PubMed Central

    Hammerbacher, Almuth; Schmidt, Axel; Wadke, Namita; Wright, Louwrance P.; Schneider, Bernd; Bohlmann, Joerg; Brand, Willi A.; Fenning, Trevor M.; Gershenzon, Jonathan; Paetz, Christian

    2013-01-01

    Norway spruce (Picea abies) forests suffer periodic fatal attacks by the bark beetle Ips typographus and its fungal associate, Ceratocystis polonica. Norway spruce protects itself against fungal and bark beetle invasion by the production of terpenoid resins, but it is unclear whether resins or other defenses are effective against the fungus. We investigated stilbenes, a group of phenolic compounds found in Norway spruce bark with a diaryl-ethene skeleton with known antifungal properties. During C. polonica infection, stilbene biosynthesis was up-regulated, as evidenced by elevated transcript levels of stilbene synthase genes. However, stilbene concentrations actually declined during infection, and this was due to fungal metabolism. C. polonica converted stilbenes to ring-opened, deglycosylated, and dimeric products. Chromatographic separation of C. polonica protein extracts confirmed that these metabolites arose from specific fungal enzyme activities. Comparison of C. polonica strains showed that rapid conversion of host phenolics is associated with higher virulence. C. polonica is so well adapted to its host’s chemical defenses that it is even able to use host phenolic compounds as its sole carbon source. PMID:23729780

  6. Drugs currently under investigation for the treatment of invasive candidiasis.

    PubMed

    McCarthy, Matthew W; Walsh, Thomas J

    2017-07-01

    The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

  7. [Predictors of the use of the early invasive strategy in women with non-ST-elevation acute coronary syndrome].

    PubMed

    de Miguel-Balsa, E; Baeza-Román, A; Pino-Izquierdo, K; Latour-Pérez, J; Coves-Orts, F J; Alcoverro-Pedrola, J M; Pavía-Pesquera, M C; Felices-Abad, F; Calvo-Embuena, R

    2014-11-01

    To identify determinants associated to an early invasive strategy in women with acute coronary syndromes without ST elevation (NSTE-ACS). A retrospective cohort study was made. Crude and adjusted analysis of the performance of the early invasive strategy using logistic regression. Coronary Units enrolled in 2010 - 2011 in the ARIAM-SEMICYUC registry. A total of 440 women with NSTE-ACS were studied. Sixteen patients were excluded due to insufficient data, together with 58 patients subjected to elective coronary angiography (> 72 h). Demographic parameters, coronary risk factors, previous medication, comorbidity. Clinical, laboratory, hemodynamic and electrocardiographic data of the episode. Women treated conservatively were of older age, had oral anticoagulation, diabetes, previous coronary lesions, and heart failure (p<0.005), increased baseline bleeding and ischemic risk (p=0.05) and a higher heart rate upon admission (p<0.05). After adjustment, only age > 80 years (OR 0.48, 95% CI 0.27 to 0.82, p=0.009), known coronary lesions (OR 0.47, 95% CI 0.26-0.84, p=0.011), and heart rate (OR 0.98, 95% CI 0.97-0.99, p=0.003) were independently associated to conservative treatment. Smoking (OR 2.50, 95% CI 1.20 to 5.19, p=0.013) and high-risk electrocardiogram (OR 2.96, 95% CI 1.72 to 4.97, p<0.001) were associated to the early invasive strategy. The exclusion of early deaths (<24 h) did not alter these results. In women with NSTE ACS, smoking and a high-risk electrocardiogram upon admission were independent factors associated to the early invasive strategy. Previous coronary lesions, age > 80 years and increased heart rate were independent factors associated to conservative treatment. Copyright © 2012 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  8. The F-box protein Fbp1 functions in the invasive growth and cell wall integrity mitogen-activated protein kinase (MAPK) pathways in Fusarium oxysporum.

    PubMed

    Miguel-Rojas, Cristina; Hera, Concepcion

    2016-01-01

    F-box proteins determine substrate specificity of the ubiquitin-proteasome system. Previous work has demonstrated that the F-box protein Fbp1, a component of the SCF(Fbp1) E3 ligase complex, is essential for invasive growth and virulence of the fungal plant pathogen Fusarium oxysporum. Here, we show that, in addition to invasive growth, Fbp1 also contributes to vegetative hyphal fusion and fungal adhesion to tomato roots. All of these functions have been shown previously to require the mitogen-activated protein kinase (MAPK) Fmk1. We found that Fbp1 is required for full phosphorylation of Fmk1, indicating that Fbp1 regulates virulence and invasive growth via the Fmk1 pathway. Moreover, the Δfbp1 mutant is hypersensitive to sodium dodecylsulfate (SDS) and calcofluor white (CFW) and shows reduced phosphorylation levels of the cell wall integrity MAPK Mpk1 after SDS treatment. Collectively, these results suggest that Fbp1 contributes to both the invasive growth and cell wall integrity MAPK pathways of F. oxysporum. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  9. Death by Edible Mushroom: First Report of Volvariella volvacea as an Etiologic Agent of Invasive Disease in a Patient following Double Umbilical Cord Blood Transplantation▿

    PubMed Central

    Salit, R. B.; Shea, Y. R.; Gea-Banacloche, J.; Fahle, G. A.; Abu-Asab, M.; Sugui, J. A.; Carpenter, A. E.; Quezado, M. M.; Bishop, M. R.; Kwon-Chung, K. J.

    2010-01-01

    We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales. PMID:20826647

  10. Interactions between abundant fungal species influence the fungal community assemblage on limestone

    PubMed Central

    Morón-Ríos, Alejandro; Ortega-Morales, Benjamin Otto; De la Rosa-García, Susana; Partida-Martínez, Laila Pamela; Quintana, Patricia; Alayón-Gamboa, José Armando; Cappello-García, Silvia; González-Gómez, Santiago

    2017-01-01

    The assembly of fungal communities on stone materials is mainly influenced by the differential bioreceptivity of such materials and environmental conditions. However, little is known about the role of fungal interactions in the colonization and establishment of fungal species. We analyzed the effects of intra- and interspecific interactions between 11 species of fungi in oligotrophic and copiotrophic media and on limestone coupons. In a previous study, these species were the most frequently isolated in the epilithic biofilms of limestone walls exposed to a subtropical climate. In the culture media, we found a greater frequency of intra- and interspecific inhibitory effects in the oligotrophic medium than in the copiotrophic medium. On the limestone coupons, all fungi were able to establish; however, the colonization success rate varied significantly. Cladosporium cladosporioides had a less extensive colonization in isolation (control) than in dual interactions (coexistence) with other species. Phoma eupyrena exhibited the highest colonization success rate and competitive dominance among all tested species. X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses revealed that Pestalotiopsis maculans and Paraconiothyrium sp. produced calcium oxalate crystals during their growth on coupon surfaces, both in isolation and in dual interactions. Our results demonstrate that interactions between abundant fungal species influence the fungal colonization on substrates, the biomineralization and the fungal community assemblage growing in limestone biofilms. PMID:29211748

  11. Fungal Exopolysaccharide: Production, Composition and Applications

    PubMed Central

    Mahapatra, Subhadip; Banerjee, Debdulal

    2013-01-01

    Fungal exopolysaccharides (EPSs) have been recognized as high value biomacromolecules for the last two decades. These products, including pullulan, scleroglucan, and botryosphaeran, have several applications in industries, pharmaceuticals, medicine, foods etc. Although fungal EPSs are highly relevant, to date information concerning fungal biosynthesis is scarce and an extensive search for new fugal species that can produce novel EPSs is still needed. In most cases, the molecular weight variations and sugar compositions of fungal EPSs are dependent to culture medium composition and different physical conditions provided during fermentation. An inclusive and illustrative review on fungal EPS is presented here. The general outline of the present work includes fungal EPS production, their compositions and applications. An emphasis is also given to listing out different fungal strains that can produce EPSs. PMID:24826070

  12. Mycotoxins: A fungal genomics perspective

    USDA-ARS?s Scientific Manuscript database

    The chemical and enzymatic diversity in the fungal kingdom is staggering. Large-scale fungal genome sequencing projects are generating a massive catalog of secondary metabolite biosynthetic genes and pathways. Fungal natural products are a boon and bane to man as valuable pharmaceuticals and harmful...

  13. Jávea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients.

    PubMed

    Pemán, Javier; Aguilar, Gerardo; Valía, Juan Carlos; Salavert, Miguel; Navarro, David; Zaragoza, Rafael

    Although the management of the invasive candidiasis has improved in the last decade, controversial issues yet remain, especially in the diagnostic and therapeutic approaches to Candida peritonitis and other forms of intra-abdominal fungal infections. We sought to identify core clinical knowledge about intra-abdominal fungal infections and to achieve high-agreement recommendations required to care for critically ill adult patients with Candida peritonitis and other forms of intra-abdominal fungal infection. A biregional Spanish survey, to elucidate the consensus about the already mentioned fungal infections by means of the Delphi technique, was conducted anonymously by e-mail with 29 multidisciplinary experts in invasive fungal infections from 14 hospitals in the Valencia and Murcia communities during 2014. Respondents included intensivists, anesthesiologists, microbiologists, pharmacologists, and infectious disease specialists, who answered 31 questions prepared by a coordination group after a strict review of the literature from the 5 previous years. The educational objectives spanned 6 categories: epidemiology, microbiological diagnosis, clinical diagnosis, antifungal treatment, de-escalation therapy, and special situations. The agreement required among the panelists for each item to be selected had to be higher than 70%. After extracting the recommendations from the selected items, a meeting at which the experts were asked to validate the previously selected recommendations in a second round of scoring took place. After the second round, 36 recommendations were validated according to the following distribution: epidemiology (5), microbiological diagnosis (4), clinical diagnosis (4), antifungal treatment (3), de-escalation therapy (4), and special situations (16). Treatment of Candida peritonitis and other forms of intra-abdominal fungal infections in ICU patients requires a broad range of knowledge application and skills that our recommendations address. Based

  14. Evaluation of hirst-type spore trap to monitor environmental fungal load in hospital

    PubMed Central

    Gustin, Marie-Paule; Cassier, Pierre; Loeffert, Sophie Tiphaine; Thibaudon, Michel; Bénet, Thomas; Vanhems, Philippe

    2017-01-01

    The main purpose was to validate the use of outdoor-indoor volumetric impaction sampler with Hirst-type spore traps (HTSTs) to continuously monitor fungal load in order to prevent invasive fungal infections during major structural work in hospital settings. For 4 weeks, outdoor fungal loads were quantified continuously by 3 HTSTs. Indoor air was sampled by both HTST and viable impaction sampler. Results were expressed as particles/m3 (HTST) or colony-forming units (CFU)/m3 (biocollector). Paired comparisons by day were made with Wilcoxon’s paired signed-rank test or paired Student’s t-test as appropriate. Paired airborne spore levels were correlated 2 by 2, after log-transformation with Pearson’s cross-correlation. Concordance was calculated with kappa coefficient (κ). Median total fungal loads (TFLs) sampled by the 3 outdoor HTSTs were 3,025.0, 3,287.5 and 3,625.0 particles/m3 (P = 0.6, 0.6 and 0.3).—Concordance between Aspergillaceae fungal loads (AFLs, including Aspergillus spp. + Penicillium spp.) was low (κ = 0.2). A low positive correlation was found between TFLs sampled with outdoor HTST and indoor HTST with applying a 4-hour time lag, r = 0.30, 95% CI (0.23–0.43), P<0.001. In indoor air, Aspergillus spp. were detected by the viable impaction sampler on 63.1% of the samples, whereas AFLs were found by HTST-I on only 3.6% of the samples. Concordance between Aspergillus spp. loads and AFLs sampled with the 2 methods was very low (κ = 0.1). This study showed a 4-hour time lag between increase of outdoor and indoor TFLs, possibly due to insulation and aeraulic flow of the building. Outdoor HTSTs may permit to quickly identify (after 48 hours) time periods with high outdoor fungal loads. An identified drawback is that a too low sample area read did not seem to enable detection of Aspergillaceae spores efficiently. Indoor HTSTs may not be recommended at this time, and outdoor HTSTs need further study. Air sampling by viable impaction sampler remains

  15. Evaluation of hirst-type spore trap to monitor environmental fungal load in hospital.

    PubMed

    Dananché, Cédric; Gustin, Marie-Paule; Cassier, Pierre; Loeffert, Sophie Tiphaine; Thibaudon, Michel; Bénet, Thomas; Vanhems, Philippe

    2017-01-01

    The main purpose was to validate the use of outdoor-indoor volumetric impaction sampler with Hirst-type spore traps (HTSTs) to continuously monitor fungal load in order to prevent invasive fungal infections during major structural work in hospital settings. For 4 weeks, outdoor fungal loads were quantified continuously by 3 HTSTs. Indoor air was sampled by both HTST and viable impaction sampler. Results were expressed as particles/m3 (HTST) or colony-forming units (CFU)/m3 (biocollector). Paired comparisons by day were made with Wilcoxon's paired signed-rank test or paired Student's t-test as appropriate. Paired airborne spore levels were correlated 2 by 2, after log-transformation with Pearson's cross-correlation. Concordance was calculated with kappa coefficient (κ). Median total fungal loads (TFLs) sampled by the 3 outdoor HTSTs were 3,025.0, 3,287.5 and 3,625.0 particles/m3 (P = 0.6, 0.6 and 0.3).-Concordance between Aspergillaceae fungal loads (AFLs, including Aspergillus spp. + Penicillium spp.) was low (κ = 0.2). A low positive correlation was found between TFLs sampled with outdoor HTST and indoor HTST with applying a 4-hour time lag, r = 0.30, 95% CI (0.23-0.43), P<0.001. In indoor air, Aspergillus spp. were detected by the viable impaction sampler on 63.1% of the samples, whereas AFLs were found by HTST-I on only 3.6% of the samples. Concordance between Aspergillus spp. loads and AFLs sampled with the 2 methods was very low (κ = 0.1). This study showed a 4-hour time lag between increase of outdoor and indoor TFLs, possibly due to insulation and aeraulic flow of the building. Outdoor HTSTs may permit to quickly identify (after 48 hours) time periods with high outdoor fungal loads. An identified drawback is that a too low sample area read did not seem to enable detection of Aspergillaceae spores efficiently. Indoor HTSTs may not be recommended at this time, and outdoor HTSTs need further study. Air sampling by viable impaction sampler remains the

  16. Acute versus subacute community-acquired meningitis: Analysis of 611 patients.

    PubMed

    Sulaiman, Tarek; Salazar, Lucrecia; Hasbun, Rodrigo

    2017-09-01

    Community-acquired meningitis can be classified into acute and subacute presentations by the duration of illness of ≤ or >5 days, respectively. There are currently no studies comparing the clinical features, management decisions, etiologies, and outcomes between acute and subacute presentations.It is a retrospective study of adults with community-acquired meningitis hospitalized in Houston, TX between January 2005 and January 2010. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of ≤4.A total of 611 patients were identified, of which 458 (75%) were acute and 153 subacute (25%). The most common etiologies were unknown in 418 (68.4%), viral in 94 (15.4%), bacterial in 47 (7.7%), fungal in 42 patients (6.9%), and other noninfectious etiologies in 6 (1%). Patients with subacute meningitis were more likely to be immunosuppressed or have comorbidities, had fungal etiologies, and had higher rates of hypoglycorrachia and abnormal neurological findings (P <.05). Patients with an acute presentation were more likely to be treated empirically with intravenous antibiotics and had higher cerebrospinal fluid pleocytosis and serum white blood cell counts (P <.05). On logistic regression, age >65 years and abnormal neurological findings were predictive of an adverse clinical outcome in both acute and subacute meningitis, whereas fever was also a significant prognostic factor in acute meningitis. (P <.05).Acute and subacute meningitis differ in regards to clinical presentations, etiologies, laboratory findings, and management decisions, but did not differ in rates of adverse clinical outcomes. Future studies including thoroughly investigated patients with new diagnostic molecular methods may show different results and outcomes.

  17. An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation

    PubMed Central

    Ishaq, Suzanne L.; AlZahal, Ousama; Walker, Nicola; McBride, Brian

    2017-01-01

    Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly (P < 0.05) affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix, and Phoma were increased, while Alternaria, Candida Orpinomyces, and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor (P = 0.001, Monte Carlo correction) for protozoa. Diet

  18. An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation.

    PubMed

    Ishaq, Suzanne L; AlZahal, Ousama; Walker, Nicola; McBride, Brian

    2017-01-01

    Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae ) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly ( P < 0.05) affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix , and Phoma were increased, while Alternaria, Candida Orpinomyces , and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor ( P = 0.001, Monte Carlo correction) for protozoa. Diet

  19. Staged minimally invasive plate osteosynthesis of proximal tibial fractures with acute compartment syndrome.

    PubMed

    Kim, Joon-Woo; Oh, Chang-Wug; Oh, Jong-Keon; Kyung, Hee-Soo; Park, Kyeong-Hyeon; Kim, Hee-June; Jung, Jae-Wook; Jung, Young-Soo

    2017-06-01

    High-energy proximal tibial fractures often accompany compartment syndrome and are usually treated by fasciotomy with external fixation followed by secondary plating. However, the initial soft tissue injury may affect bony union, the fasciotomy incision or external fixator pin sites may lead to postoperative wound infections, and the staged procedure itself may adversely affect lower limb function. We assess the results of staged minimally invasive plate osteosynthesis (MIPO) for proximal tibial fractures with acute compartment syndrome. Twenty-eight patients with proximal tibial fractures accompanied by acute compartment syndrome who underwent staged MIPO and had a minimum of 12 months follow-up were enrolled. According to the AO/OTA classification, 6 were 41-A, 15 were 41-C, 2 were 42-A and 5 were 42-C fractures; this included 6 cases of open fractures. Immediate fasciotomy was performed once compartment syndrome was diagnosed and stabilization of the fracture followed using external fixation. After the soft tissue condition normalized, internal conversion with MIPO was done on an average of 37 days (range, 9-158) after index trauma. At the time of internal conversion, the external fixator pin site grades were 0 in 3 cases, 1 in 12 cases, 2 in 10 cases and 3 in 3 cases, as described by Dahl. Radiographic assessment of bony union and alignment and a functional assessment using the Knee Society Score and American Orthopedic Foot and Ankle Society (AOFAS) score were carried out. Twenty-six cases achieved primary bony union at an average of 18.5 weeks. Two cases of nonunion healed after autogenous bone grafting. The mean Knee Society Score and the AOFAS score were 95 and 95.3 respectively, at last follow-up. Complications included 1 case of osteomyelitis in a patient with a grade IIIC open fracture and 1 case of malunion caused by delayed MIPO due to poor wound conditions. Duration of external fixation and the external fixator pin site grade were not related to the

  20. The European Paediatric Mycology Network (EPMyN): Towards a Better Understanding and Management of Fungal Infections in Children.

    PubMed

    Warris, Adilia

    The European Paediatric Mycology Network (EPMyN) was launched in 2014 to create a European platform for research and education in the field of paediatric mycology. The EPMyN aims to address the lack of paediatric specific evidence and knowledge needed to (1) improve the management and outcome of invasive fungal infections in children and neonates and to (2) enhance and develop paediatric antifungal stewardship programmes.

  1. Candida parapsilosis Protects Premature Intestinal Epithelial Cells from Invasion and Damage by Candida albicans

    PubMed Central

    Gonia, Sara; Archambault, Linda; Shevik, Margaret; Altendahl, Marie; Fellows, Emily; Bliss, Joseph M.; Wheeler, Robert T.; Gale, Cheryl A.

    2017-01-01

    Candida is a leading cause of late-onset sepsis in premature infants and is thought to invade the host via immature or damaged epithelial barriers. We previously showed that the hyphal form of Candida albicans invades and causes damage to premature intestinal epithelial cells (pIECs), whereas the non-hyphal Candida parapsilosis, also a fungal pathogen of neonates, has less invasion and damage abilities. In this study, we investigated the potential for C. parapsilosis to modulate pathogenic interactions of C. albicans with the premature intestine. While a mixed infection with two fungal pathogens may be expected to result in additive or synergistic damage to pIECs, we instead found that C. parapsilosis was able to protect pIECs from invasion and damage by C. albicans. C. albicans-induced pIEC damage was reduced to a similar extent by multiple different C. parapsilosis strains, but strains differed in their ability to inhibit C. albicans invasion of pIECs, with the inhibitory activity correlating with their adhesiveness for C. albicans and epithelial cells. C. parapsilosis cell-free culture fractions were also able to significantly reduce C. albicans adhesion and damage to pIECs. Furthermore, coadministration of C. parapsilosis cell-free fractions with C. albicans was associated with decreased infection and mortality in zebrafish. These results indicate that C. parapsilosis is able to reduce invasion, damage, and virulence functions of C. albicans. Additionally, the results with cellular and cell-free fractions of yeast cultures suggest that inhibition of pathogenic interactions between C. albicans and host cells by C. parapsilosis occurs via secreted molecules as well as by physical contact with the C. parapsilosis cell surface. We propose that non-invasive commensals can be used to inhibit virulence features of pathogens and deserve further study as a non-pharmacological strategy to protect the fragile epithelial barriers of premature infants. PMID:28382297

  2. Starvation and Imidacloprid Exposure Influence Immune Response by Anoplophora glabripennis (Coleoptera: Cerambycidae) to a Fungal Pathogen.

    PubMed

    Fisher, Joanna J; Castrillo, Louela A; Donzelli, Bruno G G; Hajek, Ann E

    2017-08-01

    In several insect systems, fungal entomopathogens synergize with neonicotinoid insecticides which results in accelerated host death. Using the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), an invasive woodborer inadvertently introduced into North America and Europe, we investigated potential mechanisms in the synergy between the entomopathogenic fungus Metarhizium brunneum Petch and the insecticide imidacloprid. A potential mechanism underlying this synergy could be imidacloprid's ability to prevent feeding shortly after administration. We investigated whether starvation would have an impact similar to imidacloprid exposure on the mortality of fungal-inoculated beetles. Using real-time PCR to quantify fungal load in inoculated beetles, we determined how starvation and pesticide exposure impacted beetles' ability to tolerate or resist a fungal infection. The effect of starvation and pesticide exposure on the encapsulation and melanization immune responses of the beetles was also quantified. Starvation had a similar impact on the survival of M. brunneum-inoculated beetles compared to imidacloprid exposure. The synergy, however, was not completely due to starvation, as imidacloprid reduced the beetles' melanotic encapsulation response and capsule area, while starvation did not significantly reduce these immune responses. Our results suggest that there are multiple interacting mechanisms involved in the synergy between M. brunneum and imidacloprid. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants.

    PubMed

    Marr, Kieren A; Crippa, Fulvio; Leisenring, Wendy; Hoyle, Maggie; Boeckh, Michael; Balajee, S Arunmozhi; Nichols, W Garrett; Musher, Benjamin; Corey, Lawrence

    2004-02-15

    Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P <.001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P =.46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P =.03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P =.03), but similar protection against candidiasis (3% versus 2%, P =.69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.

  4. Neck Pain and Acute Dysphagia.

    PubMed

    Simões, João; Romão, José; Cunha, Anita; Paiva, Sofia; Miguéis, António

    2017-02-01

    The acute tendinitis of the longus colli muscle is an unusual diagnosis in the cases of acute dysphagia with cervical pain. Is a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the prevertebral space and can cause pharyngeal swelling with impaired swallow. It is absolutely critical to make the differential diagnosis with deep cervical infections in order to avoid invasive treatments.

  5. Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

    PubMed

    Lemesle, Gilles; Laine, Marc; Pankert, Mathieu; Puymirat, Etienne; Cuisset, Thomas; Boueri, Ziad; Maillard, Luc; Armero, Sébastien; Cayla, Guillaume; Bali, Laurent; Motreff, Pascal; Peyre, Jean-Pascal; Paganelli, Franck; Kerbaul, François; Roch, Antoine; Michelet, Pierre; Baumstarck, Karine; Bonello, Laurent

    2018-01-01

    According to recent literature, pretreatment with a P2Y 12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y 12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y 12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y 12 ADP receptor antagonist pretreatment. © 2018 Wiley Periodicals, Inc.

  6. Fungal Infections and New Biologic Therapies.

    PubMed

    Vallabhaneni, Snigdha; Chiller, Tom M

    2016-05-01

    The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality.

  7. Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis.

    PubMed

    Dagenais, Taylor R T; Keller, Nancy P

    2009-07-01

    Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease.

  8. Emerging issues with diagnosis and management of fungal infections in solid organ transplant recipients.

    PubMed

    Farmakiotis, D; Kontoyiannis, D P

    2015-05-01

    Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de-escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug-drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs. © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Fungal microbiota dysbiosis in IBD

    PubMed Central

    Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

    2017-01-01

    Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508

  10. Management of Acute Respiratory Failure in the Patient with Sepsis or Septic Shock.

    PubMed

    Moore, Sarah; Weiss, Brian; Pascual, Jose L; Kaplan, Lewis J

    Sepsis and septic shock are each commonly accompanied by acute respiratory failure and the need for invasive as well as non-invasive ventilation throughout a patient's intensive care unit course. We explore the underpinnings of acute respiratory failure of pulmonary as well as non-pulmonary origin in the context of invasive and non-invasive management approaches. Both pharmacologic and non-pharmacologic adjuncts to ventilatory and oxygenation support are highlighted as well. Finally, rescue modalities are positioned within the intensivist's armamentarium for global care of support of the critically ill or injured patient with sepsis or septic shock.

  11. Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes.

    PubMed

    Chellan, G; Neethu, K; Varma, A K; Mangalanandan, T S; Shashikala, S; Dinesh, K R; Sundaram, K R; Varma, N; Jayakumar, R V; Bal, A; Kumar, H

    2012-09-01

    To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep-seated fungal infections. We carried out a randomized, controlled, open-label, parallel-arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty-seven patients (control group) were given standard care (surgical debridement + culture-specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met. By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm(2) in the treatment group, as opposed to 67.1 from 87.3 cm(2) in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10. Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep-seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  12. Differences in stability of seed-associated microbial assemblages in response to invasion by phytopathogenic microorganisms.

    PubMed

    Rezki, Samir; Campion, Claire; Iacomi-Vasilescu, Beatrice; Preveaux, Anne; Toualbia, Youness; Bonneau, Sophie; Briand, Martial; Laurent, Emmanuelle; Hunault, Gilles; Simoneau, Philippe; Jacques, Marie-Agnès; Barret, Matthieu

    2016-01-01

    Seeds are involved in the vertical transmission of microorganisms from one plant generation to another and consequently act as reservoirs for the plant microbiota. However, little is known about the structure of seed-associated microbial assemblages and the regulators of assemblage structure. In this work, we have assessed the response of seed-associated microbial assemblages of Raphanus sativus to invading phytopathogenic agents, the bacterial strain Xanthomonas campestris pv. campestris (Xcc) 8004 and the fungal strain Alternaria brassicicola Abra43. According to the indicators of bacterial (16S rRNA gene and gyrB sequences) and fungal (ITS1) diversity employed in this study, seed transmission of the bacterial strain Xcc 8004 did not change the overall composition of resident microbial assemblages. In contrast seed transmission of Abra43 strongly modified the richness and structure of fungal assemblages without affecting bacterial assemblages. The sensitivity of seed-associated fungal assemblage to Abra43 is mostly related to changes in relative abundance of closely related fungal species that belong to the Alternaria genus. Variation in stability of the seed microbiota in response to Xcc and Abra43 invasions could be explained by differences in seed transmission pathways employed by these micro-organisms, which ultimately results in divergence in spatio-temporal colonization of the seed habitat.

  13. Differences in stability of seed-associated microbial assemblages in response to invasion by phytopathogenic microorganisms

    PubMed Central

    Rezki, Samir; Campion, Claire; Iacomi-Vasilescu, Beatrice; Preveaux, Anne; Toualbia, Youness; Bonneau, Sophie; Briand, Martial; Laurent, Emmanuelle; Hunault, Gilles; Simoneau, Philippe; Jacques, Marie-Agnès

    2016-01-01

    Seeds are involved in the vertical transmission of microorganisms from one plant generation to another and consequently act as reservoirs for the plant microbiota. However, little is known about the structure of seed-associated microbial assemblages and the regulators of assemblage structure. In this work, we have assessed the response of seed-associated microbial assemblages of Raphanus sativus to invading phytopathogenic agents, the bacterial strain Xanthomonas campestris pv. campestris (Xcc) 8004 and the fungal strain Alternaria brassicicola Abra43. According to the indicators of bacterial (16S rRNA gene and gyrB sequences) and fungal (ITS1) diversity employed in this study, seed transmission of the bacterial strain Xcc 8004 did not change the overall composition of resident microbial assemblages. In contrast seed transmission of Abra43 strongly modified the richness and structure of fungal assemblages without affecting bacterial assemblages. The sensitivity of seed-associated fungal assemblage to Abra43 is mostly related to changes in relative abundance of closely related fungal species that belong to the Alternaria genus. Variation in stability of the seed microbiota in response to Xcc and Abra43 invasions could be explained by differences in seed transmission pathways employed by these micro-organisms, which ultimately results in divergence in spatio-temporal colonization of the seed habitat. PMID:27077013

  14. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    PubMed

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-05

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.

    PubMed

    Dix, Andreas; Czakai, Kristin; Leonhardt, Ines; Schäferhoff, Karin; Bonin, Michael; Guthke, Reinhard; Einsele, Hermann; Kurzai, Oliver; Löffler, Jürgen; Linde, Jörg

    2017-01-01

    Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by Candida albicans and Aspergillus fumigatus . The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with C. albicans and A. fumigatus as well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4 , and SPN , on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during

  16. Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units.

    PubMed

    Shahin, Jason; Allen, Elizabeth J; Patel, Krishna; Muskett, Hannah; Harvey, Sheila E; Edgeworth, Jonathan; Kibbler, Christopher C; Barnes, Rosemary A; Biswas, Sharmistha; Soni, Neil; Rowan, Kathryn M; Harrison, David A

    2016-09-09

    Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk

  17. Fungal Fragments as Indoor Air Biocontaminants

    PubMed Central

    Górny, Rafał L.; Reponen, Tiina; Willeke, Klaus; Schmechel, Detlef; Robine, Enric; Boissier, Marjorie; Grinshpun, Sergey A.

    2002-01-01

    The aerosolization process of fungal propagules of three species (Aspergillus versicolor, Penicillium melinii, and Cladosporium cladosporioides) was studied by using a newly designed and constructed aerosolization chamber. We discovered that fungal fragments are aerosolized simultaneously with spores from contaminated agar and ceiling tile surfaces. Concentration measurements with an optical particle counter showed that the fragments are released in higher numbers (up to 320 times) than the spores. The release of fungal propagules varied depending on the fungal species, the air velocity above the contaminated surface, and the texture and vibration of the contaminated material. In contrast to spores, the release of fragments from smooth surfaces was not affected by air velocity, indicating a different release mechanism. Correlation analysis showed that the number of released fragments cannot be predicted on the basis of the number of spores. Enzyme-linked immunosorbent assays with monoclonal antibodies produced against Aspergillus and Penicillium fungal species showed that fragments and spores share common antigens, which not only confirmed the fungal origin of the fragments but also established their potential biological relevance. The considerable immunological reactivity, the high number, and the small particle size of the fungal fragments may contribute to human health effects that have been detected in buildings with mold problems but had no scientific explanation until now. This study suggests that future fungal spore investigations in buildings with mold problems should include the quantitation of fungal fragments. PMID:12089037

  18. Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases.

    PubMed

    Griffiths, James S; Thompson, Aiysha; Stott, Matthew; Benny, Ankita; Lewis, Natalie A; Taylor, Philip R; Forton, Julian; Herrick, Sarah; Orr, Selinda J; McGreal, Eamon P

    2018-06-01

    Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result in IgE sensitization and the development of allergic bronchopulmonary aspergillosis, or invasive infections, such as Aspergillus bronchitis. Lung disease in patients with CF is associated with neutrophil-dominated inflammation and elevated levels of the serine protease, neutrophil elastase (NE). Various C-type lectin-like receptors (CLRs), including Dectin-1 and Dectin-2, are involved in the immune response to Aspergillus. Here, we show that purified NE cleaves Dectin-1 in an isoform-specific manner. Bronchoalveolar lavage fluid from patients with CF, which contains high NE activity, induces Dectin-1 cleavage. Similarly, filtrate from a protease-producing strain of Aspergillus fumigatus induces isoform-specific cleavage of Dectin-1. Dectin-1 knockout (KO) cells and NE-treated cells demonstrated reduced phagocytosis of zymosan, a fungal cell wall preparation. In addition, NE cleaves 2 other CLRs, Dectin-2 and Mincle, and fungal-induced cytokine production was reduced in Dectin-1 KO cells, Dectin-2 KO cells, and NE-treated cells. Thus, Dectin-1 and Dectin-2 cleavage by NE and/or A. fumigatus-derived proteases results in an aberrant antifungal immune response that likely contributes to disease pathology in patients with CF.-Griffiths, J. S., Thompson, A., Stott, M., Benny, A., Lewis, N. A., Taylor, P. R., Forton, J., Herrick, S., Orr, S. J., McGreal, E. P. Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases.

  19. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis

    PubMed Central

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-01-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of > 50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. From the Clinical Editor Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. PMID:25791815

  20. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.

    PubMed

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-07-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Evaluation of fluorescence in situ hybridisation (FISH) for the detection of fungi directly from blood cultures and cerebrospinal fluid from patients with suspected invasive mycoses.

    PubMed

    Da Silva, Roberto Moreira; Da Silva Neto, João Ricardo; Santos, Carla Silvana; Frickmann, Hagen; Poppert, Sven; Cruz, Kátia Santana; Koshikene, Daniela; De Souza, João Vicente Braga

    2015-01-31

    The aim of this study was to evaluate the diagnostic performance of in-house FISH (fluorescence in situ hybridisation) procedures for the direct identification of invasive fungal infections in blood cultures and cerebrospinal fluid (CSF) samples and to compare these FISH results with those obtained using traditional microbiological techniques and PCR targeting of the ITS1 region of the rRNA gene. In total, 112 CSF samples and 30 positive blood cultures were investigated by microscopic examination, culture, PCR-RFLP and FISH. The sensitivity of FISH for fungal infections in CSF proved to be slightly better than that of conventional microscopy (India ink) under the experimental conditions, detecting 48 (instead of 46) infections in 112 samples. The discriminatory powers of traditional microbiology, PCR-RFLP and FISH for fungal bloodstream infections were equivalent, with the detection of 14 fungal infections in 30 samples. However, the mean times to diagnosis after the detection of microbial growth by automated blood culture systems were 5 hours, 20 hours and 6 days for FISH, PCR-RFLP and traditional microbiology, respectively. The results demonstrate that FISH is a valuable tool for the identification of invasive mycoses that can be implemented in the diagnostic routine of hospital laboratories.

  2. Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002-20121.

    PubMed

    Strollo, Sara; Lionakis, Michail S; Adjemian, Jennifer; Steiner, Claudia A; Prevots, D Rebecca

    2016-01-01

    Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis-associated hospitalizations in the United States. We extracted data for 33 states for 2002-2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005-2012 for men (annual change -3.9%) and women (annual change -4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease.

  3. Fungal Endocarditis Due to Aspergillus oryzae: The First Case Reported in the Literature.

    PubMed

    Mazza, Andrea; Luciani, Nicola; Luciani, Marco; Cammertoni, Federico; Giaquinto, Alessia; Pavone, Natalia; Bruno, Piergiorgio; Massetti, Massimo

    2017-03-01

    Infective endocarditis (IE) is a severe disease with high mortality and morbidity. Prosthetic valve endocarditis is a life-threatening complication which can occur in less than 10% of patients with valve prosthesis. A fungal etiology of IE is rare and accounts for only 2-4% of all case of endocarditis, but is associated with a higher mortality and morbidity. Herein is reported the first case of fungal endocarditis of aortic valve prosthesis due to Aspergillus oryzae in a 67-year-old caucasian man who nine years previously underwent mitral and aortic valve replacement with mechanical prostheses, and tricuspid annuloplasty for acute IE due to Enterococcus spp. Seven months previously, the patient also underwent a redo cardiac procedure to replace a mitral valve prosthesis with a new mechanical device due to a leakage. Aspergillus oryzae showed impressive growth with strong and unexpected virulence in both local and systemic settings.

  4. A prospective survey of air and surface fungal contamination in a medical mycology laboratory at a tertiary care university hospital.

    PubMed

    Sautour, Marc; Dalle, Frédéric; Olivieri, Claire; L'ollivier, Coralie; Enderlin, Emilie; Salome, Elsa; Chovelon, Isabelle; Vagner, Odile; Sixt, Nathalie; Fricker-Pap, Véronique; Aho, Serge; Fontaneau, Olivier; Cachia, Claire; Bonnin, Alain

    2009-04-01

    Invasive filamentous fungi infections resulting from inhalation of mold conidia pose a major threat in immunocompromised patients. The diagnosis is based on direct smears, cultural symptoms, and culturing fungi. Airborne conidia present in the laboratory environment may cause contamination of cultures, resulting in false-positive diagnosis. Baseline values of fungal contamination in a clinical mycology laboratory have not been determined to date. A 1-year prospective survey of air and surface contamination was conducted in a clinical mycology laboratory during a period when large construction projects were being conducted in the hospital. Air was sampled with a portable air system impactor, and surfaces were sampled with contact Sabouraud agar plates. The collected data allowed the elaboration of Shewhart graphic charts. Mean fungal loads ranged from 2.27 to 4.36 colony forming units (cfu)/m(3) in air and from 0.61 to 1.69 cfu/plate on surfaces. Strict control procedures may limit the level of fungal contamination in a clinical mycology laboratory even in the context of large construction projects at the hospital site. Our data and the resulting Shewhart graphic charts provide baseline values to use when monitoring for inappropriate variations of the fungal contamination in a mycology laboratory as part of a quality assurance program. This is critical to the appropriate management of the fungal risk in hematology, cancer and transplantation patients.

  5. JGI Fungal Genomics Program

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functionalmore » genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here« less

  6. MycoCosm, an Integrated Fungal Genomics Resource

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shabalov, Igor; Grigoriev, Igor

    2012-03-16

    MycoCosm is a web-based interactive fungal genomics resource, which was first released in March 2010, in response to an urgent call from the fungal community for integration of all fungal genomes and analytical tools in one place (Pan-fungal data resources meeting, Feb 21-22, 2010, Alexandria, VA). MycoCosm integrates genomics data and analysis tools to navigate through over 100 fungal genomes sequenced at JGI and elsewhere. This resource allows users to explore fungal genomes in the context of both genome-centric analysis and comparative genomics, and promotes user community participation in data submission, annotation and analysis. MycoCosm has over 4500 unique visitors/monthmore » or 35000+ visitors/year as well as hundreds of registered users contributing their data and expertise to this resource. Its scalable architecture allows significant expansion of the data expected from JGI Fungal Genomics Program, its users, and integration with external resources used by fungal community.« less

  7. Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials.

    PubMed

    Damman, Peter; Clayton, Tim; Wallentin, Lars; Lagerqvist, Bo; Fox, Keith A A; Hirsch, Alexander; Windhausen, Fons; Swahn, Eva; Pocock, Stuart J; Tijssen, Jan G P; de Winter, Robbert J

    2012-02-01

    To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome. A meta-analysis was performed of patient-pooled data from the FRISC II-ICTUS-RITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management. Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged <65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients <65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar. The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged <65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy. Trial registration http://www.controlled-trials.com/ISRCTN82153174 (ICTUS), http://www.controlled-trials.com/ISRCTN07752711 (RITA-3).

  8. Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

    PubMed

    Zhao, Ying Jiao; Khoo, Ai Leng; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

    2016-01-01

    Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care

  9. Non-invasive mechanical ventilation with spinal anesthesia for cesarean delivery.

    PubMed

    Erdogan, G; Okyay, D Z; Yurtlu, S; Hanci, V; Ayoglu, H; Koksal, B; Turan, I O

    2010-10-01

    We present the successful use of perioperative non-invasive mechanical ventilation in a morbidly obese pregnant woman with bronchial asthma, severe preeclampsia and pulmonary edema undergoing an emergency cesarean delivery with spinal anesthesia. The combination of non-invasive mechanical ventilation with neuraxial anesthesia may be of value in selected parturients with acute or chronic respiratory insufficiency requiring surgery. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

    PubMed Central

    Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

    2016-01-01

    Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

  11. [Fungal diseases of vulva and vagina caused by Candida species].

    PubMed

    Stock, Ingo

    2010-09-01

    Fungal diseases of vulva and vagina attributed to Candida species (vulvovaginal candidosis) are the most frequent mycoses of women. They show acute or chronic courses and different disease patterns which can strongly affect the quality of life of the women who are concerned. In general, the most common cause of acute vulvovaginal candidosis is Candida albicans, followed by C. glabrata. In chronic recurrent vulvovaginal candidosis, C. albicans and C. glabrata are often equally distributed. In several cases, treatment requires an antimycotic therapy which refers to the severity and main form of disease as well as to the aetiological agent. Most vulvovaginal candidoses are accessible to the treatment with local and systemic antimycotic agents. Generally, in Germany azoles such as clotrimazole, fluconazole and itraconazole, the polyens nystatin and Amphotericin B and the hydroxypyridone derivative ciclopirox are available for antimycotic therapy of vulvovaginal candidoses. Significance of non-conventional and adjuvant therapeutic approaches is considered to be generally low.

  12. Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

    PubMed Central

    Jedrzkiewicz, Sean; Goodman, Shaun G; Yan, Raymond T; Welsh, Robert C; Kornder, Jan; DeYoung, J Paul; Wong, Graham C; Rose, Barry; Grondin, François R; Gallo, Richard; Huang, Wei; Gore, Joel M; Yan, Andrew T

    2009-01-01

    BACKGROUND: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada. OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS. METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment. RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization. CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada. PMID:19898699

  13. Review article: fungal microbiota and digestive diseases.

    PubMed

    Wang, Z K; Yang, Y S; Stefka, A T; Sun, G; Peng, L H

    2014-04-01

    The role of the fungal microbiota in digestive diseases is poorly defined, but is becoming better understood due to advances in metagenomics. To review the gastrointestinal fungal microbiota and its relationship with digestive diseases. Search of the literature using PubMed and MEDLINE databases. Subject headings including 'fungal-bacterial interactions', 'mycotoxins', 'immunity to fungi', 'fungal infection', 'fungal microbiota', 'mycobiome' and 'digestive diseases' were used. The fungal microbiota is an integral part of the gastrointestinal microecosystem with up to 10(6) microorganisms per gram of faeces. Next-generation sequencing of the fungal 18S rRNA gene has allowed better characterisation of the gastrointestinal mycobiome. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi all impact on the pathophysiology of inflammatory bowel disease and other gastrointestinal inflammatory entities such as peptic ulcers. Mycotoxins generated as fungal metabolites contribute to disturbances of gastrointestinal barrier and immune functions and are associated with chronic intestinal inflammatory conditions as well as hepatocellular and oesophagogastric cancer. Systemic and gastrointestinal disease can also lead to secondary fungal infections. Fungal genomic databases and methodologies need to be further developed and will allow a much better understanding of the diversity and function of the mycobiome in gastrointestinal inflammation, tumourigenesis, liver cirrhosis and transplantation, and its alteration as a consequence of antibiotic therapy and chemotherapy. The fungal microbiota and its metabolites impact gastrointestinal function and contribute to the pathogenesis of digestive diseases. Further metagenomic analyses of the gastrointestinal mycobiome in health and disease is needed. © 2014 John Wiley & Sons Ltd.

  14. Gastrointestinal phycomycosis in acute nonlymphatic leukemia.

    PubMed

    Mozes, B; Pines, A; Segev, S; Horowitz, A; Goldschmied-Reouven, A; Douer, D; Ben-Bassat, I

    1988-02-01

    A 37-year-old patient with acute nonlymphatic leukemia developed gastrointestinal phycomycosis during failure in bone marrow production. The clinical presentation was of acute typhlitis. Laparotomy revealed a necrotic mass in the region of the iliocecal valve, and on histologic examination hyphae of phycomycetes with invasion of the blood vessels were seen. The patient died as a result of widespread infection.

  15. Minimally invasive optical biopsy for oximetry

    NASA Astrophysics Data System (ADS)

    van der Putten, Marieke A.; Brewer, James M.; Harvey, Andrew R.

    2017-02-01

    The study of localised oxygen saturation in blood vessels can shed light on the etiology and progression of many diseases with which hypoxia is associated. For example, hypoxia in the tendon has been linked to early stages of rheumatoid arthritis, an auto-immune inflammatory disease. Vascular oximetry of deep tissue presents significant challenges as vessels are not optically accessible. In this paper, we present a novel multispectral imaging technique for vascular oximetry, and recent developments made towards its adaptation for minimally invasive imaging. We present proof-of-concept of the system and illumination scheme as well as the analysis technique. We present results of a validation study performed in vivo on mice with acutely inflamed tendons. Adaptation of the technique for minimally invasive microendoscopy is also presented, along with preliminary results of minimally invasive ex vivo vascular oximetry.

  16. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

    PubMed

    Groll, Andreas H; Castagnola, Elio; Cesaro, Simone; Dalle, Jean-Hugues; Engelhard, Dan; Hope, William; Roilides, Emmanuel; Styczynski, Jan; Warris, Adilia; Lehrnbecher, Thomas

    2014-07-01

    Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Neurons show the path: tip-to-nucleus communication in filamentous fungal development and pathogenesis.

    PubMed

    Etxebeste, Oier; Espeso, Eduardo A

    2016-09-01

    Multiple fungal species penetrate substrates and accomplish host invasion through the fast, permanent and unidirectional extension of filamentous cells known as hyphae. Polar growth of hyphae results, however, in a significant increase in the distance between the polarity site, which also receives the earliest information about ambient conditions, and nuclei, where adaptive responses are executed. Recent studies demonstrate that these long distances are overcome by signal transduction pathways which convey sensory information from the polarity site to nuclei, controlling development and pathogenesis. The present review compares the striking connections of the mechanisms for long-distance communication in hyphae with those from neurons, and discusses the importance of their study in order to understand invasion and dissemination processes of filamentous fungi, and design strategies for developmental control in the future. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. The Global Burden of Fungal Diseases.

    PubMed

    Vallabhaneni, Snigdha; Mody, Rajal K; Walker, Tiffany; Chiller, Tom

    2016-03-01

    Fungal diseases require greater attention today than ever before, given the expanding population of immunosuppressed patients who are at higher risk for these diseases. This article reports on distribution, incidence, and prevalence of various fungal diseases and points out gaps in knowledge where such data are not available. Fungal diseases that contribute substantially to global morbidity and mortality are highlighted. Long-term, sustainable surveillance programs for fungal diseases and better noninvasive and reliable diagnostic tools are needed to estimate the burden of these diseases more accurately. Published by Elsevier Inc.

  19. Non-ST-segment elevation syndromes. Pharmacologic management, conservative versus early invasive approach.

    PubMed

    Santiago, Patrick; Tadros, Peter

    2002-07-01

    Many advances have been made in the treatment of acute coronary syndromes. Patients with intermediate-risk or high-risk features should receive treatment with the newer pharmacologic agents--enoxaparin, statins and, in selected cases, clopidogrel--in addition to established standard therapies (i.e., aspirin, beta-blockers, nitroglycerin, and oxygen). Use of GpIIb-IIIa inhibitors should also be strongly considered, especially in an early invasive approach. However, there is no substitute for a good physician who has the big picture and knows the individual patient in totality. This physician can best judge the dangers of the patient's acute cardiac condition against the comorbidities that may be exacerbated by revascularization procedures. The ability to weigh the risks of the patient's acute coronary syndrome against the risks of an aggressive invasive approach ultimately provides the best care for each patient.

  20. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision.

    PubMed

    Bansal, Aditya; Bhama, Jay K; Patel, Rajan; Desai, Sapna; Mandras, Stacy A; Patel, Hamang; Collins, Tyrone; Reilly, John P; Ventura, Hector O; Parrino, P Eugene

    2016-01-01

    Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Minimally invasive LVAD therapy using the

  1. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

    PubMed

    Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

    2015-09-15

    Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect

  2. Mycotoxins: A Fungal Genomics Perspective

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, Daren W.; Baker, Scott E.

    The chemical and enzymatic diversity in the fungal kingdom is staggering. Large-scale fungal genome sequencing projects are generating a massive catalog of secondary metabolite biosynthetic genes and pathways. Fungal natural products are a boon and bane to man as valuable pharmaceuticals and harmful toxins. Understanding how these chemicals are synthesized will aid the development of new strategies to limit mycotoxin contamination of food and feeds as well as expand drug discovery programs. A survey of work focused on the fumonisin family of mycotoxins highlights technological advances and provides a blueprint for future studies of other fungal natural products. Expressed sequencemore » tags led to the discovery of new fumonisin genes (FUM) and hinted at a role for alternatively spliced transcripts in regulation. Phylogenetic studies of FUM genes uncovered a complex evolutionary history of the FUM cluster, as well as fungi with the potential to synthesize fumonisin or fumonisin-like chemicals. The application of new technologies (e.g., CRISPR) could substantially impact future efforts to harness fungal resources.« less

  3. Milbemycins: More than Efflux Inhibitors for Fungal Pathogens

    PubMed Central

    Silva, Luis Vale; Sanguinetti, Maurizio; Vandeputte, Patrick; Torelli, Riccardo; Rochat, Bertrand

    2013-01-01

    Existing antifungal agents are still confronted to activities limited to specific fungal species and to the development of resistance. Several improvements are possible either by tackling and overcoming resistance or exacerbating the activity of existing antifungal agents. In Candida glabrata, azole resistance is almost exclusively mediated by ABC transporters (including C. glabrata CDR1 [CgCDR1] and CgCDR2) via gain-of-function mutations in the transcriptional activator CgPDR1 or by mitochondrial dysfunctions. We also observed that azole resistance was correlating with increasing virulence and fitness of C. glabrata in animal models of infection. This observation motivated the re-exploitation of ABC transporter inhibitors as a possible therapeutic intervention to decrease not only the development of azole resistance but also to interfere with the virulence of C. glabrata. Milbemycins are known ABC transporter inhibitors, and here we used commercially available milbemycin A3/A4 oxim derivatives to verify this effect. As expected, the derivatives were inhibiting C. glabrata efflux with the highest activity for A3 oxim below 1 μg/ml. More surprising was that oxim derivatives had intrinsic fungicidal activity above 3.2 μg/ml, thus highlighting effects additional to the efflux inhibition. Similar values were obtained with C. albicans. Our data show that the fungicidal activity could be related to reactive oxygen species formation in these species. Transcriptional analysis performed both in C. glabrata and C. albicans exposed to A3 oxim highlighted a core of commonly regulated genes involved in stress responses, including genes involved in oxidoreductive processes, protein ubiquitination, and vesicle trafficking, as well as mitogen-activated protein kinases. However, the transcript profiles contained also species-specific signatures. Following these observations, experimental treatments of invasive infections were performed in mice treated with the commercial A3/A4

  4. Fungal keratitis.

    PubMed

    Tuli, Sonal S

    2011-01-01

    What is the most appropriate management of fungal keratitis? Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea. Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary.

  5. Aspergillus felis sp. nov., an Emerging Agent of Invasive Aspergillosis in Humans, Cats, and Dogs

    PubMed Central

    Barrs, Vanessa R.; van Doorn, Tineke M.; Houbraken, Jos; Kidd, Sarah E.; Martin, Patricia; Pinheiro, Maria Dolores; Richardson, Malcolm; Varga, Janos; Samson, Robert A.

    2013-01-01

    We describe a novel heterothallic species in Aspergillus section Fumigati, namely A. felis (neosartorya-morph) isolated from three host species with invasive aspergillosis including a human patient with chronic invasive pulmonary aspergillosis, domestic cats with invasive fungal rhinosinusitis and a dog with disseminated invasive aspergillosis. Disease in all host species was often refractory to aggressive antifungal therapeutic regimens. Four other human isolates previously reported as A. viridinutans were identified as A. felis on comparative sequence analysis of the partial β-tubulin and/or calmodulin genes. A. felis is a heterothallic mold with a fully functioning reproductive cycle, as confirmed by mating-type analysis, induction of teleomorphs within 7 to 10 days in vitro and ascospore germination. Phenotypic analyses show that A. felis can be distinguished from the related species A. viridinutans by its ability to grow at 45°C and from A. fumigatus by its inability to grow at 50°C. Itraconazole and voriconazole cross-resistance was common in vitro. PMID:23798996

  6. Athlete's foot and fungally infected toenails

    PubMed Central

    Crawford, Fay; Hart, Rachel; Bell-Syer, Sally E M; Torgerson, David J; Young, Philip; Russell, Ian

    2001-01-01

    Definition Athlete's foot is a cutaneous fungal infection that causes the skin to itch, flake, and fissure. Nail involvement is characterised by ungual thickening and discoloration. Incidence/prevalence In the United Kingdom, athlete's foot is present in about 15% of the general population,1 and 1.2 million people have fungally infected toenails.2 Aetiology/risk factors Swimming pool users and industrial workers may have increased risk of fungal foot infection. However, one survey found fungal foot infection in only 8.5% of swimmers, with the highest incidence (20%) in men aged 16 years and over.1 Prognosis Fungal infections of the foot are not life threatening in people with normal immunity, but in some people they cause persistent symptoms. Other people seem to be oblivious of persistent infection. The infection can spread to other parts of the body and to other people. Aims To control symptoms and prevent recurrence, with minimal adverse effects. Outcomes Rates of fungal eradication, shown by negative microscopy and culture, and resolution of clinical signs and symptoms at follow up. PMID:11157535

  7. The second International Symposium on Fungal Stress: ISFUS.

    PubMed

    Alder-Rangel, Alene; Bailão, Alexandre M; da Cunha, Anderson F; Soares, Célia M A; Wang, Chengshu; Bonatto, Diego; Dadachova, Ekaterina; Hakalehto, Elias; Eleutherio, Elis C A; Fernandes, Éverton K K; Gadd, Geoffrey M; Braus, Gerhard H; Braga, Gilberto U L; Goldman, Gustavo H; Malavazi, Iran; Hallsworth, John E; Takemoto, Jon Y; Fuller, Kevin K; Selbmann, Laura; Corrochano, Luis M; von Zeska Kress, Marcia R; Bertolini, Maria Célia; Schmoll, Monika; Pedrini, Nicolás; Loera, Octavio; Finlay, Roger D; Peralta, Rosane M; Rangel, Drauzio E N

    2018-06-01

    The topic of 'fungal stress' is central to many important disciplines, including medical mycology, chronobiology, plant and insect pathology, industrial microbiology, material sciences, and astrobiology. The International Symposium on Fungal Stress (ISFUS) brought together researchers, who study fungal stress in a variety of fields. The second ISFUS was held in May 8-11 2017 in Goiania, Goiás, Brazil and hosted by the Instituto de Patologia Tropical e Saúde Pública at the Universidade Federal de Goiás. It was supported by grants from CAPES and FAPEG. Twenty-seven speakers from 15 countries presented their research related to fungal stress biology. The Symposium was divided into seven topics: 1. Fungal biology in extreme environments; 2. Stress mechanisms and responses in fungi: molecular biology, biochemistry, biophysics, and cellular biology; 3. Fungal photobiology in the context of stress; 4. Role of stress in fungal pathogenesis; 5. Fungal stress and bioremediation; 6. Fungal stress in agriculture and forestry; and 7. Fungal stress in industrial applications. This article provides an overview of the science presented and discussed at ISFUS-2017. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  8. Is there a need for autopsies in the management of fungal disease?

    PubMed

    Knoke, Manfred; Bernhardt, Hannelore; Schwesinger, Günther

    2008-07-01

    The autopsy rates in Germany became low like in other European, American and Asian countries. Main reasons for this development are the lack of acceptance of autopsy in the society as well as in the medical profession, the introduction of a requirement for consent, unclear legal position, the public health system, pressure of costs and a change in the field of activity in pathology with much more diagnostics of surgical and biopsy material. The autopsy is missing with respect to the reliability of causes of death and morbidity statistics and other epidemiological studies. Published data indicate that up to 20-30% of patients who die in hospitals have important diseases/lesions that remain undetected before death but that are found at autopsy. For infectious diseases, the data are similar. Therefore, a higher incidence of invasive fungal infections was found. Some rare fungal disorders are diagnosed by autopsy. Only exact death statistics makes specific health care possible and is cost saving in a public health system in the long term. Autopsy remains an important tool for quality control in medical diagnostic and therapeutic activity. It is also essential for fundamental medical education and further training.

  9. Mycorrhizal preference promotes habitat invasion by a native Australian orchid: Microtis media

    PubMed Central

    De Long, Jonathan R.; Swarts, Nigel D.; Dixon, Kingsley W.; Egerton-Warburton, Louise M.

    2013-01-01

    Background and Aims Mycorrhizal specialization has been shown to limit recruitment capacity in orchids, but an increasing number of orchids are being documented as invasive or weed-like. The reasons for this proliferation were examined by investigating mycorrhizal fungi and edaphic correlates of Microtis media, an Australian terrestrial orchid that is an aggressive ecosystem and horticultural weed. Methods Molecular identification of fungi cultivated from M. media pelotons, symbiotic in vitro M. media seed germination assays, ex situ fungal baiting of M. media and co-occurring orchid taxa (Caladenia arenicola, Pterostylis sanguinea and Diuris magnifica) and soil physical and chemical analyses were undertaken. Key Results It was found that: (1) M. media associates with a broad taxonomic spectrum of mycobionts including Piriformospora indica, Sebacina vermifera, Tulasnella calospora and Ceratobasidium sp.; (2) germination efficacy of mycorrhizal isolates was greater for fungi isolated from plants in disturbed than in natural habitats; (3) a higher percentage of M. media seeds germinate than D. magnifica, P. sanguinea or C. arenicola seeds when incubated with soil from M. media roots; and (4) M. media–mycorrhizal fungal associations show an unusual breadth of habitat tolerance, especially for soil phosphorus (P) fertility. Conclusions The findings in M. media support the idea that invasive terrestrial orchids may associate with a diversity of fungi that are widespread and common, enhance seed germination in the host plant but not co-occurring orchid species and tolerate a range of habitats. These traits may provide the weedy orchid with a competitive advantage over co-occurring orchid species. If so, invasive orchids are likely to become more broadly distributed and increasingly colonize novel habitats. PMID:23275632

  10. Cytochemical Labeling for Fungal and Host Components in Plant Tissues Inoculated with Fungal Wilt Pathogens

    NASA Astrophysics Data System (ADS)

    Ouellette, G. B.; Baayen, R. P.; Chamberland, H.; Simard, M.; Rioux, D.; Charest, P. M.

    2004-08-01

    Antibodies to detect pectin in present investigations attached to distinct fibrils in vessel lumina. In carnation infected with an isolate of Fusarium oxysporum f.sp., labeling of pathogen cells also occurred; in a resistant cultivar (cv.), it was coincident with proximate pectin fibrils and linked to altered fungal walls, which was the opposite in the susceptible cv., indicating that hindrance of pathogen ability to degrade pectin may be related to resistance. Labeling of the fungus in culture was nil, except in media containing pectin, showing that pectin is not native to the pathogen. Labeling of fungal walls for cellulose in elm (inoculated with Ophiostoma novo-ulmi) and carnation also occurred, linked to adsorbed host wall components. The chitin probe often attached to dispersed matter, in vessel lumina, traceable to irregularly labeled fungal cells and host wall degradation products. With an anti-horseradish peroxidase probe, host and fungal walls were equally labeled, and with a glucosidase, differences of labeling between these walls were observed, depending on pH of the test solution. Fungal extracellular matter and filamentous structures, present in fungal walls, predominantly in another elm isolate (Phaeotheca dimorphospora), did not label with any of the probes used. However, in cultures of this fungus, extracellular material labeled, even at a distance from the colony margin, with an anti-fimbriae probe.

  11. Effect of air-conditioner on fungal contamination

    NASA Astrophysics Data System (ADS)

    Hamada, Nobuo; Fujita, Tadao

    Air-conditioners (AC) produce much dew and wet conditions inside their apparatus, when in operation. We studied the fungal contamination in AC and found that the average fungal contamination of AC filters was about 5-fold greater than that of a carpet, and Cladosporium and Penicillium were predominant in AC filters. The fungal contamination inside AC, which were used everyday, increased more markedly than those not used daily, e.g. a few days per week or rarely. Moreover, the airborne fungal contamination in rooms during air-conditioning was about 2-fold greater than one in rooms without AC, and was highest when air-conditioning started and decreased gradually with time. We recognized that the airborne fungal contamination was controlled by the environmental condition of the rooms, in which AC were used. It is suggested that AC might promote mold allergies in users via airborne fungal spores derived from the AC. On the other hand, AC was estimated to remove moisture in the room atmosphere and carpets, and reduce the relative humidity in rooms. It was found that the average fungal contamination in the house dust of carpets with AC was suppressed by two-third of that in rooms without AC. The use of AC for suppressing fungal hazards was discussed.

  12. Multicenter Outbreak of Infections by Saprochaete clavata, an Unrecognized Opportunistic Fungal Pathogen

    PubMed Central

    Vaux, Sophie; Criscuolo, Alexis; Desnos-Ollivier, Marie; Diancourt, Laure; Tarnaud, Chloé; Vandenbogaert, Matthias; Brisse, Sylvain; Coignard, Bruno; Garcia-Hermoso, Dea; Blanc, Catherine; Hoinard, Damien; Lortholary, Olivier; Bretagne, Stéphane; Thiolet, Jean-Michel; de Valk, Henriette; Courbil, Rémi; Chabanel, Anne; Simonet, Marion; Maire, Francoise; Jbilou, Saadia; Tiberghien, Pierre; Blanchard, Hervé; Venier, Anne-Gaëlle; Bernet, Claude; Simon, Loïc; Sénéchal, Hélène; Pouchol, Elodie; Angot, Christiane; Ribaud, Patricia; Socié, G.; Flèche, M.; Brieu, Nathalie; Lagier, Evelyne; Chartier, Vanessa; Allegre, Thierry; Maulin, Laurence; Lanic, Hélène; Tilly, Hervé; Bouchara, Jean-Philippe; Pihet, Marc; Schmidt, Aline; Kouatchet, Achille; Vandamme, Yves-Marie; Ifrah, Norbert; Mercat, Alain; Accoceberry, Isabelle; Albert, Olivier; Leguay, Thibaut; Rogues, Anne-Marie; Bonhomme, Julie; Reman, Oumédaly; Lesteven, Claire; Poirier, Philippe; Chabrot, Cécile Molucon; Calvet, Laure; Baud, Olivier; Cambon, Monique; Farkas, Jean Chistophe; Lafon, Bruno; Dalle, Frédéric; Caillot, Denis; Lazzarotti, Aline; Aho, Serge; Combret, Sandrine; Facon, Thierry; Sendid, Boualem; Loridant, Séverine; Louis, Terriou; Cazin, Bruno; Grandbastien, Bruno; Bourgeois, Nathalie; Lotthé, Anne; Cartron, Guillaume; Ravel, Christophe; Colson, Pascal; Gaudard, Philippe; Bonmati, Caroline; Simon, Loic; Rabaud, Christian; Machouart, Marie; Poisson, Didier; Carp, Diana; Meunier, Jérôme; Gaschet, Anne; Miquel, Chantal; Sanhes, Laurence; Ferreyra, Milagros; Leibinger, Franck; Geudet, Philippe; Toubas, Dominique; Himberlin, Chantal; Bureau-Chalot, Florence; Delmer, Alain; Favennec, Loïc; Gargala, Gilles; Michot, Jean-Baptiste; Girault, Christophe; David, Marion; Leprêtre, Stéphane; Jardin, Fabrice; Honderlick, Pierre; Caille, Vincent; Cerf, Charles; Cassaing, Sophie; Recher, Christian; Picard, Muriel; Protin, Caroline; Huguet, Françoise; Huynh, Anne; Ruiz, Jean; Riu-Poulenc, Béatrice; Letocart, Philippe; Marchou, Bruno; Verdeil, Xavier; Cavalié, Laurent; Chauvin, Pamela; Iriart, Xavier; Valentin, Alexis; Bouvet, Emmanuelle; Delmas-Marsalet, Béatrice; Jeblaoui, Asma; Kassis-Chikhani, Najiby; Mühlethaler, Konrad; Zimmerli, Stefan; Zalar, Polona; Sánchez-Reus, Ferran; Gurgui, Merce

    2014-01-01

    ABSTRACT Rapidly fatal cases of invasive fungal infections due to a fungus later identified as Saprochaete clavata were reported in France in May 2012. The objectives of this study were to determine the clonal relatedness of the isolates and to investigate possible sources of contamination. A nationwide alert was launched to collect cases. Molecular identification methods, whole-genome sequencing (WGS), and clone-specific genotyping were used to analyze recent and historical isolates, and a case-case study was performed. Isolates from thirty cases (26 fungemias, 22 associated deaths at day 30) were collected between September 2011 and October 2012. Eighteen cases occurred within 8 weeks (outbreak) in 10 health care facilities, suggesting a common source of contamination, with potential secondary cases. Phylogenetic analysis identified one clade (clade A), which accounted for 16/18 outbreak cases. Results of microbiological investigations of environmental, drug, or food sources were negative. Analysis of exposures pointed to a medical device used for storage and infusion of blood products, but no fungal contamination was detected in the unused devices. Molecular identification of isolates from previous studies demonstrated that S. clavata can be found in dairy products and has already been involved in monocentric outbreaks in hematology wards. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen. This report also underlines further the potential of WGS for investigation of outbreaks due to uncommon fungal pathogens. PMID:25516620

  13. H1N1-associated acute retinitis.

    PubMed

    Rifkin, Lana; Schaal, Shlomit

    2012-06-01

    To present the first reported case of bilateral H(1)N(1)-associated acute retinitis and its successful treatment. Interventional case report. A 41-year-old HIV-positive male presented with acute vision loss, panuveitis, and retinitis. A diagnostic and therapeutic vitrectomy with intravitreal injection of vancomycin and ganciclovir and endolaser was performed. One month later, the patient returned with similar symptoms in the fellow eye and underwent the same procedure. ELISA immunoassay revealed H(1)N(1) antibodies in both the vitreous and serum. PCR for herpes viruses included HSV, CMV, and VZV. Bacterial and fungal cultures were negative. On 1-year follow-up, the vision remained 20/20 in both eyes without evidence of recurrent inflammation. H(1)N(1) should be included in the differential diagnosis of any patient with a history of recent influenza A (H(1)N(1)) infection and acute retinitis. H(1)N(1) may carry a better prognosis than other viruses causing acute retinitis.

  14. Acute pancreatitis.

    PubMed

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  15. Non-invasive Positive Pressure Ventilation during Sleep at 3800m: relationship to Acute Mountain Sickness and sleeping oxyhemoglobin saturation

    PubMed Central

    Johnson, PL; Popa, DA; Prisk, GK; Sullivan, CE; Edwards, N

    2014-01-01

    Background and objectives Ascent to high altitude results in hypobaric hypoxia and some individuals will develop Acute Mountain Sickness, which has been shown to be associated with low oxyhemoglobin saturation during sleep. Previous research has shown that positive end-expiratory pressure by use of expiratory valves in a face mask while awake, results in a reduction in AMS symptoms and higher oxyhemoglobin saturation. We aimed to test whether pressure ventilation during sleep would prevent AMS by keeping oxyhaemoglobin higher during sleep. Methods We compared sleeping oxyhemoglobin saturation and the incidence and severity of Acute Mountain Sickness in seven subjects sleeping for two consecutive nights at 3800m above sea level using either non-invasive positive pressure ventilation that delivered positive inspiratory and expiratory airway pressure via a face mask, or sleeping without assisted ventilation. The presence and severity of Acute Mountain Sickness was assessed by administration of the Lake Louise questionnaire. Results We found significant increases in the mean and minimum sleeping oxyhemoglobin saturation and decreases in AMS symptoms in subjects who used positive pressure ventilation during sleep. Mean and minimum sleeping SaO2 was lower in subjects who developed AMS after the night spent without positive pressure ventilation. Conclusion The use of positive pressure ventilation during sleep at 3800m significantly increased the sleeping oxygen saturation; we suggest that the marked reduction in symptoms of AMS is due to this higher sleeping SaO2. We agree with the findings from previous studies that the development of AMS is associated with a lower sleeping oxygen saturation. PMID:20051046

  16. Invasive Plants Rapidly Reshape Soil Properties in a Grassland Ecosystem.

    PubMed

    Gibbons, Sean M; Lekberg, Ylva; Mummey, Daniel L; Sangwan, Naseer; Ramsey, Philip W; Gilbert, Jack A

    2017-01-01

    Plant invasions often reduce native plant diversity and increase net primary productivity. Invaded soils appear to differ from surrounding soils in ways that impede restoration of diverse native plant communities. We hypothesize that invader-mediated shifts in edaphic properties reproducibly alter soil microbial community structure and function. Here, we take a holistic approach, characterizing plant, prokaryotic, and fungal communities and soil physicochemical properties in field sites, invasion gradients, and experimental plots for three invasive plant species that cooccur in the Rocky Mountain West. Each invader had a unique impact on soil physicochemical properties. We found that invasions drove shifts in the abundances of specific microbial taxa, while overall belowground community structure and functional potential were fairly constant. Forb invaders were generally enriched in copiotrophic bacteria with higher 16S rRNA gene copy numbers and showed greater microbial carbohydrate and nitrogen metabolic potential. Older invasions had stronger effects on abiotic soil properties, indicative of multiyear successions. Overall, we show that plant invasions are idiosyncratic in their impact on soils and are directly responsible for driving reproducible shifts in the soil environment over multiyear time scales. IMPORTANCE In this study, we show how invasive plant species drive rapid shifts in the soil environment from surrounding native communities. Each of the three plant invaders had different but consistent effects on soils. Thus, there does not appear to be a one-size-fits-all strategy for how plant invaders alter grassland soil environments. This work represents a crucial step toward understanding how invaders might be able to prevent or impair native reestablishment by changing soil biotic and abiotic properties.

  17. Fungal keratitis

    PubMed Central

    Tuli, Sonal S

    2011-01-01

    Clinical question: What is the most appropriate management of fungal keratitis? Results: Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea. Implementation: Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary. PMID:21468333

  18. Initial fungal colonizer affects mass loss and fungal community development in Picea abies logs 6 yr after inoculation

    Treesearch

    Daniel L. Lindner; Rimvydas Vasaitis; Ariana Kubartova; Johan Allmer; Hanna Johannesson; Mark T. Banik; Jan. Stenlid

    2011-01-01

    Picea abies logs were inoculated with Resinicium bicolor, Fomitopsis pinicola or left un-inoculated and placed in an old-growth boreal forest. Mass loss and fungal community data were collected after 6 yr to test whether simplification of the fungal community via inoculation affects mass loss and fungal community development. Three...

  19. Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hast, Michael A.; Nichols, Connie B.; Armstrong, Stephanie M.

    Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities andmore » differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.« less

  20. Invasive strategy for treatment of myocardial infarction.

    PubMed

    Höfling, B; von Pölnitz, A

    1990-01-01

    The classical approach to the treatment of acute myocardial infarction (MI) has been one of stabilization and complication management. In an effort to optimize treatment, the initiation of the cardiac care unit and the use of antiarrhythmic therapy have succeeded in lowering the mortality rate substantially. More modern concepts are aimed at limiting infarct size and preserving myocardial function. These aims can be achieved medically using intravenous (i.v.) thrombolysis or invasively either with intracoronary (i.c.) thrombolysis, percutaneous transluminal coronary angioplasty (PTCA), or bypass surgery. Although i.c. thrombolysis is more effective than the i.v. route, the necessity for acute coronary catheterization makes it incompatible and difficult for routine use, and thus is usually reserved for cases in which i.v. lysis has failed. Intravenous thrombolysis is becoming the standard approach to MI, and the remaining questions are those of which drug and dosage are optimal and how to approach the patient after thrombolysis. In this regard, we favor a symptom-guided approach, as shown by the TIMI-IIA and European cooperative studies. In patients with ongoing ischemia postlysis, heart catheterization is indicated and a decision regarding PTCA or surgery is then made, depending on anatomy. In patients remaining stable after acute lysis, a predischarge stress may help in selecting patients requiring catheterization. As an alternative invasive approach to acute MI, PTCA may be the quickest and most effective method to recanalize a vessel, but, again, logistical problems make it incompatible in the acute setting. The same is true for bypass surgery, and although extensive improvements have been made in intraoperative myocardial preservation so that a 2% mortality is achievable, it is reserved for patients with extensive ischemia and anatomy unsuitable for PTCA (extensive multivessel or left main disease).

  1. Invasive forms of Candida and Aspergillus in sputum samples of pulmonary tuberculosis patients attending the tuberculosis reference laboratory in Ghaemshahr, Northern Iran: An analysis of samples collected during the past 10years.

    PubMed

    Jabbari Amiri, Mohammad Reza; Aghili, Seyed Reza; Shokohi, Tahereh; Hedayati, Mohammad Taghi; Abastabar, Mahdi; Aliyali, Masoud; Jabbari Amiri, Masoumeh; Hasanpour, Hamid

    2016-12-01

    Tuberculosis (TB) continues to be a major public health problem worldwide. This is especially true in Northern Iran, which has high TB prevalence. The chronic nature of this disease is further exacerbated if it is accompanied by fungal infection, which usually remains undiagnosed and thus untreated. Thus, mycotic infections add fatal dimensions to pulmonary TB. Our objective was to determine the prevalence of invasive forms of fungal elements in sputum samples collected from patients with pulmonary TB at a reference laboratory in Ghaemshahr, Northern Iran, during the past 10years. In this retrospective study, sputum samples collected from 430 patients were examined. Pulmonary TB in patients was confirmed in our laboratory, and samples obtained during the period from March 2006 to February 2016 were analyzed. The sputum samples were subjected to biological (bacterial) staining (Ziehl-Neelsen and fluorochrome) and mycological investigation using KOH + Calcofluor White (Sigma-Aldrich, India) by fluorescent microscopy and fungal culture on Sabouraud dextrose agar (Sigma-Aldrich, India) and CHROMagar (Paris, France). Invasive forms of fungal pathogens were observed as co-infection with Mycobacterium tuberculosis in 28/430 cases (6.51%). The frequency of Aspergillus, both branching and dichotomous infection, accounted for 3.72% (16/430): Aspergillus flavus, 1.63%; Aspergillus fumigatus, 1.16%; Aspergillus niger, 0.69%; and Aspergillus oryzae, 0.23%, respectively. Blastoconidia and pseudohyphae forms of yeast were observed as co-infection with M. tuberculosis in 2.79% (12/430) of the cases: Candida albicans, 1.86%; Candida krusei, 0.46%; and other Candida species, 0.46%, respectively. Northern Iran is a critical region in the TB world and multidrug-resistant TB is a serious problem in this region. Although it is believed that there exists a commensal relationship between fungus and TB infections, the invasive forms of fungal pathogens and their co-infection can be caused

  2. Stimulation with lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae maximizes cross-reactivity of anti-fungal T cells.

    PubMed

    Deo, Shivashni S; Virassamy, Balaji; Halliday, Catriona; Clancy, Leighton; Chen, Sharon; Meyer, Wieland; Sorrell, Tania C; Gottlieb, David J

    2016-01-01

    Invasive fungal diseases caused by filamentous fungi and yeasts are significant causes of morbidity and mortality in immunosuppressed hematology patients. We previously published a method to expand Aspergillus fumigatus-specific T cells for clinical cell therapy. In the present study, we investigated expansion of T cells specific for other fungal pathogens and creation of a broadly reactive panfungal T-cell product. Fungal strains selected were those frequently observed in the clinical hematology setting and included Aspergillus, Candida, Fusarium, Rhizopus and Lomentospora/Scedosporium. Four T-cell cultures specific to each fungus were established. We selected lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae to expand panfungal T cells. Allelic restriction of anti-fungal activity was determined through the use of specific major histocompatibility complex class II-blocking antibodies. Individual T-cell cultures specific to each fungus could be expanded in vitro, generating predominantly CD4(+) T cells of which 8% to 20% were fungus-specific. We successfully expanded panfungal T cells from the peripheral blood (n = 8) and granulocyte-colony-stimulating factor-primed stem cell products (n = 3) of normal donors by using a combination of lysates from Aspergillus terreus, Candida krusei and Rhizopus oryzae. Anti-fungal activity was mediated through human leukocyte antigen (HLA)-DR alleles and was maintained when antigen-presenting cells from partially HLA-DRB1-matched donors were used to stimulate T cells. We demonstrate a method to manufacture panfungal T-cell products with specificity against a range of clinical fungal pathogens by use of the blood and stem cells of healthy donors as the starting material. The safety and efficacy of these products will need to be tested clinically. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  3. Fungal prostatitis: an update.

    PubMed

    Mayayo, Emilio; Fernández-Silva, Fabiola

    2014-06-01

    Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

  4. Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral Renal Fungal Ball.

    PubMed

    Shukla, Abhishek; Shrivastava, Nitin; Singh, Chirom Amit; Nayak, Brusabhanu

    2016-01-01

    Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi of the class Zygomycetes. The majority of human cases are caused by Mucorales (genus-rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently negative. Case Presentation: A twenty-one-year-old young unmarried lady presented to our emergency department with bilateral flank pain, fever, nausea, and decreased urine output of one-month duration. She was found to have azotemia with sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone. Even after nephrostomy drainage and broad spectrum antibiotics, her condition worsened. She developed disseminated fungal infection, and timely systemic antifungal followed by bilateral nephroscopic clearance saved the patient. Conclusion: Although renal fungal infections are uncommon, a high index of suspicion and early antifungal and surgical intervention can give favorable outcomes.

  5. Fungal symbionts alter plant responses to global change.

    PubMed

    Kivlin, Stephanie N; Emery, Sarah M; Rudgers, Jennifer A

    2013-07-01

    While direct plant responses to global change have been well characterized, indirect plant responses to global change, via altered species interactions, have received less attention. Here, we examined how plants associated with four classes of fungal symbionts (class I leaf endophytes [EF], arbuscular mycorrhizal fungi [AMF], ectomycorrhizal fungi [ECM], and dark septate endophytes [DSE]) responded to four global change factors (enriched CO2, drought, N deposition, and warming). We performed a meta-analysis of 434 studies spanning 174 publications to search for generalizable trends in responses of plant-fungal symbioses to future environments. Specifically, we addressed the following questions: (1) Can fungal symbionts ameliorate responses of plants to global change? (2) Do fungal symbiont groups differ in the degree to which they modify plant response to global change? (3) Do particular global change factors affect plant-fungal symbioses more than others? In all global change scenarios, except elevated CO2, fungal symbionts significantly altered plant responses to global change. In most cases, fungal symbionts increased plant biomass in response to global change. However, increased N deposition reduced the benefits of symbiosis. Of the global change factors we considered, drought and N deposition resulted in the strongest fungal mediation of plant responses. Our analysis highlighted gaps in current knowledge for responses of particular fungal groups and revealed the importance of considering not only the nonadditive effects of multiple global change factors, but also the interactive effects of multiple fungal symbioses. Our results show that considering plant-fungal symbioses is critical to predicting ecosystem response to global change.

  6. Fungal microcolonies on indoor surfaces — an explanation for the base-level fungal spore counts in indoor air

    NASA Astrophysics Data System (ADS)

    Pasanen, A.-L.; Heinonen-Tanski, H.; Kalliokoski, P.; Jantunen, M. J.

    In the subarctic winter, fungal spores are found in indoor air even when outdoor spore levels are very low. The results of this study support an explanation that some indoor airborne fungal spores are derived from unnoticeable fungal microcolonies, which may develop on temporarily wet surfaces. Laboratory experiments on Penicillium verrucosum indicated that the fungus germinated on new wallpaper very quickly (about half an hour) under moist conditions. Hyphal growth and sporulation of the fungus on moist wallpaper occured within one day of incubation. In gravity-settling tape samples from occasionally wet surfaces in a suburban home, large spore aggregates, hyphal fragments with some spores and spores in the germination stage were found, indicating fungal growth. These experiments showed that fungal microcolonies can develop within a week on occasionally wet indoor surfaces.

  7. Fungal contamination in hospital environments.

    PubMed

    Perdelli, F; Cristina, M L; Sartini, M; Spagnolo, A M; Dallera, M; Ottria, G; Lombardi, R; Grimaldi, M; Orlando, P

    2006-01-01

    To assess the degree of fungal contamination in hospital environments and to evaluate the ability of air conditioning systems to reduce such contamination. We monitored airborne microbial concentrations in various environments in 10 hospitals equipped with air conditioning. Sampling was performed with a portable Surface Air System impactor with replicate organism detection and counting plates containing a fungus-selective medium. The total fungal concentration was determined 72-120 hours after sampling. The genera most involved in infection were identified by macroscopic and microscopic observation. The mean concentration of airborne fungi in the set of environments examined was 19 +/- 19 colony-forming units (cfu) per cubic meter. Analysis of the fungal concentration in the different types of environments revealed different levels of contamination: the lowest mean values (12 +/- 14 cfu/m(3)) were recorded in operating theaters, and the highest (45 +/- 37 cfu/m(3)) were recorded in kitchens. Analyses revealed statistically significant differences between median values for the various environments. The fungal genus most commonly encountered was Penicillium, which, in kitchens, displayed the highest mean airborne concentration (8 +/- 2.4 cfu/m(3)). The percentage (35%) of Aspergillus documented in the wards was higher than that in any of the other environments monitored. The fungal concentrations recorded in the present study are comparable to those recorded in other studies conducted in hospital environments and are considerably lower than those seen in other indoor environments that are not air conditioned. These findings demonstrate the effectiveness of air-handling systems in reducing fungal contamination.

  8. Symbiosis in the Context of an Invasive, Non-Native Grass: Fungal Biodiversity and Student Engagement

    NASA Astrophysics Data System (ADS)

    Lehr, Gavin

    Grasslands in the western United States face severe environmental threats including those brought about by climate change, such as changes in precipitation regimes and altered fire cycles; land-use conversion and development; and the introduction, establishment, and spread of non-native species. Lehmann's lovegrass (Eragrostis lehmanniana) was introduced to the southwestern United States in the early 1900s. Since its introduction, it has become the dominant grass in the mid-elevation grasslands of southern Arizona, including the Santa Rita Experimental Range (SRER), where it has displaced native grasses including Arizona cottontop, three awns, and gramas. Like all plants in terrestrial ecosystems, this grass harbors fungal symbionts that can be important for its establishment and persistence. This thesis focuses on fungal symbionts of Lehmann's lovegrass and has two components. First, the diversity and distributions of endophytes in Lehmann's lovegrass are evaluated in the context of biotic and abiotic factors in the SRER. Culturing from roots and shoots of Lehmann's lovegrass at points beneath and outside the canopy of native mesquites, which are encroaching on grasslands over time, provides insight into how a single plant species can exhibit local variation in the composition of its symbionts. Second, the thesis is used as the basis for engagement of students in science, technology, engineering, and mathematics (STEM) through the development and implementation of classroom- and field activities centered on endophytes, which help high school students address core learning aims while also gaining real research experience. Engaging students in important questions relevant to their local environment can catalyze interest in science and help students cross the threshold into research. The contributions of such approaches with respect to learning not only fulfills key next-generation science standards and common core objectives, but provides students with a meaningful

  9. Fungal lectins: a growing family.

    PubMed

    Kobayashi, Yuka; Kawagishi, Hirokazu

    2014-01-01

    Fungi are members of a large group of eukaryotic organisms that include yeasts and molds, as well as the most familiar member, mushrooms. Fungal lectins with unique specificity and structures have been discovered. In general, fungal lectins are classified into specific families based on their amino acid sequences and three-dimensional structures. In this chapter, we provide an overview of the approximately 80 types of mushroom and fungal lectins that have been isolated and studied to date. In particular, we have focused on ten fungal lectins (Agaricus bisporus, Agrocybe cylindracea, Aleuria aurantia, Aspergillus oryzae, Clitocybe nebularis, Marasmius oreades, Psathyrella velutina, Rhizopus stolonifer, Pholiota squarrosa, Polyporus squamosus), many of which are commercially available and their properties, sugar-binding specificities, structural grouping into families, and applications for biological research being described. The sialic acid-specific lectins (Agrocybe cylindracea and Polyporus squamosus) and fucose-specific lectins (Aleuria aurantia, Aspergillus oryzae, Rhizopus stolonifer, and Pholiota squarrosa) each showed potential for use in identifying sialic acid glycoconjugates and fucose glycoconjugates. Although not much is currently known about fungal lectins compared to animal and plant lectins, the knowledge accumulated thus far shows great promise for several applications in the fields of taxonomy, biomedicine, and molecular and cellular biology.

  10. Probing the effect of tip pressure on fungal growth: Application to Aspergillus nidulans

    NASA Astrophysics Data System (ADS)

    González-Bermúdez, Blanca; Li, Qingxuan; Guinea, Gustavo V.; Peñalva, Miguel A.; Plaza, Gustavo R.

    2017-08-01

    The study of fungal cells is of great interest due to their importance as pathogens and as fermenting fungi and for their appropriateness as model organisms. The differential pressure between the hyphal cytoplasm and the bordering medium is essential for the growth process, because the pressure is correlated with the growth rate. Notably, during the invasion of tissues, the external pressure at the tip of the hypha may be different from the pressure in the surrounding medium. We report the use of a method, based on the micropipette-aspiration technique, to study the influence of this external pressure at the hyphal tip. Moreover, this technique makes it possible to study hyphal growth mechanics in the case of very thin hyphae, not accessible to turgor pressure probes. We found a correlation between the local pressure at the tip and the growth rate for the species Arpergillus nidulans. Importantly, the proposed method allows one to measure the pressure at the tip required to arrest the hyphal growth. Determining that pressure could be useful to develop new medical treatments for fungal infections. Finally, we provide a mechanical model for these experiments, taking into account the cytoplasm flow and the wall deformation.

  11. Prediction of invasion from the early stage of an epidemic

    PubMed Central

    Pérez-Reche, Francisco J.; Neri, Franco M.; Taraskin, Sergei N.; Gilligan, Christopher A.

    2012-01-01

    Predictability of undesired events is a question of great interest in many scientific disciplines including seismology, economy and epidemiology. Here, we focus on the predictability of invasion of a broad class of epidemics caused by diseases that lead to permanent immunity of infected hosts after recovery or death. We approach the problem from the perspective of the science of complexity by proposing and testing several strategies for the estimation of important characteristics of epidemics, such as the probability of invasion. Our results suggest that parsimonious approximate methodologies may lead to the most reliable and robust predictions. The proposed methodologies are first applied to analysis of experimentally observed epidemics: invasion of the fungal plant pathogen Rhizoctonia solani in replicated host microcosms. We then consider numerical experiments of the susceptible–infected–removed model to investigate the performance of the proposed methods in further detail. The suggested framework can be used as a valuable tool for quick assessment of epidemic threat at the stage when epidemics only start developing. Moreover, our work amplifies the significance of the small-scale and finite-time microcosm realizations of epidemics revealing their predictive power. PMID:22513723

  12. Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral Renal Fungal Ball

    PubMed Central

    Shukla, Abhishek; Shrivastava, Nitin; Singh, Chirom Amit

    2016-01-01

    Abstract Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi of the class Zygomycetes. The majority of human cases are caused by Mucorales (genus—rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently negative. Case Presentation: A twenty-one-year-old young unmarried lady presented to our emergency department with bilateral flank pain, fever, nausea, and decreased urine output of one-month duration. She was found to have azotemia with sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone. Even after nephrostomy drainage and broad spectrum antibiotics, her condition worsened. She developed disseminated fungal infection, and timely systemic antifungal followed by bilateral nephroscopic clearance saved the patient. Conclusion: Although renal fungal infections are uncommon, a high index of suspicion and early antifungal and surgical intervention can give favorable outcomes. PMID:27704055

  13. Invasive and noninvasive hemodynamic monitoring of patients with cerebrovascular accidents.

    PubMed Central

    Velmahos, G C; Wo, C C; Demetriades, D; Bishop, M H; Shoemaker, W C

    1998-01-01

    Seventeen patients with hemodynamic instability from acute cerebrovascular accidents were evaluated shortly after arrival at the emergency department of a university-run county hospital with both invasive Swan-Ganz pulmonary artery catheter placement and a new, noninvasive, thoracic electrical bioimpedance device. Values were recorded and temporal patterns of survivors and nonsurvivors were described. Cardiac indices obtained simultaneously by the 2 techniques were compared. Of the 17 patients, 11 (65%) died. Survivors had higher values than nonsurvivors for mean arterial pressure, cardiac index, and oxygen saturation, delivery, and consumption at comparable times. Cardiac index values, as measured by invasive and noninvasive methods, were correlated. We concluded that hemodynamic monitoring in an acute care setting may recognize temporal circulatory patterns associated with outcome. Noninvasive electrical bioimpedance technology offers a new method for early hemodynamic evaluation. Further research in this area is warranted. PMID:9682626

  14. [Localized invasive intracranial aspergillosis with multiple cranial nerve failure -- case report and review of the literature].

    PubMed

    Winkler, F; Seelos, K; Hempel, J M; Pfister, H-W

    2002-12-01

    Contrary to the more frequent hematogenously spread cerebral aspergillosis, localized invasive intracranial aspergillosis is a fungal infection that can also occur in patients who are not severely immunosuppressed. This illness can be effectively treated in some of these patients by early and rigorous therapy. Localized invasion of the fungus, generally from one of the nasal sinuses, causes intracranial growth mainly along the base of the skull and larger vessels,where fibrous, granulomatous tissue develops. This generally leads to damage of the cranial nerves (primarily I-VI) as well as localized pain syndromes. We report on the clinical course documented by MRI of a patient with localized invasive intracranial aspergillosis who had multiple failure of cranial nerves following surgery for an aspergilloma of the maxillary sinus. Clinical course, imaging findings, and treatment of the illness are discussed with a review of the relevant literature.

  15. Fungal arthritis

    MedlinePlus

    ... examine you. Tests that may be ordered include: Culture of joint fluid that grows fungus Joint x-ray showing joint changes Positive antibody test (serology) for fungal disease Synovial biopsy showing fungus

  16. Oral Bacterial and Fungal Microbiome Impacts Colorectal Carcinogenesis.

    PubMed

    Klimesova, Klara; Jiraskova Zakostelska, Zuzana; Tlaskalova-Hogenova, Helena

    2018-01-01

    Host's physiology is significantly influenced by microbiota colonizing the epithelial surfaces. Complex microbial communities contribute to proper mucosal barrier function, immune response, and prevention of pathogen invasion and have many other crucial functions. The oral cavity and large intestine are distant parts of the digestive tract, both heavily colonized by commensal microbiota. Nevertheless, they feature different proportions of major bacterial and fungal phyla, mostly due to distinct epithelial layers organization and different oxygen levels. A few obligate anaerobic strains inhabiting the oral cavity are involved in the pathogenesis of oral diseases. Interestingly, these microbiota components are also enriched in gut inflammatory and tumor tissue. An altered microbiota composition - dysbiosis - and formation of polymicrobial biofilms seem to play important roles in the development of oral diseases and colorectal cancer. In this review, we describe the differences in composition of commensal microbiota in the oral cavity and large intestine and the mechanisms by which microbiota affect the inflammatory and carcinogenic response of the host.

  17. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision

    PubMed Central

    Bansal, Aditya; Bhama, Jay K.; Patel, Rajan; Desai, Sapna; Mandras, Stacy A.; Patel, Hamang; Collins, Tyrone; Reilly, John P.; Ventura, Hector O.; Parrino, P. Eugene

    2016-01-01

    Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Conclusion

  18. The effects of climate change on fungal diversity patterns in the UK and Greece: Contrasting trends and ecological interpretations

    NASA Astrophysics Data System (ADS)

    Damialis, A.; Gange, A. C.; Mohammad, A. B.; Halley, J. M.

    2013-05-01

    It is well known that climate change has been affecting the ecology of living organisms. However, very little research has been done concerning alterations in fungal ecology. The changes in climate are expected to have an impact on fungal biodiversity patterns. Such changes in turn might have implications for public health since the spores of certain fungal taxa (e.g. Alternaria, Cladosporium) cause respiratory problems in sensitised individuals, with symptoms manifested even as acute respiratory failure. The objectives of this study were: a) to perform a comprehensive analysis of trends in long-term time series of fungal fruiting and sporulation variables for a wide range of fungal taxa, b) to investigate the response of fungal abundance and diversity to environmental variability. Data from two different geoclimatic areas were used: a) England, UK from more than 350 fungal species belonging to 10 different functional groups and with phenological records of fungal fruiting (start, end and duration) since 1950, b) Thessaloniki, Greece for 14 airborne fungal types with quantitative records (total annual concentration) and phenological records (start, peak, end, duration) of the atmospheric spore season since 1987. In parallel, various meteorological factors were examined in both areas in order to elucidate the relationship between climate and fungal diversity patterns. Long-term trends were found in most cases: these were particularly pronounced in the UK, where more than 300 species (~82%) displayed trends. Of these, ~77% were towards an earlier beginning and ~81% towards a later ending of the fruiting season; overall, an extension of the fruiting season seems to occur in more than 200 species. On a per-functional-group basis, except for manure, soil and mycorrhizal deciduous fungal species, all the other (137 species) exhibited earlier first fruiting dates and extended seasons. On the other hand, in Greece, although a tendency was observed towards lower yearly

  19. Fueling the Future with Fungal Genomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigoriev, Igor V.

    2014-10-27

    Genomes of fungi relevant to energy and environment are in focus of the JGI Fungal Genomic Program. One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts and pathogens) and biorefinery processes (cellulose degradation and sugar fermentation) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Science Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 400 fungal genomes have beenmore » sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics will lead to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such ‘parts’ suggested by comparative genomics and functional analysis in these areas are presented here.« less

  20. Grassland invaders and their mycorrhizal symbionts: a study across climate and invasion gradients

    PubMed Central

    Bunn, Rebecca A; Lekberg, Ylva; Gallagher, Christopher; Rosendahl, Søren; Ramsey, Philip W

    2014-01-01

    Controlled experiments show that arbuscular mycorrhizal fungi (AMF) can increase competitiveness of exotic plants, potentially increasing invasion success. We surveyed AMF abundance and community composition in Centaurea stoebe and Potentilla recta invasions in the western USA to assess whether patterns were consistent with mycorrhizal-mediated invasions. We asked whether (1) AMF abundance and community composition differ between native and exotic forbs, (2) associations between native plants and AMF shift with invading exotic plants, and (3) AMF abundance and/or community composition differ in areas where exotic plants are highly invasive and in areas where they are not. We collected soil and roots from invaded and native forb communities along invasion gradients and in regions with different invasion densities. We used AMF root colonization as a measure of AMF abundance and characterized AMF communities in roots using 454-sequencing of the LSU-rDNA region. All plants were highly colonized (>60%), but exotic forbs tended to be more colonized than natives (P < 0.001). We identified 30 AMF operational taxonomic units (OTUs) across sites, and community composition was best predicted by abiotic factors (soil texture, pH). Two OTUs in the genera Glomus and Rhizophagus dominated in most communities, and their dominance increased with invasion density (r = 0.57, P = 0.010), while overall OTU richness decreased with invasion density (r = −0.61, P = 0.006). Samples along P. recta invasion gradients revealed small and reciprocal shifts in AMF communities with >45% fungal OTUs shared between neighboring native and P. recta plants. Overall, we observed significant, but modest, differences in AMF colonization and communities between co-occurring exotic and native forbs and among exotic forbs across regions that differ in invasion pressure. While experimental manipulations are required to assess functional consequences, the observed patterns are not consistent with those

  1. Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002–20121

    PubMed Central

    Strollo, Sara; Lionakis, Michail S.; Adjemian, Jennifer; Steiner, Claudia A.

    2017-01-01

    Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis–associated hospitalizations in the United States. We extracted data for 33 states for 2002–2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005–2012 for men (annual change –3.9%) and women (annual change –4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease. PMID:27983497

  2. Sentinel trees as a tool to forecast invasions of alien plant pathogens.

    PubMed

    Vettraino, AnnaMaria; Roques, Alain; Yart, Annie; Fan, Jian-ting; Sun, Jiang-hua; Vannini, Andrea

    2015-01-01

    Recent disease outbreaks caused by alien invasive pathogens into European forests posed a serious threat to forest sustainability with relevant environmental and economic effects. Many of the alien tree pathogens recently introduced into Europe were not previously included on any quarantine lists, thus they were not subject to phytosanitary inspections. The identification and description of alien fungi potentially pathogenic to native European flora before their introduction in Europe, is a paramount need in order to limit the risk of invasion and the impact to forest ecosystems. To determine the potential invasive fungi, a sentinel trees plot was established in Fuyang, China, using healthy seedlings of European tree species including Quercus petreae, Q. suber, and Q. ilex. The fungal assemblage associated with symptomatic specimens was studied using the tag-encoded 454 pyrosequencing of the nuclear ribosomal internal transcribed spacer-1 (ITS 1). Taxa with probable Asiatic origin were identified and included plant pathogenic genera. These results indicate that sentinel plants may be a strategic tool to improve the prevention of bioinvasions.

  3. Sentinel Trees as a Tool to Forecast Invasions of Alien Plant Pathogens

    PubMed Central

    Vettraino, AnnaMaria; Roques, Alain; Yart, Annie; Fan, Jian-ting; Sun, Jiang-hua; Vannini, Andrea

    2015-01-01

    Recent disease outbreaks caused by alien invasive pathogens into European forests posed a serious threat to forest sustainability with relevant environmental and economic effects. Many of the alien tree pathogens recently introduced into Europe were not previously included on any quarantine lists, thus they were not subject to phytosanitary inspections. The identification and description of alien fungi potentially pathogenic to native European flora before their introduction in Europe, is a paramount need in order to limit the risk of invasion and the impact to forest ecosystems. To determine the potential invasive fungi, a sentinel trees plot was established in Fuyang, China, using healthy seedlings of European tree species including Quercus petreae, Q. suber, and Q. ilex. The fungal assemblage associated with symptomatic specimens was studied using the tag-encoded 454 pyrosequencing of the nuclear ribosomal internal transcribed spacer-1 (ITS 1). Taxa with probable Asiatic origin were identified and included plant pathogenic genera. These results indicate that sentinel plants may be a strategic tool to improve the prevention of bioinvasions. PMID:25826684

  4. Fungal Tests

    MedlinePlus

    ... preparation is needed. See More See Less Accordion Title Common Questions How is it used? Fungal tests ... involving skin, nails, or mucous membranes appear, for example: Itchy, red, scaly areas of skin Nails that ...

  5. Invasive candidiasis: future directions in non-culture based diagnosis.

    PubMed

    Posch, Wilfried; Heimdörfer, David; Wilflingseder, Doris; Lass-Flörl, Cornelia

    2017-09-01

    Delayed initial antifungal therapy is associated with high mortality rates caused by invasive candida infections, since accurate detection of the opportunistic pathogenic yeast and its identification display a diagnostic challenge. diagnosis of candida infections relies on time-consuming methods such as blood cultures, serologic and histopathologic examination. to allow for fast detection and characterization of invasive candidiasis, there is a need to improve diagnostic tools. trends in diagnostics switch to non-culture-based methods, which allow specified diagnosis within significantly shorter periods of time in order to provide early and appropriate antifungal treatment. Areas covered: within this review comprise novel pathogen- and host-related testing methods, e.g. multiplex-PCR analyses, T2 magnetic resonance, fungus-specific DNA microarrays, microRNA characterization or analyses of IL-17 as biomarker for early detection of invasive candidiasis. Expert commentary: Early recognition and diagnosis of fungal infections is a key issue for improved patient management. As shown in this review, a broad range of novel molecular based tests for the detection and identification of Candida species is available. However, several assays are in-house assays and lack standardization, clinical validation as well as data on sensitivity and specificity. This underscores the need for the development of faster and more accurate diagnostic tests.

  6. Human Fungal Pathogens of Mucorales and Entomophthorales.

    PubMed

    Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S; Voigt, Kerstin; Lee, Soo Chan

    2014-11-06

    In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term "zygomycosis" is often used as a synonym for "mucormycosis." In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are monophyletic. Thus, the term "zygomycosis" needed to be further specified, resulting in the terms "mucormycosis" and "entomophthoramycosis." This review covers these two different types of fungal infections. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Human Fungal Pathogens of Mucorales and Entomophthorales

    PubMed Central

    Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S.; Voigt, Kerstin; Lee, Soo Chan

    2015-01-01

    In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term “zygomycosis” is often used as a synonym for “mucormycosis.” In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are monophyletic. Thus, the term “zygomycosis” needed to be further specified, resulting in the terms “mucormycosis” and “entomophthoramycosis.” This review covers these two different types of fungal infections. PMID:25377138

  8. Viability of fungal and actinomycetal spores after microwave radiation of building materials.

    PubMed

    Górny, Rafał L; Mainelis, Gediminas; Wlazło, Agnieszka; Niesler, Anna; Lis, Danuta O; Marzec, Stanisław; Siwińska, Ewa; Łudzeń-Izbińska, Beata; Harkawy, Aleksander; Kasznia-Kocot, Joanna

    2007-01-01

    The effects of microwave radiation on viability of fungal and actinomycetal spores growing on agar (medium optimal for growth) as well as on wooden panel and drywall (common building construction/finishing materials) were studied. All materials were incubated at high (97-99%) and low (32-33%) relative humidity to mimic "wet" and "dry" environmental conditions. Two microwave power densities (10 and 60 mW/cm2) and three times of exposure (5, 30, and 60 min) were tested to find the most effective parameters of radiation which could be applied to non-invasive reduction or cleaning of building materials from microbial contaminants. Additionally, a control of the surface temperature during the experiments allowed differentiation between thermal and microwave effect of such radiation. The results showed that the viability of studied microorganisms differed depending on their strains, growth conditions, power density of microwave radiation, time of exposure, and varied according to the applied combination of the two latter elements. The effect of radiation resulting in a decrease of spore viability on "wet" wooden panel and drywall was generally observed at 60 min exposure. Shorter exposure times decreased the viability of fungal spores only, while in actinomycetes colonizing the studied building materials, such radiation caused an opposite (supporting growth) effect.

  9. Invasive tracheobronchial aspergillosis in a patient with systemic lupus erythematosus-dermatomyositis overlap syndrome.

    PubMed

    Sada, Mitsuru; Saraya, Takeshi; Tanaka, Yasutaka; Sato, Shinji; Wakayama, Megumi; Shibuya, Kazutoshi; Uchiyama, Takashi; Ogata, Hideo; Takizawa, Hajime; Goto, Hajime

    2013-01-01

    A 45-year-old man was referred to our hospital with a 3-month history of dyspnea, polyarthralgia, myalgia and weight loss. He was diagnosed with systemic lupus erythematosus/dermatomyositis overlap syndrome with lung involvement, which presented as organizing pneumonia. However, a bronchoscopic examination revealed the presence of multiple plaque-like white lesions with ulcers on the bronchial membrane, located mainly in the central airway. The pathological specimens obtained from bronchoscopy showed numerous filamentous fungal hyphae that were aggressively invading the bronchial walls, suggesting a diagnosis of invasive tracheobronchial aspergillosis. The present case, along with a review of the literature, demonstrates that invasive tracheobronchial aspergillosis can occur in patients who do not appear to be immunosuppressed. This case of aspergillosis should thus be recognized as an extremely rare presentation of an Aspergillus infection.

  10. SERUM metabolomics of acute lymphoblastic leukaemia and acute myeloid leukaemia for probing biomarker molecules.

    PubMed

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Naz, Arshi

    2017-12-01

    Acute leukaemia (AL) is a critical neoplasm of white blood cells. Diagnosing AL requires bone marrow puncture procedure, which many patients do not consent to for it is invasive. Hence sensitive and specific early diagnostic biomarkers are essential for non-invasive diagnosis, new therapeutics and improving the disease prognosis. To differentiate the metabolic alterations associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), we investigated serum of ALL and AML patients in comparison with two controls using gas chromatography coupled with triple quadrupole tandem mass spectrometry and multivariate statistical analysis. Twenty seven out of 1425 metabolites were found differentiative among ALL, AML, aplastic anaemia (APA) patients and healthy control using p-value ≤ 0.001. ALL is the most dissimilar group from other three groups as in hierarchical clustering showed 72.1% dissimilarity. Model generation using PLSDA gave an overall accuracy of 91.9%. This study helps in metabolic fingerprinting of control and disease serum at high significance levels and could be used for early diagnosing of AL. Based on pathways analysis, fatty acid metabolism is deregulated in patients with AL and may represent an underlying metabolic pathway associated with disease progression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Skin temperature reveals the intensity of acute stress

    PubMed Central

    Herborn, Katherine A.; Graves, James L.; Jerem, Paul; Evans, Neil P.; Nager, Ruedi; McCafferty, Dominic J.; McKeegan, Dorothy E.F.

    2015-01-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. PMID:26434785

  12. New subfamilies of major intrinsic proteins in fungi suggest novel transport properties in fungal channels: implications for the host-fungal interactions

    PubMed Central

    2014-01-01

    Background Aquaporins (AQPs) and aquaglyceroporins (AQGPs) belong to the superfamily of Major Intrinsic Proteins (MIPs) and are involved in the transport of water and neutral solutes across the membranes. MIP channels play significant role in plant-fungi symbiotic relationship and are believed to be important in host-pathogen interactions in human fungal diseases. In plants, at least five major MIP subfamilies have been identified. Fungal MIP subfamilies include orthodox aquaporins and five subgroups within aquaglyceroporins. XIP subfamily is common to both plants and fungi. In this study, we have investigated the extent of diversity in fungal MIPs and explored further evolutionary relationships with the plant MIP counterparts. Results We have extensively analyzed the available fungal genomes and examined nearly 400 fungal MIPs. Phylogenetic analysis and homology modeling exhibit the existence of a new MIP cluster distinct from any of the known fungal MIP subfamilies. All members of this cluster are found in microsporidia which are unicellular fungal parasites. Members of this family are small in size, charged and have hydrophobic residues in the aromatic/arginine selectivity filter and these features are shared by small and basic intrinsic proteins (SIPs), one of the plant MIP subfamilies. We have also found two new subfamilies (δ and γ2) within the AQGP group. Fungal AQGPs are the most diverse and possess the largest number of subgroups. We have also identified distinguishing features in loops E and D in the newly identified subfamilies indicating their possible role in channel transport and gating. Conclusions Fungal SIP-like MIP family is distinct from any of the known fungal MIP families including orthodox aquaporins and aquaglyceroporins. After XIPs, this is the second MIP subfamily from fungi that may have possible evolutionary link with a plant MIP subfamily. AQGPs in fungi are more diverse and possess the largest number of subgroups. The aromatic

  13. Development of acute parotitis after non-invasive ventilation

    PubMed Central

    Martinez, Eduardo

    2017-01-01

    A 90-year-old woman underwent laparoscopic exploratory laparotomy for evaluation of suspected mesenteric ischemia. She was promptly extubated postoperatively and transferred to the intensive care unit, where on the first postoperative day she developed hypoxemia necessitating initiation of noninvasive ventilation (NIV) with bilevel positive airway pressure (BiPAP). After 8 hours of BiPAP, she was noted to have swelling, erythema and tenderness in the right preauricular area. Ultrasound evaluation demonstrated an enlarged right parotid gland. With discontinuation of BiPAP and supportive measures, parotitis resolved within 6 days. The mechanism of NIV-induced acute parotitis likely involves transmission of positive pressure to the oral cavity, causing obstruction to salivary flow within the parotid (Stensen) duct. Conditions that increase salivary viscosity and promote salivary stasis, such as advanced age, dehydration, and absence of salivary gland stimulation due to restriction of oral intake, may render patients more susceptible to this complication. As NIV will continue to be a commonly-used modality for the treatment of acute respiratory failure, clinicians should be aware of this phenomenon. PMID:28840025

  14. Fungal genome sequencing: basic biology to biotechnology.

    PubMed

    Sharma, Krishna Kant

    2016-08-01

    The genome sequences provide a first glimpse into the genomic basis of the biological diversity of filamentous fungi and yeast. The genome sequence of the budding yeast, Saccharomyces cerevisiae, with a small genome size, unicellular growth, and rich history of genetic and molecular analyses was a milestone of early genomics in the 1990s. The subsequent completion of fission yeast, Schizosaccharomyces pombe and genetic model, Neurospora crassa initiated a revolution in the genomics of the fungal kingdom. In due course of time, a substantial number of fungal genomes have been sequenced and publicly released, representing the widest sampling of genomes from any eukaryotic kingdom. An ambitious genome-sequencing program provides a wealth of data on metabolic diversity within the fungal kingdom, thereby enhancing research into medical science, agriculture science, ecology, bioremediation, bioenergy, and the biotechnology industry. Fungal genomics have higher potential to positively affect human health, environmental health, and the planet's stored energy. With a significant increase in sequenced fungal genomes, the known diversity of genes encoding organic acids, antibiotics, enzymes, and their pathways has increased exponentially. Currently, over a hundred fungal genome sequences are publicly available; however, no inclusive review has been published. This review is an initiative to address the significance of the fungal genome-sequencing program and provides the road map for basic and applied research.

  15. Fungal infections and treatment in cystic fibrosis.

    PubMed

    Middleton, Peter G; Chen, Sharon C-A; Meyer, Wieland

    2013-11-01

    This review summarizes some of the important recent findings concerning fungal airway infections in patients with cystic fibrosis (CF). For many years, both researchers and clinicians have focused on the problems in CF caused by chronic bacterial airway infection with organisms such as Haemophilus, Staphylococcus and Pseudomonas. However, until recently, the lack of sensitive culture techniques to isolate fungi in sputum, bronchoalveolar lavage fluid and other respiratory tract samples has limited the recognition of fungal species and their possible role in CF airway infections. Recent studies using fungal-selective culture media and molecular techniques have shown a plethora of different fungal species in the sputum expectorated from CF patients. Cross-sectional studies have shown associations between Aspergillus and Candida in the sputum and worse lung function. The presence of allergic bronchopulmonary aspergillosis is likely to be a negative prognostic factor, but whether simple fungal colonization itself indicates future problems is not clear. Current research is now examining these epidemiological associations to try to determine the clinical implications. This will help determine whether fungal colonization/infection is associated with worse outcome in CF patients. At present, there is no conclusive evidence that fungal organisms cause respiratory decline. Recent studies of antifungal therapy in CF patients have reported differing results, so further investigations in this area are needed.

  16. Red turpentine beetle: innocuous native becomes invasive tree killer in China.

    PubMed

    Sun, Jianghua; Lu, Min; Gillette, Nancy E; Wingfield, Michael J

    2013-01-01

    The red turpentine beetle (RTB), Dendroctonus valens LeConte (Coleoptera: Curculionidae: Scolytinae), is a secondary pest of pines in its native range in North and Central America. Outbreaks and tree mortality attributed to RTB alone are rare in its native range. RTB was introduced into China in the early 1980s and spread rapidly from Shanxi Province to four adjacent provinces; it has infested over 500,000 ha of pine forest and has caused extensive tree mortality since 1999. We provide a historical background on RTB outbreaks, explanations for its invasive success, management options, and economic impacts of RTB in China. Genetic variation in RTB fungal associates, interactions between RTB and its associated fungi, behavioral differences in Chinese RTB, and other factors favoring RTB outbreaks are considered in an effort to explain the invasiveness of RTB in China. The promise of semiochemicals as a management tool is also discussed.

  17. Respiratory training during rehabilitation of acute organic fluorine-poisoned patients treated by non-invasive positive pressure ventilation.

    PubMed

    Liu, L; Liu, D Z; Wang, Q P; Zhu, Z L; Li, H M; Lu, X Y

    2017-01-01

    This paper aimed to analyze the effects of respiratory training on pulmonary function during the rehabilitation period for acute organic fluorine-poisoned patients treated by non-invasive positive pressure ventilation (NIPPV). Sixty-two acute organic fluorine-poisoned patients admitted to the Xinxiang Central Hospital, Xinxiang City, China, from May 2012 to March 2016 were selected and randomly divided into an observation group and a control group, with 31 cases in each. Both groups received NIPPV. The patients in the control group exercised daily, while the patients in the observation group received contracting lips-abdominal breathing training. The therapeutic effects, pulmonary ventilation function, serum levels of α-antitrypsin1 (α-AT1), surfactant protein D (SP-D), neutrophil elastase (NE), transforming growth factor beta 1 (TGF-β1), and quality of life were analyzed and compared between the two groups both before and after the administration of treatment. The total effective rate of the observation group was 93.55%, which was significantly higher when compared with the control group (74.19%) (P less than 0.05). The levels of forced expiratory volume in one second (FEV1), FEV1/FVC ratio, vital capacity (VC), carbon monoxide diffusion capacity (DLco), and maximal voluntary ventilation (MVV) of the observation group were better when compared with the control group and had statistical significance (P less than 0.05). Before treatment, the serum levels of α-AT1, SP-D, NE, and TGF-β1, and quality of life had no statistical significance in either group (P>0.05); after treatment, these indexes and the quality of life for the observation group were significantly higher when compared with the control group, with statistical significance (P less than 0.05). The respiratory training in acute organic fluorine-poisoned patients treated by NIPPV can improve the serum indexes, dilute toxicity, and recover pulmonary function, which play key roles in improving the

  18. Fungal Endophytes: Beyond Herbivore Management

    PubMed Central

    Bamisile, Bamisope S.; Dash, Chandra K.; Akutse, Komivi S.; Keppanan, Ravindran; Wang, Liande

    2018-01-01

    The incorporation of entomopathogenic fungi as biocontrol agents into Integrated Pest Management (IPM) programs without doubt, has been highly effective. The ability of these fungal pathogens such as Beauveria bassiana and Metarhizium anisopliae to exist as endophytes in plants and protect their colonized host plants against the primary herbivore pests has widely been reported. Aside this sole role of pest management that has been traditionally ascribed to fungal endophytes, recent findings provided evidence of other possible functions as plant yield promoter, soil nutrient distributor, abiotic stress and drought tolerance enhancer in plants. However, reports on these additional important effects of fungal endophytes on the colonized plants remain scanty. In this review, we discussed the various beneficial effects of endophytic fungi on the host plants and their primary herbivore pests; as well as some negative effects that are relatively unknown. We also highlighted the prospects of our findings in further increasing the acceptance of fungal endophytes as an integral part of pest management programs for optimized crop production. PMID:29628919

  19. High-throughput sequencing-based analysis of endogenetic fungal communities inhabiting the Chinese Cordyceps reveals unexpectedly high fungal diversity

    PubMed Central

    Xia, Fei; Chen, Xin; Guo, Meng-Yuan; Bai, Xiao-Hui; Liu, Yan; Shen, Guang-Rong; Li, Yu-Ling; Lin, Juan; Zhou, Xuan-Wei

    2016-01-01

    Chinese Cordyceps, known in Chinese as “DongChong XiaCao”, is a parasitic complex of a fungus (Ophiocordyceps sinensis) and a caterpillar. The current study explored the endogenetic fungal communities inhabiting Chinese Cordyceps. Samples were collected from five different geographical regions of Qinghai and Tibet, and the nuclear ribosomal internal transcribed spacer-1 sequences from each sample were obtained using Illumina high-throughput sequencing. The results showed that Ascomycota was the dominant fungal phylum in Chinese Cordyceps and its soil microhabitat from different sampling regions. Among the Ascomycota, 65 genera were identified, and the abundant operational taxonomic units showed the strongest sequence similarity to Ophiocordyceps, Verticillium, Pseudallescheria, Candida and Ilyonectria Not surprisingly, the genus Ophiocordyceps was the largest among the fungal communities identified in the fruiting bodies and external mycelial cortices of Chinese Cordyceps. In addition, fungal communities in the soil microhabitats were clustered separately from the external mycelial cortices and fruiting bodies of Chinese Cordyceps from different sampling regions. There was no significant structural difference in the fungal communities between the fruiting bodies and external mycelial cortices of Chinese Cordyceps. This study revealed an unexpectedly high diversity of fungal communities inhabiting the Chinese Cordyceps and its microhabitats. PMID:27625176

  20. Fungal Genomics for Energy and Environment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigoriev, Igor V.

    2013-03-11

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Sequencing Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for usersmore » to nominate new species for sequencing. Over 200 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.« less

  1. Industrial Fungal Enzymes: An Occupational Allergen Perspective

    PubMed Central

    Green, Brett J.; Beezhold, Donald H.

    2011-01-01

    Occupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes. PMID:21747869

  2. Severe invasive listeriosis--case report.

    PubMed

    Teodor, Andra; Teodor, D; Miftode, Egidia; Prisăcaru, D; Leca, Daniela; Petrovici, Cristina; Dorneanu, Olivia; Dorobăt, Carmen-Mihaela

    2012-01-01

    Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

  3. Fungal Endocarditis: Update on Diagnosis and Management.

    PubMed

    Pasha, Ahmed Khurshid; Lee, Justin Z; Low, See-Wei; Desai, Hem; Lee, Kwan S; Al Mohajer, Mayar

    2016-10-01

    Fungal endocarditis is an extremely debilitating disease associated with high morbidity and mortality. Candida spp. are the most common isolated organisms in fungal endocarditis. It is most prevalent in patients who are immunosuppressed and intravenous drug users. Most patients present with constitutional symptoms, which are indistinguishable from bacterial endocarditis, hence a high index of suspicion is required for pursuing diagnosis. Diagnosis of fungal endocarditis can be very challenging: most of the time, blood cultures are negative or take a long time to yield growth. Fungal endocarditis mandates an aggressive treatment strategy. A medical and surgical combined approach is the cornerstone of therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Decolorization of different textile dyes by Penicillium simplicissimum and toxicity evaluation after fungal treatment

    PubMed Central

    Bergsten-Torralba, L.R.; Nishikawa, M.M.; Baptista, D.F.; Magalhães, D.P.; da Silva, M.

    2009-01-01

    The objective of this study was to investigate the capacity of decolorization and detoxification of the textile dyes Reactive Red 198 (RR198), Reactive Blue 214 (RB214), Reactive Blue 21 (RB21) and the mixture of the three dyes (MXD) by Penicillium simplicissimum INCQS 40211. The dye RB21, a phthalocyanine, was totally decolorized in 2 days, and the others, the monoazo RR198, the diazo RB214 and MXD were decolorized after 7 days by P. simplicissimum. Initially the dye decolorization involved dye adsorption by the biomass followed by degradation. The acute toxicity after fungal treatment was monitored with the microcrustacean Daphnia pulex and measured through Effective Concentration 50% (EC50). P. simplicissimum reduced efficiently the toxicity of RB21 from moderately acutely toxic to minor acutely toxic and it also reduced the toxicity of RB214 and MXD, which remained minor acutely toxic. Nevertheless, the fungus increased the toxicity of RR198 despite of the reduction of MXD toxicity, which included this dye. Thus, P. simplicissimum INCQS 40211 was efficient to decolorize different textile dyes and the mixture of them with a significant reduction of their toxicity. In addition this investigation also demonstrated the need of toxicological assays associated to decolorization experiments. PMID:24031428

  5. Towards a Cancer Drug of Fungal Origin

    PubMed Central

    Kornienko, Alexander; Evidente, Antonio; Vurro, Maurizio; Mathieu, Véronique; Cimmino, Alessio; Evidente, Marco; van Otterlo, Willem A. L.; Dasari, Ramesh; Lefranc, Florence; Kiss, Robert

    2015-01-01

    Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed and potential solutions that could be pursued by researchers are highlighted. PMID:25850821

  6. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

    PubMed Central

    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  7. A Comparison of Aspergillus and Mucorales PCR Testing of Different Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive Pulmonary Fungal Disease.

    PubMed

    Springer, Jan; White, P Lewis; Kessel, Johanna; Wieters, Imke; Teschner, Daniel; Korczynski, Daniel; Liebregts, Tobias; Cornely, Oliver A; Schwartz, Stefan; Elgeti, Thomas; Meintker, Lisa; Krause, Stefan W; Posso, Raquel B; Heinz, Werner J; Fuhrmann, Sandra; Vehreschild, Jörg Janne; Einsele, Hermann; Rickerts, Volker; Loeffler, Juergen

    2018-02-01

    In patients with hematological malignancies, bronchoalveolar lavage fluid (BALF) specimens are commonly used for the diagnosis of mold infections. However, it is not clear whether the cell pellet (P) or the supernatant fraction (S) of the BALF specimen is optimal for molecular diagnostic testing. Thus, 99 BALF specimens were collected from 96 hematology patients with or without allogeneic hematopoietic stem cell transplant. The cell pellets and supernatants were processed alone and in combination (S/P) for testing by two fungus-specific real-time PCR assays compliant with international recommendations. The results achieved with S/P were revealed to be superior in comparison to those achieved with S and P alone, with the use of each single fraction showing a reduced sensitivity for the detection of Aspergillus DNA (82% and 43% for S and P, respectively). In 57% of the samples, testing of the combination of S and P generated a lower quantification cycle value than testing of S or P alone. Molds would have been missed in 5 and 16 out of 28 samples if only S or P, respectively, was analyzed. No sample was positive by testing of S or P only. Similar results were obtained for the detection of Mucorales DNA in BALF specimens (reduced sensitivity of 67% and 50% for S and P, respectively). Study patients were categorized according to the current European Organization for the Research and Treatment of Cancer/Mycoses Study Group classification for invasive fungal disease (IFD), revealing that 35 patients had proven/probable IFD (36%), 47 patients had possible IFD (49%), and 14 patients had undetermined IFD (15%). Copyright © 2018 American Society for Microbiology.

  8. Air Contamination With Fungals In Museum

    NASA Astrophysics Data System (ADS)

    Scarlat, Iuliana; Haiducu, Maria; Stepa, Raluca

    2015-07-01

    The aim of the studies was to determine the level and kind of fungal contamination of air in museum, deposits patrimony, restoration and conservation laboratories and their effects on health of workers. Microbiological air purity was measured with a SAS-100 Surface Air System impactor. The fungal contamination was observed in all 54 rooms where we made determinations. The highest levels of fungal were recorded at rooms with hygroscopic patrimony objects, eg carpets, chairs, upholstered chairs, books etc. The most species identified included under common allergens: Aspergillus, Penicillium, and Mucor. There fungal species belonging to the genus identified in this study, can trigger serious diseases museum workers, such as for example Aspergillus fumigatus, known allergies and toxic effects that may occur. In some places of the museum, occupational exposure limit values to fungi present in the air in the work environment, recommended by the specialized literature, have been overcome.

  9. An alternative anionic bio-sustainable anti-fungal agent: Investigation of its mode of action on the fungal cell membrane.

    PubMed

    Stenbæk, Jonas; Löf, David; Falkman, Peter; Jensen, Bo; Cárdenas, Marité

    2017-07-01

    The potential of a lactylate (the sodium caproyl lactylate or C10 lactylate), a typical food grade emulsifier, as an anionic environmental friendly anti-fungal additive was tested in growth medium and formulated in a protective coating for exterior wood. Different laboratory growth tests on the blue stain fungus Aureobasidium pullulans were performed and its interactions on a model fungal cell membrane were studied. Promising short term anti-fungal effects in growth tests were observed, although significant but less dramatic effects took place in coating test on wood panels. Scanning electron microscope analysis shows clear differences in the amount of fungal slime on the mycelium of Aureobasidium pullulans when the fungus was exposed of C10 lactylate. This could indicate an effect on the pullulan and melanin production by the fungus. Moreover, the interaction studies on model fungal cell membranes show that C10 lactylate affects the phospholipid bilayer in a similar manner to other negative charged detergents. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22.

    PubMed

    Lilly, Lauren M; Gessner, Melissa A; Dunaway, Chad W; Metz, Allison E; Schwiebert, Lisa; Weaver, Casey T; Brown, Gordon D; Steele, Chad

    2012-10-01

    Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

  11. Fungal endophytes: modifiers of plant disease.

    PubMed

    Busby, Posy E; Ridout, Mary; Newcombe, George

    2016-04-01

    Many recent studies have demonstrated that non-pathogenic fungi within plant microbiomes, i.e., endophytes ("endo" = within, "phyte" = plant), can significantly modify the expression of host plant disease. The rapid pace of advancement in endophyte ecology warrants a pause to synthesize our understanding of endophyte disease modification and to discuss future research directions. We reviewed recent literature on fungal endophyte disease modification, and here report on several emergent themes: (1) Fungal endophyte effects on plant disease span the full spectrum from pathogen antagonism to pathogen facilitation, with pathogen antagonism most commonly reported. (2) Agricultural plant pathosystems are the focus of research on endophyte disease modification. (3) A taxonomically diverse group of fungal endophytes can influence plant disease severity. And (4) Fungal endophyte effects on plant disease severity are context-dependent. Our review highlights the importance of fungal endophytes for plant disease across a broad range of plant pathosystems, yet simultaneously reveals that complexity within plant microbiomes presents a significant challenge to disentangling the biotic environmental factors affecting plant disease severity. Manipulative studies integrating eco-evolutionary approaches with emerging molecular tools will be poised to elucidate the functional importance of endophytes in natural plant pathosystems that are fundamental to biodiversity and conservation.

  12. Burden of serious fungal infections in Guatemala.

    PubMed

    Medina, N; Samayoa, B; Lau-Bonilla, D; Denning, D W; Herrera, R; Mercado, D; Guzmán, B; Pérez, J C; Arathoon, E

    2017-06-01

    Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.

  13. Whole-cell fungal transformation of precursors into dyes

    PubMed Central

    2010-01-01

    Background Chemical methods of producing dyes involve extreme temperatures and unsafe toxic compounds. Application of oxidizing enzymes obtained from fungal species, for example laccase, is an alternative to chemical synthesis of dyes. Laccase can be replaced by fungal biomass acting as a whole-cell biocatalyst with properties comparable to the isolated form of the enzyme. The application of the whole-cell system simplifies the transformation process and reduces the time required for its completion. In the present work, four fungal strains with a well-known ability to produce laccase were tested for oxidation of 17 phenolic and non-phenolic precursors into stable and non-toxic dyes. Results An agar-plate screening test of the organic precursors was carried out using four fungal strains: Trametes versicolor, Fomes fomentarius, Abortiporus biennis, and Cerrena unicolor. Out of 17 precursors, nine were transformed into coloured substances in the presence of actively growing fungal mycelium. The immobilized fungal biomass catalyzed the transformation of 1 mM benzene and naphthalene derivatives in liquid cultures yielding stable and non-toxic products with good dyeing properties. The type of fungal strain had a large influence on the absorbance of the coloured products obtained after 48-hour transformation of the selected precursors, and the most effective was Fomes fomentarius (FF25). Whole-cell transformation of AHBS (3-amino-4-hydroxybenzenesulfonic acid) into a phenoxazinone dye was carried out in four different systems: in aqueous media comprising low amounts of carbon and nitrogen source, in buffer, and in distilled water. Conclusions This study demonstrated the ability of four fungal strains belonging to the ecological type of white rot fungi to transform precursors into dyes. This paper highlights the potential of fungal biomass for replacing isolated enzymes as a cheaper industrial-grade biocatalyst for the synthesis of dyes and other commercially important

  14. Neutrophil extracellular traps in fungal infection.

    PubMed

    Urban, Constantin F; Nett, Jeniel E

    2018-04-03

    Fungal infections are a continuously increasing problem in modern health care. Understanding the complex biology of the emerging pathogens and unraveling the mechanisms of host defense may form the basis for the development of more efficient diagnostic and therapeutic tools. Neutrophils play a pivotal role in the defense against fungal pathogens. These phagocytic hunters migrate towards invading fungal microorganisms and eradicate them by phagocytosis, oxidative burst and release of neutrophil extracellular traps (NETs). In the last decade, the process of NET formation has received unparalleled attention, with numerous studies revealing the relevance of this neutrophil function for control of various mycoses. Here, we describe NET formation and summarize its role as part of the innate immune defense against fungal pathogens. We highlight factors influencing the formation of these structures and molecular mechanisms employed by fungi to impair the formation of NETs or subvert their antifungal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Serpentine Soils Do Not Limit Mycorrhizal Fungal Diversity

    PubMed Central

    Branco, Sara; Ree, Richard H.

    2010-01-01

    Background Physiologically stressful environments tend to host depauperate and specialized biological communities. Serpentine soils exemplify this phenomenon by imposing well-known constraints on plants; however, their effect on other organisms is still poorly understood. Methodology/Principal Findings We used a combination of field and molecular approaches to test the hypothesis that serpentine fungal communities are species-poor and specialized. We conducted surveys of ectomycorrhizal fungal diversity from adjacent serpentine and non-serpentine sites, described fungal communities using nrDNA Internal Transcribed Spacer (ITS) fragment and sequence analyses, and compared their phylogenetic community structure. Although we detected low fungal overlap across the two habitats, we found serpentine soils to support rich fungal communities that include representatives from all major fungal lineages. We failed to detect the phylogenetic signature of endemic clades that would result from specialization and adaptive radiation within this habitat. Conclusions/Significance Our results indicate that serpentine soils do not constitute an extreme environment for ectomycorrhizal fungi, and raise important questions about the role of symbioses in edaphic tolerance and the maintenance of biodiversity. PMID:20668696

  16. Elimination of fungicides in biopurification systems: Effect of fungal bioaugmentation on removal performance and microbial community structure.

    PubMed

    Murillo-Zamora, Sergio; Castro-Gutiérrez, Víctor; Masís-Mora, Mario; Lizano-Fallas, Verónica; Rodríguez-Rodríguez, Carlos E

    2017-11-01

    Bioaugmentation with ligninolytic fungi represents a potential way to improve the performance of biomixtures used in biopurification systems for the treatment of pesticide-containing agricultural wastewater. The fungus Trametes versicolor was employed in the bioaugmentation of a biomixture to be used in the simultaneous removal of seven fungicides. Liquid cultures of the fungus were able to remove tebuconazole, while no evidence of carbendazim, metalaxyl and triadimenol depletion was found. When applied in the biomixture, the bioaugmented matrix failed to remove all the triazole fungicides (including tebuconazole) under the assayed conditions, but was efficient to eliminate carbendazim, edifenphos and metalaxyl (the latter only after a second pesticide application). The re-addition of pesticides markedly increased the elimination of carbendazim and metalaxyl; nonetheless, no clear enhancement of the biomixture performance could be ascribed to fungal bioaugmentation, not even after the re-inoculation of fungal biomass. Detoxification efficiently took place in the biomixture (9 d after pesticide applications) according to acute tests on Daphnia magna. DGGE-analysis revealed only moderate time-divergence in bacterial and fungal communities, and a weak establishment of T. versicolor in the matrix. Data suggest that the non-bioaugmented biomixture is useful for the treatment of fungicides other than triazoles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Fungal symbiosis unearthed

    Treesearch

    Daniel Cullen

    2008-01-01

    Associations between plant roots and fungi are a feature of many terrestrial ecosystems. The genome sequence of a prominent fungal partner opens new avenues for studying such mycorrhizal interactions....

  18. Skin temperature reveals the intensity of acute stress.

    PubMed

    Herborn, Katherine A; Graves, James L; Jerem, Paul; Evans, Neil P; Nager, Ruedi; McCafferty, Dominic J; McKeegan, Dorothy E F

    2015-12-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Page Kidney in Wunderlich Syndrome Causing Acute Renal Failure and Urosepsis: Successful Timely Minimally Invasive Management of a Devastating Clinical Entity.

    PubMed

    Vijayganapathy, Sundaramoorthy; Karthikeyan, Vilvapathy Senguttuvan; Mallya, Ashwin; Sreenivas, Jayaram

    2017-06-01

    Wunderlich Syndrome (WS) is an uncommon condition where acute onset of spontaneous bleeding occurs into the subcapsular and perirenal spaces. It can prove fatal if not recognized and treated aggressively at the appropriate time. A 32-year-old male diagnosed elsewhere as acute renal failure presented with tender left loin mass, fever and hypovolemic shock with serum creatinine 8.4 mg/dl. He was started on higher antibiotics and initiated on haemodialysis. Ultrasonogram (USG), Non-Contrast Computed Tomography (NCCT) and Magnetic Resonance Imaging (MRI) showed bilateral perirenal subcapsular haematomas - right 3.6 x 3.1 cm and left 10.3 x 10.3 cm compressing and displacing left kidney, fed by capsular branch of left renal artery on CT angiogram. Initial aspirate was bloody but he persisted to have febrile spikes, renal failure and urosepsis and he was managed conservatively. Repeat NCCT 10 days later revealed left perinephric abscess and Percutaneous Drainage (PCD) was done. Patient improved, serum creatinine stabilized at 2 mg/dl without haemodialysis and PCD was removed after two weeks. To conclude, bilateral idiopathic spontaneous retroperitoneal haemorrhage with renal failure is a rare presentation. This case highlights the need for high index of suspicion, the role of repeated imaging and successful minimally invasive management with timely PCD and supportive care.

  20. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans.

    PubMed

    Koch, Barbara; Tucey, Timothy M; Lo, Tricia L; Novakovic, Stevan; Boag, Peter; Traven, Ana

    2017-01-01

    The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae , the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans . There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1 Δ / Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1 Δ / Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1 Δ / Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans . We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing

  1. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

    PubMed Central

    Koch, Barbara; Tucey, Timothy M.; Lo, Tricia L.; Novakovic, Stevan; Boag, Peter; Traven, Ana

    2017-01-01

    The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1Δ/Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1Δ/Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1Δ/Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans. We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing Network

  2. Untangling the fungal niche: the trait-based approach.

    PubMed

    Crowther, Thomas W; Maynard, Daniel S; Crowther, Terence R; Peccia, Jordan; Smith, Jeffrey R; Bradford, Mark A

    2014-01-01

    Fungi are prominent components of most terrestrial ecosystems, both in terms of biomass and ecosystem functioning, but the hyper-diverse nature of most communities has obscured the search for unifying principles governing community organization. In particular, unlike plants and animals, observational studies provide little evidence for the existence of niche processes in structuring fungal communities at broad spatial scales. This limits our capacity to predict how communities, and their functioning, vary across landscapes. We outline how a shift in focus, from taxonomy toward functional traits, might prove to be valuable in the search for general patterns in fungal ecology. We build on theoretical advances in plant and animal ecology to provide an empirical framework for a trait-based approach in fungal community ecology. Drawing upon specific characteristics of the fungal system, we highlight the significance of drought stress and combat in structuring free-living fungal communities. We propose a conceptual model to formalize how trade-offs between stress-tolerance and combative dominance are likely to organize communities across environmental gradients. Given that the survival of a fungus in a given environment is contingent on its ability to tolerate antagonistic competitors, measuring variation in combat trait expression along environmental gradients provides a means of elucidating realized, from fundamental niche spaces. We conclude that, using a trait-based understanding of how niche processes structure fungal communities across time and space, we can ultimately link communities with ecosystem functioning. Our trait-based framework highlights fundamental uncertainties that require testing in the fungal system, given their potential to uncover general mechanisms in fungal ecology.

  3. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed Central

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

  4. POSSIBLE ROLE OF FUNGAL HEMOLYSINS IN SICK BUILDING SYNDROME

    EPA Science Inventory

    Many fungi produce proteinaceous hemolytic agents. Like bacterial hemolysins, fungal hemolysins create pores or holes in membranes. Depending on which membranes are damaged, fungal hemolysins can produce a variety of effects. Fungal hemolysins can cause histamine release from ...

  5. Sorting of fungal-damaged white sorghum

    USDA-ARS?s Scientific Manuscript database

    A high-speed, color image-based sorting machine was modified to separate white sorghum with symptoms of fungal damage. Most of the sorghum tested was typically white, but over 27% of the bulk contained grains with fungal damage of various degrees, from severe to very slight. Grains with slight fun...

  6. Developments in Fungal Taxonomy

    PubMed Central

    Guarro, Josep; Gené, Josepa; Stchigel, Alberto M.

    1999-01-01

    Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales). PMID:10398676

  7. Fungal and Bacterial Pigments: Secondary Metabolites with Wide Applications

    PubMed Central

    Narsing Rao, Manik Prabhu; Xiao, Min; Li, Wen-Jun

    2017-01-01

    The demand for natural colors is increasing day by day due to harmful effects of some synthetic dyes. Bacterial and fungal pigments provide a readily available alternative source of naturally derived pigments. In contrast to other natural pigments, they have enormous advantages including rapid growth, easy processing, and independence of weather conditions. Apart from colorant, bacterial and fungal pigments possess many biological properties such as antioxidant, antimicrobial and anticancer activity. This review outlines different types of pigments. It lists some bacterial and fungal pigments and current bacterial and fungal pigment status and challenges. It also focuses on possible fungal and bacterial pigment applications. PMID:28690593

  8. Immune Recognition of Fungal Polysaccharides.

    PubMed

    Snarr, Brendan D; Qureshi, Salman T; Sheppard, Donald C

    2017-08-28

    The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal drugs, and rising resistance to these agents has led to interest in the development of novel preventative and therapeutic strategies targeting these devastating infections. One approach to combat fungal infections is to augment the host immune response towards these organisms. The polysaccharide-rich cell wall is the initial point of contact between fungi and the host immune system, and therefore, represents an important target for immunotherapeutic approaches. This review highlights the advances made in our understanding of the mechanisms by which the immune system recognizes and interacts with exopolysaccharides produced by four of the most common fungal pathogens: Aspergillus fumigatus , Candida albicans , Cryptococcus neoformans , and Histoplasma capsulatum . Work to date suggests that inner cell wall polysaccharides that play an important structural role are the most conserved across diverse members of the fungal kingdom, and elicit the strongest innate immune responses. The immune system senses these carbohydrates through receptors, such as lectins and complement proteins. In contrast, a greater diversity of polysaccharides is found within the outer cell walls of pathogenic fungi. These glycans play an important role in immune evasion, and can even induce anti-inflammatory host responses. Further study of the complex interactions between the host immune system and the fungal polysaccharides will be necessary to develop more effective therapeutic strategies, as well as to explore the use of immunosuppressive polysaccharides as therapeutic agents to modulate inflammation.

  9. Hospital variability in use of anticoagulant strategies during acute myocardial infarction treated with an early invasive strategy.

    PubMed

    Arnold, Suzanne V; Li, Shu-Xia; Alexander, Karen P; Spertus, John A; Nallamothu, Brahmajee K; Curtis, Jeptha P; Kosiborod, Mikhail; Gupta, Aakriti; Wang, Tracy Y; Lin, Haiqun; Dharmarajan, Kumar; Strait, Kelly M; Lowe, Timothy J; Krumholz, Harlan M

    2015-06-15

    During a myocardial infarction, no single best approach of systemic anticoagulation is recommended, likely due to a lack of comparative effectiveness studies and trade-offs between treatments. We investigated the patterns of use and site-level variability in anticoagulant strategies (unfractionated heparin [UFH] only, low-molecular-weight heparin [LMWH] only, UFH+LMWH, any bivalirudin) of 63 796 patients with a principal diagnosis of myocardial infarction treated with an early invasive strategy with percutaneous coronary intervention at 257 hospitals. About half (47%) of patients received UFH only, 6% UFH+LMWH, 7% LMWH only, and 40% bivalirudin. Compared with UFH, the median odds ratio was 2.90 for LMWH+UFH, 4.70 for LMWH only, and 3.09 for bivalirudin, indicating that 2 "identical" patients would have a 3- to 4-fold greater likelihood of being treated with anticoagulants other than UFH at one hospital compared with another. We then categorized hospitals as low- or high-users of LMWH and bivalirudin. Using hierarchical, multivariate regression models, we found that low bivalirudin-using hospitals had higher unadjusted bleeding rates, but the risk-adjusted and anticoagulant-adjusted bleeding rates did not differ across the hospital anticoagulation phenotypes. Risk-standardized mortality and risk-standardized length of stay also did not differ across hospital phenotypes. We found substantial site-level variability in the choice of anticoagulants for invasively managed acute myocardial infarction patients, even after accounting for patient factors. No single hospital-use pattern was found to be clinically superior. More studies are needed to determine which patients would derive the greatest benefit from various anticoagulants and to support consistent treatment of patients with the optimal anticoagulant strategy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. The Interface between Fungal Biofilms and Innate Immunity.

    PubMed

    Kernien, John F; Snarr, Brendan D; Sheppard, Donald C; Nett, Jeniel E

    2017-01-01

    Fungal biofilms are communities of adherent cells surrounded by an extracellular matrix. These biofilms are commonly found during infection caused by a variety of fungal pathogens. Clinically, biofilm infections can be extremely difficult to eradicate due to their resistance to antifungals and host defenses. Biofilm formation can protect fungal pathogens from many aspects of the innate immune system, including killing by neutrophils and monocytes. Altered immune recognition during this phase of growth is also evident by changes in the cytokine profiles of monocytes and macrophages exposed to biofilm. In this manuscript, we review the host response to fungal biofilms, focusing on how these structures are recognized by the innate immune system. Biofilms formed by Candida, Aspergillus , and Cryptococcus have received the most attention and are highlighted. We describe common themes involved in the resilience of fungal biofilms to host immunity and give examples of biofilm defenses that are pathogen-specific.

  11. Molecular Identification of Fungal Contamination in Date Palm Tissue Cultures.

    PubMed

    Abass, Mohammed H

    2017-01-01

    Fungal contamination of in vitro cultures of date palm (Phoenix dactylifera L.) is the major constraint to their initiation and maintenance. Different molecular approaches have been applied successfully to analyze both inter- and intraspecific variation among fungal species as well as determine their identity. This chapter describes step-by-step procedures of molecular identification of fungal contaminants by internal transcribed spacer (ITS) products of the most common fungal contaminants of date palm tissue culture. To begin with, samples of genera Alternaria, Aspergillus, Cladosporium, Epicoccum, and Penicillium were collected to isolate each fungal genus and extraction of genomic DNA. Polymerase chain reactions were accomplished by ITS primers (ITS1 and ITS4) for each fungal contaminant as well as for sequencing. Subsequently, they are analyzed by Basic Local Alignment Search Tool (BLAST) search of ITS sequence to reveal the identity of each individual fungal contaminant species. The molecular identification herein is a rapid and reliable procedure to identify date palm fungal contaminants which is very important in their control and treatment.

  12. Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

    PubMed

    Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

    2017-01-01

    Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

  13. Acute hospital costs after minimally invasive versus open lumbar interbody fusion: data from a US national database with 6106 patients.

    PubMed

    Wang, Michael Y; Lerner, Jason; Lesko, James; McGirt, Matthew J

    2012-08-01

    Retrospective multi-institutional database review. To determine if minimally invasive interbody fusion is associated with cost savings when compared with open surgery. Minimally invasive spine (MIS) surgeries are increasingly recognized as equivalent to open procedures. Although these techniques have been advocated for reducing pain, disability, and length of hospitalization, to date there has been little data demonstrating these benefits. This study analyzed inpatient hospital records from the Premier Perspective database (2002 to 2009), including patients who underwent a posterior lumbar fusion with interbody cage placement by ICD-9 code, and had implant charge codes that allowed determination if MIS pedicle screws were utilized. Exclusion criteria included a refusion surgery, deformity, >2 levels, and anterior fusion. Total costs were adjusted for covariates (age, sex, race, hospital geography and setting, payor, and comorbidities) using an analysis of covariance model. A total of 6106 patients were identified (1667 MIS and 4439 open). Length of stay (LOS) for 1-level MIS surgery averaged of 3.35 days versus 3.6 days for open surgery (P≤0.006). For 2-level MIS surgery LOS averaged of 3.4 days versus 4.03 days for open surgery (P≤0.001). Total inflation-adjusted acute hospitalization cost averaged $29,187 for 1-level MIS procedures versus $29,947 for open surgery, a nonsignificant difference (P=0.55). Total inflation-adjusted acute hospitalization cost averaged $2106 lower for 2-level MIS surgery (total costs of $33,879 for MIS vs. $35,984 for open surgery, P=0.0023). Cost savings were attributable primarily to lower room and board ($857), operating room ($359), pharmacy ($304), and laboratory ($166) costs in the MIS group. High variances in the 2-level open surgery with prolonged hospital stay also accounted for overall cost differences. This data from a large nationwide sample of hospitalizations demonstrates that MIS lumbar interbody fusion results in a

  14. Severe infections in children with acute leukemia undergoing intensive chemotherapy can successfully be prevented by ciprofloxacin, voriconazole, or micafungin prophylaxis.

    PubMed

    Yeh, Ting-Chi; Liu, Hsi-Che; Hou, Jen-Yin; Chen, Kuan-Hao; Huang, Ting-Huan; Chang, Ching-Yi; Liang, Der-Cherng

    2014-04-15

    The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia. Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/μL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded. During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period. Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy. © 2013 American Cancer Society.

  15. Invasive pulmonary aspergillosis: current diagnostic methodologies and a new molecular approach.

    PubMed

    Moura, S; Cerqueira, L; Almeida, A

    2018-05-13

    The fungus Aspergillus fumigatus is the main pathogenic agent responsible for invasive pulmonary aspergillosis. Immunocompromised patients are more likely to develop this pathology due to a decrease in the immune system's defense capacity. Despite of the low occurrence of invasive pulmonary aspergillosis, this pathology presents high rates of mortality, mostly due to late and unspecific diagnosis. Currently, the diagnostic methods used to detect this fungal infection are conventional mycological examination (direct microscopic examination, histological examination, and culture), imaging, non-culture-based tests for the detection of galactomannan, β(1,3)-glucan and an extracellular glycoprotein, and molecular tests based on PCR. However, most of these methods do not detect the species A. fumigatus; they only allow the identification of genus Aspergillus. The development of more specific detection methods is of extreme importance. Fluorescent in situ hybridization-based molecular methods can be a good alternative to achieve this purpose. In this review, it is intended to point out that most of the methods used for the diagnosis of invasive pulmonary aspergillosis do not allow to detect the fungus at the species level and that fluorescence in situ hybridization-based molecular method will be a promising approach in the A. fumigatus detection.

  16. Common fungal diseases of Russian forests

    Treesearch

    Evgeny P. Kuz' michevl; Ella s. Sokolova; Elena G. Kulikova

    2001-01-01

    Describes common fungal diseases of Russian forests, including diagnostic signs and symptoms, pathogen biology, damage caused by the disease, and methods of control. The fungal diseases are divided into two groups: those that are the most common in Russian forests and those that are found only in Russia. Within each group, diseases are subdivided by plant organ...

  17. Chemoinformatic expedition of the chemical space of fungal products.

    PubMed

    González-Medina, Mariana; Prieto-Martínez, Fernando D; Naveja, J Jesús; Méndez-Lucio, Oscar; El-Elimat, Tamam; Pearce, Cedric J; Oberlies, Nicholas H; Figueroa, Mario; Medina-Franco, José L

    2016-08-01

    Fungi are valuable resources for bioactive secondary metabolites. However, the chemical space of fungal secondary metabolites has been studied only on a limited basis. Herein, we report a comprehensive chemoinformatic analysis of a unique set of 207 fungal metabolites isolated and characterized in a USA National Cancer Institute funded drug discovery project. Comparison of the molecular complexity of the 207 fungal metabolites with approved anticancer and nonanticancer drugs, compounds in clinical studies, general screening compounds and molecules Generally Recognized as Safe revealed that fungal metabolites have high degree of complexity. Molecular fingerprints showed that fungal metabolites are as structurally diverse as other natural products and have, in general, drug-like physicochemical properties. Fungal products represent promising candidates to expand the medicinally relevant chemical space. This work is a significant expansion of an analysis reported years ago for a smaller set of compounds (less than half of the ones included in the present work) from filamentous fungi using different structural properties.

  18. Currency notes and coins as a possible source of transmitting fungal pathogens of man and plants.

    PubMed

    Wanule, Dinesh; Jalander, Vaghmare; Gachande, B D; Sirsikar, A N

    2011-10-01

    Currency (notes and coins) handling by people during transaction is one of the most mobile objects within the community, which has a potential of transmitting pathogens. A survey carried out recently in Nanded city (Maharashtra) revealed heavy contamination of currency notes and coins by important fungal pathogens of plants and man, i.e. Aspergillus niger (60.37%), A. flavus (3.98%), A.nidulans (0.2%), Penicillium citrinum (17.80%), Alternaria tenuis (0.20%), Curvularia pallescens (0.20%), Cladosporium cladosporioides (10.69%), Rhizopus stolonifer (1.04%), an unidentified Aspergillus species .1 (0.20%) and another unidentified Aspergillus species.2 (3.14%), Fusarium sp. (0.20%), Trichoderma viride (0.20%),white sterile mycelium (0.62%) and brown sterile mycelium (0.62%). The study highlights the importance of preventing and controlling fungal contamination of currency notes and coins in public health and plant protection. Currency notes or coins are rarely suspected as infection sources and often not quarantined at airport or seaport terminal. Possible transmission of pathogens or "alien", invasive species through currency across borders or across countries needs to be taken into consideration especially under circumstances of serious outbreak of important disease or when there is a threat of biological warfare.

  19. Deep venous thrombosis and postthrombotic syndrome: invasive management.

    PubMed

    Comerota, A J

    2015-03-01

    Invasive management of postthrombotic syndrome encompasses the two ends of the deep vein thrombosis spectrum, patients with acute iliofemoral deep vein thrombosis and those with chronic postthrombotic iliofemoral venous obstruction. Of all patients with acute deep vein thrombosis, those with involvement of the iliofemoral segments have the most severe chronic postthrombotic morbidity. Catheter-based techniques now permit percutaneous treatment to eliminate thrombus, restore patency, potentially maintain valvular function, and improve quality of life. Randomized trial data support an initial treatment strategy of thrombus removal. Failure to eliminate acute thrombus from the iliofemoral system leads to chronic postthrombotic obstruction of venous outflow. Debilitating chronic postthrombotic symptoms of the long-standing obstruction of venous outflow can be reduced by restoring unobstructed venous drainage from the profunda femoris vein to the vena cava. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. Minimal Invasive Left Ventricular Lead Repositioning is Safe and Effective in Distal Left Ventricular Lead Positions.

    PubMed

    Osztheimer, István; Szilágyi, Szabolcs; Pongor, Zsuzsanna; Zima, Endre; Molnár, Levente; Tahin, Tamás; Merkely, Béla; Gellér, László

    2017-05-01

    Treatment of left ventricular electrode dislocation and phrenic nerve stimulation remains an issue in the era of new electrode designs. Safety and efficacy of minimal invasive lead repositioning and pocket opening reposition procedures were evaluated between December 2005 and December 2012 at our center. Minimal invasive method was developed and widely utilized at our center to treat phrenic nerve stimulation. The distally positioned left ventricular lead is looped around by a deflectable catheter in the right atrium introduced from the femoral vein access and then pulled back. Coronary stent implantation was used afterwards for lead stabilization in some patients. 42 minimal invasive and 48 electrode repositions with pacemaker pocket opening were performed at 77 patients for left ventricular lead problems. Minimal invasive reposition could be carried out successfully in 69% of (29 patients) cases. Note that in 14.3% of the cases (six patients) minimal invasive procedures were acutely unsuccessful and crossover was necessary. In 16.6% of the cases (seven patients) lead issues were noted later during follow-up. Opening of the pocket could be carried out successfully in 81.2% (39 patients) and was unsuccessful acutely in 6.25% (three patients). Repeated dislocation was noticed, 12.5%, in this group (six patients). Complication during minimal invasive procedures was electrode injury in one case. Pocket openings were associated with several complications: atrial fibrillation, pericardial effusion, fever, hematoma, and right ventricular electrode dislodgement. Minimal invasive procedure-as the first line approach-is safe and feasible for left ventricular electrode repositioning in selected cases. © 2017 Wiley Periodicals, Inc.

  1. Exploiting the fungal highway: development of a novel tool for the in situ isolation of bacteria migrating along fungal mycelium.

    PubMed

    Simon, Anaele; Bindschedler, Saskia; Job, Daniel; Wick, Lukas Y; Filippidou, Sevasti; Kooli, Wafa M; Verrecchia, Eric P; Junier, Pilar

    2015-11-01

    Fungi and bacteria form various associations that are central to numerous environmental processes. In the so-called fungal highway, bacteria disperse along fungal mycelium. We developed a novel tool for the in situ isolation of bacteria moving along fungal hyphae as well as for the recovery of fungi potentially involved in dispersal, both of which are attracted towards a target culture medium. We present the validation and the results of the first in situ test. Couples of fungi and bacteria were isolated from soil. Amongst the enriched organisms, we identified several species of fast-growing fungi (Fusarium sp. and Chaetomium sp.), as well as various potentially associated bacterial groups, including Variovorax soli, Olivibacter soli, Acinetobacter calcoaceticus, and several species of the genera Stenotrophomonas, Achromobacter and Ochrobactrum. Migration of bacteria along fungal hyphae across a discontinuous medium was confirmed in most of the cases. Although the majority of the bacteria for which migration was confirmed were also positive for flagellar motility, not all motile bacteria dispersed using their potential fungal partner. In addition, the importance of hydrophobicity of the fungal mycelial surface was confirmed. Future applications of the columns include targeting different types of microorganisms and their interactions, either by enrichment or by state of the art molecular biological methods. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. High turnover of fungal hyphae in incubation experiments.

    PubMed

    de Vries, Franciska T; Bååth, Erland; Kuyper, Thom W; Bloem, Jaap

    2009-03-01

    Soil biological studies are often conducted on sieved soils without the presence of plants. However, soil fungi build delicate mycelial networks, often symbiotically associated with plant roots (mycorrhizal fungi). We hypothesized that as a result of sieving and incubating without plants, the total fungal biomass decreases. To test this, we conducted three incubation experiments. We expected total and arbuscular mycorrhizal (AM) fungal biomass to be higher in less fertilized soils than in fertilized soils, and thus to decrease more during incubation. Indeed, we found that fungal biomass decreased rapidly in the less fertilized soils. A shift towards thicker hyphae occurred, and the fraction of septate hyphae increased. However, analyses of phospholipid fatty acids (PLFAs) and neutral lipid fatty acids could not clarify which fungal groups were decreasing. We propose that in our soils, there was a fraction of fungal biomass that was sensitive to fertilization and disturbance (sieving, followed by incubation without plants) with a very high turnover (possibly composed of fine hyphae of AM and saprotrophic fungi), and a fraction that was much less vulnerable with a low turnover (composed of saprotrophic fungi and runner hyphae of AMF). Furthermore, PLFAs might not be as sensitive in detecting changes in fungal biomass as previously thought.

  3. Multifocal Renal Fungal Abscesses.

    PubMed

    Cho, Eric Y; Kaplan, Joshua R; Mamone, Linda; Mydlo, Jack H; Reese, Adam C

    2016-07-01

    We report a case of multiple fungal renal abscesses in a 36-year-old woman with a history of diabetes and intravenous substance use disorder. The patient presented with fever and hematuria, and was found to be bacteremic and fungemic. She was initially managed with broad-spectrum antibiotics and antifungals. She remained febrile and imaging on treatment day 14 showed no improvement of the renal abscesses. Thus, a nephrectomy was performed, after which the patient defervesced and follow-up blood cultures were negative. There is a paucity of literature regarding management of multifocal fungal renal abscesses that fail to respond to medical management. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The growth and phosphorus acquisition of invasive plants Rudbeckia laciniata and Solidago gigantea are enhanced by arbuscular mycorrhizal fungi.

    PubMed

    Majewska, Marta L; Rola, Kaja; Zubek, Szymon

    2017-02-01

    While a number of recent studies have revealed that arbuscular mycorrhizal fungi (AMF) can mediate invasive plant success, the influence of these symbionts on the most successful and high-impact invaders is largely unexplored. Two perennial herbs of this category of invasive plants, Rudbeckia laciniata and Solidago gigantea (Asteraceae), were thus tested in a pot experiment to determine whether AMF influence their growth, the concentration of phosphorus in biomass, and photosynthesis. The following treatments, including three common AMF species, were prepared on soils representative of two habitats that are frequently invaded by both plants, namely fallow and river valley: (1) control-soil without AMF, (2) Rhizophagus irregularis, (3) Funneliformis mosseae, and (4) Claroideoglomus claroideum. The invaders were strongly dependent on AMF for their growth. The mycorrhizal dependency of R. laciniata was 88 and 63 % and of S. gigantea 90 and 82 % for valley and fallow soils, respectively. The fungi also increased P concentration in their biomass. However, we found different effects of the fungal species in the stimulation of plant growth and P acquisition, with R. irregularis and C. claroideum being the most and least effective symbionts, respectively. None of AMF species had an impact on the photosynthetic performance indexes of both plants. Our findings indicate that AMF have a direct effect on the early stages of R. laciniata and S. gigantea growth. The magnitude of the response of both plant species to AMF was dependent on the fungal and soil identities. Therefore, the presence of particular AMF species in a site may determine the success of their invasion.

  5. Effects of fungal species, cultivation time, growth substrate, and air exposure velocity on the fluorescence properties of airborne fungal spores.

    PubMed

    Saari, S; Mensah-Attipoe, J; Reponen, T; Veijalainen, A M; Salmela, A; Pasanen, P; Keskinen, J

    2015-12-01

    Real-time bioaerosol monitoring is possible with fluorescence based instruments. This study provides information on major factors that can affect the fluorescence properties of airborne fungal spores. Two fluorescence-based bioaerosol detectors, BioScout, and ultraviolet aerodynamic particle sizer (UVAPS), were used to study fluorescent particle fractions (FPFs) of released spores of three fungal species (Aspergillus versicolor, Cladosporium cladosporioides, and Penicillium brevicompactum). Two culture media (agar and gypsum board), three ages of the culture (one week, one month, and four months), and three aerosolization air velocities (5, 15, and 27 m/s) were tested. The results showed that the FPF values for spores released from gypsum were typically lower than for those released from agar indicating that poor nutrient substrate produces spores with lower amounts of fluorescent compounds. The results also showed higher FPF values with lower air velocities in aerosolization. This indicates that easily released fully developed spores have more fluorescent compounds compared to forcibly extracted non-matured spores. The FPFs typically were lower with older samples. The FPF results between the two instruments were similar, except with four-month-old samples. The results can be utilized in field measurements of fungal spores to estimate actual concentrations and compare different instruments with fluorescence-based devices as well as in instrument calibration and testing in laboratory conditions. Fluorescence-based instruments are the only choice for real-time detection of fungal spores at the moment. In general, all fluorescence-based bioaerosol instruments are tested against known bacterial and fungal spores in laboratory conditions. This study showed that fungal species, growth substrate, age of culture, and air current exposure rate have an effect on detection efficiency of fungal spores in the fluorescence-based instruments. Therefore, these factors should be

  6. Fungal endophytes characterization from four species of Diplazium Swartz

    NASA Astrophysics Data System (ADS)

    Affina-Eliya, A. A.; Noraini, T.; Nazlina, I.; Ruzi, A. R.

    2014-09-01

    Four species on genus Diplazium namely Diplazium tomentosum, D. sorzogonense, D. asperum and D. accedens of Peninsular Malaysia were studied for presence of fungal endophyte. The objective of this study is to characterize fungal endophytes in the rhizome of four Diplazium species. The rhizome was surface sterilized and incubated to isolate fungal endophytes. Characterization of the colonies was performed by macroscopic morphological, microscopic identification, types of hyphae and mycelium, and spore structure. For isolation that produces spores, the structure of conidiophores and conidia were identified. From this study, four fungal have been isolated and determined as Aspergillus sp. (isolates AE 1), Aspergillus fumigatus (isolates AE 2), Aspergillus versicolor (isolates AE 3) and Verticillium sp. (isolates AE 4). The fungal isolates from this study were classified from the same family Moniliaceae.

  7. Pentraxin 3 levels in bronchoalveolar lavage fluid of lung transplant recipients with invasive aspergillosis.

    PubMed

    Kabbani, Dima; Bhaskaran, Archana; Singer, Lianne G; Bhimji, Alyajahan; Rotstein, Coleman; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

    2017-09-01

    Invasive aspergillosis is the most common invasive fungal infection in lung transplant recipients. The use of galactomannan testing in bronchoalveolar lavage (BAL) fluid has improved diagnosis of invasive aspergillosis; however, false-positive results can lead to overdiagnosis and unnecessary treatment. The use of proinflammatory markers such as pentraxin 3 (PTX3) may help differentiate between Aspergillus colonization and disease. BAL PTX3 concentrations were measured by enzyme-linked immunosorbent assay in 151 lung transplant recipients and 9 healthy control subjects. Patients were characterized as having Aspergillus colonization or invasive disease according to International Society of Heart and Lung Transplantation criteria. Concomitant PTX3values were compared using Mann-Whitney U and Kruskal-Wallis tests. We analyzed 322 BAL stored samples and identified 15 invasive aspergillosis events, 38 Aspergillus colonizations, and 17 positive galactomannan with negative Aspergillus cultures. Median BAL PTX3 level was significantly higher in patients with invasive aspergillosis compared with patients with Aspergillus colonization and healthy control subjects (439.20 pg/ml [interquartile range (IQR) 168.18-778.90], 68.93 pg/ml [IQR 13.67-156.74], and 13.67 pg/ml [IQR 13.67-121.18]; p < 0.001). Patients with BAL PTX3 value >319 pg/ml with positive galactomannan and patients with BAL PTX3 value >312 pg/ml with positive Aspergillus culture were 4.5 and 5.5 times more likely to have invasive pulmonary aspergillosis, respectively. Our study shows that PTX3 measurements in BAL samples were significantly higher among patients with invasive aspergillosis and may help to identify patients with Aspergillus colonization and false-positive galactomannan in BAL samples. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. 50-plus years of fungal viruses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ghabrial, Said A., E-mail: saghab00@email.uky.edu; Castón, José R.; Jiang, Daohong

    2015-05-15

    Mycoviruses are widespread in all major taxa of fungi. They are transmitted intracellularly during cell division, sporogenesis, and/or cell-to-cell fusion (hyphal anastomosis), and thus their life cycles generally lack an extracellular phase. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups, although recent advances have established expanded experimental host ranges for some mycoviruses. Most known mycoviruses have dsRNA genomes packaged in isometric particles, but an increasing number of positive- or negative-strand ssRNA and ssDNA viruses have been isolated and characterized. Although many mycoviruses do not have marked effects on their hosts, thosemore » that reduce the virulence of their phytopathogenic fungal hosts are of considerable interest for development of novel biocontrol strategies. Mycoviruses that infect endophytic fungi and those that encode killer toxins are also of special interest. Structural analyses of mycoviruses have promoted better understanding of virus assembly, function, and evolution. - Highlights: • Historical perspective of fungal virus research. • Description, classification and diversity of fungal virus families. • Structural features of fungal virus particles. • Hypovirulence and exploitation of mycoviruses in biological control of plant pathogenic fungi.« less

  9. Phylogenetic structure of arbuscular mycorrhizal fungal communities along an elevation gradient.

    PubMed

    Egan, Cameron P; Callaway, Ragan M; Hart, Miranda M; Pither, Jason; Klironomos, John

    2017-04-01

    Despite the importance of arbuscular mycorrhizal (AM) fungi within terrestrial ecosystems, we know little about how natural AM fungal communities are structured. To date, the majority of studies examining AM fungal community diversity have focused on single habitats with similar environmental conditions, with relatively few studies having assessed the diversity of AM fungi over large-scale environmental gradients. In this study, we characterized AM fungal communities in the soil along a high-elevation gradient in the North American Rocky Mountains. We focused on phylogenetic patterns of AM fungal communities to gain insight into how AM fungal communities are naturally assembled. We found that alpine AM fungal communities had lower phylogenetic diversity relative to lower elevation communities, as well as being more heterogeneous in composition than either treeline or subalpine communities. AM fungal communities were phylogenetically clustered at all elevations sampled, suggesting that environmental filtering, either selection by host plants or fungal niches, is the primary ecological process structuring communities along the gradient.

  10. Developments in the invasive diagnostic–therapeutic cascade of women and men with acute coronary syndromes from 2005 to 2011: a nationwide cohort study

    PubMed Central

    Hansen, Kim Wadt; Soerensen, R; Madsen, M; Madsen, J K; Jensen, J S; von Kappelgaard, L M; Mortensen, P E; Galatius, S

    2015-01-01

    Objectives To investigate for trends in sex-related differences in the invasive diagnostic–therapeutic cascade in a population of patients with acute coronary syndromes (ACS). Design A nationwide cohort study. Setting Administrative and clinical registries covering all hospitalisations, invasive cardiac procedures and deaths in the Danish population of 5.6 million inhabitants. Participants We included 52 565 patients aged 30–90 years who were hospitalised with a first ACS from January 2005 to November 2011. Follow-up was 60 days from the day of index admission. Main outcome measures Diagnostic coronary angiography, percutaneous coronary intervention or coronary artery bypass within 60 days of index admission. Results Women constituted 36%, were older, had more comorbidity and were less likely to be admitted to a hospital with cardiac catheterisation facilities than men. Mortality rates were similar for both sexes. Diagnostic coronary angiography was performed less frequently on women compared with men, both within 1 day (31% vs 42%; p<0.001) and within 60 days (67% vs 80%; p<0.001), yielding adjusted female–male HRs of 0.83 (0.79–0.87) and 0.86 (0.84–0.89), respectively.Among the 39 677 patients undergoing coronary angiography, non-obstructive coronary artery disease was more frequent among women than men (22% vs 9%; p<0.001). Women were less likely to undergo percutaneous coronary intervention (58% vs 72%; p<0.001) and coronary artery bypass (6% vs 11%, p<0.001) within 60 days than men, yielding adjusted HRs of 0.96 (0.92–0.99) and 0.81 (0.74–0.89), respectively. The sex-related differences were not attenuated over time for any of the invasive cardiac procedures (p values for trend >0.05). Conclusions In this nationwide study, men were more likely to undergo an invasive approach than women when hospitalised with a first ACS—a difference persisting from 2005 to 2011. Future studies should focus on the potential mechanisms behind this

  11. Plasma membrane lipids and their role in fungal virulence.

    PubMed

    Rella, Antonella; Farnoud, Amir M; Del Poeta, Maurizio

    2016-01-01

    There has been considerable evidence in recent years suggesting that plasma membrane lipids are important regulators of fungal pathogenicity. Various glycolipids have been shown to impart virulent properties in several fungal species, while others have been shown to play a role in host defense. In addition to their role as virulence factors, lipids also contribute to other virulence mechanisms such as drug resistance, biofilm formation, and release of extracellular vesicles. In addition, lipids also affect the mechanical properties of the plasma membrane through the formation of packed microdomains composed mainly of sphingolipids and sterols. Changes in the composition of lipid microdomains have been shown to disrupt the localization of virulence factors and affect fungal pathogenicity. This review gathers evidence on the various roles of plasma membrane lipids in fungal virulence and how lipids might contribute to the different processes that occur during infection and treatment. Insight into the role of lipids in fungal virulence can lead to an improved understanding of the process of fungal pathogenesis and the development of new lipid-mediated therapeutic strategies. Published by Elsevier Ltd.

  12. Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.

    PubMed

    Morgand, Marjolaine; Rammaert, Blandine; Poirée, Sylvain; Bougnoux, Marie-Elisabeth; Tran, Hugo; Kania, Romain; Chrétien, Fabrice; Jouvion, Gregory; Lortholary, Olivier

    2015-12-01

    Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-β-d-glucan test results were initially positive, in contrast to galactomannan antigen results. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Model simulations of fungal spore distribution over the Indian region

    NASA Astrophysics Data System (ADS)

    Ansari, Tabish U.; Valsan, Aswathy E.; Ojha, N.; Ravikrishna, R.; Narasimhan, Balaji; Gunthe, Sachin S.

    2015-12-01

    Fungal spores play important role in the health of humans, animals, and plants by constituting a class of the primary biological aerosol particles (PBAPs). Additionally, these could mediate the hydrological cycle by acting as nuclei for ice and cloud formation (IN and CCN respectively). Various processes in the biosphere and the variations in the meteorological conditions control the releasing mechanism of spores through active wet and dry discharge. In the present paper, we simulate the concentration of fungal spores over the Indian region during three distinct meteorological seasons by combining a numerical model (WRF-Chem) with the fungal spore emissions based on land-use type. Maiden high-resolution regional simulations revealed large spatial gradient and strong seasonal dependence in the concentration of fungal spores over the Indian region. The fungal spore concentrations are found to be the highest during winter (0-70 μg m-3 in December), moderately higher during summer (0-35 μg m-3 in May) and lowest during the monsoon (0-25 μg m-3 in July). The elevated concentrations during winter are attributed to the shallower boundary layer trapping the emitted fungal spores in smaller volume. In contrast, the deeper boundary layer mixing in May and stronger monsoonal-convection in July distribute the fungal spores throughout the lower troposphere (∼5 km). We suggest that the higher fungal spore concentrations during winter could have potential health impacts. While, stronger vertical mixing could enable fungal spores to influence the cloud formation during summer and monsoon. Our study provides the first information about the distribution and seasonal variation of fungal spores over the densely populated and observationally sparse Indian region.

  14. Plasmonic gold nanoparticles for detection of fungi and human cutaneous fungal infections.

    PubMed

    Sojinrin, Tobiloba; Conde, João; Liu, Kangze; Curtin, James; Byrne, Hugh J; Cui, Daxiang; Tian, Furong

    2017-07-01

    Fungi, which are common in the environment, can cause a multitude of diseases. Warm, humid conditions allow fungi to grow and infect humans via the respiratory, digestive and reproductive tracts, genital area and other bodily interfaces. Fungi can be detected directly by microscopy, using the potassium hydroxide test, which is the gold standard and most popular method for fungal screening. However, this test requires trained personnel operating specialist equipment, including a fluorescent microscope and culture facilities. As most acutely infected patients seek medical attention within the first few days of symptoms, the optimal diagnostic test would be rapid and self-diagnostic simplifying and improving the therapeutic outcome. In suspensions of gold nanoparticles, Aspergillus niger can cause a colour change from red to blue within 2 min, as a result of changes in nanoparticle shape. A similar colour change was observed in the supernatant of samples of human toenails dispersed in water. Scanning electron microscopy, UV/Vis and Raman spectroscopy were employed to monitor the changes in morphology and surface plasmon resonance of the nanoparticles. The correlation of colour change with the fungal infection was analysed using the absorbance ratio at 520 nm/620 nm. We found a decrease in the ratio when the fungi concentration increased from 1 to 16 CFU/mL, with a detection limit of 10 CFU/mL. The test had an 80% sensitivity and a 95% specificity value for the diagnosis of athlete's foot in human patients. This plasmonic gold nanoparticle-based system for detection of fungal infections measures the change in shape of gold nanoparticles and generates coloured solutions with distinct tonality. Our application has the potential to contribute to self-diagnosis and hygiene control in laboratories/hospitals with fewer resources, just using the naked eye. Graphical abstract Colorimetric method for fungi detection with gold nano particles.

  15. Epigenetic regulation of development and pathogenesis in fungal plant pathogens.

    PubMed

    Dubey, Akanksha; Jeon, Junhyun

    2017-08-01

    Evidently, epigenetics is at forefront in explaining the mechanisms underlying the success of human pathogens and in the identification of pathogen-induced modifications within host plants. However, there is a lack of studies highlighting the role of epigenetics in the modulation of the growth and pathogenicity of fungal plant pathogens. In this review, we attempt to highlight and discuss the role of epigenetics in the regulation of the growth and pathogenicity of fungal phytopathogens using Magnaporthe oryzae, a devastating fungal plant pathogen, as a model system. With the perspective of wide application in the understanding of the development, pathogenesis and control of other fungal pathogens, we attempt to provide a synthesized view of the epigenetic studies conducted on M. oryzae to date. First, we discuss the mechanisms of epigenetic modifications in M. oryzae and their impact on fungal development and pathogenicity. Second, we highlight the unexplored epigenetic mechanisms and areas of research that should be considered in the near future to construct a holistic view of epigenetic functioning in M. oryzae and other fungal plant pathogens. Importantly, the development of a complete understanding of the modulation of epigenetic regulation in fungal pathogens can help in the identification of target points to combat fungal pathogenesis. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  16. Classical methods and modern analysis for studying fungal diversity

    Treesearch

    John Paul Schmit

    2005-01-01

    In this chapter, we examine the use of classical methods to study fungal diversity. Classical methods rely on the direct observation of fungi, rather than sampling fungal DNA. We summarize a wide variety of classical methods, including direct sampling of fungal fruiting bodies, incubation of substrata in moist chambers, culturing of endophytes, and particle plating. We...

  17. Classical Methods and Modern Analysis for Studying Fungal Diversity

    Treesearch

    J. P. Schmit; D. J. Lodge

    2005-01-01

    In this chapter, we examine the use of classical methods to study fungal diversity. Classical methods rely on the direct observation of fungi, rather than sampling fungal DNA. We summarize a wide variety of classical methods, including direct sampling of fungal fruiting bodies, incubation of substrata in moist chambers, culturing of endophytes, and particle plating. We...

  18. Consensus guidelines for the treatment of invasive mould infections in haematological malignancy and haemopoietic stem cell transplantation, 2014.

    PubMed

    Blyth, C C; Gilroy, N M; Guy, S D; Chambers, S T; Cheong, E Y; Gottlieb, T; McGuinness, S L; Thursky, K A

    2014-12-01

    Mould species represent the pathogens most commonly associated with invasive fungal disease in patients with haematological malignancies and patients of haemopoietic stem cell transplants. Invasive mould infections in these patient populations, particularly in the setting of neutropenia, are associated with high morbidity and mortality, and significantly increase the complexity of management. While Aspergillus species remain the most prevalent cause of invasive mould infections, Scedosporium and Fusarium species and the Mucormycetes continue to place a significant burden on the immunocompromised host. Evidence also suggests that infections caused by rare and emerging pathogens are increasing within the setting of broad-spectrum antifungal prophylaxis and improved survival times placing immunosuppressed patients at risk for longer. These guidelines present evidence-based recommendations for the antifungal management of common, rare and emerging mould infections in both adult and paediatric populations. Where relevant, the role of surgery, adjunctive therapy and immunotherapy is also discussed. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  19. A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

    PubMed

    Imataki, O; Kami, M; Kim, S-W; Gotoh, M; Komaba, S; Kasai, M; Hashino, S; Naito, K; Masuda, M; Anan, K; Teshima, H; Togitani, K; Inoue, T; Nishimura, M; Adachi, Y; Fukuhara, T; Yamashita, T; Uike, N; Kobayashi, Y; Hamaguchi, M; Higuchi, M; Kawakami, K; Takaue, Y

    2004-06-01

    We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

  20. Emerging fungal threats to animal, plant and ecosystem health

    PubMed Central

    Fisher, Matthew C.; Henk, Daniel. A.; Briggs, Cheryl J.; Brownstein, John S.; Madoff, Lawrence C.; McCraw, Sarah L.; Gurr, Sarah J.

    2013-01-01

    The past two decades have seen an increasing number of virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide. PMID:22498624