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Sample records for aspergillosis

  1. Aspergillosis

    Science.gov (United States)

    ... Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth Head Neck ... Body Aspergillosis is an infection that frequently affects the lungs. It is caused by the fungus Aspergillus. Species of Aspergillus are found on decaying vegetation and ...

  2. Abdominal aspergillosis: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Suk Keu, E-mail: pagoda20@hanmail.net [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Hye Jin, E-mail: kimhyejin@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Byun, Jae Ho, E-mail: jhbyun@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Ah Young, E-mail: aykim@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Lee, Moon-Gyu, E-mail: mglee@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Ha, Hyun Kwon, E-mail: hkha@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of)

    2011-03-15

    Objective: In order to retrospectively evaluate the CT findings of abdominal aspergillosis in immunocompromised patients. Materials and methods: CT scans were reviewed with regard to the sites, number, morphologic appearance, attenuation, and the contrast enhancement patterns of the lesions in six patients (5 women, 1 man; mean age, 43.4 years; range, 23-59 years) with pathologically proved abdominal aspergillosis by two gastrointestinal radiologists in consensus. Medical records were also reviewed to determine each patient's clinical status and outcome. Results: All patients were immunocompromised state: 4 patients received immunosuppressive therapy for solid organ transplantation and 2 patients received chemotherapy for acute myeloid leukemia. Aspergillosis involved blood vessels (n = 3), liver (n = 2), spleen (n = 2), gastrointestinal tract (n = 2), native kidney (n = 1), transplanted kidney (n = 1), peritoneum (n = 1), and retroperitoneum (n = 1). CT demonstrated solid organ or bowel infarction or perforation secondary to vascular thrombosis or pseudoaneurysm, multiple low-attenuating lesions of solid organs presenting as abscesses, concentric bowel wall thickening mimicking typhlitis, or diffuse or nodular infiltration of the peritoneum and retroperitoneum. Conclusion: Familiarity with findings commonly presenting as angioinvasive features or abscesses on CT, may facilitate the diagnosis of rare and fatal abdominal aspergillosis.

  3. [Pseudotumoral allergic bronchopulmonary aspergillosis].

    Science.gov (United States)

    Otero González, I; Montero Martínez, C; Blanco Aparicio, M; Valiño López, P; Verea Hernando, H

    2000-06-01

    Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and radiological presentation can be atypical, requiring a high degree of suspicion on the part of the physician who treats such patients. We report the cases of two patients with APBA in whom the form of presentation--with few asthma symptoms, images showing lobar atelectasia and hilar adenopathy--led to an initial suspicion of lung cancer.

  4. Risk and Prevention of Aspergillosis

    Science.gov (United States)

    ... recommendations, please visit CDC’s Basic Facts about Mold webpage . If you are a healthcare provider or healthcare ... on diagnostic strategies of invasive aspergillosis. Curr Pharm Design 2013;19(20):3595-614. Weber DJ et ...

  5. Pulmonary aspergillosis: Atypical presentation in immunocompetent individuals

    OpenAIRE

    Ramakrishna Pai Jakribettu; Rekha Boloor; Shreevidya Kinila; Thomas S Kuruvilla

    2013-01-01

    Aspergillosis, an opportunistic infection, is a major cause of morbidity and mortality in immunocompromised patients. But, Aspergillus is also known to cause Pulmonary aspergillosis in immunocompetent host too. Only few cases have been reported in literature of Aspergillosis in Immunocompetent individuals so far. Here, we report 4 different cases of Pulmonary Aspergillosis , who have presented with acute symptoms.The possibility of pulmonary mycosis needs to be considered in patients with acu...

  6. Pulmonary aspergillosis: Atypical presentation in immunocompetent individuals

    Directory of Open Access Journals (Sweden)

    Ramakrishna Pai Jakribettu

    2013-01-01

    Full Text Available Aspergillosis, an opportunistic infection, is a major cause of morbidity and mortality in immunocompromised patients. But, Aspergillus is also known to cause Pulmonary aspergillosis in immunocompetent host too. Only few cases have been reported in literature of Aspergillosis in Immunocompetent individuals so far. Here, we report 4 different cases of Pulmonary Aspergillosis , who have presented with acute symptoms.The possibility of pulmonary mycosis needs to be considered in patients with acute pulmonary symptoms like breathlessness , hemoptysis, etc with signs of infection even in immunocompetent individuals, without underlying pulmonary disease.

  7. Pulmonary aspergillosis: a clinical review

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    M. Kousha

    2011-09-01

    Full Text Available Aspergillus is a mould which may lead to a variety of infectious, allergic diseases depending on the host's immune status or pulmonary structure. Invasive pulmonary aspergillosis occurs primarily in patients with severe immunodeficiency. The significance of this infection has dramatically increased with growing numbers of patients with impaired immune state associated with the management of malignancy, organ transplantation, autoimmune and inflammatory conditions; critically ill patients and those with chronic obstructive pulmonary disease appear to be at an increased risk. The introduction of new noninvasive tests, combined with more effective and better-tolerated antifungal agents, has resulted in lower mortality rates associated with this infection. Chronic necrotising aspergillosis is a locally invasive disease described in patients with chronic lung disease or mild immunodeficiency. Aspergilloma is usually found in patients with previously formed cavities in the lung, whereas allergic bronchopulmonary aspergillosis, a hypersensitivity reaction to Aspergillus antigens, is generally seen in patients with atopy, asthma or cystic fibrosis. This review provides an update on the evolving epidemiology and risk factors of the major manifestations of Aspergillus lung disease and the clinical manifestations that should prompt the clinician to consider these conditions. Current approaches for the diagnosis and management of these syndromes are discussed.

  8. Invasive aspergillosis in developing countries.

    Science.gov (United States)

    Chakrabarti, Arunaloke; Chatterjee, Shiv Sekhar; Das, Ashim; Shivaprakash, M R

    2011-04-01

    To review invasive aspergillosis (IA) in developing countries, we included those countries, which are mentioned in the document of the International Monetary Fund (IMF), called the Emerging and Developing Economies List, 2009. A PubMed/Medline literature search was performed for studies concerning IA reported during 1970 through March 2010 from these countries. IA is an important cause of morbidity and mortality of hospitalized patients of developing countries, though the exact frequency of the disease is not known due to inadequate reporting and facilities to diagnose. Only a handful of centers from India, China, Thailand, Pakistan, Bangladesh, Sri Lanka, Malaysia, Iran, Iraq, Saudi Arabia, Egypt, Sudan, South Africa, Turkey, Hungary, Brazil, Chile, Colombia, and Argentina had reported case series of IA. As sub-optimum hospital care practice, hospital renovation work in the vicinity of immunocompromised patients, overuse or misuse of steroids and broad-spectrum antibiotics, use of contaminated infusion sets/fluid, and increase in intravenous drug abusers have been reported from those countries, it is expected to find a high rate of IA among patients with high risk, though hard data is missing in most situations. Besides classical risk factors for IA, liver failure, chronic obstructive pulmonary disease, diabetes, and tuberculosis are the newly recognized underlying diseases associated with IA. In Asia, Africa and Middle East sino-orbital or cerebral aspergillosis, and Aspergillus endophthalmitis are emerging diseases and Aspergillus flavus is the predominant species isolated from these infections. The high frequency of A. flavus isolation from these patients may be due to higher prevalence of the fungus in the environment. Cerebral aspergillosis cases are largely due to an extension of the lesion from invasive Aspergillus sinusitis. The majority of the centers rely on conventional techniques including direct microscopy, histopathology, and culture to diagnose IA

  9. Aspergillosis

    Science.gov (United States)

    ... overview Aspiration pneumonia Asthma Blindness and vision loss Cancer Chemotherapy HIV/AIDS Immunodeficiency disorders Invasive Pneumonia - adults (community acquired) Pulmonary aspergilloma Pulmonary tuberculosis Review Date 5/1/2015 ...

  10. Invasive aspergillosis in near drowning nonneutropenic patient

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    Kartik Munta

    2015-01-01

    Full Text Available Invasive aspergillosis in immunosuppressed people has been well documented, but to diagnose and treat in an immunocompetent individual after near drowning, it requires early suspicion and proper empirical treatment. We report a case diagnosed to have invasive aspergillosis with systemic dissemination of the infection to the brain, gluteal muscles, and kidneys after a fall in a chemical tank of a paper manufacturing company. He was ventilated for acute respiratory distress syndrome and managed with antibiotics and vasopressors. Due to nonresolving pneumonia and positive serum galactomannan, trans-tracheal biopsy was performed which confirmed invasive aspergillosis and was treated with antifungals. With the availability of galactomannan assay and better radiological investigative modalities, occurrence of such invasive fungal infections in cases of drowning patients should be considered early in such patients and treated with appropriate antifungals.

  11. Invasive aspergillosis in near drowning nonneutropenic patient.

    Science.gov (United States)

    Munta, Kartik; Gopal, Palepu B N; Vigg, Ajit

    2015-12-01

    Invasive aspergillosis in immunosuppressed people has been well documented, but to diagnose and treat in an immunocompetent individual after near drowning, it requires early suspicion and proper empirical treatment. We report a case diagnosed to have invasive aspergillosis with systemic dissemination of the infection to the brain, gluteal muscles, and kidneys after a fall in a chemical tank of a paper manufacturing company. He was ventilated for acute respiratory distress syndrome and managed with antibiotics and vasopressors. Due to nonresolving pneumonia and positive serum galactomannan, trans-tracheal biopsy was performed which confirmed invasive aspergillosis and was treated with antifungals. With the availability of galactomannan assay and better radiological investigative modalities, occurrence of such invasive fungal infections in cases of drowning patients should be considered early in such patients and treated with appropriate antifungals.

  12. Invasive aspergillosis: results of multicenter study

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    N. N. Klimko

    2014-09-01

    Full Text Available We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008. Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %, main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %, cytostatic chemotherapy (57 %, corticosteroid treatment (45 %, and allogeneic hematopoietic stem cells transplantation (29 %. The pathogens – A. fumigatus (42 %, A. niger (33 %, and A. flavus (21 %. The main site of infection were lungs (86 %. 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01, adequatetherapy with voriconazole (p = 0.002 and secondary antifungal prophylaxis (p = 0.0003 were positive prognostic factors for survival of patients with invasive aspergillosis.

  13. Invasive aspergillosis: new insights into disease, diagnostic and treatment.

    Science.gov (United States)

    Karthaus, Meinolf; Buchheidt, Dieter

    2013-01-01

    Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate survival advantages. Prophylaxis makes sense, since diagnosis and treatment of invasive aspergillosis remain difficult. The introduction of non-culture based tools for the diagnosis of invasive aspergillosis is an important step forward for early and sensitive diagnosis of invasive aspergillosis. Early treatment is the cornerstone of a successful management of invasive aspergillosis. Substantial improvement came with the introduction of lipid formulations of amphotericin B in the early 1990s. Voriconazole was the first azole that improved the overall survival for patients with invasive aspergillosis. Newer azoles and the echinocandins were introduced for the treatment of invasive aspergillosis in the late 1990s. Voriconazole and liposomal amphotericin B allow a safer and more effective treatment of invasive aspergillosis when compared with amphotericin B-desoxycholate. Combination of antifungal agents has been introduced in clinical trials. Up to now no significant benefit has been obtained with antifungal combination compared to voriconazole alone. Because mortality of invasive aspergillosis remains up to more than 50%, prophylaxis, early diagnosis and early initiation of antifungal therapy are of utmost importance for the reduction of invasive aspergillosis related mortality. Despite all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state and new insights in the management of invasive aspergillosis and points out clinicians unmet needs.

  14. Manifestation of invasive pulmonary aspergillosis in the formation of mycetoma

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    Roos, N.; Peters, P.E.; Schellong, S.; Eiff, M. von

    1989-05-01

    Invasive pulmonary aspergillosis is characterized by radiological signs allowing a correct diagnosis, including differentiation from pulmonary candidiasis, when they are associated with appropriate clinical symptoms (neutropenia and fever persisting despite broad-spectrum antibiotics). In particular the formation of a pulmonary mycetoma in a previously normal lung is one of these signs. Unlike a simple fungus ball (the saprophytic form of aspergillosis), the rounded density of invasive pulmonary aspergillosis consists of sequestrum of devitalized lung tissue owing to blood vessel invasion by Aspergillus hyphae. This morphologic phenomenon is demonstrated in the present case report and is discussed together with the other roentgenological signs of the invasive aspergillosis.

  15. CT findings in rhinocerebral mucormycosis and aspergillosis

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    Kim, Dong Ik; Suh, Jung Ho; Lee, Jong Doo; Lee, Kyu Chang [Yeonsei University College of Medicine, Seoul (Korea, Republic of)

    1986-12-15

    Invasive aspergillosis or mucormycosis of the paranasal sinuses involving the cranial cavity is termed rhinocerebral mycosis, which is often difficult to differentiate from malignancy. Prognosis of rhinocerebral mycosis is disastrous and usually fatal. The authors herein report 6 cases of rhinocerebral mycosis; two of them were mucormycosis and four were aspergillosis histopathologically. Main CT features are nodular mucosal thickening in the multiple sites of the paranasal sinuses that extend to orbital apex or cavernous sinus through focal destruction of bony wall. In spite of their invasiveness beyond bony boundary, destruction is not so remarkable and it is always accompanied by bony sclerosis. Awareness of these disease and CT patterns discussed in this report should be helpful in leading to early biopsy and treatment.

  16. Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia

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    Mazen O. Al-Qadi

    2014-01-01

    Full Text Available Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles. BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.

  17. Cerebral Air Embolism from Angioinvasive Cavitary Aspergillosis

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    Chen Lin

    2014-01-01

    Full Text Available Background. Nontraumatic cerebral air embolism cases are rare. We report a case of an air embolism resulting in cerebral infarction related to angioinvasive cavitary aspergillosis. To our knowledge, there have been no previous reports associating these two conditions together. Case Presentation. A 32-year-old female was admitted for treatment of acute lymphoblastic leukemia (ALL. Her hospital course was complicated by pulmonary aspergillosis. On hospital day 55, she acutely developed severe global aphasia with right hemiplegia. A CT and CT-angiogram of her head and neck were obtained demonstrating intravascular air emboli within the left middle cerebral artery (MCA branches. She was emergently taken for hyperbaric oxygen therapy (HBOT. Evaluation for origin of the air embolus revealed an air focus along the left lower pulmonary vein. Over the course of 48 hours, her symptoms significantly improved. Conclusion. This unique case details an immunocompromised patient with pulmonary aspergillosis cavitary lesions that invaded into a pulmonary vein and caused a cerebral air embolism. With cerebral air embolisms, the acute treatment option differs from the typical ischemic stroke pathway and the provider should consider emergent HBOT. This case highlights the importance of considering atypical causes of acute ischemic stroke.

  18. Disseminated Aspergillosis due to Aspergillus niger in Immunocompetent Patient: A Case Report

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    Ulku Ergene

    2013-01-01

    Full Text Available Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Many cases of pulmonary, cutaneous, cerebral, and paranasal sinus aspergillosis in immunocompetent patient were defined in literature but disseminated aspergillosis is very rare. Here we present an immunocompetent case with extrapulmonary disseminated aspergillosis due to Aspergillus niger, totally recovered after effective antifungal treatment with voriconazole.

  19. CT in childhood allergic bronchopulmonary aspergillosis

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    Shah, A.; Bhagat, R.; Panchal, N. (Delhi Univ. (India). Vallabhabhai Patel Chest Inst.); Pant, C.S. (Institute of Nuclear Medicine and Allied Sciences, Delhi (India). Imaging Div.)

    1992-06-01

    CT of the thorax done during acute severe asthma in two paediatric patients demonstrated central bronchiectasis, a sine qua non for the diagnosis of allergic bronchopulmonary aspergillosis. Bronchography, regarded as the gold standard, was done subsequently on recovery. A comparative segmental analysis revealed that CT was able to identify immediately 24 of 27 segments which showed central bronchiectasis on bronchography. Early diagnosis with the aid of CT enabled immediate intervention which may have helped to prevent further lung damage in the paediatric patients. (orig.).

  20. Plasminogen alleles influence susceptibility to invasive aspergillosis.

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    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  1. Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis

    NARCIS (Netherlands)

    Seyedmousavi, S.; Mouton, J.W.; Melchers, W.J.G.; Verweij, P.E.

    2015-01-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazo

  2. Isolated Aspergillosis Myocardial Abscesses in a Liver-Transplant Patient

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    Kim-Diêp Dang-Tran

    2014-01-01

    Full Text Available Cardiac abscess is an uncommon and fatal complication after transplantation. We report a case of an initially isolated aspergillosis myocardial abscess diagnosed by cardiac magnetic resonance imaging (CMRI. At that time, there was no other biological evidence or other extracardiac manifestations. A three-month course of dual antifungal therapy followed by a single antifungal therapy was empirically given. Six month after admission, Aspergillus fumigatus was isolated for the first time and the patient deceased from a disseminated aspergillosis.

  3. Allergic Broncho Pulmonary Aspergillosis Complicated by Nocardiosis

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    Brijesh Sharma

    2012-01-01

    Full Text Available We describe a 70-year-old male with a history of diabetes mellitus, hypertension, and asthma who presented with increasing breathlessness for 5 months. He was diagnosed to have allergic bronchopulmonary aspergillosis (ABPA by serological and radiographic criteria. He was treated with steroids and itraconazole. After initial improvement, he developed fever with cough and mucopurulent sputum. X-ray chest revealed multiple cavities with air fluid level. Patient was treated with antibiotics without any response. Sputum was negative for acid fast bacilli (AFB. Sputum culture for bacteria and fungus did not reveal any significant growth; however a delayed growth of Nocardia was noted on fungal plates. Modified Ziehl Nelsen stain was positive for AFB. Patient was treated with cotrimoxazole. We discuss the serological and radiological criteria of ABPA, presentation and treatment of nocardia pulmonary infection and other possible causes of necrotizing pneumonia in immunocompromised settings.

  4. Intracranial Aspergillosis in an Immunocompetent Young Woman.

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    Panda, Prasan Kumar; Mavidi, Sunil Kumar; Wig, Naveet; Garg, Ajay; Nalwa, Aasma; Sharma, M C

    2017-01-04

    Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.

  5. Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes, and echinocandins.

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    Ibrahim, Ashraf S; Gebremariam, Teclegiorgis; Luo, Guanpingsheng; Fu, Yue; French, Samuel W; Edwards, John E; Spellberg, Brad

    2011-04-01

    Liposomal amphotericin B (LAmB) combined wither either micafungin or deferasirox was synergistic in previous murine studies with mucormycosis or aspergillosis. We hypothesized that triple therapy using LAmB, micafungin, and deferasirox could further improve outcomes of mucormycosis or aspergillosis. Triple therapy improved survival and reduced tissue fungal burden of mice with mucormycosis and to a lesser extent with aspergillosis. Continued investigation into the use of triple therapy against mucormycosis and aspergillosis is warranted.

  6. Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis

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    Hoffer, F.A. [Dept. of Diagnostic Imaging, St. Jude Children' s Research Hospital, Memphis, TN (United States); Gow, K.; Davidoff, A. [Dept. of Surgery, St. Jude Children' s Research Hospital, Memphis, TN (United States); Flynn, P.M. [Dept. of Infectious Diseases, St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2001-03-01

    Background. Invasive pulmonary aspergillosis is fulminant and often fatal in immunosuppressed patients. Percutaneous biopsy may select patients who could benefit from surgical resection. Objective. We sought to determine the accuracy of percutaneous biopsy for pediatric invasive pulmonary aspergillosis. Materials and methods. We retrospectively reviewed 28 imaging-guided percutaneous biopsies of the lungs of 24 children with suspected pulmonary aspergillosis. Twenty-two were being treated for malignancy and two for congenital immunodeficiency; 15 had received bone-marrow transplants. The accuracy of the percutaneous lung biopsy was determined by subsequent surgical resection, autopsy, or clinical course. Results. Histopathological studies showed ten biopsy specimens with septate hyphae, indicating a mold, and seven with Aspergillus flavus colonies in culture. The remaining 18 biopsies revealed no fungi. No patient had progressive aspergillosis after negative biopsy. Invasive pulmonary mold was detected by percutaneous biopsy with 100 % (10/10) sensitivity and 100 % (18/18) specificity. Percutaneous biopsy results influenced the surgical decision in 86 % (24 of 28) of the cases. Bleeding complicated the biopsy in 46 % (13/28) and hastened one death. Conclusion. Percutaneous biopsy of the lung is an accurate technique for the diagnosis of invasive pulmonary aspergillosis and correctly determines which immunosuppressed pediatric patients would benefit from therapeutic pulmonary resection. (orig.)

  7. Immunopathology and Immunogenetics of Allergic Bronchopulmonary Aspergillosis

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    Alan P. Knutsen

    2011-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF patients. Sensitization to A. fumigatus is common in both atopic asthmatic and CF patients, yet only 1%–2% of asthmatic and 7%–9% of CF patients develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response is characterized by Th2 responses to Aspergillus allergens, increased serum IgE, and eosinophilia. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA polymorphisms, IL-10 −1082GA promoter polymorphisms, surfactant protein A2 (SP-A2 polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR mutations. The studies indicate that ABPA patients are genetically at risk to develop skewed and heightened Th2 responses to A. fumigatus antigens. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4, and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA.

  8. Radiological aspects of Aspergillosis in the paranasal sinuses

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    Kopp, W.; Fotter, R.; Ebner, F.; Beaufort, F.; Stammberger, H.

    1986-08-01

    A retrospective radiographic study was performed on 142 proven cases of Aspergillosis in the paranasal sinuses. In all but two cases the mycosis was unilateral and in all cases the maxillary sinus was infected. A common radiographic presentation was a homogeneous opacity of the infected maxillary sinus, while about 50% of the cases showed nonspecific infectious changes of other paranasal sinuses additionally. Earlier stages of the disease showed an intraluminal soft tissue mass, representing the mycelium conglomerate. Bone destruction due to Aspergillosis could not be proven. 58% of the cases presented with intraluminal structures of metallic density. Histochemical studies proved these to consist mainly of tertiary Calciumphosphate. These concrements are considered to be pathognomonic of Aspergillosis.

  9. State of immune status in hematological patients with invasive aspergillosis

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    E. V. Frolova

    2012-01-01

    Full Text Available Invasive aspergillosis – is severe mycotic infection that often occurs in hematological patients and is characterized by high mortality. We examined the immunological parameters of hematological patients with invasive aspergillosis developed after cytostatic chemotherapy. Was founded, disruption of all parts of the immune respons: reduction in the absolute number of T-helper cells (CD4 +, natural killer cells (CD16 +, lowering of IFN-γ and IL-10 production, reduction in the number of B-lymphocytes and immunoglobulin levels of all classes, suppression killer ability of neutrophils are features of immune status in hematological patients with invasive aspergillosis receiving cytostatic chemotherapy.

  10. Aspergillosis and other systemic mycoses. The growing problem.

    Science.gov (United States)

    Fraser, D W; Ward, J I; Ajello, L; Plikaytis, B D

    1979-10-12

    To measure the incidence in the United States of systemic mycoses necessitating hospitalization, we reviewed discharge records of 1,875 hospitals participating in the Professional Activity Study of the Commission on Professional and Hospital Activities. Projected incidence rates in 1976 ranged from 23.0 per million for histoplasmosis to 0.2 per million for blastomycosis. High prevalences of leukemia or lymphoma (5.9% to 10.2%) or of other malignancies (9.9% to 13.2%) were recorded in patients with aspergillosis, candidasis, or cryptococcosis. High prevalences of chronic obstructive lung disease (9.6% to 9.9%) were recorded in those with aspergillosis or histoplasmosis. Marked increases from 1970 to 1976 were found in the incidence of aspergillosis (158%), actinomycosis (92%), cryptococcosis (78%), and coccidioidomycosis (74%). Increasing numbers of persons with immunosuppressive conditions, migration of susceptible persons into hyperendemic areas, and aging of the population contributed to the increases.

  11. Invasive Aspergillosis: Current Strategies for Diagnosis and Management.

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    Cadena, Jose; Thompson, George R; Patterson, Thomas F

    2016-03-01

    Aspergillosis remains a significant cause of morbidity and mortality in the immunocompromised population. The spectrum of disease is broad, ranging from severe and rapidly fatal infection to noninvasive disease. The diversity of patients and risk factors complicates diagnostic and therapeutic decision-making. Invasive procedures are often precluded by host status; noninvasive diagnostic tests vary in their sensitivity and specificity. Advancements in understanding the pathophysiology of invasive aspergillosis and host genetics in differential risk have also occurred. Future work may assist in therapeutic decision-making and patient prognosis. Voriconazole remains the preferred agent for treatment. Additional alternatives have emerged.

  12. Aspergillosis of the sphenoid sinus simulating a pituitary tumor

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    Larranaga, J.; Fandino, J.; Gomez-Bueno, J.; Botana, C.; Rodriguez, D.; Gonzalez-Carrero, J.

    1989-09-01

    Sphenoidal aspergillosis is an unusual cause of sella turcica enlargement. Pituitary abscess secondary to Aspergillus had been reported. In the present case, a woman with sphenoid sinus aspergillosis mimiced a pituitary tumor. This patient survived her infection with intact pituitary function following a transsphenoidal approach. No postoperative amphotericine-B and 5-fluorocytosine were necessary. CT scan revealed a mass occupying the sphenoid sinus extending to the sella turcica. Factors that should alert the clinican to the presence of a sphenoidal and pituitary abscess in a patient with sella turcica enlargement are prior episodes of sinusitis, meningitis and immunosuppression and, as in the present case, hyperglycemia. (orig.).

  13. Sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence.

    Science.gov (United States)

    Upadhyay, Rashmi; Kant, Surya; Prakash, Ved; Saheer, S

    2014-11-04

    Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder that is characterised by a hyper-responsiveness of the airways to Aspergillus fumigatus. Although several other fungi may also present with similar clinical conditions, Aspergillus remains the most common fungal pathogen causing airway infections. Co-existence of ABPA with allergic Aspergillus sinusitis (AAS) is an uncommon presentation. The concept of one airway/one disease justifies the co-existence of ABPA with AAS, but it does not always hold true. We report a case of a 35-year-old woman who presented with symptoms suggestive of bronchial asthma. On further investigation, the radiological pattern showed fleeting shadows and CT scan showed central cystic bronchiectatic changes characteristic of ABPA. The nasal secretions were investigated for the presence of Aspergillus and were found to be positive. Hence a diagnosis of ABPA with AAS was established. The patient was treated with oral steroids and antifungal drugs.

  14. Sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence

    Science.gov (United States)

    Upadhyay, Rashmi; Kant, Surya; Prakash, Ved; Saheer, S

    2014-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder that is characterised by a hyper-responsiveness of the airways to Aspergillus fumigatus. Although several other fungi may also present with similar clinical conditions, Aspergillus remains the most common fungal pathogen causing airway infections. Co-existence of ABPA with allergic Aspergillus sinusitis (AAS) is an uncommon presentation. The concept of one airway/one disease justifies the co-existence of ABPA with AAS, but it does not always hold true. We report a case of a 35-year-old woman who presented with symptoms suggestive of bronchial asthma. On further investigation, the radiological pattern showed fleeting shadows and CT scan showed central cystic bronchiectatic changes characteristic of ABPA. The nasal secretions were investigated for the presence of Aspergillus and were found to be positive. Hence a diagnosis of ABPA with AAS was established. The patient was treated with oral steroids and antifungal drugs. PMID:25371437

  15. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults.

    Science.gov (United States)

    Denning, David W; Pleuvry, Alex; Cole, Donald C

    2013-05-01

    Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and may lead to chronic pulmonary aspergillosis (CPA) yet global burdens of each have never been estimated. Antifungal therapy has a place in the management of ABPA and is the cornerstone of treatment in CPA, reducing morbidity and probably mortality. We used the country-specific prevalence of asthma from the Global Initiative for Asthma (GINA) report applied to population estimates to calculate adult asthma cases. From five referral cohorts (China, Ireland, New Zealand, Saudi Arabia and South Africa), we estimated the prevalence of ABPA in adults with asthma at 2.5% (range 0.72-3.5%) (scoping review). From ABPA case series, pulmonary cavitation occurred in 10% (range 7-20%), allowing an estimate of CPA prevalence worldwide using a deterministic scenario-based model. Of 193 million adults with active asthma worldwide, we estimate that 4,837,000 patients (range 1,354,000-6,772,000) develop ABPA. By WHO region, the ABPA burden estimates are: Europe, 1,062,000; Americas, 1,461,000; Eastern Mediterranean, 351,000; Africa, 389,900; Western Pacific, 823,200; South East Asia, 720,400. We calculate a global case burden of CPA complicating ABPA of 411,100 (range 206,300-589,400) at a 10% rate with a 15% annual attrition. The global burden of ABPA potentially exceeds 4.8 million people and of CPA complicating ABPA ˜ 400,000, which is more common than previously appreciated. Both conditions respond to antifungal therapy justifying improved case detection. Prospective population and clinical cohort studies are warranted to more precisely ascertain the frequency of ABPA and CPA in different locations and ethnic groups and validate the model inputs.

  16. Aspergillosis of the Petrous Apex and Meckel's Cave

    OpenAIRE

    Ederies, Ash; Chen, Joseph; Aviv, Richard I.; Pirouzmand, Farhad; Bilbao, Juan M.; Thompson, Andrew L.; Symons, Sean P.

    2010-01-01

    Cranial cerebral aspergillosis is a rare entity in immunocompetent patients. Invasive disease involving the petrous apex and Meckel's cave has rarely been described. We present a case of localized invasive petrous apical and Meckel's cave disease in an immunocompetent patient who presented with hemicranial neuralgic pain.

  17. Aspergillosis of the Petrous Apex and Meckel's Cave.

    Science.gov (United States)

    Ederies, Ash; Chen, Joseph; Aviv, Richard I; Pirouzmand, Farhad; Bilbao, Juan M; Thompson, Andrew L; Symons, Sean P

    2010-05-01

    Cranial cerebral aspergillosis is a rare entity in immunocompetent patients. Invasive disease involving the petrous apex and Meckel's cave has rarely been described. We present a case of localized invasive petrous apical and Meckel's cave disease in an immunocompetent patient who presented with hemicranial neuralgic pain.

  18. Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

    DEFF Research Database (Denmark)

    Skov, M; Koch, C; Reimert, C M;

    2000-01-01

    The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity...

  19. Invasive pulmonary aspergillosis: A study of 39 cases at autopsy

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2004-01-01

    Full Text Available Background: Aspergillus is a common cause of invasive mycosis, especially in immunocompromised or immunosuppressed individuals. Aims: To study the incidence of invasive pulmonary aspergillosis and evaluate the predisposing factors and clinico-pathological manifestations. Settings and Design: Retrospective analysis of autopsy material from a tertiary care hospital. Material and Methods: All autopsies performed over a 12-year period were reviewed and cases with invasive aspergillosis were analysed with respect to their clinical presentation, predisposing factors, gross and histological features, complications and causes of death. Results: Among a total of 20475 autopsies performed in 12 years, 39 patients (0.19 % had invasive pulmonary aspergillosis. There were 28 males and 11 females. Their ages ranged from five months to 67 years. Dyspnoea, fever, cough with mucopurulent expectoration, chest pain and haemoptysis were commonly encountered symptoms. Forty-one per cent of the patients had no respiratory symptoms. Fungal aetiology was not entertained clinically in any of the patients. The major underlying conditions were prolonged antibiotic therapy, steroid therapy, and renal transplantation, often associated with underlying lung diseases. Pneumonia, abscesses, vascular thrombosis and infarction were common findings at autopsy. Antecedent tuberculosis, mucormycosis, Pneumocystis carinii pneumonia and Cytomegalovirus infection were also present. In most cases, death was related to extensive pulmonary involvement or fungal dissemination. Conclusion: A diagnosis of invasive pulmonary aspergillosis should always be borne in mind whenever one is dealing with recalcitrant lung infections even with subtle immunosuppression. Radiological investigations and serologic markers can be utilised for confirmation and prompt therapy.

  20. Bronchopulmonary allergic aspergillosis Aspergilosis broncopulmonar alérgica

    Directory of Open Access Journals (Sweden)

    Rodrigo Ramírez

    1990-03-01

    Full Text Available

    A series of well defined entitles associated with colonization or invasion by fungi of the genus Aspergillus are grouped under the term Aspergillosis; there are various modalities of pulmonary involvement, namely, extrinsec asthma, extrinsec allergic alveolitis, allergic bronchopulmonary aspergillosis, aspergilloma and an invasive form in debilitated terminal patients; besldes there exists a form of food poisoning. We report on the case of a 45 year-old asthmatic woman suffering from allerglc bronchopulmonary aspergillosis and sum. maryze the clinical and laboratory features of the different pulmonary forms of aspergillosis.

    El término Aspergllosis reúne una serle de entidades bien definidas, causadas por hongos del género Aspergillus. En este artículo se presenta el caso de una mujer de 45 años con aspergllosis broncopulmonar alérgica, atendida en el Hospital Universitario San Vicente de Paúl, de Medellín y se hace una somera revisión clínico-patológica de las diferentes formas de aspergllosis pulmonar.

  1. Disseminated aspergillosis attributable to Aspergillus deflectus in a springer spaniel.

    Science.gov (United States)

    Kahler, J S; Leach, M W; Jang, S; Wong, A

    1990-10-01

    Disseminated aspergillosis attributable to Aspergillus deflectus was diagnosed in a Springer Spaniel with lethargy, lameness, anorexia, weight loss, pyrexia, lymphadenopathy, hematuria, and urinary incontinence. Necropsy revealed granulomatous inflammation and numerous fungal hyphae in many organs. The conidial heads of the fungus have a characteristic briar-pipe appearance in culture.

  2. [Primitive aspergillosis of the posterior cerebral fossa in immunocompetent patient].

    Science.gov (United States)

    Seffar, M; Tligui, H; Kabbaj, H; Agoumi, A; Rifi, L; Alaoui, A E; Harmouch, A; Jiddane, M; Sefiani, S

    2011-03-01

    Cerebral aspergillosis arises in the great majority of cases during an invasive aspergillosis with hematogene scattering from the lung hurts. The cerebral, not rare location is one of the worse criteria forecast during the invasive aspergillosis. We report the case of patient who was hospitalized in the neurosurgery department for syndrome of increased intracranial pressure, hemiparesis and cerebellar syndrome in febrile context. The radiological exploration objectified a collection of the posterior fossa. A stereotactic biopsy was performed. It collected fragments biopsy and pus. The pathological and microbiological analysis allowed the identification of Aspergillus fumigatus. The originality of this observation comes from the rare location in the posterior fossa of aspergillosis and because the patient is immunocompetent and no primary location is found. The patient presents however a viral hepatitis B of fortuitous discovery. He is put under treatment by amphotericin B. The evolution is marked by meningitis comment-diversion. Antibiotics are prescribed, and then the patient is operated for total ablation of the tumor. He dies following an osmolar coma associated with thrombopenia and a secondary renal insufficiency due to his treatment by the amphotericin B.

  3. Conidial heads (Fruiting Bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis

    OpenAIRE

    Lanzarin, Luciana Depiere; Mariano,Livia Caroline Barbosa; Macedo,Maria Cristina Martins de Almeida; Batista, Marjorie Vieira; Duarte, Amaro Nunes

    2015-01-01

    Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman w...

  4. Efficacy of Posaconazole in a Murine Model of Central Nervous System Aspergillosis

    OpenAIRE

    Imai, Jackie K.; Singh, Gaurav; Clemons, Karl V.; Stevens, David A.

    2004-01-01

    Human central nervous system (CNS) aspergillosis has >90% mortality. We compared posaconazole with other antifungals for efficacy against murine CNS aspergillosis. All tested regimens of posaconazole were equivalent to those of amphotericin B and superior in prolonging survival and reducing CFU to those of itraconazole and caspofungin and to vehicle controls. No antifungal regimen effected cure. No toxicity was noted. Overall, posaconazole shows potential for treating CNS aspergillosis.

  5. Cutaneous Invasive Aspergillosis: Retrospective Multicenter Study of the French Invasive-Aspergillosis Registry and Literature Review.

    Science.gov (United States)

    Bernardeschi, Céline; Foulet, Francoise; Ingen-Housz-Oro, Saskia; Ortonne, Nicolas; Sitbon, Karine; Quereux, Gaëlle; Lortholary, Olivier; Chosidow, Olivier; Bretagne, Stéphane

    2015-07-01

    Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors aimed to provide prevalence data and a clinical and histologic description of cutaneous manifestations of primary cutaneous IA (PCIA) and secondary CIA (SCIA) in a unique clinical series of IA and present the results of an exhaustive literature review of CIA. Cases of proven and probable IA with cutaneous manifestations were retrospectively extracted from those registered between 2005 and 2010 in a prospective multicenter aspergillosis database held by the National Reference Center for Invasive Mycoses and Antifungals, Pasteur Institute, France. Patients were classified as having PCIA (i.e., CIA without extracutaneous manifestations) or SCIA (i.e., disseminated IA). Among the 1,410 patients with proven or probable IA, 15 had CIA (1.06%), 5 PCIA, and 10 SCIA. Hematological malignancies were the main underlying condition (12/15). Patients with PCIA presented infiltrated and/or suppurative lesions of various localizations not related to a catheter site (4/5), whereas SCIA was mainly characterized by disseminated papules and nodules but sometimes isolated nodules or cellulitis. Histologic data were available for 11 patients, and for 9, similar for PCIA and SCIA, showed a dense dermal polymorphic inflammatory infiltrate, with the epidermis altered in PCIA only. Periodic acid Schiff and Gomori-Grocott methenamine silver nitrate staining for all but 2 biopsies revealed hyphae compatible with Aspergillus. Aspergillus flavus was isolated in all cases of PCIA, with Aspergillus fumigatus being the most frequent species (6/10) in SCIA. Two out 5 PCIA cases were treated surgically. The 3-month survival rate was 100% and 30% for PCIA and SCIA, respectively. Our study is the largest adult series of CIA and provides complete clinical and histologic data for the disease. Primary cutaneous IA should be recognized early

  6. Imaging features of gastric invasive aspergillosis: A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dong Jin; Cho, Seung Hyun; Kim, Seong Hoon; Shin, Ji Yeol; Lee, Yil Gi [Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2012-05-15

    Invasive aspergillosis is an opportunistic infection that usually occurs in immunocompromised patients. Although there are a few rare reports of isolated invasive aspergillosis affecting the small intestine, isolated or disseminated gastric invasive aspergillosis is extremely rare. Herein, we report 2 cases of gastric invasive aspergillosis in a 72 year old woman and a 43 year old man; the woman had been recovering from ruptured left posterior communicating artery aneurysm, which presented as emphysematous gastritis and the man from acute subdural haemorrhage in the intensive care unit, which presented as a pseudoaneurysm on CT imaging.

  7. Nasal Aspergillosis in a Dog: A Case Report

    Directory of Open Access Journals (Sweden)

    Camilo Padilla Peñuela

    2014-07-01

    Full Text Available Nasal aspergillosis is a major chronic disease affecting the nostrils in dogs. Clinical sinology is typical in every chronic nasal disease. Epistaxis and occasional pain occurs. Rhinoscopic assessment of the area evidences findings associated with the pathology and allows collecting samples for cytology and culture. Systemic therapy with oral antifungals has had variable utility, but now it has been replaced by direct topical medication to the affected area. This article describes the case of a 4-years-old male dog, submitted to consultation by unilateral muco-bloody nasal discharge with a week of evolution. The patient was treated by another vet center with cyclonamine and vitamin K for a possible clotting disorder. After a series of tests that included rhinoscopy and fungal culture, nasal aspergillosis was diagnosed. Intranasal clotrimazole was applied twice and it allowed the resolution of the clinical signs.

  8. Role of inhaled amphotericin in allergic bronchopulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    I S Sehgal

    2014-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is an immunological pulmonary disorder caused by immune reactions mounted against the ubiquitous fungus Aspergillus fumigatus. The disease clinically manifests with poorly controlled asthma, hemoptysis, systemic manifestations like fever, anorexia and weight loss, fleeting pulmonary opacities and bronchiectasis. The natural course of the disease is characterized by repeated episodes of exacerbations. Almost 30-40% of the patients require prolonged therapy, which currently consists of corticosteroids and anti-fungal azoles; both these agents have significant adverse reactions. Amphotericin B administered via the inhaled route can achieve a high concentration in the small airways with minimal systemic side-effects. Nebulized amphotericin B has been used in the management of invasive pulmonary aspergillosis. The aim of this review is to study the utility of inhaled amphotericin in ABPA.

  9. Aspergillosis and proventricular impaction in an ostrich (Struthio camelus

    Directory of Open Access Journals (Sweden)

    Shahrzad Azizi

    2014-08-01

    Full Text Available Aspergillosis is the most common mycotic infection in a wide variety of bird and causes significant economic losses. The present study described concurrent occurrence of aspergillosis and proventricular impaction in a 4-year-old male ostrich. The bird had respiratory problems, coughing and anorexia. Postmortem examination revealed numerous greenish-white caseous foci, 0.5 to 1 cm in diameter distributed on the surfaces of the air sacs and throughout the lungs. In histopathological study, multifocal areas of caseous necrosis that surrounded by inflammatory cells including heterophils, lymphocytes and macrophages were present. Long branching septated hyphae were visible in the necrotic areas with hematoxylin and eosin and Periodic acid-Schiff staining. Thrombi were present in the blood vessels. The proventriculus was full of gravel.

  10. Chronic aspergillosis of the lungs: Unravelling the terminology and radiology

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Hedayati, V.; Patel, K. [King' s College Hospital NHS Foundation Trust, The Department of Radiology, King' s Health Partners, King' s College London, London (United Kingdom); Hansell, D.M. [The Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, London (United Kingdom)

    2015-10-15

    The propensity for Aspergillus spp. to cause lung disease has long been recognised but the satisfactory classification of these disorders is challenging. The problems caused by invasive disease in severely neutropenic patients, saprophytic infection of pre-existing fibrotic cavities and allergic reactions to Aspergillus are well documented. In contrast, a more chronic form of Aspergillus-related lung disease that has the potential to cause significant morbidity and mortality is under-reported. The symptoms of this form of Aspergillus infection may be non-specific and the radiologist may be the first to suspect a diagnosis of chronic pulmonary aspergillosis. The current review considers the classification conundrums in diseases caused by Aspergillus spp. and discusses the typical clinical and radiological profile of patients with chronic pulmonary aspergillosis. (orig.)

  11. Primary cutaneous aspergillosis due to Aspergillus flavus: a case report

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiang-qiang; LI Li; ZHU Min; ZHANG Chao-ying; WANG Jia-jun

    2005-01-01

    @@ Infections caused by opportunistic organisms which have been known as etiologic agents of disease become more and more frequent.Aspergillus spp. is one of the agents. Fungi of aspergillus genus are widely distributed in nature, particularly in the soil and in the decomposed vegetation. They are frequent opportunist pathogens in immunocompromised patients. The most frequent causative organisms that cause cutaneous aspergillosis are A.fumigatus and A.flavus.1-3 In this report, we present a case of primary cutaneous aspergillosis manifested by ulceration of the shank due to A. flavus. The patient had no deficiency of immunological status and severe disease associated with fungal infection. Excellent response was shown to anti-fungal therapy.

  12. Beware of the devastating pulmonary aspergillosis syndromes In certain environments

    LENUS (Irish Health Repository)

    Kooblall, M

    2016-02-01

    Nowadays with more stem cell transplants and immunosuppressive therapies there has been a rise in pulmonary aspergillosis syndromes. The following illustrates such a case. A 49 year old man had a past history of ankylosing spondylitis with a bilateral hip replacement. He was also on surveillance for a superficial bladder tumour since 2007. His chest x-ray in 2008 was normal. In 2010 his CXR showed patchy opacification in the right apex. CT thorax confirm fibrotic changes.

  13. Allergic bronchopulmonary aspergillosis treated successfully for one year with omalizumab

    OpenAIRE

    Collins J; de Vos G; Hudes G; Rosenstreich D

    2012-01-01

    Jennifer Collins,1 Gabriele deVos,2 Golda Hudes,2 David Rosenstreich21New York Eye and Ear Infirmary, New York, NY, 2Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USABackground: Current therapy for allergic bronchopulmonary aspergillosis (ABPA) uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF), but the...

  14. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    Science.gov (United States)

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  15. Childhood allergic bronchopulmonary aspergillosis presenting as a middle lobe syndrome

    OpenAIRE

    Shah, Ashok; Gera, Kamal; Panjabi, Chandramani

    2016-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is infrequently documented in children with asthma. Although collapse is not uncommon, middle lobe syndrome (MLS) as a presentation of ABPA is rather a rarity. A 9-year-old female child with asthma presented with increase in intensity of symptoms along with a right midzone patchy consolidation on a chest radiograph. In addition, an ill-defined opacity abutting the right cardiac border with loss of cardiac silhouette was noted. A right lateral vie...

  16. Pseudomembranous necrotizing tracheobronchial aspergillosis:an analysis of 16 cases

    Institute of Scientific and Technical Information of China (English)

    HUANG Hai-dong; LI Qiang; HUANG Yi; BAI Chong; WU Ning; WANG Qing; YAO Xiao-peng; CHEN Bin

    2012-01-01

    Background In our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA).In this study we analyzed the clinical data from patients with PNTA,so as to guide the diagnosis and treatment of the disease.@@Methods A total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009.Their clinical data,including the demographic information,clinical symptoms,imaging findings,bronchoscopy findings,treatment strategies and efficacy,and prognosis,were retrospectively analyzed.@@Results All 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focal airways.Nine patients (9/16,56.3%) had pulmonary and tracheobronchial tumors,5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors,and 2/16 (12.5%) had lung transplantation.The most common causes of PNTA included local radiotherapy (10/16,62.5%),repeated chemotherapy (7/16,43.8%) and recurrent intervention therapy by bronchoscope (4/16,25.0%).Aspergillus fumigatus was the most frequent pathogen (62.5%,10/16).The main clinical manifestations included progressive dyspnea (14/16,87.5%) and irritable cough (12/16,75.0%).The trachea was involved in 9/16 patients (56.3%),right main bronchus in 10/16 (62.5%).All 16 patients were treated with systemic anti-aspergillosis agents,local anti-aspergillosis agents with amphotedcin B inhalation and direct perfusion of amphotericin B by bronchoscope,and interventional treatment by bronchoscope to ensure an unobstructed airway.The total efficiency was 31.3%.@@Conclusions PNTA is an infectious disease caused by aspergillus and it mainly involves the trachea,primary bronchus and segmental bronchus.A.fumigatus is the most common pathogen.PNTA can pose a severe clinical threat and often occurs after systemic immunodeficiency and

  17. Chronic invasive aspergillosis of paranasal sinuses: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Avinash P Tamgadge

    2012-01-01

    Full Text Available Aspergillosis of the nasal and paranasal sinuses is recognized as being second to candidiasis, among opportunistic fungal infections in immunocompromised patients. However, invasive variant in normal and mildly immunocompromised hosts is a very rare occurrence. We report one such case of aspergillosis involving paranasal sinuses in mildly immunocompromised patient.

  18. [Esophageal aspergillosis in a patient with acute myelogenous leukemia and febrile neutropenia].

    Science.gov (United States)

    Besa, Santiago; Kattan, Eduardo; Cid, Ximena; Claro, Juan C

    2014-04-01

    Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients.

  19. Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations

    Science.gov (United States)

    Sabou, Marcela; Lannes, Béatrice; Cotton, François; Meyronet, David; Galanaud, Damien; Cottier, Jean-Philippe; Grand, Sylvie; Desal, Hubert; Kreutz, Julie; Schenck, Maleka; Meyer, Nicolas; Schneider, Francis; Dietemann, Jean-Louis; Koob, Meriam

    2016-01-01

    Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection. PMID:27097323

  20. Allergic bronchopulmonary aspergillosis: a unique presentation in a pediatric patient

    Energy Technology Data Exchange (ETDEWEB)

    Huppmann, Michael V.; Monson, Matthew [Walter Reed Army Medical Center, Department of Radiology, Washington, DC (United States)

    2008-08-15

    Infection by the Aspergillus species of fungus can result in a variety of clinically and radiographically unique pulmonary diseases. The specific disease manifested is most dependent upon the immunocompetency of the infected individual. Allergic bronchopulmonary aspergillosis (ABPA) is most commonly seen in patients with asthma and cystic fibrosis. Since its original description in 1952, much has been published describing the radiographic manifestations of this disease. In this article, we present the unusual case of a 13-year-old whose initial radiographic presentation was that of a dense lobar consolidation. Additionally, we highlight the contributory role of the radiologist in guiding the appropriate clinical work-up and treatment of this disease. (orig.)

  1. Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

    OpenAIRE

    Seyedmousavi, Seyedmojtaba; Mouton, Johan W.; Melchers, Willem J. G.; Verweij, Paul E.

    2014-01-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effec...

  2. Standardization and characterization of antigens for the diagnosis of aspergillosis.

    Science.gov (United States)

    Stopiglia, Cheila Denise Ottonelli; Arechavala, Alicia; Carissimi, Mariana; Sorrentino, Julia Medeiros; Aquino, Valério Rodrigues; Daboit, Tatiane Caroline; Kammler, Luana; Negroni, Ricardo; Scroferneker, Maria Lúcia

    2012-04-01

    The aim of this study was to develop and characterize antigens for the diagnosis of aspergillosis. Nine strains of Aspergillus species Aspergillus fumigatus , Aspergillus flavus , and Aspergillus niger were grown in Sabouraud and Smith broth to produce exoantigens. The antigens were tested by immunodiffusion against sera from patients with aspergillosis and other systemic mycoses. The protein fraction of the antigens was detected by SDS-PAGE; Western blot and representative bands were assessed by mass spectrometry coupled to a nano Acquity UltraPerformance LC and analyzed by the Mascot search engine. Concurrently, all sera were tested with Platelia Aspergillus EIA. The most reactive antigens to sera from patients infected by A. fumigatus were produced by A. fumigatus MG2 Sabouraud and pooled A. fumigatus Sabouraud samples, both with a sensitivity of 93% and specificity of 100% and 97%, respectively. Aspergillus niger and A. flavus antigens were reactive against A. niger and A. flavus sera, each one with a sensitivity and specificity of 100%. Two proteins, probably responsible for antigenic activity, β-glucosidase in A. fumigatus and α-amylase in A. niger were attained. The commercial kit had a specificity of 22%, sensitivity of 100%, positive predictive value of 48%, and negative predictive value of 100%. The antigens produced showed high sensitivity and specificity and can be exploited for diagnostics of aspergilloma.

  3. Allergic bronchopulmonary aspergillosis: a rare cause of pleural effusion.

    LENUS (Irish Health Repository)

    O'Connor, T M

    2012-02-03

    Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis, and is characterized by hypersensitivity to chronic colonization of the airways with A. fumigatus. We report the case of a patient with ABPA presenting with pleural effusion. A 27-year-old male was referred with recurrent right pleural effusion. Past medical history was remarkable for asthma, allergic sinusitis, and recurrent pleurisy. Investigations revealed peripheral eosinophilia with elevated serum immunoglobulin E and bilateral pleural effusions with bilateral upper lobe proximal bronchiectasis. Precipitating serum antibodies to A. fumigatus were positive and the A. fumigatus immediate skin test yielded a positive reaction. A diagnosis of ABPA associated with bilateral pleural effusions was made and the patient was commenced on prednisolone. At review, the patient\\'s symptoms had considerably improved and his pleural effusions had resolved. ABPA may present with diverse atypical syndromes, including paratracheal and hilar adenopathy, obstructive lung collapse, pneumothorax and bronchopleural fistula, and allergic sinusitis. Allergic bronchopulmonary aspergillosis is a rare cause of pleural effusion and must be considered in the differential diagnosis of patients presenting with a pleural effusion, in particular those with a history of asthma.

  4. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections

    Directory of Open Access Journals (Sweden)

    Donnelley MA

    2016-06-01

    Full Text Available Monica A Donnelley,1,2 Elizabeth S Zhu,1 George R Thompson 3rd3 1Department of Inpatient Pharmacy, University of California – Davis, Sacramento, 2Department of Clinical Sciences, Touro University College of Pharmacy, Vallejo, 3Department of Medicine, Division of Infectious Diseases, University of California – Davis, Davis, CA, USAAbstract: We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole’s broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy. Keywords: isavuconazonium, antifungal, zygomycosis, mucor, mould infection, pharmacokinetics, pharmacodynamics, clinical efficacy, therapy, new agent

  5. Mycological and serological study of pulmonary aspergillosis in central India

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    Kurhade A

    2002-01-01

    Full Text Available PURPOSE: To study the prevalence and predisposing factors of Aspergillus infection and correlate microscopic, culture and serological findings along with drug sensitivity. METHODS: Sputum samples from 123 patients of pulmonary disease with clinical suspicion of having fungal, especially Aspergillus infections, were examined microscopically and for culture. Minimum inhibitory concentration (MIC of itraconazole was tested against the isolates. Serum samples from these patients were tested for precipitin against Aspergillus antigen using immunodiffusion (ID technique. RESULTS: Aspergillus species were isolated in 20 (16.26% cases and Aspergillus fumigatus was the predominant species isolated in 16 (80% cases. Precipitins were detected in 29 (23.58% cases. Serum samples collected from 50 healthy individuals to serve as controls showed no precipitin against Aspergillus antigen galactomannan. This fungus was found to be sensitive to itraconazole with MIC range 0.125-1µg/mL. CONCLUSIONS: Serological tests have an edge over routine smear and culture methods for the diagnosis of pulmonary aspergillosis. Itraconazole is more effective than amphotericin B and fluconazole in the treatment of aspergillosis.

  6. Case report: allergic bronchopulmonary aspergillosis and allergic fungal sinusitis successfully treated with voriconazole.

    Science.gov (United States)

    Erwin, Gary E; Fitzgerald, John E

    2007-12-01

    Allergic bronchopulmonary aspergillosis and allergic fungal sinusitis are closely related disorders that rarely present in the same individual. The mainstay of treatment for allergic bronchopulmonary aspergillosis is systemic corticosteroids. Itraconazole is used as adjunctive therapy in refractory cases. Allergic fungal sinusitis requires initial sinus surgery followed by systemic steroids. Antifungal therapy has not proven to be beneficial in allergic fungal sinusitis. We report a case of concomitant allergic bronchopulmonary aspergillosis and allergic fungal sinusitis that was refractory to standard therapy but had dramatic clinical response following treatment with voriconazole.

  7. Efficacy of Orally Delivered Cochleates Containing Amphotericin B in a Murine Model of Aspergillosis

    OpenAIRE

    Delmas, G.; Park, S.; Chen, Z W; Tan, F.; Kashiwazaki, R.; Zarif, L.; Perlin, D. S.

    2002-01-01

    Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.

  8. Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis.

    Science.gov (United States)

    Delmas, G; Park, S; Chen, Z W; Tan, F; Kashiwazaki, R; Zarif, L; Perlin, D S

    2002-08-01

    Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.

  9. Efficacy of PTX3 and Posaconazole Combination in a Rat Model of Invasive Pulmonary Aspergillosis

    OpenAIRE

    Marra, Emanuele; Sousa, Vitor L.; Gaziano,Roberta; Pacello, M. Lucrezia; Arseni, Brunilde; Aurisicchio, Luigi; De Santis, Rita; Salvatori, Giovanni

    2014-01-01

    Posaconazole is currently used for the prophylaxis of invasive pulmonary aspergillosis (IPA). Limitations to posaconazole usage are drug-drug interactions and side effects. PTX3 is an innate immunity glycoprotein with opsonic activity, proven to be protective in IPA animal models. This study investigated the combination of posaconazole with PTX3. The results indicate synergy between PTX3 and posaconazole against aspergillosis, suggesting that a combination of reduced doses of posaconazole wit...

  10. Opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis.

    Science.gov (United States)

    Perusquía-Ortiz, Ana María; Vázquez-González, Denisse; Bonifaz, Alexandro

    2012-09-01

    Opportunistic filamentous mycoses are widely distributed all over the world. They are rarely observed in Europe but are common in developing countries. The most common are the aspergilloses (due to Aspergillus spp.) mostly in neutropenia and immunosuppression; the mucormycoses characterized by rapid progression in patients with diabetic ketoacidosis; the phaeohyphomycoses due to pigmented fungi causing either a mild superficial or a very serious deep disease and the hyalohyphomycoses due to hyaline filamentous fungi (Fusarium spp., Pseudallescheria spp., Scopulariopsis spp.). Cutaneous manifestations are usually secondary to dissemination from pulmonary or visceral disease; primary cases are less frequent and due to direct inoculation into the skin. We review epidemiological, clinical, diagnostic, and therapeutic data on the four most important opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis.

  11. [Pharmacology of the antifungals used in the treatment of aspergillosis].

    Science.gov (United States)

    Azanza, José Ramón; Sádaba, Belén; Gómez-Guíu, Almudena

    2014-01-01

    The treatment of invasive aspergillosis requires the use of drugs that characteristically have complex pharmacokinetic properties, the knowledge of which is essential to achieve maximum efficacy with minimal risk to the patient. The lipid-based amphotericin B formulations vary significantly in their pharmacokinetic behaviour, with very high plasma concentrations of the liposomal form, probably related to the presence of cholesterol in their structure. Azoles have a variable absorption profile, particularly in the case of itraconazole and posaconazole, with the latter very dependent on multiple factors. This may also lead to variations in voriconazole, which requires considering the possibility of monitoring plasma concentrations. The aim of this article is to review some of the most relevant aspects of the pharmacology of the antifungals used in the prophylaxis and treatment of the Aspergillus infection. For this reason, it includes the most relevant features of some of the azoles normally prescribed in this infection (itraconazole, posaconazole and voriconazole) and the amphotericin B formulations.

  12. [An unusual cause of acute respiratory distress: obstructive bronchial aspergillosis].

    Science.gov (United States)

    Margery, J; Perez, J-P; Vaylet, F; Bordier, E; Dot, J-M; Saint-Blancard, P; Bonnichon, A; Guigay, J; Pats, B; L'Her, P

    2004-06-01

    We report the case of a 77-Year-old immunocompetent woman who required intensive care for acute dyspnea revealing complete atelectasia of the left lung related to an aspergillus mycelium plug blocking the principal bronchus. The clinical course was favorable after deobstruction by thermocoagulation and oral itraconazole given for six Months. The patient was free of parenchymatous or endobronchial sequelae. Adjuvant oral corticoid therapy was given temporarily during the second Month of treatment when signs of transition towards allergic aspergillosis developed. Four Months after discontinuing the antifungal treatment, the patient developed a new episode of acute dyspnea caused by atelectasia limited to the right lower lobe. Treatment by itraconazole was resumed and continued as long-term therapy. No recurrence has been observed for eighteen Months. The diagnostic and therapeutic problems raised by Aspergillus fumigatus are well known in the immunocompromised subject, but can also be encountered in the immunocompetent subject.

  13. Allergic bronchopulmonary aspergillosis in an adult with Kartagener syndrome.

    Science.gov (United States)

    Sehgal, Inderpaul Singh; Dhooria, Sahajal; Bal, Amanjit; Agarwal, Ritesh

    2015-08-06

    Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder resulting from immune responses directed against inhaled Aspergillus fumigatus antigens. It manifests with poorly controlled asthma, fleeting pulmonary opacities and structural lung damage in the form of bronchiectasis. Initially defined in individuals suffering from bronchial asthma and cystic fibrosis, it has also been described in patients with other structural lung disorders such as chronic obstructive pulmonary disease, pulmonary tuberculosis, idiopathic bronchiectasis and others. Kartagener syndrome is a manifestation of primary ciliary dyskinesia characterised by the presence of dextrocardia, bronchiectasis and chronic sinusitis. We report a case of ABPA in an adult suffering from Kartagener syndrome. We also performed a systematic review of the literature on the association between Kartagener syndrome and ABPA.

  14. Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Frederic eLamoth

    2015-02-01

    Full Text Available Invasive aspergillosis (IA is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B or cell wall (echinocandins are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90, an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.

  15. Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis.

    Science.gov (United States)

    Seyedmousavi, Seyedmojtaba; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E

    2015-03-01

    We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effective in A. fumigatus with posaconazole MICs of ≤0.5 mg/liter, where 100% survival was reached. However, breakthrough infection was observed in mice infected with the isolate for which the posaconazole MIC was >16 mg/liter.

  16. Post-influenza aspergillosis, do not underestimate influenza B

    Science.gov (United States)

    Nulens, Eric FL; Bourgeois, Marc JC; Reynders, Marijke BML

    2017-01-01

    Our objective is to highlight and focus on post-influenza aspergillosis, triggered by influenza B virus. This relatively new clinical entity is often associated with a fulminant course of respiratory decline and high mortality. A 51-year immunocompetent woman, without any medical history or risk factors for developing a complicated influenza infection, was admitted to the intensive care unit. During admission, she presented with an afebrile flu-like syndrome, myocarditis, rhabdomyolysis, multiple organ failure, and evolved to severe respiratory distress. The broncho-alveolar lavage contained influenza B RNA, and the culture revealed Aspergillus fumigatus. Despite maximal organ support, immunoglobulin, antiviral and antifungal therapy, the patient died. This case demonstrates that influenza B virus may be life threatening even to immunocompetent adults and may trigger an invasive Aspergillus superinfection.

  17. Allergic bronchopulmonary aspergillosis treated successfully for one year with omalizumab

    Directory of Open Access Journals (Sweden)

    Collins J

    2012-11-01

    Full Text Available Jennifer Collins,1 Gabriele deVos,2 Golda Hudes,2 David Rosenstreich21New York Eye and Ear Infirmary, New York, NY, 2Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USABackground: Current therapy for allergic bronchopulmonary aspergillosis (ABPA uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF, but there is little information on its efficacy against ABPA in patients with bronchial asthma without CF.Objective: To examine the effects of omalizumab, measured by asthma control, blood eosinophilia, total serum immunoglobulin E (IgE, oral corticosteroid requirements, and forced expiratory volume spirometry in patients with ABPA and bronchial asthma.Methods: A retrospective review of charts from 2004–2006 of patients treated with omalizumab at an academic allergy and immunology practice in the Bronx, New York were examined for systemic steroid and rescue inhaler usage, serum immunoglobulin E levels, blood eosinophil counts, and asthma symptoms, as measured by the Asthma Control Test (ACT.Results: A total of 21 charts were screened for the diagnosis of ABPA and bronchial asthma. Four patients with ABPA were identified; two of these patients were male. The median monthly systemic corticosteroid use at 6 months and 12 months decreased from baseline usage. Total serum IgE decreased in all patients at 12 months of therapy. Pre-bronchodilator forced expiratory vital capacity at one second (FEV1 was variable at 1 year of treatment. There was an improvement in Asthma Control Test (ACT symptom scores for both daytime and nighttime symptoms.Conclusions: Treatment with omalizumab creates a steroid-sparing effect, reduces systemic inflammatory markers, and results in improvement in ACT scores in patients with ABPA.Keywords: allergic bronchopulmonary aspergillosis

  18. Conidial heads (Fruiting Bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis

    Science.gov (United States)

    Lanzarin, Luciana Depiere; Mariano, Livia Caroline Barbosa; Macedo, Maria Cristina Martins de Almeida; Batista, Marjorie Vieira

    2015-01-01

    Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman who was submitted to autologous hematopoietic stem cell transplantation in the pursuit of multiple myeloma treatment. The post-transplantation period was troublesome with the development of severe neutropenia, human respiratory syncytial virus pneumonia, and disseminated aspergillosis, which was suspected because of a positive serum galactomannan antigen determination, and resulted in a fatal outcome. The autopsy findings showed diffuse alveolar damage associated with angioinvasive pulmonary aspergillosis with numerous hyphae and conidial heads in the lung parenchyma histology. The authors call attention to the aid of autopsy in confirming the diagnosis of this deep mycosis, since only the research of the galactomannan antigen may be insufficient and uncertain due to its specificity and of the possibility of false-positive results. PMID:26894041

  19. Chronic necrotizing pulmonary aspergillosis presenting as bilateral pleural effusion: a case report

    Directory of Open Access Journals (Sweden)

    Rajalingham Sakthiswary

    2012-02-01

    Full Text Available Abstract Introduction Chronic necrotizing pulmonary aspergillosis is an uncommon subacute form of Aspergillus infection. It typically occurs in immunocompromised individuals and in those with underlying lung disease. This interesting case highlights the occurrence of this entity of aspergillosis in an immunocompetent middle-aged woman with atypical radiological findings. To the best of our knowledge this is the first case report of chronic necrotizing pulmonary aspergillosis presenting with pleural effusion. Case presentation Our patient was a 64-year-old Malay woman with a background history of epilepsy but no other comorbidities. She was a lifelong non-smoker. She presented to our facility with a six-month history of productive cough and three episodes of hemoptysis. An initial chest radiograph showed bilateral pleural effusion with bibasal consolidation. Bronchoscopy revealed a white-coated endobronchial tree and bronchoalveolar lavage culture grew Aspergillus niger. A diagnosis of chronic necrotizing pulmonary aspergillosis was made based on the clinical presentation and microbiological results. She responded well to treatment with oral itraconazole. Conclusions The radiological findings in chronic necrotizing pulmonary aspergillosis can be very diverse. This case illustrates that this condition can be a rare cause of bilateral pleural effusion.

  20. Economic considerations in the treatment of invasive aspergillosis: a review of voriconazole pharmacoeconomic studies

    Directory of Open Access Journals (Sweden)

    Kem P Krueger

    2009-08-01

    Full Text Available Kem P Krueger, A Christie NelsonSchool of Pharmacy, University of Wyoming, Laramie, WY, USAAbstract: Invasive aspergillosis is a life-threatening fungal infection predominately affecting immunocompromised individuals. The incidence of inpatient-treated aspergillosis cases in the US is estimated to be between 3.02 and 3.80 per 10,000 hospitalized patients. The estimated difference in hospital costs of patients with an aspergillosis infection is US$36,867 to US$59,356 higher than those of patients without the infection. Voriconazole is a synthetic, broad spectrum triazole antifungal agent, with FDA-approved indications for the treatment of invasive aspergillosis, esophageal candidiasis, candidemia in nonneutropenic patients, invasive candidiasis, and infections due to Scedosporium apiospermum and Fusarium species in patients refractory to or intolerant of other therapy. Eight cost-effectiveness analyses, one cost-minimization analysis, and one cost analysis were identified from a Medline search. The 10 pharmacoeconomic analyses were conducted in six different countries comparing voriconazole to conventional amphotericin B, liposomal amphotericin B, itraconazole, and caspofungin. All the cost-effectiveness and cost-minimization analyses identified voriconazole as the most cost-effective therapy. The cost analysis demonstrated voriconazole cost-savings. While the acquisition costs of voriconazole are higher than those of conventional amphotericin B, the toxicity profile and rate of treatment success associated with voriconazole result in lower total treatment costs per successfully treated patient.Keywords: voriconazole, antifungal agents, invasive aspergillosis, pharmacoeconomics 

  1. Immunoproteome of Aspergillus fumigatus Using Sera of Patients with Invasive Aspergillosis

    Directory of Open Access Journals (Sweden)

    Emylli D. Virginio

    2014-08-01

    Full Text Available Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of Platelia™ Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS. A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units.

  2. INCIDENCE DENSITY, PROPORTIONATE MORTALITY, AND RISK FACTORS OF ASPERGILLOSIS IN MAGELLANIC PENGUINS IN A REHABILITATION CENTER FROM BRAZIL.

    Science.gov (United States)

    Silva Filho, Rodolfo Pinho da; Xavier, Melissa Orzechowski; Martins, Aryse Moreira; Ruoppolo, Valéria; Mendoza-Sassi, Raúl Andrés; Adornes, Andréa Corrado; Cabana, Ângela Leitzke; Meireles, Mário Carlos Araújo

    2015-12-01

    Aspergillosis, an opportunistic mycosis caused by the Aspergillus genus, affects mainly the respiratory system and is considered one of the most significant causes of mortality in captive penguins. This study aimed to examine a 6-yr period of cases of aspergillosis in penguins at the Centro de Recuperação de Animais Marinhos (CRAM-FURG), Rio Grande, Brazil. A retrospective cohort study was conducted using the institution's records of penguins received from January 2004 to December 2009. Animals were categorized according to the outcome "aspergillosis," and analyzed by age group, sex, oil fouling, origin, prophylactic administration of itraconazole, period in captivity, body mass, hematocrit, and total plasma proteins. A total of 327 Magellanic penguins (Spheniscus magellanicus) was studied, 66 of which died of aspergillosis. Proportionate mortality by aspergillosis was 48.5%, and incidence density was 7.3 lethal aspergillosis cases per 100 penguins/mo. Approximately 75% of the aspergillosis cases occurred in penguins that had been transferred from other rehabilitation centers, and this was considered a significant risk factor for the disease. Significant differences were also observed between the groups in regard to the period of time spent in captivity until death, hematocrit and total plasma proteins upon admission to the center, and body mass gain during the period in captivity. The findings demonstrate the negative impacts of aspergillosis on the rehabilitation of Magellanic penguins, with a high incidence density and substantial mortality.

  3. Childhood allergic bronchopulmonary aspergillosis presenting as a middle lobe syndrome.

    Science.gov (United States)

    Shah, Ashok; Gera, Kamal; Panjabi, Chandramani

    2016-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is infrequently documented in children with asthma. Although collapse is not uncommon, middle lobe syndrome (MLS) as a presentation of ABPA is rather a rarity. A 9-year-old female child with asthma presented with increase in intensity of symptoms along with a right midzone patchy consolidation on a chest radiograph. In addition, an ill-defined opacity abutting the right cardiac border with loss of cardiac silhouette was noted. A right lateral view confirmed a MLS, which was further corroborated by high resolution computed tomography. Central bronchiectasis was also observed, which prompted a work-up for ABPA. The child met 7/8 major diagnostic criteria for ABPA. She was then initiated on oral prednisolone that resulted in a marked clinical improvement within a fortnight. Radiological clearance occurred at 3 months with inflation of the middle lobe. ABPA presenting with MLS in a child is yet to be reported. A high index of suspicion is required to establish the diagnosis of ABPA in a child presenting with MLS. This would obviate the invasive investigations usually done to ascertain the cause of MLS.

  4. Primary diagnostic approaches of invasive aspergillosis--molecular testing.

    Science.gov (United States)

    Bretagne, Stéphane

    2011-04-01

    The PCR methods published for the diagnosis of invasive aspergillosis (IA) are diverse in terms of amplification protocols and methods, equipment, fluorescent detection dyes, PCR chemistries, and clinical specimens used. This explains why PCR is still not included in the revised EORTC/MSG definitions of IA despite encouraging results. Therefore, achieving consensual PCR procedures at the international level is mandatory. When using PCR as a diagnostic tool, emphasis must be put on limiting false positive results due to contamination either with previously amplified products or with environmental commensals. Internal amplification controls are compulsory to evidence false negative results. For most of these aspects, quantitative PCR (qPCR) should improve both the results' reliability and the clinicians' confidence. A checklist of items (Minimum information for publication of quantitative real-time PCR experiments) has been proposed to help scientists and reviewers. Currently, the main limitation relies in the DNA extraction procedure the choice of which dramatically depends on the still unknown origin of the Aspergillus DNA to amplify. There is an urgent need for basic studies to elucidate the origin and kinetics of Aspergillus DNA in blood. Once a technical consensus is achieved, clinical studies should be initiated to integrate qPCR in the diagnostic armentarium of IA.

  5. Sinonasal aspergillosis in a British Shorthair cat in the UK

    Directory of Open Access Journals (Sweden)

    Alice Tamborini

    2016-06-01

    Full Text Available Case summary A 13-year-old, castrated male, British Shorthair cat presented for investigation of chronic, intermittent, bilateral epistaxis and stertor. CT revealed severe asymmetric bilateral intranasal involvement with extensive turbinate lysis, increased soft tissue attenuation and lysis of the sphenopalatine bone and cribriform plate. On retroflexed pharyngoscopy, a plaque-like mass occluded the choanae. Rostral rhinoscopic examination revealed extensive loss of nasal turbinates, necrotic tissue and mucosal fungal plaques in the left nasal cavity. The right nasal cavity was less severely affected. The nasal cavities were debrided extensively of plaques and necrotic tissue. Aspergillus fumigatus was isolated on fungal culture, and species identity was confirmed using comparative sequence analysis of the partial β-tubulin gene. On histopathology of nasal biopsies, there was ulcerative lymphoplasmacytic and neutrophilic rhinitis, and fungal hyphae were identified on nasal mucosa, consistent with a non-invasive mycosis. The cat was treated with oral itraconazole after endoscopic debridement, but signs relapsed 4.5 months from diagnosis. Residual left nasal fungal plaques were again debrided endoscopically and oral posaconazole was administered for 6 months. Fourteen months from diagnosis, the cat remains clinically well with mild intermittent left nasal discharge secondary to atrophic rhinitis. Relevance and novel information This is the first case of rhinoscopically confirmed sinonasal aspergillosis to be diagnosed in a cat in the UK. Endoscopic confirmation of resolution of infection is useful in cases where mild nasal discharge persists after treatment.

  6. Visual loss due to paranasal sinus invasive aspergillosis in a diabetic patient.

    Science.gov (United States)

    Rallis, George; Gkinis, George; Dais, Panayotis; Stathopoulos, Panagiotis

    2014-01-01

    Aspergillus species are commonly found in the soil and decaying organic matter. The spores can be typically inhaled or ingested, yet disease due to tissue invasion is rarely seen in the immunocompetent host. In the immunocompromised patient, there has been an increased incidence of invasive aspergillosis in the last 20 years. Invasive aspergillosis of the maxillary sinus with orbital and cranial spread can be lethal, therefore, necessitates early diagnosis and prompt treatment. The predilection of Aspergillus for infiltration of blood vessels can result in serious ocular complications which can lead to loss of vision. We present the case of an uncontrolled diabetic patient with invasive maxillary sinus aspergillosis and extension to the orbital contents. Our purpose was to emphasize the need of early recognition and prompt initiation of combined antifungal treatment and surgical intervention with the intent to preserve the involved vital structures.

  7. CLINICAL AND PATHOLOGICAL FINDINGS OF ASPERGILLOSIS IN MAGELLANIC PENGUINS (Spheniscus magellanicus

    Directory of Open Access Journals (Sweden)

    MELISSA ORZECHOWSKI XAVIER

    2011-09-01

    Full Text Available We studied a series of fifteen fatal cases of aspergillosis in penguins (Spheniscus magellanicus, seen over a 4-year period at a rehabilitation center in Southern Brazil. The clinical and pathological findings based on the lesions found at necropsy are described herein. The majority of animals (11/15 had sudden death without clinical signs. In 33.3% (5/15 of the cases, aspergillosis was restricted to the respiratory system and 66.6% showed disseminateddisease, with liver, kidney, adrenal gland and gastrointestinal tract involvement. Typical lesions were characterized as white-yellowish granulomatous nodules. To the best of our knowledge, this is the largest series of aspergillosis cases described in penguins in SouthAmerica.

  8. Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons

    Directory of Open Access Journals (Sweden)

    Walter Tarello

    2011-01-01

    Full Text Available The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (=36 or multiple coinfections (=28. Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS (=29, Caryospora sp. (=16, Serratospiculum seurati infestation (=14, cestodiasis (=6, bumblefoot (=5, trematodosis due to Strigea falconispalumbi (=5, trichomoniasis (=4, Babesia shortti (=4, Mannheimia (Pastorella haemolytica (=4, interstitial hepatitis (=4, Escherichia coli (=3, and Clostridium perfringens enterotoxemia (=2. Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  9. Invasive aspergillosis in a user of inhaled cocaine: rhinosinusitis with bone and cartilage destruction

    Directory of Open Access Journals (Sweden)

    Luna Azulay-Abulafia

    2014-07-01

    Full Text Available Aspergillosis is an infection caused by saprophytic fungi of the genus Aspergillus, which typically occurs in immunosuppressed individuals, but has also been reported in immunocompetent patients. The main routes of entry are the respiratory tract, skin, cornea, and ear, and the infection may be localized or disseminated by contiguity or vascular invasion. We report a severe case of rhinosinusitis with cutaneous involvement, caused by invasive aspergillosis, in an immunocompetent user of inhaled cocaine. Invasive aspergillosis related to cocaine abuse has not yet been reported in the literature. After itraconazole treatment and surgical debridement, complete clinical remission was achieved. Nasal reconstruction with a skin graft over a silicone prosthesis resulted in a satisfactory esthetic outcome.

  10. Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic aspergillosis.

    Science.gov (United States)

    Oliva, A; Flori, P; Hennequin, C; Dubus, J-C; Reynaud-Gaubert, M; Charpin, D; Vergnon, J M; Gay, P; Colly, A; Piarroux, R; Pelloux, H; Ranque, S

    2015-01-01

    Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method.

  11. MR imaging of cerebral aspergillosis in an infant with normal-immunity : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ji Yeoun; Choi, Jin Ok; Lee, Kang Soo; Chae, Soo Hyun; Joo, Myung Jin [Presbyterian Medical Center, Chunju (Korea, Republic of)

    2000-04-01

    Cerebral aspergillosis is a rare condition, and like other opportunistic fungal infections, it most commonly occurs in immunocompromised patients. Because of the increasing use of chemotherapy in organ transplantation, cases involving neoplasms, corticosteroid therapy, and cases of lymphoma and leukemia, the incidence of fungal infections in the brain has recently increased. Cerebral aspergillosis in an infant with normal immunity is a very rare condition, and has not been reported in Korea. We report the MR findings of this condition in an infant with normal immunity. (author)

  12. Pleuritis clinically diagnosed as aspergillosis during the course of microscopic polyangiitis.

    Science.gov (United States)

    Kimoto, Yasutaka; Oryoji, Kensuke; Uchino, Ayumi; Yoshizawa, Shigeru; Niiro, Hiroaki; Tsukamoto, Hiroshi; Horiuchi, Takahiko

    2014-01-01

    Pleural aspergillosis is a rare fungal infection. We herein report a case of pleuritis clinically diagnosed as aspergillosis without apparent Aspergillus lung lesions. A 75-year-old man receiving immunosuppressive therapy due to microscopic polyangiitis was admitted for treatment of massive pleural effusion. Histology of the parietal pleura revealed septate hyphae. In addition, a hematological marker of Aspergillus indicated Aspergillus pleuritis. The pleural effusion resolved after administration of the voriconazole. The trigger for invasion of Aspergillus into the pleura was thought to be spontaneous pneumothorax, which had occurred five months earlier.

  13. Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid.

    Science.gov (United States)

    Kawazu, Masahito; Kanda, Yoshinobu; Goyama, Susumu; Takeshita, Masataka; Nannya, Yasuhito; Niino, Miyuki; Komeno, Yukiko; Nakamoto, Tetsuya; Kurokawa, Mineo; Tsujino, Shiho; Ogawa, Seishi; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Ohishi, Nobuya; Hirai, Hisamaru

    2003-01-01

    Polymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real-time PCR method to resolve this problem, and we report herein a successful application of real-time PCR to diagnose invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in bronchial lavage fluid from an affected area to that from an unaffected area. This novel tool will provide rapid, sensitive, and specific diagnosis of pulmonary aspergillosis.

  14. Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbaek, B.; Lind, Peter

    1996-01-01

    Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The supernatants of in vitro cultured hybridomas were in.......e., aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and-2) raised against the WF of A. fumigatus in ELISA and immunoblotting and immunohistochemical assays justify their application for the in situ diagnosis of systemic aspergillosis of cattle....

  15. Efficacy of PTX3 and posaconazole combination in a rat model of invasive pulmonary aspergillosis.

    Science.gov (United States)

    Marra, Emanuele; Sousa, Vitor L; Gaziano, Roberta; Pacello, M Lucrezia; Arseni, Brunilde; Aurisicchio, Luigi; De Santis, Rita; Salvatori, Giovanni

    2014-10-01

    Posaconazole is currently used for the prophylaxis of invasive pulmonary aspergillosis (IPA). Limitations to posaconazole usage are drug-drug interactions and side effects. PTX3 is an innate immunity glycoprotein with opsonic activity, proven to be protective in IPA animal models. This study investigated the combination of posaconazole with PTX3. The results indicate synergy between PTX3 and posaconazole against aspergillosis, suggesting that a combination of reduced doses of posaconazole with the immune response enhancer PTX3 might represent a treatment option with a higher therapeutic index than posaconazole.

  16. Pulmonary aspergillosis and aflatoxins in chronic lung diseases.

    Science.gov (United States)

    Ali, Sana; Malik, Abida; Shahid, Mohd; Bhargava, Rakesh

    2013-10-01

    Fungal infections of lung have become increasingly common during the last few decades. Aspergillosis and the role of aflatoxins in various chronic lung diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples and sera from 40 patients of chronic lung diseases were analyzed for galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay. Direct microscopy and culture of BAL samples were also done to detect the Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13 (86.7 %) patients were positive for galactomannan antigen also. About 62.5 % cases did not show growth of Aspergillus in BAL culture. However, galactomannan antigen could be detected in 20 % of these patients. Overall, 20 % patients were diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD, 17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and 53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5 % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their samples. Aflatoxin positivity was found to be more in patients with proven IFD than in probable IFD, and higher level of aflatoxins was detected in cases with proven IFD. Significant difference was observed in aflatoxin positivity among food grain workers when compared to other occupations.

  17. Renal infarction secondary to invasive aspergillosis in a 5-year-old girl with acute lymphoblastic leukemia.

    Science.gov (United States)

    Lee, Ju Hyun; Im, Soo Ah; Cho, Bin

    2014-07-01

    Aspergillus species have angioinvasive properties and can involve extrapulmonary organs by hematogenous spread from the lungs. However, renal involvement by Aspergillus is uncommon and is usually associated with the formation of abscesses. We report an unusual case of invasive renal aspergillosis presenting with extensive renal infarction in a 5-year-old girl with acute lymphoblastic leukemia. This case emphasizes the fact that renal aspergillosis initially presents with only renal infarction, and metastatic-embolism by invasive aspergillosis should be considered in differential diagnosis for any focal lesion of kidney in a patient with leukemia.

  18. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis.

    NARCIS (Netherlands)

    Mennink-Kersten, M.A.S.H.; Donnelly, J.P.; Verweij, P.E.

    2004-01-01

    The availability of the Platelia Aspergillus, a sandwich ELISA kit that detects circulating galactomannan, has been a major advance for managing patients at risk for invasive aspergillosis because of the early detection of the antigen. The assay is now widely used throughout the world, including the

  19. Early proinflammatory cytokines and C-reactive protein trends as predictors of outcome in invasive Aspergillosis.

    NARCIS (Netherlands)

    Chai, L.; Netea, M.G.; Teerenstra, S.; Earnest, A.; Vonk, A.G.; Schlamm, H.T.; Herbrecht, R.; Troke, P.F.; Kullberg, B.J.

    2010-01-01

    BACKGROUND: Monitoring treatment response in invasive aspergillosis is challenging, because an immunocompromised host may not exhibit reliable symptoms and clinical signs. Cytokines play a pivotal role in mediating host immune response to infection; therefore, the profiling of biomarkers may be an a

  20. Diagnostic and Therapeutic Challenges in a Liver Transplant Recipient with Central Nervous System Invasive Aspergillosis

    Science.gov (United States)

    Dionissios, Neofytos; Shmuel, Shoham; Kerry, Dierberg; Katharine, Le; Simon, Dufresne; Sean, Zhang X; Kieren, Marr A

    2012-01-01

    This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients. PMID:22676861

  1. Experimental and Clinical Studies on Invasive Pulmonary Aspergillosis: pathophysiology, diagnosis and management

    NARCIS (Netherlands)

    M.J. Becker (Martin)

    2004-01-01

    markdownabstract__Abstract__ Aspergillus is a saprofytic fungus that grows in humid environments on decaying organic matter. Its ability to adapt to a wide variability of conditions accounts for its worldwide distribution. Invasive aspergillosis (IA) is a disease characterised by invasion of normal

  2. Rapid diagnosis of azole-resistant aspergillosis by direct PCR using tissue specimens.

    NARCIS (Netherlands)

    Linden, J.W.M. van der; Snelders, E.; Arends, J.P.; Daenen, S.M.G.J.; Melchers, W.J.G.; Verweij, P.E.

    2010-01-01

    We report the use of PCR techniques on a formalin-fixed and paraffin-embedded tissue specimen for direct detection of one dominant azole resistance mechanism in a case of disseminated invasive aspergillosis. Rapid detection of mutations associated with azole resistance directly in tissue significant

  3. Rapid Diagnosis of Azole-Resistant Aspergillosis by Direct PCR Using Tissue Specimens

    NARCIS (Netherlands)

    van der Linden, Jan W. M.; Snelders, Eveline; Arends, Jan P.; Daenen, Simon M.; Melchers, Willem J. G.; Verweij, Paul E.

    2010-01-01

    We report the use of PCR techniques on a formalin-fixed and paraffin-embedded tissue specimen for direct detection of one dominant azole resistance mechanism in a case of disseminated invasive aspergillosis. Rapid detection of mutations associated with azole resistance directly in tissue significant

  4. Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands.

    NARCIS (Netherlands)

    Jansen, J.P.; Meis, J.F.G.M.; Blijlevens, N.M.A.; Wout, J.W. van 't

    2005-01-01

    OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was ev

  5. Aspirin induced asthma accompanied with allergic bronchopulmonary aspergillosis: a case report

    Institute of Scientific and Technical Information of China (English)

    TANG Rui; ZHANG Hong-yu

    2010-01-01

    @@ In this paper, we describe a patient with a rather severe form of aspirin-induced asthma (AIA) and allergic bronchopulmonary aspergillosis (ABPA). The patient is a man born in 1948, who first presented with rhinorrhea,nasal congestion and chronic urticaria, and had an episode of asthma after ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) for the further eight years.

  6. Radiological and clinical findings of pulmonary aspergillosis following solid organ transplant

    Energy Technology Data Exchange (ETDEWEB)

    Park, Y.S. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center (Korea, Republic of); Seo, J.B. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center (Korea, Republic of)], E-mail: seojb@amc.seoul.kr; Lee, Y.K. [Department of Radiology, Bundang CHA Hospital, University of Pocheon Jungmoon College of Medicine (Korea, Republic of); Do, K.H.; Lee, J.S.; Song, J.-W.; Song, K.S. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center (Korea, Republic of)

    2008-06-15

    Aim: To evaluate the radiological and clinical findings in patients with pulmonary aspergillosis after solid organ transplantation. Materials and methods: This study included 13 consecutive patients (five liver, four kidney, and four heart transplant; 10 male and three female; median age 54 years; range 13-63 years) with histologically confirmed pulmonary aspergillosis after solid organ transplantation at a tertiary referral hospital. Chest radiographs and computed tomography (CT) examinations performed for diagnosis were available in all patients. Radiological findings, such as lesion characteristics, location, and associated findings, were assessed retrospectively by two radiologists. The changes in radiological findings and clinical response after treatment were also assessed. Clinical findings, such as time of onset, initial symptoms, clinical course, and laboratory findings, were reviewed. Results: The most common radiographic and CT findings were pulmonary nodules or masses (n = 12). The number of nodules or masses was less than 10 in eight patients. Associated findings were surrounding ground-glass opacity (n = 4), central low density (n = 8), central air cavity (n = 5), and air bronchogram (n = 3). Follow-up radiographs and/or CT after treatment showed improvement in eight patients, persistence in two, and deterioration in three. The onset time of pulmonary aspergillosis was a median of 32 days (range 15-165 days). The most common symptom at diagnosis was fever (n = 6). Ten of 13 patients did not have leucopaenia. There were two aspergillosis-associated deaths during the follow-up period. Conclusion: The most common radiological finding of pulmonary aspergillosis after solid organ transplantation is multiple nodules or masses, which commonly appear within 1 month following transplantation.

  7. Investigation of dissemination of aspergillosis in poultry and possible control measures

    Directory of Open Access Journals (Sweden)

    Kapetanov Miloš C.

    2011-01-01

    Full Text Available Fungi belonging to genus Aspegillus are ubiquitous saprophytic microorganisms which are, in certain circumstances, responsible for clinical infections of respiratory tract in all poultry, particularly in young birds. In case of a lung form, Aspergillus fumigatus, A. niger and A. glaucus are the most frequently isolated fungi. In general, poultry is constantly exposed to these fungi in its environment. Predisposing factors, such as long exposition and highly contaminated environment and litter, high humidity in poultry houses, poor ventilation, malnutrition and stress, all contribute to clinical aspergillosis. Some geographic and seasonal regularities are observed in relation to the distribution of disease outbreaks. In this sense, cases of aspergillosis in our country were more frequently noted in wild areas located northern from the rivers Sava and Danube. Influence of some factors on the outbreak and spreading, as well as predominant clinical features of aspergillosis in poultry were investigated in this paper. Possible prophylactic and intervention measures were discussed. The occurrence of Aspergillus sp. in poultry was analyzed according to the clinical and laboratory investigations performed during the two selected years, 2000 and 2010. Widespread aspergillosis was noted in poultry flocks of different age, both in young and adult birds. During the years 2000 and 2010, acute aspergillosis was found in 12 and 16 commercial flocks of chickens and turkeys, respectively. Ocular infection with Aspergillus was determined in 10 day old broilers from two flocks. Aspergillus sp. was isolated from unhatched eggs (6.86%, litter (23.07%, environmental (36.17% and hatchery swabs (3.85%. Besides the appropriate antifungal therapy, enforcement of proper sanitary-hygiene measures on poultry farms and hatcheries, as well as microbiological control of feed are considered essential for an efficient control of infection and its spreading.

  8. Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia

    Directory of Open Access Journals (Sweden)

    Ursavas Ahmet

    2006-07-01

    Full Text Available Abstract Background Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. Case presentation We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. Conclusion This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.

  9. Quantitative galactomannan detection is superior to PCR in diagnosing and monitoring invasive pulmonary aspergillosis in an experimental rat model

    NARCIS (Netherlands)

    M.J. Becker (Martin); S. de Marie (Siem); D. Willemse; H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma)

    2000-01-01

    textabstractTwo diagnostic tests, an Aspergillus-specific PCR and an enzyme-linked immunosorbent assay (ELISA) for the quantitative determination of galactomannan, were compared for diagnosing and monitoring invasive pulmonary aspergillosis. Persistently neutropenic rat

  10. Intrapulmonary posaconazole penetration at the infection site in an immunosuppressed murine model of invasive pulmonary aspergillosis receiving oral prophylactic regimens

    NARCIS (Netherlands)

    Seyedmousavi Tasieh, S.; Bruggemann, R.J.M.; Melchers, W.J.G.; Verweij, P.E.; Mouton, J.W.

    2014-01-01

    Adequate penetration to the infection/colonization site is crucial to attain optimal efficacy of posaconazole against Aspergillus fumigatus diseases. We evaluated posaconazole exposure in pulmonary epithelial lining fluid (ELF) in a murine model of invasive pulmonary aspergillosis. The posaconazole

  11. Invasive pulmonary aspergillosis accompanied by soft tissue lesions during treatment of a patient with hyperthyroidism: a case report

    OpenAIRE

    Fan, Xiao-Yun; Wang, Wei-Min; Yan, Xue-Bo; Wang, Cong-Hui; Liu, Rong-Yu

    2015-01-01

    Invasive pulmonary aspergillosis (IPA) is difficult to diagnose because it requires histopathology and tissue culture, as well as due to its rapid progression. Invasive pulmonary aspergillosis is the primary cause of pulmonary mycosis in China, which can occur in patients with neutrophil deficiency, leukaemia or lymphoma, malignant tumours, or chronic obstructive pulmonary disease with long-term corticosteroid use or bacterial exacerbations. Such fungal infections can lead to disseminated dis...

  12. Invasive aspergillosis osteomyelitis in children - a case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Winterstein, Anton R.; Bohndorf, Klaus; Vollert, Kurt [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Wagner, Theodor [Klinikum Augsburg, Department of Pathology, Augsburg (Germany); Gnekow, Astrid [Klinikum Augsburg, Department of Pediatrics, Augsburg (Germany); Roemer, Frank W. [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Boston University School of Medicine, Department of Radiology, Boston, MA (United States)

    2010-08-15

    Immunocompromised patients are at high risk of secondary infection associated with high morbidity. In children these complications include fungal osteomyelitis due to continuous infiltration or hematogenous spread. The case of a 4-year-old boy is presented who developed lumbalgia and thigh pain during ongoing chemotherapy for acute lymphatic leukemia. MRI revealed infarct-like lesions in the femur and L5 vertebra, which were biopsied. The histologic diagnosis was consistent with angioinvasive aspergillosis. A multifocal osseous presentation has rarely been described in children and an overview of the literature is presented. Invasive aspergillosis is a rare complication to be considered in children with MRI-detected bony lesions of infarct-like appearance. (orig.)

  13. [Asthma, alveolitis, aspergillosis, berylliosis. What to do when there is allergic reaction of the lung?].

    Science.gov (United States)

    Vier, H; Protze, M; Brunner, R; Gillissen, A

    2003-03-06

    Among the major allergic pulmonary disorders are bronchial asthma, extrinsic allergic alveolitis, allergic aspergillosis and berylliosis. Asthma is diagnosed on the basis of clinical symptoms (wheezing, respiratory distress, tight chest, coughing) and lung function tests possibly supplemented by allergic and provocative testing. Asthma treatment is differentiated into long-term medication and as-required medication. Specific immunotherapy is considered the sole causal therapy. Extrinsic allergic alveolitis is work- or hobby-related (farmer's/cheese worker's/bird-fancier's lung) and manifests as diffuse pneumonitis with dyspnea, coughing and fever. For the diagnosis, the antigen provocative test in particular plays a major role. In the main, treatment comprises strict avoidance of allergens. The diagnosis of allergic pulmonary aspergillosis is based on the history, clinical findings, skin tests, serology and radiography. Treatment is stage-related by means of immunosuppressive agents. In terms of radiographic and pulmonary function findings, berylliosis is similar to sarcoidosis. Here, too, immunosuppressive agents are to the fore.

  14. Aspergillosis of bilateral breast and chest wall in an immunocompetent male masquerading as breast cancer

    Directory of Open Access Journals (Sweden)

    Jitendra G Nasit

    2013-01-01

    Full Text Available Fungal species are not frequently encountered in an immunocompetent host. Invasive aspergillosis typically occurs in severely immunocompromised patient. Aspergillus infection of breast and chest wall are rarely encountered in an immunocompetent as well as in immunocompromised host. Till date only 13 cases of fungal infection of breast and chest wall have been reported in the literature. This report presents a case of aspergillosis of bilateral breast and chest wall in an immunocompetent male, clinically mimicking breast cancer. Diagnosis was achieved by fine-needle aspiration cytology and subsequently Aspergillus flavus was identified on fungal culture. The patient was successfully treated with voriconazole. Prompt diagnosis by cytology and appropriate treatment is necessary to prevent adverse outcome. Here, we present this rare case of fungal infection of breast and chest wall with relevant review of the literature.

  15. Laboratory Diagnosis of Invasive Aspergillosis: From Diagnosis to Prediction of Outcome

    OpenAIRE

    Barton, Richard C.

    2013-01-01

    Invasive aspergillosis (IA), an infection caused by fungi in the genus Aspergillus, is seen in patients with immunological deficits, particularly acute leukaemia and stem cell transplantation, and has been associated with high rates of mortality in previous years. Diagnosing IA has long been problematic owing to the inability to culture the main causal agent A. fumigatus from blood. Microscopic examination and culture of respiratory tract specimens have lacked sensitivity, and biopsy tissue f...

  16. Pulmonary Aspergillosis in a Previously Healthy 13-Year-Old Boy

    Directory of Open Access Journals (Sweden)

    Jonathan H. Rayment

    2016-01-01

    Full Text Available Chronic granulomatous disease (CGD is a rare, polygenic primary immunodeficiency. In this case report, we describe a previously healthy 13-year-old boy who presented with multifocal pulmonary aspergillosis and was subsequently diagnosed with an autosomal recessive form of chronic granulomatous disease. CGD has a variable natural history and age of presentation and should be considered when investigating a patient with recurrent or severe infections with catalase-positive organisms.

  17. The Diagnosis of Invasive and Noninvasive Pulmonary Aspergillosis by Serum and Bronchoalveolar Lavage Fluid Galactomannan Assay

    Directory of Open Access Journals (Sweden)

    Shuzhen Zhang

    2015-01-01

    Full Text Available The incidence and mortality of invasive pulmonary aspergillosis (IPA are rising, particularly in critically ill patients and patients with severe chronic obstructive pulmonary disease (COPD. Noninvasive aspergillosis occurring in these patients requires special attention because of the possibility of developing subsequent IPA, given the poor health and worsened immune state of these patients. We compared the performance of the Platelia galactomannan (GM enzyme immunoassay in the bronchoalveolar lavage fluid (BALF and serum. The sensitivity, and specificity of BALF-GM were 85.4% and 62.4%, and those of serum-GM were 67.9% and 93.5% at the cutoff index of 0.5. As the cutoff index increased, the specificity of BALF-GM detection was increased with the detriment of sensitivity. The area under the ROC curves was 0.817 (95% CI: 0.718–0.916 for BALF-GM and 0.819 (95% CI: 0.712–0.926 for serum-GM. The optimal cutoff index was 1.19 for BALF-GM, and the sensitivity and specificity were 67.9% and 89.2%. The BALF-GM assay is more sensitive in detecting pulmonary aspergillosis than serum-GM assay and fungal cultures. However, BALF-GM assay has a high false-positive rate at the cutoff index of 0.5. Hence, the diagnostic cutoff index of the BALF-GM assay should be improved to avoid the overdiagnosis of pulmonary aspergillosis in clinic.

  18. Invasive aspergillosis in the aortic arch with infectious Aspergillus lesions in pulmonary bullae

    Directory of Open Access Journals (Sweden)

    Isao Watanabe

    2015-03-01

    Full Text Available A patient with pulmonary bullae died of massive hemoptysis. At autopsy a hole was observed in the aortic wall. A microscopic examination indicated small Aspergillus lesions in pulmonary bullae and extensive necrotic lesions with Aspergillus hyphae in the media of the thoracic aorta. These findings led to a diagnosis of invasive aspergillosis in the aortic arch. This is a rare case in which Aspergillus invaded the aorta in a patient without hematologic neoplasms or neutropenia.

  19. Aspergillosis in Intensive Care Unit (ICU patients: epidemiology and economic outcomes

    Directory of Open Access Journals (Sweden)

    Baddley John W

    2013-01-01

    Full Text Available Abstract Background Few data are available regarding the epidemiology of invasive aspergillosis (IA in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection. Methods Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005–2008. Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6 who received initial antifungal therapy (AF in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models. Results From 6,424 aspergillosis patients in the database, 412 (6.4% ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%, acute respiratory failure (76% and acute renal failure (41%. In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once. Mean length of stay (LOS was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p  Conclusions Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients.

  20. Non-invasive aspergillosis of the paranasal sinuses: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Robert, Y. [Service de Radiologie Ouest, Hopital Claude Huriez, 59 Lille (France); Lamy, O. [Service de Radiologie Ouest, Hopital Claude Huriez, 59 Lille (France); Chevalier, D. [Service d`Orl, Hopital Claude Huriez, 59 Lille (France); Rocourt, N. [Service de Radiologie Ouest, Hopital Claude Huriez, 59 Lille (France); Darras, J. [Service d`Orl, Hopital Claude Huriez, 59 Lille (France); Piquet, J.J. [Service d`Orl, Hopital Claude Huriez, 59 Lille (France); Lemaitre, L. [Service de Radiologie Ouest, Hopital Claude Huriez, 59 Lille (France)

    1995-08-01

    Aspergillosis is the most common fungal infection of the paranasal sinuses, and needs to be recognized because it requires surgical removal. Twenty proven cases of aspergillosis of the paranasal sinuses are reported here. CT was performed in all the cases and MRI in 2 cases. The maxillary sinus was affected in 19 patients and the sphenoid sinus in 1. Mycosis was unilateral in all but 1 of the cases. Foci of increased attenuation at CT were observed in 18 cases, with calcification in 10 cases and/or dental material in 13 cases. An increased bony wall thickness was observed in 16 cases. All the patients but 1 had at least one of the signs. At MRI the fungal mass displayed a hypointense signal on T1- and T2-weighted images. No enhancement was noted on post-contrast T1-weighted images. The diagnosis of paranasal sinus aspergillosis is suggested by the CT findings, when a hyperdense mass with calcifications and/or dental material is noted with thickening of the sinus wall. MRI may have a complementary diagnostic role in doubtful cases. (orig.)

  1. Aspergillus felis sp. nov., an emerging agent of invasive aspergillosis in humans, cats, and dogs.

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    Vanessa R Barrs

    Full Text Available 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.

  2. Etiologic agents and diseases found associated with clinical aspergillosis in falcons.

    Science.gov (United States)

    Tarello, Walter

    2011-01-01

    The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  3. Erythropoietin combined with liposomal amphotericin b improves outcome during disseminated aspergillosis in mice

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    nathalie erousseau

    2014-10-01

    Full Text Available Disseminated aspergillosis is responsible for a high mortality rate despite the use of antifungal drugs. Adjuvant therapies are urgently needed to improve the outcome. The aim of this study was to demonstrate that the cytoprotective effect of erythropoietin combined to amphotericin b can reduce the mortality rate in a murine model of disseminated aspergillosis. After infection with Aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7,5 mg/Kg of Liposomal Amphotericin B (LAmB or 7,5 mg/Kg of LAmB combined with 1000 IU/Kg of EPO (16 mice per group. Aspergillus galactomannan and organ cultures were performed to evaluate fungal burden at day 5. Cumulative long-term survival was analyzed at day 12 post-infection according to the Kaplan-Meier method. At day 5, fungal burden was similar between non-treated and treated groups. At day 12, mortality rates were 75 %, 62.5 % and 31 % in control group, LAmB group and EPO/LAmB group, respectively. We observed a significant decreased in mortality using EPO/LAmB combination compared to control group (p < 0.01. LAmB single treatment did not improve the survival rate compared to control group (p = 0.155.Our results provided the first evidence that erythropoietin improved the outcome of mice presenting disseminated aspergillosis when combined with amphotericin b.

  4. Role of innate immune receptors in paradoxical caspofungin activity in vivo in preclinical aspergillosis.

    Science.gov (United States)

    Moretti, Silvia; Bozza, Silvia; D'Angelo, Carmen; Casagrande, Andrea; Della Fazia, Maria Agnese; Pitzurra, Lucia; Romani, Luigina; Aversa, Franco

    2012-08-01

    This study investigated the possible mechanisms underlying the paradoxical caspofungin activity in vivo in preclinical aspergillosis. We evaluated the activity of escalating doses of caspofungin in vivo in different preclinical models of invasive aspergillosis, including mice deficient for selected innate immune receptors. The therapeutic efficacy of caspofungin in experimental invasive aspergillosis was strictly dose dependent, being observed at doses of 0.1 and 1 mg/kg of body weight depending on the experimental models. Paradoxical increase in pulmonary fungal burden as well as inflammatory pathology was observed at the highest dose of caspofungin (5 mg/kg), occurred independently of the so-called Eagle effect and susceptibility to caspofungin in vitro, and was contingent upon the presence of TLR2, Dectin-1, and TLR9. Increased expression of Dectin-1 and TLR9 were observed upon exposure to caspofungin in vitro and in vivo. Together, these findings suggest that the net activity of caspofungin in vivo is orchestrated by the activation, directly or indirectly, of multiple innate immune receptors.

  5. Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model.

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    Michaël Schwarzinger

    Full Text Available BACKGROUND: The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. METHODS: We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. RESULTS: The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010, independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53. CONCLUSIONS: The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan

  6. A new and clinically relevant murine model of solid-organ transplant aspergillosis

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    Susanne Herbst

    2013-05-01

    Invasive fungal infections (IFIs are a major cause of death in organ transplant patients. The murine hydrocortisone-mediated immunosuppression model of pulmonary aspergillosis is commonly used to characterise IFIs in these patients. However, this model does not take into account the effects of calcineurin inhibitors on transplant immunity to IFIs or the fungal calcineurin pathway, which is required for both virulence and antifungal drug resistance. To address these two issues, a new and clinically relevant transplant immunosuppression model of tacrolimus (FK506 and hydrocortisone-associated pulmonary aspergillosis was developed. We first characterised IFIs in 406 patients with a lung transplant. This showed that all of the patients with pulmonary aspergillosis were immunosuppressed with calcineurin inhibitors and steroids. Murine pharmacokinetic studies demonstrated that an ideal dose of 1 mg/kg/day of FK506 intraperitoneally produced blood trough levels in the human therapeutic range (5–12 ng/ml. There was increased mortality from pulmonary aspergillosis in a transplant-relevant immunosuppression model using both FK506 and hydrocortisone as compared with immunosuppression using hydrocortisone only. Lung histopathology showed neutrophil invasion and tracheobronchitis that was associated with reduced lung tumour necrosis factor-α (TNFα, JE (homologue of human MCP-1 and KC (homologue of human IL-8 at 24 hours, but increased lung TNFα, JE and KC at 48 hours when fungal burden was high. Furthermore, FK506 directly impaired fungal killing in alveolar macrophages in vitro, with FK506-mediated inhibition of the radial growth of Aspergillus fumigatus in vitro occurring at the low concentration of 5 ng/ml. Taken together, these findings show that the immunosuppressive activity of FK506 outweighs its antifungal activity in vivo. These observations demonstrate that FK506 impairs innate immune responses and leads to an incremental increase in susceptibility to IFIs when

  7. CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergillosis.

    Science.gov (United States)

    Hartigan, Adam J; Westwick, John; Jarai, Gabor; Hogaboam, Cory M

    2009-10-15

    Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment and is easily cleared from immunocompetent hosts. Invasive aspergillosis develops in immunocompromised patients, and is a leading cause of mortality in hematopoietic stem cell transplant recipients. CCR7 and its ligands, CCL19 and CCL21, are responsible for the migration of dendritic cells from sites of infection and inflammation to secondary lymphoid organs. To investigate the role of CCR7 during invasive aspergillosis, we used a well-characterized neutropenic murine model. During invasive aspergillosis, mice with a CCR7 deficiency in the hematopoietic compartment exhibited increased survival and less pulmonary injury compared with the appropriate wild-type control. Flow cytometric analysis of the chimeric mice revealed an increase in the number of dendritic cells present in the lungs of CCR7-deficient chimeras following infection with Aspergillus conidia. An adoptive transfer of dendritic cells into neutropenic mice provided a protective effect during invasive aspergillosis, which was further enhanced with the adoptive transfer of CCR7-deficient dendritic cells. Additionally, CCR7-deficient dendritic cells activated in vitro with Aspergillus conidia expressed higher TNF-alpha, CXCL10, and CXCL2 levels, indicating a more activated cellular response to the fungus. Our results suggest that the absence of CCR7 is protective during invasive aspergillosis in neutropenic mice. Collectively, these data demonstrate a potential deleterious role for CCR7 during primary immune responses directed against A. fumigatus.

  8. Fulminant Laryngeal-tracheobronchial-pulmonary Aspergillosis: A Rare and Fatal Complication in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

    Science.gov (United States)

    Tao, Tao; Zhang, Ying-Hui; Xue, Sheng-Li; Wu, De-Pei; Chen, Feng

    2017-01-01

    A 23-year-old man who had previously undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia was diagnosed with invasive laryngeal-tracheobronchial-pulmonary aspergillosis after presenting with a persistent dry cough at six months post-transplantation based on the findings of laryngoscopy and fiberoptic bronchoscopy. A fiberoptic bronchoscope was used to remove the obstructive material from the patient's airway and posaconazole plus caspofungin were administered to successfully to treat the patient. Our report suggests that laryngoscopy and fiberoptic bronchoscopy should be considered as alternative approaches to the diagnosis and treatment of allo-HSCT recipients with persistent respiratory symptoms when invasive laryngeal aspergillosis and invasive tracheobronchial aspergillosis are suspected. PMID:28154281

  9. Protective Effector Cells of the Recombinant Asp f3 Anti-Aspergillosis Vaccine

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    Diana eDiaz-Arevalo

    2012-08-01

    Full Text Available An Aspergillus fumigatus vaccine based on recombinant Asp f3 protein has the potential to prevent aspergillosis in humans, a devastating fungal disease that is the prime obstacle to the success of hematopoietic cell transplantation. This vaccine protects cortisone acetate (CA-immunosuppressed mice from invasive pulmonary aspergillosis via CD4+ T cell mediators. Aside from these mediators, the nature of downstream fungicidal effectors is not well understood. Neutrophils and macrophages protect immunocompetent individuals from invasive fungal infections, and selective neutrophil depletion rendered mice susceptible to aspergillosis whereas macrophage depletion failed to increase fungal susceptibility. We investigated the effect of neutrophil depletion on rAsp f3 vaccine protection, and explored differences in pathophysiology and susceptibility between CA-immunosuppression and neutrophil depletion. In addition to being protective under CA-immunosuppression, the vaccine also had a protective effect in neutrophil-depleted mice. However, in non-immunized mice, a ten-fold higher conidial dose was required to induce similar susceptibility to infection with neutrophil-depletion than with CA- immunosuppression. The lungs of non-immunized neutrophil-depleted mice became invaded by a patchy dense mycelium with highly branched hyphae, and the peribronchial inflammatory infiltrate consisted mainly of CD3+ T cells and largely lacked macrophages. In contrast, lungs of non-immunized CA-immunosuppressed mice were more evenly scattered with short hyphal elements. With rAsp f3-vaccination, the lungs were largely clear of fungal burden under either immunosuppressive condition. We conclude that neutrophils, although substantial for innate antifungal protection of immunocompetent hosts, are not the relevant effectors for rAsp f3-vaccine derived protection of immunosuppressed hosts. It is therefore more likely that macrophages represent the crucial effectors of the r

  10. Chest radiographic staging in allergic bronchopulmonary aspergillosis: relationship with immunological findings.

    LENUS (Irish Health Repository)

    Kiely, J L

    2012-02-03

    The question of whether a chest radiographic severity staging system could be correlated with standard blood\\/serum diagnostic indices in allergic bronchopulmonary aspergillosis (ABPA) was addressed in 41 patients. Asthma and positive Aspergillus fumigatus (AF) serology were considered essential diagnostic inclusion criteria. Eosinophil count, serum immunoglobulin (Ig)E and immediate skin hypersensitivity were also tested to grade patients as "definite" or "likely" ABPA. Definite cases had all five of these factors present, whereas likely cases had three or more. Chest radiographs were examined by experienced radiologists blinded to the clinical data. The six-stage radiographic score (0-5) was based on the severity and duration of changes seen: stage 0: normal; stage 1: transient hyperinflation; stage 2: transient minor changes; stage 3: transient major changes; stage 4: permanent minor changes; and stage 5: permanent major changes. Significant positive correlations (p<0.05) were observed between peak AF titres (expressed as an index), peak eosinophil count and radiographic severity stage. When considered as subgroups, these correlations approached, but did not reach, significance for the group with "likely" ABPA (n=28), but in the group with definite ABPA (n=13), there was a high correlation between radiographic score and peak AF index (r=0.59), as well as peak eosinophil count (r=0.62). This study suggests that the peak Aspergillus fumigatus index and eosinophil counts correlate best with the severity of radiographic stages in allergic bronchopulmonary aspergillosis. This chest radiographic staging system may be useful in the clinical assessment and management of patients with allergic bronchopulmonary aspergillosis, particularly in those patients with more severe radiographic stages.

  11. Galactomannan and Real-Time PCR in the diagnosis of invasive Aspergillosis: preliminary data

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    Cristina Pedrotti

    2014-03-01

    Full Text Available The diagnosis of invasive aspergillosis is notoriously difficult. The standard culture-based methods have shown considerable limitations in performance. For this reason, non-culture methods have been increasingly employed for the diagnosis of invasive aspergillosis, and, among them, the methods based on Real-Time polymerase chain reaction (RT-PCR. In this study we assess the contribution in lowering diagnosis errors provided by the RT-PCR method when run alongside other methods. We analyzed 23 biological samples, 14 serum samples, and 9 bronchoalveolar lavage samples (BAL from 10 immunocompromised patients who were selected according to EORTC/MSG criteria (European Organization for Research and Treatment of Cancer/Mycoses Study Group. On the serum sample we searched the galactomannan (GM (Platelia Aspergillus® and the fungal genome (MycAssayTMAspergillus; the BAL samples were subjected also to the culture tests. In 11 serum samples the results showed concordance between GM and RT–PCR tests, while in 3 samples we report discordance: 2 results were GM positive and RT-PCR negative, and 1 results GM negative and RT-PCR indeterminate. In 5 BAL samples the results showed concordance between the two methods, while 4 were GM positive and RT-PCR negative. The data, although still preliminary, suggest an increased accuracy in the diagnosis of suspected invasive aspergillosis when employing both RT-PCR and GM tests given that the RT-PCR test eliminates the false positive results of the GM test. The PCR methods require, however, further applications of this type of diagnostic because of the severe limit given by the lack of standardization.

  12. Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile.

    Science.gov (United States)

    Anand, R; Shankar, J; Tiwary, B N; Singh, A P

    2015-04-01

    Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.

  13. Treatment strategies for invasive aspergillosis in neutropenic patients: voriconazole or liposomal amphotericin-B?

    Science.gov (United States)

    Pagano, L; Valentini, C G; Fianchi, L; Caira, M

    2011-02-01

    The proportion of patients with cancers who develop invasive fungal infections has increased dramatically over the past few decades. Most of these infections are diagnosed in patients with hematological malignancies, mainly in patients with acute myeloid leukemia and those undergoing allogeneic hematopoietic stem cell transplantation. For years deoxycolate amphotericin B has been considered the drug of choice for the treatment of invasive aspergillosis, but it has been outclassed by its lipid formulations and new triazoles (i.e. voriconazole), that produced better response rates; nonetheless recovery from neutropenia remains the most important factor influencing outcome.

  14. Extramedullary plasmacytoma of maxilla with cervical nodal metastasis associated with sinonasal aspergillosis

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    Virender Suhag

    2015-12-01

    Full Text Available Extramedullary plasmacytoma (EMP is defined as neoplastic proliferation of plasma cells in the soft tissue. It represents approximately 3% of all plasma cell neoplasms. EMP of the head and neck are very uncommon tumors, representing approximately 0.4% of all head and neck malignancies; amongst them, plasmacytoma of the maxilla is extremely rare. We present a rare case of EMP which had metastasized to multiple cervical lymph nodes and was associated with aspergillosis. The possibility of extramedullary plasmacytoma should be considered when an elderly patient presents with symptoms of recurrent rhinosinusitis not responding to conservative management and imaging shows a destructive soft tissue mass.

  15. Causes of Death in a Contemporary Cohort of Patients with Invasive Aspergillosis

    OpenAIRE

    Carolina Garcia-Vidal; Maddalena Peghin; Carlos Cervera; Carlota Gudiol; Isabel Ruiz-Camps; Asunción Moreno; Cristina Royo-Cebrecos; Eva Roselló; Jordi Puig de la Bellacasa; Josefina Ayats; Jordi Carratalà

    2015-01-01

    Information regarding the processes leading to death in patients with invasive aspergillosis (IA) is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011) of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensu...

  16. Voriconazole in the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis.

    LENUS (Irish Health Repository)

    Glackin, L

    2009-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) can cause a significant clinical deterioration in patients with cystic fibrosis. There is very little research in the current literature with regard to alternatives for treatment, apart from long courses of steroids. We conducted a retrospective review of all our patients with ABPA treated with the antifungal voriconazole and found there was a significant drop in IgE levels post treatment as well as a decrease in steroid dosing. The improvement in FEV was not statistically significant; however there was a very wide variation in pre-treatment levels.

  17. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

    Science.gov (United States)

    Schmiedel, Yvonne; Zimmerli, Stephan

    2016-01-01

    Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of

  18. Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient

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    Mohapatra S

    2009-01-01

    Full Text Available Primary cutaneous aspergillosis is a rare entity, usually caused by A. fumigatus and A. flavus . Here, we present such a case, manifested by ulceration due to A. niger, which remained undiagnosed for a prolonged period. The immunological status was intact, although the patient had associated severe fungal infection. Recurrence of the lesion occurred despite repeated anti-fungal therapies. Anti fungal testing was done based on the broth dilution (M-38A, NCCLS, USA method. The culture isolate was found to be sensitive to fluconazole and amphotericin B. Continuation of antifungal therapy improved the symptoms, reducing the size of the lesion.

  19. Pulmonary toxocariasis mimicking invasive aspergillosis in a patient with ulcerative colitis.

    Science.gov (United States)

    Park, Eun Jin; Song, Joon Young; Choi, Min Ju; Jeon, Ji Ho; Choi, Jah-Yeon; Yang, Tae Un; Hong, Kyung Wook; Noh, Ji Yun; Cheong, Hee Jin; Kim, Woo Joo

    2014-08-01

    A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.

  20. Invasive orbital aspergillosis in an apparently immunocompetent host without evidence of sinusitis

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    Jennifer Primeggia

    2012-09-01

    Full Text Available Invasive aspergillosis is uncommon in healthy individuals. We report a case of Aspergillus fumigatus orbital cellulitiswith intracranial extension in an apparently immunocompetent patient with a history of benign lymphoid hyperplasiaof the lacrimal gland. A 68 year-old man with no significant past medical history underwent orbitotomy and biopsy of alacrimal gland mass. Pathology showed benign lymphoid hyperplasia of the lacrimal gland and he completed radiationtherapy. Three months after orbitotomy and one month after completion of radiation therapy, he presented with orbitalcellulitis. Brain magnetic resonance imaging demonstrated invasion into the frontal lobe. Clinical and radiographicfindings failed to improve with prolonged antibiotic therapy; transcranial orbitotomy with right frontal craniotomy forabscess drainage and orbit washout was performed. Intraoperative cultures grew Aspergillus fumigatus. The patientcompleted a six month course of therapy with oral voriconazole and has remained free from relapse with long-termfollow-up. Efficacy of voriconazole was guided by serial imaging and voriconazole trough levels. Aspergillus may causeinvasive disease in immunocompetent hosts, even without evidence of sinusitis, and should be considered in the differentialdiagnosis when patients do not demonstrate clinical improvement with antibiotic therapy. J Microbiol Infect Dis2012; 2(3: 113-116Key words: Aspergillosis, orbital cellulitis, brain abscess

  1. Retrospective evaluation of caspofungin therapy in invasive aspergillosis (RECAM-IA).

    Science.gov (United States)

    Wisniewski, Tami; Klimko, Nikolay; Laverdiere, Michel; Kiertiburanakul, Sasisopin; Kliasova, Galina; Trenschel, Rudolf; Kumar, Ritesh N

    2011-07-01

    To evaluate caspofungin in high-risk invasive aspergillosis (IA) patient, a retrospective review of patient characteristics, antifungal therapies and clinical outcomes on hospitalised patients at sites in Russia, Canada, Germany, and Thailand was performed. Fifty-five patients were included, six with proven and 49 with probable aspergillosis; 76.4% had haematological diseases, 80% were on immunosuppressive drugs, 32.7% were neutropenic at caspofungin initiation. Median duration of prior antifungal therapy was 9 days (range 1-232). Reasons for initiating caspofungin included: disease refractory to first-line antifungal (49.1%) and toxicities with prior antifungals (18.2%). Median caspofungin therapy duration was 14 days (range 2-62), with a median of 13 days (range 1-62) as monotherapy. Favourable responses were observed in 45.5% of the patients, complete responses in 40% and partial responses in 5.5%; 74.5% survived 7 days after completion of caspofungin therapy with 69.1% having been successfully discharged from the hospital. Few patients (14.6%) on caspofungin switched because of suspected resistance, lack of response or adverse events. There were no increases in hospital stay as a result of adverse events or drug-drug interactions related to caspofungin; 7.3% of patients had a mean value of 13 (± 14.11) days of increased stay attributable to treatment failure. Caspofungin was well-tolerated. It exhibited effectiveness and high survival in treating severe IA patients.

  2. Progressive increase in cavitation with the evolution of fungus ball: A clue to the diagnosis of chronic necrotizing pulmonary aspergillosis

    OpenAIRE

    Prasad R.; Garg Sanjay

    2009-01-01

    Chronic necrotizing pulmonary aspergillosis (CNPA) is an uncommon pulmonary infection seen in the patients with chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis, diabetes mellitus, alcoholism, poor nutrition or low dose corticosteroid therapy. Here, we are presenting a case of CNPA with diabetes mellitus that was misdiagnosed as pulmonary tuberculosis.

  3. Progressive increase in cavitation with the evolution of fungus ball: A clue to the diagnosis of chronic necrotizing pulmonary aspergillosis

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    Prasad R

    2009-01-01

    Full Text Available Chronic necrotizing pulmonary aspergillosis (CNPA is an uncommon pulmonary infection seen in the patients with chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis, diabetes mellitus, alcoholism, poor nutrition or low dose corticosteroid therapy. Here, we are presenting a case of CNPA with diabetes mellitus that was misdiagnosed as pulmonary tuberculosis.

  4. Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

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    Michaela Döring

    2012-01-01

    Full Text Available Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day and caspofungin (CAS, 50 mg/day during the first allogeneic hematopoietic stem cell transplantation (HSCT improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

  5. Aspergillus Septic Arthritis of the Hip in an Immunocompetent Middle-aged Female with Undiagnosed Recurrent Pulmonary Aspergillosis

    OpenAIRE

    Yoon, Pil Whan; Song, Joo Ho; Yoon, Kang Sup; Chang, Jae Suk; Kim, Hee Joong; Rhyu, Kee Hyung

    2015-01-01

    We present a case of Aspergillus septic hip arthritis in an immunocompetent patient with undiagnosed recurrent pulmonary aspergillosis who underwent arthroscopic surgery. Biopsy specimens of synovium revealed fungal hyphae, confirming Aspergillus infection. Aspergillus septic hip arthritis can occur in immunocompetent patients, and arthroscopy can be a noninvasive surgical option in these cases.

  6. Immunochemical analysis of fumigaclavine mycotoxins in respiratory tissues and in blood serum of birds with confirmed aspergillosis.

    Science.gov (United States)

    Latif, Hadri; Gross, Madeleine; Fischer, Dominik; Lierz, Michael; Usleber, Ewald

    2015-11-01

    The ergoline alkaloid fumigaclavine A (FuA) is one of the major mycotoxins produced by Aspergillus fumigatus, the main causative fungal agent of avian aspergillosis. To study in situ production of FuA, post-mortem respiratory tissues of various avian species, as well as blood samples of falcons (Falco sp.), were analysed by enzyme immunoassay (EIA). At a detection limit of 1.5 ng/ml, FuA EIA positive results were obtained for tissue samples from seven (64%) out of 11 birds with confirmed aspergillosis, with a maximum concentration of 38 ng/g, while all controls (n = 7) were negative. No FuA could be detected in blood serum (detection limit 0.7 ng/ml) of 15 falcons, experimentally inoculated with A. fumigatus conidia. Fungal mycelium material from tissue of clinical aspergillosis cases, cultured on malt extract agar, was highly positive in the FuA EIA in milligrams per gram range. Chromatographic analysis of mycelium extracts revealed the co-presence of FuA and the structurally related fumigaclavine C (FuC). Alkaline hydrolysis of FuA and FuC yielded the corresponding deacetylation products, FuB and FuE. This is the first report showing that fumigaclavine alkaloids are produced by A. fumigatus in situ during the course of clinical aspergillosis in birds; however, the role of these compounds in the pathogenesis of this disease is still unknown.

  7. Case report - Bilateral renal aspergillosis in a patient with AIDS : A case report and review of reported cases

    NARCIS (Netherlands)

    Oosten, A.W.; Sprenger, H.G.; Van Leeuwen, J.T.M.; Meessen, N.E.L.; Van Assen, S.

    2008-01-01

    Renal aspergillosis is an extremely uncommon complication in HIV-infected patients. In general, prognosis is poor and the need for nephrectomy is emphasized. We report the case of a 37-year-old patient with AIDS since April 2003 (CD4 count 10 cells/mm(3), a high viral load, Candida esophagitis, bila

  8. Evidence Supporting a Role for Mammalian Chitinases in Efficacy of Caspofungin against Experimental Aspergillosis in Immunocompromised Rats

    NARCIS (Netherlands)

    P.E.B. Verwer (Patricia); M.T. ten Kate (Marian); F.H. Falcone (Franco); S. Morroll (Shaun); H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma); W.W.J. van de Sande (Wendy)

    2013-01-01

    textabstractObjectives:Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA), strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activi

  9. Failure of posaconazole therapy in a renal transplant patient with invasive aspergillosis due to Aspergillus fumigatus with attenuated susceptibility to posaconazole

    NARCIS (Netherlands)

    Kuipers, S.; Bruggemann, R.J.M.; Sevaux, R.G. de; Heesakkers, J.P.F.A.; Melchers, W.J.G.; Mouton, J.W.; Verweij, P.E.

    2011-01-01

    We report the case of a kidney transplant recipient with invasive aspergillosis due to Aspergillus fumigatus resistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under t

  10. Aspergilosis necrotizante crónica en un paciente con secuelas de tuberculosis pulmonar Chronic necrotizing aspergillosis in a patient with pulmonary tuberculosis sequelae

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    Alcides Zambrano F

    2007-03-01

    Full Text Available Aspergillus fumigatus puede causar diferentes patologías en el ser humano: aspergiloma, aspergilosis broncopulmonar alérgica, aspergilosis necrotizante crónica, aspergilosis invasora. En la aspergilosis necrotizante crónica hay invasión local del parénquima y destrucción. A diferencia de la aspergilosis invasora no invade vasos sanguíneos ni se disemina a otros órganos. La aspergilosis necrotizante crónica se presenta en pacientes de edad media o ancianos con patología pulmonar previa: EPOC, secuelas de tuberculosis, resección pulmonar, neumoconiosis, radioterapia, infarto pulmonar o sarcoidosis. La clínica es indolente e inespecífica, con fiebre, tos, expectoración y baja de peso. Se desconoce la incidencia de aspergilosis necrotizante crónica en nuestro medio. La aspergilosis necrotizante crónica es potencialmente fatal, por lo que requiere de un diagnóstico y tratamiento oportuno. Creemos que, debe considerarse esta entidad ante un cuadro consuntivo y febril prolongado, en pacientes con enfermedades predisponentes que producen una leve baja de la inmunidad. Describimos el caso de un paciente atendido en el Instituto Nacional del TóraxAspergillus fumigatus is the causative agent of differents pathologies in the human being: aspergilloma, allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis and invasive aspergillosis. In chronic necrotizing aspergillosis there is local invasion of the lung tissue and parenchyma destruction. Chronic necrotizing aspergillosis is different from invasive aspergillosis, because the abscence of vascular invasion or dissemination. Chronic necrotizing aspergillosis is seen in middle-aged and elderly with underlying lung diseases: COPD, tuberculosis sequelae, lung resection, pneumoconiosis, radiotherapy, lung infarction or sarcoidosis. Clinical manifestations are non specific, being the most usual fever, cough, sputum production and weight loss. Incidence of chronic necrotizing

  11. Aspergilosis: una patología a considerar Aspergillosis: a phatology to be considered

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    Héctor Guillermo Oxilia

    2008-03-01

    Full Text Available La aspergilosis pulmonar es una infección micótica causada por el Aspergillus fumigatus, saprófito del esputo humano normal. Se estudiaron cinco casos de pacientes con aspergilosis, cuatro de ellos adultos, tres del sexo femenino y uno masculino, todos de presentación no invasiva, y uno, pediátrico, sexo masculino, del tipo invasiva. Fueron estudiados con radiología convencional, tomografía computada (TC helicoidal, TC multislice y video cápsula endoscópica. Afecta 3:1 a los hombres en relación con las mujeres. Hay tres formas de presentación: a invasiva: en los pacientes neutropénicos, donde predomina la afectación pulmonar, con diseminación a cerebro, corazón, riñón, tracto gastrointestinal, hígado, tiroides y bazo; tiene mal pronóstico y la mortalidad es muy elevada; b semiinvasiva: compromete fundamentalmente a pacientes con patología pulmonar preexistente; c no invasiva: afecta cavidades preexistentes, cavernas TBC ( tuberculosis o quistes, donde coloniza el hongo, y se denomina aspergiloma o micetoma.Pulmonary aspergillosis is a mycotic infection caused by the Aspergillus fumigatus, saprophyte of the normal human sputum. Five patients with non invasive aspergillosis were studied, of whom 4 were adults (3 women, 1 man and one, pediatric, with invasive aspergillosis. All of them were studied by conventional X-ray, spiral CT, multislice CT and video capsule endoscopy. The presentation is predominant among men (3 to 1. There are three forms of presentation: a invasive: in neutropenic patients it prevails the lung affectation; the brain, heart, kidney gastrointestinal tract, liver, thyroid and spleen spreading has a bad prognosis and mortality rate is very high; b semiinvasive: it mainly compromises patients with pre-existing pulmonary pathology; c non invasive: affects pre-existing cavities, TBC caverns or cysts where the fungus establishes; it is called aspergilloma or mycetoma.

  12. Successful Off-Label Use of Recombinant Factor VIIa and Coil Embolization in an Adolescent with Massive Hemoptysis Due to Invasive Pulmonary Aspergillosis

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    Dilek Gürlek Gökçebay

    2015-03-01

    Full Text Available Invasive fungal infections have turned out to be a significant cause of morbidity and mortality in pediatric patients with malignant disorders. Massive hemoptysis, a rare complication of invasive pulmonary aspergillosis, may threaten the lives of patients, usually during the resolution of neutropenia. In this report, we describe a patient with massive hemoptysis due to invasive pulmonary aspergillosis whose bleeding was controlled successfully with off-label use of recombinant factor VIIa and subsequent coil embolization of the right pulmonary artery.

  13. Failure of Posaconazole Therapy in a Renal Transplant Patient with Invasive Aspergillosis Due to Aspergillus fumigatus with Attenuated Susceptibility to Posaconazole ▿

    OpenAIRE

    Kuipers, Saskia; Brüggemann, Roger J. M.; Ruud G.L. de Sévaux; Heesakkers, John P. F. A.; Melchers, Willem J. G.; Mouton, Johan W.; Verweij, Paul E.

    2011-01-01

    We report the case of a kidney transplant recipient with invasive aspergillosis due to Aspergillus fumigatus resistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under the concentration-time curve over the MIC. Posaconazole should be used with caution for invasive aspergillosis caused by strains with attenuated posaconazole susceptibility, as drug exposure may be ...

  14. Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

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    Katia Paciaroni

    2015-08-01

    Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

  15. Novel and sensitive qPCR assays for the detection and identification of aspergillosis causing species.

    Science.gov (United States)

    Paholcsek, Melinda; Leiter, Eva; Markovics, Arnold; Biró, Sándor

    2014-09-01

    Despite concerted efforts, diagnosis of aspergillosis is still a great challenge to clinical microbiology laboratories. Along with the requirement for high sensitivity and specificity, species-specific identification is important. We developed rapid, sensitive and species-specific qPCR assays using the TaqMan technology for the detection and identification of Aspergillus fumigatus and Aspergillus terreus. The assays were designed to target orthologs of the Streptomyces factor C gene that are only found in a few species of filamentous fungi. Fungi acquired this gene through horizontal gene transfer and divergence of the gene allows identification of species. The assays have potential as a molecular diagnosis tool for the early detection of fungal infection caused by Aspergillus fumigatus and Aspergillus terreus, which merits future diagnostic studies. The assays were sensitive enough to detect a few genomic equivalents in blood samples.

  16. Blood and tissue distribution of posaconazole in a rat model of invasive pulmonary aspergillosis.

    Science.gov (United States)

    Cendejas-Bueno, E; Forastiero, A; Ruiz, I; Mellado, E; Gavaldà, J; Gomez-Lopez, A

    2017-02-01

    Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue. The PK behavior of posaconazole in this particular experimental model is similar to that observed in humans. Thus, we believe this model could be a valid tool to evaluate posaconazole exposure-response relationship.

  17. Aspergillosis in a Patient Receiving Temozolomide for the Treatment of Glioblastoma

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    Rodrigo Ramella Munhoz

    2013-08-01

    Full Text Available Leukopenia and selective CD4+ lymphopenia represent major adverse events associated with the use of temozolomide (TMZ, an oral alkylating agent incorporated in the treatment of glioblastoma (GBM. The increased risk of opportunistic infections, including those caused by Pneumocystis jiroveci and cytomegalovirus, has been previously described in the literature. Here we report the case, the first to our knowledge, of a patient with pulmonary invasive aspergillosis immediately after the completion of chemoradiation with TMZ for GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had excellent response to systemic voriconazole. This case illustrates that TMZ can be associated with severe opportunistic infections, presumably associated with T lymphocyte immune dysfunction, and patients exposed to this agent should be carefully monitored.

  18. Systemic Aspergillosis in Emu Chicks in an organised farm in Kerala

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    Sunitha Karunakaran1

    Full Text Available Systematic post mortem examination was carried out on seven Emu chicks submitted for disease diagnosis to Clinical Laboratory, District Veterinary Centre, Palakkad. On examination, numerous small greyish white nodules were seen in the lungs, air sacs, kidney and serosal surface of proventriculus. Dark red liver with necrotic areas and dark coloured spleen were the other lesions. Microscopically the lungs revealed granulomas with central areas of caseation surrounded by mononuclear cells and fibroblasts. PAS positive fungal hyphae could be seen in the lesion. Aspergillus fumigatus could be isolated in Sabouraud Dextrose Agar from the lesions. This is the first report on the occurrence of systemic aspergillosis in Emus from Kerala. [Veterinary World 2010; 3(10.000: 453-455

  19. Allergic bronchopulmonary aspergillosis in garden waste (compost) collectors--occupational implications.

    Science.gov (United States)

    Poole, C J M; Wong, M

    2013-10-01

    The separation of rotting garden material from general domestic waste and its collection for processing in industrial composting sites is a relatively new industry in the UK. Two cases of allergic bronchopulmonary aspergillosis and the results of health surveillance are described in a team of 28 garden waste (compost) collectors. A few cases of extrinsic allergic alveolitis due to Aspergillus fumigatus have previously been reported in compost workers. In the absence of any guidance from research and to prevent similar cases of a potentially serious illness, we advise that new starters to the job of collecting or processing compost are screened for asthma and aspergillus sensitivity, cystic fibrosis, bronchiectasis and immunodeficiency if their exposure to high levels of Aspergillus sp cannot be controlled. Annual health surveillance for these workers is also recommended.

  20. Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.

    Science.gov (United States)

    Amin, Muhammad Umar; Mahmood, Rabia

    2008-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting.

  1. Case Report Associated with Aspergillosis and Hepatitis E Virus Coinfection in Himalayan Griffons

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    Heng Li

    2015-01-01

    Full Text Available This study involved a death which occurred in four Himalayan griffons housed in Beijing zoo, China. Based on pathogen identification and the pathological changes observed, we did characterize the fungi and Hepatitis E virus (HEV in four dead Himalayan griffons. Pathological changes were severe. Membranous-like material was observed on the surface of the internal organs. Spleen was necrotic. Focal lymphocyte infiltration in the liver and many sunflower-like fungi nodules were evident in the tissues, especially in the kidney. PCR was used to identify the pathogen. Based on the 18SrRNA genomic sequence of known fungi, the results confirmed that all four dead Himalayan griffons were infected with Aspergillus. At the same time the detection of HEV also showed positive results. To the best of our knowledge, this work appears to be the first report of concurrent presence of Aspergillosis and Hepatitis E virus in rare avian species.

  2. Hospital-acquired invasive pulmonary aspergillosis in patients with hepatic failure

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    Tao Ran

    2008-07-01

    Full Text Available Abstract Background Invasive pulmonary aspergillosis (IPA is a rapid, progressive, fatal disease that occurs mostly in immunocompromised patients. Patients with severe liver disease are at a heightened risk for infections. Little is known about the clinical presentation including predisposing factors and treatment of IPA in patients with hepatic failure. Methods Medical records of patients with hepatic failure between November 2005 and February 2007 were reviewed for lung infection. Nine medical records of definitive diagnosis of IPA and three of probable IPA were identified. Results The main predisposing factors were found to be prolonged antibiotic therapy and steroid exposure. Clinical signs and radiological findings were non-specific and atypical. Timely use of caspofungin was found to reduce the mortality due to the disease. Conclusion A high index of suspicion is required for early IPA diagnosis in patients with hepatic failure.

  3. Complete heart block in a neutropenic patient with aspergillosis: An unusual adverse effect of caspofungins

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    Sasmita Biswal

    2012-01-01

    Full Text Available We present a case of complete heart block (CHB in a 58-year-old female patient with acute myeloid leukemia (AML with no past history of cardiac disease, who received caspofungin in the treatment of disseminated fungal infection. To our knowledge, this is the first case of CHB associated with caspofungins. Subsequent to induction chemotherapy the patient developed invasive pulmonary aspergillosis with sudden tachypnea, dyspnoea, fever, bilateral pulmonary infiltrates and acute respiratory insufficiency consequent to neutropenia with ANC<500. During the first dose of antifungal therapy with caspofungins, she developed complete atrioventricular block and cardiac arrest. Complete heart block is an unusual adverse effect of caspofungins which has not been reported previously. Caspofungins release histamine in peripheral blood cells, so possible histamine-mediated symptoms ranging from severe fatal anaphylaxis can occur. These data suggest that infusion-related reactions associated with caspofungin may be mediated by histamine release secondary to caspofungin therapy.

  4. Diagnosis and treatment of pulmonary aspergillosis%肺曲霉菌病的诊治分析

    Institute of Scientific and Technical Information of China (English)

    卢旭东; 陆益民

    2015-01-01

    目的:探讨肺曲霉菌病的临床特征、影像学特点、诊断和治疗方法,提高对该病的认识。方法回顾性分析2003—2013年昆山市第一人民医院收治的肺曲霉菌病患者58例的临床资料。结果58例患者中,仅28例初步诊断考虑有肺曲霉菌感染,19例误诊为肺癌或肺结核;26例经手术治疗,32例为内科保守治疗;53例治疗后好转,5例患者死亡。结论肺曲霉菌病诊断困难,且常需与支气管哮喘、支气管扩张、肺结核及肺癌等疾病相鉴别。肺曲霉菌球经手术切除及抗真菌药物治疗后预后较好;变应性支气管肺曲霉菌病需长期激素联合抗真菌治疗;而侵袭性肺曲霉菌病病死率较高,预后较差。%Objective To explore the clinical characteristic,imaging features,diagnosis and therapies of pulmonary aspergillosis,to improve the cognition of pulmonary aspergillosis. Methods The clinical data of 58 pulmonary aspergillosis pa-tients were retrospectively analyzed from 2003 to 2013 in the First People's Hospital of Kunshan. Results In the 58 patients, only 28 cases were primary diagnosed,19 cases were misdiagnosed as tuberculosis or lung cancer;26 cases were treated with operation,32 cases were treated with conservative treatmen;53 cases were improved after treatment,5 patients died. Conclu-sion Clinical diagnosis of pulmonary aspergillosis is difficult,needs to differentiate from bronchial asthma,bronchiectasis, pulmonary tuberculosis and lung cancer. The prognosis of aspergilloma patients is good after operation resection and antifungal therapy;allergic bronchopulmonary aspergillosis patients need long - term hormone combined with antifungal therapy;the mor-tality of invasive pulmonary aspergillosis patients is high,has a poor prognosis.

  5. Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

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    Natesan SK

    2016-12-01

    Full Text Available Suganthini Krishnan Natesan,1,2 Pranatharthi H Chandrasekar1 1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, 2John D Dingell VA Medical Center, Detroit, MI, USA Abstract: The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. Keywords: isavuconazole, aspergillosis, mucormycosis, efficacy, antifungal therapy, novel azole, tolerability, drug interactions

  6. Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive Aspergillosis in an Animal Model.

    Science.gov (United States)

    White, P Lewis; Wiederhold, Nathan P; Loeffler, Juergen; Najvar, Laura K; Melchers, Willem; Herrera, Monica; Bretagne, Stephane; Wickes, Brian; Kirkpatrick, William R; Barnes, Rosemary A; Donnelly, J Peter; Patterson, Thomas F

    2016-04-01

    The EuropeanAspergillusPCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and β-d-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and β-d-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and β-d-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and β-d-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.

  7. Combination Therapy of Advanced Invasive Pulmonary Aspergillosis in Transiently Neutropenic Rats Using Human Pharmacokinetic Equivalent Doses of Voriconazole and Anidulafungin▿

    OpenAIRE

    van de Sande, Wendy W. J.; Mathot, Ron A.A.; ten Kate, Marian T.; van Vianen, Wim; Tavakol, Mehri; Rijnders, Bart J. A.; Bakker-Woudenberg, Irma A. J. M.

    2009-01-01

    At present, voriconazole (VOR) is the drug of first choice for treating invasive pulmonary aspergillosis (IPA). However, particularly in advanced stages of disease and in the severely immunocompromised host, the mortality remains substantial. The combination of VOR with an echinocandin may improve the therapeutic outcome. We investigate here whether combining VOR and anidulafungin (ANI) in advanced IPA in transiently neutropenic rats results in a higher therapeutic efficacy. Since VOR is meta...

  8. Fatal Case of Probable Invasive Aspergillosis after Five Years of Heart Transplant: A Case Report and Review of the Literature

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    Toufik Mahfood Haddad

    2015-01-01

    Full Text Available Invasive fungal infections are very common in solid organ transplants and occur most frequently in the first three months after transplant. A 49-year-old female with a history of two remote heart transplants with the most recent one occurring 5 years ago was admitted for increasing shortness of breath, cough, and fever. Computerized tomography (CT scan of the chest showed left lower lung ground-glass and tree-in-bud opacities. She was started on broad spectrum antibiotics along with ganciclovir and micafungin. Ganciclovir was added due to the patient’s past history of CMV infection and empiric fungal coverage with micafungin. Bronchoalveolar lavage (BAL was performed as her respiratory status worsened and voriconazole was added for possible aspergillosis in combination therapy with micafungin. BAL galactomannan returned positive which was suggestive of aspergillosis. Patient worsened clinically and subsequently succumbed to cardiorespiratory arrest despite our best efforts. It is important to have a high degree of clinical suspicion for invasive aspergillosis in transplant patients even many years after transplant and initiate aggressive therapy due to poor outcomes.

  9. Costo-efficacia dell’amfotericina B liposomiale nella terapia dell’aspergillosi invasiva

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    Mario Eandi

    2004-03-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infectious complication of immune system depression. Amphotericin B deoxycholate (AMB-d has been considered standard therapy for IA for over 40 years, despite the fact that success rates rarely exceed 40% and adverse effects are quite common. At present two more recent pharmacological agents are available for the treatment of IA: liposomal amphotericin B (L-AMB and voriconazole (VOR. In this article, we present a pharmaco-economical study comparing the relative costeffectiveness of 5 alternative strategies in the treatment of invasive aspergillosis, analysed from the point of view of the Italian hospital: administration of L-AMB as first line therapy, followed by no rescue treatment in case of failure (L-AMB I°; administration of L-AMB as first line therapy, followed by VOR in case of failure (LAMB I° + VOR rescue; AMB-d as first line, followed by L-AMB in case of failure (L-AMB rescue; AMB-d as first line, followed by other antifungals as needed (AMB-d I° and VOR as first line, followed by rescue treatments in case of failure (VOR I°. The cost-effectiveness analysis was conducted using decision tree modelling techniques: efficacy data were obtained from published clinical trials; costs parameters were fitted on the Italian setting. The results indicate that two strategies, L-AMB rescue and VOR I°, are dominated, i.e. induce higher costs and lower success rates than the alternatives. The three remaining strategies are neither dominated nor dominate the others, but are associated with different clinical and economical outcomes: AMB-d I° has the lowest total cost, but also the highest cost-effectiveness ratio and the lowest overall efficacy; L-AMB I° has the best cost-effectiveness, but requires the willingness to pay 2,100 euro for each additional success; L-AMB I° + VOR rescue is the most effective treatment, but this choice is associated with incremental costs of 17,200 euro

  10. Management of invasive aspergillosis in patients with COPD: rational use of voriconazole

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    Florence Ader

    2009-07-01

    Full Text Available Florence Ader1, Anne-Lise Bienvenu2, Blandine Rammaert3, Saad Nseir41Service des Maladies Infectieuses et Tropicales; 2Service de Parasitologie et Mycologie Médicale, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Hôpital de La Croixrousse, Lyon, France; 3Service des Maladies Infectieuses et Tropicales, Université Paris Descartes, Hôpital Necker Enfants Malades, Centre d’infectiologie Necker-Pasteur, Paris, France; 4Service de Réanimation Médicale, Hôpital A. Calmette, Centre Hospitalier Régional Universitaire, Lille, FranceAbstract: Invasive pulmonary aspergillosis (IPA is an important cause of mortality in patients with hematologic malignancies. The reported incidence of IPA in the context of chronic obstructive pulmonary disease (COPD seems to increase. Approximately 1%–2% of overall fatal cases of IPA occur in COPD patients. The combination of factors such as lung immune imbalance, long-term corticosteroid use, increasing rate of bacterial exacerbations over time, and malnutrition are responsible for the emergence of IPA in these patients. The diagnosis of IPA is difficult to establish, which explains the delay in implementing accurate antifungal therapy and the high mortality rate. Persistent pneumonia nonresponsive to appropriate antibiotic treatment raises the concern of an invasive fungal infection. Definite diagnosis is obtained from tissue biopsy evidencing Aspergillus spp. on microscopic examination or in culture. Culture and microscopy of respiratory tract samples have a sensitivity and specificity of around 50%. Other diagnostic tools can be useful in documenting IPA: computed tomography (CT scan, nonculture-based tests in serum and/or in bronchoalveolar lavage such as antibody/antigen tests for Aspergillus spp. More recent tools such as polymerase chain reaction or [1→3]-β-D-glucan have predictive values that need to be further investigated in COPD patients. Antifungal monotherapy using azole

  11. Laboratory Diagnosis of Invasive Aspergillosis: From Diagnosis to Prediction of Outcome

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    Richard C. Barton

    2013-01-01

    Full Text Available Invasive aspergillosis (IA, an infection caused by fungi in the genus Aspergillus, is seen in patients with immunological deficits, particularly acute leukaemia and stem cell transplantation, and has been associated with high rates of mortality in previous years. Diagnosing IA has long been problematic owing to the inability to culture the main causal agent A. fumigatus from blood. Microscopic examination and culture of respiratory tract specimens have lacked sensitivity, and biopsy tissue for histopathological examination is rarely obtainable. Thus, for many years there has been a great interest in nonculture-based techniques such as the detection of galactomannan, β-D-glucan, and DNA by PCR-based methods. Recent meta-analyses suggest that these approaches have broadly similar performance parameters in terms of sensitivity and specificity to diagnose IA. Improvements have been made in our understanding of the limitations of antigen assays and the standardisation of PCR-based DNA detection. Thus, in more recent years, the debate has focussed on how these assays can be incorporated into diagnostic strategies to maximise improvements in outcome whilst limiting unnecessary use of antifungal therapy. Furthermore, there is a current interest in applying these tests to monitor the effectiveness of therapy after diagnosis and predict clinical outcomes. The search for improved markers for the early and sensitive diagnosis of IA continues to be a challenge.

  12. Galactomannan and 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Aspergillosis

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    Frédéric Lamoth

    2016-07-01

    Full Text Available Invasive aspergillosis (IA is a severe complication among hematopoietic stem cell transplant recipients or patients with hematological malignancies and neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed in other populations, such as solid-organ transplant recipients, patients with solid tumors or auto-immune diseases, and among intensive care unit patients. Frequent delay in diagnosis is associated with high mortality rates. Cultures from clinical specimens remain sterile in many cases and the diagnosis of IA often only relies on non-specific radiological signs in the presence of host risk factors. Tests for detection of galactomannan- (GM and 1,3-β-d-glucan (BDG are useful adjunctive tools for the early diagnosis of IA and may have a role in monitoring response to therapy. However, the sensitivity and specificity of these fungal biomarkers are not optimal and variations between patient populations are observed. This review discusses the role and interpretation of GM and BDG testing for the diagnosis of IA in different clinical samples (serum, bronchoalveolar lavage fluid, cerebrospinal fluid and different groups of patients (onco-hematological patients, solid-organ transplant recipients, other patients at risk of IA.

  13. Second-Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis

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    Brian W. P. Seymour

    2003-01-01

    Full Text Available Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS on a murine model of allergic bronchopulmonary aspergillosis (ABPA. BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

  14. Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis

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    Joseph Romagnuolo

    2000-01-01

    Full Text Available Acute graft-versus-host disease (GVHD is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.

  15. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis

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    Ibrahim, Ashraf S.; Gebremariam, Teclegiorgis; French, Samuel W.; Edwards, John E.; Spellberg, Brad

    2010-01-01

    Objectives Increased bone marrow iron levels in patients with haematological malignancies is an independent risk factor for developing invasive pulmonary aspergillosis (IPA), suggesting an important role for iron uptake in the pathogenesis of IPA. We sought to determine the potential for combination therapy with the iron chelator deferasirox + liposomal amphotericin B (LAmB) to improve the outcome of murine IPA compared with LAmB monotherapy. Methods In vitro MIC and minimum fungicidal concentration (MFC) values of the iron chelator, deferasirox, for Aspergillus fumigatus were determined by microdilution assay. In addition, we studied the efficacy of deferasirox alone or combined with LAmB in treating immunocompromised mice infected with A. fumigatus via inhalation. Results Deferasirox was cidal in vitro against A. fumigatus, with an MIC and MFC of 25 and 50 mg/L, respectively. Deferasirox monotherapy modestly prolonged survival of mice with IPA. Combination deferasirox + LAmB therapy synergistically improved survival and reduced lung fungal burden compared with either monotherapy alone. Conclusions Iron chelation therapy with deferasirox alone or in combination with LAmB is effective in treating experimental IPA. Further study of deferasirox is warranted as adjunctive therapy for IPA infections. PMID:19942619

  16. Combination therapy for chronic invasive rhinocerebral aspergillosis in a clinically immunocompetent patient

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    Lujber, László; Gerlinger, Imre; Kuncz, Ádám; Pytel, József

    2003-01-01

    Background: Adequate therapy for chronic invasive rhinocerebral aspergillosis in immunocompetent patients is controversial. The incidence of the disease is high in the Sudan and the Middle East. Misinterpretation of diagnostic criteria, failure to verify tissue invasion of fungi, and a lack of understanding of the pathophysiology of various forms of fungal rhinosinusitis lead to controversies in nomenclature, diagnosis, and therapy. Objective: The aim of this report was to detail the clinical presentation and the endoscopic and imaging study findings of a patient with invasive Aspergillus rhinosinusitis with endocranial and orbital extension. This patient was treated with surgical débridement and a combination of antifungal drugs and immunomodulatory therapy. Methods: Endoscopic débridement and high-dose liposomal amphotericin B, in combination with flucytosine and immunomodulators, were used to treat this patient. Results: After treatment, the patient experienced 3 years of disease-free follow-up. Conclusion: Surgical débridement and high-dose systemic combined antifungal therapy with immunomodulatory drugs produced an excellent long-term result for this apparently immunocompetent patient with extensive invasive fungal rhinosinusitis with cerebral and orbital involvement. PMID:24944397

  17. Successful non-standard approaches to massive hemoptysis in invasive pulmonary aspergillosis

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    Mitrović Mirjana

    2012-01-01

    Full Text Available Introduction. Invasive pulmonary aspergillosis (IA is the most frequent invasive fungal infection in patients with hematological malignancies. Massive hemoptysis (MH with blood loss more than 300- 600 ml in 24 hours is a rare (5-10% of IA patients but frequently fatal complication. Standard treatment of MH, such as oxygenation, a semi-sitting position with the bleeding site down, bronchoscopical suctioning, antifungal therapy, transfusion support and surgical resection might be either ineffective or not feasible in some cases. Outline of Cases. We report two patients with life threatening, non-controlled, massive hemoptysis who were successfully managed by non-standard measures. A 61-year-old male with acute myeloid leukemia developed pulmonary IA and massive hemoptysis after consolidation cure by chemotherapy. The bleeding site was localized in the VI lung segment by bronchoscopy. Local application of fibrinogen-thrombin concentrate (fibrin glue stopped the bleeding. A 22-year-old female patient with the diagnosis of severe aplastic anemia developed IA and massive hemoptysis early after application of immunosuppressive therapy (antilymphocyte globulin, cyclosporine and corticosteroids. Conventional transfusion therapy, desmopresine and antifibrinolytics were ineffective. This urgent condition was successfully treated with human activated recombinant factor VII (rFVIIa, NovoSeven®. Conclusion. Our experience together with data from the available literature suggests a potential benefit of fibrinogen-thrombin concentrate and rFVIIa in the treatment of refractory critical bleeding in hematooncological patients.

  18. Fatal Hemoptysis due to Chronic Cavitary Pulmonary Aspergillosis Complicated by Nontuberculous Mycobacterial Tuberculosis

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    Ioannis Kokkonouzis

    2011-01-01

    Full Text Available A 51-year-old man, with a history of severe COPD and bilateral pneumothorax, who was under treatment for pulmonary tuberculosis due to mycobacterium avium, was admitted due to high-grade fever, weight loss, cough, and production of purulent sputum, for almost one month without any special improvement despite adequate antibiotics treatment in outpatient setting. A CT scan revealed multiple consolidations, fibrosis, scaring, and cavitary lesions in both upper lobes with newly shadows which were fungus balls inside them. Aspergillus flavius was isolated in three sputum samples, a diagnosis of chronic cavitary pulmonary aspergillosis was made, and treatment with intravenous amphotericin B was started. An initially clinical improvement was noted, and a first episode of minor hemoptysis was treated with conservative measures. Unfortunately a second major episode of hemoptysis occurred and he died almost immediately. Aspergilloma is defined as the presence of a fungus ball inside a preexisting pulmonary cavity or dilated airway and is one of the clinical conditions associated with the clinical spectrum of pulmonary colonization. Tuberculosis is the most common underling disease. Hemoptysis is the most common symptom. Antifungal antibiotics, surgical interventions, bronchial arteries embolization, and intracavity infusion of antibiotics have been proposed without always adequate sufficiency.

  19. Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia

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    Hirano,Teiichi

    2009-08-01

    Full Text Available A 23-year old woman with acute biphenotypic leukemia (ABL complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis. We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

  20. Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

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    Natesan, Suganthini Krishnan; Chandrasekar, Pranatharthi H

    2016-01-01

    The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ) seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA) for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. PMID:27994475

  1. Chest computed tomography of late invasive aspergillosis after allogeneic hematopoietic stem cell transplantation.

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    Kojima, Rie; Tateishi, Ukihide; Kami, Masahiro; Murashige, Naoko; Nannya, Yasuhito; Kusumi, Eiji; Sakai, Miwa; Tanaka, Yuji; Kanda, Yoshinobu; Mori, Shin-Ichiro; Chiba, Shigeru; Kusumoto, Masahiko; Miyakoshi, Shigesaburo; Hirai, Hisamaru; Taniguchi, Shuichi; Sakamaki, Hisashi; Takaue, Yoichi

    2005-07-01

    Computed tomography (CT) is a powerful diagnostic tool for invasive aspergillosis (IA) after allogeneic stem cell transplantation (allo-SCT); however, little information is available concerning CT findings of late IA after allo-SCT. To characterize CT findings of late IA, we retrospectively examined medical records and high-resolution CT findings of 27 allo-SCT recipients with late IA. Either acute or chronic GVHD was diagnosed in 24 patients. All 27 patients were given corticosteroids at IA diagnosis. High-resolution CT findings included halo (n=12), centrilobular nodules (n=12), ill-defined consolidation (n=13), ground-glass attenuation (n=8), pleural effusion (n=7), pleural-based consolidation (n=4), and cavitation (n=4). CT findings showing centrilobular nodules and either halo or cavitation were classified into bronchopneumonia type and angioinvasive type, respectively. Angioinvasive-type, bronchopneumonia-type, and combination-type IA were diagnosed in 11, 8, and 4 patients, respectively. CT findings were nonspecific in the other 4 patients. One bronchopneumonia-type case and 2 angioinvasive-type IA cases were subsequently diagnosed as combination type. Although there were no significant differences in patient characteristics between the 2 types of IA, bronchopneumonia-type IA had a poorer prognosis than angioinvasive IA ( P=.022). Halo is a useful diagnostic marker in late IA as well as early IA, and late IA frequently manifests as bronchopneumonia.

  2. Neonatal cutaneous disseminated aspergillosis in a preterm extremely-low-birth-weight infant with favourable outcome at 3-year follow-up: a case report.

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    Manzoni, P; Rizzollo, S; Monetti, C; Carbonara, C; Priolo, C; Mastretta, E; Barberis, L; Galletto, P; Cigna, P; Leonessa, M L; Sala, U; Gomirato, G; Mostert, M; Stronati, M; Ruffinazzi, G; Tzialla, C; Jacqz-Aigrain, E; Kaguelidou, F; Farina, D

    2012-05-01

    Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

  3. Percutaneous treatment with amphotericin B of mycotic lung lesions from invasive aspergillosis: results in 10 immunocompromised patients

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    Veltri, A.; Anselmetti, G.C.; Bartoli, G.; Martina, M.C.; Galli, J. [Sezione di Scienze Radiologiche, DiUniv. Torino (Italy); Regge, D. [Servizio di Radiodiagnostica, Istituto di Ricerca e Cura per il Cancro, Ordine Mauriziano, Candiolo (Italy); Bertini, M. [U.O.A. Ematologia, Azienda Ospedaliera San Giovanni Battista, Torino (Italy)

    2000-12-01

    The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i. v. therapy; under CT guidance, a median of 10 cm{sup 3} per session of a 1 mg/cm{sup 3} diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences. (orig.)

  4. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3

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    Hulya Gunbatar

    2015-01-01

    Full Text Available A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3. During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  5. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3).

    Science.gov (United States)

    Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi

    2015-01-01

    A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  6. Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

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    Horger, Marius [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)]. E-mail: mshorger@med.uni-tuebingen.de; Hebart, Holger [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Einsele, Hermann [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Lengerke, Claudia [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Claussen, C.D. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Vonthein, Reinhard [Department of Medical Biometry, Eberhard-Karls-University Tuebingen, Westbahnhofstrasse 55, 72070 Tuebingen (Germany); Pfannenberg, Christina [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2005-09-01

    Purpose: To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA. Material and methods: A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered. Results: Three main CT findings were identified: small nodules (<1 cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy {+-} segmental 26% (12/46), or peribronchial distribution {+-} tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying 'halo' sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary

  7. Implementation of different histochemical methods in diagnostics of brain Aspergillosis in turkey chicks

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    Kureljušić Branislav

    2011-01-01

    Full Text Available Aspergillosis is a frequent fungal disease in different species of birds and mammals caused by fungi of the genus Aspergillus. It is characterized by inflammatory changes primarily in the respiratory system, even though it sometimes takes on a generalized form when several organ systems are affected. Mucotic-granulomatous meningoencephalitis with a predominant localization in the cerebellum has been described in turkeys, ducks and geese. Within this paper, examinations have been performed on a flock of broiler turkeys aged 12 days who had sustained evident neurological disorders in the form of ataxy, torticollis, paresis, and paralysis of the hind extremities and wings. In three of the ten autopsied chicks the macroscopic findings indicated granulomatous encephalitis of the cerebellum. A white-coloured granuloma, around 3mm in diameter, was situated cranioventrally and was clearly visible on the sagital section of the cerebellum. Mucological examinations of the cerebellum lesion resulted in the isolation of the fungi Aspergillus fumigatus. Haematoxylin-eosin (HE, Grocott and PAS methods were used for the evaluation of histopathological changes and proving Aspergillus fumigatusa hyphae. The microscopic examination of brain tissue sections stained with the HE method revealed the existence of a granuloma with a centrally placed necrotic area. The necrotic area was infiltrated with heterophilic granulocytes and surrounded by macrophage, giant cells and lymphocytes. A connective tissue capsule was located on the periphery of the granuloma. The fungi hyphae, as integral parts of the granuloma, were difficult to observe, and in some samples stained using the HE method they could not be seen at all. On the other hand, sections stanied using the Grocott and PAS methods showed prominent septed and branched hyphae in different parts of the granuloma. With the objective of making an etiological diagnosis of mucotic diseases, it is necessary to apply several

  8. Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation.

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    Iwen, P C; Rupp, M E; Bishop, M R; Rinaldi, M G; Sutton, D A; Tarantolo, S; Hinrichs, S H

    1998-12-01

    The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described. The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation. She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl. Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge. Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500. Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus. The patient was placed on ganciclovir. A biopsy specimen from a leg lesion also noted on day 67 p.t. revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus. Confirmation detection of A. ustus was made by demonstration of characteristic reproductive structures with the presence of Hülle cells. On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated. The patient's condition worsened, and she died 79 days p.t. At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A. ustus. In vitro susceptibility testing indicated probable resistance to AMB but not to ITR. This case supports the need for the development of rapid methods to determine antifungal susceptibility.

  9. Monitoring of nosocomial invasive aspergillosis and early evidence of an outbreak using cumulative sum tests (CUSUM).

    Science.gov (United States)

    Menotti, J; Porcher, R; Ribaud, P; Lacroix, C; Jolivet, V; Hamane, S; Derouin, F

    2010-09-01

    In order to provide a statistically based evaluation of the incidence of invasive aspergillosis (IA) over time, we applied the cumulative sums (CUSUM) methodology, which was developed for quality control and has already been applied for the surveillance of hospital-acquired infections. Cases of IA were recorded during a 5-year period. Incidence rates of cases assumed to be hospital-acquired, i.e. nosocomial IA (NIA), were analysed using CUSUM tests. Relationships between NIA, fungal contamination and construction or renovation work were tested using time-series methods. Between January 2002 and December 2006, 81 cases of NIA were recorded. CUSUM analysis of NIA incidence showed no significant deviation from the expected monthly number of cases until August 2005, and then the CUSUM crossed the decision limit, i.e. identified a significant increase in NIA as compared with the reference period (January 2002 to December 2004). Up to April 2006, the learning-curve CUSUM stayed over its limit, supporting an ongoing outbreak involving 24 patients, and then it significantly decreased in May 2006. Follow-up after May 2006 indicated no out-of-control situation, supporting a return to the baseline situation. In haematology wards, significant links were found between NIA incidence and fungal contamination of several sites at each ward (mainly unprotected common sites). An environmental source of contamination could be suspected, but no significant relationship was found between NIA incidence and ongoing construction or renovation. In conclusion, the CUSUM test proved to be well suited for real-time monitoring of NIA and for early identification and follow-up of an outbreak.

  10. Impaired T cell responsiveness to interleukin-6 in hematological patients with invasive aspergillosis.

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    Jose F Camargo

    Full Text Available Invasive mold infections (IMI are among the most devastating complications following chemotherapy and hematopoietic stem cell transplantation (HSCT, with high mortality rates. Yet, the molecular basis for human susceptibility to invasive aspergillosis (IA and mucormycosis remain poorly understood. Herein, we aimed to characterize the immune profile of individuals with hematological malignancies (n = 18 who developed IMI during the course of chemotherapy or HSCT, and compared it to that of hematological patients who had no evidence of invasive fungal infection (n = 16. First, we measured the expression of the pattern recognition receptors pentraxin 3, dectin-1, and Toll-like receptors (TLR 2 and 4 in peripheral blood of chemotherapy and HSCT recipients with IMI. Compared to hematological controls, individuals with IA and mucormycosis had defective expression of dectin-1; in addition, patients with mucormycosis had decreased TLR2 and increased TLR4 expression. Since fungal recognition via dectin-1 favors T helper 17 responses and the latter are highly dependent on activation of the signal transducer and activator of transcription (STAT 3, we next used phospho-flow cytometry to measure the phosphorylation of the transcription factors STAT1 and STAT3 in response to interferon-gamma (IFN-γ and interleukin (IL-6, respectively. While IFN-γ/STAT1 signaling was similar between groups, naïve T cells from patients with IA, but not those with mucormycosis, exhibited reduced responsiveness to IL-6 as measured by STAT3 phosphorylation. Furthermore, IL-6 increased Aspergillus-induced IL-17 production in culture supernatants from healthy and hematological controls but not in patients with IA. Altogether, these observations suggest an important role for dectin-1 and the IL-6/STAT3 pathway in protective immunity against Aspergillus.

  11. Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis.

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    Jung, J; Kim, M Y; Lee, H J; Park, Y S; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Kim, S-H

    2015-07-01

    Because there are no available molecular markers for pulmonary mucormycosis (PM), which has low culture sensitivity, early diagnosis and treatment rely heavily on imaging modes such as computed tomography (CT). However, there are limited data comparing CT findings for PM with those for invasive pulmonary aspergillosis (IPA). Adult patients who met the modified criteria for proven and probable PM (over an 11-year period) and IPA (over a 6-year period, owing to the availability of the galactomannan assay) according to the modified European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions were retrospectively enrolled. IPA cases were selected at a 1 : 4 (PM/IPA) ratio. Thoracic CT scans were reviewed by two experienced radiologists blinded to the patients' demographics and clinical outcomes. A total of 24 patients with PM, including 20 (83%) with proven PM and four (17%) with probable PM, and 96 patients with IPA, including 12 (13%) with proven IPA and 84 (87%) with probable IPA, were eventually analysed. The reverse halo sign was more common in patients with PM (54%) than in those with IPA (6%, p < 0.001), whereas some airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, were more common in patients with IPA (IPA 52% vs. PM 29%, p 0.04; IPA 49% vs. PM 21%, p 0.01; IPA 34% vs. PM 4%, p 0.003, respectively). The reverse halo sign was more common, and airway-invasive features were less common, in patients with PM than in those with IPA. These findings may help physicians to initiate Zygomycetes-active antifungal treatment earlier.

  12. Causes of death in a contemporary cohort of patients with invasive aspergillosis.

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    Carolina Garcia-Vidal

    Full Text Available Information regarding the processes leading to death in patients with invasive aspergillosis (IA is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011 of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensus using a six-member review panel. A multivariate analysis was performed to determine risk factors for IA-related death. Of 152 patients with IA, 92 (60.5% died. Mortality was judged to be IA-related in 62 cases and IA-unrelated in 30. The most common cause of IA-related death was respiratory failure (50/62 patients, caused primarily by Aspergillus infection, although also by concomitant infections or severe comorbidities. Progression of underlying disease and bacteremic shock were the most frequent causes of IA-unrelated death. IA-related mortality accounted for 98% and 87% of deaths within the first 14 and 21 days, respectively. Liver disease (HR 4.54; 95% CI, 1.69-12.23 was independently associated with IA-related mortality, whereas voriconazole treatment was associated with reduced risk of death (HR 0.43; 95% CI, 0.20-0.93. In conclusion, better management of lung injury after IA diagnosis is the main challenge for physicians to improve IA outcomes. There are significant differences in causes and timing between IA-related and IA-unrelated mortality and these should be considered in future research to assess the quality of IA care.

  13. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005-2007).

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    Lortholary, O; Gangneux, J-P; Sitbon, K; Lebeau, B; de Monbrison, F; Le Strat, Y; Coignard, B; Dromer, F; Bretagne, S

    2011-12-01

    A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (<42%; p <10(-3)). When positive (n = 245), cultures mainly yielded Aspergillus fumigatus (79.7%). First-line antifungal therapy consisted of voriconazole, caspofungin, lipid formulations of amphotericin, or any combination therapy (52%, 14%, 8% and 19.9%, respectively). Twelve-week overall mortality was 44.8% (95% CI, 39.8-50.0); it was 41% when first-line therapy included voriconazole and 60% otherwise (p <0.001). Independent factors for 12-week mortality were older age, positivity for both culture and galactomannan and central nervous system or pleural involvement, while any strategy containing voriconazole was protective.

  14. Allergic bronchopulmonary aspergillosis: A review of 42 patients from a tertiary care center in India

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    Prasad R

    2009-01-01

    Full Text Available Objective: To study the clinical, radiological, and laboratory profile in patients of allergic bronchopulmonary aspergillosis (ABPA. Materials and Methods: Retrospective analysis of 42 cases of ABPA, diagnosed over a period of 10 years from 1995 to 2005, for their clinical, radiological, and laboratory profiles. Results: Of 42 ABPA patients, 27 were men and 17 were women. Their mean age at the time of diagnosis was 31.2 years and mean duration of illness was 12.2 years. Breathlessness was the chief symptom. Other allergic disorders existed in 17 (40.5% patients, and family history suggestive of allergic disease was present in 22 (52.4% patients. Most common chest radiographic finding was fleeting pulmonary shadows in 28 (66.7% patients. High resolution CT thorax revealed central bronchiectasis as predominant finding. Peripheral blood eosinophilia more than 1000 cells/µl, Type I and type III cutaneous reactivity to Aspergillus antigen, elevated serum titers of total IgE antibody, A. fumigatus specific IgE and IgG antibodies, and serum precipitin against A. fumigatus were positive in majority of patients, who underwent these tests. Thirty eight (90.5% patients had had history of antitubercular treatment during the course of their illness. All 42 patients met at least four criteria for the diagnosis of ABPA. Conclusion: Any patient of bronchial asthma, presenting with recurrent shadows in chest radiograph and high peripheral blood eosinophilia, should be investigated for ABPA. Efforts need to be intensified to improve the awareness level among general physicians for early diagnosis and prompt treatment of this disease to avoid misuse of antitubercular drugs.

  15. Clinical and economic analysis of voriconazole using for treatment of invasive aspergillosis in Russian Federation

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    V. I. Ignatieva

    2015-06-01

    Full Text Available Introduction. Based on clinical studies data voriconazole is recommended as the drug of choice for treatment of invasive aspergillosis (IA – a widespread infectious complications occurring in immunocompromised patients and is characterized by severe clinical course and high mortality.The aim of this study was to assess the cost-effectiveness of voriconazole compared to other preparations recommended in the Russian practice for the treatment of IA in adult patients.Materials and methods. The authors constructed a «decision tree» type of model, which compared the three treatment alternatives for the IA in adult patients, depending on the drug in first-line therapy: 1 voriconazole, 2, caspofungin, or 3 amphotericin B lipid complex (LC. Efficacy was assessed as the probability of patient survival within 14 weeks of starting treatment. We took into account the drugs cost and an increase in the hospitalization duration due to the development of serious adverse events. The model parameters were determined on the basis of the published results of clinical studies, the costs were calculated on the basis of medicines prices in the public procurement and the average bed-day cost in system of obligatory health insurance. Probabilistic sensitivity analysis was performed.Results. It has been shown that the use of voriconazole for treatment of IA is the dominant strategy compared to the use of caspofungin and amphotericin B LC, providing cost reduction while achieving maximum effect. Probabilistic sensitivity analysis (1000 simulations showed stability of the revealed pattern.Conclusion. The use of voriconazole in the treatment of IA allows to save the greatest number of lives at minimal cost compared to other preparations recommended in the Russian practice.

  16. Common genetic polymorphisms within NFκB-related genes and the risk of developing invasive aspergillosis

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    Carmen Belén Lupiañez

    2016-08-01

    Full Text Available Invasive Aspergillosis (IA is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mould. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a 6-fold increased risk of developing the infection when compared with those carrying the C allele (OR-Rec=6.24, 95%CI 1.25-31.2, P=0.026, the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.

  17. Antigenic and anticorpal diagnosis of invasive aspergillosis and candidosis in immunocompromised host

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    Marco Machetti

    2009-03-01

    Full Text Available Invasive aspergillosis (IA and candidemia are an increasing cause of morbidity and mortality in immunocompromised patients, but diagnostic procedures are often hampered by critical patients conditions. In recent years, non-culture methods have reached a standardization level suitable to be marketed and widely employed. A method for a panfungal antigenic diagnosis, is the detection in serum of (1→3-ß-D-Glucan (BDG, a polisaccaridic component of fungal cell wall. Best results can be obtained in Aspergillus, Candida and Fusarium infections, while the test performs poorly with Cryptococcus and in zygomycosis. The use of this method are limited by the high costs and by the need of disposable materials certified as glucan-free, in order to avoid false positive results. Galactomannan (GM antigen detection is a method for non-invasive diagnosis of IA. The assay, in latex agglutination (LA and enzymeimmunoassay (EIA format, detect GM in serum, whose presence correlates with IA. Sensitivity and specificity strongly fluctuate (50-100% and 81-98% respectively depending on the time of sampling, the positivity cut-off employed, the concomitant administration of antifungal drugs and of some antibiotics. Nevertheless the method is a very useful and widely employed tool for the diagnosis of IA. For the diagnosis of candidemia, two Candida antigens may be detected in serum: the 56°C heat-labile antigen in LA format, and the mannan antigen, in LA and EIA format. Both the methods perform quite well, but sensitivities and specificities are not so good to allow a routinely and useful use in clinical practice.

  18. Comparative pharmacodynamics of posaconazole in neutropenic murine models of invasive pulmonary aspergillosis and mucormycosis.

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    Lewis, Russell E; Albert, Nathaniel D; Kontoyiannis, Dimitrios P

    2014-11-01

    We used two established neutropenic murine models of pulmonary aspergillosis and mucormycosis to explore the association between the posaconazole area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC) and treatment outcome. Posaconazole serum pharmacokinetics were verified in infected mice to ensure that the studied doses reflected human exposures with the oral suspension, delayed-release tablet, and intravenous formulations of posaconazole. Sinopulmonary infections were then induced in groups of neutropenic mice with Aspergillus fumigatus strain 293 (posaconazole MIC, 0.5 mg/liter) or Rhizopus oryzae strain 969 (posaconazole MIC, 2 mg/liter) and treated with escalating daily dosages of oral posaconazole, which was designed to achieve AUCs ranging from 1.10 to 392 mg · h/liter. After 5 days of treatment, lung fungal burden was analyzed by quantitative real-time PCR. The relationships of the total drug AUC/MIC and the treatment response were similar in both models, with 90% effective concentrations (EC90s) corresponding to an AUC/MIC threshold of 76 (95% confidence interval [CI], 46 to 102) for strain 293 versus 87 (95% CI, 66 to 101) for strain 969. Using a provisional AUC/MIC target of >100, these exposures correlated with minimum serum posaconazole concentrations (Cmins) of 1.25 mg/liter for strain 293 and 4.0 mg/liter for strain 969. The addition of deferasirox, but not liposomal amphotericin or caspofungin, improved the activity of a suboptimal posaconazole regimen (AUC/MIC, 33) in animals with pulmonary mucormycosis. However, no combination was as effective as the high-dose posaconazole monotherapy regimen (AUC/MIC, 184). Our analysis suggests that posaconazole pharmacodynamics are similar for A. fumigatus and R. oryzae when indexed to pathogen MICs.

  19. Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Report

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    Mehmet Akif Yazar

    2016-04-01

    Full Text Available SUMMARY Invasive pulmonary aspergillosis (IPA is an infection rarely seen in intensive care units (ICU. We aimed to discuss the case of IPA found in a patient followed up in our ICU due to chronic obstructive pulmonary disease (COPD. A 58-year old patient diagnosed with COPD has been admitted to our ICU due to respiratory failure. There were not any other diseases except from COPD. In his radiological imaging there were diffuse bilateral infiltrates in the chest X-ray and diffuse infiltration in the thorax tomography. Aspergillus spp was isolated in the bronchoalveolar lavage sample from patient and caspofungin was added to the treatment. On the 12th day of the treatment, it was observed that the results of the control radiological imaging became normal and there was no isolation in the control cultures. In recent years, fungal infections have been determined at an increasing rate in the patients who are not immunosuppressed and hospitalized in ICU. In the IPA cases, it has been shown that such underlying causes as diabetes, malnutrition, use of steroid, uremia, cirrhosis and COPD may create risk. Our patient did not have other disease except from COPD and there was a story of prolonged using of steroid. Steroids are quite frequently used in the ICUs. In the patients with chronic pulmonary diseases, even if it is low dose and short-term, the treatment of steroid is accepted as a risk factor in terms of IPA. Since signs and symptoms are atypical in this group of patients, it is rather difficult to diagnose IPA in the short term. The isolation of aspergillus in our patient’s tracheal aspirate taken earlier enabled us to start the treatment early. Although there are not comprehensive studies, it should be kept in mind that İPA may develop in the patients who is using long-term steroid, is admitted to the ICUs due to COPD exacerbations without any other disease.

  20. Pharmacokinetics, efficacy, and safety of caspofungin in Japanese pediatric patients with invasive candidiasis and invasive aspergillosis.

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    Mori, Masaaki; Imaizumi, Masue; Ishiwada, Naruhiko; Kaneko, Takashi; Goto, Hiroaki; Kato, Koji; Hara, Junichi; Kosaka, Yoshiyuki; Koike, Kazutoshi; Kawamoto, Hiroshi; Maeda, Naoko; Yoshinari, Tomoko; Kishino, Hiroyuki; Takahashi, Kenichi; Kawahara, Shizuko; Kartsonis, Nicholas A; Komada, Yoshihiro

    2015-06-01

    The antifungal agents approved in Japan for pediatric use are limited and many unapproved drugs are actually used without clear instruction for dosage. We investigated the pharmacokinetics of caspofungin for the treatment of invasive candidiasis and invasive aspergillosis in 20 Japanese pediatric patients using a pediatric-specific dosage based on body surface area. Caspofungin was administered intravenously over 60 min as 70 mg/m(2) on Day 1, followed by 50 mg/m(2) per day. Five or 4 point blood sampling were done in 15 patients on Day 4-5 to calculate AUC0-24 h. The geometric means (95% confidence interval) of C24 h and AUC0-24 h in the pediatric patients were 3.3(2.5, 4.4) μg/mL and 175.1 (139.3, 220.1) μg hr/mL, respectively, which were comparable to those in Japanese adult patients [3.2 (2.8, 3.5) μg/mL and 144.9 (131.7, 159.3) μg hr/mL, respectively]. Among the 20 patients, 10 (50%) had at least 1 drug-related adverse event which was considered related to caspofungin therapy. No drug-related serious adverse event and no death occurred. The most common drug-related adverse events were events relating to hepatic function (mainly increases in ALT and AST). The overall success in efficacy was observed in 13 of 20 patients. In conclusion, once daily administration of caspofungin (70 mg/m(2) on Day 1, followed by 50 mg/m(2) [maximum daily dose not to exceed 70 mg]), which is the same dosage being used in overseas, achieved sufficient drug exposure and a favorable efficacy and acceptable safety profile in Japanese pediatric patients with invasive fungal infections.

  1. Clinical and economic analysis of voriconazole using for treatment of invasive aspergillosis in Russian Federation

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    V. I. Ignatieva

    2015-01-01

    Full Text Available Introduction. Based on clinical studies data voriconazole is recommended as the drug of choice for treatment of invasive aspergillosis (IA – a widespread infectious complications occurring in immunocompromised patients and is characterized by severe clinical course and high mortality.The aim of this study was to assess the cost-effectiveness of voriconazole compared to other preparations recommended in the Russian practice for the treatment of IA in adult patients.Materials and methods. The authors constructed a «decision tree» type of model, which compared the three treatment alternatives for the IA in adult patients, depending on the drug in first-line therapy: 1 voriconazole, 2, caspofungin, or 3 amphotericin B lipid complex (LC. Efficacy was assessed as the probability of patient survival within 14 weeks of starting treatment. We took into account the drugs cost and an increase in the hospitalization duration due to the development of serious adverse events. The model parameters were determined on the basis of the published results of clinical studies, the costs were calculated on the basis of medicines prices in the public procurement and the average bed-day cost in system of obligatory health insurance. Probabilistic sensitivity analysis was performed.Results. It has been shown that the use of voriconazole for treatment of IA is the dominant strategy compared to the use of caspofungin and amphotericin B LC, providing cost reduction while achieving maximum effect. Probabilistic sensitivity analysis (1000 simulations showed stability of the revealed pattern.Conclusion. The use of voriconazole in the treatment of IA allows to save the greatest number of lives at minimal cost compared to other preparations recommended in the Russian practice.

  2. Immunodiagnosis of systemic aspergillosis. I. Antigenemia detected by radioimmunoassay in experimental infection. [/sup 125/I tracer technique

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    Weiner, M.H.; Coats-Stephen, M.

    1979-01-01

    Because systemic aspergillosis is difficult to diagnose ante mortem, a study to improve immunodiagnosis was undertaken in a rabbit model of disseminated infection. We found that the predominant humoral response of infected animals was directed against four Aspergillus antigens identified by crossed immunoelectrophoresis. One of these antigens, a cell-wall carbohydrate, was purified by gel-filtration chromatography and was used to develop a radiommunoassay. The sensitivity of this assay was increased by testing for serum-bound antigen as well as for free antigen. When the sensitivity of the RIA was evaluated in the animal model, antigenemia was detected in 78% of 51 rabbits with disseminated infection and ante mortem in 86% of 42 rabbits with lethal infection. By contrast, with immunoprecipitin analysis only eight of 51 rabbits were positive for antigen, and six of 51 rabbits were positive for Aspergillus antibody. The specificity of the RIA was also tested. Negative controls for antigen included sera from 76 normal rabbits and sera from 25 rabbits with systemic candidiasis. The Candida control group is pertinent because 48% of these rabbits had specific Candida antigenemia detected by a mannan RIA. This study demonstrates that Aspergillus antigenemia occurs during the course of experimental disseminated aspergillosis and illustrates the potential of an Aspergillus antigen RIA for sensitive, specific immunodiagnosis of human infections.

  3. Aspergillosis, a Natural Infection in Poultry: Mycological and Molecular Characterization and Determination of Gliotoxin in Aspergillus fumigatus Isolates.

    Science.gov (United States)

    de Oca, Verónica Montes; Valdés, Sara Esther; Segundo, Carolina; Gómez, Gabriela Guadalupe; Ramírez, José; Cervantes, Roberto Arnulfo

    2017-03-01

    Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis. A mycological culture was performed on the injured lungs of diseased birds, as was chloroform extraction of the GT, a thin-layer chromatography analysis (TLC), and a histopathology analysis with hematoxylin-eosin and Grocott stainings. The A. fumigatus identification was confirmed by PCR, where the ITS 1 5.1-5.8S-ITS 2 fragment of the rDNA complex was amplified. The in vitro GT production was studied by TLC in the recovered isolates from A. fumigatus . Seven isolates of A. fumigatus were obtained and in six of them, GT-like compounds were detected. In a lung sample, a compound with the same retention time (RF) as the reference GT was detected; whereas RF compounds different from the GT standard were observed in three lung samples.

  4. Enhanced antifungal efficacy in experimental invasive pulmonary aspergillosis by combination of AmBisome with Fungizone as assessed by several parameters of antifungal response

    NARCIS (Netherlands)

    M.J. Becker (Martin); S. de Marie (Siem); M.H.A.M. Fens (Marcel); W.C.J. Hop (Wim); H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma)

    2002-01-01

    textabstractIn common with a proportion of patients with invasive pulmonary aspergillosis (IPA), the efficacy of AmBisome treatment regimens in our rat model remains suboptimal. To investigate whether this might be the result of initially low antifungal activity of amphotericin B a

  5. In vitro release by Aspergillus fumigatus of galactofuranose antigens, 1,3-beta-D-glucan, and DNA, surrogate markers used for diagnosis of invasive aspergillosis.

    NARCIS (Netherlands)

    Mennink-Kersten, M.A.S.H.; Ruegebrink, D.; Wasei, N.; Melchers, W.J.G.; Verweij, P.E.

    2006-01-01

    Aspergillus markers are becoming increasingly important for the early diagnosis of invasive aspergillosis. The kinetics of release of these surrogate markers, however, is largely unknown. We investigated the release of beta-(1-5)-galactofuranosyl (galf) antigens (Platelia Aspergillus), 1,3-beta-D-gl

  6. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    NARCIS (Netherlands)

    L. Slobbe (Lennert); S. Polinder (Suzanne); J.K. Doorduijn (Jeanette); P.J. Lugtenburg (Pieternella); A. el Barzouhi (Abdelilah); E.W. Steyerberg (Ewout); B.J.A. Rijnders (Bart)

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods

  7. Pharmacodynamics of voriconazole against wild-type and azole-resistant aspergillus flavus isolates in a nonneutropenic murine model of disseminated aspergillosis

    NARCIS (Netherlands)

    S.M. Rudramurthy; S. Seyedmousavi (Seyedmojtaba); Dhaliwal, M. (Manpreet); A. Chakrabarti; J.F. Meis (Jacques F.); J.W. Mouton (Johan)

    2016-01-01

    textabstractInvasive aspergillosis (IA) due to Aspergillus flavus is associated with high mortality. Although voriconazole (VRC) is widely recommended as the first-line treatment for IA, emergence of azole resistance in Aspergillus spp. is translating to treatment failure. We evaluated the efficacy

  8. Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation

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    Tiziana Toffolutti

    2011-06-01

    Full Text Available An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT. He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.

  9. Prophylactic inhalation of Amphotericin B in invasive pulmonary aspergillosis: distribution study. Prophylaktische Inhalation von Amphotericin B bei invasiver Aspergillose: Verteilungsstudie

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    Barzen, G. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik); Beyer, J. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Medizinische Klinik und Poliklinik); Farshidfar, G. (Freie Univ. Berlin (Germany). Inst. fuer Diagnostikforschung); Kramp, W. (Freie Univ. Berlin (Germany). Inst. fuer Diagnostikforschung); Richter, W. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik); Felix, R. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik)

    1993-04-01

    Invasive pulmonary aspergillosis (IPA) during periods of immunosuppression or prolonged neutropenia is a serious condition with high mortality. Prophylaxis is unsatisfactory bcause of the low effectiveness of systemic administration of amphotericin B (AMB) and because of its side effects. Prophylactic inhalation of AMB by means of a nebulizing system may be able to reduce the incidence of IPA. Therefore, we studied the distribution of nebulized [sup 99m]Tc-labeled AMB and estimated its particle size. AMB is homogeneously distributed in the lung and partly deposited in the terminal respiratory unit; it remains there with a half-life of at least 14 h. Therefore, prophylaxis of IPA with AMB nebulized as described can be recommended. (orig.)

  10. Percutaneous treatment with amphotericin B in a case of invasive pulmonary aspergillosis; Tratamiento percutaneo con anfotericina B en un caso de aspergilosis pulmonar invasiva

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    Ruiz, A.; Lonjedo, E.; Agramunt, M.; Martinez-Rodrigo, J. J.; Palomero, J. [Hospital Universitario Dr. Peset. Valencia (Spain)

    2001-07-01

    Invasive pulmonary aspergillosis (IPA) is a serious complications that occurs in immunocompromised patients. We need a rapid and effective treatment both to treat the aspergillosis as well as to be able to continue, as soon as possible, treatment of the baseline disease. We present a case of a percutaneous treatment of the pulmonary lesions in a 55 year old male with IPA in the context of acute myeloid leukemia (AML). With Computerized Tomography (CT) control and using a fine needle, we injected intralesionally a solution of Amphotericin B (AB) (5 mg/cc of 5% glucose solution). We evaluated the complications and efficacy in relationship to the clinical improvement and reduction in lesion size. (Author) 18 refs.

  11. In vitro release by Aspergillus fumigatus of galactofuranose antigens, 1,3-beta-D-glucan, and DNA, surrogate markers used for diagnosis of invasive aspergillosis.

    OpenAIRE

    Mennink-Kersten, M.A.S.H.; Ruegebrink, D.; Wasei, N.; Melchers, W. J. G.; Verweij, P. E.

    2006-01-01

    Aspergillus markers are becoming increasingly important for the early diagnosis of invasive aspergillosis. The kinetics of release of these surrogate markers, however, is largely unknown. We investigated the release of beta-(1-5)-galactofuranosyl (galf) antigens (Platelia Aspergillus), 1,3-beta-D-glucan (BG) (Fungitell), and DNA (PCR) in an in vitro model of Aspergillus fumigatus. The results showed that release is correlated to the growth phase of the fungus, which depends on available nutri...

  12. Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence - a National Centre’s experience

    Science.gov (United States)

    2013-01-01

    Background Surgery for pulmonary aspergillosis is infrequent and often challenging. Risk assessment is imprecise and new antifungals may ameliorate some surgical risks. We evaluated the medical and surgical management of these patients, including perioperative and postoperative antifungal therapy. Methods Retrospective study of patients who underwent surgery for pulmonary aspergillosis between September 1996 and September 2011. Results 30 patients underwent surgery with 23 having a preoperative tissue diagnosis while 7 were confirmed post-resection. The median age was 57 years (17–78). The commonest presenting symptoms were cough (40%, n = 12) and haemoptysis (43%, n = 13). Twelve (40%) patients had simple aspergilloma (including 2 with Aspergillus nodules) while the remaining 18 (60%) had chronic cavitary pulmonary aspergillosis (CCPA) (complex aspergilloma). Most of the patients had underlying lung disease: tuberculosis (20%, n = 6), asthma (26%, n = 8) and COPD (20%, n = 6). The procedures included lobectomy 50% (n = 15), pneumonectomy 10% (n = 3), sublobar resection 27% (n = 8), decortication 7% (n = 2), segmentectomy 3% (n = 1), thoracoplasty 3% (n = 1), bullectomy and pleurectomy 3% (n = 1), 6% (n = 2) lung transplantation for associated disease. Median hospital stay was 9.5 days (3–37). There was no operative and 30 day mortality. Main complications were prolonged air leak (n = 7, 23%), empyema (n = 6, 20%), respiratory failure requiring tracheostomy /reintubation (n = 4, 13%). Recurrence of CCPA was noted in 8 patients (26%), most having prior CCPA (75%). Taurolidine 2% was active against all 9 A. fumigatus isolates and used for pleural decontamination during surgery. Conclusions Surgery in patients with chronic pulmonary aspergillosis offered good outcomes with an acceptable morbidity in a difficult clinical situation; recurrence is problematic. PMID:23915502

  13. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    OpenAIRE

    Slobbe, Lennert; Polinder, Suzanne; Doorduijn, Jeanette; Lugtenburg, Pieternella; Barzouhi, Abdelilah; Steyerberg, Ewout; Rijnders, Bart

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods. In 269 patients treated for acute myelogenous leukemia-myelodysplastic syndrome (AML-MDS) during 2002-2007, evidence of IA was collected using high-resolution computed tomography and galactomanna...

  14. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-10-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

  15. Research progress on animal model of invasive pulmonary aspergillosis%侵袭性肺曲霉病动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    张冬梅; 宋泽庆

    2011-01-01

    近20年来,随着广谱抗生素、糖皮质激素、放疗、化疗的广泛应用,烧伤、器官移植、血液透析、肠外营养人数的增加以及艾滋病的流行等,侵袭性肺曲霉病的发病率日益增加.随着侵袭性肺曲霉病的发病机制以及早期诊断等相关研究不断深入,相关研究需建立在成功的动物模型基础上,所以动物模型的建立具有重要意义.本文对近几年肺曲霉病的动物模型研究作一综述.%In recent twenty years, with the extensive use of broad-spectrum antibiotics, corticosteroids, radiotherapy, chemotherapy, the increase of burns, organ transplantation, hemodialysis, parenteral nutrition, and the prevalence of acquired immune deficiency syndrome, the morbidity of invasive pulmonary aspergillosis is increasing. With the deep researches on mechanism and early diagnosis of invasive pulmonary aspergillosis, relevant research should be based on successful animal model, so the animal model is important. This article summaries the researches about animal model of pulmonary aspergillosis in recent years.

  16. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis.

    Science.gov (United States)

    Abad, Ana; Fernández-Molina, Jimena Victoria; Bikandi, Joseba; Ramírez, Andoni; Margareto, Javier; Sendino, Javier; Hernando, Fernando Luis; Pontón, Jose; Garaizar, Javier; Rementeria, Aitor

    2010-01-01

    Aspergillus fumigatus is an opportunistic pathogen that causes 90% of invasive aspergillosis (IA) due to Aspergillus genus, with a 50-95% mortality rate. It has been postulated that certain virulence factors are characteristic of A. fumigatus, but the "non-classical" virulence factors seem to be highly variable. Overall, published studies have demonstrated that the virulence of this fungus is multifactorial, associated with its structure, its capacity for growth and adaptation to stress conditions, its mechanisms for evading the immune system and its ability to cause damage to the host. In this review we intend to give a general overview of the genes and molecules involved in the development of IA. The thermotolerance section focuses on five genes related with the capacity of the fungus to grow at temperatures above 30°C (thtA, cgrA, afpmt1, kre2/afmnt1, and hsp1/asp f 12). The following sections discuss molecules and genes related to interaction with the host and with the immune responses. These sections include β-glucan, α-glucan, chitin, galactomannan, galactomannoproteins (afmp1/asp f 17 and afmp2), hydrophobins (rodA/hyp1 and rodB), DHN-melanin, their respective synthases (fks1, rho1-4, ags1-3, chsA-G, och1-4, mnn9, van1, anp1, glfA, pksP/alb1, arp1, arp2, abr1, abr2, and ayg1), and modifying enzymes (gel1-7, bgt1, eng1, ecm33, afpigA, afpmt1-2, afpmt4, kre2/afmnt1, afmnt2-3, afcwh41 and pmi); several enzymes related to oxidative stress protection such as catalases (catA, cat1/catB, cat2/katG, catC, and catE), superoxide dismutases (sod1, sod2, sod3/asp f 6, and sod4), fatty acid oxygenases (ppoA-C), glutathione tranferases (gstA-E), and others (afyap1, skn7, and pes1); and efflux transporters (mdr1-4, atrF, abcA-E, and msfA-E). In addition, this review considers toxins and related genes, such as a diffusible toxic substance from conidia, gliotoxin (gliP and gliZ), mitogillin (res/mitF/asp f 1), hemolysin (aspHS), festuclavine and fumigaclavine A

  17. Aspergilose orbitária: relato de caso Ocular aspergillosis: case report

    Directory of Open Access Journals (Sweden)

    Patrícia Ioschpe Gus

    2005-02-01

    inicia-se o manejo, segundo o quadro de sintomas.Presence of fungus in the conjunctiva is a constant threat to the eyes, because these microorganisms, defined as opportunistic, may provoke severe ocular infections, in situations as low organic resistance, use of immunosuppressants, antibiotics and epithelial alteration. Our goal here is to report a case of ocular aspergillosis in an immunosupressed patient where paroxysmal nocturnal hemoglobinuria was diagnosed. A 51-year-old immunosupressed, thrombocytopenic patient was hospitalized with a diagnosis of paroxysmal nocturnal hemoglobinuria. On examination, she had a visual acuity of 20/40 in the right eye (RE and light perception in the left (LE. She presented hyposphagma, bilateral conjunctival edema on biomicroscopy and had some multiple and circumscribed conjunctival abscesses in both eyes; clear cornea in both eyes. Fundoscopy of the RE did show any particularity, in the LE there was a smear hemorrhage. Computed tomograph showed a fat periocular infiltration. Magnetic resonance lead to the same finding, compatible with orbital cellulitis. Hemoculture showed Aspergillus growth and direct smears of conjunctival material was negative. There was great improvement while treating her with amphotericin B, but there was complete remission after using 5% natamicyn eye drops. Orbital infections caused by Aspergillus are uncommon, usually appearing in immunosuppressed patients. Frequently they progress insidiously, and can be confounded with other orbital processes. Immunological impairment can inhibit the expression of local and systemic symptoms, resulting in diagnostic confusion. The diagnosis is established by laboratory tests, but culture can be negative in spite of the classical presentation, making the beginning of treatment difficult. In these cases management starts according to the symptoms.

  18. mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats

    Institute of Scientific and Technical Information of China (English)

    Na Cui; Long-Xiang Su; Hao Wang; Meng Xiao; Fei Yang; Min Zheng; Xin Li

    2016-01-01

    Background:Aspergillosis infection is common in the patients with insufficient immunity.The role of mammalian target ofrapamycin (mTOR),T-box expressed in T-cells (T-bet),and eomesodermin (EOMES) in mediating T lymphocytes differentiation in response to Aspergillus fumigatus infection in immunocompromised rats was investigated in this study.Methods:Invasive pulmonary aspergillosis (IPA) ofimmtmosuppressive twenty male rats were established and sacrificed at 24 h (n =5),48 h (n =5),72 h (n =5),and 96 h (n =5) after A.fumigatus infection.In addition,control (n =5),cyclophosphamide (CTX) (n =5),and aspergillosis (n =5) group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining.CD8+ T-cells was sorted by flow cytometry.Serum mTOR,S6K,T-bet,and EOMES were quantified by enzyme-linked immunosorhent assay.Results:Histology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells,alveolar wall damage or degradation,blood congestion,and hemorrhage in the CTX,IPA,and CTX + IPA rats.Hyphae were seen in the IPA,and CTX + IPA groups.The proportion of CD8+ T-cells was significantly increased in the animals ofCTX + IPA.Memory CD8+ T-cells was significantly increased in early stage (24 h and 48 h,P < 0.001),but decreased in the late phase of fungal infection (72 h and 96 h) in the animals of CTX + IPA.In addition,at early stage of fungal infection (24 h and 48 h),serum mTOR (P < 0.001),S6K (P < 0.001),and T-bet (P < 0.05) was significantly higher,while EOMES was significantly lower (P < 0.001),in CTX + IPA group than that in control,CTX alone or IPA alone group.Conversely,serum mTOR,S6K,T-bet,and EOMES showed opposite changed in the late stage (72 h and 96 h).Pearson's correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet (r =0.901 and 0.91,respectively,P < 0.001),but negatively and significantly correlated with EOMES (r =-0.758 and-0

  19. New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    Duret C

    2012-10-01

    -based DPI (<10 ng/mL.Conclusion: Embedding ITZ NP in inhalable microparticles is a very effective method to produce DPI formulations with optimal aerodynamic properties and enhanced ITZ solubility. These formulations could be applied to other poorly water-soluble drugs and could be a very effective alternative for treating invasive pulmonary aspergillosis.Keywords: aspergillosis, spray-drying, homogenization, inhalation, saturation, solubility

  20. [Management of aspergillosis in immunocompromised patients. Recommendations of Lille University Hospital--4th version--November 2004].

    Science.gov (United States)

    Alfandari, S; Leroy, O; de Botton, S; Yakoub-Agha, I; Durand-Joly, I; Leroy-Cotteau, A; Beaucaire, G

    2005-03-01

    Invasive aspergillosis is a severe complication in immunocompromised patients. The arrival of new antifungal agents motivated the redaction of guidelines, regularly updated, by a Lille University hospital multidisciplinary task force. These guidelines assess diagnostic and therapeutic issues. The main recommended diagnosis tool is the chest CT scan, ordered at the smallest suspicion and, also, measure of the blood and broncho alveolar lavage fluid galactomannan. Treatment guidelines assess prophylaxis, empirical and documented therapy. Primary prophylaxis is warranted in only two cases, pulmonary graft or stem cell transplant in patients with chronic GVH and receiving corticosteroids. Empirical therapy should use one of the available amphotericin B formulations, chosen according to the patient history. Caspofungin is another choice. Documented therapy, depending on presentation, can be a single drug or a combination. First line therapy for single drug is i.v. voriconazole. Lipid formulations of amphotericin B are another choice. A combination therapy can be used as a first line treatment, for multiple lesions, or as salvage therapy. It must include caspofungin, associated with liposomal amphotericin B or voriconazole. A tight cooperation with thoracic surgeons is recommended.

  1. Potential of polymerase chain reaction and galactomannan for the diagnosis of invasive aspergillosis in patients with febrile neutropenia.

    Science.gov (United States)

    Aslan, Muge; Oz, Yasemin; Aksit, Filiz; Akay, Olga M

    2015-06-01

    The incidence of invasive aspergillosis (IA) has increased over the last years, especially in immuncompromised patients with high mortality rates. Because of difficulties about the diagnosis; serological methods [galactomannan (GM) antigen test] and polymerase chain reaction (PCR) developed in recent years. MycAssay Aspergillus PCR performance in the diagnosis of IA was evaluated and compared with the GM and in-house PCR. This study was conducted with 358 serum samples obtained from 99 patient with febrile neutropenic episodes who were followed in haematology and bone marrow transplantation units. Patients were classified by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 18 of them is proven and probable IA. GM antigen test and two different real-time PCR; one of them is fist commercial PCR for IA; Mycassay Aspergillus and the other one is in-house real-time PCR performed. Sensitivity values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and 23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR and sensitivity is increased by using a combination of diagnostic methods. GM antigen test and real-time PCR could be beneficial for early diagnosis and treatment of IA. For routine usage of PCR as diagnostic assay more studies needed in future.

  2. Is a biomarker-based diagnostic strategy for invasive aspergillosis cost effective in high-risk haematology patients?

    Science.gov (United States)

    Macesic, N; Morrissey, C O; Liew, D; Bohensky, M A; Chen, S C-A; Gilroy, N M; Milliken, S T; Szer, J; Slavin, M A

    2017-01-27

    Empirical antifungal therapy is frequently used in hematology patients at high risk of invasive aspergillosis (IA), with substantial cost and toxicity. Biomarkers for IA aim for earlier and more accurate diagnosis and targeted treatment. However, data on the cost-effectiveness of a biomarker-based diagnostic strategy (BDS) are limited. We evaluated the cost effectiveness of BDS using results from a randomized controlled trial (RCT) and individual patient costing data. Data inputs derived from a published RCT were used to construct a decision-analytic model to compare BDS (Aspergillus galactomannan and PCR on blood) with standard diagnostic strategy (SDS) of culture and histology in terms of total costs, length of stay, IA incidence, mortality, and years of life saved. Costs were estimated for each patient using hospital costing data to day 180 and follow-up for survival was modeled to five years using a Gompertz survival model. Treatment costs were determined for 137 adults undergoing allogeneic hematopoietic stem cell transplant or receiving chemotherapy for acute leukemia in four Australian centers (2005-2009). Median total costs at 180 days were similar between groups (US[Formula: see text] for SDS [IQR US[Formula: see text

  3. Avian morbidity and mortality from botulism, aspergillosis, and salmonellosis at Jamaica Bay Wildlife Refuge, New York, USA

    Science.gov (United States)

    Brand, C.J.; Windingstad, R.M.; Siegfried, L.M.; Duncan, R.M.; Cook, R.M.

    1988-01-01

    During the summers of 1981 and 1982, studies were conducted at Jamaica Bay Wildlife Refuge, Long Island, New York, to determine whether annual water-level drawdowns used to create shorebird habitat also led to the occurrence of avian botulism (Clostridium botulinum type C). Low levels of morbidity and mortality from avian botulism occurred on the two ponds throughout both summers, but there was no apparent relationship between the occurrence or rates of botulism losses and drawdowns of the ponds. Botulism also occurred throughout both summers on other areas of the refuge. Botulinal toxin was found in fly larvae associated with avian carcasses, including birds that did not die from botulism. Toxin was not found in other samples of aquatic biota in the ponds, although it was demonstrated in a single sample of decomposing sea lettuce (Ulva lactuca) in Jamaica Bay. Aspergillosis (Aspergillus fumigatus) and salmonellosis (Salmonella spp.) were also frequently-diagnosed causes of morbidity and mortality. We believe that botulinal toxin present in carcasses of birds dying from botulism, or produced postmortem in birds dying from other causes, on the two ponds and other areas in Jamaica Bay were a major source of botulinal toxin. Toxin could be ingested by birds through direct scavenging on carcasses, or by consumption of toxic fly larvae associated with carcasses. Diligent carcass pickup at the two ponds is recommended to reduce mortality from avian botulism.

  4. Interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model.

    Science.gov (United States)

    Zhang, Chang-Ran; Lin, Jian-Cong; Xu, Wen-Ming; Li, Ming; Ye, Hui-Shao; Cui, Wei-Ling; Lin, Qing

    2013-03-01

    Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin-12 (IL-12) and IL-2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL-12 and IL-2, interferon-γ (IFN-γ) was detected in the sera using ELISA, quantification of IFN-γ mRNA using real-time RT-PCR and lung Colony-forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL-12 and/or IL-2 could enhance the IFN-γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL-12 and IL-2 could assist in increasing the IFN-γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL-12 and IL-2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.

  5. Evidence supporting a role for mammalian chitinases in efficacy of caspofungin against experimental aspergillosis in immunocompromised rats.

    Directory of Open Access Journals (Sweden)

    Patricia E B Verwer

    Full Text Available OBJECTIVES: Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA, strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activity is reached. Caspofungin is known to increase the amount of chitin in the fungal cell wall. Mammals produce two chitinases, chitotriosidase and AMCase, which can hydrolyse chitin. We hypothesized that the mammalian chitinases play a role in the in vivo efficacy of caspofungin. METHODS: In order to determine the role of chitotriosidase and AMCase in IPA, both chitinases were measured in rats which did or did not receive caspofungin treatment. In order to understand the role of each chitinase in the breakdown of the caspofungin-exposed cells, we also exposed caspofungin treated fungi to recombinant enzymes in vitro. RESULTS: IPA in immunocompromised rats caused a dramatic increase in chitinase activity. This increase in chitinase activity was still noted when rats were treated with caspofungin. In vitro, it was demonstrated that the action of both chitinases were needed to lyse the fungal cell wall upon caspofungin exposure. CONCLUSION: Caspofungin seemed to alter the cell wall in such a way that the two chitinases, when combined, could lyse the fungal cell wall and assisted in clearing the fungal pathogen. We also found that both chitinases combined had a direct effect on the fungus in vitro.

  6. Diagnosis and Treatment of Chicken Aspergillosis%鸡曲霉菌病的诊断和治疗

    Institute of Scientific and Technical Information of China (English)

    范成英; 顾阳; 付朋飞; 陈红英

    2013-01-01

    In May 2013,there was a suspected chicken Aspergillosis in a chicken farm in Weihui County. Nodules on the lung and air sac were collected aseptically from sick and deed chickens. Characteristic hyphae and spores of Aspergillus were observed under the microscope,and its biochemical identifications were performed and Aspergillus was isolated.After the epidemiology investigation,the pathogenic in autopsy,the laboratory diagnosis, and clinical symptom,the chicken Aspergillus infection was diagnosed. Feeding chickens on nysfungin and copper sulfate solution in drinking water had some effect.%2013年5月河南省卫辉县某鸡场发生疑似曲霉菌感染的病例。无菌采集病鸡肺、气囊上的结节病灶,在显微镜下观察到特征性的曲霉菌的菌丝和孢子,分离出曲霉菌。实验室检查结果结合发病情况、临床症状和剖检变化,诊断为曲霉菌感染。通过饲喂制霉菌素并硫酸铜溶液饮水,取得了一定疗效。

  7. Computer tomography in pulmonary invasive aspergillosis in hematological patients with neutropenia: An useful tool for diagnosis and assessment of outcome in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Caillot, Denis, E-mail: denis.caillot@chu-dijon.f [Dijon University Hospital Center, Dijon (France); Latrabe, Valerie [Bordeaux University Hospital Center, Bordeaux (France); Thiebaut, Anne [Lyon University Hospital Center, Lyon (France); Herbrecht, Raoul [Strasbourg Regional University Hospital Center, Strasbourg (France); De Botton, Stephane [Lille Regional University Hospital Center, Lille (France); Pigneux, Arnaud [Bordeaux University Hospital Center, Bordeaux (France); Monchecourt, Francoise; Mahi, Lamine [Gilead Sciences, Paris (France); Alfandari, Serge [Lille Regional University Hospital Center, Lille (France); Couaillier, Jean-Francois [Dijon University Hospital Center, Dijon (France)

    2010-06-15

    Background and objective: The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial. Design and methods: Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n = 26) or proven (n = 4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT). Results: For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p = 0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p = 0.003 for D14 vs. D7, but with p = 0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p < 0.001) but it was not significantly different when compared to D0 (p = 0.11). Conclusions: The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials.

  8. Comparative Efficacies of Four Amphotericin B Formulations—Fungizone, Amphotec (Amphocil), AmBisome, and Abelcet—against Systemic Murine Aspergillosis

    OpenAIRE

    Clemons, Karl V.; Stevens, David A.

    2004-01-01

    We compared various amphotericin B formulations (no treatment or 0.8 mg of Fungizone [conventional deoxycholate amphotericin B] per kg of body weight, or 0.8, 4, or 8 mg of Amphocil, AmBisome, or Abelcet per kg of body weight) for treatment of systemic murine aspergillosis. In two studies, all formulations prolonged survival, with the results for AmBisome nearly equivalent to those for Fungizone; Amphocil and Abelcet were less effective or equivalent depending on the severity of infection. No...

  9. Correlation between high-resolution computed tomography and galactomannan antigenemia in adult hematologic patients at risk for invasive aspergillosis

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, A. [Department of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona, Barcelona (Spain)], E-mail: alhidalgop@yahoo.es; Parody, R.; Martino, R. [Department of Hematology, Hospital de Sant Pau, Universidad Autonoma de Barcelona, Barcelona (Spain); Sanchez, F. [Department of Microbiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona, Barcelona (Spain); Franquet, T.; Gimenez, A.; Blancas, C. [Department of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona, Barcelona (Spain)

    2009-07-15

    Objectives: To analyse the predominant radiological pattern of pulmonary lesions in adult hematologic patients at risk for invasive aspergillosis (IA) together with the results of serial serum Aspergillus galactomannan antigen testing (GM). Material and methods: In a prospective study for patients at high risk of aspergillus pulmonary infection, serum GM were performed 2-3 times per week during the periods of high risk for IA and high-resolution CT (HRCT) was performed in case of abnormal chest X-ray (CXR) and/or persistent fever after 5 days of antibiotic treatment. Changes on HRCT scan were classified as airway IA and angioinvasive IA. IA was classified as proven or probable in accordance with the definitions stated by the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC-MS). Positive GM testing was not considered as microbiological criterion. Results: 38 hematological patients were diagnosed of probable (n = 28) or proven (n = 10) IA. 55% patients had a neutrophil count less than 500 mm{sup -3} (n = 21), and 37% patients {>=}2 risk factors for IA. All probable IA were diagnosed by bronchoalveolar lavage (BAL). Proven IA was reached by positive histopathologic and culture results of samples obtained by autopsy (n = 4), percutaneous (n = 3) or transbronchial biopsy (n = 3). 18 patients had airway IA, and 60% had a GM level {>=}1.5. 20 patients were diagnosed of angioinvasive IA from which 80% had a GM level {>=}1.5. Conclusion: Serum GM levels may be lower in patients with airway IA than in those with an angioinvasive form. HRCT and serum GM are complementary tests in the diagnosis of IA.

  10. Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.

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    Allan R Brasier

    Full Text Available Invasive pulmonary aspergillosis (IPA is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides, fungal polysaccharides (galactomannan, and cell wall components (β-D glucan were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS produced a greater case classification accuracy than galactomannan (GM or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients

  11. Evaluation of PCR on bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis: a bivariate metaanalysis and systematic review.

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    Wenkui Sun

    Full Text Available BACKGROUND: Nucleic acid detection by polymerase chain reaction (PCR is emerging as a sensitive and rapid diagnostic tool. PCR assays on serum have the potential to be a practical diagnostic tool. However, PCR on bronchoalveolar lavage fluid (BALF has not been well established. We performed a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays on BALF for invasive aspergillosis (IA. METHODS: Relevant published studies were shortlisted to evaluate the quality of their methodologies. A bivariate regression approach was used to calculate pooled values of the method sensitivity, specificity, and positive and negative likelihood ratios. Hierarchical summary receiver operating characteristic curves were used to summarize overall performance. We calculated the post-test probability to evaluate clinical usefulness. Potential heterogeneity among studies was explored by subgroup analyses. RESULTS: Seventeen studies comprising 1191 at-risk patients were selected. The summary estimates of the BALF-PCR assay for proven and probable IA were as follows: sensitivity, 0.91 (95% confidence interval (CI, 0.79-0.96; specificity, 0.92 (95% CI, 0.87-0.96; positive likelihood ratio, 11.90 (95% CI, 6.80-20.80; and negative likelihood ratio, 0.10 (95% CI, 0.04-0.24. Subgroup analyses showed that the performance of the PCR assay was influenced by PCR assay methodology, primer design and the methods of cell wall disruption and DNA extraction. CONCLUSIONS: PCR assay on BALF is highly accurate for diagnosing IA in immunocompromised patients and is likely to be a useful diagnostic tool. However, further efforts towards devising a standard protocol are needed to enable formal validation of BALF-PCR.

  12. NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

    Institute of Scientific and Technical Information of China (English)

    Peng XU; Jie-ming QU; Jin-fu XU; Jing ZHANG; Hong-ni JIANG; Hui-jun ZHANG

    2009-01-01

    Aim:Neutropenic individuals are at high risk for invasive pulmonary aspergillosis (IPA),a life-threatening infection.To evaluate the therapeutic potential of antioxidants,IPA was induced in neutropenic mice and the effect of N-acetyl-l-cysteine (NAC) on oxidative stress levels and lung injury was analyzed.Methods:Mice were pretreated with three daily intraperitoneal injections of 150 mg/kg cyclophosphamide,followed by intratracheal inoculation with 4.5×106 conidia of Aspergillus fumigatus.The infected mice were then randomly assigned to an amphotericin B (AMB) group,an AMB plus NAC group,or an untreated control (C) group.In each group,the duration of treatment was 24,48,or 72 h,and activities such as appearance,feeding,and dermal temperature were observed throughout the experiment.Sera and lung tissues were collected and analyzed by quantitative enzyme-linked immunosorbent assay (ELISA) for total protein,superoxide dismutase(SOD),malondialdehyde (MDA),tumor necrosis factor-α (TNF-α),and interleukin-lO (IL-10) levels.The wet/dry weight ratio of the lung was also calculated and lung sections were stained with hematoxylin-eosin for pathological examination and with methenamine silver stain for fungus detection.Results:Compared with the mice untreated with NAC,mice in the AMB plus NAC group had increased SOD and reduced MDA levels both systemically and locally at 24,48,and 72 h after inoculation with conidia.NAC treatment also decreased the pulmonary protein content at 48 and 72 h and the lung wet/dry weight ratio at 24 and 48 h.Additionally,NAC enhanced pulmonary production of TNF-α and IL-10 at 24 h and 48 h.Conclusion:In combination with antifungal therapy,NAC treatment can alleviate oxidative stress and lung injury associated with IPA in neutropenic mice.

  13. Caspofungin for treatment of invasive aspergillosis in Germany: results of a pre-planned subanalysis of an international registry

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    Egerer Gerlinde

    2012-04-01

    Full Text Available Abstract Background This study is a pre-planned country-specific subanalysis of results in Germany from a multinational multicenter registry to prospectively assess real-world experience with caspofungin administered for treatment of proven or probable invasive aspergillosis (IA. Methods Data from patients treated with caspofungin for a single episode of IA were collected. Effectiveness was determined by the local investigator as favorable (complete or partial response or unfavorable (stable disease, failure or death at the end of caspofungin therapy. Descriptive statistics with binomial exact confidence intervals were employed. Results Forty-two consecutive patients were identified in three German centers. Three patients (7% had proven IA and 39/42 (93% had probable IA (modified European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG criteria. Forty-one patients had pulmonary IA and one had tracheal IA. Caspofungin monotherapy was received by 36/42 patients (86%; of these, 26/36 (72% received salvage therapy. A favorable response was observed in 29/42 patients (69%; 95% CI 53 to 82%; of these, 21/29 (72% had a complete and 8/29 (28% a partial response. Favorable response rate was 69% in patients with monotherapy (95% CI 52% to 84%; 25/36 patients, and 67% in patients receiving combination therapy (95% CI 22% to 96%; 4/6 patients. Favorable response rate in patients with first line therapy was 64% (95% CI 31% to 89%; 7/11 patients, and 73% in patients with second line therapy (95% CI 54% to 88%; 20/30 patients. No adverse events were reported. In total, 35/42 patients (83%; 95% CI 69 to 93% survived seven days after completion of caspofungin therapy. Conclusions These real-life findings in Germany are consistent with the international findings from this registry and with findings from randomized studies.

  14. Caspofungin Use in Daily Clinical Practice for Treatment of Invasive Aspergillosis: Results of a Prospective Observational Registry

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    Chandwani Sheenu

    2010-06-01

    Full Text Available Abstract Background A prospective observational registry assessed real world experience with caspofungin monotherapy or combination therapy for the initial or salvage treatment of proven or probable invasive aspergillosis (IA. Methods Data were collected from April 2006 to September 2007 for patients treated with caspofungin for a single episode of IA. Clinical effectiveness was categorized as favorable (complete or partial or unfavorable (stable disease or failure at the end of caspofungin therapy (EOCT. Results Consecutive patients (n = 103 with proven or probable IA (per EORTC/MSG criteria were identified from 11 countries. Malignancy (76.7%, neutropenia (64.1%, allogeneic hematopoietic stem cell transplantation (HSCT, 22.3%, solid organ transplantation (8.7%, autologous HSCT (4.9%, and HIV/AIDS (2.9% were the most common underlying conditions. Most patients (84.5% had pulmonary IA. Aspergillus fumigatus was the most frequently isolated species. The majority of patients received caspofungin monotherapy (82.5% primarily as salvage therapy (82.4%. The main reason for switching to salvage therapy was clinical failure of the first-line therapy (69%. A favorable response at EOCT was seen in 56.4% (57/101 of patients overall, including 56.5% (48/85 and 56.3% (9/16 of patients receiving caspofungin monotherapy and combination therapy, respectively. Favorable response rates in clinically relevant subgroups were: malignancy, 51.9% (41/79; allogeneic HSCT, 56.5% (13/23; and neutropenia at time of hospitalization, 53.0% (35/66. There was a 72.3% (73/101 survival at 7 days after EOCT. Serious adverse events related to caspofungin were reported in 4 cases (3.9%; 3 patients (2.9% discontinued treatment due to an adverse event related to caspofungin. Conclusions Caspofungin was both effective and well tolerated among high-risk patient groups such as those with neutropenia and active malignancies.

  15. Application of a low molecular weight antifungal protein from Penicillium chrysogenum (PAF) to treat pulmonary aspergillosis in mice.

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    Palicz, Zoltán; Gáll, Tamás; Leiter, Éva; Kollár, Sándor; Kovács, Ilona; Miszti-Blasius, Kornél; Pócsi, István; Csernoch, László; Szentesi, Péter

    2016-11-09

    PAF, a small antifungal protein from Penicillium chrysogenum, inhibits the growth of several pathogenic filamentous fungi, including members of the Aspergillus genus. PAF has been proven to have no toxic effects in vivo in mice by intranasal application. To test its efficacy against invasive pulmonary aspergillosis (IPA), experiments were carried out in mice suffering from IPA. Adult mice were immunosuppressed and then infected with Aspergillus fumigatus. After stable infection, the animals were inoculated with PAF intranasally at a concentration of 2.7 mg/kg twice per day. At this concentration-which is highly toxic in vitro to A. fumigatus-the mortality of the animals was slightly delayed but finally all animals died. Histological examinations revealed massive fungal infections in the lungs of both PAF-treated and untreated animal groups. Because intranasally administered PAF was unable to overcome IPA, modified and combined therapies were introduced. The intraperitoneal application of PAF in animals with IPA prolonged the survival of the animals only 1 day. Similar results were obtained with amphotericin B (AMB), with PAF and AMB being equally effective. Combined therapy with AMB and PAF-which are synergistic in vitro-was found to be more effective than either AMB or PAF treatment alone. As no toxic effects of PAF in mammals have been described thus far, and, moreover, there are so far no A. fumigatus strains with reported inherent or acquired PAF resistance, it is worth carrying out further studies to introduce PAF as a potential antifungal drug in human therapy.

  16. Aspergilose broncopulmonar alérgica com imagem radiológica em "dedo de luva" Allergic bronchopulmonary aspergillosis presenting a glove-finger shadow in radiographic images

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    Marta Elizabeth Kalil

    2006-10-01

    Full Text Available A aspergilose broncopulmonar alérgica é uma doença pulmonar que ocorre em pacientes com asma ou fibrose cística, desencadeada pela reação de hipersensibilidade à presença do fungo Aspergilus fumigatus nas vias aéreas. Relatamos aqui um caso em que uma paciente com quadro clínico sugestivo de asma apresentou critérios clínicos, laboratoriais e radiológicos compatíveis com o diagnóstico de aspergilose broncopulmonar alérgica. A importância de tais achados deve-se ao fato de que quanto mais precocemente for feito o diagnóstico, menores serão os riscos de agravamento do quadro respiratório e de aparecimento de fibrose.Allergic bronchopulmonary aspergillosis is a lung disease occurring in patients with asthma or cystic fibrosis, triggered by a hypersensitivity reaction to the presence of Aspergillus fumigatus in the airways. We report herein the case of a patient presenting a clinical profile suggestive of asthma and meeting the clinical, laboratory testing and radiological criteria for a diagnosis of allergic bronchopulmonary aspergillosis. The importance of such findings is that early diagnosis can reduce the risk of respiratory exacerbations and fibrosis.

  17. Aspergilosis pulmonar necrotizante crónica como complicación de silicosis Chronic necrotizing pulmonary aspergillosis as a complication of silicosis

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    J.J. Blanco

    2011-04-01

    Full Text Available La aspergilosis pulmonar necrotizante crónica es una rara enfermedad que tiende a afectar a personas con enfermedad pulmonar subyacente o inmunocomprometidos en grado leve. Es una complicación excepcional de la silicosis y su diagnóstico precisa un alto índice de sospecha pues simula otras enfermedades como tuberculosis y neoplasia, complicaciones más frecuentes en estos pacientes. Presentamos tres casos con larga historia de exposición a sílice y diagnóstico de fibrosis masiva progresiva que presentaron aspergilosis pulmonar. Revisamos sus características clínicas, radiológicas y tratamiento.Chronic necrotizing pulmonary aspergillosis is un uncommon disease which is found in people with underlying lung disease or in mildly immunocompromised patients. It is an exceptional complication in silicosis and its diagnosis is difficult because it simulates other diseases like tuberculosis and cancer which are more common in such patients. We report on three cases with a long history of silica dust exposure with pulmonary aspergillosis complicating progressive massive fibrosis (PMF. We review their clinical, radiological and treatment features.

  18. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients.

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    Bowden, Raleigh; Chandrasekar, Pranatharthi; White, Mary H; Li, Xin; Pietrelli, Larry; Gurwith, Marc; van Burik, Jo-Anne; Laverdiere, Michel; Safrin, Sharon; Wingard, John R

    2002-08-15

    We report a randomized, double-blind, multicenter trial in which amphotericin B colloidal dispersion (ABCD [Amphotec]; 6 mg/kg/day) was compared with amphotericin B (AmB; 1.0-1.5 mg/kg/day) for the treatment of invasive aspergillosis in 174 patients. For evaluable patients in the ABCD and AmB treatment groups, respective rates of therapeutic response (52% vs. 51%; P=1.0), mortality (36% vs. 45%; P=.4), and death due to fungal infection (32% vs. 26%; P=.7) were similar. Renal toxicity was lower (25% vs. 49%; P=.002) and the median time to onset of nephrotoxicity was longer (301 vs. 22 days; P<.001) in patients treated with ABCD. Rates of drug-related toxicity in patients receiving ABCD and AmB, respectively, were 53% versus 30% (chills), 27% versus 16% (fever), 1% versus 4% (hypoxia) and 22% versus 24% (toxicity requiring study drug discontinuation). ABCD appears to have equivalent efficacy and superior renal safety, compared with AmB, in the treatment of invasive aspergillosis. However, infusion-related chills and fever occurred more frequently in patients receiving ABCD than in those receiving AmB.

  19. Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients.

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    Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Forghieri, Fabio; Beauvais, Anne; Beau, Remi; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Zanetti, Eleonora; Quadrelli, Chiara; Codeluppi, Mauro; Guaraldi, Giovanni; Pagano, Livio; Caira, Morena; Del Giovane, Cinzia; Maccaferri, Monica; Stefani, Alessandro; Morandi, Uliano; Tazzioli, Giovanni; Girardis, Massimo; Delia, Mario; Specchia, Giorgina; Longo, Giuseppe; Marasca, Roberto; Narni, Franco; Merli, Francesco; Imovilli, Annalisa; Apolone, Giovanni; Carvalho, Agostinho; Comoli, Patrizia; Romani, Luigina; Latgè, Jean Paul; Luppi, Mario

    2013-01-01

    Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1-3glucan, β1-3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens

  20. Comparative Efficacies of Four Amphotericin B Formulations—Fungizone, Amphotec (Amphocil), AmBisome, and Abelcet—against Systemic Murine Aspergillosis

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    Clemons, Karl V.; Stevens, David A.

    2004-01-01

    We compared various amphotericin B formulations (no treatment or 0.8 mg of Fungizone [conventional deoxycholate amphotericin B] per kg of body weight, or 0.8, 4, or 8 mg of Amphocil, AmBisome, or Abelcet per kg of body weight) for treatment of systemic murine aspergillosis. In two studies, all formulations prolonged survival, with the results for AmBisome nearly equivalent to those for Fungizone; Amphocil and Abelcet were less effective or equivalent depending on the severity of infection. No survivors were cured in both kidneys and brain, but each formulation showed efficacy, especially in the kidneys. Although higher doses could be given, no lipid-based formulation showed consistent superiority over Fungizone or over each other. PMID:14982807

  1. Effective management of pulmonary aspergillosis invading the thoracic spine in a child with high risk ALL requiring allogeneic bone marrow transplantation.

    Science.gov (United States)

    Dornbusch, Hans Jürgen; Sovinz, Petra; Lackner, Herwig; Schwinger, Wolfgang; Benesch, Martin; Strenger, Volker; Urban, Christian

    2008-08-01

    Due to unacceptably high mortality, invasive fungal infections (IFI) have long been considered a contraindication against allogeneic stem cell transplantation. Despite severe immunosuppression an 11-year-old girl requiring allogeneic bone marrow transplant (BMT) for relapsed acute lymphoblastic leukemia was cured of a concurrent invasive pulmonary aspergillosis. Treatment comprised combinations of liposomal amphotericin B, caspofungin and voriconazole with donor granulocyte transfusions. This therapeutic regimen, including the choice of reduced intensity conditioning (RIC), allowed the patient to receive an allogeneic BMT. In hematological remission the child later developed fatal chronic graft-versus-host disease. Combined antifungal treatment and granulocyte support allow for effective management of IFI even in allogeneic stem cell transplant recipients. However, short-term benefits of RIC may be outweighed by late complications.

  2. Orbital Apex Syndrome Caused by Invasive Aspergillosis as an Adverse Effect of Systemic Chemotherapy for Metastatic Colorectal Cancer: a Case Report.

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    Miyamoto, Yuji; Sakamoto, Yasuo; Ohuchi, Mayuko; Tokunaga, Ryuma; Shigaki, Hironobu; Kurashige, Junji; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2016-02-01

    Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy.

  3. Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes

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    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

  4. Comparative efficacies of four amphotericin B formulations--Fungizone, amphotec (Amphocil), AmBisome, and Abelcet--against systemic murine aspergillosis.

    Science.gov (United States)

    Clemons, Karl V; Stevens, David A

    2004-03-01

    We compared various amphotericin B formulations (no treatment or 0.8 mg of Fungizone [conventional deoxycholate amphotericin B] per kg of body weight, or 0.8, 4, or 8 mg of Amphocil, AmBisome, or Abelcet per kg of body weight) for treatment of systemic murine aspergillosis. In two studies, all formulations prolonged survival, with the results for AmBisome nearly equivalent to those for Fungizone; Amphocil and Abelcet were less effective or equivalent depending on the severity of infection. No survivors were cured in both kidneys and brain, but each formulation showed efficacy, especially in the kidneys. Although higher doses could be given, no lipid-based formulation showed consistent superiority over Fungizone or over each other.

  5. Primary aspergilloma and subacute invasive aspergillosis in two AIDS patients Aspergiloma primário e aspergilose invasiva subaguda em dois pacientes com AIDS

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    Roberto Martinez

    2009-02-01

    Full Text Available Although uncommon, invasive aspergillosis in the setting of AIDS is important because of its peculiar clinical presentation and high lethality. This report examines two AIDS patients with a history of severe cellular immunosuppression and previous neutropenia, who developed subacute invasive aspergillosis. One female patient developed primary lung aspergilloma, with dissemination to the mediastinum, vertebrae, and spine, which was fatal despite antifungal treatment. The second patient, who had multiple cavitary brain lesions, and eye and lung involvement, recovered following voriconazole and itraconazole, and drugs for increasing neutrophil and CD4+ lymphocyte levels. These cases demonstrate the importance of Aspergillus infections following neutropenia in AIDS patients, and emphasize the need for early and effective antifungal therapy.A aspergilose invasiva em pacientes com aids, embora incomum, é relevante pela apresentação clínica peculiar e alta letalidade. Este relato descreve os casos de dois pacientes com aids com grave imunossupressão celular e neutropenia prévia, os quais tiveram aspergiloma pulmonar primário, com disseminação para mediastino, vértebras e medula espinhal, evoluindo para óbito apesar do tratamento antifúngico. O segundo paciente, que tinha lesões cavitárias múltiplas no cérebro e infecção ocular e pulmonar, recuperou-se após tratamento com voricanazol, itraconazol e com drogas para aumentar o número de neutrófilos e de linfócitos CD4+. Estes casos demonstram o risco de infecção por Aspergillus após episódios de neutropenia em pacientes com aids e alertam para o início precoce de terapia antifúngica eficaz.

  6. Aspergilosis broncopulmonar alérgica. Complicaciones poco usuales de la afección ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS. UNUSUAL COMPLICATIONS

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    EDGARDO CARRASCO C.

    2004-01-01

    Full Text Available Se revisa definición, etiología, etapas clínicas, tratamiento y complicaciones de la Aspergilosis Broncopulmonar Alérgica (ABPA. En el Instituto Nacional del Tórax se han seguido 35 casos de ABPA durante un promedio de 15 años. De esta serie se presentan dos pacientes de sexo femenino que corresponden a ABPA complicada por infección por Mycobacterium avium-intracellulare (MAI. Las pacientes que tenían 71 y 72 años de edad respectivamente, presentaron una infección pulmonar por MAI, 3 y diez años después de habérseles diagnosticado ABPA. El diagnóstico de ABPA se basó en sus características clínicas, radiológicas y en sus pruebas inmunológicas (prueba cutánea y Elisa IgG + para A. fumigatus. En ambos casos la infección pulmonar por MAI -confirmada por dos cultivos positivos- estuvo asociada a agravación clínica y radiológica. Las pacientes fueron tratadas exitosamente con claritromicina y etambutol durante 12 meses; este tratamiento estuvo asociado a estreptomicina y minociclina durante los primeros dos meses. La infección por MAI es una complicación poco frecuente de la ABPA. Esta asociación se debe sospechar si una TAC de alta resolución muestra nódulos asociados a bronquiectasias difusas ubicadas más allá de las bronquiectasias centrales (lesiones típicas de la ABPA no complicada. La infección pulmonar por MAI debe ser confirmada a través de cultivos de MAI en expectoración o en el líquido de lavado broncoalveolarDefinition, etiology, clinical stages, treatment and complications of Allergic Bronchopulmonary Aspergillosis (ABPA are reviewed. Thirty five cases of ABPA have been followed during an average of 15 years at Instituto Nacional del Tórax-Chile. From this series two female patients, corresponding to ABPA complicated by Mycobacterium avium-intracellulare (MAI infection are presented. The patients that were 71 and 72 years old respectively, presented a MAI pulmonary infection 3 and ten years after

  7. Allergic Bronchopulmonary Aspergillosis (ABPA)

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    ... Education Center Fellows-in-Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice Tools Running a Practice Statements and Practice Parameters About AAAAI Advocacy Allergist / Immunologists: ...

  8. Azole-resistant Aspergillus fumigatus isolate with the TR34/L98H mutation in both a fungicide-sprayed field and the lung of a hematopoietic stem cell transplant recipient with invasive aspergillosis.

    Science.gov (United States)

    Rocchi, Steffi; Daguindau, Etienne; Grenouillet, Frédéric; Deconinck, Eric; Bellanger, Anne-Pauline; Garcia-Hermoso, Dea; Bretagne, Stéphane; Reboux, Gabriel; Millon, Laurence

    2014-05-01

    A French farmer developed invasive aspergillosis with azole-resistant Aspergillus fumigatus with the TR34/L98H mutation following a hematopoietic stem cell transplantation. He had worked in fungicide-sprayed fields where a non-genetically related A. fumigatus TR34/L98H isolate was collected. If azole resistance detection increases, voriconazole as first-line therapy might be questioned in agricultural areas.

  9. High diversity of non-sporulating moulds in respiratory specimens of immunocompromised patients: should all the species be reported when diagnosing invasive aspergillosis?

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    Garcia-Hermoso, Dea; Alanio, Alexandre; Cabaret, Odile; Olivi, Martine; Foulet, Françoise; Cordonnier, Catherine; Costa, Jean-Marc; Bretagne, Stéphane

    2015-09-01

    Non-sporulating moulds (NSMs) isolated from respiratory specimens are usually discarded without further testing although they may have pathogenic effects in immunocompromised patients. The objective of this study was to determine the identity and frequency of NSMs in patients with haematological malignancies. We analysed the mycological results of 251 consecutive respiratory samples from 104 haematology patients. Yeast and sporulating moulds were identified at the genus/species level according to their phenotypic features. NSMs were identified by internal transcribed spacer (ITS) sequencing. We detected 179 positive samples, of which 10.1% (18/179) were mixtures of moulds and 26.3% (47/179) were mixtures of moulds and yeast. We identified 142 moulds belonging to 11 different genera/species or groups, with Aspergillus fumigatus (n = 50), Penicillium spp. (n = 31) and NSM (n = 24) being the most frequently isolated species. Twenty-two NSMs were successfully sequenced: 18 were basidiomycetes and six were ascomycetes, corresponding to 16 different genera/species. NSMs were isolated with A. fumigatus in the same sample or in a subsequent sample in five patients with probable invasive aspergillosis. The conclusion is that the respiratory specimens of immunocompromised patients frequently contain very diverse mould species that may increase the virulence of pathogenic species. Reporting all mould species isolated when diagnosing invasive fungal infection could test this hypothesis.

  10. New therapeutic strategies for invasive aspergillosis in the era of azole resistance: how should the prevalence of azole resistance be defined?

    Science.gov (United States)

    Alanio, Alexandre; Denis, Blandine; Hamane, Samia; Raffoux, Emmanuel; Peffault de la Tour, Régis; Touratier, Sophie; Bergeron, Anne; Bretagne, Stéphane

    2016-08-01

    Given reports showing a high prevalence of azole resistance in Aspergillus fumigatus, alternatives to azole therapy are discussed when a threshold of 10% of azole-resistant environmental isolates is reached. This raises the issue of calculation of this threshold, either on the prevalence of azole-resistant isolates as a whole or on the prevalence of azole-resistant cases in populations at risk of invasive aspergillosis (IA). For isolate evaluation, there are high disparities in routine microbiological procedures for the isolation of A. fumigatus and azole resistance detection. There are also huge differences between the microbiological work-up for diagnosing IA. Some centres rely on galactomannan detection alone without actively trying to culture appropriate samples, which affects reliability of the figures on the prevalence of resistance and thus the threshold of resistance. Moreover, reports from the laboratory could mix up figures from completely different patient populations: frequent azole-resistant isolates from pneumology patients and rare azole-resistant isolates from haematology patients. Therefore, to sum isolates from different specimens and different wards can lead to erroneous calculations for the restricted populations at risk of developing IA. In conclusion, assessing the incidence of azole resistance in A. fumigatus should be based on harmonized consensual microbiological methods and reports should be restricted to IA episodes in identified populations at risk of IA when the issue is to define an operational threshold for modifying recommendations.

  11. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study.

    Science.gov (United States)

    Herbrecht, R; Maertens, J; Baila, L; Aoun, M; Heinz, W; Martino, R; Schwartz, S; Ullmann, A J; Meert, L; Paesmans, M; Marchetti, O; Akan, H; Ameye, L; Shivaprakash, M; Viscoli, C

    2010-07-01

    Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/microl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22-63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

  12. Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies.

    Science.gov (United States)

    Raad, Issam I; Zakhem, Aline El; Helou, Gilbert El; Jiang, Ying; Kontoyiannis, Dimitrios P; Hachem, Ray

    2015-03-01

    Invasive aspergillosis (IA) is a life-threatening infection in severely immunocompromised haematological malignancy patients. In this study, the efficacy and safety of caspofungin, voriconazole or the combination as primary and salvage therapy in patients with IA were compared. The study included 181 patients with haematological malignancies and IA who received primary or salvage therapy with caspofungin, voriconazole or the combination. In total, 138 patients who received treatment for ≥7 days were analysed; 86 underwent primary antifungal therapy (15 with caspofungin, 38 with voriconazole and 33 with both). Among the salvage therapy patients, 17 received caspofungin, 24 received voriconazole and 35 received both. In the primary therapy group, no difference in therapy response was found, but caspofungin was associated with higher IA mortality rates. A multivariate competing risk analysis of primary antifungal therapy revealed that voriconazole was independently associated with lower IA-associated mortality rates than caspofungin (hazard ratio=0.2, 95% confidence interval 0.06-0.96; P=0.04). In the salvage therapy group, the three treatment groups had similar responses and IA-associated mortality rates. The combination of voriconazole and caspofungin did not result in better outcomes compared with voriconazole alone, as primary or salvage therapy, in haematological malignancy patients. However, voriconazole was associated with a lower Aspergillus-associated mortality rate compared with caspofungin monotherapy.

  13. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

    Directory of Open Access Journals (Sweden)

    Grau S

    2016-12-01

    Full Text Available Santiago Grau,1 Jose Ramon Azanza,2 Isabel Ruiz,3 Carlos Vallejo,4 Josep Mensa,5 Johan Maertens,6 Werner J Heinz,7 Jon Andoni Barrueta,8 Carmen Peral,9 Francisco Jesús Mesa,8 Miguel Barrado,10 Claudie Charbonneau,11 Darío Rubio-Rodríguez,12 Carlos Rubio-Terrés12 1Pharmacy Department, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, 2Clinical Pharmacology Department, Clínica Universidad de Navarra, Pamplona, 3Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, 4Hematology Department, Hospital Universitario Donostia, San Sebastián, 5Infectious Diseases Department, Hospital Clínic de Barcelona, Barcelona, Spain; 6Hematology Department, University Hospital Gasthuisberg, Leuven, Belgium; 7Hematology/Oncology Department, Medizinische Klinik und Poliklinik II, Universitätsklinikum, Würzburg, Germany; 8Medical Department, 9Economics and Outcomes Research Department, Pfizer S.L.U, Alcobendas, 10Clinical Trials Department, Trial Form Support, Madrid, Spain; 11Pharmacoeconomics Department, Pfizer International Operations, Paris, France; 12Pharmacoeconomics Department, Health Value, Madrid, Spain Objective: According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI with VOR monotherapy for invasive aspergillosis (IA in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System.Methods: An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were

  14. Significance of Aspergillus spp.isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    HE Hang-yong; CHANG Shuo; DING Lin; SUN Bing; LI Fang; ZHAN Qing-yuan

    2012-01-01

    Background Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus.Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA).The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.Methods Clinical record with Aspergillus spp.isolation in COPD and immunocompromised patients was reviewed in a retrospective study.Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).Results Multivariate statistical analysis showed that,combined with Aspergillus spp.isolation,APACHE Ⅱ scores >18,high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076,P=0.001; OR=4.073,P=-0.026; OR=4.448,P=0.021,respectively).The incidence of IPA,overall mortality,mortality of patients with IPA and mortality of patients with Aspergillus spp.colonization were higher in COPD patients in ICU than in general ward,but were similar between COPD and immunocompromised patients.Conclusions Aspergilltus spp.isolation from LRT in COPD may be of similar importance as in immunocompromised patients,and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids,antibiotics,and need to admit to ICU.Aspergillus spp.isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

  15. Performance of MycAssay Aspergillus DNA real-time PCR assay compared with the galactomannan detection assay for the diagnosis of invasive aspergillosis from serum samples.

    Science.gov (United States)

    Danylo, Alexis; Courtemanche, Chantal; Pelletier, René; Boudreault, Alexandre A

    2014-08-01

    Invasive aspergillosis (IA) is a major problem in the immunocompromised population, and its diagnosis is difficult due to the low sensitivity of available tests. Detection of Aspergillus nucleic acid by polymerase chain reaction (PCR) in serum samples is a promising diagnostic tool; however, use of multiple "in-house" methods precludes standardization. The first commercial PCR assay, MycAssay Aspergillus (Myconostica, Ltd), became available recently, and its performance in the diagnosis of IA was evaluated and compared with the galactomannan (GM) assay. Serum samples obtained from patients with hematological cancer were tested retrospectively with MycAssay Aspergillus PCR. Per-episode and per-test analyses were undertaken with 146 sera from 35 hematological patients. Sixteen patients had proven or probable IA and 19 had possible or no IA. In per-episode analysis, MycAssay Aspergillus had a sensitivity of 43.8% (95% confidence interval [CI], 19.8%-70.1%) and a specificity of 63.2% (95% CI, 38.4%-83.7%) for IA diagnosis. In per-test analyses, MycAssay Aspergillus had a lower specificity than the GM assay (83.3% vs. 93.1%, P = 0.04). The addition of PCR to routine clinical practice would have permitted the diagnosis of one additional probable IA in our cohort. Use of PCR instead of GM assay would have delayed the diagnosis in two cases. Aspergillus DNA detection by PCR with serum specimens using MycAssay showed a lower specificity than the GM assay and was associated with a low sensitivity for IA diagnosis. More studies are needed to determine the exact role of MycAssay in IA diagnosis in patients with hematological malignancy.

  16. Detection of Aspergillus-specific antibodies by agar gel double immunodiffusion and IgG ELISA in feline upper respiratory tract aspergillosis.

    Science.gov (United States)

    Barrs, V R; Ujvari, B; Dhand, N K; Peters, I R; Talbot, J; Johnson, L R; Billen, F; Martin, P; Beatty, J A; Belov, K

    2015-03-01

    Feline upper respiratory tract aspergillosis (URTA) is an emerging infectious disease. The aims of this study were: (1) to assess the diagnostic value of detection of Aspergillus-specific antibodies using an agar gel double immunodiffusion (AGID) assay and an indirect immunoglobulin G (IgG) ELISA; and (2) to determine if an aspergillin derived from mycelia of Aspergillus fumigatus, Aspergillus niger and Aspergillus flavus can be used to detect serum antibodies against cryptic Aspergillus spp. in Aspergillus section Fumigati. Sera from cats with URTA (group 1: n = 21) and two control groups (group 2: cats with other upper respiratory tract diseases, n = 25; group 3: healthy cats and cats with non-respiratory, non-fungal illness, n = 84) were tested. Isolates from cats with URTA comprised A. fumigatus (n = 5), A. flavus (n = 1) and four cryptic species: Aspergillus felis (n = 12), Aspergillus thermomutatus (Neosartorya pseudofischeri, n = 1), Aspergillus lentulus (n = 1) and Aspergillus udagawae (n = 1). Brachycephalic purebred cats were significantly more likely to develop URTA than other breeds (P = 0.013). The sensitivity (Se) of the AGID was 43% and the specificity (Sp) was 100%. At a cut-off value of 6 ELISA units/mL, the Se of the IgG ELISA was 95.2% and the Sp was 92% and 92.9% for groups 2 and 3 cats, respectively. Aspergillus-specific antibodies against all four cryptic species were detected in one or both assays. Assay Se was not associated with species identity. Detection of Aspergillus-specific antibodies by IgG ELISA has high Se and Sp for diagnosis of feline URTA.

  17. A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis.

    Science.gov (United States)

    Kohno, S; Izumikawa, K; Yoshida, M; Takesue, Y; Oka, S; Kamei, K; Miyazaki, Y; Yoshinari, T; Kartsonis, N A; Niki, Y

    2013-03-01

    The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: -15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.

  18. Second-hand Smoke Increases Nitric Oxide and Alters the IgE Response in a Murine Model of Allergic Aspergillosis

    Directory of Open Access Journals (Sweden)

    Brian W. P. Seymour

    2005-01-01

    Full Text Available This study was performed to determine the effects of environmental tobacco smoke (ETS on nitric oxide (NO and immunoglobulin (Ig production in a murine model of allergic bronchopulmonary aspergillosis (ABPA. Adult BALB/c mice were exposed to aged and diluted sidestream cigarette smoke from day 0 through day 43 to simulate “second-hand smoke”. During exposure, mice were sensitized to soluble Aspergillus fumigatus (Af antigen intranasally between day 14 and 24. All Af sensitized mice in ambient air (Af + AIR made elevated levels of IgE, IgG1, IgM, IgG2a and IgA. Af sensitized mice housed in ETS (Af + ETS made similar levels of immunoglobulins except for IgE that was significantly reduced in the serum and bronchoalveolar lavage (BAL. However, immunohistochemical evaluation of the lung revealed a marked accumulation of IgE positive cells in the lung parenchyma of these Af + ETS mice. LPS stimulation of BAL cells revealed elevated levels of NO in the Af + AIR group, which was further enhanced in the Af+ETS group. In vitro restimulation of the BAL cells on day 45 showed a TH0 response with elevated levels of IL3, 4, 5, 10 and IFN-γ. However, by day 28 the response shifted such that TH2 cytokines increased while IFN-γ decreased. The Af + ETS group showed markedly reduced levels in all cytokines tested, including the inflammatory cytokine IL6, when compared to the Af+AIR group. These results demonstrate that ETS affects ABPA by further enhancing the NO production and reduces the TH2 and the inflammatory cytokines while altering the pattern of IgE responses.

  19. Aspergillosis in immunocompromised children acute myeloid leukemia and bone marrow aplasia.: Report of two cases Aspergilose em crianças imunocomprometidas com leucemia mielóide aguda e aplasta de medula óssea: Registro de 2 casos

    Directory of Open Access Journals (Sweden)

    Maria Zilda de Aquino

    1994-10-01

    Full Text Available Two cases of Aspergillosis in immunocompromised children are reported. Both were caused by Aspergillns flavus. Early diagnosis and treatment led to the remission of the process. One patient had acute myeloid leukemia; the fungus was isolated from the blood. The other patient with bone marrow aplasia, presented an invasive aspergillosis of the paranasal sinuses with dissemination of fungal infection; the diagnosis was obtained by histology and culture of biopsied tissue from a palatal ulceration.No presente trabalho são registrados dois casos de aspergilose em crianças imunocomprometidas. O estudo micológico completo identificou Aspergillus flavus como agente dos dois processos. A presença cada vez mais frequente da aspergilose invasiva deve-se ao número crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos à quimioterapia. O diagnóstico precoce em um dos casos possibilitou remissão do processo. Tratava-se de paciente com leucemia mielóide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para óbito, com infecção fúngica generalizada.

  20. Invasive aspergillosis in 4 children with chronic granulomatous disease%慢性肉芽肿病患儿侵袭性曲霉菌病4例分析

    Institute of Scientific and Technical Information of China (English)

    贺建新; 殷菊; 刘秀云; 赵顺英; 徐保平; 胡英惠; 申昆玲; 江载芳

    2012-01-01

    目的 观察慢性肉芽肿病患儿患侵袭性曲霉菌病的临床特点.方法 收集4例经基因检测明确诊断慢性肉芽肿病伴侵袭性曲霉菌病患儿的临床资料并总结其起病时间、症状、体征、组织病理、影像学表现、治疗、转归情况.结果 4例患儿均为烟曲霉菌感染.3例经肺组织或脓液培养确诊为侵袭性肺曲霉菌病.起病年龄17 d ~ 3月,入院前病程为17 ~ 40 d.有发热、咳嗽等不典型症状,无感染中毒貌;肺内体征为呼吸音减弱,肺部影像学异常出现时间10 ~ 13 d,肺CT表现为结节、不规则、球形或类圆形高密度灶,不伴有晕轮征、新月征及空洞;肺组织病理均示肉芽肿性化脓性炎症,无菌丝血管侵蚀或凝固坏死.1例伊曲康唑治疗治愈,1例切除受累肺叶后治愈,1例卡泊芬净治疗死亡,另1例曲霉菌关节炎伊曲康唑治疗控制.结论 对慢性肉芽肿病患儿,在新生儿期或婴儿早期,呼吸道症状及体征不典型,但影像学异常明显,肺CT表现为结节或团块影,肺组织病理表现为化脓性肉芽肿性炎症者,应注意侵袭性肺曲霉菌病可能.%Objective To investigate the clinical features of invasive aspergillosis cases with chronic granuloma-tous disease (CGD). Methods From Jul 2007 to Oct 2010, invasive aspergillosis was definitely diagnosed in 4 CGD cases. The records were reviewed, including the first presenting sign and its occurring age, physical examinations, radiological and histopathological features, treatment and pharmaceutical effect. Results Aspergillosis fumagitus was positive for all 4 cases. Invasive pulmonary aspergillosis was diagnosed in 3 cases whose isolation was from lung specimen in 2 cases, lung specimen pus in 1 case. The occurring age was 17 days to 3 months, with nonspecific fever and cough symptoms. Physical examination showed decreased breath sound. 10 - 13 days was needed for radiologic infiltrates to occur. Chest CT showed nodules

  1. Prognostic value of serum galactomannan index in critically ill patients with chronic obstructive pulmonary disease at risk of invasive pulmonary aspergillosis

    Institute of Scientific and Technical Information of China (English)

    He Hangyong; Li Qian; Chang Shuo; Ding Lin; Sun Bing; Li Fang; Zhan Qingyuan

    2014-01-01

    Background Critically ill chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ICU) due to respiratory failure are at particularly high risk of Aspergillus infection.The serum galactomannan index (GMI) has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis (IPA) in classical immunocompromised patients.However,the prognostic value of serum GMI in critically ill COPD patients needs evaluation.The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.Methods In this single-center prospective cohort study,serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients' discharge or death.Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission.Univariate analysis and survival analysis were tested in these two groups.Results One hundred and fifty-three critically ill COPD patients were included and were divided into survival group (106 cases) and non-survival group (47 cases) according to their outcome.Univariate analysis showed that the highest GMI level during the first week after admission (GMI-high 1st week) was statistically different between the two groups.Independent prognostic factors for poor outcome in severe COPD patients were:GMI-high 1st week >0.5 (RR:4.04,95% CI:2.17-7.51) combined with accumulative dosage of corticosteroids >216 mg before the RICU admission (RR:2.25,95% CI:1.11-4.56) and clearance of creatinine (Ccr) <64.31 ml/min (RR:2.48,95% CI:1.22-5.07).Conclusions The positive GMI-high 1st week (>0.5) combined with an accumulative dosage of corticosteroids >216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

  2. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

    Science.gov (United States)

    Grau, Santiago; Azanza, Jose Ramon; Ruiz, Isabel; Vallejo, Carlos; Mensa, Josep; Maertens, Johan; Heinz, Werner J; Barrueta, Jon Andoni; Peral, Carmen; Mesa, Francisco Jesús; Barrado, Miguel; Charbonneau, Claudie; Rubio-Rodríguez, Darío; Rubio-Terrés, Carlos

    2017-01-01

    Objective According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI) with VOR monotherapy for invasive aspergillosis (IA) in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System. Methods An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG) for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were obtained from clinical trial data. The costs (in 2015 euros [€]) of the drugs and the adverse event-related costs were obtained from Spanish sources. A Tornado plot and a Monte Carlo simulation (1,000 iterations) were used to assess uncertainty of all model variables. Results According to the deterministic analysis, for each patient treated with VOR+ANI compared with VOR monotherapy, there would be a total of 0.348 LYG (2.529 vs 2.181 years, respectively) at an incremental cost of €5,493 (€17,902 vs €12,409, respectively). Consequently, the additional cost per LYG with VOR+ANI compared with VOR would be €15,785. Deterministic sensitivity analyses confirmed the robustness of these findings. In the probabilistic analysis, the cost per LYG with VOR+ANI was €15,774 (95% confidence interval: €15,763–16,692). The probability of VOR+ANI being cost-effective compared with VOR was estimated at 82.5% and 91.9%, based on local cost-effectiveness thresholds of €30,000 and €45,000, respectively. Conclusion According to the present economic study, combination therapy with VOR+ANI is cost-effective as primary therapy of IA in galactomannan

  3. HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

    Science.gov (United States)

    Muro, Manuel; Mondejar-López, Pedro; Moya-Quiles, María Rosa; Salgado, Gema; Pastor-Vivero, María Dolores; Lopez-Hernandez, Ruth; Boix, Francisco; Campillo, José Antonio; Minguela, Alfredo; Garcia-Alonso, Ana; Sánchez-Solís, Manuel; Álvarez-López, María Rocío

    2013-03-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.

  4. Evaluation of the Double Agar Gel Immunodiffusion Test and of the Enzyme-Linked Immunosorbent Assay in the Diagnosis and Follow-Up of Patients with Chronic Pulmonary Aspergillosis.

    Directory of Open Access Journals (Sweden)

    Priscila Zacarias de Azevedo

    Full Text Available The diagnosis of chronic pulmonary aspergillosis (CPA depends on the radiologic image and the identification of specific antibodies. The present study aimed to evaluate accuracy parameters of enzyme-linked immunosorbent assay (ELISA and of the determination of serum galactomannan level in the diagnosis of patients with CPA, comparing these results with the double agar gel immunodiffusion (DID test. In addition, the prevalence of cross-reactivity and the serological progression after treatment were evaluated by comparing DID and ELISA. Six study groups were formed: G1: 22 patients with CPA, 17 of whom had Aspergillus fungus ball, one chronic cavitary pulmonary aspergillosis (CCPA and four chronic fibrosing pulmonary aspergillosis (CFPA; G2: 28 patients with pulmonary tuberculosis (TB; G3: 23 patients with histoplasmosis (HST; G4: 50 patients with paracoccidioidomycosis (PCM; G5: 20 patients with cryptococcosis (CRC; and G6: 200 healthy controls. Serum antibodies were measured by DID and ELISA, with two antigen preparations--Aspergillus fumigatus (DID1, ELISA1 and a pool of A. fumigatus, A. flavus and A. niger antigens (DID2, ELISA2. The Platélia Aspergillus Enzyme Immunoassay (EIA kit was used to measure galactomannan. The cut-off points of ELISA were determined for each antigen preparation and for the 95% and 99% confidence intervals. Despite the low sensitivity, DID was the technique of choice due to its specificity, positive and negative predictive values and positive likelihood ratio-especially with the antigen pool and due to the low frequency of cross-reactivity. ELISA1 and a 0.090 cut-off showed high sensitivity, specificity and negative predictive value, but a high frequency of cross-reactivity with CRC. The best degree of agreement was observed between ELISA1 and ELISA2. The detection of serum galactomannan showed high sensitivity, comparable to ELISA2. The immunodiffusion test showed an excellent relationship with the progression after

  5. Elevated levels of manna-binding lectin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associated with a novel intronic polymorphism in MBL

    DEFF Research Database (Denmark)

    Kaur, S.; Gupta, G.K.; Shah, A.;

    2006-01-01

    Mannan-binding lectin (MBL), an important component of innate immunity, binds to a range of foreign antigens and initiates the lectin complement pathway. Earlier studies have reported high plasma MBL levels in allergic patients in comparison to healthy controls. In view of varied plasma MBL levels...... being determined by genetic polymorphisms in its collagen region, we investigated the association of single nucleotide polymorphisms (SNPs) in the collagen region of human MBL with respiratory allergic diseases. The study groups comprised patients of bronchial asthma with allergic rhinitis (n = 49......) and allergic bronchopulmonary aspergillosis (APBA) (n = 11) and unrelated age-matched healthy controls of Indian origin (n = 84). A novel intronic SNP, G1011A of MBL, showed a significant association with both the patient groups in comparison to the controls (P

  6. Aspergillosis: a limiting factor during recovery of captive magellanic penguins Aspergilose: um fator limitante na reabilitação de pingüins-de-Magalhães

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    Melissa O. Xavier

    2007-09-01

    Full Text Available The article describes the epidemiology, macroscopic and histological lesions as well as the isolation of Aspergillus flavus and A. fumigatus from Magellanic penguins (Spheniscus magellanicus during recovery in the Center for Recovery of Marine Animals (CRAM - 32ºS/52ºW, over a period of two years. From January 2004 to December 2005 the Center received 52 Magellanic penguins, and 23% (12/52 died. Necropsies were performed and tissue samples were collected for histological and microbiological examination. From 12 dead animals, aspergillosis was confirmed in five animals, corresponding to 42% of the mortality. Granulomatous nodules were observed mainly on air sacs and lungs. Histologically, septate and branching hyphae, measuring 3-5 µm and PAS positive were found. Two of these cases were caused by A. fumigatus, two other by A. flavus, and in one the diagnostic was established by macroscopic lesions observed in the necropsy without sample collection for fungal isolation and identification. The five aspergillosis cases occurred in the first year of the study, when a disinfection program was not yet established in the CRAM. This paper points out the importance of aspergillosis in the rehabilitation process of captive penguins, and emphasize the necessity of an environmental disinfection on the aspergillosis prevention, mycosis that caused a high rate of mortality of the seabirds found on the Brazilian coast and admitted in the CRAM.O trabalho descreve fatores epidemiológicos, achados de necropsia, histológicos e o isolamento de Aspergillus flavus e A. fumigatus em pingüins-de-Magalhães (Spheniscus magellanicus em reabilitação no Centro de Recuperação de Animais Marinhos (CRAM - 32ºS/52ºW, durante um período de dois anos. De janeiro de 2004 a dezembro de 2005 foram recebidos no Centro, 52 pingüins-de-Magalhães, dos quais 23% (12/52 morreram. Esses animais foram necropsiados e amostras de tecidos foram coletadas para exame histol

  7. Altered CD8+ T-cell counts as an early predictor of prognosis in critically ill immunocompromised patients with invasive pulmonary aspergillosis

    Institute of Scientific and Technical Information of China (English)

    Cui Na; Wang Hao; Long Yun; Liu Dawei

    2014-01-01

    Background The number of critically ill immunocompromised (CIIC) patients has increased dramatically in recent years,and they represent a high risk population for invasive pulmonary aspergillosis (IPA) infection.Host immunity should play a major role in determining the outcome and recovery of these patients.The purpose of this study was to evaluate the dynamic changes in host immune status and its potential influence on prognosis in CIIC patients with IPA.Methods We monitored the evolution of a number of key cellular and humoral parameters on days 1,3,and 10 (D1,D3 and D10) following ICU admission in sixty-two CIIC patients with microbiological evidence of IPA.We included immunoglobulins IgG,IgA and IgM,complement factors C3 and C4,and lymphocyte subgroups CD3+,CD4+,CD8+,CD28+CD4+,and CD28+CD8+ T cells,CD19+B cells,and CD3-CD16+CD56+ natural killer cells (NK).Results The primary outcome was 28-day mortality.Thirty-eight (61.3%) patients died within the 28 days following ICU admission.Compared to patients who died,CD3+,CD8+,CD28+CD8+ T-cell counts on D1,D3,and D10,CD28+CD4+ T-cell counts on D3 and D10,and NK counts on D3 and D10 were significantly higher in survivors.Receiver operating characteristic (ROC) analysis of immune parameters predicting 28-day mortality revealed area under the curve (AUC) values of 0.82 (95% CI 0.71-0.92),0.94 (95% CI 0.87-0.99),and 0.94 (95% CI 0.85-0.99) for CD8+ T-cell counts for D1,D3,and D10 respectively,and 0.84 (95% CI 0.75-0.94),0.92 (95% CI 0.85-0.99),and 0.90 (95% CI 0.79-0.99) for CD28+CD8+ T-cell counts for D1,D3,and D10 respectively.Kaplan-Meier survival analysis showed that CD8+ T-cell counts <149.5×106 cells/L and CD28+CD8+ T-cell counts <75×106 cells/L at ICU admission were associated with lower survival probabilities in CIIC patients with IPA (both Log rank:P<0.001).Conclusions Low CD8+ and CD28+CD8+ T-cell counts were associated with high mortality in CIIC patients with IPA.Early counts of CD8+ and

  8. Azole-Resistant Invasive Aspergillosis

    DEFF Research Database (Denmark)

    Stensvold, Christen Rune; Jørgensen, Lise Nistrup; Arendrup, Maiken Cavling

    2012-01-01

    for the highest fungicide use in the global perspective (37 % and 24 %, respectively). Among the 25 azole fungicides, five have been associated with the potential to select for the TR34/L98H genotype; three of these are among those most frequently used. Although the number of antifungal fungicide compounds...

  9. Tomografia computadorizada na avaliação da aspergilose pulmonar angioinvasiva em pacientes com leucemia aguda Computed tomography in the assessment of angioinvasive pulmonary aspergillosis in patients with acute leukemia

    Directory of Open Access Journals (Sweden)

    Renata Carneiro Leão

    2006-10-01

    Full Text Available OBJETIVO: O objetivo deste trabalho foi avaliar os principais achados na tomografia computadorizada de pacientes portadores de leucemia aguda complicada com aspergilose pulmonar angioinvasiva. MATERIAIS E MÉTODOS: Foram estudadas, retrospectivamente, as tomografias computadorizadas de 19 pacientes, avaliando-se a presença de consolidações, nódulos e massas, com ou sem sinal do halo, escavação e sinal do crescente aéreo. RESULTADOS: Áreas de consolidação foram o achado mais comum, ocorrendo em 12 dos 19 casos. A maioria delas apresentou o sinal do halo, enquanto escavação foi encontrada em 5 dos 12 casos com consolidações, sendo um deles com sinal do crescente aéreo. Nódulos e massas ocorreram em, respectivamente, seis e quatro casos, a maioria com sinal do halo. Escavação foi encontrada em apenas um caso de massa. Outros achados observados foram pavimentação em mosaico (dois casos, áreas de vidro fosco esparsas (três casos e envolvimento pleural (sete casos, sob a forma de derrame ou espessamento. CONCLUSÃO: Áreas de consolidação, massas ou nódulo, mesmo solitário, com sinal do halo, quando vistos na tomografia computadorizada em um contexto clínico apropriado, são altamente sugestivos de aspergilose angioinvasiva.OBJECTIVE: The aim of this study was to evaluate the main findings of computed tomography in patients presenting acute leukemia complicated by angioinvasive aspergillosis. MATERIALS AND METHODS: Computed tomography images of 19 patients were retrospectively studied for the presence of consolidations, nodules and masses, with or without presentation of halo sign, cavitation and air crescent sign. RESULTS: Consolidation was the most frequent finding, occurring in 12 of the 19 cases, most of them presenting the halo sign; cavitation was found in 5 of 12 cases, one of them with air crescent sign. Nodules and masses occurred respectively in six and four cases, most of them with halo sign. Cavitation was found

  10. Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells.

    Science.gov (United States)

    Mezger, Markus; Steffens, Michael; Beyer, Melanie; Manger, Carolin; Eberle, Johannes; Toliat, Mohammad-Reza; Wienker, Thomas F; Ljungman, Per; Hebart, Holger; Dornbusch, Hans Jürgen; Einsele, Hermann; Loeffler, Juergen

    2008-01-15

    Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n=81) or without IA (n=58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) ligand 10 (CXCL10, 4q21, 11,101 C>T, P=.007; 1642 C

  11. 血清甘露聚糖结合凝集素检测在诊断肺烟曲霉菌感染中的意义%Application of detecting mannose-binding lectins in pulmonary aspergillosis in rats

    Institute of Scientific and Technical Information of China (English)

    胡华; 杨燕; 陈影; 李学政; 滕隔玲; 张琳琳

    2014-01-01

    Objective To explore the effects of mannose-binding lectins (MBL) in pulmonary aspergillosis.Methods A total of 96 adult Wistar rats were randomly divided into 3 groups of aspergillus fumigatus (A.fumigatus) pulmonary,colonization and normal (n =32 each).An intramuscular injection (0.6 mg/kg × 3 d) of dexamethasone sodium phosphate and a nostril drop (1 × 107 cfu/ml) were administered for modeling.The animals were sacrificed at Days 3,7,14 and 28 post-inoculation and blood samples were obtained by cardiac puncture for MBL detection.Lung tissues were prepared for routine pathology examinations.The lung tissues infected with A.fumigatus showed remarkable inflammatory reactions.The serum value of MBL was detected by enzyme-linked immunosorbent assay (ELISA).And the results were compared and analyzed.Results All infected lung tissues showed remarkable inflammatory reactions.The serum MBL levels of A.fumigatus pulmonary and colonization groups were (8.57 ±0.88) and (7.87 ± 0.45) ng/ml and both significantly increased compared with non-pulmonary aspergillosis group (P < 0.05).The area under the curve was 0.744 (P =0.002).The diagnosis of MBL had a sensitivity of 75.0%,a specificity of 86.7%,a positive predictive value of 87.1% and a negative predictive value of 74.3% for pulmonary aspergillosis.The inflammatory cells infiltration were detected in pathology in infection and colonization groups at Day 3 and Day 7.Conclusion The detection of serum MBL may be used for the diagnosis of pulmonary aspergillosis.%目的 探讨血清甘露聚糖结合凝集素(MBL)动态检测在诊断肺烟曲霉菌感染中的意义.方法 成年Wistar大鼠96只,雌雄各半,按随机数字表法随机分为3组,每组32只:(1)对照组:未免疫抑制,未接种烟曲霉菌;(2)感染组(免疫抑制+接种烟曲霉菌):采用地塞米松0.6 mg/kg肌肉注射×3d,通过双侧鼻孔分别滴入烟曲霉菌孢子(1×107 cfu/ml),建立大鼠肺曲菌病模型;(3)定植组:仅双侧

  12. Diagnosis and treatment of invasive pulmonary aspergillosis in 21 children with non-hematologic diseases%非血液病患儿侵袭性肺曲霉病21例的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    张晓艳; 赵顺英; 钱素云; 胡英慧; 曾津津; 江载芳

    2009-01-01

    Objective To explore diagnosis and treatments of invasive pulmonary aspergillosis (IPA) in children with non-hematologic diseases. Method Twenty one patients without hematological malignancy were diagnosed with proven or possible IPA from July 2002 to June 2008. The risk factors, clinical manifestations, chest radiographic findings, microbiological and histopathological evidence, diagnostic procedures, treatment and prognosis were retrospectively reviewed. Result Five children had proven IPA, and 16 patients had possible IPA. Thirteen children were classified as having acute invasive pulmonary asergillosis (AIPA), eight children as having chronic necrotizing pulmonary aspergillosis (CNPA). Definitive diagnosis of primary immunodeficiency (PID) was made in 6 children (4 with chronic granulomatous disease, 2 with cellular immunodeficiency); three children were suspected of having PID. Corticosteroids and multiple broad-spectrum antibiotics had been administered in 5 patients (3 of these 5 patients also had invasive mechanical ventilation). Two children had underlying pulmonary disease. Three patients had unknown risk factors. Among these three patients, two had history of environmental exposure. Fever and cough were present in all the children. Fine rales were found in nineteen children. Six children had hepatosplenomegaly. The common roentgenographic feature of AIPA in 13 patients was nodular or mass-like consolidation with multiple cavity. "air-crescent" was seen in 10 of patients with AIPA. Lobar consolidation with cavity and adjacent pleural thickening was found in all children with CNPA. The positive rate of sputum and/or BALF culture in MPA and CNFA were 72.1% and 22.4%, respectively. A large number of septate hyphae on wet smear were found in all of the children whose sputum and/or BALF culture were positive. Lung biopsy was performed in 3 children with CNPA, and necrosis, granulomatous inflammation, as well as septate, branching hyphae were observed on

  13. Literature review of 35 cases of chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis%慢性阻塞性肺疾病合并侵袭性肺曲霉病35例文献分析

    Institute of Scientific and Technical Information of China (English)

    刘菁; 刘学东

    2013-01-01

    Objective To review the reported cases of invasive pulmonary aspergillosis (IPA) in the patients with chronic obstructive pulmonary disease (COPD) in recent 10 years in China in terms of risk factors,clinical and imaging characteristics,in an attempt to provide important clues for prompt and accurate diagnosis.Methods The literature reports of COPD complicated with IPA from 2002 to 2012 in China were analyzed retrospectively.A total of 35 cases were identfied and reviewed in terms of the relevant clinical data.Results Broad spectrum antibiotic treatment was found in 33 of the 35 cases.Long-term use of glucocorticoids was documented in 34 cases.The most common clinical symptoms included dyspnea,chest tightness,breathlessness,chest pain,fever and pulmonary rales.Conclusions Broad spectrum antibiotic treatment,long-term use of glucocorticoids and invasive procedures are the risk factors of IPA in COPD patients.The clinical manifestations are variable and nonspecific.Early diagnosis and empirical antifungal treatment are effective for improving the outcome.%目的 总结10年来国内报道的慢性阻塞性肺疾病(COPD)合并侵袭性肺曲霉病(IPA)的危险因素、临床特点、影像学特点、诊断方法,为临床医师早期、快速、准确地诊断该病提供依据.方法 回顾性分析2002-2012年国内有关COPD合并IPA的文献资料,统计分析并总结了35例COPD合并IPA患者的临床资料.结果 35例患者中应用广谱抗生素33例,长期应用糖皮质激素34例.常见症状是呼吸困难、胸闷憋气、胸痛、发热和肺部啰音.结论 使用广谱抗生素、长期激素治疗、有创操作是COPD合并IPA的危险因素,患者临床和胸部CT表现多样,缺乏特异性;减少危险因素,做到早期诊断和早期治疗是改善预后的有效方法.

  14. Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil Aspergilosis cerebral causada por Aspergillus fumigatus en paciente con SIDA: primer reporte de caso demostrado por cultivo en Brasil

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    José E. Vidal

    2005-06-01

    Full Text Available Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.La aspergilosis cerebral es una causa rara de lesión expansiva cerebral en pacientes con SIDA. Presentamos el primer reporte de un absceso cerebral causado por Aspergillus fumigatus en un paciente brasileño con SIDA. El paciente, de 26 años de edad, presentaba antecedentes de infección por el virus de la inmunodeficiencia humana (VIH, tuberculosis pulmonar y toxoplasmosis cerebral. Manifestó fiebre, tos, disnea y dos episódios de convulsiones. La tomografía computadorizada (TC demostró una lesión hipodensa parasagital y bi-parietal con

  15. Cerebral Aspergillosis Caused by Neosartorya hiratsukae, Brazil

    Science.gov (United States)

    Kallas, Esper G.; Godoy, Patricio; Karenina, Anna; Gené, Josepa; Stchigel, Alberto; Colombo, Arnaldo Lopes

    2002-01-01

    We report the first case of infection by Neosartorya hiratsukae, an ascomycete in which the conidial state resembles Aspergillus fumigatus. The fungus caused a brain infection in a Brazilian woman, who died despite itraconazole treatment. Diagnosis was established by direct microscopic examination, computed tomographic scan, and magnetic resonance imaging of the brain, and repeated cultures from the lesions. The in vitro antifungal susceptibility of the isolate is provided. PMID:12194781

  16. Clinical analysis of chronic airway diseases combined with invasive pulmonary aspergillosis%慢性气道疾病合并侵袭性肺曲霉病临床分析

    Institute of Scientific and Technical Information of China (English)

    戴然然; 张旻

    2013-01-01

    目的 回顾性总结慢性气道疾病合并侵袭性肺曲霉病(IPA)患者的临床资料,分析慢性气道疾病患者发生IPA的危险因素、临床特点、诊断、治疗和预后.方法 收集2007年1月-2012年8月上海交通大学医学院附属瑞金医院呼吸科和上海交通大学附属第一人民医院呼吸科病房收治的慢性气道疾病合并IPA患者的临床资料.分析其危险因素、临床表现、实验室检查和影像学检查特征、诊断、治疗及预后.结果 共入选18例患者,2例患者经肺活组织穿刺病理学检查明确诊断为IPA,16例患者临床诊断为IPA.男14例,女4例,年龄29~80岁,中位年龄为62.2岁.慢性阻塞性肺疾病(COPD) 13例,支气管哮喘3例,支气管扩张2例.COPD和支气管哮喘患者住院后均应用糖皮质激素治疗,包括静脉注射甲泼尼龙及口服泼尼松,疗程均>2周.3例支气管哮喘患者平时均不规则口服泼尼松.2例COPD和2例支气管哮喘患者有口服邮购的“中成药”(含糖皮质激素)史,疗程均>半年.2例支气管扩张患者因反复感染,长期口服抗生素.13例COPD患者中4例合并糖尿病.所有患者均接受抗真菌药物治疗,其中6例患者死于IPA和呼吸衰竭.结论 慢性气道疾病易合并严重的IPA,大部分患者由于基础疾病急性加重反复使用糖皮质激素治疗,临床和影像学检查无特异性,当临床高度怀疑IPA时应给予尽早诊断和治疗,可以降低病死率.%Objective To retrospectively study the clinical data of the patients with chronic airway disease combined with invasive pulmonary aspergillosis (IPA), and to analyze the risk factors, clinical features, diagnosis, treatment and prognosis of IPA. Methods Clinical data of chronic airway disease patients with IPA were collected. All the patients were hospitalized in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Shanghai First People's Hospital Affiliated to Shanghai

  17. 血清半乳甘露聚糖检测诊断侵袭性曲霉病的临床研究%Evaluation of the galactomannan assay for the diagnosis of invasive aspergillosis in patients

    Institute of Scientific and Technical Information of China (English)

    文昱婷; 赵蓓蕾; 吕沛华; 施毅

    2008-01-01

    目的 评价血清半乳甘露聚糖(GM)检测对侵袭性曲霉病(IA)的诊断价值.方法 南京军区南京总医院2005年1月至2007年2月确诊的侵袭性真菌感染(IFI)住院患者49例,平均年龄55岁,男34例,女15例,其中IA 11例,其他IFI 20例,曲霉气道定植18例.采用Platelia Aspergillus(法国Bio-Rad公司)双夹心ELISA检测试剂盒检测患者的血清GM吸光度指数(简称GM值),IA患者中6例于治疗后7 d重复检测.正态分布计量资料以-x±s表示,多组间比较采用单因素方差分析,治疗前后比较采用配对t检验,采用SPSS统计软件处理实验数据.结果 IA患者血清GM值为1.63±0.29,其他IFI和曲霉气道定植患者分别为0.96±0.49和0.83±0.43,IA患者与后两者比较差异有统计学意义(F=12.681,P<0.05).6例IA患者治疗前后GM值分别为1.67±0.24和1.62±0.28(t=0.475,P>0.05).以GM值为1.5作为诊断阈值诊断IA的敏感度、特异度、阳性预测值和阴性预测值分别为72.7%、84.2%、57.1%和94.1%.结论 血清GM检测对IA具有诊断价值,可区分IA与其他IFI和曲霉气道定植;以GM值为1.5作为诊断阈值诊断IA的敏感度、特异度较理想.%Objective To assess the value of Aspergillus galactomannan(GM)double-direct sandwich enzyme-linked immunosorbent assay(ELISA)in the diagnosis of invasive aspergillosis(IA).Methods Forty nine patients were divided into IA group(n=11),other invasive fungal infection group (n=20)and Aspergillus colonization group(n=18).The serum samples of all patients and 6 patients with IA after 7 day treatment were used for GM detection.A double-direct sandwich ELISA was employed to detect GM optical density index(ODI)in the serum samples.Measurement data followed the Gaussian distribution were expressed as-x±s.Differences among groups were tested using a one factor analysis of variance.The significance of variation before and after therapy was tested with paired t test.P<0.05 were considered to represent a

  18. Clinical features of invasive pulmonary aspergillosis in critically ill patients with chronic respiratory diseases%重症慢性呼吸道疾病合并侵袭性肺曲霉病的临床特点

    Institute of Scientific and Technical Information of China (English)

    詹庆元; 贺航咏; 童朝晖; 栗芳; 孙兵; 王辰

    2008-01-01

    目的 总结重症慢性呼吸道疾病(CRD)合并侵袭性肺曲霉病(IPA)的临床特点,为早期诊断和治疗提供依据.方法 分析2004年10月至2007年2月在北京朝阳医院呼吸科重症监护室(RICU)住院的149例痰或BALF分离出曲霉的CRD患者资料.以SPSS 10.0统计软件进行数据处理,所有计量资料以均数±标准差表示,计数资料以例数表示.计量资料采用t检验,计数资料采用X2检验.结果 149例CRD患者中共收集16例IPA病例(COPD 11例,COPD合并支气管哮喘4例,支气管扩张症1例),其中3例确诊,10例临床诊断,3例拟诊.12例在人RICU前使用过大量糖皮质激素,15例使用广谱抗生素.15例临床表现为严重气道痉挛,9例行无创通气失败,14例因严重呼吸衰竭而需有创机械通气.12例X线胸片可见明显渗出影.外周血白细胞及中性粒细胞比例在疾病后期迅速增高;早期气管镜检查可见气道黏膜充血、水肿、糜烂,气道痉挛,痰液黏稠,后期气道黏膜可出现伪膜;早期真菌病原学检查阳性率低(2/12),后期阳性率高(10/12);早期治疗的患者存活率高(4/4),晚期治疗效果差(11/12),由呼吸衰竭迅速进展为多脏器衰竭是最主要的死亡原因.结论 CRD合并IPA并不少见,预后差.根据临床特点进行早期诊断及经验性治疗可改善患者的预后.%Objective To describe the clinical features of invasive pulmonary aspergillosis(IPA) in critically ill patients with chronic respiratory diseases(CRD)and to estimate its value for early diagnosis and treatment. Methods Retrospective study of critically ill CRD patients with Dositive Aspergillus from sputum or bronchial alveolar lavage fluid in a respiratory ICU of a teaching hospital.Results There were 149 CRD patients admitted between October 2004 and February 2007. Among these patients,16 cases of IPA(11 COPD,4 COPD with asthma,1 bronchiectasis)were collected.Three cases fulfilled the criteria of proven IPA,10 of probable

  19. The diagnostic value in bronchoalveolar lavage galactomannan antigen detection of invasive pulmonary aspergillosis in patients without granulocyte deficiency%支气管肺泡灌洗液半乳甘露聚糖抗原检测对非粒细胞缺乏患者的侵袭性肺曲霉病诊断价值

    Institute of Scientific and Technical Information of China (English)

    郭庆玲; 郭禹标; 廖康; 朱智文

    2016-01-01

    目的:探讨针对感染的肺组织局部进行支气管肺泡灌洗术得到支气管肺泡灌洗液(BALF)进行半乳甘露聚糖(GM)检测是否能协助提高非粒细胞缺乏的患者并侵袭性肺曲霉病(IPA)的诊断效率,并了解其最佳GM界值. 方法: 收集并分析2011年1月至2013年12月在呼吸科内镜中心检查考虑IPA可能并行BALF GM检测的患者173例. 按照国内外诊断标准,将病例分为4组,IPA组(n=23),肺结核组(n=11),细菌性肺炎组(n = 90),非感染组(n = 49).采用ELISA方法测定血清及BALF GM.用统计学方法了解BALF GM检测在非粒细胞缺乏的患者并发IPA中的诊断价值. 结果:在非粒细胞缺乏的患者并发IPA的诊断中,与非IPA患者相比,IPA患者的BALF GM检测数值高, 组间差异有统计学意义; 与血清GM检测相比, BALF GM检测的IPA诊断效率高.ROC曲线分析发现,当BALF GM检测界值为≥0.95时,IPA的诊断效率最高.结论:BALF GM检测有利于非粒细胞缺乏患者并IPA的早期鉴别与诊断.同时研究发现BALF GM值最佳界值为≥0.95.%Objective To study infection of the lung tissue by bronchoalveolar lavage for BALF and explore whether GM can help improve the he diagnosis efficiency in patients without granulocyte deficiency with IPA, and find the threshold of GM values. Methods Between January 2011 and December 2011, 173 cases of patients were considered possible invasive pulmonary aspergillosis in parallel BALF GM detection in the center of the respiratory endoscopic examination.. According to the diagnostic criteria at home and abroad, all the cases were divided into four groups, including group of IPA, group of tuberculosis, group of bacterial pneumonia and group of non-infection. Using ELISA method for determination of serum and BALF GM. The diagnostic value was made by statistical methods in BALF GM detection without patients of granulocyte deficiency with IPA. Results There were 11 cases in the group of IPA, 23 cases in the

  20. Prospective Comparison of the Diagnostic Potential of Real-Time PCR, Double-Sandwich Enzyme-Linked Immunosorbent Assay for Galactomannan, and a (1→3)-β-d-Glucan Test in Weekly Screening for Invasive Aspergillosis in Patients with Hematological Disorders

    Science.gov (United States)

    Kawazu, Masahito; Kanda, Yoshinobu; Nannya, Yasuhito; Aoki, Katsunori; Kurokawa, Mineo; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru; Ogawa, Seishi

    2004-01-01

    The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (1→3)-β-d-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (β-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using two consecutive positive results (0.97; P = 0.036 for ELISA versus PCR, P = 0.055 for ELISA versus BDG). Based on the ROC curve, the cutoff for the ELISA could be reduced to an optical density index (O.D.I.) of 0.6. With the use of this cutoff for ELISA and cutoffs for PCR and BDG that give a comparable level of specificity, the sensitivity/specificity/positive predictive value/negative predictive value of the ELISA and the PCR and BDG tests were 1.00/0.93/0.55/1.00, 0.55/0.93/0.40/0.96, and 0.55/0.93/0.40/0.96, respectively. In conclusion, among these weekly screening tests for IA, the double-sandwich ELISA test was the most sensitive at predicting the diagnosis of IA in high-risk patients with hematological disorders, using a reduced cutoff of 0.6 O.D.I. PMID:15184460

  1. Prospective comparison of the diagnostic potential of real-time PCR, double-sandwich enzyme-linked immunosorbent assay for galactomannan, and a (1-->3)-beta-D-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders.

    Science.gov (United States)

    Kawazu, Masahito; Kanda, Yoshinobu; Nannya, Yasuhito; Aoki, Katsunori; Kurokawa, Mineo; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru; Ogawa, Seishi

    2004-06-01

    The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (1-->3)-beta-d-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (beta-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using two consecutive positive results (0.97; P = 0.036 for ELISA versus PCR, P = 0.055 for ELISA versus BDG). Based on the ROC curve, the cutoff for the ELISA could be reduced to an optical density index (O.D.I.) of 0.6. With the use of this cutoff for ELISA and cutoffs for PCR and BDG that give a comparable level of specificity, the sensitivity/specificity/positive predictive value/negative predictive value of the ELISA and the PCR and BDG tests were 1.00/0.93/0.55/1.00, 0.55/0.93/0.40/0.96, and 0.55/0.93/0.40/0.96, respectively. In conclusion, among these weekly screening tests for IA, the double-sandwich ELISA test was the most sensitive at predicting the diagnosis of IA in high-risk patients with hematological disorders, using a reduced cutoff of 0.6 O.D.I.

  2. 雾化吸人两性霉素B对侵袭性肺曲霉病预防效果的Meta分析%Efficacy and Safety of Inhaled Amphotericin B in Prophylaxis of Invasive Pulmonary Aspergillosis:A Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    卢鑫; 孙文逵; 高伟; 苏欣; 施毅

    2012-01-01

    目的 采用Meta分析方法对现已发表的关于雾化吸入两性霉素B(AmB)预防侵袭性肺曲霉病(IPA)的文献进行综合分析,从动物实验和临床研究两个方面分别评价雾化吸入AmB对IPA的预防作用.方法 检索MEDLINE生物医学数据库、科学引文索引(ISI)、医学文摘资料库(EMBASE)及万方数据库,检索发表于2011年3月以前关于雾化吸入AmB预防IPA的文献,由2名评价员分别筛选符合标准的文献,进行质量评价和数据提取.采用RevMan4.22软件进行异质性分析,合并效应量的检验采用优势比(OR)及95%可信区间(95%CI).结果 共纳入符合标准的动物实验文献5篇,包括实验动物626只;临床研究文献6篇,包括1354例真菌感染高危病人.Meta分析结果显示感染前雾化吸入AmB的实验动物存活率高于安慰剂对照组(38.3%比9.7%,OR=13.93,95%CI7.46 ~26.01,P<0.000 01).真菌感染高危人群中,预防性雾化吸入AmB的患者IPA发生率较安慰剂或空白对照组为低(2.6%比9.2%,OR =0.27,95%CI0.16 ~0.46,P<0.000 01);雾化预防组与对照组患者IPA相关病死率及总死亡率差异无统计学意义(RR =0.65,95% CI0.33~1.30,P=0.23;OR=1.17,95% CI0.73 ~ 1.89,P=0.51);雾化吸入AmB绝大部分不良反应程度轻微.结论 预防性雾化吸入AmB能有效降低实验动物肺曲霉感染死亡率,对粒细胞缺乏等高危人群预防性雾化吸入AmB能有效降低IPA发生率,不良反应轻微,但未降低曲霉感染相关病死率及总死亡率.需要更多高质量大型临床研究进一步提供循证医学证据.%Objective To evaluate the efficacy and safety of inhaled amphotericin B ( AmB) in prophylaxis of invasive pulmonary aspergillosis ( IP A) in both animal studies and clinical researches. Methods MEDLINE.ISI.EMBASE and Wanfang Periodical Databases were searched until march 2011 for case-control study on the efficacy and safety of inhaled AmB in prophylaxis of IPA. The

  3. The application of nucleic acid sequence?based amplification,real?time PCR and GM test in invasive aspergillosis diagnosis%核酸序列依赖性扩增、Real?time PCR及GM试验诊断侵袭性曲霉菌感染的临床应用评价

    Institute of Scientific and Technical Information of China (English)

    王立朋; 鲍翠霞; 于丽梅; 张晓录; 于威娟; 张霞; 李玮; 黄葆华; 李杰

    2015-01-01

    Objective To study the diagnostic performance of nucleic acid sequence?based amplification ( NASBA) assay,real?time PCR and GM test in detecting invasive aspergillosis for clinical diagnosis.Methods Blood samples from 80 patients at a high risk for IA were collected during from November 2013 to June 2014.These patients were categorized as 8 proven IA,26 probable IA, and 46 non?IA according to the 2008 revised definitions of EORTC/MSG.Blood samples were tested by NASBA,real?time PCR and GM test and their diagnostic parameters were calculated,respectively.Result The sensitivity of NASBA,real?time PCR and GM test was 76.47%,67.65% and 52.94%,while their specificity was 80.43%,89.13%,80.43%,respectively.The efficiency of various com?binations of tests was also evaluated.Perfect specificity (100%) and positive predictive value (100%) were achieved by combining NASBA and real?time PCR as a serial testing.A combination of NASBA and real?time PCR as a parallel testing was the most sensitive (94.12%).Conclusion The sensitivity and specificity of NASBA and real?time PCR were superior to GM test.Combination of these assays could be particularly useful in specific clinical situations.%目的 核酸序列依赖性扩增 ( nucleic acid sequence?based amplification,NASBA)、Real?time PCR及GM试验在侵袭性曲霉菌感染中的诊断价值. 方法 收集2013年11月~2014年6月临床上曲霉菌感染高危病患的血液标本80例,并根据EORTC/MSG诊断标准分为确诊组8例,拟诊组26例,非感染组46例,分别利用NASBA、real?time PCR及GM试验进行检测,计算3种方法的诊断指标并分析评价. 结果 NASBA、real?time PCR及GM试验3种方法的灵敏度分别为76.47%、67.65%、52.94%,特异度分别为80.43%、89.13%、80.43%. 联合诊断结果显示,NASBA与real?time PCR串联方案有最好的特异度 (100%)及阳性预测值(100%);NASBA与real?time PCR并联方案则最为灵敏(94.12%). 结论 NASBA用于诊断IA最为敏感,而real?time PCR

  4. Equine pulmonary aspergillosis with encephalitic, myocardial, and renal dissemination.

    Science.gov (United States)

    Headley, Selwyn Arlington; de Carvalho, Pedro Henrique; Cunha Filho, Luiz Fernando C; Yamamura, Aline Artioli Machado; Okano, Werner

    2014-02-01

    The cause of the death of a 16-month-old Brasileiro-de-Hipismo filly and a 3-year-old male Paint Horse with clinical manifestations of anemia and apathy from southern Brazil was investigated. These horses were maintained at the same stable; received hay as part of their diet and were submitted for routine necropsy evaluations. Significant gross findings included several nodules randomly distributed throughout the pulmonary lobes of both horses, and the kidneys, myocardium, and the frontal lobes of the cerebrum of the filly. Histopathological evaluation revealed pyogranulomatous bronchopneumonia in both horses; granulomatous interstitial nephritis, myocarditis, and encephalitis were observed in the filly. All lesions contained vasculitis and thrombosis associated with myriads of intralesional, branching, septate fungi consistent with Aspergillus spp.; intralesional fungi were more easily identified by the Grocott methenamine silver stain. Mycological culture of fresh pulmonary sections from both horses and the brain of the filly revealed pure growths of A. fumigatus. These findings confirmed the participation of A. fumigatus in the etiopathogenesis of the lesions observed in the lungs of both horses, and the cerebrum, myocardium and kidneys of the filly and might represent the first description of A. fumigatus-induced encephalitis in horses. Additionally, we believe that infection occurred during the ingestion of contaminated hay or by inhalation of spores within contaminated bedding that resulted in transient nasal mycosis, which progressed to pyogranulomatous bronchopneumonia in both horses with embolic encephalitic, myocardial, and renal dissemination of A. fumigatus occurring only in the filly.

  5. [Aspergillosis located on polycystic kidney treated with retroperitoneal nephrectomy].

    Science.gov (United States)

    Rabii, R; Hoznek, A; Salomon, L; Bourg, S; Chopin, D K; Abbou, C C

    2001-03-01

    We reported an uncommon case of 40 years old man, cardiac transplant recipient with chronic renal faillure who consulted for infected left polycystic renal. The serum creatinine level was 750 mmol/L, and urine culture isolated a E. Ecol germe. The abdominopelvic computed tomography showed a bilateral large polycystic renal cortex and suspected the infected cyst in lower pole of left kidney. The retroperitoneal laparoscopic nephrectomy was performed confirming a renal invasive aspergillosa. About this case we should have a high index of suspicion for fungal aetiology in kidney infection in transplant patients and the management of non functioning infected polycystic kidney can use laparoscopic retroperitoneal nephrectomy. This approach can offers a minimal morbidity and alternative to open surgery.

  6. Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence

    Directory of Open Access Journals (Sweden)

    Ethan R. Stewart

    2016-09-01

    Full Text Available Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the environment, an invasive fungal infection (IFI is a rare outcome that is often reserved for those patients who are immunocompromised. Given the potential for significant morbidity and mortality within this patient population from IFI due to Aspergillus spp., along with the rise in the use of therapies that confer immunosuppression, there is an increasing need for appropriate initial clinical suspicion leading to accurate diagnosis and effective treatment. Voriconazole remains the first line agent for therapy; however, the use of polyenes, novel triazole agents, or voriconazole in combination with an echinocandin may also be utilized. Consideration as to which particular agent and for what duration should be made in the individual context for each patient based upon underlying immunosuppression, comorbidities, and overall tolerance of therapy.

  7. Immunohistochemistry for the diagnosis of aspergillosis in turkey poults

    DEFF Research Database (Denmark)

    Jensen, H.E.; Christensen, J.P.; Bisgaard, M.;

    1997-01-01

    poults from flock A in which minute circular areas of cerebral malacia were seen. Histopathologically, the brain lesions contained fungal elements, and so did some of the pulmonary granulomas detected in three and six poults out of four and six birds examined from flock A and B, respectively. Mycological...

  8. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  9. 慢性阻塞性肺疾病合并变应性支气管肺曲霉病三例临床分析%Allergic bronchopulmonary aspergillosis in patients with chronic obstructive pulmonary disease:report of 3 cases

    Institute of Scientific and Technical Information of China (English)

    刘晓芳; 孙永昌; 金建敏; 李然; 刘涌

    2013-01-01

    目的 了解慢性阻塞性肺疾病(简称慢阻肺)合并变应性支气管肺曲霉病(ABPA)的临床表现及影像学特征,以提高认知水平.方法 回顾性分析北京同仁医院2009年1月至2012年12月诊断的3例慢阻肺合并ABPA病例的临床资料.结果 3例慢阻肺合并ABPA患者均为男性,年龄68 ~ 82岁,均以咳嗽、咳痰、活动后气短为主要表现,伴发作性喘息;既往均无支气管扩张症、支气管哮喘、变应性鼻炎、鼻窦炎及湿疹等疾病史及支气管哮喘家族史.均有吸烟史.肺功能检查显示阻塞性通气功能障碍,吸入支气管舒张剂后FEV1/FVC分别为30%、33%和43%,均符合慢阻肺的诊断标准,依据慢阻肺诊断、处理和预防全球策略的肺功能严重程度分级,1例为Ⅲ级,2例为Ⅳ级.高分辨率CT均显示肺气肿伴或不伴有肺大疱.3例均存在曲霉抗原皮试速发反应阳性,血清总IgE>1000kU/L,血清曲霉特异性IgE增高(>0.35 kU/L),血清曲霉特异性IgG增高(>40 mg/L),高分辨率CT显示不同程度的支气管扩张.此外,3例的外周血嗜酸粒细胞比值均>0.05,曾出现肺部浸润阴影,2例曾咳褐色痰栓,1例痰培养烟曲霉阳性,3例均符合ABPA的诊断标准.确诊后给予口服泼尼松治疗,呼吸困难和FEV1均明显改善.结论 慢阻肺合并ABPA在临床上较为少见,及时诊断和治疗有利于改善症状和预后.临床上对于反复出现发作性喘息及常规治疗不能控制的慢阻肺病例,应考虑有合并ABPA的可能性.%Objective To improve the clinical knowledge on allergic bronchopulmonary aspergillosis (ABPA) combined with COPD by report of cases.Methods We retrospectively analyzed the clinical information of 3 cases of ABPA combined with COPD diagnosed in our hospital from Jan.2009 to Dec.2012.Results The 3 patients were all males,and aged from 68 to 82 years.The main complaints of all the patients were exertional dyspnea,cough and sputum production

  10. The potential impact of the pulmonary microbiome on immunopathogenesis of Aspergillus-related lung disease

    NARCIS (Netherlands)

    Kolwijck, E.; Veerdonk, F.L. van de

    2014-01-01

    Aspergillosis is an infection or allergic response caused by fungi of the genus Aspergillus. The most common forms of aspergillosis are allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis. Aspergillus also plays an important role in fungal s

  11. Microwave-assisted synthesis of antimicrobial dihydropyridines and tetrahydropyrimidin-2-ones: novel compounds against aspergillosis.

    Science.gov (United States)

    Chhillar, Anil K; Arya, Pragya; Mukherjee, Chandrani; Kumar, Pankaj; Yadav, Yogesh; Sharma, Ajendra K; Yadav, Vibha; Gupta, Jyotsana; Dabur, Rajesh; Jha, Hirday N; Watterson, Arthur C; Parmar, Virinder S; Prasad, Ashok K; Sharma, Gainda L

    2006-02-15

    Ten 4-aryl-1,4-dihydropyridine and three 4-aryl-1,2,3,4-tetrahydropyrimidin-2-one derivatives have been synthesized and examined for their activity against pathogenic strains of Aspergillus fumigatus and Candida albicans. Although none of the three compounds belonging to pyrimidin-2-one series showed any activity against two pathogens, two of the compounds of the dihydropyridine series, that is, diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate and dimethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate, exhibited significant activity against A. fumigatus in disc diffusion, microbroth dilution and percent spore germination inhibition assays. The most active diethyl dihydropyridine derivative exhibited a MIC value of 2.92 microg/disc in disc diffusion and 15.62 microg/ml in microbroth dilution assays. The MIC(90) value of the most active compound by percent germination inhibition assay was found to be 15.62 microg/ml. The diethyl dicarboxylate derivative of dihydropyridine also exhibited appreciable activity against C. albicans. The in vitro toxicity of the most active diethyl dihydropyridine derivative was evaluated using haemolytic assay, in which the compound was found to be non-toxic to human erythrocytes even at a concentration of 625 microg/ml. The standard drug amphotericin B exhibited 100% lysis of erythrocytes at a concentration almost 16 times less than the safer concentration of the most active dihydropyridine derivative.

  12. Detection of antigen in sera of patients with invasive aspergillosis : Intra- and interlaboratory reproducibility

    NARCIS (Netherlands)

    Verweij, PE; Erjavec, Z; Sluiters, W; Goessens, W; Rozenberg-Arska, M; Debets-Ossenkopp, YJ; Guiot, HFL; Meis, JFGM

    1998-01-01

    The intra-and interlaboratory reproducibilities of a commercial sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan in serum (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-La-Coquette, France) were evaluated in six laboratories of university h

  13. Specific IgG(4) responses during chronic and transient antigen exposure in aspergillosis

    NARCIS (Netherlands)

    Tomee, JFC; Dubois, AEJ; Koeter, GH; Beaumont, F; vanderWerf, TS; Kauffman, HF

    1996-01-01

    The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG(4) responses may be related to prolonged antigen exposure. We present data showing that increased IgG(4) responses are found under conditions of chronic expos

  14. Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

    NARCIS (Netherlands)

    Eerd-Vismale, J.E.M. van; Rennen, H.J.J.M.; Oyen, W.J.G.; Harris, T.D.; Edwards, D.S.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we dec

  15. Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease

    Science.gov (United States)

    Waqas, Muhammed; Zafar, Sidra; Rehman, Tooba; Riyaz, Muhammed; Bari, Muhammed E.; Idrees, Romana

    2016-01-01

    Background: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians. Case Description: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed tomography scan revealed multiple cerebral abscesses. These abscesses were excised. The microbiological specimen was determined to be positive for Aspergillus fumigatus. His tracheal aspirate was positive for Mycobacterium tuberculosis polymerase chain reaction assay. Further work-up confirmed the diagnosis of CGD in the child. Conclusion: This report describes the course of the patient's illness in order to highlight the challenges associated with the management of these infections. We also aim to stress on the importance of pathological diagnosis before starting a therapy. PMID:27308089

  16. Sudden death of a Siamese crocodile (Crocodylus siamensis) due to systemic aspergillosis

    Science.gov (United States)

    KIM, Kyoo-Tae; LEE, Seung-Hun; KWAK, Dongmi

    2016-01-01

    A 4-year-old female Siamese crocodile (Crocodylus siamensis) housed at a zoo died without any prior clinical signs. During necropsy, numerous scattered, well-demarcated, yellowish-white, firm nodules were observed throughout the liver and lungs. Microscopic examination with periodic acid-Schiff staining revealed granulomatous inflammation in the liver and lungs. Liver granulomas were characterized by the presence of a connective tissue barrier and hyphae, and the centers of the granulomas showed signs of necrosis. Lung samples showed characteristics similar to those observed in the liver samples. The fungus was identified as Aspergillus fumigatus based on its appearance on Sabouraud dextrose agar, microscopic examination with lactophenol cotton blue staining and genetic sequencing. Therefore, zoo veterinarians should pay close attention to fungal infections in captive animals. PMID:27476559

  17. Invasive pulmonary aspergillosis in an immunocompetent patient with severe dengue fever.

    Science.gov (United States)

    Nasa, Prashant; Yadav, Rohit; Nagrani, S K; Raina, Sanjay; Gupta, Ankur; Jain, Shakti

    2014-05-01

    We report a case of a 65-year-old female diagnosed with sever dengue fever. She started showing recovery from dengue fever with medical management. On day 6 of admission, she had leukocytosis, altered mental sensorium, and hemoptysis. Chest tomography showed air space consolidation with multiple nodules in the left upper and middle lobe sputum and bronchoalveolar lavage cultures were positive for Aspergillus flavus. The patient showed improvement with voriconazole and therapy was continued for 6 weeks.

  18. A pulmonary aspergillosis case with fatal course in a patient with SIRS clinic

    Directory of Open Access Journals (Sweden)

    Nedim Çekmen

    2011-01-01

    Full Text Available A 77-year-old male patient with a history of tuberculosis applied to emergency service with complaints of confusion, shortness of breath, tachycardia, hypothermia and hypotension. A bronchoalveolar lavage culture was collected because a fungus ball was seen on repeat chest X-ray and thoracic CT of the patient. Aspergillus fumigatus grew and voricona-zole treatment was started, but the patient was lost from multiple organ failure (MOF. In diagnosis of patients with SIRS clinic, causative factor may be aspergillus located in an old tuberculosis cavity, and this may have a fatal course in an old patient having previous pulmonary and systemic diseases.

  19. Clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries

    Institute of Scientific and Technical Information of China (English)

    Kheirandish Reza; Askari Nasrin; Salehi Mahmoud

    2013-01-01

    Objective:To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously. Methods:This study was performed on a breeding colony (about 100 canaries) affected by fatal wasting disease. Necropsy was undertaken on 10 severely affected canaries, and gross lesions were recorded. Samples from internal organs displaying lesions were obtained for histopathological evaluation. Tracheal swap samples of internal organs of the all infected animals with lesions at necropsy were cultured in Sabouraud Dextrose Agar for mycological examination. Results: At necropsy, caseous foci were determined in the lungs, on the air sacs, liver, spleen, heart. Swelling of the eyelids, diffuse hemorrhages in the subcutaneous tissue with small papular lesions of the skin were other typical necropsy findings. Histopathologically, pathognomonic eosinophilic intracytoplasmic inclusion bodies, which called Bollinger bodies, in both skin cells and vacuolated air way epithelial cells confirmed canary pox infection. Moreover, histopathological examination of the white-yellowish caseous foci revealed necrotic granulomatous reaction consisting of macrophages, heterophil leukocytes and giant cells encapsulated with a fibrous tissue. After the culture of the tissue samples, the formation of bluish green colonies confirmed A. fumigatus infection. Conclusions:Canary pox has been known as the disease that can result in high losses in a short time, as a re-emerging disease that has not been present during recent years in canary flocks in Iran. So, the current paper provides useful information to prevent misdiagnosed of canary pox disease which can cause secondary mycotic infection.

  20. Post-transplant aspergillosis and the role of combined neurosurgical and antifungal therapies under belatacept immunosuppression

    DEFF Research Database (Denmark)

    Ekkehard, Kasper; Bartek, Jiri; Johnson, Jesper Scott

    2011-01-01

    Opportunistic CNS-infection represent a major threat to patients after organ transplantation due to the need for ongoing immunosuppression and belatacept is a novel CTL4A inhibitor, which is increasingly used for patients following cadaveric kidney transplantation. Among the CNS infections, intra...

  1. Utility of the serum galactomannan assay for the diagnosis of invasive aspergillosis in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2017-01-01

    Conclusions: GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA.

  2. 肺曲菌病的临床与影像学%Clinic and Imaging of Pulmonary Aspergillosis

    Institute of Scientific and Technical Information of China (English)

    党明海; 郭佑民

    2006-01-01

    肺曲菌病(pulmonarya spergillosis)是一种由曲菌引起的感染性、进展性、变态反应性疾病。曲菌广泛的存在于腐烂的有机物中,如霉变的谷物、腐烂的植被等。自然界大约有200多种曲菌,但是仅仅有10种左右可以致病,常见的致病菌株是烟曲菌(aspergillus fumigatus)、黄曲菌(aspergillus flavus)和黑曲菌(aspergillus niger)。曲菌为条件致病菌,只有当人体抵抗力下降或有大量菌丝侵入时才可致病。曲菌病的高危人群包括患有癌症、艾滋病、白血病的患者,以及器官移植者、高剂量的皮质甾类应用者、接受化学疗法的患者等,诸如此类长期处于白细胞计数较低的人群。

  3. The use of abatacept in debilitating cavitating lung disease associated with rheumatoid arthritis, bronchocentric granulomatosis and aspergillosis.

    LENUS (Irish Health Repository)

    Neff, K

    2010-06-01

    A case of debilitating cavitating lung disease associated with rheumatoid arthritis and bronchocentric granulomatosis, which failed to respond to conventional medical or surgical treatment, is described. The patient was treated over 10 years with steroids, antimicrobial agents, disease-modifying antirheumatoid drugs and surgery. Lung function continued to decline and the patient presented for admission with recurrent pneumonia. Abatacept was initiated to modify the underlying immunopathology. Following 12 months of treatment with abatacept the patient has demonstrable improvement in lung function and lung anatomy, and has not presented to hospital with pneumonia. She has tolerated the treatment without complication. The use of abatacept has stabilised the lung disease in this case in the medium term and prevented readmission to hospital. These results suggest a larger role for abatacept in those with such disease in the future and may warrant further investigation.

  4. Image findings of a false positive radioactive iodine-131 uptake mimicking metastasis in pulmonary aspergillosis identified on single photon emission computed tomography-computed tomography

    Directory of Open Access Journals (Sweden)

    Kamaleshwaran Koramadai Karuppusamy

    2015-01-01

    Full Text Available High doses of iodine-131 are commonly used in patients with differentiated thyroid cancer after total or subtotal thyroidectomy, in order to ablate the remaining cancer or normal thyroid tissue. Multiple different false-positive scans can occur in the absence of residual thyroid tissue or metastases. The authors present a case of abnormal uptake of radioactive iodine in the aspergilloma, potentially masquerading as pulmonary metastases.

  5. 实体器官移植后侵袭性肺曲菌病的CT表现%CT manifestations of invasive pulmonary aspergillosis after solid organ transplantation

    Institute of Scientific and Technical Information of China (English)

    董莘; 李海斌

    2013-01-01

    BACKGROUND:The morbidity and mortality of lung infection after solid organ transplantation remains high, especial y the opportunistic aspergil osis infection. The early diagnosis of invasive pulmonary aspergil osis is difficult. OBJECTIVE:To summarize the CT manifestations of invasive pulmonary aspergil osis after solid organ transplantation. METHODS:The VIP database, CNKI database, Medline database, Highwire database and Foreign Journals Integration System were retrieved with the key words of“solid organ transplantation/renal transplantation/liver transplantation/lung transplantation/heart transplantation, aspergil osis, fungus, mold, pulmonary invasive, tomography computerized”in Chinese and English for the articles published from January 2001 to October 2012. The clinical reports related with the CT manifestations of invasive pulmonary aspergil osis among the reports of pulmonary aspergil osis infections and the fungus or mold lung infections were selected. Secondary manual retrieval of solid organ transplantation was performed, and the literatures on the CT manifestations of invasive pulmonary aspergil osis after solid organ transplantation were included. Reproductive research and atypical report were excluded. RESULTS AND CONCLUSlON:The typical chest CT manifestations of invasive pulmonary aspergil osis after solid organ transplantation included nodules, masses, consolidations and ground-glass opacities. With infection time prolonged, the halo sign, reversed halo sign, cavitis and air crescent sign appeared successively. Different incidences of these signs may be associated with the time interval between onset to a CT examination, fungus preventive treatment time and early antifungal treatment. Meaningful results are the relationship between invasive pulmonary aspergil osis signs and the prognosis of patients. No consolidations or masses and presence of smal cavitis may be related with a better prognosis. Greater nodules, multi-infarct consolidation, renal replacement therapy and persistent positive serum galactomannan is a 90-day independent predictor for mortality. Halo sign on behalf of bleeding has nothing to do with the 90-day mortality. Although the report is less, the CT pulmonary angiography is a promising diagnostic tool for the diagnosis of invasive fungal pneumonia, which can early detect the vascular occlusion used to reflect the invasive vascular involvement, and its sensitivity and specificity are better than the halo sign, and approximate to serum galactomannan test.%背景:实体器官移植后肺部感染的发病率和死亡率居高不下,尤其是作为机会感染的曲菌,早期诊断侵袭性肺曲霉菌病是困难的。目的:总结实体器官移植后侵袭性曲菌性肺炎的CT表现。方法:以“实体器官移植/肾移植/肝移植/肺移植/心脏移植,曲菌,真菌,霉菌,肺,侵袭性,体层摄影术,X线计算机”为中文捡索词,以“solid organ transplantation/renal transplantation/liver transplantation/lung transplantation/heart transplantation, aspergil osis , fungus , mold , pulmonary invasive, tomography computerized”为英文检索词,检索维普和中国知网(CNKI)期刊全文数据库、Medline,highwire和外文生物医学期刊全文数据库(Foreign Journals Integration System)2001年1月至2012年10月有关肺曲菌感染和真菌或霉菌肺感染报告中主要涉及曲菌的侵袭性曲菌肺炎 CT 表现的临床报道。然后二次人工检索实体器官移植后,纳入有关实体器官移植后侵袭性曲菌肺炎CT表现的文献,排除重复性研究和不典型报道。结果与结论:实体器官移植后侵袭性肺曲霉菌病典型的胸部 CT 表现包括结节、肿块、实变以及磨玻璃影。随感染时间依次出现晕征、反晕征、空洞和空气半月征。这些征象的发生率的不同可能与 CT 检查时间和早期抗真菌治疗已经真菌预防性治疗有关。有意义的结果是侵袭性肺曲霉菌病征象与患者预后的关系。无实变或肿块和

  6. Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

    Directory of Open Access Journals (Sweden)

    Miguel E. Pinto

    2012-06-01

    Full Text Available Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf. After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

  7. Economic evaluation of targeted treatments of invasive aspergillosis in adult haematopoietic stem cell transplant recipients in the Netherlands: a modelling approach.

    NARCIS (Netherlands)

    Ament, A.J.; Hubben, M.W.; Verweij, P.E.; Groot, R. de; Warris, A.; Donnelly, J.P.; Wout, J. van 't; Severens, J.L.

    2007-01-01

    OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a targeted treatment model of antifungal treatment strategies for adult haematopoietic stem cell transplant (HSCT) recipients in the Netherlands from a hospital perspective, using a decision analytic modelling approach. METHOD

  8. 变应性支气管肺曲菌病误诊原因及影像特点分析%Misdiagnosis Cause and Imaging Feature of Allergic Bronchopulmonary Aspergillosis

    Institute of Scientific and Technical Information of China (English)

    蔡志钢; 靳伟; 张卓然

    2011-01-01

    Objective To investigate the clinical features and manifests of chest CT of allergic bronchopulmonary aspergilosis (ABPA) to reduce the misdiagnosis. Methods The clinical and eikonic data of 4 patients with ABPA diagnosed in our hospital were retrospectively analyzed. Results 4 patients had different degrees of cough and expectoration, and they were misdiagnosed as bronchiectasis with infection, bronchial asthma, pulmonary tuberculosis, and pneumonia respectively. Chest CT mainly showed central bronchiectasis and bronchial mucus plug forming. Peripheral blood eosinophils and serum IgE increased. Serum IgE-Af showed medium saitivity. Intracutaneous test of aspergillus fumigatus antigen showed quick positive reaction. All the patients were diagnosed as having ABPA. Conclusion The diagnosis of ABPA can be suggested when central bronchiectasis and bronchial mucus plug forming appear in multiple lung fields in the patients with long term of gasping and cough, and combined serological test is necessary in diagnosis.%目的 探讨变应性肺曲菌病(allergic bronchopulmonary aspergilosis,ABPA)的临床特点及胸部CT表现,减少误诊误治.方法 回顾性分析我院明确诊断4例ABPA临床及影像学资料.结果 4例均有不同程度的咳嗽、咳痰,分别误诊为支气管扩张并感染、支气管哮喘、肺结核和肺炎.胸部CT主要表现为中心性支气管扩张和支气管黏液栓形成;实验室检查表现为外周血嗜酸粒细胞增高,血清IgE升高,血清IgE-Af中度敏感,烟曲菌抗原皮内试验呈速发反应阳性,均确诊ABPA.结论 在长期喘息、咳嗽的患者中出现中上肺野多发的中心性支气管扩张及支气管腔内黏液栓形成可提示ABPA,确诊需结合血清学检查.

  9. CLINICAL ANALYSIS OF CASPOFUNGIN IN TREATMENT OF HEMATOLOGICAL MALIGNANCIES COMBINED INVASIVE PULMONARY ASPERGILLOSIS INFECTION%卡泊芬净治疗恶性血液病合并IPA感染临床分析

    Institute of Scientific and Technical Information of China (English)

    梁莉; 申徐良; 张梅香; 张国香; 魏武

    2014-01-01

    目的:评估卡泊芬净治疗恶性血液病合并侵袭性肺曲霉菌(IPA)感染的临床疗效和安全性。方法:2008年1月-2012年12月恶性血液病合并IPA感染患者49例,所有患者均经CT检查和GM试验临床诊断;采用注射用醋酸卡泊芬净进行治疗,根据临床疗效标准,评价卡泊芬净治疗的疗效和安全性。结果:49例患者的治疗总有效率为91.84%(45/49)。卡泊芬净治疗过程中9例发生不良反应,不良反应发生率为18.37%。结论:卡泊芬净有很好的抗真菌活性,是治疗恶性血液病合并肺曲霉菌感染安全有效的药物。%Objective:To evaluate the clinical efficacy and safety of caspofungin in treatment of hematological malignanciescombinedinvasivepulmonaryaspergillosis(IPA)infection.Methods:49hematologicalmalignanciescombined IPA infection patients (2008.1-2012.12) that were diagnosed by CT and galactomannan test were treated with caspofungin. The clinical efficacy and safety of caspofungin were evaluated according to clinical curative effect standard.Results:The total effective rate of 49 patients was 91.84%(45/49) after caspofungin treatment;and the incidence of drug related adverse events was 18.37%(9/49).Conclusions:Caspofungin has good antifungal activity, and it is a safe and effective drug for treating hematological malignancies combinedIPAinfection.

  10. Pharmacodynamics of Voriconazole in Children : Further Steps along the Path to True Individualized Therapy

    NARCIS (Netherlands)

    Huurneman, Luc J.; Neely, Michael; Veringa, Anette; Docobo Perez, Fernando; Ramos-Martin, Virginia; Tissing, Wim J.; Alffenaar, Jan-Willem C.; Hope, William

    2016-01-01

    Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this

  11. Exploring azole antifungal drug resistance in Aspergillus fumigatus with special reference to resistance mechanisms

    NARCIS (Netherlands)

    Chowdhary, A.; Sharma, C.; Hagen, F.; Meis, J.F.G.M.

    2014-01-01

    Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with v

  12. Monoclonal Antibodies to Hyphal Exoantigens Derived from the Opportunistic Pathogen Aspergillus terreus

    Science.gov (United States)

    Aspergillus terreus has been difficult to identify in cases of aspergillosis, and clinical identification has been restricted to the broad identification of aspergillosis lesions in affected organs or the detection of fungal carbohydrates. As a result, there is a clinical need to...

  13. USE OF THE GEOGRAPHIC INFORMATION SYSTEM TO INVESTIGATE MERCURY LEVELS IN CORRELATION WITH POSTMORTEM FINDINGS OF ASPERGILLUS INDUCED LESIONS IN THE COMMON LOON (GAVIA IMMER) IN THE NORTHEASTERN USA

    Science.gov (United States)

    This study employed the Geographic Information System (GIS) to correlate total mercury levels in liver tissue with post-mortem findings of aspergillosis in common loons (Gavia immer) in the northeast United States of America (USA). Aspergillosis is an opportunistic fungal infecti...

  14. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  15. Diagnose in beeld (92). Een man met koorts tijdens chemotherapie. Invasieve pulmonale mycose

    NARCIS (Netherlands)

    van Spronsen, D J; Daenen, S M G J; Kluin-Nelemans, J C

    2002-01-01

    A 64-year-old male was treated for acute myeloid leukemia with idarubicin and cytarabin. He developed pulmonary mycosis (radiologically consistent with aspergillosis), which responded to intravenous amphotericin B.

  16. Aspergillus antigen skin test (image)

    Science.gov (United States)

    ... After 48 to 72 hours the site of injection is evaluated by a physician. If a positive reaction occurs (the test site is inflamed), the person has been exposed to the aspergillus mold and is at risk for developing aspergillosis.

  17. Susceptibility breakpoints for amphotericin B and Aspergillus species in an in vitro pharmacokinetic-pharmacodynamic model simulating free-drug concentrations in human serum

    NARCIS (Netherlands)

    Elefanti, A.; Mouton, J.W.; Verweij, P.E.; Zerva, L.; Meletiadis, J.

    2014-01-01

    Although conventional amphotericin B was for many years the drug of choice and remains an important agent against invasive aspergillosis, reliable susceptibility breakpoints are lacking. Three clinical Aspergillus isolates (Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus) were tes

  18. Density and molecular epidemiology of Aspergillus in air and relationship to outbreaks of Aspergillus infection

    NARCIS (Netherlands)

    A.C.A.P. Leenders (Alexander); A.F. van Belkum (Alex); M.D. Behrendt (Myra); A. Luijendijk (Ad); H.A. Verbrugh (Henri)

    1999-01-01

    textabstractAfter five patients were diagnosed with nosocomial invasive aspergillosis caused by Aspergillus fumigatus and A. flavus, a 14-month surveillance program for pathogenic and nonpathogenic fungal conidia in the air within and outside the University Hospital in

  19. A case report of severe Aspergillus flavus penile infection

    Institute of Scientific and Technical Information of China (English)

    Bing-Kun Li; Xiang Wang; Qiang Ding

    2009-01-01

    @@ Dear Sir, My name is Xiang Wang, from the Department of Urology of Huashan Hospital at Fudan University in China. In this letter, we present our experience with the diagnosis and treatment of a patient with severe penile aspergillosis.

  20. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.

    NARCIS (Netherlands)

    Kullberg, B.J.; Sobel, J.D.; Ruhnke, M.; Pappas, P.; Viscoli, C.; Rex, J.H.; Cleary, J.D.; Rubinstein, E.; Church, L.W.; Brown, J.M.; Schlamm, H.T.; Oborska, I.T.; Hilton, F.; Hodges, M.R.

    2005-01-01

    BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients. ME

  1. Microsatellite typing of Aspergillus flavus from clinical and environmental avian isolates

    OpenAIRE

    2013-01-01

    Aspergillosis is one of the most common causes of death in captive birds. Aspergillus fumigatus accounts for approximately 95 % of aspergillosis cases and Aspergillus flavus is the second most frequent organism associated with avian infections. In the present study, the fungi were grown from avian clinical samples (post-mortem lung material) and environmental samples (eggs, food and litter). Microsatellite markers were used to type seven clinical avian isolates and 22 environmental isolates o...

  2. CT "halo sign" in pulmonary tuberculoma.

    Science.gov (United States)

    Gaeta, M; Volta, S; Stroscio, S; Romeo, P; Pandolfo, I

    1992-01-01

    The CT halo sign has been described as the CT finding of a low-attenuation zone surrounding a pulmonary nodule. It is an early clue to the diagnosis of invasive pulmonary aspergillosis. We describe a case of CT halo sign associated with a pulmonary tuberculoma. Therefore, we think that a diagnosis other than invasive pulmonary aspergillosis should be considered in the presence of the CT halo sign in immunocompetent patients.

  3. Nationwide Surveillance of Azole Resistance in Aspergillus Diseases.

    Science.gov (United States)

    Vermeulen, Edith; Maertens, Johan; De Bel, Annelies; Nulens, Eric; Boelens, Jerina; Surmont, Ignace; Mertens, Anna; Boel, An; Lagrou, Katrien

    2015-08-01

    Aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental Aspergillus strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on Aspergillus resistance among patients with Aspergillus disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patient's inclusion. A total of 220 Aspergillus isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (n = 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n = 39 patients), chronic pulmonary aspergillosis (n = 10 patients), Aspergillus bronchitis (n = 7 patients), and aspergilloma (n = 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of Aspergillus fumigatus resistance was limited in our patient population with Aspergillus diseases.

  4. Anestesia para tratamento de aspergilose cardíaca em paciente com trombocitopenia: o uso criterioso da aprotinina Anestesia para tratamiento de aspergilosis cardiaca en paciente con trombocitopenia: el uso con criterio de la aprotinina Anesthesia for treatment of cardiac aspergillosis in a patient with thrombocytopenia and the judicious use of aprotinin

    Directory of Open Access Journals (Sweden)

    Raquel Reis Soares

    2007-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A aprotinina tem sido muito utilizada em intervenções cirúrgicas cardíacas como recurso terapêutico para redução dos efeitos da circulação extracorpórea (CEC sobre a coagulação e fibrinólise. A recuperação da hemostasia adequada ao final do procedimento é um dos objetivos do anestesiologista. Porém, o uso da aprotinina tem indicação específica. O objetivo deste trabalho foi apresentar o caso de um paciente com plaquetopenia intensa submetido à intervenção cirúrgica cardíaca no qual a interconsulta com a Hematologia e o planejamento adequado permitiram o sucesso do procedimento. RELATO DO CASO: Paciente do sexo masculino, 18 anos, 64 kg, estado físico ASA IV, portador de aplasia de medula, em investigação para ser submetido a transplante de medula. Apresentava febre persistente, de um mês de evolução, sem melhora com antibioticoterapia. Na investigação com métodos de imagem, diagnosticou-se massa intra-atrial esquerda. Ao exame laboratorial apresentava hemoglobina de 9 g.dL-1 e trombocitopenia - 6.000 plaquetas.mm-3. Foi submetido à esternotomia com CEC para retirada de trombo intracavitário. Com objetivo de controlar o sangramento intra-operatório foram administrados: plaquetaférese, hidrocortisona e aprotinina. Durante a intervenção cirúrgica não houve aumento do sangramento nem instabilidade hemodinâmica e o paciente foi encaminhado à Unidade de Terapia Intensiva (UTI sem intercorrências. O exame anatomopatológico revelou trombo repleto de Aspergillus (massa fúngica. No sétimo dia de pós-operatório o paciente evoluiu com insuficiência respiratória e parada cardiorrespiratória sem resposta às manobras de reanimação. CONCLUSÕES: Apesar do grande risco de sangramento no paciente descrito, conseguiu-se realizar intervenção cirúrgica cardíaca com CEC sem intercorrências graças ao uso de aprotinina e plaquetoaférese.JUSTIFICATIVA Y OBJETIVOS: La aprotinina ha sido muy utilizada en intervenciones quirúrgicas cardiacas como recurso terapéutico para la reducción de los efectos de la circulación extracorpórea (CEC sobre la coagulación y la fibrinólisis. La recuperación de la hemostasia adecuada al final del procedimiento es uno de los objetivos del anestesiólogo. Sin embargo, el uso de la aprotinina tiene una indicación específica. El objetivo de este trabajo fue presentar el caso de un paciente con plaquetopenia intensa sometido a la intervención quirúrgica cardiaca en el cual la interconsulta con hematología y la planificación adecuada permitieron el éxito del procedimiento. RELATO DEL CASO: Paciente del sexo masculino, 18 años, 64 kg, estado físico ASA IV, portador de aplasia de medula, en investigación para ser sometido al transplante de médula. Presentaba fiebre persistente, de un mes de evolución, sin mejoría con antibioticoterapia. En la investigación con métodos de imagen, se diagnosticó masa intra atrial izquierda. En el examen de laboratorio presentaba hemoglobina de 9 g.dL-1 y trombocitopenia - 6.000 plaquetas mm-3. Se sometió a la esternotomía con CEC para retirada de trombo intracavitario. Con el objetivo de controlar el sangramiento intraoperatorio fueron administrados: plaqueto-aferesis, hidrocortisona y aprotinina. Durante la intervención quirúrgica no hubo aumento del sangramiento ni inestabilidad hemodinámica y el paciente fue llevado a la Unidad de Terapia Intensiva (UTI sin intercurrencias. El examen anátomo patológico reveló trombo repleto de Aspergilus (masa fúngica. Al sétimo día del postoperatorio el paciente evolucionó con insuficiencia respiratoria y parada cardiorrespiratoria sin respuesta a las maniobras de reanimación. CONCLUSIONES: A pesar del gran riesgo de sangramiento en el paciente descrito, se logró realizar la intervención quirúrgica cardiaca con CEC sin intercurrencias gracias al uso de aprotinina y plaquetoaféresis.BACKGROUND AND OBJECTIVES: Aprotinin has been widely used in cardiac surgeries as a therapeutic resource for reducing the effects of cardiopulmonary bypass (CPB on coagulation and fibrinolysis. Recovery of adequate hemostasia at the end of the procedure is one of the objectives of the anesthesiologist. However, aprotinin has specific indications. The objective of this report was to present the case of a patient with severe thrombocytopenia undergoing cardiac surgery in which consultation with Hematology and adequate planning were responsible for the success of the procedure. CASE REPORT: An 18-year old male patient, weighing 64 kg, physical status ASA IV, with a diagnosis of bone marrow aplasia, was being investigated to undergo bone marrow transplantation. He had persistent fever for a month, which did not improve with antibiotics. During the investigation with imaging exams, a left atrial mass was discovered. Laboratory exams revealed hemoglobin 9 g.dL-1 and thrombocytopenia with 6,000 platelets.mm³. He underwent a sternotomy with CPB to remove the intracavitary thrombus. In order to control intraoperative bleeding, the following was administered: plateletpheresis, hydrocortisone, and aprotinin. Increased bleeding and hemodynamic instability did not develop during the surgery, and the patient was transferred to the Intensive Care Unit (ICU without intercurrences. The anatomo-pathologic exam revealed the thrombus to be filled with Aspergillus (fungal mass. On the seventh postoperative day the patient developed respiratory failure and cardiorespiratory arrest that did not respond to resuscitation maneuvers. CONCLUSIONS: Despite the increased risk of bleeding in this patient, cardiac surgery with CPB was performed without intercurrences due to the use of aprotinin and plateletpheresis.

  5. Aspergilosis broncopulmonar alérgica, una complicación del paciente con fibrosis quística: reporte de dos casos y revisión de la literatura = Allergic bronchopulmonary aspergillosis, a complication of patients with cystic fibrosis: Report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Ballesteros Calderón, Alicia Lucía

    2012-01-01

    Full Text Available La aspergilosis broncopulmonar alérgica (ABPA es la enfermedad pulmonar resultante de hipersensibilidad a Aspergillus, que lleva a alteración de la depuración mucociliar, impactación mucosa con obstrucción de la vía aérea e infiltración pulmonar. Se caracteriza clínicamente por disnea, sibilancias, fiebre, malestar general y expectoración de color marrón o negro, y por la mala respuesta clínica al tratamiento habitual instaurado para las exacerbaciones en pacientes con enfermedad pulmonar crónica. En los pacientes con fibrosis quística (FQ puede ser difícil establecer el diagnóstico de ABPA debido a la superposición de las características clínicas, radiológicas e inmunológicas de las dos enfermedades y a la presencia frecuente de infecciones bacterianas pulmonares. Por ello, se recomienda que en el seguimiento de dichos pacientes se haga medición anual de la inmunoglobulina E (IgE sérica total y, según su resultado y el contexto clínico, se plantee el diagnóstico de ABPA y se haga el tratamiento oportuno con esteroides con el cual mejoran los síntomas, la función pulmonar, la calidad de vida y el pronóstico. Presentamos dos pacientes pediátricos con diagnóstico de FQ de difícil control, en quienes se hizo el diagnóstico de ABPA y cuya sintomatología pulmonar mejoró con el tratamiento esteroide.

  6. Analysis of the clinical value of GM test and G test in invasive Pulmonary Aspergillosis in the Examination%GM试验和G试验在肺侵袭性曲霉菌感染检查中的临床价值分析

    Institute of Scientific and Technical Information of China (English)

    胡海宗; 谢小丽

    2014-01-01

    目的 分析GM试验和G试验在肺侵袭性曲霉菌感染检查中的临床价值.方法 选取我院收治的疑似肺曲霉菌感染患者49例,对其痰液、肺泡灌洗液以及静脉血展开培养、G试验、GM试验,分析实验结果.结果 本组49例患者经痰液与肺泡灌洗液培养均发现丝状菌生长,G试验阳性者44例,GM试验者41例.结论 G试验与GM试验的操作简单、报告迅速,在临床肺曲霉菌感染诊断中发挥了重要作用,值得关注.

  7. 血清半乳甘露聚糖检测对血液肿瘤患者侵袭性曲霉病诊断价值的评估%Cinical value of serum galactomannan detection for invasive aspergillosis patients with hematologic disease/cancer

    Institute of Scientific and Technical Information of China (English)

    姜华; 贺兆斌; 袁代; 王相华; 王欣

    2012-01-01

    目的:探讨血清半乳甘露聚糖(GM)抗原检测对于血液肿瘤患者侵袭性曲霉病(invasive aspergillo-sis,IA)的早期诊断和疗效评判的临床意义.方法:选取127例血液肿瘤并发中性粒细胞减少伴发热、广谱抗生素治疗无效的患者治疗前后的402份血清标本.采用ELISA法进行血清GM浓度测定,同时收集患者的临床资料.评价GM测定对于血液肿瘤患者IA的诊断价值和抗真菌治疗前后GM浓度变化的意义,并进行统计学分析.结果:拟将本观察组血液肿瘤患者并发IA的血清GM检测结果的单次Ⅰ≥0.7,或连续2次Ⅰ≥0.5做为阳性界值时,本试验的敏感性、特异性、阳性预测值和阴性预测值分别为92.3%、82.4%、57.1%和97.7%,与试剂盒提供的血清GM试验结果的Ⅰ≥1.5的阳性界值相比灵敏度提高,而特异性无明显降低,因此能够有效区分临床诊断和拟诊两个IA级别.在其他实验室检测和影像学结果基础上加入GM试验后,临床诊断病例组的人数明显增加.根据我们确定的阳性界值标准,GM实验阳性早于痰培养或涂片平均(6.1士4.5) d(1~11 d);也早于CT影像学证据平均(7.2±5.5) d(1~15 d).抗真菌治疗有效患者的GM水平随着治疗呈波动性下降,无效患者GM水平无变化.GM浓度与本观察组患者疾病的治疗及预后具有相关性.结论:血清GM抗原检测是早期诊断IA的一种有效方法.将单次Ⅰ≥0.7或连续2次Ⅰ≥0.5作为阳性界值比单用一种界值敏感性提高,特异性理想.在高危血液肿瘤伴粒细胞缺乏患者中以GM实验阳性为起点抢先抗曲霉菌治疗,可降低IA病死率,监测血清GM浓度的动态变化具有评判疗效的重要价值.%Objective:To assess the value of serum galactomannan(GM) detection for early diagnosis and therapeutic effect of invasive aspeigillosis (IA) in patients with hematologic disease/cancer. Method: Four Hundred and two serum samples of 127 inpatients with high IA risk were selected according to the domestic diagnosis standard of invasive fungus infection in patients with hematologic disease/cancer. The serum GM concentration was detected by platelia Aspeigillus double-sandwich enzyme linked immunosorbent assay(PADSELISA). According to the diagnostic criteria of invasive fungal infections in China, the changes of GM concentration before and after antifungal treatment and its value for diagnosis were evaluated by statistical analyse. Result: The sensitivity, specificity, positive predictive value and negative predictive value of the PADSELISA -were 92. 3% ,82. 4% ,57.1% ,and 97. 7% respectively by using the serum GM cut-off value of single index≥0. 7 and(or) 2 consecutive indexes≥0. 5. Comparing with the provided reagent serum GM cut-off index≥ 1. 5,it had an increased sensitivity without obviously decreasing specificity,which effectively distinguished the two IA levels between probable and possible patients. The probable IA cases were increased from 10 to 19 after adding the GM detection. GM test was positive (6.1±4. 5) d(l-11 d)ahead of sputum culture,and (7. 2±5. 5) d(l-15 d) ahead of CT scan. A fluctuant reduction of GM level was found in patients sensitive to antifungal treatment,and an increased or constant GM level was seen in insensitive patients. The GM false positive rate could become obviously high in control group patients with intravenous injection of piperacillin-Tazobactam. The GM level of IA patients after using echinocandin increased in early stage and showed a decreased trend during the whole course. The concentration of GM had a relation with the prognosis of the disease. Conclusion: Serum GM antigen detection is an effective method for early diagnosis of IA Comparing with other diagnostic accessory examination, such as typical CT imaging and direct microbiological test.GM test has an obvious advantage on the positive rate and time. Comparing with single value, single index≥ 0. 7 and (or) 2 consecutive index≥0. 5 can increase the sensitivity without obviously decreasing specificity. Among patients with high risk of hematologic disease/cancer,using GM test positive as a starting point to preemption of the anti-Aspergillus treatment can reduce mortality of IA patients. We can estimate the anti-fungal effect by dynamic detection of serum GM.

  8. Serological monitoring of antibodies for an early diagnosis ofaspergillosis in captive penguins

    Directory of Open Access Journals (Sweden)

    Ângela L. Cabana

    2015-06-01

    Full Text Available Abstract: This study aimed to evaluate the efficacy of detection of anti-Aspergillus fumigatus antibodies in captive penguins by double radial agar gel immunodiffusion (AGID for the aspergillosis diagnosis. We included 134 Magellanic penguins (Spheniscus magellanicus in rehabilitation at the Center for Recovery of Marine Animals (CRAM / FURG. All of them were monitored by AGID weekly until its final destination (death or release, totalizing 660 serum samples studied. All animals were clinically accompanied and post-mortem examinations was performed in penguins that died during the studied period. A total of 28% (37/134 of the penguins died, 89.2% (33/37 due to aspergillosis, 11% (4/37 by other causes and 97 were released. From the 33 animals with proven aspergillosis, 21 presented anti- A. fumigatus antibodies by AGID, being the average interval between death and positive AGID 16.4 days. Twelve animals with negative serology died of aspergillosis. The sensitivity and specificity rates were 63.6% and 95% respectively, and the positive and negative predictive values were 80.7% and 88.9% respectively. These data demonstrate that the serological monitoring for detection of antibodies by AGID can be an important tool for the diagnosis of aspergillosis in penguins.

  9. Clinical evidence for caspofungin monotherapy in the first-line and salvage therapy of invasive Aspergillus infections.

    Science.gov (United States)

    Heinz, Werner J; Buchheidt, Dieter; Ullmann, Andrew J

    2016-08-01

    In 2001, caspofungin received market authorisation by the FDA and EMA and is globally licensed for several indications, including candidiasis, empirical antifungal therapy in patients with neutropenic fever of unknown origin and treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B or itraconazole. Despite the lack of phase III data in first-line treatment of invasive aspergillosis, increasing evidence supports the use of first-line therapy. Here, we analyse the evidence of therapeutic activity, represented by favourable response rates, of caspofungin for invasive aspergillosis. A systematic literature search was conducted to identify international presentations and papers reporting monotherapy with caspofungin. Efficacy data are summarised separately for first-line and salvage therapy. Thirty-one papers and published abstracts reported caspofungin therapy for aspergillosis. Fifteen full papers and two abstracts fulfilled the criteria of reporting significant outcome data for caspofungin monotherapy for invasive aspergillosis. Consistent with other analyses and the known safety profile, few adverse events and associated terminations of caspofungin medication have been reported. Although a randomised, comparative, prospective study using caspofungin in this indication is still lacking, growing evidence supports the efficacy of this echinocandin not only for salvage but also for first-line therapy.

  10. Aspergillus-Related Lung Disease

    Directory of Open Access Journals (Sweden)

    Alia Al-Alawi

    2005-01-01

    Full Text Available Aspergillus is a ubiquitous dimorphic fungus that causes a variety of human diseases ranging in severity from trivial to life-threatening, depending on the host response. An intact host defence is important to prevent disease, but individuals with pre-existing structural lung disease, atopy, occupational exposure or impaired immunity are susceptible. Three distinctive patterns of aspergillus-related lung disease are recognized: saprophytic infestation of airways, cavities and necrotic tissue; allergic disease including extrinsic allergic alveolitis, asthma, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis and chronic eosinophilic pneumonia; and airway and tissue invasive disease -- pseudomembranous tracheobronchitis, acute bronchopneumonia, angioinvasive aspergillosis, chronic necrotizing aspergillosis and invasive pleural disease. A broad knowledge of these clinical presentations and a high index of suspicion are required to ensure timely diagnosis and treatment of the potentially lethal manifestations of aspergillus-related pulmonary disease. In the present report, the clinical, radiographic and pathological aspects of the various aspergillus-related lung diseases are briefly reviewed.

  11. Successful Treatment of Fungal Osteomyelitis with Voriconazole in a Patient with CGD

    Directory of Open Access Journals (Sweden)

    Mahsa Oaji

    2010-12-01

    Full Text Available Background:Chronic granulomatous disease (CGD is an immunodeficiency affecting phagocytic leukocytes. Defective respiratory burst mechanism renders the affected patients to be susceptible to catalase positive microorganisms. With the great successes in antibacterial prophylaxis and therapy, fungal infections are a persistent problem. Invasive aspergillosis is the most important cause of mortality in CGD. Case Presentation: We describe a nine year-old boy with CGD who presented with aspergillus induced skull osteomyelitis. He was successfully treated with voriconazole after initial failure of amphotericin B therapy. Conclusion: Currently, newer triazoles are recommended as initial therapy for invasive aspergillosis in immunodeficiency states such as CGD.

  12. Aspergillus in the lung: diverse and coincident forms

    Energy Technology Data Exchange (ETDEWEB)

    Buckingham, Susan J.; Hansell, David M. [Department of Radiology, Royal Brompton Hospital, Sydney Street, London SW3 6NP (United Kingdom)

    2003-08-01

    Pulmonary disease caused by the fungus Aspergillus has traditionally been regarded as belonging to one of the following, apparently distinct, entities: saprophytic aspergilloma; allergic bronchopulmonary aspergillosis (ABPA); and invasive aspergillosis (IPA); which may be further categorised as angioinvasive, acute or chronic airway invasive [1]. It is not always obvious that there is overlap between these entities, and that in any given patient more than one Aspergillus-related pathological process can co-exist [2]. The aim of this article is to review the clinical and imaging features of the main categories of Aspergillus-related pulmonary disease and, in particular, to highlight the overlap between them. (orig.)

  13. Cerebralt aspergillom hos patient med immundefekt og follikulært lymfom

    DEFF Research Database (Denmark)

    Lorentzen, Kristian; Talibi, Monica Nicole; Hansen, Per Boye

    2014-01-01

    We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen in the s......We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen...

  14. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

    NARCIS (Netherlands)

    L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng; A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

    2010-01-01

    textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relat

  15. Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms

    NARCIS (Netherlands)

    Henriet, S.S.V.; Hermans, P.W.M.; Verweij, P.E.; Simonetti, E.R.; Holland, S.M.; Sugui, J.A.; Kwon-Chung, K.J.; Warris, A.

    2011-01-01

    Invasive aspergillosis is a major threat for patients suffering from chronic granulomatous disease (CGD). Although Aspergillus fumigatus is the most commonly encountered Aspergillus species, the presence of A. nidulans appears to be disproportionately high in CGD patients. The purpose of this study

  16. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity.

    NARCIS (Netherlands)

    Chai, L.; Veerdonk, F.L. van de; Marijnissen, R.J.; Cheng, S.C.; Khoo, A.L.; Hectors, M.P.C.; Lagrou, K.; Vonk, A.G.; Maertens, J.; Joosten, L.A.B.; Kullberg, B.J.; Netea, M.G.

    2010-01-01

    Both interferon-gamma-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relative importance o

  17. Calcineurin-dependent galactomannan release in Aspergillus fumigatus

    NARCIS (Netherlands)

    Mennink-Kersten, M.A.S.H.; Ruegebrink, D.; Verweij, P.E.; Steinbach, W.J.

    2011-01-01

    The galactomannan assay to diagnose invasive aspergillosis is recommended and clinically utilized, yet the mechanism of galactomannan release from Aspergillus fumigatus is unknown. We used an A. fumigatus strain lacking calcineurin A (cnaA), already shown to be critically important for pathogenicity

  18. Issues with galactomannan testing.

    NARCIS (Netherlands)

    Verweij, P.E.; Mennink-Kersten, M.A.S.H.

    2006-01-01

    Within the past decade detection of the aspergillus antigen galactomannan has become an important and reliable tool for the early diagnosis of invasive aspergillosis. The galactomannan molecule, that is detected by the commercial sandwich ELISA (Platelia Aspergillus, Biorad), was found not to be a s

  19. Occurrence of triazole-resistant Aspergillus fumigatus with TR34/L98H mutations in outdoor and hospital environment in Kuwait

    NARCIS (Netherlands)

    Ahmad, S.; Khan, Z.; Hagen, F.; Meis, J.F.G.M.

    2014-01-01

    BACKGROUND: Invasive aspergillosis due to triazole-resistant Aspergillus fumigatus, a common airborne fungal pathogen, has emerged in some European and Asian countries, likely due to exposure to azole fungicides in the environment. This study determined the occurrence of triazole-resistant A. fumiga

  20. Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi.

    NARCIS (Netherlands)

    Warris, A.; Netea, M.G.; Verweij, P.E.; Gaustad, P.; Kullberg, B.J.; Weemaes, C.M.R.; Abrahamsen, T.G.

    2005-01-01

    There is substantial evidence that the production of proinflammatory cytokines is important in host resistance to invasive aspergillosis. Knowledge of the host response towards other filamentous fungi is scarce, as most studies have focused on Aspergillus fumigatus. In addition, interferon-gamma (IF

  1. A case of pseudomembranous colitis after voriconazole therapy.

    Science.gov (United States)

    Kwon, Jae-Cheol; Kang, Min-Kyu; Kim, Si-Hyun; Choi, Su-Mi; Kim, Hee-Je; Min, Woo-Sung; Lee, Dong-Gun

    2011-09-01

    This is a case report on a 35-year-old man with acute myelogenous leukemia who presented fever and intermittent mucoid loose stool to the emergency center. He had been taking voriconazole for invasive pulmonary aspergillosis. The flexible sigmoidoscopy was consistent with the diagnosis of pseudomembranous colitis.

  2. Aspergillus PCR: one step closer to standardization.

    NARCIS (Netherlands)

    White, P.L.; Bretagne, S.; Klingspor, L.; Melchers, W.J.G.; McCulloch, E.; Schulz, B.; Finnstrom, N.; Mengoli, C.; Barnes, R.A.; Donnelly, J.P.; Loeffler, J.

    2010-01-01

    PCR has been used as an aid in the diagnosis of invasive aspergillosis for almost 2 decades. A lack of standardization has limited both its acceptance as a diagnostic tool and multicenter clinical evaluations, preventing its inclusion in disease-defining criteria. In 2006, the European Aspergillus P

  3. Aspergillus and aspergilloses in wild and domestic animals : a global health concern with parallels to human disease

    NARCIS (Netherlands)

    Seyedmousavi, Seyedmojtaba; Guillot, Jacques; Arné, Pascal; de Hoog, G Sybren; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E

    2015-01-01

    The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fata

  4. A Case of Chronic Granulomatous Disease with a Necrotic Mass in the Bronchus: A Case Report and a Review of Literature

    Directory of Open Access Journals (Sweden)

    Ali Cheraghvandi

    2012-01-01

    Full Text Available Chronic granulomatous disease is a rare phagocytic disorder with recurrent, severe bacterial and fungal infections. We describe an unusual case of chronic granulomatous disease manifesting as an invasive pulmonary aspergillosis with an obstructive necrotic mass at the right middle bronchus. The patient was successfully treated with a bronchoscopic intervention for the removal of the obstructive mass and a medical therapy.

  5. Invasive fungal disease in PICU: epidemiology and risk factors.

    Science.gov (United States)

    Brissaud, Olivier; Guichoux, Julie; Harambat, Jerome; Tandonnet, Olivier; Zaoutis, Theoklis

    2012-02-22

    Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%).

  6. Infectious complications in hematology patients: A clinical focus on prevention

    NARCIS (Netherlands)

    L. Slobbe (Lennert)

    2010-01-01

    textabstractThe aim of this thesis was to contribute to infection preventive strategies in hematology patients with prolonged neutropenia. Invasive pulmonary aspergillosis (IPA) develops by pulmonary deposition of conidia. A placebo-controlled trial on the efficacy of prophylactic aerosolized lipos

  7. Aspergillus Tracheobronchitis Causing Subtotal Tracheal Stenosis in a Liver Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Sonia Radunz

    2013-01-01

    Full Text Available Invasive aspergillosis is recognized as one of the most significant opportunistic infections after liver transplantation. Diagnosis of invasive aspergillosis in transplant recipients has been proven to be challenging, and optimal approach to the treatment of invasive aspergillosis is still controversial. We here present an unusual case of Aspergillus tracheobronchitis in the setting of liver transplantation. A 47-year-old female patient with persistent dry cough after liver transplantation developed respiratory insufficiency and was readmitted to the intensive care unit 55 days after liver transplantation. A CT scan revealed subtotal tracheal stenosis; bronchoscopy was performed, and extended white mucus coverings causative of the tracheal stenosis were removed. Microbiological assessment isolated Aspergillus fumigatus. The diagnosis was obstructive Aspergillus tracheobronchitis. The patient was started on a treatment of voriconazole 200 mg orally twice daily, adjusted to a trough level of 1–4 mg/L. For further airway management, a tracheal stent had to be implanted. The patient is alive and well 28 months after liver transplantation. Invasive aspergillosis should be considered a possible etiology in liver transplant patients presenting with unspecific symptoms such as persistent dry cough. Optimal strategies for improved and early diagnosis as well as prophylaxis need to be defined.

  8. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease

    NARCIS (Netherlands)

    Henriet, S.S.V.; Jans, J.; Simonetti, E.R.; Kwon-Chung, K.J.; Rijs, A.J.M.M.; Hermans, P.W.M.; Holland, S.M.; Jonge, M.I. de; Warris, A.

    2013-01-01

    Invasive aspergillosis is a major threat to patients with chronic granulomatous disease (CGD). Fungal pathogenesis is the result of a diminished antifungal capacity and dysregulated inflammation. A deficient NADPH-oxidase complex results in defective phagolysosomal alkalization. To investigate the c

  9. Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

    DEFF Research Database (Denmark)

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R.;

    2016-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and teste...

  10. Fatal coinfection with Legionella pneumophila serogroup 8 and Aspergillus fumigatus.

    Science.gov (United States)

    Guillouzouic, Aurélie; Bemer, Pascale; Gay-Andrieu, Françoise; Bretonnière, Cédric; Lepelletier, Didier; Mahé, Pierre-Joachim; Villers, Daniel; Jarraud, Sophie; Reynaud, Alain; Corvec, Stéphane

    2008-02-01

    Legionella pneumophila is an important cause of community-acquired and nosocomial pneumonia. We report on a patient who simultaneously developed L. pneumophila serogroup 8 pneumonia and Aspergillus fumigatus lung abscesses. Despite appropriate treatments, Aspergillus disease progressed with metastasis. Coinfections caused by L. pneumophila and A. fumigatus remain exceptional. In apparently immunocompetent patients, corticosteroid therapy is a key risk factor for aspergillosis.

  11. Azole resistance in Aspergillus fumigatus: a side-eff ect of environmental fungicide use?

    NARCIS (Netherlands)

    Verweij, P.A.; Snelders, E.; Kema, G.H.J.; Mellado, E.; Melchers, W.J.G.

    2009-01-01

    Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6·0–12·8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A an

  12. Chronic granulomatous disease associated with chronic glomerulonephritis

    DEFF Research Database (Denmark)

    Frifelt, J J; Schønheyder, Henrik Carl; Valerius, Niels Henrik

    1985-01-01

    A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia...... from which he eventually died. The glomerulonephritis was of unknown origin, and a possible relationship between CGD and glomerulonephritis is discussed....

  13. Variation in copy number of the 28S rDNA of Aspergillus fumigatus measured by droplet digital PCR and analog quantitative real-time PCR.

    Science.gov (United States)

    Alanio, Alexandre; Sturny-Leclère, Aude; Benabou, Marion; Guigue, Nicolas; Bretagne, Stéphane

    2016-08-01

    Droplet digital PCR (ddPCR) after DNA digestion yielded a 28S rDNA copy number of 61 to 86 copies/genome when testing 10 unrelated Aspergillus fumigatus isolates, higher than with quantitative PCR. Unfortunately, ddPCR after DNA digestion did not improve the sensitivity of our PCR assay when testing serum patients with invasive aspergillosis.

  14. Increasing fungal infections in the intensive care unit

    NARCIS (Netherlands)

    Pauw, B.E. de

    2006-01-01

    BACKGROUND: Yeasts and molds now rank among the most common pathogens in intensive care units. Whereas the incidence of Candida infections peaked in the late 1970s, aspergillosis is still increasing. METHOD: Review of the pertinent English-language literature. RESULTS: Most factors promoting an inva

  15. How Building Systems Affect Worker Wellness

    Science.gov (United States)

    1994-03-01

    humidity fever ( allergic alveolitis ), and aspergillosis. A number of allergens can be found in indoor air. Pollen found indoors is primarily produced...These mites can flourish in climates where the winters are humid and mild. Health Effects. Airborne microorganisms and allergens can cause allergic

  16. Aflatoxin and Ochratoxin Production by Aspergillus Species Under Ex Vivo Conditions

    Science.gov (United States)

    Aspergillus species are increasingly important human pathogens. It is not known whether toxic metabolites of many of these pathogenic species can act as virulence factors in aspergillosis. We examined isolates of aflatoxin and ochratoxin-producing species for toxin production in ‘near human’ condit...

  17. Utility of Aspergillus antigen detection in specimens other than serum specimens.

    NARCIS (Netherlands)

    Klont, R.R.; Mennink-Kersten, M.A.S.H.; Verweij, P.E.

    2004-01-01

    The detection of circulating galactomannan in serum is an important tool for the early diagnosis of invasive aspergillosis. A commercial enzyme-linked immunosorbent assay (Platelia Aspergillus; BioRad) was shown to be both highly sensitive and specific for detection of galactomannan in serum samples

  18. Hide, Keep Quiet, and Keep Low : Properties That Make Aspergillus fumigatus a Successful Lung Pathogen

    NARCIS (Netherlands)

    Escobar, Natalia; Ordonez Alvarez, Soledad; Wosten, Han; Haas, Pieter-Jan A; de Cock, Hans; Haagsman, Henk P

    2016-01-01

    Representatives of the genus Aspergillus are opportunistic fungal pathogens. Their conidia can reach the alveoli by inhalation and can give rise to infections in immunocompromised individuals. Aspergillus fumigatus is the causal agent of invasive aspergillosis in nearly 90% of the cases. It is not y

  19. Disease: H01328 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01328 Aspergillosis Infectious disease Aspergillus fumigatus [GN:afm] Aspergillus flavus [GN:afv] Asperg...illus nidulans [GN:ani] Aspergillus niger [GN:ang] ICD-10: B44 MeSH: D001228 MedlinePlus: 001326 ...

  20. In vitro activity of isavuconazole against 208 Aspergillus flavus isolates in comparison with 7 other antifungal agents: assessment according to the methodology of the European Committee on Antimicrobial Susceptibility Testing

    NARCIS (Netherlands)

    Rudramurthy, S.M.; Chakrabarti, A.; Geertsen, E.; Mouton, J.W.; Meis, J.F.G.M.

    2011-01-01

    Aspergillus flavus is the second most common species causing invasive aspergillosis after A. fumigatus. In certain countries like India, Sudan, and Saudi Arabia, A. flavus is most frequently isolated from patients with fungal rhinosinusitis and endophthalmitis. A. flavus exhibit an increased resista

  1. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    Elst, K.C. van der; Bruggemann, R.J.M.; Rodgers, M.G.; Alffenaar, J.W.C.

    2012-01-01

    The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

  2. Chitinases in Invasive Fungal Infections : Novel diagnostic and therapeutic approaches

    NARCIS (Netherlands)

    P.E.B. Verwer (Patricia)

    2016-01-01

    markdownabstractImmunocompromised people (due to e.g. illness or chemotherapy) are at risk for a pulmonary fungal infection: invasive aspergillosis. Treatment of this infection is challenging. Caspofungin is an agent with antifungal action in high concentrations in vitro, but when given to patients

  3. Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model

    NARCIS (Netherlands)

    Siopi, M.; Mavridou, E.; Mouton, J.W.; Verweij, P.E.; Zerva, L.; Meletiadis, J.

    2014-01-01

    BACKGROUND: Although voriconazole reached the bedside 10 years ago and became the standard care in the treatment of invasive aspergillosis, reliable clinical breakpoints are still in high demand. Moreover, this has increased due to the recent emergence of azole resistance. METHODS: Four clinical wil

  4. In vitro antifungal activity of isavuconazole against 345 mucorales isolates collected at study centers in eight countries.

    NARCIS (Netherlands)

    Verweij, P.E.; Gonzalez, G.M.; Wiedrhold, N.P.; Lass-Florl, C.; Warn, P.; Heep, M.; Ghannoum, M.A.; Guinea, J.

    2009-01-01

    Although mucormycoses (formerly zygomycoses) are relatively uncommon, they are associated with high mortality and treatment options are limited. Isavuconazole is a novel, water soluble, broad-spectrum azole in clinical development for the treatment of invasive aspergillosis and candidiasis. The obje

  5. Extrapulmonary Aspergillus infection in patients with CARD9 deficiency

    Science.gov (United States)

    Gazendam, Roel P.; Freeman, Alexandra F.; Hsu, Amy P.; Collar, Amanda L.; Sugui, Janyce A.; Drummond, Rebecca A.; Rongkavilit, Chokechai; Hoffman, Kevin; Henderson, Carolyn; Clark, Lily; Mezger, Markus; Swamydas, Muthulekha; Engeholm, Maik; Schüle, Rebecca; Neumayer, Bettina; Mikelis, Constantinos M.; Pittaluga, Stefania; Prasad, Vinod K.; Singh, Anurag; Milner, Joshua D.; Williams, Kelli W.; Lim, Jean K.; Kwon-Chung, Kyung J.; Holland, Steven M.; Hartl, Dominik; Kuijpers, Taco W.

    2016-01-01

    Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25. Neither patient developed Aspergillus infection of the lungs. One patient had homozygous M1I CARD9 (caspase recruitment domain family member 9) mutation, while the other had homozygous Q295X CARD9 mutation; both patients lacked CARD9 protein expression. The patients had normal monocyte and Th17 cell numbers in peripheral blood, but their mononuclear cells exhibited impaired production of proinflammatory cytokines upon fungus-specific stimulation. Neutrophil phagocytosis, killing, and oxidative burst against Aspergillus fumigatus were intact, but neither patient accumulated neutrophils in infected tissue despite normal neutrophil numbers in peripheral blood. The neutrophil tissue accumulation defect was not caused by defective neutrophil-intrinsic chemotaxis, indicating that production of neutrophil chemoattractants in extrapulmonary tissue is impaired in CARD9 deficiency. Taken together, our results show that CARD9 deficiency is the first known inherited or acquired condition that predisposes to extrapulmonary Aspergillus infection with sparing of the lungs, associated with impaired neutrophil recruitment to the site of infection. PMID:27777981

  6. A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist.

    Directory of Open Access Journals (Sweden)

    Mark S Gresnigt

    2014-03-01

    Full Text Available The galactosaminogalactan (GAG is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra, a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases.

  7. Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent.

    Science.gov (United States)

    Miceli, Marisa H; Kauffman, Carol A

    2015-11-15

    Isavuconazole is a new extended-spectrum triazole with activity against yeasts, molds, and dimorphic fungi. It is approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. A randomized, double-blind comparison clinical trial for treatment of invasive aspergillosis found that the efficacy of isavuconazole was noninferior to that of voriconazole. An open-label trial that studied primary as well as salvage therapy of invasive mucormycosis showed efficacy with isavuconazole that was similar to that reported for amphotericin B and posaconazole. In patients in these studies, as well as in normal volunteers, isavuconazole was well tolerated, appeared to have few serious adverse effects, and had fewer drug-drug interactions than those noted with voriconazole. As clinical experience increases, the role of this new triazole in the treatment of invasive fungal infections will be better defined.

  8. [symbol: see text]Caspofungin and [symbol: see text]voriconazole for fungal infections.

    Science.gov (United States)

    2004-01-01

    Systemic fungal infections are difficult to treat and often fatal. Established treatment options include conventional amphotericin B or one of its lipid-based or liposomal formulations, or a triazole antifungal such as fluconazole or itraconazole. [symbol: see text]Caspofungin (Cancidas--Merck Sharp & Dohme) and [symbol: see text]voriconazole (Vfend--Pfizer) are two new antifungals for severe infections caused by Candida spp. (invasive candidiasis) and Aspergillus spp. (invasive aspergillosis). Caspofungin is the first licensed echinocandin antifungal, while voriconazole is a triazole. Promotional claims for caspofungin include that it "provides an effective, yet less toxic, alternative to amphotericin B" while voriconazole is claimed to offer "significantly improved survival in invasive aspergillosis compared with amphotericin B". Here we consider the place of caspofungin and voriconazole in managing patients with severe fungal infections.

  9. Delivering on Antimicrobial Resistance Agenda Not Possible without Improving Fungal Diagnostic Capabilities

    Science.gov (United States)

    Perlin, David S.; Muldoon, Eavan G.; Colombo, Arnaldo Lopes; Chakrabarti, Arunaloke; Richardson, Malcolm D.; Sorrell, Tania C.

    2017-01-01

    Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance. PMID:27997332

  10. Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system.

    Directory of Open Access Journals (Sweden)

    Fabrice N Gravelat

    Full Text Available Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.

  11. Fungal infections of the central nervous system: The clinical syndromes

    Directory of Open Access Journals (Sweden)

    Murthy J.M.K

    2007-01-01

    Full Text Available Fungal infections of the central nervous system (CNS are being increasingly diagnosed both in immunocompromised and immunocompetent individuals. Sinocranial aspergillosis is more frequently described from countries with temperate climates, more often in otherwise immunocompetent individuals. The clinical syndromes with which fungal infections of the CNS can present are protean and can involve most part of the neuroaxis. Certain clinical syndromes are specific for certain fungal infections. The rhinocerebral form is the most common presenting syndrome with zygomycosis and skull-base syndromes are often the presenting clinical syndromes in patients with sinocranial aspergillosis. Subacute and chronic meningitis in patients with HIV infection is more likely to be due to cryptococcal infection. Early recognition of the clinical syndromes in an appropriate clinical setting is the first step towards achieving total cure in some of these infections.

  12. P67-phox (NCF2 lacking exons 11 and 12 is functionally active and leads to an extremely late diagnosis of chronic granulomatous disease (CGD.

    Directory of Open Access Journals (Sweden)

    Joachim Roesler

    Full Text Available Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox gene, c.1000 + 2T → G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.

  13. Aspergillus and aspergilloses in wild and domestic animals: a global health concern with parallels to human disease.

    Science.gov (United States)

    Seyedmousavi, Seyedmojtaba; Guillot, Jacques; Arné, Pascal; de Hoog, G Sybren; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E

    2015-11-01

    The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals.

  14. [Clinically documented fungal infections].

    Science.gov (United States)

    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.

  15. Transcriptional activation of heat shock protein 90 mediated via a proximal promoter region as trigger of caspofungin resistance in Aspergillus fumigatus.

    Science.gov (United States)

    Lamoth, Frédéric; Juvvadi, Praveen R; Gehrke, Christopher; Asfaw, Yohannes G; Steinbach, William J

    2014-02-01

    Invasive aspergillosis is a deadly infection for which new antifungal therapies are needed. Heat shock protein 90 (Hsp90) is an essential chaperone in Aspergillus fumigatus representing an attractive antifungal target. Using a thiamine-repressible promoter (pthiA), we showed that genetic repression of Hsp90 significantly reduced virulence in a murine model of invasive aspergillosis. Moreover, substituting the A. fumigatus hsp90 promoter with 2 artificial promoters (potef, pthiA) and the Candida albicans hsp90 promoter resulted in hypersensitivity to caspofungin and abolition of the paradoxical effect (resistance at high caspofungin concentrations). By inducing truncations in the hsp90 promoter, we identified a 100-base pair proximal sequence that triggers a significant increase of hsp90 expression (≥1.5-fold) and is essential for the paradoxical effect. Preventing this increase of hsp90 expression was sufficient to abolish the paradoxical effect and therefore optimize the antifungal activity of caspofungin.

  16. Pathogens spectrum of deep human mycosis

    Directory of Open Access Journals (Sweden)

    A. B. Kulko

    2012-01-01

    Full Text Available The article describes characteristics of two different etiology groups of deep human mycosis — extremely dangerous endemic deep mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, penicilliosis due to Penicillium marneffei and opportunistic deep mycosis (candidiasis, cryptococcosis, aspergillosis, mucormycosis. Information on fungal pathogens and antifungal agents is presented. The own results of cultural studies obtained during pneumomycosis diagnosis in patients with tuberculosis are shown.

  17. Aspergillus spinal epidural abscess

    Energy Technology Data Exchange (ETDEWEB)

    Byrd, B.F. III (Vanderbilt Univ. School of Medicine, Nashville, TN); Weiner, M.H.; McGee, Z.A.

    1982-12-17

    A spinal epidural abscess developed in a renal transplant recipient; results of a serum radioimmunoassay for Aspergillus antigen were positive. Laminectomy disclosed an abscess of the L4-5 interspace and L-5 vertebral body that contained hyphal forms and from which Aspergillus species was cultured. Serum Aspergillus antigen radioimmunoassay may be a valuable, specific early diagnostic test when systemic aspergillosis is a consideration in an immunosuppressed host.

  18. La aspergilosis pulmonar invasiva en la enfermedad pulmonar obstructiva crónica

    OpenAIRE

    VALLE,JOSÉ MANUEL; González-Barcala, Francisco Javier; ÁLVAREZ-DOBAÑO,JOSÉ MANUEL; VALDÉS C,LUIS

    2010-01-01

    Invasive pulmonary aspergillosis (IPA) is a severe disease, specially among immunocompromised patients. Its frequency increases in other patients such as those with Chronic Obstructive Pulmonary Disease (COPD), mainly when steroids are prescribed. The most common form of presentation is a respiratory tract infection with poor response to antimicrobial treatment. The delay in its diagnosis is one of the main causes of its high lethality. Once suspected, respiratory secretion cultures, chest X ...

  19. Posaconazole: SCH 56592.

    Science.gov (United States)

    2003-01-01

    Posaconazole [SCH 56592, SPRIAFIL, Noxafil] is an orally active triazole derivative that is in phase III trials with the Schering-Plough Research Institute (SPRI) in the US for the treatment of serious opportunistic fungal infections, including aspergillosis, candidiasis, coccidioidomycosis and fusariosis. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. Preclinical studies have also been conducted in Italy for the potential treatment of Cryptococcus neoformans infection (cryptococcosis).

  20. In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

    OpenAIRE

    Bugli, Francesca; Posteraro, Brunella; Papi, Massimiliano; Torelli, Riccardo; Maiorana, Alessandro; Paroni Sterbini, Francesco; Posteraro, Patrizia; Sanguinetti, Maurizio; De Spirito, Marco

    2013-01-01

    Aspergillus fumigatus biofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treat Aspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poor...

  1. Death of a SARS case from secondary aspergillus infection

    Institute of Scientific and Technical Information of China (English)

    王慧君; 丁彦青; 徐军; 李欣; 李学锋; 杨磊; 张文丽; 耿健; 申洪; 蔡俊杰; 康伟; 吴正容; 赵菲; 钟南山

    2004-01-01

    @@ Severe acute respiratory syndrome (SARS) is an acute infectious disease which has been found to spread mainly via respiration. The first case was idnetified in Guangdong, southem China in November 2002. This disease has resulted in a severe epidemic outbreak in 27 countries and regions. In order to investigate the etiology and clinicopathologic characteristics of SARS, we reported here a patient with SARS who died of aspergillosis after prolonged treatment with corticosteroids.

  2. Pulmonary fungal infections after bone marrow transplantation: the value of high-resolution computed tomography in predicting their etiology

    Institute of Scientific and Technical Information of China (English)

    LI Xiang-sheng; ZHU Hong-xian; FAN Hong-xia; ZHU Ling; WANG Heng-xiang; SONG Yun-long

    2011-01-01

    Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy.This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT.Methods Eighty-five cases were enrolled.According to the pathogens responsible for fungal infections,the patients were classified into three groups including invasive aspergillosis (n=52),candidiasis (n=19) and cryptococcosis (n=14)groups.All the patients underwent HRCT scans.Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality.Results Most fungal infections in the three groups occurred in the neutropenic phase.There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups.Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k>0.75).There was a significant difference in occurrence ratio of mass among the three groups (P=0.02).Occurrence ratio of mass (43.3%,13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%,2/10;14.3%,1/7).There was no significant difference in other CT characteristics of nodules or masses; including number,margin,halo sign,cavitation and air-crescent sign.There was no significant difference in number,margin,air bronchogram and distribution of air-space consolidation.Conclusions The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific.Mass is more common in invasive aspergillosis,which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.

  3. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  4. Aspergillus deflectus infection in four dogs.

    Science.gov (United States)

    Jang, S S; Dorr, T E; Biberstein, E L; Wong, A

    1986-04-01

    Four cases of disseminated aspergillosis caused by Aspergillus deflectus in German Shepherds are presented. Three of the cases, which involved multiple organs, terminated in euthanasia. One case, with bony involvement of the limbs and skull, lived. The unique morphological characteristic of the conidial head resembling a briar pipe led to the identification of A. deflectus. To the authors' knowledge these are the first reported cases of infections caused by A. deflectus in man or animal.

  5. Pulmonary infections by the fungus aspergillus

    Directory of Open Access Journals (Sweden)

    Rao P

    1979-01-01

    Full Text Available Five cases of respiratory infection by Aspergillus fumigates are described. Species of aspergillus is ubiquitous in nature. Therefore, repeated demonstration of fungus, serological evidence tend radiological findings are essential for diagnosis. Potassium iodide is a useful drug in aspergillus infection of the lung when other drugs are not available. Injection Emetine hydrochloride is promising as a therapeutic agent in pulmonary aspergillosis, where the lung parenchyma is involved.

  6. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience.

    Science.gov (United States)

    Adler-Moore, Jill; Proffitt, Richard T

    2002-02-01

    Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1-30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5-24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.

  7. Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia

    Directory of Open Access Journals (Sweden)

    Anuradha eChowdhary

    2015-05-01

    Full Text Available Aspergillus fumigatus causes varied clinical syndromes ranging from colonization to deep infections. The mainstay of therapy of Aspergillus diseases is triazoles but several studies globally highlighted variable prevalence of triazole resistance, which hampers the management of aspergillosis. We studied the prevalence of resistance in clinical A. fumigatus isolates during 4 years in a referral Chest Hospital in Delhi, India and reviewed the scenario in Asia and the Middle East. Aspergillus species (n=2117 were screened with selective plates for azole resistance. The isolates included 45.4% A. flavus, followed by 32.4% A. fumigatus, 15.6% Aspergillus species and 6.6% A. terreus. Azole resistance was found in only 12 (1.7% A. fumigatus isolates.These triazole resistant A. fumigatus (TRAF isolates were subjected to (a calmodulin and β tubulin gene sequencing (b in vitro antifungal susceptibility testing against triazoles using CLSI M38-A2 (c sequencing of cyp51A gene and real-time PCR assay for detection of mutations and (d microsatellite typing of the resistant isolates. TRAF harbored TR34/L98H mutation in 10 (83.3% isolates with a pan-azole resistant phenotype. Among the remaining 2 TRAF isolates, one had G54E and the other had three non-synonymous point mutations. The majority of patients were diagnosed as invasive aspergillosis followed by allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. The Indian TR34/L98H isolates had a unique genotype and were distinct from the Chinese, Middle East and European TR34/L98H strains. This resistance mechanism has been linked to the use of fungicide azoles in agricultural practices in Europe as it has been mainly reported from azole naïve patients. Reports published from Asia demonstrate the same environmental resistance mechanism in A. fumigatus isolates from two highly populated countries in Asia i.e., China and India and also from the neighboring Middle East.

  8. Bronchial asthma with ABPA presenting as PTE

    Directory of Open Access Journals (Sweden)

    Chandrika Azad

    2013-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA, as a complication of asthma, is rare in children. The persistent and poorly-controlled asthma leading to cor pulmonale is not uncommon in adults but rarely described in the pediatric age group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo-embolism and cor pulmonale. To the best of our knowledge, such association has never been reported in the pediatric age group.

  9. Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Cross-Reactivity Caused by Invasive Geotrichum capitatum

    Science.gov (United States)

    Giacchino, Mareva; Chiapello, Nadia; Bezzio, Stefania; Fagioli, Franca; Saracco, Paola; Alfarano, Alda; Martini, Vincenza; Cimino, Giuseppe; Martino, Pietro; Girmenia, Corrado

    2006-01-01

    We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan. PMID:16954294

  10. Septic arthritis of the temporomandibular joint caused by Aspergillus flavus infection as a complication of otitis externa.

    Science.gov (United States)

    Varghese, Lalee; Chacko, Rabin; Varghese, George M; Job, Anand

    2015-03-01

    Septic arthritis of the temporomandibular joint (TMJ) is a very rare complication of otitis externa that can lead to ankylosis and destruction of the joint. We report the case of a 74-year-old man who developed aspergillosis of the TMJ following otitis externa. To the best of our knowledge, this is the first reported case of TMJ septic arthritis secondary to otitis externa caused by Aspergillus flavus. The patient was successfully managed with condylectomy, debridement, and drug treatment with voriconazole.

  11. Microsatellite typing of Aspergillus flavus from clinical and environmental avian isolates.

    Science.gov (United States)

    Hadrich, Inès; Drira, Inès; Neji, Sourour; Mahfoud, Nedia; Ranque, Stéphane; Makni, Fattouma; Ayadi, Ali

    2013-01-01

    Aspergillosis is one of the most common causes of death in captive birds. Aspergillus fumigatus accounts for approximately 95 % of aspergillosis cases and Aspergillus flavus is the second most frequent organism associated with avian infections. In the present study, the fungi were grown from avian clinical samples (post-mortem lung material) and environmental samples (eggs, food and litter). Microsatellite markers were used to type seven clinical avian isolates and 22 environmental isolates of A. flavus. A. flavus was the only species (28 % prevalence) detected in the avian clinical isolates, whereas this species ranked third (19 %) after members of the genera Penicillium (39 %) and Cladosporium (21 %) in the environmental samples. Upon microsatellite analysis, five to eight distinct alleles were detected for each marker. The marker with the highest discriminatory power had eight alleles and a 0.852 D value. The combination of all six markers yielded a 0.991 D value with 25 distinct genotypes. One clinical avian isolate (lung biopsy) and one environmental isolate (egg) shared the same genotype. Microsatellite typing of A. flavus grown from avian and environmental samples displayed an excellent discriminatory power and 100 % reproducibility. This study showed a clustering of clinical and environmental isolates, which were clearly separated. Based upon these results, aspergillosis in birds may be induced by a great diversity of isolates.

  12. Development and characterization of spray dried microparticles for pulmonary delivery of antifungal drug.

    Science.gov (United States)

    Mathpal, Divita; Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    Invasive pulmonary aspergillosis is a life threatening fungal infection mainly caused by Aspergillus species. Available treatment strategy against pulmonary aspergillosis is having very limited applicability, due to its toxicity and low circulation half-life. Pulmonary drug delivery is one of the strategies that can minimize these pitfalls. In the present study, polymeric and lipidic nanoparticles of amphotericin B were prepared by spray drying technique using hydroxypropylmethylcellulose (HPMC) and stearylamine with oleic acid respectively. Formulations were characterized for particle size, zeta potential, entrapment efficiency, in-vitro release studies, uptake analysis and in-vivo bio distribution studies. Developed polymeric and nanostructured lipid carriers (NLCs) were found in submicron size (600-700nm) and spherical in shape. Studies suggested that NLCs have better entrapment efficiency (77.1±5.5 %) as compared to HPMC carrier (71.28±5.22 %). Both formulations provided sustained drug release (HPMC, 82.05% releases up to 32 hrs and NLC, 88.2 % up to 40 hrs) and reduced dose dumping that may be helpful to reduce the toxicity and improve patient compliance. In-vitro antifungal studies suggested that stearylamine formulations exhibited better antifungal activity over control and HPMC formulations. Pharmacokinetic and organ distribution studies also support our hypothesis i.e. localized drug delivery for prolong period, improving the therapeutic effectiveness of the encapsulated drug against pulmonary aspergillosis. Studies suggested that drug delivery by pulmonary route is beneficial for local action in lungs.

  13. Burden of fungal infections in Senegal.

    Science.gov (United States)

    Badiane, Aida S; Ndiaye, Daouda; Denning, David W

    2015-10-01

    Senegal has a high rate of tuberculosis and a low HIV seropositivity rate and aspergilloma, life-threatening fungal infections, dermatophytosis and mycetoma have been reported in this study. All published epidemiology papers reporting fungal infection rates from Senegal were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in each to estimate national incidence or prevalence. The results show that tinea capitis is common being found in 25% of children, ~1.5 million. About 191,000 Senegalese women get recurrent vaginal thrush, ≥4 times annually. We estimate 685 incident cases of chronic pulmonary aspergillosis (CPA) following TB and prevalence of 2160 cases. Asthma prevalence in adults varies from 3.2% to 8.2% (mean 5%); 9976 adults have allergic bronchopulmonary aspergillosis (ABPA) and 13,168 have severe asthma with fungal sensitisation (SAFS). Of the 59,000 estimated HIV-positive patients, 366 develop cryptococcal meningitis; 1149 develop Pneumocystis pneumonia and 1946 develop oesophageal candidiasis, in which oral candidiasis (53%) and dermatophytosis (16%) are common. Since 2008-2010, 113 cases of mycetoma were diagnosed. In conclusion, we estimate that 1,743,507 (12.5%) people in Senegal suffer from a fungal infection, excluding oral candidiasis, fungal keratitis, invasive candidiasis or aspergillosis. Diagnostic and treatment deficiencies should be rectified to allow epidemiological studies.

  14. Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

    Science.gov (United States)

    Wlaź, Piotr; Knaga, Sebastian; Kasperek, Kornel; Wlaź, Aleksandra; Poleszak, Ewa; Jeżewska-Witkowska, Grażyna; Winiarczyk, Stanisław; Wyska, Elżbieta; Heinekamp, Thorsten; Rundfeldt, Chris

    2015-08-01

    Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

  15. Aspergillus citrinoterreus, a new species of section Terrei isolated from samples of patients with nonhematological predisposing conditions.

    Science.gov (United States)

    Guinea, Jesús; Sandoval-Denis, Marcelo; Escribano, Pilar; Peláez, Teresa; Guarro, Josep; Bouza, Emilio

    2015-02-01

    The use of molecular identification techniques has revealed an increasing number of new species within Aspergillus section Terrei. We phenotyped a set of 26 clinical isolates that showed genetic differences from Aspergillus terreus sensu stricto by analyzing sequences from PCR-amplified β-tubulin and calmodulin genes and the internal transcribed spacer region. Since the isolates were phylogenetically and morphologically different from all of the members of Aspergillus section Terrei, they are described here as a new species, Aspergillus citrinoterreus, so named because it produces a diffusible yellowish pigment in agar. A. citrinoterreus isolates were significantly more susceptible to itraconazole, voriconazole, and posaconazole than A. terreus sensu stricto isolates were; in contrast, the amphotericin B MICs for both species were high. A. citrinoterreus was found in clinical samples from patients with proven or probable invasive aspergillosis and colonized patients, none of whom had hematological malignancies as predisposing conditions. However, they did have other underlying conditions such as chronic obstructive pulmonary disease, cirrhosis, and cancer or had received a solid organ transplants and presented not only with invasive pulmonary aspergillosis but also with mediastinitis. A. citrinoterreus isolates were detected for the first time in 2002. In all cases of invasive aspergillosis, A. citrinoterreus was found to be a copathogen, mostly with A. fumigatus.

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

    Science.gov (United States)

    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.

  17. Burden of serious fungal infections in Belgium.

    Science.gov (United States)

    Lagrou, Katrien; Maertens, Johan; Van Even, Ellen; Denning, David W

    2015-10-01

    We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis.

  18. Clinical efficacy and tolerability of caspofungin in a renal transplant patient with Aspergillus flavus lung infection: case report.

    Science.gov (United States)

    Pasticci, M B; Barchiesi, F; Fallani, S; Palladino, N; Lapalorcia, L M; Gubbiotti, M; Cozzari, M; Novelli, A; Baldelli, F

    2006-10-01

    Organ transplant recipients are at increased risk for severe invasive aspergillosis, and amphotericin deoxycholate has been the standard treatment for many years. Currently, however, lipid formulations are preferred due to their few side effects. Also, a number of new antifungal drugs have been developed including new azoles and echinocandins. Caspofungin is the first of the echinocandin derivatives patented to treat patients with invasive aspergillosis who are refractory or intolerant to other therapies. A renal transplant patient on immunosuppressive treatment with chronic hepatitis B virus infection was admitted with fever, hemophthisis and lung consolidation, diagnosed to be probably caused by Aspergillus flavus. The patient developed cholestatic hepatitis most likely related to itraconazole. Clinical failure and in vitro itraconazole resistance of the isolate was also documented while the patient was receiving itraconazole at a reduced dosage. Caspofungin was administered once a day as ambulatory treatment and was well tolerated. Clinical improvement was observed after 6 weeks of treatment and no hepatic toxicity was documented. Caspofungin seems to be a potentially useful antifungal agent in renal transplant patients with invasive aspergillosis. Further evaluation of the efficacy of caspofungin is needed.

  19. Immune Function Changes in Patients with Invasive Pulmonary Fungal Infections by Chronic Obstructive Pulmonary Disease%慢性阻塞性肺病合并肺部真菌感染免疫功能的变化

    Institute of Scientific and Technical Information of China (English)

    杨青茹; 武焱旻; 张敬浩

    2013-01-01

    目的:探讨慢性阻塞性肺病(慢阻肺)合并肺部真菌感染患者免疫功能的变化及其意义。方法对2010年1月至2012年12月在徐州市中心医院呼吸科(含呼吸ICU)住院患者中慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)合并肺部念珠菌感染患者53例及合并肺部曲霉菌感染患者25例作为研究对象,对其免疫功能进行检测,并与20名正常健康人群(健康对照组)进行对比分析。采用流式细胞仪检测周血T淋巴细胞亚群(CD3+CD4+、CD3+CD8+、CD4+/CD8+)的表达率,采用全自动蛋白分析仪检测患者血清IgM、IgG、IgA含量。结果念珠菌组和曲霉菌组的CD3+CD4+百分比及CD4+/CD8+均明显低于健康对照组(P<0.01),念珠菌组及曲霉菌组CD3+CD8+百分比高于健康对照组(P<0.05),念珠菌组的CD3+CD4+百分比及CD4+/CD8+均低于曲霉菌组(P<0.01),而CD3+CD8+百分比在曲霉菌组及念珠菌组之间无统计学差异。与健康对照组比较,念珠菌组和曲霉菌组的IgG明显低于健康对照组,(P<0.01),IgA均高于健康对照组,(P<0.05),念珠菌组的IgG高于曲霉菌组(P<0.01),而念珠菌组及曲霉菌组IgA比较及三组间IgM比较,无统计学差异。结论慢性阻塞性肺病合并肺部念珠菌及曲霉菌感染时,细胞免疫及体液免疫均受损,其中合并曲霉菌感染时的免疫受损状况较合并念珠菌感染时更重。%Objective To investigate the changes of immune function in patients with invasive pulmonary fungal infections by chronic obstructive pulmonary disease. Methods 78 patients with invasive pulmonary fungal infections by chronic obstructive pulmonary disease were slected, in which ,53 patients were pulmonary candidiasis and 25 patients were pulmonary aspergillosis. The T lymphocyte subsets in peripheral whole blood samples were derected by flow cytometry. The levels of IgM,IgG, IgA were

  20. Estimated Burden of Serious Fungal Infections in Jamaica by Literature Review and Modelling

    Science.gov (United States)

    Gugnani, HC; Denning, DW

    2015-01-01

    ABSTRACT Objective: Jamaica is one of the largest countries in the Caribbean with a population of 2 706 500. Prevalence of human immunodeficiency virus (HIV) in Jamaica is high, while that of tuberculosis (TB) is recorded to be low. In this study, we have estimated the burden of serious fungal infections and some other mycoses in Jamaica. Methods: All published papers reporting on rates of fungal infections in Jamaica and the Caribbean were identified through extensive search of the literature. We also extracted data from published papers on epidemiology and from the World Health Organization (WHO) TB Programme and UNAIDS. Chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) rates were derived from asthma and TB rates. Where there were no available data on some mycoses, we used specific populations at risk and frequencies of fungal infection of each to estimate national prevalence. Results: Over 57 600 people in Jamaica probably suffer from serious fungal infections each year, most related to ‘fungal asthma’ (ABPA and SAFS), recurrent vulvovaginal candidiasis and AIDS-related opportunistic infections. Histoplasmosis is endemic in Jamaica, though only a few clinical cases are known. Pneumocystis pneumonia is frequent while cryptococcosis and aspergillosis are rarely recorded. Tinea capitis was common in children. Recurrent vulvovaginal candidiasis is very common (3154/100 000) and candidaemia occurs. Subcutaneous mycoses such as chromoblastomycosis and mycetoma also seem to be relatively common. Conclusion: Local epidemiological studies are urgently required to validate or modify these estimates of serious fungal infections in Jamaica. PMID:26426178

  1. The relationship between gorgonian coral (Cnidaria: Gorgonacea) diseases and African dust storms

    Science.gov (United States)

    Weir-Brush, J. R.; Garrison, V.H.; Smith, G.W.; Shinn, E.A.

    2004-01-01

    The number of reports of coral diseases has increased throughout the world in the last 20 years. Aspergillosis, which primarily affects Gorgonia ventalina and G. flabellum, is one of the few diseases to be characterized. This disease is caused by Aspergillus sydowii, a terrestrial fungus with a worldwide distribution. Upon infection, colonies may lose tissue, and ultimately, mortality may occur if the infection is not sequestered. The spores of A. sydowii are <5 ??m, small enough to be easily picked up by winds and dispersed over great distances. Aspergillosis is prevalent in the Caribbean, and it appears that this primarily terrestrial fungus has adapted to a marine environment. It has been proposed that dust storms originating in Africa may be one way in which potential coral pathogens are distributed and deposited into the marine environments of the Caribbean. To test the hypothesis that African dust storms transport and deposit pathogens, we collected air samples from both dust storms and periods of nondust in St. John, U.S. Virgin Islands. Because we focused on fungal pathogens and used A. sydowii as a model, we isolated and cultured fungi on various types of media. Fungi including Aspergillus spp. were isolated from air samples taken from dust events and non-dust events. Twenty-three separate cultures and seven genera were isolated from dust event samples whereas eight cultures from five genera were isolated from non-dust air samples. Three isolates from the Virgin Islands dust event samples morphologically identified as Aspergillus spp. produced signs of aspergillosis in seafans, and the original pathogens were re-isolated from those diseased seafans fulfilling Koch's Postulates. This research supports the hypothesis that African dust storms transport across the Atlantic Ocean and deposit potential coral pathogens in the Caribbean.

  2. Invasive fungal disease in allogeneic hematopoietic stem cell transplant recipients: an autopsy-driven survey.

    Science.gov (United States)

    Sinkó, J; Csomor, J; Nikolova, R; Lueff, S; Kriván, G; Reményi, P; Bátai, A; Masszi, T

    2008-04-01

    Invasive mycoses are pre-eminent causes of morbidity and mortality in the allogeneic stem cell transplant setting. In spite of novel diagnostic modalities, the timely and specific identification of invasive mycoses still remains challenging. We analyzed the case history of 97 consecutive patients receiving 103 allogeneic stem cell transplants between January 2003 and October 2006 performed by a single team at 2 transplant centers in Budapest, Hungary. All patients with febrile neutropenia not responding to broad-spectrum antibacterial therapy received amphotericin B deoxycholate empirically. In cases of proven or probable invasive aspergillosis, intravenous voriconazole was instituted. Patients who failed to improve on initial therapy were treated with an antifungal combination, while responders were switched to oral voriconazole. A total of 38 patients died following allografting. Both centers had an autopsy rate of 100% due to central health care regulations. An infectious cause of death could be identified in 15 cases, invasive fungal disease being the most prevalent and accounting for 10 fatalities. Six patients died of invasive aspergillosis, while invasive candidiasis and mucormycosis led to a fatal outcome in 2 cases each. Despite the regular use of galactomannan antigen detections and imaging, an ante mortem diagnosis of proven/probable invasive fungal disease could only be established in 4 of 10 autopsy-verified cases (aspergillosis: 3, candidiasis: 1, mucormycosis: 0). In the remaining 6 patients, deep mycoses were missed clinically and were revealed only by postmortem histology. Present diagnostic and therapeutic strategies still seem to be suboptimal for the management of invasive fungal diseases in the high-risk allogeneic stem cell transplant population.

  3. Serious fungal infections in Ecuador.

    Science.gov (United States)

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

    2017-02-04

    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.

  4. Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy

    Directory of Open Access Journals (Sweden)

    Burgel PR

    2016-09-01

    Full Text Available Pierre-Régis Burgel,1,2 André Paugam,2,3 Dominique Hubert,1,2 Clémence Martin1,2 1Department of Respiratory Medicine, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, 2Université Paris Descartes, Sorbonne Paris Cité, 3Parasitology-Mycology Laboratory, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France Abstract: Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF. Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy. Keywords: itraconazole, voriconazole, posaconazole, azole resistance, allergic bronchopulmonary aspergillosis

  5. Proposed national strategies for the prevention of leading work-related diseases and injuries. Part 1

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    Preliminary strategies developed at the National Symposium on the Prevention of Leading Work Related Diseases and Injuries, held in Atlanta, Georgia on May 1 to 3, 1985 were revised, elaborated, and further developed. Strategies were developed for the prevention of occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. Lung diseases considered included silicosis, asbestosis, lung cancer mesothelioma, coal workers' pneumoconiosis, byssinosis, occupational asthma, hypersensitivity pneumonitis, asphyxiation, irritation, pulmonary edema, brucellosis, psitticosis, anthrax, mycobacterioses, histoplasmosis, aspergillosis, and coccidioidomycosis. Occupational cancers were discussed as they occur in the lung, pleura, peritoneum, bladder, kidneys, blood, nasal cavity, skin, nasal sinuses, and liver.

  6. Amphotericin B cochleates: a vehicle for oral delivery.

    Science.gov (United States)

    Perlin, David S

    2004-02-01

    Cochleates are a novel lipid-based delivery vehicle consisting of crystalline phospholipid-cation structures that form spiral lipid sheets. They represent a new technology platform for oral delivery of clinically important drugs that possess poor oral bioavailability. Orally administered cochleates containing amphotericin B (CAMB) showed broad-spectrum activity in murine infection models of candidiasis, aspergillosis and cryptococcosis. Initial biodistribution studies of CAMB administered orally in mice demonstrated that cochleates delivered significant levels of AMB to target organs. The lipid particulate nature of cochleates also imparted reduced toxicity that mimics other lipid-amphotericin B complexes. Cochleates are a promising new vehicle for oral delivery of amphotericin B at therapeutic levels.

  7. Drug delivery by lipid cochleates.

    Science.gov (United States)

    Zarif, Leila

    2005-01-01

    Drug delivery technology has brought additional benefits to pharmaceuticals such as reduction in dosing frequency and side effects, as well as the extension of patient life. To address this need, cochleates, a precipitate obtained as a result of the interaction between phosphatidylserine and calcium, have been developed and proved to have potential in encapsulating and delivering small molecule drugs. This chapter discusses the molecules that can be encapsulated in a cochleate system and describes in detail the methodology that can be used to encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent antifungal agent. Some efficacy data in animal models infected with candidiasis or aspergillosis are described as well.

  8. Single Nodula opacity of granulomatous Pneumocystis jirovecii pneumoniain an asymptomatic lymphoma patient

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Soo; Shin, Kyung Eun; Lee, Ju Hie [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2015-04-15

    The radiologic findings of a single nodule from Pneumocystis jirovecii pneumonia (PJP) have been rarely reported. We described a case of granulomatous PJP manifesting as a solitary pulmonary nodule with a halo sign in a 69-year-old woman with diffuse large B cell lymphoma during chemotherapy. The radiologic appearance of the patient suggested an infectious lesion such as angioinvasive pulmonary aspergillosis or lymphoma involvement of the lung; however, clinical manifestations were not compatible with the diseases. The nodule was confirmed as granulomatous PJP by video-assisted thoracoscopic surgery biopsy.

  9. A rare case of spontaneous Aspergillus spondylodiscitis with epidural abscess in a 45-year-old immunocompetent female

    Directory of Open Access Journals (Sweden)

    K Ambedkar Raj

    2013-01-01

    Full Text Available Vertebral osteomyelitis and discitis are mainly due to bacterial infections though fungal infections are one of the important causes of morbidity and mortality in immunocompromised patients. Aspergillus involving intervertebral disc space is extremely rare. We report a case of aspergillosis of intervertebral L5-S1 disc space with spinal epidural abscess in an immunocompetent 45-year-old female which can add on to a few case reports described in literature as well as an insight for clinicians regarding this rare spontaneous infection in an immunocompetent patient.

  10. Aspergillus keratitis: A cause of blindness in Tropical India

    Directory of Open Access Journals (Sweden)

    Kafil Akhtar

    2012-01-01

    Full Text Available Mycotic keratitis is a fungal infection of the cornea, which constitute an important eye problem in outdoor workers. This infection is difficult to treat, and it can lead to severe visual impairment or blindness. Trauma is the major predisposing factor, followed by ocular and systemic defects, prior application of corticosteroids and prolonged use of antibiotic eye-drops. We report this case because of the rarity of endogenous Aspergillosis presenting as blindness in tropical India and review of the relevant literature.

  11. Differential diagnosis of infections in a patient with Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Paolo Ghiringhelli

    2008-12-01

    Full Text Available We describe a case of a 65-years-old patient with Chronic Obstructive Pulmonary Disease (COPD, receiving oxygen therapy and resistant to antibiotic therapy. He was admitted with high fever, productive cough, marked leukocytosis, and chest X-ray findings of infiltration and fluid levels within lung cysts. A differential diagnosis was essential to start an adequate treatment and avoid the rapid worsening of patients respiratory status. In patients with chronic pulmonary diseases under immunotherapy, micotic infections should be considered. Aspergillus fumigatus was cultured from bronchial washing fluid and we diagnosed chronic necrotizing pulmonary aspergillosis (CNPA. Oral itraconazole was started and his symptoms and laboratory data markedly improved.

  12. Opportunistic infections in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Vijaya V. Mysorekar

    2012-01-01

    Full Text Available With the present progress in transplantation procedures, there is an improvement in patient and allograft survival. However, the immunosuppression necessary to sustain the allograft predisposes these transplant recipients to infection, which is now a significant cause of morbidity and mortality. We describe a case of a 30-year-old renal transplant recipient with two opportunistic infections, namely, primary cutaneous aspergillosis and intestinal tuberculosis, with terminal enterococcal pleuritis and peritonitis. Control of the degree of immunosuppression, and prompt recognition and treatment of infection are vital for successful organ transplantation.

  13. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient.

    Science.gov (United States)

    Tedja, R; El-Sherief, A; Olbrych, T; Gordon, S

    2013-08-01

    Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms.

  14. Emerging and reemerging diseases of avian wildlife

    Science.gov (United States)

    Pello, Susan J.; Olsen, Glenn H.

    2013-01-01

    Of the many important avian wildlife diseases, aspergillosis, West Nile virus, avipoxvirus, Wellfleet Bay virus, avian influenza, and inclusion body disease of cranes are covered in this article. Wellfleet Bay virus, first identified in 2010, is considered an emerging disease. Avian influenza and West Nile virus have recently been in the public eye because of their zoonotic potential and links to wildlife. Several diseases labeled as reemerging are included because of recent outbreaks or, more importantly, recent research in areas such as genomics, which shed light on the mechanisms whereby these adaptable, persistent pathogens continue to spread and thrive.

  15. Surgical management of complications of multimodal therapy.

    Science.gov (United States)

    Chui, Chan-Hon

    2012-08-01

    Multimodality therapies that include surgery, chemotherapy, radiotherapy, and various newer forms of targeted therapies have been commonly applied in childhood cancers. Such modalities are associated with complications that may adversely affect the outcome of cancer treatment. Acute complications that require surgical management form the focus of our discussion. These patients are often compromised by immunosuppression, thrombocytopenia, and malnutrition. The complications discussed include typhlitis, invasive aspergillosis (IA), pancreatitis, hemorrhagic cystitis, gastrointestinal hemorrhage, necrotizing skin and soft-tissue infections, and perianal infection. Familiarity with the spectrum of complications and their appropriate management approaches will minimize the patients' morbidity.

  16. Deep-sea fungi

    Digital Repository Service at National Institute of Oceanography (India)

    Raghukumar, C.; Damare, S.

    ealco fluor (72), which enhances fluorescence of the cellulose and chitin, the latter being a fin gerprint molecule of mycelial fungi (58). A total of48 out of 255 sediment samples exam ined by u') showed the presence of fungi by this method (18...> and can reach fresh habitats. It has been recently reported that spores of Aspergillus sydowii are croTied from the Saharan deserts across the Atlantic Ocean during dust storm!) to the Carihhean islands and cause aspergillosis disease in seafan~(87). Fungi...

  17. Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia.

    Science.gov (United States)

    Klimko, Nikolay N; Khostelidi, Sofya N; Volkova, Alisya G; Popova, Marina O; Bogomolova, Tatyana S; Zuborovskaya, Ludmila S; Kolbin, Aleksey S; Medvedeva, Nadezhda V; Zuzgin, Ilya S; Simkin, Sergey M; Vasilyeva, Nataliya V; Afanasiev, Boris V

    2014-12-01

    We prospectively observed 36 haematological patients with mucormycosis from nine hospitals of St. Petersburg during 2004-2013. The most frequent underlying diseases were acute leukaemia (64%), and main risk factors were prolonged neutropenia (92%) and lymphocytopenia (86%). In 50% of the patients, mucormycosis was diagnosed 1-65 days after invasive aspergillosis. Main clinical form of mucormycosis was pulmonary (64%), while two or more organ involvement was noted in 50% of the cases. The most frequent aetiological agents of mucormycosis were Rhizopus spp. (48%). Twelve-week survival rate was 50%. Combination therapy (echinocandins + amphotericin B forms) and recovery from the underlying disease significantly improved the survival rate.

  18. Zygomycosis Associated with HIV Infection and Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Larry Nichols

    2011-01-01

    Full Text Available Zygomycosis is an increasing threat to patients with human immunodeficiency virus (HIV infection. Zygomycosis (formerly called mucormycosis is the fungal infection with Mucor, Rhizopus, or other species that share a common morphology of large empty pauciseptate hyphae with rare random-angle branching and a collapsed “twisted ribbon” appearance. Morphology allows a specific diagnosis on frozen section or smear prior to growth and identification of the fungi in culture which makes it improtant because treatment is different than that for more common mycoses such as candidiasis and aspergillosis. We present an informative and illustrative case of zygomycosis in a patient with HIV infection and liver transplantation.

  19. Mucormycosis in a surgical defect masquerading as osteomyelitis: a case report and review of literature.

    Science.gov (United States)

    Mengji, Ashwini Kumar; Yaga, Uday Shankar; Gollamudi, Nishanth; Prakash, Bhanu; Rajashekar, Edunuri

    2016-01-01

    Mucormycosis is a rare, highly lethal opportunistic fungal disease affecting immune compromised and diabetic patients. Mucormycosis is considered as the 3(rd) most common invasive mycosis after candidiasis and aspergillosis in debilitating patients. It is caused by the filamentous fungi of the class zygomycetes. The infection usually begins in the nose due to inhalation of fungal spores. This fatal fungal disease needs a prompt and early definitive diagnosis, aggressive surgical therapy and high dose anti-fungal therapy. Here, we present a case report of Mucormycosis in a 64 year elderly diabetic male patient who was previously operated for myiasis and also the extensive review of the literature of the mucormycosis.

  20. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

    Energy Technology Data Exchange (ETDEWEB)

    Weigel, S.; Kloska, S.; Freund, M. [Dept. of Clinical Radiology, Univ. Hospital of Muenster, Muenster (Germany); Kehl, H.G. [Dept. of Pediatric Cardiology, Univ. Hospital of Muenster, Muenster (Germany)

    2003-12-01

    A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

  1. Rhino-oculo-cerebral aspergillus and mucor co-infections in an immunocompromised patient with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Kalidas Rit

    2014-01-01

    Full Text Available Mucormycosis are pathogenic moulds of the mucorales species usually occurring in immunocompromised patients or in patients with uncontrolled diabetes mellitus. Aspergillosis is the clinical condition caused by Aspergillus species and may cause an invasive disease with high case fatality rate, especially in immunosuppressed patients. A 46-year-old male patient with Type 2 diabetes mellitus with underlying malignancy presented with proptosis of left eye. Combined infections of Mucor and Aspergillus were diagnosed by means of computed tomography (CT scan and biopsy. Treatment with Amphotericin B and Voriconazole was started, the patient died within 3 months, from multi-organ failure.

  2. Posaconazole

    Directory of Open Access Journals (Sweden)

    Bhattacharya M

    2010-01-01

    Full Text Available Posaconazole is a novel second-generation Triazole oral antifungal agent. It is highly effective in the prophylaxis of invasive fungal infections in immunocompromised patients. It is used as a first-line agent as well as for salvage therapy in invasive fungal infections including aspergillosis, oropharyngeal and esophageal candidiasis. It has a good adverse effect profile. With the rising incidence of invasive fungal infections due to the HIV pandemic and medical advancements in transplantation and cancer therapy, these features make posaconazole a valuable addition in the family of antifungal agents.

  3. Correlation between the elastase activity index and invasiveness of clinical isolates of Aspergillus fumigatus.

    Science.gov (United States)

    Blanco, Jose L; Hontecillas, Raquel; Bouza, Emilio; Blanco, Isabel; Pelaez, Teresa; Muñoz, Patricia; Perez Molina, Jose; Garcia, Marta E

    2002-05-01

    We calculated an elastase activity index (EAI) by dividing the diameter of the elastin lysis halo by the fungal growth diameter. After 10 days' incubation at 37 degrees C, all strains but one obtained from invasive aspergillosis showed an EAI > or = 1. Of the 18 strains obtained from colonized patients, only 4 (22.2%) had an EAI > or = 1, whereas neither of the strains isolated from patients with fungus ball reached this value. Overall, 44 out of the 142 strains obtained from the environment had an EAI > or = 1 (30.9%).

  4. Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases

    Science.gov (United States)

    Demir, Sevliya Öcal; Atici, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; İkizoğlu, Nilay Baş; Eralp, Ela Erdem; Soysal, Ahmet; Bakir, Mustafa

    2016-01-01

    Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients. PMID:27313918

  5. Update on epidemiology of and preventive strategies for invasive fungal infections in cancer patients.

    Science.gov (United States)

    Perfect, John R; Hachem, Ray; Wingard, John R

    2014-11-15

    Changes in antineoplastic treatments and transplant practices are driving shifts in the epidemiology of invasive fungal diseases (IFDs). Patients with acute myelogenous leukemia (AML) and those undergoing bone marrow transplant (BMT) are at greatest risk for contracting IFDs. Unfortunately, there are few large population studies that can be used to track trends and help us to better understand why certain individuals within recognized high-risk groups are at greater risks than others for contracting IFDs. The growing use of antifungals in prophylaxis and treatment influences which species will cause an IFD as well as the resistance patterns of these fungi. On the one hand, antifungal prophylaxis has mitigated, but not eliminated, the threat of candidiasis. Furthermore, prophylaxis trials have shown trends of reduced aspergillosis in BMT patients; however, no survival benefits were seen, and 1 trial indicated a lower rate of aspergillosis and survival benefits in patients with AML. Future prophylaxis trials should reduce the heterogeneity of risk in study participants in order to better assess benefit; these trials should also incorporate fungal biomarkers into their design. The threat of emerging fungal resistance in prophylaxis strategies is real and must be monitored.

  6. Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy.

    Science.gov (United States)

    Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

    2016-01-01

    Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy.

  7. Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases

    Directory of Open Access Journals (Sweden)

    Sevliya Öcal Demir

    2016-01-01

    Full Text Available Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients.

  8. The Aspergillus nidulans alcA promoter drives tightly regulated conditional gene expression in Aspergillus fumigatus permitting validation of essential genes in this human pathogen.

    Science.gov (United States)

    Romero, Beatriz; Turner, Geoffrey; Olivas, Israel; Laborda, Fernando; De Lucas, J Ramón

    2003-11-01

    Aspergillus fumigatus causes invasive aspergillosis, a mycosis that is usually fatal in immunocompromised patients. Functional genomics in this fungus will aid the discovery of novel antifungal drugs to treat invasive aspergillosis. However, there is still a need for appropriate molecular genetic tools to facilitate such functional studies. Here, we describe the use of a conditional gene expression system allowing the identification of novel therapeutic targets through validation of essential genes in A. fumigatus. This system is based on the capacity of the Aspergillus nidulans alcA promoter (alcA(p)) to tightly regulate gene expression in this fungus. Conditionally regulated gene expression in A. fumigatus was demonstrated by transcriptional and phenotypic analyses of strains expressing a nuclear migration gene with a terminal phenotype, the A. fumigatus nudC gene, under control of this promoter. This conditional expression system, the first one described in A. fumigatus, will also be useful for investigating the function of essential genes by altering the threonine/glucose ratio in the growth medium.

  9. CT findings in severe thoracic sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Hennebicque, Anne-Sophie; Brillet, Pierre-Yves; Moulahi, Hassen; Brauner, Michel W. [UFR Bobigny, Department of Radiology, Federation MARTHA and EA 2363, Bobigny Cedex (France); Nunes, Hilario; Valeyre, Dominique [UFR Bobigny, Department of Pneumology, Federation MARTHA and EA 2363, Bobigny Cedex (France)

    2005-01-01

    Severe thoracic sarcoidosis includes manifestations with significant clinical and functional impairment and a risk of mortality. Severe thoracic sarcoidosis can take on various clinical presentations and is associated with increased morbidity. The purpose of this article was to describe the CT findings in severe thoracic sarcoidosis and to explain some of their mechanisms. Subacute respiratory insufficiency is a rare and early complication due to a high profusion of pulmonary lesions. Chronic respiratory insufficiency due to pulmonary fibrosis is a frequent and late complication. Three main CT patterns are identified: bronchial distortion, honeycombing and linear opacities. CT can be helpful in diagnosing some mechanisms of central airway obstruction such as bronchial distortion due to pulmonary fibrosis or an extrinsic bronchial compression by enlarged lymph nodes. An intrinsic narrowing of the bronchial wall by endobronchial granulomatous lesions may be suggested by CT when it shows evidence of bronchial mural thickening. Pulmonary hypertension usually occurs in patients with end-stage pulmonary disease and is related to fibrotic destruction of the distal capillary bed and to the resultant chronic hypoxemia. Several other mechanisms may contribute to the development of pulmonary hypertension including extrinsic compression of major pulmonary arteries by enlarged lymph nodes and secondary pulmonary veno-occlusive disease. Aspergilloma colonization of a cavity is the main cause of hemoptysis in sarcoidosis. Other rare causes are bronchiesctasis, necrotizing bronchial aspergillosis, semi-invasive pulmonary aspergillosis, erosion of a pulmonary artery due to a necrotic sarcoidosis lesion, necrosis of parenchymal sarcoidosis lesions and specific endobronchial macroscopic lesions. (orig.)

  10. Aspergillus pragensis sp. nov. discovered during molecular reidentification of clinical isolates belonging to Aspergillus section Candidi.

    Science.gov (United States)

    Hubka, Vit; Lyskova, Pavlina; Frisvad, Jens C; Peterson, Stephen W; Skorepova, Magdalena; Kolarik, Miroslav

    2014-08-01

    The identity of nine clinical isolates recovered from Czech patients and presumptively identified as Aspergillus sp. section Candidi based on colony morphology was revised using sequences of β-tubulin, calmodulin gene sequence, and internal transcribed spacer rDNA. Six isolates were from suspected and proven onychomycosis, one from otitis externa, and two associated with probable invasive aspergillosis. The results showed that one Aspergillus candidus isolate was the cause of otitis externa, and both isolates obtained from sputa of patients with probable invasive aspergillosis were reidentified as A. carneus (sect. Terrei) and A. flavus (sect. Flavi). Three isolates from nail scrapings were identified as A. tritici, a verified agent of nondermatophyte onychomycosis. One isolate from toenail was determined to be A. candidus and the two isolates belonged to a hitherto undescribed species, Aspergillus pragensis sp. nov. This species is well supported by phylogenetic analysis based on β-tubulin and calmodulin gene and is distinguishable from other members of sect. Candidi by red-brown reverse on malt extract agar, slow growth on Czapek-Dox agar and inability to grow at 37°C. A secondary metabolite analysis was also provided with comparison of metabolite spectrum to other species. Section Candidi now encompasses five species for which a dichotomous key based on colony characteristics is provided. All clinical isolates were tested for susceptibilities to selected antifungal agents using the Etest and disc diffusion method. Overall sect. Candidi members are highly susceptible to common antifungals.

  11. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

    Science.gov (United States)

    Lee, Kim-Chung; Tam, Emily W T; Lo, Ka-Ching; Tsang, Alan K L; Lau, Candy C Y; To, Kelvin K W; Chan, Jasper F W; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2015-06-17

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

  12. Poor compliance with antifungal drug use guidelines by transplant physicians: a framework for educational guidelines and an international consensus on patient safety.

    Science.gov (United States)

    Muñoz, Patricia; Rojas, Loreto; Cervera, Carlos; Garrido, Gregorio; Fariñas, Maria Carmen; Valerio, Maricela; Giannella, Maddalena; Bouza, Emilio

    2012-01-01

    The rate of compliance with antifungal drug use guidelines by transplant physicians is mostly unknown. We performed a nationwide electronic survey to assess antifungal use by different types of transplant physicians. Sixty-one percent (53/87) of the transplant programs responded (accounting for 85% of heart transplant procedures, 65% of kidney transplantations, and 71.5% of liver transplantations). Antifungal prophylaxis was used in 41.5% programs (liver 93.3%, heart 30.8%, and kidney 16%). Prophylaxis was universal in 32% of the programs and targeted only to selected patients in 68%, mainly indicated after re-transplantation (73.3%), re-intervention (66.7%) and hemodialysis (60%). Main drugs for universal prophylaxis were fluconazole and itraconazole (42.9% each), while fluconazole (60%), L-amphotericin B (AMB), and caspofungin (13.4% each) were preferred for targeted prophylaxis. Overall, 84.9% of the programs used galactomannan for the diagnosis of invasive aspergillosis (only 34% in BAL) and 66.6% used voriconazole as first-line monotherapy. Combination first-line therapy for invasive aspergillosis was used by 31.3%, mainly with voriconazole with caspofungin (40%) or anidulafungin (26.7%) or L-AMB-caspofungin (26.7%). Adherence of transplant physicians to current recommendations on antifungal treatment and prophylaxis is poor. An international consensus that responds to differences in patients and centers and emphasizes patient safety is clearly needed.

  13. Pulmonary echinococcal cyst with a filamentous fungus co-infection.

    Science.gov (United States)

    Pandey, P; Dixit, A K; Tanwar, A; Mahajan, N C

    2013-09-01

    Fungal infections are known to colonize the pre-existing lung cavities formed as a result of diseases like tuberculosis, sarcoidosis, bronchiectasis and cavitatary neoplasia, mostly encountered in immunocompromised patients. Pulmonary echinococcal cysts have been reported coexistent with cryptococcosis and other saprophytic mycosis, but the coexistence of aspergillosis and echinococcal cyst is extremely rare and occasionally been reported in English literature. Active invasion and proliferation of the fungi in the laminated ectocyst of the echinococcal cyst is very unusual. We report a case of 60 years old immunocompetent female, presented with cough, chest pain and shortness of breath. The chest X-ray showed a large thick walled cavity in the lower and mid zone of right lung with positive water lily sign. Surgical enucleation of the echinococcal cyst revealed aspergilloma involving the cavity with massive invasion of laminated ectocyst by filamentous fungus, morphologically resembling an Aspergillus species and was further treated with Itraconazole for 3 months. This unique coexistence of active pulmonary echinococcosis and aspergillosis is being reported because of its rarity and clinical importance for its management.

  14. Performance evaluation of multiplex PCR including Aspergillus-not so simple!

    Science.gov (United States)

    Alanio, Alexandre; Bretagne, Stéphane

    2017-01-01

    Multiplex PCRs have been designed for including species other than Aspergillus fumigatus for the diagnosis of invasive aspergillosis, such as microarrays, liquid-phase array, and electrospray-ionization mass spectrometry (PCR/ESI MS). These methods are based on the selection of multiple primers to amplify different species with the specificity checked by hybridization to a probe or by base composition of the amplicon for the PCR/ESI MS. When testing complex samples such as respiratory specimens, some clinically relevant species can be missed. Indeed, it is impossible to design primers able to amplify all the known fungal species with the same efficiency. Therefore, the best amplified species may not be the most clinically relevant. Multiplex assays have also been proposed to detect A. fumigatus DNA and azole resistance. Since the gene responsible for azole resistance is single copy and the gene used for detection is multicopy, only the high fungal loads can be evaluated. Thus, although interesting for investigating mycobiome, the multiplex assays should be used with cautious for the diagnosis of IA or the detection of resistance. For the diagnosis of invasive aspergillosis, validated quantitative PCRs specifically targeting A. fumigatus or a limited set of species to increase sensitivity is a safer option.

  15. Secondary glaucoma associated with bilateral Aspergillus niger endophthalmitis in an HIV-positive patient: case report Glaucoma secundário a endoftalmite bilateral por Aspergillus niger em paciente HIV-positivo: relato de caso

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    Jayter Silva Paula

    2006-06-01

    Full Text Available Aspergillus endophthalmitis is usually related to systemic or local dissemination in immunosuppressed subjects. The authors report a rare case of severe bilateral glaucoma secondary to an intraocular infection with Aspergillus niger, in the absence of any detectable focus of aspergillosis, in an HIV-infected patient. There were no confirming signs of injection drug use, and the agent was isolated after inoculation in experimental animals. This case shows that Aspergillus endophthalmitis should be considered in non-injecting drug users and HIV-infected patients even in the absence of systemic aspergillosis.Endoftalmite por Aspergillus é geralmente relacionada à disseminação local ou sistêmica do agente em indivíduos imunocomprometidos. Os autores relatam um caso raro de glaucoma bilateral grave secundário a uma infecção intra-ocular por Aspergillus niger, na ausência de qualquer foco detectável de aspergilose em paciente HIV-positivo. Foram afastados sinais e antecedentes de uso de drogas injetáveis e o agente foi isolado após inoculação em animais experimentais. Este caso demonstra que a endoftalmite por Aspergillus deve ser considerada em pacientes HIV-positivos não-usuários de drogas injetáveis, mesmo na ausência de aspergilose sistêmica.

  16. Mucormycosis of the hard palate masquerading as carcinoma

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    Bhari Sharanesha Manjunatha

    2012-02-01

    Full Text Available A growing number of medically compromised patients are encountered by dentists in their practices. Opportunistic fungal infections such as mucormycosis usually occur in immunocompromised patients but can infect healthy individuals as well. Mucormycosis is an acute opportunistic, uncommon, frequently fatal fungal infection, caused by a saprophytic fungus that belongs to the class of phycomycetes. Among the clinical differential diagnosis we can consider squamous cell carcinoma. Such cases present as chronic ulcers with raised margins causing exposure of underlying bone. There is a close histopathological resemblance between mucormycosis and aspergillosis. Microscopically, aspergillosis has septate branching hyphae, which can be distinguished from mucormycotic hyphae by a smaller width and prominent acute angulations of branching hyphae. A definitive diagnosis of mucormycosis can be made by tissue biopsy that identifies the characteristic hyphae, by positive culture or both. The culture of diseased tissue may be negative and histopathologic examination is essential for early diagnosis. Mucormycosis was long regarded as a fatal infection with poor prognosis. However with early medical and surgical management survival rates are now thought to exceed 80%. In the present case, the fungus was identified by hematoxylin and eosin stain and confirmed by Grocott’s silver methenamine special staining technique. Removal of the necrotic bone, which acted as a nidus of infection, was done. Post-operatively patient was advised an obturator to prevent oronasal regurgitation. Since mucormycosis occurs infrequently, it may pose a diagnostic and therapeutic dilemma for those who are not familiar with its clinical presentation.

  17. In vitro and in vivo antifungal activity of Cassia surattensis flower against Aspergillus niger.

    Science.gov (United States)

    Sumathy, Vello; Zakaria, Zuraini; Jothy, Subramanion L; Gothai, Sivapragasam; Vijayarathna, Soundararajan; Yoga Latha, Lachimanan; Chen, Yeng; Sasidharan, Sreenivasan

    2014-12-01

    Invasive aspergillosis (IA) in immunocompromised host is a major infectious disease leading to reduce the survival rate of world population. Aspergillus niger is a causative agent causing IA. Cassia surattensis plant is commonly used in rural areas to treat various types of disease. C. surattensis flower extract was evaluated against the systemic aspergillosis model in this study. Qualitative measurement of fungal burden suggested a reduction pattern in the colony forming unit (CFU) of lung, liver, spleen and kidney for the extract treated group. Galactomannan assay assessment showed a decrease of fungal load in the treatment and positive control group with galactomannan index (GMI) value of 1.27 and 0.25 on day 28 but the negative control group showed high level of galactomannan in the serum with GMI value of 3.58. Histopathology examinations of the tissues featured major architecture modifications in the tissues of negative control group. Tissue reparation and recovery from infection were detected in extract treated and positive control group. Time killing fungicidal study of A. niger revealed dependence of the concentration of C. surattensis flower extract.

  18. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    Science.gov (United States)

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  19. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

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    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  20. Disparate Proteome Responses of Pathogenic and Non-pathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)

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    Wiedner, Susan D.; Ansong, Charles; Webb-Robertson, Bobbie-Jo M.; Pederson, Leeanna M.; Fortuin, Suereta; Hofstad, Beth A.; Shukla, Anil K.; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2013-07-01

    Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. Genomic analysis shows high synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. To investigate the presence of unique or highly inducible protein reactivity in the pathogen, we applied activity-based protein profiling to compare protein reactivity of all three fungi over time in minimal media growth and in response to human serum. We found 350 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culture in serum. Though the fungi are highly orthologous, A. fumigatus has significantly more activity across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Human serum induced processes uniquely or significantly represented in A. fumigatus include actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher reactivity over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely aspergilli. These unique protein reactivity responses may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.

  1. Heterogeneity Confounds Establishment of "a" Model Microbial Strain.

    Science.gov (United States)

    Keller, Nancy P

    2017-02-21

    Aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al. (mBio 7:e01515-16, 2016, https://doi.org/10.1128/mBio.01515-16) demonstrated that variation in 16 environmental and clinical isolates of A. fumigatus correlated virulence with fitness in low oxygen, whereas Fuller et al. (mBio 7:e01517-16, 2016, https://doi.org/10.1128/mBio.01517-16) showed wide variation in light responses at a physiological and protein functionality level in 15 A. fumigatus isolates. In both studies, two commonly used type strains, Af293 and CEA10, displayed significant differences in physiological responses to abiotic stimuli and virulence in a murine model of IPA.

  2. A controlled study to determine the efficacy of Loxostylis alata (Anacardiaceae in the treatment of aspergillus in a chicken (Gallus domesticus model in comparison to ketoconazole

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    Suleiman Mohammed M

    2012-10-01

    Full Text Available Abstract Background The poultry industry due to intensive methods of farming is burdened with losses from numerous infectious agents, of which one is the fungus Aspergillus fumigatus. In a preliminary study, the extracts of Loxostylis alata A. Spreng, ex Rchb. showed good activity in vitro against A. fumigatus with a minimum inhibitory concentration of 0.07 mg/ml. For this study crude, a crude acetone extract of L. alata leaves was evaluated for its acute toxicity in a healthy chicken model and for efficacy in an infectious model of aspergillosis (A. fumigatus. Results At a dose of 300 mg/kg, the extract induced some toxicity characterised by decreased feed intake and weight loss. Consequently, 100 and 200 mg/kg were used to ascertain efficacy in the infectious model. The plant extract significantly reduced clinical disease in comparison to the control in a dose dependant manner. The extract was as effective as the positive control ketoconazole dosed at 60 mg/kg. Conclusions The results indicate that a crude extract of L. alata leaves has potential as an antifungal agent to protect poultry against avian aspergillosis.

  3. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-01-01

    Full Text Available

    Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.

    Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  4. Fungal allergy in asthma-state of the art and research needs.

    Science.gov (United States)

    Denning, David W; Pashley, Catherine; Hartl, Domink; Wardlaw, Andrew; Godet, Cendrine; Del Giacco, Stefano; Delhaes, Laurence; Sergejeva, Svetlana

    2014-01-01

    Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies.

  5. Echinocandins: A ray of hope in antifungal drug therapy

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    Grover Neeta

    2010-01-01

    Full Text Available Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.

  6. Standard methods for fungal brood disease research.

    Science.gov (United States)

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

    2013-01-01

    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.

  7. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

    Science.gov (United States)

    Lee, Robert J.; Workman, Alan D.; Carey, Ryan M.; Chen, Bei; Rosen, Phillip L.; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.

    2016-01-01

    Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6–12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases. PMID:27623953

  8. 急性侵袭性肺曲霉菌病合并糖尿病引起致死性咯血三例报告并文献复习

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    华静娜; 李莉

    2016-01-01

    目的:分析急性侵袭性肺曲霉菌病合并糖尿病引起致死性咯血病例的特点。方法回顾性分析天津市海河医院2013-08—2014-02收治的3例A IPA 合并糖尿病引起致死性咯血患者的临床资料,并复习文献。结果3例A IPA 患者基础疾病均为糖尿病,且血糖控制差,糖化血糖水平9.2%~14.5%。以“ Invasive pulmonary as-pergillosis”&“ hem optysis”为关键词在pubm ed搜索从1980—2015年文献44篇,报告侵袭性肺曲霉菌病共543例,其中咯血病例200例,占总病例数的36.8%,致死性咯血病例17例,占咯血病例的8.5%,占总病例数的3.1%。543例侵袭性曲霉菌病例中,仅1例为糖尿病患者。以“侵袭性肺曲霉菌病”为关键词在万方、清华同方数据库搜索2006—2015年的中文文献共46篇,其中19篇文献共报道358例侵袭性肺曲霉菌病例,其中咯血病例194例,占总病例数的54.2%,致死性咯血病例35例,占咯血病例的18.0%,占总病例数的9.8%。358例侵袭性肺曲霉菌病例中,47例为糖尿病患者,占总病例数的13.1%,1例为致死性咯血患者。结论侵袭性肺曲霉菌病咯血病例多见,由咯血致死病例不足10%。 A IPA 患者发生大咯血主要与曲霉菌侵犯大血管有关,与凝血功能异常无必然联系。是否发生大咯血与临床情况不成平行关系。%O bjective To analyze the characteristics of fatal hemoptysis caused by acute invasive pulmonary as-pergillosis complicated with diabetes.M e th o d s A retrospective analysis was carried out on the clinical data of 3 cases with fatal hemoptysis caused by acute invasive pulmonary aspergillosis ( AIPA ) complicated with diabetes in Tianjin Hai-he Hospital from August 2013 to February 2014,and the relevant literatures were reviewed.R esults The underlying disease of the 3 AIPA patients was diabetes . The blood glucose control of the patients was poor , and the saccharifed blood

  9. Isolation and identification of Aspergillus spp. from brown kiwi (Apteryx mantelli) nocturnal houses in New Zealand.

    Science.gov (United States)

    Glare, Travis R; Gartrell, Brett D; Brookes, Jenny J; Perrott, John K

    2014-03-01

    Aspergillosis, a disease caused by infection with Aspergillus spp., is a common cause of death in birds globally and is an irregular cause of mortality of captive kiwi (Apteryx spp.). Aspergillus spp. are often present in rotting plant material, including the litter and nesting material used for kiwi in captivity. The aim of this study was to survey nocturnal kiwi houses in New Zealand to assess the levels of Aspergillus currently present in leaf litter. Samples were received from 11 nocturnal kiwi houses from throughout New Zealand, with one site supplying multiple samples over time. Aspergillus was isolated and quantified by colony counts from litter samples using selective media and incubation temperatures. Isolates were identified to the species level by amplification and sequencing of ITS regions of the ribosomal. Aspergillus spp. were recovered from almost every sample; however, the levels in most kiwi houses were below 1000 colony-forming units (CFU)/g of wet material. The predominant species was Aspergillus fumigatus, with rare occurrences of Aspergillus niger, Aspergillus nidulans, and Aspergillus parasiticus. Only one site had no detectable Aspergillus. The limit of detection was around 50 CFU/g wet material. One site was repeatedly sampled as it had a high loading of A. fumigatus at the start of the survey and had two recent clinical cases of aspergillosis diagnosed in resident kiwi. Environmental loading at this site with Aspergillus spp. reduced but was not eliminated despite changes of the litter. The key finding of our study is that the background levels of Aspergillus spores in kiwi nocturnal houses in New Zealand are low, but occasional exceptions occur and are associated with the onset of aspergillosis in otherwise healthy birds. The predominant Aspergillus species present in the leaf litter was A. fumigatus, but other species were also present. Further research is needed to confirm the optimal management of leaf litter to minimize Aspergillus

  10. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism.

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    Eveline Snelders

    2008-11-01

    Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more

  11. ANTIFUNGAL PROPHYLAXIS IN IMMUNOCOMPROMISED PATIENTS

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    Lourdes Vazquez

    2016-09-01

    Full Text Available Invasive fungal infections (IFIs represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication.

  12. T cell immunity and vaccines against invasive fungal diseases.

    Science.gov (United States)

    Ito, James Isami

    2011-01-01

    Over the past two decades much has been learned about the immunology of invasive fungal infection, especially invasive candidiasis and invasive aspergillosis. Although quite different in their pathogenesis, the major common protective host response is Th1 mediated. It is through Th1 cytokine production that the effector cells, phagocytes, are activated to kill the fungus. A more thorough understanding of the pathogenesis of disease, the elicited protective Th1 immune response, the T cell antigen(s) which elicit this response, and the mechanism(s) whereby one can enhance, reconstitute, or circumvent the immunosuppressed state will, hopefully, lead to the development of a vaccine(s) capable of protecting even the most immunocompromised of hosts.

  13. Vaccination approaches against opportunistic fungal infections caused by Aspergillus fumigatus.

    Science.gov (United States)

    Reichard, Utz; Herrmann, Sahra; Asif, Abdul R

    2014-01-01

    Although innate immunity primarily combats systemic infections of opportunistic fungi such as Aspergillus and Candida spp., acquired and protective immunoreactions were observed long ago in animal trials following sublethal systemic infections caused by viable fungi or after challenging animals with inactivated fungal cells. Based on these observations, fungal antigens should exist which mediate such protective immunoreactions and have in part already been identified. In this context, this review focuses primarily on the various approaches that have been used to identify protection-mediating Aspergillus-antigens and their rationale. Emphasis is placed on screening methods that have exploited genetic or proteomic approaches on the basis of the corresponding fungal genome projects. Thereby, a survey and description is given of the antigens so far known to be capable of inducing immune responses that protect animals against acquiring lethal systemic aspergillosis.

  14. Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability.

    Science.gov (United States)

    Tiphine, M; Letscher-Bru, V; Herbrecht, R

    1999-12-01

    Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%. Moreover, amB is toxic, especially for the kidneys. New formulations have been developed in an attempt to improve both efficacy and tolerability. In an attempt to reduce toxicity, a number of investigators have reconstituted amB in a lipid emulsion, but few data are available on efficacy in documented infections. An improvement in immediate and renal tolerance was obtained with equivalent daily dose regimens, but the therapeutic index does not appear to be improved. This approach cannot be recommended at present. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (AmBisome). The efficacy of ABCD on various fungal infections has been assessed in open trials, with a response rate of 49% in aspergillosis, 70% in candidiasis, and 67% in mucormycosis. In two randomized trials comparing ABCD with amB in invasive aspergillosis and in persistent febrile neutropenia, the response rates were equivalent. ABCD was less nephrotoxic. In contrast, immediate reactions to ABCD were as frequent and severe as with amB. These immediate effects are more frequent during the first infusions and lessen as treatment continues. The recommended dose is 3-4 mg/kg/day. ABLC appeared to be effective as rescue therapy in various types of invasive mycoses, with a response rate of 42% in aspergillosis, 67% in candidiasis, and 82% in fusariosis. Efficacy identical to that of amB was demonstrated in a comparative randomized trial involving patients with invasive candidiasis. General and renal tolerability is improved compared with amB. The recommended dose regimen is 5 mg/kg/day. Liposomal amB (AmBisome) is the only truly liposomal formulation. The response rates in preliminary trials were 66% in aspergillosis and 81% in

  15. Curvularia lunata, a rare fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD); a rare case report

    Science.gov (United States)

    Subramanyam, Haritha; Elumalai, Ramprasad; Kindo, Anupma Jyoti; Periasamy, Soundararajan

    2016-01-01

    Peritonitis is an inflammation of the peritoneum that occurs in patients with end-stage renal disease (ESRD) treated by peritoneal dialysis. Fungal peritonitis is a dreaded complication of peritoneal dialysis. Curvularia lunata is known to cause extra renal disease like endocarditis, secondary allergic bronchopulmonary aspergillosis and endophthalmitis. This case report presents a case of continuous ambulatory peritoneal dialysis peritonitis with this disease and its management. This case is of a 45-year-old man, presented with ESRD, secondary to diabetic nephropathy. After 3 months of hemodialysis the patient was put on continuous ambulatory peritoneal dialysis (CAPD). Local Examination at catheter site showed skin excoriation and purulent discharge. Further peritoneal dialysis (PD) fluid analysis showed neutrophilic leukocytosis and diagnosis of Curvularia lunata PD peritonitis.

  16. Aneurysms complicating inflammatory diseases in immunocompromised hosts: value of contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Heussel, C.P. [Dept. of Radiology, Univ. of Mainz (Germany); Kauczor, H.U. [Dept. of Radiology, Univ. of Mainz (Germany); Heussel, G. [Dept. of Hematology, Univ. of Mainz (Germany); Mildenberger, P. [Dept. of Radiology, Univ. of Mainz (Germany); Dueber, C. [Dept. of Radiology, Univ. of Mainz (Germany)

    1997-04-01

    We studied the value of contrast-enhanced CT in the detection of aneurysms in immunocompromised patients suffering from inflammatory diseases eventually complicated by hemorrhage. Contrast-enhanced spiral CT was applied in three patients with immunocompromise due to chemotherapy, alcohol abuse or HIV. They suffered from invasive aspergillosis, chronic pancreatitis with pseudocyst formation, and acute pancreatitis together with HIV-associated lymphadenopathy. Complicating hemorrhage was present in two cases. Contrast-enhanced CT showed aneurysms complicating the underlying inflammatory disease in all three cases. The feeding vessels were identified and the patients with signs of bleeding were subsequently referred for angiography and embolization. Contrast-enhanced spiral CT is suited to detect aneurysms in immunocompromised patients suffering from inflammatory disease. It is recommended in these patients prior to angiography and intervention. (orig.). With 3 figs.

  17. Curvularia lunata, a rare fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD; a rare case report

    Directory of Open Access Journals (Sweden)

    Subramanyam Haritha

    2016-01-01

    Full Text Available Peritonitis is an inflammation of the peritoneum that occurs in patients with end-stage renal disease (ESRD treated by peritoneal dialysis. Fungal peritonitis is a dreaded complication of peritoneal dialysis. Curvularia lunata is known to cause extra renal disease like endocarditis, secondary allergic bronchopulmonary aspergillosis and endophthalmitis. This case report presents a case of continuous ambulatory peritoneal dialysis peritonitis with this disease and its management. This case is of a 45-year-old man, presented with ESRD, secondary to diabetic nephropathy. After 3 months of hemodialysis the patient was put on continuous ambulatory peritoneal dialysis (CAPD. Local Examination at catheter site showed skin excoriation and purulent discharge. Further peritoneal dialysis (PD fluid analysis showed neutrophilic leukocytosis and diagnosis of Curvularia lunata PD peritonitis.

  18. Posterior reversible encephalopathy syndrome in an AIDS patient with acute renal failure and hypertension

    Directory of Open Access Journals (Sweden)

    Olivia Bargiacchi

    2013-03-01

    Full Text Available Introduction: The posterior reversible encephalopathy syndrome (PRES is a neurological entity characterized by magnetic resonance imaging (MRI evidence of bilateral subcortical edema in the occipital regions of the brain. Case report: We report the case of a female patient with AIDS, pulmonary aspergillosis, CMV infection, and acute renal failure due to Clostridium difficile diarrhea. Her clinical course was complicated by seizures and hypertension. MRI findings were consistent with PRES. The patient was treated with anticonvulsants and antihypertensive agents with clinical improvement. Discussion and conclusions: Few cases of PRES in HIV-infected patients have been described, and it is not clear whether HIV infection is a predisposing factor for this syndrome. The article reviews the literature on PRES in HIV and discusses the role of HIV-associated endothelial damage in the pathogenesis of this syndrome.

  19. Serum immunoglobulin A concentrations in normal and diseased dogs.

    Science.gov (United States)

    Day, M J; Penhale, W J

    1988-11-01

    The normal level of serum IgA in Western Australian dogs was defined by single radial immunodiffusion using sera from 100 healthy randomly selected adult crossbred animals. Serum IgA values of 185 animals from six breeds were also determined. The mean and variance of serum IgA of these groups were similar to the crossbred dogs with the exception of German shepherd dogs where these values were statistically greater. In addition, 210 dogs with a range of chronic diseases (autoimmune, hypersensitivity, pyoderma, neoplasia, demodecosis, disseminated aspergillosis) were assayed and low values recorded in five cases. In all disease groups the mean serum IgA value was significantly greater than in the crossbred group and the variance significantly greater in most of these groups. The German shepherd group were the only normal dogs with a mean and variance similar to those of the clinical series suggesting that this breed may have a primary defect in IgA metabolism.

  20. Silicosis: controversy in detection

    Directory of Open Access Journals (Sweden)

    Diemen Darwin Delgado García

    2014-03-01

    Full Text Available In many countries, the work of mining, quarrying, construction of tunnels and galleries, abrasive jet cleaning and smelting continue to present significant risks of silica exposure and silicosis epidemics still occur, even in developed countries. Patients with silicosis are particularly susceptible to opportunistic lung infections such as aspergillosis and tuberculosis. Occasionally silicosis is associated with scleroderma, systemic lupus erythematosus, nephritis and cancer. Early detection of silicosis is made by chest X-ray method, being the presence of rounded opacities the main sign of illness. However, no systematic information is available that allows use as a standard method of evaluation because their interpretation remains operator dependent both conventional radiological technique, digital and interpretation of computed tomography with high resolution.

  1. CD103+ Dendritic Cells Control Th17 Cell Function in the Lung

    Directory of Open Access Journals (Sweden)

    Teresa Zelante

    2015-09-01

    Full Text Available Th17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103+ dendritic cells (DCs would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem-cell-like population. Although several cell types may be affected by deficient IL-2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection.

  2. A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia.

    Science.gov (United States)

    Toya, Takashi; Shinohara, Akihito; Tatsuno, Keita; Seo, Sachiko; Nannya, Yasuhito; Ichikawa, Motoshi; Makimura, Koichi; Moriya, Kyoji; Kurokawa, Mineo

    2013-08-01

    Schizophyllum commune is a globally distributed basidiomycete fungus that is known as a rare cause of sinusitis, for which no prompt treatment has been established. We describe the first report of S. commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. Thirteen days after transplantation, a 23-year-old female developed maxillary and ethmoid sinusitis. The sinusitis was antimicrobial-resistant, and the sinus aspirate culture revealed white wooly mold, which was identified as S. commune by nucleotide sequencing. The patient was successfully treated with intravenous administration of liposomal amphotericin B for 2 months, followed by oral voriconazole. This report suggests the effectiveness of liposomal amphotericin B and voriconazole for S. commune infection in immunocompromised patients. Given the difficulty in distinguishing S. commune infection from aspergillosis by standard culture methods, the incidence of S. commune infection following allogeneic hematopoietic stem cell transplantation may be underestimated. Nucleotide sequencing may be useful in the diagnosis of S. commune infection.

  3. Immunodiagnosis of systemic candidiasis: mannan antigenemia detected by radioimmunoassay in experimental and human infections.

    Science.gov (United States)

    Weiner, M H; Coats-Stephen, M

    1979-12-01

    A radioimmunoassay (RIA) that detects candida mannan was developed so that immunodiagnosis of systemic candidiasis could be improved. The RIA was evaluated in an animal model of disseminated disease and in a panel of patient sera. Mannan antigenemia was detected with the RIA in 52% of 29 rabbits with systemic candidasis, but not in 60 normal rabbits or 31 rabbits with systemic aspergillosis. In an evaluation of human sera, mannan antigenemia was detected in five of 11 patients with systemic candidiasis, one of three patients with invasive gastrointestinal candidiasis, and one patient with a sustained candidemia associated with an infected intravenous catheter. Mannan was not detected in sera from 11 patients with superficial candida infections, seven patients colonized with Candida, three patients with chronic mucocutaneous candidiasis, eight patients with other systemic mycoses, or 22 normal donors. This study demonstrates the utility of this RIA for early, specific immunodiagnosis of invasive candidiasis.

  4. Diseases diagnosed in wild turkeys (Meleagris gallopavo) of the southeastern United States.

    Science.gov (United States)

    Davidson, W R; Nettles, V F; Couvillion, C E; Howerth, E W

    1985-10-01

    Diagnostic findings are presented on 139 sick or dead wild turkeys examined during the period 1972 through 1984. Turkeys originated from eight southeastern states (Alabama, Arkansas, Florida, Georgia, South Carolina, Tennessee, Virginia, West Virginia) and included 31 turkeys categorized as capture-related mortalities and 108 turkeys categorized as natural mortalities. Frequent diagnoses (greater than or equal to 10% of case accessions) in the natural mortality group were trauma, avian pox, and histomoniasis. Less frequent diagnoses (less than or equal to 4% of case accessions) included malnutrition/environmental stress syndrome, coligranuloma-like condition, crop impaction, bumblefoot, organophosphate toxicosis, infectious sinusitis, a lympho-proliferative disease, salmonellosis, aspergillosis, toxoplasmosis, crop trichomoniasis, and melorheostosis.

  5. Current status and future perspectives on molecular and serological methods in diagnostic mycology.

    Science.gov (United States)

    Lau, Anna; Chen, Sharon; Sleiman, Sue; Sorrell, Tania

    2009-11-01

    Invasive fungal infections are an important cause of infectious morbidity. Nonculture-based methods are increasingly used for rapid, accurate diagnosis to improve patient outcomes. New and existing DNA amplification platforms have high sensitivity and specificity for direct detection and identification of fungi in clinical specimens. Since laboratories are increasingly reliant on DNA sequencing for fungal identification, measures to improve sequence interpretation should support validation of reference isolates and quality control in public gene repositories. Novel technologies (e.g., isothermal and PNA FISH methods), platforms enabling high-throughput analyses (e.g., DNA microarrays and Luminex xMAP) and/or commercial PCR assays warrant further evaluation for routine diagnostic use. Notwithstanding the advantages of molecular tests, serological assays remain clinically useful for patient management. The serum Aspergillus galactomannan test has been incorporated into diagnostic algorithms of invasive aspergillosis. Both the galactomannan and the serum beta-D-glucan test have value for diagnosing infection and monitoring therapeutic response.

  6. High-attenuation mucus plugs on MDCT in a child with cystic fibrosis: potential cause and differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Morozov, Andrey; Brown, Shanaree [Indiana University Medical School, Indianapolis, IN (United States); Applegate, Kimberly E. [Riley Hospital for Children, Department of Radiology, Indiana University Medical Center, Indianapolis, IN (United States); Howenstine, Michelle [Riley Hospital for Children, Department of Pulmonology, Indiana University Medical Center, Indianapolis, IN (United States)

    2007-06-15

    High-attenuation mucus plugging is a rare finding in both adults and children. When it occurs, the field of differential diagnoses is typically quite small and includes acute hemorrhage, aspiration of radiodense material, and allergic bronchopulmonary aspergillosis (ABPA). The last of these three diagnoses is the most difficult to make, although ABPA is more commonly seen in children with cystic fibrosis (CF) or asthma. ABPA is radiographically characterized by recurrent mucus plugging, atelectasis, and central bronchiectasis. Thus far, high-attenuation mucus plugs have only been reported in adults. We report a rare case of a child with CF who had high-attenuation mucus plugs and atelectasis that raised the possibility of ABPA. We discuss the differential diagnoses of this finding and the role of multidetector CT in these children. (orig.)

  7. Fungal infection following renal transplantation.

    Science.gov (United States)

    Gallis, H A; Berman, R A; Cate, T R; Hamilton, J D; Gunnells, J C; Stickel, D L

    1975-09-01

    Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

  8. Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Garcia-Effron, Guillermo; Buzina, Walter

    2009-01-01

    and evaluate the capability of susceptibility methods to identify candin resistance. The susceptibility of C. albicans to caspofungin and anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1...... with this isolate (P > 0.05 compared to untreated control animals), while both candins completely sterilized the kidneys in animals infected with a control isolate. Disk diffusion and agar dilution methods clearly separated the two isolates. Immunohistochemistry and sequencing confirmed the presence of A. fumigatus...... without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from...

  9. [Odontogenic maxillary sinusitis based on overextension of root canal filling material].

    Science.gov (United States)

    Badarne, O; Koudstaal, M J; van Elswijk, J F A; Wolvius, E B

    2012-10-01

    In a 48-year-old woman and a 35-year-old man, a sinusitis maxillaris resulting from overextension of root canal filling material after an endodontic treatment ofa maxillary molar could be diagnosed through computed tomography. The woman complained of nasal congestion and in the man 2 radiopaque abnormalities in the maxillary sinus were discovered coincidentally. The corpora aliena were removed surgically. Root canal filling materials containing zinc oxide or hydrocortisone may cause aspergillosis of the maxillary sinus because they encountergrowth of Aspergillus species. In case ofmaxillary sinusitis, surgical removal of overextended root canal filling material from the maxillary sinus is indicated. No treatment consensus consists for cases without maxillary sinusitis symptoms.

  10. Successful Treatment of Liver Aspergilloma by Caspofungin Acetate First-Line Therapy in a Non-Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Hong-Juan Dong

    2012-09-01

    Full Text Available Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

  11. Voriconazole-induced periostitis in a patient with overlap syndromes.

    Science.gov (United States)

    Hirota, Keisho; Yasoda, Akihiro; Fujii, Toshihito; Inagaki, Nobuya

    2014-03-05

    A 52-year-old woman with overlap syndrome and interstitial pneumonia underwent immunosuppressive therapy and she was suspected to suffer from pulmonary aspergillosis. Oral voriconazole was initiated, and a rapid elevation of alkaline phosphatase (ALP) occurred after 4 weeks. After 2 months, the patient presented diffuse pain in bilateral skeletal regions, and bone scintigraphy revealed bilateral multiple areas of increased radiotracer uptake. We suspected the skeletal involvement as voriconazole-induced periostitis. Actually, the plasma fluoride level was increased. Voriconazole was replaced with itraconazole, and after 3 weeks, the patient stopped complaining of bone pain concomitant with the decrease in ALP. Voriconazole-induced periostitis is a rare condition but had previously been reported in solid organ or patients with bone marrow transplant who received a long-term voriconazole therapy. Our present case is distinctive of previous ones, because it occurred in a patient with connective tissue disease which had its rapid progression.

  12. Endothelial cells, tissue factor and infectious diseases

    Directory of Open Access Journals (Sweden)

    Lopes-Bezerra L.M.

    2003-01-01

    Full Text Available Tissue factor is a transmembrane procoagulant glycoprotein and a member of the cytokine receptor superfamily. It activates the extrinsic coagulation pathway, and induces the formation of a fibrin clot. Tissue factor is important for both normal homeostasis and the development of many thrombotic diseases. A wide variety of cells are able to synthesize and express tissue factor, including monocytes, granulocytes, platelets and endothelial cells. Tissue factor expression can be induced by cell surface components of pathogenic microorganisms, proinflammatory cytokines and membrane microparticles released from activated host cells. Tissue factor plays an important role in initiating thrombosis associated with inflammation during infection, sepsis, and organ transplant rejection. Recent findings suggest that tissue factor can also function as a receptor and thus may be important in cell signaling. The present minireview will focus on the role of tissue factor in the pathogenesis of septic shock, infectious endocarditis and invasive aspergillosis, as determined by both in vivo and in vitro models.

  13. Recognizing asthma mimics and asthma complications.

    Science.gov (United States)

    Amundson, Dennis; Seda, Gilbert; Daheshia, Massoud

    2011-10-01

    Asthma is a chronic inflammatory disorder of the airways characterized by airflow obstruction, bronchial hyperreactivity, and underlying inflammation. Two common reasons asthmatics fail standard therapy are incorrect diagnosis and failure to recognize underlying contributing factors. A correct diagnosis of asthma is of great importance to military practitioners since misdiagnosis or uncontrolled asthma affects an individual's operational readiness or determines whether one can receive a medical waiver to enlist in military service. This article presents four cases of patients with dyspnea that have conditions which mimic asthma or complicate asthma management: vocal cord dysfunction misdiagnosed as asthma, respiratory bronchiolitis interstitial lung disease mistaken as asthma, difficult-to-control asthma because of bronchiectasis and allergic bronchopulmonary aspergillosis, and difficult and fatal asthma. Asthma is contrasted to other respiratory disorders, and an outlined approach to asthma diagnosis and management is presented using the Global Initiative for Asthma guidelines.

  14. [General epidemiology of invasive fungal disease].

    Science.gov (United States)

    Pemán, Javier; Salavert, Miguel

    2012-02-01

    Invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. Candida, Cryptococcus, Pneumocystis and Aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. The latest multicentre candidaemia survey conducted in Spain, showed C. albicans as the most frequently isolated species followed by C. parapsilosis, C. glabrata, C. tropicalis and C. krusei in contrast with other European or American studies where C. glabrata was second in rank. Aspergillus spp. is the leading agent causing invasive mycoses among filamentous fungi followed by Fusarium spp., Scedosporium spp. and zygomycetes. Aspergillus fumigatus is the most common agent in invasive aspergillosis (and azole-resistant isolates have been reported) but in the last few years Aspergillus flavus, Aspergillus nidulans and Aspergillus terreus have been isolated with increasing frequency variable with geographical factors, patients' underlying conditions or previous antifungal treatments.

  15. Treatment principles for the management of mold infections.

    Science.gov (United States)

    Kontoyiannis, Dimitrios P; Lewis, Russell E

    2014-11-06

    Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal treatment options. Yet, increasing antifungal resistance, breakthrough infections with intrinsically resistant fungi, and potentially life-threatening adverse effects and drug interactions are becoming more problematic, especially with prolonged therapy. Evidence-based recommendations for treating invasive aspergillosis and mucormycosis provide excellent guidance on the initial workup and treatment of these molds, but they cannot address all of the key management issues. Herein, we discuss 10 general treatment principles in the management of invasive mold disease in immunocompromised patients and discuss how these principles can be integrated to develop an effective, individualized treatment plan.

  16. Aspergilloma of the maxillary sinus: report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ju Han; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan [School of Dentistry, Kung Hee University, Seoul (Korea, Republic of); Yu, Jae Jung [Kangdong Scared Heart Hospital, Hallym Medical Center, Seoul (Korea, Republic of)

    2010-12-15

    Aspergilloma of the paranasal sinus is a non-invasive form of aspergillosis, most often in the maxillary sinus. This case presents an 86-year-old female with aspergilloma of the left maxillary sinus. The patient's chief complaint was intermittent pain on the left maxillary first premolar area. A radiopacification of the left maxillary sinus was observed on the panoramic radiograph. Cone-beam computed tomography revealed complete radiopacification of the left maxillary sinus and scattered multiple radiopaque mass inside the lesion. Biopsy was performed under local anesthesia. On microscopic examination, numerous fungal hyphae, which branch at acute angle, were observed. The diagnosis was made as an aspergilloma based on the histopathologic examination.

  17. Intestinal candidiasis in a loggerhead sea turtle (Caretta caretta): an immunohistochemical study.

    Science.gov (United States)

    Orós, J; Arencibia, A; Fernández, L; Jensen, H E

    2004-03-01

    Post mortem examination of a juvenile loggerhead sea turtle (Caretta caretta) stranded in the Canary Islands revealed a fishing-line in the small intestine. Histologically, severe necrotic enteritis, multiple haemorrhages, and marked oedema of the intestinal submucosa were observed. Yeast cells and fungal hyphae were seen in the lamina propria of the intestinal mucosa and in the connective tissue of the submucosa. Because fungal cultures were not taken at the time of necropsy, an immunohistochemical study was performed in order to identify the fungus involved. Specific monoclonal and heterologously absorbed polyclonal antibodies served as the primary reagents for identification of aspergillosis, candidiasis, fusariosis, geotricosis, scedosporiosis, and zygomycosis, using an indirect immunofluorescence staining technique. The fungal elements were strongly stained only by a polyclonal antibody against Candida albicans and a monoclonal antibody against C. albicans. There are no known previous reports of Candida sp. causing skin disease or systemic mycotic infection in sea turtles.

  18. Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus.

    Science.gov (United States)

    Boyle, Keith B; Stephens, Len R; Hawkins, Phillip T

    2012-12-01

    Upon infection of the respiratory system with the fungus Aspergillus fumigatus various leukoctytes, in particular neutrophils, are recruited to the lung to mount an immune response. Neutrophils respond by both phagocytosing conidia and mediating extracellular killing of germinated, invasive hyphae. Of paramount importance to an appropriate immune response is the neutrophil NADPH oxidase enzyme, which mediates the production of various reactive oxygen species (ROS). This is evidenced by the acute sensitivity of both oxidase-deficient humans and mice to invasive aspergillosis. Herein we briefly review the mechanisms and functions of oxidase activation and discuss our recent work identifying at least some of the important players in hyphal-induced oxidase activation and neutrophil function. Among these we define the phosphoinositide 3-kinase enzyme and the regulatory protein Vav to be of critical importance and allude to a kinase-independent role for Syk.

  19. Advances in synthetic approach to and antifungal activity of triazoles

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Sharma

    2011-05-01

    Full Text Available Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded.

  20. Management of invasive fungal infections: a role for polyenes.

    Science.gov (United States)

    Chandrasekar, Pranatharthi

    2011-03-01

    The spectrum of invasive fungal infections (IFIs) continues to evolve with the emergence of rare and resistant fungal pathogens. Clinicians are faced with difficult diagnostic and treatment challenges in the management of immunocompromised patients at high risk of developing IFIs. Early and appropriate antifungal therapy is essential for a successful outcome when treating invasive mycoses. The armamentarium of antifungal drugs continues to grow; the three main classes of commonly administered drugs are the polyenes, azoles and echinocandins. The newer triazoles and the echinocandins have changed primary treatment options for some fungal infections, such as aspergillosis and candidiasis. However, despite their toxic potential, the oldest antifungal drugs, polyenes, remain useful in the treatment of IFIs because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients with breakthrough fungal infections. This review highlights important issues in the treatment of IFIs for consideration by clinicians.

  1. Diffuse infiltration of Aspergillus hyphae in the thyroid gland with multinodular goiter

    Directory of Open Access Journals (Sweden)

    Havva Erdem

    2011-01-01

    Full Text Available A 35-year-old woman presented with a thyroid mass, weakness and shortness of breath of 3 years duration. On physical examination, she had a diffusely enlarged thyroid gland with multiple nodules. There were no signs to suggest immune suppression. The patient farmed and raised livestock. Biochemical tests and hemogram were normal. She underwent surgery, and a histological examination of the surgical specimen revealed nodular hyperplasia. Microscopically, silver methenamine (PASM stain-positive hyphae that divided into branches at 45° and conidia were detected beside the thyroid capsule, with conidia in the cystic nodule. Moreover, ischemic changes of the thyroid tissue were observed closer to the capsule. We report a case of Aspergillosis of the thyroid of a patient who underwent surgery for a multinodular goiter.

  2. Cost-effectiveness of Voriconasole in treatment of invasive aspregillosis

    Directory of Open Access Journals (Sweden)

    N. N. Climko

    2009-01-01

    Full Text Available Invasive aspergillosis (IA is widespread infectious implication in immunodeficient patients, characterized by severe clinical manifestations and high mortality. This article presents the first case of pharmacoeconomical analysis of Voriconasole in treatment of IA compared with alternative therapies in Russia. Using mathematic modeling methods, we evalued total costs (including costs of IA treatment, clinical effectiveness and IA-related mortality in each therapy group. Obtained results showed the dominating of Voriconasole because of its high effectiveness and lower costs compared with caspofungine or amphotericine B. Total costs of therapy with Voricinasole were up to 30% lower compared with caspofungine and up to 70% lower compared with amphotericine B. Performed univariate sensitivity analysis showed that cost-effectiveness of anti-IA treatment depends mostly on clinical effectiveness of antimycotics rather than drug costs. Thus, treatment with Voriconasole is cost-effective in IA patients.

  3. Extracorporeal membrane oxygenation after living-related liver transplant.

    Science.gov (United States)

    Gedik, Ender; Çelik, Muhammet Reha; Otan, Emrah; Dişli, Olcay Murat; Erdil, Nevzat; Bayındır, Yaşar; Kutlu, Ramazan; Yılmaz, Sezai

    2015-04-01

    Various types of extracorporeal membrane oxygenation methods have been used in liver transplant operations. The main indications are portopulmonary or hepatopulmonary syndromes and other cardiorespiratory failure syndromes that are refractory to conventional therapy. There is little literature available about extracorporeal membrane oxygenation, especially after liver transplant. We describe our experience with 2 patients who had living-related liver transplant. A 69-year-old woman had refractory aspergillosis pneumonia and underwent pumpless extracorporeal lung assist therapy 4 weeks after liver transplant. An 8-month-old boy with biliary atresia underwent urgent liver transplant; he received venoarterial extracorporeal membrane oxygenation therapy on postoperative day 1. Despite our unsuccessful experience with 2 patients, extracorporeal membrane oxygenation and pumpless extracorporeal lung assist therapy for liver transplant patients may improve prognosis in selected cases.

  4. A retrospective study of postmortem findings in red-tailed hawks

    Science.gov (United States)

    Franson, J.C.; Thomas, N.J.; Smith, M.R.; Robbins, A.H.; Newman, S.; McCartin, P.C.

    1996-01-01

    We studied necropsy results from carcasses of 163 red-tailed hawks (Buteo jamaicensis) submitted to the National Wildlife Health Center from 1975 through 1992. The most frequent postmortem finding was emaciation of unknown etiology, diagnosed in 33 (20%) carcasses. Proportionally more juveniles than adults were emaciated. Evidence of non-gunshot trauma, often suggestive of collision with vehicles or structures near roadways, was found in 29 (18%) birds. Of 25 (15%) toxicoses, 20 were attributed to agricultural pesticides, including famphur (4), fenthion (3), carbofuran (2), phosphamidon (2), endrin (1), and unidentified organophosphorus compounds (8). Lead and strychnine poisoning were diagnosed in two birds each, and selenium poisoning in one. Diseases, including aspergillosis, tuberculosis, pasteurellosis, and pox, were found in 21 (13%) hawks. Gunshot and electrocution were each diagnosed in six (4%) birds, one (0.6%) was trapped, miscellaneous conditions were found in 10 (6%), and no diagnosis could be determined for 32 (19%) of the carcasses.

  5. Winter mortality of common loons in Florida coastal waters

    Science.gov (United States)

    Forrester, Donald J.; Davidson, W.R.; Lange, R.E.; Stroud, R.K.; Alexander, L.L.; Franson, J.C.; Haseltine, S.D.; Littell, R.C.; Nesbitt, S.A.

    1997-01-01

    Diagnostic findings are presented for 434 common loons (Gavia imrner) found sick or dead on Florida beaches from 1970 through 1994, primarily during the months of December to April. The most commonly recognized problem was an emaciation syndrome (66%), followed by oiling (18%), aspergillosis (7%), trauma (5%) and miscellaneous disease entities (1%). The cause-of-death for 3% of the birds was not determined. Many of the carcasses examined (n = 173) were obtained during an epizootic which occurred from January to March of 1983 in which more than 13,000 loons were estimated to have died. An emaciation syndrome, characterized by severe atrophy of pectoral muscles, loss of body fat and hemorrhagic enteritis, was the primary finding in this epizootic. It was postulated to have a complex etiologic basis involving synergistic effects and energy costs of migration, molting and replacement of flight feathers, food resource changes, salt-loading, intestinal parasitism, environmental contaminants, and inclement weather.

  6. CT and MR findings of mycotic infection of the paranasal sinus: Differentiation from sinonasal neoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kil Woo; Lim, Hyo Keun; Seo, Gwy Suk; Bae, Sang Hoon [College of Medicine, Hallyum University, Seoul (Korea, Republic of); Lee, Shin Hyung [National Medical Center, Seoul (Korea, Republic of)

    1992-03-15

    When a soft tissue mass in the bony wall of the paranasal sinus is present. It is difficult to make a distinction between tumor and inflammatory mass on CT. Fungal sinusitis may have soft tissue attenuation on the bony wall of the sinus, bony sclerosis, focal bony destruction, and calcific areas on CT. This is a report of four proven cases of fungal sinusitis, aspergillosis in 3 cases and mucormycosis in 1 case. All 4 patients had CT and one patient had MRI. On CT, bony sclerosis and destruction were well visualized in all cases. On MRI, mycetoma in the maxillary sinus was hypointense on T1 weighted images and more hypointense on T2 weighted images. Although CT appears to be the best modality for initial examination of the patient with sinusitis, the differentiation of fungal sinusitis from tumor mass or other entity may be better accomplished with MRI.

  7. Genetic regulation of conidiation in Aspergillus fumigatus:an update%烟曲霉无性产孢的调控机制研究

    Institute of Scientific and Technical Information of China (English)

    桑红; 张彩云

    2015-01-01

    Aspergillus fumigatus is one of the most important human pathogen,causing invasive aspergillosis by releasing numer?ous asexual spores (conidia).Conidia can grow on almost every microbiological culture medium under various environmental condi?tions.In this paper,the recent research progress in the genetic regulatory system which dictates conidiation in Aspergillus fumigatus was discussed.%烟曲霉是侵袭性曲霉菌病的重要病原菌之一,它通过产生无性分生孢子进行感染. 孢子的生存能力极强,能在多种微生物培养基上和环境条件下生长. 现对烟曲霉无性产孢的基因调控机制的研究进展作一阐述.

  8. Aspergillus fumigatus in Poultry

    Directory of Open Access Journals (Sweden)

    Pascal Arné

    2011-01-01

    Full Text Available Aspergillus fumigatus remains a major respiratory pathogen in birds. In poultry, infection by A. fumigatus may induce significant economic losses particularly in turkey production. A. fumigatus develops and sporulates easily in poor quality bedding or contaminated feedstuffs in indoor farm environments. Inadequate ventilation and dusty conditions increase the risk of bird exposure to aerosolized spores. Acute cases are seen in young animals following inhalation of spores, causing high morbidity and mortality. The chronic form affects older birds and looks more sporadic. The respiratory tract is the primary site of A. fumigatus development leading to severe respiratory distress and associated granulomatous airsacculitis and pneumonia. Treatments for infected poultry are nonexistent; therefore, prevention is the only way to protect poultry. Development of avian models of aspergillosis may improve our understanding of its pathogenesis, which remains poorly understood.

  9. Pharmacologic and clinical evaluation of posaconazole.

    Science.gov (United States)

    Moore, Jason N; Healy, Jason R; Kraft, Walter K

    2015-05-01

    Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be a valuable pharmaceutical agent for the treatment of life-threatening fungal infections. This review will examine the development history of posaconazole and highlight the most recent advances.

  10. Patterns of infection in patients with myelodysplastic syndromes and acute myeloid leukemia receiving azacitidine as salvage therapy. Implications for primary antifungal prophylaxis.

    Science.gov (United States)

    Falantes, Jose F; Calderón, Cristina; Márquez-Malaver, Francisco J; Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Martino, María L; Montero, Isabel; González, Jose; Parody, Rocío; Pérez-Simón, Jose A; Espigado, Ildefonso

    2014-02-01

    Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.

  11. Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) in children with cancer: A single-center experience.

    Science.gov (United States)

    Tragiannidis, Athanasios; Gombakis, Nikolaos; Papageorgiou, Maria; Hatzipantelis, Emmanuel; Papageorgiou, Theodotis; Hatzistilianou, Maria

    2016-12-01

    Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) is a devastating early or late complication of treatment for childhood cancer related with a significant morbidity and mortality. We retrospectively studied survivors of childhood cancer. Overall, 287 patients were recorded in the databases and we identified three (1.04%) with t-MDS. The primary cancer diagnoses were Langerhans cell histiocytosis (one patient) and acute lymphoblastic leukemia (ALL; two patients). The mean age of patients was 12.1 years. All patients had received systemic antifungal treatment for invasive pulmonary aspergillosis successfully treated with voriconazole and liposomal amphotericin B before diagnosis of t-MDS. Two patients (66%) remain alive after a median follow-up period of 3.5 years.

  12. Expansion of a recent class of broad-spectrum antifungal agents: the echinocandins

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2009-09-01

    Full Text Available The echinocandins show comparable efficacy in the treatment of candidemia and invasive candidiasis. Caspofungin and micafungin appear to be similarly efficacious in salvage therapy in aspergillosis; anidulafungin has excellent in vitro activity against Aspergillus species but as yet there are no sufficient clinical data for anidulafungin in this disease state. Each drug has minor advantages and disadvantages compared to the others of the same classe; however, there are large differences in the approved indications for the different drugs. The formulary selection process should consider the direct and indirect costs of the single agents; the characteristics of the patient population at risk for invasive mycosis, such as frequent use of interacting drugs and the burden of monitoring plasma drug levels of drugs; and the implications of using products for indications which have not been still approved (off-label indications.

  13. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

    Science.gov (United States)

    Savers, Amélie; Rasid, Orhan; Parlato, Marianna; Brock, Matthias; Jouvion, Gregory; Ryffel, Bernhard; Cavaillon, Jean-Marc; Eberl, Gerard; Ibrahim-Granet, Oumaïma

    2016-01-01

    Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection. PMID:27078879

  14. New methods of delivery of amphotericin B.

    Science.gov (United States)

    Schmitt, H J

    1993-11-01

    Fungal infections continue to be a major problem in the management of immunocompromised patients. Despite its formidable toxicity and treatment failures, amphotericin B is still the drug of choice for most of these infections. One strategy for reducing the toxicity of amphotericin B and thus permitting administration of higher doses is that of using less toxic formulations. Entrapping amphotericin B into liposomes or binding it to other substances reduces its toxicity to host cells, whereas the selective binding of amphotericin B to ergosterol preserves its toxicity to fungal cells. Adding fungus-specific antibodies to such liposomes may further increase the efficiency of drug targeting. The initial unpublished data from controlled clinical trials of various liposomal preparations of amphotericin B are less encouraging than anticipated, but additional trials are needed for a proper evaluation. Another strategy for improving efficacy of amphotericin B is that of bringing it directly into contact with the body sites most likely to be infected. Intranasal delivery of amphotericin B for prevention of invasive aspergillosis has been evaluated in at least three different clinical trials with conflicting results; no controlled trials are available. Prophylactic administration of low doses of amphotericin B as an aerosol was the most effective of the regimens tested in an animal model of pulmonary aspergillosis and was also judged to be effective in a clinical trial using historical controls. Independent of the route of administration, in both an animal model was various clinical studies, early administration of amphotericin B was more effective than late administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Development of a method to detect and quantify Aspergillus fumigatus conidia by quantitative PCR for environmental air samples.

    Science.gov (United States)

    McDevitt, James J; Lees, Peter S J; Merz, William G; Schwab, Kellogg J

    2004-10-01

    Exposure to Aspergillus fumigatus is linked with respiratory diseases such as asthma, invasive aspergillosis, hypersensitivity pneumonitis, and allergic bronchopulmonary aspergillosis. Molecular methods using quantitative PCR (qPCR) offer advantages over culture and optical methods for estimating human exposures to microbiological agents such as fungi. We describe an assay that uses lyticase to digest A. fumigatus conidia followed by TaqMan qPCR to quantify released DNA. This method will allow analysis of airborne A. fumigatus samples collected over extended time periods and provide a more representative assessment of chronic exposure. The method was optimized for environmental samples and incorporates: single tube sample preparation to reduce sample loss, maintain simplicity, and avoid contamination; hot start amplification to reduce non-specific primer/probe annealing; and uracil-N-glycosylase to prevent carryover contamination. An A. fumigatus internal standard was developed and used to detect PCR inhibitors potentially found in air samples. The assay detected fewer than 10 A. fumigatus conidia per qPCR reaction and quantified conidia over a 4-log10 range with high linearity (R2 >0.99) and low variability among replicate standards (CV=2.0%) in less than 4 h. The sensitivity and linearity of qPCR for conidia deposited on filters was equivalent to conidia calibration standards. A. fumigatus DNA from 8 isolates was consistently quantified using this method, while non-specific DNA from 14 common environmental fungi, including 6 other Aspergillus species, was not detected. This method provides a means of analyzing long term air samples collected on filters which may enable investigators to correlate airborne environmental A. fumigatus conidia concentrations with adverse health effects.

  16. Interpretation of guidelines for invasive pulmonary fungal disease%侵袭性肺真菌病诊治指南解读

    Institute of Scientific and Technical Information of China (English)

    张静; 何礼贤

    2011-01-01

    Invasive fungal disease is currently a common type of infections in daily clinical practice. It is acknowledged as a major cause of death in patients with immunosuppression. Three leading types of invasive fungal disease are aspergillosis, cryptococcosis and candidiasis. Chinese Respiratory Society and the editorial committee of Chinese Journal of Internal Medicine have released guidelines and consensus on the diagnosis and treatment of invasive fungal diseases. Infectious Diseases Society of America and American Thoracic Society also updated their relevant guidelines and statements recently. Based on these guidelines and statements, this article discussed the definition and grading diagnosis for invasive pulmonary fungal disease. The diagnosis, therapeutic principles, drug selection and course of treatment of invasive pulmonary aspergillosis, cryptococcosis and candidiasis were also described respectively.%侵袭性肺真菌病日益成为临床常见的感染类型以及免疫抑制患者的重要死亡原因.曲霉、隐球菌和念珠菌是导致侵袭性肺真菌病的主要病原体.本文结合我国编委会、中华医学会呼吸病学分会以及美国感染病学会、美国胸科学会等学术团体最新发布的指南和共识讨论侵袭性肺真菌病的分级诊断及其适用范围,分别探讨侵袭性肺曲霉病、隐球菌病和念珠菌病的诊断、治疗原则、药物选择及疗程.

  17. Misidentification of Aspergillus nomius and Aspergillus tamarii as Aspergillus flavus: characterization by internal transcribed spacer, β-Tubulin, and calmodulin gene sequencing, metabolic fingerprinting, and matrix-assisted laser desorption ionization-time of flight mass spectrometry.

    Science.gov (United States)

    Tam, Emily W T; Chen, Jonathan H K; Lau, Eunice C L; Ngan, Antonio H Y; Fung, Kitty S C; Lee, Kim-Chung; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2014-04-01

    Aspergillus nomius and Aspergillus tamarii are Aspergillus species that phenotypically resemble Aspergillus flavus. In the last decade, a number of case reports have identified A. nomius and A. tamarii as causes of human infections. In this study, using an internal transcribed spacer, β-tubulin, and calmodulin gene sequencing, only 8 of 11 clinical isolates reported as A. flavus in our clinical microbiology laboratory by phenotypic methods were identified as A. flavus. The other three isolates were A. nomius (n = 2) or A. tamarii (n = 1). The results corresponded with those of metabolic fingerprinting, in which the A. flavus, A. nomius, and A. tamarii strains were separated into three clusters based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC MS) analysis. The first two patients with A. nomius infections had invasive aspergillosis and chronic cavitary and fibrosing pulmonary and pleural aspergillosis, respectively, whereas the third patient had A. tamarii colonization of the airway. Identification of the 11 clinical isolates and three reference strains by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) showed that only six of the nine strains of A. flavus were identified correctly. None of the strains of A. nomius and A. tamarii was correctly identified. β-Tubulin or the calmodulin gene should be the gene target of choice for identifying A. flavus, A. nomius, and A. tamarii. To improve the usefulness of MALDI-TOF MS, the number of strains for each species in MALDI-TOF MS databases should be expanded to cover intraspecies variability.

  18. High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

    Science.gov (United States)

    Nabili, Mojtaba; Shokohi, Tahereh; Moazeni, Maryam; Khodavaisy, Sadegh; Aliyali, Masoud; Badiee, Parisa; Zarrinfar, Hossein; Hagen, Ferry; Badali, Hamid

    2016-06-01

    Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the β-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR34/L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

  19. Non-toxic agarose/gelatin-based microencapsulation system containing gallic acid for antifungal application.

    Science.gov (United States)

    Lam, P-L; Gambari, R; Kok, S H-L; Lam, K-H; Tang, J C-O; Bian, Z-X; Lee, K K-H; Chui, C-H

    2015-02-01

    Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.

  20. Imaging of rhinosinusitis and its complications: plain film, CT, and MRI.

    Science.gov (United States)

    Mafee, Mahmood F; Tran, Brandon H; Chapa, Ajay R

    2006-06-01

    Conventional plain-film radiography may be used as a screening method for various pathological conditions of the sinonasal cavities. However, CT scanning remains the study of choice for the imaging evaluation of acute and chronic inflammatory diseases of sinonasal cavities. MRI is superior to CT in differentiating inflammatory conditions from neoplastic processes. The most common complications of rhinosinusitis in children occur in the orbit. The information obtained from the CT scan and MRI, together with clinical findings, may be the best guidelines for clinical management and the mode of treatment. Although intracranial complications of sinusitis are relatively rare, prompt recognition of these disease states is important to prevent permanent neurological deficit or fatality. It is prudent to obtain MRI of the sinuses, orbits, and brain whenever extensive or multiple complications of sinusitis are suspected, in addition to CT scanning. Chronic rhinosinusitis is a clinical diagnosis, confirmed and staged with the CT scan of sinonasal cavities. Chronic inflammatory disease is often associated with mucosal thickening and sclerosis of the bone, particularly within the sinuses. Chronic extramucosal fungal sinusitis develops as a saprophytic growth in retained secretions in a sinus cavity. The imaging manifestations of chronic mycotic rhinosinusitis may be nonspecific or highly suggestive of the presence of fungal infection. The presence of diffuse increased attenuation within the paranasal sinuses and nasal cavity should be considered as chronic allergic hypersensitivity aspergillosis (chronic noninvasive aspergillosis) or chronic hyperplastic sinusitis and polyposis associated with desiccated, retained mucosal secretions. The MRI characteristics of fungal sinusitis depend on the stage of the disease.