WorldWideScience

Sample records for aspergillosis

  1. [Cerebral aspergillosis].

    Science.gov (United States)

    Tattevin, P; Jauréguiberry, S; Gangneux, J-P

    2004-05-01

    The brain is almost always a localization of invasive aspergillosis, after hematogenous spread from pulmonary aspergillosis. Brain aspergilosis is not rare and is one of the worst prognosis factors of invasive aspergillosis. The incidence of this severe mycosis is currently on the rise due to the development of major immunosuppressive treatments. Brain aspergillosis is noteworthy for its vascular tropism, leading to infectious cerebral vasculitis, mainly involving thalamoperforating and lenticulostriate arteries, with a high frequency of thalamic or basal nuclei lesions. Extra-neurologic features that suggest this diagnosis are: i) risk factors for invasive aspergillosis (major or prolonged neutropenia, hematologic malignancies, prolonged corticosteroid treatment, bone marrow or solid organ transplant, AIDS); ii) persistent fever not responding to presumptive antibacterial treatment; iii) respiratory signs (brain aspergillosis is associated with pulmonary aspergillosis in 80 to 95 p. 100 of cases). Perspectives. Two recent major improvements in brain aspergillosis management must be outlined: i) for diagnostic purposes, the development of testing for Aspergillus antigenemia (a non-invasive procedure with good diagnostic value for invasive aspergillosis); ii) for therapeutic purposes, the demonstration that voriconazole is better than amphotericin B in terms of clinical response, tolerance and survival, for all types of invasive aspergillosis, the benefit being probably even greater in case of brain aspergillosis because of the good diffusion of voriconazole into the central nervous system. Brain aspergillosis is a severe emerging opportunistic infection for which diagnostic and therapeutic tools have recently improved. Thus, this diagnostic must be suspected early, especially in the immunocompromised patient, in the event of respiratory symptoms and when the brain lesions are localized in the central nuclei and the thalamus.

  2. Bronchopulmonary aspergillosis

    International Nuclear Information System (INIS)

    Strepetova, T.N.; Solov'eva, T.N.

    1993-01-01

    Case histories of 510 patients operated on for chronic destructive puimonary tuberculosis and mycetoma are analyzed, as are the findings of examinations of 56 patients with cavitary forms of lung involvement. X-ray and tomographic examinations were carried out according to the routine methods. Blood serum IgC antibodies to aspergillosis antigen were determined in the enzyme immunoassay. An X-ray symptom of the foamy nuclear (septal) structure of pulmonary shifts was revealed, that represents a sort of a pathologic tissue response in one of bronchopulmonary aspergillosis forms

  3. Allergic Bronchopulmonary Aspergillosis

    Directory of Open Access Journals (Sweden)

    Juan Carlos Fernández de Córdova-Aguirre

    2014-03-01

    Full Text Available Allergic bronchopulmonary aspergillosis is a slowly progressive disease, caused by the fungus Aspergillus fumigatus hypersensitivity when it is found in the airway. It usually affects asthmatics and patients with cystic brosis. We report the case of a 20-year-old male patient, student, farmer and rancher with chronic respiratory disease. The diagnosis of allergic bronchopulmonary aspergillosis was made on the basis of the clinical symptoms and complementary studies.

  4. 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.

  5. CT findings of pulmonary aspergillosis

    International Nuclear Information System (INIS)

    Cheon, Jung Eun; Im, Jung Gi; Goo, Jin Mo; Kim, Hong Dae; Han, Man Chung

    1995-01-01

    The fungus aspergillus can cause a variety of pulmonary disorders. Aspergilloma is a noninvasive aspergillus colonization of virtually any type of preexisting pulmonary cavity or cystic space. Invasive pulmonary aspergillosis is serious, usually fatal infection in patients being treated with immunosuppressants or who have chronic debilitating disease. Allergic bronchopulmonary aspergillosis is characterized clinically by asthma, blood and sputum eosinophilia and positive immunologic reaction to aspergillus antigen. Awareness of the radiographic and CT findings of pulmonary aspergillosis is important in making the diagnosis of aspergillus-caused pulmonary disorders. In this pictorial essay, we illustrated various radiological findings of pulmonary aspergillosis focused on CT findings correlated with gross pathologic specimens

  6. [Invasive nosocomial pulmonary aspergillosis].

    Science.gov (United States)

    Germaud, P; Haloun, A

    2001-04-01

    Immunodepressed patients, particularly those with neutropenia or bone marrow or organ grafts, are at risk of developing nosocomial invasive pulmonary aspergilosis. The favoring factors, early diagnostic criteria and curative treatment protocols are well known. Prognosis remains however quite severe with a death rate above 50%. Preventive measures are required for the treatment of these high-risk patients and epidemiology surveillance is needed in case of aspergillosis acquired in the hospital.

  7. Allergic Bronchopulmonary Aspergillosis

    Directory of Open Access Journals (Sweden)

    Michael C. Tracy

    2016-06-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA, a progressive fungal allergic lung disease, is a common complication of asthma or cystic fibrosis. Although ABPA has been recognized since the 1950s, recent research has underscored the importance of Th2 immune deviation and granulocyte activation in its pathogenesis. There is also strong evidence of widespread under-diagnosis due to the complexity and lack of standardization of diagnostic criteria. Treatment has long focused on downregulation of the inflammatory response with prolonged courses of oral glucocorticosteroids, but more recently concerns with steroid toxicity and availability of new treatment modalities has led to trials of oral azoles, inhaled amphotericin, pulse intravenous steroids, and subcutaneously-injected anti-IgE monoclonal antibody omalizumab, all of which show evidence of efficacy and reduced toxicity.

  8. [Invasive pulmonary aspergillosis].

    Science.gov (United States)

    Blanchard, E; Gabriel, F; Jeanne-Leroyer, C; Servant, V; Dumas, P-Y

    2018-02-01

    Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in a wide range of patients. Early recognition and diagnosis have become a major focus in improving the management and outcomes of this life-threatening disease. IPA typically occurs during a period of severe and prolonged neutropenia. However, solid organ transplant recipients, patients under immunosuppressive therapy or hospitalized in intensive care units are also at risk. The diagnosis is suspected in the presence of a combination of clinical, biological and CT scan evidence. The microbiological diagnostic strategy should be adapted to the patient's profile. Conventional methods with culture and species identification remain the standard but early diagnosis has been improved by the use of biomarkers such as galactomannan antigen in serum or in bronchoalveolar lavage. The epidemiology of IPA should change with the increased use of antifungal prophylactic regimens and the arrival of targeted therapies. Other microbiological tools, such as PCR and other biomarkers, are currently being assessed. IPA must be considered in a wide range of patients. Its prognosis remains poor despite progress in the microbiological diagnosis and therapeutic management. Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  9. Aspergillosis of the sphenoid sinus.

    Science.gov (United States)

    Miglets, A W; Saunders, W H; Ayers, L

    1978-01-01

    Three of the four previously described patients with isolated aspergilosis of the sphenois sinus died, owing to intracranial extension of the infection. The case reports of two patients with sphenoid aspergillosis are presented in which surgical exteriorization and aeration of the involved sinus was curative.

  10. Radiologic aspects in invasive aspergillosis

    International Nuclear Information System (INIS)

    Feger, C.; Kerviler, E. de; Zagdanski, A.M.; Attal, P.; Cyna-Gorse, F.; Frija, J.; Laval-Jeantet, M.

    1994-01-01

    Invasive aspergillosis is a life-threatening illness, whose diagnosis is difficult: clinical signs are indeed not specific, and biological and mycological exams are not always conclusive. Radiological exams are essential for the diagnosis of this disease allowing to start an early intensive appropriate therapy. According to the literature and to their own experience the authors report the main radiological patterns with emphasis on the pulmonary and cerebral affections. (authors). 26 refs., 5 figs

  11. Invasive Aspergillosis in Hematological Patients.

    Science.gov (United States)

    Kimura, Shun-Ichi

    2016-01-01

    Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.

  12. Aspergillosis

    Science.gov (United States)

    ... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations ...

  13. Aspergillosis

    Science.gov (United States)

    ... cancers. Your doctor might do a variety of tests to make the diagnosis, including a chest x-ray, CT scan of the lungs, and an examination of tissues for signs of the fungus. Treatment is with antifungal drugs. If you have ABPA, you may also take ...

  14. Aspergillosis

    Science.gov (United States)

    ... Testing Treatment & Outcomes Health Professionals Statistics More Resources Candidiasis Candida infections of the mouth, throat, and esophagus Vaginal candidiasis Invasive candidiasis Definition Symptoms Risk & Prevention Sources Diagnosis ...

  15. TOO MANY MOULDY JOINTS – MARIJUANA AND CHRONIC PULMONARY ASPERGILLOSIS

    Directory of Open Access Journals (Sweden)

    Youssef Gargani

    2011-01-01

    Full Text Available Chronic pulmonary aspergillosis is a progressive debilitating disease with multiple underlying pulmonary diseases described. Here we report the association of chronic pulmonary aspergillosis and long term marijuana smoking in 2 patients and review the literature related to invasive and allergic aspergillosis

  16. TOO MANY MOULDY JOINTS – MARIJUANA AND CHRONIC PULMONARY ASPERGILLOSIS

    Directory of Open Access Journals (Sweden)

    Youssef Gargani

    2011-01-01

    Full Text Available Chronic pulmonary aspergillosis is a progressive debilitating disease with multiple underlying pulmonary diseases described. Here we report the association of chronic pulmonary aspergillosis and long term marijuana smoking in 2 patients and review the literature related to invasive and allergic aspergillosis

  17. Pictorial essay: Allergic bronchopulmonary aspergillosis

    International Nuclear Information System (INIS)

    Agarwal, Ritesh; Khan, Ajmal; Garg, Mandeep; Aggarwal, Ashutosh N; Gupta, Dheeraj

    2011-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is the best-known allergic manifestation of Aspergillus-related hypersensitivity pulmonary disorders. Most patients present with poorly controlled asthma, and the diagnosis can be made on the basis of a combination of clinical, immunological, and radiological findings. The chest radiographic findings are generally nonspecific, although the manifestations of mucoid impaction of the bronchi suggest a diagnosis of ABPA. High-resolution CT scan (HRCT) of the chest has replaced bronchography as the initial investigation of choice in ABPA. HRCT of the chest can be normal in almost one-third of the patients, and at this stage it is referred to as serologic ABPA (ABPA-S). The importance of central bronchiectasis (CB) as a specific finding in ABPA is debatable, as almost 40% of the lobes are involved by peripheral bronchiectasis. High-attenuation mucus (HAM), encountered in 20% of patients with ABPA, is pathognomonic of ABPA. ABPA should be classified based on the presence or absence of HAM as ABPA-S (mild), ABPA-CB (moderate), and ABPA-CB-HAM (severe), as this classification not only reflects immunological severity but also predicts the risk of recurrent relapses

  18. Pictorial essay: Allergic bronchopulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    Ritesh Agarwal

    2011-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is the best-known allergic manifestation of Aspergillus-related hypersensitivity pulmonary disorders. Most patients present with poorly controlled asthma, and the diagnosis can be made on the basis of a combination of clinical, immunological, and radiological findings. The chest radiographic findings are generally nonspecific, although the manifestations of mucoid impaction of the bronchi suggest a diagnosis of ABPA. High-resolution CT scan (HRCT of the chest has replaced bronchography as the initial investigation of choice in ABPA. HRCT of the chest can be normal in almost one-third of the patients, and at this stage it is referred to as serologic ABPA (ABPA-S. The importance of central bronchiectasis (CB as a specific finding in ABPA is debatable, as almost 40% of the lobes are involved by peripheral bronchiectasis. High-attenuation mucus (HAM, encountered in 20% of patients with ABPA, is pathognomonic of ABPA. ABPA should be classified based on the presence or absence of HAM as ABPA-S (mild, ABPA-CB (moderate, and ABPA-CB-HAM (severe, as this classification not only reflects immunological severity but also predicts the risk of recurrent relapses.

  19. 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.

  20. Invasive Aspergillosis Mimicking Metastatic Lung Cancer

    Directory of Open Access Journals (Sweden)

    Michiel J. E. G. W. Vanfleteren

    2018-06-01

    Full Text Available In a patient with a medical history of cancer, the most probable diagnosis of an 18FDG-avid pulmonary mass combined with intracranial abnormalities on brain imaging is metastasized cancer. However, sometimes a differential diagnosis with an infectious cause such as aspergillosis can be very challenging as both cancer and infection are sometimes difficult to distinguish. Pulmonary aspergillosis can present as an infectious pseudotumour with clinical and imaging characteristics mimicking lung cancer. Even in the presence of cerebral lesions, radiological appearance of abscesses can look like brain metastasis. These similarities can cause significant diagnostic difficulties with a subsequent therapeutic delay and a potential adverse outcome. Awareness of this infectious disease that can mimic lung cancer, even in an immunocompetent patient, is important. We report a case of a 65-year-old woman with pulmonary aspergillosis disseminated to the brain mimicking metastatic lung cancer.

  1. [The different manifestations of pulmonary aspergillosis: multidetector computed tomography findings].

    Science.gov (United States)

    Koren Fernández, L; Alonso Charterina, S; Alcalá-Galiano Rubio, A; Sánchez Nistal, M A

    2014-01-01

    Pulmonary aspergillosis is a fungal infection usually caused by inhaling Aspergillus fumigatus spores. However, when we talk about aspergillosis, we normally refer to the spectrum of clinical and radiological findings that depend directly on the patient's immune status, on the prior existence of lung disease, and on the virulence of the infective organism. There are four types of pulmonary aspergillosis (aspergilloma, allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and invasive aspergillosis), and each type has its own distinct radiologic findings. We review the signs of pulmonary aspergillosis on multidetector computed tomography and we correlate them with patients' symptoms and immune responses. Likewise, we discuss the differential diagnoses. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

  2. Invasive aspergillosis in paediatric oncology patients.

    Science.gov (United States)

    Muda, Z; Ibrahim, H; Abdulrahman, E J; Menon, B S; Zahari, Z; Zaleha, A M; Talib, A

    2008-12-01

    Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

  3. Semiinvasive Aspergillosis Case Coexisting to Metastatic Renal Cell Cancer

    Directory of Open Access Journals (Sweden)

    Hatice Kilic

    2013-10-01

    Full Text Available Chronic necrotizing pulmonary aspergillosis (CNPA is defined as an cavity or mass lesion in the lung due to invasion of lung tissue by a fungus of the Aspergillosis species. It was described also as semiinvasive aspergillosis. Semiinvasive pulmonary aspergillosis is generally seen in patients with primer immunocompromised and it can be fatal in the event of late diagnose. We present 60 years old patient who had had renal cell cancer admitted to hospital with metastatic nodules in his chest X-ray and Thorax computed tomography. We have seen yellow colour of bronchial secretion in his bronchoscopy. Multipl mantar hyphae by A. Fumigatus was detected in his bronchial lavage cytology. Itrakonazol was administred to this patient. We review to this cases due to a semiinvasive aspergillosis was detected randomly when this case who had not both symptomatic and clinical sign by Aspergillosis is investigated.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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. (orig.) [de

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. CT findings in rhinocerebral mucormycosis and aspergillosis

    International Nuclear Information System (INIS)

    Kim, Dong Ik; Suh, Jung Ho; Lee, Jong Doo; Lee, Kyu Chang

    1986-01-01

    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.

  7. Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia

    Directory of Open Access Journals (Sweden)

    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.

  8. Cutaneous Aspergillosis at the site of ulceration from radiation

    International Nuclear Information System (INIS)

    Matsuo, Fumiko; Okabe, Tomohiro.

    1979-01-01

    A 52-year-old woman with cutaneous aspergillosis caused by Aspergillus nidulans was observed. The infection developed at the site of ulceration from radiation, which occurred after operation and radiotherapy for breast cancer. In cases of cutaneous aspergillosis, saprophytic lesions can be seen. (Nishio, M.)

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

    Directory of Open Access Journals (Sweden)

    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.

  10. CT in childhood allergic bronchopulmonary aspergillosis

    International Nuclear Information System (INIS)

    Shah, A.; Bhagat, R.; Panchal, N.; Pant, C.S.

    1992-01-01

    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.)

  11. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    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.

  12. ASPERGILLOSIS OF MANDIBLE : A RARE CASE OF OSTEOMYELITIS

    OpenAIRE

    ÖZTÜRK, Nurdan; ERSOY, Burak; SÖNMEZ, Ahmet; ÇELEBİLER, Özhan; NUMANOĞLU, Ayhan

    2007-01-01

    Aspergillus species are saprophyticus fungi which may be the cause of infection predominantly in immunocompromised hosts. Aspergillosis is usually manifested in the respiratory system and bone involvement is rarely encountered. Osteomyelitis of the mandible with aspergillus species has been reported in only two cases in the literature. Treatment mainly consists of antimicrobial therapy in combination with surgery. We report a case of aspergillosis of the mandible in a patient who was under im...

  13. Allergic Broncho Pulmonary Aspergillosis Complicated by Nocardiosis

    Directory of Open Access Journals (Sweden)

    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.

  14. Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  15. Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis

    International Nuclear Information System (INIS)

    Hoffer, F.A.; Gow, K.; Davidoff, A.; Flynn, P.M.

    2001-01-01

    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.)

  16. Inflammation in aspergillosis: the good, the bad, and the therapeutic.

    Science.gov (United States)

    Carvalho, Agostinho; Cunha, Cristina; Iannitti, Rossana G; De Luca, Antonella; Giovannini, Gloria; Bistoni, Francesco; Romani, Luigina

    2012-12-01

    Aspergillosis includes a spectrum of diseases caused by different Aspergillus spp. New insights into the cellular and molecular mechanisms of resistance and immune tolerance to the fungus in infection and allergy have been obtained in experimental settings. The fact that virulence factors, traditionally viewed as fungal attributes, are contingent upon microbial adaptation to various environmental stresses encountered in the human host implies that the host and fungus are jointly responsible for pathogenicity. Ultimately, despite the occurrence of severe aspergillosis in immunocompromised patients, clinical evidence indicates that aspergillosis also occurs in the setting of a heightened inflammatory response, in which immunity occurs at the expense of host damage and pathogen eradication. Thus, targeting pathogenicity rather than microbial growth, tolerance rather than resistance mechanisms of defense may pave the way to targeted anti-inflammatory strategies in difficult-to-treat patients. The challenge now is to translate promising results from experimental models to the clinic. © 2012 New York Academy of Sciences.

  17. Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series

    Directory of Open Access Journals (Sweden)

    Poynard Thierry

    2007-01-01

    Full Text Available Abstract Background Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. Case presentation We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment. Conclusion Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

  18. Pulmonary aspergillosis in immunosuppressed patients with haematological malignancies.

    Science.gov (United States)

    Spearing, R L; Pamphilon, D H; Prentice, A G

    1986-06-01

    Invasive pulmonary aspergillosis as a cause of mortality and morbidity in patients with haematological malignancies is becoming more common. Predisposing factors are powerful immunosuppressive chemotherapy, neutropenia and synergistic combinations of antibiotics of great potency and wide spectrum of activity. Clinical and radiological signs are heterogeneous, sometimes misleading and often absent. Treatment is often empirical on suspicion alone. Amphotericin B is the only effective drug but it has marked toxicity, mainly renal. Infection is usually fatal without adequate treatment. This paper describes eight cases of invasive pulmonary aspergillosis seen in one centre in two years, reviews the literature and assesses associated problems.

  19. Aspergillosis of the sphenoid sinus simulating a pituitary tumor

    Energy Technology Data Exchange (ETDEWEB)

    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.).

  20. Prevalence of aspergillosis in chronic lung diseases

    Directory of Open Access Journals (Sweden)

    Shahid M

    2001-01-01

    Full Text Available Eighty eight patients of chronic lung diseases (CLD attending TB and Chest department of J.N. Medical college Hospital were studied to find out the prevalence of Aspergillus in Broncho-alveolar Lavage (BAL and anti- aspergillus antibodies in their sera. Direct microscopy and fungal culture of BAL was done. Antibodies were studied by immunodiffusion (ID and Enzyme linked immunosorbent assay (ELISA. Dot blot assay for anti-aspergillus antibodies was also performed in sera of patients which were either positive by ID or by ELISA. Aspergillus was isolated in culture from 13(14.7% cases of CLD, while, 30.6% cases showed anti-aspergillus antibodies by serological methods. Aspergillus fumigatus was the predominant species isolated. 17(19.3% cases of CLD showed antibody against Aspergillus by ID, 22(25% by ELISA, while 19 of 27 seropositive cases also showed positive results by Dot Blot assay. In cases of bronchogenic carcinoma and pulmonary tuberculosis, anti-aspergillus antibodies were detected equally by ID and ELISA in 21.42% and 21.05% cases respectively. In bronchial asthma, the antibodies could be detected in 60% cases by ELISA, while, in only 10% cases by ID. ELISA was found more sensitive than ID for detection of anti-aspergillus antibodies. The sensitivity of Dot Blot lies some what between ID and ELISA. It is concluded that prevalence of Aspergillosis is quite high in chronic lung diseases, culture and serological test should be performed in conjunction and more than one type of serological tests should be performed to establish the diagnosis.

  1. Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.

    Science.gov (United States)

    Kim, Sung-Han; Kim, Mi Young; Hong, Sun In; Jung, Jiwon; Lee, Hyun Joo; Yun, Sung-Cheol; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

    2015-07-01

    Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    OpenAIRE

    Benjamin Arthurs, MD; Kathy Wunderle, MD; Maylee Hsu, MD; Suil Kim, MD, PhD

    2017-01-01

    We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  3. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Arthurs, MD

    2017-01-01

    Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  4. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia.

    Science.gov (United States)

    Arthurs, Benjamin; Wunderle, Kathy; Hsu, Maylee; Kim, Suil

    2017-01-01

    We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus . Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  5. 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...

  6. Allergic bronchopulmonary aspergillosis as a cause of bronchial ...

    African Journals Online (AJOL)

    Background: Allergic bronchopulmonary aspergillosis (ABPA) occurs in patients with asthma and cystic fibrosis. When aspergillus fumigatus spores are inhaled they grow in bronchial mucous as hyphae. It occurs in non immunocompromised patients and belongs to the hypersensitivity disorders induced by Aspergillus.

  7. Sino-orbital aspergillosis with central nervous system complication ...

    African Journals Online (AJOL)

    A central nervous system (CNS) complication (cerebral abscess) was diagnosed following seizures in the patient. The patient died a few days later. Conclusion: The diagnosis of aspergillosis of the orbit was only made from fungal culture after the patient's death. It requires a high index of suspicion to make a diagnosis of ...

  8. 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.

  9. Clinical utility and development of biomarkers in invasive aspergillosis.

    Science.gov (United States)

    Patterson, Thomas F

    2011-01-01

    The diagnosis of invasive aspergillosis remains very difficult, and there are limited treatment options for the disease. Pre-clinical models have been used to evaluate the diagnosis and treatment of Aspergillus infection and to assess the pathogenicity and virulence of the organism. Extensive efforts in Aspergillus research have significantly expanded the genomic information about this microorganism. The standardization of animal models of invasive aspergillosis can be used to enhance the evaluation of genomic information about the organism to improve the diagnosis and treatment of invasive aspergillosis. One approach to this process has been the award of a contract by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to establish and standardize animal models of invasive aspergillosis for the development of new diagnostic technologies for both pulmonary and disseminated Aspergillus infection. This work utilizes molecular approaches for the genetic manipulation of Aspergillus strains that can be tested in animal-model systems to establish new diagnostic targets and tools. Studies have evaluated the performance characteristics of assays for cell-wall antigens of Aspergillus including galactomannan and beta-D-glucan, as well as for DNA targets in the organism, through PCR. New targets, such as proteomic and genomic approaches, and novel detection methods, such as point-of-care lateral-flow devices, have also been evaluated. The goal of this paper is to provide a framework for evaluating genomic targets in animal models to improve the diagnosis and treatment of invasive aspergillosis toward ultimately improving the outcomes for patients with this frequently fatal infection.

  10. Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

    International Nuclear Information System (INIS)

    Guermazi, Ali; Gluckman, Eliane; Tabti, Bachir; Miaux, Yves

    2003-01-01

    Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

  11. Performance of Aspergillus PCR in cerebrospinal fluid for the diagnosis of cerebral aspergillosis.

    Science.gov (United States)

    Imbert, S; Brossas, J-Y; Palous, M; Joly, I; Meyer, I; Fekkar, A

    2017-11-01

    Cerebral aspergillosis is a rare but often fatal form of invasive aspergillosis that remains difficult to diagnose. The literature has shown the value of Aspergillus PCR in blood-derived samples for the diagnosis of invasive aspergillosis but provides far less information for cerebrospinal fluid (CSF) in cerebral aspergillosis. Here, we evaluated the usefulness of an Aspergillus PCR assay performed on CSF for the diagnosis of cerebral aspergillosis. This retrospective study involved 72 patients with suspected cerebral aspergillosis for a total of 88 CSF samples in whom CSF Aspergillus PCR was performed. Seventeen patients had proven/probable invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, including 12 cases of proven/probable cerebral aspergillosis. Aspergillus PCR in CSF was positive in nine of the twelve patients with cerebral aspergillosis, i.e. 75% sensitivity. In contrast, CSF culture was positive for Aspergillus in only two patients. In the non-cerebral aspergillosis group (60 patients), PCR was positive in one patient, i.e. 98.3% specificity. In this particular population of high-risk patients with suspicion of cerebral aspergillosis, the disease incidence was 16.7%. Therefore, the positive and negative predictive values of PCR were 90% and 95.2%, respectively. The results of this study indicate that Aspergillus PCR in CSF is an interesting tool that may eliminate the need for cerebral biopsy in patients with suspected cerebral aspergillosis. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Aspergillosis in the common sea fan Gorgonia ventalina: isolation of waterborne hyphae and spores.

    Science.gov (United States)

    Troeger, Victoria J; Sammarco, Paul W; Caruso, John H

    2014-07-03

    The octocoral disease aspergillosis is caused by the terrestrial fungus Aspergillus sydowii. The possibility of secondary (horizontal) transmission of aspergillosis among common sea fans Gorgonia ventalina would require waterborne transmission of hyphae and/or spores. A laboratory filtration experiment confirmed that fungal hyphae and spores were shed into the water by infected fans. This suggests that secondary infection might be possible in this species. It remains to be determined whether healthy fans actually develop aspergillosis after contact with hyphae-laden water.

  13. 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.

  14. 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.

  15. Aspergillosis in Larus cachinnans micaellis: survey of eight cases.

    Science.gov (United States)

    Nardoni, Simona; Ceccherelli, Renato; Rossi, Giacomo; Mancianti, Francesca

    2006-05-01

    Avian aspergillosis is reported in several avian species, with Aspergillus fumigatus as the main aetiological agent. Predisposing factors such as starvation, thermal stress, migratory stress, primary infectious disease or toxicosis may play a role. Eight cases of disseminated aspergillosis in free ranging seagulls sheltered at C.R.U.M.A. (Centro Recupero Uccelli Marini e Acquatici, Livorno, Italy) with different clinical histories are presented. The infection was demonstrated by cultural and histological methods from lesions of all birds, and the presence of airborne A. fumigatus viable elements ranging from 450 to 525 CFU/m(3) inside and outside the shelter by means of a surface air sampler (SAS) Super-90 was also assessed. The role of this fungal species as an opportunistic factor in the captivity of seagulls is considered and some control measures, such as a clean and stress free environment and the use of antifungal drugs are suggested.

  16. 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.)

  17. 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.

  18. Skin aspergillosis induced in the region of radiation ulcer

    International Nuclear Information System (INIS)

    Niimura, Yumiko; Nakauchi, Yohichi; Ushijima, Tsugako

    1980-01-01

    A case of skin aspergillosis in the region of radiation ulcer which was caused by Aspergillus fumigatus was reported. The patient was a 51 year-old man. This fungal infection was probably induced by a local factor, that is, chronic radiation ulcer. Histological findings suggested that Aspergillus fumigatus which increased saprophytically at the beginning possessed parasitic nature gradually, invaded into connective tissues in the deep layer of true skin, and made radiation ulcer more intractable. (Tsunoda, M.)

  19. 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...

  20. 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.

  1. Micafungin in the treatment of invasive candidiasis and invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Nathan P Wiederhold

    2009-01-01

    Full Text Available Nathan P Wiederhold1, Jason M Cota2, Christopher R Frei11University of Texas at Austin College of Pharmacy, Austin, Texas, USA; 2University of the Incarnate Word Feik School of Pharmacy, San Antonio, Texas, USAAbstract: Micafungin is an echinocandin antifungal agent available for clinical use in Japan, Europe, and the United States. Through inhibition of β-1,3-glucan production, an essential component of the fungal cell wall, micafungin exhibits potent antifungal activity against key pathogenic fungi, including Candida and Aspergillus species, while contributing minimal toxicity to mammalian cells. This activity is maintained against polyene and azole-resistant isolates. Pharmacokinetic and pharmacodynamic studies have demonstrated linear kinetics both in adults and children with concentration-dependent activity observed both in vitro and in vivo. Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations. This review will focus on the pharmacology, clinical microbiology, mechanisms of resistance, safety, and clinical efficacy of micafungin in the treatment of invasive candidiasis and invasive aspergillosis.Keywords: micafungin, echinocandin, Candida, Aspergillus, invasive candidiasis, invasive aspergillosis

  2. Resolution of orbitocerebral aspergillosis during combination treatment with voriconazole and amphotericin plus adjunctive cytokine therapy.

    Science.gov (United States)

    Bethell, Delia; Hall, Georgina; Goodman, T Robin; Klein, Nigel; Pollard, Andrew J

    2004-05-01

    Orbitocerebral aspergillosis has a very high fatality rate and cure is unusual. We describe the successful management of a child with cereberal aspergillosis who had a dramatic response to therapy with a combination of liposomal amphotericin and voriconazole with adjunctive cytokine therapy during immunosuppresive chemotherapy for acute lymphoblastic leukaemia.

  3. Aspergillus felis sp nov., an Emerging Agent of Invasive Aspergillosis in Humans, Cats, and Dogs

    NARCIS (Netherlands)

    Barrs, Vanessa R.; van Doorn, Tineke M.; Houbraken, Jos; Kidd, Sarah E.; Martin, Patricia; Pinheiro, Maria Dolores; Richardson, Malcolm; Varga, Janos; Samson, Robert A.

    2013-01-01

    We describe a novel heterothallic species in Aspergillus section Fumigati, namely A. felis (neosartorya-morph) isolated from three host species with invasive aspergillosis including a human patient with chronic invasive pulmonary aspergillosis, domestic cats with invasive fungal rhinosinusitis and a

  4. Scrotal granulomatous aspergillosis in a dromedary camel (Camelus dromedarius)

    DEFF Research Database (Denmark)

    Scaglione, Frine Eleonora; Peano, Andrea; Piga, Sara

    2017-01-01

    a firm consistency and was painful at palpation. Histopathology revealed dermal granulomatous inflammation with a necrotic centre, surrounded by plasma cells, macrophages, neutrophils, and sparse fungal hyphae characterised by parallel cell walls, distinct septa, and dichotomous branching. Fungal culture...... was not performed, but a panel of mono- and polyclonal antibodies specific for different fungal genera identified the hyphae as Aspergillus sp. Conclusions The occurrence of subcutaneous lesions is a rare manifestation of aspergillosis in animals, and this appears to be the first case reported in the dromedary...

  5. 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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Allergic bronchopulmonary aspergillosis with aspergillus sinusitis-′9′ year old boy

    Directory of Open Access Journals (Sweden)

    Das Pratima

    2008-01-01

    Full Text Available A case of Broncho Pulmonary Aspergillosis with Aspergillus Sinusitis was diagnosed in a nine year old boy after clinical and immunological investigations. He responded well after treatment with steroid and itraconazol.

  9. Falciparum malaria infection with invasive pulmonary aspergillosis in immunocompetent host – case report

    Science.gov (United States)

    Andriyani, Y.

    2018-03-01

    Invasive pulmonary aspergillosis is an extraordinary rare in the immunocompetent host. Falciparum malaria contributes to high morbidity and mortality of malaria infection cases in the world. The impairments of both humoral and cellular immunity could be the reason of invasive pulmonary aspergillosis in falciparum malaria infection. Forty-nine years old patient came with fever, jaundice, pain in the right abdomen, after visiting a remote area in Africa about one month before admission. Blood films and rapid test were positive for Plasmodium falciparum. After malaria therapy in five days, consciousness was altered into somnolence and intubated with respiratory deterioration. Invasive pulmonary aspergillosis after falciparum malaria infection is life-threatening. There should be awareness of physicians of invasive pulmonary aspergillosis in falciparum malaria infection.

  10. Direct molecular diagnosis of aspergillosis and CYP51A profiling from respiratory samples of French patients

    OpenAIRE

    Yanan Zhao; Cécile Garnaud; Cécile Garnaud; Marie-Pierre Brenier-Pinchart; Marie-Pierre Brenier-Pinchart; Anne Thiébaut-Bertrand; Anne Thiébaut-Bertrand; Christel Saint-Raymond; Boubou Camara; Rebecca Hamidfar-Roy; Odile Cognet; Danièle Maubon; Danièle Maubon; Muriel Cornet; Muriel Cornet

    2016-01-01

    Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive...

  11. Direct Molecular Diagnosis of Aspergillosis and CYP51A Profiling from Respiratory Samples of French Patients

    OpenAIRE

    Zhao, Yanan; Garnaud, C?cile; Brenier-Pinchart, Marie-Pierre; Thi?baut-Bertrand, Anne; Saint-Raymond, Christel; Camara, Boubou; Hamidfar, Rebecca; Cognet, Odile; Maubon, Dani?le; Cornet, Muriel; Perlin, David S.

    2016-01-01

    Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invas...

  12. Pulmonary aspergillosis and central nervous system hemorrhage as complications of autoimmune hemolytic anemia treated with corticosteroids.

    Science.gov (United States)

    Cleri, Dennis J; Moser, Robert L; Villota, Francisco J; Wang, Yue; Husain, Syed A; Nadeem, Shahzinah; Anjari, Tarek; Sajed, Mohammad

    2003-06-01

    Warm, active antibody adult autoimmune hemolytic anemia is the most common form of hemolytic anemia not related to drug therapy. Mortality in adult autoimmune hemolytic anemia is related to the inability to successfully treat patients' underlying disease, or the infectious complications of splenectomy and prolonged steroid therapy. Predisposing factors for invasive aspergillosis are neutropenia and steroid therapy. We present a fatal case of aspergillosis complicating a nonneutropenic case of warm active antibody adult autoimmune hemolytic anemia treated with prolonged steroid therapy.

  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. 2015 BMJ Publishing Group Ltd.

  14. A rare disease mimics postoperative bile leakage: Invasive aspergillosis.

    Science.gov (United States)

    Yazar, Fatih Mehmet; Urfalıoğlu, Aykut; Boran, Ömer Faruk; Sayar, Hamide; Kanat, Burhan Hakan; Emre, Arif; Cengiz, Emrah; Bülbüloğlu, Ertan

    2016-09-01

    Aspergillus fungi can cause serious infections, including intra-abdominal infection, particularly in patients with compromised immune system. Described in the present report is case of 46-year-old female patient who had undergone laparoscopic cholecystectomy (LC) at another healthcare facility. In early postoperative period, she had increasing complaints of swelling, nausea, and vomiting. On postoperative 19th day, she was referred to our clinic with diagnosis of acute abdomen. Surgery was performed with suspected possibility of bile leakage. However, pathological examination of soft, yellow-green mass found in subhepatic space determined it was fungus ball caused by fungi of the genus Aspergillus. Patient was diagnosed postoperative intra-abdominal aspergillosis (IAA).

  15. Radiological diagnosis of maxillary sinus aspergillosis. Radiologische Diagnostik der Kieferhoehlenaspergillose

    Energy Technology Data Exchange (ETDEWEB)

    Schulte, B.; Beyer, D. (Akademisches Lehrkrankenhaus, Porz (Germany). Radiologische Abt.)

    1992-11-01

    Aspergillosis of the maxillary sinuses shows an increasing incidence in even otherwise healthy patients. Next to inhalation as the mode of infection, a dental root canal filling with an orosinusal fistula can be the cause. As most infections remain initially undetected or underestimated as common sinusitis, early diagnosis must be achieved. Standard X-ray of the paranasal sinuses, conventional tomography as well as CT scans are of major importance. Centrally located hyperdense opacifications are a good criterion and can be best seen in CT. Even when the case has not progressed too much, radical surgery combined with Amphotericin B therapy is still the treatment of choice since the infection may progress rapidly. (orig.).

  16. 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.

  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. Allergic aspergillosis and the antigens of Aspergillus fumigatus.

    Science.gov (United States)

    Singh, Bharat; Singh, Seema; Asif, Abdul R; Oellerich, Michael; Sharma, Gainda L

    2014-01-01

    Incidence of fungal infections has increased alarmingly in past few decades. Of the fungal pathogens, the Aspergillus fumigatus has been a major cause of allergic bronchopulmonary aspergillosis (ABPA) which has five main stages--the acute, remission, exacerbation, glucocorticoid dependent and fibrotic stage. The diagnosis of ABPA remains difficult due to its overlapping clinical and radiological features with tuberculosis and cystic fibrosis. From past few decades, the crude fractions of A. fumigatus have been used for immunodiagnosis of ABPA. Most of the detection kits based on crude fractions of A. fumigatus are quite sensitive but have low specificity. Till date 21 known and 25 predicted allergens of A. fumigatus have been identified. Of these allergens, only five recombinants (rAsp f1-f4 and f6) are commercially used for diagnosis of allergic aspergillosis. Remaining allergens of A. fumigatus have been restricted for use in specific diagnosis of ABPA, due to sharing of common antigenic epitopes with other allergens. Complete sequencing of A. fumigatus genome identified 9926 genes and the reports on the proteome of A. fumigatus have shown the presence of large number of their corresponding proteins in the pathogen. The analysis of immunoproteomes developed from crude fractions of A. fumigatus by IgG/IgE reactivity with ABPA patients and animal sera have identified the panel of new antigens. A brief description on the current status of A. fumigatus antigens is provided in this review. The implementation of advance recombinant expression and peptidomic approaches on the A. fumigatus antigens may help in the selection of appropriate molecules for the development of tools for more specific early diagnosis of ABPA, and desensitization therapies for patients of allergic disorders.

  19. Functional protease profiling for laboratory based diagnosis of invasive aspergillosis.

    Science.gov (United States)

    Sabbagh, Bassel; Costina, Victor; Buchheidt, Dieter; Reinwald, Mark; Neumaier, Michael; Findeisen, Peter

    2015-07-01

    Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic criteria according to EORTC/MSG guidelines are often not met and have low sensitivity. Hence there is an urgent need to improve diagnostic procedures by developing novel approaches. In the present study, we present a proof of concept experiment for the monitoring of Aspergillus associated protease activity in serum specimens for diagnostic purpose. Synthetic peptides that are selectively cleaved by proteases secreted from Aspergillus species were selected from our own experiments and published data. These so called reporter peptides (RP, n=5) were added to serum specimens from healthy controls (HC, n=101) and patients with proven (IA, n=9) and possible (PIA, n=144) invasive aspergillosis. Spiked samples were incubated ex vivo under strictly standardized conditions. Proteolytic fragments were analyzed using MALDI-TOF mass spectrometry. Spiked specimens of IA patients had highest concentrations of RP-fragments followed by PIA and HC. The median signal intensity was 116.546 (SD, 53.063) for IA and 5.009 (SD, 8.432) for HC. A cut-off >36.910 was chosen that performed with 100% specificity and sensitivity. Patients with PIA had either values above [53% (76/144)] or below [47% (67/144)] this chosen cut-off. The detection of respective reporter peptide fragments can easily be performed by MALDI TOF mass spectrometry. In this proof of concept study we were able to demonstrate that serum specimens of patients with IA have increased proteolytic activity towards selected reporter peptides. However, the diagnostic value of functional protease profiling has to be validated in further prospective studies. It is likely that a combination of existing and new methods will be required to achieve optimal performance for diagnosis of IA in the future.

  20. Therapeutic Bronchoalveolar Lavage with Conventional Treatment in Allergic Bronchopulmonary Aspergillosis

    International Nuclear Information System (INIS)

    Khalil, K. F.

    2015-01-01

    Objective: To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up. Study Design: Aquasi-experimental study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2010 to December 2013. Methodology: The study was carried out on 132 patients who fulfilled the Greenberger and Patterson criteria and underwent a chest X-ray, an HRCT chest and classified radiologically as with Central Bronchiectasis (CB), High Attenuation Mucus (HAM) or Other Radiological Features (ORF). Baseline serum IgE levels were noted. All patients were given treatment including prednisolone and antifungal agent itraconazole for 4 months. Patients with ORF on HRCT chest and just received the medical treatment were labeled as conventional group. Those patients who had CB or HAM radiological features also underwent bronchoscopy with therapeutic Bronchoalveolar Lavage (BAL), labeled as BAL group. Clinical recurrence and serum IgE levels were noted at 3 and 6 months. Values were compared using chi-square and Mann-Whitney tests respectively. Results: Around 78 (59.1 percentage) of patients underwent bronchoscopy with therapeutic bronchoalveolar lavage to remove the mucus plugs. The mean serum IgE levels at baseline were 3312.04 ± 2526.217 and 3486.15 ± 2528.324 IU/ml in the BAL and conventional groups respectively. There was a statistically significant reduction in the mean serum IgE levels at 3 (p < 0.00) and 6 months (p < 0.001) of follow-up in BALas compared to conventional group. There was no significant difference in the clinical recurrence rate in both the groups (p=0.078 at 3 and 0.343 at 6 months respectively). Conclusion: Therapeutic bronchoalveolar lavage may be a useful adjunct to treatment in patients with allergic bronchopulmonary

  1. Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

    NARCIS (Netherlands)

    P.E. Bunskoek (Paulien); S. Seyedmousavi (Seyedmojtaba); S. Gans (Steven); van Vierzen, P.B.J. (Peter B.J.); W.J. Melchers (Willem); C.E. van Elk; J.W. Mouton (Johan); P.E. Verweij (Paul)

    2017-01-01

    textabstractInvasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded,

  2. 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.

  3. Early invasive pulmonary aspergillosis with fatal outcome in a patient with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Gaspar, M.; Poczova, M.; Sladekova, M.; Drgona, L.

    2015-01-01

    Purpose: The main objective of this publication is to highlight the complexity of the issue of care for patients with hemato-oncological disease, with a focus on infectious complication - invasive pulmonary aspergillosis. Case: We present a case report of a 49-year-old patient treated for acute lymphoblastic leukemia. In the early post-transplant period, in spite of combined antimicrobial treatment, an onset of fever and dyspnoea occurred. Because of the clinical condition of our immunosuppressed patient, as well as radiological finding of suspected inflammatory changes in the lung, antibiotic and antifungal therapy was changed. Respiratory symptoms progressed and the state extorted artificial ventilation. Realized bronchoscopy showed structural changes in bronchial mucosa. The results of laboratory analyses of bronchoalveolar lavage testified to fungal infection - pulmonary aspergillosis, with the cultures of Aspergillus flavus. Despite intensive complex treatment, the patient's condition led to multiple organ failure and on the Day D +27 after transplantation physicians stated exitus letalis. Autopsy confirmed invasive pulmonary aspergillosis. Conclusion: Acute leukemia and its treatment is an increased risk of systemic fungal infections in those patients - especially invasive aspergillosis. The fatality rate for invasive aspergillosis in this risk group represents on average 50 %. With this in mind, it is necessary for life-saving to diagnose the infection in time and treat it appropriately. (author)

  4. 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 

  5. 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.

  6. Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

    Science.gov (United States)

    Withington, S; Chambers, S T; Beard, M E; Inder, A; Allen, J R; Ikram, R B; Schousboe, M I; Heaton, D C; Spearing, R I; Hart, D N

    1998-01-01

    The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

  7. Invasive pulmonary aspergillosis in immune-compromised children

    International Nuclear Information System (INIS)

    Kramer, S.S.; Jakaki, R.I.

    1991-01-01

    Invasive pulmonary aspergillosis (IPA) is a potentially lethal complication of prolonged neutropenia occurring most commonly in patients with leukemia or aplastic anemia. Early diagnosis is important for prompt therapy but may prove difficult. This paper assesses the role of CT in the early diagnosis and follow-up of IPA in children. Nine proved cases and 2 cases clinically consistent with IPA were the group for both retrospective and prospective analysis. Medical records, chest radiographs, and CT scans were reviewed. Eight children had acute leukemia, and 3 had aplastic anemia. five patients died; 2 underwent lobectomy. Typical CT findings included multiple found parenchymal nodules, larger confluent masslike infiltrates, and peripheral pleural-based nodules/infiltrates resembling infarcts. No adenopathy or pleural effusions occurred. Some lesions later cavitated or developed an air crescent. CT clearly depicted several unusual complications, including involvement of bronchus (resulting in luminal narrowing, unilateral pulmonary overinflation, and air leak) and mycotic thrombosis or aneurysim of the pulmonary artery. Resolution of lesions with therapy was also documented by CT

  8. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Ibrahim Ahmed Janahi

    2017-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a pulmonary disorder that often occurs in patients with asthma or cystic fibrosis (CF and is characterized by a hypersensitivity response to the allergens of the fungus Aspergillus fumigatus. In patients with CF, growth of A. fumigatus hyphae within the bronchial lumen triggers an immunoglobulin E (IgE-mediated hypersensitivity response that results in airway inflammation, bronchospasm, and bronchiectasis. In most published studies, the prevalence of ABPA is about 8.9% in patients with CF. Since the clinical features of this condition overlap significantly with that of CF, ABPA is challenging to diagnose and remains underdiagnosed in many patients. Diagnosis of ABPA in CF patients should be sought in those with evidence of clinical and radiologic deterioration that is not attributable to another etiology, a markedly elevated total serum IgE level (while off steroid therapy and evidence of A. fumigatus sensitization. Management of ABPA involves the use of systemic steroids to reduce inflammation and modulate the immune response. In patients who do not respond to steroids or cannot tolerate them, antifungal agents should be used to reduce the burden of A. fumigatus allergens. Recent studies suggest that omalizumab may be an effective option to reduce the frequency of ABPA exacerbations in patients with CF. Further randomized controlled trials are needed to better establish the efficacy of omalizumab in managing patients with CF and ABPA.

  9. [Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Barberán, José; Mensa, José

    2014-01-01

    Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD). Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD≥III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain. The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  10. [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. Copyright © 2014. Published by Elsevier Espana.

  11. 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.

  12. Invasive tracheobronchial aspergillosis in a patient with systemic lupus erythematosus-dermatomyositis overlap syndrome.

    Science.gov (United States)

    Sada, Mitsuru; Saraya, Takeshi; Tanaka, Yasutaka; Sato, Shinji; Wakayama, Megumi; Shibuya, Kazutoshi; Uchiyama, Takashi; Ogata, Hideo; Takizawa, Hajime; Goto, Hajime

    2013-01-01

    A 45-year-old man was referred to our hospital with a 3-month history of dyspnea, polyarthralgia, myalgia and weight loss. He was diagnosed with systemic lupus erythematosus/dermatomyositis overlap syndrome with lung involvement, which presented as organizing pneumonia. However, a bronchoscopic examination revealed the presence of multiple plaque-like white lesions with ulcers on the bronchial membrane, located mainly in the central airway. The pathological specimens obtained from bronchoscopy showed numerous filamentous fungal hyphae that were aggressively invading the bronchial walls, suggesting a diagnosis of invasive tracheobronchial aspergillosis. The present case, along with a review of the literature, demonstrates that invasive tracheobronchial aspergillosis can occur in patients who do not appear to be immunosuppressed. This case of aspergillosis should thus be recognized as an extremely rare presentation of an Aspergillus infection.

  13. 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.

  14. [Localized invasive intracranial aspergillosis with multiple cranial nerve failure -- case report and review of the literature].

    Science.gov (United States)

    Winkler, F; Seelos, K; Hempel, J M; Pfister, H-W

    2002-12-01

    Contrary to the more frequent hematogenously spread cerebral aspergillosis, localized invasive intracranial aspergillosis is a fungal infection that can also occur in patients who are not severely immunosuppressed. This illness can be effectively treated in some of these patients by early and rigorous therapy. Localized invasion of the fungus, generally from one of the nasal sinuses, causes intracranial growth mainly along the base of the skull and larger vessels,where fibrous, granulomatous tissue develops. This generally leads to damage of the cranial nerves (primarily I-VI) as well as localized pain syndromes. We report on the clinical course documented by MRI of a patient with localized invasive intracranial aspergillosis who had multiple failure of cranial nerves following surgery for an aspergilloma of the maxillary sinus. Clinical course, imaging findings, and treatment of the illness are discussed with a review of the relevant literature.

  15. [Invasive aspergillosis after near-drowning: case reports and review of the literature].

    Science.gov (United States)

    Li, Pei; Cao, E-hong; Zhao, Bei-lei; Sun, Hui-ming; Li, Miao-miao; Xu, Jin; Song, Yong; Shi, Yi

    2011-09-01

    The purpose of this study was to analyze the clinical presentations and disease courses of invasive aspergillosis (IA) in patients after near-drowning. The clinical data of 3 cases of invasive aspergillosis after near-drowning from Oct. 2005 to Aug. 2010 in this hospital were retrospectively analyzed, and the related literature was reviewed. There were 1 male and 2 female patients, aged from 18 to 72 years. All of them had been immunocompetent before drowning. Two patients drowned because of traffic accident, and 1 fell in sewage by accident. All of the 3 patients were intubated because of acute respiratory failure, and received broad-spectrum antibiotic therapy. One had transient leucopenia, and 2 patients received glucocorticoid therapy. The condition of the 3 cases deteriorated 9 to 11 days after near-drowning. Aspergillus was isolated from sputum samples of 2 patients at the same time. Thoracic CT findings included multiple nodules, consolidation and cavity formation. Multiple abscesses in cerebral parenchyma were found in 1 patient with invasive cerebral aspergillosis. One patient died, whose lungs, cerebral parenchyma, myocardium and kidney were all infected by aspergillus. The other 2 patients, whose infection limited to the lungs, had a positive prognosis. Using the terms "aspergillosis" and "near-drowning" a PUBMED search yielded 7 articles, published between 1984 and 2010. Using the terms "invasive pulmonary aspergillosis" and "near-drowning", searching Wangfang data and CHED data, encompass 1 article, published in 2009. In all of the 8 articles, there are 5 final diagnosis cases and 3 clinical diagnosis cases. IA was very rare in immunocompetent hosts but had been reported in previously healthy individuals after near-drowning. Aspergillosis might develop 1 to 2 weeks after near-drowning, and the prognosis was poor in patients with central nervous system involvement.

  16. Direct molecular diagnosis of aspergillosis and CYP51A profiling from respiratory samples of French patients

    Directory of Open Access Journals (Sweden)

    Yanan Zhao

    2016-07-01

    Full Text Available Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL, bronchial aspirates (BA, tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n=12, chronic pulmonary aspergillosis (n=3, allergic bronchopulmonary aspergillosis (n=7 or colonization (n=11 and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. Results: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3% were cultured from 20 samples. Culture positivity was 62.5%, 75%, 42.9%, and 15.8% in ABPA, CPA, IA and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5% vs 42.9%; P<0.05 and colonization group (73.7% vs 15.8%; P<0.05. The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations, yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL. Conclusion: Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study.

  17. Radiodense concretions in maxillary sinus aspergillosis: pathogenesis and the role of CT densitometry

    International Nuclear Information System (INIS)

    Lenglinger, F.X.; Krennmair, G.; Mueller-Schelken, H.; Artmann, W.

    1996-01-01

    The purpose of this study was to investigate by CT the origin of radiodense maxillary sinus concretions and whether CT densitometry is effective in the prediction of maxillary sinus aspergillosis and in the differentiation of the origin of these concretions. In a prospective study in 21 patients with radiodense maxillary sinus concretions detected by radiography, a preoperative CT study of the paranasal sinuses and the concretions was undertaken. Additional scans of the upper alveolar ridge were also performed. Radiological findings were compared with clinical symptoms and with CT findings, especially CT densitometry of the sinus concretions and dental root-filling material. All patients underwent a functional Caldwell-Luc operation; histological and microbiological examinations were performed. Fifteen of the 21 patients (71.4%) with radiodense concretions had a histological and microbiological diagnosis of sinus aspergillosis. The sinus concretions had CT densities higher than 2000 HU (Housfield units) in 15 patients and lower than 2000 HU in 6. Fourteen of 15 patients (93.3%) with concretions ahving CT densities higher than 2000 HU had a postoperative diagnosis of maxillary sinus aspergillosis. The mean CT density of the sinus concretions in patients with maxillary sinus aspergillosis was 2868 HU (range 1870-3070 HU), and in patients without aspergiollosis was 778 HU (range 228-2644 HU). The mean CT density of the dental root-filling material was 2866 HU (range 2156-3070 HU). Paranasal sinus CT with CT densitometry of a sinus concretion has a higher accuracy than standard radiogrpahy and clinical findings in the prediction of maxillary sinus aspergillosis (93.3% vs 71.4%). CT densitometry helps to confirm the dental origin of maxillary sinus concretions and to explain a possible dental pathogenesis of maxillary sinus aspergillosis. (orig.)

  18. Acute aspergillosis in mallards at Oahe seep near Pierre, South Dakota

    Science.gov (United States)

    Bair, W.C.; Simpson, S.G.; Windingstad, R.M.

    1988-01-01

    Aspergillosis was diagnosed at the cause of death of 158 mallards (Anas platyrhynchos) in January and February 1985 and 11 mallards in December 1985 near Pierre, SD. Isolation of Aspergillus fumigatus from carcass tissues confirmed the diagnosis. The sex ratio of mallards dead from aspergillosis in January and February 1985 was significantly different from the sex ratio in the local population at that time. The source of the fungus was not determined, but severe weather caused physiologically stressed mallards to feeds on corn stored in open piles on the ground, a likely source of the Aspergillus fungus.

  19. Excellent outcome of Aspergillous endophthalmitis in a case of allergic bronchopulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    Balbir Khan

    2014-01-01

    Full Text Available While invasive aspergillosis occurs typically in severely immunocompromised patients, cases of surgical site infections have been reported in immunocompetent individuals. The purpose is to report an eye with post-operative Aspergillus endophthalmitis, which achieved a good visual outcome following early and aggressive treatment. A young patient, known case of allergic bronchopulmonary aspergillosis presented to us with post-cataract surgery endophthalmitis. He was treated with pars plana vitrectomy and intravitreal voriconazole and systemic itraconazole. The patient regained a vision of 20/30 with follow up of 2 years.

  20. Aspergillus niger: an unusual cause of invasive pulmonary aspergillosis

    Science.gov (United States)

    Person, A. K.; Chudgar, S. M.; Norton, B. L.; Tong, B. C.; Stout, J. E.

    2010-01-01

    Infections due to Aspergillus species cause significant morbidity and mortality. Most are attributed to Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus terreus. Aspergillus niger is a mould that is rarely reported as a cause of pneumonia. A 72-year-old female with chronic obstructive pulmonary disease and temporal arteritis being treated with steroids long term presented with haemoptysis and pleuritic chest pain. Chest radiography revealed areas of heterogeneous consolidation with cavitation in the right upper lobe of the lung. Induced bacterial sputum cultures, and acid-fast smears and cultures were negative. Fungal sputum cultures grew A. niger. The patient clinically improved on a combination therapy of empiric antibacterials and voriconazole, followed by voriconazole monotherapy. After 4 weeks of voriconazole therapy, however, repeat chest computed tomography scanning showed a significant progression of the infection and near-complete necrosis of the right upper lobe of the lung. Serum voriconazole levels were low–normal (1.0 μg ml−1, normal range for the assay 0.5–6.0 μg ml−1). A. niger was again recovered from bronchoalveolar lavage specimens. A right upper lobectomy was performed, and lung tissue cultures grew A. niger. Furthermore, the lung histopathology showed acute and organizing pneumonia, fungal hyphae and oxalate crystallosis, confirming the diagnosis of invasive A. niger infection. A. niger, unlike A. fumigatus and A. flavus, is less commonly considered a cause of invasive aspergillosis (IA). The finding of calcium oxalate crystals in histopathology specimens is classic for A. niger infection and can be helpful in making a diagnosis even in the absence of conidia. Therapeutic drug monitoring may be useful in optimizing the treatment of IA given the wide variations in the oral bioavailability of voriconazole. PMID:20299503

  1. CD4+ T Cells Mediate Aspergillosis Vaccine Protection.

    Science.gov (United States)

    Diaz-Arevalo, Diana; Kalkum, Markus

    2017-01-01

    Adaptive effector CD4 + T cells play essential roles in the defense against fungal infections, especially against invasive aspergillosis (IA). Such protective CD4 + T cells can be generated through immunization with specialized antifungal vaccines, as has been demonstrated for pulmonary Aspergillus fumigatus infections in mouse experiments. Adaptive transfer of fungal antigen-specific CD4 + T cells conferred protection onto non-immunized naive mice, an experimental approach that could potentially become a future treatment option for immunosuppressed IA patients, focusing on the ultimate goal to improve their otherwise dim chances for survival. Here, we describe the different techniques to analyze CD4 + T cell immune responses after immunization with a recombinant fungal protein. We present three major methods that are used to analyze the role of CD4 + T cells in protection against A. fumigatus challenge. They include (1) transplantation of CD4 + T cells from vaccinated mice into immunosuppressed naive mice, observing increasing protection of the cell recipients, (2) depletion of CD4 + T cells from vaccinated mice, which abolishes vaccine protection, and (3) T cell proliferation studies following stimulation with overlapping synthetic peptides or an intact protein vaccine. The latter can be used to validate immunization status and to identify protective T cell epitopes in vaccine antigens. In the methods detailed here, we used versions of the well-studied Asp f3 protein expressed in a bacterial host, either as the intact full length protein or its N-terminally truncated version, comprised of residues 15-168. However, these methods are generally applicable and can well be adapted to study other protein-based subunit vaccines.

  2. Aspergillus Galactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid

    OpenAIRE

    Musher, Benjamin; Fredricks, David; Leisenring, Wendy; Balajee, S. Arunmozhi; Smith, Caitlin; Marr, Kieren A.

    2004-01-01

    Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in hematopoietic stem cell transplant patients. Diagnosis requires microbiological or histopathologic demonstration of the organism in tissues; however, cultivation of Aspergillus species from respiratory secretions has low diagnostic sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal therapy and obviating the need for addit...

  3. Ibrutinib in PCNSL: The Curious Cases of Clinical Responses and Aspergillosis.

    Science.gov (United States)

    Grommes, Christian; Younes, Anas

    2017-06-12

    In this issue of Cancer Cell, Lionakis et al. demonstrate that the combination of temozolomide, etoposide, doxorubicin, dexamethasone, rituximab, and the Bruton tyrosine kinase (BTK) inhibitor ibrutinib induced frequent responses in patients with primary central nervous system lymphoma but was associated with significant toxicity, including pulmonary and cerebral aspergillosis infections. Copyright © 2017. Published by Elsevier Inc.

  4. The radiological spectrum of invasive aspergillosis in children: a 10-year review

    International Nuclear Information System (INIS)

    Thomas, Karen E.; Owens, Catherine M.; Veys, Paul A.; Novelli, Vas; Costoli, Vera

    2003-01-01

    Invasive aspergillosis is an uncommon but life-threatening event in the immunocompromised child. Attempts at fungal isolation are often unrewarding and a high index of radiological suspicion is essential in the early diagnosis of infected children. To document the radiological spectrum of disease in invasive aspergillosis in the paediatric population. A retrospective review of the imaging performed in 27 consecutive patients (age 7 months to 18 years) with documented invasive Aspergillosis encountered over a 10-year period at a single institution. Radiographic findings of pulmonary disease (20 patients) included segmental and multilobar consolidation, perihilar infiltrates, multiple small nodules, peripheral nodular masses and pleural effusions. No cavitating lesions were seen on CXR. Small cavitating nodules were present on CT in two of eight children. Chest wall disease was particularly associated with underlying chronic granulomatous disease. Disseminated disease manifested as osteomyelitis (n=5), cerebral (n=3), oesophageal (n=1), hepatic (n=2), renal (n=2) and cutaneous (n=5) involvement. Imaging findings are discussed. Twelve patients (44%) subsequently died from Aspergillus-related complications. Invasive aspergillosis presents with a wide variety of radiographic findings involving multiple organ systems. Respiratory findings are varied but often non-specific, and a high index of suspicion is necessary in immunocompromised patients. In contrast to adult disease, the incidence of cavitation of pulmonary lesions appears low. (orig.)

  5. [Molecular markers: an important tool in the diagnosis, treatment and epidemiology of invasive aspergillosis].

    Science.gov (United States)

    Frías-de León, María Guadalupe; Acosta-Altamirano, Gustavo; Duarte-Escalante, Esperanza; Martínez-Hernández, José Enrique; Martínez-Rivera, María de Los Ángeles; Reyes-Montes, María Del Rocío

    2014-01-01

    Increase in the incidence of invasive aspergillosis has represented a difficult problem for management of patients with this infection due to its high rate of mortality, limited knowledge concerning its diagnosis, and therapeutic practice. The difficulty in management of patients with aspergillosis initiates with detection of the fungus in the specimens of immunosuppressed patients infected with Aspergillus fumigatus; in addition, difficulty exists in terms of the development of resistance to antifungals as a consequence of their indiscriminate use in prophylactic and therapeutic practice and to ignorance concerning the epidemiological data of aspergillosis. With the aim of resolving these problems, molecular markers is employed at present with specific and accurate results. However, in Mexico, the use of molecular markers has not yet been implemented in the routine of intrahospital laboratories; despite the fact that these molecular markers has been widely referred in the literature, it is necessary for it to validated and standardized to ensure that the results obtained in any laboratory would be reliable and comparable. In the present review, we present an update on the usefulness of molecular markers in accurate identification of A. fumigatus, detection of resistance to antifugal triazoles, and epidemiological studies for establishing the necessary measures for prevention and control of aspergillosis.

  6. The radiological spectrum of invasive aspergillosis in children: a 10-year review

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Karen E. [Department of Diagnostic Radiology, Great Ormond Street Hospital for Children, Great Ormond Street, London (United Kingdom); Department of Diagnostic Radiology, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8 (Canada); Owens, Catherine M. [Department of Diagnostic Radiology, Great Ormond Street Hospital for Children, Great Ormond Street, London (United Kingdom); Veys, Paul A.; Novelli, Vas; Costoli, Vera [Host Defence Unit, Great Ormond Street Hospital for Children, London (United Kingdom)

    2003-07-01

    Invasive aspergillosis is an uncommon but life-threatening event in the immunocompromised child. Attempts at fungal isolation are often unrewarding and a high index of radiological suspicion is essential in the early diagnosis of infected children. To document the radiological spectrum of disease in invasive aspergillosis in the paediatric population. A retrospective review of the imaging performed in 27 consecutive patients (age 7 months to 18 years) with documented invasive Aspergillosis encountered over a 10-year period at a single institution. Radiographic findings of pulmonary disease (20 patients) included segmental and multilobar consolidation, perihilar infiltrates, multiple small nodules, peripheral nodular masses and pleural effusions. No cavitating lesions were seen on CXR. Small cavitating nodules were present on CT in two of eight children. Chest wall disease was particularly associated with underlying chronic granulomatous disease. Disseminated disease manifested as osteomyelitis (n=5), cerebral (n=3), oesophageal (n=1), hepatic (n=2), renal (n=2) and cutaneous (n=5) involvement. Imaging findings are discussed. Twelve patients (44%) subsequently died from Aspergillus-related complications. Invasive aspergillosis presents with a wide variety of radiographic findings involving multiple organ systems. Respiratory findings are varied but often non-specific, and a high index of suspicion is necessary in immunocompromised patients. In contrast to adult disease, the incidence of cavitation of pulmonary lesions appears low. (orig.)

  7. Omalizumab Treatment for Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis.

    Science.gov (United States)

    Emiralioglu, Nagehan; Dogru, Deniz; Tugcu, Gokcen Dilsa; Yalcin, Ebru; Kiper, Nural; Ozcelik, Ugur

    2016-03-01

    Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by destructive changes in the airways. Long-term treatment with oral corticosteroids is often required for repeated exacerbations. Because elevated total IgE is a cardinal abnormality of ABPA, omalizumab has been used sporadically to decrease corticosteroid dose or totally replace corticosteroids. The aim of this report is to describe our experience with omalizumab treatment in patients with CF and ABPA. We conducted a review of 6 CF patients with ABPA receiving omalizumab. All patients were treated with oral prednisolone and itraconazole. Omalizumab was started if the patient was not responding to steroid treatment, which was determined according to serum IgE levels and/or clinical findings or depending on if there were side effects caused by steroid treatment. The mean age of patients at the beginning of omalizumab treatment was 16.1 years. One patient had a new diagnosis of ABPA; however, the others had the first to third exacerbation when treated with omalizumab. The mean duration of ABPA by the time that treatment with omalizumab started was 13 ± 12.4 months (range = 2-29 months). With omalizumab treatment, IgE levels were decreased in all patients, and Aspergillus-specific IgE levels were decreased in 4 patients; however, FEV1(% predicted) improved only in 2 patients who had mild disease. Corticosteroids were reduced in the first, second, and third months of omalizumab treatment in 2, 1, and 3 patients, respectively. In 2 patients, steroid treatment was stopped. None of the patients suffered from side effects of omalizumab. The mean duration of omalizumab treatment was 12.5 months (range = 6-18 months). This study showed steroid-sparing effect, decreasing IgE levels, and improvement in respiratory symptoms in 6 CF patients with omalizumab treatment. Although this is a small sample of the population, omalizumab may be an alternative therapy for ABPA in CF patients who fail

  8. A case of allergic bronchopulmonary aspergillosis successfully treated with mepolizumab.

    Science.gov (United States)

    Terashima, Takeshi; Shinozaki, Taro; Iwami, Eri; Nakajima, Takahiro; Matsuzaki, Tatsu

    2018-03-27

    Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard therapy for ABPA, but long-term use of systemic corticosteroids often causes serious side effects. A 64-year-old woman was diagnosed with ABPA based on a history of bronchial asthma (from 40 years of age), elevated total IgE, the presence of serum precipitating antibodies and elevated specific IgE antibody to A. fumigatus, and pulmonary infiltration. Bronchoscopy showed eosinophilic mucoid impaction. Systemic corticosteroid therapy was initiated, and her symptoms disappeared. Peripheral eosinophilia and pulmonary infiltration recurred five months after cessation of corticosteroid treatment. Systemic corticosteroids were re-initiated and itraconazole was added as an anti-fungal agent. The patient was free of corticosteroids, aside from treatment with a short course of systemic corticosteroids for asthma exacerbation, and clinically stable with itraconazole and asthma treatments for 3 years. In 2017, she experienced significant deterioration. Laboratory examination revealed marked eosinophilia (3017/μL) and a chest computed tomography (CT) scan demonstrated pulmonary infiltration in the left upper lobe and mucoid impaction in both lower lobes. The patient was treated with high-dose inhaled corticosteroid/long-acting beta-agonist, a long-acting muscarinic antagonist, a leukotriene receptor antagonist, and theophylline; spirometry revealed a forced expiratory volume in 1 s (FEV 1 ) of 1.01 L. An uncontrolled asthma state was indicated by an Asthma Control Test (ACT) score of 18. Mepolizumab, 100 mg every 4 weeks, was initiated for the treatment of severe bronchial asthma with ABPA exacerbation. Bronchial asthma symptoms dramatically improved, and ACT score increased to 24

  9. Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis.

    Science.gov (United States)

    Carsin, A; Romain, T; Ranque, S; Reynaud-Gaubert, M; Dubus, J-C; Mège, J-L; Vitte, J

    2017-11-01

    A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  10. Prevalence and fungal profile of pulmonary aspergillosis in immunocompromised and immunocompetent patients of a tertiary care hospital

    OpenAIRE

    Prakash Ved, Mishra Prem P, Verma Shashi K, Sinha Shivani, Sharma Mahendra

    2014-01-01

    Background: Aspergillus is a fungus which may present an array of pulmonary manifestations, depending on the patient’s immunological and physiological state. Although the incidence of pulmonary aspergillosis occurs primarily in immunocompromised patients but the incidence is also rising in immunocompetent individuals, especially in developing countries. Aim: The objective of the study was to determine the prevalence and predisposing factors of pulmonary aspergillosis along with species identi...

  11. Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

    Science.gov (United States)

    Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

    2018-03-18

    Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one

  12. Actualización en Aspergilosis con énfasis en Aspergilosis invasora Aspergillosis update with focus in invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Sonia Isabel Cuervo-Maldonado

    2010-12-01

    fungus in the form of invasive aspergillosis (IA. The IA presents diagnostic difficulties in non-immunocompetent hosts; therefore using non-invasive diagnosis methods for this group of patients offers therapeutic approach guidance. Antifungal drugs such as azoles (voriconazole and echinocandins (caspofungin, that have improved the AI group results, are available nowadays. This article updates the literature on AI diagnosis and treatment.

  13. Pulmonary aspergillosis in immunocompetent patients without air-meniscus sign and underlying lung disease: CT findings and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Soon Ho; Park, Chang Min; Goo, Jin Mo; Lee, Hyun Ju (Dept. of Radiology and Institute of Radiation Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)), email: rosaceci@radiol.snu.ac.kr

    2011-09-15

    Background: Pulmonary aspergillosis in immunocompetent patients has been described as a saprophytic infection with pre-existing lung lesions showing an air-meniscus sign on chest radiograph or CT scans. There have been rare articles dealing with pulmonary aspergillosis in immunocompetent patients without pre-existing lung lesions. Purpose: To evaluate the CT findings of pulmonary aspergillosis in immunocompetent patients without air-meniscus and underlying lung disease and to correlate the CT findings and pathologic features of pulmonary aspergillosis in these patients. Material and Methods: A total of seven surgically proven pulmonary aspergillosis found in immunocompetent patients without an air-meniscus and underlying lung disease (M:F = 1:6; mean age 63.4 years) were included. On CT, the lesion shape, margin, type, location, diameter, presence of satellite nodules, presence of CT halo sign or hypodense sign, and interval growth were evaluated. Histopathologic features of each lesion were classified as one of the following; primary aspergilloma, chronic necrotizing pulmonary aspergillosis, or invasive pulmonary aspergillosis. Correlation between CT findings and pathological features was performed. Results: All lesions presented as a nodule or mass unable to differentiate from malignancy. Most lesions had well-defined margins (n = 4), appeared as solid lesions (n = 7), and were located in the upper lobe (n = 5). Mean diameter of lesions was 2.3 cm. Satellite nodules (n = 2), CT halo sign (n = 1), and hypodense sign (n = 4) were found. Only one lesion increased in size during follow-up. Lesions were pathologically classified as primary aspergilloma (n = 3) and chronic necrotizing pulmonary aspergillosis (n = 4). The hypodense sign on CT was pathologically proved as dense fungal hyphae filled in bronchus and CT halo sign as parenchymal hemorrhage. Conclusion: Pulmonary aspergillosis predominantly presented as a nodule or mass mimicking malignancy in the upper lobes

  14. Pulmonary aspergillosis in immunocompetent patients without air-meniscus sign and underlying lung disease: CT findings and histopathologic features

    International Nuclear Information System (INIS)

    Yoon, Soon Ho; Park, Chang Min; Goo, Jin Mo; Lee, Hyun Ju

    2011-01-01

    Background: Pulmonary aspergillosis in immunocompetent patients has been described as a saprophytic infection with pre-existing lung lesions showing an air-meniscus sign on chest radiograph or CT scans. There have been rare articles dealing with pulmonary aspergillosis in immunocompetent patients without pre-existing lung lesions. Purpose: To evaluate the CT findings of pulmonary aspergillosis in immunocompetent patients without air-meniscus and underlying lung disease and to correlate the CT findings and pathologic features of pulmonary aspergillosis in these patients. Material and Methods: A total of seven surgically proven pulmonary aspergillosis found in immunocompetent patients without an air-meniscus and underlying lung disease (M:F = 1:6; mean age 63.4 years) were included. On CT, the lesion shape, margin, type, location, diameter, presence of satellite nodules, presence of CT halo sign or hypodense sign, and interval growth were evaluated. Histopathologic features of each lesion were classified as one of the following; primary aspergilloma, chronic necrotizing pulmonary aspergillosis, or invasive pulmonary aspergillosis. Correlation between CT findings and pathological features was performed. Results: All lesions presented as a nodule or mass unable to differentiate from malignancy. Most lesions had well-defined margins (n = 4), appeared as solid lesions (n = 7), and were located in the upper lobe (n = 5). Mean diameter of lesions was 2.3 cm. Satellite nodules (n = 2), CT halo sign (n = 1), and hypodense sign (n = 4) were found. Only one lesion increased in size during follow-up. Lesions were pathologically classified as primary aspergilloma (n = 3) and chronic necrotizing pulmonary aspergillosis (n = 4). The hypodense sign on CT was pathologically proved as dense fungal hyphae filled in bronchus and CT halo sign as parenchymal hemorrhage. Conclusion: Pulmonary aspergillosis predominantly presented as a nodule or mass mimicking malignancy in the upper lobes

  15. Pulmonary carcinosarcoma initially presenting as invasive aspergillosis: a case report of previously unreported combination

    Directory of Open Access Journals (Sweden)

    Van Thien

    2010-01-01

    Full Text Available Abstract Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for diagnosis, and mortality rate is high. We describe a case of primary carcinosarcoma of the lung concurrently occurring with invasive pulmonary aspergillosis in a 66-year old patient.

  16. 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.)

  17. An Important Finding of Systemic Aspergillosis: Skin Involvement and Amphotericin B Resistance in an Adolescent

    Directory of Open Access Journals (Sweden)

    Aslinur Ozkaya-Parlakay

    2016-08-01

    Full Text Available Invasive aspergillosis is a life-threatening infectious complication in immunocompromised patients, especially with malignancy, and in some cases, it causes extensive tissue destruction and subsequent systemic illness, leading to multiorgan failure and death. Skin involvement and amphotericin B resistance are very rare findings of aspergillosis. Herein, we report the case of a primary hemophagocytic syndrome patient who developed subcutaneous nodules in the 3rd month of bone marrow transplantation from which Aspergillus fumigatus was cultivated despite the fact that she was under antifungal therapy. In immunocompromised patients with prolonged fever, atypical presentations of invasive mycosis should be kept in mind, and early appropriate therapy should be initiated promptly to decrease morbidity and mortality.

  18. Patho-radiologic correlation of invasive pulmonary aspergillosis in the compromised host.

    Science.gov (United States)

    Orr, D P; Myerowitz, R L; Dubois, P J

    1978-05-01

    The autopsy findings and antemortem radiographic abnormalities were correlated in 20 patients with invasive pulmonary aspergillosis to define typical radiographic patterns, their progression and anatomic basis. Sixteen (80%) patients had radiographic abnormalities due to aspergillosis. Fifty-nine percent of the specific radiographic abnormalities seen in these patients were caused by anatomic lesions of asperigillosis and 67% of such anatomic lesions were radiographically definable. The most common initial radiographic pattern was a patchy density (single or multifocal) or a well defined nodule. The densities remained stable in half the patients but progressed, over several weeks to either diffuse consolidation or cavitation in the others. Most anatomic lesions were categorized as either nodular ("target") lesions (1-3 cm in diameter) or hemorrhagic infarctions (5-10 cm in diameter), both due to vascular invasion causing thrombosis and ischemic necrosis. Unlike pulmonary candidiasis, which is usually radiographically undetectable, invasive pulmonary asperigillosis frequently caused radiographically visible lesions.

  19. Donor-derived aspergillosis from use of a solid organ recipient as a multiorgan donor.

    Science.gov (United States)

    Mueller, N J; Weisser, M; Fehr, T; Wüthrich, R P; Müllhaupt, B; Lehmann, R; Imhof, A; Aubert, J-D; Genoni, M; Kunz, R; Weber, M; Steiger, J

    2010-02-01

    The growing need for organs and the scarcity of donors has resulted in an increased use of extended criteria donors. We report a case where a recipient of a cardiac graft was used as an organ donor. Death of the recipient occurred 9 days after transplantation and was attributed to presumed cerebral hemorrhage, which post mortem was diagnosed as invasive aspergillosis of the brain. One recipient of a kidney transplant lost the graft due to infection with Aspergillus fumigatus, whereas prompt initiation of therapy successfully prevented disseminated aspergillosis in the other recipients. Despite the pressure to extend the use of organs by lowering the acceptance criteria, organs should only be accepted if the cause of death of the donors is unequivocally explained.

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

    International Nuclear Information System (INIS)

    Winterstein, Anton R.; Bohndorf, Klaus; Vollert, Kurt; Wagner, Theodor; Gnekow, Astrid; Roemer, Frank W.

    2010-01-01

    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.)

  1. Causative Agents of Aspergillosis Including Cryptic Aspergillus Species and A. fumigatus.

    Science.gov (United States)

    Toyotome, Takahito

    2016-01-01

    Aspergillosis is an important deep mycosis. The causative agents are Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, of which A. fumigatus is the most prevalent. Cryptic Aspergillus spp., which morphologically resemble representative species of each Aspergillus section, also cause aspergillosis. Most of the cryptic species reveal different susceptibility patterns and/or different secondary metabolite profiles, also called exometabolome in this manuscript, from those representative species. On the other hand, azole-resistant A. fumigatus strains in clinical specimens and in the environment have been reported. Therefore, it is imperative to precisely identify the species, including cryptic Aspergillus spp., and evaluate the susceptibility of isolates.In this manuscript, some of the causative cryptic Aspergillus spp. are briefly reviewed. In addition, the exometabolome of Aspergillus section Fumigati is described. Finally, azole resistance of A. fumigatus is also discussed, in reference to several studies from Japan.

  2. Percutaneous treatment with amphotericin B in a case of invasive pulmonary aspergillosis

    International Nuclear Information System (INIS)

    Ruiz, A.; Lonjedo, E.; Agramunt, M.; Martinez-Rodrigo, J. J.; Palomero, J.

    2001-01-01

    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

  3. 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.

  4. Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies

    OpenAIRE

    Reischies, Frederike M. J.; Raggam, Reinhard B.; Prattes, Juergen; Krause, Robert; Eigl, Susanne; List, Agnes; Quehenberger, Franz; Strenger, Volker; Wölfler, Albert; Hoenigl, Martin

    2016-01-01

    Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with...

  5. Long-term outcome in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole

    OpenAIRE

    Schuller, S.; Clercx, Cécile

    2007-01-01

    Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal aspergillosis after successful medical treatment using intranasal infusions of 1% or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment protocols were good, with half of the dogs being asymptomatic throughout the follow-up period. The remaining dogs showed mild clinical signs compatible with chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic lymphoplasmacytic r...

  6. 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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Treatment of refractory sino-nasal aspergillosis with posaconazole and terbinafine in 10 dogs.

    Science.gov (United States)

    Stewart, J; Bianco, D

    2017-09-01

    To determine the safety and efficacy of posaconazole and terbinafine for the treatment of naturally occurring sino-nasal aspergillosis in dogs refractory to conventional topical and systemic treatment. Ten client-owned dogs with sino-nasal aspergillosis and not responsive to conventional treatments were prospectively enrolled to receive a dose of 5 mg/kg posaconazole orally every 12 hours for six months. All dogs were concurrently treated with doses of 30 mg/kg terbinafine orally every 12 hours and 5 mg/kg doxycycline orally every 12 hours for 6 to 18 months. All 10 enrolled dogs completed the study. The treatment response was defined as complete clinical remission (n=7) or partial clinical remission (n=3). Two dogs relapsed after cessation of combination therapy. All dogs lived more than one year after starting combination therapy and eight dogs are alive at the time of writing. No clinically relevant adverse reactions or increases in hepatic enzyme activity occurred during the combination therapy. The results of this study suggest that this combination therapy appears safe and well-tolerated for the treatment of refractory sino-nasal aspergillosis in dogs. Long-term survival is possible with prolonged treatment, but relapse is possible. Larger prospective studies are warranted to further evaluate these preliminary findings. © 2017 British Small Animal Veterinary Association.

  12. Primary aspergillosis of vocal cord: Long-term inhalational steroid use can be the miscreant

    Directory of Open Access Journals (Sweden)

    Arpita Saha

    2015-12-01

    Full Text Available Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis.

  13. The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis.

    Science.gov (United States)

    Sarrafzadeh, Shokooh Azam; Hoseinpoor Rafati, Ali; Ardalan, Maryam; Mansouri, Davood; Tabarsi, Payam; Pourpak, Zahra

    2010-09-01

    Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients. Immunocompromised patients diagnosed with invasive pulmonary aspergillosis (IPA) based on the European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Group (EORTC/MSG) with three levels of certainty proven, probable and possible, referred for GM antigen measurement at Immunology, Asthma and Allergy Research Institute (IAARI) from 2006 to 2009 and if they met the criteria were enrolled in this study. Totally 49 patients with IPA were enrolled in our study. According to EORTC/MSG, patients categorized into three levels of certainty: They were diagnosed as 'proven' invasive pulmonary aspergillosis 16(32.7%), 'probable' 18(36.7%) and 'possible' 15(30.6%). The most common host risk factor was solid tumors 17(34.7%). The accuracy of Galactomannan assay increased from 0.5 to 2 cutoffs. The optimum sensitivity and specificity obtained at the index cutoff of ≥1.5 for diagnosis of "proven" IPA; which were respectively, 69.2% and 72.2%. Other cutoffs had high variance between sensitivity and specificity for diagnosis of IPA. The calculated cutoff gained by receiver operating characteristic (ROC) analysis for detecting proven IPA was 1.5. Intermediate accuracy of serum GM test in conjunct with clinical findings would help early IPA detection among immunocompromised patients.

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

    Directory of Open Access Journals (Sweden)

    Michaël Schwarzinger

    Full Text Available 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.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.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.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 antigenemia and a standardized quantitative PCR assay.

  15. A challenging case of invasive pulmonary aspergillosis after near-drowning: a case report and literature review.

    Science.gov (United States)

    Jenks, Jeffrey D; Preziosi, Michael

    2015-09-01

    Near-drowning, a relatively common event, is often complicated by subsequent pneumonia. While endogenous and exogenous bacteria are typical pathogens, rarely fungi are as well. We report a complicated case of invasive pulmonary aspergillosis in a 30-year-old man after a near-drowning event. We also review the medical literature for similar cases. All cases of invasive pulmonary aspergillosis after near-drowning reported in the literature involve Aspergillus fumigatus . The majority of cases involved submersion in stagnant water after a motor vehicle accident (MVA). Treatment varied considerably, with amphotericin B used in the majority of cases. Morbidity was considerable with prolonged hospitalization occurring in every case, and mortality occurring in fifty percent of the reported cases. Although a rare complication of near-drowning, invasive pulmonary aspergillosis can occur and lead to significant morbidity and mortality. After near-drowning A. fumigatus isolated from the respiratory tract should be assumed to be a true pathogen and treated accordingly.

  16. Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

    Directory of Open Access Journals (Sweden)

    Paulien E. Bunskoek

    2017-06-01

    Full Text Available Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum levels of 3–9.5 mg/l were achieved without significant side-effects. Follow-up bronchoscopy and computed tomography showed complete resolution of the lesions.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies.

    Science.gov (United States)

    Reischies, Frederike M J; Raggam, Reinhard B; Prattes, Juergen; Krause, Robert; Eigl, Susanne; List, Agnes; Quehenberger, Franz; Strenger, Volker; Wölfler, Albert; Hoenigl, Martin

    2016-03-01

    Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. 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.

  2. Progression of hepatic aspergillosis following second renal transplantation in a patient with recurrent glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Krishan L Gupta

    2012-01-01

    Full Text Available Invasive aspergillosis is a serious complication in renal transplant recipients. Hepatic involvement, although seen in liver transplant recipients, has not been reported following renal transplantation. We describe here an interesting occurrence of hepatic Aspergillus infection in a renal transplant recipient. The infection responded to anti-fungal therapy, but there was re-activation following a second renal transplant. In addition, the patient had recurrence of the underlying membrano-proliferative glomerulonephritis following both transplants. The relevant existing literature relating to these problems has been reviewed.

  3. 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

    ) in immunohistochemical and immunoblotting assays. In immunohistochemical assays, all MAbs raised against WSSA cross-reacted heavily with a number of other fungal species. All 4 MAbs (MAb-WF-AF-1-4) raised against the WF reacted strongly with hyphae of Aspergillus spp.; hyphae of Scedosporium apiospermum were also......), the MAb-WF-AF-1 and the polyclonal anti-Aspergillus antibodies reacted in a similar pattern, i.e., positively in 41 aspergillosis lesions and negatively in 92 zygomycotic lesions. Hyphae in 3 of 12 lesions that were not stained by the polyclonal antibodies reacted with the specific MAb-WF-AF-1; i...

  4. Tumor shape pulmonary mucormycosis associated with sinonasal aspergillosis in a diabetic patient

    Directory of Open Access Journals (Sweden)

    Sophie Point

    2018-03-01

    Full Text Available Mucormycosis is a rare and life-threatening fungal infection of the Mucorales order occurring mainly in immunosuppressed patients. The most common forms are rhinocerebral but pulmonary or disseminated forms may occur. We report the case of a 61-year-old patient in whom pulmonary mucormycosis was diagnosed during his first-ever episode of diabetic ketoacidosis. While receiving liposomal amphotericin B, a sinusal aspergillosis due to Aspergillus fumigatus occurred. Evolution was slowly favorable under antifungal tritherapy by liposomal amphotericin B, posaconazole and caspofungin.

  5. Post-influenzal triazole-resistant aspergillosis following allogeneic stem cell transplantation.

    Science.gov (United States)

    Talento, Alida Fe; Dunne, Katie; Murphy, Niamh; O'Connell, Brian; Chan, Grace; Joyce, Eimear Ann; Hagen, Ferry; Meis, Jacques F; Fahy, Ruauri; Bacon, Larry; Vandenberge, Elisabeth; Rogers, Thomas R

    2018-03-23

    Influenza virus infection is now recognised as a risk factor for invasive pulmonary aspergillosis (IPA). Delays in diagnosis contribute to delayed commencement of antifungal therapy. Additionally, the emergence of resistance to first-line triazole antifungal agents puts emphasis on early detection to prevent adverse outcomes. We present 2 allogeneic stem cell transplant patients who developed IPA due to triazole-resistant Aspergillus fumigatus following influenza infection. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole-resistance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Computed tomography in the assessment of angioinvasive pulmonary aspergillosis in patients with acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Leao, Renata Carneiro [Clinica Radiologica Luiz Felippe Mattoso, Rio de Janeiro, RJ (Brazil); Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia]. E-mail: edmarchiori@bol.com.br; Rodrigues, Rosana [Universidade Federal, Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Servico de Radiodiagnostico; Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Radiologia; Gasparetto, Emerson L. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Radiologia; Escuissato, Dante L. [Parana Univ., Curitiba, PR (Brazil). Dept. de Radiologia

    2006-09-15

    Objective: the aim of this study was to evaluate the main findings of computed tomography in patients presenting acute leukemia complicated by angio invasive 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 in only one case of mass. Other findings observed were: crazy-paving pattern (two cases), patchy areas of ground-glass attenuation opacity (three cases) and pleural involvement (seven cases) under the form of effusion or thickening. Conclusion: areas of consolidation, mass or nodule, even a solitary one, presenting halo sign on CT images evaluated in an appropriate clinical context are highly suggestive of angio invasive aspergillosis. (author)

  7. [Studies on usefullness of imidasol preparations for treatment of pulmonary and air sacks aspergillosis in geese].

    Science.gov (United States)

    Ramisz, A; Balicka-Ramisz, A

    2001-01-01

    The studies were carried out in two geese farms with a total number of 11.143 - 4 weeks old birds. Two imidazol preparations--5 per cent Miconazole powder and 2 Clotrimazole solution were used in these studies. Miconazole was applied as feed additive for 200 with aspergillosis infected geese, in a dosis of 10 mg of active substance on one kg of body weight. Clotrimazole was administered in a form of inhalation in a dose of 1,5 1 of 2 per cent solution per geese house of 3000 m3. Spraying was performed using gas-pipes of steam ganerator joined to the air compressor of the type 3 JW - 60 (6hp). In this way 5 - 10 microm partiches were obtained. The preparation was sprayed twice ad 2 - 4 days intervals. After Miconazole administration the recovery of sick birds and inhibition of the disease in geese were observed. The Clotrimazole preparations may be also administered prophylactically in geese houses, were stationary aspergillosis has been observed.

  8. [Economical evaluation of the treatment of invasive aspergillosis in pediatric oncology patients. Santiago. Chile].

    Science.gov (United States)

    Moreno, Claudia; del Valle, Gladys; Coria, Paulina

    2010-08-01

    Invasive aspergillosis (IA) is a serious opportunistic infection in immunocompromised patients. Transplant recipients and patients with cancer represent the highest risk group. The antifungal treatment involves prolonged hospitalization and high economic resources. to estimate costs represented by IA as an intercurrent complication of oncologic treatment. Retrospective case-control study. Estimation of the cost of treatment in pediatric oncologic patients with IA in the Hospital Luis Calvo Mackenna during the years 2007-2008 was done. A control for each case of IA paired by sex, age, number of diagnosis and clinical department was selected. There were 13 patients during the observation period. The attributable cost of treatment of aspergillosis was US $23,600 and the cost for each indicator was: hospital days US $16,500; antifungal therapy US $7,000; and serum galactomannan US $100. In this study, the cost of treating IA is mainly due to hospitalization and antifungal medications. Three patients acquired IA in spite of staying in a protected environment.

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

    Directory of Open Access Journals (Sweden)

    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

  10. Immunodiagnosis of systemic aspergillosis. I. Antigenemia detected by radioimmunoassay in experimental infection

    International Nuclear Information System (INIS)

    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

  11. [Posttraumatic primary cutaneous aspergillosis with Candida guilliermondii infection in a healthy host].

    Science.gov (United States)

    Türkşen, Zeynep; Yağcı, Server; Karadağ, Ayşe Serap; Tezer, Ayla; Taner, Omer Faruk; Tekin, Fatih; Arıkan Akdağlı, Sevtap

    2010-10-01

    Opportunistic fungal infections are usually seen in immunocompromised patients. While Candida is the most prevalent agent in such infections, Aspergillus is at the second order. Primary cutaneous aspergillosis is most common in immunocompromised patients but can rarely be seen in healthy hosts as well. We report a case of posttraumatic primary cutaneous aspergillosis and Candida guilliermondii coinfection in a 70-years-old healthy man. The patient had an ulcerous lesion which developed in the site of a trauma on the middle finger of the right hand. Histopathological examination of the biopsy specimens revealed septate hyphae with dichotomous branching small circular blastospores. The cultures of the biopsy specimen yielded yellow-green colored, granular mold colonies and creamy white yeast colonies. Microscopic examination of the lactophenol cotton blue stained mold colonies indicated long conidiophores with vesicles surrounded by uniseriate phialides, compatible with Aspergillus flavus. Yeast colonies were identified as Candida guilliermondii by ID32C (BioMerieux, France) and by their microscopical morphology detected in corn meal-Tween 80 agar incubated at 25°C for 72 hours. The patient was treated properly with surgical debridement and itraconazole therapy. Since the immune system is compressed as a consequence of aging, cutaneous opportunistic fungal infections should be considered in the differential diagnosis of posttraumatic necrotic ulcers and black eschar in aged patients.

  12. A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism.

    Science.gov (United States)

    Laskaris, Paris; Vicentefranqueira, Rocío; Helynck, Olivier; Jouvion, Grégory; Calera, José Antonio; du Merle, Laurence; Suzenet, Franck; Buron, Frédéric; de Sousa, Rodolphe Alves; Mansuy, Daniel; Cavaillon, Jean-Marc; Latgé, Jean-Paul; Munier-Lehmann, Hélène; Ibrahim-Granet, Oumaima

    2018-06-01

    Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good in vitro activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy. Copyright © 2018 American Society for Microbiology.

  13. Invasive pulmonary aspergillosis mimicking organizing pneumonia after mTOR inhibitor therapy: A case report

    Directory of Open Access Journals (Sweden)

    Yuki Iijima

    2018-04-01

    Full Text Available A 67-year-old man presented to the hospital with complaints of fever and cough. He had a past medical history of renal cell carcinoma and had just started treatment with temsirolimus, a mammalian target of rapamycin (mTOR inhibitor. A 1-week course of antibiotics did not have any effect on his symptoms. A chest computed tomography (CT scan showed the reversed halo sign (RHS. Organizing pneumonia induced by mTOR inhibitor treatment was initially considered. However, transbronchial biopsy revealed clusters of fungal organisms, suggesting infection with Aspergillus spp. Within just 2 weeks, a CT scan showed drastic enlargement of the cavitary lesion, with multiple newly formed consolidations. The patient was diagnosed with invasive pulmonary aspergillosis. Concomitant treatment with voriconazole and micafungin was started. Two weeks after the initiation of treatment, he became afebrile with gradual regression of the cavitary lesion and consolidations. Keywords: mTOR inhibitor, Organizing pneumonia, Reversed halo sign, Invasive pulmonary aspergillosis, Immunocompromise

  14. History of treated pulmonary tuberculosis will also be an underlying symptom of opportunistic aspergillosis by Aspergillus flavus: A case report

    Directory of Open Access Journals (Sweden)

    Akbar Hossein Nejad

    2015-01-01

    Conclusion: The importance of tuberculosis (TB in the development of aspergillosis, even after treatment, has been highlighted by multiple studies. Microbiological and molecular evaluation are needed to detect PA quickly and accurately. The WHO reported about 8.8 million new cases of TB in 2010. Therefore, it is essential to focus more on monitoring of diagnosis and treatment of PA.

  15. A Case Of Invasive Aspergillosis In A Patient With No identifiable Immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Carey MP

    2008-01-01

    Full Text Available Invasive fungal infections usually affect patients with immunodeficiencies and very rarely patients with no known or identifiable risk factors. Diagnosis could be delayed in patients without previously known immunodeficiencies due to a low index of suspicion, leading to a delay in treatment and a potential poor outcome. We report a case of a postpartum woman with no history of immuno-compromised disease who developed left hemiparesis with evidence of invasive aspergollosis affecting the nervous system, and leading to fatal outcome. The patient had a mass-like lesion in the neuroimaging with soft tissue shadowing in the chest x-ray leading to initial diagnosis of tuberculosis. The brain biopsy showed changes consistent with a diagnosis of aspergillosis. The source of the aspergillus infection was not clear. Aspergillus infection should be considered in patients with no identifiable immunodeficiencies who have abnormal brain imaging and chest x-ray, as early treatment may alter the outcome.

  16. Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.

    Science.gov (United States)

    Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C

    2017-10-01

    The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Combined Churg-Strauss syndrome and allergic bronchopulmonary aspergillosis - case report and review of the literature.

    Science.gov (United States)

    Ren, Shaohua

    2013-01-01

    A rare case of combined Churg-Strauss syndrome (CSS) and allergic bronchopulmonary aspergillosis (ABPA) was presented. A 41-year-old woman was diagnosed with CSS based upon asthma, eosinophilia (23%), chest radiographic findings, paranasal sinusitis, peripheral neuropathy and positive p- anti-neutrophil cytoplasmic antibodies (pANCA). The diagnosis of ABPA was established on the pathological findings of allegic mucin impaction and fungal hyphae on lung biopsy. It was further proved by positive serum IgE and IgG antibodies specific to afumigatus. The clinical investigation features were reviewed in the patients with combined CSS and ABPA. All patients had the time sequence of the development of CSS after ABPA uniformly, suggesting immunopathogenesis involving the emergence of CSS. The role of lung biopsy in the diagnosis of the condition was emphasized. © 2012 Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India.

    Directory of Open Access Journals (Sweden)

    Ritesh Agarwal

    Full Text Available It would be of considerable interest to clinicians if the burden of chronic pulmonary aspergillosis (CPA and allergic bronchopulmonary aspergillosis (ABPA in India were known. Herein, we estimate the burden of CPA following pulmonary tuberculosis (PTB, and ABPA (and severe asthma with fungal sensitization [SAFS] complicating asthma.We used the population estimates for India from the 2011 census data. The burden of asthma was estimated using three different methods (Global Initiative against Asthma [GINA] report statement, World Health Survey [WHS] estimates, Indian study on the epidemiology of asthma and chronic bronchitis [INSEARCH]. Global and India-specific figures were used for calculating the prevalence of ABPA and SAFS. The World Health Organization estimates were used for calculating PTB rates while the frequency of CPA was assessed from a previously published scoping review. Sensitivity analysis was performed to determine the burden in various scenarios.The total Indian population in 2011 was 1.2 billion. The asthma prevalence in adults was estimated at about 27.6 (range, 17-30 million. The burden of ABPA ranged from 0.12-6.09 million with different assumptions (best estimate, 1.38 [range, 0.86-1.52] million. The prevalence of SAFS was approximated at about 0.52-1.21 million (best estimate, 0.96 [range, 0.6-1.06] million. The incident TB cases were about 2.1 million while the annual incidence of CPA varied 27,000-0.17 million cases, with different estimates. If the mortality of CPA is estimated as 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000.There is a significant burden of ABPA, SAFS and CPA in India. Prospective community-based studies are required to accurately determine the prevalence of these disorders.

  1. Therapeutic effect of Sepia ink extract against invasive pulmonary aspergillosis in mice

    Directory of Open Access Journals (Sweden)

    Sohair R. Fahmy

    2014-10-01

    Full Text Available Invasive pulmonary aspergillosis (IPA is a life-threatening disease in immunocompromised patients that requires aggressive therapy. Because of the widespread use of antibiotics, corticosteroids, antitumor drugs, and immunosuppressive drugs, the morbidity of IPA is currently increasing. The ink secretion of molluscan species was identified as one of the novel sources of bioactive compounds. So the present study designed to investigate the antifungal and antioxidant effects of Sepia officinalis ink extract against IPA in mice. Eighty neutropenic infected mice were randomly assigned into four main groups (20 mice/group. The 1st group was treated with saline, neutropenic infected, the 2nd group was treated with ink (200 mg/kg and the 3rd group was treated with amphotericin B (150 mg/kg and the 4th group was treated with ink plus amphotericin B (Ink 200 mg/kg and AMB 150 mg/kg. Treatment was started at 24 h after fungal inoculation and was administered for 3 consecutive days. The present study demonstrated good in vitro and in vivo antifungal activity of IE against Aspergillus fumigatus. Compared with IPA group; IE-treated, AMB-treated, and AMB + IE-treated animals had a 67.80%, 83.41%, and 72.68% reduction in the pulmonary fungal burden, respectively. Treatment with IE and/or AMB for one and three days significantly decreased MDA and increased GSH and SOD levels in the lung tissues as compared with the infected untreated group. In conclusion, the results of our in vivo and in vitro studies demonstrate that IE has therapeutic effect against invasive pulmonary aspergillosis via reducing oxidative stress.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Disseminated aspergillosis in an immunocompetent patient with detectable bis(methylthio)gliotoxin and negative galactomannan.

    Science.gov (United States)

    Vidal-García, Matxalen; Sánchez-Chueca, Pilar; Domingo, María Pilar; Ballester, Carlos; Roc, Lourdes; Ferrer, Isabel; Revillo, María José; Pardo, Julián; Gálvez, Eva María; Rezusta, Antonio

    Disseminated invasive aspergillosis is an exceptional finding in immunocompetent hosts. As in immunocompromised patients, it has high mortality rates. Early diagnostic methods are required in order to properly manage the patient. Bis(methylthio)gliotoxin (bmGT) is a novel biomarker, useful in onco-hematological patients. A 70-year-old male, with non-insulin dependent type II diabetes mellitus and a past surgery history of aortic valve replacement with coronary by-pass five years ago, was seen in the emergency department with blurred vision. Three days later, endogen endophthalmitis was diagnosed in the ophthalmology clinic. During admission for the vitrectomy, he suffered an ischemia of the right lower limb. A thoracic computed tomography revealed a mycotic aneurysm of the ascending thoracic aorta and parietal thrombus. The ascending aorta was replaced and abundant brittle material of infectious appearance, found between the aortic valve graft and the aneurysm, was removed. Aspergillus fumigatus sensu stricto grew in both vitreous and aorta cultures. BmGT was detected in two serum samples obtained prior to intravenous antifungal treatment, which was then reduced after voriconazole treatment was started. Disseminated invasive aspergillosis is a severe disease regardless of the immune status of the patient. This case report suggests that bmGT could be a suitable early diagnostic biomarker, not only in neutropenic patients, but also in immunocompetent hosts. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Prevalence and fungal profile of pulmonary aspergillosis in immunocompromised and immunocompetent patients of a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Prakash Ved, Mishra Prem P, Verma Shashi K, Sinha Shivani, Sharma Mahendra

    2014-03-01

    Full Text Available Background: Aspergillus is a fungus which may present an array of pulmonary manifestations, depending on the patient’s immunological and physiological state. Although the incidence of pulmonary aspergillosis occurs primarily in immunocompromised patients but the incidence is also rising in immunocompetent individuals, especially in developing countries. Aim: The objective of the study was to determine the prevalence and predisposing factors of pulmonary aspergillosis along with species identification. Materials and Methods: One hundred and three patients admitted to the Department of Chest and Tuberculosis and in the Department of Medicine from Jan 2012 to Jan 2013 were included in this study. The patients were epitomized on the basis of clinical signs and symptoms, physical examination, chest radiography, CT scans, histopathological examination, bronchoscopy and fungal examination including potassium hydroxide mount, fungal culture of sputum and bronchoalveolar lavage. Species identification was done by colony characteristics, slide culture and Lactophenol Cotton blue mount. Results: Out of the 103 patients, (63 males and 40 females Aspergillus species has been isolated from 17 (16.5% males and 07 (6.79% females. Various predisposing factors of pulmonary aspergillosis have been identified in which pulmonary tuberculosis, chronic smoking and environmental exposure to asbestos, cement its tops the list. Many of the patients had multiple predisposing factors. Aspergillus species were isolated in 24 (23.3% cases. Aspergillus fumigatus was the predominant species isolated in 13 (54.16% cases followed by Aspergillus flavus in 07 (29.16% cases, Aspergillus niger in 03 (12.5 % and Aspergillus terrus in 1 (4.16% cases. Conclusion: It is concluded that the prevalence of pulmonary Aspergillosis is quite high in immunocompromised individuals and low in immunocompetent individuals. An adequate and efficient evaluation of the etiological agents has a

  5. Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis.

    Science.gov (United States)

    Baxter, C G; Denning, D W; Jones, A M; Todd, A; Moore, C B; Richardson, M D

    2013-04-01

    Detection of Aspergillus IgG antibodies is important in the diagnosis of chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Immunoprecipitation techniques to detect these antibodies appear to lack sensitivity and accurate quantitation compared with enzyme immunoassays (EIA). This study assessed the performance of two commercial EIAs compared with counterimmunoelectrophoresis (CIE). This was a prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies were detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG. Inter-assay reproducibility was determined for each method and 25 patients had two serum samples analysed within a 6-month interval. When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively) for detection of Aspergillus IgG antibodies. The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE titre. ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas Platelia IgG was 33%. Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL. The direction of CIE titre change over 6 months was mirrored by ImmunoCap IgG levels in 92% of patients, and by Platelia IgG in 72% of patients. Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to have better reproducibility and may be more suitable for monitoring patient disease. © 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  6. Angioinvasive pulmonary aspergillosis after allogeneic bone marrow transplantation: clinical and high-resolution computed tomography findings in 12 cases

    OpenAIRE

    Gasparetto, Emerson L.; Souza, Carolina A.; Tazoniero, Priscilla; Davaus, Taisa; Escuissato, Dante L.; Marchiori, Edson

    2007-01-01

    The aim of this study was to present the clinical and high-resolution CT scan findings of angioinvasive pulmonary aspergillosis (APA) in 12 patients who underwent allogeneic bone marrow transplantation (BMT). The CT scans were reviewed by three chest radiologists who assessed the pattern and distribution of findings by consent. There were 7 (58%) female and 5 (42%) male patients, with aging between 5 and 50 years (average of 26 years). All patients were submitted to BMT for the treatment of h...

  7. Prophylaxis of invasive aspergillosis with caspofungin during construction works in patient with acute lymphoblasic leukemia treated with vincristin

    Directory of Open Access Journals (Sweden)

    Mojca Modic

    2012-12-01

    Case presentation: A 59-year old woman with common ALL relapsed after 22 years (normal cytogenetics. She was treated according to the UKALL XII regimen and achieved complete second remission. She received four cycles of vincristine 2 mg i.v. In a retrospective cohort study, prolonged neutropenia, use of steroids, nursing unit without laminar air flow during a period of construction works were associated with an increased incidence of invasive aspergillosis in patients who did not receive primary antifungal prophylaxis. Intravenous caspofungin was administered to the patient as primary aspergillosis prophylaxis on the first day of chemotherapy. Galactomannan antigen tests were negative during the period of neutropenia. There was no infection in the period of prolonged neutropenia. Conclusions: The author discusses primary prophylaxis of invasive aspergillosis with caspofungin during construction works in patients with acute lymphoblastic leukemia treated with vincristine. Because of non-conventional unit without laminar air flow during induction chemotherapy treatment, which leads to an increased risk of invasive fungal infection with Aspergillus, caspofungin prophylaxis is recommended at least until upgrade to laminar flow or cessation of construction works.

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

    International Nuclear Information System (INIS)

    Veltri, A.; Anselmetti, G.C.; Bartoli, G.; Martina, M.C.; Galli, J.; Regge, D.; Bertini, M.

    2000-01-01

    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 3 per session of a 1 mg/cm 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.)

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

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

    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. Proteomic demonstration of the recurrent presence of inter-alpha-inhibitor H4 heavy-chain during aspergillosis induced in an animal model.

    Science.gov (United States)

    Desoubeaux, Guillaume; Jourdan, Marie-Lise; Valera, Lionel; Jardin, Bénédicte; Hem, Sonia; Caille, Agnès; Cormier, Bénédicte; Marchand-Adam, Sylvain; Bailly, Éric; Diot, Patrice; Chandenier, Jacques

    2014-05-01

    Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-valuevalue0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Fulminant Invasive Pulmonary Aspergillosis After a Near-Drowning Accident in an Immunocompetent Patient.

    Science.gov (United States)

    Ratermann, Kelley L; Ereshefsky, Benjamin J; Fleishaker, Elise L; Thornton, Alice C; Buch, Ketan P; Martin, Craig A

    2014-09-01

    To report on invasive aspergillosis infection in an immunocompetent adult after a near-drowning event, which allowed this pathogen to easily gain access to the human respiratory system and result in rapid, severe infection. A 51-year-old female developed severe pneumonia after a near-drowning accident. Two days after admission, a bronchial alveolar lavage (BAL) was performed and was positive for Aspergillus fumigatus. After a 30-day hospital course, multiple antifungals, and various routes of administration, the patient expired. Pneumonia is particularly common because of the aspiration of contaminated water. Whereas pneumococci, staphylococci, and Gram-negative bacteria are all common pathogens for this type of infection, fungi such as Aspergillus spp can also be involved and may be life threatening. Typically, these cases are reported in individuals with an immunodeficiency such as from receipt of myelosuppressive chemotherapy, bone marrow transplants, or lung transplants. Despite initiation of an appropriate empirical antifungal regimen, the rapid recovery of A fumigatus from pulmonary alveolar lavage and BAL samples as well as extremely elevated levels of galactomannan and (1→3)-β-D glucan may have indicated an invasive fungal infection (IFI). IFIs are uncommon in immunocompetent adults, but in the event of a near-drowning accident, environmental fungi can gain access to the human respiratory system and result in rapid, severe infection. Based on this case and the others described, it appears that near-drowning patients need an early initial evaluation for IFI. © The Author(s) 2014.

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

    Science.gov (United States)

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

    2018-04-26

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

  15. Two year follow-up of a garbage collector with allergic bronchopulmonary aspergillosis (ABPA).

    Science.gov (United States)

    Allmers, H; Huber, H; Baur, X

    2000-04-01

    Separate collection of biodegradable garbage and recyclable waste is expected to become mandatory in some western countries. A growing number of persons engaged in garbage collection and separation might become endangered by high loads of bacteria and fungi. Case history and examination A 29 year old garbage collector involved in emptying so-called biological garbage complained of dyspnea, fever, and flu-like symptoms during work beginning in the summer of 1992. Chest x-ray showed streaky shadows near both hili reaching into the upper regions. IgE- and IgG-antibodies (CAP, Pharmacia, Sweden) were strongly positive for Aspergillus fumigatus with 90.5 kU/L and 186%, respectively. Total-IgE was also strongly elevated with 5430 kU/L. Bronchial challenge testing with commercially available Aspergillus fumigatus extract resulted in an immediate-type asthmatic reaction. Two years later he was still symptomatic and antibodies persisted at lower levels. Our diagnosis was allergic bronchopulmonary aspergillosis (ABPA) including asthmatic responses as well as hypersensitivity pneumonitis (extrinsic allergic alveolitis) due to exposure to moldy household waste. A growing number of persons engaged in garbage collection and handling are exposed and at risk to develop sensitization to fungi due to exposure to dust of biodegradable waste. Further studies are necessary to show if separate collection of biodegradable waste increases the health risks due to exposure to bacteria and fungi in comparison to waste collection without separation. Copyright 2000 Wiley-Liss, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Epidemiology of invasive pulmonary aspergillosis in patients with liver failure: Clinical presentation, risk factors, and outcomes.

    Science.gov (United States)

    Zhang, Xuan; Yang, Meifang; Hu, Jianhua; Zhao, Hong; Li, Lanjuan

    2018-02-01

    Objective Invasive pulmonary aspergillosis (IPA) is a severe and often lethal infection. The possible risk factors, clinical presentation, and treatment of patients with simultaneous liver failure and IPA have received little attention in previous studies. The aim of this study was to investigate the epidemiology of IPA in patients with liver failure in an effort to reduce patient mortality. Methods The patients with liver failure (including acute liver failure , sub-acute liver failure , acute-on-chronic liver failure and chronic liver failure) were recruited from 2011 to 2016. The clinical data of these patients were retrieved for the study. Results In total, 1077 patients with liver failure were included in this study. Of the 1077 patients, 53 (4.9%) had IPA. Forty-four (83%) patients with IPA died. Independent risk factors for IPA were male sex (hazard ratio [HR] = 2.542), hepatorenal syndrome (HR = 2.463), antibiotic use (HR = 4.631), and steroid exposure (HR = 18.615). Conclusions IPA is a fatal complication in patients with liver failure. Male sex, hepatorenal syndrome, antibiotic use, and steroid exposure were independent risk factors for IPA. When patients with liver failure have these risk factors and symptoms of pneumonia such as cough or hemoptysis, clinicians should be cautious about the possibility of IPA.

  18. Beneficial effects of Omalizumab therapy in allergic bronchopulmonary aspergillosis: A synthesis review of published literature.

    Science.gov (United States)

    Li, Jian-Xiong; Fan, Li-Chao; Li, Man-Hui; Cao, Wei-Jun; Xu, Jin-Fu

    2017-01-01

    Omalizumab, a humanized mAb that binds to IgE, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of Omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA) except some case reports. To assess the clinical and immunological effects of Omalizumab in ABPA patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of Omalizumab therapy in ABPA and conducted subgroup analyses to determine factors that influenced the therapy endpoints. We found that Omalizumab treatment not only provided a clinically important reduction in serum IgE, exacerbation rates and steroid requirement, but also showed attenuated asthma symptoms and improved pulmonary function parameters in patients with ABPA. Moreover, further discussion was made when interpretating the results. Double-blind, randomized, placebo-controlled trials are necessary to establish the efficacy and safety of this novel therapeutic intervention for ABPA patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Simon F Dufresne

    Full Text Available Mortality associated with invasive aspergillosis (IA remains high, partly because of delayed diagnosis. Detection of microbial exoantigens, released in serum and other body fluids during infection, may help timely diagnosis. In course of IA, Aspergillus galactomannan (GM, a well established polysaccharide biomarker, is released in body fluids including urine. Urine is an abundant, safely collected specimen, well-suited for point-of-care (POC testing, which could play an increasing role in screening for early disease. Our main objective was to demonstrate GM antigenuria as a clinically relevant biological phenomenon in IA and establish proof-of-concept that it could be translated to POC diagnosis. Utilizing a novel IgM monoclonal antibody (MAb476 that recognizes GM-like antigens from Aspergillus and other molds, we demonstrated antigenuria in an experimental animal IA model (guinea pig, as well as in human patients. In addition, we investigated the chemical nature of the urinary excreted antigen in human samples, characterized antigen detection in urine by immunoassays, described a putative assay inhibitor in urine, and indicated means of alleviation of the inhibition. We also designed and used a lateral flow immunochromatographic assay to detect urinary excreted antigen in a limited number of IA patient urine samples. In this study, we establish that POC diagnosis of IA based on urinary GM detection is feasible. Prospective studies will be necessary to establish the performance characteristics of an optimized device and define its optimal clinical use.

  20. Invasive pulmonary aspergillosis - CT findings in context with the clinical course

    International Nuclear Information System (INIS)

    Seyfarth, H.J.; Winkler, J.; Wirtz, H.; Nenoff, P.; Krahl, R.; Kloeppel, R.; Borte, G.

    2002-01-01

    Purpose: To investigate the impact of chest radiographs and CT in patients suffering from invasive pulmonary aspergillosis (IPA) compared to the clinical course. Patients and Methods: Twenty-three patients with confirmed diagnosis of IPA between January 1996 and September 1999 were included in this study. Signs of inflammatory infiltrates on chest radiographs and CT were retrospectively evaluated in relation to the onset of the clinical symptoms. Infiltrates on CT were analyzed in detail with respect to number, morphology, and localization. Results: Seventy-six infiltrates were found on the CT of 22 patients; one patient had diffuse areas of lung infiltrates. Both lungs were affected by infiltrates in 14 patients. Pleural effusions were confirmed in 12 patients. Twelve patients had typically round foci with halo and nine patients crescent air signs. The preferred localization of lung infiltrates was segment 6. The median interval between the onset of clinical symptoms and the first radiographic changes was 5.5 days, with an additional interval of 4.5 days until confirmation by CT. Localization, number of infiltrates, and clinical course were not related. Conclusion: In immune-compromised patients with fever, a CT of the chest should be carried out as soon as possible to detect signs indicative of IPA. Morphological changes on CT like a round focus with halo and crescent air sign support the diagnosis of IPA. In this context, special attention should be directed to pulmonary segment 6. (orig.) [de

  1. Cerebral aspergillosis: comparison of radiological and neuropathologic findings in patients with bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, U. [Dept. of Neuroradiology, University Hospital, Essen (Germany); Dept. of Neuroradiology, Gilead Hospital, Bielefeld (Germany); Hettmann, M.; Schwechheimer, K. [Dept. of Neuropathology, University Hospital, Essen (Germany); Maschke, M. [Dept. of Neurology, University Hospital, Essen (Germany); Doerfler, A.; Forsting, M. [Dept. of Neuroradiology, University Hospital, Essen (Germany)

    2001-07-01

    Thirty-six lesions in six patients who died from cerebral Aspergillus infection after bone marrow transplantation (BMT) were studied with regard to signal intensity, contrast enhancement, size, and location. The diagnosis was confirmed in all cases by autopsy. Retrospective correlation of histopathological and radiological findings was possible for 14 lesions. Most of the lesions (22/36) had isointense to low signal intensity on T2-weighted images (T2WI). Histopathologically, hemorrhagic necrosis was determined in three of them. Areas of high signal intensity on T1-weighted images (T1WI) were related to gross hemorrhage. Two infarctions showed intravascular accumulation of fungal hyphae with secondary thrombosis of the vessel. The remaining 12 lesions had high signal intensity on T2WI and low on T1WI. Histopathologically, four were infectious and four were unspecific demyelinated lesions. In conclusion, cerebral aspergillosis typically presented with large lesions showing isointense to low signal intensity on T2WI that could have areas of high signal on T1WI. Contrast enhancement was only visible in 15 lesions, and the predominant locations were the subcortical white matter, the cerebellum, and the basal ganglia. Small lesions with high signal on T2WI and low signal on T1WI could not necessarily be related to Aspergillus infection. (orig.)

  2. Cerebral aspergillosis: comparison of radiological and neuropathologic findings in patients with bone marrow transplantation

    International Nuclear Information System (INIS)

    Dietrich, U.; Hettmann, M.; Schwechheimer, K.; Maschke, M.; Doerfler, A.; Forsting, M.

    2001-01-01

    Thirty-six lesions in six patients who died from cerebral Aspergillus infection after bone marrow transplantation (BMT) were studied with regard to signal intensity, contrast enhancement, size, and location. The diagnosis was confirmed in all cases by autopsy. Retrospective correlation of histopathological and radiological findings was possible for 14 lesions. Most of the lesions (22/36) had isointense to low signal intensity on T2-weighted images (T2WI). Histopathologically, hemorrhagic necrosis was determined in three of them. Areas of high signal intensity on T1-weighted images (T1WI) were related to gross hemorrhage. Two infarctions showed intravascular accumulation of fungal hyphae with secondary thrombosis of the vessel. The remaining 12 lesions had high signal intensity on T2WI and low on T1WI. Histopathologically, four were infectious and four were unspecific demyelinated lesions. In conclusion, cerebral aspergillosis typically presented with large lesions showing isointense to low signal intensity on T2WI that could have areas of high signal on T1WI. Contrast enhancement was only visible in 15 lesions, and the predominant locations were the subcortical white matter, the cerebellum, and the basal ganglia. Small lesions with high signal on T2WI and low signal on T1WI could not necessarily be related to Aspergillus infection. (orig.)

  3. Proteomic Profiling of Serological Responses to Aspergillus fumigatus Antigens in Patients with Invasive Aspergillosis.

    Science.gov (United States)

    Teutschbein, Janka; Simon, Svenja; Lother, Jasmin; Springer, Jan; Hortschansky, Peter; Morton, C Oliver; Löffler, Jürgen; Einsele, Hermann; Conneally, Eibhlin; Rogers, Thomas R; Guthke, Reinhard; Brakhage, Axel A; Kniemeyer, Olaf

    2016-05-06

    Aspergillus fumigatus is the species that most commonly causes the opportunistic infection invasive aspergillosis (IA) in patients being treated for hematological malignancies. Little is known about the A. fumigatus proteins that trigger the production of Aspergillus-specific IgG antibodies during the course of IA. To characterize the serological response to A. fumigatus protein antigens, mycelial proteins were separated by 2-D gel electrophoresis. The gels were immunoblotted with sera from patients with probable and proven IA and control patients without IA. We identified 49 different fungal proteins, which gave a positive IgG antibody signal. Most of these antigens play a role in primary metabolism and stress responses. Overall, our analysis identified 18 novel protein antigens from A. fumigatus. To determine whether these antigens can be used as diagnostic or prognostic markers or exhibit a protective activity, we employed supervised machine learning with decision trees. We identified two candidates for further analysis, the protein antigens CpcB and Shm2. Heterologously produced Shm2 induced a strongly proinflammatory response in human peripheral blood mononuclear cells after in vitro stimulation. In contrast, CpcB did not activate the immune response of PBMCs. These findings could serve as the basis for the development of an immunotherapy of IA.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  6. Diagnostic potential of nested PCR, galactomannan EIA, and beta-D-glucan for invasive aspergillosis in pediatric patients.

    Science.gov (United States)

    Badiee, Parisa; Alborzi, Abdolvahab; Karimi, Mahammad; Pourabbas, Bahman; Haddadi, Pedram; Mardaneh, Jalal; Moieni, Mahsa

    2012-04-13

    Limited specific data and investigations are available for invasive aspergillosis (IA) in pediatric patients. We evaluated the diagnostic potential of three noninvasive tests including the Platelia Aspergillus EIA kit for using galactomannan antigen, (1,3)-β-D-glucan Detection Reagent Kit, and nested-PCR for Aspergillus DNA in sera. We evaluated the diagnostic potential of three noninvasive tests including EIA for galactomannan antigen  (Platelia Aspergillus), nested  PCR assay for Aspergillus DNA and test for (1→3)-β-D-glucan (Glucatell assay Kit). All pediatric patients treated at the hematology/oncology unit who were at increased risk of developing invasive aspergillosis were enrolled. Clinical samples were examined for Aspergillus infections by mycological methods. Serial blood samples were collected twice weekly and evaluated by noninvasive tests. We analyzed 230 consecutive blood samples from 62 pediatric patients. The incidence rate of invasive aspergillosis in the patients was found to be 27.4%, and the etiologic agents were Aspergillus flavus, Aspergillus fumigatus, and Aspergillus spp.  The sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results of galactomannan in patients with proven and probable IA were 90%, 92%, 81.8%, 96%, 11.25, and 0.1; for beta-D-glucan they were 50%, 46%, 26%, 70.6%, 0.9, 0.9; and for nested-PCR they were 80%, 96.2%, 88.9%, 92.6%, 21, and 0.2, respectively. The conventional methods are not able to detect IA, due to the lack of valid and proper sampling. Galactomannan and nested-PCR tests in serum, with enough accuracy and reliability, can serve as noninvasive methods for the detection of IA in pediatric patients. However, the beta-D-glucan test cannot serve as an efficient diagnostic tool in those with hematologic disorders. 

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

    International Nuclear Information System (INIS)

    Horger, Marius; Hebart, Holger; Einsele, Hermann; Lengerke, Claudia; Claussen, C.D.; Vonthein, Reinhard; Pfannenberg, Christina

    2005-01-01

    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 hemorrhage occurred in 19% (9

  8. [Invasive aspergillosis of sphenoidal sinus in a patient in Djibouti, revealed by palsy of cranial nerves: a case report].

    Science.gov (United States)

    Crambert, A; Gauthier, J; Vignal, R; Conessa, C; Lombard, B

    2013-05-01

    The authors report a case of invasive aspergillosis of a sphenoid sinus mucocele revealed in a patient with diabetes in Djibouti by homolateral palsy of the 3rd, 4th, 5th and 6th nerves. This rare condition occurs preferentially in immunodeficient subjects. Because of its clinical polymorphism, its diagnosis is difficult and is often not made until complications develop. Endonasal surgery with anatomopathological and mycological examination is both a diagnostic and therapeutic procedure. It must be performed early, to avoid functional or even life-threatening complications.

  9. Aspergillus Galactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid

    Science.gov (United States)

    Musher, Benjamin; Fredricks, David; Leisenring, Wendy; Balajee, S. Arunmozhi; Smith, Caitlin; Marr, Kieren A.

    2004-01-01

    Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in hematopoietic stem cell transplant patients. Diagnosis requires microbiological or histopathologic demonstration of the organism in tissues; however, cultivation of Aspergillus species from respiratory secretions has low diagnostic sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal therapy and obviating the need for additional costly and potentially morbid diagnostic evaluation. We evaluated the performance of a galactomannan enzyme immunoassay (GM EIA; Bio-Rad) by using a range of index cutoffs to define positivity and a quantitative PCR (qPCR) assay for the detection of Aspergillus species from BAL samples of patients with proven and probable IPA (case patients; n = 49) and without IPA (control patients; n = 50). The sensitivity of the GM EIA was 61% with an index cutoff of 1.0 and 76% with an index cutoff of 0.5; the corresponding specificities were 98 and 94%, respectively. The sensitivity and specificity of qPCR assay were 67 and 100%, respectively. The sensitivity with 22 culture-negative BAL specimens from patients with IPA was 41% for GM EIA with an index cutoff of 1.0, 59% for GM EIA with an index cutoff of 0.5, and 36% for qPCR assay. GM EIA indices and DNA quantities corresponded to BAL fungal burdens, with culture-positive samples having larger amounts of antigen and DNA compared to culture-negative samples. GM EIA and qPCR assay add to the sensitivity of BAL for diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use of these tests may reduce dependence on invasive diagnostic procedures. PMID:15583275

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

    Directory of Open Access Journals (Sweden)

    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.

  11. COMPUTED TOMOGRAPHIC ANATOMY AND CHARACTERISTICS OF RESPIRATORY ASPERGILLOSIS IN JUVENILE WHOOPING CRANES.

    Science.gov (United States)

    Schwarz, Tobias; Kelley, Cristin; Pinkerton, Marie E; Hartup, Barry K

    2016-01-01

    Respiratory diseases are a leading cause of morbidity and mortality in captivity reared, endangered whooping cranes (Grus americana). Objectives of this retrospective, case series, cross-sectional study were to describe computed tomography (CT) respiratory anatomy in a juvenile whooping crane without respiratory disease, compare CT characteristics with gross pathologic characteristics in a group of juvenile whooping cranes with respiratory aspergillosis, and test associations between the number of CT tracheal bends and bird sex and age. A total of 10 juvenile whooping cranes (one control, nine affected) were included. Seven affected cranes had CT characteristics of unilateral extrapulmonary bronchial occlusion or wall thickening, and seven cranes had luminal occlusion of the intrapulmonary primary or secondary bronchi. Air sac membrane thickening was observed in three cranes in the cranial and caudal thoracic air sacs, and air sac diverticulum opacification was observed in four cranes. Necropsy lesions consisted of severe, subacute to chronic, focally extensive granulomatous pathology of the trachea, primary bronchi, lungs, or air sacs. No false positive CT scan results were documented. Seven instances of false negative CT scan results occurred; six of these consisted of subtle, mild air sacculitis including membrane opacification or thickening, or the presence of small plaques found at necropsy. The number of CT tracheal bends was associated with bird age but not sex. Findings supported the use of CT as a diagnostic test for avian species with respiratory disease and tracheal coiling or elongated tracheae where endoscopic evaluation is impractical. © 2015 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Radiology.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Omalizumab in the treatment of allergic bronchopulmonary aspergillosis: One center's experience with 14 cases.

    Science.gov (United States)

    Aydın, Ömür; Sözener, Zeynep Çelebi; Soyyiğit, Şadan; Kendirlinan, Reşat; Gençtürk, Zeynep; Mısırlıgil, Zeynep; Mungan, Dilşad; Sin, Betül Ayşe; Demirel, Yavuz Selim; Çelik, Gülfem Elif; Bavbek, Sevim

    2015-01-01

    Omalizumab has been a valuable option for patients with severe allergic asthma, but there are only case reports regarding effectiveness of omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA). To evaluate the clinical and functional effectiveness of omalizumab in patients with asthma and ABPA in long-term follow-up. The study was conducted as a retrospective chart review of patients with ABPA who were treated with omalizumab injections between December 2008 and June 2014. Once treatment with omalizumab was started, data were collected at three time points: at baseline, after 1 year, and, in June 2014, at the last follow-up. Fourteen patients with ABPA (seven women and seven men; mean [± standard deviation (SD)] age, 44.21 ± 13.01 years) were included. The treatment period was 31.5 ± 3.99 months (mean ± SD). The difference between the baseline and the last evaluation of the mean percentage of forced expiratory volume in 1 second (FEV1) was significant (p = 0.02). The mean asthma control test score was increased at all-time points compared with the basal score (p = 0.001). After omalizumab treatment was initiated, the patients' mean oral corticosteroid dosage significantly decreased (p = 0.001). The baseline exacerbation rate was 2.7 ± 1.5/y (mean ± SD), and the hospitalization rate was 1.4/y, and both were zero at the last assessment (p = 0.001). Eleven of the patients (78.6%) responded perfectly, and three (21.4%) partially responded to treatment. The patients who had a total immunoglobulin E level of 1000 IU/mL (p = 0.05). Omalizumab provided a clinically important reduction in exacerbations and steroid requirement, and improved asthma symptoms and pulmonary function parameters in patients with asthma and ABPA who had previously shown an unsatisfactory response to Global Initiative for Asthma step 4 treatment.

  15. Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis.

    Science.gov (United States)

    Voskamp, Astrid L; Gillman, Andrew; Symons, Karen; Sandrini, Alessandra; Rolland, Jennifer M; O'Hehir, Robyn E; Douglass, Jo A

    2015-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma. The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial. Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry. Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo. Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients.

    Science.gov (United States)

    Nové-Josserand, Raphaële; Grard, Soazic; Auzou, Lila; Reix, Philippe; Murris-Espin, Marlène; Brémont, François; Mammar, Benyebka; Mely, Laurent; Hubert, Dominique; Durieu, Isabelle; Burgel, Pierre-Régis

    2017-02-01

    Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti-IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab-related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow-up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy in CF patients with ABPA. A randomized-controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost-effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

    Science.gov (United States)

    Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

    2016-01-01

    Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

  18. Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis

    Energy Technology Data Exchange (ETDEWEB)

    Vehreschild, J.J.; Vehreschild, M.J.G.T. [University Hospital of Cologne, Department I of Internal Medicine, Cologne (Germany); German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne (Germany); Heussel, C.P. [Chest Clinic at University Hospital Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); University Hospital of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Groll, A.H. [University Children' s Hospital, Infectious Disease Research Program, Department of Paediatric Haematology/Oncology, Muenster (Germany); Silling, G. [University of Muenster, Department of Medicine A, Haematology/Oncology, Muenster (Germany); Wuerthwein, G. [University Hospital Muenster, Centre for Clinical Trials, ZKS Muenster (Germany); Brecht, M. [Chest Clinic at University Hospital Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Cornely, O.A. [University Hospital of Cologne, Department I of Internal Medicine, Cologne (Germany); University of Cologne, Clinical Trials Center Cologne, ZKS Koeln (BMBF 01KN1106), Cologne (Germany); Center for Integrated Oncology CIO Koeln Bonn, Cologne (Germany); University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne (Germany)

    2017-08-15

    Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. (orig.)

  19. Staphylococcus aureus septic pulmonary emboli presenting as angioinvasive aspergillosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    McKerlie, I. [Montreal General Hospital, Dept. of Diagnostic Radiology, Montreal, Quebec (Canada); Bloom, C. [Jewish General Hospital, Dept. of Diagnostic Imaging, Montreal, Quebec (Canada); Kreisman, H. [Jewish General Hospital, Pulmonary Div., Dept. of Medicine, Montreal, Quebec (Canada)

    2001-12-01

    Septic pulmonary emboli (SPE) have a wide spectrum of radiologic and clinical presentations. The characteristic chest radiographic findings of SPE have been well documented in the literature, but a significant number of patients present with nonspecific or equivocal infiltrates that are not definitive for septic emboli. Studies comparing computed tomographic (CT) scans and chest radiographs of patients with documented SPE suggest that CT provides a more characteristic and recognizable pattern of parenchymal involvement than can be routinely identified on plain radiographs. These findings include multiple peripheral nodules ranging in size from 0.5 cm to 3.5 cm, a feeding vessel sign, cavitation, wedge-shaped peripheral lesions abutting the pleura, air bronchograms within the nodules and extension into the pleural space. Patients with leukemia or lymphoma and prolonged bone marrow suppression are at high risk for developing opportunistic infections of the lung. Angioinvasive aspergillosis (AIA) can occur in any severely immunocompromised or chronically debilitated patient. By far, the most common clinical setting is the patient with prolonged granulocytopenia during treatment for acute leukemia. On CT images, AIA presents as round soft-tissue lung masses surrounded by a 'halo' of ground-glass attenuation. This appearance was once considered pathognomonic of AIA but is now known to be associated with a wide variety of hemorrhagic and vasculitic pulmonary processes. We report a case of SPE presenting radiographically as multiple lung nodules with surrounding halos, thus mimicking the diagnosis of AIA. To the best of our knowledge, these findings have not been reported in the literature. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.

    Science.gov (United States)

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-07-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

    Science.gov (United States)

    Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

    2017-01-01

    Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

  3. Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs.

    Directory of Open Access Journals (Sweden)

    Steven Schalekamp

    Full Text Available Chest radiographs (CXR are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA.The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies. The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs and 132 normal cases (or lungs. For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100. The area under the receiver operating characteristics curve (AUC served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive.The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01. Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%.The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity.

  4. Blood Aspergillus RNA is a promising alternative biomarker for invasive aspergillosis.

    Science.gov (United States)

    Zhao, Yanan; Paderu, Padmaja; Railkar, Radha; Douglas, Cameron; Iannone, Robert; Shire, Norah; Perlin, David S

    2016-11-01

    A critical challenge for the successful application of antifungal therapies for invasive aspergillosis (IA) is a lack of reliable biomarkers to assess early treatment response. Patients with proven or probable IA were prospectively enrolled, and serial blood samples were collected at 8 specified time points during 12-week antifungal therapy. Total nucleic acid was extracted from 2.5 ml blood and tested for Aspergillus-specific RNA by a pan-Aspergillus real-time nucleic acid sequence-based amplification (NASBA) assay. Serum 1, 3-β-D-glucan (BG) and galactomannan (GM) were measured in parallel. Clinical outcome was evaluated at 6 and 12 weeks. Overall, 48/328 (14.6%) blood samples from 29/46 (63%) patients had positive NASBA detection at baseline and/or some point during the study. Positive NASBA results during the first 4 and 6 weeks of treatment are significantly associated with the 12-week outcome. Blood RNA load change during weeks 4-6 may be informative to predict outcome at 12 weeks. While independent of serum GM, the kinetic change of circulating Aspergillus RNA appears to be well correlated with that of BG on some patient individuals. Monitoring blood Aspergillus RNA during the first 4-6 weeks of antifungal treatment may help assess therapeutic response. Combination of circulating Aspergillus RNA and BG may be a useful adjunct to assess response. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  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.

  7. Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996)

    International Nuclear Information System (INIS)

    Mathews, K.G.; Davidson, A.P.; Koblik, P.D.; Richardson, E.F.; Komtebedde, J.; Pappagianis, D.; Hector, R.F.; Kass, P.H.

    1998-01-01

    To examine the clinical response to topical administration of clotrimazole in dogs with nasal aspergillosis, to compare effect of surgically placed versus nonsurgically placed catheters used for administration on outcome, and to examine whether subjective scoring of computed tomographic images can predict outcome. Retrospective case series. 60 dogs with nasal aspergillosis. Information including signalment, history, diagnostics, treatment method, and outcome was retrieved from medical records of dogs with nasal aspergillosis treated between 1990 and 1996 at the University of California School of Veterinary Medicine or cooperating referral practices. Final outcome was determined by telephone conversations with owners and referring veterinarians. Images obtained before treatment were subjectively assessed to develop an algorithm for predicting outcome. Clotrimazole solution (1%) was infused during a 1-hour period via catheters surgically placed in the frontal sinus and nose (27 dogs) and via nonsurgically placed catheters in the nose (18). An additional 15 dogs received 2 to 4 infusions by either route. Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. The scoring system correctly classified dogs with unfavorable and favorable responses 71 to 78% and 79 to 93% of the time, respectively. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications

  8. Cavitating lung disease due to concomitant drug resistant tuberculosis and invasive pulmonary Aspergillosis in a post-partum patient: A case report.

    Science.gov (United States)

    Ray, Animesh; Suri, J C; Sen, M K; Chakrabarti, S; Gupta, Ayush; Capoor, Malini

    2015-01-01

    Many disorders can present as cavitating lesions in the lung. In this case report, a case of mixed infection with drug resistant tuberculosis and invasive pulmonary aspergillosis in a post-partum patient has been presented. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  9. Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis.

    Directory of Open Access Journals (Sweden)

    Dionysios Neofytos

    Full Text Available Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA. We examined whether early changes in serum galactomannan (GM and/or β-D-glucan (BDG can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47 and 65.9% (27/41 had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03 and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02. Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03 and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01. Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47 and 79.1% (34/43, respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03 and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007. Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Invasive maxillary aspergillosis masquerading as malignancy in two cases: Utility of cytology as a rapid diagnostic tool

    Directory of Open Access Journals (Sweden)

    Divya Sharma

    2012-01-01

    Full Text Available Fungi have emerged as important etiological agents for chronic sinusitis. Invasive aspergillosis has been reported in immunocompromised individuals or diabetics; however, it is uncommonly seen in immunocompetent patients. Definitive diagnosis of these lesions is based on histological examination and fungal culture. We report two cases of invasive maxillary lesions in immunocompetent patients, clinically suspected of malignancy; however, fine needle aspiration cytology showed fungal hyphae, morphologically suggestive of Aspergillus, which was later confirmed on histopathology. Aspiration cytology thus plays a crucial role in the early and definitive diagnosis of fungal sinusitis in cases clinico-radiologically suspected of malignancy. An early diagnosis will help the clinician for early and appropriate management and follow-up in order to decrease the high morbidity and mortality associated with it.

  12. Status of aspergillosis and sea fan populations in Curaçao ten years after the 1995 Caribbean epizootic

    Directory of Open Access Journals (Sweden)

    M. M Nugues

    2006-12-01

    Full Text Available In 1995, a survey of sea fan corals was conducted in Curaçao during a Caribbean-wide outbreak of the sea fan disease aspergillosis. The survey was repeated in 2005 using the same methodology and identical sites to examine changes in sea fan populations 10 years after the initial epizootic. Necrotic lesions typical of aspergillosis were present on as many sea fans in 2005 as in 1995 (mean ± SE: 52 ± 6 vs 43 ± 10%. The disease also showed no significant variation in virulence (9.6 ± 1.2 vs 8.8 ± 1.0% tissue loss per diseased colony. However, the average number of sea fan colonies per 10 m² decreased from 2.7 ± 1.1 to 0.7 ± 0.2 over the 10-year period, a decline of almost 75%. This decrease occurred for all colony sizes, but was more pronounced among small colonies, resulting in an overall trend of domination by large colonies. These results support that aspergillosis can have a significant, long-term impact on sea fan population size and structure. The continued presence of the disease in 2005 could be contributing to reduced recruitment and/or selective mortality among the smallest colonies. This study provides no indication that host resistance against aspergillosis could reverse the decline of Caribbean sea fan corals. Rev. Biol. Trop. 54 (Suppl. 3: 153-160. Epub 2007 Jan. 15.En 1995, se realizó un sondeo de los abanicos de mar durante un brote de aspergilosis, una enfermedad de abanicos de mar extendida en todo el Caribe. En el año 2005 se repitió el sondeo utilizando exactamente la misma metodología y los mismos sitios para examinar cambios en las poblaciones tras 10 años del inicio del brote. Se presentaron lesiones necróticas típicas de la aspergilosis en tantos abanicos en el 2005, como en 1995 (promedio ± ES: 52 ± 6 vs 43 ± 10%. La enfermedad tampoco mostró variaciones significativas en la virulencia (9.6 ± 1.2 vs 8.8 ± 1.0%, pérdida de tejido por colonia enferma. Sin embargo, el número promedio de colonias de

  13. Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during therapy for drug-induced hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Tomoo Ikari

    2017-01-01

    Full Text Available A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS caused by salazosulfapyridine. Human herpes virus 6 (HHV-6 variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA, and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.

  14. Immunoproteomics based identification of thioredoxin reductase GliT and novel Aspergillus fumigatus antigens for serologic diagnosis of invasive aspergillosis.

    Science.gov (United States)

    Shi, Li-ning; Li, Fang-qiu; Huang, Mei; Lu, Jing-fen; Kong, Xiao-xiang; Wang, Shi-qin; Shao, Hai-feng

    2012-01-18

    There has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus. Extracellular proteins of A. fumigatus were separated by two-dimensional electrophoresis (2-DE) and probed with the sera from critically ill patients with proven IA. The immunoreactive protein spots were identified by MALDI-TOF mass spectrometry (MALDI-TOF -MS). Forty spots from 2DE gels were detected and 17 different proteins were identified as immunogenic in humans. Function annotation revealed that most of these proteins were metabolic enzymes involved in carbohydrate, fatty acid, amino acid, and energy metabolism. One of the proteins, thioredoxin reductase GliT (TR), which showed the best immunoactivity, was analyzed further for secretory signals, protein localization, and homology. The results indicated that TR is a secretory protein with a signal sequence exhibiting a high probability for secretion. Furthermore, TR did not match any human proteins, and had low homology with most other fungi. The recombinant TR was recognized by the sera of all proven IA patients with different underlying diseases in this study. The immunoreactive proteins identified in this study may be helpful for the diagnosis of IA in critically ill patients. Our results indicate that TR and other immunodominant antigens have potential as biomarkers for the serologic diagnosis of invasive aspergillosis.

  15. Immunoproteomics based identification of thioredoxin reductase GliT and novel Aspergillus fumigatus antigens for serologic diagnosis of invasive aspergillosis

    Directory of Open Access Journals (Sweden)

    Shi Li-ning

    2012-01-01

    Full Text Available Abstract Background There has been a rising incidence of invasive aspergillosis (IA in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus. Results Extracellular proteins of A. fumigatus were separated by two-dimensional electrophoresis (2-DE and probed with the sera from critically ill patients with proven IA. The immunoreactive protein spots were identified by MALDI-TOF mass spectrometry (MALDI-TOF -MS. Forty spots from 2DE gels were detected and 17 different proteins were identified as immunogenic in humans. Function annotation revealed that most of these proteins were metabolic enzymes involved in carbohydrate, fatty acid, amino acid, and energy metabolism. One of the proteins, thioredoxin reductase GliT (TR, which showed the best immunoactivity, was analyzed further for secretory signals, protein localization, and homology. The results indicated that TR is a secretory protein with a signal sequence exhibiting a high probability for secretion. Furthermore, TR did not match any human proteins, and had low homology with most other fungi. The recombinant TR was recognized by the sera of all proven IA patients with different underlying diseases in this study. Conclusions The immunoreactive proteins identified in this study may be helpful for the diagnosis of IA in critically ill patients. Our results indicate that TR and other immunodominant antigens have potential as biomarkers for the serologic diagnosis

  16. Angioinvasive pulmonary aspergillosis after allogeneic bone marrow transplantation: clinical and high-resolution computed tomography findings in 12 cases

    Directory of Open Access Journals (Sweden)

    Emerson L. Gasparetto

    Full Text Available The aim of this study was to present the clinical and high-resolution CT scan findings of angioinvasive pulmonary aspergillosis (APA in 12 patients who underwent allogeneic bone marrow transplantation (BMT. The CT scans were reviewed by three chest radiologists who assessed the pattern and distribution of findings by consent. There were 7 (58% female and 5 (42% male patients, with aging between 5 and 50 years (average of 26 years. All patients were submitted to BMT for the treatment of hematological conditions. The diagnosis of APA was defined between 5 and 373 days after BMT, with average of 111 days. Three cases (25% were diagnosed in the neutropenic phase after the BMT, five (42% in the early phase and four patients in the late phase post-BMT. Regarding high-resolution CT (HRCT scan findings, nodules were found in 75% of the cases (9/12, most of the cases with more than 10 lesions (7/9 and of centrilobular localization (6/9. Consolidations were identified in seven patients (58%, being single in six, and commonly presenting ill defined borders (n=3 and subsegmental localization (n=5. Ground glass attenuation was found in six patients (50%. The halo sign was observed in nine cases (75%. Cavitations were seen in two air-space consolidations and one large nodule (2.5 cm. Patients submitted to BMT presenting respiratory symptoms and nodules or consolidations with halo sign at HRCT scan need to have the diagnosis of angioinvasive pulmonary aspergillosis included in all the post BMT phases.

  17. Angioinvasive pulmonary aspergillosis after allogeneic bone marrow transplantation: clinical and high-resolution computed tomography findings in 12 cases.

    Science.gov (United States)

    Gasparetto, Emerson L; Souza, Carolina A; Tazoniero, Priscilla; Davaus, Taisa; Escuissato, Dante L; Marchiori, Edson

    2007-02-01

    The aim of this study was to present the clinical and high-resolution CT scan findings of angioinvasive pulmonary aspergillosis (APA) in 12 patients who underwent allogeneic bone marrow transplantation (BMT). The CT scans were reviewed by three chest radiologists who assessed the pattern and distribution of findings by consent. There were 7 (58%) female and 5 (42%) male patients, with aging between 5 and 50 years (average of 26 years). All patients were submitted to BMT for the treatment of hematological conditions. The diagnosis of APA was defined between 5 and 373 days after BMT, with average of 111 days. Three cases (25%) were diagnosed in the neutropenic phase after the BMT, five (42%) in the early phase and four patients in the late phase post-BMT. Regarding high-resolution CT (HRCT) scan findings, nodules were found in 75% of the cases (9/12), most of the cases with more than 10 lesions (7/9) and of centrilobular localization (6/9). Consolidations were identified in seven patients (58%), being single in six, and commonly presenting ill defined borders (n=3) and subsegmental localization (n=5). Ground glass attenuation was found in six patients (50%). The halo sign was observed in nine cases (75%). Cavitations were seen in two air-space consolidations and one large nodule (2.5 cm). Patients submitted to BMT presenting respiratory symptoms and nodules or consolidations with halo sign at HRCT scan need to have the diagnosis of angioinvasive pulmonary aspergillosis included in all the post BMT phases.

  18. Clinical characteristics of patients with Aspergillus species isolation from respiratory samples: Comparison of chronic pulmonary aspergillosis and colonization.

    Science.gov (United States)

    Ohara, Sayaka; Tazawa, Yoko; Tanai, Chiharu; Tanaka, Yoshiaki; Noda, Hiromichi; Horiuchi, Hajime; Usui, Kazuhiro

    2016-03-01

    With advancements in anti-fungal drugs, it has become more important to correctly diagnose chronic pulmonary aspergillosis (CPA); however, it is not easy to distinguish CPA from colonization when Aspergillus species are isolated from respiratory samples. The aim of the study was to clarify the particular clinical characteristics of patients with CPA vs. those with colonization. We retrospectively reviewed the medical records of 110 patients with Aspergillus species isolation from respiratory samples, to analyze and compare the differences between CPA and colonization of the Aspergillus species. The median age of all analyzed was 71 years (range: 31-92 years); 64 were female (58%). The most frequently cultured Aspergillus species was Aspergillus fumigatus (48.3%), followed by A. niger (29.2%). Thirty patients (27.4%) were diagnosed with CPA, vs. 75 (68.2%) with colonization and 5 (4.5%) with allergic bronchopulmonary aspergillosis. Compared with the colonization group, the CPA group included more males (CPA vs. colonization: 49.3% vs. 13.3%) and subjects with a low body mass index (18.45 kg/m2 vs. 21.09 kg/m2). As for the underlying pulmonary diseases, the patients with CPA showed a significantly higher prevalence of sequelae of pulmonary tuberculosis (40% vs. 8%) and a history of thoracic surgery (43% vs. 13%) than those with colonization. Asthma was less frequent in the CPA group than in the colonization group (0% vs. 20%). We found no significantly important underlying extrapulmonary diseases. Patients with CPA display clinical characteristics distinct from those seen in subjects with colonization. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  19. [Expression and differential diagnostic value of serum microRNA for invasive pulmonary aspergillosis].

    Science.gov (United States)

    Wen, Z N; Ling, Z G; Huang, Y; Li, X

    2017-04-12

    Objective: To explore the expression and the clinical diagnostic value of serum miR-21 for invasive pulmonary aspergillosis (IPA). Methods: Outpatients and inpatients from the Fourth Affiliated Hospital of Guangxi Medical University were included in the study during June 2014 to September 2015. The IPA group had 40 patients, male 22, female 18, aged 55-68 years (mean 60 ), while the control groups included 50 patients with pulmonary tuberculosis [male 23, female 27, aged 50-62 years (mean 55 )], 50 patients with lung cancer [male 30, female 20, aged 55-70 years (mean 62)], and 50 healthy controls [male 25, female 25, aged 50-67 years (mean 60) ]. Serum were obtained and the levels of miR-21 and galactomannan (GM test) and (1, 3)-beta-D-glucan (G test) were measured. The related indexes were analyzed by logistic regression and ROC curves. Results: The serum miR-21 expression in IPA and lung cancer patients were increased, the median values ( P (25) and P (75)) being 0.42(0.31, 0.62)and 0.80(0.65, 0.94) respectively, both of which were significantly higher than those of the healthy controls [ 0.09(0.04, 0.15)] and the tuberculosis cases [ 0.08(0.03, 0.16)], P tuberculosis cases and lung cancer cases were 0.914, 0.897 and 0.863 respectively, with the Youden index being 0.780, 0.700 and 0.605 respectively. The serum levels of miR-21 in between 0.198 and 0.723 had preferable diagnostic accuracy. ROC analysis for miR-21 in IPA compared to healthy controls showed that the AUCs of miR-21 combined with G test or GM test were 0.992 and 0.966 respectively, the sensitivity being 95% (38/40) and 93% (37/40) respectively, the specificity being 98% (49/50) and 96% (48/50) respectively, and the Youden index being 0.930 and 0.885 respectively. If miR-21 was combined with G test and GM test, the AUC was 0.994, the sensitivity and the specificity being 98% (38/40) and 96% (48/50) respectively, and the Youden index increased to 0.935. ROC analysis for miR-21 in IPA compared to

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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.

  2. 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

    2011-01-01

    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. PMID:21788462

  3. Usefulness of molecular biology performed with formaldehyde-fixed paraffin embedded tissue for the diagnosis of combined pulmonary invasive mucormycosis and aspergillosis in an immunocompromised patient

    Directory of Open Access Journals (Sweden)

    Vénissac Nicolas

    2010-01-01

    Full Text Available Abstract Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories.

  4. [Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy].

    Science.gov (United States)

    Rácil, Z; Mayer, J; Kocmanová, I; Wagnerová, B; Winterová, J; Folber, F; Lengerová, M; Moulis, M; Zácková, D; Smardová, L; Janíková, A; Navrátil, M; Dvoráková, D; Vorlícek, J

    2008-02-01

    Invasive aspergillosis (IA) is a leading invasive fungal infection in hematooncological patients. The aim of this study was to analyse the incidence, diagnostic procedures and treatment of IA in hematooncological department in large hospital in the Czech Republic. A retrospective analysis of medical and laboratory records from patients hospitalised in our department with proven/probable IA between January 2000 and December 2006 was performed. 52 cases of IA in 51 patients were identified (17.3% proven IA/82.7% probable IA). Number of IA cases notably increased during study period (1 case of IA in 2000 vs 21 cases of IA in 2006) and majority of them was of nosocomial origin (61.5%). Pulmonary aspergillosis was diagnosed in 46 cases (88.5%). Patients treated for acute leukemia or undergoing allogeneic stem cell transplantation represent the group at the highest risk of IA (in total 52% of cases). Fever and signs of pulmonary involvement were the most common clinical signs of infection (presented in 92.3% and 69.2 cases respectively). Conventional diagnostic methods including autopsy were able to diagnose only 15 cases of IA (28.8%). In all other cases (71.2%) the diagnosis was done by detection of galactomannan (GM) in serum. Introduction of GM monitoring enabled erlier initiation of antifungal treatment by 4 days. Initial therapy of IA led to the treatment response (partial and complete) in 18 (34.6%) of infections--the highest percentage of response has been seen in voriconazole monotherapy group (42%) and when combination of voriconazole and caspofungin has been used (83%). Salvage therapy was initiated due to the failure of initial treatment in 21 (40.3%) of cases. Patients were treated mostly with combination ofvoriconazole and caspofungin and/or monotherapy with voriconazole has been used with treatment response 55% and 50% respectively. Introduction of new antifungal drugs together with increased number of patients with IA led to the marked increase of total

  5. Serum galactomannan antigen as a prognostic and diagnostic marker for invasive aspergillosis in heterogeneous medicine ICU patient population.

    Science.gov (United States)

    Dabas, Yubhisha; Mohan, Anant; Xess, Immaculata

    2018-01-01

    This study was conducted to get a complete clinical and mycological picture of invasive aspergillosis (IA) in respiratory medicine ICU of a tertiary care hospital. From the cohort of 235 patients only one had proven IA. Based on AspICU algorithm, 21 had putative IA (8.9%), 12 were colonised (5.1%). Adjusting the confounding factors, significant risk factors for IA were chronic obstructive pulmonary disease (COPD), temperature of ≥38°C, pneumonia and acute respiratory distress syndrome (ARDS). The best predictor of IA was AspICU algorithm (AUC, 1) followed by serum galactomannan antigen (GM) cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.822). For 37% of patients, IA diagnoses was made earlier with serum GM than radiology. There were 70/235 (29.8%) deaths within 30 days of enrolment in the study. Aspergillus culture positivity (34/235, 14.5%) was associated with very high mortality (27/34, 79.4%), (p<0.05). The best predictor of mortality was GM cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.835). This study imparts the focus on relatively underestimated Aspergillus infections prevalent in ICUs. The AspICU algorithm was found to be useful over others for IA diagnosis. The prognostic usefulness of serum GM antigen detection test highlighted overlooking the same may not be rewarding for the outcome of IA suspected ICU subpopulation.

  6. Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

    Science.gov (United States)

    Gonçalves, Samuel M.; Lagrou, Katrien; Rodrigues, Cláudia S.; Campos, Cláudia F.; Bernal-Martínez, Leticia; Rodrigues, Fernando; Silvestre, Ricardo; Alcazar-Fuoli, Laura; Maertens, Johan A.; Cunha, Cristina; Carvalho, Agostinho

    2017-01-01

    Background: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution. Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk. Results: Among the 32 analytes tested, IL-1β, IL-6, IL-8, IL-17A, IL-23, and TNFα were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels ≥904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%). Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, which might be useful in supporting current diagnostic approaches for IPA. PMID:29238334

  7. Allergic bronchopulmonary aspergillosis in Italian cystic fibrosis patients: Prevalence and percentage of positive tests in the employed diagnostic criteria

    International Nuclear Information System (INIS)

    Taccetti, Giovanni; Procopio, Elena; Marianelli, Lore; Campana, Silvia

    2000-01-01

    The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is difficult to determine because the data in the literature are not homogeneous or comparable. ABPA and CF have similar clinical symptoms which make diagnosis difficult and underestimate the real dimensions of the problem. We conducted an epidemiological study on 3089 Italian CF patients to determine the prevalence of ABPA in Italy and verify the percentage of positive tests in the employed diagnostic criteria. Our results indicate that the prevalence of ABPA in Italian CF patients is 6.18%, mainly in adolescents and young adults. ABPA is diagnosed using clinical symptoms (presence of episodic bronchial obstructions or typical radiographic features) and on the basis of other criteria which can only be partially fulfilled in paediatric patients. Among the diagnostic tests the most sensitive are the total IgE (84.5%), specific IgE anti-Aspergillus fumigatus (81.6%) and the prick test (68.3%). In the absence of clinical symptoms and gold standard diagnostic tests, serological positivity and/or the skin test are not sufficient evidence to confirm the presence of ABPA

  8. Bronchocele density in cystic fibrosis as an indicator of allergic broncho-pulmonary aspergillosis: A preliminary study.

    Science.gov (United States)

    Occelli, Aurélie; Soize, Sébastien; Ranc, Caroline; Giovannini-Chami, Lisa; Bailly, Carole; Leloutre, Béatrice; Boyer, Corinne; Baque-Juston, Marie

    2017-08-01

    Allergic broncho-pulmonary aspergillosis (ABPA) is a severe and under-diagnosed complication of cystic fibrosis (CF). The aim of the study was to determine whether the mucus content of bronchoceles in cystic fibrosis complicated with ABPA reveals a higher density than the mucus content of non-ABPA cystic fibrosis. We studied retrospectively 43 computed tomography scans (CT scans) of a pediatric population of cystic fibrosis patients. We measured the mucus attenuation in Hounsfield Units (HU) of all bronchoceles >5mm in diameter. We found bronchoceles >5mm in 13/43 patients. 5/13 patients had a positive diagnosis of ABPA. The median HU value of bronchoceles was higher in patients with than without ABPA [98 HU (26-135) vs 28 HU (10-36); P=0,02]. Moreover, all patients with a bronchocele density >36HU were ABPA positive. CF complicated with ABPA shows higher attenuation bronchoceles on CT scans of the chest. Systematic density measurements of bronchoceles could help to raise the difficult diagnosis of ABPA in patients suffering from cystic fibrosis. Larger series could confirm a threshold in HU which could become a new imaging criterion for the diagnosis of ABPA. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Differential role of gpaB and sidA gene expressions in relation to virulence in Aspergillus species from patients with invasive aspergillosis.

    Science.gov (United States)

    Ghods, Nayereh; Falahati, Mehraban; Roudbary, Maryam; Farahyar, Shirin; Shamaei, Masoud; Pourabdollah, Mahin; Seif, Farhad

    2018-02-03

    The virulence genes in invasive aspergillosis (IA) have not been analyzed adequately. The present study was designed to evaluate the expression of gpaB and sidA genes, which are important virulence genes in Aspergillus spp. from bronchoalveolar lavage (BAL) samples. Direct examination and culture on Czapek Agar and Sabouraud Dextrose Agar media were performed for 600 BAL specimens isolated from patients with possible aspergillosis. A Galactomannan ELISA assay was also carried out. The expression levels of the gpaB and sidA genes in isolates were analyzed using quantitative real-time PCR (qRT-PCR). We identified 2 species, including Aspergillus flavus (A. flavus) and Aspergillus fumigatus (A. fumigatus) in 25 positive samples for invasive aspergillosis as validated using GM-ELISA. A. flavus is the main pathogen threatening transplant recipients and cancer patients worldwide. In this study, A. flavus had low levels of the gpaB gene expression compared to A. fumigatus (p=0.006). The highest sidA expression was detected in transplant recipients (p=0.05). There was no significant correlation between sidA expression and underlying disease (p=0.15). The sidA and gpaB gene expression patterns may provide evidence that these virulence genes play important roles in the pathogenicity of Aspergillus isolates; however, there are several regulatory genes responsible for the unexpressed sidA and gpaB genes in the isolates. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  10. 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.

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

    International Nuclear Information System (INIS)

    Hidalgo, A.; Parody, R.; Martino, R.; Sanchez, F.; Franquet, T.; Gimenez, A.; Blancas, C.

    2009-01-01

    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 -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.

  12. Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.

    Science.gov (United States)

    Martin, Judith M; Macias-Parra, Mercedes; Mudry, Peter; Conte, Umberto; Yan, Jean L; Liu, Ping; Capparella, M Rita; Aram, Jalal A

    2017-01-01

    Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited. Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored. Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established. Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis.

    Science.gov (United States)

    Koyama, Kazuya; Ohshima, Nobuharu; Suzuki, Junko; Kawashima, Masahiro; Okuda, Kenichi; Sato, Ryota; Suzukawa, Maho; Nagai, Hideaki; Matsui, Hirotoshi; Ohta, Ken

    2015-11-01

    There have been scarce data evaluating the differences of clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) depending on underlying pulmonary diseases. We tried to clarify them in CPA patients who had pulmonary emphysema or previous pulmonary tuberculosis. We reviewed and evaluated CPA patients diagnosed between 2007 and 2013 with pulmonary emphysema (PE group; n = 29), with previous pulmonary tuberculosis (PT group; n = 47) and with combination of these 2 underlying conditions (CTE group; n = 24). In CT findings, fungus balls were rare in PE group (7% in PE group and 36% in PT group; p = 0.006). Compared with PT group, PE group patients exhibited more frequent preceding antibiotics administration (45% vs 11%; p = 0.002) and fever (52% vs 17%; p = 0.002), less frequent hemosputum (24% vs 57%; p = 0.008), and more frequent consolidations in imaging (79% vs 38%; p = 0.001) and respiratory failure (34% vs 13%; p = 0.020), possibly suggesting more acute clinical manifestations of CPA in emphysematous patients. Trend of the differences between PT and PE group was not changed when patients with fungal balls were excluded. Multivariate Cox regression analysis of risks for all-cause mortality revealed age (HR, 1.079; p = 0.002) and emphysema (HR, 2.45; p = 0.040) as risk factors. Assessment of underlying lung diseases is needed when we estimate prognosis and consider treatment of CPA patients. Particularly, emphysematous patients can be presented as refractory pneumonia and show poor prognosis. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  16. Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

    Science.gov (United States)

    Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

    2017-01-01

    Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Gamma scintigraphy imaging of murine invasive pulmonary aspergillosis with a {sup 111}In-labeled cyclic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Yang Zhi [Department of Experimental Diagnostic Imaging, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Kontoyiannis, Dimitrios P. [Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Wen Xiaoxia; Xiong Chiyi; Zhang Rui [Department of Experimental Diagnostic Imaging, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Albert, Nathaniel D. [Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Li Chun [Department of Experimental Diagnostic Imaging, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States)], E-mail: cli@mdanderson.org

    2009-04-15

    Introduction: Invasive pulmonary aspergillosis (IPA) is a leading cause of infection-associated death in immunosuppressed patients. Early detection and early administration of antifungal therapy are critical factors in improving outcome for patients with IPA. Here, we evaluated the imaging properties of a {sup 111}In-labeled cyclic peptide targeted to Aspergillus fumigatus in an immunosuppressed murine model of IPA. Methods: A cyclic peptide c(CGGRLGPFC)-NH{sub 2} was labeled with {sup 111}In by means of diethylenetriaminepentaacetic acid (DTPA). Two days after intranasal inoculation of 17.5x10{sup 6} conidia of A. fumigatus, mice were injected {sup 111}In-DTPA-c(CGGRLGPFC)-NH{sub 2} intravenously. Biodistribution data were obtained at 2 h, and {gamma}-images were acquired at 10 min and 2 h after radiotracer injection. Healthy mice were used as controls. In addition, a group of infected mice were co-injected with the radiotracer and unlabeled c(CGGRLGPFC)-NH{sub 2} to evaluate the inhibition of radiotracer's binding to infected lungs. Autoradiographs of lungs from infected and healthy mice were compared with corresponding photographs of transaxial sections of the lung tissues stained for A. fumigatus hyphae. Results: The labeling efficiency was >98%, with specific radioactivity of up to 74 MBq/nmol peptide. Significantly higher uptake of {sup 111}In-DTPA-c(CGGRLGPFC)-NH{sub 2} was observed in the lungs of mice infected with A. fumigatus than in those of healthy mice (0.37{+-}0.06 %ID/g vs. 0.14{+-}0.02 %ID/g, P=.00044). Simultaneous injection with unlabeled peptide reduced radioactivity in the infected lungs by 41% (P=.0037). Increased radioactivity in the lungs of infected mice was visible in {gamma} images at both 10 min and 2 h after radiotracer injection. Moreover, autoradiography confirmed radiotracer uptake in infected lungs, but not in the lungs of healthy mice or infected mice co-injected with unlabeled peptide. Conclusions: {gamma}-Imaging with {sup

  19. Characterization of Specific Immune Responses to Different Aspergillus Antigens during the Course of Invasive Aspergillosis in Hematologic Patients

    Science.gov (United States)

    Beauvais, Anne; Beau, Remi; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Zanetti, Eleonora; Quadrelli, Chiara; Codeluppi, Mauro; Guaraldi, Giovanni; Pagano, Livio; Caira, Morena; Giovane, Cinzia Del; 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

  20. Assessment of carvacrol for control of avian aspergillosis in intratracheally challenged chickens in comparison to voriconazole with a reference on economic impact.

    Science.gov (United States)

    Tartor, Y H; Hassan, F A M

    2017-11-01

    This study was designed to investigate the efficacy of essential oils as an alternative prophylaxis and treatment for avian aspergillosis. The in vitro susceptibility of Aspergillus fumigatus strains to antifungal drugs and carvacrol, thymol, eugenol, thymoquinone and cinnamon was determined using the macrodiffusion and microdilution methods. Carvacrol has antifungal activity in comparison to voriconazole (VCZ) (MIC 0·5, 0·25 μg ml -1 respectively). While cinnamon, euganol, thymol and thymoquinone displayed moderate to weak inhibitory activity. For the efficacy study, five groups of 10-day-old chicks (n = 48) were infected intratracheally either with A. fumigatus conidia or saline (negative control). Chicks in carvacrol prophylactic and treatment (CRPT) group were fed for 10 days beginning from hatch with carvacrol (200 mg kg -1 per diet) supplemented diets. VCZ (VCZT:20 mg kg -1 body weight (BW)), carvacrol treatment (CRT, CRPT) was started upon appearance of the first clinical signs and continued for 10 days. Birds were monitored for an additional 15 days following treatment. Fungal burden and therapeutic efficacy were assessed by survival, BW, quantitative (q) culture (CFU), quantitative real-time PCR (qPCR) and histopathological changes at several time points. Serum biochemical changes were also assessed. VCZT, CRPT, CRT in comparison to the sham-treated (SHAM) group have prolonged survival (87·5, 83·4, 79·2, 41·7% respectively). In VCZT and CRPT, a significant reduction in clinical signs, lesions, CFU and qPCR counts to the limit of detection were observed. CRPT has the lowest BW reduction, economic losses and significant low total cholesterol levels. Carvacrol has a promising potential to be used as a prophylactic and treatment against A. fumigatus. Prognosis of avian aspergillosis is often poor due to delayed diagnosis and treatment failure. However, the widespread uses of azole prophylaxis in birds are thought to be the major driver of

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Galactomannan enzyme immunoassay and quantitative Real Time PCR as tools to evaluate the exposure and response in a rat model of aspergillosis after posaconazole prophylaxis.

    Science.gov (United States)

    Cendejas-Bueno, Emilio; Forastiero, Agustina; Ruiz, Isabel; Mellado, Emilia; Buitrago, María José; Gavaldà, Joan; Gomez-Lopez, Alicia

    2016-11-01

    A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole. Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used. Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain. This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  3. Successful treatment of cerebral aspergillosis: case report of a patient with T-cell large granular lymphocytic leukemia (T-LGL).

    Science.gov (United States)

    Turki, Amin T; Rashidi-Alavijeh, Jassin; Dürig, Jan; Gerken, Guido; Rath, Peter-Michael; Witzke, Oliver

    2017-12-28

    Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients. We report a case of a 53 year old patient with T-LGL, Immune-Thrombocytopenia (ITP) and combined antibody deficiency, who presented with fever and reduced general condition. The patient revealed a complicated infection involving the lungs and later the brain, with the presentation of vomiting and seizures. Broad microbiological testing of blood-, lung- and cerebrospinal fluid samples was inconclusive. In the absence of mycological proof, Aspergillus infection was confirmed by pathological examination of a brain specimen and finally successfully treated with liposomal amphotericin B and voriconazole, adopting a long-term treatment scheme. Beyond typical problems in the clinical practice involving fungal infections and hematologic malignancies, this case of invasive aspergillosis in a patient with T-LGL illustrates caveats in diagnosis, therapy and follow-up. Our data support careful ambulatory monitoring for patients with T-LGL, even in the absence of neutropenia. Especially those patients with combined hematologic malignancies and immune defects are at risk. Long-term treatment adhesion for 12 months with sufficient drug levels was necessary for sustained clearance from infection.

  4. Characteristics of culture-positive invasive pulmonary aspergillosis in patients with hematologic diseases: Comparison between Aspergillus fumigatus and non-fumigatus Aspergillus species.

    Science.gov (United States)

    Cho, Sung-Yeon; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Kim, Si-Hyun; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong; Park, Yeon-Joon; Lee, Jong-Wook

    2017-12-01

    While the epidemiology and clinical differences of various Candida spp. has been relatively well-identified, data regarding invasive aspergillosis (IA) caused by different Aspergillus spp. are insufficient.We aimed to determine the epidemiology of culture-positive invasive pulmonary aspergillosis (IPA) and to compare the characteristics and outcomes of Aspergillus fumigatus IPA with those of non-fumigatus IPA in patients with hematologic diseases. All consecutive cases of IPA from 2011 to 2015 were reviewed retrospectively.There were 430 proven/probable IPA and 76 culture-positive proven/probable IPA. Excluding cases of multiple species of fungi or cases having difficulties in species-level identification, 41 A fumigatus and 22 non-fumigatus IPA (Aspergillus flavus [n = 11], Aspergillus niger [n = 6], and Aspergillus terreus [n = 5]) were compared. There were no significant differences in baseline characteristics between the 2 groups. However, disseminated IA was more common in non-fumigatus IPA (2.4% vs 18.2%; P = .046). Paranasal sinus (PNS) involvement was more common in non-fumigatus IPA. There was a trend towards higher peak serum galactomannan values in non-fumigatus IPA than in A fumigatus IPA group (median 1.33 [interquartile 0.98-3.29] vs 0.97 [0.66-1.97]; P = .084). Clinical response and mortality did not differ between groups.The culture-positive rate of proven/probable IPA was 17.7%, of which non-fumigatus Aspergillus accounted for about one-third. Disseminated IA, especially involving the PNS, was more frequent in non-fumigatus IPA than in A fumigatus IPA.

  5. Incidence of pulmonary aspergillosis and correlation of conventional diagnostic methods with nested PCR and real-time PCR assay using BAL fluid in intensive care unit patients.

    Science.gov (United States)

    Zarrinfar, Hossein; Makimura, Koichi; Satoh, Kazuo; Khodadadi, Hossein; Mirhendi, Hossein

    2013-05-01

    Although the incidence of invasive aspergillosis in the intensive care unit (ICU) is scarce, it has emerged as major problems in critically ill patients. In this study, the incidence of pulmonary aspergillosis (PA) in ICU patients has evaluated and direct microscopy and culture has compared with nested polymerase chain reaction (PCR) and real-time PCR for detection of Aspergillus fumigatus and A. flavus in bronchoalveolar lavage (BAL) samples of the patients. Thirty BAL samples obtained from ICU patients during a 16-month period were subjected to direct examinations on 20% potassium hydroxide (KOH) and culture on two culture media. Nested PCR targeting internal transcribed spacer ribosomal DNA and TaqMan real-time PCR assay targeting β-tubulin gene were used for the detection of A. fumigatus and A. flavus. Of 30 patients, 60% were men and 40% were women. The diagnosis of invasive PA was probable in 1 (3%), possible in 11 (37%), and not IPA in 18 (60%). Nine samples were positive in nested PCR including seven samples by A. flavus and two by A. fumigatus specific primers. The lowest amount of DNA that TaqMan real-time PCR could detect was ≥40 copy numbers. Only one of the samples had a positive result of A. flavus real-time PCR with Ct value of 37.5. Although a significant number of specimens were positive in nested PCR, results of this study showed that establishment of a correlation between the conventional methods with nested PCR and real-time PCR needs more data confirmed by a prospective study with a larger sample group. © 2013 Wiley Periodicals, Inc.

  6. Allergic Bronchopulmonary Aspergillosis

    Science.gov (United States)

    ... Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy ... care. Clinician Awards Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: ...

  7. Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination.

    Science.gov (United States)

    Schwienbacher, M; Israel, L; Heesemann, J; Ebel, F

    2005-11-01

    Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS-PAGE. Protein identification was performed using MALDI-TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. A hyphae-specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese-dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA-specific allergen, was detected in hyphae and conidia. Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.

  8. Serum galactomannan screening for diagnosis of invasive pulmonary aspergillosis in children after stem cell transplantation or with high-risk leukemia.

    Science.gov (United States)

    Gefen, Aharon; Zaidman, Irina; Shachor-Meyouhas, Yael; Avidor, Israela; Hakim, Fahed; Weyl Ben-Arush, Myriam; Kassis, Imad

    2015-03-01

    Both transplanted and leukemia patients are at high risk (HR) for invasive pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our objective was to investigate the impact of serial serum galactomannan assay (GMA) screening on IPA diagnosis in children. Between January 2010 and December 2011, all children following stem cell transplantation (SCT) or with HR leukemia were prospectively included. Serum samples for GMA were taken once-twice weekly. Results >.5 were considered positive. Patients suspected of having IPA were stratified as possible, probable, and definite. Forty-six children (median age, 8 years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total of 510 samples were taken; screening period was 1-6 months for 34 patients. GMA was negative in 28 patients, all but one without suspicion of IPA. Eighteen patients had positive GMA: while four (22%) were upgraded to probable IPA, fourteen (78%) were considered as false positives (FP), some associated with piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and 0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22 and 0.96, respectively. GMA may have a role in evaluating HR children for IPA. Both NPV and FP rates are high. The cost benefit of early detection versus over-diagnosis should be further studied.

  9. Galactomannan and Polymerase Chain Reaction-Based Screening for Invasive Aspergillosis Among High-Risk Hematology Patients: A Diagnostic Meta-analysis.

    Science.gov (United States)

    Arvanitis, Marios; Anagnostou, Theodora; Mylonakis, Eleftherios

    2015-10-15

    Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods has not been studied. We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model. Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

    Science.gov (United States)

    Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

    2018-04-01

    Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

  11. Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

    Science.gov (United States)

    Urabe, Naohisa; Sakamoto, Susumu; Sano, Go; Suzuki, Junko; Hebisawa, Akira; Nakamura, Yasuhiko; Koyama, Kazuya; Ishii, Yoshikazu; Tateda, Kazuhiro; Homma, Sakae

    2017-06-01

    We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA. Copyright © 2017 American Society for Microbiology.

  12. Cytokine and transcription factor expression by Aspergillus fumigatus-stimulated peripheral blood mononuclear cells in dogs with sino-nasal aspergillosis.

    Science.gov (United States)

    Vanherberghen, M; Bureau, F; Peters, I R; Day, M J; Lynch, A; Fievez, L; Billen, F; Clercx, C; Peeters, D

    2013-08-15

    The causal agent of sino-nasal aspergillosis is usually Aspergillus fumigatus, which is a saprophytic and ubiquitous fungus that causes a severe rhinosinusitis in apparent healthy dogs. Affected dogs do not have systemic immuno-suppression. It has been shown previously that dogs affected by this disease have local over-expression of interleukin (IL)-10 and Th1 cytokines in nasal mucosal tissue. The aim of the present study was to assess the response of peripheral blood mononuclear cells (PBMC) from affected and unaffected dogs to antigen-specific stimulation with heat-inactivated Aspergillus spp. conidia, by quantifying gene expression for specific Th1, Th2, Th17 and Treg cytokines and their related transcription factors. Quantification of IL-4 and IFN-γ protein in culture supernatant was performed by enzyme-linked immunosorbent assay (ELISA). PBMC from dogs with SNA produced adequate mRNA encoding IFN-γ and IFN-γ protein. The expression of IL-17A mRNA was significantly greater in PBMC of affected compared with unaffected dogs. The amount of IL-10 mRNA in PBMC from affected dogs decreased after antigen-specific challenge. These results suggest that the incapacity of affected dogs to clear these fungal infections is not related to a defect in Th1 immunity or to an overwhelming regulatory reaction, but rather to an uncontrolled pro-inflammatory reaction driven by Th17 cells. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Diagnostic performance of the (1-3-β-D-glucan assay in patients with Pneumocystis jirovecii compared with those with candidiasis, aspergillosis, mucormycosis, and tuberculosis, and healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Hyo-Ju Son

    Full Text Available Diagnosis of pneumocystis pneumonia (PCP relies on microscopic visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory specimens, which involves invasive procedures such as bronchoalveolar lavage. The (1-3-β-D-glucan (BG assay has been proposed as a less invasive and less expensive diagnostic test to rule out PCP. We therefore compared blood levels of BG in patients with PCP with those of patients with candidemia, chronic disseminated candidiasis (CDC, invasive aspergillosis, mucormycosis, and tuberculosis and those of healthy volunteers.Adult patients who were diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and tuberculosis whose blood samples were available, and healthy volunteers were enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period. The blood samples were assayed with the Goldstream Fungus (1-3-β-D-glucan test (Gold Mountain River Tech Development, Beijing, China.A total of 136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15 invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy volunteers were included. The mean±SD of the concentration of 1-3-β-D-glucan in the patients with PCP (290.08 pg/mL±199.98 were similar to those of patients with candidemia (314.14 pg/mL±205.60, p = 0.90 at an α = 0.005 and CDC (129.74 pg/mL±182.79, p = 0.03 at an α = 0.005, but higher than those of patients with invasive aspergillosis (131.62 pg/mL±161.67, p = 0.002 at an α = 0.005, mucormycosis (95.08 pg/mL±146.80, p 31.25 pg/mL, which is highly sensitive for PCP versus tuberculosis plus healthy volunteers at the expense of specificity, the BG assay had a sensitivity of 92% (95% CI 81%-98% and a specificity of 55% (95% CI 39%-71%.The BG assay appears to be a useful adjunct test for PCP.

  14. Halo sign nodules in angio invasive pulmonary aspergillosis: correlation of high-resolution computed tomography findings with anatomopathology; Nodulos com sinal do halo na aspergilose pulmonar angioinvasiva: correlacao da tomografia computadorizada de alta resolucao com a anatomopatologia

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Valiante, Paulo Marcos [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Patologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Disciplina de Radiologia

    2002-08-01

    The aim of this study was to correlate the early findings observed on high-resolution computed tomography with anatomopathology results of patients with angio invasive aspergillosis. The authors studied two patients with leukemia. The nodules seen on high-resolution computed tomography corresponded to areas of hemorrhagic infarction, necrotic coagulation and fungal hyphae infiltration whereas ground glass halo corresponded to intra alveolar hemorrhage. Nodules with halo sign were closely correlated with anatomopathology findings. We concluded that the anatomopathology findings can clearly explain the image features of the lesions observed on high-resolution computed tomography. (author)

  15. 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

  16. Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis.

    Science.gov (United States)

    Walsh, Thomas J; Wissel, Mark C; Grantham, Kevin J; Petraitiene, Ruta; Petraitis, Vidmantas; Kasai, Miki; Francesconi, Andrea; Cotton, Margaret P; Hughes, Johanna E; Greene, Lora; Bacher, John D; Manna, Pradip; Salomoni, Martin; Kleiboeker, Steven B; Reddy, Sushruth K

    2011-12-01

    Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P ≤ 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients.

  17. Evaluation of serum galactomannan enzyme immunoassay at two different cut-offs for the diagnosis of invasive aspergillosis in patients with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Ritin Mohindra

    2017-01-01

    Full Text Available Background: Invasive aspergillosis (IA is an increasingly common and fatal opportunistic fungal infection in patients with haematological diseases. Early diagnosis is difficult as mycological culture techniques have low sensitivity and the radiological tools have low specificity. Galactomannan enzyme immunoassay (GEI detects galactomannan in the human serum with a reported sensitivity and specificity between 30% and 100%. Aims: The aim of this study was to analyse the role of GEI in diagnosis of IA in patients with febrile neutropenia and to evaluate the role of GEI in the diagnosis of IA as per the revised (2008 European Organization for Research and Treatment of Cancer–Mycoses Study Group (EORTC–MSG criteria at two different optical density (OD cut-offs of 0.5 and 1.0. Setting: This prospective study was conducted in Safdarjung Hospital, New Delhi, India. Methods: GEI testing was performed in adult patients of febrile neutropenia with evidence of IA. Results at two different OD indices (ODIs of 0.5 and 1.0 were analysed. The evaluation of the diagnostic parameter, that is, GEI was measured in terms of sensitivity, specificity and positive and negative predictive value and was validated with the revised (2008 EORTC–MSG diagnostic criteria of IA. Results: One hundred and eleven patients had evidence of IA, of which 79 patients were GEI positive when cut-off ODI was 0.5, whereas with cut-off ODI 1.0, 55 patients were GEI positive. Conclusion: ODI of 1.0 should be considered as positive while in patients with OD between 0.5 and 1.0, repeat sampling from the patient is recommended.

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

    Science.gov (United States)

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

    2017-11-25

    Monitoring fungal aerocontamination is an essential measure to prevent severe invasive aspergillosis (IA) infections in hospitals. One central block among 32 blocks of Edouard Herriot Hospital (EHH) was entirely demolished in 2015, while care activities continued in surrounding blocks. The main objective was to undertake broad environmental monitoring and clinical surveillance of IA cases to document fungal dispersion during major deconstruction work and to assess clinical risk. A daily environmental survey of fungal loads was conducted in eight wards located near the demolition site. Air was collected inside and outside selected wards by agar impact samplers. Daily spore concentrations were monitored continuously by volumetric samplers at a flow rate of 10 L.min -1 . Daily temperature, wind direction and speed as well as relative humidity were recorded by the French meteorological station Meteociel. Aspergillus fumigatus strains stored will be genotyped by multiple-locus, variable-number, tandem-repeat analysis. Antifungal susceptibility will be assessed by E-test strips on Roswell Park Memorial Institute medium supplemented with agar. Ascertaining the adequacy of current environmental monitoring techniques in hospital is of growing importance, considering the rising impact of fungal infections and of curative antifungal costs. The present study could improve the daily management of IA risk during major deconstruction work and generate new data to ameliorate and redefine current guidelines. This study was approved by the clinical research and ethics committees of EHH. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. The impact of portable high-efficiency particulate air filters on the incidence of invasive aspergillosis in a large acute tertiary-care hospital.

    Science.gov (United States)

    Abdul Salam, Zakir-Hussain; Karlin, Rubiyah Binte; Ling, Moi Lin; Yang, Kok Soong

    2010-05-01

    Worldwide, the frequency of invasive fungal infections has been increasing, with a corresponding increase in the numbers of high-risk patients. Exposure reduction through the use of high-efficiency particulate air (HEPA) filters has been the preferred primary preventive strategy for these high-risk patients. Although the efficiency and benefits of fixed HEPA filters is well proven, the benefits of portable HEPA filters are still inconclusive. This was a retrospective study to assess the impact of 48 portable HEPA filter units deployed in selected wards in Singapore General Hospital, an acute tertiary-care hospital in Singapore. Data were extracted between December 2005 and June 2008 on the diagnoses at discharge and microbiological and histological laboratory findings. All patients with possible, probable, or proven invasive aspergillosis (IA) were included. In wards with portable HEPA filters, the incidence rate of IA of 34.61/100,000 patient-days in the pre-installation period was reduced to 17.51/100,000 patient-days in the post-installation period (P = .01), for an incidence rate ratio of 1.98 (95% confidence interval [CI], 1.10-2.97). In wards with no HEPA filters, there was no significant change in the incidence rate during the study period. Portable HEPA filters were associated with an adjusted odds ratio of 0.49 (95% CI, 0.28-0.85; P = .01), adjusted for diagnosis and length of hospital stay. Portable HEPA filters are effective in the prevention of IA. The cost of widespread portable HEPA filtration in hospitals will be more than offset by the decreases in nosocomial infections in general and in IA in particular. Copyright (c) 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  1. 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.

  2. Azole-Resistant Invasive Aspergillosis

    DEFF Research Database (Denmark)

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

    2012-01-01

    with point mutation (s) in CYP51A (TR34/L98H and TR46/Y121F/T289A). In the third a single target enzyme alteration (G432S) is found. These resistant “environmental” strains have been detected in many West-European countries as well as in the Asia- Pacifics. Noticeably, these two continents account...... and classes available is impressive compared to the armamentarium in human medicine, azoles will remain the most important group in agriculture due to superior field performance and significant resistance in fungal pathogens to other compounds. Hence, further spread of environmental resistant Aspergillus...

  3. Treatment and Outcomes of Aspergillosis

    Science.gov (United States)

    ... Testing Treatment & Outcomes Health Professionals Statistics More Resources Candidiasis Candida infections of the mouth, throat, and esophagus Vaginal candidiasis Invasive candidiasis Definition Symptoms Risk & Prevention Sources Diagnosis ...

  4. Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report Aspergillus niger causando traqueobronquite e aspergilose pulmonar invasiva em transplantado de pulmão: relato de caso

    Directory of Open Access Journals (Sweden)

    Melissa Orzechowski Xavier

    2008-04-01

    Full Text Available A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.Descreve-se um caso de aspergilose invasiva causada por Aspergillus niger em um paciente transplantado de pulmão com quadros hiperglicêmicos desde o pós-operatório e outras complicações como infecção por citomegalovírus. Os fatores predisponentes associados e outras implicações são discutidos. Aspergillus niger parece ser uma espécie fúngica de baixa virulência, necessitando a presença de um hospedeiro gravemente imunodeprimido para causar doença invasiva.

  5. 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

    Directory of Open Access Journals (Sweden)

    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

  6. Pituitary aspergillosis abscess in an immunocompetent black ...

    African Journals Online (AJOL)

    The diagnosis of aspergillus was confirmed by histopathology. The postoperative course was good with the administration of antifungal chemotherapy. Conclusion Pituitary Aspergellosis is not only rare, but also bears clinical, biological and radiological resemblance to pituitary adenoma; it should therefore be regarded as a ...

  7. Subcutaneous aspergillosis with coexisting atypical mycobacterial infection.

    Science.gov (United States)

    Duraipandian, Jeyakumari; Rengasamy, Gopal; Madasamy, Balamurugan; Kulanthaivelu, Ambedkarraj; Subramanian, Girija

    2010-01-01

    A 60-year-old woman, a known diabetic and asthmatic, was admitted for acute exacerbation of chronic obstructive pulmonary disease. Physical examination revealed two soft nodules in the left infra axillary region. Fine needle aspiration cytology (FNAC) showed fungal granulomatous reaction suggestive of fungal infection. Periodic acid Schiff stain (PAS stain) revealed PAS positive, acutely branching, septate fungal hyphae. Wet mount of the aspirate revealed plenty of pus cells and branching septate hyphae. Ziehl-Neelsen (ZN) stain showed moderate numbers of acid fast bacilli. Culture yielded Aspergillus flavus and Mycobacterium fortuitum.

  8. Subcutaneous aspergillosis with coexisting atypical mycobacterial infection

    Directory of Open Access Journals (Sweden)

    Duraipandian Jeyakumari

    2010-04-01

    Full Text Available A 60-year-old woman, a known diabetic and asthmatic, was admitted for acute exacerbation of chronic obstructive pulmonary disease. Physical examination revealed two soft nodules in the left infra axillary region. Fine needle aspiration cytology (FNAC showed fungal granulomatous reaction suggestive of fungal infection. Periodic acid Schiff stain (PAS stain revealed PAS positive, acutely branching, septate fungal hyphae. Wet mount of the aspirate revealed plenty of pus cells and branching septate hyphae. Ziehl-Neelsen (ZN stain showed moderate numbers of acid fast bacilli. Culture yielded Aspergillus flavus and Mycobacterium fortuitum.

  9. Aspergillosis - chest x-ray (image)

    Science.gov (United States)

    ... usually occurs in immunocompromised individuals. Here, a chest x-ray shows that the fungus has invaded the lung ... are usually seen as black areas on an x-ray. The cloudiness on the left side of this ...

  10. Primary Cutaneous Aspergillosis in an Immunocompetent Patient

    African Journals Online (AJOL)

    are the lungs, central nervous system (CNS), and sinuses, however, the rare cutaneous infection is usually associated with immunodeficiency. Primary cutaneous infection, especially in immunocompetent patients, is extremely rare, but an increase in prevalence has been noted in the last. 20 years. The predisposing factors ...

  11. Lung aspergillosis in an adult woman

    International Nuclear Information System (INIS)

    Toledano Grave de Peralta, Yanara; Campos IuñozII, Martha; Silveria DigónIII, Serguei

    2016-01-01

    The case report of a 44 years mixed race patient from an urban area is described, with a personal history of alcoholic liver disease who was admitted in the Pneumology Service of 'Dr. Juan Bruno Zayas Alfonso' Teaching General Hospital in Santiago de Cuba, after being referred from her health area due to expectoration episodes with blood and dry cough. Laboratory studies, sputum culture, thorax X rays, lung computerized axial tomography and fine-needle aspiration biopsy were carried out that lead to the mycetoma diagnosis due to Aspergillus fumigatus, which facilitated to indicate the appropriate treatment and to carry out the clinical follow up of the affected patient. (author)

  12. Allergic bronchopulmonary aspergillosis--a case report.

    Science.gov (United States)

    Chokhani, Ramesh; Neupane, Saraswoti; Kandel, Ishwar Sharma

    2004-12-01

    A 24 years old male presented with recurrent symptoms of cough and breathlessness for 6 years but increased in past 6 months. Fleeting radiological opacities, peripheral eosinophilia and central type bronchiectasus in high resolution CT scan gave the suspicion of allergic bronchopolmonary aspergilosis. Confirmation of the diagnosis was done by skin prick and immunological tests. The patient showed an excellent response to oral prednisolone.

  13. 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.

  14. Maxillary cementoblastoma (true cementoma) and secondary aspergillosis in a horse

    DEFF Research Database (Denmark)

    De Miguel, Ricardo; Molin, Jessica; Asin, Javier

    2018-01-01

    and an irregular surface. Histologically, the mass consisted of an abundant deposit of eosinophilic cementum-like organic matrix with frequent basophilic reversal lines and heterogeneous distribution of empty lacunae. Surrounded by this organic matrix there were numerous fungal hyphae positive for Aspergillus...

  15. Pulmonary aspergillosis in an African elephant (Loxodonta africana).

    Science.gov (United States)

    Kaim, Ute; Paltian, Vanja; Krudewig, Christiane; Nieder, Anne; Wohlsein, Peter

    2009-04-01

    A 26-year-old female African elephant (Loxodonta africana) with a history of purulent pododermatitis, recurrent abdominal pain, and severe weight loss died spontaneously after a period of deteriorating disease. The main pathological finding was a severe bilateral pyogranulomatous, partially necrotizing pneumonia with numerous intralesional fungal hyphae. At microbiological examination Aspergillus spp. were isolated. The present case indicates that mycotic pneumonia should to be considered as a differential diagnosis of pulmonary disorders in elephants.

  16. Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000-2009.

    Science.gov (United States)

    Hsiue, H-C; Wu, T-H; Chang, T-C; Hsiue, Y-C; Huang, Y-T; Lee, P-I; Hsueh, P-R

    2012-07-01

    We reviewed 776 patients who were culture positive for Aspergillus species at the hospital from 2000 to 2009. The isolates were collected for species identification by oligonucleotide hybridization and sequence analysis. A total of 96 cases of proven or probable IA were identified according to published criteria. The incidence of IA has increased significantly during the study period. Aspergillus fumigatus and A. flavus (41.7% each) were equally prevalent causative species. IA due to unusual species including A. nidulans (n=2), A. versicolor (n=2), and A. tubingensis (n=1) were also found. Among patients with IA, 55.2% had hematological disorder, 19.8% had underlying lung disorder, and 10.4% had autoimmune disease. The isolates species (Pculture with invasive disease. The overall mortality at three months was 62.5%, which remained stable throughout the study period. Multivariate analysis identified prior steroid use (P=0.007) as a significant risk factor for death, while surgery (P=0.030) and voriconazole (P=0.012) had protective effects. In conclusion, autoimmune disorders and underlying pulmonary diseases should also be considered as important predisposing factors of IA. Further emphasis on surgery and voriconazole in the management of IA might be beneficial.

  17. Immunodiagnosis of opportunistic mycoses: detection of fungal antigenemia by radioimmunoassays in systemic candidiasis and aspergillosis

    International Nuclear Information System (INIS)

    Weiner, M.H.

    1980-01-01

    The authors have developed radioimmunoassays to the Candida carbohydrate, mannan, and to an Aspergillus cell wall carbohydrate. They evaluate these radioimmunoassays with sera from rabbit models of disseminated mycoses, and further evaluate the radioimmunoassays for their diagnostic usefulness in a panel of patient sera. (Auth.)

  18. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  19. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    International Nuclear Information System (INIS)

    Kang, Si Won

    2006-01-01

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  20. 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

    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

  1. Radiodense concrements in sinus maxillaris-CT diagnosis of sinus aspergillosis

    International Nuclear Information System (INIS)

    Krennmair, G.; Lugmayr, H.; Lenglinger, F.

    1993-01-01

    11 patients with radiodense concrements in the sinus maxillaris underwent a preoperative computertomographic examination of the sinus maxillaris and the sinus concrements. 8 patients (72.7%) with the occurrence of radiodense concrements presented postoperative a histological and microbiological infection with aspergillus fumigatus. The CT-numbers of radiodense concrements in patients with aspergillus were 2802±302.4 HU (Hounsfield Unit). Concrements of patients without aspergillus infection (n=3) had lower density (368.6±149.1 HU; p [de

  2. Fatal fungal endocarditis by Aspergillus udagawae: an emerging cause of invasive aspergillosis.

    Science.gov (United States)

    Seki, Atsuko; Yoshida, Atsushi; Matsuda, Yoko; Kawata, Mitsuhiro; Nishimura, Takashi; Tanaka, Jun; Misawa, Yoshiki; Nakano, Yuta; Asami, Ryoko; Chida, Koji; Kikuchi, Ken; Arai, Tomio

    Aspergillus udagawae has morphological similarities to Aspergillusfumigatus; however, it shows a low susceptibility to common antifungal drugs and poor in vitro sporulation. We present the first reported case of infectious endocarditis caused by A. udagawae. An awareness of this newly described Aspergillus species is vital for further clarification. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Evidence for possible involvement of an elastolytic serine protease in aspergillosis.

    OpenAIRE

    Kolattukudy, P E; Lee, J D; Rogers, L M; Zimmerman, P; Ceselski, S; Fox, B; Stein, B; Copelan, E A

    1993-01-01

    A number of isolates of Aspergillus fumigatus obtained from the hospital environment produced extracellular elastolytic activity. This activity was found to be catalyzed by a single 33-kDa protein which was purified and characterized to be a serine protease. A. fumigatus, when grown on the insoluble structural material obtained from murine and bovine lung, produced the same extracellular 33-kDa elastolytic protease, indicating that this enzyme is likely to be produced when the organism infect...

  4. Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Luptáková, Dominika; Pluháček, Tomáš; Petřík, M.; Novák, Jiří; Palyzová, Andrea; Sokolová, Lucie; Škríba, Anton; Šedivá, Blanka; Lemr, Karel; Havlíček, Vladimír

    2017-01-01

    Roč. 7, NOV 28 (2017), č. článku 16523. ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1509; GA ČR(CZ) GA16-20229S Institutional support: RVO:61388971 Keywords : FUMIGATUS * SIDEROPHORES * GA-68-SIDEROPHORES Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 4.259, year: 2016

  5. A case of invasive Aspergillosis in a patient with no identifiable ...

    African Journals Online (AJOL)

    Invasive fungal infections usually affect patients with immunodeficiencies and very rarely patients with no known or identifiable risk factors. Diagnosis could be delayed in patients without previously known immunodeficiencies due to a low index of suspicion, leading to a delay in treatment and a potential poor outcome.

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

    Science.gov (United States)

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

    2012-08-01

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

  7. [Immunodiagnosis of endemic mycoses and bronchopulmonary aspergillosis: a multicenter study in Argentina].

    Science.gov (United States)

    Canteros, C E; Rivas, M C; Soria, M; Lee, W; Perrotta, D; Rodero, L; Davel, G

    2004-01-01

    In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01-2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order were PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study.

  8. [The use of galactomannan detection in diagnosing invasive aspergillosis in hemato-oncological patients].

    Science.gov (United States)

    Rácil, Z; Kocmanová, I; Wagnerová, B; Winterová, J; Lengerová, M; Moulis, M; Mayer, J

    2008-01-01

    PREMISES AND OBJECTIVES: Timely diagnosis is of critical importance for the prognosis of invasive aspergilosis (IA) patients. Over recent years, IA detection of galactomannan using the ELISA method has assumed growing importance. The objective of the study was to analyse the usability of the method in current clinical practice of a hemato-oncological ward. From May 2003 to October 2006, blood samples were taken from patients at IA risk to detect galactomannan (GM) in serum using the ELISA method. The patients who underwent the tests were classified by the probability of IA presence on the basis of the results of conventional diagnostic methods and section findings. A total of 11,360 serum samples from 911 adult patients were tested for GM presence. IA (probable/proven) was diagnosed in 42 (4.6%) of them. The rates of sensitivity, specificity, positive and negative predictive value of galactomannan detection for IA diagnosis in our ward were, respectively, 95.2%, 90.0%, 31.5% and 99.7%. The principal causes of the limited positive predictive value of the test were the high percentage of false-positive test results (mainly caused by concomitant administration of some penicillin antibiotics or Plasma-Lyte infusion solution), as well as the fact that a large percentage of patients we examined fell within the group of patients with hematological malignity with a very low prevalence of IA. GM detection in serum is associated with high sensitivity and excellent negative predictive value in IA diagnosis in hemato-oncological patients. Knowledge and elimination of possible causes of false-positive results as well as focusing the screening on patients at greatest risk of infection are necessary for an even better exploitation of the test.

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

    Science.gov (United States)

    Reza, Kheirandish; Nasrin, Askari; Mahmoud, Salehi

    2013-03-01

    To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously. 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. 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. 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.

  10. Combined Allergic Bronchopulmonary Aspergillosis and Eosinophilic Granulomatosis with Polyangiitis: Three Cases and a Review of the Literature.

    Science.gov (United States)

    Ishiguro, Takashi; Takayanagi, Noboru; Takaku, Yotaro; Kagiyama, Naho; Kurashima, Kazuyoshi; Sugita, Yutaka

    2016-01-01

    Previous reports of combined allergic bronchopulmonary mycosis (ABPM) and eosinophilic granulomatosis with polyangiitis (EGPA) are limited; however, among 41 cases of ABPM and 18 cases of EGPA treated at our hospital, we experienced three cases of combined ABPM and EGPA. In two of these cases, the diagnosis of EGPA preceded that of ABPM, however, one of the two cases had already shown findings suggestive of ABPM, such as mucous plugs and central bronchiectasis, at the time of the diagnosis of EGPA. In six previously reported cases of combined ABPM and EGPA, ABPM preceded EGPA in four cases. In the other two cases in which EGPA was diagnosed before or simultaneously with ABPM, findings suggestive of ABPM had been detected when EGPA was diagnosed, which suggests that sensitization to fungi resulting in ABPM may play an important role in the development of EGPA. Careful attention should therefore be paid to the possibility that these diseases may coexist during the course of either disease.

  11. Inhalation of amphotericin B formulations for prevention and treatment of invasive pulmonary aspergillosis : an experimental study in rats

    NARCIS (Netherlands)

    E.J. Ruijgrok (Elisabeth)

    2002-01-01

    textabstractBecause current knowledge of inhalational AMB is limited, a rigorous scientific approach is warranted to establish opt"1mal dose, frequency and durat"1on of administration. We therefore decided to study in detail the fu II potential of nebulised AMB in different formulations, with the

  12. Fatal invasive aspergillosis: a rare co-infection with an unexpected image presentation in a patient with dengue shock syndrome.

    Science.gov (United States)

    Wang, Hui-Ching; Chang, Ko; Lu, Po-Liang; Tsai, Kun-Bow; Chen, Huang-Chi

    2017-03-01

    Pulmonary infiltration and pleural effusion caused by permeability syndrome are the hallmark of pulmonary manifestation of dengue cases. We report a 95-year-old chronic obstructive pulmonary disease case having dengue shock syndrome. Chest X-ray examination revealed diffuse lung infiltration. However, bilateral pneumotoceles were unexpectedly found in computed tomography (CT) images. Dengue virus type 2 infection was confirmed by virus culture, serology and reverse transcriptase-polymerase chain reaction. Profound shock with bilateral lung infiltration developed rapidly in 2 days with supportive care and empirical ampicillin/ sulbactam. Bronchoscopy revealed a whitish plaque over bilateral upper bronchi. Biopsy via bronchoscopy revealed moulds with vascular invasion. Culture of bronchial alveolar lavage yielded Aspergillus flavus. The patient died despite amphotericin B treatment, which was started since finding the whitish plaque with bronchoscopy examination. Besides to considering capillary leakage syndrome, our case report and literature review alert clinicians that CT and bronchoscopy may help to identify the true pathogen though all cases with concurrent dengue and Aspergillus infections had fatal outcomes. © 2015 John Wiley & Sons Ltd.

  13. 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.

  14. Virtual screening and evaluation of Ketol-Acid Reducto-Isomerase (KARI as a putative drug target for Aspergillosis

    Directory of Open Access Journals (Sweden)

    Morya Vivek K

    2012-02-01

    Full Text Available Abstract Aspergillus is a leading causative agent for fungal morbidity and mortality in immuno-compromised patients. To identify a putative target to design or identify new antifungal drug, against Aspergillus is required. In our previous work, we have analyzed the various biochemical pathways, and we found Ketol Acid Reducto-Isomerase (KARI an enzyme involves in the amino acid biosynthesis, could be a better target. This enzyme was found to be unique by comparing to host proteome through BLASTp analysis. A homology based model of KARI was generated by Swiss model server. The generated model had been validated by PROCHECK and WHAT IF programs. The Zinc library was generated within the limitation of the Lipinski rule of five, for docking study. Based on the dock-score six molecules have been studied for ADME/TOX analysis and subjected for pharmacophore model generation. The Zinc ID of the potential inhibitors is ZINC00720614, ZINC01068126, ZINC0923, ZINC02090678, ZINC00663057 and ZINC02284065 and found to be pharmacologically active agonist and antagonist of KARI. This study is an attempt to Insilco evaluation of the KARI as a drug target and the screened inhibitors could help in the development of the better drug against Aspergillus.

  15. Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis?

    Science.gov (United States)

    Eaton, T E; Weiner Miller, P; Garrett, J E; Cutting, G R

    2002-05-01

    Previous work suggests that cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations may be implicated in the aetiology of allergic bronchopulmonary aspergilosis (ABPA). To compare the frequency of CF gene mutations in asthmatics with ABPA of varying severity with asthmatics who were skin prick test (SPT)-positive to Aspergillus fumigatus (Af) without evidence of ABPA and asthmatics SPT-negative to Af. Thirty-one Caucasian patients with ABPA were identified, together with asthmatics SPT positive to Af without evidence of ABPA (n = 23) and SPT negative to Af (n = 28). Genomic DNA was tested for 16 CF mutations accounting for approximately 85% of CF alleles in Caucasian New Zealanders. Four (12.9%) ABPA patients were found to be carriers of a CF mutation (DeltaF508 n = 3, R117H n = 1), one (4.3%) asthmatic SPT positive to Af without ABPA (DeltaF508), and one (3.6%) asthmatic SPT negative to Af (R117H). All patients with a CF mutation had normal sweat chloride (< 40 mM). There was no significant difference between the frequency of CF mutations in the ABPA patients and asthmatics without ABPA. However, the frequency of CF mutations in the ABPA patients was significantly different (P = 0.0125) to the expected carrier rate in the general population. These results lend further support to a possible link between CF mutations and ABPA.

  16. Comparison of serum PCR assay and histopathology for the diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients with sinus involvement

    Directory of Open Access Journals (Sweden)

    Shervin Shokouhi

    2016-12-01

    Conclusion: Using serum PCR, we detected Aspergillus and Mucoralean species in patients with suspected fungal sinus infection. While this test may have utility in diagnosis directly from biopsy site, it appears unreliable for use as a noninvasive blood test.  

  17. Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

    DEFF Research Database (Denmark)

    Davies, Genna; Rolle, Anna-Maria; Maurer, Andreas

    2017-01-01

    and magnetic resonance imaging (immunoPET/MRI) using a [64Cu] DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung...... of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography...... infection using a [64Cu] NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu] NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds...

  18. 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.

  19. 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.

  20. A case report of IPA with chronic mass calcification in a neutropenic patient

    Directory of Open Access Journals (Sweden)

    Sudheesh Raveendran

    2017-06-01

    Full Text Available Aspergillosis is a serious pathologic condition caused by Aspergillus organisms and is frequently seen in immunocompromised patients. Invasive pulmonary aspergillosis (IPA which is rare, has been identified as one of the histological subtypes of aspergillosis. It is one of the rare chronic infectious diseases of respiratory system in China, and presents high morbidity, high drug resistance and specific imaging characteristics. This paper focused on a rare case report of invasive pulmonary aspergillosis with chronic mass calcification. CT imaging was discussed by contrast with clinical manifestations, aiming to survey the invasive pulmonary aspergillosis and the mass calcification and to improve the clinical differential diagnosis.

  1. Clinical utility from the determination of serico galactomannan in the diagnosis of invasive aspergillosis in hematological patients of the Hospital San Juan de Dios, between January 2009 and December 2012

    International Nuclear Information System (INIS)

    Li Sandi, Silvia

    2014-01-01

    Nosocomial infections have become more important to the health system by the high costs of these, but are little data available about them in recent years. The clinical utility of the determination of serum galactomannan (GMS) in patients with high risk of contracting the infection by Aspergillus spp, was assessed, between January 2009 and December 2012 at the Hospital San Juan de Dios. Several existing studies in the scientific literature have already evaluated the clinical usefulness, specific data have been inexistent for Costa Rica or for Central America and the Caribbean; so it is important to have known whether the conduct of the test has been similar to the other populations or have specific variations [es

  2. Standard methods for fungal brood disease research

    DEFF Research Database (Denmark)

    Jensen, Annette Bruun; Aronstein, Kathrine; Manuel Flores, Jose

    2013-01-01

    . 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...

  3. 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...

  4. 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.

  5. Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

    Science.gov (United States)

    Kim, Tae-Seok; Ahn, Keun Soo; Kim, Yong Hoon; Kim, Hyoung Tae; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Il-Man; Kang, Yu Na; Kang, Koo Jeong

    2017-02-01

    Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

  6. Mycoses

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.S.

    1983-01-01

    Roentgenological pictures of lungs mycoses: actinomycosis, aspergillosis, c andidiasis, histoplasmosis, cryptococcosis, and coccidioidomycosis, have been studied. Special attention is paid to the problems of high-quality X-ray diagn osis in case of the above-mentioned pneumomycoses

  7. 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

  8. Immunohistochemical diagnosis of fusariosis with monoclonal antibodies

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbæk, B.; Jungersen, Gregers

    Objectives: Fusariosis is an emerging fungal infection, especially in neutropenic patients. Proper identification of Fusarium spp. is important because the choice of antifungal treatment of fusariosis differs from that of aspergillosis, candidosis or scedosporidiosis (pseudalleceriosis). Cultural...

  9. Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered from treated patients.

    NARCIS (Netherlands)

    Danaoui, E.; Meletiadis, J.; Tortorano, A.M.; Symoens, F.; Nolard, N.; Viviani, M.A.; Piens, M.A.; Lebeau, B.; Verweij, P.E.; Grillot, R.

    2004-01-01

    Two-hundred sequential Aspergillus fumigatus isolates recovered from 26 immunocompromised patients with invasive aspergillosis or bronchial colonization were tested for their in vitro susceptibility to posaconazole, itraconazole, voriconazole, terbinafine and amphotericin B. Twenty-one patients were

  10. Disease: H01328 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01328 Aspergillosis Pulmonary aspergillus infections can be classified based on c... ... ICD-10: B44 MeSH: D001228 MedlinePlus: 001326 PMID:25135079 ... AUTHORS ... Warris A ... TITLE ... The biology of pulmonary aspergillus

  11. Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

    NARCIS (Netherlands)

    van der Elst, Kim C. M.; Span, Lambert F. R.; van Hateren, Kai; Vermeulen, Karin M.; van der Werf, Tjip S.; Greijdanus, Ben; Kosterink, Jos G. W.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

    2013-01-01

    Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of

  12. 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.G.; 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.

  13. Polyphasic identification of Aspergillus isolates belonging to section Nigri with clinical relevance

    OpenAIRE

    Maciel, Marília; Santos, Cledir; Lima, Nelson; Souza-Motta, Cristina Maria

    2012-01-01

    Aspergillosis is the name of a group of diseases in humans and animals caused by opportunist moulds of the genus Aspergillus. The vast majority of infections are caused by A. fumigatus, followed by other species such as A. flavus, A. terreus and A. niger. Among the pulmonary infection, aspergillosis is gaining prominent position not only in immunocompromised patients, but also in immunosuppressed. The absence of a reliable fungal identification system affects the control of ...

  14. Cerebral aspergilloma in a SLE patient: A case report with short literature review

    OpenAIRE

    Chowdhury, Forhad Hossain; Haque, Mohammod Raziul; Khan, Shafiqul Kabir; Alam, Sarwar Morshed

    2014-01-01

    Aspergillosis of brain is very rare, and commonly seen in immunocompromised or immunosuppressed patient. Here, we report a cerebral aspergillosis condition in a late teen girl who is a Systemic Lupus Erythromatosis patient with steroid therapy. She developed headaches, vomitings, and convulsions. On the basis of clinical and neuroimaging, a diagnosis of cerebral tuberculoma was made, and she was put on anti-TB therapy, but she did not respond. Later, surgical partial excision biopsy confirmed...

  15. 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

    Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery...... 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...

  16. Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death

    OpenAIRE

    Armstrong-James, DPH

    2016-01-01

    RATIONALE: Pulmonary aspergillosis is a lethal mould infection in the immunocompromised host. Understanding initial control of infection, and how this is altered in the immunocompromised host, is a key goal for understanding the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterise the outcome of human macrophage infection with Aspergillus fumigatus, and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of ...

  17. Pseudomembranous aspergillus bronchitis in a double-lung transplanted patient: unusual radiographic and CT features

    International Nuclear Information System (INIS)

    Ducreux, D.; Chevallier, P.; Raffaelli, C.; Padovani, B.; Perrin, C.; Jourdan, J.; Hofman, P.

    2000-01-01

    Pseudomembranous aspergillus bronchitis is considered as an early form of invasive pulmonary aspergillosis, a well-known airway infection in immunocompromised patients. Radiologic features concerning invasive aspergillosis of the airways have been reported. However, we describe here an unusual feature of invasive aspergillus bronchitis, never reported to date, observed in a double-lung transplanted patient. Chest radiograph and CT revealed significant peribronchial thickening without any parenchymal involvement. (orig.)

  18. Two non-invasive diagnostic tools for invasive aspergilosis: (1-3)-beta-D-glucan and the galactomannan assay.

    Science.gov (United States)

    Kelaher, Amy

    2006-01-01

    Invasive aspergillosis (IA) is a serious cause of morbidity and mortality among immunocompromised patients. Prompt and non-invasive methods for diagnosing IA are needed to improve the management of this life-threatening infection in patients with hematological disorders. In summary, this retrospective review of studies performed on the two assays finds that both assays have high sensitivity and specificity but are more useful when used together as a diagnostic strategy for patients with invasive aspergillosis.

  19. Aspergillus serology: Have we arrived yet?

    Science.gov (United States)

    Richardson, Malcolm D; Page, Iain D

    2017-01-01

    Aspergillosis presents in various clinical forms, among them chronic pulmonary aspergillosis, which is a spectrum of disease entities including aspergilloma, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. Aspergillus also contributes to fungal allergy and sensitization. Analysis of the immune response to Aspergillus and its antigens is an integral part of the diagnosis of these diseases. Over the past half century, the techniques used to determine antibody titers have evolved from testing for precipitating and agglutinating antibodies by agar gel double diffusion and immunolectrophoresis to enzyme-linked immunosorbent assays using recombinant proteins as capture antigens. A resurgence of interest in the detection of immunoglobulins, primarily Aspergillus-specific IgG, has hinted at the possibility of distinguishing between colonization and invasion in immunocompromised patients with invasive aspergillosis. Even though there appears to be a greater degree of discrimination between the clinical forms of aspergillosis there is still a long way to travel. This review presents illustrative examples of where new diagnostic platforms and technologies have been applied to this intriguing spectrum of diseases. © The Authors 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. 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.

  1. Clinical utility from the determination of serico galactomannan in the diagnosis of invasive aspergillosis in hematological patients of the Hospital San Juan de Dios, between January 2009 and December 2012; Utilidad clinica de la determinacion de galactomanano serico en el diagnostico de aspergilosis invasiva en pacientes hematologicos del Hospital San Juan de Dios, entre enero 2009 y diciembre 2012

    Energy Technology Data Exchange (ETDEWEB)

    Li Sandi, Silvia

    2014-07-01

    Nosocomial infections have become more important to the health system by the high costs of these, but are little data available about them in recent years. The clinical utility of the determination of serum galactomannan (GMS) in patients with high risk of contracting the infection by Aspergillus spp, was assessed, between January 2009 and December 2012 at the Hospital San Juan de Dios. Several existing studies in the scientific literature have already evaluated the clinical usefulness, specific data have been inexistent for Costa Rica or for Central America and the Caribbean; so it is important to have known whether the conduct of the test has been similar to the other populations or have specific variations [Spanish] Las enfermedades nosocomiales han cobrado mayor importancia para el sistema de salud por el gasto elevado que han representado, pero son pocos los datos disponibles respecto a ellas en los ultimos anos. La utilidad clinica de la determinacion de galactomanano serico (GMS) en pacientes con alto riesgo a contraer la infeccion por Aspergillus spp, fue evaluada, entre enero del 2009 y diciembre del 2012 en el Hospital San Juan de Dios. Varios estudios existentes en la literatura cientifica ya han evaluado esta utilidad clinica, datos especificos han sido inexistentes para Costa Rica, o para la region Centroamericana y el Caribe, por lo que es importante haber conocido si el comportamiento de la prueba ha sido similar a las otras poblaciones o tiene variaciones.

  2. 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.

  3. Aspergillus fumigatus and Related Species

    Science.gov (United States)

    Sugui, Janyce A.; Kwon-Chung, Kyung J.; Juvvadi, Praveen R.; Latgé, Jean-Paul; Steinbach, William J.

    2015-01-01

    The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologically resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequate antifungal therapy are key elements for treatment of the disease, especially in cases of pulmonary invasive aspergillosis that often advance very rapidly. Incorporating knowledge of the basic biology of Aspergillus species to that of the diseases that they cause is fundamental for further progress in the field. PMID:25377144

  4. disease patient

    Directory of Open Access Journals (Sweden)

    Setareh Mamishi

    2016-09-01

    Full Text Available Background and Purpose: Chronic granulomatous disease (CGD is an inherited disorder of the nicotinamide adenine dinucleotide phosphate (NADPH oxidase complex. This disorder results in recurrent life-threatening bacterial and fungal infections. Aspergillus species are the most common fungal infections in these patients. Case Report: Herein, we present a case of fungal infection in a girl with CGD. We confirmed aspergillosis through the positive microscopic and macroscopic examinations, as well as radiology results. Invasive aspergillosis in this patient with pneumonia, lung abscess, and osteomyelitis of the ribs was not initially treated with amphotericin B (Am B and recombinant interferon-gamma. Conclusion: Among infectious diseases, fungal infections, in particular aspergillosis, remain a serious problem in CGD patients. Considering poor clinical response and deficient immune system, rapid diagnosis of fungal infection and optimizing the treatment of these patients are recommended.

  5. [Radiographic findings in raptors affected with a mycosis of the respiratory tract].

    Science.gov (United States)

    Vorbrüggen, S; Bailey, T; Krautwald-Junghanns, M-E

    2013-01-01

    Summary of typical radiographic signs in birds of prey with aspergillosis compared to signs previously established in parrots. Evaluation of radiographs of 110 falcons (Falco spp.) with aspergillosis confirmed by endoscopy. Compared to parrots primarily subtle radiographic signs were detected in falcons (especially inhomogeneously increased radiodensities of the airsacs/lungs). Two typical signs for diseased falcons consisted of the poor delineation of the cardiac silhouette and the line-shaped increased radiodensity of the caudal lung border. Radiographic diagnosis of the lung is limited due to the strong flight musculature. The varying results between avian species can be explained by the different radiographic anatomy, husbandry conditions and x-ray technique (digital versus analog). A pet bird-experienced practitioner should be aware of specific radiographic signs in birds of prey suspected of having aspergillosis.

  6. Home Environment as a Source of Life-Threatening Azole-Resistant Aspergillus fumigatus in Immunocompromised Patients.

    Science.gov (United States)

    Lavergne, Rose-Anne; Chouaki, Taieb; Hagen, Ferry; Toublanc, Bénédicte; Dupont, Hervé; Jounieaux, Vincent; Meis, Jacques F; Morio, Florent; Le Pape, Patrice

    2017-01-01

    A case of fatal aspergillosis due to a TR 46 /Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR 46 /Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. 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...

  8. [Utility of Aspergillus-LFD: first experience in Chile].

    Science.gov (United States)

    Alvarez, Eduardo

    2015-02-01

    The diagnosis of invasive aspergillosis remains a challenge. Detection of galactomannan in serum and bronchoalveolar lavage is a useful tool; however due to methodological and economic reasons, the test frequencies of galactomannan assays vary from daily to weekly, which constitute a risk to the patient. In this study, we aimed to evaluate and correlate the performance of the new kit Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast, economical and simple test; showed a good performance and excellent correlation with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an alternative to consider in the early diagnosis of invasive aspergillosis.

  9. Aspergillus in the lung: diverse and coincident forms

    International Nuclear Information System (INIS)

    Buckingham, Susan J.; Hansell, David M.

    2003-01-01

    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.)

  10. Aspergillus infection monitored by multimodal imaging in a rat model

    Czech Academy of Sciences Publication Activity Database

    Pluháček, Tomáš; Petrík, M.; Luptáková, Dominika; Benada, Oldřich; Palyzová, Andrea; Lemr, Karel; Havlíček, Vladimír

    2016-01-01

    Roč. 16, 11-12 (2016), s. 1785-1792 ISSN 1615-9853 R&D Projects: GA MŠk LO1509; GA ČR GAP206/12/1150 Institutional support: RVO:61388971 Keywords : Animal model * Aspergillosis * Biomedicine Subject RIV: CE - Biochemistry Impact factor: 4.041, year: 2016

  11. 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 (Shih-Chin); 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

  12. Azole resistance surveillance in Aspergillus fumigatus: beneficial or biased?

    NARCIS (Netherlands)

    Verweij, P.E.; Lestrade, P.P.A.; Melchers, W.J.G.; Meis, J.F.G.M.

    2016-01-01

    Azole resistance is a growing concern with Aspergillus fumigatus, and may cause increased mortality in patients with azole-resistant invasive aspergillosis (IA). Microbial surveillance has been recognized as a fundamental component of resistance management. Surveillance information may be used to

  13. 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

  14. 35 REVIEW ARTICLE

    African Journals Online (AJOL)

    boaz

    include;1) Invasive aspergillosis seen mostly in stem cell and organ transplant recipients, patients with haematological malignancies, cancer ...... 1977; 86(4): p. ... 1982; 96(3): p. 286-91. 46. Denning, D.W. O'Driscoll, B.R., Powell, G., et al.

  15. Antifungal and Antihepatotoxic Effects of Sepia Ink Extract against ...

    African Journals Online (AJOL)

    Background: There is a great need for novel strategies to overcome the high mortality associated with invasive pulmonary aspergillosis (IPA) in immunocompromised patients. To evaluate the antifungal and antihepatotoxic potentials of Sepia ink extract, its effect on liver oxidative stress levels was analyzed against IPA in ...

  16. Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry

    NARCIS (Netherlands)

    Gerritsen, M G; Brinkman, P; Escobar Salazar, Natalia; Bos, L D; de Heer, K; Meijer, M; Janssen, H-G; de Cock, H; Wösten, H A B; Visser, C.E.; van Oers, M H J; Sterk, P J

    Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a

  17. 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.

  18. Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

    NARCIS (Netherlands)

    Masih, A.; Singh, P.K.; Kathuria, S.; Agarwal, K.; Meis, J.F.G.M.; Chowdhary, A.

    2016-01-01

    Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study

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

    Science.gov (United States)

    2013-01-01

    Verweij PE. Non culture based diagnostics for opportunistic fungi . Infect Dis Clin North Am 2006;20:711 27. [9] Persat F, Ranque S, Derouin F, Michel...and their analysis. J Med Microbiol 2010;59:1016 22. [12] Wheat LJ, Walsh TJ. Diagnosis of invasive Aspergillosis by galactomannan antigenemia detection

  20. Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry

    NARCIS (Netherlands)

    Gerritsen, M. G.; Brinkman, P.; Escobar, N.; Bos, L. D.; de Heer, K.; Meijer, M.; Janssen, H.-G.; de Cock, H.; Wösten, H. A. B.; Visser, C. E.; van Oers, M. H. J.; Sterk, P. J.

    2018-01-01

    Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a

  1. Kroniske pulmonale aspergilloser

    DEFF Research Database (Denmark)

    Davidsen, Jesper Rømhild; Rosenvinge, Flemming S; Assing, Kristian

    2018-01-01

    Chronic pulmonary aspergillosis (CPA) is an overlooked disease category in which delay of diagnosis and treatment is associated with increased mortality. A prerequisite for prognostic optimization of CPA is an increased focus on predisposing factors and patients at risk. Diagnosis of CPA is chall...

  2. Geographically predominant genotypes of Aspergillus terreus species complex in Austria: s microsatellite typing study

    NARCIS (Netherlands)

    Lackner, M.; Coassin, S.; Haun, M.; Binder, U.; Kronenberg, F.; Haas, H. de; Jank, M.; Maurer, E.; Meis, J.F.; Hagen, F.; Lass-Florl, C.

    2016-01-01

    Aspergillus terreus species complex is recognized as a frequent agent of invasive aspergillosis in Tyrol. The reason for this specific epidemiological situation is unclear. Aspergillus terreus strains isolated from environmental and clinical sources were genotyped using a novel panel of short tandem

  3. Rare and new etiological agents revealed among 178 clinical Aspergillus strains obtained from Czech patients and characterized by molecular sequencing

    Czech Academy of Sciences Publication Activity Database

    Hubka, Vít; Kubátová, A.; Mallátová, N.; Sedláček, P.; Melichar, J.; Skořepová, M.; Mencl, K.; Lysková, P.; Šrámková, B.; Chudíčková, Milada; Hamal, P.; Kolařík, Miroslav

    2012-01-01

    Roč. 50, č. 6 (2012), s. 601-610 ISSN 1369-3786 Institutional research plan: CEZ:AV0Z50200510 Keywords : invasive aspergillosis * non-dermatophytic onychomycosis * otomycosis Subject RIV: EE - Microbiology, Virology Impact factor: 1.979, year: 2012

  4. 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.

  5. On the evolution of azole resistance in Aspergillus fumigatus

    NARCIS (Netherlands)

    Zhang, J.

    2016-01-01

    During the last decade azole resistance has increasingly been reported in Aspergillus fumigatus, which is a fungal pathogen involved in the vast majority of invasive aspergillosis infections in humans, and is now a global public health concern. Antifungal azoles, especially triazoles,

  6. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  7. Omental Pedicled Flap for Pulmonary Tuberculosis Sequelae ...

    African Journals Online (AJOL)

    The omental flap should be prophylactically used in post-pneumonectomy bronchial stump reinforcement where the underlying chronic inflammatory condition poses high risk for bronchial dehiscence. We present a unique case of pulmonary tuberculosis (TB) complicated by empyema, chronic pulmonary aspergillosis and ...

  8. Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.

    Science.gov (United States)

    Shah, Anand; Kannambath, Shichina; Herbst, Susanne; Rogers, Andrew; Soresi, Simona; Carby, Martin; Reed, Anna; Mostowy, Serge; Fisher, Matthew C; Shaunak, Sunil; Armstrong-James, Darius P

    2016-11-01

    Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape. These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

  9. 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.

  10. Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection model

    NARCIS (Netherlands)

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

    2015-01-01

    Azole resistance is an emerging problem in Aspergillus fumigatus which translates into treatment failure. Alternative treatments with new azoles may improve therapeutic outcome in invasive aspergillosis (IA) even for strains with decreased susceptibility to current azoles. The in vivo efficacy of

  11. Determining the analytical specificity of PCR-based assays for the diagnosis of IA: What is Aspergillus?

    NARCIS (Netherlands)

    Morton, C.O.; White, P.L.; Barnes, R.A.; Klingspor, L.; Cuenca-Estrella, M.; Lagrou, K.; Bretagne, S.; Melchers, W.J.; Mengoli, C.; Caliendo, A.M.; Cogliati, M.; Debets-Ossenkopp, Y.; Gorton, R.; Hagen, F.; Halliday, C.; Hamal, P.; Harvey-Wood, K.; Jaton, K.; Johnson, G.; Kidd, S.; Lengerova, M.; Lass-Florl, C.; Linton, C.; Millon, L.; Morrissey, C.O.; Paholcsek, M.; Talento, A.F.; Ruhnke, M.; Willinger, B.; Donnelly, J.P.; Loeffler, J.

    2017-01-01

    A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help

  12. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    van der Elst, K.C.; 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

  13. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    van der Elst, K. C. M.; Bruggemann, R. J. M.; Rodgers, M. G. G.; Alffenaar, J. W. C.

    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

  14. Autopsy case of pulmonary aspergilloma. [After long chemotherapy for TB

    Energy Technology Data Exchange (ETDEWEB)

    II, Yohei; Akizuki, S

    1973-01-01

    A 73-year-old female received anti-TB chemotherapy for pulmonary tuberculosis for a long period and died from severe hemoptysis which suddenly developed after recovery from the disease. Autopsy showed a large aspergilloma in the upper lobe of the right lung. This case is reported along with a review of the literature on aspergillosis. (30 refs) (DLC)

  15. Differential diagnosis of vertebral lesions with paraspinal mass with MRI

    International Nuclear Information System (INIS)

    Choi, Jae Ho; Choi, Jin Ok; Nam, Mee Young; Baek, In Gee; Park, Yang Sin; Rhee, Hak Song

    1997-01-01

    To assess the characteristic features of MR findings which would be useful for the differentiation of various spinal diseases involving paraspinal soft tissue mass. We retrospectively reviewed MR findings in 31 cases(M : F = 20 : 11) of spinal disease in which paraspinal mass was involved. The breakdown of cases was as follows : spinal tuberculosis, 12; spinal metastasis, 13; multiple myeloma, 3; pyogenic spondylitis, 2; spinal aspergillosis, 1. The pattern of bone marrow invasion in spinal metastasis, multiple myeloma, spinal tuberculosis and aspergillosis was mixed; focal, homogeneously diffuse and inhomogeneously patterns were seen. Pyogenic spondylitis showed inhomogeneously diffuse invasion; an intravertebral abscess was seen in the only five cases of spinal tuberculosis. Vertebral posterior compartment invasion was observed in seven cases of spinal tuberculosis, two of multiple myeloma, the one case of spinal aspergillosis and in all 13 cases of spinal metastasis. This and multiple myeloma showed no disc space invasion, in any case, but all cases of infectious spondylitis showed such invasion. Peripheral rim-enhancement in the paravertebral mass was seen in 11 cases of spinal tuberculosis, one case of pyogenic spondylitis and the case of aspergillosis. Bilobate anterior epidural mass was noted in 60% of spinal tuberculosis cases, 36% of spinal metastasis and one case of pyogenic spondylitis. MR findings of spinal disease involving a paraspinal soft tissue mass were useful for differentiation

  16. Aspergillus of the lung with haemoptysis: A surgical emergency ...

    African Journals Online (AJOL)

    Background: Aspegillus is an important pathogen in patients with impaired host defences. These mycelial fungi can cause local as well disseminated disease. Two forms of pulmonary aspergillosis are frequently seen : 1. pulmonary or brochial aspergilloma (fungus ball) due to secondary invasion of a a tuberculous cavity ...

  17. Elevated Voriconazole Level Associated With Hallucinations and Suicidal Ideation: A Case Report.

    Science.gov (United States)

    Jansen, Jeffrey W; Sen, Sumon K; Moenster, Ryan P

    2017-01-01

    Voriconazole, a broad-spectrum antifungal, has been associated with visual and auditory hallucinations. We report the case of patient being treated with voriconazole for pulmonary aspergillosis who developed visual hallucinations and new suicidal ideation with plan. Voriconazole troughs were supratherapeutic (9.0 mcg/mL) and the patient was positive for the CYP2C19*1/*2 allele.

  18. A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist

    Science.gov (United States)

    Gresnigt, Mark S.; Bozza, Silvia; Becker, Katharina L.; Joosten, Leo A. B.; Abdollahi-Roodsaz, Shahla; van der Berg, Wim B.; Dinarello, Charles A.; Netea, Mihai G.; Fontaine, Thierry; De Luca, Antonella; Moretti, Silvia; Romani, Luigina; Latge, Jean-Paul; van de Veerdonk, Frank L.

    2014-01-01

    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 (Th)1 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. PMID:24603878

  19. Rapidly Growing Thyroid Mass in an Immunocompromised Young Male Adult

    Directory of Open Access Journals (Sweden)

    Mónica Santiago

    2013-01-01

    Full Text Available We describe a 20-year-old man diagnosed with a myelodysplastic syndrome (MDS, admitted to our hospital due to pancytopenia and fever of undetermined origin after myelosuppression with chemotherapy. Disseminated aspergillosis (DIA was suspected when he developed skin and lung involvement. A rapidly growing mass was detected on the left neck area, during hospitalization. A thyroid ultrasound reported a 3.7×2.5×2.9 cm oval heterogeneous structure, suggestive of an abscess versus a hematoma. Fine needle aspiration of the thyroid revealed invasion of aspergillosis. Fungal thyroiditis is a rare occurrence. Thyroid fungal infection is difficult to diagnose; for this reason it is rarely diagnosed antemortem. To our knowledge, this is the 10th case reported in the literature in an adult where the diagnosis of fungal invasion to the thyroid was able to be corroborated antemortem by fine needle aspiration biopsy.

  20. [Cavitating lung lesions in the course of ANCA-associated vasculitis: differential diagnostic aspects].

    Science.gov (United States)

    Kirchner, J; Raab, H P; Länger, F; Wigand, R; Mitrou, P; Jacobi, V

    1998-05-01

    Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite variable courses. Clinical features of the full blown generalized systemic vasculitis are usually found in the respiratory tract and the kidney. Pulmonary involvement of Wegener's granulomatosis shows commonly nodules and cavitations but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and tinitus. Specimen of the kidney showed segmental glomerulosclerosis and tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease was assumed. Pulmonary infiltrates developed under immunosuppressive treatment with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we considered invasive pulmonary aspergillosis as well as infiltrates due to Wegener's granulomatosis. In spite of maximal therapeutic management of patient died of respiratory and cardiovascular failure. The findings at autopsy showed distinct invasive pulmonary aspergillosis and perifocal hemorrhage.

  1. The role of interleukin-1 family members in the host defence against Aspergillus fumigatus.

    Science.gov (United States)

    Gresnigt, Mark S; van de Veerdonk, Frank L

    2014-12-01

    The interleukin (IL)-1 family consists of 11 members, which all play significant roles in regulating inflammatory responses in the host. IL-1α and IL-1β exert potent pro-inflammatory effects and are key players in the recruitment of neutrophils to the site of inflammation. Protective anti-Aspergillus host responses during the early stages of invasive aspergillosis are critically dependent on neutrophil recruitment, and several lines of evidence support that there is an important role for IL-1 in this process. However, IL-1-mediated inflammation needs to be tightly regulated, since uncontrolled inflammation can result in inflammatory pathology and thereby be detrimental for the host. Aspergillus-induced IL-1-mediated inflammation could therefore be amendable for IL-1 blockade under specific circumstances. This review describes the current understanding of the role of IL-1 family members in the host response against Aspergillus fumigatus and highlights the importance of balanced IL-1 responses in aspergillosis.

  2. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

    Directory of Open Access Journals (Sweden)

    Erdoğan Çetinkaya

    2016-01-01

    Full Text Available Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp. are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved.

  3. A prospective survey of Aspergillus spp. in respiratory tract samples: prevalence, clinical impact and antifungal susceptibility

    DEFF Research Database (Denmark)

    Mortensen, K L; Johansen, H K; Fuursted, Kurt

    2011-01-01

    for routine microbiologic investigation were examined for Aspergillus following routine procedures and with extended incubation (5 days). Identification was done by morphologic criteria and susceptibility testing using EUCAST method for azoles and amphotericin B E-test. Invasive aspergillosis (IA......) was evaluated using modified EORTC/MSG criteria. A total of 11,368 airway samples were received. Growth of Aspergillus spp. was found in 129 and 151 patients using routine and extended incubation, respectively. Three patients had proven IA (2%), 11 probable (7%), four had allergic bronchopulmonary aspergillosis...... μg/ml (3/112 A. fumigatus, 1/2 A. terreus). In conclusion, Aspergillus appears to be an important pathogen in Denmark. Elevated itraconazole MICs were detected in 4% of the isolates including a multi-azole resistant isolate....

  4. The burden of serious fungal diseases in Russia.

    Science.gov (United States)

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

    2015-10-01

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

  5. The Platelia Aspergillus ELISA in diagnosis of invasive pulmonary aspergilosis (IPA).

    Science.gov (United States)

    Siemann, M; Koch-Dörfler, M

    2001-01-01

    The sensitivity of a sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was evaluated with 66 serum samples and 113 specimens of the respiratory tract obtained from 52 patients with pulmonary diseases. The patients were divided into five groups: proven invasive pulmonary aspergillosis (IPA) (five patients), probable IPA (seven patients), Aspergillus colonization (eight patients) or unlikely Aspergillus infection (27 patients). Another five patients with doubtful diagnostic test results are discussed in detail. The results of the Platelia Aspergillus ELISA (Sanofi Pasteur, Freiburg, Germany) in testing specimens of the respiratory tract were 90% sensitivity in proven (serum 38%), 60% in probable (serum 37%) and 71% in Aspergillus colonization (serum 0%). Furthermore, 85% of the Aspergillus spp. from positive cultures of specimens of the respiratory tract were also detected in the ELISA. A total of 57% of the culture negative specimens of patients with a least one positive culture or proven aspergillosis in a series of specimens were positive in the ELISA.

  6. Aspergilloma of the brain: an overview

    Directory of Open Access Journals (Sweden)

    Nadkarni T

    2005-01-01

    Full Text Available Fungal infections of the central nervous system (CNS are almost always a clinical surprise. Their presentation is subtle, often without any diagnostic characteristics, and they are frequently mistaken for tuberculous meningitis, pyogenic abscess, or brain tumor. Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Aspergillus fumigatus is the most common human pathogen in the genus Aspergillus .Maxillary sinusitis of dental origin or the lungs are the most common sites of primary Aspergillus infection. Infection reaches the brain directly from the nasal sinuses via vascular channels or is blood borne from the lungs and gastrointestinal tract. Single or multiple abscess formation with blood vessel invasion leading to thrombosis is a characteristic feature of Aspergillosis on neuropathologic examination. Aspergillosis should be considered in cases manifesting with acute onset of focal neurologic deficits resulting from a suspected vascular or space-occupying lesion especially in immunocompromised hosts. Aspergillosis is diagnosed on direct examinations and culture, however the diagnosis of aspergillosis of the CNS is difficult. Diagnosis of an intracranial mass lesion is best confirmed with a computed tomography or magnetic resonance imaging of the head with or without intravenous contrast. Aggressive neurosurgical intervention for surgical removal of Aspergillus abscesses, granulomas, and focally infracted brain; correction of underlying risk factors; Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. Off late Liposomal Amphotericin B was found to be more effective and safe than conventional Amphotericin B in the management of Apergillus infections Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter

  7. Aspergillus fumigatus Does Not Require Fatty Acid Metabolism via Isocitrate Lyase for Development of Invasive Aspergillosis▿

    OpenAIRE

    Schöbel, Felicitas; Ibrahim-Granet, Oumaïma; Avé, Patrick; Latgé, Jean-Paul; Brakhage, Axel A.; Brock, Matthias

    2006-01-01

    Aspergillus fumigatus is the most prevalent airborne filamentous fungus causing invasive aspergillosis in immunocompromised individuals. Only a limited number of determinants directly associated with virulence are known, and the metabolic requirements of the fungus to grow inside a host have not yet been investigated. Previous studies on pathogenic microorganisms, i.e., the bacterium Mycobacterium tuberculosis and the yeast Candida albicans, have revealed an essential role for isocitrate lyas...

  8. Molecular epidemiology and virulence assessment of Aspergillus fumigatus isolates from white stork chicks and their environment.

    Science.gov (United States)

    Olias, Philipp; Gruber, Achim D; Hafez, Hafez M; Lierz, Michael; Slesiona, Silvia; Brock, Matthias; Jacobsen, Ilse D

    2011-03-24

    Aspergillus fumigatus is a common pathogen in poultry and captive wild birds and an emerging opportunistic fungal pathogen in immunocompromised humans. Although invasive aspergillosis is frequently reported in free-ranging wild birds, the incidence and epidemiology of the disease in a natural setting is unknown. We recently reported endemic outbreaks of invasive aspergillosis at white stork nesting sites close to human habitation in Germany with significant subsequent breeding losses. Therefore, we hypothesized that A. fumigatus strains with higher virulence in birds may have evolved in this environment and performed the first epidemiological analysis of invasive aspergillosis in free-ranging wild birds. Sixty-one clinical and environmental A. fumigatus isolates from six affected nesting sites were genotyped by microsatellite analysis using the STRAf-assay. The isolates showed a remarkable high genomic diversity and, contrary to the initial hypothesis, clinical and environmental isolates did not cluster significantly. Interestingly, storks were infected with two to four different genotypes and in most cases both mating types MAT-1.1 and MAT-1.2 were present within the same specimen. The majority of selected clinical and environmental strains exhibited similar virulence in an in vivo infection model using embryonated chicken eggs. Noteworthy, virulence was not associated with one distinct fungal mating type. These results further support the assumption that the majority of A. fumigatus strains have the potential to cause disease in susceptible hosts. In white storks, immaturity of the immune system during the first three weeks of age may enhance susceptibility to invasive aspergillosis. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Typing clinical and animal environment Aspergillus fumigatus gliotoxin producer strains isolated from Brazil by PCR-RFLP markers.

    Science.gov (United States)

    Soleiro, C A; Pena, G A; Cavaglieri, L R; Coelho, I; Keller, L M; Dalcero, A M; Rosa, C A R

    2013-12-01

    Aspergillus fumigatus, a well-known human and animal pathogen causing aspergillosis, has been historically identified by morphological and microscopic features. However, recent studies have shown that species identification on the basis of morphology alone is problematic. The aim of this work was to confirm the taxonomic state at specie level of a set of clinical (human and animal) and animal environment A. fumigatus strains identified by morphological criteria applying a PCR-RFLP assay by an in silico and in situ analysis with three restriction enzymes. The A. fumigatus gliotoxin-producing ability was also determined. Previous to the in situ PCR-RFLP analysis, an in silico assay with BccI, MspI and Sau3AI restriction enzymes was carried out. After that, these enzymes were used for in situ assay. All A. fumigatus strains isolated from corn silage, human aspergillosis and bovine mastitis and high per cent of the strains isolated from cereals, animal feedstuff and sorghum silage were able to produce high gliotoxin levels. Also, all these strains identified by morphological criteria as A. fumigatus, regardless of its isolation source, had band patterns according to A. fumigatus sensu stricto by PCR-RFLP markers. Aspergillus fumigatus is a well-known human and animal pathogen causing aspergillosis. In this study, clinical (human and animal) and animal environment strains were able to produce high gliotoxin levels and had band profiles according to A. fumigatus sensu stricto by PCR-RFLP markers. The results obtained here suggest that strains involved in human and animal aspergillosis could come from the animal environment in which A. fumigatus is frequently found. Its presence in animal environments could affect animal health and productivity; in addition, there are risks of contamination for rural workers during handling and storage of animal feedstuffs. © 2013 The Society for Applied Microbiology.

  10. Rapid enzyme-linked immunosorbent assay (ELISA) for Aspergillus fumigatus antibodies.

    OpenAIRE

    Richardson, M D; Stubbins, J M; Warnock, D W

    1982-01-01

    A rapid enzyme-linked immunosorbent assay (ELISA) where component incubation periods were shortened to one hour, was compared with agar gel double diffusion (AGDD) and a standard ELISA procedure for detecting antibodies to Aspergillus fumigatus in 28 asthmatic patients with suspected allergic aspergillosis. Using two A fumigatus antigens the rapid ELISA compared well with AGDD and the standard ELISA method. Eleven sera that reacted with both antigens in AGDD were all positive against antigen ...

  11. [Two cases of pulmonary aspergilosis, which deteriorated with generic itraconazole].

    Science.gov (United States)

    Saito, Wakana; Shishikura, Yutaka; Nishimaki, Katsushi; Kikuchi, Tadashi; Sasamori, Kan; Kikuchi, Yoshihiro; Miki, Hiroshi

    2014-07-01

    We experienced two cases of pulmonary aspergillosis, which deteriorated during treatment with generic itraconazole (ITCZ) because of low plasma concentration. One case was chronic pulmonary aspergillosis and the other was allergic bronchopulmonary aspergillosis (ABPA). Treatment of both cases was started with a brand-name-ITCZ, and changed to a generic ITCZ. Deterioration of pulmonary aspergillosis occurred after 8 months and 9 months from change to generic ITCZ respectively. In the first case, the ITCZ-plasma concentration was 46.9 ng/mL and of OH-ITCZ 96.5 ng/mL with generic ITCZ at the dose of 300 mg/day, but increased to 1,559.7 ng/mL and to 2,485.0 ng/mL with the brand-name-ITCZ 300 mg/day, respectively. In the second case, the ITCZ-plasma concentration was 27.2 ng/mL and of OH-ITCZ 20.1 ng/mL with 150 mg/day for generic ITCZ, but reached 857.3 ng/mL and to 1,144.2 ng/ml with the brand-name-ITCZ 300 mg/day, respectively. After treatment failure, the first case was changed to voriconazole, then brand-name-ITCZ 300 mg/day, and the second case to the brand-name-ITCZ 300 mg/day, with successful clinical course. Plasma concentrations of ITCZ can differ significantly depending on the patient or type of ITCZ. The ITCZ-plasma concentration should be controlled after changing from a brand-name-ITCZ to a generic ITCZ.

  12. [Economic evaluation of voriconazole versus amphotericin B in the treatment of invasive aspergilosis].

    Science.gov (United States)

    Grau Cerrato, S; Mateu-de Antonio, J; Soto Alvarez, J; Muñoz Jareño, M A; Salas Sánchez, E; Marín-Casino, M; Rubio Terrés, C

    2005-01-01

    Invasive aspergillosis is an infection with high incidence and mortality. Voriconazole is a new antifungal agent that presents a high efficacy against Aspergillus. The aim of this evaluation was to carry out a pharmacoeconomic analysis of the use of voriconazole versus amphotericin B deoxycholate in the treatment of invasive aspergillosis in Spain. A cost-effectiveness analysis has been performed by building a decision analytical model. Effectiveness data, probabilities of the different branches of the decision tree and consumption of healthcare resources were obtained from a clinical trial that compared voriconazole versus amphotericin B in the treatment of invasive aspergillosis and from a local expert panel in order to incorporate the model in the daily medical practice in our country. Only direct medical costs were included in the model (drug acquisition, length of hospital stay, analytical tests and treatment of therapeutic failures). The perspective chosen for this analysis was hospital assistance and the time horizon selected was 12 weeks, the maximum time that patients were followed up in the referenced clinical trial. Therapeutic success was reached in 52.8% of patients treated with voriconazole and in 31.6% of the group treated with amphotericin B. The cost of treating a patient with voriconazole or amphotericin B was of 56,296 and 56,382 Euros respectively, while the cost/effectiveness ratio was of 106,621 and 178,424 Euros. The incremental analysis performed shows how the use of voriconazole versus amphotericin B produces a healthcare resources saving of 406 Euros per patient. Voriconazole is more efficient than amphotericin B deoxycholate in the treatment of invasive aspergillosis, (thus) resulting in healthcare resources saving due to better clinical results with lower associated costs.

  13. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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. © 2015 Blackwell Verlag GmbH.

  15. Plasma Concentrations of Itraconazole, Voriconazole, and Terbinafine When Delivered by an Impregnated, Subcutaneous Implant in Japanese Quail ( Coturnix japonica ).

    Science.gov (United States)

    Souza, Marcy J; Redig, Patrick; Cox, Sherry K

    2017-06-01

    Aspergillosis is a common fungal infection in both wild and pet birds. Although effective antifungal medications are available, treatment of aspergillosis can require months of medication administration, which entails stressful handling one or more times per day. This study examined the delivery of the antifungal drugs itraconazole, voriconazole, and terbinafine to Japanese quail ( Coturnix japonica ) via an impregnated implant. Implants contained 0.5, 3, 8, or 24 mg of itraconazole, voriconazole, or terbinafine. The implants were administered subcutaneously over the dorsum and between the scapulae. Blood was collected from birds before and 2, 7, 21, 42, and 56 days after implant placement. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole, voriconazole, or terbinafine, as appropriate. During the course of the study, targeted terbinafine concentrations were achieved in some birds at various time points, but concentrations were inconsistent. Itraconazole and voriconazole concentrations were also inconsistent and did not reach targeted concentrations. Currently, the implant examined in this study cannot be recommended for treatment of aspergillosis in avian species.

  16. Aspergillus vaccines: Hardly worth studying or worthy of hard study?

    Science.gov (United States)

    Levitz, Stuart M

    2017-01-01

    Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.

    Science.gov (United States)

    Dudakova, Anna; Spiess, Birgit; Tangwattanachuleeporn, Marut; Sasse, Christoph; Buchheidt, Dieter; Weig, Michael; Groß, Uwe; Bader, Oliver

    2017-10-01

    The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus . This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant A. fumigatus strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of cyp51 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates. Copyright © 2017 American Society for Microbiology.

  18. Burden of serious fungal infections in Bangladesh.

    Science.gov (United States)

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

    2017-06-01

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

  19. Burden of serious fungal infections in Ukraine.

    Science.gov (United States)

    Osmanov, Ali; Denning, David W

    2015-10-01

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

  20. [Pulmonary infections in patients with rheumatoid arthritis].

    Science.gov (United States)

    Takayanagi, Noboru; Tsuchiya, Yutaka; Tokunaga, Daidou; Miyahara, Yousuke; Yamaguchi, Shouzaburo; Saito, Hiroo; Ubukata, Mikio; Kurashima, Kazuyoshi; Yanagisawa, Tsutomu; Sugita, Yutaka

    2007-06-01

    We studied 149 rheumatoid arthritis (RA) patients (mean age 68.0 years; 68 men, 81 women) with pulmonary infections. The mean age at the onset of RA and the duration of RA was 57.2 +/- 15.2 years and 10.9 +/- 11.5 years, respectively. Pulmonary infections included nontuberculous mycobacteriosis in 59 patients (Mycobacterium avium complex infection, 50 cases : Mycobacterium kansasii infection, 4 cases; others, 5 cases), pneumonia in 46 patients, pulmonary tuberculosis in 28 patients, pulmonary aspergillosis in 12 patients, pulmonary cryptococcosis in 5 patients, Pneumocystis jiroveci pneumonia in 5 patients, lung abscess in 9 patients, exacerbation of bronchiectasis in 7 patients, and empyema in 4 patients. One hundred percent of patients with exacerbation of bronchiectasis, 91.7% of patients with pulmonary aspergillosis, 87% of patients with pneumonia, and 81.4% of patients with nontuberculous mycobacteriosis had underlying lung diseases. The pulmonary infections during therapy with steroids were pulmonary tuberculosis (78.6%), pneumonia (65.2%), and pulmonary aspergillosis (58.3%), while the pulmonary infections during methotrexate treatment were Pneumocystis jiroveci pneumonia (80%), pulmonary cryptococcosis (40%), and pulmonary tuberculosis (28.6%). Pulmonary infections in RA patients who were taking TNFalpha inhibitors included 1 patient each with nontuberculous mycobacteriosis, pneumonia, pulmonary tuberculosis, and Pneumocystis jiroveci pneumonia. Among the RA patients with lung abscess, malignancy was noted in 55.6%, and diabetes mellitus in 22.2%. Pseudomonas aeruginosa was the second-most-common cause of pneumonia and cause of all exacerbations of bronchiectasis. As well as immunosuppressive medications (steroids, methotrexate, TNFalpha inhibitors) and systemic comorbid diseases, underlying lung diseases could be one of the risk factor for pulmonary infections in patients with RA. The dominant risk factor for each pulmonary infection in patients with RA

  1. Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India.

    Science.gov (United States)

    Masih, Aradhana; Singh, Pradeep K; Kathuria, Shallu; Agarwal, Kshitij; Meis, Jacques F; Chowdhary, Anuradha

    2016-09-01

    Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization-time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. β-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in-house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of ≥2 μg/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 μg/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

    Science.gov (United States)

    Masih, Aradhana; Singh, Pradeep K.; Kathuria, Shallu; Agarwal, Kshitij

    2016-01-01

    Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization–time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. β-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in-house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of ≥2 μg/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 μg/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma. PMID:27413188

  3. Fungus infection in immunocompromised rabbits: correlation of thin-section CT findings and histopathology

    International Nuclear Information System (INIS)

    Xue Feng; Liu Shiyuan; Xie Lixuan; Liu Kai; Zhang Jian; Chen Yousan; Li Huimin; He Jin

    2009-01-01

    Objective: To compare the thin-section CT findings of pulmonary candidiasis, aspergillosis and cryptococcosis with histopathology in immunocompromised rabbits and improve the diagnostic accuracy of fungus infection. Methods: Healthy New Zealand white rabbits were used for immunocompromised animal models. Thin-section CT scan was performed before and 2, 4, 6, 8, 10, 12, 14 d after inoculation. The pattern and distribution of the pulmonary abnormalities were retrospectively assessed by two thoracic radiologists and compared with histopathology. The granulocyte count was compared before and after administration of immunosuppressive agents. The paired t test, chi square test and the Fisher's exact test were used for the statistics. Results: Fourteen rabbits had candidiasis, 16 rabbits had eryptococcosis, 15 rabbits had aspergillosis. The granulocyte counts before and after administration of immunosuppressive agents were (2.91±0.92) and (0.35±0.19) x 10 9 /L respectively in candidiasis group, there was a significant difference (t=12.484, P 9 /L in aspergillosis group, there was a significant difference (t=5.792, P 9 /L in cryptococcosis group, there was a significant difference (t=8.199, P 0.05). Ground glass opacity (GGO) and consolidation were the two most common findings in immunocompromised rabbits with three fungus infections, areas of GGO was correlated with the congestion, hemorrhage, inflammatory cell infiltration and interstitial hyperplasia in pathology. Consolidation was correlated with the severe congestion, hemorrhage, inflammatory cell infiltration, interstitial hyperplasia, necrosis and vascular embolism in pathology. Conclusion: GGO and consolidation are the two most common findings of fungus infections in immunocompromised animal models and thin-section CT findings can reflect the pathological changes. (authors)

  4. Comparative performance of Aspergillus galactomannan ELISA and PCR in sputum from patients with ABPA and CPA.

    Science.gov (United States)

    Fayemiwo, Samuel; Moore, Caroline B; Foden, Philip; Denning, David W; Richardson, Malcolm D

    2017-09-01

    Galactomannan (GM) and Aspergillus DNA detection are useful tools for the diagnosis of invasive pulmonary aspergillosis (IPA), primarily in blood and bronchoscopy samples. This study aimed to evaluate the utility of both markers for detection of Aspergillus in sputum from patients with allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). ABPA or CPA demographic patient data were retrieved. This retrospective observational audit included 159 patients with at least one sputum pair. 223 sputum sample pairs were analysed, as well as six control samples for GM only. Real time PCR was performed following sputum DNA extraction using the MycAssay™ Aspergillus kit and cycle thresholds were subtracted from 38 to give positive values (transformed Ct, TCt). The mean age of the patients was 61.81years (SD: ±11.06; range 29-100). One hundred and twenty-six (79.2%) had CPA. Cultures were positive for fungi in 13.1% of the samples, and A. fumigatus was the commonest (11.9%) fungus isolated. Receiver operating characteristic (ROC curve) analysis of sputum GM comparing TCt of >0.0, and >2.0 to derive GMI cut-off values showed a cut-off of 6.5. About 50% of sputa with strongly positive PCR values had GM values>6.5. Two of six (33%) control samples had GM indices>6.5. It is not clear that GM determinations in sputum are useful for diagnosis of either CPA or ABPA, or following therapy. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  5. A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

    Science.gov (United States)

    Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya

    2017-01-01

    Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140

  6. Surgical treatment for pulmonary aspergilloma in seventeenth years old female: case report

    Science.gov (United States)

    Yanni, G. N.; Lubis, M.; Yoel, C.

    2018-03-01

    Aspergillosis is defined as a mycosis group caused by various pathogenic fungi of the Aspergillus genus. Aspergillus has more than 900 species that cause infection in human. The most common Aspergillus species that cause infection is Aspergillus fumigatus, about 90%. Other species, Aspergillus flavus, about 10% cause invasive disease. Have been reported a young girl 17-year-8-month-old woman was admitted to emergency with complaints of coughing up blood. The patient has diagnosed an aspergilloma and treated with thoracotomy bi-lobectomy right lower lung based on thorax scan. The patient took Fluconazole and surgical bilobectomyfor treated the aspergilloma and got improvement.

  7. 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.

  8. Comparison of Two Molecular Assays for Detection and Characterization of Aspergillus fumigatus Triazole Resistance and Cyp51A Mutations in Clinical Isolates and Primary Clinical Samples of Immunocompromised Patients

    OpenAIRE

    Patricia Postina; Julian Skladny; Tobias Boch; Oliver A. Cornely; Oliver A. Cornely; Axel Hamprecht; Peter-Michael Rath; Jörg Steinmann; Oliver Bader; Thomas Miethke; Anne Dietz; Natalia Merker; Wolf-Karsten Hofmann; Dieter Buchheidt; Birgit Spiess

    2018-01-01

    In hematological patients, the incidence of invasive aspergillosis (IA) caused by azole resistant Aspergillus fumigatus (ARAf) is rising. As the diagnosis of IA is rarely based on positive culture in this group of patients, molecular detection of resistance mutations directly from clinical samples is crucial. In addition to the in-house azole resistance ARAf polymerase chain reaction (PCR) assays detecting the frequent mutation combinations TR34/L98H, TR46/Y121F/T289A, and M220 in the Aspergi...

  9. Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach.

    Science.gov (United States)

    Gautam, P; Sundaram, C S; Madan, T; Gade, W N; Shah, A; Sirdeshmukh, R; Sarma, P U

    2007-08-01

    Approximately 20% of the world's asthmatics are suffering from Aspergillus fumigatus (Afu)-induced allergies. The characterization of specific IgE-inducing allergens in allergic aspergillosis patients is fundamental for clinical diagnosis and for immunotherapy. Immunoproteomics combined with mass spectrometric analysis was used to identify proteins of third-week culture filtrate (3wcf) potentially responsible for Afu-specific IgE immunoreactivity, using pooled sera from Afu-sensitized asthmatics. Their allergenic potential was also tested against patients with allergic bronchopulmonary aspergillosis (ABPA), by two-dimensional (2-D) gel electrophoresis immunoblotting of 3wcf proteins with individual sera from such patients. This helped us to establish a set of candidate allergens, which could be explored further for diagnostic application in allergic aspergillosis asthmatics including ABPA. Peptide mass fingerprint using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and/or de novo sequencing by MS/MS analysis of the protein spots from 2-D gels led to the identification of a total of 16 allergens of Afu. Eleven of them are being reported as allergens for the first time and five had been reported earlier. Putative isoforms of the proteins Asp f 13 and chitosanase have been observed for the first time. When studied for reactivity of these proteins among patients with ABPA using their individual sera, these patients exhibited sensitization although the pattern was varying. Taken together, these proteins could thus be considered as potential allergens even among patients with ABPA. Three of these proteins viz. the hypothetical protein (# spot no. 5), extracellular arabinase (# spot no. 6) and chitosanase (# spot no. 11) could be major allergens with specific IgE immunoreactivity with six out of eight patients' sera. The immunoproteomic approach applied to the analysis of culture filtrate proteins resulted in the

  10. 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.

  11. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

    International Nuclear Information System (INIS)

    Weigel, S.; Kloska, S.; Freund, M.; Kehl, H.G.

    2003-01-01

    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.)

  12. 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.

  13. Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.

    Science.gov (United States)

    Morgand, Marjolaine; Rammaert, Blandine; Poirée, Sylvain; Bougnoux, Marie-Elisabeth; Tran, Hugo; Kania, Romain; Chrétien, Fabrice; Jouvion, Gregory; Lortholary, Olivier

    2015-12-01

    Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-β-d-glucan test results were initially positive, in contrast to galactomannan antigen results. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Fusariosis as solitary pulmonary nodule

    International Nuclear Information System (INIS)

    Moreno, Nelson; Saavedra R, Alfredo; Sanchez Edgar A

    2008-01-01

    Invasive fungal infections are common cause of morbidity and mortality in immunocompromised patients. Of these the most frequents are: aspergillosis and Fusariosis, both grouped under the term Hyalohyphomycosis. One of the organs most commonly affected is the lung.Unfortunately the clinical manifestations as cough, pain and bleeding pleuritic such are none specific. The chest Rx may show since alveolar infiltration, or nodular lesions until cavitaciones. This is the first report on Colombia of a single pulmonary nodule by Fusarium fungi in an immunocompetent patient.

  15. 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.

  16. Diagnosis and treatment of invasive fungal diseases in patients with severe liver diseases

    Directory of Open Access Journals (Sweden)

    ZANG Hong

    2016-09-01

    Full Text Available Invasive fungal diseases (IFDs are an important factor affecting the prognosis of patients with severe liver diseases, and their early diagnosis remains a challenge for clinicians. The four most commonly seen IFDs are candidiasis, aspergillosis, cryptococcosis, and pneumocystis pneumonia. We should pay attention to the risk of developing IFDs in patients with severe liver diseases during clinical management. Particularly, early diagnosis and proper treatment of IFDs are important in high-risk patients. These are vital to improving the prognosis of patients with severe liver diseases.

  17. Emerging and reemerging diseases of avian wildlife.

    Science.gov (United States)

    Pello, Susan J; Olsen, Glenn H

    2013-05-01

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Real-time visualization of immune cell clearance of Aspergillus fumigatus spores and hyphae.

    Science.gov (United States)

    Knox, Benjamin P; Huttenlocher, Anna; Keller, Nancy P

    2017-08-01

    Invasive aspergillosis (IA) is a disease of the immunocompromised host and generally caused by the opportunistic fungal pathogen Aspergillus fumigatus. While both host and fungal factors contribute to disease severity and outcome, there are fundamental features of IA development including fungal morphological transition from infectious conidia to tissue-penetrating hyphae as well as host defenses rooted in mechanisms of innate phagocyte function. Here we address recent advances in the field and use real-time in vivo imaging in the larval zebrafish to visually highlight conserved vertebrate innate immune behaviors including macrophage phagocytosis of conidia and neutrophil responses post-germination. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, K. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Zoarski, G.H.; Rothman, M.I.; Zagardo, M.T. [Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Nishimura, T. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Sun, C.C.J. [Dept. of Pathology, Univ. of Maryland Medical Center, Baltimore MD (United States)

    2001-07-01

    We present a case of cerebral aspergillosis in an immunocompetent patient. The MRI signal characteristics were compared with the histologic findings. Irregular low-signal zones were demonstrated between the wall of the abscess and the central necrosis on T2-weighted images; the pathology specimen revealed concentrated iron in these transitional zones but no hemosiderin. Iron is an essential element for the growth of fungal hyphae. The low-signal zones may represent the areas where there was active proliferation of aspergillus, and the unique location of the low signal may be a helpful imaging characteristic for the diagnosis of an aspergillus abscess. (orig.)

  20. Reproducibility of positive results for the detection of serum galactomannan by Platelia™ aspergillus EIA.

    Science.gov (United States)

    Pedroza, Kelly C M C; de Matos, Sócrates B; de Moura, Daniel L; Oliveira, Mônica B B; Araújo, Marco A S; Nascimento, Roberto J M; Lima, Fernanda W M

    2013-10-01

    Galactomannan (GM) was recently included in consensus guidelines as an indirect mycological criterion for the diagnosis of invasive aspergillosis. Currently, there is an enzyme immunoassay available to detect GM in biological samples, the Platelia™ Aspergillus EIA. In this study, the reproducibility of positive results obtained using this assay was evaluated using serum samples from neutropenic patients. A trend toward lower values was observed, and 55 %(27/49) of positive results were negative after retesting. A low reproducibility of positive results for the detection of GM in serum was observed.

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

    Science.gov (United States)

    Herrera, Sabina; Husain, Shahid

    2018-05-21

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

  2. 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.

  3. 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.

  4. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    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.

  5. CT findings in severe thoracic sarcoidosis

    International Nuclear Information System (INIS)

    Hennebicque, Anne-Sophie; Brillet, Pierre-Yves; Moulahi, Hassen; Brauner, Michel W.; Nunes, Hilario; Valeyre, Dominique

    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.)

  6. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

    Science.gov (United States)

    Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

    2017-01-01

    To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  7. Estimating the Burden of Serious Fungal Infections in Uruguay

    Directory of Open Access Journals (Sweden)

    Marina Macedo-Viñas

    2018-03-01

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

  8. 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

    Directory of Open Access Journals (Sweden)

    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.

  9. Aspergillus fumigatus from normal and condemned carcasses with airsacculitis in commercial poultry

    Directory of Open Access Journals (Sweden)

    Andréia Spanamberg

    2013-09-01

    Full Text Available Carcass inspection is important for the detection of certain diseases and for monitoring their prevalence in slaughterhouses. The objective of this study was to assess the occurrence of aspergillosis caused by Aspergillus fumigatus in commercial poultry, through mycological and histopathological diagnosis, and to verify the causal association between the aspergillosis diagnosis criteria and condemnation due to airsacculitis in broilers through a case-control study. The study was carried out with 380 samples. Lungs were collected from broilers that were condemned (95 or not condemned (285 due to airsacculitis directly from the slaughter line. Forty-six (12% lung samples were positive for A. fumigatus in mycological culture. Among all samples, 177 (46.6% presented histopathological alterations, with necrotic, fibrinous, heterophilic pneumonia; heterophilic pneumonia and lymphoid hyperplasia being the most frequent. Out of the 380 lungs analyzed, 65.2% (30 showed histopathological alterations and isolation of fungi. The statistical analysis (McNemar's chi-square test indicated a significant association between the presence of histopathological lesions and the isolation of A. fumigatus. Mycological cultivation and histopathological diagnosis increase the probability of detecting pulmonary alterations in birds condemned by the Final Inspection System, which suggests that such diagnostic criteria can improve the assessment and condemnation of birds affected by airsacculitis.

  10. Sensitisation to Aspergillus fumigatus and Penicillium notatum in laboratory workers.

    Science.gov (United States)

    Boscolo, P; Piccolomini, R; Benvenuti, F; Catamo, G; Di Gioacchino, M

    1999-01-01

    Four workers in medical research laboratories, located in a basement level of a University facility equipped with a humidified air conditioning system, complained of cough and/or asthma and/or rhinitis during their normal working activities. Since exposure to toxic compounds was very low (similar to that of the outdoor environment) only microbiological monitoring was performed. Aspergillus fumigatus and Penicillium notatum were found in some laboratories. Eight laboratory workers (including the 4 symptomatic subjects) out of 26 investigated were found to be atopic. Specific IgE sensitisation to Aspergillus fumigatus was found in the 8 atopic and in the 6 non-atopic workers, while Penicililum notatum was found in 7 atopic and 4 non-atopic subjects. History, physical examination and laboratory data excluded the presence of aspergillosis or allergic bronchial aspergillosis in the sensitised subjects. Our results suggest that evaluation of immune parameters, along with monitoring of the working environment, may reduce the risk of sensitisation and/or allergic symptoms in atopic laboratory workers.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Rukumani Devi Velayuthan

    2018-03-01

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

  13. Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

    Directory of Open Access Journals (Sweden)

    Felix Bongomin

    2017-10-01

    Full Text Available Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population. These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.

  14. 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 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.

  15. Burden of serious fungal infections in Mexico.

    Science.gov (United States)

    Corzo-León, D E; Armstrong-James, D; Denning, D W

    2015-10-01

    Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100,000) followed by allergic bronchopulmonary aspergillosis (60 per 100,000), chronic pulmonary aspergillosis (15.9 per 100,000), fungal keratitis (10.4 per 100,000), invasive candidiasis (8.6 per 100,000) and SFIs in HIV (8.2 per 100,000); coccidioidomycosis (7.6 per 100,000), IA (4.56 per 100,000). These correspond to 2,749,159 people affected in any year (2.45% of the population), probably >10,000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists. © 2015 Blackwell Verlag GmbH.

  16. 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.

  17. Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

    Science.gov (United States)

    Chotirmall, Sanjay H.; Al-Alawi, Mazen; Logan, P. Mark; Greene, Catherine M.; McElvaney, Noel G.

    2013-01-01

    Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit. PMID:23971044

  18. Aspergillus flavus: human pathogen, allergen and mycotoxin producer.

    Science.gov (United States)

    Hedayati, M T; Pasqualotto, A C; Warn, P A; Bowyer, P; Denning, D W

    2007-06-01

    Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulomatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.

  19. Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Sanjay H. Chotirmall

    2013-01-01

    Full Text Available Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

  20. [Iron and invasive fungal infection].

    Science.gov (United States)

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

    2013-01-01

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

  1. Characterization and identification of proteases secreted by Aspergillus fumigatus using free flow electrophoresis and MS.

    Science.gov (United States)

    Neustadt, Madlen; Costina, Victor; Kupfahl, Claudio; Buchheidt, Dieter; Eckerskorn, Christoph; Neumaier, Michael; Findeisen, Peter

    2009-06-01

    Early diagnosis of life-threatening invasive aspergillosis in neutropenic patients remains challenging because current laboratory methods have limited diagnostic sensitivity and/or specificity. Aspergillus species are known to secrete various pathogenetically relevant proteases and the monitoring of their protease activity in serum specimens might serve as a new diagnostic approach.For the characterization and identification of secreted proteases, the culture supernatant of Aspergillus fumigatus was fractionated using free flow electrophoresis (Becton Dickinson). Protease activity of separated fractions was measured using fluorescently labeled reporter peptides. Fractions were also co-incubated in parallel with various protease inhibitors that specifically inhibit a distinct class of proteases e.g. metallo- or cysteine-proteases. Those fractions with high protease activity were further subjected to LC-MS/MS analysis for protease identification. The highest protease activity was measured in fractions with an acidic pH range. The results of the 'inhibitor-panel' gave a clear indication that it is mainly metallo- and serine-proteases that are involved in the degradation of reporter peptides. Furthermore, several proteases were identified that facilitate the optimization of reporter peptides for functional protease profiling as a diagnostic tool for invasive aspergillosis.

  2. Detection of Galactomannan Antigenemia in Patients Receiving Piperacillin-Tazobactam and Correlations between In Vitro, In Vivo, and Clinical Properties of the Drug-Antigen Interaction

    Science.gov (United States)

    Walsh, Thomas J.; Shoham, Shmuel; Petraitiene, Ruta; Sein, Tin; Schaufele, Robert; Kelaher, Amy; Murray, Heidi; Mya-San, Christine; Bacher, John; Petraitis, Vidmantas

    2004-01-01

    Recent case reports describe patients receiving piperacillin-tazobactam who were found to have circulating galactomannan detected by the double sandwich enzyme-linked immunosorbent assay (ELISA) system, leading to the false presumption of invasive aspergillosis. Since this property of piperacillin-tazobactam and galactomannan ELISA is not well understood, we investigated the in vitro, in vivo, and clinical properties of this interaction. Among the 12 reconstituted antibiotics representing four classes of antibacterial compounds that are commonly used in immunocompromised patients, piperacillin-tazobactam expressed a distinctively high level of galactomannan antigen in vitro (P = 0.001). After intravenous infusion of piperacillin-tazobactam into rabbits, the serum galactomannan index (GMI) in vivo changed significantly (P = 0.0007) from a preinfusion mean baseline value of 0.27 to a mean GMI of 0.83 by 30 min to slowly decline to a mean GMI of 0.44 24 h later. Repeated administration of piperacillin-tazobactam over 7 days resulted in accumulation of circulating galactomannan to a mean peak GMI of 1.31 and a nadir of 0.53. Further studies revealed that the antigen reached a steady state by the third day of administration of piperacillin-tazobactam. Twenty-six hospitalized patients with no evidence of invasive aspergillosis who were receiving antibiotics and ten healthy blood bank donors were studied for expression of circulating galactomannan. Patients (n = 13) receiving piperacillin-tazobactam had significantly greater mean serum GMI values (0.74 ± 0.14) compared to patients (n = 13) receiving other antibiotics (0.14 ± 0.08) and compared to healthy blood bank donors (0.14 ± 0.06) (P 0.5 compared to none of thirteen subjects receiving other antibiotics (P = 0.039) and to none of ten healthy blood bank donors (P = 0.046). These data demonstrate that among antibiotics that are commonly used in immunocompromised patients, only piperacillin-tazobactam contains

  3. [The incidence, etiology and clinical significance of visceral mycoses in patients with AIDS].

    Science.gov (United States)

    Manfredi, R; Nanetti, A; Mazzoni, A; Mastroianni, A; Chiodo, F

    1993-01-01

    The incidence, aetiology and clinical significance of visceral mycoses in HIV-infected subjects were evaluated by a retrospective survey of the clinical and microbiological records of 237 consecutive AIDS patients followed-up since 1984. Seventy-four patients out of 237 (31.2%) (56 males, 18 females; 55 IV drug abusers, 7 heterosexuals, 6 homobisexuals, 3 blood recipients and 3 children with congenitally-acquired HIV infection) presented 77 different episodes of visceral fungal infection as a whole, represented by candidiasis in 56 cases (oesophageal 45, pulmonary 5, sepsis 2, eye involvement 2, endocarditis and invasive oropharyngeal infection in the remaining 2 patients), cryptococcosis in 17 cases (meningoencephalitis in all subjects, with disseminated infection in 11 of them), and aspergillosis in 4 cases (pulmonary 2, cerebral and cranio-facial in the remaining 2 patients). In 57 out of 74 patients (77%), visceral mycoses were diagnostic or concurrent with the diagnosis of AIDS. Fungal diseases, as a whole, showed a significantly higher incidence (p drug abusers, whereas homobisexual men presented a significantly lower frequency (p test) than AIDS patients with other risk factors for HIV infection. The onset of cryptococcosis was significantly associated with the male sex (p test). All subjects suffering from a visceral mycosis were severely immunosuppressed, with a higher rate of neutropenia in patients developing Candida and Aspergillus spp. infection (23 out of 56 patients with visceral candidiasis and 3 out of 4 cases of aspergillosis had an absolute neutrophil count lower than 1500 cells/mm3), while a severe reduction in CD4+ lymphocyte count was more evident among patients with cryptococcosis (13 out of 17 patients had a CD4+ cell count lower than 50/mm3). After remission of the primary episode of fungal infection (obtained in 80.5% of cases), the incidence of relapse observed in a long follow-up period (mean time 57.6 +/- 39.2 weeks) was elevated both

  4. Burden of Serious Fungal Infections in Jordan

    Directory of Open Access Journals (Sweden)

    Jamal Wadi

    2018-01-01

    Full Text Available Objective: To estimate the burden of fungal infections in Jordan for the first time. Material and Methods: Population data was from UN 2011 statistics and TB cases from WHO in 2012. Fewer than 100 patients with HIV were recorded in Jordan in 2013. Approximately 100 renal transplants and eight liver transplants are performed annually. There were 12,233 major surgical procedures in Jordan in 2013, of which 5.3% were major abdominal surgeries; candidemia was estimated in 5% of the population based on other countries, with 33% occurring in the ICU. Candida peritonitis/intra-abdominal candidiasis was estimated to affect 50% of the number of ICU candidemia cases. No adult asthma rates have been recorded for Jordan, so the rate from the Holy Land (8.54% clinical asthma from To et al. has been used. There are an estimated 49,607 chronic obstructive pulmonary disease (COPD patients in Jordan, with 64% symptomatic, 25% Gold stage 3% or 4%, and 7% (3472 are assumed to be admitted to hospital each year. No cystic fibrosis cases have been recorded. Literature searches on fungal infections revealed few data and no prevalence data on fungal keratitis or tinea capitis, even though tinea capitis comprised 34% of patients with dermatophytoses in Jordan. Results: Jordan has 6.3 million inhabitants (65% adults, 6% are >60 years old. The current burden of serious fungal infections in Jordan was estimated to affect ~119,000 patients (1.9%, not including any cutaneous fungal infections. Candidemia was estimated at 316 cases and invasive aspergillosis in leukemia, transplant, and COPD patients at 84 cases. Chronic pulmonary aspergillosis prevalence was estimated to affect 36 post-TB patients, and 175 in total. Allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS prevalence in adults with asthma were estimated at 8900 and 11,748 patients. Recurrent vulvovaginal candidiasis was estimated to affect 97,804 patients, using a 6

  5. Detection of Aspergillus fumigatus pulmonary fungal infections in mice with 99mTc-labeled MORF oligomers targeting ribosomal RNA

    International Nuclear Information System (INIS)

    Wang Yuzhen; Chen Ling; Liu Xinrong; Cheng Dengfeng; Liu Guozheng; Liu Yuxia; Dou Shuping; Hnatowich, Donald J.; Rusckowski, Mary

    2013-01-01

    Purpose: Invasive aspergillosis is a major cause of infectious morbidity and mortality in immunocompromised patients. The fungus Aspergillus fumigatus (A. fumigatus) is the primary causative agent of invasive aspergillosis. However, A. fumigatus infections remain difficult to diagnose particularly in the early stages due to the lack of a rapid, sensitive and specific diagnostic approach. In this study, we investigated 99m Tc labeled MORF oligomers targeting fungal ribosomal RNA (rRNA) for the imaging detection of fungal infections. Procedures: Three phosphorodiamidate morpholino (MORF) oligomer (a DNA analogue) probes were designed: AGEN, complementary to a sequence of the fungal 28S ribosomal RNA (rRNA) of Aspergillus, as a genus-specific probe; AFUM, complementary to the 28S rRNA sequence of A. fumigatus, as a fungus species-specific probe; and cMORF, irrelevant to all fungal species, as a control probe. The probes were conjugated with Alexa Fluor 633 carboxylic acid succinimidyl ester (AF633) for fluorescence imaging or with NHS-mercaptoacetyl triglycine (NHS-MAG3) for nuclear imaging with 99m Tc and then evaluated in vitro and in vivo. Results: The specific binding of AGEN and AFUM to fungal total RNA was confirmed by dot blot hybridization while specific binding of AGEN and AFUM in fixed and live A. fumigatus was demonstrated by both fluorescent in situ hybridization (FISH) analysis and accumulation in live cells. SPECT imaging of BALB/c mice with pulmonary A. fumigatus infections and administered 99m Tc labeled AGEN and AFUM showed immediate and obvious accumulation in the infected lungs, while no significant accumulation of the control 99m Tc-cMORF in the infected lung was observed. Compared to non-infected mice, with sacrifice at 1 h, the accumulation of 99m Tc-AGEN and 99m Tc-AFUM in the lungs of mice infected with A. fumigatus was 2 and 2.7 fold higher respectively. Conclusions: In vivo targeting fungal ribosomal RNA with 99m Tc labeled MORF probes AGEN

  6. [Radiologic picture of maxillary sinus aspergilloma].

    Science.gov (United States)

    Kaczmarek, I; Bilska, J; Osmola, K; Nowaczyk, M T

    2010-06-01

    Mycotic infection of paranasal sinus could be the etiological factor of chronic sinusitis. The increase in number of fungal sinusitis cases have been reported recently among nonimmunocompromised patient after endodontic treatment of maxillary teeth. Nonspecific clinical signs and incorrect radiologic pictures interpretation as well as loss of therapeutic standards seems to be the cause of false negative diagnosis and difficulties in treatment of fungal sinusitis. Clinical and radiological picture of maxillary sinus aspergillosis was described in this paper. In the period of 2006-2009 in the Department of Maxillo-Facial Surgery 19 patient with fungal maxillary sinusitis was treated. The endodontic treatment of maxillary teeth of the related side was performed previously in 80% examined cases. In 2 cases there were immunocompromised patients with immunosuppressive treatment. In 16 cases patients were referred to our Department due to metallic foreign body of the maxillary sinus. Routine diagnostic radiological imaging was performed in each case: paranasal sinus view--Water's view and panoramic radiograph (orthopantomograph). In 4 cases imaging was extended with computer tomography (CT) visualization. The surgical treatment was performed in each case. The final diagnosis was puted on histopathological examination and fungal culture. In 16 cases of analysed group histopathological examination and fungal culture revealed aspergilosis. In 2 cases fungal culture was negative, but histopathology slices confirm presence of hyphae of Aspergillus. In 1 case the root canal sealer was found in the maxillary sinus. In none case invasive form of aspergillosis was confirmed. In all cases Water's view of paranasal sinuses and ortopantomograph showed partially or totally clouded sinus with well-defined, single or multifocal radiopaque object similar to metallic foreign body. Characteristic finding in CT imaging was well-defined radiodence concretions that have been attributed to

  7. Agents of coral mortality on reef formations of the Colombian Pacific

    Directory of Open Access Journals (Sweden)

    Raúl Navas-Camacho

    2010-05-01

    Full Text Available The National Monitoring System for Coral Reefs of Colombia (SIMAC monitors the impact of some of the most important agents of coral tissue loss (bleaching and/or disease in the Colombian Pacific coral formations since 1998. Physiological bleaching is among the main results of stress in the area. Signs of coral diseases resembling bacterial bleaching such as White Plague and White Band, were observed in Malpelo and Gorgona islands. Damage to the Pacific gorgonian Pacifigorgia spp., similar to those produced by Aspergillosis in Caribbean corals, was detected in Utría Bay. The presence of tumors in colonies of massive corals was also recorded. Even though coral diseases are globally widespread, their occurrence in American Pacific reefs has been poorly documented to date. Rev. Biol. Trop. 58 (Suppl. 1: 133-138. Epub 2010 May 01.

  8. Agents of coral mortality on reef formations of the Colombian Pacific.

    Science.gov (United States)

    Navas-Camacho, Raúl; Rodríguez-Ramírez, Alberto; Reyes-Nivia, María Catalina

    2010-05-01

    The National Monitoring System for Coral Reefs of Colombia (SIMAC) monitors the impact of some of the most important agents of coral tissue loss (bleaching and/or disease) in the Colombian Pacific coral formations since 1998. Physiological bleaching is among the main results of stress in the area. Signs of coral diseases resembling bacterial bleaching such as White Plague and White Band, were observed in Malpelo and Gorgona islands. Damage to the Pacific gorgonian Pacifigorgia spp., similar to those produced by Aspergillosis in Caribbean corals, was detected in Utria Bay. The presence of tumors in colonies of massive corals was also recorded. Even though coral diseases are globally widespread, their occurrence in American Pacific reefs has been poorly documented to date.

  9. Biological evaluation of 99mTc-Voriconazole as a potential agent for diagnosis of fungal infections by gamma scintigraphy

    International Nuclear Information System (INIS)

    Reyes, Laura; Martinez, Elena; Giglio, Javier; Teran, Mariella

    2011-01-01

    The spread of HIV has led to an increase of fungal infections such as candidiasis and invasive aspergillosis. Several types of antifungals are used to treat them and some of them can be radiolabeled with a gamma emitting agent to allow detection by scintigraphy of foci of infection. Voriconazole is a triazole agent, suitable for the synthesis of a complex linked with the precursor [ 99m Tc(H 2 O) 3 (CO) 3 ] + . The aim of his work was to label and determine the physicochemical and biological characteristics of voriconazole with 99m Tc for the early detection of fungal infections. Radiochemical purity was determined by HPLC and the complex remained stable during at least 120 min. In vivo studies in rats bearing either sterile inflammation, infection with C. Albicans or A. Niger showed differentiation of the processes not only in biodistribution but also in scintigraphic images

  10. Mucoid impaction presenting as multiple pulmonary nodules in cystic fibrosis

    International Nuclear Information System (INIS)

    Carpenter, L.D.; Lambie, N.K.; Wilsher, M.L.

    1996-01-01

    Mucoid impaction has been described as a complication of asthma and more commonly in patients with allergic bronchopulmonary aspergillosis. In such cases, the impacted pools of mucus may present as discrete nodules on chest X-ray and hence simulate the appearance of metastatic malignancy. A case of mucoid impaction presenting as multiple pulmonary nodules in a patient with cystic fibrosis is described. The chest X-ray showed hyperinfiltration and scattered changes consistent with bronchiectasis. Computed tomography scan confirmed these and additional intra-pulmonary nodular densities. This report illustrates that mucus impaction as a cause of pulmonary nodules should be considered in any patient with chronic lung disease characterised by excess mucus production. 6 refs., 3 figs

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

    Science.gov (United States)

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

    2012-03-01

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

  12. Infectious Causes of Right Middle Lobe Syndrome.

    Science.gov (United States)

    Rashid, Aatif; Nanjappa, Sowmya; Greene, John N

    2017-01-01

    Right middle lobe (RML) syndrome is defined as recurrent or chronic obstruction or infection of the middle lobe of the right lung. Nonobstructive causes of middle lobe syndrome include inflammatory processes and defects in the bronchial anatomy and collateral ventilation. We report on 2 case patients with RML syndrome, one due to infection with Mycobacterium avium complex followed by M asiaticum infection and the other due to allergic bronchopulmonary aspergillosis. A history of atopy, asthma, or chronic obstructive pulmonary disease has been reported in up to one-half of those with RML. The diagnosis can be made by plain radiography, computed tomography, and bronchoscopy. Medical treatment consists of bronchodilators, mucolytics, and antimicrobials. Patients whose disease is unresponsive to treatment and those with obstructive RML syndrome can be offered surgical treatment.

  13. Pulmonary and systemic fungal infections in an Atlantic spotted dolphin and a Bryde's whale, Brazil.

    Science.gov (United States)

    Groch, Kátia R; Díaz-Delgado, Josué; Sacristán, Carlos; Oliveira, Denyiélim E; Souza, Gabriela; Sánchez-Sarmiento, Angélica M; Costa-Silva, Samira; Marigo, Juliana; Castilho, Pedro V; Cremer, Marta J; Rodrigues Hoffmann, Aline; Esperón, Fernando; Catão-Dias, José L

    2018-03-22

    We report the gross and microscopic findings and molecular identification of 2 cases of hyphate fungal infection in cetaceans from Brazil. The first case involved an adult male Atlantic spotted dolphin Stenella frontalis with localized pulmonary disease characterized by pyogranulomatous and necrotizing bronchopneumonia with intralesional hyphae. The second case involved an adult male Bryde's whale Balaenoptera edeni with orchitis, periorchitis, mesenteric lymphadenitis and pyogranulomatous bronchopneumonia with intralesional hyphae. PCR analysis from the dolphin's lung yielded Aspergillus fumigatus, and the fungus from the whale's mesenteric lymph node showed the greatest identity to Nanniziopsis obscura and Stagonosporopsis cucurbitacearum These cases represent the first reports of pulmonary aspergillosis by A. fumigatus in an Atlantic spotted dolphin and systemic mycosis by a possibly novel Onygenales in marine mammals.

  14. Aspergilloma of the maxillary sinus: report of a case

    International Nuclear Information System (INIS)

    Kang, Ju Han; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan; Yu, Jae Jung

    2010-01-01

    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.

  15. 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.

  16. 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.

  17. 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.

  18. A monoclonal IgM directed against immunodominant catalase B of cell wall of Aspergillus fumigatus exerts anti-A. fumigatus activities.

    Science.gov (United States)

    Chaturvedi, Ashok K; Kumar, Rohitashw; Kumar, Awanit; Shukla, Praveen K

    2009-11-01

    Aspergillus fumigatus, a ubiquitous fungus, has been reported to cause human diseases like allergic pulmonary aspergillosis, aspergilloma and invasive infection. Limited spectrum and emergence of resistance has become a serious problem with available antifungals. Therefore, an alternative approach is required for successful treatment of mycoses. In the present study, immunogenic protein profile of A. fumigatus cell wall was generated using two-dimensional-gel electrophoresis and three hybridomas producing monoclonal antibodies (MAbs; IgM) were selected after fusion experiments. Of these three MAbs, MAb-7 exhibited potent in vitro inhibitory activity, which was confirmed by MTT assay, fluorescence-activated cell sorter analysis and immuno-fluorescence studies, and the protein was identified as catalase B using MALDI-TOF-MS.

  19. Aspergillus tracheobronchitis in a mild immunocompromised host.

    Science.gov (United States)

    Cho, Byung Ha; Oh, Youngmin; Kang, Eun Seok; Hong, Yong Joo; Jeong, Hye Won; Lee, Ok-Jun; Chang, You-Jin; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

    2014-11-01

    Aspergillus tracheobronchitis is a form of invasive pulmonary aspergillosis in which the Aspergillus infection is limited predominantly to the tracheobronchial tree. It occurs primarily in severely immunocompromised patients such as lung transplant recipients. Here, we report a case of Aspergillus tracheobronchitis in a 42-year-old man with diabetes mellitus, who presented with intractable cough, lack of expectoration of sputum, and chest discomfort. The patient did not respond to conventional treatment with antibiotics and antitussive agents, and he underwent bronchoscopy that showed multiple, discrete, gelatinous whitish plaques mainly involving the trachea and the left bronchus. On the basis of the bronchoscopic and microbiologic findings, we made the diagnosis of Aspergillus tracheobronchitis and initiated antifungal therapy. He showed gradual improvement in his symptoms and continued taking oral itraconazole for 6 months. Physicians should consider Aspergillus tracheobronchitis as a probable diagnosis in immunocompromised patients presenting with atypical respiratory symptoms and should try to establish a prompt diagnosis.

  20. [Zygomycetes and zygomycosis in the new era of antifungal therapies].

    Science.gov (United States)

    Torres-Narbona, M; Guinea, J; Muñoz, P; Bouza, E

    2007-12-01

    Zygomycosis or mucormycosis is the third most invasive fungal infection after candidiasis and aspergillosis. Traditionally, it has been considered a community-acquired disease, but it is becoming a frequent nosocomial-acquired disease. Recently, several publications from different institutions have reported an increase in the number of cases of invasive zygomycosis as a result of the new antifungal and immunosuppresive therapies and the emerging immunocompromised population. In addition, the diagnosis of zygomycosis is elusive, mainly in pulmonary and disseminated forms. One of the main limitations in isolating Zygomycetes from clinical samples is the interpretation of results. The increasing number of invasive fungal infections caused by multiresistant fungi has led to the development of new antifungal drugs with variable activity against Zygomycetes.

  1. Impact of Aspergillus fumigatus in allergic airway diseases

    Directory of Open Access Journals (Sweden)

    Chaudhary Neelkamal

    2011-06-01

    Full Text Available Abstract For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA, known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF. The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed.

  2. MYCOBACTERIUM GENAVENSE IN AN AFRICAN PENGUIN (SPHENISCUS DEMERSUS).

    Science.gov (United States)

    Krause, Kristian J; Reavill, Drury; Weldy, Scott H; Bradway, Daniel S

    2015-12-01

    A 19-yr-old female African penguin (Spheniscus demersus) presented with labored breathing and anorexia. Radiographs revealed soft-tissue density lesions in the left lung fields and fluid in the right. The penguin died during the night. Postmortem examination demonstrated multiple granulomas in the lungs and air sacs. The right coelom was filled with opaque fluid. Histopathology of the lung, liver, kidney, and spleen identified Mycobacterium as a primary disease etiology. Large numbers of acid fast-positive, rod-shaped bacteria were recognized on tissue staining. Mycobacterium genavense was detected by polymerase chain reaction (PCR) using primers specific for the species. Further confirmation of M. genavense was accomplished using PCR with universal Mycobacterium spp. primers followed by sequencing of the amplicon obtained. To our knowledge, this is the first reported case of mycobacteriosis-and specifically M. genavense -in an African penguin. This case also demonstrates the similarities of presentation between the more commonly suspected and encountered aspergillosis and mycobacteriosis.

  3. ANTIFUNGAL SUSCEPTIBILITY TESTING: CURRENT ROLE FROM THE CLINICAL LABORATORY PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Brunella Posteraro

    2014-04-01

    Full Text Available Despite availability of many antifungal agents, antifungal clinical resistance occurs, perhaps as a result of an infecting organism found to be resistant in vitro to one or more antifungals tested. Thus, antifungal susceptibility testing (AFST results, if timely generated by the clinical microbiology and communicated to clinicians, can aid them in the therapeutic decision making, especially for difficult-to-treat invasive candidiasis and aspergillosis. Although recently refined AFST methods are commercially available to allow a close antifungal resistance surveillance in many clinical setting, novel assays, relying on short-time antifungal drug exposure of fungal isolates, are upcoming tools for AFST. Based on emerging technologies such as flow cytometry, MALDI-TOF mass spectrometry, and isothermal microcalorimetry, these assays could provide a reliable means for quicker and sensitive assessment of AFST.

  4. 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.

  5. Treatment of deep mycoses with liposomal amphotericin B.

    Science.gov (United States)

    Berenguer, J; Muñoz, P; Parras, F; Fernández-Baca, V; Hernández-Sampelayo, T; Bouza, E

    1994-06-01

    Amphotericin B is the mainstay of therapy of many deep mycoses, but its use is seriously hampered by dose-limiting nephrotoxicity. In this study a liposomal formulation of amphotericin B was administered to ten patients with proven deep mycoses: invasive aspergillosis (n = 4), deep candidiasis (n = 4) and zygomycosis (n = 2). The mean daily dosage of liposomal amphotericin B was 3.0 mg/kg (range 2.5 to 4 mg/kg), the mean total dosage of liposomal amphotericin B 2,781 mg (range 87 to 5,220 mg) and the mean duration of treatment 17 days (range 3 to 33 days). Treatment with liposomal amphotericin B was associated with little nephrotoxicity and an overall survival rate of 50%. The median increase of serum creatinine from baseline levels was 0.38 mg/dl (-1.2 to 2.6 mg/dl).

  6. Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006.

    Science.gov (United States)

    Prado, Marli; Silva, Marcelo Barbosa da; Laurenti, Ruy; Travassos, Luiz R; Taborda, Carlos P

    2009-05-01

    Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (approximately 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

  7. Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

    Directory of Open Access Journals (Sweden)

    Marli Prado

    2009-05-01

    Full Text Available Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%. When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9% appeared at the top of the list, followed by candidiasis (30.2%, histoplasmosis (10.1% and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

  8. Fungal infections in animals: a patchwork of different situations

    DEFF Research Database (Denmark)

    Seyedmousavi, Seyedmojtaba; Bosco, Sandra De M G; De Hoog, Sybren

    2018-01-01

    The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans....... In addition, the endemic infections with indirect transmission from the environment, the zoophilic fungal pathogens with near-direct transmission, the zoonotic fungi that can be directly transmitted from animals to humans, mycotoxicoses and antifungal resistance in animals will also be discussed....... Opportunistic mycoses are responsible for a wide range of diseases from localized infections to fatal disseminated diseases, such as aspergillosis, mucormycosis, candidiasis, cryptococcosis and infections caused by melanized fungi. The amphibian fungal disease chytridiomycosis and the Bat White-nose syndrome...

  9. High-attenuation mucus plugs on MDCT in a child with cystic fibrosis: potential cause and differential diagnosis

    International Nuclear Information System (INIS)

    Morozov, Andrey; Brown, Shanaree; Applegate, Kimberly E.; Howenstine, Michelle

    2007-01-01

    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.)

  10. 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.

  11. Dental technician pneumoconiosis mimicking pulmonary tuberculosis: a case report.

    Science.gov (United States)

    Tan, Han Loong; Faisal, Mohamed; Soo, Chun Ian; Ban, Andrea Y L; Manap, Roslina Abdul; Hassan, Tidi M

    2016-09-07

    Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.

  12. Triazole Resistance in Aspergillus spp.: A Worldwide Problem?

    Science.gov (United States)

    Rivero-Menendez, Olga; Alastruey-Izquierdo, Ana; Mellado, Emilia; Cuenca-Estrella, Manuel

    2016-01-01

    Since the first description of an azole-resistant A. fumigatus strain in 1997, there has been an increasing number of papers describing the emergence of azole resistance. Firstly reported in the USA and soon after in Europe, it has now been described worldwide, challenging the management of human aspergillosis. The main mechanism of resistance is the modification of the azole target enzyme: 14-α sterol demethylase, encoded by the cyp51A gene; although recently, other resistance mechanisms have also been implicated. In addition, a shift in the epidemiology has been noted with other Aspergillus species (mostly azole resistant) increasingly being reported as causative agents of human disease. This paper reviews the current situation of Aspergillus azole resistance and its implications in the clinical setting. PMID:29376938

  13. Aspergillus specific IgE estimation by radioallergosorbent technique (RAST) in obstructive airways disease at Agra

    International Nuclear Information System (INIS)

    Sharma, S.K.; Singh, R.; Mehrotra, M.P.; Patney, N.L.; Sachan, A.S.; Shiromany, A.

    1986-01-01

    The radioallergosorbent technique (RAST) was used to measure the levels of Aspergillus specific IgE in 25 normal controls, 25 cases of extrinsic bronchial asthma and 25 cases of allergic broncho-pulmonary aspergillosis with a view to study the clinical role and its correlation with sputum culture, skin sensitivity and severity of airways obstruction. The test was performed using Pharmacia diagnostic kits with antigen derived from Aspergillus fumigatus. Abnormal levels of Aspergillus specific IgE were observed in 84 per cent cases of bronchial asthma but none of the controls. 86.7 per cent of all cases with positive skin test had positive radioallergosorbent test and there was no false positive reaction. There was a positive correlation of Aspergillus specific IgE with skin test positivity and with FEV 1 /FVC per cent. (author)

  14. Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?

    Directory of Open Access Journals (Sweden)

    Praveen R Juvvadi

    2015-12-01

    Full Text Available Studies on fungal pathogens belonging to the ascomycota phylum are critical given the ubiquity and frequency with which these fungi cause infections in humans. Among these species, Aspergillus fumigatus causes invasive aspergillosis, a leading cause of death in immunocompromised patients. Fundamental to A. fumigatus pathogenesis is hyphal growth. However, the precise mechanisms underlying hyphal growth and virulence are poorly understood. Over the past 10 years, our research towards the identification of molecular targets responsible for hyphal growth, drug resistance and virulence led to the elucidation of calcineurin as a key signaling molecule governing these processes. In this review, we summarize our salient findings on the significance of calcineurin for hyphal growth and septation in A. fumigatus and propose future perspectives on exploiting this pathway for designing new fungal-specific therapeutics.

  15. 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.)

  16. Pulmonary complications of induction therapy for acute myeloid leukemia in adults. Findings of chest X-rays and computed tomography

    International Nuclear Information System (INIS)

    Kirchner, J.; Huettmann, C.; Jacobi, V.; Boehme, A.

    1998-01-01

    To exclude pulmonary complications, 359 chest radiographs and 50 computed tomographs of the lung were performed in 95 patients suffering from acute myeloid leukemia. The radiological findings were registered, described and correlated with clinical findings in the present study on 2395 days of observation. Results: In summary, 52 patients showed alterations of the lung. Pulmonary hyperhydration was seen in 21 cases, bacterial pneumonia was found in 18 cases, invasive pulmonary aspergillosis was documented in 14 cases, and 5 cases of severe haemorrhage were seen. An unexplained pulmonary edema in 13 patients with interstitial and alveolar infiltrates is considered to be a complication of treatment with cytosine-arabinoside. Conclusion: The results demonstrate that chest X-ray and computed tomography have a high impact in detection and treatment of pulmonary complications following intensive chemotherapy. We may expect the development of diffuse opacity following administration of cytosine-arabinoside in medium-sized doses. (orig.) [de

  17. 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. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  18. [Mycoses in domestic animals].

    Science.gov (United States)

    García, M E; Blanco, J L

    2000-03-01

    In the present paper we will present a general view of the main mycoses affecting domestic animals. In the dog, we show the importance of the dermatophytoses, increased by its zoonosic character and the problem of the false negatives in the traditional microbiological culture. Under the general term of systemic mycoses we include a series of conditions considered usually as aspergillosis, bat with more and more fungal species implicated as possible etiological agents. In addition, fungi, especially yeasts, are being implicated in canine otitis; in our laboratory 86 % of canine chronic otitis involve a yeast etiology, alone or in collaboration with bacteria. In the cat, dermatophytes are more common than in the dog, and are the main source of infection in man, with the description of a high percentage of healthy carrier animals. Cryptococcosis is a severe disease, usually secondary to other process, especially feline immunodeficiency. In cows we refer to fungal abortion, with three main fungi implicated: Aspergillus, Candida and Zygomycetes. In some areas of our country the percentage of fungal abortion is around 10 %. A consequence of the multiple use of antibiotics in mastitis is selection of yeasts, especially those included in the genera Candida and Cryptococcus. Bovine dermatophytoses is an extensively disseminated disease in our country, with a commercial specific vaccine available. In small ruminants, Cryptococcus causes severe pneumonic processes that could be confused clinically with other conditions. An additional important question is the description of isolation of this fungus from tree leaves. In poultry, aspergillosis is a known and controlled disease, but with more importance in captive wild birds with an ecological value. In horses, we emphasize the lung infections by different fungi, specially Pneumocystis carinii, and arthritis by yeasts as consequence of wound contamination or surgery.

  19. The Aspergillus fumigatus Sialidase (Kdnase Contributes to Cell Wall Integrity and Virulence in Amphotericin B-Treated Mice

    Directory of Open Access Journals (Sweden)

    Jason R. Nesbitt

    2018-01-01

    Full Text Available Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening invasive pulmonary aspergillosis (IPA in immunocompromised individuals. We previously characterized an exo-sialidase from A. fumigatus that prefers the sialic acid substrate, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (Kdn; hence it is a Kdnase. Sialidases are known virulence factors in other pathogens; therefore, the goal of our study was to evaluate the importance of Kdnase in A. fumigatus. A kdnase knockout strain (Δkdnase was unable to grow on medium containing Kdn and displayed reduced growth and abnormal morphology. Δkdnase was more sensitive than wild type to hyperosmotic conditions and the antifungal agent, amphotericin B. In contrast, Δkdnase had increased resistance to nikkomycin, Congo Red and Calcofluor White indicating activation of compensatory cell wall chitin deposition. Increased cell wall thickness and chitin content in Δkdnase were confirmed by electron and immunofluorescence microscopy. In a neutropenic mouse model of invasive aspergillosis, the Δkdnase strain had attenuated virulence and a significantly lower lung fungal burden but only in animals that received liposomal amphotericin B after spore exposure. Macrophage numbers were almost twofold higher in lung sections from mice that received the Δkdnase strain, possibly related to higher survival of macrophages that internalized the Δkdnase conidia. Thus, A. fumigatus Kdnase is important for fungal cell wall integrity and virulence, and because Kdnase is not present in the host, it may represent a potential target for the development of novel antifungal agents.

  20. 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.

  1. 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

    2014-01-01

    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. PMID:24452174

  2. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Silva Monteiro

    2017-10-01

    Full Text Available Abstract Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs in systemic granulomatous infections in comparison with gallium-67 (67Ga citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  3. Burden of serious fungal infections in Guatemala.

    Science.gov (United States)

    Medina, N; Samayoa, B; Lau-Bonilla, D; Denning, D W; Herrera, R; Mercado, D; Guzmán, B; Pérez, J C; Arathoon, E

    2017-06-01

    Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.

  4. Detection of Aspergillus flavus and A. fumigatus in Bronchoalveolar Lavage Specimens of Hematopoietic Stem Cell Transplants and Hematological Malignancies Patients by Real-Time Polymerase Chain Reaction, Nested PCR and Mycological Assays

    Science.gov (United States)

    Zarrinfar, Hossein; Mirhendi, Hossein; Fata, Abdolmajid; Khodadadi, Hossein; Kordbacheh, Parivash

    2015-01-01

    Background: Pulmonary aspergillosis (PA) is one of the most serious complications in immunocompromised patients, in particular among hematopoietic stem cell transplants (HSCT) and patients with hematological malignancies. Objectives: The current study aimed to evaluate the incidence of PA and utility of molecular methods in HSCT and patients with hematological malignancies, four methods including direct examination, culture, nested polymerase chain reaction (PCR) and real-time PCR were performed on bronchoalveolar lavage (BAL) specimens in Tehran, Iran. Patients and Methods: During 16 months, 46 BAL specimens were obtained from individuals with allogeneic HSCT (n = 18) and patients with hematological malignancies (n = 28). Direct wet mounts with 20% potassium hydroxide (KOH) and culture on mycological media were performed. The molecular detection of Aspergillus fumigatus and A. flavus was done by amplifying the conserved sequences of internal transcribed spacer 1 (ITS1) ribosomal DNA by nested-PCR and the β-tubulin gene by TaqMan real-time PCR. Results: Seven (15.2%) out of 46 specimens were positive in direct examination and showed branched septate hyphae; 11 (23.9%) had positive culture including eight (72.7%) A. flavus and three (27.3%) A. fumigatus; 22 (47.8%) had positive nested-PCR and eight (17.4%) had positive real-time PCR. The incidence of invasive pulmonary aspergillosis (IPA) in these patients included proven IPA in 1 (2.2%), probable IPA in 10 (21.7%), possible IPA in 19 (41.3%) and not IPA in 16 cases (34.8%). Conclusions: The incidence of IPA in allogeneic HSCT and patients with hematological malignancies was relatively high and A. flavus was the most common cause of PA. As molecular methods had higher sensitivity, it may be useful as screening methods in HSCT and patients with hematological malignancies, or to determine when empirical antifungal therapy can be withheld. PMID:25763133

  5. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    International Nuclear Information System (INIS)

    Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío

    2017-01-01

    Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

  6. Burden of Serious Fungal Infections in Argentina

    Directory of Open Access Journals (Sweden)

    Fernando O. Riera

    2018-04-01

    Full Text Available The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS are major problems. An estimated 432 cases of cryptococcal meningitis (CM—90% of them in AIDS patients—and 1177 cases of Pneumocystis pneumonia (PCP occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01% in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality.

  7. High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients

    International Nuclear Information System (INIS)

    Gazzoni, Fernando Ferreira; Hochhegger, Bruno; Severo, Luiz Carlos; Marchiori, Edson; Pasqualotto, Alessandro; Sartori, Ana Paula Garcia; Schio, Sadi; Camargo, José

    2014-01-01

    Objective: The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection. Materials and methods: We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case. Conclusion: The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients

  8. Monoclonal antibodies to hyphal exoantigens derived from the opportunistic pathogen Aspergillus terreus.

    Science.gov (United States)

    Nayak, Ajay P; Green, Brett J; Janotka, Erika; Hettick, Justin M; Friend, Sherri; Vesper, Steve J; Schmechel, Detlef; Beezhold, Donald H

    2011-09-01

    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 identify species-specific biomarkers that can be used to detect invasive A. terreus disease. Monoclonal antibodies (MAbs) were developed to a partially purified preparation of cytolytic hyphal exoantigens (HEA) derived from A. terreus culture supernatant (CSN). Twenty-three IgG1 isotype murine MAbs were developed and tested for cross-reactivity against hyphal extracts of 54 fungal species. Sixteen MAbs were shown to be specific for A. terreus. HEA were detected in conidia, hyphae, and in CSN of A. terreus. HEA were expressed in high levels in the hyphae during early stages of A. terreus growth at 37°C, whereas at room temperature the expression of HEA peaked by days 4 to 5. Expression kinetics of HEA in CSN showed a lag, with peak levels at later time points at room temperature and 37°C than in hyphal extracts. Serum spiking experiments demonstrated that human serum components do not inhibit detection of the HEA epitopes by MAb enzyme-linked immunosorbent assay (ELISA). Immunoprecipitation and proteomic analysis demonstrated that MAbs 13E11 and 12C4 immunoprecipitated a putative uncharacterized leucine aminopeptidase (Q0CAZ7), while MAb 19B2 recognized a putative dipeptidyl-peptidase V (DPP5). Studies using confocal laser scanning microscopy showed that the uncharacterized leucine aminopeptidase mostly localized to extracellular matrix structures while dipeptidyl-peptidase V was mostly confined to the cytoplasm.

  9. Complications of hematopoietic stem transplantation: Fungal infections.

    Science.gov (United States)

    Omrani, Ali S; Almaghrabi, Reem S

    2017-12-01

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

  10. QPCR detection of Mucorales DNA in bronchoalveolar lavage fluid to diagnose pulmonary mucormycosis.

    Science.gov (United States)

    Scherer, Emeline E; Iriart, Xavier; Bellanger, Anne Pauline; Dupont, Damien; Guitard, Juliette; Gabriel, Frederic; Cassaing, Sophie; Charpentier, Eléna; Guenounou, Sarah; Cornet, Murielle; Botterel, Françoise; Rocchi, Steffi; Berceanu, Ana; Millon, Laurence

    2018-06-06

    Early diagnosis and treatment are essential to improving the outcome of mucormycosis. The aim of this retrospective study was to assess the contribution of quantitative PCR detection of Mucorales DNA in bronchoalveolar lavage fluids for early diagnosis of pulmonary mucormycosis.Bronchoalveolar lavage fluids (n=450) from 374 patients with pneumonia and immunosuppressive conditions were analyzed using a combination of 3 quantitative PCR assays targeting the main genera involved in mucormycosis in France ( Rhizomucor, Mucor/Rhizopus, Lichtheimia ).Among these 374 patients, 24 had at least one bronchoalveolar lavage with a positive PCR; 23/24 patients had radiological criteria for invasive fungal infections according to consensual criteria : 10 patients with probable or proven mucormycosis, and 13 additional patients with other invasive fungal infections (4 probable aspergillosis, 1 proven fusariosis, and 8 possible invasive fungal infections). Only 2/24 patients with a positive PCR on bronchoalveolar lavage had a positive Mucorales culture.PCR was also positive on serum in 17/24 patients. In most cases, PCR was first detected positive on sera (15/17). However, a positive PCR on bronchoalveolar lavage was the earliest and/or the only biological test revealing mucormycosis in 4 patients with a final diagnosis of probable or proven mucormycosis, 3 patients with probable aspergillosis and one patient with a possible invasive fungal infection.Mucorales PCR performed on bronchoalveolar lavage could provide additional arguments for earlier administration of Mucorales-directed antifungal therapy, thus improving the outcome of lung mucormycosis. Copyright © 2018 American Society for Microbiology.

  11. 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.

  12. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío, E-mail: paulohsm42@gmail.com [Universidade de Campinas (UNICAMP), SP (Brazil). Escola de Medicina; Mengatti Jair [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-11-15

    Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ({sup 67}Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of {sup 99m}Tc-EDDA-HYNIC-TOC, and 21 after injection of {sup 111}In-DTPA-octreotide. All patients also underwent {sup 67}Ga citrate imaging, except for one patient who died before the {sup 67}Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by {sup 67}Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than {sup 67}Ga uptake in 11 of the 20 patients with positive images and similar to {sup 67}Ga uptake in the other 9 patients. The only patient who did not undergo {sup 67}Ga scintigraphy underwent {sup 99m}Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with {sup 99m}Tc-EDDA-HYNIC-TOC or {sup 111}In-DTPA-octreotide seems to be a good alternative to {sup 67}Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

  13. Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings

    International Nuclear Information System (INIS)

    Diederich, S.; Scadeng, M.; Flower, C.D.R.; Dennis, C.; Stewart, S.

    1998-01-01

    The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a ''halo'' of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances. (orig.)

  14. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

    Science.gov (United States)

    Verweij, Paul E.

    2016-01-01

    Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus. However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides. Although ubiquitously distributed, A. fumigatus is not a phytopathogen. However, agricultural fungicides deployed against plant pathogenic moulds such as Fusarium, Mycospaerella and A. flavus also show activity against A. fumigatus in the environment and exposure of non-target fungi is inevitable. Further, similarity in molecule structure between azole fungicides and antifungal drugs results in cross-resistance of A. fumigatus to medical azoles. Clinical studies have shown that two-thirds of patients with azole-resistant infections had no previous history of azole therapy and high mortality rates between 50% and 100% are reported in azole-resistant invasive aspergillosis. The resistance phenotype is associated with key mutations in the cyp51A gene, including TR34/L98H, TR53 and TR46/Y121F/T289A resistance mechanisms. Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis, azole monotherapy should be avoided. Liposomal amphotericin B or a combination of voriconazole and an echinocandin are recomended for azole-resistant aspergillosis. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080986

  15. Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

    International Nuclear Information System (INIS)

    Petrik, Milos; Franssen, Gerben M.; Laverman, Peter; Haas, Hubertus; Schrettl, Markus; Hoertnagl, Caroline; Lass-Floerl, Cornelia; Helbok, Anna; Decristoforo, Clemens

    2012-01-01

    Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with 68 Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising 68 Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). Siderophores were labelled with 68 Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic μPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. 68 Ga-siderophores were labelled with high radiochemical purity and specific activity. 68 Ga-TAFC and 68 Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, 68 Ga-TAFC and 68 Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by μPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. 68 Ga-TAFC and 68 Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging. (orig.)

  16. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

    Science.gov (United States)

    Ullmann, A J; Aguado, J M; Arikan-Akdagli, S; Denning, D W; Groll, A H; Lagrou, K; Lass-Flörl, C; Lewis, R E; Munoz, P; Verweij, P E; Warris, A; Ader, F; Akova, M; Arendrup, M C; Barnes, R A; Beigelman-Aubry, C; Blot, S; Bouza, E; Brüggemann, R J M; Buchheidt, D; Cadranel, J; Castagnola, E; Chakrabarti, A; Cuenca-Estrella, M; Dimopoulos, G; Fortun, J; Gangneux, J-P; Garbino, J; Heinz, W J; Herbrecht, R; Heussel, C P; Kibbler, C C; Klimko, N; Kullberg, B J; Lange, C; Lehrnbecher, T; Löffler, J; Lortholary, O; Maertens, J; Marchetti, O; Meis, J F; Pagano, L; Ribaud, P; Richardson, M; Roilides, E; Ruhnke, M; Sanguinetti, M; Sheppard, D C; Sinkó, J; Skiada, A; Vehreschild, M J G T; Viscoli, C; Cornely, O A

    2018-05-01

    The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging. Copyright © 2018 European Society of

  17. Training should be the first step toward an antifungal stewardship program.

    Science.gov (United States)

    Valerio, Maricela; Muñoz, Patricia; Rodríguez-González, Carmen; Sanjurjo, María; Guinea, Jesús; Bouza, Emilio

    2015-04-01

    The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Spatial variability of disease incidence and mortality in the sea fan Gorgonia ventalina in Puerto Rico (Alcyonacea: Goorgoniidae

    Directory of Open Access Journals (Sweden)

    Anabella Zuluaga-Montero

    2012-06-01

    Full Text Available Populations of the common sea fan (Gorgonia ventalina were decimated by an aspergillosis outbreak throughout the Caribbean two decades ago. Since then, aspergillosis has been considered as the principal cause of mortality in sea fans. However, prevalence and presumably incidence of this disease have been declining in the Caribbean since the mid 1990s. Incidence indicates new cases of disease in previously healthy colonies, while prevalence indicates percent of diseased colonies at a given sample. Most coral disease studies use prevalence rather than incidence to assess the temporal dynamics of diseases. Nevertheless, conclusions based only on prevalence should be handled carefully to avoid misinterpretation. This study was carried out at six reefs in Eastern Puerto Rico. We monitored a total of 448 colonies to (1 obtain estimates of incidence and prevalence of disease and other types of lesions, and (2 to determine causes of sea fan mortality plus their spatial and temporal variation. Three transects (10x1m were haphazardly placed at each study site. At each transect, every colony was numbered and photographed and its height measured to the nearest cm. Transects were monitored at six months intervals and health status of the colonies was recorded. Also, the colonies were divided into height classes (small, medium and large for incidence, prevalence and mortality analyses. Incidence and prevalence of disease were low in all reefs, suggesting that disease currently plays a minor role in the regulation of sea fans populations. Detachment was the main cause of mortality, and size structure data suggest that recruitment may compensate for mortality rates in two of the reefs. Spatial differences in size structure and density may be related to environmental and physical characteristics at the reef scale that allow sea fans to reach a safe colony size. Rev. Biol. Trop. 60 (2: 517-526. Epub 2012 June 01.

  19. Eosinofilia pulmonar Pulmonary eosinophilia

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Mendes Campos

    2009-06-01

    and treatment. Clinical and radiological presentations can include simple pulmonary eosinophilia, chronic eosinophilic pneumonia, acute eosinophilic pneumonia, allergic bronchopulmonary aspergillosis and pulmonary eosinophilia associated with a systemic disease, such as in Churg-Strauss syndrome and hypereosinophilic syndrome. Asthma is frequently concomitant and can be a prerequisite, as in allergic bronchopulmonary aspergillosis and Churg-Strauss syndrome. In diseases with systemic involvement, the skin, the heart and the nervous system are the most affected organs. The radiological presentation can be typical, or at least suggestive, of one of three types of pulmonary eosinophilia: chronic eosinophilic pneumonia, acute eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. The etiology of pulmonary eosinophilia can be either primary (idiopathic or secondary, due to known causes, such as drugs, parasites, fungal infection, mycobacterial infection, irradiation and toxins. Pulmonary eosinophilia can be also associated with diffuse lung diseases, connective tissue diseases and neoplasia.

  20. Infectious and non-infectious neurologic complications in heart transplant recipients.

    Science.gov (United States)

    Muñoz, Patricia; Valerio, Maricela; Palomo, Jesús; Fernández-Yáñez, Juan; Fernández-Cruz, Ana; Guinea, Jesús; Bouza, Emilio

    2010-05-01

    Neurologic complications are important causes of morbidity and mortality in heart transplant (HT) recipients. New immunomodulating agents have improved survival rates, although some have been associated with a high rate of neurologic complications (infectious and non-infectious). We conducted this study to analyze the frequency of these complications, before and after the use of daclizumab induction therapy. We reviewed all neurologic complications in our HT cohort, comparing infectious with non-infectious complications over 2 periods of time in which different induction therapies were used (316 patients with OKT3 or antithymocyte globulin from 1988 to 2002, and 68 patients with daclizumab from 2003 to 2006). Neurologic complications were found in 75/384 patients (19.5%) with a total of 78 episodes. Non-infectious complications accounted for 68% of the 78 episodes of neurologic complications. A total of 51 patients and 53 episodes were detailed as follows: 25 episodes of stroke (25 of 78 total episodes, 32%; 19 ischemic, 6 hemorrhagic); 7 neuropathies; 6 seizures; 4 episodes of transient ischemic attack (TIA); 3 anoxic encephalopathy; 2 each brachial plexus palsy and metabolic encephalopathy; and 1 each myoclonia, central nervous system (CNS) lymphoma, subdural hematoma, and Cotard syndrome. Mean time to presentation of stroke, TIA, and encephalopathy was 1 day (range, 1-19 d) posttransplant. Mortality rate among non-infectious complications was 12/53 (22.6%). Infectious complications accounted for 32% of the 78 total episodes. We found 25 episodes in 24 patients: 17 herpes zoster (median, 268 d after HT), 3 CNS aspergillosis (median, 90 d after HT), 1 CNS toxoplasmosis and tuberculosis (51 d after HT), 1 pneumococcal meningitis (402 d after HT), and 2 Listeria meningitis (median, 108 d after HT). The 3 patients with CNS aspergillosis died. The mortality rate among patients with infectious neurologic complications was 12% (42.8% if the CNS was involved). When we

  1. Characterization of the FKBP12-Encoding Genes in Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Katie Falloon

    Full Text Available Invasive aspergillosis, largely caused by Aspergillus fumigatus, is responsible for a growing number of deaths among immunosuppressed patients. Immunosuppressants such as FK506 (tacrolimus that target calcineurin have shown promise for antifungal drug development. FK506-binding proteins (FKBPs form a complex with calcineurin in the presence of FK506 (FKBP12-FK506 and inhibit calcineurin activity. Research on FKBPs in fungi is limited, and none of the FKBPs have been previously characterized in A. fumigatus. We identified four orthologous genes of FKBP12, the human FK506 binding partner, in A. fumigatus and designated them fkbp12-1, fkbp12-2, fkbp12-3, and fkbp12-4. Deletional analysis of the four genes revealed that the Δfkbp12-1 strain was resistant to FK506, indicating FKBP12-1 as the key mediator of FK506-binding to calcineurin. The endogenously expressed FKBP12-1-EGFP fusion protein localized to the cytoplasm and nuclei under normal growth conditions but also to the hyphal septa following FK506 treatment, revealing its interaction with calcineurin. The FKBP12-1-EGFP fusion protein didn't localize at the septa in the presence of FK506 in the cnaA deletion background, confirming its interaction with calcineurin. Testing of all deletion strains in the Galleria mellonella model of aspergillosis suggested that these proteins don't play an important role in virulence. While the Δfkbp12-2 and Δfkbp12-3 strains didn't show any discernable phenotype, the Δfkbp12-4 strain displayed slight growth defect under normal growth conditions and inhibition of the caspofungin-mediated "paradoxical growth effect" at higher concentrations of the antifungal caspofungin. Together, these results indicate that while only FKBP12-1 is the bona fide binding partner of FK506, leading to the inhibition of calcineurin in A. fumigatus, FKBP12-4 may play a role in basal growth and the caspofungin-mediated paradoxical growth response. Exploitation of differences between A

  2. Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses.

    Science.gov (United States)

    Neves, Gabriela Westerlund Peixoto; Curty, Nathália de Andrade; Kubitschek-Barreira, Paula Helena; Fontaine, Thierry; Souza, Gustavo Henrique Martins Ferreira; Cunha, Marcel Lyra; Goldman, Gustavo H; Beauvais, Anne; Latgé, Jean-Paul; Lopes-Bezerra, Leila M

    2017-01-16

    Aspergillus fumigatus, the main etiologic agent causing invasive aspergillosis, can induce an inflammatory response and a prothrombotic phenotype upon contact with human umbilical vein endothelial cells (HUVECs). However, the fungal molecules involved in this endothelial response remain unknown. A. fumigatus hyphae produce an extracellular matrix composed of galactomannan, galactosaminogalactan and α-(1,3)-glucan. In this study, we investigated the consequences of UGM1 gene deletion in A. fumigatus, which produces a mutant with increased galactosaminogalactan production. The ∆ugm1 mutant exhibited an HUVEC-hyperadhesive phenotype and induced increased endothelial TNF-α secretion and tissue factor mRNA overexpression in this "semi-professional" immune host cell. Using a shotgun proteomics approach, we show that the A. fumigatus ∆ugm1 strain can modulate the levels of proteins in important endothelial pathways related to the inflammatory response mediated by TNF-α and to stress response pathways. Furthermore, a purified galactosaminogalactan fraction was also able to induce TNF-α secretion and the coincident HUVEC pathways regulated by the ∆ugm1 mutant, which overexpresses this component, as demonstrated by fluorescence microscopy. This work contributes new data regarding endothelial mechanisms in response to A. fumigatus infection. Invasive aspergillosis is the main opportunistic fungal infection described in neutropenic hematologic patients. One important clinical aspect of this invasive fungal infection is vascular thrombosis, which could be related, at least in part, to the activation of endothelial cells, as shown in previous reports from our group. It is known that direct contact between the A. fumigatus hyphal cell wall and the HUVEC cell surface is necessary to induce an endothelial prothrombotic phenotype and secretion of pro-inflammatory cytokines, though the cell surface components of this angioinvasive fungus that trigger this endothelial

  3. Role of isavuconazole in the treatment of invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Wilson DT

    2016-08-01

    Full Text Available Dustin T Wilson,1,2 V Paul Dimondi,1,3 Steven W Johnson,1,4 Travis M Jones,1 Richard H Drew1,5 1Department of Pharmacy Practice, Campbell University College of Pharmacy & Health Sciences, Buies Creek, NC, USA; 2Department of Pharmacy, Duke University Hospital, Durham, NC, USA; 3Department of Pharmacy, Durham VA Medical Center, Durham, NC, USA; 4Department of Pharmacy, Forsyth Medical Center, Winston-Salem, NC, USA; 5Division of Infectious Diseases, Duke University Hospital, Durham, NC, USA Abstract: Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug–drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation, and reduced drug–drug interactions (relative to voriconazole. Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of

  4. The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression

    Directory of Open Access Journals (Sweden)

    Mark S. Gresnigt

    2017-12-01

    Full Text Available One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA. Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1−/− mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1−/− mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1−/− mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1−/− cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the

  5. Phytochemical analysis and antifungal activity of selected seaweeds from Okha coast, Gujarat, India

    Directory of Open Access Journals (Sweden)

    Isaiah Nirmal Kumar

    2015-07-01

    Full Text Available Objective: To deal with the assessment of the chemical composition of carbohydrate, protein, phenol, flavanoid, chlorophyll, and carotenoid and antifungal activity of various marine seaweeds collected from Okha coast, Gujarat during September, 2013. Methods: Biochemical compounds of selected seaweeds were quantified and antifungal activity of these species belonging to red, green, and brown seaweeds was explored and the seaweeds were extracted in acetone, ethanol and chloroform. Results: The carbohydrate content was highest in Cystoseira indica Mairh, protein was highest in Gracilaria corticata J. Agardh and phenol content was highest in Padina boergesenii; flavanoid content was found greater in Cystoseira indica, chlorophyll content was found greater in Monostroma latissimum Wittrock and carotenoid content was more in Dictyopteris acrostichoides Bornet. The highest inhibiting effect was noted for Sargassum tenerrimum J. Agardh and Turbinaria ornata J. Agardh belonging to brown algae, against Aspergillus niger and Penicillium janthinellum in chloroform extracts and ethanolic extracts, which caused opportunistic infection of HIV-infected person, lung disease, aspergillosis, and otomycosis (fungal ear infections. Conclusions: The study reveals that the seaweeds contain high amount of biochemical constituents. Besides, the crude extracts of the seaweeds showed promising activity against the tested fungal pathogens. Therefore, seaweeds collected from Okha coast, Gujarat region are biochemical compounds with potential capacity which make them useful for screening natural products for pharmaceutical industry.

  6. Reintroduction medicine: whooping cranes in Wisconsin.

    Science.gov (United States)

    Keller, Dominique L; Hartup, Barry K

    2013-01-01

    This paper presents veterinary management strategies and diagnostic findings in the reintroduction of the endangered whooping crane (Grus americana). Between 2005 and 2010, 63 (27 male, 36 female) hatchling whooping cranes were assigned to a reintroduction project involving autumn release of costume-reared chicks in Wisconsin. Veterinary care included preventive measures and comprehensive pre-release evaluations to improve fitness and reduce translocation of potential disease agents to native habitats. A total of 44 clinically normal birds were released (70% of assigned individuals). Cases of morbidity were classified according to primary body system affected. Musculoskeletal disorders were described in 57 birds (90%); five birds were removed from the project prior to release (8%), all for abnormalities that prevented normal function. Fourteen birds died or were euthanized prior to release (22%); pre-release mortality was attributed to developmental abnormality, predation, trauma or infectious disease. Chronic respiratory aspergillosis, diagnosed in seven birds (11%), was the most common infectious disease of concern. Predation and trauma were primary causes of post-release mortality; no evidence of infectious disease of captive origin was detected in the study population by the end of 2010. The assessment of data accumulated by this project helped to outline successful health management strategies, as well as identify and mitigate ongoing risks to captive whooping cranes that impede reintroduction efforts and achieving management goals for species recovery. © 2013 Wiley Periodicals, Inc.

  7. [Diseases to differentiate from COPD, with emphasis on bronchial asthma].

    Science.gov (United States)

    Kanazawa, Minoru

    2007-04-01

    Differential diagnosis of chronic obstructive pulmonary disease (COPD) from asthma is not a difficult task for many clinicians. Patients with COPD have a history of heavy smoking and show a slowly progressive dyspnea on exertion and there is little variability in symptoms, and they show a poor response to bronchodilators and corticosteroids. Asthma usually begins in early childhood with atopy, shows episodic dyspnea with wheezing, especially during night and early morning. Some patients, however, show adult onset, irreversible airflow limitation, and neutrophilic airway inflammation. The airway remodeling in asthma may be the cause of confusing pathophysiology. Other diseases showing airway hyperresponsiveness, such as allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, and left heart failure presenting cardiac asthma, may sometimes show similar clinical pictures to COPD. Chronic airway diseases are also possible candidates for differential diagnosis of COPD. Bronchiectasis, sinobronchial syndrome, diffuse panbronchiolitis, obliterative bronchiolitis, and other chronic airway diseases should be considered. Some interstitial lung diseases, such as smoking-related interstitial lung diseases and lymphangioleiomyomatosis, often show obstructive ventilatory impairment, and therefore should be considered in differential diagnosis of COPD.

  8. [Non allergic simple eosinophilic pneumonia--Löffler syndrome--a case report study].

    Science.gov (United States)

    Meta-Jevtović, Ivana; Tomović, Miroslav S; Mojsilović, Slavica; Petrović, Marina

    2008-01-01

    Löffler syndrome is an acute, pneumonia of unknown ethiology. This disease is not often associated with bronchial asthma. In its asymptomatic form, this disease is reversible, transient, self-limited with no requests for specific therapy regimen. In the symptomatic form, as well as during its progression, treatment with steroids is very effective. Furthermore, in both acute eosinophilic and idiopathic chronic eosinophilic form, this kind of therapy ensures survival. The case of a 53-year-old Caucasian woman was presented with 2-month history of low grade fever, shortness of breath, cough and reduced exercise tolerance. Although she had an allergic accident on insects in history, non allergy reactions as well as an obstructive disease with that kind of origin were not detected on admission. The diagnosis of simple eosinophilic pneumonia (SEP) (Löffler's syndrome) was confirmed by transbronchial biopsy and by sternal testing. The peripheral blood eosinophilia with pulmonary eosinophilic infiltrates on X ray chest radiography were observed during clinical examination. Biopsy specimen of the lung parenchym showed changes associated with Löffler's syndrome. The diagnosis was, also, confirmed according to the radiographic findings of unilateral migratory infiltrates consistent pneumonia. Churg Strauss syndrome (CSS) has to be considered in this differential diagnosis. Frequently, this disease has extrinsic bronchial asthma with eosinophilic pneumonia in history: asthma is often associated with allergic bronchopulmonary aspergillosis. In the reported case, treatment with steroids resulted in a marked clinical improvement compared to nonsteroid therapy.

  9. Aspergillus fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis through Modulation of Chitin Synthase Activity

    Directory of Open Access Journals (Sweden)

    Arsa Thammahong

    2017-04-01

    Full Text Available Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA and tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall integrity, and significantly alters cell wall structure. To gain mechanistic insights into the role that TslA plays in cell wall homeostasis, immunoprecipitation assays coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS were used to reveal a direct interaction between TslA and CsmA, a type V chitin synthase enzyme. TslA regulates not only chitin synthase activity but also CsmA sub-cellular localization. Loss of TslA impacts the immunopathogenesis of murine invasive pulmonary aspergillosis through altering cytokine production and immune cell recruitment. In conclusion, our data provide a novel model whereby proteins in the trehalose pathway play a direct role in fungal cell wall homeostasis and consequently impact fungus-host interactions.

  10. Research Progress on Diagnosis Methods for Fungal Infection

    Directory of Open Access Journals (Sweden)

    Feng Hua

    2015-12-01

    Full Text Available In recent years, owing to abuse of antibiotics, extensive use of antitumor drugs and immunosuppressive agents and other reasons, an increasing number of people suffered from fungal infection. In this situation, researchers proposed new diagnosis methods, such as G test, galactomannan (GM test, and polymerase chain reaction (PCR. G test is simple, quick, and highly sensitive and can detect multiple fungi; however, it cannot distinguish fungal types and may result in false positive and false negative results. GM test is less time consuming and feature highly positive detection rates but can simply be used in inspection of invasive aspergillosis. However, optimal positive critical values of GM test remain controversial. PCR is currently one of the fastest methods but is not formally used in clinical practice because of its lack of standardized operation and evaluation criteria. This study reviews the above three methods with the aim of discovering and summarizing their advantages and disadvantages to facilitate research and development of new diagnosis methods.

  11. Clinical expression of patients with the D1152H CFTR mutation.

    Science.gov (United States)

    Terlizzi, Vito; Carnovale, Vincenzo; Castaldo, Giuseppe; Castellani, Carlo; Cirilli, Natalia; Colombo, Carla; Corti, Fabiola; Cresta, Federico; D'Adda, Alice; Lucarelli, Marco; Lucidi, Vincenzina; Macchiaroli, Annamaria; Madarena, Elisa; Padoan, Rita; Quattrucci, Serena; Salvatore, Donatello; Zarrilli, Federica; Raia, Valeria

    2015-07-01

    Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole

    Directory of Open Access Journals (Sweden)

    Oliveira J.S.R.

    2002-01-01

    Full Text Available Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD. In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1 A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2 Invasive pulmonary aspergillosis (Aspergillus fumigatus was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3 A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis was observed in a transplanted patient who presented severe chronic GvHD. 4 A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5 A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.

  13. Necrotizing Encephalitis Caused by Disseminated Aspergillus Infection after Orthotopic Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Luis E. Barrera-Herrera

    2015-01-01

    Full Text Available Liver transplantation is the only available treatment for some patients with end-stage liver disease. Despite reduction in mortality rates due to advances related to surgical techniques, intensive medical management and immunosuppressive therapy, invasive fungal infections remain a serious complication in orthotopic liver transplantation. We report the case of an 18-year-old male diagnosed with autoimmune cirrhosis in 2009 who was assessed and listed for liver transplantation for massive variceal hemorrhage. One year after listing a successful orthotopic liver transplantation was performed. Uneventful early recovery was achieved; however, he developed pulmonary and neurological Aspergillus infection 23 and 40 days after surgery, respectively. Antibiotic therapy with voriconazole and amphotericin was started early, with no major response. Neuroimaging revealed multiple right frontal and right parietal lesions with perilesional edema; surgical management of the brain abscesses was performed. A biopsy with periodic acid-Schiff and Gomori stains revealed areas with mycotic microorganisms morphologically consistent with Aspergillus, later confirmed by culture. The patient developed necrotizing encephalitis secondary to aspergillosis and died. Necrotizing encephalitis as a clinical presentation of Aspergillus infection in an orthotopic liver transplant is not common, and even with adequate management, early diagnosis and prompt antifungal treatment, mortality rates remain high.

  14. SCF Ubiquitin Ligase F-box Protein Fbx15 Controls Nuclear Co-repressor Localization, Stress Response and Virulence of the Human Pathogen Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Bastian Jöhnk

    2016-09-01

    Full Text Available F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm. The F-box of Fbx15 is required for an appropriate oxidative stress response, which results in rapid dephosphorylation of Fbx15 and a shift of the cellular interaction with SkpA to the nucleus. Fbx15 binds SsnF/Ssn6 as part of the RcoA/Tup1-SsnF/Ssn6 co-repressor and is required for its correct nuclear localization. Dephosphorylated Fbx15 prevents SsnF/Ssn6 nuclear localization and results in the derepression of gliotoxin gene expression. fbx15 deletion mutants are unable to infect immunocompromised mice in a model for invasive aspergillosis. Fbx15 has a novel dual molecular function by controlling transcriptional repression and being part of SCF E3 ubiquitin ligases, which is essential for stress response, gliotoxin production and virulence in the opportunistic human pathogen A. fumigatus.

  15. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

    Science.gov (United States)

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

    2016-04-19

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

  16. Ground-glass opacity in diffuse lung diseases: high-resolution computed tomography-pathology correlation

    International Nuclear Information System (INIS)

    Santos, Maria Lucia de Oliveira; Vianna, Alberto Domingues; Marchiori, Edson; Souza Junior, Arthur Soares; Moraes, Heleno Pinto de

    2003-01-01

    Ground-glass opacity is a finding frequently seen in high-resolution computed tomography examinations of the chest and is characterized by hazy increased attenuation of lung, however without blurring of bronchial and vascular margins. Due to its un specificity, association with other radiological, clinical and pathological findings must be considered for an accurate diagnostic interpretation. In this paper were reviewed 62 computed tomography examinations of patients with diffuse pulmonary diseases of 14 different etiologies in which ground-glass opacity was the only or the most remarkable finding, and correlated this findings with pathology abnormalities seen on specimens obtained from biopsies or necropsies. In pneumocystosis, ground-glass opacities correlated histologically with alveolar occupation by a foaming material containing parasites, in bronchiole alveolar cell carcinoma with thickening of the alveolar septa and occupation of the lumen by mucus and tumoral cells, in paracoccidioidomycosis with thickening of the alveolar septa, areas of fibrosis and alveolar bronchopneumonia exudate, in sarcoidosis with fibrosis or clustering of granulomas and in idiopathic pulmonary fibrosis with alveolar septa thickening due to fibrosis. Alveolar occupation by blood was found in cases of leptospirosis, idiopathic hemo siderosis, metastatic kidney tumor and invasive aspergillosis whereas oily vacuole were seen in lipoid pneumonia, proteinaceous and lipo proteinaceous material in silico proteinosis and pulmonary alveolar proteinosis, and edematous fluid in cardiac failure. (author)

  17. Diagnosis of IPA in HIV: The role of the chest X-ray and radiologist

    International Nuclear Information System (INIS)

    Zaspel, Uta; Denning, David W.; Lemke, Arne J.; Roettgen, Rainer; Bittner, Roland; Oestmann, Joerg W.; Greene, Reginald; Schuermann, Dirk; Maschmeyer, Georg; Ruhnke, Markus; Herbrecht, Raoul; Ribaud, Patricia; Lortholary, Olivier; Zonderland, Harmien; Rabe, Klaus F.; Neumann, Klaus

    2004-01-01

    The role of clinical information and chest film for the discrimination between invasive pulmonary aspergillosis (IPA) and its differential diagnoses in human immunodeficiency virus (HIV) infection was studied. The diagnostic performance of clinical information and chest film alone and in combination was studied for eight internists and eight radiologists with regular exposure to IPA patients. The multicenter case sample consisted of 25 patients with proven IPA and 25 with other pulmonary diseases typical for HIV. The cases were presented on a CD-ROM. Receiver operating characteristics (ROC) methodology was employed. With clinical information alone, internists achieved the highest diagnostic performance (area under curve/AUC=0.84). Viewing the chest films did not contribute to their performance (AUC=0.80, P=0.26). The radiologist's performance on the basis of viewing the chest film (AUC=0.75) increased significantly (P=0.012) when clinical information (AUC=0.83) was supplied. IPA cases with characteristic radiological appearance were correctly identified in 90% with chest film. For radiologists with regular exposure to HIV patients, chest films hold relevant information and contribute to the determination in cases with characteristic radiological appearance. Overall and especially in cases with less characteristic radiological appearance, they have significant profit from full access to the clinical data. For internists with regular exposure to HIV patients, chest films do not provide information essential for the verification or differentiation of potential IPA. (orig.)

  18. Antifungal Activity of Maytenin and Pristimerin

    Directory of Open Access Journals (Sweden)

    Fernanda P. Gullo

    2012-01-01

    Full Text Available Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa. It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents.

  19. Contaminação do ar por Aspergillus em ambiente de reabilitação de animais marinhos

    Directory of Open Access Journals (Sweden)

    Melissa Orzechowski Xavier

    2008-06-01

    Full Text Available Aspergillosis in captivity seabirds is often associated with elevated rates of mortality. The infection is usually acquired by inhalation of airborne fungal conidia. The aim of this study was to evaluate the presence of Aspergillus species in the indoor environment of a rehabilitation centre for marine animals in Southern Brazil. This centre continuously receives injured penguins, seagulls, albatrosses and petrels. Petri dishes plates with Agar Sabouraud dextrose and chloramphenicol were left open for 15 minutes in 3 distinct points in the rehabilitation centre and then incubated at 25ºC. During a period of two years the indoor air was sampled in 81 occasions. A total of 43 isolates belonging to 7 different Aspergillus species were recovered. Aspegillus fumigatus was the predominant species (27.9%, followed by A. niger (25.6%, and A. flavus (16.3%. Four other Aspergillus species were isolated. This study demonstrates that seabirds were exposed to pathogenic Aspergillus species in our rehabilitation centre, reinforcing the need for a strict microbiology control of the indoor air in the captivity environment.

  20. Simple and highly discriminatory VNTR-based multiplex PCR for tracing sources of Aspergillus flavus isolates.

    Directory of Open Access Journals (Sweden)

    Dong Ying Wang

    Full Text Available Aspergillus flavus is second only to A. fumigatus in causing invasive aspergillosis and it is the major agent responsible for fungal sinusitis, keratitis and endophthalmitis in many countries in the Middle East, Africa and Southeast Asia. Despite the growing challenge due to A. flavus, data on the molecular epidemiology of this fungus remain scarce. The objective of the present study was to develop a new typing method based on the detection of VNTR (Variable number tandem repeat markers. Eight VNTR markers located on 6 different chromosomes (1, 2, 3, 5, 7 and 8 of A. flavus were selected, combined by pairs for multiplex amplifications and tested on 30 unrelated isolates and six reference strains. The Simpson index for individual markers ranged from 0.398 to 0.818. A combined loci index calculated with all the markers yielded an index of 0.998. The MLVA (Multiple Locus VNTR Analysis technique proved to be specific and reproducible. In a second time, a total of 55 isolates from Chinese avian farms and from a Tunisian hospital have been evaluated. One major cluster of genotypes could be defined by using the graphing algorithm termed Minimum Spanning Tree. This cluster comprised most of the isolates collected in an avian farm in southern China. The MLVA technique should be considered as an excellent and cost-effective typing method that could be used in many laboratories without the need for sophisticated equipment.