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Latest articles on diagnosis (most recent listed first):

  • Allergic Bronchopulmonary Aspergillosis in a child by Slavin RG, Laird TS, Cherry JD (1970) Abstract

    The syndrome of allergic bronchopulmonary aspergillosis is exceedingly rare in the United States. We have studied a 9-year-old child who fulfills all of the clinical and laboratory criteria of this syndrome, and who is believed to be the first patient in the pediatric age range reported in this country. Clinical and laboratory features include wheezing with fever, transient pulmonary infiltrates, eosinophilia of blood and sputum, septate hyphae and positive culture for Aspergillus fumigatus in the sputum, and skin-sensitizing antibody and precipitating antibody to Aspergillus fumigatus. Successful treatment included administration of corticosteroids orally and of amphotericin B by aerosol.

  • Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis by Koo S, Bryar JM, Baden LR, Marty FM (2010) Abstract

    Background: Prognostic features of serum galactomannan (GM) remain poorly defined in patients with galactomannan-positive invasive aspergillosis (GPA). Materials and Methods: We identified 93 patients with proven or probable invasive aspergillosis (IA) and GM >/= 0.50 from January 2005 to March 2009. We used Cox modeling of time to 6- and 12-week mortality for GM at diagnosis (GM0), GM decay in the week following diagnosis in 72 patients with >/= 2 GM values, other predictors of mortality, and antifungal use during the week following diagnosis. Results: Six-week mortality was 55% in the whole cohort and 43% in patients with >/=2 GM determinations. The HR of GM0 per unit increase and one-week GM decay per unit decline per week were 1.25 (95% CI 1.01-1.54, p=0.04) and 0.78 (95% CI 0.63-0.96, p=0.02), respectively, adjusting for other predictors of IA mortality; these values remained stable after adjusting for antifungal use and were predictive of all-cause mortality at 12 weeks with similar adjusted HR values. Conclusions: The combination of GM0 and one-week GM decay are predictive of all-cause mortality in patients with GPA, independent of other traditional risk factors for mortality and antifungal exposure, supporting GM decay as a potential surrogate endpoint for future antifungal therapeutic trials.

  • Aspergillus and the paediatric lung by Hatziagorou E, Walsh TJ, Tsanakas JN, Roilides E (2009) Abstract

    Aspergillus spp produce a wide range of saprophytic and invasive syndromes in the lungs, including allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and invasive pulmonary aspergillosis (IPA). ABPA results from hypersensitivity to the fungus, and mainly affects patients with asthma or cystic fibrosis (CF). The treatment of choice consists of systemic corticosteroids and itraconazole. Aspergilloma is managed by observation or surgery. IPA is predominantly seen in patients with haematological malignancies, chronic granulomatous disease or immunosuppressive treatment. With the use of aggressive therapies for end-stage CF, such as heart-lung transplantation, the potential for a patient to convert from colonization or ABPA to IPA has increased. Suggestive clinical and radiological findings, supplemented with mycological data using serology and molecular biology, have enhanced the capacity to diagnose IPA in paediatric patients. While voriconazole is considered the first-line therapy in IPA, several other antifungal agents may be appropriate alternatives.

  • Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation by Castagnola E, Furfaro E, Caviglia I, Licciardello M, Faraci M, Fioredda F, Tomà P, Bandettini R, Machetti M, Viscoli C (2010) Abstract

    Clin Microbiol Infect Abstract Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

  • Organising pneumonia mimicking invasive fungal disease in patients with leukaemia by Forghieri F, Potenza L, Morselli M, Maccaferri M, Pedrazzi L, Barozzi P, Vallerini D, Riva G, Zanetti E, Quadrelli C, Rossi G, Rivasi F, Messino M, Rumpianesi F, Grottola A, Venturelli C, Pecorari M, Codeluppi M, Torelli G, Luppi M (2010) Abstract

    Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organizing pneumonia (OP) in 5 cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in leukemic patients with probable/possible IFD.

  • Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm by Eaton T, Garrett J, Milne D, Frankel A, Wells AU (2000) Abstract

    OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) occurs in cases of atopic asthma and may result in important lung disease. Early diagnosis is essential as this disease is responsive to steroids. However, while asthma is common, ABPA is infrequently diagnosed. CT allows precision in the diagnosis of central bronchiectasis (which is virtually pathognomonic of ABPA) and may enable earlier diagnosis. DESIGN: A prospective evaluation of 255 patients with asthma for ABPA, using skin prick testing (SPT) for Aspergillus fumigatus (AF) as a screening tool and incorporating CT into the diagnostic algorithm. SETTING: Asthma clinic, Green Lane Hospital, Auckland, New Zealand. PARTICIPANTS: Patients with asthma. INTERVENTIONS: ABPA was diagnosed using "essential" criteria (ie, asthma, SPT positivity to AF, elevated serum total IgE, elevated serum AF-specific IgE, and pulmonary infiltrates seen on chest radiography or central bronchiectasis seen on CT scan) and "minimal essential" criteria (ie, asthma, SPT positivity, and central bronchiectasis). MEASUREMENTS AND RESULTS: Two hundred fifty-five consecutive patients with asthma who consented to SPT were studied: 218 of 255 patients (86.8%) were atopic; and 47 of 255 patients (21.6%) were AF-positive, of whom 35 accepted further evaluation including CT scanning. A secure diagnosis of ABPA, satisfying all essential criteria, was evident in 9 of 35 patients (25.7%), a proportion that increased to 13 of 35 patients (37.1%) by using the minimal essential diagnostic criteria. CONCLUSIONS: SPT positivity to AF was present in approximately 20% of patients in the asthma clinic. A diagnosis of ABPA is disclosed by CT in 25 to 40% of SPT-positive patients, depending on the selection of diagnostic criteria. These findings support the use of SPT as a screening tool in the asthma clinic and indicate that a routine CT scan is warranted in SPT-positive patients.

  • Allergic bronchopulmonary aspergillosis by Greenberger PA (2002) Abstract

    Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis. The survival factors in Aspergillus fumigatus that support saprophytic growth in bronchial mucus are not understood. Prednisone remains the most definitive treatment but need not be administered indefinitely. MHC II -restricted CD4(+) T( H)2 clones have been derived from patients with ABPA. The total serum IgE concentration is elevated sharply but is "nonspecific. " IgE serum isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast to the situation for patients with asthma without ABPA. High-resolution computed tomography of the chest demonstrates multiple areas of bronchiectasis in most patients with ABPA and is a useful radiologic tool. Some asthma control patients might have a few bronchiectatic airways, but not to the extent seen in or of the same character as those in ABPA. This review discusses clinical, radiologic, investigational, pathogenetic, and treatment issues of ABPA.

  • Allergic bronchopulmonary aspergillosis: the spectrum of computed tomography appearances by Panchal N, Bhagat R, Pant C, Shah A (1997) Abstract

    Although computed tomography (CT) of the thorax has been compared to plain chest radiography and bronchography for demonstration of central bronchiectasis (CB) in allergic bronchopulmonary aspergillosis (ABPA), the CT presentation of the disease is yet to be highlighted. With this in view, the CT appearances in 23 patients with ABPA were evaluated. The scans were assessed for bronchial, parenchymal and pleural abnormalities. Central bronchiectasis was identified in all patients, involving 114 (85%) of the 134 lobes and 210 (52%) of the 406 segments studied. Other bronchial abnormalities such as dilated and totally occluded bronchi (11 patients), air-fluid levels within dilated bronchi (five patients), bronchial wall thickening (10 patients) and parallel-line shadows (seven patients) were also observed. Parenchymal abnormalities, which had a predilection for upper lobes, included consolidation in 10 (43%) patients, collapse in four (17%) patients and parenchymal scarring in 19 (83%) patients. A total of six cavities were seen in three (13%) patients, and an emphysematous bullae was detected in one (4%) patient. The pleura was involved in 10 (43%) patients. Ipsilateral pleural effusion with collapse was observed in one patient, while in nine other patients, parenchymal, lesions extended up to the pleura. Concomitant allergic Aspergillus sinusitis (AAS) was also detected in three (13%) of the 23 patients. Computed tomography of the thorax in patients with ABPA provides a sensitive method for the assessment of bronchial, parenchymal and pleural abnormalities, and should constitute a part of the diagnostic work of the disease.

  • Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients by Hsu LY, Ding Y, Phua J, Koh LP, Chan DS, Khoo KL, Tambyah PA (2010) Abstract

    ABSTRACT: BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking. METHODS: We performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions. RESULTS: There were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA. CONCLUSIONS: Our results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.

  • Detection of Aspergillus fumigatus in A Rat Model of Invasive Pulmonary Aspergillosis by Real-time Nucleic Acid Sequence-Based Amplification (NASBA) by Zhao Y, Park S, Warn P, Shrief R, Harrison E, Perlin DS (2010) Abstract

    Rapid and sensitive detection of Aspergillus from clinical samples may facilitate an early diagnosis of invasive pulmonary aspergillosis (IPA). A real-time nucleic acid sequence-based amplification (NASBA) method was investigated in an inhalational rat model of IPA. Immunosuppressed male SD rats were exposed to A. fumigatus spores for an hour in an aerosol chamber. Bronchoalveolar lavage (BAL) fluid, lung tissues and whole blood were collected from 5 infected rats at 1, 24, 48, 72, and 96 h postinfection and 5 uninfected rats at the end of experiment. Total nucleic acid (TNA) was extracted on an easyMAG instrument. A primer-molecular beacon set targeting 28S rRNA was designed to detect Aspergillus spp. The results were compared to qPCR (18S rDNA) and quantitative culture. The analytical sensitivity of the real-time NASBA assay was < 1 CFU/assay. A linear range of detection was demonstrated over 5 logs of conidia (10 to 10(5) spores). Both NASBA and qPCR showed a progressive increase in lung burdens, whilst CFU counting was stable over time. The BAL fungal burdens were more variable and not indicative of a progressive infection. Both real-time assays correlated well on both sample types (r = 0.869; P < 0.0001 & r = 0.887; P < 0.0001). For all whole bloods, NASBA identified positive samples from 72 h (3/5) and 96 h postinfection group (5/5), but no positive results obtained by culture and PCR. Real-time NASBA is highly sensitive and useful in detecting Aspergillus from an experimental model of IPA.

  • The radiological appearances in allergic broncho-pulmonary aspergillosis by McCarthy DS, Simon G, Hargreave FE (1970) Abstract

    The X-Ray appearances in 111 cases of asthma complicated by broncho-pulmonary aspergillosis and eosinophilia are described. The incidence of these changes is tabulated. Emphasis is made on the importance of the radiological appearances in suggesting the diagnosis, and in assessing the lung damage when the diagnosis is established.

  • Aspergillosis of the central nervous system: a catastrophic opportunistic infection by Pongbhaesaj P, Dejthevaporn C, Tunlayadechanont S, Witoonpanich R, Sungkanuparph S, Vibhagool A (2004) Abstract

    The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

  • Aspergillus fumigatus necrotizing meningo-encephalitis following a road accident with open depressed fracture of the skull (article in French) by Guiot P, Kummerlen C, Gutbub AM, Laplatte G, Plas JY, Haegy JM (1993) Abstract

    We report a case of brain aspergillosis occurring after a road accident with open depressed fracture of the skull. Clinical presentation features a necrotizing meningo-encephalitis in an immuno-responsive patient with no underlying disease. Two cerebro-spinal fluid samples drawn at different times grow Aspergillus fumigatus thus establishing the diagnosis. Diagnosis is in general difficult owing to frequent negative isolates from blood or cerebro-spinal fluid. Immunological investigations are questionable and in many cases, only surgical procedures provide clues to the diagnosis showing typical molds. Treatment of such a condition combines surgical removal of lesions if possible and systemic antifungal therapy, the latter having a poor penetration in the cerebro-spinal fluid and needing careful monitoring owing to its numerous side-effects. Prognosis is poor, with a mortality rate about 70 %.

  • Aspergillosis in 25 renal transplant patients. Epidemiology, clinical presentation, diagnosis, and management by Weiland D, Ferguson RM, Peterson PK, Snover DC, Simmons RL, Najarian JS (1983) Abstract

    In immunocompromised renal transplant patients, aspergillosis can be a life-threatening opportunistic infection. During an 8-year period, 25 renal transplant recipients at the University of Minnesota Hospitals developed unequivocal invasive aspergillosis that occurred in epidemic-like patterns in immunocompromised patients throughout the hospital. The premortem diagnosis was made in only 14 of the 25 patients. Seventeen patients died, and three of the eight survivors lost their allografts. The prognosis was dependent upon the clinical pattern of illness: three clinical patterns emerged: (1) cavitary lung disease, (2) diffuse pulmonary disease, and (3) central nervous system disease. All patients in the latter two categories died. The best results were with those patients treated with both amphotericin B and excision of cavitary lung lesions. All three patients treated in this manner survived with functioning grafts. Traditionally, sputum cultures have been thought to be unreliable because Aspergillus is a common colonizer of the upper respiratory tract and a contaminant in laboratories. In this study, false positive sputum cultures were common. A positive sputum culture can be helpful, however, all patients with two positive sputum cultures proved to have invasive aspergillosis. In addition, 86% of patients with positive sputum cultures who were clinically ill proved to have invasive infection. Bronchoscopy is a useful technique to follow up a positive sputum culture or investigate negative sputum cultures with typical clinical patterns. Routine bronchoscopy, unfortunately, also yields a high incidence of false positive cultures. Since the use of covered brush bronchoscopy technique, however, no false positive transbronchial cultures have been found. Transbronchial biopsy is a useful adjunct and is proof of the presence of invasive disease when the results are positive. However, false negative results are also found. Overall, the highest diagnostic yield is obtained both with transbronchial lung biopsy and covered brush bronchoscopy culture. All eight patients with both these procedures were correctly identified as having invasive pulmonary aspergillosis.

  • Fungal infections in patients with acute leukemia by DeGregorio MW, Lee WM, Linker CA, Jacobs RA, Ries CA (1982) Abstract

    We reviewed the records of 32 patients with acute leukemia and proved invasive fungal infections to determine the clinical and pathologic characteristics of systemic mycosis in patients undergoing intensive induction chemotherapy. The incidence of invasive fungal infections among our patients was at least 27 percent, and Candida and Aspergillus accounted for the majority of these infections. Patients with systemic candidiasis generally had prolonged severe neutropenia, fever refractory to antibiotics, and evidence of mucosal colonization by fungi. At autopsy, Candida was always widely disseminated. Patients with aspergillosis generally had neutropenia, fever, and pulmonary infiltrates at the time of admission to the hospital and, at autopsy, their infections were primarily confined to the lungs. Patients infected with both Candida and Aspergillus had clinical and pathologic findings that were a combination of the features of each type of infection. A diagnosis of invasive fungal infection was established before death in only nine of the patients, all of whom had systemic candidiasis. Four of these patients were successfully treated and survived their hospitalization. The reasons for frequently misdiagnosing and unsuccessfully treating systemic mycosis in patients with acute leukemia are examined, and suggestions are made for improved management of patients at high risk for these infections. These suggestions are based upon recognition of the clinical settings in which fungal infections occur, the aggressive use of invasive diagnostic procedures, and the early empiric use of amphotericin B.

  • Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years' experience by McWhinney PH, Kibbler CC, Hamon MD, Smith OP, Gandhi L, Berger LA, Walesby RK, Hoffbrand AV, Prentice HG (1993) Abstract

    Over 13 years, we have seen 16 cases of proven invasive aspergillosis in 446 bone marrow transplant recipients, an incidence of 3.6%. The incidence of infection is low in patients with uncomplicated allogeneic or autologous bone-marrow transplants (< 2% and 0, respectively). Of the 16 episodes following transplantation, 10 occurred in patients with late transplant complications who were no longer in protective isolation. In patients who had focal pulmonary lesions (as diagnosed by computed tomographic scanning), culture of bronchoalveolar lavage (BAL) fluid was not an effective diagnostic procedure. In diffuse pulmonary disease due to Aspergillus, culture of BAL fluid had a sensitivity of 100%. Aspergillus species were isolated from an additional six patients who had no evidence of invasive aspergillosis. Graft rejection was a significant predisposing factor for the development of invasive aspergillosis (P < .001, log-rank test), and in our hospital, these patients now receive intravenous amphotericin B as prophylaxis. None of the six patients whose chest roentgenograms showed abnormalities before transplantation and who underwent surgical resection as part of the treatment for invasive aspergillosis developed recurrent infection.

  • Pulmonary fungal infections in patients with hematological malignancies - diagnostic approaches by von Eiff M, Zühlsdorf M, Roos N, Hesse M, Schulten R, van de Loo J (1995) Abstract

    In a retrospective study of 56 patients with hematological malignancies and fungal pneumonia we have analyzed the value of different diagnostic procedures. In all patients (Candida n = 29, Aspergillus n = 23, mixed fungal infection n = 4) bronchoscopy and/or high-resolution computed tomography of the lungs was performed. Cultural detection of fungi in bronchoalveolar lavage was successful in 23/32 Candida and 11/23 Aspergillus pneumonias. Other relevant pathogens were identified by bronchoscopy in 21 cases. Thorax CT scans showed diagnostic evidence of fungal pneumonia in 10/13 Candida and in 16/18 Aspergillus infections. Blood cultures were positive in 9/33 Candida pneumonias and in none of aspergillosis cases. Serological testing and surveillance cultures had only limited value for the early diagnosis of pulmonary mycosis. Our data suggest that bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools with high sensitivity in patients with hematological malignancies and new pulmonary infiltrates. These procedures facilitate the early and reliable recognition of invasive fungal disease which may have a bearing on the initiation, length, and differential therapy of antimycotic drugs.

  • Aspergillus PCR: one step closer towards standardisation by White PL, Bretagne S, Klingspor L, Melchers WJ, McCulloch E, Schulz B, Finnstrom N, Mengoli C, Barnes RA, Donnelly JP; Juergen Loeffler on behalf of the European Aspergillus PCR Initiative (2010) Abstract

    PCR has been used as an aid in the diagnosis of invasive aspergillosis for approaching two decades. A lack of standardisation limited both its acceptance as a diagnostic tool and multi-centre clinical evaluation preventing its inclusion in disease defining criteria. In 2006 the European Aspergillus PCR Initiative was formed whose aim was to provide optimal standardised protocols for widespread clinical evaluation of Aspergillus PCR to determine its diagnostic role and allow inclusion in disease diagnosis criteria. Quality control panels were developed and circulated to centres for evaluation of existing methodology before recommendations based on initial results were proposed for further panels. Centres were anonymously classified as "compliant" or "non-compliant" according to whether centres had followed the proposed recommendations before performance parameters and meta-regression analysis were performed. Most PCR amplification systems provided similar detection thresholds, although positivity was a function of fungal burden. When combining PCR amplification with DNA extraction 50% of centres failed to achieve the same level of detection. Meta-regression analysis showed positive correlations between sensitivity and extraction protocols incorporating the proposed recommendations, the use of bead-beating, white cell lysis buffer and an internal control PCR. The use of elution volumes above 100μL showed a negative correlation with sensitivity. The efficiency of Aspergillus PCR is limited by the extraction procedure and not by PCR amplification. For PCR testing of whole blood it is essential that large blood volumes (>3mL) are efficiently lysed, before bead-beating to disrupt the fungal cell and an internal control PCR to exclude false negativity. DNA should be eluted in volumes <100μL.

  • Eight-year study of allergic bronchopulmonary aspergillosis in an Indian teaching hospital by Chakrabarti A, Sethi S, Raman DS, Behera D (2002) Abstract

    A total of 651 patients with clinically suspected allergic bronchopulmonary aspergillosis (ABPA) were evaluated during the 8-year period from January 1991 to December 1998. Overall, 338 cases (51.9%) were positive either by sputum microscopy/culture (66 of 203 patients), by skin reactivity (150 of 309 cases), or by precipitating antibodies (122 of 338 patients) against Aspergillus species. However, in 89 patients, diagnosis of ABPA was confirmed on the basis of Rosenberg's criteria. Clinical profile and laboratory findings of those patients were analysed. The disease was found to be more common among males. Poor control of asthma, constitutional symptoms, mucopurulent expectoration, increased dyspnoea and wheezing and rhonchi were the main presenting features. Skin reactivity against aspergillin was seen in 73 (82%), precipitating antibodies against Aspergillus species were positive in 64 (72%) and sputum microscopy/culture was positive in 56 (63%) of those 89 patients. Central bronchiectasis and fleeting shadows were the most common radiological findings. This study highlights the importance of ABPA in north India and draws attention to the need for further analysis of criteria to use in the diagnosis of patients with ABPA.

  • Bronchial Aspergillosis (article in German) by Dobbertin I, Friedel G, Jaki R, Michl M, Kimmich M, Hofmann A, Eulenbruch HP, Weber J, Spengler W, Ott G, Kohlhäufl M (2010) Abstract

    Bronchopulmonary aspergillosis is becoming more frequent, is often hard to diagnose and with today's antimycotics better to treat than before. It is therefore of current interest. This also concerns bronchial aspergillosis which is less common than pulmonary aspergillosis and the topic of this paper. A total of 39 patients with bronchial aspergillosis are presented: 1) 4 cases with endobronchial aspergilla, two which are visual bronchoscopically, 2) one case with chronic necrotising pulmonary aspergillosis (CNPA), where a bronchus has necrotised, 3) an invasive aspergillosis in the region of a bronchial anastomosis, 4) 7 cases with an Aspergillus invasion from endobronchial tumour tissue and 5) 26 cases with allergic bronchopulmonary aspergillosis (ABPA). 37 of the 39 cases are part of a single centre study with a total of 116 bronchopulmonary aspergilloses, which were collected over seven years. The focus of attention in this paper is on the bronchoscopic and radiological results.

  • Antifungal agents of use in animal health--practical applications. by Rochette F, Engelen M, Vanden Bossche H. (2003) Abstract

    The purpose of this paper is to provide an overview of antifungal agents currently in use in veterinary medicine. The practical applications and the therapeutic regimens that have proved successful in the treatment and prevention of fungal infections in dogs and cats, cattle and sheep, horse, pig, poultry and other birds, rodents, rabbits and fur animals are summarized.

  • Diagnostic and therapeutic thoracic surgery in leukemia and severe aplastic anemia by Habicht JM, Gratwohl A, Tamm M, Drewe J, Proske M, Stulz P (1997) Abstract

    BACKGROUND: Pulmonary complications often occur in patients with leukemia and severe aplastic anemia. Particularly in patients having undergone bone marrow transplantation, respiratory diseases account for a significant number of deaths. In a retrospective study, we evaluated 41 patients with leukemia and severe aplastic anemia who were operated on consecutively from 1980 to 1995. METHODS: Fourteen open lung biopsies, four video-assisted lung biopsies, and 24 lung resections were performed in 24 male and 17 female patients. Mean age was 32.2 years. RESULTS: Eleven (27%) early deaths occurred (30-day mortality): ten in patients after lung biopsy (56%) and one after lung resection (4%) (p < 0.001). Perioperative morbidity relating to pulmonary disease or operation included 10 (24.4%) cases of prolonged (> 24 hours) postoperative mechanical ventilation and two (4.8%) cases of bleeding or hematoma. In one (2.4%) patient a slowly developing, contained bronchial stump insufficiency appeared after lobectomy, which was successfully operated on 3 weeks later. CONCLUSION: We conclude that resection of localized pulmonary lesions, be it for diagnostic or therapeutic (or combined) purposes, can be carried out with low morbidity and mortality in patients with leukemia and severe aplastic anemia. However, early mortality is high after open or thoracoscopic lung biopsies in patients with acute-onset diffuse pulmonary disease, and little therapeutic benefit is realized in these cases.

  • Prospective monitoring for invasive aspergillosis using galactomannan and polymerase chain reaction in high risk pediatric patients by Armenian SH, Nash KA, Kapoor N, Franklin JL, Gaynon PS, Ross LA, Hoffman JA (2009) Abstract

    BACKGROUND: The diagnosis of invasive aspergillus remains a challenge in the care of high-risk patients. Outcomes are improved when invasive aspergillus is diagnosed early, prompting the initiation of appropriate antifungal therapy. We evaluated the utility of prospective monitoring for invasive aspergillosis (IA) using biomarkers such as serum galactomannan (GM) and/or blood polymerase chain reaction (PCR) in high-risk pediatric patients. METHODS: Patients with high-risk leukemia (HRL) or allogenic hematopoietic cell transplant (HCT) recipients were prospectively monitored twice weekly for IA using GM and PCR for Aspergillus species. RESULTS: Sixty-eight patients had collected >or=2 specimens. The 1086 specimens were collected; 627 from HRL (58%) and 459 (42%) from HCT recipients. Median specimens/patient was 11.0 (2 to 58), and median follow-up/patient was 98.5 days (14 to 437). Fifty-six percent of samples were obtained from patients receiving mold-active agents; 32% HRL and 89% HCT. There were no proven, 3 probable, and 20 possible episodes of IA. Thirteen specimens (1.2%) from 4 patients (5%) were GM+. None were positive by PCR. CONCLUSIONS: The prospective use of GM and PCR in this high-risk pediatric population did not identify cases of proven IA. A high false positive rate was not detected. It is speculated that changes in clinical practice, such as early use of empiric and/or prophylactic mold-active agent and frequent imaging studies have impacted the epidemiology of IA. In a population with low incidence of IA, the use of these assays as a screening device on blood may not further enhance current outcomes.

  • Highly sensitive detection of fungal antigens by ultrasound-enhanced latex agglutination by Grundy MA, Barnes RA, Coakley WT (1995) Abstract

    Treatment with ultrasound has been employed to greatly enhance the sensitivity of commercially available latex agglutination tests for fungal antigens. This 5 min procedure detects 40 pg ml-1 of Candida albicans mannan and 70 pg ml-1 of Aspergillus fumigatus galactomannan, a 250 and 500-fold improvement respectively over conventional agglutination test sensitivities. The ultrasound-enhanced test offers the possibility of improved diagnosis and management of patients with systemical candidosis or invasive aspergillosis.

  • Invasive aspergillosis in patients with AIDS by Khoo SH, Denning DW (1994) Abstract

    The prolonged survival of profoundly immunocompromised patients with AIDS has contributed to the increasing recognition of aspergillus infections as an emerging problem. Nevertheless, many of these infections continue to be diagnosed only at autopsy. In this article we review details of 293 reported cases. Invasive aspergillosis occurs in advanced AIDS and most commonly affects the lungs, although brain involvement has also been frequently reported. The diagnosis is often difficult to make while the patient is alive, although examination of specimens obtained via bronchoalveolar lavage, percutaneous needle aspiration, or biopsy is often successful. Biopsy of the affected organ along with histologic examination and culture may be necessary for diagnosis. The dismal prognosis of invasive aspergillosis in patients with AIDS can be improved only with earlier diagnosis of disease and the availability of more-effective antifungal regimens.

  • Fungal sinusitis: diagnosis with CT and MR imaging by Zinreich SJ, Kennedy DW, Malat J, Curtin HD, Epstein JI, Huff LC, Kumar AJ, Johns ME, Rosenbaum AE (1988) Abstract

    Of 293 patients who underwent computed tomography (CT), surgery, and pathologic examination for chronic sinusitis, 25 had a diagnosis of fungal sinusitis at pathologic examination. Of these, 22 had foci of increased attenuation at CT (in four patients the mean representative CT number [Hounsfied unit] was 122.2 HU [SD, 8.2 HU]), and three did not. Of the 22, 19 patients (76%) met the CT criterion of this study (there was a 12% false-positive and a 12% false-negative diagnostic rate). Six of the 19 patients and one additional patient underwent magnetic resonance (MR) imaging, and all demonstrated remarkably hypointense signal characteristics on T2-weighted images. The findings at MR imaging therefore appear more characteristic of fungal sinusitis than the findings at CT. Furnace atomic absorption spectrometry showed increased concentrations of iron and manganese in mycetoma compared with their concentrations in bacterially infected mucus. This finding and the presence of calcium in the fungal concretion may explain the hypointense T2-weighted signal on MR images.

  • Aspergillosis of the nose and paranasal sinuses by Romett JL, Newman RK (1982) Abstract

    Aspergillosis is becoming an increasingly recognized pathogen in the sinonasal tract. The courses of two patients, one seemingly healthy and one with a terminal malignancy, are reviewed. These patients illustrate the clinical course, difficulties in diagnosis, and management of patients with aspergillosis of the sinonasal tract. Aspergillus is a common endogenous contaminant of the upper respiratory tract; however, bacterial sinusitis may trigger its growth and proliferation. Aspergillus fumigatus is the most common species implicated in paranasal sinus disease in the United States. The maxillary antrum is the most commonly involved site in the paranasal sinuses. Originally, aspergillosis was described in healthy patients, but it has become increasingly recognized in the immunocompromised and the chronically debilitated. Paranasal sinus Aspergillus infections are classified as non-invasive and fulminant. The treatment is primarily surgical. Antifungal chemotherapeutic agents are used in the treatment of central nervous system involvement and in the fulminant form of the disease.

  • Carotid-cavernous sinus thrombosis caused by Aspergillus fumigatus. Case report by Sekhar LN, Dujovny M, Rao GR (1980) Abstract

    A case is presented of Aspergillus fumigatus granuloma involving the sphenoid sinus, sella turcica, cavernous sinus, and the internal carotid artery. The diagnosis was established by a transsphenoidal biopsy. The infection proved difficult to treat and finally remitted after chemotherapy with a combination of amphotericin B, rifampin (rifampicin), and flucytosine (5-fluorocytosine). The spectrum of aspergillosis of the central nervous system is reviewed, and difficulties in treating this infection are considered.

  • Aspergillosis of the sphenoid sinus simulating a pituitary tumor by Larrañaga J, Fandiño J, Gomez-Bueno J, Rodriguez D, Gonzalez-Carrero J, Botana C (1989) Abstract

    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 mimicked 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.

  • Fungal nail disease: a guide to good practice (report of a Working Group of the British Society for Medical Mycology) by Denning DW, Evans EG, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, Warnock DW, Warren RE (1995) Abstract

    The term onychomycosis refers to fungal infection of the nails whether this is a primary event or a secondary infection of a previously diseased or traumatised nail. Infection may be due to dermatophyte (ringworm, tinea unguium), yeast, or other non-dermatophyte (mould) species, and the clinical appearance may indicate the nature of the infecting organism. In paronychia chronic infection of the nail fold is most often caused by Candida species, but bacterial infection with Gram negative species such as Pseudomonas may coexist. Acute paronychia (whitlow) due to staphylococcal infection may also occur, and the presence of these bacterial infections will influence management. Invasion of the nail plate by Candida species may occur in the presence of paronychia, immune deficiency states (including chronic mucocutaneous candidiasis), Raynaud's disease, or endocrine disorders.

  • Aspergillus thyroiditis in a living donor liver transplant recipient by Matsui Y, Sugawara Y, Tsukada K, Kishi Y, Shibahara J, Makuuchi M (2006) Abstract

    Aspergillosis is increasingly recognized as an important nosocomial pathogen in immunocompromised patients. Infection is difficult to diagnose and typically has a fatal outcome. We describe a liver transplant patient with fulminant hepatic failure, who had persistent fever of undetected origin postoperatively and an increased (1-3)-beta-d glucan level. Gallium-67 citrate scanning showed abnormal uptake in the thyroid bilaterally. Fine needle biopsy of the thyroid revealed thyroidal invasion of Aspergillosis. Total thyroidectomy was performed and the C reactive protein level decreased to 1.01 mg/dl. The patient died of liver sepsis due to Pseudomonas aeruginosa. (1-3)-beta-d Glucan monitoring and systematic radionuclide images are useful modalities for early diagnosis of Aspergillosis.

  • Pulmonary aspergilloma - radiological observations by Singh P, Kumar P, Bhagi RP, Singla R (1989) Abstract

    The radiological appearances of 49 cases of aspergilloma seen over a period of 6 years among 36,340 hospital admissions are described. All the 49 patients had pulmonary tuberculosis as underlying disease with 6 (12.2%) having bacteriologically active disease. One patient had concomitant allergic bronchopulmonary aspergillosis (ABPA). Upper zone distribution, large cavity size, moderately thick cavity wall and overlying pleural thickening were some of the prominent features observed. Two cases of multiple (3 each) and 4 of bilateral aspergilloma were seen. Of 57 aspergillomas 47 were round or oval, 7 oblong, 2 polypoidal and 1 lobulated. Positional movement was observed in 30 cases. Spontaneous lysis was seen in one case. Tomography and lordotic view were found to be very useful techniques when postero-anterior films were unrevealing. The radiologic diagnosis of aspergilloma was confirmed by demonstration of serum precipitins against aspergilli in 44 cases.

  • Postmortem analysis of invasive aspergillosis in a tertiary care hospital by Vogeser M, Haas A, Aust D, Ruckdeschel G (1997) Abstract

    To estimate the incidence of fatal invasive aspergillosis in a 1500-bed tertiary-care hospital and to investigate the utility of laboratory diagnostic approaches, necropsy protocols and microbiological data from 1994 and 1995 were reviewed. Among 694 necropsies from 1693 patients who died in these two years, 27 (4%) cases of invasive aspergillosis were identified. Twelve cases of invasive aspergillosis were found after transplantation of solid organs, three after bone marrow transplantation, four in patients with haematological malignancies, and five in patients with solid tumours. In 15 cases (56%) invasive aspergillosis was not suspected before death. In patients in whom serum sampling was performed seven days antemortem, the Aspergillus latex agglutination test had a sensitivity of 53% (9/17). Culture of tracheal secretions or bronchoalveolar lavage fluid from patients with pulmonary aspergillosis yielded Aspergillus fumigatus in 88% (14/16).

  • Invasive aspergillosis. Progress in early diagnosis and treatment by Fisher BD, Armstrong D, Yu B, Gold JW (1981) Abstract

    Ninety-one patients with documented invasive infections due to an Aspergillus species were identified at Memorial Sloan-Kettering Cancer Center from July 1, 1971, through December 31, 1976. Of the 29 patients in whom the diagnosis was made during life, 10 had successful treatment and survived the Aspergillus infection by two to 17 months. An immunodiffusion test was useful in the early diagnosis of invasive aspergillosis, and in 11 patients in whom the diagnosis was supported by seroconversion and who underwent treatment, the survival rate was 64 percent. Cultures of respiratory secretions were not reliable because they often reflected only colonization. In one year, only 9 percent of he patients with Aspergillus species isolated from the sputum had an invasive infection. The lung was the commonest site of involvement, 91 percent of the patients having pulmonary lesions. The most frequently affected extrapulmonary organ was the brain (18.3 percent). Eight patients had nonpulmonary aspergillosis as the only manifestation of this infection. Most of the 91 patients had hematologic neoplasms as the underlying disease, and neutropenia and antibacterial therapy preceded the diagnosis of aspergillosis in the majority of cases.

  • Clinically Driven Diagnostic Antifungal Approach in Neutropenic Patients: A Prospective Feasibility Study by Girmenia C, Micozzi A, Gentile G, Santilli S, Arleo E, Cardarelli L, Capria S, Minotti C, Cartoni C, Brocchieri S, Guerrisi V, Meloni G, Foà R, Martino P (2009) Abstract

    PURPOSE: Preemptive strategies in neutropenic patients based on serum galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. PATIENTS AND METHODS: Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions. RESULTS: Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found. CONCLUSION: A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.

  • Development of an HPTLC-based diagnostic method for invasive aspergillosis by Puri A, Ahmad A, Panda BP (2009) Abstract

    A rapid, sensitive and specific high-performance thin-layer chromatographic (HPTLC) method was developed and validated for determination of gliotoxin in Aspergillus infected immunocompromised patients with invasive aspergillosis (IA). Densitometric analysis of gliotoxin was carried out in the absorbance mode at 254 nm after single-step extraction with chloroform. The method uses TLC aluminum plates pre-coated with silica gel 60F-254 as a stationary phase and toluene-isoamyl alcohol-methanol (10:0.5:0.5, v/v/v) as mobile phase, which gives compact spot of gliotoxin (R(f) = 0.51). The calibration curve was linear (r(2) >/= 0.994) between peak area and concentration in the tested range of 100-1000 ng spot(-1) with minimum detectable range 0.025 ng mu(-1) of serum sample. The mean +/- SD value of slope and intercept of the standard chromatogram of gliotoxin were found to be 523.2 +/- 1.555635 and 915.8 +/- 30.68843, respectively. The developed method is simple, rapid, precise and less costly than earlier diagnostic methods, and different serum samples can be run on a single TLC plate for comparative analysis. The proposed method can be used to analyze gliotoxin in patient serum for easy, rapid and cost-effective diagnosis of IA.

  • Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients by Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, Spriet I, Verbeken E, Van Wijngaerden E (2008) Abstract

    RATIONALE: Invasive aspergillosis (IA) is an important cause of mortality in patients with hematologic malignancies. However, IA appears to be gaining a foothold in the intensive care unit (ICU) in patients without classical risk factors. A recent study described 89 cases of IA in patients in a medical ICU without leukemia or cancer. The diagnosis of IA remains difficult and is often established too late. Galactomannan (GM) is an exo-antigen released from Aspergillus hyphae while they invade host tissue. OBJECTIVES: This prospective single-center study was conducted to investigate the role of GM in bronchoalveolar lavage (BAL) fluid as a tool for early diagnosis of IA in the ICU. METHODS: All patients with risk factors identified in our earlier study were evaluated. BAL for culture and GM detection, serum GM levels, and computed tomography scan were obtained for all included patients with signs of pneumonia. Patients were classified as having proven, probable, or possible IA. MEASUREMENTS AND MAIN RESULTS: A total of 110 patients out of 1,109 admissions were eligible. There were 26 proven IA cases. Using a cutoff index of 0.5, the sensitivity and specificity of GM detection in BAL fluid was 88 and 87%, respectively. The sensitivity of serum GM was only 42%. In 11 of 26 proven cases, BAL culture and serum GM remained negative, whereas GM in BAL was positive. CONCLUSIONS: IA is common in immunocompromised, critically ill patients. GM detection in BAL fluid seems to be useful in establishing or excluding the diagnosis of IA in the ICU.

  • Monitoring of nosocomial invasive aspergillosis and early evidence of an outbreak using cumulative sum tests (CUSUM) by Menotti J, Porcher R, Ribaud P, Lacroix C, Jolivet V, Hamane S, Derouin F (2009) Abstract

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

  • Bronchoscopic and CT findings of invasive tracheobronchial and pulmonary aspergillosis in patients without immnunodeficiency (article in Chinese) by Li YP, Chen CS, Ye M, Ye JR, Zhou Y, Wu XL (2009) Abstract

    OBJECTIVE: To explore the bronchoscopic and CT findings of invasive tracheobronchial and pulmonary aspergillosis in patients without immunodeficiency. METHODS: Clinical data and bronchoscopic and CT findings of 6 patients with tracheobronchial and pulmonary aspergillosis were reviewed from January 2004 to August 2008. RESULTS: All the patients had no immunodificiency diseases. The bronchoscopic findings mostly presented in 2 forms: single endobronchial nodule and ulcerative or pseudomembranous tracheobronchitis. The lesions were diffusely distributed or localized. Chest CT showed tracheal or bronchial wall thickening in the early stage, and with disease progression, local consolidation or multiple nodules and cavitation became the most common findings. The nodules and cavities were predominantly peribronchial. A solitary nodule was found in 2 patients. All the cases had been misdiagnosed as other diseases, and repeated courses of antibiotics or corticosteroids had been tried. CONCLUSIONS: Ulcerative or pseudomembranous tracheobronchitis and single nodule are the most common bronchoscopic findings of invasive tracheobronchial aspergillosis. Local consolidation, multiple nodules and cavitation with predominantly peribronchial distribution are the most common CT findings.

  • Clinical and pathological analysis of allergic bronchopulmonary aspergillosis in China (article in Chinese) by Ye F, Zhang NF, Zhong NS (2009) Abstract

    OBJECTIVE: To describe the clinical features and diagnosis of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Three cases of ABPA from this hospital were presented. Chinese Biomedical Disk (CBM-Disk) was searched to identify Chinese ABPA cases from 1991 to 2008, and a retrospective analysis of all the cases was made. RESULTS: Fifty-seven cases of ABPA were collected, including 33 male and 24 female patients, with a mean age of (41 +/- 15) yrs. The main clinical manifestations included cough (n = 51), expectoration (n = 50), wheeze (n = 47), dyspnea (n = 44), fever (n = 33), hemoptysis (n = 28), sputum plugs (n = 18), chest pain (n = 13) and weight loss (n = 8). Forced expired volume in one second (FEV1) was (64 +/- 25)% predicted, and FEV1/forced vital capacity (FVC) was (63 +/- 11)%. Chest CT was performed in 33 cases. Patchy infiltration was present in 32, central bronchiectasis in 25, mucoid impaction (glover-finger/band linear opacities) in 12, nodular opacities in 11, consolidation in 8 and mediastinal adenopathy in 13 cases, while 24 cases presented fleeting infiltrations. CONCLUSION: ABPA is a rare disease. Measurement of total IgE, A. fumigatus-specific IgE, and immediate cutaneous reaction to A. fumigatus are help for confirmation of the diagnosis.

  • PCR-based diagnosis of human fungal infections by Khot PD, Fredricks DN (2009) Abstract

    PCR is a very appealing technology for the detection of human pathogens, but the detection of fungal pathogens is particularly challenging. Fungi have cell walls that impede the efficient lysis of organisms and liberation of DNA, which can lead to false-negative PCR results. Conversely, some human pathogens are also ubiquitous environmental saprophytes that can contaminate PCR reagents and cause false-positive results. We examine the quality of PCR-based studies for fungal diagnostics using 42 variables within the Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines. This review focuses on taxon-directed PCR assays for the diagnosis of invasive aspergillosis, candidiasis and Pneumocystis pneumonia. Finally, we evaluate broad-range fungal PCR assays capable of detecting a wide spectrum of human pathogens.

  • Investigation of Blood Culture Negative Early Prosthetic Valve Endocarditis Reveals High Prevalence of Fungi by Thuny F, Fournier PE, Casalta JP, Gouriet F, Lepidi H, Riberi A, Collart F, Habib G, Raoult D (2009) Abstract

    CONTEXT: Early prosthetic valve endocarditis is a deadly disease and blood cultures remain negative in 14% to 30% of cases. OBJECTIVES: To analyze the clinical and microbiological profile of patients with blood culture negative early prosthetic valve endocarditis ("BCN early PVE") in order to define the most appropriate empiric treatment. Design, SETTING AND PARTICIPANTS: From June 2001 to February 2009, a prospective multimodal strategy incorporating serological, molecular and histopathological assays was performed in all the samples referred to our laboratory for a suspicion of blood culture negative endocarditis from France and abroad (n=718). A total of 31 patients with "BCN early PVE" were identified. Their microbiological profile was compared with that of 22 patients with blood culture positive early prosthetic valve endocarditis ("PBC early PVE") and 628 patients with "Community-acquired BCNE" identified during the same period. RESULTS: A pathogen was identified in 10 patients (32%) with "BCN early PVE". Fungi were the most common pathogens identified being found in 16% versus 4.5% in case of "PBC early PVE" and 0.5% in "Community-acquired BCNE" (p<0.0001). The global microbiological profile of "BCN early PVE" differed strongly from that of "PBC early PVE" and "Community-acquired BCNE". A higher rate of microbiological diagnosis was obtained in patients who underwent surgery (9/21 [43%] versus 1/10 [10%], p=0.07) and an increased rate of recurrences was observed when a pathogen could not be identified (9/21 [43%] versus 1/10 [10%], p=0.07). CONCLUSIONS: "BCN early PVE" exhibit specific aetiologies as fungi are the most frequent pathogens identified. Therefore, we suggest investigating fungi particularly by molecular methods on surgical specimen and that an antifungal drug might be added to the empiric treatment.

  • Comparison of three antigenic extracts of Eurotium amstelodami in farmer's lung disease serological diagnosis by Roussel S, Reboux G, Rognon B, Monod M, Grenouillet F, Quadroni M, Fellrath JM, Aubert JD, Dalphin JC, Millon L (2009) Abstract

    In France and Finland, farmer's lung disease (FLD), a hypersensitivity pneumonitis common in agricultural areas, is caused mainly by Eurotium species. The presence of antibodies in patients' serum is an important criterion for diagnosis. Our study aimed to improve serological diagnosis of FLD by using common fungal particles that pollute the farm environment as antigens. Fungal particles of the Eurotium species were observed in handled hay. A strain of Eurotium amstelodami was grown in vitro using selected culture media, and antigen extracts from sexual (ascospores), asexual (conidia) and vegetative (hyphae) forms were made. Antigens were tested by Enzyme Linked Immunosorbent Assay (ELISA), testing for immunoglobulin G antibodies from the sera of 17 FLD patients, 40 healthy exposed farmers and 20 non-exposed controls. The antigens were compared by Receiver Operating Characteristic analysis and a threshold was then established. Ascospores contained in asci enclosed within cleistothecia were present in 38% of the hay blades observed; conidial heads of aspergilli conidial heads of aspergilli were less present. The same protocol was followed to make the three antigen extracts. A comparison of results for FLD patients and exposed controls showed the area under the curve to be 0.850 for ascospore antigen, 0.731 for conidia and 0.690 for hyphae. The cut-off we determined, with the standard deviation for measures taken into account, showed 67% for sensitivity and 92% for specificity with the ascospore antigen. In conclusion, serological diagnosis of FLD by ELISA was improved by the adjunction of ascospore antigen.

  • Use of the immunodiffusion test in the serodiagnosis of aspergillosis by Coleman RM, Kaufman L (1972) Abstract

    The diagnostic value of an immunodiffusion (ID) test with standardized precipitinogens derived from five Aspergillus species was determined with sera from 60 proven and 12 suspected cases of aspergillosis. The data demonstrated that the greatest number of aspergillosis cases were detected by the concurrent use of A. fumigatus and A. niger precipitinogens. With these precipitinogens, the ID test permitted the serodiagnosis of aspergillosis in 82% of the 60 proven cases and in 83% of the 12 suspected cases. The presence of one or more precipitins was indicative of aspergilloma, of allergic bronchopulmonary aspergillosis, or of invasive aspergillosis. Precipitins were detected in 93% of the sera from patients with aspergilloma, in 50% of the sera from patients with allergic bronchopulmonary aspergillosis, and in 88% of the sera from patients with invasive aspergillosis. Although the presence of one or two precipitin bands could indicate any form of aspergillosis, the presence of three or four was strong evidence of either aspergilloma or invasive aspergillosis. The ID test was found to be 100% specific in an evaluation of its effectiveness with 65 sera from individuals with other systemic mycotic infections, bacterial or neoplastic diseases, and from apparently normal humans. In diagnosed cases of aspergillosis, the examination of serial serum specimens provided information about the clinical course of the disease. A reduction in the number of precipitin bands and significant titer changes were noted as the patients responded to therapy.

  • Galactomannan Antigenemia in Invasive Aspergillosis by Reiss E, Lehmann PF (1979) Abstract

    Galactomannan (GM) extracted from mycelia of Aspergillus fumigatus with cold dilute alkali reacted with antiserum specific for an antigen that circulated in invasive aspergillosis in rabbits and humans. The GM was purified by its affinity for concanavalin A and was separated from a nonantigenic glucan by gel permeation on Sephacryl S-200. The GM molecular weight of between 25,000 to 75,000 was smaller than the antigen present in infected rabbit serum which was retained by an ultrafiltration membrane that had a nominal molecular weight limit of 125,000. The ratio of galactose to mannose present in GM was 1:1.17. The serological activity of GM was stable to boiling but labile to 0.01 N HCl, implicating galactofuranose as an antigenic determinant. Analysis of purified GM by methylation-gas chromatography suggested a structure consisting of a 1 leads to 6-linked mannan backbone with oligogalactoside side chains 3 units long, terminating in galactofuranose. The presence of mannose as a side chain component was also inferred. Another antigen of A. fumigatus, which did not bind to concanavalin A, was isolated after tandem chromatography on diethylaminoethyl- and carboxymethyl-Sephadex and was identified as a galactan. The galactan inhibited the immune precipitation of GM was specific antiserum.

  • Detection of circulating antigen of Aspergillus fumigatus in sera of mice and rabbits by enzyme-linked immunosorbent assay by Richardson MD, White LO, Warren RC (1979) Abstract

    Circulating antigen of Aspergillus fumigatus was demonstrated in the sera of experimentally infected, cortisone-treated mice and rabbits by enzyme-linked immunosorbent assay (micro-ELISA), confirming earlier results where fungal antigen had been detected by counter-immunoelectrophoresis (CIE). Peaks of detection of circulating antigen by CIE and micro-ELISA in mice were not simultaneous suggesting that the nature of the predominant antigens may have altered during the course of infection. CIE failed to detect fungal antigen in infected rabbits whereas micro-ELISA monitored antigenemia until death. Both CIE and micro-ELISA demonstrated the rapid clearance of intravenously inoculated Aspergillus-antigen from the rabbit circulation.

  • Antifungal activity of itraconazole and voriconazole against clinical isolates obtained from animals with mycoses by Okabayashi K, Imaji M, Osumi T, Murakami Y, Maruyama H, Kano R, Hasegawa A, Watanabe T (2009) Abstract

    Animal mycosis, particularly deep mycosis, is one of the most challenging conditions encountered by veterinarians. Pathogens causing mycotic infections in animals include fungi such as Cryptococcus neoformans, Candida spp., and Aspergillus spp. The antifungal drugs used for the treatment of deep mycoses in animals as well as humans are polyenes and azoles. However, the sensitivity of clinical isolates obtained from animals toward these drugs has rarely been assayed. In this study, the antifungal activities of itraconazole and voriconazole against clinical isolates of C. neoformans, Candida spp., and A. fumigatus isolated from animals with mycoses were examined using the broth microdilution method performed according to the guidelines provided by the Clinical and Laboratory Standards Institute. The minimum inhibitory concentrations (MICs) of itraconazole toward the C. neoformans, Candida spp., and A. fumigatus isolates were 0.125 - 1, 0.125 - 2, and 0.25 - 2 microg/ml, respectively, and those of voriconazole were 0.0625 - 0.5, < or =0.0313 - 0.0625, and 0.0625 - 1 microg/ml, respectively. The results of the MIC analyses implied that the fungal isolates obtained from infected animals exhibit an equivalent degree of susceptibility to itraconazole and voriconazole, as is observed in the case of isolates obtained from humans. The appropriate antifungal therapeutic strategy for the treatment of mycoses in animals must be selected taking into consideration the host immune status and organ function as well as the in vitro sensitivity of the pathogens to antifungal drugs.

  • Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome by Eppinger TM, Greenberger PA, White DA, Brown AE, Cunningham-Rundles C (1999) Abstract

    BACKGROUND: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species-induced pneumonia. OBJECTIVE: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE. METHODS: We measured A fumigatus-specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities). RESULTS: Twelve (67%) of 18 patients were sensitized to A fumigatus, as evidenced by precipitating A fumigatus-specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA. CONCLUSIONS: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA.

  • Toward a comprehensive understanding of allergic lung disease by Corry DB, Kheradmand F (2009) Abstract

    Allergic asthma is a respiratory disease induced by exposure to environmental agents that elicit allergic inflammation and transient airway obstruction and which produce the characteristic symptoms of cough and dyspnea. Prior to the advent of experimental models, asthma was believed to be caused primarily by the degranulation of mast cells and eosinophils primed by antigen-specific immunoglobulin E (IgE). More recent studies in mice have shown that T cells primarily mediate antigen-dependent airway obstruction and allergic inflammation through secretion of the cytokines interleukin 4 (IL- 4) and IL-13. Our additional studies indicate that a major environmental link to asthma may be through exposure to environmental proteinases and especially airway infection by proteinase-producing organisms such as fungi. Pending verification in humans, these findings suggest entirely new therapeutic interventions in asthma that include the restricted use of anti-inflammatory therapy and universal application of anti-fungal agents.

  • Clinical Itraconazole-Resistant Strains of Aspergillus fumigatus, Isolated Serially from a Lung Aspergilloma Patient with Pulmonary Tuberculosis, can be Detected with Real-Time PCR Method by Xu H, Chen W, Li L, Wan Z, Li R, Liu W (2009) Abstract

    The invasive aspergillosis, which is commonly caused by Aspergillus fumigatus (A. fumigatus), has increased in recent years. Traditional methods for finding out antifungal resistant strains would take more than 2 weeks, which cannot satisfy the needs of rapid detection. In this study, a real-time PCR method for detection of the serial itraconazole-resistant strains of A. fumigatus isolated from a lung aspergilloma patient was developed. The results showed that the TacMAN-MGB probes, which were covered the loci Gly54, Leu98, Gly138, and Met220 of the enzyme CYP51A coded by the gene cyp51A, as well as the 34-bp tandem repeated sequence in the promoter region (-288 and -322 from the start codon) of this gene, could detect the serial itraconazole-resistant strains of A. fumigatus in our study. Besides, this method takes just 6 h to complete the whole detection.

  • Diagnostic utility of polymerase chain reaction on intraocular specimens to establish the etiology of infectious endophthalmitis by Sowmya P, Madhavan HN (2009) Abstract

    PURPOSE: To evaluate the utility of polymerase chain reaction (PCR) on intraocular clinical specimens (aqueous humor [AH] and vitreous fluid [VF]) as an etiologic diagnostic tool relative to microbiological culture methods in infectious endophthalmitis. METHODS: Conventional bacterial and mycologic cultures and PCR for eubacterial and panfungal genomes were applied for etiologic diagnosis on pairs of AH and VF obtained from 72 patients with clinically established infectious endophthalmitis. RESULTS: Based on cultures, an infectious etiology was established in 27 (37.5%) of 72 patients. PCR detected infectious etiology in all 72 patients. PCR increased the clinical sensitivity over culture by 62.5% (p<0.0001, McNemar test). The frequency of culture positivity, single infections, and polymicrobial infection varied significantly among the types of endophthalmitis (p<0.0001, chi-square test). PCR detected an infectious etiology in 48 patients and polymicrobial infection in 24 patients. An etiology was established by PCR on 56 (77.8%) AH and 65 (90.3%) VF of the 72 patients and this difference had no statistical significance. CONCLUSIONS: PCR on intraocular specimens as an etiologic diagnostic tool has been shown to be specific and severalfold more sensitive than cultures and clinically useful. Therefore, PCR may be considered the gold standard to establish the etiology of infectious endophthalmitis. As there is no statistically significant difference in the results of PCR on AH and VF, PCR on AH could be the method of choice considering safety and simplicity of the procedure of its collection.

  • Spectrum of fungal rhinosinusitis; histopathologist's perspective by Das A, Bal A, Chakrabarti A, Panda N, Joshi K (2009) Abstract

    AIMS: Clinical presentation can provide a clue to the subcategories of fungal rhinosinusitis (FRS); however, tissue examination provides accurate classification. The aim was to analyse the incidence and histopathological spectrum of FRS. METHODS AND RESULTS: A retrospective analysis of all the cases of rhinosinusitis reported in the last 5 years was carried out. Haematoxylin and eosin-stained sections along with special stains such as periodic acid-Schiff and Grocott's were examined. These cases were subclassified based on the presence of allergic mucin, mycelial elements and tissue reaction. Out of a total of 665 cases of rhinosinusitis, 284 (42.7%) were of FRS. On histopathological examination they were broadly categorized as: (i) non-invasive FRS (n = 171, 60.2%), which included 160 cases (56.3%) of allergic fungal rhinosinusitis (AFRS) and eleven (3.9%) of fungal ball; (ii) invasive FRS (n = 101, 35.6%), which included 48 cases (16.9%) of chronic invasive granulomatous FRS, four (1.4%) of chronic invasive FRS and 49 (17.3%) of acute fulminant FRS; and (iii) mixed pattern FRS, comprising 12 cases (4.25%). CONCLUSIONS: AFRS is the most common type of FRS. Cases with mixed reaction pattern suggest that different types of FRS represent a progressive spectrum of disease. An exact histopathological categorization of FRS is important as regards treatment.

  • Can serum mannose-binding lectin levels aid with the diagnosis of invasive aspergillosis? by Kalil AC (2009) Abstract

    Editorial commentary; no abstract. First paragraph: The innate immune system is our first line of defense against infections. Pattern recognition molecules, such as Toll-like receptors, ficolins, pentraxins (e.g., C-reactive protein), and collectins (e.g., mannose-binding lectin [MBL]), are among the most important players of innate immunity. These molecules detect general patterns of structures common to a variety of infectious microorganisms, such as lipopolysaccharide (gram-negative bacteria), lipoteichoic acid (gram-positive bacteria), glycans (bacteria), mannans, and b-glucans (fungi); they are also collectively known as pathogen-associated molecular patterns. Because this general recognition pattern was probably not ideal to discriminate self from infectious nonself and/or for a wider range of infections, the immune response had to be adapted to have a more specific recognition process, which culminated in the development of the adaptive immune system(e.g., B lymphocytes, immunoglobulins, T cells) 90 million years after the surge of the innate immune system ~500 million years ago

 
   
  (N.B. The Aspergillus website used to maintain a bibliographic database which was compiled from Medline and Web of Science (GRAsp), but as all users now have access to the former free of charge via the NCBI website and most will have access to Web of Science via their own libraries this resource is currently not being updated. It contains papers dating up to 7th October 2002. Search the GRASp Database here.)