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Recently published diagnosis articles (2010-2012) Intracranial fungal granulomas are rare and of the histologically verified granulomas, Aspergillus spp. is the commonest causative fungal pathogen. Most of the reported large series of aspergillus granulomas are from countries with temperate climate like India, Pakistan, Sudan, and Saudi Arabia. In contrast to disseminated aspergillosis that occurs in immunosuppressed individuals, most of the intracranial aspergillus granulomas are reported in immunocompetent individuals. The temperature, humidity, high spore content in the atmosphere during ploughing, and occupation as agricultural worker are implicated in the pathogenesis. The sinocranial spread is the most common route of intracranial extension. Extracerebral firm fibrotic lesions and skull base lesions are common. Extensive fibrosis and large number of multinucleated giant cells are the characteristic histological features and these pathological features have therapeutic relevance. What should be the optimal cut-off of serum 1,3-β-d-glucan for the detection of invasive pulmonary aspergillosis in patients with haematological malignancies? by Metan G, Nedret Koç A, Atalay A, Kaynar LG, Ozturk A, Alp E, Eser B (2011) Abstract The detection of 1,3-β-d-glucan (BDG), a cell wall component of several medically important fungi, is a promising tool for the diagnosis of invasive pulmonary aspergillosis. The aim of this study was to evaluate the diagnostic accuracy of the BDG test in invasive pulmonary aspergillosis (IPA) by focusing on the optimal cut-off value. Methods: The records of the Infection Control Committee were reviewed to identify patients with haematological malignancies and stem cell transplantation who had at least 1 BDG (Fungitell kit) measurement during the period January 2008 through April 2011. The European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria (independent of BDG results) were used to categorize the patients with IPA. Patients with possible IPA were not included in the study. Results: A total of 128 patients (50 with proven or probable IPA) were included in the study. At the manufacturer's recommended cut-off value of 80 pg/ml, the sensitivity of BDG was 66% (95% CI 51.2-78.7), specificity 75.6% (95% CI 64.6-84.5), positive predictive value (PPV) 63.4%, and negative predictive value (NPV) 77.6%. A receiver operating characteristic (ROC) curve was constructed to define the optimum serum BDG cut-off for the diagnosis of IPA. At a cut-off value of 181 pg/ml, the sensitivity was 52% (95% CI 37.4-66.3), specificity 94.8% (95% CI 87.4-98.6), PPV 86.7%, and NPV 75.5%. Conclusions: Although higher cut-off levels increased the specificity of the BDG test, sensitivity decreased to an unacceptable level; the commercially recommended cut-off value appears to be appropriate for screening purposes. Diagnosis and Treatment Outcome of Mycotic Keratitis at a Tertiary Eye Care Center in Eastern India by Rautaraya B, Sharma S, Kar S, Das S, Sahu SK (2011) Abstract
Mycotic keratitis is an important cause of corneal blindness world over including India. Geographical location and climate are known to influence the profile of fungal diseases. While there are several reports on mycotic keratitis from southern India, comprehensive clinico-microbiological reports from eastern India are few. The reported prevalence of mycotic keratitis are 36.7%,36.3%,25.6%,7.3% in southern, western , north- eastern and northern India respectively. This study reports the epidemiological characteristics, microbiological diagnosis and treatment outcome of mycotic keratitis at a tertiary eye care center in eastern India. Detection and Measurement of Fungal Burden in a Guinea Pig Model of Invasive Pulmonary Aspergillosis by Novel Quantitative Nested Real-time PCR Compared with Galactomannan and (1,3)-β-D-glucan Detection by Lengerova M, Kocmanova I, Racil Z, Hrncirova K, Pospisilova S, Mayer J, Najvar LK, Wiederhold NP, Kirkpatrick WR, Patterson TF (2011) Abstract We developed and assessed the diagnostic value of a novel quantitative nested real-time PCR (QNRT) assay targeting the internal-transcribed (ITS) region of ribosomal DNA (rDNA) in a guinea pig model of invasive pulmonary aspergillosis. Groups of 5 immunosuppressed animals that were infected using an aerosol chamber with A. fumigatus conidia were humanely terminated 1 hour post-inoculation and at days 3, 5, 7 and 11 post challenge, and lung tissue, bronchoalveolar lavage fluid (BAL), whole blood and serum samples were collected. The QNRT-PCR results in the serum and BAL were compared to those achieved with galactomannan and (1→3)-β-D-glucan assays. High levels of fungal burden were detected by QNRT-PCR in both lung tissue and BAL in all infected animals at each time point, and the sensitivity of each assay in BAL was 100% by day 3 and remained so through the remainder of the study. The sensitivity of detection of fungi in whole blood and serum samples was significantly lower and some samples remained negative by all three assays despite the advanced stage of the infection. From these data we can conclude that this novel QNRT-PCR method was highly sensitive for the detection of A. fumigatus from different types of samples in this model. In addition, BAL samples appeared to be the most suitable for the early diagnosis of invasive pulmonary aspergillosis. When testing serum, the use of a combination of available assays may increase the possibility of early detection of this opportunistic mycosis. Evaluation of a Recombinant Antigen-Based EIA for the Diagnosis of Non-Invasive Aspergillosis by Guitard J, Sendid B, Thorez S, Gits M, Hennequin C (2011) Abstract Antibody detection is a key diagnostic tool for non-invasive aspergillosis (NIA) such as allergic broncho-pulmonary aspergillosis and chronic pulmonary aspergillosis. Specific immuno-precipitins detection (IPD) is considered as the reference but lacks standardization and is time-consuming. To evaluate the performance of a new anti-Aspergillus fumigatus IgG enzyme immunoassay (EIA) kit using a recombinant A. fumigatus antigen (Bio-Rad), a retrospective study was performed on 551 sera collected from patients with a definite diagnosis of NIA (group 1; n=64), bronchial Aspergillus colonization (group 2; n=26), probable aerial Aspergillus-contamination (group 3; n=44), patients suspected of NIA with negative serologic and mycologic investigations (group 4; n=49) and a group of 222 patients not suspected of NIA (group 5). The EIA test exhibited excellent reproducibility with coefficients of variation below 10%. Agreement with IPD was calculated between 62.5 and 84.4% according to the group of patients with a Cohen's Kappa coefficient at 0.6196 ± 0.077. Taking as reference a composite status including clinical, radiological, mycological and serological data, sensitivity (group 1) and specificity (other groups) were calculated between 90.2 and 93.8%, and, 54.3 and 100%, respectively. Lower specificity was observed for patients with Aspergillus colonization. However, Yule Q coefficients estimating the correlation between EIA result and the definite diagnosis of NIA was calculated between 0.97 and 0.98. The method is a highly useful screening tool for the diagnosis of NIA, reducing the need for confirmatory IPD tests. Molecular mechanism of ochratoxin a transport in the kidney by Anzai N, Jutabha P, Endou H (2010) Abstract The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA-induced nephrotoxicity. Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients by Bergeron A, Porcher R, Menotti J, Poirot JL, Chagnon K, Vekhoff A, Cornet M, Isnard F, Raffoux E, Brethon B, Lacroix C, Touratier S, Latgé JP, Bouges-Michel C, Tazi A, Derouin F, Ribaud P, Sulahian A (2011) Abstract Early evaluation of treatment efficacy in invasive aspergillosis (IA), a leading cause of morbidity and mortality in hematological patients, remains a challenge. We conducted a prospective study to evaluate the performance of different markers in predicting the outcome of patients with IA. Both clinical and biological criteria were assessed 7, 14, 21 and 45 days after inclusion in the study, and mortality was assessed at day 60. The association between baseline data and their evolution with day 45 response to treatment was analyzed.A total of 57 patients (4 with proven, 44 with probable and 9 with possible aspergillosis according to the revised EORTC-MSG definitions) were included. At day 45, 30 patients (53%) were determined to be responders, 25 (44%) were non-responders, and 2 were not able to be evaluated. Twenty patients died within the 60 days of follow-up. We found that a poor day 45 outcome was associated with patients who had high baseline serum galactomannan (GM) antigen levels and those receiving steroids at the time of IA. A consistently negative serum GM index was associated with a good outcome, and the day 14 clinical evaluation was predictive of the day 45 outcome. No association was found between Aspergillus antibodies or DNA detection and patients' outcome. We conclude that the GM index value at diagnosis of IA, GM index kinetics and clinical evaluation at day 14 are good markers for predicting the outcome of patients with IA and should be taken into account for adapting antifungal treatment. Increased chitinase expression and fungal-specific antibodies in the bronchoalveolar lavage fluid of asthmatic children by Goldman DL, Li X, Tsirilakis K, Andrade C, Casadevall A, Vicencio AG (2011) Abstract
BACKGROUND: Increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma. Outbreak of invasive aspergillosis after major heart surgery caused by spores in the air of the intensive care unit by Peláez T, Muñoz P, Guinea J, Valerio M, Giannella M, Klaassen CH, Bouza E (2012) Abstract Background. Outbreaks of invasive aspergillosis (IA) are believed to be caused by airborne Aspergillus conidia. Few studies have established a correlation between high levels of Aspergillus fumigatus conidia and the appearance of new cases of IA or have demonstrated matching genotypes between clinical isolates and those from the environment. Methods. We detected an outbreak of IA (December 2006 through April 2008) in the major heart surgery intensive care unit (MHS-ICU) of our institution. Our local surveillance program consists of monthly environmental air sampling in operating rooms and ICUs for quantitative and qualitative identification of filamentous fungi. During the study period, we obtained 508 environmental samples from 3 different periods: 6 months before the outbreak, during it, and 6 months after it. Available environmental and clinical strains were genotyped according to the short tandem repeats assay. Results. Seven patients developed proven or probable IA (5 with lung infection, 1 with mediastinitis, and 1 with lung infection and mediastinitis). A. fumigatus was involved in 6 cases. The underlying conditions of the patients were heart transplantation (n = 3), corticosteroid-dependent conditions (n = 2), and diabetes mellitus (n = 2). The mortality rate was 85.7%. Before and after the outbreak (±6 months), the median airborne A. fumigatus conidia levels were 0 colony-forming units (CFUs) per cubic meter, and no cases of IA occurred during these periods. However, during the outbreak period, the occurrence of the 6 cases of IA caused by A. fumigatus was linked to peaks of abnormally high A. fumigatus airborne conidia levels (175, 50, 25, 20, 160, and 400 CFUs/m(3)) in the MHS-ICU, whereas counts in the air of both operating rooms remained negative. Matches between A. fumigatus genotypes collected from the air of the MHS-ICU and from representative clinical samples were found in 3 of the 6 patients. The outbreak abated when high-efficiency particulate air filters were installed in the affected areas. Conclusions. Our study revealed that abnormally high levels of airborne A. fumigatus conidia correlated with new cases of IA, even in patients who were not severely immunocompromised. The demonstration of matches between air and clinical genotypes reinforces the role of environmental air in the acquisition of IA during the period following MHS. Environmental monitoring of Aspergillus spores in the air of postoperative units is mandatory, even when these units receive nonimmunocompromised patients undergoing major surgery. Pictorial essay: Allergic bronchopulmonary aspergillosis by Agarwal R, Khan A, Garg M, Aggarwal AN, Gupta D (2011) Abstract 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. |
Earlier diagnosis articles Aflatoxin and ochratoxin production by Aspergillus species under ex vivo conditions by Klich MA, Tang S, Denning DW (2009) AbstractAspergillus species are increasingly important human pathogens. It is not known whether toxic metabolites of many of these pathogenic species can act as virulence factors in aspergillosis. We examined isolates of aflatoxin and ochratoxin-producing species for toxin production in ex vivo conditions. Seven of the 21 aflatoxin-producing isolates screened produced aflatoxin at 35 and 37 degrees C on the general medium yeast extract sucrose agar (YES). However, none of them produced toxin at these temperatures on brain heart infusion agar (BHA), a medium that mimics human tissue, or on BHA with modified pH or sugar levels. Six of the 12 ochratoxin-producing isolates examined produced toxin at 35 degrees C on YES. All three isolates of A. alliaceus produced ochratoxin on BHA or modified BHA at 37 degrees C. One strain of A. pseudoelegans produced a minute amount of ochratoxin on modified BHA at 37 degrees C. These data indicate that aflatoxin is an unlikely virulence, factor but that ochratoxin may be a potential virulence factor in aspergillosis. Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans by Studer-Rohr I, Schlatter J, Dietrich DR (2000) Abstract The mycotoxin ochratoxin A (OTA) is a rodent carcinogen produced by species of the ubiquitous fungal genera Aspergillus and Penicillium. OTA is found in a variety of food items and as a consequence is also found in human plasma (average concentrations found in this study: 0.1-1 ng OTA/ml plasma). To improve the scientific basis for cancer risk assessment the toxicokinetic profile of OTA was studied in one human volunteer following ingestion of 395 ng 3H-labeled OTA (3.8 microCi). A two-compartment open model consisting of a central compartment was found to best describe the in vivo data. This two-compartment model consisted of a fast elimination and distribution phase (T1/2 about 20 h) followed by a slow elimination phase (renal clearance about 0.11 ml/min.) and a calculated plasma half-life of 35.55 days. This half-life was approximately eight times longer than that determined previously in rats. In addition, the intraindividual fluctuation of OTA plasma levels was investigated in eight individuals over a period of 2 months. The concentrations determined ranged between 0.2 and 0.9 ng OTA/ml plasma. The plasma levels in some individuals remained nearly constant over time, while others varied considerably (e.g. increase of 0.4 ng/ml within 3 days, decrease of 0.3 ng/ml within 5 days) during the observation period. This intraindividual fluctuation in OTA plasma levels, which may represent differences in OTA exposure and/or metabolism, as well as the large difference in plasma half-life in humans compared to rats must be taken into consideration when the results of rat cancer study data are extrapolated to humans for risk assessment purposes. Immunotoxic activity of ochratoxin A by Al-Anati L, Petzinger E (2006) Abstract Ochratoxin A (OTA) is an immunosuppressant fungal compound, produced by toxigenic species of Aspergillus and Penicillium fungi in a wide variety of climates and geographical regions. The contamination of food by this mycotoxin takes place primarily during preharvest periods. Almost all types of food can be contaminated. In addition, its chemical stability against heat and during industrial food processing makes OTA one of the most abundant food contaminating mycotoxins. Due in part to its long serum half-life in man, almost 100% of all human blood samples from some geographic regions may be positive for OTA. The immunosuppressant activity of OTA is characterized by size reduction of vital immune organs, such as thymus, spleen, and lymph nodes, depression of antibody responses, alterations in the number and functions of immune cells, and modulation of cytokine production. The immunotoxic activity of OTA probably results from degenerative changes and cell death following necrosis and apoptosis, in combination with slow replacement of affected immune cells, due to inhibition of protein synthesis. Medically unexplained symptoms and neuropsychological assessment by Binder LM, Campbell KA (2004) Abstract Several illnesses expressed somatically that do not have clearly demonstrated pathophysiological origin and that are associated with neuropsychological complaints are reviewed. Among them are nonepileptic seizures, fibromyalgia, chronic fatigue syndrome, Persian Gulf War unexplained illnesses, toxic mold and sick building syndrome, and silicone breast implant disease. Some of these illnesses may be associated with objective cognitive abnormalities, but it is not likely that these abnormalities are caused by traditionally defined neurological disease. Instead, the cognitive abnormalities may be caused by a complex interaction between biological and psychological factors. Nonepileptic seizures serve as an excellent model of medically unexplained symptoms. Although nonepileptic seizures clearly are associated with objective cognitive abnormalities, they are not of neurological origin. There is evidence that severe stressors and PTSD are associated with immune system problems, neurochemical changes, and various diseases; these data blur the distinctions between psychological and organic etiologies. Diagnostic problems are intensified by the fact that many patients are poor historians. Patients are prone to omit history of severe stressors and psychiatric problems, and the inability to talk about stressors increases the likelihood of suffering from physiological forms of stress. 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. Comparison of the skin test and ImmunoCAP system in the evaluation of mold allergy by Liang KL, Su MC, Jiang RS (2006) Abstract
BACKGROUND: Mold is ubiquitous in our environment and is a common allergen in allergic diseases. The skin test and the Pharmacia ImmunoCAP system (CAP) for assay-specific immunoglobulin E (IgE) antibodies are both widely used. The goal of this study was to compare the performance of the skin test and CAP in the evaluation of mold allergy. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma by Maurya V, Gugnani HC, Sarma PU, Madan T, Shah A (2005) Abstract
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA), which is predominantly a disease of asthmatic subjects, is caused by hypersensitivity to Aspergillus antigens. Screening for Aspergillus sensitization in asthmatic subjects could identify those who are at risk for ABPA. Few studies have shown that fungal sensitization could be an important risk factor for asthma severity. We sought to determine the frequency of sensitization to Aspergillus antigens in asthmatic subjects and its effect on disease severity. We also determined the occurrence of ABPA in these subjects. Frequency of familial occurrence in 164 patients with allergic bronchopulmonary aspergillosis by Shah A, Kala J, Sahay S, Panjabi C (2008) Abstract
BACKGROUND: Asthma is known to run in families. Allergic bronchopulmonary aspergillosis (ABPA) occurs predominantly in patients with asthma. However, there are only 6 reports of familial occurrence over a period of 35 years. Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis: a review of an uncommon association* by Shah A, Panchal N, Agarwal AK (2001) Abstract
BACKGROUND: Although thought to have common immunopathological processes, concomitant occurrence of allergic bronchopulmonary aspergillosis (ABPA) and allergic Aspergillus sinusitis (AAS) appears to be rarely reported as to date only five detailed case reports are available. Asthma outbreak during a thunderstorm by Packe GE, Ayres JG (1985) Abstract An outbreak of acute asthma occurred in Birmingham and the surrounding area on July 6 and 7, 1983. In most patients symptoms began at the time of sudden climatic changes associated with a thunderstorm. Air pollution was not a factor. The large and sudden increase in numbers of airborne fungal spores, especially Didymella exitialis and Sporobolomyces, around the time of the outbreak suggests that they may have been partly contributory, although a direct causal effect has not yet been established. |
(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.) |
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