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PubMed1991

Invasive aspergillosis in AIDS.

Invasive pulmonary aspergillosis was diagnosed in two patients with HIV infection, one with prolonged neutropenia and another receiving corticosteroid therapy. We found 17 additional cases in the literature. A known predisposing risk factor for invasive aspergillosis, eg, neutropenia, corticosteroid use, or intravenous drug abuse, was present in 79% of the cases. That the known immunologic defect of AIDS is not a major host defense against Aspergillus is supported by the empiric observation of the relative rarity of aspergillosis in patients with AIDS. The lung was the most common site of Aspergillus infection (75%), and transbronchial biopsy is diagnostically useful. Central nervous system involvement was seen in 55% and appears to be more frequent in HIV-infected patients than in other immunosuppressed patients with invasive aspergillosis. Prognosis is grim. Despite early institution of amphotericin B therapy in a few cases, the disease was uniformly fatal. Efficacy of therapy with amphotericin B plus rifampin or itraconazole remains to be evaluated. We conclude that aspergillosis is not an AIDS-related opportunistic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Spectrum of invasive pulmonary aspergillosis in immunocompetent patients with chronic obstructive pulmonary disease.

Invasive pulmonary aspergillosis is a well-recognized complication in immunocompromised patients, especially those with neutropenia. We report four cases of invasive pulmonary aspergillosis in patients whose main underlying disease was chronic obstructive pulmonary disease (COPD). Two patients had an acute fatal course, one had chronic necrotizing pulmonary aspergillosis ending in an acute fatal course, and the other had a semiacute disease that responded to amphotericin B. Autopsy on three patients showed invasive pulmonary aspergillosis in both lungs, and tissue invasion was documented by transbronchial biopsy in the patient who survived. Retrospective review of all cultures that grew Aspergillus species from bronchoscopic specimens showed no false-positive results, and this procedure proved to be the most useful maneuver in making the diagnosis. Invasive pulmonary aspergillosis should be in the differential diagnosis in patients with COPD and unexplained pulmonary infiltrates.

Acute Disease↗
PubMed2007

Allergic bronchopulmonary aspergillosis: a US perspective.

PURPOSE OF REVIEW: The present article is an update of allergic bronchopulmonary aspergillosis. Although a rare condition, allergic bronchopulmonary aspergillosis does affect a number of patients with asthma and cystic fibrosis. Prompt recognition and treatment of the disease is critical to improving patient outcomes. RECENT FINDINGS: There is currently much active research being performed in the area of allergic bronchopulmonary aspergillosis. Fascinating insights are being made into the pathophysiology and genetics of the disease. Additionally, research is ongoing on the use of recombinant Aspergillus allergens as an aid to the diagnosis of allergic bronchopulmonary aspergillosis. SUMMARY: These new insights into the genetics and pathophysiology of allergic bronchopulmonary aspergillosis and the development of these new diagnostic techniques could ultimately lead to improved patient treatment. These areas form an important basis for further research.

Antibodies, Fungal↗
PubMed1993

Detection of galactomannan and the 18 kDa antigen from Aspergillus fumigatus in serum and urine from cattle with systemic aspergillosis.

Serum and urine samples from cattle with experimental and spontaneous systemic mycotic infections were tested for the presence of galactomannan and the 18 kDa antigen from Aspergillus fumigatus by an inhibition ELISA and immunoblotting, respectively. High levels of galactomannan (approximately 80 ng/ml.) were detected in serum from two of three calves experimentally infected with A. fumigatus. In two out of three cows with spontaneous acquired aspergillosis a similar amount of galactomannan was detected. Galactomannan was not found in serum samples of 20 cows which aborted due to either experimental or spontaneous placental aspergillosis. Twenty-four of forty urine samples from normal cattle reacted positively in the ELISA, consequently, the assay was not applicable on bovine urine. The 18 kDa antigen from A. fumigatus was detected in the urine from one calf out of three calves experimentally infected with aspergillosis and in the urine from one cow with spontaneous aspergillosis. It is concluded that detection of galactomannan in serum and the 18 kDa antigen in urine may be used as an aid for the diagnosis of disseminated bovine aspergillosis with the exception of placental and probably gastrointestinal localization.

Abortion, Veterinary↗
PubMedDate not supplied

Chronic bronchopulmonary aspergillosis in a horse with Cushing's syndrome.

An atypical case of chronic equine bronchopulmonary aspergillosis with an unusual hyphal morphology was diagnosed in a horse with Cushing's syndrome. Because of the hyphal localization in chronic ectatic bronchi and bronchioles, and juxtabronchiolar processes, the observed type of aspergillosis is similar to 'saprophytic bronchopulmonary aspergillosis' or 'semi-invasive pulmonary aspergillosis' in humans. The aetiological diagnosis of aspergillosis was accomplished by the application of a panel of monospecific polyclonal and monoclonal antibodies in immunohistochemical techniques.

Animals↗
PubMed2002

Itraconazole--perspectives for the management of invasive aspergillosis.

Itraconazole has become an important option in the management of invasive aspergillosis. The compound has potent and broad spectrum antifungal activity in vitro against Aspergillus spp. with a species- and strain dependent fungicidal mode of action. In vivo, the antifungal efficacy of itraconazole has been demonstrated in several non-immunocompromised and immunocompromised animal models of disseminated and invasive pulmonary aspergillosis. Itraconazole is available in oral and intravenous formulations, displays non-linear plasma pharmacokinetics, and is usually well tolerated. Non-comparative clinical data of itraconazole for therapy of suspected or proven invasive aspergillosis suggest response rates similar to those of conventional amphotericin B; however, the experience with itraconazole for induction therapy of invasive aspergillosis is limited, particularly in profoundly neutropenic patients. Itraconazole has an important role for consolidation and maintenance therapy of patients with invasive aspergillosis, and novel combination therapies involving itraconazole are currently under intensive preclinical investigation as to their usefulness for primary therapy.

Animals↗
PubMed2005

Primary cutaneous aspergillosis (PCA)--a case report.

UNLABELLED: Primary cutaneous aspergillosis is a rare diagnosis. Predisposing factors are immunodeficiency and macerated skin. The mortality of infections with Aspergillus species is high, especially in neonatal intensive care units (NICUs). We present a premature (24 wk of gestation) infant with primary cutaneous aspergillosis appearing on the sixth day of life. Predisposing factors in this patient were prematurity, extremely vulnerable skin, treatment with antibiotics and renovation in the radiology department nearby. The patient was treated with amphotericin B intravenously for a total of 40 d. He did not have, nor develop, disseminated aspergillosis, and suffered no side effects from the treatment. The only remaining trace of his infection was scarring in the affected area. CONCLUSION: After having treated this patient successfully and having gone through the available literature, we conclude that treating primary cutaneous aspergillosis with intravenous amphotericin B prevents disseminated aspergillosis and is the treatment of choice.

Amphotericin B↗
PubMed2004

[The performance of (1, 3)-beta-D-glucan and Aspergillus galactomannan measurement for early diagnosis of invasive aspergillosis in patients with hematological diseases].

We analyzed the performance of (1, 3)-Beta-D-glucan (measurement by the alkaline-kinetic chromogenic Limulus method (FUNGITEC G test-MK, Fungitec) and the kinetic turbidimetric Limulus method [Beta-Glucan test WAKO, Wako]) and we carried out Aspergillus galactomannan antigen detection (enzyme-linked immunosorbent assay, ELISA test) for the early diagnosis of invasive aspergillosis in patients with hematological diseases at the time of febrile episodes of unknown origin that did not respond to antibacterial therapy for more than 3 days. During a one-year period (April 2002 to March 2003), a total of 69 febrile episodes in 58 patients were studied; 8 cases of invasive aspergillosis were diagnosed according to the definition of the European Organization for Research and Treatment of Cancer/Mycosis Study Group, and 61 cases were found to be non-mycotic diseases. Based on the analysis of 69 results with confirmed disease status, the overall performance of the Fungitec, the Wako, and the ELISA test were as follows: sensitivity was 0.88, 0.63, and 0.50, respectively, whereas the specificity was 0.85, 0.98, and 1.0, respectively. Moreover, there was a strong relationship between the log-transformed values of the (1, 3)-Beta-D-glucan levels measured by the two methods (r = 0.92 [95%CI, 0.89-0.94] ; p<0.001). For the statistical analysis of these serological tests a receiver operating characteristic curve (ROC) was used, as well as the resulting area under the ROC curve (ROC AUC). The ROC AUC and the cut-off values that gave the highest accuracy were as follows: 0.92, 24.9 pg/ml for the Fungitec, 0.84, 7.3 pg/ml for the Wako, and 0.89, 0.9 COI for the ELISA test, respectively. In conclusion, these results indicate that both of the two (1, 3)-Beta-D-glucan measurement approaches served equally well as surveillance tools for determining the extent of invasive aspergillosis; in addition, the log-transformed value of these tests can be used for comparison. Moreover, the ELISA test was found to have clinical utility, both as a surveillance and as a diagnostic tool when invasive aspergillosis was suspected. It should be noted that the galactomannan assay had sensitivity-related limitations; lowering the cut-off value is expected to increase the diagnostic value for use in cases of invasive aspergillosis.

Adult↗
PubMed2005

[Two cases of pulmonary aspergillosis successfully treated with combinated micafungin and itraconazole therapy].

We report 2 cases of pulmonary aspergillosis treated successfully by combining micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea on effort treated for pulmonary tuberculosis and aspergillosis was found on chest CT on admission to have a fungus ball in the left upper lobe and increasing consolidation around the cavity of both lung fields. Bronchoscopy proved positive for aspergillus PCR in bronchial lavage. He was diagnosed with chronic necrotizing pulmonary aspergillosis, based on clinical and radiological findings and the positive reaction for aspergillus PCR. He was treated with micafungin alone at first, this proved ineffective, so itraconazole was added, resulting in improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease (mixed). She had suffered from a cough and back pain, and chest CT showed increasing consolidation inside and around a giant bulla. She was diagnosed with chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus sp. in sputum culture and a positive reaction for Aspergillus antigen in bronchial lavage and Aspergillus antibody in serum. She was treated with the combined micafungin and itraconazole, which rapidly improved symptoms and radiological findings. Pulmonary aspergillosis therapy is often difficult, because delivery of the drug to the infection site is limited and drug tolerance is poor. We found that combination micafungin and itraconazole therapy is tolerable and effective in these cases.

Adult↗
PubMed1995

Therapeutic monitoring of experimental invasive pulmonary aspergillosis by ultrafast computerized tomography, a novel, noninvasive method for measuring responses to antifungal therapy.

Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (UFCT) in persistently granulocytopenic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compared with those measured by conventional chest radiography, histopathological resolution of lesions, and microbiological clearance of Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously. Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continued to progress in untreated controls, whereas lesions in treated rabbits initially increased and then decreased in response to antifungal therapy in a dosage-dependent manner (P < or = 0.05 to P < or = 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiological clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions due to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the groups compared). These findings establish a correlation among UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of organism-mediated tissue injury.

Amphotericin B↗
PubMed2004

Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B.

We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.

Adolescent↗
PubMed1980

Significance of Aspergillus species isolated from respiratory secretions in the diagnosis of invasive pulmonary aspergillosis.

To determine the significance of Aspergillus species isolated from sputum or other respiratory secretions with respect to the diagnosis of invasive pulmonary aspergillosis, the clinical records and radiographs of all patients whose respiratory secretion cultures yielded an Aspergillus species between 1972 and 1978 were reviewed. All known predispositions to invasive aspergillosis, e.g., presence of cancer or granulocytopenia, and therapy with corticosteroids, antibiotics, and cytotoxic drugs, were significantly associated with proven or probable invasive pulmonary aspergillosis. Most notable were patients with acute leukemia and granulocytopenia. Prolonged duration of hospitalization between initial isolation (greater than 2 weeks) and multiple isolates (greater than three isolates) were also significantly associated with a high frequency of proven or probable disease. Isolation of A. niger was only rarely associated with proven or probable disease (one of eight patients). The isolation of A. fumigatus and A. flavus from respiratory secretions does not usually represent laboratory contamination and must be interpreted in the light of known predispositions to aspergillosis. In some situations, e.g., granulocytopenic patients with acute leukemia, even a single isolation carries a high likelihood of invasive aspergillosis.

Adrenal Cortex Hormones↗
PubMed1999

Comparison between PCR and detection of antigen in sera for diagnosis of pulmonary aspergillosis.

We evaluated the usefulness of PCR and antigen detection for the diagnosis of pulmonary aspergillosis. Forty-four serum samples from patients with pulmonary aspergillosis (33 with pulmonary aspergilloma, 4 with allergic bronchopulmonary aspergillosis, 4 with invasive pulmonary aspergillosis, and 3 with aspergillus pyothorax) were used in this study. PCR detection of Aspergillus DNA in serum samples was successful in 39 patients. Galactomannan antigen was detected by sandwich enzyme-linked immunosorbent assay in 25 patients and by latex agglutination test in 13 patients. Detection of Aspergillus DNA in serum samples by nested PCR had the highest sensitivity of the three methods tested for the diagnosis of pulmonary aspergillosis.

Antigens, Fungal↗
PubMed1995

Clinical evaluation and reproducibility of the Pastorex Aspergillus antigen latex agglutination test for diagnosing invasive aspergillosis.

AIMS: The performance of the Pastorex Aspergillus antigen latex agglutination test for the detection of galactomannan in sera of patients at risk for invasive aspergillosis was evaluated, and the impact of storage on the reproducibility of the antigen titre was tested. METHODS: During a one year period, 392 serum samples were obtained from 46 patients at risk for invasive aspergillosis and tested for the presence of galactomannan using an Aspergillus latex agglutination test (Pastorex). Twenty three positive serum samples which had been stored at -20 degrees C for 2-16 months were retrospectively retested. Furthermore, two positive serum samples were stored at -20 degrees C and -70 degrees C and prospectively tested at three month intervals for a period of 15 months. RESULTS: The Pastorex Aspergillus test was positive in eight patients with microbiological, radiological, or histological evidence for invasive aspergillosis, but was negative in the initial serum sample from five of these patients. In two patients with histological evidence for invasive aspergillosis no positive reaction was found in six samples. Six of 13 (45%) serum samples which had been stored at -20 degrees C for longer than six months had lost reactivity, while one of 10 (10%) samples had lost reactivity when stored up to six months. Two serum samples which had been stored at -20 degrees C and -70 degrees C and prospectively retested at three month intervals for 15 months, maintained stable antigen titres. CONCLUSIONS: The Pastorex Aspergillus test is too insensitive to diagnose invasive aspergillosis in an early stage, but may contribute to the diagnosis when cultures remain negative and serial samples are obtained. To maintain a good reproducibility, serum samples should be stored at -70 degrees C when the period of storage exceeds six months.

Adolescent↗
PubMed1996

Aspergillosis in immunocompromised paediatric patients: associations with building hygiene, design, and indoor air.

BACKGROUND: Nosocomial aspergillosis is a well known complication of immunosuppression in cancer patients and those undergoing transplantation and has usually been associated with major building construction or demolition. An observational study is reported of the hospital environment associated with an outbreak of aspergillosis in a paediatric oncology ward. METHODS: All cases of aspergillosis were identified from the hospital records and categorised as definite or probable according to the extent of supportive clinical and laboratory findings. All relevant aspects of building ventilation, air filtration, and aerosol generation considered relevant were examined and air samples for fungi were taken in triplicate at 25 sites using a slit sampler with appropriate culture media. RESULTS: Six cases of aspergillosis were identified over one year out of the 148 patients who attended the unit - the only part of the hospital where cases were found. Examination of the building services and function suggested that the cause or source was isolated to this paediatric oncology/haematology ward and may have been attributed to a defective disposal conduit door as well as the dispersal of a contaminated aerosol from the ward vacuum cleaner which had the highest measured concentrations of Aspergillus fumigatus in or around the building (65 colony forming units (cfu)/m3 compared with 0-6 cfu/m3 elsewhere). No further cases were identified in the two years after these hygiene arrangements were changed. CONCLUSIONS: The investigation of this outbreak of nosocomial aspergillosis identified several possible sources of fungally contaminated aerosol which could have been implicated as the cause. Their modification was followed by a reduction in the incidence of further cases. Each should be incorporated as an issue of importance in hospital building design and hygiene.

Air Pollution, Indoor↗
PubMed2002

Invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis usually occurs in immunocompromised patients. Mild abnormality of host defence is usually present in the chronic necrotising form of the disease. Acute aspergillus pneumonia usually affects patients who are seriously immunocompromised. OBJECTIVES: The purpose of the study was to highlight the possibility of occurrence of invasive pulmonary aspergillosis also in patients with mild abnormality of host defence. METHODS: In a retrospective study 6 patients were analysed. The inclusion criterion was evidence of Aspergillus sp. invasion in lung tissue. Lung tissue was obtained by biopsy or post mortem examination. RESULTS: There were 4 patients with acute aspergillus pneumonia. Two of them were severely immunocompromised - one with dermatomyositis, who was treated with high doses of corticosteroids and methotrexate, and the other with undiscovered miliary tuberculosis, who was treated for myelodysplastic syndrome instead with low doses of corticosteroids. The other 2 had mild immunosuppression: one was suffering from sarcoidosis and was treated with low doses of corticosteroids, the other had dilated cardiomyopathy, renal insufficiency and diabetes mellitus. The two patients with chronic necrotising pulmonary aspergillosis had mild abnormality of host defence: one had reactivation of tuberculosis and diabetes mellitus, the other had inactive tuberculosis and aspergilloma. CONCLUSIONS: Invasive pulmonary aspergillosis must be considered also in patients with mild immunosuppression and pulmonary infiltrates which do not respond to conventional treatment with antibiotic chemotherapy. The key to the diagnosis of invasive pulmonary aspergillosis is the histopathological demonstration of fungal invasion in lung tissue.

Aged↗
PubMed1976

Bronchopulmonary aspergillosis. An epidemiological study in a hospital population.

In order to determine the incidence of bronchopulmonary aspergillosis in patients with other types of pulmonary pathology, 586 in-patients, out-patients and controls were examined during the period 1968-1970 in Baguley Hospital, Manchester, England. It was found that from the 344 in-patients and out-patients with other pulmonary pathology, 6 had a definite diagnosis of allergic aspergillosis. 1 had pulmonary aspergilloma while 53 other patients demonstrated some evidence of bronchopulmonary aspergillosis. These 53 patients had insufficient criteria to be classified in one of the recognised forms of aspergillosis. The number of controls examined was 242, none of whom were found to have allergic or other forms of aspergillosis. Eleven of these had a positive immediate skin test the other test being negative. In addition to the above groups 534 patients with bronchial asthma attending the out-patient department, were investigated with multiple intradermal tests, including Aspergillus fumigatus. Positive intradermal Aspergillus test was found in 130 of the patients with bronchial asthma. This investigation showed that the bronchopulmonary asperigillosis is more prevalent in patients with a pulmonary disease than in persons without this pathology.

Aspergillosis↗
PubMed1996

Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

Two patients admitted to two different medical wards of our institution following respiratory decompensation of chronic obstructive pulmonary disease (COPD) were subsequently transferred to the same room of the medical intensive care unit (ICU) and intubated. Both patients developed invasive pulmonary aspergillosis and died soon after. Because COPD itself is rarely associated with lethal pulmonary aspergillosis, both cases were reviewed, and a retrospective investigation was conducted. Both patients had repeated sputum cultures while on the medical ward before their admission to the ICU; none of the sample grew Aspergillus spp. A. fumigatus was found in tracheal aspirates of both patients from the first day of their intubation while in the ICU. The pulmonary condition of both patients worsened, and invasive aspergillosis was diagnosed by bronchoalveolar lavage. Despite therapy with amphotericin B, the patients died 16 and 22 d after intubation, respectively. Both deaths were attributed to pulmonary aspergillosis; autopsy confirmed a massive pneumonia of the five lobes due to A. fumigatus in one patient. Investigation revealed that an air filter had been replaced 30 h before the first patient was admitted to the room. Experimental air filter replacement performed 12 d after the second patient died revealed the presence of A. fumigatus on the surface of the filters as well as a 10-fold increase in room air fungal counts during the procedure. This study shows that exposure to high concentrations of airborne Aspergillus spp. related to air filter change was associated with fatal invasive aspergillosis in two mechanically ventilated patients. Such infection can be prevented by the establishment and application of guidelines for air filter replacement.

Aged↗