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PubMed2000

Diagnosis of pulmonary aspergillosis using optical brighteners.

Invasive pulmonary aspergillosis (IPA) is increasingly recognized especially in immunocompromised patients, but early diagnosis remains a problem. Fungal elements in clinical specimens can be directly stained with an optical brightener. The high intensity of the elicited fluorescence allows for rapid and reliable microscopic screening. In the present study the authors aimed to validate this method. All specimens from bronchial secretions or pleural fluid suspected of mycosis (n=94) and all bronchoalveolar lavages (n=439) were prospectively evaluated by culture and staining with the optical brightener Blankophor-P-Flüssig. IPA was diagnosed for 17 specimens from 13 patients, using a combination of clinical, culture and radiological data, and by biopsy (n=3) or autopsy (n=3). The overall incidence of IPA was 3.3%. Nine of the 13 patients with IPA died (mortality=69%). Staining with the optical brightener and consecutive microscopic screening took 9+/-3 min. For the diagnosis of invasive aspergillosis, sensitivity was 0.88 and specificity was 0.99. Using culture, sensitivity was 0.76 and specificity was 0.99. In conclusion, direct examination of clinical specimens using the optical brightener has a high diagnostic potential for the diagnosis of invasive pulmonary aspergillosis. The reliability, simplicity and speed of the method render it suitable for routine diagnostic work.

Aspergillosis↗
PubMed2000

Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus that may progress to bronchiectasis. The aim of the present study was to characterize airway inflammation in patients with clinically stable ABPA and asthma, and to correlate this with bronchiectasis severity. Subjects with ABPA and central bronchiectasis (ABPA-CB; n=16) and ABPA with serological evidence alone (ABPA-S; n=10) were studied. Comparison groups were A. fumigatus-sensitized asthma (n=19), non-A. fumigatus-sensitized asthma (n=15) and healthy controls (n=8). Hypertonic saline challenge, sputum induction and high-resolution computed tomography (HRCT) of the chest were performed. Sputum eosinophil numbers were markedly elevated in ABPA-CB (median 8.4%) compared to ABPA-S (2.4%), A. fumigatus-sensitized asthma (1.8%), asthma (1.8%) and controls (0.3%) (p<0.01); sputum eosinophil cationic protein levels were higher in ABPA-CB (median 13,706 ng.mL(-1)), compared to ABPA-S (1,633.5 ng.mL(-1)), A. fumigatus-sensitized asthma (1,550.7 ng.mL(-1)), asthma (309.2 ng.mL(-1)), and controls (110 ng.mL(-1)) (p<0.001). ABPA-CB also showed increased sputum neutrophil number (median 60.3%) compared to the other groups (controls 29.3%) (p=0.01). The severity of bronchiectasis on HRCT correlated with sputum neutrophil (r=0.6) and eosinophil number (r=0.5) but not serum immunoglobulin-E levels. In conclusion, clinically stable allergic bronchopulmonary aspergillosis with bronchiectasis is characterized by an intense heterogenous inflammatory infiltrate consisting of eosinophils and neutrophils, which correlates closely with the severity of bronchiectasis on high-resolution computed tomography. Sputum analysis may be useful in monitoring the course of allergic bronchopulmonary aspergillosis.

Adult↗
PubMed2000

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.

Aspergillosis↗
PubMed1999

Primary renal aspergillosis: extremely uncommon presentation in patients treated with bone marrow transplantation.

Invasive aspergillosis affects 3 to 11% of BMT patients with a high mortality rate (60 to 95%). Extra-pulmonary disease is an unusual event, and primary renal aspergillosis is extremely uncommon. A patient with CML treated with BMT, who developed primary renal and subsequently hepatic aspergillosis, is described. Dysfunction of the mucosal barrier secondary to conditioning therapy, was a possible portal of entry for the fungus. Fine needle aspiration was very useful, as is direct microscopic examination of the urine, for diagnosis of the fungal infection. Surgical drainage of the abscess followed by antifungal therapy is the treatment of choice. Unconducive situations, such as refractory thrombocytopenia, are associated with the worst outcome in these patients.

Aspergillosis↗
PubMed1999

Early diagnosis of central nervous system aspergillosis using polymerase chain reaction, latex agglutination test, and enzyme-linked immunosorbent assay.

To investigate the usefulness of examination of cerebrospinal fluids (CSF) in the diagnosis of central nervous system (CNS) aspergillosis, we examined five patients with either brain abscesses or cerebral infarctions and 11 control patients. CSF samples were subjected to enzyme-linked immunosorbent assay (EIA), latex agglutination test (LA) and polymerase chain reaction (PCR). Cultures of CSF samples were negative in all the patients, but PCR, EIA and LA were positive in five, four and four patients with CNS aspergillosis, respectively. None of these tests were positive in the control patients. CSF examination may be beneficial in the diagnosis of CNS aspergillosis.

Adult↗
PubMed1999

Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.

The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.

Adolescent↗
PubMed2000

Case report. Chronic necrotizing pulmonary aspergillosis in a non-neutropenic patient treated with liposomal amphotericin B.

Chronic necrotizing pulmonary aspergillosis is a rare infection encountered mainly in immunocompromised patients. We present the case of a young woman where the diagnosis of chronic necrotizing pulmonary aspergillosis was established after an open biopsy of the right lung. Liposomal amphotericin B was administered postoperatively for 10 days with moderate success. In a concise review we summarize the basic notions of chronic necrotizing pulmonary aspergillosis.

Adult↗
PubMed2002

Case Report. Disseminated aspergillosis complicating pregnancy.

We report a case of disseminated aspergillosis in a hitherto healthy 24-year-old woman during her 24th week of pregnancy. Relevant findings at autopsy revealed innumerable septate, dichotomously branched (45 degrees ) hyphae compatible with Aspergillus in lung and liver tissues. Cerebral histology showed cerebral vessels occluded by hyphae causing cerebral infarction. There was no evidence of invasive aspergillosis in the placenta and fetal tissues. Aspergillus sp. was confirmed by amplification of a specific 357-base-pair amplicon from a paraffin block containing lung tissue. This case illustrates a previously uncharacterized spectrum of disseminated aspergillosis, indicating the need for a heightened awareness that Aspergillus species are opportunistic agents for invasive and disseminated infection in pregnancy.

Adult↗
PubMed2001

Allergic bronchopulmonary aspergillosis: new concepts of pathogenesis and treatment.

Allergic bronchopulmonary aspergillosis (ABPA) is a condition that results from a hypersensitivity reaction to the fungus Aspergillus fumigatus. The purpose of the present review is to examine the pathogenesis of this condition and the evidence for treatments available. Allergic bronchopulmonary aspergillosis is characterized by an intense airway inflammation with eosinophils and the formation of mucus plugs. Clinically, there are periods of exacerbation and remission that may lead to proximal bronchiectasis and fibrotic lung disease. New evidence confirms the role of intense airway inflammation with eosinophils, but also suggests a role for interleukin (IL)-8/neutrophil-mediated inflammation in this process, and the potential deficiency of anti-inflammatory cytokines such as reduced IL-10. Treatment for ABPA has so far focused on corticosteroids to suppress eosinophilic airway inflammation. An expanding knowledge of the pathology of ABPA also suggests other therapies may be of potential benefit, particularly the use of azole antifungal agents. Allergic bronchopulmonary aspergillosis is itself an important complication of asthma and cystic fibrosis. A greater understanding of the condition is required to improve management and well-designed clinical trials need to be carried out to critically assess new and current treatments. In addition, the information gained from the studies of its pathogenesis has the potential to benefit our understanding of the disease processes in asthma and bronchiectasis.

Adrenal Cortex Hormones↗
PubMed2000

Characterization of a possible nosocomial aspergillosis outbreak.

OBJECTIVE: To study the epidemiologic aspects of a suspected outbreak of nosocomial invasive aspergillosis. METHODS: Sixteen Aspergillus fumigatus strains were isolated from bronchoalveolar washings or sputa of 10 patients during a 9-month period. Furthermore, two environmental samples, isolated in a microbiological screening of the hospital, were also available for analysis. Random amplified polymorphic DNA analysis (RAPD) was carried out. RESULTS: The analysis performed by RAPD clearly demonstrated substantial genetic variation among the isolates. Both of the two different primers selected for RAPD analysis (R-108 and AP12h) were able to demonstrate that the strains isolated from all patients infected with the same fungal species and the environmental samples were genotypically distinct. The results by RAPD typing demonstrated that this technique could detect variability among isolates of Aspergillus fumigatus from different patients and even from the same patient. CONCLUSIONS: RAPD genotyping proved that the outbreak of invasive aspergillosis consisted of a series of events, non-related, and probably not coming from the same source within the hospital. This type of analysis is an easy, quick and highly discriminatory technique that may help in planning epidemiologic studies of aspergillosis.

Aspergillosis↗
PubMedDate not supplied

CT assessment of bone marrow transplant patients with rhinocerebral aspergillosis.

PURPOSE: Invasive rhinocerebral aspergillosis is a hazardous complication of bone marrow transplantation. A study was conducted to describe the computed tomography (CT) features of this disease. MATERIALS AND METHODS: Charts and CT scans of bone marrow transplant patients with invasive rhinocerebral aspergillosis were reviewed. The diagnosis was confirmed by otolaryngologic examination and biopsy of suspected lesions. Sinus CT scans were conducted without contrast material. They were repeated with contrast if intracranial or intraorbital extension was suspected. CT scans were correlated with physical examination, history of disease, and histology. RESULTS: Of 1,013 bone marrow transplantations carried out over a 10-year period, 21 patients (2.07%) developed invasive rhinocerebral aspergillosis. In most cases the infection was unilateral. Air-fluid levels and calcifications were rarely encountered. Mucosal thickening, soft tissue hyperdense masses in the nasal cavity and/or sinuses, and clear (uninvolved) ethmoid cells amid diseased cells, were significant CT features that characterized invasive fungal infection. Opacification of the sinus represented extensive disease with tissue necrosis. When bone destruction was encountered, fulminant infection was already present, usually with significant orbital and/or brain invasion. CONCLUSIONS: When correlated with clinical findings and histologic results, the above CT features can help identify early infection so that appropriate medical and surgical treatment can be instituted.

Adolescent↗
PubMed2002

Central nervous system aspergillosis: a 20-year retrospective series.

Over the past 20 years at my institution, 71 patients with invasive necrotizing aspergillosis have been encountered; 42 have shown central nervous system (CNS) involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis patients had invasive disease confined to the lung, and only 2 with dissemination to 3 or more organs did not have spread to the CNS. In addition to the expected post-transplantation and hematologic malignancy cases, other risk groups identified included those with chronic asthma and steroid use, acquired immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses. The extent of gross neuropathologic disease ranged from subtle abscesses to massive hemorrhagic necrosis causing herniation and death. In addition to the expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis, and subtle bland infarctions were also seen. Distinctive microscopic findings encountered included 1 case with numerous meningeal granulomas and multinucleated giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same period, single cases of cerebritis caused by morphologically similar fungi (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum, Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis clinically and pathologically.

AIDS-Related Opportunistic Infections↗
PubMed2002

Invasive subglottal aspergillosis in a patient with severe aplastic anemia: a case report.

A 19-year-old female with aplastic anemia who developed subglottal aspergillosis is reported. She presented with fever, cough and stridor. Inspiratory dyspnea progressed rapidly and emergent tracheostomy was performed, which confirmed the diagnosis. In spite of intensive anti-fungal treatment combined with adoptive immunotherapy, Aspergillus infection expanded and she died of pulmonary aspergillosis. Autopsy revealed the fungal mass obstructing the trachea and disseminated pulmonary aspergillosis. Difficulties in diagnosis and management of subglottal Aspergillus infection are discussed.

Adult↗
PubMed2003

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis.

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

Adolescent↗
PubMed1988

Surgery for pulmonary aspergilloma and pleural aspergillosis.

Pulmonary aspergilloma and pleural aspergillosis are a potentially lifethreatening disease resulting from the colonization of lung or pleural cavities by the ubiquitous fungus Aspergillus fumigatus. Twenty four patients with pulmonary aspergilloma and five with pleural aspergillosis underwent major thoracic procedures at our hospital between 1976 and 1986. Fourteen of the patients had haemoptysis, in 9 it was recurrent, and in 5 life-threatening. Tuberculosis, pneumonia, and sarcoidosis were the most common preexisting lung lesions. Surgical procedures included 7 pleuropneumonectomies, 18 lobectomies and 4 wedge resections. The postoperative mortality rate was approximately 7% (2 pat.). Based on the pathological examination 4 patients had unexpectedly a bronchial carcinoma in addition to the aspergilloma. Bronchopleural fistula with persistent air space was a serious complication only for patients after pleuropneumonectomy. 23 patients including those with complex aspergilloma and pleural infection had no postoperative complications; in none of the 27 operative survivors were there any recurrent symptoms over a follow-up between one and ten years. Good-risk patients with documented aspergilloma, even asymptomatic, should be resected, because of the danger of exsanginating haemorrhage. For patients with pleural aspergillosis only the aggressive resection can provide effective long term palliation.

Aspergillosis↗
PubMed1983

[Invasive aspergillosis with an intrapulmonary fungus ball in childhood].

The clinical and radiological findings of invasive aspergillosis in two children with leukemia are reported. The diagnosis of invasive aspergillosis is still a problem. The fungus is only rarely demonstrated by mycological or serological methods. Therefore the radiological demonstration of an intrapulmonary "fungus ball" in the compromised host is of clinical significance, because it is characteristic of invasive aspergillosis.

Adolescent↗
PubMed2000

A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy. METHODS: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks. RESULTS: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse. CONCLUSIONS: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity.

Adrenal Cortex Hormones↗
PubMed2002

Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.

Adolescent↗