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PubMed1991

[Cerebral aspergillosis in immunocompromised patients].

Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported. All three had neurological symptoms with normal cerebrospinal fluid (CSF). The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium. They also had pulmonary signs and fever despite antibiotic treatment. Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid. Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine. Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit. Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney. The CT scan signs were quite different from those seen with the more usual bacterial ring lesions. In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis. Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis. Early antifungal treatment is the only chance of survival. Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise.

Adult↗
PubMed2006

[Semi-invasive necrotic aspergillosis in a child with cystic fibrosis].

INTRODUCTION: Aspergillosis colonisation in cystic fibrosis (CF), usually due to Aspergillus fumigatus (AF), classically presents as allergic bronchopulmonary aspergillosis. However, aspergillus infection can produce a range of manifestations: from minor colonization to an invasive infection. CASE REPORT: A 14-year-old CF patient, chronically colonized with Staphylococcus aureus and Pseudomonas aeruginosa, presented with acute right-sided chest pain, a moderate fever and no modification of the sputum. The chest X-ray showed a 5 cm round opacity. Laboratory parameters were WBC 24,500 G/l, CRP 27 mg/l, Total IgE 1527 UI/l, Specific Aspergillus fumigatus IgE 31 UI/l. Bronchoscopy revealed external compression of the middle lobe bronchus with mucopurulent secretions coming from apical segment of the lower lobe. Bronchoalveolar lavage revealed the presence of pseudomonas aeruginosa 103 CFA/ml, staph aureus 107 CFA/ml and one colony of AF. Chest CT scan showed a large necrotic mass with an air-fluid level located in the apical segment of the right lower lobe. Initial therapy with itraconazole and corticosteroid was replaced by voriconazole, caspofungin, metronidazole and linezolide. Treatment was well tolerated and after 8 weeks the chest X-ray appearances had returned to normal. CONCLUSIONS: The possible diagnoses and therapeutic options are discussed. Conventional antifungal treatment with amphotericin B is limited by nephrotoxicity. These newer antifungal agents appear to be effective and well-tolerated.

Adolescent↗
PubMed2003

Polyene and cytokine treatment of experimental aspergillosis.

The aim of the present study was to assess the efficacy of amphotericin B (AMB), AMB-intralipid admixture (AMB-IL) or nystatin-IL formulation (Ny-IL) in combination with granulocyte colony stimulating factor (G-CSF) in treatment of experimental murine aspergillosis. ICR mice were immunosuppressed by cyclophosphamide and 3 days later inoculated intravenously (i.v.) with Aspergillus fumigatus. Treatment was initiated 2 h later and administered for 5 consecutive days (polyenes, i.v.; G-CSF, intraperitoneally). Combination therapy, particularly G-CSF with AMB or AMB-IL, significantly increased the survival rate (up to 87.3%) and prolonged the mean survival time (MST) (up to 28.8 days) in comparison to untreated controls (0% survival, MST 6.7 days) and to treatment with polyenes alone (up to 51.5% survival, MST 18.4 days). These data indicate that combination therapy could be beneficial for management of disseminated aspergillosis in humans.

Amphotericin B↗
PubMed2002

Scintigraphic imaging using 99mTc-labeled PEG liposomes allows early detection of experimental invasive pulmonary aspergillosis in neutropenic rats.

The value of scintigraphic imaging using 99mTc labeled poly(ethyleneglycol) (PEG) -liposomes for detecting invasive pulmonary aspergillosis at different stages of the disease was investigated in a rat model. At 24, 48, 72, 120 and 168 h after fungal inoculation scintigraphic images were obtained and biodistribution of the radiolabel was determined. Findings were compared with serum galactomannan detection and other parameters of progression of fungal infection. At 48 h liposomal uptake in the infected left lung was increased significantly and 82% of the scintigraphic images was assessed positive. Serum galactomannan was only detected at 72 h and later. Liposomal uptake in the infected left lung increased over time and was significantly correlated with both the size of the pulmonary hemorrhagic lesion and the levels of circulating galactomannan. It was concluded that scintigraphic imaging using 99mTc-PEG-liposomes allows early detection of invasive pulmonary aspergillosis in this model, and that liposomal uptake in the infected lung was strongly associated with the severity of the disease.

Animals↗
PubMed2000

Aspergillosis in bone marrow transplant recipients.

Invasive aspergillosis in bone marrow transplant recipient is associated with a high mortality. Diagnosis is often delayed because the inflammatory response is blunted by immunosuppression. The gold standard of tissue biopsy is often considered too in invasive as the procedure is often complicated by bleeding and secondary infection. Recent finding on non-invasive tests such as serial measurement of peripheral blood galactomannan antigen or DNA appears to be promising. However, the limited availability of such tests and requirement for expertise are still hampering their use in routine clinical management. More often than not, initiation of antifungal therapy is empirical and based on suggestive radiological changes. Amphotericin B remains the gold standard of therapy but liposconal preparation may prove to be less nephrotoxic and equally effective. Treatment outcome depends more on the acceleration of the recovery of the immune system and the reduction of anti-GVHD therapy than the antifungal agent followed by surgical resection. The efficacy of many reported anti-aspergillosis prophylactic regimen has not been proved in randomized control trials. Despite the absence of data, such policy should still be considered in transplant units with high incidence of aspergillus or undergoing renovation.

Air Microbiology↗
PubMed1996

Aspergillosis of the paranasal sinuses. A case report and radiographic review.

Aspergillosis of the paranasal sinuses is uncommon; however, its incidence in recent years has shown a marked increase, and it is believed that it may account for a number of cases of nonspecific sinusitis. It may present in one of four forms, one of which is the noninvasive Aspergillus mycetoma. One such case affecting the maxillary sinus is reported, and reference is made to its possible sequelae and management. The significance of its presentation as a radiodense focus within the antrum on plain radiographs and computed tomography is discussed, as is the use of magnetic resonance imaging for excluding aspergillosis from the differential diagnosis.

Adult↗
PubMed2006

A case of pulmonary aspergillosis with lack of response to caspofungin.

Currently, susceptibility testing of Aspergillus isolates towards caspofungin is hampered by a lack of interpretative cut-off values. Nevertheless, caspofungin has been widely recommended for the treatment of invasive aspergillosis. This antifungal, however, could lead to therapy failure as demonstrated by the case in this report of a 55-year-old patient, who eight months after the diagnosis of leukemia and successful allogenic hematopoietic stem cell transplantation (HSCT), succumbed to a fatal pulmonary aspergillosis infection, which resisted treatment with caspofungin.

Acute Disease↗
PubMed2004

Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis.

The availability of the Platelia Aspergillus, a sandwich ELISA kit that detects circulating galactomannan, has been a major advance for managing patients at risk for invasive aspergillosis because of the early detection of the antigen. The assay is now widely used throughout the world, including the USA. Although initial studies that assessed the performance characteristics of this assay reported high sensitivity and specificity, more recent studies show significant variation in performance. The causes of this variability are multifactorial and, in large part, cannot be explained because there is insufficient understanding of the kinetics of galactomannan in vivo. We explored some of the factors that affect the release of the aspergillus antigen that bears the epitope that reacts with the monoclonal antibody used in the ELISA, its leakage from the site of infection into the blood, and its binding to substances present in the blood. Factors that affect the detection of antigen in blood are also discussed, most notably the pretreatment procedure aimed at liberating the antigen from immune complexes. Understanding the biology of galactomannan release by aspergillus will greatly enhance our understanding of the kinetics of this and other surrogate markers and allow their optimum use in the management of invasive aspergillosis.

Antigens, Fungal↗
PubMed1994

Aspergillosis of the larynx.

Primary infection of the larynx with Aspergillus spp. is rare. It is more commonly seen as part of a wider infection involving the respiratory system in an immunocompromised host. In noncompromised patients laryngeal aspergillosis may represent colonization rather than invasion requiring no systemic anti-fungal treatment. The diagnosis is important as the presenting symptoms are suggestive of malignant laryngeal disease. We present a 62-year-old man with a short history of hoarseness. Direct laryngoscopy and biopsy confirmed the diagnosis of aspergillosis. Clinical presentation, diagnosis and the important pathological characteristics of this infection are discussed.

Aspergillosis↗
PubMed1997

Invasive aspergillosis of the paranasal sinuses: a medical emergency.

A rare case of invasive aspergillosis of the paranasal sinuses in a previously healthy individual is presented. The disease caused severe complications and proved fatal. Classification, aetiology and presentation of sinus aspergillosis are discussed. Early diagnosis and management is stressed to avoid the high incidence of morbidity and mortality.

Aged↗
PubMed1987

Construction activity: an independent risk factor for invasive aspergillosis and zygomycosis in patients with hematologic malignancy.

Between November 1982 and July 1984, five patients at a 110-bed pediatric hospital were diagnosed with invasive filamentous fungal infection; three had invasive aspergillosis (IA) and two had invasive zygomycosis (IZ). All five had underlying hematologic malignancy (HM). In a case-control study, these five HM patients (cases) were compared to 10 autopsied HM patients without evidence of aspergillosis or zygomycosis (controls). Cases and controls did not differ in underlying disease or in the degree of immunosuppression, as measured by duration of granulocytopenia and number of platelet transfusions. However, case-patients were more likely than controls to have been hospitalized during the construction of a hospital addition (p less than 0.02, Fisher's exact test [FET]). Four (80%) of five HM patients autopsied during the period of construction had IA or IZ compared with one (5%) of 21 autopsied before construction began (p = 0.001, FET). These findings suggest that, in a population of comparably immunosuppressed patients, construction activity may represent an independent risk factor for IA or IZ. Hospitals caring for such patients should take precautions which minimize exposure of these patients to construction or renovation activity.

Adolescent↗
PubMed2002

Animal models of allergic bronchopulmonary aspergillosis.

Among the allergic fungi, Aspergillus fumigatus, a saprophytic mold, distributed widely in the environment is a frequently recognized etiologic agent in a number of allergic conditions. Among the different allergic diseases caused by this fungus, allergic bronchopulmonary aspergillosis (ABPA) is by far the most significant one. The immunopathogenesis of this disease is not fully understood. Although several immunomodulatory treatments are available for allergic disease, none of them are applicable or relevant or useful in fungal induced allergy. It is essential to understand the pathogenesis of the disease including the antigen induced immunoregulation and the resulting factors, such as cytokine, chemokines, pathways activating factors, inflammatory and airway remodeling factors need to be understood for intervening with appropriate treatment. Animal models are essential in understanding these features of the disease. Several models of allergic aspergillosis have been developed in recent years in various animals. However, murine models have been studied more carefully and extensively. The exposure to antigen in mice leads to allergy very similar to ABPA with high IgE, elevated peripheral blood and lung eosinophils, pulmonary inflammation, and airway hyperreactivity. The role of various cytokines and chemokines and their receptors were also studied. In addition, immunotherapy and vaccination have been attempted in recent years using the murine model of ABPA. This review covers the murine model of Aspergillus induced allergy and asthma and presented critically our current understanding of the subject and the potential application of such a model in future for developing treatment modalities.

Animals↗
PubMed2004

Pulmonary aspergillosis outbreak in Rhea americana in southern Brazil.

Commercial raising of rheas is currently in expansion in the south of Brazil, and many diseases previously restricted to other avian species are currently emerging on rhea farms, especially as a result of careless management of these animals. The objective of the present article is to report a pulmonary aspergillosis outbreak that occurred in great rhea (Rhea americana) in the south of Brazil. About 50 birds aged 30 to 60 days died suddenly and one of them was submitted to autopsy which revealed the presence of white caseous nodules 0.5 mm in diameter occupying 95% of the lung area. One lung was sent to the Federal University of Santa Maria for histopathological and mycological analyses. Histopathological analysis revealed multifocal areas with necrosis and inflammatory infiltrates and the presence of fungal hyphae, giant cells and fibrous tissue proliferation at the periphery. Aspergillus fumigatus was recovered as pure culture from all culture media. This appears to be the first report of aspergillosis among great rhea in Brazil and the second in the world.

Animals↗
PubMed2002

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants.

BACKGROUND: Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. OBJECTIVE: To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. PATIENTS: The 2,046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. METHODS: Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. RESULTS: We identified 33 cases of IA (28% disseminated) in 2,046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1,000 patient-years (33 cases/6,813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1,000-pt year vs. heart 0.4% (3/686) or 1.4 per 1,000-pt year vs. liver 0.7% (3/439) or 2.1 per 1,000-pt year vs. renal 0.4% (3/733) or 1.2 per 1,000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). CONCLUSIONS: The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.

Adult↗
PubMed1996

Exacerbation of invasive aspergillosis by the immunosuppressive fungal metabolite, gliotoxin.

Invasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority of strains of the main causative agent, Aspergillus fumigatus, produce gliotoxin, a secondary metabolite with demonstrated in vitro immunosuppressive activity. Pretreatment of normally resistant mice with a single injection of a sublethal dose of gliotoxin was sufficient to make them susceptible to infection and subsequent death, after challenge with A. fumigatus spores. Animals infected with the non-gliotoxin producing strain survived significantly longer than those infected with a gliotoxin producer. We propose that the release of gliotoxin by A. fumigatus hyphae during infection can exacerbate the pathogenesis of aspergillosis.

Animals↗
PubMed1997

Resolution of invasive central nervous system aspergillosis in a transplant recipient.

Central nervous system (CNS) aspergillosis carries a uniformly poor prognosis in bone marrow transplant recipients. Amphotericin B can be bound to lipid carriers leading to improvement of its therapeutic index. We describe the successful medical management of CNS aspergillosis in an allogeneic bone marrow transplant patient with administration of Amphotericin B Lipid Complex.

Adolescent↗
PubMed1998

Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients.

The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients.

Antigens, Fungal↗