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PubMed1991

Aspergillosis in the acquired immunodeficiency syndrome.

The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Murine model of invasive aspergillosis.

The growing importance of infectious caused by Aspergillus species during the last decade has created a need for practical and reproducible animal models of invasive aspergillosis suitable for studying fungal virulence, infection pathogenesis, diagnostic markers, and testing of antifungal therapy. Murine models remain the most commonly used models for studying aspergillosis because of their ease of manipulation and the large number of reagents available for studying disease-host responses. This chapter provides describes a murine model of invasive aspergillosis suitable for basic and translational studies of invasive pulmonary aspergillosis and highlights experimental variables that affect the course and reproducibility of infection.

Animals↗
PubMed2006

Invasive pulmonary and central nervous system aspergillosis after near-drowning of a child: case report and review of the literature.

Invasive aspergillosis is extremely rare in immunocompetent children. Here we describe the clinical, radiologic, and laboratory course of fatal invasive pulmonary and central nervous system aspergillosis in a previously healthy child after a near-drowning incident with submersion in a pond. Findings were compared with data from the literature, which is reviewed. Serum Aspergillus galactomannan levels were determined retrospectively and were compared with the results of routine microbiological and radiologic examinations, showing a significant diagnostic and therapeutic delay of the routine diagnostic approach in comparison with the use of the Aspergillus galactomannan assay. This delay may have contributed to the fatal course. Serial determination of serum Aspergillus galactomannan may be helpful in diagnosing invasive aspergillosis early in case of pulmonary disease after near-drowning and may contribute to an early appropriate treatment. Currently voriconazole, eventually in combination with caspofungin, should be considered as the drug of choice in the management of invasive aspergillosis after near-drowning.

Aspergillosis↗
PubMed2005

Aspergillus susceptibility testing in patients with cancer and invasive aspergillosis: difficulties in establishing correlation between in vitro susceptibility data and the outcome of initial amphotericin B therapy.

STUDY OBJECTIVES: As the failure of amphotericin B therapy in patients with invasive aspergillosis often exceeds 50%, we sought to determine the relationship between in vitro amphotericin B resistance and clinical failure of amphotericin B against invasive aspergillosis. DESIGN: Retrospective study. SETTING: University cancer center. PATIENTS: One hundred sixteen patients with cancer and invasive aspergillosis. MEASUREMENTS AND MAIN RESULTS: The correlation between in vitro amphotericin B susceptibility, defined by both the National Committee for Clinical Laboratory Standards and Etest methods, and other prognostic factors with failure of initial amphotericin B therapy was retrospectively evaluated. Data for correlation could be clearly assessed in only 18 (16%) of the 116 patients. Admission to the intensive care unit was the only prognostic factor associated with failure of initial amphotericin B treatment in these 18 patients (p = 0.01). CONCLUSIONS: Several important obstacles underlie the correlation of in vitro susceptibility testing with in vivo efficacy of individual antifungal agents in the treatment of invasive aspergillosis. Such correlations could be determined in only a small subset of patients.

Amphotericin B↗
PubMed2000

Semiinvasive pulmonary aspergillosis in chronic obstructive pulmonary disease: radiologic and pathologic findings in nine patients.

OBJECTIVE: The purpose of this study is to assess the radiographic, thin-section CT, and histologic findings of semiinvasive aspergillosis in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: The study included nine patients with COPD seen at the Hospital de Sant Pau during a 3-year period who had histopathologically proven aspergillosis with tissue invasion. Chest radiography and thin-section (2-mm collimation) CT of the chest were available in all cases. RESULTS: Nine patients had semiinvasive aspergillosis proven at autopsy (n = 7) or by thoracoscopically guided lung biopsy (n = 2). The radiologic findings consisted of parenchymal consolidation (n = 6) and nodules larger than 1 cm in diameter (n = 3). Parenchymal consolidation involved the upper lobes in five patients and was bilateral in four. Cavitation was present in two of the patients with consolidation and in two of the patients with nodular opacities. Adjacent pleural thickening was revealed by CT in four patients. Histologically, the areas of consolidation represented active inflammation and intraalveolar hemorrhage containing Aspergillus organisms. In the three patients with multiple cavitated nodules, a variable degree of central necrosis was observed. The inflammatory infiltrate extended into the surrounding lung parenchyma, and adjacent areas of hemorrhage were also seen. Aspergillus colonies were identified within the lung tissue. CONCLUSION: Upper lobe consolidation or multiple nodules in patients with COPD should raise the possibility of semiinvasive aspergillosis.

Aged↗
PubMed2002

Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs.

OBJECTIVE: To determine effectiveness of infusion of 1 and 2% enilconazole for treatment of nasal and sinusal aspergillosis, respectively, in dogs. DESIGN: Case series. ANIMALS: 26 client-owned dogs with aspergillosis. PROCEDURE: All dogs had typical clinical signs of aspergillosis and rhinoscopically visible intrasinusal or intranasal fungal plaques associated with turbinate destruction. During rhinoscopy, affected nasal cavities and frontal sinuses were debrided meticulously. Nineteen dogs (group A) were treated with 1% enilconazole by use of a modified noninvasive infusion procedure. Seven dogs (group B) were treated with 2% enilconazole via catheters that were placed via endoscopic guidance into the frontal sinuses. All dogs underwent follow-up rhinoscopy for determination of further treatment until cure was established. RESULTS: Age, disease duration, clinical score, and rhinoscopic score were similar for both groups before treatment. In group A, 17 of 19 dogs were cured; 9, 6, and 2 dogs were cured after 1, 2, or 3 treatments, respectively. The remaining 2 dogs were euthanatized before the end of the treatment protocol. In group B, all dogs were cured; 6 dogs and 1 dog were cured after 1 or 2 treatments, respectively. Only minor adverse effects such as nasal discharge, epistaxis, and sneezing developed. CONCLUSIONS AND CLINICAL RELEVANCE: After extensive rhinoscopic debridement, 1 and 2% enilconazole infused into the nasal cavities and the frontal sinuses, respectively, were effective for treatment of aspergillosis in dogs. Intrasinusal administration via endoscopically placed catheters appeared to require fewer infusions for success. Follow-up rhinoscopy is strongly advised.

Administration, Intranasal↗
PubMed2004

Radiographic, magnetic resonance imaging, computed tomographic, and rhinoscopic features of nasal aspergillosis in dogs.

OBJECTIVE: To determine radiographic, magnetic resonance imaging (MRI), computed tomography (CT), and rhinoscopic features of nasal aspergillosis in dogs. DESIGN: Prospective study. ANIMALS: 15 client-owned dogs. PROCEDURE: All dogs had clinical signs of chronic nasal disease; the diagnosis of nasal aspergillosis was made on the basis of positive results for at least 2 diagnostic tests (serology, cytology, histology, or fungal culture) and detection of typical intrasinusal and intranasal fungal colonies and turbinate destruction via rhinoscopy. Radiography, MRI, and CT were performed under general anesthesia. Rhinoscopy was repeated to evaluate lesions and initiate treatment. Findings of radiography, MRI, CT, and rhinoscopy were compared. RESULTS: MRI and CT revealed lesions suggestive of nasal aspergillosis more frequently than did radiography. Computed tomography was the best technique for detection of cortical bone lesions; the nature of abnormal soft tissue, however, could not be identified. Magnetic resonance imaging allowed evaluation of lesions of the frontal bone and was especially useful for differentiating between a thickened mucosa and secretions or fungal colonies; however, fungal colonies could not be differentiated from secretions. Rhinoscopy allowed identification of the nature of intranasal and intrasinusal soft tissue but was not as useful as CT and MRI for defining the extent of lesions and provided no information regarding bone lesions. CONCLUSIONS AND CLINICAL RELEVANCE: The value of CT and MRI for diagnosis of nasal aspergillosis was similar and greater than that of radiography. Rhinoscopy is necessary because it is the only technique that allows direct visualization of fungal colonies.

Animals↗
PubMed2006

Results of rhinoscopy alone or in conjunction with sinuscopy in dogs with aspergillosis: 46 cases (2001-2004).

OBJECTIVE: To determine results of diagnostic testing, including detection of nasal or frontal sinus fungal plaques, in dogs with nasal aspergillosis. DESIGN: Retrospective case series. ANIMALS: 46 dogs with nasal aspergillosis. PROCEDURES: Medical records were reviewed for information on computed tomographic findings; rhinoscopic findings, including whether fungal plaques were seen in the nasal cavity; results of frontal sinus trephination and sinuscopy, including whether fungal plaques were seen in the frontal sinus; and results of histologic examination of biopsy specimens. RESULTS: In 38 (83%) dogs, fungal plaques were seen in the nasal cavity during rhinoscopy, whereas in the remaining 8 (17%), fungal plaques were not seen in the nasal cavity but were seen in the frontal sinus. Duration of clinical signs, proportions of dogs in which the referring veterinarian had performed a nasal examination prior to referral, proportions of dogs with computed tomographic evidence of nasal cavity cavitation or sinus involvement, and proportions of dogs with rhinoscopic evidence of destructive rhinitis were not significantly different between dogs with nasal fungal plaques and dogs with fungal plaques only in the frontal sinus. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm that frontal sinus involvement is common in dogs with nasal aspergillosis and suggest that frontal sinus trephination and sinuscopy may aid in the diagnosis of aspergillosis in dogs, particularly dogs with rhinoscopic evidence of destructive rhinitis and computed tomographic evidence of sinus involvement that lack detectable fungal plaques in the nasal cavity.

Animals↗
PubMed1987

Invasive pulmonary aspergillosis: a diagnostic and therapeutic problem. Clinical experience with eight haematologic patients.

Eight patients with haematologic malignancies contracted fatal invasive aspergillosis during an outbreak. Five patients were neutropenic. Bronchofiberoscopic examination with microbiology specimen brush and bronchoalveolar lavage yielded Aspergillus fumigatus in only 2/5 patients examined. The specific diagnosis reached during lifetime in 5 patients was based on a combination of invasive procedures (lung biopsy in 2, percutaneous lung puncture in 1), the presence of a lung abscess (3 patients), seroconversion (1 patient), and purulent maxillary sinusitis caused by A. fumigatus together with repeated abundant growth of A. fumigatus in the sputum (1 patient). Six patients received amphotericin B. The infection was temporarily controlled only in 2 bone marrow transplant recipients whose granulocyte counts recovered. In 3/8 patients the pneumonia was of polymicrobial aetiology, Mycobacterium tuberculosis (2 patients), Pneumocystis carinii (1 patient), and Legionella pneumophila (1 patient) being the other microbes involved. 3/4 bone marrow transplant recipients with aspergillosis had been transplanted for chronic myeloid leukaemia, supporting the previously reported association of bone marrow transplantation for chronic myeloid leukaemia and the risk of invasive aspergillosis. Improved diagnostic methods for earlier definitive diagnosis of invasive aspergillosis as well as more efficacious and less toxic antifungal agents are needed to allow early treatment.

Adult↗
PubMedDate not supplied

Complicated pulmonary aspergillosis with pneumothorax and pneumopericardium in a child with acute lymphoblastic leukemia.

Invasive aspergillosis is a fungal infection that is being observed increasingly in immunocompromised patients due to the use of more aggressive chemotherapeutic regimens. To our knowledge, no case of pneumothorax and pneumopericardium associated with invasive pulmonary aspergillosis has been reported to date. High-dose amphotericin B (1 to 1.5 mg/kg/day) is the treatment of choice, although severe side effects, especially hypokalemia, are very common. Itraconazole is considered to be a therapeutic alternative for invasive pulmonary aspergillosis in immunocompromised patients. A rare combination of pneumothorax and pneumopericardium associated with systemic aspergillosis in a child with acute lymphoblastic leukemia is described. Treatment with low-dose amphotericin B and itraconazole achieved complete resolution of the foregoing complications.

Amphotericin B↗
PubMed2000

[Transformation of the fungus ball type pulmonary aspergillosis].

Though the concept of semi-invasive pulmonary aspergillosis was advocated in 1981 by Gefter et al., its histopathological appearance has not yet been reported in detail. Pathological studies on fungus ball type pulmonary aspergillosis (PA) were originally made mainly in regard to related bronchi. Chronic-progressive destructive changes cannot be completely explained from this viewpoint alone. Clinically, since bloody sputum and hemoptysis appeared frequently, further studies on the pulmonary vasculature were considered necessary. In the resected lungs of 3 cases of semi-invasive pulmonary aspergillosis, the pathological features of pulmonary vasculature were characterized by numerous fungal clots within pulmonary arteries and veins, marked destruction of pulmonary blood vessels and extensive intravascular fibrin deposition. Intravascular fibrin deposition causes stasis of blood flow, promotes intravascular proliferation of aspergilli and probably accelerates pulmonary destruction caused by blood stasis. Important pathological findings of fungus ball type pulmonary aspergillosis of the semi-invasive subtype with clinical aspects of chronic-progressive lung destruction caused by severe inflammation, were reported for both the vascular and the bronchial system.

Adult↗
PubMed2006

[Invasive multisystemic aspergillosis in an immunocompetent child: case report].

Invasive aspergillosis is a severe disease, with an increased incidence in last decades. It occurs mainly in immunocompromised patients and rarely affects immunocompetent hosts. We describe a previously healthy 8 -year-old boy who acquired an invasive aspergillosis of abdominal origin associated with an opened laparotomy; within three weeks the patient progressed to a multiple organic failure syndrome and died despite amphotericin B deoxycolate plus voriconazole treatment and aggressive surgical debridement. Necropsy revealed multiple parenchyma involvement with characteristic findings of angioinvasive aspergillosis. Invasive aspergillosis must be considered an emergent infection in critical pediatric patients, including previously immunocompetent hosts; it is associated with high mortality despite adequate and opportune therapy.

Amphotericin B↗
PubMed1999

[Three cases of semi-invasive pulmonary aspergillosis occurring in healthy or diabetic individuals].

We encountered three cases of suspected semi-invasive pulmonary aspergillosis, occurring in healthy or diabetic patients. Radiographic findings disclosed cavity formation in 2 of the patients, but only nodular lesions in 1. The beta-D glucan level was elevated in 1 patient, but was within the normal range in the other 2. Morphological findings indicated that all 3 patients had pulmonary aspergillosis. Following the oral administration of FLCZ to 1 patient and ITCZ to the other 2 for about 2 months, the radiographic lesions resolved and hematologic inflammatory reactions cleared up. Gefter et al and Sider et al have defined 2 types of aspergillosis that occur in mildly immuno-compromised or healthy individuals: the semi-invasive type, which destroys pulmonary tissue without vascular invasion and leads to cavity formation; and the locally invasive type, which is characterized by nodular or massive radiographic lesions without cavity formation. Semi-invasive aspergillosis was diagnosed in all 3 of the cases we reported.

Adult↗
PubMed2000

Diagnostic dilemma: aspergillosis.

Two cases of varied forms of Aspergillosis are reported who were being diagnosed and treated on different lines. One case, who was treated on lines of allergic bronchitis, had very high total eosinophil count and, fleeting pulmonary infiltrates over a period of 5 years along with history of cough, fever and weight loss. Aspergillus fumigatus was grown on sputum culture. On the background of a long standing history of bronchial asthma with evidence of peripheral as well as central eosinophilia, fleeting pulmonary infiltrates and A. fumigatus grown on sputum culture, we kept the diagnosis of Allergic Bronchopulmonary aspergillosis (ABPA) and put the patient on steroids and Itraconazole. Patient showed good response to therapy. Another case, a 50 year old male, presented to us with clinical picture of subacute myelitis. Being a known case of ABPA and on steroid therapy for long duration, we kept the diagnosis of invasive aspergillosis. Growth of Aspergillus fumigatus on sputum culture on three occasions and MR imaging of spine further supported our view. Aspergillosis of the lung do not have characteristic clinico-radiological features of permit the diagnosis and should be considered in the differential diagnosis of tuberculosis, pneumonia, bronchiectasis, lung abscess and bronchial asthma.

Aspergillosis↗
PubMed2001

Allergic bronchopulmonary aspergillosis mimicking pulmonary Tuberculosis.

Allergic bronchopulmonary aspergillosis is an uncommon disease in which cystic bronchiectasis is a common feature. The presence of central bronchiectasis with constitutional symptoms of cough, fever, weight loss, and pulmonary infiltration in patients with allergic bronchopulmonary aspergillosis has been misdiagnosed as cavitating pulmonary tuberculosis. Herein, we report 2 cases of allergic bronchopulmonary aspergillosis that were misdiagnosed as pulmonary tuberculosis and treated with antituberculous therapy. They all have negative sputum and bronchoalveolar lavage for acid-fast bacillus as well as their tuberculin tests. The diagnosis of pulmonary tuberculosis was based on the presence of symptoms and radiological changes. In both cases the presence of long standing asthma, high peripheral eosinophilic counts and wide spread of central bronchiectasis besides the poor response of antituberculous therapy has drawn our attention towards the diagnosis of allergic bronchopulmonary aspergillosis. This was confirmed by the presence of high immunoglobulin E level, positive skin prick test and positive specific serum immunoglobulin E to aspergillus fumigatus. Therefore, a high index of clinical suspicion with appropriate laboratory tests is required to identify such cases.

Adult↗
PubMedDate not supplied

[Diagnosis of aspergillosis and other invasive filamentous fungal infections in hematology].

OBJECTIVE: Invasive filamentous fungal infections (FFI) are difficult to diagnose in the department of hematology; a variety of arguments are necessary to confirm the fungal origin. Our study evaluated prospectively, in a large population in South Eastern France, the diagnostic techniques used ante and post mortem (mycology, anatomopathology, serology and aspergillosis antigens) to prove an FFI. METHODS: Two hundred and twenty eight neutropenic patients with obvious, probable, highly probable or presumed FFI were selected. Since completion of this study, a new classification of aspergillosis, with 3 instead of 4 levels of diagnosis, has been defined by the ICAAC in San Francisco but has not yet been published. Mycological or histological examinations were been performed on broncho-alveolar washings (BAW), puncture liquids or biopsies. Serology used precipitation, hemagglutination, immunofluorescence or ELISA techniques. Aspergillosis antigens were researched using the Pastorex method (agglutination of latex particles), launched at the beginning of the study. RESULTS: Invasive aspergillosis was diagnosed in 43.4% of patients, a non-aspergilla FFI in 6.5%, and no fungi was isolated in the cultures of 50% of patients. Ante mortem, 160 patients underwent BAW with a total of 175 samples. Among the latter, 41.7% mycological examinations were positive (presence of mycelium filaments and/or positive cultures) with 68.7% of Aspergillus fumigatus. Of the 48 puncture liquids, 25% of direct examinations and 29% of cultures were positive. Biopsies were taken from 59 patients and explored for mycology: 63.8% of direct examinations and 46.8% of cultures were positive; for those explored histologically, 76.7% revealed the presence of mycelium filaments. Post mortem, 17 patients out of 79 deceased underwent a total of 24 autopsy or biologic sampling. For 5 patients, FFI was diagnosed post mortem. Aspergillus serology and antigen explorations were conducted respectively in 202 and 182 patients and were positive in 31% and 33%. The presence of antibodies appears to be a good prognostic factor compared with the presence of antigens. CONCLUSION: Biological diagnosis of FFI relies on the multiplicity of examinations and renewal of mycological sampling.

Antigens, Fungal↗
PubMed2003

[Invasive cerebral aspergillosis in an immunocompetent patient: a case report].

A 32-year-old immunocompetent female presented with sensory aphasia and psychomotor seizure due to aspergillosis in the left temporal lobe spreaded from the left orbita. In spite of oral administration of itraconazole, the symptoms continued to deteriorate due to extension of the lesion to the left temporoparietal white matter. As a result of the stereotactic biopsy of the lesion, she was histologically diagnosed as intracerebral aspergillosis. Intravenous administration of fluconazole and amphotericin B was apparently effective for the lesion, and the symptoms subsided. Ga-67 scintigram could serve as useful adjuncts to magnetic resonance images for evaluation of the therapy. This case is unusual in that an immunocompetent patient suffered from the intracerebral aspergillosis, which invasively spreaded into the parenchyma. We discussed about her pathology, diagnosis, therapy and the route of invasive aspergillosis to the parenchyma.

Adult↗
PubMed1992

Aspergillosis of the paranasal air sinuses (case reports and review of literature).

Aspergillosis of the paranasal air sinuses is a rare entity. It is endemic in Sudan and a few states in South America. It affects healthy and immunocompromised individuals alike. It presents in two forms--the invasive and non-invasive Aspergillosis. The former is difficult to distinguish from carcinoma on clinical examination. Conventional radiographs of the sinus, a CT scan evaluation and a selective culture of the sinus fluid for fungus aid in achieving a positive diagnosis. The treatment of invasive Aspergillosis is always surgical--some form of antrostomy to facilitate sinus drainage or sinus excision supplemented with topical and/or systemic anti-fungal chemotherapy. The authors report two cases of Invasive Aspergillosis, clinically type 'benign' and 'malignant' of the paranasal air sinuses, affecting non-immunocompromised individuals. In both the cases, complete surgical excision was achieved.

Adult↗