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PubMed2005

An immunohistochemical study of canine nasal aspergillosis.

In this study, histochemistry and immunohistochemistry were used to characterize the phenotype and distribution of leucocytes in the distal nasal mucosa of 15 dogs with nasal aspergillosis. The most consistent histopathological finding was a severe, predominantly lymphoplasmacytic, inflammatory infiltration of the lamina propria. Fungal hyphae were not observed to invade the mucosa but were found at the mucosal surface and within material collected from the nasal cavity. The main immunohistochemical findings were (1) a predominance of IgG(+) plasma cells over IgA(+) and IgM(+) plasma cells, (2) significant numbers of macrophages and dendritic cells expressing MHC class II molecules, (3) macrophages and neutrophils expressing L1 antigen and (4) a mixture of CD4(+) and CD8(+) T cells. These findings are consistent with a dominant Th1-regulated cell-mediated immune response. The nature of the inflammatory infiltrate and the lack of invasiveness of the mucosa by the fungus, together with the clinical course of the disease and the apparent immunocompetence of the affected dogs, suggest that canine nasal aspergillosis resembles the chronic erosive non-invasive fungal sinusitis described in human patients.

Animals↗
PubMed2005

Hospital-wide prospective mandatory surveillance of invasive aspergillosis in a French teaching hospital (2000-2002).

A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.

Aspergillosis↗
PubMed2004

Invasive pulmonary aspergillosis with spontaneous resolution and the diagnostic utility of PCR from tissue specimens.

This case describes a 61-year-old apparently immunocompetent female with invasive pulmonary aspergillosis (IPA) and eosinophilia who demonstrated spontaneous clinical and radiological recovery. The patient had a history of asthma and had been corticosteroid dependent until 2 months prior to her presentation. This report explores the role of PCR in confirming the diagnosis of invasive aspergillosis in circumstances where only histological data are available and highlights the fact that invasive infections with Aspergillus spp. can occur without profound immunological deficiency. The case also documents the resolution of IPA without specific therapy.

Aspergillosis↗
PubMed2006

The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis.

Voriconazole is the second oral drug licensed for the treatment of aspergillosis. A retrospective non-comparative study was conducted in 16 patients with chronic cavitary pulmonary aspergillosis (CCPA) treated with voriconazole. All patients had failed or were intolerant of itraconazole. The duration of therapy varied from 3 days to 16.5 months. Eleven patients received at least 3 months of therapy with no significant adverse events. Overall seven (64%) patients had a response at 3 months as assessed by at least some fall in inflammatory markers, weight gain and reduction in pulmonary symptoms and two (18%) remained stable. Inflammatory markers improved in 5/11 (46%) with a mean fall in CRP of 0.08 mg/l and ESR of 12.8 mm/h. Aspergillus precipitins were quantitated by numbers of arcs and serum dilution and 11 (100%) showed improvement of at least one band or fall of titre. Total serum IgE was elevated (>200 IU/mL) in 5/11, and fell by a median of 118 kIU/l. Two patients failed therapy. Of the 17 patients, five (27%) had to discontinue therapy as a result of adverse events (three in under 1 week). Adverse events included erythematous rash (5), headaches (4), hepatotoxicity (3), photosensitive rash (3), retinal flashes (3) and neurological symptoms (3). Voriconazole is a useful alternative therapy for CCPA, with a response rate of 64%, over 3 months, and continuing partial remission of disease for much longer periods.

Antifungal Agents↗
PubMed2005

Efficacy of amphotericin B or amphotericin B-intralipid in combination with caspofungin against experimental aspergillosis.

OBJECTIVE: Infections caused by Aspergillus species are increasing in importance, especially among immunocompromised hosts. The objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin B (AMB) or amphotericin B-intralipid admixture (AMB-IL) and the echinocandin caspofungin (CAS) in experimental murine systemic aspergillosis. Inhibition of synthesis of a major component of the fungal cell wall and an effect on the cell membrane, by combining echinocandin and a polyene, may result in a synergistic interaction in vitro and in vivo against Aspergillus fumigatus. METHODS: ICR mice were immunosuppressed by intraperitoneal (ip) administration of cyclophosphamide (CY). Three days post-CY administration the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan). RESULTS: The data showed that combined CAS and AMB or AMB-IL treatment increased the survival of the mice (up to 69.2%) as compared to those treated with each agent alone (44.4, 40.7 and 50%, respectively), and prolonged their mean survival time to 22.5 days. These combinations also resulted in reduction of fungal burden in organs, and decrease in serum galactomannan. CONCLUSION: The successful results obtained in the experimental animal model of this study may possibly open the way to more effective management of aspergillosis in humans.

Amphotericin B↗
PubMed1981

Pleural effusion in allergic bronchopulmonary aspergillosis: two case reports.

Two cases of pleural effusion associated with allergic bronchopulmonary aspergillosis are described. This association has not previously been reported. In one case the effusion cleared with prednisolone. It is suggested that the effusions were directly related to the aspergillosis.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1987

Comparison of narrow section computed tomography and plain chest radiography in chronic allergic bronchopulmonary aspergillosis.

Narrow section (3 mm width slices every 10 mm) computed tomography on an Elscint 2002 scanner and plain chest radiography were performed in 10 patients with allergic bronchopulmonary aspergillosis. No patient was experiencing an acute exacerbation. The investigations were reported separately and in random order. Bronchiectasis was reported in 31 of 60 lobes on computed tomography compared with only 15 on plain chest radiographs. Computed tomography was also more sensitive for proximal bronchiectasis detected in 16 lobes compared with only in 10 on plain chest radiographs. Serial computed tomography may allow earlier identification of progression of lung damage in patients with allergic bronchopulmonary aspergillosis and so help in planning treatment.

Adult↗
PubMed1983

Invasive aspergillosis of paranasal tissues in children with malignancies.

Paranasal aspergillosis was encountered in five children with relapsed malignancies. All had received broad-spectrum antibiotics within two weeks of development of aspergillosis, and all had absolute granulocyte counts less than 200/mm3 for at least three weeks. None had received prior antifungal therapy. There was an average delay of eight days before the correct diagnosis was established by either biopsy or culture. These data emphasize the need to obtain surveillance cultures of the upper respiratory tract passages in severely neutropenic patients receiving prolonged antibiotic therapy, and raise a question concerning prophylactic use of antifungal therapy in this group.

Adolescent↗
PubMed1987

Invasive aspergillosis diagnosed by immunohistochemistry with monoclonal and polyclonal reagents.

Therapies differ for invasive infection due to the various filamentous fungi. However, histopathologic identification of Aspergillus, Pseudallescheria, Fusarium, Trichosporon, dematiacious Hyphomycetes, Candida, and Zygomycetes may be confused, and microbiologic isolation is often delayed. To improve diagnosis, we examined the utility of polyclonal and monoclonal antibodies to identify Aspergillus organisms by peroxidase immunohistochemical techniques. Tissues obtained from 68 infected patients were examined. Fungal antigen was detected in all 26 cases of aspergillosis by the monoclonal immunohistochemical test. Hyphae of Aspergillus organisms exhibited strong intracellular and cell wall staining, and extracellular localization was also observed. In contrast, negative tests were observed in tissues from five cases of infection with Pseudallescheria boydii, three with Trichosporon, three with Zygomycetes, six with Candida species, and one with Curvularia, from as well as 20 cases of nonfungal pneumonia. However, cross-reactivity to Coccidioides immitis spherules was noted in three cases. Staining of Candida was observed with the polyclonal antibody but not the monoclonal reagent. This is the first immunohistochemical demonstration of aspergillus antigen with a monoclonal reagent. The study indicates that the monoclonal immunohistochemical technique can distinguish Aspergillus species from other filamentous fungi and may facilitate the clinical diagnosis of invasive aspergillosis.

Adult↗
PubMed1998

Aspergillosis of the testis in a renal transplant recipient.

Aspergillus is ubiquitous worldwide. It is found primarily in soil, dust, vegetation, and decaying matter. While disseminated aspergillosis affects the testis only 1% of the time, testicular aspergillosis in the absence of disseminated disease is exceedingly rare, as demonstrated in the present case report.

Aspergillosis↗
PubMed1982

Disseminated aspergillosis occurring in patients with respiratory, renal, and hepatic failure.

Respiratory, renal, and hepatic insufficiency developed in five patients who had been admitted to hospital for a variety of reasons. Although in four cases Aspergillus had been isolated from tracheal secretions before death, the significance of this finding was not fully appreciated, and in all five the diagnosis of aspergillosis was made at necropsy. Since treatment has to be started early if it is to be effective, patients with any combination of respiratory, renal, and hepatic failure should have their tracheal secretions examined daily. If Aspergillus is cultured, and hyphae are present in a fresh smear, and the patient has features of a generalised infection without an obvious site of infection, treatment for aspergillosis should be considered.

Acute Kidney Injury↗
PubMed1985

Comparison of serial diagnostic tests in a patient with invasive aspergillosis.

Studies on a liver transplant recipient with fatal disseminated aspergillosis are described. The concentration of IgG antibodies to Aspergillus rose sharply with the onset of fever and changes in the chest X-ray, reaching a peak on day 10. Thereafter, antibody concentrations fell and were within the normal range by day 21, when Aspergillus was first isolated from an endotracheal aspirate and one day before death. The fall in antibodies preceded a rise in circulating immune complexes but Aspergillus antigens were not detected in the serum. Serial quantitative assay for antibodies to Aspergillus may be more appropriate than culture or attempts to detect antigen in the early diagnosis of invasive aspergillosis in immunocompromised patients.

Antibodies, Fungal↗
PubMed1998

Cerebral aspergillosis in a liver transplant recipient: a case report of long-term survival after combined treatment with liposomal amphotericin B and surgery.

Cerebral aspergillosis is a life-threatening complication in liver transplant recipients, with mortality rates approaching 100%; treatment with amphotericin B is of limited efficacy because of its poor distribution in the cerebrospinal fluid and its systemic side effects. We report the case of a liver transplant recipient who developed recurrent cerebral Aspergillus fumigatus infection, and was successfully treated by combined surgical excision of the lesion and administration of liposomal amphotericin B. This first report of long-term complication-free survival in a liver transplant recipient suggests that therapy with liposomal amphotericin B may reduce the risk of recurrence of cerebral aspergillosis in these immunocompromised patients.

Amphotericin B↗
PubMed1986

Aspergillus fumigatus antigens used in the serodiagnosis of aspergillosis.

The diagnostic antigens in Aspergillus serology are mycelial or culture filtrate concentrates. Recent work has been directed towards the separation of defined, reproducible products of greater sensitivity and specificity than crude extracts. Conventional methods of separation have been used; they include fractional precipitation, detergent extraction, chromatography, and preparative isoelectric focusing. Selective staining of the separated fractions has shown many of the more reactive components to be glycoproteins. Affinity binding to Concanavalin A has demonstrated the presence in these of alpha-D-glucopyranose, alpha-D-mannopyranose and/or terminal alpha-D-N-acetylglucosamine. Major amino acid constituents are serine and threonine, together with glutamic and aspartic acids. The more reactive and specific components, as judged by their antibody binding capacity, have molecular weights greater than 70,000; in some cases they are as high as 150,000 to 180,000. Isoelectric focusing gave products with acidic pI values which specifically bound the IgG present in sera from aspergillosis patients. Results from a number of laboratories suggest that a group of acidic glycoproteins constitute the most promising source of a diagnostic reagent for aspergillosis. However, further analysis and a comparison of these substances in an international collaborative study is needed before agreement can be reached on a "standard" antigen preparation.

Animals↗
PubMed1979

Aspergillosis of the nose and paranasal sinuses.

Aspergillosis of the nose and paranasal sinuses should not be considered an innocuous disease. In a review of 103 cases, other than in the Sudan, the mortality rate was 16 per cent. Intracranial extension of the fungus from the nose and sinuses carries a grave prognosis. Although aspergillosis occurs frequently in patients debilitated from other diseases, this is not always the case, and most deaths in the review series occurred in otherwise healthy individuals. The authors present eight cases of their own.

Adult↗
PubMed1982

Invasive aspergillosis of the hand.

Aspergillosis is a fungal infection which may disseminate from the lung to bone, meninges, heart, or other organs. It is commonly found in patients with debilitating disease and those undergoing chemotherapy. A 6-year-old boy, seen at Fitzsimons Army Medical Center while being treated for acute monomyelocytic leukemia, developed invasive aspergillosis of the hand, requiring resection of the central three rays. This rare presentation of the disease required radical surgery to control its local manifestations and to prevent widespread dissemination.

Amputation, Surgical↗
PubMed1996

Cutaneous aspergillosis.

Aspergillosis comprises a spectrum of diseases caused by species of a ubiquitous saprophytic mold, Aspergillus, that usually live on decaying vegetation. Aspergillus organisms rarely behave as pathogens in an immunocompetent host. In the presence of immunosuppression, however, aspergillus may be invasive and take a fulminant course. Aspergillosis is the second most frequent opportunistic fungal infection surpassed only by candidiasis; therefore, early detection and treatment are essential to minimize morbidity and mortality. This article reviews the historical aspects, etiology, epidemiology, clinical manifestations, pathology, and treatment of this disease and focuses on the cutaneous aspects of species of Aspergillus known to infect humans.

Antifungal Agents↗