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PubMed1972

Experimental visceral aspergillosis.

Studies conducted to gain insight into the pathogenesis of experimental aspergillosis indicated that mice pretreated with cortisone acetate and then injected intraperitoneally with nongerminating spores of Aspergillus flavus developed a high incidence of lethal visceral hyphal aspergillosis. A similar, high incidence of fatal infections was observed in cortisone-treated animals in which the number of peritoneal macrophages had been increased by prior injection of thioglycollate. To determine whether germination of spores within the host was important to the subsequent development of disseminated hyphal aspergillosis, germinating spores of A flavus were injected intraperitoneally into normal animals. While a similar dose of nongerminating spores, administered intraperitoneally into normal mice, induced a low incidence of lethal injection, germinating spores induced a high incidence of fatal disease associated with widely disseminated visceral hyphal aspergillosis. Our studies indicate that phagocytic cells in the peritoneal cavity of normal mice are able to ingest nonperminating spores of A flavus and kill them, preventing germination. However, the phagocytic cells are unable to cope with early germinating spores, which then continue to proliferate, leading to extensive hyphal invasion of visceral organs and death.

Adrenal Glands↗
PubMed1983

Studies on experimental aspergillosis in immunodeficient mice.

Mice with either chemically suppressed immune response or with specifically induced T cell or B cell immunodeficiency were challenged with Aspergillus fumigatus spores. Chemical immunosuppressants used were cortisone, cyclophosphamide or silica. T cell deficiency was produced by thymectomy and ALS administration, whereas, B cell deficiency was produced by administration of anti-mouse IgM antibodies in newborn mice. The susceptibility of such animals to A. fumigatus challenge was monitored by mortality pattern and by demonstration of dissemination of fungus in different organs. The administration of cortisone or silica made mice highly susceptible to A. fumigatus infection, whereas, cyclophosphamide initially lowered host's resistance but later had little effect. Mice with B cell deficiency also did not differ significantly from normal animals. Similarly passive transfer of specific antibodies to A. fumigatus did not enhance the protection of the host to experimental aspergillosis. However, the deficiency of T cells and macrophages either alone or in combination made the animals highly susceptible to experimental aspergillosis. The results provide evidence that T cells and macrophages play essential role in immunity to murine aspergillosis. Whereas, B cell deficiency or even passive transfer of specific antibodies to A. fumigatus does not alter much the host's susceptibility to experimental aspergillosis.

Animals↗
PubMed1982

[Relations between sinus aspergillosis, primary rhinoliths and dental pathology].

Sinus aspergilloses, which can be classified as aspergillar sinusitis and pseudo-tumoral forms, are probably much more prevalent than would appear form the published literature. Many cases of caseous sinusitus reported since the end of the last century were probably unrecognized aspergillosis infections. In the same way, primary rhinoliths can probably be related to aspergillosis. Many cases of sinus aspergillosis appear to be of dental origin, particularly when radiography detects the presence of dental obturation paste in the sinus opacity: this appearance in the sinus opacity: this appearance is almost pathognomic of the affection. Sinus aspergillosis should be recognized as recovery can be obtained in the majority of cases by simple sinus washouts, without the need for chemotherapy.

Adult↗
PubMed1995

[Disseminated aspergillosis with pulmonary and cardiac localization in an HIV-infected patient].

The authors report a case of invasive aspergillosis with pulmonary and cardiac involvement revealed by a pericarditis in a seropositive patient (VIH1). Clinical findings, differential diagnosis and outcome underly the issues encountered in the management of aspergillosis in AIDS patients. Indeed, the low prevalence of aspergillosis in AIDS and the insidious features of aspergillosis locations make the early diagnosis difficult. It is though essential for a favourable outcome under specific treatment. The risk factors, clinical characteristics and diagnostic procedures are mentioned as well as the various available treatments.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Role of chemoprophylaxis in the prevention of invasive aspergillosis].

Invasive aspergillosis remains a severe infection, and the mortality is high, specially in some patients such as bone marrow transplants. Prophylaxis may be considered either in patients without previous aspergillosis, or in patients cured from previous aspergillosis and exposed again to immunosuppression. The efficacy of prophylaxis may be difficult to demonstrate, due to the relatively low incidence of aspergillosis and the possible lack of proven mycologic diagnosis. The different possibilities of prophylaxis (systemic antifungal treatment, local therapy) will be discussed.

Aerosols↗
PubMed1994

Destructive noninvasive paranasal sinus aspergillosis: component of a spectrum of disease.

A chronic, destructive form of paranasal sinus aspergillosis may exist without evidence of tissue fungal invasion. In this state, the pathogen results in progressive, chronic inflammation intermediate between previously described saprophytic and invasive states. We report three such cases. This variety of aspergillosis and an analysis of the clinical and histopathologic findings of previously reported cases support the concept that infection with the organism may produce a spectrum of pathologic changes and is akin to the range of aspergillosis disease states described affecting the lung. We classify paranasal and nasal aspergillosis as (1) noninvasive, either an aspergilloma or allergic type, (2) destructive, noninvasive, and (3) invasive, either slowly progressive or fulminant. Any form may progress to, or be associated with, more aggressive disease.

Adult↗
PubMed1993

[Placental aspergillosis: myth or reality? Apropos of a case with fetal death in utero].

The authors report an original case-history of massive aspergillosis of the placenta that occurred in a 24 year old primigravida who had had no previous history or clinical changes in pregnancy. It caused fetal death in utero with retention and maceration of the fetus. Macroscopic examination showed that the left lip was cleft and that the placenta was studded with isolated confluent diffuse whitish granulations. Histologic examination made us think that these appearances were those of aspergillar granulomas occurring even in the placental villi and intravillous spaces. Laboratory findings showed that there was Aspergillus Niger in the blood of the mother. A wide search of the literature failed to find any case in humans. On the other hand aspergillosis occurs frequently in animals causing intrauterine growth retardation and prematurity with abortion. There is great economic loss as a result. Why the animal placenta should be susceptible to infection of aspergillosis and how it acquires it is discussed! Finally the association of aspergillosis of the placenta with a cleft lip found in our case, is unique and one wonders if there is any relationship.

Adult↗
PubMed1996

[Invasive aspergillosis in the hematologic patient: the usefulness of computed tomographic and high-resolution computed tomographic studies].

Invasive aspergillosis is an emerging cause of death in hematologic patients. Several patterns of lung involvement are described: acute tracheobronchitis, bronchopneumonia, pleural aspergillosis and angioinvasive aspergillosis. The latter pattern is the most common one; it is characterized by different signs, some of which, supported by clinical data, are quite suggestive for fungal etiology. Particularly, nodules and/or wedge-shaped lesions with a ground-glass halo are a useful early feature, best detected by HRCT. Early therapy with amphotericin B may improve survival chances. Therefore, in neutropenia patients we decided, when possible, to perform high-resolution computed tomography (HRCT) as soon as fever appears. This was feasible in 8 of 32 patients with invasive aspergillosis examined with HRCT. Immediate treatment with amphotericin B in one such patient showing a nodule with the halo sign allowed the lesion to completely disappear. The authors describe the frequency of different radiologic signs in 32 patients, as observed in 54 HRCT exams; the results are compared with those obtained with conventional CT and chest X-ray. Compared to chest X-ray, CT detects more lesions and is more sensitive to small pneumothorax and minimal pleural effusion or thickening. HRCT is more suitable to detect initial cavitation and thin ground-glass haloes.

Aspergillosis↗
PubMed1997

[Genetic diagnosis of aspergillosis].

Aspergillosis is an opportunistic infection caused by pathogenic Aspergillus species (spp.) and is a major hazard for immunocompromised patients and even for non-immunocompromised individuals. Clinical diagnosis of aspergillosis, especially invasive pulmonary aspergillosis (IPA) is difficult and is largely presumptive, typically based on spiking fevers not responding to antibiotics in a patient with the risk factors. It is well known that Aspergillus spp. can be only infrequently cultured from clinical specimens, and that the cultural examination is laborious and time-consuming. Moreover, positive culture from bronchoalveolar lavage or sputa is indicative, but not proof of infection. The criterion for diagnosis of pulmonary infection by aspergilli requires repeated isolation of the same species of Aspergillus from respiratory specimens. There have been some successful attempts using serological assays to detect circulating antibodies to Aspergillus spp. in the noninvasive form of the disease, but these are generally negative in an acute phase IPA patient. A currently available serodiagnostic kit, Pastrex Aspergillus is limited in clinical usefulness because of low sensitivity and specificity in spite of being simple and rapid. Contamination of clinical specimens with various saprophytic filamentous fungi other than aspergilli also often give false positive. Diagnostic methods using such molecular biological techniques, as polymerase chain reaction (PCR) have recently been employed to identify DNA from a number of pathogens when diagnostic means are limited. PCR is known as the most sensitive and specific technique by which to detect a specific DNA sequence. In this paper we have reviewed new genetic methods of diagnosing aspergillosis including PCR and in situ hybridization.

Aspergillosis↗
PubMed1997

[Saprophytic and invasive pulmonary aspergillosis].

The characteristics of chest x-ray films in 19 patients with saprophytic pulmonary aspergillosis secondary to acid-fast bacilli infection were reported. The saprophytic form, exemplified by the classic fungus ball or mycetoma, results from the growth of fungal mycelia within a pre-existing area of destroyed lung, typically a pre-existing cavity such as that resulting from tuberculosis. Aspergillus fumigatus was detected in 52.6% of sputum cultures from 19 patients. Aspergillus precipitin test was positive in 68.4% of patients. Thickening of cavitary walls was first found in 85% of chest x-ray films. Eighty percent of patients had pulmonary aspergillosis within 3 years after cavitary lesions were stable. Invasive pulmonary aspergillosis (IPA) is characterized by hyphal invasion and destruction of pulmonary tissue. The risk of acquiring IPA correlates with the duration and degree of immunosuppression or neutropenia. IPA recently has been encountered in patients with human immunodeficiency virus (HIV) infection. The number of case reports on chronic necrotizing pulmonary aspergillosis is increasing, but it is supposed the clinical entity of this disease still has not been established.

Aspergillosis↗
PubMed1998

Itraconazole for the treatment of pulmonary aspergillosis in heart transplant recipients.

The objective of this study was to evaluate the effects of itraconazole as a first choice drug in the treatment of pulmonary aspergillosis in heart transplant recipients. Heart transplant recipients suffering from invasive pulmonary aspergillosis were included in this study. Group 1 included 4 patients treated with i.v. itraconazole (Janssen Pharmaceutica) 400 mg daily, as a first choice drug for 28 d. Itraconazole was discontinued and amphotericin-B was started before the 28th day if clinical or radiographic worsening was observed. Group 2 included 3 patients treated with amphotericin-B as a first choice drug. Itraconazole was discontinued in all patients of Group 1 after 12-26 d of treatment because of radiographic worsening (n = 3) or combined clinical and radiographic worsening (n = 1). Subsequent treatment with amphotericin-B resulted in improvement of all patients. On a 5-yr follow-up period no relapse of aspergillosis was observed in 3 of them. The fourth patient expired from cerebral hemorrhage. The 3 patients of Group 2 treated with amphotericin-B showed a gradual improvement, and all were doing well on a 2-yr follow-up. In conclusion, in our study population consisted of heart transplant recipients amphotericin-B was superior to itraconazole in the treatment of invasive pulmonary aspergillosis.

Adult↗
PubMed1998

[Successful therapy of pulmonary aspergillosis in a patient with non-Hodgkin lymphoma].

UNLABELLED: ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma developed severe invasive pulmonary aspergillosis during a state of leucopenia after chemotherapy. INVESTIGATION: The initial manifestation was an infiltration in the right upper lobe of the lung, identified by lung scintigraphy as a peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage extreme high titre of Aspergillus antigen were seen as a laboratory indication of an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly isolated from bronchoalveolar lavage and bronchial secretion. THERAPY AND CLINICAL COURSE: Treatment was started with amphotericin B plus 5-flucytosine together with repeatedly bronchoscopic instillation of miconazole followed by thoracosurgical intervention with resection of the right upper lobe of the lung. Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred three months later probably due to persistence of aspergillus fungal elements in the left lung. The aspergillosis relapse was treated at first with liposomal amphotericin B. After eighteen days of treatment this was changed to a combination of 5-flucytosine with oral application of itraconazole, and cure was achieved.

Aged↗
PubMed1998

Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996).

OBJECTIVE: To examine the clinical response to topical administration of clotrimazole in dogs with nasal aspergillosis, to compare effect of surgically placed versus nonsurgically placed catheters used for administration on outcome, and to examine whether subjective scoring of computed tomographic images can predict outcome. DESIGN: Retrospective case series. ANIMALS: 60 dogs with nasal aspergillosis. PROCEDURE: Information including signalment, history, diagnostics, treatment method, and outcome was retrieved from medical records of dogs with nasal aspergillosis treated between 1990 and 1996 at the University of California School of Veterinary Medicine or cooperating referral practices. Final outcome was determined by telephone conversations with owners and referring veterinarians. Images obtained before treatment were subjectively assessed to develop an algorithm for predicting outcome. RESULTS: Clotrimazole solution (1%) was infused during a 1-hour period via catheters surgically placed in the frontal sinus and nose (27 dogs) and via nonsurgically placed catheters in the nose (18). An additional 15 dogs received 2 to 4 infusions by either route. Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. The scoring system correctly classified dogs with unfavorable and favorable responses 71 to 78% and 79 to 93% of the time, respectively. CLINICAL IMPLICATIONS: Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications.

Administration, Intranasal↗
PubMed2003

Cerebral aspergillosis in an infant with corticosteroid-resistant nephrotic syndrome.

Cerebral aspergillosis is a devastating disease in patients with a compromised immune system. A unique case of a male infant with corticosteroid-resistant nephrotic syndrome complicated by pulmonary and cerebral aspergillosis is described. The patient rapidly developed coma and neurological symptoms and died soon thereafter. Central nervous system aspergillosis was diagnosed radiologically and by detection of Aspergillus DNA and antigen (galactomannan) in blood and cerebrospinal fluid. Moderate immunosuppressive therapy and antifungal phagocytic dysfunction due to nephrotic syndrome per se may have contributed to the occurrence of invasive aspergillosis in our patient. Awareness of this serious complication and early application of diagnostic procedures and antifungal therapy may improve the dismal outcome.

Adrenal Cortex Hormones↗
PubMed2005

Diagnostic MR imaging features of craniocerebral Aspergillosis of sino-nasal origin in immunocompetent patients.

BACKGROUND: Craniocerebral invasive Aspergillosis of sino-nasal origin has been reported with a very high mortality due to a peculiarly fulminant clinical course. Early diagnosis based on clinical radiological imaging may have an impact on final clinical outcome. This retrospective study focuses on characteristic MR imaging features of Aspergillosis (of sinonasal origin) in immunocompetent patients. METHODS: Medical records of patients were reviewed retrospectively during the period from 1991 to 2003 in the two tertiary care hospitals. All the patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. Immunocompetence of patients was assessed on clinical and radiological data. MRI scans (n=20) were reviewed by both clinical neurosurgeons and neuroradiologists separately. MRI was done on 1.5 tesla scanners and both T2-weighted and T1 weighted sequences were obtained followed gadolinium enhanced images. Patients were categorized into three types based on their anatomical location on MRI scans; type-1 being intracerebral, type-2 as intracranial extradural and type-3 invading orbit and/or skull base only. All these patient had the epicenter of disease in the nose and/or paranasal sinuses as evident on MR imaging. All patients underwent standard surgical intervention followed by antifungal therapy. Clinical outcome was assessed on Glasgow outcome scale with mean duration of clinical follow up of 13.9 months. FINDINGS: Mean age of patents (n=20) was 31.1 years with male preponderance (3:1). MRI scans showed evidence of disease in paranasal sinuses including mucosal thickening (n=11) and complete filling of sinuses (n=9). T2-weighted images showed extremely hypo-intense fungal mass (n=19) while T1-weighted images had iso-intense signals (n=18). Gadolinium-enhanced images showed bright homogenous contrast enhancement (n=18) and peripheral ring enhancement pattern (n=2). All patients underwent appropriated surgical procedures depending upon anatomical location followed by standard antifungal therapy. Tissue diagnoses were established by histopathology (n=20) and culture growth (n=5). Overall mortality remained 15 percent. INTERPRETATION: Craniocerebral Aspergillosis of sinonasal origin has typical MR imaging features. These features include a mass lesion producing hypo-to-iso-intense signals on T1-weighted, extremely low signals (hypo-intense) on T2-weighted images, with bright homogenous enhancement on post-gadolinium T1-weighted imaging. These features in the clinical background may be helpful in early diagnosis and management of Aspergillosis of sino-nasal origin in immunocompetent hosts. Prospective clinical study is required to make firm clinical therapeutic recommendations.

Adolescent↗
PubMed2002

Aspergillus galactomannan antigen in the cerebrospinal fluid of bone marrow transplant recipients with probable cerebral aspergillosis.

The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 patients with probable cerebral aspergillosis and from 16 control patients. Cerebrospinal fluid galactomannan levels were significantly higher in aspergillosis patients, and most galactomannan was produced intrathecally. Comparison of serum galactomannan values in pulmonary and cerebral aspergillosis patients showed significant overlapping. Detection of Aspergillus galactomannan in cerebrospinal fluid may be diagnostic of cerebral aspergillosis.

Antigens, Fungal↗
PubMed2006

Invasive aspergillosis causing small bowel infarction in a patient of carcinoma breast undergoing chemotherapy.

BACKGROUND: To report a 45 year old lady presenting with proximal jejunal gangrene due to invasive Aspergillosis. The patient was undergoing adjuvant chemotherapy for advance carcinoma of breast (Stage IV). METHODS: The patient was referred to our surgical emergency for acute abdominal symptoms for 6 hours. Histopathology revealed bowel wall necrosis and vascular invasion by Aspergillus Fumigatus. Postoperative recovery was uneventful and the patient received Amphotericin-B (1 mg/kg/day) for invasive aspergillosis. Invasive pulmonary aspergillosis was confirmed by isolating Aspergillus Fumigatus from bronchoalveolar lavage and by a positive circulating galactomannan test (ELISA Assay). RESULTS: Detailed history revealed dry cough and two episodes of haemoptesis for 2 weeks. Haemogram and counts revealed anemia and neutropenia. Plain X-ray of the abdomen showed multiple air fluid levels and ultrasound of the abdomen revealed distended bowel loops. On exploration small bowel was found to be gangrenous. The patient was successfully managed by supportive treatment and conventional intravenous Amphotericin-B for 2 weeks. The lady was discharged one week after completion of antifungal therapy and one month later she underwent toilet mastectomy. The lady came to follow up for 1 year and she is currently under hormone therapy. CONCLUSION: With the emergence of new and powerful immunosuppressive, anticancer drugs and potent antibiotics the survival of transplant and critically ill patients has remarkably increased but it has shown a significant rise in the incidence of invasive opportunistic fungal infections. We conclude hat the diagnosis of invasive gastrointestinal aspergillosis may be considered in a neutropenic patient with acute abdominal symptoms.

Journal Article↗