Efficacy of the Combination of Voriconazole and Caspofungin in Experimental Pulmonary Aspergillosis by Different Aspergillus Species

Objectives

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high mortality. We evaluated the efficacy and compared the therapeutic effect differences of voriconazole (VRC) in combination with caspofungin (CAS) in transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger.

Methods

Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1 mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day), and no drug for 10 consecutive days. The efficacy and the difference in the treatments were evaluated through prolongation of survival, reduction in serum galactomannan levels and residual fungal burden, and histological studies.

Results

For all the strains, the combination of VRC and CAS led to significant prolongation in survival (P < 0.05) and reduction in residual fungal burden (P < 0.05) compared with CAS alone, and decrease in serum galactomannan levels (P < 0.05) compared with either agent alone. The survival in the combined therapy groups was significantly improved compared to VRC monotherapy for the strains of A. flavus and A. niger (P < 0.05), but no significant difference for the strains of A. fumigatus (P > 0.05).

Conclusions

Combination of VRC and CAS was synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA by A. fumigatus.     

Case Series Study of Invasive Pulmonary Aspergillosis

Diagnosis of invasive pulmonary aspergillosis (IPA) is challenging. The objective of the study was to assess the value of microbiological tests to the diagnosis of IPA in the absence of non-specific radiological data. A retrospective study of 23 patients with suspicion of IPA and positivity of some microbiological diagnostic tests was performed. These tests included conventional microbiological culture, detection of Aspergillus galactomannan (GM) antigen and in some patients (1 → 3)-β-d-glucan (BDG) and Aspergillus fumigatus DNA using the LightCycler^® SeptiFast test. In 10 patients with hematological malignancy, 6 cases were considered ‘probable’ and 4 ‘non-classifiable.’ In 8 patients with chronic lung disease, 7 cases were classified as ‘probable’ and 1 as ‘proven,’ and in 5 patients with prolonged ICU stay (>7 days), there were 2 ‘proven’ cases, 2 ‘non-classifiable’ and 1 putative case. Microbiological culture was positive in 17 cases and 18 Aspergillus spp. were isolated (one mixed culture). A. fumigatus was the most frequent (44.4%) followed by A. tubingensis. The Aspergillus galactomannan (GM) antigen assay was positive in 21 cases (91.3%). The GM antigen and the (1 → 3)-β-d-glucan (BDG) assays were both performed in 12 cases (52.2%), being positive in 9. The SeptiFast test was performed in 7 patients, being positive in 4. In patients with non-classifiable pulmonary aspergillosis and one or more positive microbiological tests, radiological criteria may not be considered a limiting factor for the diagnosis of IPA.     

Characteristics of Invasive Aspergillosis in Neutropenic Haematology Patients (Sousse,Tunisia)

Although scarce, available data suggest that the epidemiology of invasive aspergillosis (IA) in North Africa differs from northern countries, where more than 80 % is caused by Aspergillus fumigatus. This study aimed at describing the epidemiology of IA in the region of Sousse, Tunisia, and at assessing the usefulness of the available diagnostic tools. For 2 years, clinical and mycological data were prospectively collected from 175 neutropenia episodes of 91 patients hospitalised in the haematology department at the Farhat Hached hospital in Sousse (Tunisia). Screening for galactomannan antigen was positive in 40 % of neutropenia episodes; Aspergillus PCR was positive in 42 % of the tested sera. Nine patients were classified as probable and two as possible IA according to the EORTC/MSG criteria. Twelve patients who prematurely died, had no CT scan and could not be classified. Fifty-six Aspergillus spp. were isolated in 53 (6.5 %) sputa collected from 35 (20 %) patients. The following species were identified with MALDI-TOF mass spectrometry and DNA sequencing: A. niger, 35 %; A. flavus, 38 %; A. tubingensis, 19 %; A. fumigatus, 4 %; A. westerdijkiae, 2 % and A. ochraceus, 2 %. Our findings highlight the epidemiological features of IA in Tunisia, which is characterised by the predominance of Aspergillus spp. from sections Nigri and Flavi.     

Gliotoxinogenic Aspergillus fumigatus in the dairy herd environment

The potential association between hygienic conditions in the environment of lactating cows and the presence of gliotoxinogenic Aspergillus fumigatus strains was studied. Milk samples (individual cow’s milk [ICM], bulk tank milk [BTM]) from 44 dairy farms were sampled. In ICM samples, eight different species of Aspergillus were identified. A. flavus and A. fumigatus were predominant, with 37.8 % and 26.1 % relative densities, respectively. A. fumigatus strains were isolated from 61.4 % of the BTM samples, and 34 % of these strains were able to produce gliotoxin. Principal component analysis was used to associate the presence of A. fumigatus with some hygienic and sanitary practices. A significant and positive correlation was observed between dry cow therapy and forestripping. The presence of A. fumigatus gliotoxin producers in milk was associated with high somatic cells count (SCC) samples. Good hygienic and sanitary practices were associated with absence of A. fumigatus and relatively low SCCs of <250,000 cells/ml. In general, a high percentage of dairy farms were positive for A. fumigatus in BTM samples. This is the first work that indicates the positive effects of adequate hygienic and sanitary practices in dairy herds on the control of A. fumigatus and related species. By reducing the frequency of Aspergillus spp. in the dairy environment, the risk of farm handlers’ exposure and the risk of intramammary fungal infections would also be reduced.     

The Application of Laser Microdissection in Molecular Detection and Identification of Aspergillus fumigatus from Murine Model of Acute Invasive Pulmonary Aspergillosis

Invasive aspergillosis (IA) is a major concern in patients with severe immune deficiency. As antifungal susceptibility varies in different fungal pathogens, accurate and timely identification of species is becoming imperative for guidance of therapy and reducing high mortality rates in patients with IA. But, in fact, the diagnosis is challenging and new validated techniques are required for the detection and identification of clinically relevant isolates. The laser capture microdissection (LCM) system enables analysis of cytologically and/or phenotypically defined cell types from heterogeneous tissue and has been used in diagnosis and fungal species identification in pulmonary aspergillosis of white storks. To establish the experimental foundation for clinical application of the system, we microdissected and collected Blankophor-stained single hyphal strands from tissue cryosections of murine model of invasive pulmonary aspergillosis (IPA) with A. fumigatus by LCM, subsequently processed for DNA extraction, PCR sequencing, and species molecular identification. The sensitivity of LCM–PCR sequencing was 89 % (89/100), and the specificity was 100 %. Moreover, the positive predictive value and negative predictive value were 100 and 78.43 %, respectively. The result approved that the LCM-based methods had the potential for accurately diagnosis and rapidly identification fungal pathogens of IPA.     

Galactomannan-Based and PCR-Based Assays in Bronchoalveolar Lavage to Diagnose Invasive Aspergillosis: Current Status and Future Prospects

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients receiving chemotherapy or undergoing allogeneic haematopoietic stem cell transplantation for acute leukemia. The existing tools to diagnose IPA lack specificity or sensitivity, or both; the search for improved diagnostic tools for IPA has focused on novel serologic and molecular methods. Aspergillus Galactomannan enzyme-linked immunosorbent assay (GM) analyses showed sensitivity rates in serum samples ranging in a wide span; testing GM in bronchoalveolar lavage (BAL) originated from the primary site of the infection seems to be more sensitive in patients with IPA. Other novel diagnostic markers to detect fungal DNA directly in clinical samples, rapidly, early, sensitively and specifically, are provided by polymerase chain reaction (PCR) based assays; higher sensitivity and specificity rates have been observed for BAL samples in IPA, even under antifungal treatment. The clinical place value of a diagnostic approach combining PCR and GM in BAL is unclear.     

Preliminary Study of the Fungal Ecology at the Haematology and Medical-Oncology Ward in Bamako,Mali

Data on fungal epidemiology in sub-Saharan African countries are scarce. This exploratory study aimed to characterize the fungal flora at the Onco-Haematology ward of the National Teaching Hospital of Point G in Bamako, Mali. A cross-sectional survey was conducted in the dry and in the rainy seasons. Nasal swab and sputum samples were collected from the hospitalized patients while airborne fungal spores were collected using electrostatic dust-fall collectors. Fungi were identified by their morphological characteristics and MALDI-TOF mass spectrometry. Candida albicans was the most frequent yeast species colonizing patients; Aspergillus species were isolated in 86 % of the patients and were the main airborne environmental contaminants. Overall, airborne fungal contamination rates increased from 33.8 % in the dry to 66.2 % in the rainy season (p < 0.001). The most frequent Aspergillus species were Aspergillus niger (36.6 %) and Aspergillus flavus (32.92 %). In contrast, Aspergillus fumigatus (5.43 %) was relatively rare. This high level of fungal exposure raises concern regarding the management of at-risk patients in this Onco-Haematology ward and stresses the need for strengthening the mycological diagnostic capacities to accompany the implementation of adapted fungal infection prevention and management policies.     

A preliminary survey on the occurrence of mycotoxigenic fungi and mycotoxins contaminating red rice at consumer level in Selangor, Malaysia

Red rice is a fermented product of Monascus spp. It is widely consumed by Malaysian Chinese who believe in its pharmacological properties. The traditional method of red rice preparation disregards safety regulation and renders red rice susceptible to fungal infestation and mycotoxin contamination. A preliminary study was undertaken aiming to determine the occurrence of mycotoxigenic fungi and mycotoxins contamination on red rice at consumer level in Selangor, Malaysia. Fifty red rice samples were obtained and subjected to fungal isolation, enumeration, and identification. Citrinin, aflatoxin, and ochratoxin-A were quantitated by ELISA based on the presence of predominant causal fungi. Fungal loads of 1.4?×?10⁴ to 2.1?×?10⁶?CFU/g exceeded Malaysian limits. Monascus spp. as starter fungi were present in 50 samples (100 %), followed by Penicillium chrysogenum (62 %), Aspergillus niger (54 %), and Aspergillus flavus (44 %). Citrinin was present in 100 % samples (0.23–20.65 mg/kg), aflatoxin in 92 % samples (0.61–77.33 μg/kg) and Ochratoxin-A in 100 % samples (0.23–2.48 μg/kg); 100 % citrinin and 76.09 % aflatoxin exceeded Malaysian limits. The presence of mycotoxigenic fungi served as an indicator of mycotoxins contamination and might imply improper production, handling, transportation, and storage of red rice. Further confirmatory analysis (e.g., HPLC) is required to verify the mycotoxins level in red rice samples and to validate the safety status of red rice.     

A preliminary study on the occurrence of Aspergillus spp. and aflatoxin B1 in imported wheat and barley in Penang, Malaysia

Thirty samples consisting of wheat (15) and barley (15) were collected from different markets in Penang, Malaysia, originating from India and Thailand, respectively. All samples were analyzed for occurrence of Aspergillus spp. and aflatoxin B₁ (AFB1). Aspergillus flavus was dominant in all samples followed by A. niger. AFB1 could be detected in three wheat samples ranging from 0.42 to 1.89 μg/kg and one barley sample had 0.58 μg/kg of AFB1. The AFB1 levels in all the samples were below the Malaysian regulatory limits (<35 μg/kg). The frequency and quantity of AFB1 levels in this study were very low in wheat and barley samples compared to other agricultural commodities reported in India and Thailand. This is the first report on determination of Aspergillus spp. and AFB1 in imported wheat and barley grains in Penang, Malaysia.     

Effect of indigenous mycobiota on ochratoxin A production by Aspergillus carbonarius isolated from soil

This study determined the biotic interaction between 30 non-toxigenic indigenous strains of Aspergillus niger aggregate, Aspergillus flavus, Trichoderma spp., Mucor spp., Cladosporium spp., Ulocladium spp., Curvularia spp., Absidia spp., Geotrichum spp. and Acremonium spp., isolated from soil destined for maize crops, with respect to their ability to prevent ochratoxin A (OTA) production by A. carbonarius on “in vitro” assay, on liquid and solid medium. OTA production was completely inhibited when A. carbonarius was inoculated in a interactive mixed culture with all A. niger aggregate strains assayed, a 80 % of Trichoderma spp. strains, a 40 % of Cladosporium spp. strains, Acremonium spp and Geotrichum spp; only one strain of A. flavus tested was able to completely inhibit the mycotoxin accumulation. OTA production increased when A. carbonarius ACS 8 was growing on liquid interactive mixed culture with Mucor spp strains. These results demonstrated that OTA production by Aspergillua carbonarius strain was significantly influenced by the presence of different non-toxigenic fungal strains when growing together on paired cultures.     

Nested PCR for the detection of Aspergillus species in maxillary sinus samples of patients with chronic sinusitis

Background

Fungal rhinosinusitis has become an increasingly recognized disease, being Aspergillus species responsible for most of the cases. Its diagnosis is quite difficult because of the non-specific symptoms and low sensitivity of the current diagnostic methods.

Detection of Leishmania infantum in animals and their ectoparasites by conventional PCR and real time PCR

Visceral leishmaniosis (VL) is a parasitic disease caused by Leishmania infantum, which is primarily transmitted by phlebotomine sandflies. However, there has been much speculation on the role of other arthropods in the transmission of VL. Thus, the aim of this study was to assess the presence of L. infantum in cats, dogs and their ectoparasites in a VL-endemic area in northeastern Brazil. DNA was extracted from blood samples and ectoparasites, tested by conventional PCR (cPCR) and quantitative real time PCR (qPCR) targeting the L. infantum kinetoplast DNA. A total of 280 blood samples (from five cats and 275 dogs) and 117 ectoparasites from dogs were collected. Animals were apparently healthy and not previously tested by serological or molecular diagnostic methods. Overall, 213 (76.1 %) animals and 51 (43.6 %) ectoparasites were positive to L. infantum, with mean parasite loads of 795.2, 31.9 and 9.1 fg in dogs, cats and ectoparasites, respectively. Concerning the positivity between dogs and their ectoparasites, 32 (15.3 %) positive dogs were parasitized by positive ectoparasites. The overall concordance between the PCR protocols used was 59.2 %, with qPCR being more efficient than cPCR; 34.1 % of all positive samples were exclusively positive by qPCR. The high number of positive animals and ectoparasites also indicates that they could serve as sentinels or indicators of the circulation of L. infantum in risk areas.     

Peanut Pod Invasion by Aspergillus flavus in the Presence of Meloidogyne hapla

''Argentine'', ''Early Runner'' and ''Florigiant'' peanut cultivars were grown in methyl bromide treated soil in field microplots inoculated with: (i) Aspergillus flavus or (ii) A. flavus + Meloidogyne hapla. Nematode infection produced heavy root galling and light pod galling equally on all cultivars. A. flavus, A. niger, Cephalosporium spp., Colletotrichum sp., Curvularia spp., Fusarium spp., Penicillium spp. and Trichoderma viride were isolated from shells and kernels. A significantly greater incidence and density of A. flavus was obtained from kernels of plants inoculated with both organisms than from kernels of plants receiving only the fungus. Differences were not significant, however, for incidence and density of A. flavus in shells or for the total of all fungal propagules in shells and kernels. Shells of ''Early Runner'' contained significantly greater incidence and density of A. flavus than the other two cultivars; also, kernels of this cultivar contained more fungal propagules than kernels of ''Argentine.'' A significantly larger number of total fungi was isolated from kernels of ''Argentine'' than from ''Florigiant.'' Aflatoxins were found only in two shell samples and not in kernels.     

Evaluation for the Clinical Diagnosis of Pythium insidiosum Using a Single-Tube Nested PCR

Pythiosis is a rare infectious disease caused by Pythium insidiosum, which typically occurs in tropical and subtropical regions. The high mortality rate may be in consequence of the lack of diagnosis. The objective of this study was to evaluate reliability of a new single-tube nested PCR for detection of P. insidiosum DNA. A total of 78 clinical isolates of various fungi and bacteria, 106 clinical specimens and 80 simulated positive blood samples were tested. The developed primer pairs CPL6–CPR8 and YTL1–YTR1 are located on 18S subunit of the rRNA gene of P. insidiosum. The specificity, negative and positive predictive values were 100, 100 and 87.5 %, respectively, as compared with direct microscopy and cultivation. The detection limit of the single-tube nested PCR was 21 zoospores corresponding to 2.7 pg of the DNA. The results demonstrate that the new single-tube nested PCR offers a highly sensitive, specific and rapid genetic method for detecting P. insidiosum.     

Effect of essential oil from fresh leaves of Ocimum gratissimum L. on mycoflora during storage of peanuts in Benin

The aim of this study was to evaluate the effect of essential oil from fresh leaves of Sweet Fennel (Ocimum gratissimum) on mycoflora and Aspergillus section Flavi populations in stored peanuts. Aspergillus, Fusarium and Mucor spp. were the most common genera identified from peanuts at post-harvest in Benin by using a taxonomic schemes primarily based on morphological characters of mycelium and conidia. The isolated fungi include Aspergillus niger, A. parasiticus, A. flavus, A. ochraceus, Fusarium graminearum, F. solani, F. oxysporum and Mucor spp. The most prevalent fungi recorded were A. niger (94.18 %), A. flavus (83.72 %), A. parasiticus (77.90 %), A. ochraceus (72.09 %), F. graminearum (59.30 %) and F. oxysporum (51.16 %). Antifungal assay, performed by the agar medium assay, indicated that essential oil exhibited high antifungal activity against the growth of A. flavus, A. parasiticus, A. ochraceus and F. oxysporium. The minimal inhibitory concentration (MIC) of the essential oil was found to be 7.5 μl/ml for A. flavus and A. parasiticus and 5.5 μl/ml for A. ochraceus and F. oxysporium. The minimal fungicidal concentration (MFC) was recorded to be 8.0 μl/ml for A. flavus and A. parasiticus, 6,5 μl/ml for A. ochraceus and 6.0 μl/ml for F. oxysporium. The essential oil was found to be strongly fungicidal and inhibitory to aflatoxin production. Chemical analysis by GC/MS of the components of the oil led to the identification of 31 components characterized by myrcene (6.4 %), α-thujene (8.2 %), p-cymene (17.6 %), γ-terpinene (20.0 %), and thymol (26.9 %) as major components. The essential oil of Sweet Fennel, with fungal growth and mycotoxin inhibitory properties, offers a novel approach to the management of storage, thus opening up the possibility to prevent mold contamination in stored peanuts.     

Ixodid fauna and zoonotic agents in ticks from dogs: first report of Rickettsia rickettsii in Rhipicephalus sanguineus in the state of Mato Grosso do Sul, mid-western Brazil

Ticks from 148 dogs from the urban area of the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil, were collected, classified and analyzed using polymerase chain reaction (PCR) for the identification of Rickettsia spp., Trypanosoma cruzi and Leishmania spp. A total of 2015 ticks were collected. The species Rhipicephalus sanguineus (98.9 %) and Amblyomma cajennense (1.1 %) were identified. Molecular analysis revealed that no tick samples were infected by T. cruzi. Regarding Leishmania spp., tick samples from 36 dogs spread across all regions of the municipality were positive for L. chagasi. One tick sample was positive for Rickettsia spp. (gltA gene) in the PCR reaction. This sample was submitted to further PCR based on the ompA gene and the amplicon was sequenced. Identity of 100 % was found with homologous sequences of R. rickettsii available in GenBank. This paper is the first to report the natural infection of R. sanguineus by R. rickettsii in the municipality of Campo Grande, state of Mato Grosso do Sul, mid-western Brazil.     

TR34/L98H Mutation in <Emphasis Type="Italic">CYP51A</Emphasis> Gene in <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis> Clinical Isolates During Posaconazole Prophylaxis: First Case in Korea

Azole resistance in Aspergillus fumigatus is an emerging problem, especially in immunocompromised patients. It has been reported worldwide, including in Asia, but has not yet been reported in Korea. Here, we report a case of invasive pulmonary aspergillosis (IPA) caused by azole-resistant A. fumigatus that developed in a hematopoietic stem cell transplantation recipient during posaconazole prophylaxis for immunosuppressive therapy of graft-versus-host diseases. We identified TR34/L98H/S297T/F495L mutation in the CYP51A gene of A. fumigatus clinical isolate obtained from bronchial washing fluid. Minimal inhibitory concentrations for itraconazole, voriconazole, and posaconazole were >?16, 1, and 4 μg/mL, respectively. While IPA improved partially under voriconazole treatment, the patient died from carbapenemase-producing Klebsiella pneumoniae bacteremia. Further epidemiological surveillance studies are warranted.     

Biodegradation optimization and metabolite elucidation of Reactive Red 120 by four different <Emphasis Type="Italic">Aspergillus</Emphasis> species isolated from soil contaminated with industrial effluent

Azo dyes are recalcitrant owing to their xenobiotic nature and exhibit high resistance to degradation processes. In the present study, different Aspergillus species (A. flavus, A. fumigatus, A. niger, and A. terreus) isolated from soil samples contaminated with industrial effluent, collected from Jeddah, Saudi Arabia, were analyzed for azo dye, Reactive Red 120 (RR120) biodegradation. The physicochemical parameters such as carbon (sucrose) and nitrogen (ammonium sulfate) sources, pH, and temperature affecting the biodegradation of RR120 were optimized using central composite design–response surface methodology (CCD-RSM). The maximum RR120 degradation was found to be 84% (predicted) at the optimum level of sucrose (11.73 g/L), ammonium sulfate (1.26 g/L), pH (5.71), and temperature (28.26 °C). Further, the validation results confirmed that the predicted values are in good agreement with the experimental results for RR120 degradation by A. flavus (86%), A. fumigatus (84%), A. niger (85%), and A. terreus (86%). The metabolic product of RR120 after biodegradation by different Aspergillus species was identified as sodium 2-aminobenzenesulfonate. The present study suggests that Aspergillus species are good candidates for azo dye-loaded effluent treatment.     

Aspergillus Collagen-Like Genes (acl): Identification,Sequence Polymorphism,and Assessment for PCR-Based Pathogen Detection

The genus Aspergillus is a burden to public health due to its ubiquitous presence in the environment, its production of allergens, and wide demographic susceptibility among cystic fibrosis, asthmatic, and immunosuppressed patients. Current methods of detection of Aspergillus colonization and infection rely on lengthy morphological characterization or nonstandardized serological assays that are restricted to identifying a fungal etiology. Collagen-like genes have been shown to exhibit species-specific conservation across the noncollagenous regions as well as strain-specific polymorphism in the collagen-like regions. Here we assess the conserved region of the Aspergillus collagen-like (acl) genes and explore the application of PCR amplicon size-based discrimination among the five most common etiologic species of the Aspergillus genus, including Aspergillus fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus. Genetic polymorphism and phylogenetic analysis of the aclF1 gene were additionally examined among the available strains. Furthermore, the applicability of the PCR-based assay to identification of these five species in cultures derived from sputum and bronchoalveolar fluid from 19 clinical samples was explored. Application of capillary electrophoresis on nanogels was additionally demonstrated to improve the discrimination between Aspergillus species. Overall, this study demonstrated that Aspergillus acl genes could be used as PCR targets to discriminate between clinically relevant Aspergillus species. Future studies aim to utilize the detection of Aspergillus acl genes in PCR and microfluidic applications to determine the sensitivity and specificity for the identification of Aspergillus colonization and invasive aspergillosis in immunocompromised subjects.     

Invasive aspergillosis with extrapulmonary involvement: pathogenesis, clinical characteristics and prognosis

BackgroundThe incidence of invasive aspergillosis has increased worldwide. Information regarding the clinical characteristics of patients with extrapulmonary involvement is scarce.ObjectiveWe aimed to describe the pathogenesis, characteristics and outcomes of patients with invasive aspergillosis and extrapulmonary disease.MethodsA retrospective study conducted in a university hospital in Barcelona, Spain (1995-2011).ResultsA total of 12 cases of invasive aspergillosis and extrapulmonary involvement were found. The most common clinical manifestations were invasive sinusitis, early postoperative prosthetic valve endocarditis, fungaemia, postoperative meningitis, multiple brain abscesses and lumbar spondylitis with epidural abscess. Sinusitis occurred frequently in patients without immunosuppression and had invasive brain involvement in one case. Endocarditis was associated with multiple septic metastases. Concomitant lung involvement was documented in 5 cases. The strains isolated were Aspergillus fumigatus (5), Aspergillus flavus (3), and Aspergillus niger (2). The species of Aspergillus was not established for 3 isolates. All patients were treated with antifungals and surgery was performed in 8 cases. Outcome was related with the source of infection; all patients with invasive sinusitis survived, while the remaining patients had a high mortality rate (88%).ConclusionsInvasive aspergillosis with extrapulmonary involvement is rare. The most common presentation is invasive sinusitis, which has a lower mortality. Other clinical forms with extrapulmonary involvement were associated with severe immunosuppression or previous surgery, and had a poor outcome.