Emergence of persistent Aspergillus terreus colonisation in a child with cystic fibrosis (original) (raw)
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Aspergillus terreus Causing Probable Invasive Aspergillosis in a Patient with Cystic Fibrosis
Mycopathologia, 2018
Aspergillus terreus may colonize the airways of patients with cystic fibrosis (CF). Whether this merits antifungal treatment is still unclear due to heterogeneous reports regarding its pathogenic potential. Although allergic manifestations are documented, invasive aspergillosis (IA) caused by A. terreus has not been described. We present here one case of probable IA caused by A. terreus, highlighting its role as an emerging agent of IA in CF patients. Voriconazole was effective, and the patient was healthy after 12 weeks of treatment. Serial determination of serum galactomannan level and periodic cultures from respiratory specimens may help in monitoring CF patients by identifying such pathogens. Further studies on the fungal species colonizing the CF airways are warranted, especially in India. This case report suggests A. terreus as a potential agent of IA which should not be ignored, particularly in this patient group.
Diverse clinical characteristics of aspergillus growth in patients with cystic fibrosis
The Turkish Journal of Pediatrics
Cystic fibrosis (CF) is a systemic chronic disease and abnormalities in CFTR (Cystic fibrosis transmembrane conductance regulator) function affect interactions between the epithelial surface and microorganisms such as fungi. 1 Conidial spores are usually cleared by airway epithelium; however, in CF due to disruption of epithelial barrier and germination of the fungi induce inflammatory response. Increased mucus viscosity and lung injury result in an ongoing cycle of infection, inflammation and pulmonary damage. 1,2 Aspergillus, the most commonly detected filamentous fungi in CF induces this abnormal pulmonary inflammation. 2 The main Aspergillus-associated clinical manifestations
Molecular epidemiology of Aspergillus collected from cystic fibrosis patients
Journal of Cystic Fibrosis, 2014
Background: Aspergillus respiratory infection is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function and allergic disease. Methods: Fifty-three Aspergillus isolates recovered from CF patients were identified to species by Internal Transcribed Spacer Region (ITS), β-tubulin, and calmodulin sequencing. Results: Three species complexes (Terrei, Nigri, and Fumigati) were found. Identification to species level gave a single Aspergillus terreus sensu stricto, one Aspergillus niger sensu stricto and 51 Aspergillus fumigatus sensu stricto isolates. No cryptic species were found. Conclusions: To our knowledge, this is the first prospective study of Aspergillus species in CF using molecular methods. The paucity of non-A. fumigatus and of cryptic species of A. fumigatus suggests a special association of A. fumigatus sensu stricto with CF airways, indicating it likely displays unique characteristics making it suitable for chronic residence in that milieu. These findings could refine an epidemiologic and therapeutic approach geared to this pathogen.
Early diagnosis and treatment of invasive pulmonary aspergillosis in a patient with cystic fibrosis
BMJ case reports, 2013
Invasive pulmonary aspergillosis is a rare and fatal complication in patients with cystic fibrosis (CF) who lack concomitant risk factors. The few documented cases in children have all resulted in deaths during hospitalisation. We present the case of a 12-year-old boy with CF who was admitted for an exacerbation which was unresponsive to antibiotic therapy. The findings on imaging raised concerns about a possible fungal infection. As a result, voriconazole therapy was started prior to his respiratory deterioration. He was later found to be β-D glucan and Aspergillus Ag galactomannan positive confirming the suspicion for invasive pulmonary aspergillosis. Three months after diagnosis, he was discharged home under stable condition. Voriconazole was continued beyond discharge and resulted in improvement of respiratory symptoms. This underscores the importance of early treatment of pulmonary aspergillosis in patients with CF. Unfortunately, the patient died 6 months after diagnosis from ...
Aspergillus Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis
American Journal of Respiratory and Critical Care Medicine
Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown. Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF. Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables, and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms, and admissions for exacerbations. Measurements and Main Results: Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus infections were all associated with worse CT scores in the same year (P overall , 0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; P = 0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation (P , 0.001) and respiratory admissions risk (P = 0.008). Conclusions: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk, and benefit of eradication regimens.
Multi-Country Estimate of Different Manifestations of Aspergillosis in Cystic Fibrosis
PLoS ONE, 2014
Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those. 18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were .18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was ,1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.
Unusual Aspergillus species in patients with cystic fibrosis
Medical Mycology, 2010
Poorly sporulating Aspergillus isolates from patients with cystic fi brosis (CF) are generally identifi ed in routine procedures as Aspergillus spp. In this study, we identifi ed and characterized 11 isolates belonging to two unusual Aspergillus species of the section Fumigati (A. lentulus and Neosartorya pseudofi scheri) recovered from four different patients. Aspergillus lentulus was found occasionally during a 10-year follow-up study of one CF patient colonized by A. fumigatus. Neosartorya pseudofi scheri was isolated from three patients followed in different European hospitals. This species was recovered from two sputum samples of one patient, and from four successive samples of the two other patients , suggesting that it may be responsible for chronic colonization. Both species were isolated together with A. fumigatus. Isolates from both species did not grow at 50 ° C, and DNA sequence analysis, together with further morphological observations permitted identifi cation at the species level. Growth at different temperatures and antifungal susceptibility were also investigated. All the isolates of N. pseudofi scheri exhibited a very low susceptibility to voriconazole (VRZ) whereas a very low susceptibility to VRZ and amphotericin B was seen with the A. lentulus isolates.
Molecular typing and colonization patterns of Aspergillus fumigatus in patients with cystic fibrosis
Journal of Cystic Fibrosis, 2009
Aspergillus fumigatus is a chronic colonizer of the respiratory tract of patients with cystic fibrosis (CF). A total of 204 A. fumigatus isolates from 36 CF patients from three different medical centers, collected over a period of four months till 9.5 years, were genotyped using the short tandem repeat panel for A. fumigatus (STRAf assay). Four different colonization patterns were observed. Colonization patterns with only unique genotypes were found in 36% of the patients. In contrast 17% of the patients were chronically colonized with a single genotype. The remaining patients showed a predominant genotype or genotypes that succeed each other. In this collection no relation was found between colonization patterns and allergic bronchopulmonary aspergillosis.
Pathogens, 2021
Aspergillus is increasingly associated with lung inflammation and mucus plugging in early cystic fibrosis (CF) disease during which conidia burden is low and strains appear to be highly diverse. It is unknown whether clinical Aspergillus strains vary in their capacity to induce epithelial inflammation and mucus production. We tested the hypothesis that individual colonising strains of Aspergillus fumigatus would induce different responses. Ten paediatric CF Aspergillus isolates were compared along with two systemically invasive clinical isolates and an ATCC reference strain. Isolates were first characterised by ITS gene sequencing and screened for antifungal susceptibility. Three clusters (A−C) of Aspergillus isolates were identified by ITS. Antifungal susceptibility was variable, particularly for itraconazole. Submerged CF and non-CF monolayers as well as differentiated primary airway epithelial cell cultures were incubated with conidia for 24 h to allow germination. None of the cl...