Epidemiology Of Invasive Aspergillosis Research Articles

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia.

The epidemiology of invasive aspergillosis (IA) in patients with acute lymphoid leukemia (ALL) has not been well characterized. To identify potential peculiarities in the natural history, treatment response and outcome of IA diagnosed in patients with ALL and AML. This is a retrospective cohort study conducted in seven tertiary-care hospitals between 2009 and 2017 of all consecutive episodes of IA occurring in adult patients with acute leukemia. Demographic characteristics, underlying disease and recent treatment, antifungal prophylaxis, neutropenia, receipt of corticosteroids, clinical and radiological findings, mycological results, antifungal therapy, and 6-week and 12-week survival were recorded. We identified 77 cases of IA in 54 patients with AML and 23 patients with ALL. The majority of patients developed IA in the context of induction chemotherapy for newly diagnosed (48.0%) or relapsed (41.6%) leukemia, with no differences between ALL and AML. Lung involvement was more frequent in AML (96.3% vs. 82.6%, p = 0.06) and rhinosinusitis was more common in ALL (43.5% vs. 24.1%, p = 0.09). Galactomannan was the microbiologic documentation of IA in 76.6%, with similar patterns of positivity in AML and ALL. The 6-week survival of IA in patients with AML and ALL was 63.0% and 56.5%, respectively (p = 0.60). The epidemiology, clinical presentation, diagnosis and outcome of IA in ALL patients are similar to patients with AML.

Epidemiology of invasive aspergillosis and triazole-resistant Aspergillus fumigatus in patients with haematological malignancies: a single-centre retrospective cohort study.

To investigate the epidemiology and clinical relevance of triazole resistance among patients undergoing treatment for haematological malignancies who are at risk of invasive aspergillosis (IA). This was a retrospective cohort study for which the records of consecutive patients given chemotherapy for AML or myelodysplastic syndrome (MDS) or who had received an allogeneic HSCT from 2006 to 2012 were reviewed for IA. Triazole resistance was detected by the VIPcheck™ screening method and confirmed by determining the MIC by EUCAST methodology. A total of 432 patients were included, comprising 182 (42.1%) patients who had undergone chemotherapy for AML or MDS, and 250 (57.9%) patients who had undergone an allogeneic HSCT. Probable or proven IA was diagnosed in 36 cases (8.3%, 95% CI 6.0%-11.4%). Of these, 12 (33.3%) were based on recovery of Aspergillus fumigatus from sputum, bronchoalveolar lavage or biopsy, and triazole resistance was found in 2 instances. A. fumigatus was also recovered from one or more specimens from 13 patients without probable or proven IA. Triazole resistance was documented for three patients. The survival rate of patients with IA caused by voriconazole-resistant isolates could not be assessed. The overall frequency of voriconazole-resistant IA among patients at high risk was low. However, the rate of triazole resistance may have been underestimated by the low detection rate based on recovery of A. fumigatus. Alternative diagnostic tests, such as PCR-based assays, may prove better at detecting IA due to triazole-resistant A. fumigatus.

Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study

Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes.

IntroductionInvasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.MethodsAn observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation.ResultsA total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis.ConclusionsIA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.

Invasive &amp;lt;i&amp;gt;Aspergillus&amp;lt;/i&amp;gt; Infections in a Thai Tertiary-Care Hospital during 2006-2011

From an increase in the number of immunocompromised hosts including AIDS patients, organ transplantation, solid-organ tumor, hematological malignancy, corticosteroid use, and others underlying diseases, it leads to increasing the incidence of invasive aspergillosis (IA) as one of the most prevalent opportunistic mould infections. However, the epidemiological data are still limited. Our objective is to study the epidemiology of IA, patients’ characteristics in a tertiary-care hospital, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The retrospective study of IA as principal diagnosis in both medical and laboratory records in a tertiary-care hospital, King Chulalongkorn Memorial Hospital, from January 1, 2006 to December 31, 2011, was performed. There were 69 patients who were diagnosed as IA during 2006 till 2011. They were classified as proven (45 patients), probable (3 patients), and possible (21 patients) invasive aspergillosis following the criteria of European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), 2008. The numbers of patients in 2006 to 2011 were 3, 11, 12, 10, 10, and 23 respectively. Male patients were 58 percent. The age range was from 8 months to 87 years old. Most of patients were from Medicine ward. Others were derived from Pediatrics, Surgery, and Ear Nose Throat wards. The most common underlying disease was diabetes mellitus type 2 in the proven group. The main predisposing factors of patients were the history of pulmonary tuberculosis and using of immunosuppressive drugs. The sites of infection were lung (62%), sinus (28%), and brain (8%). Aspergillus fumigatus (69%) and Aspergillus flavus (15%) were common species from the isolated culture. The treatment used mostly was surgery and followed by amphotericin B or voriconazole. The case fatality rate of IA was 20 percent. From the epidemiological data, we can conclude that in this past ten years there is an incessant increase in the number of IA in the immunocompromised hosts especially from Aspergillus fumigatus, which is the most prevalent species found in IA. Diabetes mellitus and history of pulmonary tuberculosis will play the important role for IA in the future. The plan for prevention and treatment should be concerned about those underlying diseases and predisposing factors.

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.

Invasive Aspergillosis in Children and Adolescents

Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised children. Disease control depends on prevention, early diagnosis, predictive microbiological information, prompt and appropriate treatment and restoration of host defenses. Relative to adults, invasive aspergillosis in children and adolescents is unique in its clinical presentation, epidemiology, and in particular, the utility of newer diagnostic tools and the pharmacokinetics of active antifungal agents. Here we review the presentation and epidemiology of invasive aspergillosis in children and adolescents and discuss the value of current diagnostic tools and strategies and options for treatment and prevention in this special population.

Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes

BackgroundFew data are available regarding the epidemiology of invasive aspergillosis (IA) in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs) among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection.MethodsRetrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005–2008). Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6) who received initial antifungal therapy (AF) in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS) were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models.ResultsFrom 6,424 aspergillosis patients in the database, 412 (6.4%) ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%), acute respiratory failure (76%) and acute renal failure (41%). In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once). Mean length of stay (LOS) was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p < 0.0001 for both).ConclusionsInvasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients.

Invasive Aspergillosis in Children With Acquired Immunodeficiencies

Invasive aspergillosis has emerged as an important cause of morbidity and mortality in immunocompromised children. It remains difficult to diagnose, and outcome depends on early diagnosis, appropriate treatment, and restoration of host defenses. Pediatric patients represent a unique population in their clinical presentation and epidemiology, particularly in respect to the utility of newer diagnostic tools and the pharmacokinetics of antifungal agents. This article reviews the presentation and epidemiology of invasive aspergillosis in children and adolescents with acquired immunodeficiencies and discusses the value of current diagnostic tools and the options for treatment and prevention in this population.

Aspergillus Spondylodiscitis in Solid Organ Transplant Recipients

Background Transplantation practices have had a significant effect on the epidemiology of invasive Aspergillosis. Aspergillus spondylodiscitis is rare in transplant recipients. The optimal treatment has yet to be defined because of the rarity of such cases. This article reviews the available literature on Aspergillus spondylodiscitis in solid organ transplant recipients and provides recommendations on its management. Methods We identified 15 cases of Aspergillus spondylodiscitis in transplant recipients. Most patients were heart transplant recipients. Back pain was the mode of presentation in all patients. Most cases were afebrile. The dominant location was the lumbar spine. Results Aspergillus fumigatus was responsible for 84.62% of cases and A flavus for 15.38%. The overall recovery rate was 66.67%. Delay in diagnosis remained a major impediment to the successful treatment of spinal aspergillosis. Treatment included antifungal therapy alone or combined with surgery. Initial therapy with voriconazole could lead to better curative effects. Conclusion Combined medical and operative interventions are recommended for treatment.

Combination antifungal treatment of pseudomembranous tracheobronchial invasive aspergillosis: a case report

Invasive aspergillosis (IA) is increasingly recognized in the intensive care unit (ICU), and new risk factors associated with respiratory colonization or infection by Aspergillus spp. include steroid treatment and chronic lung obstructive disease [1, 2]. In a review of 289 autopsies in the ICU, IA was the leading cause of Goldman class I discrepancy (a missed major diagnosis with major impact on patient management and survival) [3]. The epidemiology of IA indicates an increasing number of infections in immunosuppressed patients/individuals undergoing transplantation of bone marrow, hematopoietic stem cells, or organ transplantations, and those receiving intensive chemotherapy or other immunosuppressive treatments. A broad group of patients who are admitted to ICU also have some form of immunosupppression and may be susceptible to invasive mould infections. For various reasons, figures about the true incidence of IA in ICU are difficult to generate. The most important reason is the difficulty encountered in making a definite diagnosis of IA (lack of sensitivity and specificity with regard to culture and radiology) [4]. Recently, galactomannan (GM) in bronchoalveolar lavage (BAL) fluid appears to be a promising tool for early diagnosis in non-neutropenic critically ill patients and has been associated in proven cases with sensitivity and specificity of 88 and 87%, respectively [5]. Pseudomembranous and obstructive Aspergillus tracheobronchitis are still considered to have a fatal outcome and have been reported in a wide variety of patients [6]. There has been only one report in a patient with diabetes which was treated by deoxycholate amphotericin B (AmB) and subsequent addition of oral itraconazole [7]. In this paper, we report a pseudomembranous and obstructive tracheobronchitis in a diabetic patient successfully treated with caspofungin and AmB.

Invasive aspergillosis in organ transplant recipients: new issues in epidemiologic characteristics, diagnosis, and management

Changing transplantation practices, novel immunosuppressive protocols, and evolving recipient characteristics have led to notable changes in the epidemiology of invasive aspergillosis in transplant recipients. The frequency of disseminated infection and of central nervous system involvement has declined significantly in organ transplant recipients in the recent years. Amongst variables that may have contributed to these trends is an overall lesser severity of illness of transplant recipients in the current era. Calcineurin-inhibitor immunosuppressive agents may also have had a role in altering the disease course and the risk of dissemination. A new paradigm in the management of post-transplant immunosuppression is the use of calcineurin-inhibitor and corticosteroid sparing regimens by pretreatment of the recipient with T-cell depleting agents (Campath 1-H or thymoglobulin) and utilization of minimal post-transplant immunosuppression. The impact of these potent lymphoablative regimens on opportunistic mycoses in organ transplant recipients remains to be fully discerned. Although still unacceptably high, the mortality rate in organ transplant recipients with invasive aspergillosis in the current era appears to have declined. A focus of a great interest and controversy is the use of combination therapy for invasive aspergillosis in transplant recipients.

Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area

Invasive aspergillosis is the most prevalent mould infection. An epidemiological surveillance network was set up in 18 teaching hospitals in Paris and the Greater Paris area. Prospective surveillance was conducted between 1994 and 1999. Between 1994 and 1997 cases were categorized as proven or probable aspergillosis and then the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria were used. The authors analysed 621 cases (115 proven, 506 probable). No seasonal variation was found. Haematological disorders (73%) including stem-cell transplantation (36%), solid-organ transplantations (10%) and AIDS (9%) were the main underlying conditions. The crude mortality was 63%. Incidence of IA was 8% (CI95: 6.5–9.5) in acute myelocytic leukaemia and 6.3% (CI95: 4.3–8.3) in acute lymphocytic leukaemia. Incidence was 12.8% (CI95: 10.8–14.8) following allogeneic stem-cell transplantation and 1.1% (CI95: 0.7–1.5) following autologous stem-cell transplantation. In solid-organ recipients incidence ranged from 11% following heart–lung transplantation and small bowel to 0.4% following kidney transplantation. Incidence in HIV infected patients ranged from 0.02 to 0.13% per annum. This large series confirmed that patients with haematologic disorders and transplantations are the most at risk for IA.

Relationship between environmental fungal contamination and the incidence of invasive aspergillosis in haematology patients

Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Spore inhalation is the usual route of Aspergillus infection, suggesting a determining role of environmental contamination by spores in the epidemiology of IA. We prospectively examined the relationship between environmental contamination by Aspergillus and other fungal species and the incidence of invasive nosocomial aspergillosis (INA) in a bone marrow transplantation unit and two haematology wards. During a four-year period, levels of air and surface fungal contamination were determined bi-monthly in patients' rooms(some equipped with HEPA filters and LAF systems), and various common sites in each ward (corridors, nursing stations, etc.). Results were compared to the incidence of INA. A total of 3100 air and 9800 surface samples were collected, and 79 cases of IA were diagnosed, of which 64 were probably or possibly INA. Patterns of fungal contamination were comparable in the three wards, with a gradient ranging fromhigh levels in common sites to a virtual absence in rooms equipped with HEPA filters and LAF systems. Using a regression model, a significant relationship was found between the incidence of INA and the degree of fungal contamination of air and surfaces in conventional patient rooms (not equipped with HEPA) and common sites. This study shows that in a non-epidemic setting, there is a significant relationship between environmental fungal contamination in haematology wards and the incidence of INA. Ourfindings underline the importance of environmental surveillance and strict application of preventivemeasures.

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients.

Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients. Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach. Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon-gamma, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value. This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.

Epidemiology of nosocomial fungal infections: invasive aspergillosis and the environment

The incidence rates of invasive aspergillosis have increased dramatically during the last two decades, and, despite all diagnostic and therapeutic efforts, outcome is often fatal. Therefore, preventive measures are of major importance in the control of invasive aspergillosis, and require full understanding of the epidemiology of this devastating disease. The environment has been suggested to play a crucial role in the epidemiology of invasive aspergillosis. Aspergillus spores are released in the air and may remain airborne for prolonged periods. As a result, spores are ubiquitously found in air and contaminate anything in contact with air. It has been hypothesized that the inhalation of airborne Aspergillus spores, either directly or through intermediate nasopharyngeal colonization, is a direct cause of pulmonary infection in immunocompromised patients. Recently, water has been suggested as an additional source of “airborne” Aspergillus spp. This review summarizes the current knowledge on the role of the environment in the epidemiology of invasive aspergillosis.

Epidemiology of invasive aspergillosis in European cancer centres

Epidemiology of invasive aspergillosis in European cancer centres