Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

Aspergillus fumigatus and Aspergillosis

SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

Aspergillus fumigatus and aspergillosis.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America

This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.

/pdf/guidelines-for-preventing-health-care-associated-pneumonia-3ebalxrxyl.pdf

Guidelines for Preventing Health-Care-- Associated Pneumonia, 2003 Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee

No controlled trials of therapy for invasive aspergillosis have been done. This review appraises 2,121 cases reported in 497 articles in the literature and analyzes 440 courses of treatment of infection at various body sites in 379 patients. The exclusion of early failures of therapy skews the results toward a favorable outcome. The rate of response to amphotericin B is 55%. Mortality from pulmonary aspergillosis in bone marrow transplant recipients exceeds 94% regardless of therapy, as does that from cerebral aspergillosis in all hosts. Amphotericin B (1 mg/[kg.d]) with flucytosine lowers mortality in neutropenic patients with pulmonary aspergillosis who did not receive a bone marrow transplant; relapse is common. Surgical debridement of aspergillus maxillary sinusitis is usually curative in nonimmunocompromised patients, whereas it increases mortality among neutropenic patients. Valve replacement is essential for aspergillus endocarditis. Both vitrectomy and intravitreal amphotericin B treatment are essential for aspergillus endophthalmitis. Flucytosine is somewhat useful clinically. Itraconazole shows efficacy in the treatment of pulmonary, skeletal, and pericardial aspergillosis. Although liposomal amphotericin B is less toxic than standard preparations of the drug, relevant data are limited. The proposed potentiation of amphotericin B by rifampin is unsupported by clinical data. Despite "conventional" therapy, mortality from invasive aspergillosis remains high; new approaches must be investigated.

https://www.jstor.org/stable/pdfplus/4455714.pdf

Antifungal and Surgical Treatment of Invasive Aspergillosis: Review of 2,121 Published Cases

Aspergillosis complicating neoplastic disease.

Invasive Aspergillosis: Progress in early diagnosis and treatment

Diffuse pulmonary infiltrates in immunosuppressed patients. Prospective study of 80 cases.

An Aspergillus fumigatus immunodiffusion test was performed biweekly for one year on 80 hos­ pitalized patients with acute leukemia to determine if serologic conversion accompanied clinical aspergillosis. A micro-ouchterlony technique with agarose was used. The antigens were prepared from concentrated A. fumigatus culture filtrates and the sera were concentrated 3-fold before test­ ing. Of 80 patients, lO were proved at autopsy, lung biopsy, or closed space culture to have in­ vasive aspergillosis. Six of 10 patients converted from a negative to a positive immunodiffusion test, whereas a seventh patient's weakly positive test became strongly positive. Three patients with documented aspergillosis did not develop a positive immunodiffusion test. Four of the patients who converted from a negative to a positive test were treated early and successfully with amphotericin B. A fifth patient developed immunodiffusion test antibody late in the course and died despite therapy. A sixth patient died of concomitant mucormycosis despite early therapy. Six additional patients who converted from a negative to a positive immunodiffusion test could not be evaluated because of inadequate documentation of aspergillosis. In severely immunosuppressed patients, our immunodiffusion test proved to be a specific but not always a sensitive test for aspergillosis. In 4 patients, biweekly tests showed conversion associated with invasive aspergillosis, which was diagnosed early and treated successfully.

An Aspergillus Immunodiffusion Test in the Early Diagnosis of Aspergillosis in Adult Leukemia Patients

Six patients developing cytomegalovirus infection following renal transplantation were studied to evaluate the type of infection that might occur. All developed virological or serological evidence of infection, while two developed symptomatic illness. A syndrome resembling mononucleosis was evident in one, while a hepatitis was seen in the other. Both patients were viremic during their illness and from two weeks to two months after they returned to normal health. A third patient showing no evidence of a viral illness was viremic. Cytomegalovirus was isolated from the erythrocyte layer of all three patients, but less regularly from the leukocytes, plasma, and serum. High-titer complement-fixing antibody was present during the viremic periods, and immunosuppression appeared to have no effect on the specific antibody response and little on semiquantitatively measured lgM, lgG, and lgA levels.

Bessie Yu

Papers

Aspergillosis complicating neoplastic disease.

Invasive Aspergillosis: Progress in early diagnosis and treatment

Diffuse pulmonary infiltrates in immunosuppressed patients. Prospective study of 80 cases.

An Aspergillus Immunodiffusion Test in the Early Diagnosis of Aspergillosis in Adult Leukemia Patients

Cytomegalovirus infections with viremia following renal transplantation.