Information for Healthcare Professionals about Aspergillosis

Clinical features

In immunosuppressed hosts: invasive pulmonary infection, usually with fever, cough, and chest pain. Infection may disseminate to other organs, including brain, skin and bone.

In immunocompetent hosts: Localized pulmonary infection in people with underlying lung disease, allergic bronchopulmonary disease, and allergic sinusitis.

Etiologic agent

Most commonly, Aspergillus fumigatus and A. flavus. Less common species include A. terreus, A. nidulans, A. niger, and A. versicolor. 

Reservoir

Aspergillus is ubiquitous in the environment; it can be found in soil, decomposing plant matter, household dust, building materials, plants, food, and water.

Transmission

Transmission occurs through inhalation of airborne conidia. Hospital-acquired infections may be sporadic or may be associated with dust exposure during building renovation or construction. Occasional outbreaks of cutaneous infection have been traced to contaminated biomedical devices. The incubation period for aspergillosis is unclear and likely varies depending on the dose of Aspergillus and the host immune response.

CDC’s Healthcare Infection Control Practices Advisory Committee (HICPAC) has developed guidelines for environmental infection control.

Diagnosis

A definitive diagnosis of aspergillosis typically requires a positive culture from a normally sterile site and histopathological evidence of infection. Other diagnostic tools include radiology, galactomannan antigen detection, Beta-D-glucan detection, and polymerase chain reaction (PCR).

  • Microscopy: Evaluation of respiratory specimens after the application of special stains can allow for visualization of Aspergillus elements. They appear as septated hyphae with acute angle branching. However, definitive identification is difficult to make by this method alone as it is insensitive and even when positive, several filamentous fungi have a similar microscopic appearance.
  • Histopathology: Important for documentation of invasive disease. Similar to microscopy, Aspergillus appears as septated hyphae with acute angle branching and can be mistaken for other filamentous molds.
  • Culture: Can be done on a variety of sterile specimens and Aspergillus spp. present as rapidly growing molds that are visible 1-3 days after incubation. Culture allows for the microscopic identification down to the species level; however, this method is relatively insensitive, so patients with invasive aspergillosis may have negative cultures.
  • Galactomannan antigen test: This test detects a polysaccharide that makes up part of the cell wall of Aspergillus spp. and other fungi. The Platelia (Bio-Rad Laboratories) assay is approved by the US Food and Drug Administration (FDA) for serum and bronchoalveolar lavage fluid. False positive tests have been reported in association with administration of certain antibiotics and cross reactivity exists with other fungal infections, such as those due to Fusarium spp. or Histoplasma capsulatum.
  • Beta-d-glucan assay: This test also detects a component in the cell wall of Aspergillus spp, as well as other fungi. The Fungitell® assay has been approved by the FDA for diagnosis of invasive fungal infections, including those due to Aspergillus, Candida, and Pneumocystis. Similar to galactomannan testing, the specificity of this assay is reduced in a variety of clinical settings, including exposure to certain antibiotics, hemodialysis, and co-infection with certain bacteria.
  • Polymerase Chain Reaction (PCR): PCR for detection of Aspergillus spp. from clinical specimens, including tissue and bronchoalveolar lavage fluid, is offered by some laboratories.
Treatment and antifungal resistance

Treatment

First-line treatment for invasive aspergillosis is voriconazole. Alternative treatments include lipid amphotericin formulations, posaconazole, isavuconazole, itraconazole, caspofungin, and micafungin. Prophylaxis against aspergillosis is recommended during prolonged neutropenia for patients who are at high risk for aspergillosis, allogeneic stem cell transplant patients with graft versus host disease, lung transplant recipients, and certain other solid organ transplant recipients under certain conditions.

For more detailed recommendations on treatment and prophylaxis, please refer to the Infectious Diseases Society of America’s Practice Guidelines for the Diagnosis and Management of AspergillosisExternal.

Antifungal resistance

Even with antifungal treatment, aspergillosis can cause death in more than half of infected patients with weakened immune systems. Infections with resistant strains of Aspergillus fumigatus can be even harder to treat. Some A. fumigatus strains carry resistance markers that have been associated with environmental fungicide use rather than previous patient exposure to antifungals. Aspergillus fumigatus resistant to all azole antifungal medications (including voriconazole, itraconazole, and posaconazole) is emerging in the United States 1,2,3 and clinicians and public health personnel should be aware that resistant infections are possible even in patients not previously exposed to these medications. Further research is needed to determine how widespread this resistance is.

For more detailed information on antifungal resistant Aspergillus fumigatus, please see the CDC Antifungal Resistance page.

Risk groups

Risk groups for invasive aspergillosis include persons who have severe/prolonged granulocytopenia, hematologic malignancies, receipt of a hematopoietic stem cell or solid organ transplant, and high-dose corticosteroids or other immunosuppressive therapies.

Risk groups for allergic aspergillosis include persons who have asthma, cystic fibrosis, or other underlying lung diseases.

Surveillance and statistics

Aspergillosis is not a reportable infection. Click here for aspergillosis statistics.

Areas for further research
  • Developing more sensitive and specific methods for earlier diagnosis
  • Improving our understanding of environmental sources and routes of transmission
  • Improved availability of advanced molecular typing methods to assist in epidemiologic studies
  • Developing surveillance for resistant Aspergillus infections

Improving our understanding of invasive aspergillosis among patients with severe influenza

The Concern

Aspergillosis usually occurs in people with severely weakened immune systems. However, several reports describe Aspergillus lung infections that caused death in previously healthy patients who were hospitalized for severe illness associated with influenza virus infection. The Aspergillus infections involved pneumonia or severe tracheobronchitis (infection of the lung’s airways) 4–6. A retrospective cohort study at seven intensive care units (ICU) in Belgium and the Netherlands found that invasive pulmonary aspergillosis occurred in 19% of patients with severe influenza requiring admission to the ICU. Approximately half of the patients with invasive pulmonary aspergillosis and severe influenza did not have an immunocompromising condition 7.

Severe lung infections caused by influenza and other viruses can damage the respiratory epithelium (or lining of the lung). Some researchers suspect that this damage can allow Aspergillus to invade and cause infection 8. This process may be similar to how some bacteria, for example Streptococcus pneumoniae and Staphylococcus aureus, cause pneumonia in patients with severe illness associated with influenza virus infections.

More research is needed to determine how commonly these types of Aspergillus infections occur among influenza patients with functioning immune systems and in those who are severely immunocompromised in countries other than the Netherlands and Belgium. Another question is whether previously healthy patients who have severe lung infections caused by viruses other than influenza virus get invasive aspergillosis.

Testing for Aspergillus in Patients with Severe Lung Infections

Several types of tests may be helpful in diagnosing aspergillosis in patients with severe lung infections caused by influenza and other respiratory viruses. Aspergillus can be cultured from patient samples taken by bronchoalveolar lavage (a rinse of the lung’s airways using a specialized device). These samples can also be tested using a galactomannan antigen test, although this test can sometimes be falsely positive or negative. Biopsies, or tissue samples, of the lung can be used to detect Aspergillus. Note that Aspergillus fungi can sometimes be found in the lung airways of patients who do not have an Aspergillus infection (a situation called colonization). Patients with Aspergillus colonization, but without a weakened immune system or other typical risk factors, can develop severe Aspergillus infections when critically ill 9 and show evidence of invasive aspergillosis 4,10.

Vigilance for Aspergillosis

Influenza viral pneumonitis, or bacterial co-infection secondary to influenza can lead to respiratory failure, sepsis, and multi-organ failure. Healthcare providers should continue to consider Aspergillus infection in critically ill patients with influenza who are severely immunocompromised or who received corticosteroids. Recent studies suggest that healthcare providers may also consider Aspergillus infection as a possible cause of worsening respiratory function and sepsis in critically ill immunocompetent patients with severe influenza 7.

For any questions, please contact CDC at aspergillus@cdc.gov.

References
  1. Fisher MC, Hawkins NJ, Sanglard D, Gurr SJ. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 2018 May; 360(6390): 739-742.
  2. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: Can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. 2016 Feb 1;62(3): 362-368.
  3. Beer KD, et al. Multidrug-resistant Aspergillus fumigatus carrying mutations linked to environmental fungicide exposure — three states, 2010–2017. MMWR 2018 Sept 28; 67(38): 1064–1067.
  4. Van de Veerdonk FL, Kolwijck E, Lestrade PPA, Hodiamont CJ, Rijnders BJA, van Paassen J, et al. Influenza-associated aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2017 Apr 7;196(4):524–7.
  5. Alshabani K, Haq A, Miyakawa R, Palla M, Soubani AO. Invasive pulmonary aspergillosis in patients with influenza infection: report of two cases and systematic review of the literature. Expert Rev Respir Med. 2015 Jan 2;9(1):89–96.
  6. Wauters J, Baar I, Meersseman P, Meersseman W, Dams K, Paep RD, et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study. Intensive Care Med. 2012 Nov 1;38(11):1761–8.
  7. Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Tienen CV, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med [Internet]. 2018 Jul 31 [cited 2018 Aug 1];0(0). Available from: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(18)30274-1/abstractExternal
  8. Crum-Cianflone NF. Invasive aspergillosis associated with severe influenza infections. Open Forum Infect Dis [Internet]. 2016 May 1 [cited 2018 Jan 27];3(3). Available from: https://academic.oup.com/ofid/article/3/3/ofw171/2593326External
  9. Shah MM, Hsiao EI, Kirsch CM, Gohil A, Narasimhan S, Stevens DA. Invasive pulmonary aspergillosis and influenza co-infection in immunocompetent hosts: case reports and review of the literature. Diagn Microbiol Infect Dis [Internet]. 2018 Feb 2 [cited 2018 Mar 28]; Available from: http://www.sciencedirect.com/science/article/pii/S0732889318300191External
  10. Lat A, Bhadelia N, Miko B, Furuya EY, Thompson GR. Invasive aspergillosis after pandemic (H1N1) 2009. Emerg Infect Dis. 2010 Jun;16(6):971–3.