Intensive Care Medicine

, Volume 29, Issue 11, pp 2068–2071 | Cite as

Immunoparalysis as a cause for invasive aspergillosis?

  • Koen J. Hartemink
  • Marinus A. Paul
  • Jan Jaap Spijkstra
  • Armand R. J. Girbes
  • Kees H. Polderman
Brief Report


Aspergillus infections are among the most feared opportunistic infections in humans. These organisms are ubiquitous in nature; protection against infection is usually provided by anatomical barriers and by the immune system. Tissue invasion by Aspergillus is uncommon, occurring primarily in the setting of immunosuppression. The prognosis of invasive aspergillosis is very poor. Although it is widely recognised that critically ill patients in the Intensive Care Unit (ICU) are at risk for nosocomial infections, it is not generally appreciated that such patients may also be at risk for opportunistic infections usually seen only in immunocompromised patients. This might be explained by a biphasic immunological pattern during sepsis: an early hyperinflammatory phase followed by an anti-inflammatory response, leading to a hypo-inflammatory state, the so-called compensatory anti-inflammatory response syndrome (CARS or immunoparalysis). We describe four patients admitted to our ICU for various reasons, without a history of abnormal immune function, who developed invasive pulmonary aspergillosis. We hypothesise that the occurrence of these opportunistic infections in our patients may have been due to immunoparalysis, and that perhaps all ICU patients with sepsis and multiple organ dysfunction syndrome (MODS) may be at risk for opportunistic infections such as aspergillosis as a result of this syndrome. Physicians treating critically ill patients in the ICU should be aware of the CARS/immunoparalysis syndrome and its potential to cause opportunistic infections, even in patients with normal immune function prior to ICU admission.


Aspergillosis Compensatory anti-inflammatory response syndrome (CARS) Immunoparalysis Sepsis Multiple organ dysfunction syndrome (MODS) Opportunistic infection 


  1. 1.
    Maertens J, Vrebos M, Boogaerts M (2001) Assessing risk factors for systemic fungal infections. Eur J Cancer Care 10:56–62CrossRefGoogle Scholar
  2. 2.
    Janssen JJ, Strack van Schijndel RJ, van der Poest Clement EH, Ossenkoppele GJ, Thijs LG, Huijgens PC (1996) Outcome of ICU treatment in invasive aspergillosis. Intensive Care Med 22:1315–1322PubMedGoogle Scholar
  3. 3.
    Denning DW, Stevens DA (1990) Antifungal and surgical treatment of invasive aspergillosis: review of 2121 published cases. Rev Infect Dis 12:1147Google Scholar
  4. 4.
    Sarel R (1991) Candida and Aspergillus infections in immunocompromised patients: an overview. Rev Infect Dis 13:487–492PubMedGoogle Scholar
  5. 5.
    Andriole VT (1996) Aspergillus infections: problems in diagnosis and treatment. Infect Agents Dis 5:47PubMedGoogle Scholar
  6. 6.
    Robinson LA (1999) Aspergillus and other fungi. Chest Surg Clin N Am 9:193–225Google Scholar
  7. 7.
    Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115:457–469PubMedGoogle Scholar
  8. 8.
    Matsushima K, Oppenheim JJ (1989) Novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1:2–13PubMedGoogle Scholar
  9. 9.
    Volk HD, Reinke P, Döcke WD (2000) Clinical aspects: from systemic inflammation to 'immunoparalysis'. Chem Immunol 74:162–177PubMedGoogle Scholar
  10. 10.
    Bone RC (1996) Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 24:1125–1128Google Scholar
  11. 11.
    Kox WJ, Bone RC, Krausch D, Döcke WD, Kox SN, Wauer H, Egerer K, Querner S, Asadullah K, van Baehr R, Volk HD (1997) Interferon gamma-1b in the treatment of compensatory anti inflammatory response syndrome. A new approach: proof of principle. Arch Intern Med 157:389–393Google Scholar
  12. 12.
    Kox WJ, Volk T, Kox SN, Volk HD (2000) Immunomodulatory therapies in sepsis. Intensive Care Med 26: S124-S128CrossRefPubMedGoogle Scholar
  13. 13.
    Adrie C, Pinsky MR (2000) The inflammatory balance in human sepsis. Intensive Care Med 26:364–375PubMedGoogle Scholar
  14. 14.
    Iwen PC, Davis JC, Reed EC, Winfield BA, Hinrichs SH (1994) Airborne fungal spore monitoring in a protective environment during hospital construction, and correlation with an outbreak of invasive aspergillosis. Infect Control Hosp Epidemiol 15:303–306PubMedGoogle Scholar
  15. 15.
    Oren I, Haddad N, Finkelstein R, Rowe JM (2001) Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters. Am J Hematol 66:257–262CrossRefPubMedGoogle Scholar
  16. 16.
    Pegues DA, Lasker BA, McNeil MM, Hamm PM, Lundal JL, Kubak BM (2002) Cluster of cases of invasive aspergillosis in a transplant intensive care unit: evidence of person-to-person airborne transmission. Clin Infect Dis 34:412–416CrossRefPubMedGoogle Scholar
  17. 17.
    Pittet D, Huguenin T, Dharan S, Sztajzel-Boissard J, Ducel G, Thorens JB, Auckenthaler R, Chevrolet JC (1996) Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 154:541–544PubMedGoogle Scholar
  18. 18.
    Rello J, Esandi ME, Mariscal D, Gallego M, Domingo C, Valles J (1998) Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: report of eight cases and review. Clin Infect Dis 26:1473–1475PubMedGoogle Scholar
  19. 19.
    Vazquez JA, Sobel JD (1995) Fungal infections in diabetes. Infect Dis Clin North Am 9:97–116PubMedGoogle Scholar
  20. 20.
    Thommi G, Bell G, Liu J, Nugent K (1991) Spectrum of invasive pulmonary aspergillosis in immunocompetent patients with chronic obstructive pulmonary disease. South Med J 84:828–831PubMedGoogle Scholar
  21. 21.
    Polderman KH, Girbes ARJ (2002) Central venous catheter use, part 2: infectious complications. Intensive Care Med 28:18–28PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Koen J. Hartemink
    • 1
  • Marinus A. Paul
    • 2
  • Jan Jaap Spijkstra
    • 1
  • Armand R. J. Girbes
    • 1
  • Kees H. Polderman
    • 1
  1. 1.Department of Intensive CareVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of SurgeryVU University Medical CenterAmsterdamThe Netherlands

Personalised recommendations