Skip to main content
SpringerLink
Log in

Invasive Fungal Infections and Their Epidemiology: Measures in the Clinical Scenario

  • Review Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Fungi are increasingly recognized as major clinical pathogens in critically ill patients. Emerging groups of fungal pathogens such as Candida and Cryptococcus spp. are most frequently isolated from clinical setup, including filamentous fungi. Assessment of risk factors of these infections such as hospital-acquired fungal infection and environmental factors, including changes in medical practices and epidemiology as well as fungal infection mediated immunomodulation have provided important therapeutic options in the diagnosis of the fungal infections for clinicians. This review aims to furnish information on the factors affecting invasive fungal infections in a clinical scenario, especially for immunocompromised patients. A review of the recently published literature via PubMed, Elsevier and Medline database was performed. Relevant invasive fungal diseases and their worldwide cases were reviewed. Data on the immune response to the fungal infections in terms of release of anti-fungal effectors have been provided. Information on the anti-fungal mechanistic action via upregulation of immunity through predominant cytokines has been summarized, as well as factors affecting disease scenario of invasive fungal infections in clinical practices. The epidemiology and clinical features of fungal infections have also been reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Enoch, D. and N. Brown (2006). Invasive fungal infections: a review of epidemiology and management options. J. Med. Microbiol. 55: 809–818.

    Article  CAS  PubMed  Google Scholar 

  2. Gullo, A. (2009). Invasive fungal infections. Drugs 69: 65–73.

    Article  PubMed  Google Scholar 

  3. Pagano, L, M. Caira, A. Candoni, M. Offidani, L. Fianchi, and B. Martino (2006). The epidemiology of fungal infections in patients with hematologic malignancies: The SEIFEM-2004 study. Hematologica: J. Eur. Hematol. Assoc. 91: e1068.

    Google Scholar 

  4. Chayakulkeeree, M, M. Ghannoum, and J. Perfect (2006). Zygomycosis: The re-emerging fungal infection. Eur. J. Clin. Microbiol. Infect. Dis. 25: 215–229.

    Article  CAS  PubMed  Google Scholar 

  5. Garber, G. (2001). An overview of fungal infections. Drugs 61: 1–12.

    Article  PubMed  Google Scholar 

  6. Schuetz, A. (2013). Invasive fungal infections. Clin. Lab. Med. 33: 505–525.

    Article  PubMed  Google Scholar 

  7. Lehrnbecher, T., C. Frank, K. Engels, S. Kriener, A. H. Groll, and D. Schwabe (2010). Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 61: 259–265.

    Article  CAS  PubMed  Google Scholar 

  8. Upton, A. and K. Marr (2006). Emergence of opportunistic mould infections in the hematopoietic stem cell transplant patient. Curr. Infect. Dis. Rep. 8: 434–441.

    Article  PubMed  Google Scholar 

  9. Natesan, S. (2016). Emerging fungal infections in cancer patients — A brief overview. Med. Mycol. 2: e8521.

    Google Scholar 

  10. Leventakos, K., R. Lewis, and D. Kontoyiannis (2010). Fungal infections in leukemia patients: How do we prevent and treat them?. Clin. Infect. Dis. 50: 405–415.

    Article  PubMed  Google Scholar 

  11. Vincent, J., J. Rello, and J. Marshall (2009). International study of the prevalence and outcomes of infection in intensive care units. JAMA 302: e2323.

    Article  Google Scholar 

  12. Paramythiotou, E., F. Frantzeskaki, A. Flevari, A. Armaganidis, and G. Dimopoulos (2014). Invasive fungal infections in the ICU: How to approach, how to treat. Molecules 19: 1085–1119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wisplinghoff, H., T. Bischoff, S. Tallent, H. Seifert, R. Wenzel, and M. Edmond (2004). Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39: 309–317.

    Article  PubMed  Google Scholar 

  14. de Irala-Estévez, J., D. Martínez-Concha, C. Diaz-Molina, J. Masa-Calles, A. Serrano del Castillo, and R. Fernández-Crehuet Navajas (2001). Comparison of different methodological approaches to identify risk factors of nosocomial infection in intensive care units. Intensive Care Med. 27: 1254–1262.

    Article  PubMed  Google Scholar 

  15. Hobson, R. (2003). The global epidemiology of invasive Candida infections — is the tide turning?. J. Hosp. Infect. 55: 159–168.

    Article  CAS  PubMed  Google Scholar 

  16. Chapman, R. (2003). Candida infections in the neonate. Curr. Opin. Pediatr. 15: 97–102.

    Article  PubMed  Google Scholar 

  17. Richardson, M. and D. Warnock (2008). Other invasive yeast infections. Fungal Infect. 27: 346–353.

    Google Scholar 

  18. Romani, L. (2004). Immunity to fungal infections. Nat. Rev. Immunol. 4: 11–24.

    Article  CAS  Google Scholar 

  19. Richardson, M. (2005). Changing patterns and trends in systemic fungal infections. J. Antimicrob. Chemother. 56: 5–11.

    Article  CAS  Google Scholar 

  20. De Pauw, B., T. Walsh, J. Donnelly, D. Stevens, J. Edwards, and T. Calandra (2008). Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group. Clin. Infect. Dis. 46: 1813–1821.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Klaenhammer, T., M. Kleerebezem, M. Kopp, and M. Rescigno (2012). The impact of probiotics and prebiotics on the immune system. Nat. Rev. Immunol. 12: 728–734.

    Article  CAS  PubMed  Google Scholar 

  22. CDC (2017). Types of Fungal Diseases Fungal Diseases. Cdc.gov. Retrieved 6 September 2017; https://www.cdc.gov/fungal/diseases/index.html#one.

  23. Konkel, L. (2017). Fungal diseases are on the rise. Is environmental change to blame?. Ensia. Retrieved 6 September 2017, from https://ensia.com/features/19036/.

  24. Dworecka-Kaszak, B. (2008). Animals as a potential source of human fungal infections. Wiad. Parazytol. 54: 101–108.

    PubMed  Google Scholar 

  25. Warris, A. and P. Verweij (2005). Clinical implications of environmental sources for Aspergillus. Med. Mycol. 43: 59–65.

    Article  Google Scholar 

  26. Burge, H. (2010). Sources and control of opportunistic fungi in the hospital environment. Environ. Rep. 8(1).

  27. Bartley, J. (2007). Hospital construction: stirring up trouble. Eng. Sys. 24: e36.

    Google Scholar 

  28. Kanamori, H., W. Rutala, E. Sickbert-Bennett, and D. Weber (2015). Review of fungal outbreaks and infection prevention in healthcare settings during construction and renovation. Clin. Infect. Dis. 61: 433–444.

    Article  PubMed  Google Scholar 

  29. Fisher, M., D. Henk, C. Briggs, J. Brownstein, L. Madoff, S. McCraw, and S. Gurr (2012). Emerging fungal threats to animal, plant and ecosystem health. Nature 484: 186–194.

    Article  CAS  PubMed  Google Scholar 

  30. Olsen, L., E. Relman, and L. Pray, (2011). Fungal diseases: an emerging threat to human, animal and plant health. https://www.nap.edu/read/13147/chapter/1.

  31. Rosenzweig, C., A. Iglesias, X. Yang, P. Epstein, and E. Chivian (2001). Climate change and extreme weather events; Implications for food production, plant diseases, and pests. Global Change Human Health 2: e1023.

    Article  Google Scholar 

  32. Green, A., N. Victoria, and D. Fisman (2008). Climate change and infectious diseases in North America: the road ahead. Can. Med. Assoc. 178: e081325.

    Google Scholar 

  33. La Porta, N., P. Capretti, I. Thomsen, R. Kasanen, A. Hietala, and K. Von Weissenberg (2008). Forest pathogens with higher damage potential due to climate change in Europe. Can. J. Plant Pathol. 30: 177–195.

    Article  Google Scholar 

  34. Garcia-Solache, M. and A. Casadevall (2010). Global warming will bring new fungal diseases for mammals. Mbio 1: e00061.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Baddley, J., T. Stroud, D. Salzman, and P. Pappas (2001). Invasive mold infections in allogeneic bone marrow transplant recipients. Clin. Infect. Dis. 32: 1319–1324.

    Article  CAS  PubMed  Google Scholar 

  36. Singh, N. (2001). Trends in the epidemiology of opportunistic fungal infections: Predisposing factors and the impact of antimicrobial use practices. Clin. Infect. Dis. 33: 1692–1696.

    Article  CAS  PubMed  Google Scholar 

  37. Eggimann, P., J. Garbino, and D. Pittet (2003). Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect. Dis. 3: 685–702.

    Article  PubMed  Google Scholar 

  38. Garbino, J., L. Kolarvo, P. Rohner, D. Lew, P. Pichna, and D. Pittet (2002). Secular trends of candidemia over 12 years in adult patients at a tertiary care hospital. Medicine 81: 425–433.

    Article  PubMed  Google Scholar 

  39. Clark, T. and R. Hajjeh (2002). Recent trends in the epidemiology of invasive mycoses. Curr. Opin. Infect. Dis. 15: 569–574.

    Article  PubMed  Google Scholar 

  40. Hobson, R. P. (2003). The global epidemiology of invasive Candida infections–is the tide turning? J. Hosp. Infect. 55: 159–168.

    Article  CAS  PubMed  Google Scholar 

  41. Cornet, M., L. Fleury, C. Maslo, J. Bernard, and G. Brücker (2002). Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J. Hosp. Infect. 51: 288–296.

    Article  CAS  PubMed  Google Scholar 

  42. Armstrong-James, D., G. Meintjes, and G. Brown (2014). A neglected epidemic: fungal infections in HIV/AIDS. Trends Microbiol. 22: 120–127.

    Article  CAS  PubMed  Google Scholar 

  43. Trick, W., S. Fridkin, J. Edwards, R. Hajjeh, and R. Gaynes (2002). Secular trend of hospital?acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin. Infect. Dis. 35: 627–630.

    Article  CAS  PubMed  Google Scholar 

  44. Pfaller, M. and D. Diekema (2004). Rare and emerging opportunistic fungal pathogens: Concern for resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol. 42: 4419–4431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Redding, S., M. Dahiya, W. Kirkpatrick, B. Coco, T. Patterson, and A. Fothergill (2004). Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol. 97: 47–52.

    Article  Google Scholar 

  46. Bennett, J., K. Izumikawa, and K. Marr (2004). Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob. Agents Chemother. 48: 1773–1777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Marr, K., R. Carter, F. Crippa, A. Wald, and L. Corey (2002). Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 34: 909–917.

    Article  PubMed  Google Scholar 

  48. Nucci, M. (2003). Emerging moulds: Fusarium, Scedosporium and Zygomycetes in transplant recipients. Curr. Opin. Infect. Dis. 16: 607–612.

    Article  PubMed  Google Scholar 

  49. Kauffman, C. (2004). Zygomycosis: Reemergence of an old pathogen. Clin. Infect. Dis. 39: 588–590.

    Article  PubMed  Google Scholar 

  50. Husain, S., B. Alexander, P. Munoz, R. Avery, S. Houston, and T. Pruett (2003). Opportunistic mycelial fungal infections in organ transplant recipients: Emerging importance of non-Aspergillus mycelial fungi. Clin. Infect. Dis. 37: 221–229.

    Article  PubMed  Google Scholar 

  51. Perea, S., T. Patterson, and G. Eliopoulos (2002). Antifungal resistance in pathogenic fungi. Clin. Infect. Dis. 35: 1073–1080.

    Article  PubMed  Google Scholar 

  52. Nucci, M. and K. Marr (2005). Emerging fungal diseases. Clin. Infect. Dis. 41: 521–526.

    Article  PubMed  Google Scholar 

  53. Netea, M., L. Joosten, J. Van Der Meer, B. Kullberg, and F. Van De Veerdonk (2015). Immune defence against Candida fungal infections. Nat. Rev. Immunol. 15: 630–642.

    Article  CAS  PubMed  Google Scholar 

  54. Brown, G. D. (2011). Innate antifungal immunity: the key role of phagocytes. Annu. Rev. Immunol. 29: 1–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Conti, H. R., F. Shen, and N. Nayyar (2009). Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206: 299–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Brown, G., D. Denning, N. Gow, S. Levitz, M. Netea, and T. White (2012). Hidden killers: Human fungal infections. Sci. Trans. Med. 4: e3004404.

    Article  CAS  Google Scholar 

  57. Jarvis, J., A. Percival, S. Bauman, J. Pelfrey, G. Meintjes, and G. Williams (2011). Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis. Clin. Infect. Dis. 53: 1019–1023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cole, D., N. Govender, A. Chakrabarti, J. Sacarlal, and D. Denning (2017). Improvement of fungal disease identification and management: Combined health systems and public health approaches. Lancet Infect. Dis. 17: e30308.

    Article  Google Scholar 

  59. Marr, K., S. Balajee, L. McLaughlin, M. Tabouret, C. Bentsen, and T. Walsh (2004). Detection of Galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: Variables that affect performance. J. Infect. Dis. 190: 641–649.

    Article  CAS  PubMed  Google Scholar 

  60. Clancy, C., R. Jaber, H. Leather, J. Wingard, B. Staley, and L. Wheat (2007). Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J. Clin. Microbiol. 45: 1759–1765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kosmidis, C. and D. Denning (2015). Republished: The clinical spectrum of pulmonary aspergillosis. Postgraduate Med. J. 91: 403–410.

    Article  Google Scholar 

  62. Ostrosky-Zeichner, L., A. Casadevall, J. Galgiani, F. Odds, J. Rex (2010). An insight into the antifungal pipeline: Selected new molecules and beyond. Nat. Rev. Drug Dis. 9: 719–727.

    Article  CAS  Google Scholar 

  63. Denning, D. and W. Hope (2010). Therapy for fungal diseases: opportunities and priorities. Trends Microbiol. 18:195–204.

    Article  CAS  PubMed  Google Scholar 

  64. Brown, G., D. Denning, S. Levitz (2012). Tackling human fungal infections. Science 336: 647–647.

    Article  CAS  PubMed  Google Scholar 

  65. Badiee, P. and Z. Hashemizadeh (2014). Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J. Med. Res. 139: 195–204.

    PubMed  PubMed Central  Google Scholar 

  66. Stevens, D., V. Kan, M. Judson, V. Morrison, S. Dummer, and D. Denning (2000). Practice guidelines for diseases caused by Aspergillus. Clin. Infect. Dis. 30: 696–709.

    Article  CAS  PubMed  Google Scholar 

  67. Allen, D., D. Wilson, R. Drew, and J. Perfect (2015). Azole antifungals: 35 years of invasive fungal infection management. Expert Rev. Anti-Infect. Ther. 13: 787–798.

    Article  CAS  PubMed  Google Scholar 

  68. Cassone, A. (2008). Fungal vaccines: real progress from real challenges. Lancet Infect. Dis. 8: 114–124.

    Article  CAS  PubMed  Google Scholar 

  69. Hong, G., M. White, N. Lechtzin, N. E. West, R. Averyd, H. Miller, R. Lee, R. J. Lovari, C. Massire, L. B. Blyn, X. Liang, D. A. Dutton, J. Fu, B. L. Wickes, N. P. Wiederhold, and S. X. Zhang (2017). Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation. J. Cystic. Fibrosis. 17: 3–7.

    Article  Google Scholar 

  70. Singh, K., M. R. Capoor, D. Nair, and K. T. Bhowmik (2017). Spectrum of fungal infection in head and neck cancer patients on chemoradiotherapy. J. Egypt Nat. Cancer Inst. 29: 33–37.

    Article  PubMed  Google Scholar 

  71. Byrnes, E. J., K. H. Bartlett, J. R. Perfect, and J. Heitman (2011). Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals. Microbes Infect. 13: 895–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Limper, H., A. Adenis, T. Le, and T. S. Harrison (2017). Fungal infections in HIV/AIDS. Lancet Infect. Dis. 17: 30303–30311.

    Article  Google Scholar 

  73. Rossmann, S. N., P. L. Cernoch, J. R. Davis (1996). Dematiaceous fungi are an increasing cause of human disease. Clin. Infect. Dis. 22: 73–80.

    Article  CAS  PubMed  Google Scholar 

  74. Melnychuk, M., B. D. Emt, and D. P. Sole (2017). A rare central nervous system fungal infection resulting from brown heroin use Eric. J. Emerg. Med. 52: 314–317.

    Article  PubMed  Google Scholar 

  75. Bandh, S. A., A. N. Kamili, B. A. Ganai, and B. A. Lone (2016). Opportunistic fungi in lake water and fungal infections in associated human population in Dal Lake, Kashmir. Microbial Pathogen. 93: 105–110.

    Article  Google Scholar 

  76. Azadeh, N., A. H. Limper, E. M. Carmona, J. H. Ryu (2017). The role of infection in interstitial lung diseases: A review. Chest 152: 842–852.

    Article  PubMed  Google Scholar 

  77. Pahlavan, S. and N. N. Bhatia (2016). Fungal spine. Sem. Spine Surg. 28: 163–172.

    Article  Google Scholar 

  78. Gugnani, H. C. and D. W. Denning (2016). Burden of serious fungal infections in the Dominican Republic. J. Infect. Public Health 9: 7–12.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the 2016 Yeungnam University Research Grant. Also, we acknowledge financial support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A5A1009799).

Author information

Authors and Affiliations

  1. Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul, 04620, Korea

    Vivek K. Bajpai, Shruti Shukla & Young-Kyu Han

  2. Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon, 22212, Korea

    Imran Khan & Yun Suk Huh

  3. Department of Forestry, North Eastern Regional Institute of Science and Technology (Deemed University), Nirjuli, 791109, Arunachal Pradesh, India

    Pradeep Kumar

  4. Department of Applied Microbiology and Biotechnology, Yeungnam University, Gyeongsan, 38541, Korea

    Irfan A. Rather & Yong-Ha Park

Authors
  1. Vivek K. Bajpai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Imran Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shruti Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pradeep Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irfan A. Rather
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong-Ha Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yun Suk Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Young-Kyu Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yong-Ha Park, Yun Suk Huh or Young-Kyu Han.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bajpai, V.K., Khan, I., Shukla, S. et al. Invasive Fungal Infections and Their Epidemiology: Measures in the Clinical Scenario. Biotechnol Bioproc E 24, 436–444 (2019). https://doi.org/10.1007/s12257-018-0477-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-018-0477-0

Keywords

Search

Navigation