Fungal Pathogens of Humans

Abstract

Most fungi that cause human infections are free‐living saprobes and only accidental pathogens. The most prevalent mycoses are caused by fungi that are either members of the normal human microbiota, such as species of Candida and Malassezia, or ubiquitous, exogenous fungi that are highly adapted for survival on the human host, such as species of Aspergillus and Cryptococcus. This article will summarise the aetiology, risk factors and clinical manifestations of the most common mycoses. Strategies for their diagnoses include traditional methods of microscopy and culture, as well as the detection of fungal antigens and antifungal antibodies, fungal deoxyribonucleic acid and structural components. Because both infectious fungi and their human hosts are eukaryotes, they share many cellular processes and macromolecules. Consequently, it is difficult to identify targets for antifungal drugs that do not inflict collateral damage on the patients.

Key Concepts

  • Superficial and cutaneous mycoses are among the most common of all communicable diseases.
  • Geophilic and zoophilic dermatophytes usually cause acute, inflammatory lesions that respond to topical treatment within weeks and rarely recur. Conversely, anthropophilic dermatophytes tend to cause relatively mild, chronic lesions that may require months or years of treatment and frequently relapse.
  • Subcutaneous mycoses may be caused by dozens of environmental moulds associated with vegetation and soil. These fungi are usually acquired by contamination of minor wounds. The infections are generally chronic and rarely spread to deeper tissues.
  • The endemic mycoses (coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis) are caused by dimorphic environmental moulds and associated with distinct geographic regions.
  • More than 90% of endemic mycoses are caused by inhaling airborne conidia, and, in immunocompetent persons, the infections are asymptomatic or self‐limited; however, latent, viable fungal cells may persist and subsequently reactivate to cause overt disease. Risk factors for the manifestation of disease include compromised cell‐mediated immunity, genetic predisposition and male gender.
  • Opportunistic mycoses are caused by globally distributed fungi that are either members of the human microbiota or ubiquitous environmental fungi. These mycoses have the highest global mortality.
  • Innate immune responses (e.g. neutrophils, monocytes) provide crucial protection from systemic candidiasis, invasive aspergillosis and mucormycosis.
  • Most patients with HIV/AIDS develop mucosal candidiasis (e.g. thrush, oesophagitis). Those with CD4+ counts less than 100 cells μL−1 are at risk for invasive fungi, such as Cryptococcus, Aspergillus and others.
  • Effective treatment of invasive mycoses relies on rapid identification of the fungus, administration of the appropriate antifungal drug and management of any underlying disease or condition.

Keywords: mycosis; infectious fungi; yeast; mould; clinical mycology; medical mycology

Figure 1. Yeast cells of Candida species.
Figure 2. Pityriasis versicolor.
Figure 3. Microscopic appearance of the short hyphae and spherical cells of Malassezia causing pityriasis versicolor.
Figure 4. Lymphocutaneous sporotrichosis.
Figure 5. Cutaneous and subcutaneous phaeohyphomycosis due to Alternaria.
Figure 6. Cutaneous blastomycosis.
Figure 7. Paronychia due to Candida species.
Figure 8. Direct microscopic examination of centrifuged cerebrospinal fluid from a 10‐month‐old infant with meningitis, revealing yeasts and pseudohyphae indicative of candidiasis.
Figure 9. Cutaneous cryptococcosis.
Figure 10. Hyphae of Aspergillus fumigatus (identified after subsequent culture) in the sputum of a patient with acute pulmonary aspergillosis. Typical appearance of vegetative hyphae produced by moulds, whether in culture or tissue, causing an infection.
Figure 11. Hyphae of Aspergillus fumigatus (identified after subsequent culture) in a histopathological section of lung tissue from a patient with pulmonary aspergillosis.
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References

Ampel NM (2010) New perspectives on coccidioidomycosis. Proceedings of the American Thoracic Society 7: 181–185.

Chakrabarti A, Bonifaz A, Gutierrez‐Galhardo MC, Mochizuki T and Li S (2015) Global epidemiology of sporotrichosis. Medical Mycology 53: 3–14.

Chiller TM, Roy M, Nguyen D, et al. (2013) Clinical findings for fungal infections caused by methylprednisolone injections. New England Journal of Medicine 369: 1610–1619.

Colombo AL, Tobón AM, Restrepo A, Queiroz‐Telles F and Nucci M (2011) Epidemiology of endemic systemic fungal infections in Latin America. Medical Mycology 49: 785–798.

Cushion MT (2004) Pneumocystis: unraveling the cloak of obscurity. Trends in Microbiology 12: 243–249.

Dagenais TRT and Keller NP (2009) Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clinical Microbiology Reviews 22: 447–465.

Denning DW, Pleuvry A and Cole DC (2013) Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Medical Mycology 51: 361–370.

Edmond MB, Wallace SE, McClish DK, et al. (1999) Nosocomial bloodstream infections in United States hospitals: a three‐year analysis. Clinical Infectious Diseases 29: 239–244.

Galgiani JN, Ampel NM, Blair JE, et al. (2005) Coccidioidomycosis. Clinical Infectious Diseases 41: 1217–1223.

Gomes MZR, Lewis RE and Kontoyiannis DP (2011) Mucormycosis caused by unusual Mucormycetes, non‐Rhizopus, ‐Mucor, and ‐Lichtheimia species. Clinical Microbiology Reviews 24: 411–445.

Heitman J, Kozel TR, Kwon‐Chung KJ, Perfect JR and Casadevall A (2010) Cryptococcus: From Human Pathogen to Model Yeast, pp. 1–630. Washington, DC: ASM Press.

Jarvis JN, Percival A, Bauman S, et al. (2011) Evaluation of a novel point‐of‐care cryptococcal antigen test on serum, plasma, and urine from patients with HIV‐associated cryptococcal meningitis. Clinical Infectious Diseases 53: 1019–1023.

Kauffman CA (2007) Histoplasmosis: a clinical and laboratory update. Clinical Microbiology Reviews 20: 115–132.

Mancini N, Carletti S, Ghidoli N, et al. (2010) The era of molecular and other non‐culture‐based methods in diagnosis of sepsis. Clinical Microbiology Reviews 23: 235–251.

de Melo TM, Theodoro RC, de Oliveira FFM, et al. (2014) Paracoccidioides lutzii sp. nov.: biological and clinical implications. Medical Mycology 52: 19–28.

Miceli MH and Kauffman CA (2015) Isavuconazole: a new broad‐spectrum triazole antifungal agent. Clinical Infectious Diseases 61 (10): 1558–1565.

Mitchell TG and Perfect JR (1995) Cryptococcosis in the era of AIDS—100 years after the discovery of Cryptococcus neoformans. Clinical Microbiology Reviews 8: 515–548.

Mitchell TG (2010) Population genetics of pathogenic fungi in humans and other animals. In: Xu J (ed) Microbial Population Genetics. Hethersett, UK: Horizon Scientific Press.

Muskett H, Shahin J, Eyres G, et al. (2011) Risk factors for invasive fungal disease in critically ill, adult patients: a systematic review. Critical Care 15: R287.

Park BJ, Wannemuehler KA, Marston BJ, et al. (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23: 525–530.

Pemán J, Salavert M, Cantón E, et al. (2006) Voriconazole in the management of nosocomial invasive fungal infections. Therapeutics and Clinical Risk Management 2: 129–158.

Pound MW, Townsend ML, Dimondi V, Wilson D and Drew RH (2011) Overview of treatment options for invasive fungal infections. Medical Mycology 49: 561–580.

Pyrgos V, Shoham S and Walsh TJ (2008) Pulmonary zygomycosis. Seminars in Respiratory and Critical Care Medicine 29: 111–120.

Queiroz‐Telles F, Esterre P, Perez‐Blanco M, et al. (2009) Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment. Medical Mycology 47: 3–15.

Rüping MJ, Vehreschild JJ and Cornely OA (2008) Patients at high risk of invasive fungal infections: when and how to treat. Drugs 68: 1941–1962.

Saccente M and Woods GL (2010) Clinical and laboratory update on blastomycosis. Clinical Microbiology Reviews 23: 367–381.

Seyedmousavi S, Guillot J and de Hoog GS (2013) Phaeohyphomycoses, emerging opportunistic diseases in animals. Clinical Microbiology Reviews 26: 19–35.

Seyedmousavi S, Netea MG, Mouton JW, et al. (2014) Black yeasts and their filamentous relatives: principles of pathogenesis and host defense. Clinical Microbiology Reviews 27: 527–542.

Theel ES and Doern CD (2013) β‐D‐Glucan testing Is important for diagnosis of invasive fungal infections. Journal of Clinical Microbiology 51: 3478–3483.

Vermout S, Tabart J, Baldo A, et al. (2008) Pathogenesis of dermatophytosis. Mycopathologia 166: 267–275.

White TC, Oliver BG, Gräser Y and Henn MR (2008) Generating and testing molecular hypotheses in the dermatophytes. Eukaryotic Cell 7: 1238–1245.

Wisplinghoff H, Seifert H, Tallent SM, et al. (2003) Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities. Pediatric Infectious Disease Journal 22: 686–691.

Further Reading

Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM and Mylonakis E (2014) Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clinical Microbiology Reviews 27: 490–526. DOI: 10.1128/CMR.00091-13.

Larone DH (2011) Medically Important Fungi. A Guide to Identification. Washington, DC: ASM Press.

Merz WG and Hay RJ (eds) (2005) Topley & Wilson's Microbiology and Microbial Infections, 10th edn, vol. 4 Medical Mycology. Arnold: London.

Mitchell TG, Verweij P and Hoepelman AIM (2010) Opportunistic and systemic fungi. In: Cohen J, Opal SM and Powderly WG (eds) Infectious Diseases, 3rd edn, vol. 2, pp.1823–1852. London: Mosby.

Mitchell TG (2016) Medical mycology. In: Carroll KC, Butel JS and Morse SA (eds.) Jawetz, Melnick, & Adelberg's Medical Microbiolgy, 27th edn. pp. 657–703. New York: McGraw Hill Education.

Reiss E, Shadomy HJ and Lyon GM III (2012) Fundamental Medical Mycology. Wiley‐Blackwell: Hoboken, NJ.

Richardson MD, Moore CB, Summerbell RC and Gupta AK (2010) Superficial and subcutaneous fungal pathogens. In: Cohen J, Opal SM and Powderly WG (eds) Infectious Diseases, 3rd edn, vol. 2, pp. 1853–1867. London: Mosby.

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Mitchell, Thomas G(Jan 2016) Fungal Pathogens of Humans. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000359.pub2]