**Fungal Infections in Immunosuppressed Patients**

Luis Enrique Jerez Puebla

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/51512

#### **1. Introduction**

148 Immunodeficiency

Infectious Diseases 2011; 53(7): 732-742.

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Fungal infections, also called mycoses, are important causes of morbidity and mortality in humans. Some fungal infections are endemic, and these infections are usually caused by fungi that are present in the environment and whose spores enter humans. Other fungal infections are said to be opportunistic because the causative agents cause mild or no disease in healthy individuals but may infect and cause severe disease in immunodeficient persons. The human airway is continuously open to the nonsterile environment where fungal spores have the potential to reach lung tissue and produce disease. In the immunocompromised host, many fungi, including species of fungi typically considered nonpathogenic, have the potential to cause serious morbidity and mortality. Over the last several decades the advent of the human immunodeficiency virus (HIV) epidemic and the increasing use of immunosuppressive drugs for serious medical conditions have dramatically increased the number of persons who are severely immunocompromised. In addition, the range and diversity of fungi that cause disease have broadened. Although *Candida* and *Aspergillus* species continue to be the fungal pathogens that most frequently cause invasive fungal disease in immunocompromised persons overall, infections due to previously uncommon hyaline and dematiaceous filamentous fungi are being reported with increasing frequency. This is significant because, despite marked advances in antifungal therapy, infections caused by opportunistic fungal infections (rare and emerging) continue to be associated with high morbidity, high mortality, and poor patient outcomes. This results from a combination of drug-resistant strains, lack of robust clinical studies evaluating treatments, and severe underlying diseases in the patient [2].

The principal mediators of innate immunity against fungi are neutrophils and macrophages. Patients with neutropenia are extremely susceptible to opportunistic fungal infections. Phagocytes and dendritic cells sense fungal organisms by TLRs and lectin-like receptors called dectins . Neutrophils presumably liberate fungicidal substances, such as reactive oxygen species and lysosomal enzymes, and phagocytose fungi for intracellular

<sup>© 2012</sup> Jerez Puebla, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

killing. Many extracellular fungi elicit strong TH17 responses, which are driven in part by the activation of dendritic cells by fungal products binding to the dectin receptor and resulting production of TH17- inducing cytokines (IL-6, IL-23) from the dendritic cells. The TH17 cells stimulate inflammation, and the recruited neutrophils and monocytes destroy the fungi. *Candida* infections often start at mucosal surfaces, and cell-mediated immunity is believed to prevent spread of the fungi into tissues. TH1 responses are protective in intracellular fungal infections, such as histoplasmosis, but these responses may elicit granulomatous inflammation, which is an important cause of host tissue injury in these infections. Fungi also elicit specific antibody responses that are of protective value [2].

Fungal Infections in Immunosuppressed Patients 151

*Candida* species are the most common cause of fungal infection in immunocompromised persons. Oropharyngeal colonization is found in 30-55% of healthy young adults, and

*Candida* species are yeastlike fungi that can form pseudohyphae and some species can develop true hyphae, as *Candida albicans* do. For the most part, *Candida* species are confined to human and animal reservoirs; however, they are frequently recovered from the hospital environment, including on foods, countertops, air-conditioning vents, floors, respirators, and medical personnel. They are also normal commensals of diseased skin and mucosal

*Candida* species also contain their own set of well-recognized but not well-characterized virulence factors that may contribute to their ability to cause infection. The main virulence

• Surface molecules that permit adherence of the organism to other structures (eg, human

• Acid proteases and phospholipases that involve penetration and damage of cell

As with most fungal infections, host defects also play a significant role in the development of candidal infections. Host defense mechanisms against *Candida* infection and their

• Intact mucocutaneous barriers - Wounds, intravenous catheters, burns, ulcerations

*Candida* species may be detected in 40-65% of normal fecal microbiota [6, 7].

membranes of the gastrointestinal, genitourinary, and respiratory tracts [8-10].

factors include the following [11]:

envelopes

cells, extracellular matrix, prosthetic devices)

associated defects that allow infection are as follows:

• Monocytic cells -Myeloperoxidase deficiency

• Immunoglobulins -Hypogammaglobulinemia

• Solid organ transplantation (liver, kidney)

• Recent chemotherapy or radiation therapy

• Phagocytic cells -Granulocytopenia

• Complement -Hypocomplementemia

• Bone marrow transplantation

• Parenteral hyperalimentation • Hematologic malignancies

• Broad-spectrum antibiotics

• Prolonged hospitalization • Gastrointestinal tract surgery • Central intravascular access devices

• Foley catheters • Solid neoplasms

• Corticosteroids

• Premature birth

• Burns

• Ability to convert to a hyphal form (phenotypic switching)

• Polymorphonuclear leukocytes - Chronic granulomatous disease
