Fungal infections, also known as mycoses, are caused by various fungi that can infect any part of the body, including the skin, nails, scalp, lungs, and genitals. Although fungal infections are relatively common, especially among people with compromised immune systems, identifying the root cause can sometimes be complex due to the opportunistic nature of fungal pathogens.
What are fungi?
Fungi are eukaryotic organisms that belong to their own kingdom separate from plants and animals. There are over 1.5 million species of fungi on Earth with a variety of forms, ranging from microscopic single-celled yeasts to large mushroom-producing multicellular fungi. Fungi obtain nutrients by breaking down organic matter, either as saprobes feeding on dead or decaying organic material, or as parasites deriving nutrients from living hosts. The cell walls of fungi contain chitin and polysaccharides, giving them a structure distinctly different from animal and plant cells.
How do fungal infections occur?
Fungal infections occur when there is an overgrowth of fungi or a fungal invasion into human tissue. The human body naturally hosts some fungi as part of the skin, gut, and mucous membrane microbiota. These fungi live in equilibrium with the immune system and other microorganisms in healthy individuals. However, certain circumstances can trigger fungal overgrowth, tissue invasion, and infection. Some of the main factors that create conditions suitable for fungal infections include:
- Weakened immune system – Immune deficiency due to AIDS, chemotherapy drugs, steroids, and other conditions suppress the body’s defenses against fungal overgrowth.
- Skin injury – Breaks in the skin or mucous membranes allow fungi to penetrate surface barriers and infect deeper tissues.
- Moist environments – Warm, moist areas of the body favor fungal growth. Excessive sweating and inadequate drying also promote fungal proliferation.
- Diabetes – High blood sugar allows fungi to thrive and impairs immune function.
- Medications – Antibiotics kill off competing bacteria and create an environment for fungal overgrowth. Other medications like immunosuppressants directly impair immunity.
- Foreign devices – Indwelling catheters, pacemakers, dental appliances, and prostheses provide surfaces for fungi to adhere and accumulate on.
What are the most common fungal pathogens?
While there are thousands of fungal species, only a few are significant human pathogens responsible for most fungal infections:
Candida
Candida species like C. albicans commonly reside in the digestive and genitourinary tracts but can cause opportunistic infections known as candidiasis. Thrush, vaginal yeast infections, invasive bloodstream infections, and candiduria are different manifestations of candidiasis.
Aspergillus
Aspergillus is a very common mold found in soil, plant debris, household dust, and ventilation systems. Inhalation of airborne spores can lead to allergic bronchopulmonary aspergillosis and invasive aspergillosis in the lungs and sinuses of immunocompromised patients.
Cryptococcus
This encapsulated yeast is often found in soil enriched with bird droppings. Immunosuppressed individuals are susceptible to lung infections and meningoencephalitis caused by inhaled Cryptococcus spores.
Trichophyton
Dermatophytes like T. rubrum are highly adapted fungal species that infect keratinized tissues like skin, hair, and nails. Trichophyton causes many common superficial cutaneous mycoses such as athlete’s foot, jock itch, and ringworm.
Blastomyces
This dimorphic fungus switches form based on temperature conditions. Blastomyces primarily causes blastomycosis, a respiratory infection, when spores are inhaled from the soil.
Histoplasma
Like Blastomyces, this dimorphic fungus is commonly found in soil and releases infectious spores when disturbed. Histoplasmosis primarily affects the lungs but can disseminate to other organs.
Pneumocystis
Pneumocystis jirovecii (formerly P. carinii) causes opportunistic pneumonia in immunocompromised patients, especially those with advanced AIDS.
Coccidioides
This fungus resides in the soils of arid regions and produces spores that cause Valley fever, a lung infection, when inhaled. Severe disseminated disease can occur.
What enables fungi to cause infections?
Fungi have certain biological characteristics and virulence factors that enable them to establish infections under the right conditions:
- Opportunism – Unlike obligate pathogens, fungal pathogens can live innocuously in a host and only cause infection when host defenses are compromised.
- Dimorphism – Some fungal pathogens transition between mold and yeast forms depending on temperature conditions.
- Adhesins – Fungal proteins allow adherence to host cells and tissues.
- Biofilm production – Fungi produce biofilms that act as shields against immune attack and antifungal penetration.
- Morphological switching – Phenotypic changes allow fungi to evade immune recognition and adapt to host environments.
- Toxin secretion – Fungal toxins damage host cells to facilitate tissue invasion and impair immune responses.
- Thermotolerance – Adaptation to mammalian body temperature supports deep tissue infection.
What host factors predispose to fungal infections?
In addition to pathogen-specific virulence attributes, certain host conditions increase susceptibility to developing fungal infections:
- Impaired neutrophil function
- Deficient cell-mediated immunity
- Loss of mucosal and skin integrity
- Altered microbiota equilibrium
- Presence of foreign bodies like IV lines and urinary catheters
- High blood glucose concentration
- Acidic pH at certain tissue sites
- Impaired phagocytic clearance of fungi
- Nutritional deficiencies like vitamin D deficiency
- Genetic defects in immune pathways
What are the steps in the pathogenesis of fungal infections?
The progression of events enabling fungal pathogens to establish infection include:
- Exposure – Coming into contact with a fungal infectious agent from the environment.
- Adhesion – Fungal adhesins mediate attachment to host cells.
- Invasion – Penetration and entry into host tissue, often enabled by fungal hydrolytic enzymes and morphogenesis.
- Growth – Conversion to pathogenic form and proliferation within host tissue.
- Dissemination – Spread from initial site of infection to other body sites via blood or lymphatics.
- Tissue damage – Caused by fungal pathways like protease secretion, reactive oxygen species production, and epithelial invasion.
- Immune evasion – Fungal mechanisms to avoid effective immune recognition and elimination.
- Host damage – Immunopathology resulting from uncontrolled infection and inflammatory responses.
How does the immune system respond to fungal infections?
The immune system has evolved multiple defenses tailored toward identifying and clearing fungal pathogens:
- Epithelial barriers resist fungal invasion.
- Dendritic cells sample fungi and present antigens to T cells.
- Macrophages and neutrophils phagocytose and kill fungi.
- Natural killer cells release interferon-gamma to activate antimicrobial activity.
- Complement opsonizes fungi for phagocytic clearance.
- Th1 and Th17 cells orchestrate adaptive immunity through cytokine release.
- B cells produce protective antibodies against fungal antigens.
However, fungal virulence factors and host conditions can impair these immune mechanisms and tilt the balance in favor of fungal overgrowth and deep infection.
How are fungal infections diagnosed?
Diagnosing fungal infections typically involves:
- Microscopic examination of specimens stained with fungal stains like potassium hydroxide preparation
- Fungal culture to identify organisms by macroscopic and microscopic morphology
- Biochemical tests to characterize isolated fungi
- Molecular methods such as PCR to detect fungal DNA
- Serological tests for antibodies or antigens
- Radiological imaging like chest X-ray or CT scan to assess disease extent
- Biopsy for histopathological evidence of fungal infection
Identifying the fungal agent through culture, molecular assays, or histology is key for definitive diagnosis.
How are fungal infections treated?
Treatment of fungal infections involves:
- Antifungal drugs like fluconazole, amphotericin B, echinocandins targeting ergosterol, glucan synthesis, or other fungal pathways
- Surgical debridement of necrotic tissue due to invasive fungal growth
- Removal of intravenous lines, urinary catheters, and other foreign devices colonized by fungi
- Addressing underlying conditions depressing immune function
- Monitoring drug levels and signs of organ toxicity
- Follow-up exams and culture to ascertain effectiveness of therapy
The specific choice of antifungal depends on the fungal species, site of infection, host factors, and drug toxicity profile. Prompt initiation of antifungal therapy is key to positive outcomes in invasive fungal infections.
How can fungal infections be prevented?
Preventing fungal infections involves both public health measures and individual precautions:
- Improve indoor air quality and avoid overcrowded living spaces to reduce airborne fungal spores
- Proper construction and water drainage to decrease mold growth
- Safe disposal of waste and debris contaminated with fungi
- Excluding immunocompromised patients from areas of active fungal contamination
- Good hand hygiene practices
- Judicious use of antibiotics and immunosuppressants
- Strict infection control for indwelling medical devices
- Blood glucose control in diabetics
- Vaccines against specific fungal pathogens
Public health awareness and individual precautions focused on reducing fungal exposure and maintaining immune defenses are key preventive approaches.
Conclusion
Fungal infections arise from complex interactions between fungal virulence factors, host immune status, and exposure to sufficient fungal inoculum. Immunocompromised individuals are especially susceptible due to impaired immune clearance. Diagnosis can be difficult but often requires microscopy, culture, or molecular evidence. Antifungal drugs coupled with immune restoration and source control are the mainstays of treatment. Ultimately, prevention through public health measures and maintaining immune competence are the best ways to avoid fungal infections.