Table of Contents
Overview: Fungi as Human Pathogens
Fungi form their own kingdom of life and are usually decomposers or harmless co-inhabitants of our body and environment. Only a relatively small number can cause disease in humans. These diseases are called mycoses (singular: mycosis).
Compared with viruses or bacteria, fungal infections:
- are often more chronic (long-lasting),
- frequently affect the skin, nails, and mucous membranes,
- can become life-threatening when the immune system is severely weakened.
Fungi that infect humans are mostly:
- Yeasts (single-celled, e.g., Candida),
- Molds (filamentous fungi) (e.g., Aspergillus),
- Dermatophytes (specialized for skin, hair, nails).
Separate chapters discuss specific examples (yeasts, dermatophytes). Here, the focus is on general features of fungi as pathogens.
Biological Features Relevant to Pathogenicity
Eukaryotic Organization
Fungi are eukaryotes:
- They have a true nucleus and membrane-bound organelles.
- Their cell wall contains chitin and glucans (not peptidoglycan as in bacteria).
- Their ribosomes and enzymes are more similar to those of human cells than to bacteria.
Consequences for disease and treatment:
- Fungi can grow in environments similar to human tissues (pH, temperature).
- Because fungal cells resemble human cells, selective drug targets are fewer, and antifungals often have more side effects than antibiotics.
Growth Forms and Dimorphism
Pathogenic fungi can exist as:
- Yeasts: round/oval single cells that reproduce by budding (common in mucosal infections, bloodstream infections).
- Molds: multicellular filaments (hyphae) forming a network (mycelium), often with airborne spores (common in respiratory infections).
- Dimorphic fungi: can switch between yeast and mold forms depending on temperature or environment.
- Often: mold form in the environment; yeast form in warm-blooded hosts.
- This switch (dimorphism) is a virulence factor because the yeast form often survives better inside the body.
Reproduction and Spore Formation
Many pathogenic fungi form spores:
- Asexual spores (e.g., conidia) are often airborne and serve as infectious particles.
- Spores are resistant to drying and environmental stress and can survive long periods.
- Inhalation or contact with spores is a common route of infection.
Sexual reproduction plays less of a direct role in human infection but:
- increases genetic variability,
- may contribute to the emergence of drug-resistant strains.
Routes of Infection and Entry Points
Fungi do not usually invade healthy, intact tissue aggressively. Typical entry routes:
- Skin and Appendages (Hair, Nails)
- Via minor injuries, moist skin folds, or macerated skin (e.g., sweaty feet).
- Dermatophytes specialize in keratinized tissues (skin, hair, nails).
- Mucous Membranes
- Mouth, throat, esophagus, intestines, vagina, urethra.
- Local microbiota and immune defenses normally control colonizing yeasts.
- Disturbances (e.g., antibiotics, hormonal changes, immune suppression) can trigger overgrowth.
- Respiratory Tract
- Inhalation of spores from air, dust, soil, compost, bird droppings, etc.
- Spores are deposited in nasal passages, bronchi, or alveoli.
- Usually cleared by immune defenses; if not, infection may develop.
- Wounds and Medical Procedures
- Trauma, burns, contaminated needles or catheters, surgery.
- Fungi from the environment or skin can gain direct access to deeper tissues or bloodstream.
- Opportunistic Spread from Normal Flora
- Some fungi live as commensals on or in the body without causing disease.
- Under certain conditions, they become opportunistic pathogens, invading tissues and causing disease.
Types of Mycoses
Mycoses can be classified by the depth and location of infection.
Superficial and Cutaneous Mycoses
- Involve the outermost layers of skin, hair, and nails.
- Often caused by dermatophytes and certain yeasts.
- Typically:
- non-life-threatening,
- contagious via direct contact or contaminated objects (e.g., floors, towels, shoes),
- chronic and sometimes difficult to eradicate completely.
- Symptoms may include:
- itching,
- redness or scaling,
- ring-shaped lesions,
- brittle or thickened nails.
Separate sections discuss specific causative fungi and examples.
Subcutaneous Mycoses
- Infection involves deeper layers of the skin, subcutaneous tissue, sometimes underlying muscles.
- Usually follow traumatic implantation of fungal elements (e.g., thorn pricks, splinters) contaminated with soil fungi.
- More common in certain geographic regions and in people who walk barefoot or work with plants.
- Typically cause chronic, localized nodules or lesions that can slowly spread along lymphatic vessels.
Systemic (Deep) Mycoses
- Fungi invade internal organs (lungs, brain, liver, kidneys, heart, bones).
- Often begin in the lungs after inhalation of spores, then disseminate via the bloodstream.
- Can be:
- Primary pathogens: can cause disease even in previously healthy people (often geographically restricted, e.g., endemic mycoses).
- Opportunistic pathogens: mainly threaten immunocompromised patients (e.g., Aspergillus, Candida in bloodstream).
- Manifestations depend on the target organs and may resemble bacterial sepsis or cancer.
Opportunistic vs. Primary Pathogens
Opportunistic Mycoses
Opportunistic pathogens:
- are usually harmless or only mildly pathogenic in healthy people,
- cause disease if host defenses are weakened.
Factors increasing susceptibility:
- HIV infection or other causes of severe immunodeficiency,
- Cancer chemotherapy, immunosuppressive medication (e.g., after organ transplantation),
- Long-term steroid treatment,
- Diabetes mellitus and other chronic diseases,
- Broad-spectrum antibiotics, which disturb normal microbiota,
- Intensive care situations (ventilation, catheters, parenteral nutrition).
Examples (discussed in detail in other sections):
- Yeast infections of mucous membranes and bloodstream.
- Mold infections of lungs and sinuses.
- Fungal infections associated with implanted devices (catheters, prosthetic valves, artificial joints).
Primary (True) Pathogens
Primary pathogenic fungi:
- can infect immunocompetent (otherwise healthy) individuals,
- are often adapted to survive in the environment as saprophytes (soil, bird droppings, decaying wood),
- enter mainly by inhalation,
- sometimes show geographical clustering (endemic areas).
Infection outcome depends on:
- dose of inhaled spores,
- host immune response,
- genetic background and other host factors.
Host–Pathogen Interactions and Virulence Factors
Fungi interact with the host in specific ways that determine whether infection occurs and how severe it becomes.
Adherence and Invasion
To colonize, fungi must:
- adhere to host surfaces (skin, mucosa, endothelial cells),
- sometimes form biofilms on surfaces (e.g., catheters, mucosal surfaces),
- produce structures (hyphae, pseudohyphae) that can penetrate tissue.
Biofilms:
- consist of fungal cells embedded in an extracellular matrix,
- protect fungi from immune cells and antifungal agents,
- are a major factor in chronic, device-related infections.
Immune Evasion and Persistence
Pathogenic fungi can:
- mask or modify surface molecules recognized by the immune system,
- produce enzymes (e.g., proteases, lipases) that help them survive in host tissues,
- change morphology (yeast–hyphae switching) to adapt to different niches,
- survive inside phagocytic cells or resist killing mechanisms.
Host defenses (innate and adaptive immunity) are crucial:
- Local defenses (skin barrier, acidic pH, microbiota) usually prevent colonization.
- Phagocytes (neutrophils, macrophages) and T cells are particularly important against invasive mycoses.
- Disorders affecting these cells greatly increase risk.
Clinical Manifestations and General Symptoms
While details differ among fungi, common patterns include:
- Localized skin and mucosal infections
- itching, burning,
- scaling, redness, fissures,
- white or cheesy coatings on mucosa,
- nail changes (thickening, discoloration, brittleness).
- Pulmonary involvement
- cough, sometimes with bloody sputum,
- chest pain, shortness of breath,
- fever (may be low-grade or high, depending on host status),
- radiological findings (nodules, cavities, infiltrates).
- Systemic/disseminated infections
- high fever or low-grade fever in immunosuppressed patients,
- weight loss, fatigue, organ-specific symptoms (e.g., neurological deficits, jaundice, renal dysfunction),
- in severe cases: sepsis-like picture, shock, multi-organ failure.
In immunocompromised hosts, symptoms can be non-specific or even mild despite serious disease, because the typical inflammatory response is blunted.
Diagnosis of Fungal Infections
Diagnosis combines clinical evaluation with laboratory and imaging methods.
Direct Detection in Clinical Material
Specimens depend on suspected site:
- skin scrapings, nail clippings, hair,
- swabs or scrapings from mucosa,
- sputum, bronchoalveolar lavage fluid,
- blood, tissue biopsies, cerebrospinal fluid.
Methods:
- Microscopy:
- Direct examination after special stains (e.g., KOH preparation, fluorescent or histological stains).
- Reveals yeast cells, hyphae, or spores.
- Culture:
- Growth on selective media at appropriate temperature.
- Allows identification by colony morphology, microscopic features, and biochemical tests.
- Some fungi grow slowly, delaying diagnosis.
Serology and Antigen Detection
- Detection of specific antibodies in the patient’s serum can suggest prior or ongoing infection (more useful for some systemic mycoses).
- Detection of fungal antigens (cell wall components or other molecules) in blood or body fluids can indicate invasive disease and monitor therapy.
Molecular Methods
- PCR-based tests can detect fungal DNA in clinical samples.
- Often more sensitive and faster than culture, especially when fungi are difficult to cultivate.
- May identify species and resistance-associated mutations.
Imaging
- X-ray, CT, or MRI can help identify:
- pulmonary nodules, cavities,
- sinus involvement,
- abscesses or lesions in brain, liver, kidney, bone.
- Imaging is particularly important in deep and systemic mycoses.
Principles of Treatment
Because fungi are eukaryotes, antifungal drugs must target structures or pathways that differ sufficiently from human cells.
Antifungal Agents: General Principles
Important targets include:
- Cell membrane sterols (ergosterol in fungi vs. cholesterol in humans):
- Drugs that bind or interfere with ergosterol disrupt membrane integrity.
- Cell wall synthesis:
- Inhibition of β-glucan synthesis, chitin synthesis, or other wall components.
- Nucleic acid or protein synthesis:
- Some drugs interfere with fungal DNA/RNA or specific metabolic pathways.
Use of antifungals:
- Topical (creams, ointments, nail lacquers, vaginal suppositories) for localized skin and mucosal infections.
- Systemic (tablets, capsules, intravenous infusions) for:
- extensive skin or nail disease,
- pulmonary and disseminated infections,
- prophylaxis in high-risk patients.
Combination therapy may be used in severe infections or to overcome resistance.
Treatment Challenges
- Fungal infections often require prolonged therapy (weeks to months).
- Many antifungals have significant side effects (e.g., on liver, kidney, bone marrow) and drug interactions.
- Resistance can emerge, especially in long-term or prophylactic use.
- In immunocompromised patients, immune recovery (e.g., reduction of immunosuppression, effective antiretroviral therapy) is often crucial for cure.
Prevention and Control
General Preventive Measures
- Hygiene:
- Keep skin dry (especially skin folds, feet).
- Change socks and underwear regularly; use breathable materials.
- Avoid sharing towels, shoes, nail clippers.
- Avoid excessive moisture:
- Wear sandals in communal showers and swimming pools.
- Thoroughly dry skin after bathing.
- Footwear and clothing:
- Use well-ventilated shoes and socks.
- Avoid tight, non-breathable clothing that promotes sweating.
These measures reduce risk of cutaneous and mucosal mycoses, particularly by dermatophytes and yeasts.
Prevention in Healthcare Settings
- Hand hygiene and disinfection protocols to avoid transmission.
- Careful management and timely removal of catheters and invasive devices.
- Use of HEPA filters and air management systems in high-risk hospital units to reduce exposure to airborne spores.
- Antifungal prophylaxis (systemic drugs) is sometimes given to high-risk groups (e.g., certain transplant recipients, patients undergoing intensive chemotherapy), but must be balanced against toxicity and resistance risk.
Environmental and Occupational Precautions
- People with severe immune suppression should:
- avoid dusty environments (construction sites, compost heaps),
- use protective masks where spore exposure is expected,
- avoid close contact with bird droppings, moldy organic materials.
In some occupations (agriculture, gardening, forestry, demolition), awareness and protective measures (gloves, footwear, masks) help prevent trauma-related and inhalation-related mycoses.
Summary
- Fungi as human pathogens cause mycoses ranging from superficial skin infections to life-threatening systemic diseases.
- They differ fundamentally from bacteria and viruses in their eukaryotic cell structure, growth forms (yeast, mold, dimorphic), and modes of reproduction.
- Infection often occurs via skin, mucous membranes, inhalation, or contamination of wounds and medical devices.
- Opportunistic fungal infections are a major problem in immunocompromised individuals, whereas primary fungal pathogens can infect healthy hosts, often with regional distribution.
- Diagnosis relies on microscopy, culture, antigen and antibody detection, molecular methods, and imaging.
- Treatment requires antifungal drugs that target fungal-specific structures, but therapy is often prolonged and complicated by side effects and resistance.
- Prevention combines personal hygiene, environmental measures, and careful management of immunosuppression and invasive medical procedures.