1. Most Important Human Fungal Diseases
Part-14-Modified
Most Important Human Fungal Diseases
Summer Semester
So as not to be confused while studying for the final exam, the slides that contain topics that were not discussed during the lectures have been deleted

2. Part I: Basic Mycology
Fungi are eukaryotic organisms. Accordingly, the fungal cell has the general characteristics of an eukaryotic cell (the fungal cell has nucleus, mitochondria, Golgi apparatus, endoplasmic reticulum…..)
Special Components of the Fungal Cell:
The Fungal Cell Wall: it may consist of:
A- Chitin: long chains of N-acetylglucosamine
B- Glucan: long polymer of D-glucose.
2- The Fungal Cell Membrane:
Unlike human cell membrane that contains sterols, the fungal cell membrane contains Ergosterol.

3. You Need to Know (memorize) This Table

4. Accordingly to their morphology, fungi can be classified as:
1- Yeasts: Grow as single cells that reproduce asexually by budding.
2- Molds: Grow as long filaments (hyphae) that form a mat known as mycelium. Some hyphae form transverse walls (septate hyphae), whereas others do not (Non-septate hyphae)
Thermal Dimorphism: Some fungi exist as mold at ambient (environmental) temperature and as yeast at body temperature.
Note: Most of medically important fungi are thermally dimorphic

5. Reproduction of Fungi
1- Sexually: Some fungi reproduce sexually by forming sexual spores, e.g., zygospores
2- Asexually: such fungi are reproduce by asexual spores known as conidia spores.
Note: Most medically important fungi propagate asexually
Asexual spores are produced by as clusters at a special stalk or branch of the mycelium. These clusters of spores are known as conidiophores
The clusters of the conidia spores (conidiophores) formed by asexually-reproducing fungi have characteristic shape, color, and arrangement that help in the diagnosis of fungi diagnosis

6. Part II: Medical Mycology
Human Mycotic (Fungal) Infections can be classified as:
1- Exogenous mycotic infections:
Most mycotic (fungal) infections in humans are exogenous infections, which can be acquired from:
1- The environment
2- An infected human
3- An infected animal
2- Endogenous mycotic infections: The only endogenous fungal infections in human are those infections caused by Candida albicans.
Note: Candida albicans is the only fungus that can be a member of the human normal flora

7. Pathogenesis of Fungi:
A- Inflammations
1- Granulomatous inflammation: can be seen in response to many fungal infections
2- Acute suppuration (pyogenic ) inflammation: which characterized by the presence of exudates (pus).

8. B- Toxins-mediated pathogenesis
Mycotoxicoses: a clinical condition that is caused by ingestion of fungal toxins
Notes:
Most fungal toxins are chemicals that are produced as metabolic byproducts of the fungal cells
Remember that bacterial toxins include the endotoxin (LPS of Gram-negative bacteria, which is called endotoxin) and exotoxins (secreted proteins)
Examples of fungal toxins:
1- Amanitin:
Produced by Amanita mushrooms
It is a haptotixin that causes liver toxicity by inhibiting RNA
Polymerase in live cells
2- Alkaloids compounds:
Produced by the mold Claviceps purpura that infects and grows on grains
Alkaloid compounds cause a clinical condition that is known as Ergotism
Ergotism is characterized by vascular and neurologic symptoms

9. C- Allergic Reactions:
3- Aflatoxins: these are toxins that are produced by Aspergillus flavus that grows on spoiled grains and peanuts.
Aflatoxins are metabolized by the liver into epoxide, which causes sever hepatic toxicity.
Note: in animals, epoxide is believed to cause liver cancer.
C- Allergic Reactions:
Occur particularly in response to the spores of Aspergillus fungus
The allergic reaction is manifested primarily as an asthmatic reaction (rapid broncho-constriction)
Note: the allergic reaction is mediated by IgE antibodies, which triggers the release of large amount of histamine (Hypersensitivity type I) from mast cells and it is accompanied with Eosinophilia.

10. Fungal (Mycotic) Infections (Mycosis)
Fungal infection is known as mycosis or mycotic infection
There about 50 species of fungi that can cause infections in human
Fungal infections may be classified as:
Superficial
Cutaneous
Subcutaneous
Systemic infections
Opportunistic mycoses
Notes:
1 to 3 may occur in healthy people.
4 may occur in healthy individual (mild)
4 and 5 (severe mainly in immunocompromised and lead to disseminated infections that can be fatal)

11. 1- Superficial mycoses:
Piedras: fungal infections of hair shaft that is mostly most occur in tropics
Treatment, prevention, and control of Piedras:
Removal of skin scales and infected hairs
Good personal hygiene
2- Cutaneous mycoses:
Cutaneous mycotic infections are known as Dermatomycoses, which are caused by a group of fungi called Dermatophytes.
Dermatophytes can infect:
Skin
Hair
Nails
Common species of Dermatophytes that infect humans:
Epidermophyton
Trichophyton

12. Diseases caused by Dermatophytes are distinguished according to the affected area of the body:
Infection of skin: known as Ringworms
Tinea capitis: infection of the scalp
Tinea pedis: Athlete’s foot
Tinea unguium: infection of the nail bed
Tinea cruris: known as jock itching (infection of the groins)
Treatment:
Topical and systemic anti-fungal drugs

13. 3- Subcutaneous Mycoses:
These mycotic infections are caused by saprophytic fungi found in soil. Infection may occur through puncture wounds (deep wounds) contaminated with soil.
Epidemiology: Endemic in tropical and subtropical countries.
Examples:
Sporothrix schenckii
Madurella fungi
Clinical manifestations:
Develops slowly over a period of years
Characterized by nodules and ulcerations
Exudates that can be white, brown, or yellow in color with or black granules
Fungal pathogen may spread from infection site along lymphatic vessels , producing more nodules along the lymphatic vessel
Diagnosis: culture and examination of fungus from infected tissue
Treatment:
Surgical excision
Antifungal drugs
Subcutaneous Mycoses

14. 4- Systemic mycotic Infections:
Almost all systemic mycotic infections are usually acquired by inhalation of dust that contains the spores of the infecting fungus (such as fungal spores).
Accordingly, systemic mycosis are usually known as air-borne fungal infections.
Systemic mycotic infections usually start in lungs, however, in some cases, they may spread to other body sites .
Examples of Systemic Mycosis:
1- Histoplasmosis:
It is caused by Histoplasma capsulatum (dimorphic fungus) that is found in bird and bat fecal material
Humans are usually infected by the inhalation the conidia spores (asexual spores) of this fungus that found in soil contaminated with dry birds and bat dropping (feces)
The disease is most commonly seen certain parts of North and South America

15. Pathogenesis and clinical symptoms of Histoplasmosis:
In lungs: the fungus converts to yeast (dimorphic fungus)
Symptoms:
1- In healthy people: flu-like illness that rarely becomes disseminated
2- In immunocompromized individuals: lung infection with this fungus results in sever progressive that usually disseminates to other body locations, with fatal consequences.
Clinical symptoms in progressive disseminated Histoplasmosis depend mainly on infection site
Example: An acute, rapidly-fatal course with diffuse reticuloendothelial involvement characterizes the infection in immunosuppressed patients such as AIDs patients

16. 5- Opportunistic Mycotic Infections:
Caused by fungi that are harmless in its normal healthy people but are pathogenic in immunocompromised patients
Examples:
Aspergillosis:
Caused by several species such as Aspergillus flavus.
The infection is acquired through the respiratory tract by inhaling the conidia spores of this fungus
Symptoms:
Sever pulmonary infection with fever, chest pain and cough. Infected lung may become filled with mycelia
The infection disseminates to other organs such as brain and kidney
Disseminated infection could be fatal
Treatment with antifungal drugs and treat underlying disease and compromise the immune system
Note: Aspergillus flavus does not undergo thermal dimorphism. It exists as a mold both in the environment and within human body.
Aspergillosis

17. Endogenous Mycotic Infections
(Candidiasis)
Candida albicans:
Is the only fungal member of the human normal flora (it is a commensal)
About 80% of the human population harbor Candida albicans as a normal flora
As a member of normal flora, Candida albicans can be found in colon, mouth, skin and vagina
Candida albicans exists as yeast only
It replicates by budding
It may show the formation of pseudohyphae during infection
In most cases, infections with Candida albicans occur because of overgrowth of the Candida albicans.
Notes:
Infection with Candida is commonly known as candidiasis
Most cases of candidiasis are endogenous infection

18. Candidiasis: 1-In healthy people:
Candidiasis is mostly restricted to skin and mucosal membranes of the oral cavity and vagina
In healthy people, Candidiasis can be easily treated and cured
2-In immunocompromised patients: overgrowth in Candida albicans may result in disseminated candidiasis, such as candidemia, which can be fatal
Examples of Candidiasis that may occur among immunocompetent people:
A- Oropharyngeal candidiasis (known as Thrush): Common disease of newborns who become infected during passage through birth canal
B-Napkin (diaper) candidiasis: Found in infants whose diapers are not changed frequently
C- Candidal vulvovaginitis :
Occurs when vaginal lactobacilli normal flora are depleted by antibiotics
Can be transmitted to males during sexual intercourse causing infection of glans penis

19. II- Candidiasis in immunocompromised patients (Nosocomial Candidiasis)
Candida albicans can cause serious nosocomial infection that can be fatal in immunocompromised patients
Candida albicans that is found on skin of immunocompromised patients may reach the blood by needle injections. This will results in candidemia and disseminated candidiasis
Candidemia may represent up to 10% of nosocomial bloodstream infections
Candidemia and disseminated candidiasis have a mortality rate is about 50%

20. Anti-Fungal Drugs:
Because of similarity of fungal cells and human cells (both are eukaryotic cells) , the number of the drugs available for treatment of fungal infections there are less than those available for the treatment of bacterial infections.
In addition, antifungal drugs have a higher level of side effects once compared to anti-bacterial drugs. So, it is always easier to treat superficial mycoses than systemic infections.
Most of the approved anti-fungal dugs targets cellular components or biosynthetic pathways that are not present in human cells or at least have some differences to those found in our cells.

21. The most effective anti-fungal drugs are Amphotericin B and the various azoles drugs that exploit the presence of Ergosterol in fungal cell membranes (Ergosterol is not found in human cell membranes).
Examples:
Amphotericin B disrupts fungal cell membranes by binding to Ergosterol in the cell membrane of fungal cells.
Azoles: which are a group of antifungal drugs that inhibit the biosynthetic pathway of Ergosterol, which is an essential component of fungal cell membranes.
Caspofungin: it inhibits the biosynthetic pathways Glucan, which is found in fungal cell walls but ((human cells do not have a cell wall))