1. Most Important Human Fungal Diseases and Selected Parasitic Infections
Part-14

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. Treatment: amphotericin B, and other anti-fungal drugs for treatment
B- Blastomycosis: Caused by Blastomyces dermatitidis (it is a dimorphic fungus) that is endemic in North America
Transmission and Course of Infection:
Lung inhalation of dust that contain of the fungal conidia spores
The infection starts in lungs and then spreads to skin to cause cutaneous ulcers
The fungus may also spread to other body locations
Clinical symptoms:
The consequences of infection with B. dermatitidis are variable and range from subclinical infection to fatal disseminated disease
50% of infections are asymptomatic
Pulmonary symptoms (pneumonia with flue –like symptoms)
In some cases, lung infection can be associate with cutaneous ulceration
other symptoms ( depending where the infection has reached such as bone and CNS)
Note: without treatment, the infection may be fatal in some cases even in people with normal immune system. The infection is even more severe in immunocompromised patients.
Treatment: amphotericin B, and other anti-fungal drugs for treatment

17. 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

18. 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

19. 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

20. 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%

21. Pneumocystis Pneumonia (PCP)
Caused by Pneumocystis jiroveci (previously known as Pneumocystis carinii)
This fungus is found in the lungs of a wide variety of mammals
Pneumocystis Pneumonia:
Occurs almost exclusively in immunocompromised patients
Infection remains localized in lungs
It has high mortality rate
Laboratory diagnosis:
Microscopic observation of organisms in lung tissue, sputum or by PCR
Treatment, control, and prevention:
Oxygen therapy with a combination of drugs
Prevention and control: Prophylactic drugs can be given to susceptible people

22. Parasitology Protozoa:
These are single-celled eukaryotic microorganism that are wide distributed in nature.
Some of them may cause diseases in humans.
Pathogenic protozoa are transmitted to humans by:
Food and water vehicles
Arthropod (insect) vectors
Direct contact

23. Food and Waterborne Protozoan Diseases
1- Amebiasis (Amebic Dysentery):
Caused by Entamoeba histolytica
Infection occurs by ingestion of amoebic cysts from in contaminated food or water
In the digestive tract, excystment (disintegration of the cyst) occurs to release active amoebic cells (trophozoites), which start replicating and attacking intestinal mucosa to cause ulcerations.
Clinical manifestations:
Infection with Entamoeba histolytica may be asymptomatic .
However, sometimes it may result in, abdominal pain, and bloody diarrhea (dysentery) with mucus and pus cells.
Complications: Extra-intestinal Amoebiasis that may result in liver, lung and brain abscesses

24. Diagnosis: Observation of trophozoites in fresh warm stools or cysts in ordinary stools, and serological tests
Treatment, prevention, and control: Anti-protozoal drugs and
avoiding contaminated water and food as well as hyperchlorination or iodination
of water supplies to destroy waterborne cysts

25. 2- Giardiasis: Caused by Giardia intestinalis
Forms cysts and trophozoites (as in amoeba)
Transmission: ingestion of food and drinks contaminated with the cyst
Pathogenesis: Giardia intestinalis attaches to intestinal epithelium to cause mucosal irritaion and interference with nutrient absorption ( no ulcerations)
Clinical Symptoms:
Giardiasis affects mainly children
In adults: mostly asymptomatic
Clinical symptoms:
Acute Giardiasis : characterized by severe diarrhea (not bloody) with epigastric pain, flatulence, cramps, and anorexia
Chronic Giardiasis: characterized by intermittent diarrhea with periodic appearance and remission of symptoms
Diagnosis:
Observation of cysts or trophozoites in stools, and ELISA
Treatment, prevention, and control:
Antiprotozoal agents
Avoiding contaminated water and use of slow sand filters in processing of drinking water

26. Arthropod Borne Diseases
1- Malaria:
Caused by four species of Plasmodium
Transmitted by mosquito bite
Life cycle:
Sporozoite injected with mosquito bite, which then infects and replicates as merozoite in hepatic cells
Lysis of infected hepatic cells release merozoites into the blood stream. In the blood steam, the merozoites enters erythrocytes (RBCs) to replicate inside them. (Merozoite do not infect live cells again)
Merozoites are released from infected RBCs to infect other RBCs
Lyses of infected RBCs correlates with fever episodes characteristic of malaria
Clinical Manifestations:
Periodic attacks of chills and fever
Anemia can result
Hypertrophy of spleen ( spleenomegaly) and liver ( hepatomegaly)
Can cause cerebral malaria in children and immunocompromised individuals

27. Diagnosis Malaria:
Demonstration of parasites within Wright- or Giemsa-stained red blood cells and serological tests
Treatment, prevention, and control
Anti-malarial drugs:
resistance has been observed
chemoprophylaxis for individuals traveling to endemic areas
Prevention:
Use of bed netting and insecticides to control mosquitoes
New vaccine shows promise

28. 2- Leishmaniasis: Caused by Leishmanias spp
Reservoir and Source: Humans and Animals
Transmission:
Sand fly bite
Blood transfusion
Needle injections
Life cycle:
In insect: flagellated protists known as promastigot
In human body: the parasite is found within cells in a non-flagellated from known as amastigot

29. A-Cutaneous Leishmaniasis: Caused by Leishmania tropica
Lesions are seen at the site where the parasite was inoculated by the insect vector resulting in ulceration
Healing may occur spontaneously ( or with treatment) with scarring
B- Mucocutaneous Leishmaniasis:
Caused by Leishmania mexicana
Lesions occur in mouth, nose, throat to cause extensive scarring and disfigurement
C-Visceral Leishmaniasis (Kala-azar Disease):
Caused by Leishmania donovani
Involves infection of monocyte-macrophage cells of the reticuloendothelial system
Clinical manifestations:
Intermittent fever and enlargement of spleen or liver
May be fatal

30. Selected Helminthes A- Nematodes (Round worms):
1- Ascaris lumbricoides
Life-cycle

32. 2-Enterrobius Vermicularis

33. B- Cestodes (Tapeworms):

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Copyright © The McGraw-Hill Companies. Permission required for reproduction or display.

35. Copyright © The McGraw-Hill Companies
Copyright © The McGraw-Hill Companies. Permission required for reproduction or display.