Viruses and Fungi Flashcards
Fungi that cause disease are found where?
What is the associated factor of the occurrence of specific fungal diseases?
Are the fungi life cycles uni/di/pleio -morphic?
How is transmission accomplished of fungi and what is a challenge in treating fungal infections?
Most of the fungi that cause disease are naturally found in the soil and are saprobes.
Accordingly, the occurrence of specific fungal diseases is often strongly influenced by the geography of the natural habitat of the infecting fungus.
Many fungi have dimorphic or pleiomorphic life cycles; producing yeast, molds and a variety of spores.
Transmission is by contact with infected material, often in the form airborne spores. Because they are eukaryotes they cannot be treated with most common antibacterial antibiotics, but often can be treated with antifungal drugs.
GENERAL CHARACTERISTICS OF FUNGI
Fungi are eukaryotes
List the characteristics fungi may have (2)
In mold state hyphae can differentiate into NONsexual spores classified by (4) and provide 5 examples of spores.
A. Nucleus
B. Molds, yeast and mushrooms
- Yeast, single cell divide asymmetrically by budding off a daughter cell
- Molds form a mycelium normally comprised of hyphae and spores. Hyphae can either be septate or nonseptate
–Pseudomycelium is made up of elongated yeast cells
In mold state hyphae can differentiate into nonsexual spores classified by shape, size, cell wall thickness, and other morphogenetic characteristics.
- Conidia
- Arthrospores
- Blastospores
- Chlamydospores
- Aleurospores
Cell biology of bud and hyphen growth
Comment on cell wall, vesicles, microtubules, transcriptional and translational machinery, the clinical implication of a feature to the fungi cell membrane.
A. Nucleus with nucleolus, polysaccharide cell wall-usually inner glucan and outer mannan layers, mitochondria, vacuoles, vesicles, cytoskeleton of microtubules and actin microfilaments.
B. Fungi usually have two layered cell wall – glucose polymer – glucan decorated with a outer mannose polymers – manna
C. Secretory vesicles moved to growing tip by motors on the cytoskeleton
D. Microtubule comprised mitotic spindle required for cell division
E. RNA polymerase and ribosomes that are mammalian-like (not inhibited by many antibacterial antibiotics)
F. Fungi synthesize sterols (usually ergosterol) and incorporate them into membranes, important basis for much fungal chemotherapy
Sexual cycles of fungi
Describe the characterization of the sexual cycles of classified fungi. What determines different sexes genetically?
Define heterokaryon
Discuss Neurospora in terms of the development of spore production.
A. Classified fungi have sexual cycles characterized by haploid cells of different sexes that are capable of fusing to produce diploid cells that undergo meiosis to regenerate haploid cells.
Frequently vegetative growth is found for both haploid and diploid stages.
Different sexes are often due to single genetic locus, not a whole chromosome.
Hyphae of different mating types can fuse to induce heterokaryon formation and/or a sexual cycle
B. Neurospora - produces heterokaryons, two nuclei in the same cell, then like Saccharomyces haploid nuclei fuse and diploid nuclei undergo meiosis to produce haploid ascospores.
- Neurospora is a genus of Ascomycete fungi.
Classification of fungi (4)
- Ascomycetes - produce sexual haploid spores encased in a sac
- Basidiomycetes - produce sexual spores that are not in a sac, mushrooms
- Zygomycetes (Phycomycetes) - large nonseptate hyphae
- Deuteromycetes - Fungi imperfecti, sexual sates are not known yet or nonexistent
Fungi Nutrition
What is their process of alimentation, almost all and many fungi are cultural on what two types of medium?
A. Fungi are saprobic, polymeric organic material are degraded to mono and oligomers using secreted enzymes. Fungi take up small metabolites for growth.
B. Almost all fungi are culturable on Sabouraud’s medium (yeast extract plus glucose) where they show characteristic colonial morphologies. Growth on this medium sometimes can be too slow for use in diagnosis.
C. Many fungi are culturable on minimal medium (glucose, salts, NH3 and trace elements)
Many fungi show dimorphic life cycles (classic temperature dimorphism). Discuss that of yeast and mold.
A. Yeast stage 37 degrees Cel (very rich medium), budding
B. Mold stage 25 degrees Cel hyphal growth – enables organism to be disemminate and change its environment
Diagnosis of mycotic infections:
Discuss Direct microscopic observation of infected tissue (4)
Discuss two other methods for Fungal viewing/identification.
A. Direct microscopic observation of infected tissue
- 10% KOH dissolves animal tissue so fungi in skin and nails are visible. Kills the fungi as well but leave behind the cell wall.
- Calcofluor - fluorescent dye stains chitin in some fungal cell walls
- Methaneamine silver (Ag) stain fungi
- Candida and other yeasts stain purple with Gram stain
B. Several fungi that cause superficial infections fluoresce under UV light (Wood’s lamp)
C. Culturing on Sabouraud’s agar to identify specific species; often by spore morphology
Fungal Drug therapy
How does resistance arise and what is the fundamental target when synthesizing final drugs?
Discuss Polyene antibiotics. Give the two examples and MOA. What is a requirement for the antibiotics to work and what is a disadvantage to them?
- Resistance is often due to nonpermeability, long term therapy often required
- Much of it based on the presence of ergosterol rather than cholesterol in fungal membranes.
A. Polyene antibiotics –
- Amphotericin B
- Nystatin®
- Both are incorporated into sterol containing membranes and cause cells to become leaky
a. Drugs require membrane synthesis (cell growth)
b. Somewhat toxic to host since mammalian membranes also contain sterols
Fungal Drug therapy
Azoles MOA. Why are there side effects?
List examples of Azoles (4) and what’s special about one?
B. Azoles
- Inhibit mainly ergosterol biosynthesis via interfering with cyt P-450
- Side effects due to inhibition of adrenal steroid and testosterone synthesis
Ketoconazole
Itraconazole
Thiobendazole
Fluconazole
a. Fewer side effects
b. Enters cerebrospinal fluid more rapidly
Fungal Drug therapy
Discuss Terbinafine-Lamisil® MOA. What class of drug is it?
Discuss Echinocandins- give a specific example and MOA
Discuss MOA of antimitotics and give example.
Discuss other 3 classes of drugs.
- Squaline epoxidase inhibitor, Terbinafine-Lamisil®, -inhibits ergosterol biosynthesis and causes toxic buildup of squalene.
- Echinocandins
- Caspofungin (Candidas®): Inhibits 1-3 glucan synthesis by interfering with synthase. Prevents cell wall formation - Antimitotics - probably bind to tubulin and interfere with mitotic apparatus and cytoskeleton-Griseofulvin
F. Other drugs
- Sulfonamides
- Fluorocytosine
- Topical ointments and powders for superficial infections (detergents)
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Conidia: discuss the term and spores
(Gr. konis. dust)
This term is sometimes used generally for all asexual spores. Sometimes more specifically for spores born singly or at tips of specialized hyphal branches (conidiopores). Highly diversified in shape, size, color and separation.
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Aleuriospores: discuss the term and spores
(Gr. aleuron, wheaten flour)
Spores that resemble conidia but develop on short lateral branches or directly on the hyphae, rather than on specialized condiopores.
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Arthrospores: discuss the term and spores
(Gr. arthron, joint)
Cylindrical cells formed by double septation of hyphae. Individual spores are released by fragmentation of hyphae, i.e., by disjunction.
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Blastospores: discuss the term
(Gr. blastos. bud. shoot)
Buds that arise from yeast like cells.
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Chlamydospores: discuss the term and spores
(Gr. chlamy, mantle)
Thick-walled, round spores formed from terminal or intercalated hyphal cells.
ASEXUAL SPORES FORMED BY CERTAIN FUNGI:
Sporangiospores: discuss the term and spores
(Gr. angeion.vessel)
Spores within saclike structures (sporangia) at ends of hyphae or of special hyphal branches (sporangiophores). Characteristically formed by species of Phycomyces.
CONTRAST BETWEEN FUNGI (F) AND BACTERIA (B)
Fungi to Bacteria
- Cell volume (μ3)
- Nucleus
- Cytoplasm
- Cytoplasmic membrane
- Cell Wall
- Metabolism
- Sensitivity to chemotherapeutic agents
- Dimorphism
- (F) Yeast 20-50 μ3; Molds: Not definable because of indefinite size and shape: but much greater than yeast.
(B) 1 to 5 μ3 - (F) Eukaryotic (well-defined membrane)
(B) Prokaryotic (no nucleus) - (F) Mitochondria, endoplasmic reticulum
(B) No mitochondria or ER - (F) Sterols present-ergosterol
(B) Sterols absent (except Mycoplasma) - (F) Glucans: mannans: chitin. protein complexes
(B) No chitin, glucans or mannans - (F) Heterotrophic, aerobic, facultative anaerobes: not autotrophics or obligate anaerobic
(B) Obligate and facultative aerobes and anaerobes: heterotrophic; autotrophic - (F) Sensitive to polyenes and griseofulvin (dermatophytes): not sensitive to penicillins, tetracyclines, chloramphenol, streptomycin
(B) Often sensitive to penicillins, tetracyclines, chloramphenicol, streptomycin: not sensitive to polyenes, imadazoles.
- (F) Distinguishing feature to many
(B) Very rare
CLASSES OF FUNGI
CLASS: Ascomycetes
ASEXUAL SPORES
SEXUAL SPORES
MYCELIA
REPRESENTATIVE GENERA OR GROUP
ASEXUAL SPORES- Exogenous (at ends of sides of hyphae)
SEXUAL SPORES- Ascospores w/in sacs or asci
MYCELIA- Septate
REPRESENTATIVE GENERA OR GROUP- Neurospora. Penicillium. Aspergillus. true yeasts
CLASSES OF FUNGI
CLASS: Basidiomycetes
ASEXUAL SPORES
SEXUAL SPORES
MYCELIA
REPRESENTATIVE GENERA OR GROUP
ASEXUAL SPORES- Exogenous (at ends or sides of hyphae)
SEXUAL SPORES- Basidiospores on surface of basidium
MYCELIA- Septate
REPRESENTATIVE GENERA OR GROUP- Mushrooms, rusts, smuts, Cryptococcus
CLASSES OF FUNGI
CLASS: Phycomycetes
ASEXUAL SPORES
SEXUAL SPORES
MYCELIA
REPRESENTATIVE GENERA OR GROUP
ASEXUAL SPORES- Endogenous (in sacs)
SEXUAL SPORES- Anatomy variable
MYCELIA- Non-septate
REPRESENTATIVE GENERA OR GROUP- Rhizopus. Mucor watermolds (aquatic)
CLASSES OF FUNGI
CLASS: Deuteromycetes (Fungi imperfecti)
ASEXUAL SPORES
SEXUAL SPORES
MYCELIA
REPRESENTATIVE GENERA OR GROUP
ASEXUAL SPORES- Exogenous (at ends or sides of hyphae)
SEXUAL SPORES- Absent
MYCELIA- Septate
REPRESENTATIVE GENERA OR GROUP- Many human pathogens
Grouping of Most Frequently Encountered Pathogenic Fungi (for Man) in the U.S., with respect to Tissue Involved and Dimorphism.
Type of Mycotic Disease: Systemic
A. Representative Fungus (5) and MORPHOLOGY IN (Infected Tissue Room / Temperature Culture) and Life Cycle.
- Cryptococcus neoformans; Yeast (encapsulated); Yeast (encapsulated); No dimorphism (Diamond)
- Coccidioides immitis; Spherules; Mycelia; Dimorphism*
- Histoplasma capsulatum; Yeast; Mycelia; Dimorphism
- Blastomyces dermatitis; Yeast; Mycelia; Dimorphism
- Paracoccidioidis braziliensis; Yeast; Mycelia; Dimorphism
(Diamond) Except during sexual phase.
- Spherules and mold
** Different from classical temperature dimorphism
***The fungi that parasitize epidermis, nails and hair (dermatophytes) all appear alike in infected skin, but in culture may develop a variety of specialized hyphae and spore structures that differentiate diverse genera and species.
Grouping of Most Frequently Encountered Pathogenic Fungi (for Man) in the U.S., with respect to Tissue Involved and Dimorphism.
Type of Mycotic Disease: Systemic and particularly opportunistic
A. Representative Fungus (4) and MORPHOLOGY IN (Infected Tissue Room / Temperature Culture) and Life Cycle.
- Candida (especially C. albicans); Yeast and Hyphae; Yeast and Hyphae; Dimorphism**
- Aspergillus (most often A. fumigates); Mycelia; Mycelia; No Dimorphism
- Phycomycetes (Mucor and Rhizopus species); Mycelia; Mycelia; No Dimorphism
- Pneumocystis jiroveci; Yeast-like cysts; Unknown; No Dimorphism
(Diamond) Except during sexual phase.
- Spherules and mold
** Different from classical temperature dimorphism
***The fungi that parasitize epidermis, nails and hair (dermatophytes) all appear alike in infected skin, but in culture may develop a variety of specialized hyphae and spore structures that differentiate diverse genera and species.
Grouping of Most Frequently Encountered Pathogenic Fungi (for Man) in the U.S., with respect to Tissue Involved and Dimorphism.
Type of Mycotic Disease: Subcutaneous
A. Representative Fungus (1) and MORPHOLOGY IN (Infected Tissue Room / Temperature Culture) and Life Cycle.
Sporothrix schenckii; Yeast; Mycelia; Dimorphism
Grouping of Most Frequently Encountered Pathogenic Fungi (for Man) in the U.S., with respect to Tissue Involved and Dimorphism.
Type of Mycotic Disease: Cutaneous
A. Representative Fungus (3) and MORPHOLOGY IN (Infected Tissue Room / Temperature Culture) and Life Cycle.
- Microsporum species; Mycelia; Mycelia; No Dimorphism***
- Trichophyton species; Mycelia; Mycelia: No Dimorphism***
- Epidermophyton floccosum; Mycelia; Mycelia; No Dimorphism***
(Diamond) Except during sexual phase.
- Spherules and mold
** Different from classical temperature dimorphism
***The fungi that parasitize epidermis, nails and hair (dermatophytes) all appear alike in infected skin, but in culture may develop a variety of specialized hyphae and spore structures that differentiate diverse genera and species.
SUPERFICIAL MYCOSES
Define Dermatophytoses
Organisms metabolize fatty-acids present in skin and hair, often referred to as (2)
Dermatophytoses - localized fungal infections of the keratinized tissues (hairs, skin, nails). Infecting fungi secrete proteases that can degrade this insoluble protein. Organisms are usually saprobes and keratinized tissue is not alive.
- Ringworms or Tineas.
Names of clinical syndromes - Most common infecting agent(s) for:
Athlete’s foot Ringworm of the scalp jock itch, groin onychomycosis Ringworm of the body Beard
Note: Give scientific name of the common name clinical symptoms
- Tinea pedis - Athlete’s foot - T. mentagrophytes
- Tinea capitis - Ringworm of the scalp - Microsporum audouini, T. Tonsurans
- Tinea cruris - jock itch, groin – E. floccosum, T. mentogrophytes, T. rubrum
- Tinea unguium- onychomycosis - nails - T. rubrum, T. mentogrophytes
- Tinea corporis - Ringworm of the body - Microsporum sp., Trychophyton sp.
- Tinea barbi – beard- Trychophyton sp.
Note: bearded areas of the face and neck
Most common causative agents of mycotic disease
- Trichophyton mentagrophytes, tonsurans, rubrum
- Microsporum audouini, canis, gypseum
- Epidermophyton floccosum
- All produce ______?
macrocondia called aleurospores
Ecology of fungi (3)
Severity of mycotic infections (mild (4) /increasing severity(4))
- Found in soil
- Usually transferred from man to man
- Occasionally from dogs and cats, e.g. M. canis
D. Severity
- Mildest infections, typical-redness, exudate, vesicles, scales
- Increasing severity
a. Mycotic folliculitis
b. Temporary baldness
c. Suppuration and kerion
d. Connective tissue involvement - Nail infections cause nail degradation, hyperkeratosis in seniors
Superficial mycotic infections caused by other organisms
Tinea versicolor
Tinea favosa (favor)
Piedra
Tinea nigra
Give details of presentation, characteristics, and types.
- Tinea versicolor
a. Skin discoloration – inhibits melanin synthesis
b. Malessezia globosa and furfur (old name: Pityrosporum orbiculaire)
c. Dimorphic, normal flora - Tinea favosa (favus)
a. Localized to hair and torso
b. Scales, hyperkeratosis
c. Trichophyton schoeneinii - Piedra
a. Localized to the hair
b. Piedrai hortai (black) – binds very tightly to hair (tropical)
c. Trichosporon beigelii (white) – looser association (subtropical) - Tinea nigra
a. Black palms
b. Tropical regions
c. Exophiala werneckii
Diagnosis of all superficial fungal infections (3)
- KOH prep of infected tissue shows mycelia
- Slide culture, plate culture (slow growth, only for epidemiology)
- Wood’s Lamp, UV light, some fungi fluoresce when infecting hair or skin
Immunity (3) and Epidemiology (2) to mycotic infections.
- T cell reaction
- Soluble antibodies raised but have little or no role in elimination infection
- Secondary allergic response to many dermatophytes (dermtophytid response or id response)-itchy lesions devoid of organism
Note: Id reactions (also known as “Disseminated eczema,”and “Generalized eczema”) present with a variety of infectious disorders, often occurring in response to an inflammatory tinea of the feet, resulting in an eczematous dermatitis. The pruritic rash that characterizes the id reaction, which is considered immunologic in origin, has been referred to as dermatophytic.
- 80-90% of population has an infection some time in their lifetime
- Outbreaks common in college, army barracks, kindergartens
Treatment
Skin- Topical (5), Systemic (2)
Hair (2)
Nails (3)
- Skin
a. Topical
i. Terbinafin-Lamisil®
ii. Clotrimazole-Lotrimin®
iii. Desenex , Tinactin (Tolnaftate) - detergent
iv. Whitfield’s ointment - salicylate and benzoate; old remedy
v. Use combinations
b. Systemic
i. Terbinafin – for nails, long term
ii. Ketoconazole
- Hair
a. Cut hair
b. Griseofulvin - three to four weeks - Nails - Surgical removal of nail and/or systemic drug treatment
a. Terbinafin - Lamisil® - several months
b. Thiobendazole or itraconazole - several months
c. Griseofulvin - one year
SUBCUTANEOUS MYCOSES
SPOROTRICHOSIS:
Causative Agent Ecology (5) Pathogenesis and types (4) Lab Dx (3) Tx (2)
A. Causative Agent: Sporothrix (Sporotrichum) schenkii
B. Ecology: Soil, thorns, tree bark, timber, decaying vegetables
C. Pathogenesis: infection by direct inoculation below skin
- Lymphocutaneous
- Fixed cutaneous
- Pulmonary
- Systemic
D. Laboratory Diagnosis:
- Culture shows temperature dimorphism
- Serology
- Skin test
E. Treatment:
- Potassium iodide for surface lesions; inhibits yeast, not mold
- Amphotericin B
SUBCUTANEOUS MYCOSES
MADUROMYCOSIS (mycetoma, madura foot, madura hand) skin lesions usually confined to extremities
Ecology/Causative Agent (6)
Pathogenesis (2)
Lab Dx (1)
Tx (3) - assoc. with causative agent
A. Ecology: Causative agents are soil organisms:
- Pseudoallescheria boydii, Madurella, Exophiala and Aspergillus
- Nocardia braziliensis - actinomyces, a procaryote
- Streptomyces sp. - actinomyces, a procaryote
B. Pathogenesis:
- Break in skin -> subcutaneous tissue-> fascia-> bone
- Draining sinuses
C. Laboratory diagnosis requires culture of organism.
D. Treatment is difficult
- thiabendazole or 5-fluorocytosine may be effective for Pseudoallescheria.
- Sulfa and Penicillin for treating Actinomyces
- Surgical removal of infected tissue
SUBCUTANEOUS MYCOSES
CHROMOMYCOSIS:
Causative Agent (3) Ecology (1) Pathogenesis (5) Lab Dx (1) Tx (2)
A. Causative Agents: Highly pigmented molds
- Phialophora
- Cladosporium
- Fonsecea
B. Ecology: soil organisms
C. Pathogenesis:
- Break in skin
- Infection usually involves skin and subcutaneous tissue
- Occasionally obstructs lymph channels
- Dissemination is very rare
- Can be complicated by more serious secondary infections
D. Diagnosed by observing fungal materials in biopsy samples, sclerotic bodies. Laboratory diagnosis requires culture of organism to distinguish prokaryotic vs eukaryotic etiology
E. Treatment:
- Surgical removal of infected tissue
- Topical administration with Amphotericin B, Thiabendazole or Terbinafine
SYSTEMIC MYCOSES
HISTOPLASMOSIS
Causative Agent Ecology (2) Pathogenesis (4) In vivo where do the fungal cells grow? Lab Dx (3) Tx (2)
A. Causative Agent: Histoplasma capsulatum - (a/k/a Emmonsiella capsulatum), ascomycete
B. Ecology: Found in soil
- Midwestern river valleys
- High concentration in bird’s droppings
C. Pathogenesis: Inhalation of spores:
- Mild or asymptomatic in 95% of cases (approximately 40 million people are thought to be infected in U.S.)
- Pulmonary:
a. Acute: malaise, fever, respiratory problems
b. Chronic infections can recur
c. Healed infection gives calcified and fibrotic nodules that resemble tuberculosis - Disseminated throughout body:
a. Lymph nodes
b. Liver, spleen, heart, etc. - Skin involvement, eruptions
D. Macrophages: Grows inside of macrophages. Mutants isolated that do not survive in macrophages and have an altered glucan on the cell surface.
E. Laboratory Diagnosis:
- Biopsy of infected tissue shows macrophages filled with yeast cells - Methaneamine silver stain
- Culture:
a. Dimorphic - 37 yeast, 25 slow growing mycelia
b. Tuberculate chlamydospore - Serology:
a. Latex agglutination
b. Complement fixation
c. Hypersensitivity to histoplasmin (an antigen from culture medium), Skin tests are unreliable because many people have been exposed
d. Soluble antibodies have little or no role in eliminating infections
F. Treatment:
- Amphotericin B
- Itraconazole
SYSTEMIC MYCOSES
BLASTOMYCOSIS ( “ “ American Blastomycosis)
Causative Agent Ecology (1) and geographic regions (3) Pathogenesis (3) Lab Dx (3) Tx (3)
North American Blastomycosis
A. Causative Agent: Blastomyces dermatitidis (a/k/a Ajelomyces dermatitidis), ascomycete
B. Ecology:
- Not known, may be soil organism related to particular vegetation
- Mississippi Valley and Southeastern U.S., can occasionally be found further north
C. Pathogenesis:
- Inhalation or broken skin
- Cutaneous - primary or systemic
- Pulmonary - primary then hematogenously to bones, skin, other viscera
D. Laboratory Diagnosis:
1. Direct microscopic examination of infected tissue gives thick-walled, single budded, yeast-like organisms
- Culture on Sabouraud’s medium shows temperature dimorphism
a. 37 yeast like
b. 25 mycelia
c. Growth inhibited by cycloheximide and chloramphenicol - Serology - Latex agglutination and complement fixation tests
E. Treatment:
- Amphotericin B
- Itraconazole
- Stilbamidine, antiprotozoal-less toxic
SYSTEMIC MYCOSES
PARACOCCIDIOIDOMYCOSIS ( “ “ American Blastomycosis)
Causative Agent Ecology (1) and geographic regions (1) Pathogenesis (4) Lab Dx (4) Tx (2)
South American Blastomycosis
A. Causative Agent: Paracoccidioides brazilliensis
B. Ecology: Found in soil, South Texas and below
C. Pathogenesis: Inhalation
- Pulmonary - causes a mild respiratory tract infection not unlike Histoplasmosis
- First lesions of infection are in the mucous membranes of the nose or mouth and can spread to the face
- Lymphangetic
- Disseminated to wide variety of tissues
D. Laboratory Diagnosis:
- Direct microscopic observation shows thick walled, yeast like organisms with multiple buds
- Cultures show temperature dimorphism, requires rich medium for yeast phase
- Serology - Latex agglutination and complement fixation tests
- Skin test to hypersensitivity to secreted antigen
E. Treatment:
- Amphotericin B
- Sulfonamides (not curative)
SYSTEMIC MYCOSES
COCCIDIOIDOMYCOSIS (3 other common names)
Causative Agent Life cycle peculiarity Ecology (1) and geographic regions (3) Pathogenesis (3) and symptoms Lab Dx (2) Tx (2)
Valley fever, California fever, desert rheumatism
A. Causative Agent: Coccidioides immitis
B. Exhibit different dimorphism - spherule and mold
C. Ecology: Found in desert soil
- Southwestern U.S.
- Mexico
- Central and South America
D. Pathogenesis:
- Inhalation of arthrospores
- Often asymptomatic
- Primary pulmonary infections resemble tuberculosis
- Dissemination to skin, bone and viscera is rare
E. Laboratory Diagnosis:
- Direct examination of sputum shows:
a. Spherules, thick walled cells filled with ~100 endospores
b. Sometimes hyphae are observed in infected lung tissue - Culture on medium enriched with ascites fluids gives mixture of hyphae and spherules:
a. Temperature dimorphism
b. Arthrospores on hyphae have unique morphology
c. Serology -Latex agglutination and complement fixation
d. Skin test: hypersensitivity to coccidioidin (an antigen from culture fluid)
F. Treatment:
- Amphotericin B
- Ketoconazole
SYSTEMIC MYCOSES
CRYPTOCOCCOSIS
Causative agent Discuss physical feature of agent of life cycle Ecology Pathogenesis (3) Dx (5) Tx (4)
A. Causative Agent: Cryptococcus neoformans (a/k/a Filobasidiella neoformans), basidiomycete
B. Usually a small yeast, but also has a sexual mold stage and therefore is actually dimorphic, but not classical temperature dimorphism.
C. Ecology: Found in soil and especially pigeon droppings; Cryptococcus grows poorly at 42C. Organism is resistant to drying
D. Pathogenesis:
- Inhalation of urban dust
- Causes pulmonary infections and meningitis
- Capsules thought involved in resistance to immune response
E. Diagnosis:
- India ink to centrifuged CSF
- Culture on Sabouraud’s agar
a. Urease positive
b. Other cryptococci (albidus, laurentii, terreus, etc.)
c. Mycelium only during sexual stage - Cryptococcal antigen in CSF by latex agglutination
- Cryptococcal antibody appearance-good prognosis
- Additional assimilation and fermentation reactions used to identify different species
F. Treatment:
- Amphotericin B
- Fluoconazole
- 5-Fluorocytosine
- Ketoconazole
OPPORTUNISTIC FUNGAL INFECTIONS
Predisposing factors for opportunistic infections (12)
OPPORTUNISTIC FUNGAL INFECTIONS I. Predisposing factors for opportunistic infections: A. AIDS B. Pregnancy C. Trauma D. Endocrine disorders E. Malnutrition F. Malignancy G. Anemias H. Post-operative state I. Antibacterial therapy J. Immunosuppressive drugs K. Oral contraceptives L. Heroin addiction
OPPORTUNISTIC FUNGAL INFECTIONS
CANDIDIASIS
Most frequent causative agent
Type of Life cycle
Pathogenesis
Types of infections (13)
A. Most frequent causative agent - Candida albicans
B. Pleiomorphic - yeast, pseudohypha or hypha
C. Ecology - C. albicans ubiquitous - part of the normal flora of man (mouth, GI tract, vaginal)
D. Pathogenesis - transmitted in birth canal, produces a secreted protease that is an important virulence factor
E. Types of infections:
- Thrush (oral candidiasis)
- Skin
- Nails
- Vaginitis
- Esophagitis
- Gunshot wounds
- Endocarditis
- Pulmonary
- Burns
- Eye
- Balanoposthitis
- Urinary tract
- Chronic mucocutaneous
OPPORTUNISTIC FUNGAL INFECTIONS
CANDIDIASIS
Laboratory Diagnosis (4)
What species do not give rise to diagnostic criteria (7)
- Microscopy of stained specimens show yeast and pseudo mycelium
- Sabouraud’s medium culture - Yeast cells with some pseudomycelia, some blastospores, a few chlamydospores. Ferments and assimilates specific sugars
- C. albicans yeast cells or chlamydospores incubated at 37C in serum grow a germ tube
- Other pathogenic Candida species do not give rise to germ tubes when put in serum at 37C
a. C. stellatoidea
b. C. parapsilosis
c. C. krusei
d. C. tropoicalis
e. C. guillermondii
f. C. glabrata
OPPORTUNISTIC FUNGAL INFECTIONS
CANDIDIASIS
Tx (3) and type.
Treatment:
- Clotrimazole (Lotramin®) – topical
- Amphotericin B - systemic
- Ketoconazole - systemic
OPPORTUNISTIC FUNGAL INFECTIONS
Pneumocystis jiroveci (formerly carinii)
Identified as what Is it normal Flora? What is typical for symptoms and Ab production Epidemiology association Ecology Pathogenesis (4) Dx (2) Tx (3) and does this organism not contain? Discuss a potential target for Tx.
A. Recently identified as a fungus rather than a protozoa based on RNA homology. Not yet possible to culture in liquid media
B. Considered normal flora
C. Most people infected asymptomatically and show Ab by age 3
D. Early clinical manifestation of AIDS
E. Ecology - airborne pathogen
F. Pathogenesis
- Reaction of dormant organism
- 30 day incubation period
- Pulmonary
- Extrapulmonary infections have been found in AIDS patients
F. Diagnosis
- Identification of organism from BAL (bronchoalveolar lavage- bronchoalveolar irrigation)
- Silver, Calcofluor or Giemsa stain useful
G. Treatment and prophylaxis- organism does not contain ergosterol
- Trimethaprin - Sulfamethoxazole
- Echinocandins - experimental
- Pentamidine – rarely used
H. rRNA contains self-splicing introns - potential chemotherapeutic target
OPPORTUNISTIC FUNGAL INFECTIONS
Aspergillosis
Causative agents (3) Ecology (3) Pathogenesis (3) and special pt. population target Lab Dx (3) Tx (2)
A. Most common causative agents (not dimorphic)
- Aspergillus fumigatus
- Aspergillus niger
- Aspergillus flavus
B. Ecology - soil, dust, decaying food
C. Pathogenesis
- Immuno-compromised host
- Allergic rhinitis
- Burns
- Otitis externa
- Diabetics
- Invasive infections in immunocompromised patients - poor prognosis
D. Laboratory diagnosis
1. Septate hyphae (not dimorphic)
2. Serology - Aspergillus galactomannan antigen in blood is a good indicator of invasive infection (newly approved diagnostic)
3. Culture on Sabouraud’s agar produces a typical mold
A common lab contaminant so finding it is unreliable. In addition, culture takes too long to be an effective diagnostic.
E. Treatment
- Amphotericin B
- Echinocandins (Caspofungin-Cancidas®)
OPPORTUNISTIC FUNGAL INFECTIONS
Zygomycosis (Phycomycosis)
Causative agents (2) Ecology (2) Pathogenesis (2) and special pt. population target Lab Dx (2) Tx (2) and mortality rate
A. Causative agents - Mucor sp. and Rhizopus (not dimorphic)
B. Ecology - soil, decaying food (Rhizopus is a common black bread mold)
C. Pathogenesis
- Severely immunocompromised individuals
a. Uncontrolled diabetics, steroid treatment, leukemia, lymphoma, etc. - rhinocerebral, pulmonary, systemic
b. Burn patients - infection in wounds - Extremely fast growing
D. Laboratory Diagnosis
- Non-septate hyphae on smear
- Culture on Sabouraud’s medium
E. Treatment
- Amphotericin B
- Surgery
- Mortality rate > 50%
MYCOTOXICOSIS
Poisoning by by-products of fungi (Discuss)
Aflatoxins- what sp. produces it, found where, effect?
Other toxins (2) and their pathogenesis
Define actinomycetes
I. Poisoning by by-products of fungi – fungi produce antibiotics/poisons as a way of protecting themselves from predation.
II. Aflatoxins:
A. Produced by Aspergillis flavus
B. Found in foods, especially peanuts
C. Arcinogenic, causes liver cancer and liver necrosis
III. Other toxins: A. Ochrotoxin 1. Produced by Aspergillis sp. 2. Causes liver necrosis B. Amanita mushroom 1. Phalloidin - binds to microtubules 2. amanitin - binds to RNA polymerase and other proteins; also a neurotoxin
ACTINOMYCETES - filamentous bacteria related to mycobacter that produce colonies that resemble molds.
What two Genera of yeast rarely give rise to opportunistic infections?
Rhodotorula and Torulopsis
Mycotic Infections may be characterized how?
List 3 types of infections
Location of the infection
- Systemic mycoses caused by: Blastomyces Coccidioides Aspergillus Histoplasma Cryptococcus Candida Sporothrix Paracoccidioides
- Cutaneous Candidiasis Candida albicans
- mucocutaneous infections : nose, pharynx, vagina, areas of bowel. Easier to treat than systemic and not as bad as systemic - Dermatophytic infections Microsporum Trichophyton Epidermophyton
- E.g typical ringworm. Usually not life threatening. Athletes foot, jock itch. Enjoy areas warm, dark, and moist.
Note: Histoplasma usually associated with lungs, Cryptococcus may cause meningitis in immunocompromised patients, Candida is the most common causative agent of septicemia after bacteria.
Anti fungal Drugs
Systemic mycoses (3) Cutaneous Candidiasis (2) Dermatophytic infections (2)
- Systemic mycoses
Amphotericin B (IV)
Flu cytosine - restricted use
Azoles (oral) - Cutaneous Candidiasis
- Nystatin (topical, suppository, suspension )
- Azoles (topical/oral) - Dermatophytic infections
Azoles (topical/oral)
Griseofulvin
Polyene Antifungals
Type of agent
Chemical property
Examples (2)
- Fungicidal
- amphipathic
- Amphotericin B
- Nyastin -only for topical Tx. Never given systemically
Amphotericin B MOA
What is responsible for the selectivity (2)?
8 molecules of Amphotericin B interacts hydrophobically with 8 molecules of ergosterol in the fungal cell membrane forming a pore. Potassium leaves first, and the follow other small molecules leading to the death of the cell.
Note: Selective because the pores are transient. Half time of pores in Fungi cells is longer than in human cells. The affinity of Amphotericin B for ergosterol is a litter better for ergosterol than the predominant cholesterol in human cells.
Amphotericin B Pharmacokinetics
Route Where is it sequestered App Vd Half Life Preparation for administration?
Why the numbers for App Vd and Half life?
Very poor oral absorption - requires parenteral administration
•Sequestered in tissue membranes very low serum levels
- App. Vd ≈ 4 L/kg
- Half-life ≈ 15 days
•Administered as a freshly prepared suspension
- Liposomal preparations
Note: Vd and half life are high because the Amphotericin B is lodge in the cell membrane of fungi.
Amphotericin B Adverse Reactions (8)
Which adverse reaction is the worst?
- Chills, fever and vomiting
- Renal toxicity (decreased renal blood flow and direct toxicity to tubule cells)
- Normocytic, normochromic anemia (high doses may cause hemolysis)
- Hypokalemia
- Arrhythmias- hypokalemia can lead to arrythmias. Further complications can occur with Rx e.g. digitalis.
- Pain, headache, impaired vision and chemical meningitis when given intrathecally. E.g Ex. patient may become combative
- Thrombophlebitis
- Anaphylaxis- anaphylactoid- not allergenic in origin but will cause similar symptoms. (anaphylactoid reaction a reaction resembling generalized anaphylaxis but not caused by IgE-mediated allergic reaction but rather by a nonimmunologic mechanism.)
-Renal Toxicity is the worst issue.
Note: Chills and fever are part of the infusion reaction and thus may coadminister steroids or acetaminophen
Formulations of Amphotericin B
Currently, the drug is available in many forms. Either “conventionally” complexed with sodium deoxycholate (ABD)
OR
lipid complex (ABLC) cholesteryl sulfate complex (ABCD) liposomal formulation (LAMB).
Discuss the shapes of all 4 formulations, daily costs, infusion reactions, and renal toxicity.
ABD - Micelles, $76, yes, yes
ABLC - Ribbons, $740, - , less common than ABD
ABCD - Disks, $360, ++ , less common than ABD
LAMB - Spheres $1099, - - , less common than ABD
Note: Prescrive liposomal prep for immunocompromised patients. Otherwise prescribe Na+ deoxycholate prep ABD.
Note: Amphotericin has a very small TI and cannot be excreted rapidly and long half life.
Flucytosine
- Originally developed as a _______
- Chemically is a derivative of ______
- Used in combination with which drug?
- Cancer drug
- Pyrimidine derivative
•Narrow spectrum of activity
- For most strains of Cryptococcus neoformans
•Usually used in combination with amphotericin B
Note: Cryptococcus can cause meningitis
Flucytosine
Selectivity is achieved how?
Combination Tx MOA
Flucytosine is more highly permeable to fungi membrane compared to human membrane.
Flucytosine becomes more permeable with the addition of Amphotericin B. The Flucytosine enters via a permease within the fungal plasma membrane and intracellular converted to 5-Flurouracil —> 5-FdUMP.
5-FdUMP inhibits*
dUMP — Thymdylate synthase —> dTMP –> DNA
Decrease of dTMP leads to inhibition of DNA synthesis and cell division
Flucytosine Pharmacokinetics
Type of agent (2)
Route
Excretion
Penetration
Antifungal and anticancer drug.
- Well absorbed orally
- Dependent upon renal function for elimination
- Penetrates well into the CNS ≈ 70% of serum levels
Note: With combination Tx of Amphotericin B the major excretion method may be a problem since an adverse effect of Amphotericin B is renal toxicity.
Flucytosine Adverse Reactions (3) and %
Should be considered first or second line Tx
When should dosage modification be considered?
Induction Tx because it kills the organism without administration major toxic agents.
- 25% exhibit nausea, vomiting, severe diarrhea and enterocolitis
- 25% exhibit elevation of hepatic enzymes- Damage to liver. Above more than 3x the normal amount of enzyme consider reducing dosage.
- 15% exhibit bone marrow depression: anemia, leukopenia, thrombocytopenia
Azoles
Two types and 7 subtypes
Imidazole’s (5 membered ring with 2 N)
- KETOCONAZOLE
- CLOTRIMAZOLE
- miconazole
- econazole
Triazoles (5 membered ring with 3 N)
- FLUCONAZOLE
- ITRACONAZOLE
- terconazole
Azoles MOA
Type of agent
Discuss selective toxicity
Compare Ketoconazole and Fluconazole with their MOA and drug interactions.
What may happen with high doses of Ketoconazole?
All azoles have the same mechanism of inhibiting the cyt P-450 dependent 14-a-demethylation of sterols. This leads to decreased ergosterol synthesis and the accumulation of 14-methyl sterols in the fungal membrane.
Selective toxicity is based on the higher affinity of the triazole or imidazole group for the heme iron of cyt P-450 of fungi when compare human cyt P-450. In addition, humans can use preformed, exogenous sterols while Fungi must make there sterols.
- All azoles are FUNGISTATIC due to the DECREASE of ergosterol synthesis
- Ketoconazole is a really good inhibitor of CytP450 dependent enzymes. Has lots of drug interactions
- Fluconazole also and inhibitor of CytP450 dependent enzymes, but not as good and has lots of drug interactions a well.
- Normally steroid biosynthesis is in the mitochondria. High doses of ketoconazole affect production of sex steroids.
Comment on the environment requirement of Ketoconazole, Fluconazole, and Itraconazole.
Comment on bioavailability
Comment on distribution ratio of CSF:serum
And which drug would be given for an upper renal (above bladder) mycotic infection?
Ketoconazole and Itraconazole have to be in an acidic environment so that they will dissolve. We have to absorb the dissolutes. Thus don’t take antiacid with it.
- Once dissolved there is good bioavailability (more than 70%)
- Fluconazole is more than 70, Ketoconazole is less than 10, Itraconazole is less than 1
Fluconazole does not require acidic environment.
-Fluconazole should be given because at the point of urinary excretion there is more than 80% of the drug active. Ketoconazole and Itraconazole are greatly metabolized and thus 2-4 and less than 1%, respectively, are active at the point of urinary excretion.
Adverse Reactions
Ketoconazole vs Fluconazole
All azoles have a TERATOGENIC POTENTIAL during pregnancy.
Ketoconazole
- Gastrointestinal distress
- Rash, pruritis
- Elevated hepatic enzymes
- Decreased sex steroid synthesis- gynecomastia, change in menses, decreased libido
- Decreased cortisol synthesis
- Severe hepatotoxicity
Fluconazole
- Gastrointestinal distress
- Rash
- Elevated hepatic enzymes
- No effect on host steroid synthesis
Comment on the discontinuation of Ketoconazole vs Fluconazole
Only 1 to 2 % of patients must discontinue fluconazole because of adverse effects.
Ketoconazole - increase in dose leads to a higher % of patients discontinuing the Rx. 0.4g/day: 4% to 1.6g/day: 60%
Drug Interactions
Discuss the biochemical effect azoles have on metabolism.
List the drug interactions (6)
Which two drugs have an effect on the levels of azoles?
Azoles inhibit hepatic microsomal drug metabolizing enzymes to varying extents. The following interactions have been reported.
Note: caused by the inhibition of CytP450 dependent enzymes.
Arrhythmias with terfenadine & astemizole Increased levels of cyclosporine Increased bleeding time with warfarin Hypoglycemia with oral hypoglycemics Increased serum levels of phenytoin Increased serum levels of digoxin
The following two Rx decrease blood levels of azoles because they induce CytP450 dependent metabolizing enzymes, thus increases the metabolism of azoles.
- Rifampin decreases blood levels of azoles
- Phenytoin decreases INTRACONAZOLE blood levels by > 10x
Primary indications for Azole Rx (9)
Candidiasis Coccidioidomycosis Cryptococcus chronic suppression Blastomycosis Histoplasmosis Sporotrichosis Pseudallescheriasis Aspergillosis
Candidiasis
Define Causative agent Tx (route-3) Route, never administer how and why, not absorbed how? Local or systemic administration?
Infections of the mucosa of the oropharynx, esophagus, bowel or vagina caused by Candida albicans
May be treated with nystatin suspensions or creams. Topical azoles are also efficacious.
Not absorbed orally
Systemic administration may also be employed for when there is an extensive area of tissue infection.
Note: Never parenterally. Swallow a little not a big deal because does not get absorbed in GI tract. If given parenterally more toxic properties than amphotericin.
Note: Clotrimazole - suppository for Candida vagina infections
Terbinafine
Type of agent MOA Selectivity Effective Tx for \_\_\_\_\_. Discuss routes. Adverse Effects (Common-2, Rare-2)
Fungicidal synthetic allylamine
Inhibits squalene epoxidase leading to the accumulation of toxic levels of squalene in the organism. Normally Squalene is converted to Ergosterol by Squalene epoxidase. No Ergosterol also leads to death.
Mammalian enzyme is 4,000 times less sensitive.
Effective in the treatment of dermatophytic infections:
- Topical
- Oral for onychomycosis; once a day therapy for 12 weeks is 90% effective (better than griseofulvin or itraconazole)
Adverse Effects:
Headache and GI symptoms (diarrhea, abdominal pain, nausea) are most common.
Rarely, hepatotoxicity & severe skin allergy
Note: Headache occurs usually when route is ORAL
NEW TARGETS
List the new targets for and their Rx (3). Why would these be used in substitution for other antifungal Rx?
- Chitin synthesis – nikkomycins
- Glucan synthase – Caspofungin (echinocandins)
- Mannoproteins – pradimicin
- Used for more severe issues and for substitution of Rx that not as sensitive to the infection.
- These potentially useful drugs are derived from naturally occurring substances
Parasites are eukaryotic organisms that include both single cell organisms (Protozoa) and multicellular organisms (Helminths).
Parasites have developed multiple ways of living inside human hosts. These include residing in different organs of the body, evading the host immune response and reproducing and shedding their offspring in numerous ways.
Why do we need direct observation of parasite using microscopy to confirm a prediction of a causative agent?
Most parasitic infections cause non-specific and non-identifying symptoms, predictions of infectious agent must be confirmed by direct observation of the parasite using light microscopy.
Biology of parasites.
Comment what type of organisms are they, life cycles, and geographically where are they found?
- They are eukaryotes.
- Many have complex life cycles that cannot be completed without transmission to several hosts.
- They are widely dispersed throughout the world and do not occur solely in “tropical” areas.
Compare bacterial, viral, parasitic infections.
Infectious parasites fall into two main groups (2).
- Parasites are:
a. Eukaryotes, and can be single cells (protozoa), or multicellular organisms (helminths)
b. Larger than bacteria and viruses
c. In some cases, able to change their antigenic surface proteins
d. Able to use a variety of mechanism to avoid mammalian host defenses - Infectious parasites fall into two main groups:
a. Protozoans: for example: plasmodium (malaria), trypanosomes
b. Helminths: for example: Cestodes, Trematodes, Nematodes
Note differences in mode of infection: malaria requires an insect vector. Some viral agents, such as yellow fever and dengue may also be spread by arthropod vectors. However, the insect vector in malaria plays a specific role in the life cycle of Plasmodium.
Informational
Parasite control is complex/simple?
E.g. with malaria.
Parasite control is complex. For example, malaria control relies heavily on vector elimination and prevention of mosquito bites, as well as drug prophylaxis.
Differences in the Lab Dx of bacteria, viruses, and e.g. malaria.
Bacteria and viruses may be cultured, and antibodies against them may be measured.
Diagnosis of malaria currently requires direct demonstration of the organism in the blood of an infected patient.
However, ELISA tests are currently in use for some parasites.
Parasite immunity is complex/simple.
E.g malaria
Where can parasites cause disease in humans?
Parasite immunity is complex.
For example, immunity to malaria is difficult to acquire because of serological differences of the infectious agent.
Parasites cause disease at a wide variety of sites in the body. They cause disease in many organ systems.
Parasite/host interactions are complex.
Bacteria vs Parasites
Physical barriers
Innate Immunity
Antibody responses
Killing
- Physical barriers
Bacteria: Intact skin usually impenetrable. Fatty acids of skin toxic to bacteria. Vaginal flora normally produce acid pH.
Parasites: (Special modes of entry) Insect bite, Ingestion,
STD, Direct invasion
- Innate immunity
Bacteria: Recognition of bacterial LPS activates complement, TNF, IL-1. Chemotaxis, cell adhesion. NK cells activated.
Parasite: Host response varies. Parasite may coexist with host. Initial response depends on macrophages. Macrophages secrete cytokines such as TNFa, IL1; respiratory burst produces reactive O2 metabolites, NO for parasite killing.
- Antibody responses
Bacteria: Lymphocytes activated, Specific antibodies pro- duced and targeted cells attached to complement.
Parasites: TH2 response is necessary for expulsion of GI worms.
- Killing
Bacteria: Phagocyte attaches to organism, which is then ingested. Killing occurs via: NO, O2-, lysosome formation.
Parasite: Macrophage killing mechanisms activated
Define
Definitive host
Intermediate host
Definitive host- where the parasite reproduces sexually. Often where the adult stage resides.
Intermediate host-larval stage develops
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Ascaris lumbricoides:
Who carries them.
Infection causes a decrease in _______.
Disease where are the worms found?
Discuss life cycle and mode of entry into human.
What special population are usually the host?
Pathogenesis- discuss the effects and fatal cases.
Dx, symptoms, presentation
Tx and give sequential order.
Prevention and control (3)
Comment on the durability/fragility of Eggs.
ROUND WORMS-also called Nematodes
- Ascaris lumbricoides-over half of the world carries one or more of theses worms. Infection causes a decrease in allergies since the worms recruit IgE. World-wide, mainly in tropics.
a. Disease- worms in upper part of small intestine.
b. Life cycle- complex. Accidentally ingest eggs, larvae hatch in small intestine and are carried to liver. Larvae migrate to heart, then to lungs. They then break out of lungs and migrate up trachea, are swallowed and finally reside in the gut. Adults mature in the gut and lay eggs which are then passed in feces. Acquire infection by ingestion of eggs found in soil. Often an infection in children.
c. Pathogenesis-obstruction of GI tract, malabsorption of nutrients in infection children, peritonitis, Loeffler’s syndrome (type of pneumonia associated with high eosinophils). Fatal cases of Ascarisis caused by aberrant migration of adult worms to the liver.
d. Diagnosis- eggs in stool.
Adults can be vomited up when they are migrating.
Symptoms include: No symptoms, palpable abdominal mass, obstruction (biliary or intestinal), migration associated problems.
e. Treatment-mebendazole (a vermafuge), paralyzes worms that are then expelled. Surgical intervention is a last resort. Mebendazole is the treatment for most roundworms, including whipworm, hookworms, strongyloides, pinworm.
f. Prevention and control- Eggs survive well in soil under a wide variety of conditions.
ii. Eradicate reservoir hosts.
iii Sanitary disposal of feces.
iv. Avoidance of eating uncooked vegetables in epidemic areas.
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Whipworm (scientific name)
Disease determinant
Acquisition
Epidemiology
Reservoir
Life cycle, who is the definitive host?
Pathogenesis
Dx
Prevention/Control (3)
Discuss shape of eggs.
Trichuris trichiura - Whipworm
a. Disease -
i. Light worm load-usually no symptoms
ii. Heavy worm load - prolapse of rectum, diarrhea, weight loss
iii. Acquire- fecal-oral root- eating embryonated eggs from soil or vegetables contaminated with feces.
iv. Epidemiology - world wide, greatest incidence in tropics and southern United States
v. Reservoir – only humans
b. Life cycle: humans ingest eggs in soil. Larvae migrate to colon. Adult female releases eggs into human feces. Fecal-oral passage. Humans are definitive host.
c. Pathogenesis - prolapse of rectum, diarrhea, weight loss
d. Diagnosis - Eggs in stools. Football shaped eggs.
e. Prevention, control
i. Sanitary disposal of feces
ii. Avoidance of eating uncooked vegetables in epidemic area
iii. Personal cleanliness
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Hookworm (scientific names-2)
Disease determinant and causes what ailments
Acquisition and propensity in what special population?
Epidemiology
Life cycle and definitive host
Pathogenesis
-symptom determinant
Dx (2)
Prevention/control (2)
Hookworm- Necator americanus (new world) and Ancylostoma duodenale (old world)
a. Disease -
i. Depends on worm load, mainly causes anemia due to significant blood loss.
ii. Acquire - Feces in soil, infective filariform larva enter through skin (usually children)
iii. Epidemiology - Most common in tropics and subtropics
b. Life cycle: infection is via burrowing larva that develop in soil that has been contaminated with infected stool.
Definitive host – humans
c. Pathogenesis -
Symptoms - depends upon worm load
Heavy - anemia, cardiac damage, ‘pica’ (desire to eat dirt)
d. Diagnosis
i. Eggs in patient’s feces
ii. Rhabditiform larva in stool in constipated individuals or in fecal samples that have been left unexamined for hours
e. Prevention, control
i. Sanitary disposal of feces
ii. Wearing of shoes
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Strongyloides stercoralis
Disease
Definitive host
Acquisition
Epidemiology
Life cycle (discuss) - how is infection accomplished?
Pathogenesis determinant
- Symptoms
- Special population consideration
Dx (2)
Prevention/control (2)
a. Disease - diarrhea
i. Definitive host – humans
ii. Acquisition- Feces in soil, infective filariform larva enter through skin (usually children). As in Hookworm except disease can last many years due to autoinfection, even after individual has left an endemic area.
iii. Epidemiology - tropics, Southeast Asia, Appalachia
b. Life cycle- larvae migrate from bloodstream to lungs, then swallowed and live in human small intestine. Autoinfection occurs in humans. There is also a free-living soil cycle. Larvae infect humans by penetrating unbroken skin.
c. Pathogenesis
i. Many individuals asymptomatic
ii. Moderate to heavy load - diarrhea or constipation, anemia, weight loss
iii. Hyperinfection syndrome in immunocompromised hosts
d. Diagnosis
i. Rhabditiform larva in stool or duodenal aspirate
ii. Mucosol biopsy, string test, ELISA.
e. Prevention and control - same as in Hookworm
i. Sanitary disposal of feces
ii. Wearing of shoes
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Pinworm (Scientific name)
Disease
Definitive host
Epidemiology
Life cycle - mode of transmission of eggs
Pathogenesis - results in (2)
- internal progression
- Indirect result
Dx (3)
Prevention/control (1)
Property of Egg viability and effort to eradicate contaminated areas.
Enterobius vermicularis
a. Disease- itchy anal area
i. Definitive host – humans
ii. Epidemiology – world wide.
b. Life cycle: eggs expelled from gravid female pinworm in perianal area of human. Eggs are infectious to other individuals.
c. Pathogenesis
i. Pruritus ani (irritation of anus), insomnia
ii. Internal - adults may migrate to genital tract and become imbedded and result in granuloma formation.
iii. Psychic trauma to parents when their children become infected.
d. Diagnosis
i. Sticky plastic paddle pressed on perianal region on rising in the morning
ii. Three consecutive days if first and second results are negative
iii. Stools are not examined
e. Prevention and control
i. Personal cleanliness and cleanliness of living quarters
- Eggs survive on inanimate objects in the home. Entire household gets contaminated, difficult to eradicate
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Trichinosis
Causative agent
Disease Definitive host (4) w/ peculiarity
Life cycle, mode of entry, last stop where they reside
Pathogenesis
- symptom determinant (provide specific detail)
- Px
Dx- time frame, important factors (3)
Tx
Prevention/control (2)
Trichinella spiralis
a. Disease - calcified larvae in muscle
Definitive host -pigs, rats, bears, humans (dead end)
b. Life cycle: larva, infected meat is mode of entry into the human host. Adults mature in small intestine; newborn larvae carried through blood stream and enter skeletal muscle cells. Reside in muscle cell in human/animal tissue.
c. Pathogenesis – Symptoms
i. Few ingested larva - no symptoms
ii. 50 larvae/gram - diaphragm, extraocular, deltoid, gastrocnemius, etc.
iii. Fever, muscular pain, weakness, diarrhea in acute phase
iv. Periorbital edema, splinter hemorrhages
v. Prognosis - dose related
d. Diagnosis
i. Early diagnosis difficult
ii. History
iii. High eosinophilia
iv. Biopsy of striated muscle
e. Treatment-None, supportive therapy.
f. Prevention, control
i. Feed hogs cooked garbage
ii. Cook pork and pork products well
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Wuchereria bancrofti- A cause of ________ disease
Disease (2)
- discuss the location and gender roles
Life cycle
- mode of transmission
- progression subsequent to infection
- determinant to geographic source
Pathogenesis
Dx (2)
Tx (1) which is effective against ______.
Prevention (1)
A cause of parasitic tissue disease
a. Disease – elephantiasis, filariasis. The organism is a thread-like worm that locates in the lymphatic vessels and lymph nodes. There are male and female worms and the females produce sheath-covered microfilaria (~200 M long).
b. Life cycle - transmitted by the bit of a mosquito that has previously acquired microfilaria with a blood meal. The cycle is complete when infective larva in the mosquito pass into the mammalian host where they make their way into the lymph nodes and develop into adult worms in a few months.
There is a periodicity to the emergence of microfilaria in the bloodstream- the timing (nocturnal or diurnal, during the day) is indicative of the geographic source of infection.
c. Pathogenesis- adult worms live in lymphatics and cause blockages.
d. Diagnosis - periodicity of microflaria in bloodstream requires care in sampling time. Thick blood smears are also used.
e. Treatment - Diethylcarbamazine (Heteraza) is effective against the microfilaria.
f. Prevention - control of mosquitoes.
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Brugia malayi causes _____ disease.
How is infection transmitted?
another important filarial worm that causes tissue disease.
Close related to Wuchereria. There are primate reservoirs for this worm and infection to humans is zoonotic.
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Onchocerca volvulus
Mode of transmission and type of parasite
Major cause of ________ in Africa. What contributes to that cause. What helped resolve this?
Distinguishing trait
Dx
This filariae parasite is transmitted by the bite of the black fly.
a. Disease - It was the major cause of blindness in Africa before the drug Ivermectin was available.
The distinguishing trait of this filarium is that it is found in the skin and not the blood. Eye infection by microfilarial – human immune reaction contributes to blindness.
b. Diagnosis is via microfilaria in ear skin snip.
Multicellular parasites: worms.
A. ROUND WORMS-also called Nematodes
Aberrant nematode infections in humans (2)
Normal hosts for infection (2). Why is it aberrant?
Acquisition of infection
Discuss the two kinds of aberrant nematode infections.
- Pathological effects and Dx
Aberrant nematode infections in humans -Visceral and cutaneous larva migrans.
Normally infections of dogs and cats.
Numerous nematodes cause these aberrant human infections. Since these worms infect us accidentally and they cannot complete their life cycles in the human host.
Infection acquired- mainly when children eat dirt with eggs in it or when the body comes in contact with a larval form (cutaneous).
a. Visceral larval migrans (i.e. Toxocara canis) -
i. Affects liver, heart and CNS.
ii. Eosinophila - 30%
iii. Diagnosis- CSF examination, biopsy.
b. Cutanous larval migrans (i.e., Ancylostoma braziliense) -
i. Skin lesion, abscess formation
ii. Diagnosis-biopsy
FLATWORMS (Cestodes)
fish tapeworm
Pathogenesis
Diphyllobothrium latum- fish tapeworm.
a. “Jewish house wives’ disease”. Infection from eating larva in raw fish. Adult attaches to the human gut and reaches full length in 3 months.
b. Achieves 10 meters in length in the human gut! Causes anemia- B12 deficiency.
FLATWORMS (Cestodes)
Beef and Pork Tapeworms:
Lab Dx (3) Epidemiology (3)
Beef tapeworm:
Definitive host
Life cycle
Symptoms (2)
Pork tapeworm
Definitive host
Life cycle
Symptoms (2) and disease
Beef and Pork Tapeworms
a. Taenia saginata (beef tapeworm)
i. Definitive host - humans
ii. Life cycle: cystecerci (larvae) are ingested when we ingest infected beef. These larvae are released in the stomach and adults remain in the small intestines. Eggs from female adult are deposed with human feces. Cows ingest eggs which then hatch in their muscle.
iii. Symptoms
(a) Vague complaints of abdominal discomfort
(b) Awareness of movement of proglottids that emerge from anus.
Taenia solium (pork tapeworm)
i. Definitive host – humans
ii. Life cycle: as for the beef tape worm, except the eggs mature into larvae in the pig.
iii. Symptoms – same as beef tapeworm. If we ingest the tapeworm eggs, and not the larva in the meat muscle, we get aberrant parasite migration as larva develop in our brains and eyes. This disease is called cysticercosis.
c. Laboratory diagnosis for Both beef and pork tapeworms
i. Eggs in stool, identical in appearance for both species
ii. Differentiating T. solium and T. saginata by pressing proglottid between slide and counting main lateral branches
(a) T. solium - 7 to 12 pairs
(b) T. saginata - 15 to 30 pairs
iii. For Cysticercosis (pork tapeworm)-find larva/cysticercus in brain/muscle/eye by
(a) CAT scan or MRI
(b) ELISA test
d. Epidemiology
i. Incidence less than 2% in U.S.
iii. Spread by eating undercooked beef and pork
iv. Cysticercosis more common in Mexico, Central and South America
