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Text Review: Study Questions Lecture 12: Chapter 22

• Chapter 22:

– M/C: 1 -7, 9 -12

– Concept: 1 -3, 8, 10, 11, 14, 15

– Critical Thinking: 1, 5, 8

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The Fungi of Medical Importance Chapter 22 3

The Fungi of Medical Importance

Chapter 22

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Fungi as infectious agents

Mycosis (or mycoses) – disease process caused by fungi

• Infectious fungi can be grouped based on the virulence of the organism and the level of involvement of the disease

– Systemic

– Subcutaneous

– Cutaneous

– Superficial

• Fungal pathogens can be classified in 2 categories:

Primary (true) pathogens : have virulence factors that allow them to invade and grow in a healthy host

Opportunistic pathogens : weak virulence; causes disease in only weakened or compromised hosts

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Lecture 12: Outline

Part 1:

– Fungal pathogens: Chapter 22

Part 2:

– Review

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Fungi as infectious agents

• molds & yeasts are widely distributed in air, dust, fomites & normal flora

• humans are relatively resistant

• fungi are relatively nonpathogenic

• of the 100,000 fungal species, only 300 have been linked to disease in animals

• fungi are the most common plant pathogens

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Levels of invasion

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6
 

Pathogenesis of Fungi

• Enter body through respiratory, mucous, and cutaneous routes

 

• In general, primary pathogens have a respiratory portal of entry

• Spores, hyphal elements, and yeast can all be infectious; more often spores due to their durability

• Mycoses are not usually communicable (except dermatophytes and Candida species)

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• immunity to fungal infections consist of nonspecific barriers, inflammation & cell mediated defenses

 

• diagnosis & identification require microscopic examination of stained specimens, culturing in selective & enriched media & specific biochemical & serological tests

• control involves intravenous amphotericin B, flucytosine, azoles & nystatin

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Fungi of Medical Importance

 

• Primary Pathogens

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidiodes brasiliensis

• Pathogens with Intermediate Virulence

Dermatophytes

• Secondary Pathogens

 

Cryptococcus neoformans

Candida albicans

Aspergillus species

Pneumocystis carinii

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Mycoses

• most fungal pathogens do not require a host to complete their life cycles and infections are not communicable

• dermaphytes & Candida sp naturally inhabit human body & are transmissable

• dermaphytoses most prevalent

• most cases go undiagnosed or misdiagnosed

• systemic, subcutaneous, cutaneous or superficial infections

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subcutaneous, cutaneous or superficial infections 8 10 Primary Fungal Pathogens • Cause primary pulmonary
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subcutaneous, cutaneous or superficial infections 8 10 Primary Fungal Pathogens • Cause primary pulmonary

Primary Fungal Pathogens

• Cause primary pulmonary infections

• Endemic to specific regions of the world

• Virulence factors include resistant spores, thermal dimorphism, toxin

production, and invasive factors

• Thermal dimorphism – ability to switch between hyphal (mold) and

yeast cells based on temperature

• While many fungi exhibit both hyphal and yeast cell types, few show

thermal dimorphism

• Infection typically occurs when spores are inhaled

• Spores germinate to yeast cells and produce a primary pulmonary

infection (PPI)

• In some hosts, the infection becomes systemic and creates severe ,

chronic lesions

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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or dis play.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or dis play.

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Figure 22.1 Thermal Dimorphism

Histoplasma capsulatum

• cause histoplasmosis

• typically dimorphic

• distributed worldwide, most prevalent in eastern & central regions of US

• grow in moist soil high in nitrogen content

• inhaled conidia produce primary pulmonary infection that may progress to systemic involvement of a variety of organs & chronic lung disease

• amphotericin B, ketoconazole

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Histoplasma capsulatum: Histoplasmosis

• Most common true fungal pathogen

• Endemic on all continents except Australia

• Highest incidence rates in the Ohio River valley; 500 000 case/y r, few

requiring hospitalization

• Has been found in poultry house litter, caves, areas harboring b ats, and in bird roosts

• Spores are dispersed by wind and animals

• Upon inhalation of spores, growth of yeast cells occur in macrophages

• Identified by “fish -eye” yeast cells in macrophages

• Mild symptoms include aches, pain, and coughing

• More serious forms in children and AIDS patients

• Systemic disease can lead to liver and spleen enlargement, anemi a, circulatory

collapse and death

• Chronic pulmonary histoplasmosis occurs in emphysema patients and resembles Tuberculosis

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Systemic mycoses caused by true pathogens

Histoplasma capsulatum

Coccidioides immitis

Blastomyces dermatitidis

Paracoccidioidomycosis brasiliensis

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Histoplasma capsulatum

Histoplasma capsulatum Figure 22.6 16

Figure 22.6

16

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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or dis play.
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Figure 22.7 Events of Histoplasmosis

Histoplasma in a neutrophil

Histoplasma in a neutrophil 19

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Coccidioides immitis

• cause coccidioidomycosis

• distinctive morphology – blocklike arthroconidia in the free-living stage & spherules containing endospores in the lungs

• lives in alkaline soils in semiarid, hot climates & is endemic to southwestern US

• arthrospores inhaled from dust, creates spherules & nodules in the lungs

• amphotericin B treatment

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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or dis play. Figure 22.8
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or dis play.
Figure 22.8
Events in Coccidioides infection
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Systemic mycoses caused by true pathogens

Histoplasma capsulatum

Coccidioides immitis

Blastomyces dermatitidis

Paracoccidioidomycosis brasiliensis

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Coccidioides immitis:

Coccidioidomycosis

• The most virulent of all fungal pathogens

• Endemic to salty soils in arid regions of the U.S. (Southwest)

• Identified by highly distinctive spherules in sputum, spinal fluid, and

biopsies

• In 60% of cases infection is asymptomatic

• In 40% of cases, symptoms include fever, chest pain, cough, head ache, and malaise

• Rare cases (5/1000) progress to chronic pulmonary or systemic disease

• Chronic pulmonary disease is manifested by fungomas (tumor) and compromised respiration

• Disseminated disease occurs in only compromised patients and can manifest as subcutaneous abscesses

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Coccidioides immitis

Figure 22.9

Coccidioides immitis Figure 22.9 24

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Systemic mycoses caused by true pathogens

Histoplasma capsulatum

Coccidioides immitis

Blastomyces dermatitidis

Paracoccidioidomycosis brasiliensis

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Blastomyces dermatitidis

Figure 22.11

a) Hyphae and

conidia (25°C)

b) Yeast form (37°C)

Blastomyces dermatitidis Figure 22.11 a) Hyphae and conidia (25°C) b) Yeast form (37°C) 27

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Blastomyces dermatitidis

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Blastomyces dermatitidis

• causes blastomycosis

• dimorphic

• free-living species distributed in soil of a large section of the midwestern and southeastern US

• inhaled 10-100 conidia convert to yeasts & multiply in lungs

• symptoms include cough & fever

• chronic cutaneous, bone, & nervous system complications

• Treatment with amphotericin B

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system complications • Treatment with amphotericin B 26 Blastomyces dermatitidis : Blastomycosis • Endemic to

Blastomyces dermatitidis:

Blastomycosis

• Endemic to North America, Africa, and the Middle East

• Inhabits areas high in organic matter: forest soil, decaying wood, manure, abandoned buildings

• Can infect through lungs or skin

• In pulmonary form, symptoms include cough, chest pain, hoarseness

and fever

• Chronic blastomycosis can result in abscesses and tumors often

mistaken for cancer

• The cutaneous form is rather common; frequently begins on face, hands, or leg

• Can disseminate to bones resulting in arthritis and osteomyelitis

• Chronic systemic blastomycosis of spleen, liver, and urogenital tract

can last for years and eventually destroy host defenses

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can last for years and eventually destroy host defenses 28 Fungi of Medical Importance • Primary

Fungi of Medical Importance

• Primary Pathogens

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidiodes brasiliensis

Pathogens with Intermediate Virulence

Dermatophytes

• Secondary Pathogens

Cryptococcus neoformans

Candida albicans

Aspergillus species

Pneumocystis carinii

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Dermatophytes (Medical Microfile 22.2)

• Named for derma “skin” and plant “phyte”

• Cause cutaneous mycoses – strictly confined to epidermis and its derivatives (hair and nails)

• All are communicable diseases

• Well adapted to breaking down keratin; termed keratinophiles

• Most diseases are termed “ringworm” or tinea because they develop in circular scaly patches

• Treatments include topical antifungal cream, debridement of skin and UV treatments

• Difficult infections can be treated with griseofulvin; however, this drug is both hepatotoxic and nephrotoxic

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• Ringworm of scalp (tinea capitis) affects scalp & hair- bearing regions of head; hair may be lost

• Ringworm of body (tinea corporis) occurs as inflamed, red ring lesions anywhere on smooth skin

• Ringworm of groin (tinea cruris) “jock itch” affects groin & scrotal regions

• Ringworm or foot & hand (tinea pedis & tinea manuum) is spread by exposure to public surfaces; occurs between digits & on soles

• Ringworm of nails (tinea unguium) is a persistent colonization of the nails of the hands & feet that distorts the nail bed

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35 Tinea unguium Tinea pedis
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Tinea unguium
Tinea pedis

Cutaneous mycoses

• infections strictly confined to keratinized epidermis (skin, hair, nails) are called dermatophytoses - ringworm & tinea

• 39 species in the genera Trichophyton, Microsporum, Epidermophyton

• communicable among humans, animals, & soil

• infection facilitated by moist, chafed skin

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T i n e a c a p i t i s Tinea corporis 34

Tinea capitis

Tinea corporis

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Fungi of Medical Importance

• Primary Pathogens

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidiodes brasiliensis

• Pathogens with Intermediate Virulence

– Dermatophytes

• Secondary Pathogens – Cryptococcus neoformans – Candida albicans – Aspergillus species – Pneumocystis
• Secondary Pathogens
Cryptococcus neoformans
Candida albicans
Aspergillus species
Pneumocystis carinii

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Cryptococcus neoformans:

Cryptococcosis

• Widespread; associated with birds, and bird guano

 

• Transmission is through spore inhalation

• Common infection of AIDS, cancer or diabetes patients

• Infection of lung leads to cough, fever, and lung nodules

• Dissemination to meninges and brain can cause severe neurological disturbances and death

• Systemic cryptococcosis requires immediate treatment with amphotericin B and fluconazole over a period of weeks or months

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Cryptococcus neoformans

Figure 22.24

Figure 22.24 39

39

 

Fungi of Medical Importance

• Primary Pathogens

 
 

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidiodes brasiliensis

• Pathogens with Intermediate Virulence

 

Dermatophytes

Secondary Pathogens

 

Cryptococcus neoformans

Candida albicans
Candida albicans

Aspergillus species

Pneumocystis carinii

 

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Diagnosis and treatment

• Initially: negative staining of samples to detect encapsulated budding yeast

• Confirmation by pigmentation on birdseed agar or fluorescent antibody tests

• Birdseed Agar: - Cryptococcus neoformans produces phenol oxidase, which breaks down the substrate resulting in the production of melanin and developing dark brown or black colonies. Other yeasts will appear cream-colored.

• Systemic cryptococcosis requires immediate treatment with amphotericin B and fluconazole over a period of weeks or months

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Cryptococcus neoformans

Figure 22.25

Cryptococcus neoformans Figure 22.25 40

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Candida albicans

• widespread yeast

• infections can be short -lived, superficial skin irritations to overwhelming, fatal systemic diseases

• budding cells of varying size that my form both elongate pseudohyphae & true hyphae

• forms off-white, pasty colony with a yeasty odor

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Candida albicans

• Normal flora of oral cavity, genitalia, large intestine or skin of 20% of humans

• Account for 80% of nosocomial fungal infections

• Account for 30% of deaths from nosocomial infections

• Can cause short-lived superficial skin irritations to fatal systemic disease

• Candidiasis is usually endogenous, but can be communicable

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Diagnosis of Candidiasis

• Presumptive diagnosis by observing budding yeast cells andpseudohyphae in specimen

• Culturing on selective and differential yeast media ie trypan blue media – Candida appears light blue

• Also rapid yeast identification kits (multiple biochemical tests)

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Candida albicans: Candidiasis

Candida albicans : Candidiasis Thrush 47

Thrush

47

tests) 45 Candida albicans : Candidiasis Thrush 47 Candida albicans : Candidiasis • Thrush – occurs

Candida albicans: Candidiasis

• Thrush – occurs as a thick, white, adherent growth on the mucous membranes of mouth & throat

• Vulvovaginal yeast infection – painful inflammatory condition of the female genital region that causes ulceration & whitish discharge

• Cutaneous candidiasis – occurs in chronically moist areas of skin and burn patients

• Esophageal candidiasis – afflicts 70% of AIDS patients, causing painful bleeding ulcerations, nausea and vomiting

• Treatment: topical antifungals; amphotericin B in systemic infections

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topical antifungals; amphotericin B in systemic infections 44 Candida albicans Figure 22.23 46 Candida albicans 48

Candida albicans

Figure 22.23
Figure 22.23

46

topical antifungals; amphotericin B in systemic infections 44 Candida albicans Figure 22.23 46 Candida albicans 48

Candida albicans

topical antifungals; amphotericin B in systemic infections 44 Candida albicans Figure 22.23 46 Candida albicans 48

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Fungi of Medical Importance

• Primary Pathogens

 

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidiodes brasiliensis

• Pathogens with Intermediate Virulence

 

Dermatophytes

Secondary Pathogens

 

Cryptococcus neoformans

Candida albicans

   

Pneumocystis carinii

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Aspergillus

 
Figure 22.28

Figure 22.28

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Aspergillus species: Aspergillosis

Aspergillus species: Aspergillosis Aspergillus infection of the eye Chest x-ray shows where the fungus has invaded
Aspergillus species: Aspergillosis Aspergillus infection of the eye Chest x-ray shows where the fungus has invaded

Aspergillus infection of the eye

Chest x-ray shows where the fungus has invaded the lung tissue. The cloudiness on the left side of this x-ray is caused by the fungus

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Aspergillus

• very common airborne soil fungus

• 600 species, 8 involved in human disease

• inhalation of spores causes fungus balls in lungs and invasive disease in the eyes, heart, & brain

• Distinguished by septate mycelium with characteristic conidial heads

• amphotericin B & nystatin treatment

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Aspergillus species: Aspergillosis

• Poses a serious threat to AIDS, leukemia, and organ transplant patients

• Transmission is through inhalation of spores; usually in barns, granaries, and silos

• Spores germinate in the lungs and form fungus balls

• In the more invasive form, the fungus produces a necrotic pneumonia and disseminates to the brain

• It can also cause noninvasive infections of the sinuses, ear canal, eyelids, and conjunctiva

• Apergillus flavus produces a powerful toxin, aflatoxin, that is hepatotoxic and carcinogenic

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Aspergillus

54
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Fungi of Medical Importance • Primary Pathogens – Histoplasma capsulatum – Blastomyces dermatitidis –
Fungi of Medical Importance
• Primary Pathogens
– Histoplasma capsulatum
– Blastomyces dermatitidis
– Coccidioides immitis
– Paracoccidiodes brasiliensis
• Pathogens with Intermediate Virulence
– Dermatophytes
• Secondary Pathogens
– Cryptococcus neoformans
– Candida albicans
Aspergillus species
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Pneumocystis carinii

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Figure 22.26

Lecture 12: Outline

Part 1:

– Fungal pathogens: Chapter 22

Part 2:

– Review

59

Pneumocystis carinii

• a small, unicellular fungus that causes pneumonia (PCP), the most prominent opportunistic infection in AIDS patients

• this pneumonia forms secretions in the lungs that block breathing & can be rapidly fatal if not controlled with medication

• PCP is diagnosed by symptoms and by examination of lung secretions

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Pneumocystis carnii

• Small, unicellular fungus; has a weak cell wall

• Obligate parasite; normally a relatively harmless resident of the upper respiratory tract

• Transmission is likely through droplets

• Multiplies intracellularly and extracellularly in compromised patients

• Causes inflammation in the lungs; lung cells die and slough off forming a foamy exudate

• Heavy secretions can block breathing

• Symptoms include cough, fever, shallow breathing, and cyanosis

• Traditional antifungals are ineffective; primary treatments are pentamide and cotrimoxazole (10-day period)

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Diseases of the GI tract

Microbial Agent

Mode of

Virulence/Tissue

Disease Features

Transmission

tropism

Rotavirus

fecal-oral

Small intestine mucosa

diarrhea, fever, abdominal pain and vomiting (mostly in infants.)

contamination

Noroviruses (Norwalk-

fecal-oral

Small intestine

fever, abdominal pain, diarrhea, and vomiting

like agents)

Giardia lamblia

Ingestion of contaminated water or food.

attach to microvilli of small intestine

giardiasis- fatty, foul smelling diarrhea, flatulence (gas).

Cryptosporidium

Ingestion of contaminated water or food.

Small and large intestine

mild nausea, cramping and watery diarrhea,

parvum

Toxoplasma gondii

Ingestion of oocysts/ cat feces

Lymph nodes

Toxoplasmosis

Trichinella spiralis

Ingestion of cysts/ bear and pork

Intestine

Trichinosis

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Diseases of the GI tract

 

Microbial Agent

Mode of

Virulence/Tissue

Disease Features

Transmission

tropism

Entamoeba histolytica

Transmitted by the 4- F's; food, fingers, feces, and flies.

Caecum, appendix,

Amebic dysentery; bloody mucoid diarrhea, erosion of colon.

colon, rectum

Enterobius

Ingestion of eggs/ oral- fecal

Rectum, anus

Pinworm

vermicularis

Ascaris lumbricoides

Oral-fecal

Intestinal mucosa

Ascariasis

Taenia saginata

Ingestion of larva from beef

Large intestine

Beef tapeworm

Taenia solium

Ingestion of larva from pork

Large Intestine ; brain

Pork tapeworm

Paramyxovirus

Contact with salivary droplets

Parotid salivary gland

Mumps - parotitis

Hepatitis A

Oral-fecal

Liver

Infectious hepatitis

Poliovirus

Oral-Fecal

Intestinal mucosa;

Poliomyelitis

CNS

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Respiratory Infections

 

Microbial Agent

Mode of Transmission

Virulence / tissue tropisms

Disease Features

Histoplasma capsulatum

Inhalation of spores

True pathogen/ lower RT

Histoplasmosis

Blastomyces dermatitidis

Inhalation of spores

True pathogen/ lower RT

Blastomycosis

Coccidioides immitis

Inhalation of spores

True pathogen/ lower RT

Coccidioidomycosis

Cryptococcusneoformans

Inhalation of yeast

Opportunistic pathogen/ lower RT, lungs

Cryptococcosis

Pneumocystis carnii

Inhalation of spores

Opportunistic pathogen/ lower RT, lungs

Pneumocystic pneumonia

(PCP)

Aspergillus

Inhalation of spores

Opportunistic pathogen/ lower RT, lungs

Aspergillosis

Influenzavirus

Inhalation of droplets

Mucosal cells of trachea, bronchi

Influenza

Adenovirus, Rhinovirus,

Direct contact with secretions, fomites

Nasopharynx mucosal cells

Common cold

Coronavirus

 

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Systemic/Nervous/ Circulatory system Infections

Microbial Agent

Mode of Transmission

Virulence/Tissue tropism

Disease Features

Toxoplasmagondii

Ingestion of cysts; cat feces

Lymph nodes; muscle, brain

Toxoplasmosis

Plasmodium

Vector– Anopheles mosquito

Liver, red blood cells

Malaria

Cytomegalovirus

Body fluids

Lymph and salivary glands

Congenital CMV

Epstein -Barrvirus

Oral contact, saliva, fomites

Lymph and salivary glands

Infectious mononucleosis

HIV

STD; blood

T cells (CD4)

AIDS; systemic

Histoplasma capsulatum

Inhalation of spores

True pathogen/ lower RT

Histoplasmosis

Blastomyces dermatitidis

Inhalation of spores

True pathogen/ lower RT

Blastomycosis

Coccidioides immitis

Inhalation of spores

True pathogen/ lower RT

Coccidioidomycosis

Cryptococcusneoformans

Inhalation of yeast

Opportunistic pathogen/ lower RT, lungs

Cryptococcosis

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Skin and Eye Infections

 

Microbial Agent

Mode of Transmission

Virulence factors/Tissue tropism

Disease Features

Varicella-zoster virus

Contact with skin or respiratory secretions

Nerve cells; latency

Chickenpox:vesicularlesions Shingles: severe localized pain, dermatome

HSV -1

Contact with secretions

Nerve cells, mouth and lips

-Cold sores, Herpes simplex labialis; vesicular painful lesions

HSV -2

Contact with secretions, STD

Nerve cells, genitals

-Cold sores, Herpes simplex genitalis; vesicular painful lesions

Humanherpesvirus6

Contact with droplets

Skin; trunck

Roseola

Papilloma virus

Contact with warts, fomites; STD

Skin(hands);genitalia

Warts; Condyloma

Acuminatum

Rubeola virus

Contact with oral secretions

Skin on head and trunk

Red measles; red macular rash

Rubella virus

Contact with respiratory secretiosn

Skin on head and trunk

German measles; Rubella; skin rash

Dermatophytes: Trichophyton sp., Microsporum sp., and Epidermophyton sp.

Contact with infected humans or animals via direct or indirect means

Intermediate fungal pathogen

Cutaneous mycoses ( Tineas)

Candida albicans

Endogenous; communicable

Moist/ damaged skin; mucous membranes

Candidiasis

 

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Sexually transmitted disease (STDs)

 

Microbial Agent

Transmission

Virulence factors/Tissue

Disease Features

tropism

HSV -2

Contact with secretions, STD

Nerve cells, genitals

-Cold sores, Herpes simplex genitalis; vesicular painful lesions

Papilloma virus

Contact with warts, fomites; STD

Skin(hands);genitalia

rough cauliflower -like lesions,

CondylomaAcuminatum

Molluscum contagiosum

Pox lesions; STD

Skin;mucousmembranes

Molluscum contagiosum

Trichomonas vaginalis

STD

Vagina; urethra

Trichomoniasis

Hepatitis B

STD; body fluids, Blood

Liver

Hepatitis

Candida albicans

STD; mother to fetus

Vagina; urethra

Candidiasis

 

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Review: Chapter 23

 

For the parasite pathogens:

– Protozoa or helminth?

 

– Ameba/Flagellate/Apicomplexa or nematode/fluke/cestode?

 

– Cyst/trophozoite stages

 

– Disease

– Transmission

 

– Communicable or non-communicable

 

– Treatment

 

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Review: Chapters 24-25

• For a viral pathogen

– DNA/RNA; single stranded or double stranded

– Envelope/ no envelope

– Special features

– Disease

– Transmission

– Tissue Tropism

– Treatment or vaccine

• Compare Positive and Negative sense RNA viruses

• Describe retroviruses

• Compare Rubeola and Rubella

• Compare the Hepatitis viruses

• Know the common opportunistic diseases in AIDS patients

• Compare the viruses involved in the common cold

67

Review: Chapter 22

• For a fungal pathogen

– True pathogen , intermediate pathogen, or opportunist

– Disease

– Transmission

– Communicable or non-communicable

– Diagnosis/Treatment

68