Protozoal and Fungal Diseases

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Protozoal and Fungal Diseases
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How to cause an infection.

• Pathogen must have
• Host
• Access to a reservoir
• Carriers
• Means to leave the reservoir
• Way of attaching to the host
• Mechanism to enter hosts tissues
• Ability to avoid hosts defenses
• Ability to reproduce inside host
• A way to return to the reservoir

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General Principles

• Zoonosis
• Infectious disease transmitted between humans and
  animals
• Rabies, herpes, SARS
• Vector
• Incubation time

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Protozoa
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Parasitology

• Study of eucaryotic parasites, protozoa and
  helminths
• Cause 20 of all infectious diseases
• Less prevalent in industrialized countries
• Increasingly common in AIDS patients

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Typical Protozoan Pathogens

• Single-celled, animal-like microbes, most having
  some form of motility
• Estimated 100,000 species
• _at_ 25 are important pathogens
• Life cycles vary
• propagate by simple asexual cell division of the
  active feeding cell (trophozoite)
• undergo formation of a cyst
• complex life cycle that includes asexual and
  sexual phases

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Protozoan Classification

• Phyla grouping based on method of motility,
  reproduction, and life cycle
• Mastigophora
• primarily flagellar motility, some flagellar and
  amoeboid
• sexual reproduction
• cyst and trophozoite
• Sarcodina
• primarily ameba
• asexual by fission
• most are free-living
• Ciliophora
• Cilia
• trophozoites and cysts
• most are free-living, harmless
• Apicomplexa
• motility is absent except male gametes
• sexual and asexual reproduction
• complex life cycle all parasitic

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Infective Amebas
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Entamoeba histolytica

• Amebiasis
• Alternates between a large trophozoite
• has a large nucleus and lacks most other
  organelles
• Motile by means of pseudopods and a smaller
  nonmotile cyst
• Humans are the primary hosts
• Ingested
• Carried by 10 of world population

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Entamoeba histolytica

• Cysts swallowed and travel to small intestine
• alkaline pH and digestive juices stimulate cysts
  to release 4 trophozoites
• Trophozoites attach, multiply, actively move
  about and feed
• Asymptomatic in 90 of patients
• Ameba may secrete enzymes that dissolve tissues
  and penetrate deeper layers of the mucosa
• Causing dysentery, abdominal pain, fever,
  diarrhea and weight loss

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Entamoeba histolytica

• Life-threatening manifestations are
• Hemorrhage
• Perforation
• Appendicitis
• Amebomas
• Tumor-like growths
• May invade liver and lung
• Severe forms of disease result in 10 fatality
  rate
• Effective drugs are iodoquinol, metronidazole,
  and chloroquine

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Amebic Infections of the Brain

• Caused by Naegleria fowleri and Acanthamoeba
• Ordinarily inhabit standing water
• Primary acute meningoencephalitis is acquired
  though nasal contact with water or traumatic eye
  damage
• Infiltration of brain is usually fatal

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An Intestinal Ciliate Balantidium coli

• An occupant of the intestines of domestic animals
  such as pigs and cattle
• Acquired by ingesting cyst-containing food or
  water
• Trophozoite erodes intestine and elicits
  intestinal symptoms
• Healthy humans resistant
• Rarely penetrates intestine or enters blood
• Treatment tetracycline, iodoquinol,
  nitrimidazine or metronidazole

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The Pathogenic Flagellates
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Trichomonads Trichomonas species

• Small, pear-shaped
• 4 anterior flagella and an undulating membrane
• Exist only in trophozoite form
• 3 infect humans
• T. vaginalis
• T. tenax
• T. hominis

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Trichomonas vaginalis

• Causes an STD called trichomoniasis
• Reservoir is human urogenital tract
• Strict parasite
• 3 million cases yearly
• Female symptoms
• foul-smelling, green-to-yellow discharge
  vulvitis cervicitis urinary frequency and pain
• Male symptoms
• urethritis, thin, milky discharge, occasionally
  prostate infection
• Metronidazole

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Giardia lamblia

• Giardiasis
• Pathogenic flagellate
• Cysts are small, compact, and multinucleate
• Reservoirs include beavers, cattle, coyotes,
  cats, and humans
• Cysts can survive for two months in environment
• Usually ingested with water and food
• 10 to 100 cysts

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Giardia lamblia

• Cysts enter duodenum, germinate, travel to
  jejunum to feed and multiply
• Causes giardiasis
• diarrhea, abdominal pain
• Diagnosis difficult because organism is shed in
  feces intermittently
• Treatment quinacrine or metronidazole
• Agent is killed by boiling, ozone, and iodine

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Hemoflagellates Vector-Borne Blood Parasites

• Obligate parasites that live in blood and tissues
  of human host
• Cause life-threatening and debilitating zoonoses
• Spread in specific tropical regions by
  blood-sucking insects that serve as intermediate
  hosts
• Have complicated life cycles and undergo
  morphological changes
• Categorized according to cellular and infective
  stages

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Trypanosoma species and Tropanosomiasis

• Distinguished by their infective stage
• trypomastigote
• elongate, spindle-shaped cell with tapered ends,
  eel-like motility
• 2 types of trypanosomiasis
• T. brucei
• African sleeping sickness
• T. cruzi
• Chagas disease

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Trypanosoma brucei

• African Sleeping Sickness
• Spread by tsetse flies
• Biting of fly inoculates skin with
  trypomastigotes
• Multiplies in blood and damages spleen, lymph
  nodes and brain
• Harbored by reservoir mammals
• Two variants of disease caused by 2 subspecies
• T.b.gambiense Gambian strain West Africa
• T.b. rhodesiense Rhodesian strain East Africa

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Trypanosoma brucei

• Chronic disease symptoms are sleep disturbances,
  tremors, paralysis and coma.
• Blood, spinal fluid or lymph nodes
• Treatment before neurological involvement with
  melarsoprol, eflornithine
• Control involves eliminating tsetse fly

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Trypanosoma cruzi

• Chagas disease
• Endemic to Central and South America
• Reduviid bug (kissing bug) is the vector
• Bug feces is inoculated into a cutaneous portal
• Local lesion, fever, and swelling of lymph nodes,
  spleen, and liver
• Heart muscle and large intestine harbor masses of
  amastigotes
• Chronic inflammation occurs in the organs
  (especially heart and brain)
• Treatment nifurtimox and benzonidazole

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Leishmania species

• Leishmaniasis
• Endemic to equatorial regions
• Promastigotes are injected with sand fly bite
• convert to amastigote and multiply
• if macrophage is fixed the infection is localized
• systemic if macrophage migrates

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Apicomplexan parasites

• Sporozoans
• Alternate between sexual and asexual phases and
  between different animal hosts
• Most form specialized infective bodies that are
  transmitted by arthropod vectors, food, water, or
  other means
• Three important apicomplexan parasites
• Plasmodium
• Toxoplasma
• Cryptosporidium

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Plasmodium

• Malaria
• Dominant protozoan disease
• Obligate intracellular sporozoan
• 4 species
• P. malariae
• P. vivax
• P. falciparum
• P. ovale
• Female Anopheles mosquito is the primary vector
• blood transfusions, mother to fetus
• 300-500 million new cases each year
• 2 million deaths each year

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Toxoplasma gondii

• Toxoplasmosis
• Intracelllular apicomplexan parasite with
  extensive distribution
• Lives naturally in cats
• harbor oocysts in the GI tract
• Acquired by ingesting raw meats or substances
  contaminated by cat feces
• Most cases go unnoticed
• Except in fetus and AIDS patients
• Can suffer brain and heart damage
• Treatment pyrimethamine and sulfadiazine

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Cryptosporidium

• An intestinal pathogen
• Infects a variety of mammals, birds, and reptiles
• Exists in tissue and oocyst phases
• 1990s
• 370,000 cases in Milwaukee, WI due to
  contaminated water
• filtration required for removal
• Ingestion of oocysts give rise to sporozoites
  that penetrate intestinal cells
• Causes gastroenteritis, headache, sweating,
  vomiting, abdominal cramps, diarrhea
• AIDS patients may suffer chronic persistent
  diarrhea
• No effective drugs

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Fungal Diseases
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Fungi

• Eukaryotic
• Membrane-bound nucleus
• Heterotrophic
• Consumer
• Obtains Carbon through the consumption of organic
  substrates
• Dimorphic
• Can be presented in two different stages
• Change morphological form

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Fungal Organization

• Yeast
• soft, uniform texture and appearance
• Fungal Cell Structure
• Cell walls contain chitin instead of cellulose
• Energy reserve is glycogen
• Nonmotile
• Move toward food source by growing toward it
• Hyphae
• Filamentous fungi
• Mycelium
• hyphae may be divided by cross walls
• septate

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Fungal Classification

• Subkingdom Amastigomycota
• Terrestrial inhabitants including those of
  medical importance
• Zygomycota
• zygospores sporangiospores and some conidia
• Ascomycota
• ascospores conidia
• Basidiomycota
• basidiospores conidia
• Deuteromycota
• majority are yeasts and molds
• no sexual spores known conidia

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Fungal Reproduction

• Primarily through spores formed on reproductive
  hyphae
• Asexual reproduction spores are formed through
• Budding or mitosis
• Sporangiospores
• Conidia
• Arthrospore
• Chlamydospore
• Blastospore
• Phialospore
• Microconidium or macroconidium
• porospore

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Fungal Reproduction

• Sexual reproduction
• Spores are formed following fusion of male and
  female strains and formation of sexual structure
• Sexual spores and spore-forming structures are
  one basis for classification
• Zygospores
• Ascospores
• Basidiospores

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Zygospores
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Ascospores
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Basidiospores
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Opportunistic vs. Pathogenic

• Fungus is the primary problem
• Animal does not have to be immune suppressed to
  be affected by the fungus

• Fungus is a secondary invader
• Animal has other pre-existing conditions
• However, the fungus may be there all the time

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Fungal Diseases

• True or primary fungal pathogen can invade and
  grow in a healthy, noncompromised host
• Ability to switch from hyphal cells to yeast
  cells
• Thermal dimorphism
• grow as molds at 30C and as yeasts at 37C

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Emerging Fungal Pathogens

• Opportunistic fungal pathogen
• little or no virulence
• host defenses must be impaired
• Vary from superficial and colonization to
  potentially fatal systemic disease
• An emerging medical concern
• account for 10 of all nosocomial infections
• Dermatophytes may be undergoing transformation
  into true pathogens

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Epidemiology of the Mycoses

• Most do not require a host to complete their life
  cycles
• infections are not communicable
• Dermatophytes and Candida sp
• naturally inhabit human body
• transmissible
• True fungal pathogens
• distributed in a predictable geographical pattern
  
• climate, soil.
• Cases go undiagnosed or misdiagnosed

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Diagnosis of Mycotic Infections

• Diagnosis and identification require
• microscopic examination of stained specimens
• culturing in selective and enriched media
• Reverse important!!!!
• specific biochemical and serological tests

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Control of Mycotic Infections

• Immunization not usually effective
• Control involves intravenous amphotericin B,
  flucytosine, azoles and nystatin
• Surgical removal of damaged tissues
• Prevention limited to masks and protective
  clothing to reduce contact with spores

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Pathogenesis of the Fungi

• Portal of entry
• primary mycoses
• respiratory portal inhaled spores
• subcutaneous
• inoculated skin trauma
• cutaneous and superficial
• contamination of skin surface
• Virulence factors
• thermal dimorphism
• toxin production
• capsules and adhesion factors
• hydrolytic enzymes
• inflammatory stimulants

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Characterization of Fungal Infections

• Systemic
• Subcutaneous
• Cutaneous
• Superficial
• Opportunistic

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Systemic fungal infections by true pathogens
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1. Histoplasma capsulatum

• 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
• may progress to systemic involvement of a variety
  of organs chronic lung disease
• amphotericin B, ketoconazole

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Histoplasma capsulatum

• All continents except Australia
• Ohio Valley
• Moist soils with increase in N content
• Bat guano

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2. Coccidioides immitis

• Coccidioidomycosis
• distinctive morphology
• blocklike arthroconidia in the free-living stage
• arthrospores inhaled from dust
• Creates spherules and nodules in the lungs
• lives in alkaline soils in semiarid, hot climates
  
• endemic to southwestern US
• amphotericin B treatment

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3. Blastomyces dermatitidis

• Blastomycosis
• dimorphic
• free-living species distributed in soil
• midwestern and southeastern US
• inhaled 10-100 conidia convert to yeasts
  multiply in lungs
• symptoms include cough and fever
• chronic cutaneous, bone, nervous system
  complications
• amphotericin B

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Blastomyces dermatitidis
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4. Paracoccidioides brasiliensis

• Paracoccidioidomycosis
• distributed in Central South America
• lung infection occurs through inhalation or
  inoculation of spores
• systemic disease not common
• ketoconazole, amphotericin B, sulfa drugs

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Subcutaneous Mycoses
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1. Sporothrix schenckii

• Sporotrichosis (rose-gardeners disease)
• dimorphic
• very common saprobic fungus that decomposes plant
  matter in soil
• infects appendages and lungs
• Lymphocutaneous variety
• occurs when contaminated plant matter penetrates
  the skin
• pathogen forms a nodule
• spreads to nearby lymph nodes
• Potassium iodide orally
• Amphotericin B in unresponsive cases

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Lymphocutaneous Sporotrichosis
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2. Chromoblastomycosis

• highly visible verrucous lesions
• etiologic agents are soil saprobes with
  dark-pigmented mycelia spores
• Fonsecaea pedrosoi, Phialophora verrucosa,
  Cladosporium carrionii
• produce very large, thick, yeastlike bodies,
  sclerotic cells

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3. Mycetoma

• when soil microbes are accidentally implanted
  into the skin
• progressive, tumorlike disease of the hand or
  foot due to chronic fungal infection
• may lead to loss of body part
• caused by Pseudallescheria or Madurella

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Cutaneous Mycoses
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Cutaneous Mycoses

• Dermatophytoses
• infections strictly confined to keratinized
  epidermis (skin, hair, nails)
• 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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Examples of dermatophyte spores. (a) Regular,
numerous microconidia of Trichophyton. (b)
Macroconidia of Microsporum canis, a cause of
ringworm in cats, dogs, and humans. (c)
Smooth- surfaced macroconidia in
clusters characteristic of Epidermophyton.
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Dermatophytoses

• 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
• spread by exposure to public surfaces occurs
  between digits on soles
• Ringworm of nails
• tinea unguium
• persistent colonization of the nails of the hands
  feet that distorts the nail bed

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Ringworm Treatment

• Topicals
• ointments containing tolnaftate, miconazole or
  menthol camphor
• lamisil or griscofulvin 1-2 years

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Superficial Mycoses
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Superficial Mycoses

• Tinea versicolor causes mild scaling, mottling of
  skin
• Malassezia furfur
• White piedra is whitish or colored masses on the
  long hairs of the body
• Trichosporan beigelli
• Black piedra causes dark, hard concretions on
  scalp hairs
• Piedraia hortae

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Hortaea werneckii

• Tinea nigra
• Dematiaceous yeast-like hyphomycete found in
  tropical and subtropical areas
• Extremely halophilic environments
• Slow growing
• Pale colonies that turn olive black
• Reverse is black also
• Leathery culture

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Opportunistic Pathogens
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Candida albicans

• Candidiasis
• widespread yeast
• infections can be short-lived, superficial skin
  irritations to overwhelming, fatal systemic
  diseases
• budding cells of varying size may 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
• 20 of humans
• Account for 80 of nosocomial fungal infections
• Account for 30 of deaths from nosocomial
  infections

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Candida albicans

• Thrush
• occurs as a thick, white, adherent growth
• mucous membranes of mouth throat
• Vulvovaginal yeast infection
• painful inflammatory condition of the female
  genital region
• causes ulceration whitish discharge
• Cutaneous candidiasis
• occurs in chronically moist areas of skin and
  burn patients

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Cryptococcus neoformans

• Crypotcoccosis
• widespread encapsulated yeast
• inhabits soils around pigeon roosts
• common infection of AIDS, cancer or diabetes
  patients

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Cryptococcus neoformans

• infection of lungs leads to cough, fever, and
  lung nodules
• dissemination to meninges and brain
• causes severe neurological disturbance
• death

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Pneumocystis (carinii) jiroveci

• causes pneumonia (PCP)
• most prominent opportunistic infection in AIDS
  patients
• forms secretions in the lungs that block
  breathing
• can be rapidly fatal if not controlled with
  medication
• small, unicellular fungus
• pentamidine cotrimoxazole

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Aspergillus

• Aspergillosis
• 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
• amphotericin B nystatin

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Zygomycosis

• Zygomycota are extremely abundant saprobic fungi
• found in soil, water, organic debris, food
• Genera most often involved are Rhizopus, Absidia,
  Mucor
• usually harmless air contaminants
• invade the membranes of the nose, eyes, heart,
  brain of people with diabetes, malnutrition with
  severe consequences

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Miscellaneous Opportunists

• Any fungus can be implicated in infections when
  immune defenses are severely compromised
• Geotrichum candidum
• geotrichosis
• mold found in soil, dairy products
• primarily involved in secondary lung infections
• Fusarium species
• soil
• occasionally infects eyes, toenails, burned skin

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Fungal Allergies Mycotoxicoses

• Fungal spores are common sources of atopic
  allergies
• Asthma
• farmers lung
• chronic sometimes fatal allergy of agricultural
  workers exposed to moldy grasses
• teapickers lung
• Bagassosis
• condition caused by inhaling moldy dust from
  processed sugarcane debris
• bark strippers disease
• caused by inhaling spores from logs

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Fungal Allergies Mycotoxicoses

• Fungal toxins lead to mycotoxicoses
• usually caused by eating poisonous or
  hallucinogenic mushrooms
• aflatoxin toxic and carcinogenic
• grains, corn peanuts
• lethal to poultry and livestock
• Stachybotrys chartarum
• sick building syndrome
• severe hematologic and neurological damage