Eukaryotic Pathogens: Fungal & Protozoa Flashcards
Fungi include
- yeasts: normally grow as single cells
- molds: form branching filaments called hyphae with or without septa (cross walls)
mycelia
visible masses formed by intertwining hyphae
common fungal pathogens
Most fungi (5.1 million) are harmless to humans
Fungi are also important in medicine as both
- agents of disease
- chemotherapy
only about ____ fungal species cause ______
50, disease
In healthy individuals the
incidence of serious fungal infections is
low
-certain superficial
fungal infections are fairly common (for example, Athlete’s foot)
Fungal infections can be
systemic
-reaching even the deepest of internal tissues
Pathogenic fungi
Common fungal pathogens include both Yeast and Molds
many pathogenic fungi are
Dimorphic
-they can exists as either Yeast or in Filamentous form (Dimorphism)
Fungi cause disease through three major mechanisms
- Inappropriate immune responses
- Toxin production
- Fungal Infections: Mycosis
some fungi trigger
immune responses
- result in allergic (hypersensitivity reactions)
- following exposure to specific fungal antigens
Aspergillus sp
common saprophyte -often found in nature as a leaf mold -produces potent allergens -triggering asthma attacks or other hypersensitivity reactions in susceptible individuals
Mycotoxins e.g. Aflatoxin
Fungal disease may occur from its production
-highly toxic and
are also carcinogenic
-can produce liver damage in humans including cirrhosis and liver cancer
-adults aren’t seriously affected by low-level
Mycosis
growth of a fungus on/or in the body
-fungal infections that range in severity from superficial to life-threatening
superficial mycoses
fungus infects only the surface layers of skin, hair or nails
-quite common
subcutaneous mycoses
infections of deeper layers of skin
-typically caused by
different fungi than superficial infections
-Treated with topical drugs.
Systemic mycoses
are the most serious categories of fungal infections
- characterized by fungal growth in internal organs of the body
-primary or secondary infections
-far less common
-primarily
affects the elderly or otherwise immune compromised patients
-target those of any age whose Immune System have
been impaired or destroyed
primary infection
otherwise normal healthy individual is infected with the fungal pathogen
-rather uncommon
secondary infection
occurs in a host that harbors a predisposing condition
-makes the individual more
susceptible to infection
mycoses
two extremes of fungal infections are the superficial and the Systemic mycoses
as people age
cell-mediated immunity slowly declines due to surgeries,
transplantations, immunosuppressive drug treatments for rheumatism and
autoimmune diseases, and the onset of other conditions, such as pulmonary decline, diabetes and cancer
Trichophyton
cause infections of the feet (Athlete’s foot)
- cause flaking and itchy skin
- easily transmitted by cells or spores of the pathogen
superficial mycosis can be treated with
topical antifungal creams or liquid aerosols
-Miconazole nitrate or Griseofulvin
jock itch
infection of groin, skin folds or anus
ringworm
fungal infection
-typically localized to scalp or extremities
-infection causes hair loss and inflammation like
reactions
dermatophytes
live on keratin
-found in skin, hair and nails
Sporotrichosis
occupational hazard of agricultural workers,
miners, gardeners, and others who come into close and continual contact with the soil
-causal organism: Sporothrix schenckii
Chromoblastomycosis
due to pathogenic fungal growth in both surface and subcutaneous skin layers
-form crusty, wartlike lesions on the hand or leg
Both Sporotrichosis and Chromoblastomycosis
can be treated with oral administration of Azoles
systemic fungal pathogens
normally live in soil, and humans become infected by inhaling airborne
spores that later germinate and grow in the lungs
histoplasmosis
caused by Histoplasma capsulatum
-primarily a disease of rural
areas in Midwestern states of the US
Coccidioidomycosis
caused by Coccidioides immitis
-more restricted to the desert regions of the southwestern US
Blastomycosis
caused by Blastomyces dermatitidis
-Prevalent in more tropical climates
Cryptococcosis
caused by the dimorphic yeast Cryptococcus neoformans
-can occur in virtually any
organ of the body
-major mycosis seen in HIV/AIDS patients producing fungal meningitis
Candida auris
drug resistant germ that spreads in healthcare facilities
- can cause bloodstream infection and even death
- often resistant to medicines
candida auris treatment
Echinocandins
- systemic infections in immunocompromised patients
- Inhibit 1,3 b-D glucan synthase (no present in mammals), the enzyme that forms Glucan polymers in fungal cell wall
Histoplasma capsulatum
Causative agent: Histoplasma capsulatum
-causes a systemic
endemic Mycosis called Histoplasmosis
-thermally dimorphic ascomycete
-can survive at 2 different temperatures
-considered a facultative intracellular fungi that circulates in the
reticuloendothelial system
-remains in a saprophytic Mycelial mold form, but
at mammalian body temperature grows as parasitic yeast
-found in temperate climates
Histoplasma capsulatum
endemic to Ohio, Missouri, Iowa, Indiana and Mississippi River valleys in the U.S
-can bind directly to the CD11/CD18 integrins on Macrophages
Histoplasma clinical features
In the lungs, inhaled Mycelial fragments and microconidia of Histoplasma capsulatum are ingested by
resident macrophages
pathogenic yeast phase
occurs inside the
macrophages, mostly due to the temperature change
Histoplasma capsulatum Treatment
-self limited in majority of cases
-Clinical symptoms develop mostly in immunocompromised
individuals
-Severe cases of Acute Histoplasmosis and All cases of Chronic and disseminated disease require treatment with antifungal drugs
-Amphotericin B followed with Itraconazole (inhibits the fungalmediated
synthesis of Ergosterol, via inhibition of lanosterol 14α-demethylase
-Fluconazole and Ketoconazole or a broad spectrum antifungal drug, Imidazole
ergosterol
sterol found in fungi
parasitism
symbiotic relationship between two organisms, the parasite and the host
-parasite derives essential nutrients from the host and may have little or no harmful effect on the
host
-parasitic infections can be visceral or infec blood
visceral
inducing vomiting, diarrhea, and other intestinal symptom
infection of blood
internal tissues
visceral parasitic infections
Amoeba and Ciliates: Entamoeba, Naegleria, and Balantidium
Entamoeba and Naegleria
belong to a large group of protists that move by extending
lobe-shaped pseudopodia, the Amoebozoa
Entamoeba Histolytica
pathogenic protist transmitted to humans primarily through contaminated water and sometimes food with
human feces
-Anaerobic and produces resistant cysts, which are the means of transmission
-Infection can be asymptomatic or lead to diarrhea and dysentery
ingested cysts
germinate to form amoebae that grow both on and in intestinal mucosa
dysentery
infection of the intestines resulting in severe
diarrhea with the presence of blood and mucus in the feces
-If untreated, invasive cells can invade the liver and
occasionally the lungs and brain
diagnosis: stool examination for Cysts and parasites
-Can be treated with amoebicidal drugs e.g. Metronidazole and/or Tinidazol, followed
by intraluminal agent (Paromomycin)
Naegleria fowleri
Known as “Brain-eating amoeba
-free-living amoeba found in soil and water runoff that can also cause amebiasis
-Infections usually result from swimming or bathing in warm or hot (up to 1150F, 460C) freshwater, soil-contaminated water
sources
-not in salt waters
-Enters the human body through the nose and burrows directly
into the brain
You _____ be infected with Naegleria fowleri by drinking
contaminated _____
can’t, water
Meningoencephalitis
extensive
hemorrhage and brain damage
initial symptoms of Naegleria fowleri
headache, fever, nausea, or
vomiting. Later symptoms can include stiff neck, confusion, lack of attention to people and surroundings, loss of balance, seizures, and hallucinations
diagnosis of Naegleria fowleri
requires observation of the amoebae in CSF
(Cerebrospinal fluid)
-Drug treatment is effective if infections are identified early
balantidium coli
ciliated intestinal human and swine parasite that
alternates between the cyst and trophozoite stage
-only known ciliated parasite of humans
-infections caused by cysts
-transmitted to humans through fecally contaminated food and water
-germinates in colon and infects mucosal tissues
balantidium coli symptoms
resemble those of amebiasis:
diarrhea, dysentery, abdominal pain, nausea, vomiting
-infected patient usually experienced a spontaneous recovery or may become an
asymptomatic carrier
three medications often used to treat Balantidium coli
Tetracycline, Metronidazole,
and Iodoquinol
infective balantidium coli
spherical
-diagnostically found in feces of infected individuals
non-infective balantidium coli
occasionally found in feces,
often found in tissue biopsis of infected individuals
Diplomonads & Parabasalids
Key genera: Giardia, Trichomonas
-unicellular, flagellated, non-phototrophic protists that lack chloroplasts
-Live in anoxic habitats, such as animal intestines, either
symbiotically or as parasites, conserving energy for fermentation
diplomonads
-Have two nuclei of equal size
– Have mitosomes, limited mitochondria lacking e- transport proteins and enzymes of the citric acid cycle.
– Cause of Giardiasis, a common waterborne diarrheal disease
parabasalids
Contain a parabasal body that gives structural support to the Golgi complex.
– Lack mitochondria, but have hydrogenosomes for anaerobic metabolism
– Live in the intestinal and urogenital tract as parasites or as commensal symbionts (Trichomona vaginalis, cause a sexually transmitted disease in humans: Trichomoniasis.
– Genomes lack introns, but is huge for a parasitic organism showing evidence of horizontal gene transfer from bacteria
Giardiasis
Giardia intestinalis (also called Giardia lamblia)
-It is a Flagellated anaerobic parasite
– Has mitosomes
– Produces highly resistant cysts
-It is typically transmitted to humans in fecally contaminated water
and causes an acute gastroenteritis, giardiasis
giardiasis characterized by
Explosive foul-smelling diarrhea, intestinal
cramps, nausea, weight loss, and malaise
– Many individuals exhibit no symptoms and can act
as carriers
What distinguishes diarrhea from giardiasis?
foul-smelling diarrhea and the absence of fecal blood
Giardia Intestinalis
causes a significant number of drinking water infectious disease outbreaks in the US
-thick-walled cysts are resistance to chlorine
-most outbreaks associated with water systems
that use only chlorination as a mean of water purification. -Water subjected to proper clarification and filtration
followed by chlorination or other disinfection should be free of giardia cysts.
-Most surface water sources (lakes, ponds, and streams) contain Giardia cysts as beavers and muskrats are carriers
(remember Raw Water
Trichomonas vaginalis
Causes a sexually transmitted infection, Trichomoniasis
-Flagellated anaerobic parasite
-Has hydrogenosomes (membrane enclosed organelle)
-Transmitted person-to-person by sexual intercourse
-Can survive on moist surfaces for several hours
-Can be transmitted by toilet seats, sauna benches,
and towels
-Can survive for up to a day in urine or semen
-asymptomatic in males
-Presents a yellowish vaginal discharge that causes a
persistent itching, and burning in women
-diagnosed by observation of the
motile protists in a wet mount of fluid discharged from
the patient.
What drug is used in treatment of Trichomonas vaginalis?
Antiprotozoal drug Metronidazole
Cryptosporidium, Toxoplasma, and Cyclospora are genera of
Parasitic coccidia (which group among the alveolates)
- Transmitted to humans through fecally contaminated food or water
- can trigger serious bouts of diarrhea, or in the case of Toxoplasma, serious internal organ damage
Cryptosporidium parvum
-Protist that lives as a parasite in warm-blooded
animals in particular cattle (a) Trophozoites.
-Produces thick-walled cells (oocysts) that are shed in the feces of infected animals
-The oocysts are transmitted in fecally
contaminated water
-Oocysts are highly resistant to chlorine and UV
radiation
-sedimentation and filtration
methods are most effective at removal
Cryptosporidium parvum treatment
Nitazoxanide for treatment of diarrhea
Alveolates (Apicomplexans)
Obligate parasites of animals that causes severe human diseases such as Malaria, toxoplasmosis and coccidiosis
- Characterized by nonmotile adult stages, nutrients are taken up in soluble form across the cytoplamic membrane as in bacteria and fungi
- Produce structures called sporozoites
- Contain apicoplasts
sporozoites
which function in
transmission of the parasite to a new host.
apicoplasts
chloroplasts that lack
pigments and phototrophic capacity, carry out fatty acid, and heme biosynthesis
toxoplasmosis
due to infection with Toxoplasma gondii
-Definitive host of the parasite: cats
-Symptoms: Most primary infections produce no
symptoms. The time between exposure to the parasite and
symptom development is 1 - 2 weeks.
-disease can
affect the brain, lung, heart, eyes, or liver.
Coccidiosis:
parasitic disease of the intestinal tract
produced by coccidian protozoa
- disease spreads from
one animal to another by contact with infected feces
Toxoplasma gondii (Toxoplasmosis)
Protist that lives as a parasite in warm-blooded animals
–Produces oocysts that are shed in the feces of infected animals
– The oocysts are transmitted by cats (obligate host)
-humans and other
animals are only incidental hosts.
-Also by undercooked meat: beef, pork or lamb
Toxoplasmosis is
mainly asymptomatic
-can damage eyes, brain, and other organs in
immune-compromised individuals
-first time infection with T. gondii in expectant
mothers can lead to birth defects in newborns
Toxoplasma gondii causative agent
protozoan intracellular parasite
Toxoplasma gondii entry and spread within the body
Oocytes are shed in the feces of cats and may survive up to 18 months in the environment.
- During this time they may be ingested by other animals such as rodents
-Within the intestine of these intermediate hosts, the
oocytes release sporozoites that invade the intestinal
epithelium and multiple to form Tachyzoites
Tachyzoites
may spread to local cells or pass via the lymphatics to regional lymph nodes and then to elsewhere in the body
-At each tissue Tachyzoites multiply to form tissue cysts
Toxoplasma gondii person to person spread
Humans can pass infection vertically from pregnant mother to fetus but are NOT a source of horizontal transmission
Toxoplasma gondii clinical presentation
pregnant mothers acquire Toxoplasma gondii infection
during their pregnancy there is a risk of transplacental
transfer of Tachyzoites
-If the infection had been acquired before pregnancy
there is the possibility that reactivation of tissue
cysts will release Tachyzoites during pregnancy
The greatest risk of congenital abnormality is with infections between __
and __ weeks gestation
10, 24
Hydrocephalus
a build-up of fluid in the cavities deep within the brain
microcephaly
disturbance
of brain development can stunt its growth
chorioretinitis
inflammation of the retina in the eye
-commonest manifestation of toxoplasma gondii
Toxoplasma gondii diagnosis
main diagnostic test is serology:
-Currently ELISA techniques are used to assay for anti-Toxoplasma IgG and IgM
-Formerly live or formalin-fixed tachyzoites were used in neutralization, immunofluorescence , and
agluttination assays
-useful in excluding T. gondii infection if negative on two occasions 3 weeks apart
Toxoplasma gondii management
Pyrimethamine and Sulfadiazine
-both are folate antagonist
effective in killing tachyzoites, but do not
clear tissue cysts
-Side effects: severe BM suppression, add Folic Acid
supplements
Management of toxoplasmosis during pregnancy
-is challenging: the drug used in pregnant women is Spiramycin (macrolide antibiotic: protein synthesis inhibitor)
Spiramycin:
does not cross placenta and is only used to kill tachyzoites before they can transfer to the fetus
Malaria
-protist disease caused by Plasmodium spp, member of the alveolate group.
-Several species of the protozoal genus cause malaria-like diseases in warm-blooded hosts
-Has a complex life cycle that includes female Anopheles mosquitoes as vectors
-WHO estimates that around 350 million people infected worldwide
– Each year over 1 million people die from Malaria
– Generally found in tropical and subtropical regions
– Four species of Plasmodium: P. vivax, P. falciparum, P. ovale and P. malariae -cause most human malaria.
– The most widespread disease is caused by P. vivax, whereas the most serious disease is caused by P. falciparum
Life cycle of Plasmodium requires
both a warm-blooded host and the mosquito vector
plasmodial life cycle in RBC
proceeds with repeated division, growth, and release of Merozoites:
results in the destruction of
the host RBC
-Vomiting and severe headache
defining clinical symptoms
of malaria
chills followed by fever of up to 400C (104F)
Malaria typically causes
Anemia and some enlargement of the spleen (splenomegaly
drugs used to prevent and treat plasmodium/malaria
- Chloroquine (kills merozoites within RBC but does not kills sporozoites) -Primaquine eliminates sporozoites of P. vivax and P. ovale that may remain in the liver cells
- treatment with both drugs effectively cures most malaria
Malaria can be controlled by
draining swamps, mosquito nets or eliminating mosquitoes with insecticides
Plasmodium spp causative agent
eukaryotic protozoan that infects the RBC of humans. –vector for Malaria is the female Anopheles mosquito.
Plasmodium spp Entry and spread within the body
transmission stage is the
sporozoite, which is injected into the bloodstream of a human when the female Anopheles mosquito takes a blood meal
plasmodium person to person spread
sporozoites are injected into an individual when an infected female Anopheles mosquito feeds and the whole cycle starts again
plasmodium Non-mosquito spread
malaria can also be transmitted through blood transfusion, hypodermic needle sharing or accidents, and from mother to fetus
epidemiology of malaria
Global incidence is estimated to be 350-500 million cases each year, -300 million
carriers of the parasite
-Most malaria infections and death occur in sub-Saharan Africa
-account for 80%
of all clinical cases and about 90% of all people that carry the parasite
What provides protection against the plasmodium?
Sickle cell trait (heterozygous for HbS
- G6PD deficiency confers resistance to malaria
- alpha and in a minor degree beta-Thalassemia
plasmodium diagnosis
-Blood film: the morphological appearance of the trophozoite (or gametocyte) can be used to identify the species of malaria.
-Serology: detection of antibodies or antigen (used for
rapid identification of acute cases.
-PCR or DNA probes.
plasmodium treatment
-Drug treatment of the patients with infection
+target the RBC stage of the infection e.g. Chloroquine x 3 days followed by Primaquine x 14
days).
-prevention and control of the vector (mosquito)
Euglenozoans
Key genera: Trypanosoma, Euglena
-Unicellular free-living or parasitic flagellated eukaryotes that includes the kinetoplastids and euglenids.
– Have a crystalline rod in their flagella
Kinetoplastids
Named for the presence of the kinetoplast, a mass of circular DNA (kDNA) present in their single large mitochondrion
-Live primarily in aquatic habitats feeding on
bacteria
-Some species are parasites causing serious diseases in humans
- Trypanosoma brucei causes African sleeping sickness, a chronic an usually fatal human
disease
-parasite lives and grows in the bloodstream later stages of the disease it invades the central nervous system
-transmitted from host-to-host by the tsetse-fly
American trypanosomiasis (Chagas disease)
Trypanosoma cruzi
- acute form usually goes unnoticed and may present as a localized swelling at the site of entry
- chronic form may develop 10 to 20 years after infection
- form affects internal organs
- Affected people may die from congestive heart failure.
- Vector: reduviid bug or triatomine bug (kissing bug
