Title: Micro review week 8 I dont know, Ive lost track
1Micro reviewweek 8 (?! I dont know, Ive lost
track)
2What well cover today
- Parasites!!
- Introductory stuff
- GI protazoans
- Malaria, Babesia, Toxoplasma
- Blood Tissue flagellates
- And back to viruses for a minute
- The stuff I mistakenly covered last week -
Rabies, Hanta, Yellow fever, W. Nile, etc.
3General stuff
- Parasites can be
- Ectoparasites - live on outside of body
infestation (e.g. scabies) - Endoparasites - live inside body infection
- Must evade immune system somehow
- Humans, as hosts, can be
- Definitive harbor adult/sexual form
- Reservoir - animal with same form as we do
- Incidental - host not necessary to life cycle of
bugwe fall into this category, often - Intermediate harbor developing larval, asexual
form - Carrier harbor non-developing larval, asexual
form
4How we get infected
- Vectors
- Biologic parasite develops/multiplies
- Arthropod bite - break in skin, injects parasite
- Mechanical transmits unchanged parasite
- Ingestion
- Parasite-directed penetration
- E.g. Strongyloides - can just bore through
unbroken skin
5How they hurt us
- Toxic products
- Enzymes, amoebic pore, endotoxins
- Mechanical damage
- Block organs, pressure atrophy, migration through
tissues - Or we hurt ourselves - immune response
- Anaphylaxis, immune complexes, cell-mediated
6Immune evasion
- Antigenic variation
- common theme among parasites
- Molecular mimicry
- Concealment of antigens
- borrow host protein coat
- Being intracellular
- Limits types of immune responses available
- Suppressing our immune system
- Secrete soluble cytokine receptors, Ig binding
proteins, etc.
7Protazoa
- Free-living, single-celled, eukaryotic
- Ameba (sarcodina)
- Crawl around using pseudopods
- Reproduce by binary fission (asexual)
- Ciliates
- Reproduce by binary fission
- Flagellates
- Can live either in body tubes (gut or GU tract)
or invade into tissues - Reproduce by binary fission
- Sporozoa
- Sporogony - sexual
- Schizogony - asexual
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10Entamoeba histolytica
- Most prevalent in tropics
- Fecal-oral transmission via food contaminated
with cysts - In colon, transforms into trophozoite (motile,
feeding form) - Attaches to gut wall (via GIAP-lectin)
- Forms amoeba pore - cytolysis
- Proteolytic enzymes destroy mucosa (flask-like
ulcers), PMNs - Ingests RBCs (only protazoan that does)
- Occasionally, gets into portal circulation
11Entamoeba
12Entamoeba
13Entamoeba histolytica
- Intestinal amebiasis
- Majority are asymptomatic
- Non-dysenteric
- Intermittent diarrhea, abdominal pain, localized
ulcer - Dysenteric
- Bloody diarrhea, tenesmus, widespread ulcerations
- Complications
- Ameboma, stricture
- Perforation
- Cutaneous spread
- Postinfectious colitis
14Entamoeba histolytica
- Extraintestinal amebiasis
- Portal circulation - liver sets up camp
- liver abscess, subdiaphragmatic abscess
- Erodes through diaphragm into thoracic cavity
- Empyema, pericarditis, infection of lung
- Hematogenous spread to lung, brain, spleen
- Increased risk with immunosuppression
- Dx stool OP X3, sigmoidoscopy, Bx, serology for
invasive disease, EM - RBCs - Rx metronidazole drug to eliminate cyst passage
15Naegleria fowleri
- Free-living in fresh H2O
- Water-up-the-nose transmission in S. US,
inhalation in dust storms in Africa - Mainly healthy kids, young adults
- Meningoencephalitis
- Fever, HA, stiff neck, n/v, seizures, coma dead
in a week - Dx look for motile trophs in CSF
- Rx pretty much hopeless, but try Ampho B,
miconazole rifampin
16Acanthameba
- Free-living in soil, tap water can colonize
mouth nose - Spit-on-your-contacts transmission to eyes,
reaches CNS via upper respiratory tract - Meningoencephalitis
- Especially common fatal in immunosuppressed
necrotic granulomas in CNS - Keratitis uveitis - blindness
- In healthy hosts
- Dx cysts trophs in corneal scrapings, CSF
- Rx hard - topical miconazole, try itraconzole
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18Giardia lamblia
- fecal- oral ingestion of food and water
infected with cysts (or direct b/w people) - Converts to troph in gut, adheres to small bowel
wall - Rarely invades
- Causes malabsorption - steatorrhea
- Persists by Ag variation
- T-cell damage, increased cell turnover
- Giardiasis
- Asymptomatic in many (2/3 endemic, 1/3 epidemic)
- Sx more likely in kids, primary infection,
gastrectomy - Explosive, stinky, greasy diarrhea
- Can be chronic
- Dx - stool OP/Ag cysts, trophs with 2 nuclei,
falling leaf motility - Rx metronidazole
19Giardia
20Trichomonas vaginalis
- Troph form only - sexual transmission
- Attaches by axostyle doesnt invade
- Persists by Ag variation
- WomenVaginitis
- frothy discharge, dysuria, dyspareunia
- Men usually asymptomatic
- Occasional urethritis, prostatitis, epididymitis
- Prostatic secretions, urine movement clear
- Dx wet mount of vaginal or prostatic fluid
(Herky jerky movement), Ag detection - Rx metronidazole
21Trichomonas
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23Leishmania spp.
- Reservoirs rodents, humans, others
- Promastigote - infectious form
- Sandfly injects into humans phagocytosed by
macros, converts to - Amastigote - intracellular form
- Replicates by binary fission
- Replicates in RE system rupture, releases bugs,
invades new macros - Infected cells ingested by another sandfly
- Disease determined by host response
- Th1 - protective
- Th2 - more disseminated disease
- Dx Leishmania skin test - localized, -
disseminated artificial liquid culture, PCR - Rx pentavalent antimonial ampho B, azoles.
Resistance ?
24Cutaneous leishmaniasis
- L. tropica (urban) L. tropica major (rural)
- Mediterranean, Middle E, India, Africa
- Oriental sore - indurated, painless ulcer
- L. tropica single facial lesion can disseminate
cutaneously (like leprosy) or into viscera - L.t. major multiple leg lesions can have more
chronic infection - leishmaniasis recidiva - L. mexicana
- Central America
- Chicleros ulcer - single ear lesion, destroys
pinna - Lesions usually self-limiting, heal in 6 months
- Dx scrape ulcer base culture, serology skin
test
25Mucocutaneous leishmaniasis
- L. braziliensis
- Latin America
- Espundia
- Primary dermal ulcer at bite site satellite
lesions, lymphangitis, lymphohematogenous spread - Secondary 1-2 years later get ulceration of
mucus membranes of nose mouth slowly destroys
septum, soft palate, lips over 20-40 years - Complicated by bacterial infection
- Dx skin test
26Mucocutaneous leishmaniasis
27Disseminated leishmaniasis
- L. donovani
- E. Africa, India, S. America, Mediterranean
- Kala azar - disseminated visceral disease
- Th1 response is deficient, get chronic infection
of RE cells - see in malnourished kids
- Massive hepatosplenomegaly, abd pain, diarrhea,
weight loss, fever, severe anemia,
glomerulonephritis - Dx - skin test amastigotes in macros from Bx
- Even w/Rx, kills 10-25. Frequent relapses
28Trypanosoma brucei
- Vector tse tse fly
- Metacyclic trypomastigote is innoculated form
replicate in human blood stream, then picked up
by new fly - African Sleeping Sickness
- Acute chancre, fever, lymphadenitis, rash, HA
- Recurrent parasitemia escapes by Ag variation
- Parasites localize in small vessels of heart, CNS
- T. b. rhodesiense
- savannah tse tse, E. Africa
- cattle, antelope reservoir
- Subacute weakness, myocarditis, death in 6-9
months - T. b. gabiense
- riverine tse tse, W. Africa
- human reservoir
- Chronic gradual meningoencephalitis, death in
mo-yrs - Dx direct exam of blood CSF
- Rx Melaroprol, DFMO (really toxic)
29Tse tse
30Trypanosoma brucei rhodiense
31African sleeping sickness
32Trypanosoma cruzi
- Vector reduviid bug
- Epimastigote - in reduviid gut
- Trypomastigote - in reduviid poo
(extracellular) infectious form - Amastigote - in human cells
- Reservoir dog, cat, human, rodents, opposum
- Central/South America, S. US
- Chagas disease - American trypanosomiasis
- Chagoma at entry site - hard, red lesion local
replication - Invades blood, spreads to heart, smooth muscle,
glia - Recurrent fever, rash big liver, spleen, nodes
- Romanas sign unilateral conjunctivitis
periorbital edema - Chronic disease years later cardiac enlargement,
arrhythmias, megacolon, megaesophagus - Increased risk with immunosuppression
- Dx serology, direct exam of LN Bx, blood
- Rx acute - nitrofuramox, benznidazole
33Reduviid bug
34Romanas sign
35Megacolon
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37Sporozoa transmitted by ingestion
- Oocyst
- Isospora, Cyclospora, Cryptosporidium
- All acid-fast
- All transmitted fecal- oral via contaminated
water, food - All cause diarrhea
- Tachyzoite
- Toxoplasma
38Cryptosporidium
- Ubiquitous
- Human- human transmission, zoonoses
- Ingest oocyst - sporozoites invade brush border
- trophs in superficial vacuole - multiply
asexually - merozoites - Merozoites can invade new gut cells or form
gametocytes - fertilized - oocysts passed in
stool - Does NOT require embryonation to be infective
- Gastroenteritis
- Normal host self-limited diarrhea (? absorption)
- Compromised host unremitting diarrhea, weight
loss, fever - Dx stool OP
- Rx albendazole or paromomycin for
immunocompromised
39Cryptosporidium
40Isospora
- Found worldwide, esp in AIDS, Haiti
- Sexual asexual reproduction in intestinal
epithelium - Pass oocysts in feces
- Require embryonation in soil to be infective
- Gastroenteritis
- Can be asymptomatic - severe diarrhea
- Steatorrhea - mimics giardiasis
- Chronic intermittent diarrhea in
immunocompromised - Dx stool OP - ovoid oocysts
- Rx trimethoprim/sulfamethoxazole
41Isospora
42Cyclospora
- worldwide
- Inhabits upper bowel
- pass oocysts in feces
- Requires embryonation in soil
- Cyclosporiasis
- Asymptomatic - severe diarrhea
- More severe, prolonged in immunocompromised
- Dx stool OP - round oocysts
- Rx not usually needed
43Toxoplasma
- Alternating sexual asexual replication
- Definitive host cats
- Sporogony In GI tract, reproduce sexually -
oocysts passed in stool - Incubate in cat box for a few days - infective
- Intermediate host humans ( others)
- ingest - tachyzoites ( trophozoite) can infect
any nucleated cell, especially like lung, heart,
lymph, CNS, eye - replicate by schizogony - tissue cysts
- Transmission
- Kitty litter, cat feces
- transplacental (TOrches)
- eat tissue cysts in another intermediate host
(pork, beef)
44Toxoplasmosis
- Congenital
- 1st trimester - stillbirth
- Later - epilepsy, anemia, retardation, pneumo
- Reactivation chronic chorioretinitis - 2nd-3rd
decade - Acquired
- Primary infection
- asymptomatic
- Febrile lymphadenopathy
- Rarely, disseminated disease - myocarditis,
pneumo - Immune hosts cysts form intermittent rupture
- Relapsing chorioretinitis
- Encephalitis with immunosuppression (AIDS)
- Immunosuppressed get encephalitis, disseminated
disease - Dx serology, Bx - demonstrate trophs, cysts
- Rx pyrimethamine sulfadizaine for
disseminated, immunocompromised, pregnant
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46Plasmodium
- Vector Anopheles mosquito (definitive host,
sporogony) - Female mosquito ingests male female gametes -
sporozoites - injected into humans (intermediate
hosts) - Attach to penetrate hepatocytes
- Some transform into dormant hypnozoite - can
relapse - Non-dormant - schizogony - merozoites released
- Merozoites endocytosed by RBCs - ring shaped
trophozoite - rupture, releases more merozoites
- invade new RBCs or produce gametes - Gametes ingested by new mosquito
47Plasmodium
- Malaria is characterized by
- Rigors, fever - due to cytokine release with
rupture of RBCs - Fevers can become synchronous, especially in
semi-immune hosts (high temps kill schizonts) - May have paroxysms - cold then hot then wet
- Splenomegaly - infection of RBCs decreases
plasticity - increased removal in spleen - Anemia - due to increased clearance of RBCs in
spleen, intravascular hemolysis - Relapsing course - antigen variation, strain
diversity - Dx thin thick smears
- Rx chloroquine if sensitive
48Plasmodium falciparum
- Asia, Africa, Latin America tropics
- Malaria persists up to 1 year due to persistant
trophs in blood - Complication
- Rare paroxysms
- Synchrony - 36-48 hours
- Pernicious syndromes
- ARDS, shock, cerebral malaria, renal failure,
blackwater fever (due to ICs, hemolysis) - Dx banana shaped gametes, rings in RBCs IFA
- Rx often chloroquine resistant
49P. vivax P. ovale
- Subtropics, temperate Africa, Asia, L. Am
- Have hypnozoite (dormant) forms - can relapse
for up to 5 years - Tertian synchrony (48 hours)
- Dx rings in RBCs
- Rx mostly chloroquine sensitive need primaquine
to kill hypnozoites
50P. malariae
- Uncommon in Africa
- Quatran synchrony (72 hours)
- Persists up to 30 years due to persistant blood
forms (no hypnozoites) - Rx mostly chloroquine sensitive
51Babesia spp.
- Vector Ixodes tick (hard tick) - definitive host
- Intermediate hosts - deer, mice, cattle, us
- NE U.S.
- Like malaria, but doesnt infect liver cells
- Babesiosis
- malaise, non-periodic fever
- Complications Hemolytic anemia, renal failure
- At risk with asplenia, immunosuppression
- Dx thick thin smear - maltese cross
- Rx quinine
52Microspora
- Worldwide
- Primitive eukaryotes
- Lack mitochondria, peroxisomes, golgi
- Genera that can infect humans
- Encephalitozoon, enterocytozoon, nosema,
pleistophora, microsporidium - Fecal - oral, swimming pools?
- Causes diarrhea, biliary disease, pneumo, eye
infections, meningitis - Most severe in immunocompromised, esp HIV
- Dx stool OP spores are acid fast
- Rx Albendazole
53A couple of things
- transmitted by ingestion - cysts (except
toxoplasmaand even then, its sort of a cyst) - Parasites that cause diarrhea
- Entamoeba
- Giardia
- Cryptosporidium
- Isospora
- Cyclospora
54Which organ is most typically infected by
Leishmania mexicana?
- Skin
- Gut and skeletal muscle
- Gut
- Gut and CNS
- Blood and CNS
55Which organ is most typically infected by
Leishmania mexicana?
- Skin
- Gut and skeletal muscle
- Gut
- Gut and CNS
- Blood and CNS
56A man who has resided in rural West Africa until
he immigrated to the US 2 years ago comes to you
because of fever and chills. A blood smear shows
8 infected RBCs with early ring form
trophozoites and banana shaped gametocytes. The
most likely cause for his illness is
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium falciparum
- Plasmodium ovale
- Babesia microfti
57A man who has resided in rural West Africa until
he immigrated to the US 2 years ago comes to you
because of fever and chills. A blood smear shows
8 infected RBCs with early ring form
trophozoites and banana shaped gametocytes. The
most likely cause for his illness is
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium falciparum
- Plasmodium ovale
- Babesia microfti
58Which of the following can cause
hepatosplenomegaly in kids in Africa, India, and
Brazil?
- Leishmania mexicana
- Leishmania tropica
- Leishmania donovani
- Leishmania braziliensis
- Leshmania major
59Which of the following can cause
hepatosplenomegaly in kids in Africa, India, and
Brazil?
- Leishmania mexicana
- Leishmania tropica
- Leishmania donovani
- Leishmania braziliensis
- Leshmania major
60And now to wrap up viruses
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62Sin Nombre virus
- Hantavirus pulmonary syndrome
- High fever, cough, vomiting, pulmonary edema, CV
collapse - Endocytosis, fuses with endosome on
acidification, replicates in cytoplasm - Dx RT-PCR, IgM
- Rx ribavirin
- Found in Western US
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64Rabies virus
- Bullet shaped
- Transmitted by inhalation of aerosol, bite of
infected animal bat reservoir in NW, cats dogs - World-wide, year around
- Rabies
- Incubation weeks - months
- Prodrome 2-10 days - fever, HA, lethargy, pain
at bite site - virus is in CNS - Neurologic phase hydrophobia, encephalitis,
paralysis, death - Endocytosis, fuses w/endosome on acidification,
replicates in cytoplasm, released by budding - Carried to dorsal root - CNS - salivary glands
- Dx Negri bodies - cytoplasmic inclusions
- Rx vaccine, human If for post-exposre
- Inactivated vaccine
65Filoviruses
- Ebola marburg
- Fulminant hemorrhagic fever
- Flu-like Sx then n/v, diarrhea, rash
- Bleed from everywhere
- Death in up to 90, ebolamarburg
- Fast replication in cytoplasm, cell lysis
- Causes vascular injury, necrosis
- Dx Level 4 containment, RT-PCR, ELISA
- Rx quarantine, Ig, IFN
- Endemic in Africa
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67arenaviruses
- Transmited from rodents - people by eating
contaminated food, fomites, aerosols - LCM
- Lymphocytic choriomeningitis
- Febrile illness, meningitis
- Dx level 3 containment, serology
- No person-person spread
- Lassa fever
- Fever, coagulopathy, petechiae, hepatic/splenic
necrosis no vasculitis or CNS lesions - Dx Level 4 containment, urine serology
- Person - person by bodily fluid contact,
nosocomial - Infects macrophages, replicates in cytoplasm,
released by budding - Rx supportive
68One last thing
- Prions
- Kuru, CJD, others in humans - genetic,
spontaneous, food-borne (variant CJD) - Scrapie, BSE, etc in animals
- Normal protein (PrPc)
- Abnormal protein (PrPsc) - insoluble - amyloid
can induce misfolding of normal one - Spongiform encephalooathy
- Incubates up to 30 years
- Dementia, ataxia, aphasia, clonus, death
- Dx brain Bx
- Rx noneavoid mad cow burgers
69Virus can be commonly isolated from the sweat
glands of infected persons.
- Sin nombre virus
- Dengue virus
- St. Louis Encephalitis
- Ebola
- Yellow fever virus
70Virus can be commonly isolated from the sweat
glands of infected persons.
- Sin nombre virus
- Dengue virus
- St. Louis Encephalitis
- Ebola
- Yellow fever virus
71Potential etiologic agent of an acute pneumonia
causing respiratory insufficiency requiring
intubation in a 24 year old farmer in Walla Walla
- Sin nombre virus
- Dengue
- St. Louis encephalitis
- Ebola
- Yellow Fever
72Potential etiologic agent of an acute pneumonia
causing respiratory insufficiency requiring
intubation in a 24 year old farmer in Walla Walla
- Sin nombre virus
- Dengue
- St. Louis encephalitis
- Ebola
- Yellow Fever
73An intermediate host is
- An organism that carries the larval or asexual
form of the parasite without development - An organism harboring the adult or sexual stage
of the parasite - An organism that harbors the same parasite
species as humans - An organism in which the larval or asexual form
undergoes a process of development - An organism that is an unusual definitive host
unnecessary for the mainteneance of the parasite
in nature
74An intermediate host is
- An organism that carries the larval or asexual
form of the parasite without development - An organism harboring the adult or sexual stage
of the parasite - An organism that harbors the same parasite
species as humans - An organism in which the larval or asexual form
undergoes a process of development - An organism that is an unusual definitive host
unnecessary for the mainteneance of the parasite
in nature
75One more week to go in your first year!!!!
- Final Review Saturday May 31st
- 9-12 a.m.
- So if youre out dancing the night beforesuck it
up and show up anyway