Micro review week 8 I dont know, Ive lost track

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Micro reviewweek 8 (?! I dont know, Ive lost
track)
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What 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.

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General 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

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How 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

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How 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

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Immune 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.

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Protazoa

• 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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Entamoeba 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

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Entamoeba
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Entamoeba
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Entamoeba 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

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Entamoeba 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

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Naegleria 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

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Acanthameba

• 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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Giardia 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

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Giardia
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Trichomonas 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

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Trichomonas
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Leishmania 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 ?

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Cutaneous 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

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Mucocutaneous 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

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Mucocutaneous leishmaniasis
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Disseminated 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

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Trypanosoma 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)

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Tse tse
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Trypanosoma brucei rhodiense
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African sleeping sickness
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Trypanosoma 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

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Reduviid bug
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Romanas sign
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Megacolon
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Sporozoa transmitted by ingestion

• Oocyst
• Isospora, Cyclospora, Cryptosporidium
• All acid-fast
• All transmitted fecal- oral via contaminated
  water, food
• All cause diarrhea
• Tachyzoite
• Toxoplasma

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Cryptosporidium

• 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

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Cryptosporidium
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Isospora

• 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

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Isospora
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Cyclospora

• 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

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Toxoplasma

• 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)

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Toxoplasmosis

• 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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Plasmodium

• 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

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Plasmodium

• 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

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Plasmodium 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

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P. 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

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P. malariae

• Uncommon in Africa
• Quatran synchrony (72 hours)
• Persists up to 30 years due to persistant blood
  forms (no hypnozoites)
• Rx mostly chloroquine sensitive

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Babesia 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

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Microspora

• 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

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A 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

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Which organ is most typically infected by
Leishmania mexicana?

• Skin
• Gut and skeletal muscle
• Gut
• Gut and CNS
• Blood and CNS

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Which organ is most typically infected by
Leishmania mexicana?

• Skin
• Gut and skeletal muscle
• Gut
• Gut and CNS
• Blood and CNS

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A 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

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A 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

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Which of the following can cause
hepatosplenomegaly in kids in Africa, India, and
Brazil?

• Leishmania mexicana
• Leishmania tropica
• Leishmania donovani
• Leishmania braziliensis
• Leshmania major

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Which of the following can cause
hepatosplenomegaly in kids in Africa, India, and
Brazil?

• Leishmania mexicana
• Leishmania tropica
• Leishmania donovani
• Leishmania braziliensis
• Leshmania major

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And now to wrap up viruses
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Sin 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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Rabies 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

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Filoviruses

• 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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arenaviruses

• 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

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One 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

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Virus can be commonly isolated from the sweat
glands of infected persons.

• Sin nombre virus
• Dengue virus
• St. Louis Encephalitis
• Ebola
• Yellow fever virus

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Virus can be commonly isolated from the sweat
glands of infected persons.

• Sin nombre virus
• Dengue virus
• St. Louis Encephalitis
• Ebola
• Yellow fever virus

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Potential 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

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Potential 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

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An 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

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An 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

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One 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