• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/1158

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

1158 Cards in this Set

  • Front
  • Back
What is the #1 reason for visiting the doctor?
Respiratory infection
What is the #2 reason for visiting the doctor?
UTI
What is the most common nosocomial infection?
UTI
UTIs occur more often (30:1) in...
women
UTIs predispose patients to
sepsis and shock
UTI def'n
the microbial invasion of any tissue of the urinary tract, extending from the renal cortex to the urethral meatus
How many colonies must be present, per mL of urine, for asymptomatic bacteriuria to be dx?
10^5 colonies per mL urine
What is asymptomatic bacteriuria?
the colonization of the urinary tract in the absence of symptoms, with 10^5 colonies per mL urine, or more
What is cystitis?
an infection limited to the bladder and lower urinary tract.
How does cystitis present?
dysuria, frequency and urgency
What presents with dysuria, frequency and urgency?
Cystitis (limited to bladder and lower urinary tract)
What is dysuria?
Painful urination
What is pyelonephritis?
an inflammation and infection of the kidney
How does pyelonephritis present?
fever, chills, and flank pain, also possibly with symptoms of a lower urinary tract infection.
How does urethritis present?
pain, burning and discharge from the urethra
What is a likely cause of urethritis?
STDs
What presents as pain, burning and discharge from the urethra?
Urethritis
What presents as fever, chills and flank pain?
Pyelonephritis. Also possibly includes symptoms of a lower urinary tract infection
What are the peak times in a woman's life for getting UTIs?
Infancy, Preschool, "Honeymoon Cystitis," "Pyelitis of pregnancy," and then continue steady increase into old age
When do men tend to get UTIs?
Infancy, or elderly years (Prostatitis)
Which gender gets more symptomatic UTIs in middle age?
Women
Which gender gets more symptomatic UTIs in old age?
Men
Which gender gets more asymptomatic bacteriurias?
Women, throughout the lifespan
When might men get asymptomatic bacteriurias?
Only recorded in old age (>55yo)
Which types of bacteria are the most common causes of UTIs?
facultative bacteria of fecal origin
E. coli (90% of acute UTIs in normal patients)
Most common UTI bacteria in young women that are sexually active
E. coli
Staphylococcus saprophyticus
Most common UTI bacteria in elderly men with prostate problems
Enterococcus faecalis
Most common UTI bacteria in young boys
Proteus mirabilis
Most common UTI bacteria in patients with stones
Proteus mirabilis
Most common UTI bacteria in diabetics (esp. if poorly controlled)
Klebsiella
Group B Strep
Candida
Most common UTI bacteria in patients treated with antibiotics
Pseudomonas
Most common UTI bacteria in patients with underlying disease
Staph aureus
What % of UTIs are caused by ascending infection?
95%
What usually precedes an ascending UTI?
periurethral or introital colonization
What organisms are associated with ascending UTI?
E. coli
Other Enterobacteriaceae such as Proteus sp.,
Staphylococcus saprophyticus,
enterococci,
and Candida
What % of UTIs are caused by hematogenous route?
5%
What organisms are associated with the hematogenous UTI?
Staphylococcus aureus,
Cryptococcus neoformans,
Coccidioides immitis
and a number of viruses
What is the major facultative organism of the urinary tract?
E. coli
Which of E. coli's virulence factors contributes to its UTI pathogenicity?
K1 capsule
• Type 1 (Mannose Sensitive) fimbriae,
• Type 2 (Mannose Resistant) fimbriae,
• Hemolysin,
• Flagella,
• LPS,
• Aerobactin,
what property of K1 capsule contributes to its UTI pathogenicity?
antiphagocytic

E. coli virulence factor
Important UTI-relevant pathogenic feature of type 1 fimbriae
Type 1 (Mannose Sensitive) fimbriae enable colonization of the lower urinary tract
Important UTI-relevant pathogenic feature of type 2 fimbriae
allow colonization of the upper urinary tract.

E. coli virulence factor
Important UTI-relevant pathogenic feature of hemolysin
injures the bladder mucosa.

E. coli virulence factor
Important UTI-relevant pathogenic feature of flagella
allow the organism to be motile

E. coli virulence factor
Important UTI-relevant pathogenic feature of LPS
inhibits urinary tract peristalsis.

E. coli virulence factor
Important UTI-relevant pathogenic feature of aerobactin
siderophore which allows iron acquisition in the iron poor environment of the urinary tract

E. coli virulence factor
important virulence factors that contribute to Proteus mirabilis' UTI pathogenicity
Urease
Alkaline urine
Important UTI-relevant pathogenic feature of urease
splits urea into ammonia and carbon dioxide making the environment more hospitable. The pH can be increased from 7 up to 9.

Proteus mirabilis virulence factor
Important UTI-relevant pathogenic feature of alkaline urine
promotes the precipitation of phosphate, carbonate and magnesium. This
causes the formation of struvite stones that often form large staghorn calculi. The stones
are a great hiding place for Proteus, and they become a permanent source of bacteria,
which can produce more urease, which makes the urine alkaline and precipitates the
formation of more stones. These stones also lead to urinary stasis, which promotes
bacterial multiplication.
If you have alkaline urine, what organism likely caused the UTI?
Proteus mirabilis
Which of Klebsiella's virulence factors contributes to its UTI pathogenicity?
large capsule made in the presence of abundant glucose (i.e. uncontrolled diabetes)
Which of Staphylococcus saprophyticus' virulence factors contributes to its UTI pathogenicity?
adherence to uroepithelial cells
Most important host defense against UTI
normal urinary flow
Mechanical factors predisposing to UTI
short urinary tract (females)
close proximity to perianal and vulvar regions (females)
obstruction/flow impedance (stones, BPH, diverticula or strictures, neurogenic bladder)
reflux (esp. in kids)
foreskin (males)
urinary tract manipulation/mucosal injury (catheters)
Genetic factors predisposing to UTIs
-HLA type, P blood group phenotype and ABO/secretor status (on vaginal epithelial cells and mucus in females)
-density of receptors for the mannose sensitive or mannose resistant fimbriae
2 types of type 2 pili
P pili
X adhesions
What do P pili do?
bind to neutral glycolipids of the globoside series
What do X adhesins do?
bind to different globosides and are not well understood
Which type of fimbriae are associated with renal colonization?
Type 2
Hormonal factors predisposing to UTIs
Progesterone both dilates the upper collecting system and decreases peristalsis.
Postmenopausal estrogen deficiency
In pregnancy, the baby presses on the bladder
Immunologic/tissue factors predisposing to UTIs
renal medulla is a "desert" where complement and polys do not function
Behavioral factors predisposing to UTIs
sexual intercourse
anal sex
diaphragm/spermicide use
voiding practices
possibly carbonated beverages
Characteristics of urine protecting against UTIs
acidic pH,
high urea content,
extremes of osmolality
Host defenses against UTIs
normal urinary flow
mucosal integrity and bacteriocidal activity
urine (low pH, high urea content, extreme osmolality)
inhibitors of adherence.
Inhibitors of adherence to GU epithelia
Tamm-Horsfall protein
Bladder mucopolysaccharide
Secretory IgA
Prostatic secretions
UTI Dx
White Blood Cells in the Urine
And
105 bacteria per ml of urine on
culture
Cystitis Dx
White Blood Cells in Urine
And
102-103 bacteria per ml of urine
on culture if symptoms are
present
If you see white cell casts in someone's urine, it's indicative of...
kidney involvement
What are some problems and pitfalls in diagnosing UTIs?
• Poor collection methods
• Delayed culture
o In the absence of a urinalysis performed at the same time as
urine culture, interpreting the results of a positive urine culture
is dangerous!
• Vagaries of urine flow
• Prior antibiotic use
Untreated UTIs can cause these complications:
• Sepsis
• Low birth weight infants/premature labor
• Progressive renal parenchymal loss/renal scarring
• Renal calculi
• Perinephric/renal abscesses
• Prostatitis
Treatment of UTI
• Relieve obstructions
• Antibiotics that reach a high concentration in the urine (e.g., Septra, quinolones and cephalosporins).
• The duration of the therapy is dependent on the level and sites of infection, as well as complications.
o Cystitis is usually treated for 3 – 5 days.
o Pyelonephritis is usually treated for 2 weeks.
o Recurrent pyelonephritis and prostatitis require 6 weeks of treatment.
How long is cystitis usually treated for?
3-5 days
How long is pyelonephritis usually treated for?
2 weeks
How long is recurrent pyelonephritis and prostatitis treated for?
6 weeks
the Tamm-Horsfall protein is...
secreted by cells of the ascending loop of Henle.
has mannose containing side chain that bind to E. coli with type I pili (mannose sensitive pili) and S fimbriae.
what does the bladder mucopolysaccharide do?
decreases bacterial adherence
what do prostatic secretions do?
inhibit bacterial growth
Characteristics of a eukaryotic cell
a true nucleus,
multiple chromosomes,
membrane-bound organelles,
and 80s ribosomes
Which four kingdoms belong to Domain Eukarya
Animalia
Plantae
Protista
Fungi
What two domains used to make up Domain Prokaryotae?
Bacteria and Archaea
Which domain did Eukarya branch off from?
Archaea
Characteristic of cells in Domain Archaea
living in extreme environments
Which domain do all parasites belong to?
Domain Eukarya
Def'n of protozoa
single-celled, eukaryotic organisms
Which two protozoa phyla contain important human parasites?
Phylum Sarcomastigophora and Apicomplexan
How are protozoa subdivided?
Based on their means of locomotion.
What type of reproduction do protozoa undergo?
Asexual reproduction
Is the severity of the disease related to the infecting dose of protozoa?
No, because it multiplies inside the host.
Which 2 (of 3) subphyla of Sarcomastigophora are medically important?
Mastigophora
Sarcodina
Phylum Sarcomastigophora is composed of...
amoeboid and [animal-like] flagellated protozoans
What do Mastigophora use for locomotion?
Flagella
What do Sarcodina use for locomotion?
Pseudopods
Examples of Mastigophora
Giardia,
Trypanosoma
Trichomonas vaginalis
Leishmania
Examples of Sarcodina
Entamoeba histolytica
Dzs caused by Trypanosoma
African Sleeping Sickness and Chagas Dz
What causes African Sleeping Sickness and Chagas Dz?
Trypanosoma (brucei and cruzi, respectively)
All members of phylum Apicomplexan are...
intracellular parasites
What do Apicomplexans use for locomotion?
They are nonmotile.
How do Apicomplexans penetrate host cells?
Via a complex of organelles at the apex of their cells
How do apicomplexans reproduce?
capable of both sexual and asexual reproduction, have complex life cycles
Examples of Apicomplexans
Toxoplasma, Plasmodium, Crytosporidium, Cyclospora and Babesia
Which agent causes East African sleeping sickness?
Trypanosoma brucei rhodesiense
Which agent causes West African sleeping sickness?
Trypanosoma brucei gambiense
How is African sleeping sickness transmitted?
tsetse fly (Glossina species)
Why is African sleeping sickness produced in waves of parasitemia?
antigenic variation of the VSG (variant surface glycoprotein)
What is the natural history of African sleeping sickness?
CNS involvement in death
Which African sleeping sickness (East or West) progresses more rapidly (weeks to months, as opposed to months to years)?
East
Which type of African sleeping sickness (East or West) are tourist hunters more likely to get and why?
East, because that's where the game parks, and reserves are located.
What is another name for American trypanosomiasis?
Chagas disease
What transmits American trypanosomiasis?
Reduviid bug, aka kissing bug or assassin bug
Where is the Reduviid bug native?
South and Central America
How does the Reduviid bug infect a host?
biting and then defecating, usually when host is asleep.
Host rubs feces into skin, eyes, or mouth
Why does Chagas dz hit low income populations more than other populations?
The Reduviid bug lives in cracks in substandard housing.
How many stages does Chagas dz have?
3: acute, intermediate, chronic
Romana's sign is a sign of what dz?
acute infection with Chagas dz
What is Romana's sign?
acute swelling, often near one of the eyes, where a host has suffered a bite from the Reduviid bug and the feces have entered the mucosa.
What are symptoms of Chagas dz?
Romana's sign
fever
fatigue
weight loss
How long does it take for symptoms of Chagas dz to resolve?
4-8 weeks
What percentage of people with Chagas dz show symptoms in the acute phase?
1%
What percentage of people with Chagas dz develop the chronic phase (after 10-20 years)?
1/3
What happens in the intermediate phase of Chagas dz?
host has no sx
organism multiplying in macrophages in the GI and heart
What are symptoms of chronic infection with Chagas dz?
heart: enlargement and alteration in rate and rhythm, leads to heart failure and arrest
GI: megaesophagus and megacolon lead to constipation and difficulty swallowing
Tx of acute phase Chagas dz
nifurtimox and benznidazole : cure 50%
Tx of chronic phase Chagas Dz
supportive measures, symptom relief
Where do Leishmania live?
phagolysosome of macrophages
(they are strict intracellular pathogens)
How are Leishmania transmitted?
bite of the phlebotomine sand fly
What are the 3 classes of disease caused by Leishmania?
cutaneous leishmaniasis,
mucocutaneous leishmaniasis
and visceral leishmaniasis
Where is cutaneous leishmaniasis found?
the Old World and the New World
What about the Leishmania species that causes cutaneous leishmaniasis limits its growth to the skin?
Cannot grow at temperatures above 35 degrees
How does cutaneous leishmaniasis present?
one or more sores on the skin that heal spontaneously over time (months to years)
How long does it take a cutaneous leishmaniasis sore to heal?
months to years, but they heal spontaneously
What 3 organisms cannot grow above 35 degrees?
Leishmania (cutaneous type)
Mycobacterium marinum,
Sporothrix schenckii
Where is mucocutaneous leishmaniasis found?
Amazon forest and central plain of South America
What causes mucocutaneous leishmaniasis?
L. braziliensis
How does mucocutaneous leishmaniasis present?
single or several lesions,
perhaps a disfiguring metastasis of oronasopharyngeal mucosa...
(due to the low body temperature at this location and a defective CMI response)
What causes visceral leishmaniasis?
L. donovani complex
How does visceral leishmaniasis disseminate?
Via the blood stream, infecting the reticuloendothelial system (which, when infected chronically, loses its lymphocytic response)
What is Kala Azir?
Hindi for black poison
another name for visceral leishmaniasis
named after the dz that turns people's feet, hands, face and abdominal skin black
What is the untreated mortality rate for visceral leishmaniasis?
70-90%
Which species of Leishmania is capable of growth at core temperatures?
L. donovani (causes visceral leishmaniasis)
How is Babesiosis transmitted?
bite of the Ixodes tick
Where do Babesia species undergo their life cycle?
Inside RBCs
Some stages of Babesia species' life cycle resemble what other type of infection?
Plasmodium
except they differ in that in Babesiosis, no schizonts are produced
Manifestations of Babesiosis
most are asymptomatic
fever, chills, myalgia,
hepatosplenomegaly and anemia
Babesiosis is more severe in what type of patients?
Asplenic
Babesiosis is often misdiagnosed as...
malaria (in regions where malaria is prevalent)
Where in the U.S. is Babesia found?
Northeast (Nantucket island)
Tx for Babesiosis
clindamycin and quinine
Where is Cyclospora usually found?
tropical and subtropical regions
How is Cyclospora transmitted?
infected imported food
How does Cyclospora present?
Watery diarrhea that can be severe
Tx for Cyclospora
trimethoprim-sulfamethoxazole
How long does Cyclospora last, untreated?
12 weeks, but may relapse
Can Cyclospora be treated with trimethoprim-sulfamethoxazole?
Yes
Can Cryptosporidium be treated with trimethoprim-sulfamethoxazole?
No
What Kingdom are Helminths a part of?
Kingdom Animalia
How many worm phyla are there?
3
How many parasitic worm phyla are there?
2
Are helminthes single-celled or multicellular?
Multicellular (they are often large)
Where do helminthes multiply?
Outside the host (though they can live, metamorphose and travel within the host)
Which of the protozoa have a bimodal presentation in the population?
Helminthes.
Most have few worms and little dz, while some have high worm-loads and severe dz
Where is the highest helminth prevalence?
Developing countries,
in which infection leads to large economic impact
Describe flatworms
dorsoventrally flattened
have no body cavity
usually lack skeletal, circulatory, and respiratory systems
Which systems do most flatworms lack?
Skeletal
Circulatory
Respiratory
What are the 2 classes of flatworms?
Cestoda (tapeworms)
Flukes (trematoda)
Examples of tapeworms (Cestodas)
Taenia saginata
Taenia solium
Diphyllobothrium latum
Echinococcus
What are the 2 types of flukes (Trematodas)?
Blood flukes
Tissue flukes
Examples of blood flukes
Schistosoma mansoni
Schistosoma japonicum
Schistosoma haematobium
Examples of tissue flukes
Fasciola hepatica
Clonorchis (Opisthorchis)
Paragonimus westermani
Phylogeny of fasciola hepatica
Tissue fluke
Class Trematoda
Phylum Platyhelminthes
Kingdom Animalia
Phylogeny of Schisosoma haematobium
Blood fluke
Class Trematoda
Phylum Platyhelminthes
Kingdom Animalia
Phylogeny of Clonorchis
Tissue fluke
Class Trematoda
Phylum Platyhelminthes
Kingdom Animalia
Phylogeny of Taenia solium
Class Cestoda
Phylum Platyhelminthes
Kingdom Animalia
Phylogeny of Echinococcus
Class Cestoda
Phylum Platyhelminthes
Kingdom Animalia
Phylogeny of Diphyllobothrium latum
Class Cestoda
Phylum Platyhelminthes
Kingdom Animalia
Which 2 worm phyla (of the kingdom animalia) have parasitic members?
Phylum Platyhelminthes (flatworms)
Phylum Nematoda (roundworms)
Examples from Phylum Nematoda
Necator americanus
Ancylostoma duodenal
Ascaris
Anisakis
Strongyloides
Trichinella spiralis
Trichuris
Enterobius vermicularis
Dracunculus medinensis
Wuchereria bancrofti
Brugia malayi
Oncocerca volvulus
Phylogeny of Necator americanus
Phylum Nematoda
Kingdom Animalia
Phylogeny of Ancylostoma duodenal
Phylum Nematoda
Kingdom Animalia
Phylogeny of Ascaris
Phylum Nematoda
Kingdom Animalia
Phylogeny of Anisakis
Phylum Nematoda
Kingdom Animalia
Phylogeny of Strongyloides
Phylum Nematoda
Kingdom Animalia
Phylogeny of Trichinella spiralis
Phylum Nematoda
Kingdom Animalia
Phylogeny of Trichuris
Phylum Nematoda
Kingdom Animalia
Phylogeny of Enterobius vermicularis
Phylum Nematoda
Kingdom Animalia
Phylogeny of Dracunculus medinensis
Phylum Nematoda
Kingdom Animalia
Phylogeny of Wuchereria bancrofti
Phylum Nematoda
Kingdom Animalia
Phylogeny of Brugia malayi
Phylum Nematoda
Kingdom Animalia
Phylogeny of Oncocerca volvulus
Phylum Nematoda
Kingdom Animalia
What is Trichinella spiralis' main reservoir?
Domestic pigs
Where does Trichinella spiralis spend most of its life?
as an intracellular parasite
How is Trichinella spiralis transmitted?
its viable larvae are ingested in raw/undercooked meats.
inside the host, digestive enzymes release the larvae and they develop into adults
How is Trichinella spiralis disseminated?
Adult females shed larvae into bloodstream and lymphatics,
larvae encyst in muscle cells
How does Trichinella spiralis present?
light infections: asx
intestinal invasion: diarrhea, vomiting, ab pain
larval migration into muscle: fever, splinter hemorrhages, eosinophilia, rash, facial edema
Complications of Trichinella spiralis
myocarditis
pneumonitis
CNS infection
(life-threatening!)
Tx Trichinella spriralis
none specific,
but mebendazole administered early may reduce number of larvae
Where is Dracunculus medinensis found?
rural Africa
What is the maximum length Dracunculus medinensis can be?
3 feet
How is Dracunculus medinensis transmitted?
as larvae in copecods in drinking water
after ingestion, copecods (crustaceans) die and release the larvae
How is Dracunculus medinensis disseminated?
Larvae penetrate the stomach and intestinal wall, and mature/reproduce is abdominal cavity and retroperitoneal space
How does Dracunculus medinensis present?
A blister on the skin (usually legs) 1 year after infection, formed by female adult worms, which must be slowly extracted when the lesion comes in contact with water
What happens to adult female Dracunculus medinensis worms after reproduction?
They form blisters on legs that hopefully come in contact with water containing copecods (so that the larvae can infect them)
What happens to adult male Dracunculus medinensis worms after reproduction?
They die
What are 3 species of Filarial worms?
Wuchereria bancrofti
Brugia malayi
Onchocerca volvulus
In filariasis, where are the worms located?
Lymphatics and subcutaneous tissue
How many species of filarial worms infect humans?
8, but we only need to know the 3 that cause the most morbidity
How are filarial worms transmitted?
Larvae are transmitted by the bite of an infected arthropod
What is the vector for filarial worms?
Arthropod
How long can filarial worms live inside a human host?
several years
How do adult filarial worms infect their vector?
They produce microfilariae that infect arthropods when they bite the host
What filarial worms are the major causes of lymphatic filariasis?
Wuchereria bancrofti
Brugia malayi
Where is Wuchereria bancrofti found?
tropical regions
Where is Brugia malayi found?
Asia
How do Wuchereria bancrofti and Brugia malayi present?
mostly asymptomatic
some develop lymphedema and elephantiasis
Are antihelminthic agents effective against lymphatic filariasis?
They can kill the microfilariae (help prevent transmission), but the pathology is caused by the death of adult worms, so prevention of infection is the only effective treatment
Where does Onchocerca volvulus live within the host?
in nodules in subcutaneous tissue
Where is Onchocerca volvulus endemic?
Africa
parts of Latin America
parts of Middle East
How is Onchocerca volvulus transmitted?
black fly (Simulium)
How does Onchocerca volvulus present?
subcutaneous nodules
pruritis
dermatitis
ocular lesions that progress to blindness
In Africa, parts of Latin American and the Middle East, an antihelminthic agent is given yearly to kill the larval form of a helminth and its most serious manifestation. What is the helminth, the drug, and the manifestation?
Ochocerca volvulus
ivermectin
blindness
How do intestinal protozoa reproduce?
Asexually inside the host (therefore the infecting dose doesn't determine the severity of infection)
How does Cryptosporidium parvum reproduce?
Sexually (unlike all other intestinal protozoa)
Which three protozoa are intestinal (that we covered)?
Entamoeba histolytica
Giardia lamblia
Cryptosporidium parvum
Where in the world is Entamoeba histolytica found?
worldwide, highest incidence in developing countries?
Groups at risk of Entamoeba histolytica infection?
Male homosexuals
travelers
recent immigrants
institutionalized populations
What is the reservoir of Entamoeba histolytica?
Humans only
Are all Entamoeba strains pathogenic?
No, E. dispar is a morphologically indistinguishable zymodeme from the pathogenic E. histolytica
What is a zymodeme?
subtype of a species that can only be separated from other subtypes by their isoenzyme pattenrs
How is Entamoeba histolytica transmitted?
In fecal cysts contaminating water, food, or hands
Where do Entamoeba histolytica's trophozites migrate once ingested?
Large intestine
How long can Entamoeba cysts last in the external environment?
days to weeks (the walls of the cysts convey resistance to many environmental influences)
How long can Entamoeba trophozoites last in the external environment?
They can't! They must be encased in cysts in order to survive.
What are the possible courses of infection with Entamoeba, once the cysts have been ingested?
1) asx carrier with noninvasive infection (often E. dispar)
2) intestinal dz from trophozoites invading the mucosa
3) bloodstream dissemination to liver, brain, lungs
What makes up the cyst wall of Entamoeba histolytica?
Chitin
Are Entamoeba histolytica cysts resistant to chlorine and cold water?
Yes
Are Entamoeba histolytica cysts resistant to heat and dessication?
No
Are Entamoeba histolytica cysts removed by filtration?
Yes
What shape are the cysts of Entamoeba histolytica?
spherical, often with a halo
How many nuclei do mature Entamoeba histolytica cysts have?
4
How big are Entamoeba histolytica cysts?
12 to 15 micrometers
What are characteristic features of Entamoeba histolytica's nuclei in cysts?
centrally located karyosomes (nucleolus)
fine, uniformly distributed peripheral chromatin
Which species' trophozoites are the active, motile, feeding stage?
Entamoeba histolytica
Are Entamoeba histolytica's trophozoites aerobic?
No, they are anaerobic and LACK MITOs
Which species' trophozoites ingest RBCs (called erythrophagocytosis)
Pathognomic for Entamoeba histolytica (even differentiates it from E. dispar!)
What does Entamoeba histolytica do to tissue and how?
It causes necrosis (invasive dz), by the production of multiple virulence factors
How many nuclei do Entamoeba histolytica trophozoites have?
1
What are characteristic features of Entamoeba histolytica's trophozoites?
Nuclei: centrally placed karyosome
uniformly distributed peripheral chromatin
Cytoplasm: granular, "ground glass" appearance
How big are Entamoeba histolytica's trophozoites?
15 to 20 micrometers (range 10-60)
more elongated in diarrheal stool
How does Entamoeba histolytica present?
Asx
dysentery ("amebic dysentery") - usually protracted diarrhea
abscesses at distant sites (liver, lung, cutaneous) "extraintestinal amebiasis"
What organism causes "flask-shaped ulcers" on the colon wall (viewed on sigmoidoscopy)?
Entamoeba histolytica
Tx Entamoeba histolytica
metronidazole
Can Entamoeba histolytica trophozoites survive at high oxygen pressures?
No
Where are Entamoeba histolytica found in a cross-section of an intestinal infection?
At the margins between healthy and dead tissue
How do Entamoeba histolytica trophozoites reach the liver?
via portal vein
Dx of Entamoeba histolytica
SEROLOGY of abscess, find a cyst
Does Entamoeba histolytica infection provoke effective Abs?
No (Abs are not protective)
Does Giardia lamblia cause epidemic or endemic dz?
Both, worldwide
How is Giardia lamblia transmitted?
mostly person-to-person
water-borne (fecal/oral)
Groups at increased risk for Giardia lamblia infection
male homosexuals
kids in daycare
food handlers
mental institution patients
travelers to endemic regions (like St. Petersburg, Russia)
hikers and campers without proper water purification
Reservoirs of Giardia lamblia
humans
beavers in watershed areas
muskrats
dogs
other animals
How many trophozoites does each Giardia lamblia cyst yield?
2 trophozoites produced from each cyst
How do Giardia lamblia trophozoites multiply?
longitudinal binary fission
(either free in small intestine, or attached to mucosa by ventral sucking disk)
Are Giardia lamblia cysts resistant to water and chlorine?
Yes
Are Giardia lamblia cysts resistant to heat and dessication?
No
Are Giardia lamblia cysts removed by filtration?
Yes
What shape are Giardia lamblia cysts?
Oval
How many nuclei do mature Giardia lamblia cysts have?
4
How big are Giardia lamblia cysts?
8-12 micrometers
Are Giardia lamblia trophozoites aerobic?
No, they are anaerobic and LACK MITOs
Tx Giardia lamblia
Metronidazole
Which stage of Giardia lamblia is the active, motile feeding stage that causes pathology?
trophozoite
Do Giardia lamblia's trophozoites cause invasive dz or inflammation?
No
How do Giardia lamblia trophozoites attach to enterocytes?
Adhesive disk (ventral sucking disk)
Can Giardia lamblia trophozoites survive in the environment?
No
How many nuclei do Giardia lamblia trophozoites have? describe them
2, with a large, central karyosome (nucleolus)
Looks like eyeballs!
How big are Giardia lamblia trophozoites?
9-21 micrometers
How does Giardia lamblia present?
can be asx
can be protracted diarrhea and/or steatorrhea
can involve partial villous atrophy
can cause lactase deficiency (that can persist after treatment)
can cause Malabsorptive syndrome
What is Malabsorptive syndrome?
Steatorrhea, dissaccharide deficiency and B12 malabsorption
What causes malabsorptive syndrome?
Giardia lamblia
Dx Giardia lamblia
-find it in feces (found in 50% of an infected person's stools, 90% if you check 3 stools from different days)
-antigen detection kits (Abs against cyst or trophozoite antigens): ELISA or immunofluorescence assay
-duodenal sampling (string test)
What is the sensitivity and specificity of Giardia lamblia antigen detection tests?
Sensitivity: 90-99%
Specificity: 95-100%

(when compared to stool microscopy)
What causes traveler's diarrhea, seasonal diarrhea and diarrhea in daycare centers?
Cryptosporidium
Is Cryptosporidium obligately human or zoonotic?
Zoonotic
Cryptosporidium is a apicomplexan, which makes it related to
Toxoplasma gondii
How is Cryptosporidium transmitted?
fecal/oral
drinking/recreational water - outbreaks in waterparks, community swimming pools, day care centers,
food (chicken salad)
How does Crytosporidium reproduce?
Both sexually and asexually
How many Cryptosporidium sporozoites are contained in each sporulated oocyte?
4
What happens after Cryptosporidium sporulated oocytes are ingested?
Excystation release sporozoites, that parasitize intestinal epithelial cells, within which they multiply (schizogony or merogony) and then undergo sexual reproduction (gametogony)
What is schizogony/merogony?
asexual multiplication
What is gametogony?
sexual reproduction
What are male Cryptosporidium called?
microgamonts
What are female Cryptosporidium gametes called?
macrogamonts
Fusion of a macrogamont and microgamont produces an
oocyst, that sporulates in the infected host
Are oocysts of Cryptosporidium infective upon excretion?
Yes
Are Cryptosporidium oocysts resistant to chlorination?
Yes
What color do Cryptosporidium stain on modified acid-fast stain?
Bright red, often variable staining
How big are Cryptosporidium cysts?
3-5 microns
Which portions of the GI tract does Cryptosporidium mainly colonize?
Jejunum and ileum
Are Cryptosporidium trophozoites intra or extracellular?
Neither, really, they are covered by the intestinal microvilli, but not inside them
How does Cryptosporidium present in normal hosts? in immunocompromised?
normal host - mild, self-limited (weeks) watery diarrhea, anorexia, weight loss

immunocompromised - severe, protracted diarrhea, potentially fatal
Dx Cryptosporidium
find oocyst in stool with acid fast or auramine stain or monoclonal AB with IF
Tx Cryptosporidium
none for normal hosts,
for the immunodeficient, nitazoxanide (antiparasitic for children 1-11yo)
What causes malaria?
Protozoans from the Plasmodium genus
Which 4 Plasmodium species cause dz in humans?
Plasmodium falciparum
P. vivax
P. ovale
P. malariae
Also P. knowlesi, but only in Indonesia/West Pacific Islands
What Plasmodium species is limited in distribution to Indonesia and other Western Pacific Islands?
Plasmodium knowlesi

zoonotic from monkeys
Which species of Plasmodium causes the most severe (life-threatening) malaria?
P. falciparum
Which RBCs does P. falciparum infect?
All ages (therefore, high parasitemia)
Which RBCs do P. ovale and P. vivax infect?
Reticulocytes only
Which RBCs do P. malariae infect?
Mature RBCs
How does plasmodium falciparum cause tissue damage?
mature trophozoites and schizonts are sequestered in microvascular system
Which species of Plasmodium produce hypnozoites that are latent in the liver?
P. vivax and P. ovale
How long after infection can P. vivax and P. ovale relapse?
5 years
Duffy negative individuals are intrinsically resistant to what Plasmodium species?
Plasmodium vivax,
P. vivax uses the Duffy blood receptor to enter RBCs
How can you differentiate P. vivax and P. ovale?
P ovale can infect Duffy negative individuals but P. vivax cannot.
What characteristics do P. vivax and P. ovale share?
Appearance, life cycle, clinical presentation and treatment
What drugs are P. falciparum evolving resistance to?
Chloroquine and Fansidar (pyrimethamine, sulfadiazene)
What drugs are P. vivax evolving resistance to?
Chloroquine
Where are chloroquine-resistant P. vivax found?
Indonesia and other places in Asia
How long does P. malariae parasitemia persist?
40 years, always low grade
Which species of Plasmodium causes a glomerulonephritis?
P. malariae
Which Plasmodium species are less common?
P. ovale and P. malariae
Where is malaria endemic?
Almost every country in the Southern world, including Mexico and South, middle east, China, India and South, excluding Australia
When was malaria first documented?
China in 1700 B.C.
What % of the population lives in malaria-endemic parts?
40%
What % of those infected with malaria are symptomatic?
20%, making the other 80% reservoirs for continued transmission
Out of the 300-500 million affected with malaria each year, how many die?
1.5-2.7 million
When do children start showing malaria symptoms in endemic areas?
between 4-8 months of age
Sx that a child is infected with malaria
fever, irritability, poor feeding, vomiting, diarrhea, convulsions
What % of malaria-infected pregnant woman pass the dz to the placenta?
30%
Young children (less than 5 years old) with malaria are more or less likely to die from the dz than older children and adults?
More likely
What % of nonimmune, malaria-infected pregnant women deliver an infected baby?
10%
What % of semimmune, malaria-infected pregnant women deliver an infected baby?
less than 3%
Are primigravid (1st pregnancy) or multigravid (not 1st pregnancy) pregnant women more susceptible to severe malaria?
Primigravid are more susceptible, unless they have AIDS, in which they are equally susceptible
Why are multigravid pregnant women less susceptible to severe malaria than primigravid pregnant women?
Acquisition of humoral immunity against PfEMP1 variants that mediate binding to chondroitin sulfate A in the intervillous spaces.
What is the most common acute febrile illness that is imported?
Malaria
T/F: Malaria manifests within 6 months of returning from an endemic area
False, it can manifest months to years after leaving an endemic area
T/F: Malaria prophyllaxis prevents infection
False, it is not foolproof
T/F: Malarial Dz is often more severe in chronically exposed people than a traveler
False
Methods of malaria transmission
mosquitoes
local infection
blood transfusion
IVDA (IV drug abuse)
How many stages do Plasmodium species have, what are they and where do they occur?
Two
1. Asexual (schizogony) in human liver and RBCs
2. Sexual (sporogony) in Anopheles mosquito
What is the vector of Plasmodium?
Anopheles mosquito
When in the day do most malaria-transmitting mosquito bites occur?
between dusk and dawn
Which gender of Anopheles mosquitoes bite humans, and what does the other gender subsist on?
Females bite,
males subsist on nectar
Which species of mosquito transmits San Diego's malaria?
Anopheles freeborni
Which form of Plasmodium is passed to humans from mosquitos?
Sporozoites
What human organ does Plasmodium infect?
Liver - sporozoites infect hepatocytes and proliferate into merozoites (that are released to invade RBCs)
Describe the Plasmodium asexual cycle
In RBCs, merozoites develop into trophozoites that eat Hb, mature, and turn into schizonts that release more merozoites
What form of Plasmodium invade RBCs?
Merozoites
Describe the Plasmodium sexual cycle
Within a mosquito, gametocytes undergo genetic recombination (and potential spread of acquired drug resistance)
What are dormant Plasmodium called?
Hypnozoites
Which species of Plasmodium have a dormant hynozoite stage?
P. vivax and P. ovale
What pathogenic ability is conferred to P. vivax and P. ovale by their hypnozoites?
Recurrent infection (relapse)
Where are hypnozoites stored?
Liver
Which cycle (sexual or asexual) involves spread of acquired drug resistance?
Sexual
Which Plasmodium life cycle (sexual or asexual) involves antigenic variation?
Asexual
Which species of Plasmodium display antigenic variation?
P. falciparum for sure, likely other species
In what forms do Plasmodium adhere to the postcapillary endothelium (causing microvascular dz)?
mature trophozoites and schizonts are peripherally sequestered
Which organs suffer from Plasmodium microvascular dz?
Brain, heart, mesentery, lungs, kidney, placenta
What receptor does Plasmodium falciparum use to enter cells?
Sialic acid, though it also has a sialic acid-independent entry mechanism
Which form of Plasmodium is the "ring stage"?
trophozoites
Which type of Plasmodium replication (schizogony or sporogony) occurs in mosquitoes?
Sporogony
What is a motile, elongated Plasmodium zygote called?
Ookinetes
Where do Plasmodium microgametes and macrogametes generate zygotes?
stomach of mosquitos
Where do Plasmodium ookinetes develop into oocysts?
Midgut wall of the mosquito
After the oocysts release sporozoites within the mosquito GI tract, where do the sporozoites migrate?
Mosquito's salivary glands
How many smears for Plasmodium should come back negative before ruling malaria out of a diagnosis?
At least twice a day for at least 3 days
What additional treatment is required for P. ovale and P. vivax compared to other Plasmodium species?
tissue schizonticide (since they have a hepatic phase)
What % of malarial infections contain multiple Plasmodium species?
5-7%
Which Giemsa smear (thick or thin) is more sensitive to detecting Plasmodia?
Thick (because they can be concentrated 10-15 fold)
Which Giemsa stain (thick or thin) is better for identifying Plasmodium morphology?
Thin
Which species of Plasmodium shows Schuffner's dots?
P. vivax
Which species has banana-shaped gametocytes?
Plasmodium falciparum
What does the ring trophozoite of Plasmodium falciparum look like?
Thready ring, multiple infections, double dots, applique forms
If ameoboid trophozoites and schizonts of a Plasmodium species are seen on peripheral blood smear, which species can be ruled out?
Plasmodium falciparum, because its trophozoites and schizonts are stuck inside the body clogging microvasculature
How many merozoites are contained in a P. vivax schizont?
12-24 merozoites
What shape are the gametocytes of P. vivax?
round to oval and fills the cell, containing scattered brown pigment
What techniques are available for malaria dx?
Microscopic ID
Ag capture kits
PCR based techniques
Fluorescent techniques
Serological tests
How do malarial Ag capture kits work?
dipstick test from finger-prick blood sample
results in 10-15 minutes
expensive
low sensitivity for less concentrated (<100 parasites per mL)
How do PCR based malaria tests work?
detect DNA or MRNA sequences specific to Plasmodium
very high (near 100%) sensitivity and specificity
take hours and technical expertise to perform
expensive
When are PCR based malaria tests most useful?
Genotyping to distinguish new from recurrent infection
What are the disadvantages of fluorescent malaria tests?
Less sensitive and specific than microscopy
low sensitivity for less concentrated (<100 parasites per mL)
cannot differentiate species
require expensive microscope and skilled personnel
What are malarial serological tests useful for?
Epidemiological, but not diagnostic purposes
What are the stages of classic malarial periodic fevers paroxysms?
prodrome
cold stage
hot stage
sweating stage
Sx of malaria prodrome stage
malaise,
myalgias,
viral-like syndrome
Sx of malaria cold stage
shaking chills
Sx of malaria hot stage
102-104 degree fever for several hours
tachycardia
hypotension
headache
nausea
abdominal pain
delirium
Sx of malaria sweating stage
diaphoresis
resolution of fever
severe fatigue
sleep
How long is the cycle of P. vivax, P. ovale, and P. falciparum?
48 hours
How long is the cycle of P. malariae?
72 hours
What are the classic sx of malaria when paroxysms do not occur?
intermittent, irregular fever
anemia
jaundice
splenomegaly
Does malaria occur more often with paroxyms (synchronous infection) or without them (asynchronous infection)?
Without them (asynchronous)
What lab findings suggest malaria?
Elevated BUN/Cre
Hyponatremia
Hypoglycemia
Evidence of hemolysis
Proteinuria
Bilirubin in urine
Anemia
Thrombocytopenia
Infected RBCs
Reticulocytosis
What infection is suggested by Hypoglycemia, evidence of hemolysis,
Proteinuria, Anemia, and Reticulocytosis?
Malaria
All species of malaria can cause which clinical symptoms?
Anemia, dehydration, electrolyte abnormalities, and acute splenic rupture
What complications of malaria can occur with any of the species?
Anemia,
dehydration,
electrolyte abnormalities,
acute splenic rupture
Which complications of malaria are specific to P. falciparum?
cerebral malaria (impaired state of consciousness c or s seizures - 20-30% mortality)
pulm. edema and ARDS - 15% mortality)
severe renal failure
Blackwater fever
What is the mechanism for P. falciparum-induced pulmonary edema and ARDS?
sequestration of parasitized RBCs in the lung.
increased leakage from pulm. vasculature induced by cytokines
What causes the severe renal failure associated with P. falciparum infection?
microvascular dz,
hypovolemia,
hemolysis
What is Blackwater fever?
assoc. with P. falciparum infection
large amounts of Hb and malarial pigment in urine making it appear black
How does malaria cause anemia?
Hemolysis during schizogony
Absorption of Ab on non-parasitized RBCs (lysis mediated by complement)
Suppression of hematopoiesis by cytokines
G6PD def-associated hemolysis
How does malaria cause hypoglycemia?
decreased glycogen stores due to decreased food intake, glucose consumption by plasmodia and TNF-alpha or quinine-stimulated hyperinsulinemia
Why are P. falciparum infections more severe than infections from other Plasmodium species?
hyperparasitemia
microvascular dz
What causes P. falciparum to sequester in the microvasculature?
secreted proteins like PfEMP1 that bind endothelial receptors (CD36, ICAM-1, CSA on placenta),
PfEMP1 is concentrated on RBC membrane in knobs that cause Ag variation and cytoadherence
Besides causing pathology, what advantage is conferred to P. falciparum by its peripheral sequestration?
Prevents sequestration in the spleen
How does P. falciparum evade immune detection?
Antigenic variation via PfEMP and Rifins
What factors should be considered in choosing a schizonticide for treating malaria?
expected resistance pattern of organism,
severity of infection,
patient's immune status
What does supportive care consist of for severe cases of malaria?
monitor for complications (hypoglycemia, anemia, seizures, septicemia, renal failure, acidosis, resp. failure)
gentle IV rehydration (if low risk of pulm. edema)
possibly blood transfusions, hemodialysis, mechanical ventilation, BDZ therapy and ABX
What confers complete immunity to malaria?
Nothing
What type of immunity develops in response to repeated P. falciparum infection?
Ab (against blood stages)
and cell-mediated (against liver and blood stages)
What type of Abs confer anti-disease immunity to malaria?
Ab to parasite toxic factors (glycosylphosphatidyl inositol anchors)

prevent clinical illness
What type of Abs confer anti-infection immunity to malaria?
Abs to parasite proteins

correlates to the ability to clear parasites after inoculation (prevent parasitemia)
T/F: Immunity to one species of Plasmodium confers immunity to all species
False, immunity is species specific
T/F: Immunity to malaria fades after clearing the infection
True, fades within weeks to months
What genetic conditions protect against severe (life-threatening) malaria?
sickle cell anemia
lack of duffy blood group
G6PD def
Thalassemias
South East Asian ovalocytosis
Candidate Ags for malaria vaccine
circumsporozoite protein (CSP)
merozoite surface protein 1 (MSP-1)
erythrocyte-binding antigen 175 (EBA 175)
apical-merozoite Ag (APA-1)
gametocyte Ags (Pfs25)
pre-erythrocyte liver-stage Ag 3 (LSA-3)
Factors to consider in choosing chemoprophyllaxis for malaria
is there significant risk to warrant it?
patient's drug allergies
whether they are at risk for drug-resistant malaria
Countries where there is not a risk of contracting drug-resistant P. falciparum malaria
Dominican Republic
Haiti
Central America north of Panama Canal
Egypt
Middle Eastern countries
What is the time course for malaria chemoprophyllaxis?
at least 1-2 weeks before travel to endemic areas (so any side effects can be evaluated and treated before departure),
continuing through trip,
4 weeks after leaving endemic area
What is the malaria chemoprophyllaxis regimen for travel to areas NOT at risk for chloroquinine-resistant P. falciparum?
Once weekly chloroquine
What is the malaria chemoprophyllaxis regiment for travel to areas at risk for chloroquinine-resistant P. falciparum?
Mefloquine
Which schizonticide prevents P. vivax and P. ovale relapses?
Primaquine
Which population should primaquine NOT be used?
G6PD def (causes severe hemolytic anemia)
What herbal remedy is used to treat malaria?
Artemisinin (Qinghaosu, Chinese wormwood)
What medications make up Fansidar?
Pyrimethadine and sulfadoxine
What are the 9 drugs used for malaria-related treatment?
Chloroquine
Primaquine
Artemisinin
Quinine/quinidine
malarone
tetracycline/doxycycline
Fansidar
Proguanil (not available in US)
Clindamycin
How can you prevent malaria?
avoid contact with mosquitoes from dusk to dawn (use bed nets, pre-treat with permethrin or deltamethrin)
cover up with clothing and mosquito nets
insect repellant (esp. DEET 30-35%, and Permethrin for clothes and skin)
The common name for Nematodes
Roundworms
Common name for Trematodes
Flukes
Common name for platyhelminthes
Flatworms
Common name for Cestodes
Tapeworms
Common name for Schistosomes
Blood flukes
What are the 2 major types of Helminths?
Nematodes (roundworms) and
Platyhelminthes (flatworms)
What are the 2 types of platyhelminths?
Trematodes (flukes) and
Cestodes (tapeworms)
What are the 2 types of Trematodes?
Schistosomes (blood flukes) and
Tissue flukes
How are Nematodes divided?
Whether migration in the body is a part of the life cycle
Which Nematodes migrate in the body?
Ascaris lumbricoides
Ancyclostoma/Necator
Strongyloides stercoralis
For which Nematodes is Migration in the body not part of the life cycle?
Trichuris trichiura
Enterobius vermicularis
Anisakis species
Examples of Schistosomes
Schistosoma mansoni
Schistosoma haematobium
Schistosoma japonicum
Examples of tissue flukes
Clonorchis sinensis
Paragonimus westermani
Fasciola hepatica
Examples of Cestodes
Taenia solium (pork tapeworm)
Taenia saginata (beef tapeworm)
Diphyllobothrium latum (fish tapeworm)
Echinococcus (dog tapeworm)
What is the pork tapeworm?
Taenia solium
What is the beef tapeworm?
Taenia saginata
What is the fish tapeworm?
Diphyllobothrium latum
What is the dog tapeworm?
Echinococcus
(relevant) Phylogeny of Schistosoma japonicum
Animalia
Helminths
Platyhelminthes
Trematodes (flukes)
Schistosomes (blood flukes)
Phylogeny of Enterobius vermicularis
Helminths
Nematodes that do not migrate in body
Phylogeny of Ancyclostoma/Necator
Helminths
Nematodes that migrate in the body
Phylogeny of Echinococcus
Helminths
Platyhelminthes
Cestode
(dog tapeworm)
Phylogeny of Paragonimus westermani
Helminths
Platyhelminthes
Trematodes
Tissue fluke
Phylogeny of Fasciola hepatica
Helminths
Platyhelminths
Trematodes
Tissue fluke
How long are helminthes?
Wide variation in size
Strongyloides is just visible to naked eye
while Dracunculus is 60 cm long
Do helminths elicit protective immunity?
Yes, but ONLY after many years/decades
AND developmental stages have stage-specific antigens
Do helminthes replicate within the host?
No, though they can persist long-term.
Exception: Strongyloides
Only 1 helminth can replicate in the host- which one?
Strongyloides
Why is treating helminth infections difficult?
Antibiotics inhibiting macromolecular synthesis are not effective
How are helminths distributed in human communities?
Aggregated distribution (minority of people harbor majority of worms)
Can helminth infections be fatal?
No, they just cause morbidity
Does severity of worm burden correlated with severity of dz?
Yes
What type of immune cells are abundant in a helminth infection?
Eosinophils
Long term helminth infection can exacerbate... what?
Poor nutrition
Is host response to helminths adaptive?
No, it can itself mediate damage at sites of parasite accumulation
What chronic sequelae occur from persistent schistosomiasis?
Hepatosplenic dz
What chronic sequelae occur from persistent filariasis?
Lymphedema
Elephantiasis
What does elephantiasis result from?
Chronic filariasis
What is concomitant immunity and what type of infection causes humans to have it?
Concomitant immunity is when a host is protected against newly invading larvae while tolerating an established adult worm load.
Occurs with helminth infections
can macroparasites exhibit antigenic variation and divergence?
Only able to generate new antigen variants very slowly
(generation time is almost equivalent to host's generation time)
How do macroparasites achieve genetic heterogeneity?
genetic variation in the human community (where a few hosts are predisposed to heavy infection)
How do microparasites achieve genetic heterogeneity?
antigenic variation and divergence
What does the acquisition of immunity to helminths depend on?
Age
Differences in exposure
Susceptibility to infection
Ability to mount effective immunological responses
What defense strategies to helminths have?
-avoid initial induction of the damaging host response
-neutralize selected parts of immune system
-short term defenses (physical, or antioxidant enzymes)
What strategies allow parasites to avoid the initial induction of the damaging host response?
-uptake of host antigens
-interfere with Ag processing to induce immunological unresponsiveness/tolerance
Which helminths take up host antigens and what antigens do they take up?
Schistosomes
host MHC and decay-accelerating factor?
Which helminths interfere with Ag processing to induce immunological unresponsiveness/tolerance?
Filaria worms and Ascaris
release cystatin-like molecule and aspartic proteinase inhibitor which blocks Ag processing
Which helminths have immunoglobulin-cleaving proteases?
Dirofilaria, Fasciola and Schistosoma
Which helminths interfere with complement action?
Taenia
Echinococcus
How does Taenia interfere with complement action?
releases highly sulfated proteoglycans which activate complement in fluid phase
How does Echinococcus interfere with complement action?
secretes elastase inhibitor that blocks neutrophil attraction by C5a
How do Taenia and filaria worms interfere with specific T cell subsets?
They release prostacyclin and PGE2, which may inhibit T cell proliferation
Examples of physical (short-term) defenses of helminths
thick tegument and cuticle
Fasciola rapidly turns over its surface glycocalyx
Which enzymes are antioxidant?
Superoxide dismutase
Glutathione S-transferase
Which Platyhelminths are hermaphrodites?
All except Schistosomes (which have separate sexes)
Blood fluke hosts
Snail and human (both during their life cycle)
Tissue fluke hosts
Snail, human, and another (either fish, water plants, or crustaceans)
Describe life cycle of Schistosoma
Eggs in feces/urine
Eggs hatch, releasing miracidia
Miracidia inhabit snails as sporocysts
Cercariae released, free-swimming into water
Penetrate human skin (becoming schistosomulae when lose tail) and migrate to portal blood venules and mature
Paired adult worms lay eggs that circulate in liver, shed in stool
how do Schistosoma enter humans?
Through skin while human is in infected water
Where does each Schistosoma species migrate once inside human host?
mesenteric venules
(S. japonicum - sup. mesenteric veins draining Small Intestine)
(S. mansoni - sup. mesenteric veins draining large intestine)
(S. haematobium - venous plexus of bladder)
Which gender of Schistosoma worm is larger?
Females (7-20mm)
Where do female Schistosomes deposit their eggs?
small venules of the portal and perivesical system
Which Schistosomes are excreted in feces?
S. mansoni
S. japonicum
Which Schistosomes are excreted in urine?
S. haematobium
What are the stages of Schistosome development called before and after human entry?
Before: cercariae (with tails in water)
After: Schistosomulae (no tails)
Where within the human host do Schistosomes mature?
Portal blood in liver
What are the stages of Schistosome development called before, during and after snail infection?
Before: Miracidia
During: sporocysts
After release: Cercariae
Where is Schistosoma mansoni endemic?
Central Africa, Egypt, South America and Caribbean
At-risk populations for acute Schistosoma mansoni infection
Tourists to an endemic area
How does Katayama Fever present and what causes it?
Fever, anorexia, abdominal pain, lymphadenopathy

Schistosoma mansoni
Which stage of Schistome development is responsible for chronic Schistosoma mansoni infection?
Eggs
Sx of chronic Schistosoma mansoni infection
colonic polyps
granulomas in liver leading to pipestem fibrosis
(portal hypertension with variceal bleeding due to presinusoidal block in portal flow)
ascites
gross splenomegaly
growth retardation
Schistosoma mansoni dx
finding egg in feces
Schistosoma tx (all 3 species)
Praziquantel
Which species displays eggs with a lateral spine?
Schistosoma mansoni
What type of immunity do the eggs of Schistosoma mansoni induce?
Cell-mediated immunity
(formation of granulomata in bowel and liver)
Where is Schistosoma haematobium found?
Middle East
Africa
Which species of Schistosoma's eggs are laid in the renal veins (and where else would they be laid)?
S. haematobium eggs in renal veins
S. mansoni and S. japonicum eggs in portal veins
Excess S. japonicum eggs in brain
Where is S. japonicum endemic?
Far East
Sx. of S. japonicum infection
fever, cough, abdominal pain, diarrhea, hepatospenomegaly, (same as S. mansoni) PLUS cerebral symptoms, including convulsions
Is Schistosoma zoonotic?
yes!
What species of schistosomes cause cercarial dermatitis?
Avian schistosoma japonicum species
What causes "swimmer's itch"?
Schistosomiasis
Where is Clonorchis sinensis endemic?
China, Korea, Taiwan and Vietnam
Reservoirs of Clonorchis sinensis
dogs and cats
How do humans acquire Clonorchis infection?
Raw or undercooked fish with metacercariae under scales
Where do adult Clonorchis sinensis reside?
Biliary duct
Where does Clonorchis sinensis encyst?
Duodenum
How do the targets of Schistosome cercariae differ from the targets of Clonorchis sinensis and Fasciola hepatica?
Cercariae from Schistosome species target human skin, while cercariae from Clonorchis and Fasciola target carp and water plants, respectively.
What is the Chinese liver fluke?
Clonorchis sinensis
Where are Clonorchis sinensis' eggs?
Feces
Sx of Clonorchis sinensis infection
ab pain, diarrhea and nausea (acute)
pyogenic cholangitis and pancreatitis (chronic)
Due to inflammation and intermittent obstruction in intestines
Chronic infection with Clonorchis sinensis predisposes the host to what?
Cholangiocarcinoma of the liver
What developmental stages does Clonorchis sinensis go through while inside its snail host?
Miracidia
Sporocysts
Rediae
Cercariae
How long can Clonorchis sinensis live in distal bile dults?
30-40 years!
What does the Clonorchis sinensis egg look like?
Small and operculated (operculum at narrow end of egg)
What is the lung fluke?
Paragonimus westermani
Where is Paragonimus westermani found?
Far East
though other Paragonimus species are found elsewhere
What is the second host of Paragonimus westermani?
Crab
Reservoirs of Paragonimus westermani
domestic and wild animals (pigs, dogs, feline species)
How do humans acquire Paragonimus westermani?
Ingestion of metacercaria in raw/undercooked crab
Where do Paragonimus westermani migrate once ingested?
Lung
Sx of Paragonimus westermani infection
diarrhea, ab pain, fever, cough, hsm (acute)
TB-like pulmonary dz w/ cough and hemoptysis (chronic)
Where can you find eggs of Paragonimus westermani?
Feces or sputum
Does an infected person cough up/poop out embryonated eggs of Paragonimus westermani or unembryonated eggs?
Unembryonated eggs
Where do the metacercariae of Paragonimus westermani encyst?
Duodenum, before passing through to lungs, brain or striated muscles
Time from infection to oviposition (egg laying) for Paragonimus westermani
65-90 days
How long can Paragonimus westermani infections persist in humans?
20 years
Appearance of Paragonimus westermani egg
flat on one side,
operculum clearly visible at large end
What is the sheep liver fluke?
Fasciola hepatica
Where is Fasciola hepatica found?
Worldwide
Where are adult Fasciola hepatica found?
Biliary duct
Where do the metacercariae of Fasciola hepatica encyst?
Watercress
How do humans acquire Fasciola hepatica?
ingestion of watercress with metacercariae
How long does it take Fasciola hepatica after ingestion to find the bile duct?
Months
Sx of Fasciola hepatica infection
fever, RUQ pain, eosinophilia (acute, while fluke is finding biliary duct)
biliary obstruction and inflammation (chronic)
Appearance of Fasciola hepatica eggs
ellipsoidal
small, barely visible operculum at upper end
What type of anitfungal is amphotericin B?
Polyene
What fungi are resistant to amphotericin B?
none
What antifungal is first line for mucormycosis?
Amphotericin B
How does amphotericin B exhibit its antifungal action?
Binds to ergosterol in membrane, altering permeability of cell membrane (bacteriocidal)
What is the advantage of newer amphotericin drugs?
Complexed with lipids/liposomes to decrease renal toxicity,
BUT VERY EXPENSIVE $$$
Which antifungal is used for severe, life-threatening fungal infections?
Amphotericin B
Which drug acts synergistically with amphotericin B, and what is this combo used to treat?
Flucytosine
Serious cryptococcal infections in high-risk patients
What are the side effects of Amphotericin B?
Nephrotoxicity ( in 80% of patients! dose dependent, cumulative)
Fever, chills, HA, N/V, hypoTN 1-3 hours post-IV infusion
Hypokalemia, hypomagnesia, weight loss, malaise, anemia
How is amphotericin B administered?
IV
(poor GI absorption)
Why are serum concentration measurements useless for amphotericin?
Most of the drug is bound to plasma lipoproteins or membrane sterols
T 1/2 of amphotericin
LONG (days to weeks)
Amphotericin excretion
Slowly in urine (don't adjust dose for renal/liver failure)
Not cleared by dialysis
What antifungal agent is antagonistic to Amphotericin B?
Azoles
Describe the nephrotoxicity resulting from amphotericin B
occurs in more than 80% of patients
increase in BUN and serum cre, decrease in creatinine clearance
find RBC casts and WBC casts and albumin in urine
irreversible renal failure in large doses (>2g)
What antifungal agent, when coadministered with amphotericin B, lessens the amphotericin dose required?
Flucytosine (5FC)
What types of infections does 5FC treat?
systemic Candida or Cryptococcus infections
What types of fungus are resistant to 5FC?
Many, resistance develops rapidly when it is used alone
Mechanism of 5FC
short answer: interferes with DNA synthesis.
long answer: fluorine analog of cytosine
deaminated to 5-fluorouracil (5-FU)
converted to 5-fluorodeoxyuridylic acid monophosphate, which is a noncompetitive inhibitor of thymidylate synthetase
Side effects of 5FC
depresses bone marrow fcn (anemia, leukopenia, thrombocytopenia)
GI (vomiting, diarrhea, nausea)
What is the upper limit of safe serum levels of 5FC?
120 micrograms/mL to avoid bone marrow depression
How is 5FC administered?
Orally, good GI absorption
Where does 5FC distribute?
Well-distributed!
CSF, aqueous humor, joints, peritoneal fluid
Excretion of 5FC
70-90% unchanged in urine
cleared by dialysis
MUST be dose-adjusted for decreased renal failure
Mech for resistance to 5FC
1 step chromosomal resistance due to loss of deaminase
Mech of echinocandins
prevent glucan synthesis in fungal cell wall
What do Echinocandins treat?
Aspergillus
Fluconazole-resistant Candida

(NO activity against Cryptococcus, Fusarium, or Rhizopus)
Echinocandin admin
IV only
Disadvantage of treating with Echinocandins
very expensive ($300/day)
What is the most common cause of pneumonia in AIDs patients?
Pneumocystis jiroveci (fungus)
What is unusual about P. jiroveci?
cannot be cultured
newly classified as fungus based on rRNA sequences
Pneumocystic jiroveci treatment
High dose Septra
if sulfa-allergic, Dapsone and trimethoprim
for prophyllaxis, Septra or pentamidine (inhalation)
Side effects of high dose Septra
allergic skin rashes
Side effects of Pentamidine
renal or bone marrow toxicity
Mechanism of Azoles
depletes membrane of ergosterol
inhibit cytochrome P450-dependent 14-alpha-lanosterol demethylase enzyme
2 groups of azoles and drugs in each group
Triazoles (fluconazole, itraconazole, voriconazole)
Imidazoles (clotrimazole, ketoconazole, micronazole)
2 most widely used triazoles
Fluconazole, voriconazole
What advantages do triazoles have over earlier imidazoles?
better pharmacokinetics
safer
better efficacy treating systemic fungal infection
Imidazoles treat...
cutaneous fungal infections
vulvovaginal infection
Fluconazole (Diflucan) treats...
oral/vagina Candida (if not responding to nystatin or clotrimazole)
non-life-threatening Candida infections like esophagitis
Hepatosplenic candidiasis
Cryptococcal infections
Coccidioidal meningitis
Itraconazole (Sporanox) treats..
Fungal infections in immunocompromised or normal patients
Blastomycosis
Histoplasmosis
Aspergillosis
Onychomycosis (nail fungus)
Voriconazole (Vfend) treats...
severe aspergillosis
Fluconazole-resistant candidal infections
Posaconazole (Noxafil) treats...
Prevention of aspergillosis and candida infections in immunocompromised (>13 yo)
What is unique about posaconazole?
broader spectrum of activity than other triazoles
may cover strains resistant to other antifungal agents
Side effects of azoles
GI (N/V, diarrhea) most common
Rash, HA
Mild elevation in LFTs (7% of patients)
Hepatotoxicity leading to liver failure and death(rare)
Drug interactions (esp. itraconazole, voriconazole)
Itraconazole admin
IV or PO (with acidic drinks or food)
Excretion of itraconazole
hepatic
NO dose-adjustment for renal/liver failure
Fluconazole admin
PO
Fluconazole distribution
well-distributed to CSF and tissues
Excretion of fluconazole
in urine, 80% unchanged
ADJUST dose for renal failure
What is the drug of choice for Coccidiomycosis?
Voriconazole
Why is voriconazole the drug of choice for Coccidiodes?
well absorbed but has lower CSF levels
Does vorciconazole need dose-adjustment in renal/hepatic failure?
Yes
Ketoconazole side effects
adrenal suppression
gynecomastia
hypocholesterolemia (can interfere with XOL synthesis)
hypothyroidism
Definitive host
host inhabited by the adult form of the parasite
(where sexual reproduction happens, if it happens)
Intermediary/secondary host
host inhabited by larval form
For what Cestode is the human both the definitive and intermediary host?
Taenia solium
For what Cestode is the human only the definitive host?
Taenia saginata
Where is Taenia solium infection mostly seen?
Mexico, Latin America, Eastern Europe, Africa, Asia
What is the scolex?
the head of a tapeworm
Where in the human body does Taenia solium live?
Small intestine, attached by its scolex.
Also can enter bloodstream and encyst elsewhere (cysticercosis, neurocysticercosis)
How are Taenia (solium or saginata) eggs shed?
Proglottids breaks off of their place attached to the small intestine, and eggs are released in the colon (excreted in feces)
Dz caused by Taenia solium
Cysticercosis
How is Taenia solium acquired?
eggs ingested, larvae hatch and penetrate intestinal wall
What is neurocysticercosis?
Taenia solium larvae encysted in the brain
Neurocysticercosis sx
vomiting, HA, visual changes, seizures (increased ICP)
How is Taenia saginata acquired?
ingestion of infected meat containing larvae
Intermediary host of Taenia saginata
Cattle
How long can Taenia eggs survive in the environment?
Days to months
How long can cysticerci survive in the animal?
Years
Intermediary host of Taenia solium
Humans
Pigs
Average length of T. solium in intestines
5m or less
Average length of T. saginata in intestines
2-7m
How many eggs/gravid proglottids are passed in the stoll of a Taenia-infected person per day?
approx 6
Which Taenia species has more eggs?
T. saginata (1,000-2,000)

T. solium has avg. 1,000

T. saginata's proglottids can produce up to 100,000 eggs, while T. solium's produce up to 50,000
How many "suckers" on the scolex of Taenia species?
4,
plus solium has a double row of hooks
What is the largest human tapeworm and how long is it?
Diphyllobothrium latum
10m
What populations are most affected by Diphyllobothrium latum? Where in the world?
those who eat raw or undercooked freshwater fish
Great Lakes, Scandinavia, W. Europe, Japan, S. America
How long can Diphyllobothrium latum live in a host?
up to 25 years
Sx of Diphyllobothrium latum infection
usually asx
pernicious anemia
How does Diphyllobothrium latum cause pernicious anemia?
release a chemical that interferes with intrinsic factor and Vit. B12 absorption
What do Diphyllobothrium latum eggs look like?
Oval/ellipsoidal, with an operculum at one end.
about 65 micrometers by 45 micrometers
What do Diphyllobothrium latum proglottids look like?
strands of visible length in feces, micro look like stacked things/palm tree trunk
Intermediary host of Diphyllobothrium latum
Copecod, or Freshwater crustacean
which is then ingested by a second intermediary host
such as minnows or small freshwater fish
Where do Diphyllobothrium larvae develop into the infective stage?
Fish flesh
Where in the human body does Diphyllobothrium latum live?
Small intestine
How many eggs are passed in the feces of a Diphyllobothrium-infected person, per day?
up to 1,000,000 eggs per day per worm
Humans are only the intermediate host for
Echinococcus
What other animals can be the definitive host of Diphyllobothrium latum?
other mammals
What causes Hydatid dz?
Echinococcus LARVAE
Where is Echinococcus found?
worldwide, esp. rural farming areas
Echinococcus sx
usually asx until cyst in liver grows so large that it causes problems (hydatid dz - obstructive jaundice)
Hydratid dz tx
surgical removal of cysts without breaking them
(breaking one and leaking fluid can cause anaphylaxis)
What are the organisms called that form inside an Echinococcus cyst?
protoscolices (singular: protoscolex), and daughter cysts
How do dogs acquired Echinococcus?
Ingestion of the cyst-containing organs of infected intermediate hosts
What is the definitive host of Echinococcus?
Dogs or other canids
What is the intermediate host of Echinococcus?
Sheet, goat, swine, cattle, horses, camel, and unfortunately humans
Are nematodes segmented or unsegmented worms?
Unsegmented
Are nematodes hermaphrodites?
No they have separate sexes
How many larval molts do nematodes have?
4
What is Loeffler's syndrome?
Transient pulmonary infiltrates and peripheral eosinophilia caused by nematodes that migrate through the lungs
What is the largest nematode parasitizing the intestine and how long is it?
Ascaris lumbricoides
35 cm
Ascaris lumbricoides tx
Narcotize with piperazine (since worm's death is slow)
Mebendazole
Where is Ascaris found?
One of the most common worldwide,
highest prevalence in tropical and subtropical regions, or areas with inadequate sanitation
Where do the eggs of Ascaris mature?
Soil
How long can Ascaris eggs survive in the environment?
up to 7 years
What is the major complication of Ascaris infection?
Obstruction
Ascaris lumbricoides dx
eggs in stool
How is Ascaris transmitted?
fecal/oral (ingestion of a developed fertilized egg)
Where do adult Ascaris worms live?
lumen of small intestine
How many eggs/day are produced by female adult Ascaris worms?
approx. 200,000
How long must Ascaris eggs sit in soil before becoming fertilized and infective?
18 days (in moist, warm, shaded soil) - several weeks (in dry, cold/hot, exposed soil)
How long after ingestion does Ascaris establish in the small intestine?
2-3 months
Trace the path of Ascaris in the human host
Fertile/infective eggs are ingested, larvae hatch and invade intestinal mucosa, then are carried via portal and systemic circulation to the lungs.
Mature in the lungs, ascend bronchial tree, get swallowed down again. Stop and stay as adult worms in small intestine
How long do Ascaris adult worms live?
1-2 years
Which nematodes are considered hookworms?
Necator americanus
Ancyclostoma duodenale
What are viral capsids made of?
protein
Which is more stable, enveloped viruses or nonenveloped viruses?
Nonenveloped
(more stable to dessication, detergents, alcohols and proteolytic enzymes)
What are the two possible capsid structures and which virus fits neither?
Helical (RNA only) and icosahedral.
Pox is neither
What is the nucleocapsid?
combo of capsid and nucleic acid
What is a nonstructural protein?
A protein encoded in viral DNA/RNA that is NOT incorporated into the baby viruses (virions) that are made.
Usually have a role in virus replication
Which RNA virus is ds?
reoviruses
Tissue tropism
the cells that a virus readily infects (therefore the cell has a receptor for that virus)
What is CPE
cytopathic effects (the distinctive morphology of infected cells)
what are "susceptible" cells, vs. "permissive" cells? Which term is related to "productive" infections?
"Susceptible" cells have the receptor for a virus, thus allowing its entry.
"Permissive" cells are cells in which the virus can produce progeny (thus making it a productive infection).
What is an abortive infection and what 2 things cause it?
no viral progeny produced
either: 1) nonpermissive cell,
2) defective virus (lacking some of necessary viral genes)
What are enhancer elements?
regulatory DNA or RNA sequences in a viral genome that bind specific TFs, leading to enhanced viral gene expression and replication
Does HPV have a narrow or broad host range?
And what's special about it's permissivity?
narrow host range (human epithelial cells)
transiently permissive (must wait until epithelial cell is terminally differentiated and synthesizing keratin)
results in RESTRICTIVE infection
What persists in a latent viral infection, and what is this type of infection associated with?
Viral genomes w/o infectious virions in host cells
Associated with vertical transmission
What does it mean for a virus to have a "hit and run" strategy?
It infects a cell, causes infection/dz, then is cleared by the immune system.
Must constantly find new susceptible hosts to survive
What 2 mechanisms might be used by a virus to enter a cell?
Receptor-mediated endocytosis
Fusion
In receptor-mediated endocytosis, what facilitates the uncoating of virus?
acidification of the endosome
What ability must a virus have in order to undergo fusion with the host cell membrane?
must be able to fuse at NEUTRAL pH
What are the hallmark of viruses capable of fusion at neutral pH?
Multinucleated giant cells or syncytia
Must a viral genome completely uncoat before replication?
In some species, yes, in others, no
What must a negative sense RNA virus have in order to replicate?
RNA-dependent RNA Polymerase
Where do RNA viruses undergo replication, and what is the exception?
cytoplasm
Orthomyxoviruses
Where do DNA viruses undergo replication, and what is the exception?
nucleus
Poxviruses
what type of viruses can undergo reassortment?
segmented viruses
strategies used by viruses to utilize host metabolic machinery
alternative reading frames
splicing/cleaving primary RNA transcripts yielding multiple distinct RNAs
multifunctional viral proteins
in DNA viruses, immediate early gene products..
regulate expression of other genes
in DNA viruses, early gene products...
are directly involved in replication of viral genome
in DNA viruses, late gene products...
are structural proteins of the virions
if an animal virus is non-enveloped what kind of capsid does it have?
icosahedral
Which are more unique, the antigenic epitopes of an intact virus or a disrupted virus?
Intact virus (they elicit type-specific neutralizing Abs)
disrupted viruses elicit group-specific Abs
Picornavirus:
+/- ss/ds DNA/RNA
enveloped/naked
icosahedral/helical
rep. in cytoplasm/nucleus
+ ss RNA
naked
icosahedral
cytoplasm
Picornavirus genera
Enteroviruses
Rhinoviruses
Hepatovirus (Hep A)
Cardioviruses
Enterovirus species
Coxsackieviruses A and B
Echoviruses
Polioviruses
other, unclassified enteroviruses
At what pH are enteroviruses stable?
What are the implications?
pH = 3
can infect the ileum (b/c can survive gastric acid)
optimum enterovirus temperature for replication
37 degrees
At what temperature do enteroviruses get inactivated?
50 degrees
How can you differentiate Enteroviruses from Rhinoviruses?
Enteroviruses are inactivated at 50 degrees, rhinoviruses are not
Can enteroviruses survive in the environment (at room temperature)?
Yes
What times of year are peak enterovirus season?
late summer, early autumn
what are the most common manifestations of enterovirus infection?
rash
aseptic meningitis
How are enteroviruses transmitted?
fecal-oral
for some (polio, coxsackie) also respiratory
sx of aseptic meningitis
HA,
fever,
stiff neck,
CSF pleocytosis,
CSF [protein] increases with decreasing cell count
normal CSF [glucose]
CSF pleocytosis
150-500 cells
polys predominate early
lymphocytes predominate late

sx of aseptic meningitis, seen in enterovirus infection
Is poliovirus zoonotic?
No, humans are only natural host
Host range of poliovirus
limited (by receptor presence) to cells of primate origin
-kidney, brain, spinal cord, small bowel
Poliovirus type 1, 2 and 3 receptor
-70-80kD integral membrane protein in the Ig superfamily, encoded on chr. 19
-attaches electrostatically to floor of "canyon" in poliovirus capsid
-binding results in loss of VP4 on virus membrane
What is special about the poliovirus genome?
VPg is covalently linked at its 5' end
How is the poliovirus genome translated?
single large 2207 AA polyprotein that is sequentially cleaved into 7-8 smaller viral proteins (by virus-encoded proteases)
examples of poliovirus nonstructural proteins
RNA polymerase
viral protease
Functions of poliovirus viral protease
cleave polyprotein into structural and nonstructural proteins
destroy cellular cap-binding protein (shutting off cellular protein synthesis)
eventually break down host polyribosomes and create larger viral polyribosomes
in viral replication, which proceeds faster: protein synthesis or RNA synthesis?
RNA synthesis,
(thus as soon as enough proteins are formed, RNA is encapsidated very rapidly)
Does polio virion construction use or create energy? what are the steps?
uses it.
step 1: capsomere assembly into procapsid [(VP1+VP3+VP0)5]12
step 2: nucleic acid entry, cleavage of VP0 into VP2 and VP4

only 1 in 200 of assembled virions is infectious (Very inefficient!)
Are polioviruses released upon completion of the replication cycle?
No, mature virions retained for several hours until cell "bursts" (due in part to activation of its lysosomal enzymes)
What % of ppl infected with polio show sx? and why?
5%
in 95% of people, neutralizing Abs are elicited at the minor (primary) viremia stage
Dz caused by polio infection
asx (95%)
abortive infection
aseptic meningitis
paralytic polio :(
How does polio enter and spread to cause infection?
most often ingested, infect small bowel mucosa (Peyer's patches)
spread to mesenteric lymph nodes-->blood (minor/primary viremia)
spread to liver, spleen, bone marrow and lymph nodes
IN PPL w/o healthy immunity (5%), heavy shedding leads to major/secondary viremia and abortive polio sx
-if passes BBB (<1%) --> aseptic meningitis, self-lmtd and resolves in 1 week
-if involves motor neurons (0.1%) -> paralytic polio
Abortive polio sx
fever
HA
vomiting
diarrhea or constipation
sore throat
How does poliovirus reach motor neurons?
either hematogenous (majority of cases) or via intra-axonal transport from peripheral sensory ganglia
What is the neuropathology associated with paralytic polio?
neuronophagia
PMNs surround and phagotcytose dying neurons
What is bulbar polio?
type of paralytic polio involving motor neurons and cranial nerves in medulla
(5-10% of patients with paralytic polio)
- can have paralyzed respiratory muscles and die
What % of paralytic polio victims have permanent paralysis? what is the most common site?
0.5%
legs
How long are polio virions shed from the pharynx and in feces?
pharynx: 3-4 weeks
feces: 5-6 weeks or longer
Risk factors for polio infection
poverty
crowding
unsanitary conditions
respiratory contact with infected person
Are enteroviruses synergistic or antagonistic?
Antagonistic (one enterovirus can interfere with another's infection - or vaccination)
What is the relationship between age and severity of polio?
Older people get more severe (more often paralytic) dz
Does polio infection elicit effective immunity?
yes, lifelong type-specific immunity and type-specific resistance to GI infection
Why don't children under 6 months old get paralytic polio?
maternal antibody
Polio dx
virus isolation and a rising Ab titer
Polio-endemic regions
Nigeria, India, Pakistan, Afghanistan
Are monovalent (directed at type 1 or type 2 or 3) oral polio vaccines more effective than trivalent oral vaccines?
yes
Pros of Sabin polio vaccine
GI immunity as well as systemic immunity
immunity is transmitted
oral admin = easier, better for epidemics
relatively inexpensive
Cons of Sabin polio vaccine
risk of paralytic dz in immunocompromised ppl and their contacts
infection by other enterovirus can interfere
Pros of Salk polio vaccine
induces humoral immunity
no risk of paralytic dz
no shedding (no risk to contacts)
no interference from other enterovirus
Cons of Salk polio vaccine
requires booster doses and subq admin (decreased acceptance)
no GI immunity
more expensive
Does polio infect latently or "hit and run"?
Hit and run
no persistance of virus in host after immunity developed
What does ECHOvirus stand for and how many serotypes are there?
Enteric
Cytopathic
Human
Orphan
29 serotypes
Is Echovirus zoonotic?
don't generally cause dz in animals
dzs caused by Echovirus
aseptic meningtis
rash
generalized infections in newborn
echovirus 16- Boston exanthema
What causes Boston exanthema, and what characterizes it?
Echovirus 16
fever followed by roseola-like rash
What are human Parechoviruses 1 and 2, and what dz does parechovirus 1 cause?
ex-enterovirus members of the picornavirus genus Parechovirus

Parechovirus 1 causes infantile diarrhea and resp. illness
What are the 2 major groups of coxsackievirus and how many serotypes do each have?
A (23 serotypes)
B (6 serotypes)
What cells are used to culture poliovirus?
human embryonic kidney or rhesus monkey kidney
What numbers are assigned to unspecified enteroviruses?
68-71
Dz caused by Enterovirus 70
acute hemorrhagic conjunctivitis (often in epidemics)
Dz caused by Enterovirus 71
hand-foot-and-mouth dz,
herpangia
encephalitis
acute flaccid paralysis (resembles poliomyetlitis)
Which Coxsackie virus can be grown in cell culture?
B
The mouse injected with isolated virus from the patient demonstrates generalized myositis and flaccid paralysis from attack of striated muscle- what is the virus?
Coxsackie A
The mouse injected with isolated virus from the patient demonstrates focal myositis, spastic paralysis from encephalitis -what is the virus?
Coxsackie B
The mouse injected with isolated virus from the patient demonstrates myocarditis, pancreatic necrosis, and necrosis of brown fat - what is the virus?
Coxsackie B
Optimum rhinovirus temp
33 degrees (nasal mucosa)
Peaks seasons of rhinovirus
spring and early fall
What is the most common cause of the common cold?
Rhinovirus
How are rhinoviruses transmitted?
aerosols or fomites
what are fomites?
objects that mediate transmission (door knobs, tissues, utensils)
Which virus induces high levels of interferon?
rhinovirus
Which receptor mediates rhinovirus entry?
ICAM-1 (member of Ig supergene family)
How many rhinovirus serotypes are there that do NOT have cross-reactivity?
More than 120
Is Rhinovirus zoonotic?
Not really, monkeys can be infected but don't show sx
What cells are used to culture rhinovirus?
embryonic cell cultures, cultures of human fetal trachea
What host defenses act against rhinovirus infection?
IgA gives short-lived protection, mostly likely by blocking binding of virions to cell's receptors
Orthomyxoviruses:
+/- ss/ds RNA/DNA
icosehedral/helical
enveloped/naked
rep. in cytoplasm/nucleus
segmented (8)
- ssRNA
helical
enveloped
rep. requires nucleus (steals 5' caps from host mRNA)
What's special about Orthomyxoviruses' envelope?
has surface glycoprotein spikes (HA, NA)
Main structural protein/antigen of Influenza virus
NP: nucleoprotein
matrix proteins of influenza virus
M1: membrane protein, functions in budding and assembly
M2: forms pH activated ion channels important in viral uncoating
What do amantadine and rimantadine target?
M2
How are the matrix proteins of influenza virus created?
alternative splicing
which antigens of influenza virus elicit type-specific Abs? What function do they serve?
NP
M1
(can be used diagnostically, but are not protective)
what is hemagglutination (in the context of viruses with HA)?
formation of a lattice of virus and RBCs seen when influenza virus in incubated with RBCs
What is hemadsorption (in the context of viruses with HA)?
binding of RBCs to the HA on infected cells,
used in dx
Function of Hemagglutinin (HA)
attachment to sialic acid residues and entry into host cells
What accounts for influenza viruses' broad host range?
HA binds to sialic acid, which are common on cell surfaces
Which Abs are the most important for immunity vs. influenza?
Anti-HA Ab (prevents infection)
Anti-NA Ab (prevents spread of infection)
What is required after HA attaches to a host cell before the virus enters the cell?
Cleavage of HA by host cell serine protease
Describe the sialic acid binding site on HA and its significance
very small part of protein
trimer of globular peptides each on its own stalk
allows HA to change antigenically under selective pressure from immune system while preserving a functional binding site
functions of neuraminidase on influenza virus
1) release virus from host cell (by hydrolyzing sialic acid residues on envelopes of progeny viruses)
2) hydrolyze mucoproteins in nasal secretions (help spread virus)
How do orthomyxoviruses enter cells?
HA binds sialic acid, virus in endocytosed as host serine protease cleaves HA.
endosome is acidified, prompting fusion of viral membrane with endosome membrane, releasing nucleocapsid into cytoplasm
Why do Orthomyxoviruses need the host nucleus to replicate?
to steal host mRNA's 5' caps
How does Actinomycin D work and what principle does it demonstrate?
binds DNA (blocking txn of DNA by RNA Pol)
-blocks influenza virus production b/c orthomyxovirus requires the host to supply 5' RNA cap
Are different influenza types cross-reactive? Serologically or genotypically distinctive?
Within a type (A, B or C),yes. but not between types
The three types are serologically and genotypically distinctive
Which influenza antigens are subjected to more selective pressure, M and NP, or HA and NA?
HA and NA because they are external
Which type of Orthomyovirus must be subtyped further (based on its HA and NA)?
Influenza virus A (because it has animal reservoirs in which it can undergo reassortment)
Two types of antigenic variation
antigenic drift
antigenic shift
which type of influenza virus can undergo antigenic drift?
All of them (A, B, C)
which type of influenza virus can undergo antigenic shift?
A
What causes antigenic drift in influenza virus?
minor changes in NA and HA due to missense mutations (change antigens but not function)
What causes antigenic shift in influenza virus?
introduction of one or more "new" RNA segments acquired through reassortment between animal and human viruses when co-infected inside a cell (often pigs capable of infection with human and avian strains)
Which type of antigenic variation causes pandemics?
Antigenic shift
Which of the types of influenza virus has a more severe infection?
A>B>C
What is feared about avian flu (Influenza A H5N1)?
widespread outbreaks in birds, has killed several people.
if a virus has both human and avian virus genes, it can cause worldwide pandemic (once it establishes the ability to transmit person-to-person)
-resistant to adamantanes
Seasonal peaks of influenza
winter months
Extent and severity of influenza outbreaks depends on:
prevalence of Abs to circulating virus
intrinsic virulence of virus (B less virulent than A, but B still can be fatal)
Time course of influenza A outbreak
begins abruptly (children with febrile respiratory illness)
peaks in 2-3 weeks (adults get influenza)
lasts total of 2-3 months
typical attack rate of influenza
10-20% of susceptible population during outbreak,
>50% of susceptible population during pandemics
Influenza sx
fever (febrile illness, all sx usually self-lmtd)
HA
sore throat/cough
nasal discharge
malaise
myalgias
complications of influenza
pneumonia,
bronchitis,
sinus/ear infections
risk factors for complications from influenza (and therefore should get a flu shot)
>65 yo (ppl >50 get shot)
chronic medical conditions (COPD, DM, cardiopulmonary dz)
very young children
pregnancy women
How is influenza transmitted/acquired?
airborne transmission, enters nasopharynx and infects ciliated mucosal epithelial cells of the resp. tract
What do influenza-infected ppl's nasal/bronchial biopsies show?
desquamation of ciliated columnar epithelial cells of the bronchi
When do anti-NA and anti-HA Abs develop during an influenza infection?
beginning of 2nd week
What parts of human immune system are important defenses against influenza infection?
neutralizing antibodies vs. NA and HA (prevent new infections)
cell-mediated immunity important for clearance of infection and recovery
Influenza dx
viral culture
PCR
DFA (direct fluorescent Ab)
enzyme immunoassay
retrospective: 4x increase in Ab titers demonstrated on HA-inhibition test
Amantidine and rimantidine treat/prevent what dz?
influenza type A
Amantidine and rimantidine mechanism
M2 blockers, can't acidify endosome so can't uncoat virus
Zanamivir and oseltamivir treat/prevent what dz?
Influenza type A or B
zanamivir approved for treatment of influenza in which patients?
over 7 yo
oseltamivir approved for treatment and prophyllaxis of influenza in which patients?
treatment: >18yo
prophyllaxis: >13yo
Reye's syndrome sx
lethargy/delirium/obtundation
seizures
resp. distress
10-30% mortality
what causes Reye's syndrome?
giving aspirin to children with viral infections
What are the subfamilies of family paramyxoviridae?
paramyxovirinae
pneumoviridae
genera of subfamily paramyxovirinae
paramyxovirus (parainfluenza 1-4)
rubulavirus (mumps)
morbillivirus (measles)
henipavirus (nipah and hendra virus)
What are Nipah and Hendra viruses?
paramyxoviruses capable of jumping species, causing severe/fatal dz in humans
Natural reservoir of Nipah and Hendra virus
Pteropus bats
How are Nipah/Hendra virus acquired?
close association with infected domestic animals
Dz caused by Nipah virus
encephalitis
Nipah virus endemic areas
Southeast Asia
Australia
Dz caused by Hendra virus
resp. illness with severe flu-like sx
Genera of Paramyxoviridae subfamily pneumovirinae
pneumovirus (RSV)
metapneumovirus (metapneumovirus)
Paramyxoviridae:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked
rep in cytoplasm/nucleus
- ssRNA
helical
enveloped
rep. in cytoplasm (except measles)
what is special about the envelope of paramyxoviridae?
has surface glycoprotein spikes
Which paramyxoviridae family member replicates in the nucleus?
Measles
Paramyxoviridae CPE
syncytia formation (aka multinucleated giant cells, due to fusion at neutral pH)
eosinophilic cytoplasmic inclusion bodies
CPE specific to measles
nuclear inclusion bodies
Fusion (when creating syncytia of paramyxoviridae) requires:
cleavage of viral glycoprotein by host cell protease
How are parainfluenza viruses transmitted?
person to person via resp. secretions
How is Mumps transmitted?
person to person via resp. secretions
What surface glycoproteins do paramyxovirus (parainfluenza) and rubulavirus (mumps) share?
HN - combined hemagluttin and neuraminidase
F - fusion protein, mediates fusion of virus with host cell (F0 cleaved by host cell protease into F1 and F2)
Which receptor do paramyxovirus and rubulavirus use to enter cells?
sialic acid receptor
Do paramyxoviruses and rubulaviruses exhibit hemagglutination or hemadsoprtion?
Both
Describe croup
acute upper and lower resp. tract febrile illness in children
presents with "seal bark" stridor
age group at highest risk for croup
3 month-3 year olds
what causes croup?
parainfluenza viruses 1, 2, and 3
when do epidemics of parainfluenza viruses occur?
fall and spring
what is the 2nd leading cause of lower resp. infections in infants?
parainfluenza viruses
What dz causes bronchiolitis?
parainfluenza viruses
what organs does mumps attack?
parotid, pancreas, gonads
Mumps sx
salivary gland enlargement
fever
possibly orchitis (inflamm of testes),
meningitis (1/1000 mortality rate), or
deafness
Important members of genus morbillivirus
measles
canine distemper
Rinderpest
How is measles (and all dz from genus morbillivirus) transmitted?
person to person via resp. secretions
Surface glycoproteins of genus morbillivirus and their function
H - binds receptor and hemagglutinates
F - fuses with host cell
Receptor for viruses of genus morbillivirus
CD46 and CD150 (SLAM)
Does measles infection involve an neuraminidase?
No, the receptor is not sialic acid, so it is not needed
How does F protein mediate entering of genus morbillivirus into host cell?
F0 binds host cell,
host cell protease cleaves into F1 and F2
How does rubeola spread through the body?
rubeola = measles
local rep in nasal mucosa
moves to lymph nodes
viremia spreads infection throughout body (tho patient is asx until before rash)
Measles sx
conjunctivitis
dry cough
low grade fever
Koplik's spots
rash moving from face to trunk
Can measles change antigenically?
No, therefore it requires a large susceptible population to be maintained in nature
Animal reservoirs of measles
none
how is measles rash described?
morbilliform exanthem that moves from face to trunk
What do you give to measles-infected children in developing countries and why?
Vitamin A because it decreases morbidity and mortality
Can you get measles repeatedly?
No, natural infection confers life-long immunity, as does the live attenuated vaccine
Measles complications
acute post-infection encephalitis (some mortality)
pneumonia (less developed countries)
SSPE (subacute sclerosing panencephalitis)
What is the most common cause of death due to measles in developed countries?
encephalitis
What is the most common cause of death due to measles in developing countries?
pneumonia
What was atypical measles?
not seen anymore b/c associated with old (formalin-inactivated) vaccine.
high fever, edema of extremities, interstitial pulmonary infiltrates, vesicular rash
What is modified measles?
extremely mild form of measles in partially immune people
(seen in infants, or ppl receiving gamma globulin post-exposure).
prolonged incubation, variable sx
What is SSPE?
subacute sclerosing panencephalitis
caused by restricted viral replication in brain
latent for median of 7 years after measles infection
death within 6-12 months of onset
Two major groups of RSV and what differentiates them
RSV A and RSV B,
based on G glycoprotein
How is Pneumovirus transmitted?
fomites (major)
aerosol (minor)
How long can RSV survive in the environment?
7 hours
How long after the illness is RSV shed?
2-3 weeks
Pneumovirus surface glycoproteins
G - binds receptor
F - fusion of virus with host cell (F0 cleaved into F1+F2)
Do pneumoviruses show hemagglutination or hemadsorption?
No, no hemolysin activity either!
What age group is hit hardest by RSV?
infancy and early childhood
What is the major cause of pneumonia and bronchiolitis in children <1 year?
RSV (25-40% of all infected children, some require hospitalization)
RSV sx in young children
high fever, runny nose, severe cough, sometimes wheezing
RSV sx in adults
colds
elderly or compromised cardiac/pulm/immuno systems: pneumonia
What is the most common cause of pediatric nosocomial infections?
RSV
Is RSV immunity protective?
Only against severe infections, but repeat infections occur throughout life.
Anti-G and Anti-F Abs protect against lower resp. tract infections.
IgA Abs against URIs are short-lived
Peak of RSV epidemics
peak = winter (Feb. in SD)
last from late fall to early spring
RSV dx
gold standard: virus isolation in HEp-2 cells
most common: antigen detection assay
RSV tx
ribavirin (aerosol),
but drug is problematic with limited efficacy...
Papovavirus:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked
rep. in cytoplasm/nucleus
circular dsDNA (+histones assoc. w/ viral capsid)
icosahedral
naked
rep. in nucleus
2 genera of Papovaviruses
Papillomaviruses
Polyomaviruses
2 types of Papillomaviruses
HPV-1 to HPV-100
others (in other animal species)
3 types of Polyomaviruses
JC and BK viruses
SV40
others (in animal species)
Does papovavirus infection elicit protection from future infections?
No, chronic/persistent infections
How many distinct (<50% sequence homology) HPVs are there?
more than 100
Do papillomaviruses have broad or narrow host ranges?
Narrow
What kind of Abs (type specific or genus specific) are made against papillomaviruses?
type specific (made against intact virion). virus must be denatured to expose group-specific antigens and elicit group-specific Abs
How do Papillomaviruses make the 7 early and 2 late (capsid) genes?
splicing
What is an episome?
genetic element that either exists free from cell genome, or integrated into host chromosome
What are the important early genes of Papillomaviruses?
E2 - supresses txn of:
E5, E6, E7 - influence transformation
Can papillomaviruses be grown in cultures?
No, they require terminally differentiated squamous epithelial cells (keratinocytes)
What causes warts?
HPV
Why do warts recur after excision?
The basal layer of cells also contain viral DNA and only express early HPV genes
What is the hallmark CPE of productive HPV infection?
Koilocytes: epithelial cell with shrunken, pyknotic nucleus in the middle of a large vacuole (produced from coalescence of smaller perinuclear vacuoles)
How does HPV cause cervical cancer?
intergrates into host cell chromosome, disrupting its own tumor suppressor (E2)
Which HPV genes are responsible for cervical cancer?
E2 suppresses E5, 6, 7
E6 binds p53 and accelerates its degradation (inhibiting apoptosis)
E7 bind RB, inactivating it and increasing DNA synthesis and mitosis
Which HPV types are most associated with cervical cancer?
HPV-16, 18, 31 and 45
Are HPV-6 and 11 (genital wart types) oncogenic?
Not really! (low oncogenic potential)
How often is cervical cancer NOT caused by HPV?
10%
How is HPV transmitted?
direct contact (venereal, autoinoculation)
indirect contact (pick up via cut on bottom of foot contacting virus left by a plantar wart)
HPV tx
physical/chemical destruction of wart
HPV vaccines mech and types
empty virus shells elicit neutralizing Abs against:
types 16, 18 (70% of cervical, anal, genital cancer)
types 6, 11 (90% genital warts, laryngeal papillomatosis)
HPV dz
common wart, plantar wars (benign squamous epithelial tumors)
laryngeal papillomatosis
epidermodysplasia verruciformis
condyloma acuminatum (genital warts)
How is laryngeal papillomatosis transmitted?
to baby via birth canal
Laryngeal papillomatosis tx
surgical removal of warts (clear airway)
interferon to prevent recurrence (though they recur after interferon stopped)
Epidermodysplasia verruciformis genetics
AR
Epidermodysplasia verruciformis sx
extensive chronic cutaneous HPV infection,
1/3 go on to malignant carcinomas, only on sun-exposed skin
What HPV types most often cause epidermodysplasia verruciformis?
5 and 8
What is the most common sexually transmitted viral dz?
condyloma acuminatum (genital warts)
Are most genital wart-causing HPV infections mild or severe?
Most asx and transient, but persistent infection with oncogenic HPV is a concern!
How many of the DNA strands of papillomavirus are read (encode gene products)?
One
How many of the DNA strands of polyomavirus are read (encode gene products)?
Two.
One contains early genes, the other late
Polyomaviruses are resistant to ...
formalin and heat
How do polyomaviruses get the most out of their genome?
RNA splicing, alternative reading frames to allow encoding of multiple products
Which type of Papovavirus has enhancer elements?
Polyomaviruses - impt. determinant of host range and tissue tropism
Describe enhancer elements
not gene- or promoter-specific
located up- or down-stream of the genes they affect
can be in any orientation
not transcribed into RNA (also don't code for proteins)
just bind host TFs
How many capsid proteins and T antigens do polyomaviruses have?
2 capsid proteins
2-3 T antigens
What is the classic CPE of Polyomaviruses?
perinuclear cytoplasmic vacuolation
formation of intranuclear inclusion bodies
Do polyomaviruses cause tumors in their natural hosts?
No (only early genes are expressed)
What kind of infections do polyomaviruses cause in natural hosts?
productive infections
What kind of infections do polyomaviruses cause in hosts other than their natural host?
abortive infections, transform (tumors)
What virus causes PML (Progressive Multifocal Leukoencephalopathy)?
JC virus
PML sx
ataxia
dementia
visual field defects
weakness of the extremities
speech disturbances
coma/death within 6 months of onset
What type of cells do JC virus replicate in?
primary human fetal glial cells
How does JC virus relate to SV40 and BK virus?
70% homology among them, but different enhancer element
What % of children (10-14 yo) are infected by JC virus?
40%
What % of adults are infected by JC virus?
80%
How might JC virus be passed to a baby?
through the urine - JC virus can infect and establish latency in the kidney, and be shed in urine during acute infection and following reactivation from latency
What immunosuppressed states put ppl at risk for PML?
AIDS
organ transplantation
pregnancy
PML mech
subacute, progressive demyelinating dz in patient with impaired cellular immunity
lytic infection of oligodendrocytes (which produce myelin) and transforms astrocytes
Is PML most often caused by new JC virus infection, or reactivation of old JC virus?
reactivation
Which virus, BK or JC, infects children earlier?
BK
Which virus, BK or JC, is associated with viruria?
Both
What cell types does BK replicate in?
human embryonic kidney cells, fetal fibroblasts, fetal brain cells, newborn urinary epithelial cells
Which virus, BK or JC, has more restrictive tissue tropism?
JC
What dz does BK virus cause?
nothing in normal host
in immunocompromised: possibly nephritis in a transplanted kidney (leading to renal failure)
Dz caused by adenovirus
asx (50%)
acute resp. tract infections
conjunctivitis
hemorrhagic cystitis
gastroenteritis
Adenovirus:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked
rep. in cytoplasm/nucleus
dsDNA
icosahedral
naked
rep. in nucleus
the icosahedral capsid of adenovirus is composed of:
hexons, pentons and fibers
what is the conformation of the hexons, pentons and fibers in adenovirus capsid?
protruding fibers (containing type-specific viral attachment proteins used to attach to host cells) at vertices of pentons.
group-specific antigens located on the hexon and penton bases
what is attached to the 5' end of adenovirus' genome?
pTp (terminal protein)
neutralizing Abs are made to which adenovirus Ags?
hexon and fiber Ags
How are adenoviruses divide into subgenera?
A-F,
based on various biochem and serological criteria
what types of infection is adenovirus capable of?
lytic infection, chronic infection in human lymphoid cells, oncogenic transformation in certain animal cells
How long does it take adenovirus to replicate in tissue culture?
24-30 hours (fast!)
How does adenovirus adhere to a host cell?
CAR receptor binds its fiber, causing endocytosis
CPE of adenovirus
grape-like clustering of cells,
basophilic inclusion bodies
(host cell lyses and releases virions)
What transcribes the early RNAs of adenovirus?
cellular RNA polymerase
How does adenovirus replicate its DNA?
uses viral proteins as primer (pTp),
viral DNA polymerase,
72kD DNA-binding protein,
plus cellular factors
Functions of adenovirus E1a
codes for 2 alternatively spliced proteins with multiple functions
-turns on other early genes and late genes (major transactivator)
-binds RB
-inhibits activation of interferon response elements
Functions of adenovirus E1b
blocks host mRNA transport to cytoplasm
binds p53, preventing apoptosis
protects cells from lysis with TNF
Functions of adenovirus E2
encodes DNA replication proteins (DNA polymerase, pTp, 72kD binding protein)
Functions of adenovirus E3
dispensable for growth in tissue culture
helps virus escape immune surveillance by complexing with MHCI and preventing it from leaving ER
protects cell from lysis by TNFalpha
Functions of adenovirus E4
blocks transport of host cell RNA
encodes late genes (e.g. capsid proteins) - made after virus DNA replicated
one promoter, leading to long txn unit that is alternatively spliced into 5 families of RNA (all with polyadenylated 3' end)
Functions of adenovirus VA (VA1 and VA2)
transcribed by eukaryotic RNA Pol III
not translated but allow viral mRNA translation late in infection,
VA1 binds/inactivates a dsRNA protein kinase that usually shuts down translation when dsRNA is around
(the same kinase induced by interferon)
Dzs caused by adenovirus in neonates
pneumonia
Dzs caused by adenovirus in infants
coryza
pharyngitis
Dzs caused by adenovirus in children
colds (URIs)
pharyngoconjunctival fever
hemorrhagic cystitis
diarrhea
intussusception
Dzs caused by adenovirus in young adults
acute resp. dz
pneumonia
Dzs caused by adenovirus in adults
epidemic ketatoconjunctivitis
Dzs caused by adenovirus in immunocompromised
pneumonia with dissemination
UTI
CNS dz (incl. meningoencephalitis)
What is pharyngoconjunctival fever?
conjunctivitis with or without pharyngitis, rhinitis, cervical adenitis, fever.
aka summer camp illness, swimming pool conjunctivitis. caused by adenovirus in children
What is hemorrhagic cystitis?
gross hematuria for approx. 3 days, microscopic hematuria, dysuria and frequency for several more days.
boys>girls.
maybe caused by adenovirus in children
What is epidemic keratoconjunctivitis?
conjunctivitis of insidious onset, frequently bilateral, preauricular adenopathy common.
keratitis begins as conjunctivitis wanes, and can go on for months.
caused by adenovirus in adults
Adenovirus dx
isolated virus
EIA (enzyme immunoassay - monoclonal Ab to hexon epitope, then type-specific monoclonal Ab used to ID specific type of adenovirus)
PCR
Restriction Enzyme analysis
Adenovirus tx
none necessary: self-lmtd dz, death is rare
Adenovirus vaccine
oral live, unattenuated. inoculated into GI tract (does not lead to dz, that's only if inoculated into resp. tract).
used for military only
What is the largest and most complex virus?
Poxviridae
How many pox viruses infect humans?
9:
variola (small pox)
monkeypox (zoonotic, makes rash)
cowpox
vaccinia (avirulent, current smallpox vaccine)
orf virus (sheet and goat pox)
molluscum contagiosum (chronic localized flesh-colored dome papules on skin, spread skin to skin)
when was smallpox eradicated?
1979
What feaures of smallpox allowed its eradication?
obligate human
hit and run (no latency, immunity is lifelong)
all infections cause dz (easy to ID)
vaccine stable and easy to transport
time, money and effort were invested!
Poxvirus:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked
rep. in cytoplasm/nucleus
dsDNA
neither icosahedral nor helical (large and brick-shaped)
enveloped
rep. in cytoplasm
what shape is the core of poxvirus and what is it composed of?
dumbbell, composed of nucleoprotein
What is at the end of poxvirus genome?
haripin loops
what happens when poxvirus DNA denatured?
becomes single-stranded closed circle
How was smallpox spread?
inhalation
Where does smallpox multiply?
probably within macrophages, which then enter the bloodstream and carry virus with them to lymphoid tissue
What type of vesicles form on the skin of smallpox patients?
intraepidermal, leading to extensive scarring (pox marks)
What host defense are elicited by smallpox infection?
cytotoxic T cells
neutralizing Abs
IFN production
(restrict replication, lead to lasting immunity)
General characteristics of herpesviridae
large and complex
encode many enzymes, incl. nucleic acid synth and metab
Herpesviridae:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked
rep. in cytoplasm/nuc
dsDNA
icosahedral
enveloped
rep. in nucleus
What do herpesviridae genomes consist of?
UL and US regions bounded by inverted repeats (IR)
exact arrangement differs in different Herpesviruses
What is the amorphous protein-filled region between the envelope and the capsid called?
tegument
What antigens do Herpesviridae share?
None, no common family antigens
What kind of infection can all members of the Herpesvirus family cause?
latent
What is the Herpes subfamily division based on?
biological properties and/or genome organization and DNA sequence homology
Which viruses are included in the alpha herpesvirus subfamily?
HSV-1, HSV-2, VZV
Which viruses are included in the beta herpesvirus subfamily?
CMV, roseolaviruses (HHV-6, HHV-8)
Which viruses are included in the gamma herpesvirus subfamily?
EBV, HHV-8
What host range do alpha, beta and gamma herpesviruses have?
alpha: broad
beta: restricted
gamma: very restricted (T or B lymphs)
Which has a longer replication cycle, alpha or beta herpesviruses?
beta has a long rep. cycle, while alpha has a short one
Alpha herpesvirus CPE
Cowdry type A eosinophilic intranuclear inclusion bodies
multinuclated giant cells
lead to cell death
Beta herpesvirus CPE
cytomegalia (cell enlargement)
Where do alpha, beta, and gamma herpesviruses establish latent infections?
alpha: sensory neurons
beta: secretory glands, reticulendothelial cells, kidney, etc.
gamma: lymphoid tissue
what kind of infections do beta herpesviruses cause in cell culture?
slowly progressive infections
What is special about the HSV envelope, and how is it acquired?
radially-oriented glycoprotein spikes of 11 different types.
acquired by budding through inner lamella of nuclear membrane, exits cell using Golgi apparatus/transport vesicles
What composes the icosahedral HSV capsid?
162 hexagonal capsomers, each with a small central hole
What does the tegument of HSV contain?
viral proteins:
-alpha TIF (aka VP16): transactivator of alpha genes
-viral host shutoff (VHS) protein: promotes degradation of host mRNAs
-A phosphoprotein: allows viral DNA to circularize
Which viruses that infect humans have the largest genomes?
#1 pox
#2 hsv
What is the implications for HSV of the IR sequences?
since they flank the UL and US sequences, they permit these sequences to invert during replication, forming 4 isomers in equimolar amounts
How does HSV replicate its DNA?
circularizes its genome and uses rolling circle replication
Do latently infected cells (of HSV) die?
No, though productively infected cells do
What is Herpesvirus simiae?
Herpes B virus, monkey's equivalent to HSV
causes meningoencephalitis with 95% mortality when it infects humans
acquired by monkey bites
How long is HSV incubation period?
short (2-7 days)
Where does primary HSV infection occur?
at portal of entry
Factors inducing HSV reactivation
fever, sunlight, menses, probably stress
is it possible to spread HSV without knowing it?
Yes, 80-90% of primary infections are asx, as are most reactivations.
HSV dx
Tzanck smear (same as VZV)
How is a Tzanck smear performed?
scrape cells from base of vesicular lesion, stain with Giemsa, Papanicoleau, or another stain
Host defenses against HSV
cornified epithelium
NK cells
cellular immunity (if T-lymphocyte fcn is impaired, dz is more severe)
How does HSV enter a host cell?
HSV's gB and gC attach to heparin sulfate proteoglycans, then gD binds another receptor, leading to fusion of viral envelope and host cell membrane at neutral pH
other (yet-to-be-identified) glycoproteins are required for entry into polarized cells
How do HSV nucleocapsids enter the host nucleus?
Nuclear pores
What transcribes HSV alpha (immediately early) and beta (early) genes?
host cell RNA Pol II
which tegument protein transactivates HSV alpha genes?
VP16 (alpha-TIF)
How many HSV alpha (immediately early) genes are there?
5
alpha-0, 4, 22, 27, 47.
(gene products have same numbers with ICP prefix)
HSV - Function of ICP0
transactivates promoters and enhances ICP4 function
HSV - Function of ICP4
required for expression of late (gamma) genes
HSV - Function of ICP27
regulates many HSV genes, required for the transition between beta and gamma gene expression
HSV - Function of ICP47
blocks presentation of HSV peptides by MHC I
(prevents the recognition and lysis of HSV infected cells by CD8 cells)
What functions do HSV beta (early) gene products do?
viral ribonucleotide reductase
major DNA binding protein
thymidine kinase
DNA polymerase
topoisomerase
helicase
Can HSV beta genes be expressed in the absence of alpha genes?
No
What are the gene products of HSV gamma (late) genes?
VP16 (aka alpha TIF) - packaged in tegument, turns on alpha gene txn
envelope glycoproteins and capsid proteins
What two times are HSV gamma (late) genes made?
gamma-1: before viral DNA replication (VP16, VHSP gB, gD)
gamma-2: capsid proteins
Which HSV membranes do not receive glycoproteins?
mitochondrial membranes
all other cell membranes have viral glycoproteins inserted in them
Def'n of latency
absence of infectious virus but presence of cells with the capacity to produce it
Model of HSV latency
HSV escapes immune system by traveling up axons of sensory neurons to cell bodies in sensory ganglia, but lose virion transactivators during the trip, such that the infection is latent and no HSV proteins are synthesized nor viral mRNA transcribed.
Does HSV reactivation tend to be more or less severe than primary infection?
Less severe, since the body has humor and cellular immunity
What is LAT, and what is its proposed function?
It is an antisense RNA downstream/overlapping HSV alpha-0 ORF.
It is found in low quantities during lytic cycle, but very high quantities in latent infection, suggesting it binds alpha-0 region and prevents txn
What is the evidence that HSV-1 and HSV-2 are closely related?
share >50% genes, in same order
recombinants are viable
cross-reactive immunity
How does HSV-1 dz distribution differ from HSV-2 dz distribution?
HSV-1 transmitted by oral secretions, most infections affect oropharynx, and reactivates more frequently from oropharynx infections (trigeminal ganglion)
HSV-2 transmitted by sexual contact, and reactivates more frequently from genital infection (Sacral ganglia)
Dz caused by HSV-1 and 2
acute gingivostomatitis (children)
- reactivation: asx shedding of HSV in saliva, herpes labialis
pharyngotonsilitis (in upper class adults not exposed as children, looks like Strep A)
herpetic whitlow
keratoconjunctivitis, keratitis
genital herpes
cutaneous
herpes encephalitis- 70% untreated mortality
herpes gladiatorum
Describe gingivostomatitis
caused by HSV-1 in children
vesicles and painful ulcers
overgrowth of oral anaerobes b/c of decreased swallowing
Describe herpetic whitlow
finger infection often caused by autoinoculation (thumb sucking/finger chewing while orally infected)
Implications of HSV keratoconjunctivitis/keratitis
can result in corneal inflammation and scarring--> blindness
What is the leading cause of sporadic necrotizing encephalitis in the US and Europe?
herpes encephalitis
Describe herpes gladiatorium
skin infection in wrestlers, spread by direct contact with a person who is shedding virus
Differences between VZV and HSV
-number of serotypes (1 vs 2)
-%GC (46% vs. 68%)
host range (narrow vs. broad)
cell free virus in tissue culture (HSV only)
Acyclovir sensitivity (some vs. a lot)
incubation period (14 days vs 2-7days)
transmission (resp. vs direct contact)
%symptomatic: 95% vs 25%
reactivation dz location (dermatomal vs. focal w/in dermatome)
prodrome (long, severe vs. short, mild)
postherpetic neuralgia (common only with VZV)
frequency of symptomatic recurrence (high in HSV)
asx virus shedding (HSV)
increase in Ab titer upon recurrence (VZV)
risk of recurrence vs. age (increases vs. decreases)
VZV Tx
prevention: live attenuated vaccine for all children >12 months
VZV Ab or even vaccine early after exposure
Acyclovir w/in 24 hours of rash onset (for ppl with chronic skin/lung dz, on steroids, or >13 yo)
HHV-6 and HHV-7 show cell tropism for what kind of cells?
CD4 T lymphocytes
What dz can HHV-6 (or sometimes HHV-7) cause?
roseola infantum (aka exanthem subitum)
Roseola infantum/ exanthem subitum sx
high fever
maculopapular rash resolving uneventfully in hours/days
note: 80-100% adults seropositive, shed HHV-6 in saliva
What cancers are HHV-8 associated with?
Kaposi's sarcoma,
body cavity lymphoma

all in immunosuppressed ppl (HIV, renal transplant)
From where does CMV derive its envelope?
nuclear membrane
How can you divide CMV into strains?
restriction digests of genome
site of CMV latency
bone marrow
What cells does CMV infect in vivo?
monocytes, macrophages, PMNs, endothelial cells and sinusoidal lining cells
What cells grow CMV in culture?
human fibroblasts
Does CMV kill infected cells?
Yes
Where is CMV endemic?
Everywhere (ubiquitous)
but more widespread in developing countries and under lower socioeconomic conditions
Who is at particular risk for CMV and its implications?
Pregnant female daycare workers (may give child generalized infection - hsm, hearing loss, vision impairment, retardation, death)
CMV transmission
body secretions (blood, saliva, breast milk, urine),
sexual contact
organ transplantation
transplacental
Are people usually infected with multiple CMV strains?
no, normally just one, except if they're immunocompromised
Severe CMV presents in:
immunocompromised ppl
fetuses infected transplacentally
Dz caused by CMV
asx
mono-like syndrome ("heterophile negative mononucleosis," fever, mild hepatitis)
pneumonia (esp. transplant pt.s)
retinitis (esp. AIDS)
colitis
esophagitis
encephalitis (only AIDS)
Babies infected with CMV in utero but asx at birth...
5-10% go on to have some sort of hearing loss, chorioretinitis or mental retardation
How long does it take to culture CMV?
3-6 weeks
CMV Dx
culture
ELISA (but this requires host response)
shell vial technique detects immediate early and early genes, beware of FNs
PCR of plasma! or PBMC (peripheral blood mononuclear cells)
CMV Ag detection
Most common means of CMV Dx
PCR of plasma
CMV strategies to evade immune detection
downregulate MHC I (retain in ER, degrade heavy chains in cytosol, block peptide transporter req'd for assembly)
downregulate MHCII (HLA-Dra and HLA-Dma degraded)
CMV tx
ganciclovir
foscarnet
cidofovir
(all act on DNA Pol of CMV)
Note: ganciclovir must be phosphorylated by viral kinase encoded in UL97 CMV region
Host defense against CMV infection
humoral (IgM and IgG) and CMI
CMI critical for recovery from infection
From where does EBV acquire its envelope?
nuclear membrane
what is special about EBV's genome
It is divided into UL and US sequences and has tandomly reiterated terminal direct repeats and tandomly reiterated internal direct repeats
How many EBV strains infect humans, and how do these strains differ?
2
differ in sequence of viral genes expressed in latent infection
differ in abillity to transform B cells
no clinical difference
What types of cells does EBV infect?
B lymphocytes and nasopharyngeal epithelial cells
Where is EBV latency established?
B lymphocytes
Can EBV immortalize cells?
Yes, lymphoid ones
Which EBV membrane glycoproteins allow entry into the host cell?
gp350 binds CD21 on B cell
gH, gL and gp42 complex, and gp42 binds HLA-DR to allow penetration of cell membrane
What population is intrinsically immune to EBV?
Patients with X-linked agammaglobulinemia (lack mature B cells)
What EBV genes are expressed during latency?
Different genes in different condtions, but at least 10 possible genes:
2 RNAs (EBER-1, EBER-2),
6 nuclear proteins (EBNA-1, 2, 3A, 3B, 3C, LP)
and 3 membrane proteins (LMP-1, LMP-2A, LMP-2B)
What dz and latency genes is type 1 EBV latency associated with?
Burkitt's lymphoma,
only EBER-1, 2, and EBNA-1 are expressed
What dz and latency genes is type 2 EBV latency associated with?
nasal pharyngeal carcinoma,
only EBER-1, 2, EBNA-1 and LMP are expressed
What dz and latency genes is type 3 EBV latency associated with?
noncancerous cells
At least 10 genes are expressed
Function of EBNA-1 (EBV latency gene)
maintain EBV episome
Function of EBNA-2 (EBV latency gene)
upregulates the expression of LMP-1 and 2
Function of EBNA-3 (EBV latency gene)
a set of 3 proteins (A, B,C)
A inhibits EBNA-2's upregulation of LMP-2
B and C upregulate expression of selective B cell proteins, leading to B cell proliferation
Function of BARF-1 and BCRF-1 (EBV latency genes)
block the ability of interferon to inhibit growth of EBV transformed cells
Function of BHRF-1 and LMP-1 (EBV latency genes)
inhibit apoptosis
What % of adults have Abs to EBV?
90-95%
EBV transmission
mostly saliva (persists in oropharynx for 18 months after mono)
EBV dz
asx
minor resp. infection (infants and young children)
infectious mononucleosis
Infectious mononucleosis sx
fever
lymphadenopathy
pharyngitis
splenomegaly
jaundice, hepatomegaly, rash maybe
complications of mono
splenic rupture, hepatitis, cardiac and pulmonary problems
What virus can kill or cause B cell lymphomas in X-linked lymphoproliferative dz patients?
EBV
since X-linked lymphoprolif. dz is caused by absence of SAP (SLAM-associated protein), normal T and B cell interaction is impaired, leading to unregulated growth of EBV-infected B cells
What malignancies can occur months to years after EBV infection?
Burkitt's lymphoma,
nasopharyngeal carcinoma (esp. in South china),
Hodgkin's dz
What dz can EBV cause in immunosuppressed patients?
oral hair leukoplakia
lymphoid interstitial pneumonitis
non-Hodgkin's lymphoma
Describe Burkitt's lymphoma
high-grade malignant lymphoma of B cells,
in central Africa, assoc. with EBV and P. falciparum malaria, usually present in jaw.
In US, present as abdominal tumors, less assoc. with EBV
translocation 8: 14, 22, or 2 moves c-myc oncogene near Ig heavy or light chain, leading to abnormal regulation of c-myc gene (when expressed, increases tumorigenicity)
Host defense against EBV
humoral (IgM and IgG) and CMI
CMI critical for recovery from infection

Note: EBV depresses non-EBV specific CMI (reverses CD4+/CD8+ ratio for more than 3 months)
Mono dx
atypical lymphs (though also present in other conditions)
Monospot (heterophile test)
EBV-specific Abs
Morphology of atypical lymphocytes
larger (more cytoplasm), have nucleoli in their nuclei

cytoplasm tends to be indented by surrounding RBCs
Dzs that show atypical lymphocytes
EBV
Toxoplasmosis
Rubella
viral hepatitis
mumps
drug rxns
Which dx test is most sensitive and specific for EBV?
EBV-specific Ab test

(also more expensive)
When is a monospot most likely to be positive?
2-3 weeks after onset of illness (peak of heterophile Abs)
where are hookworm infections found? where does necator americanus predominate?
worldwide, but esp. in moist, warm climates.
N. americanus predominates in the Americas and Australia (ex. Southeast US)
what form of hookworm is infectious?
filariform larva
What is the most common symptom of hookworm infection?
iron deficiency anemia (caused by blood loss at site of intestinal attachment)
Hookworm sx
Iron deficiency anemia
"ground itch" - local skin manifestations (during larvae penetration)
respiratory symptoms (during pulmonary migration of larvae)
Hookworm dx
eggs in stool
Describe hookworm life cycle
eggs in stool, hatch into larvae in 1-2 days of warm, moist, shaded soil.
after 5-10 days (2 molts), become filariform infective larvae (survive 3-4 weeks), penetrate skin
carried in veins to heart and lungs, penetrate pulmonary alveoli, ascend bronchial tree and swallowed
reside and mature in small intestine for 1-2 years
What are diagnostic characteristics of hookworm eggs?
ellipsoidal shape and thin shell
Where is Strongyloides stercoralis found?
subtropical and tropical areas,
very low frequency in Southeastern US
How does Strongyloides' life cycle differ from other nematodes?
Can be free-living adult worms in the environment, and can also autoinfect by larvae penetrating perianal skin or interstinal mucosa
Strongyloides dx
larvae in feces
Strongyloides sx
asx
GI symptoms (ab pain, diarrhea)
pulmonary symptoms (during migration through lungs)
"creeping eruption" on back from autoinfection
How long can Strongyloides infections persist in a host?
40 years b/c capable of autoinfection
Stongyloides hyperinfection sx
ab pain
distension
shock
pulmonary complications
neurological complications
septicemia
potentially fatal!
What happens when you treat an immunosuppressed person who is hyperinfected with Strongyloides with steroids or chemo?
rapid dissemination of the organism through the body!
life-threateining!
Strongyloides tx
ivermectin
thiabendazole (alternative)
What is whipworm?
Trichuris trichiura
Where is Trichuris trichiura found?
worldwide, esp. tropical climates with poor sanitation (fecal/oral transmission)
How is trichuris trichiura transmitted/acquired?
fecal/oral - unembryonated eggs passed in feces, embryonated eggs are ingested
Does Trichuris trichiura cause eosinophilia?
No
Where inside the body do adult Trichuris trichiura reside?
large intestine
Trichuris trichiura dx
unembryonated eggs in feces
Trichuris trichiura sx
asx
heavy infection in undernourished children, cause chronic bloody diarrhea and rectal prolapse
How long can Trichuris trichiura survive in the host?
up to 6 years, avg. 3 years
How long does it take Trichuris trichiura eggs to become infective?
15 to 30 days in the soil
How long after the adult Trichuris worms are fixed in the colon do the females begin to lay eggs?
60-70 days, shedding 3,000 to 20,000 eggs/day!
Lifespan of adult Trichuris worm
1 year
What is the pinworm?
Enterobius vermicularis
What is the most common nematode infection in the US?
Enterobius vermicularis (pinworm)
Where is Enterobius found?
worldwide, just as prevalent in developed and developing countries.
more frequent in children
Is Enterobius vermicularis zoonotic?
No, obligate human
Does enterobius cause eosinophilia?
No
Enterobius dx
Scotch tape test (eggs collected from perianal area)
Enterobius sx
asx
perianal itching (can lead to excoriations and bacterial superinfection)
very occasionally appendicitis or salpingitis (due to migration)
How long does it take Enterobius to become infectious?
4-6 hours
Describe Enterobius life cycle
eggs deposited on perianal folds, autoinfection when eggs transferred from itching butt to eating, or via contaminated environmental surfaces.
Adults establish in the colon within 1 month, and nocturnally migrate to perianus and lay eggs.
Where in the host do adult Enterobius worms establish themselves?
Colon
Life span of adult Enterobius
2 months
Is Anisakis zoonotic?
Yes, larvae infect fish (herring, mackerel)
What temperatures kill the Ansakis in fish?
heat to 60 degrees, freeze to -20 degrees
FOR MORE THAN 24 hours
Ansakis sx
severe epigastric pain
vomiting
Ansakis tx
surgically remove worms
How are Ansakis species worms acquired?
eating undercooked seafood
Ansakis species reside in the stomach of what?
Marine mammals
What stage are the Ansakis larvae we ingest when eating raw fish?
3rd stage
1st stage form in embryonated eggs in the water of marine mammal feces,
2nd stage are free-swimming and are ingested by crustaceans
Factors to consider when choosing a schizonticide for malaria treatment
expected resistance pattern of organism
severity of infection
patient's background immune status
Which antimalarial drug acts on all stages of life cycle?
none
What does chloroquine phosphate treat?
Any malaria type except resistant P. falciparum
Mech of chloroquine phosphate
inhibit heme polymerase activity in intraerythrocytic form,
accumulates free heme (toxic to parasites)
inhibits release and action of TNF-alpha
Probable mech of resistance to chloroquine phosphate
reduced uptake or rapid excretion
(resistance present in P. falciparum and Asian P. vivax)
Chloroquine phosphate admin
PO
Primaquine phosphate admin
PO
What does primaquine phosphate treat?
tissue forms of P. vivax and T. ovale
Mech of primaquine phosphate
kills intrahepatic form, prevents dev of erythrocytic forms that are responsible for relapses
(also kills gametocytes)
Major side effects of primaquine phosphate
hemolytic anemia (Glucose-6-phosphate def)
Quinine gluconate admin
IV or parenteral
Quinidine sulfate admin
PO
Quinidine sulfate treats
chloroquine-resistant P. falciparum
Quinine gluconate treats
life-threatening chloroquine-resistant P. falciparum malaria
Quindine gluconate side effects
4x as cardiotoxic as quinine
Quinidine mech
inhibit heme polymerase of Plasmodium
Which drugs are considered Quinolones?
chloroquine
primaquine
mefloquine
quinine
quinidine
Which antiparasitic drugs inhibit folate metabolism?
pyrimethamine
Fansidar
sulfonamides
proguanil
Pyrimethamine treats
chloroquine-resistant P. falciparum malaria (in conjunction with quinine and sulfadoxine)
toxoplasmosis (treatment and prophyllaxis)
What is Fansidar?
combo drug of pyrimethamine and sulfadoxine
first line in developing world because cheap
2nd line in developed world because resistance exists
Pyrimethamine mech
inhibits parasitic dihydrofolate reductase, resulting in inhibition of tetrahydrofolic acid synthesis
Pyrimethamine resistance mech
point mutations in parasite dihydrofolate reductase-thymidylate synthase enzyme
(decreases drug binding at active site)
Where and for what is artemisin used?
Asia for quinine resistant P. falciparum
not licensed in US.
Mech of artemisin
bind iron in malarial pigment, produce free radicals that damage parasite proteins
What is Malarone?
atovaquone and proguanil hydrochloride (antimicrobial).
combo b/c atovaquone develops resistance when used alone
Malarone treats
acute, uncomplicated P. falciparum malaria
acute, mild-to-moderate Pneumocystis carinii pneumonia in Septra intolerance
Malarone admin
PO
Atovaquone mech
selective inhibitor of mitochondrial electron transport (cytochrome bc1 complex) of Plasmodium.
Proguanil hydrochloride mech
it's metabolite cytoguanil is a dihydrofolate reductase inhibitor (disrupts deoxythymidylate synthesis)
Atovaquone resistance mech
single point mutations in cytochrome-b gene
Ivermectin treats
intestinal Strongyloides stercoralis
larval Onchocerca volvulus
Ivermectin mech
potent agonist at GABA receptors, paralyzing parasites
(doesn't cross BBB, so not paralytic to humans)
How is ivermectin acquired?
produced by Streptomyces avermitilis
(a member of avermectins, macrocyclic lactones that are produced by this organism)