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1158 Cards in this Set
- Front
- Back
What is the #1 reason for visiting the doctor?
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Respiratory infection
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What is the #2 reason for visiting the doctor?
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UTI
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What is the most common nosocomial infection?
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UTI
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UTIs occur more often (30:1) in...
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women
|
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UTIs predispose patients to
|
sepsis and shock
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UTI def'n
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the microbial invasion of any tissue of the urinary tract, extending from the renal cortex to the urethral meatus
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How many colonies must be present, per mL of urine, for asymptomatic bacteriuria to be dx?
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10^5 colonies per mL urine
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What is asymptomatic bacteriuria?
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the colonization of the urinary tract in the absence of symptoms, with 10^5 colonies per mL urine, or more
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What is cystitis?
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an infection limited to the bladder and lower urinary tract.
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How does cystitis present?
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dysuria, frequency and urgency
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What presents with dysuria, frequency and urgency?
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Cystitis (limited to bladder and lower urinary tract)
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What is dysuria?
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Painful urination
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What is pyelonephritis?
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an inflammation and infection of the kidney
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How does pyelonephritis present?
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fever, chills, and flank pain, also possibly with symptoms of a lower urinary tract infection.
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How does urethritis present?
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pain, burning and discharge from the urethra
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What is a likely cause of urethritis?
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STDs
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What presents as pain, burning and discharge from the urethra?
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Urethritis
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What presents as fever, chills and flank pain?
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Pyelonephritis. Also possibly includes symptoms of a lower urinary tract infection
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What are the peak times in a woman's life for getting UTIs?
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Infancy, Preschool, "Honeymoon Cystitis," "Pyelitis of pregnancy," and then continue steady increase into old age
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When do men tend to get UTIs?
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Infancy, or elderly years (Prostatitis)
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Which gender gets more symptomatic UTIs in middle age?
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Women
|
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Which gender gets more symptomatic UTIs in old age?
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Men
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Which gender gets more asymptomatic bacteriurias?
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Women, throughout the lifespan
|
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When might men get asymptomatic bacteriurias?
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Only recorded in old age (>55yo)
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Which types of bacteria are the most common causes of UTIs?
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facultative bacteria of fecal origin
E. coli (90% of acute UTIs in normal patients) |
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Most common UTI bacteria in young women that are sexually active
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E. coli
Staphylococcus saprophyticus |
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Most common UTI bacteria in elderly men with prostate problems
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Enterococcus faecalis
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Most common UTI bacteria in young boys
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Proteus mirabilis
|
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Most common UTI bacteria in patients with stones
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Proteus mirabilis
|
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Most common UTI bacteria in diabetics (esp. if poorly controlled)
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Klebsiella
Group B Strep Candida |
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Most common UTI bacteria in patients treated with antibiotics
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Pseudomonas
|
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Most common UTI bacteria in patients with underlying disease
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Staph aureus
|
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What % of UTIs are caused by ascending infection?
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95%
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What usually precedes an ascending UTI?
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periurethral or introital colonization
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What organisms are associated with ascending UTI?
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E. coli
Other Enterobacteriaceae such as Proteus sp., Staphylococcus saprophyticus, enterococci, and Candida |
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What % of UTIs are caused by hematogenous route?
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5%
|
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What organisms are associated with the hematogenous UTI?
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Staphylococcus aureus,
Cryptococcus neoformans, Coccidioides immitis and a number of viruses |
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What is the major facultative organism of the urinary tract?
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E. coli
|
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Which of E. coli's virulence factors contributes to its UTI pathogenicity?
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K1 capsule
• Type 1 (Mannose Sensitive) fimbriae, • Type 2 (Mannose Resistant) fimbriae, • Hemolysin, • Flagella, • LPS, • Aerobactin, |
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what property of K1 capsule contributes to its UTI pathogenicity?
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antiphagocytic
E. coli virulence factor |
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Important UTI-relevant pathogenic feature of type 1 fimbriae
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Type 1 (Mannose Sensitive) fimbriae enable colonization of the lower urinary tract
|
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Important UTI-relevant pathogenic feature of type 2 fimbriae
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allow colonization of the upper urinary tract.
E. coli virulence factor |
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Important UTI-relevant pathogenic feature of hemolysin
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injures the bladder mucosa.
E. coli virulence factor |
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Important UTI-relevant pathogenic feature of flagella
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allow the organism to be motile
E. coli virulence factor |
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Important UTI-relevant pathogenic feature of LPS
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inhibits urinary tract peristalsis.
E. coli virulence factor |
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Important UTI-relevant pathogenic feature of aerobactin
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siderophore which allows iron acquisition in the iron poor environment of the urinary tract
E. coli virulence factor |
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important virulence factors that contribute to Proteus mirabilis' UTI pathogenicity
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Urease
Alkaline urine |
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Important UTI-relevant pathogenic feature of urease
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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 |
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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. |
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If you have alkaline urine, what organism likely caused the UTI?
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Proteus mirabilis
|
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Which of Klebsiella's virulence factors contributes to its UTI pathogenicity?
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large capsule made in the presence of abundant glucose (i.e. uncontrolled diabetes)
|
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Which of Staphylococcus saprophyticus' virulence factors contributes to its UTI pathogenicity?
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adherence to uroepithelial cells
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Most important host defense against UTI
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normal urinary flow
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Mechanical factors predisposing to UTI
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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) |
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Genetic factors predisposing to UTIs
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-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 |
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2 types of type 2 pili
|
P pili
X adhesions |
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What do P pili do?
|
bind to neutral glycolipids of the globoside series
|
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What do X adhesins do?
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bind to different globosides and are not well understood
|
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Which type of fimbriae are associated with renal colonization?
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Type 2
|
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Hormonal factors predisposing to UTIs
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Progesterone both dilates the upper collecting system and decreases peristalsis.
Postmenopausal estrogen deficiency In pregnancy, the baby presses on the bladder |
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Immunologic/tissue factors predisposing to UTIs
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renal medulla is a "desert" where complement and polys do not function
|
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Behavioral factors predisposing to UTIs
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sexual intercourse
anal sex diaphragm/spermicide use voiding practices possibly carbonated beverages |
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Characteristics of urine protecting against UTIs
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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. |
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Inhibitors of adherence to GU epithelia
|
Tamm-Horsfall protein
Bladder mucopolysaccharide Secretory IgA Prostatic secretions |
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UTI Dx
|
White Blood Cells in the Urine
And 105 bacteria per ml of urine on culture |
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Cystitis Dx
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White Blood Cells in Urine
And 102-103 bacteria per ml of urine on culture if symptoms are present |
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If you see white cell casts in someone's urine, it's indicative of...
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kidney involvement
|
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What are some problems and pitfalls in diagnosing UTIs?
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• 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 |
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Untreated UTIs can cause these complications:
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• Sepsis
• Low birth weight infants/premature labor • Progressive renal parenchymal loss/renal scarring • Renal calculi • Perinephric/renal abscesses • Prostatitis |
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Treatment of UTI
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• 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. |
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How long is cystitis usually treated for?
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3-5 days
|
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How long is pyelonephritis usually treated for?
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2 weeks
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How long is recurrent pyelonephritis and prostatitis treated for?
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6 weeks
|
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the Tamm-Horsfall protein is...
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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. |
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what does the bladder mucopolysaccharide do?
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decreases bacterial adherence
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what do prostatic secretions do?
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inhibit bacterial growth
|
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Characteristics of a eukaryotic cell
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a true nucleus,
multiple chromosomes, membrane-bound organelles, and 80s ribosomes |
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Which four kingdoms belong to Domain Eukarya
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Animalia
Plantae Protista Fungi |
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What two domains used to make up Domain Prokaryotae?
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Bacteria and Archaea
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Which domain did Eukarya branch off from?
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Archaea
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Characteristic of cells in Domain Archaea
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living in extreme environments
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Which domain do all parasites belong to?
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Domain Eukarya
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Def'n of protozoa
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single-celled, eukaryotic organisms
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Which two protozoa phyla contain important human parasites?
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Phylum Sarcomastigophora and Apicomplexan
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How are protozoa subdivided?
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Based on their means of locomotion.
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What type of reproduction do protozoa undergo?
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Asexual reproduction
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Is the severity of the disease related to the infecting dose of protozoa?
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No, because it multiplies inside the host.
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Which 2 (of 3) subphyla of Sarcomastigophora are medically important?
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Mastigophora
Sarcodina |
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Phylum Sarcomastigophora is composed of...
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amoeboid and [animal-like] flagellated protozoans
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What do Mastigophora use for locomotion?
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Flagella
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What do Sarcodina use for locomotion?
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Pseudopods
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Examples of Mastigophora
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Giardia,
Trypanosoma Trichomonas vaginalis Leishmania |
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Examples of Sarcodina
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Entamoeba histolytica
|
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Dzs caused by Trypanosoma
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African Sleeping Sickness and Chagas Dz
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What causes African Sleeping Sickness and Chagas Dz?
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Trypanosoma (brucei and cruzi, respectively)
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All members of phylum Apicomplexan are...
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intracellular parasites
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What do Apicomplexans use for locomotion?
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They are nonmotile.
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How do Apicomplexans penetrate host cells?
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Via a complex of organelles at the apex of their cells
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How do apicomplexans reproduce?
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capable of both sexual and asexual reproduction, have complex life cycles
|
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Examples of Apicomplexans
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Toxoplasma, Plasmodium, Crytosporidium, Cyclospora and Babesia
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Which agent causes East African sleeping sickness?
|
Trypanosoma brucei rhodesiense
|
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Which agent causes West African sleeping sickness?
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Trypanosoma brucei gambiense
|
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How is African sleeping sickness transmitted?
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tsetse fly (Glossina species)
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Why is African sleeping sickness produced in waves of parasitemia?
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antigenic variation of the VSG (variant surface glycoprotein)
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What is the natural history of African sleeping sickness?
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CNS involvement in death
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Which African sleeping sickness (East or West) progresses more rapidly (weeks to months, as opposed to months to years)?
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East
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Which type of African sleeping sickness (East or West) are tourist hunters more likely to get and why?
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East, because that's where the game parks, and reserves are located.
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What is another name for American trypanosomiasis?
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Chagas disease
|
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What transmits American trypanosomiasis?
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Reduviid bug, aka kissing bug or assassin bug
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Where is the Reduviid bug native?
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South and Central America
|
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How does the Reduviid bug infect a host?
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biting and then defecating, usually when host is asleep.
Host rubs feces into skin, eyes, or mouth |
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Why does Chagas dz hit low income populations more than other populations?
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The Reduviid bug lives in cracks in substandard housing.
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How many stages does Chagas dz have?
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3: acute, intermediate, chronic
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Romana's sign is a sign of what dz?
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acute infection with Chagas dz
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What is Romana's sign?
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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.
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What are symptoms of Chagas dz?
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Romana's sign
fever fatigue weight loss |
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How long does it take for symptoms of Chagas dz to resolve?
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4-8 weeks
|
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What percentage of people with Chagas dz show symptoms in the acute phase?
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1%
|
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What percentage of people with Chagas dz develop the chronic phase (after 10-20 years)?
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1/3
|
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What happens in the intermediate phase of Chagas dz?
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host has no sx
organism multiplying in macrophages in the GI and heart |
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What are symptoms of chronic infection with Chagas dz?
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heart: enlargement and alteration in rate and rhythm, leads to heart failure and arrest
GI: megaesophagus and megacolon lead to constipation and difficulty swallowing |
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Tx of acute phase Chagas dz
|
nifurtimox and benznidazole : cure 50%
|
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Tx of chronic phase Chagas Dz
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supportive measures, symptom relief
|
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Where do Leishmania live?
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phagolysosome of macrophages
(they are strict intracellular pathogens) |
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How are Leishmania transmitted?
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bite of the phlebotomine sand fly
|
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What are the 3 classes of disease caused by Leishmania?
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cutaneous leishmaniasis,
mucocutaneous leishmaniasis and visceral leishmaniasis |
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Where is cutaneous leishmaniasis found?
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the Old World and the New World
|
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What about the Leishmania species that causes cutaneous leishmaniasis limits its growth to the skin?
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Cannot grow at temperatures above 35 degrees
|
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How does cutaneous leishmaniasis present?
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one or more sores on the skin that heal spontaneously over time (months to years)
|
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How long does it take a cutaneous leishmaniasis sore to heal?
|
months to years, but they heal spontaneously
|
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What 3 organisms cannot grow above 35 degrees?
|
Leishmania (cutaneous type)
Mycobacterium marinum, Sporothrix schenckii |
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Where is mucocutaneous leishmaniasis found?
|
Amazon forest and central plain of South America
|
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What causes mucocutaneous leishmaniasis?
|
L. braziliensis
|
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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) |
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What causes visceral leishmaniasis?
|
L. donovani complex
|
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How does visceral leishmaniasis disseminate?
|
Via the blood stream, infecting the reticuloendothelial system (which, when infected chronically, loses its lymphocytic response)
|
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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 |
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What is the untreated mortality rate for visceral leishmaniasis?
|
70-90%
|
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Which species of Leishmania is capable of growth at core temperatures?
|
L. donovani (causes visceral leishmaniasis)
|
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How is Babesiosis transmitted?
|
bite of the Ixodes tick
|
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Where do Babesia species undergo their life cycle?
|
Inside RBCs
|
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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 |
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Babesiosis is more severe in what type of patients?
|
Asplenic
|
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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
|
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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
|
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Can Cyclospora be treated with trimethoprim-sulfamethoxazole?
|
Yes
|
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Can Cryptosporidium be treated with trimethoprim-sulfamethoxazole?
|
No
|
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What Kingdom are Helminths a part of?
|
Kingdom Animalia
|
|
How many worm phyla are there?
|
3
|
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How many parasitic worm phyla are there?
|
2
|
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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) |