ID Unit 1 Flashcards

Question

Intrabdominal syndromes can be caused by

Answer 1

*E coli anaerobes (esp **Bacteriodes fragilis) Klebsiella Enterococcus

Answer 2

*N gonorrhoeae Chlamydia trachoma's Treponema pallidum

Answer 3

Tumor- swelling Rubor- redness Calor- heat Dolor- pain loss of function

Answer 4

cancer lymphomas, RCC, hepatoma lung, sarcoma, myxoma, uterine, liver metastases chemicals antibiotics, anti-epileptics, cardiac collagen/vascular SLE, RA, vasculitis, Still's, Gout Clot PE, DVT, hematoma, pelvic Central fever rare consider: hyperthermia, hyperthyroid, cholesterol emboli, pheochromocytoma, sarcoid, factitious, MI

Answer 5

``` Staph aureus (incl MRSA) Group A strep (strep pyogenes) Pneumococcus Mycobacteria Fungi (Candida) Ps aeruginosa ``` Disease only: Measles Ebola Virus

Answer 6

Gram positive: Cell wall synthesis- beta lactams (PCN, cephalosporins) Glycopeptides (vancomycin) ``` Gram Negative: Cell membrane- polymyxins Outer membrane regulates- Beta lactamases permeability efflux ```

Answer 7

Is it an infection? (history, PE, labs) Where is it? (where is it not?) What are the bugs likely in this pt? (host, environment, agent) What are the drugs?

Answer 8

Bacteriostatic would expect to see constant bacterial load allows time for immune sys to kick in and eventually decrease the bac load --will not be helpful in neutropenic (immunocompromised) pts bactericidal bacterial load should decrease actively killing bacteria better- less opportunity for resistance if you have smaller load present

Answer 9

minimum inhibitory concentration: concentration required to stop growth (all drugs have this) Minimum bactericidal concentration: concentration needed to kill 99% of bac higher than MIC drug conc's will decrease until you give another dose and even fall below MBC and MIC lines -but bac growth still inhibited- post-antibiotic effect (PAE) of bactericidal drugs --the half life of these drugs doesn't necessarily reflect dosing regimen --if drug has good PAE, you want to minimize the amount of time the drug is above the toxic line- give higher conc of drug less frequently

Answer 10

absorption of drug into body (IV vs oral) Distribution- CSF, tissues, bones, etc Metabolism- whether drug passes through liver (CP450 interactions that inhibit/activate drug) Excretion- hepatic or renal dosing schedule and duration of tx: too short- resistance; reoccurrence too low- resistance too high- dose-related toxicity pt compliance

Answer 11

``` immune system status very young or very old hypersensitivities different susceptibilities pregnancy ```

Answer 12

``` narrow: act primarily on GN or GP Bacitracin Clindamycin Metronidazole Penicillin G, V Penicillinase- resistant penicillins Vancomycin Monobactams Polymyxins Daptomycin ``` ``` Extended: All can act on GP and some GN Amino glycosides Cephalosporins Extended spectrum penicillins Fluoroquinolone's Carbapenems Macrolide's Streptogramins ``` ``` Broad: bacteriostatic possibly more superinfections not useful in immunocompromised pts Chloramphenicol Sulfonamides Tetracycline Trimethoprim ```

Answer 13

beta lactams: ``` Penicillins cephalosporins carbapenems monobactams vancomycin bacitracin cycloserine ```

Answer 14

beta lactams (cell wall synthesis inhibitors) bactericidal renal excretion adverse rxns: anaphylaxis (Type 1) Rash, etc (type 3) high dose- convulsions

Answer 15

``` G = IV/IM (poor oral) V= good po ``` ``` spectrum/uses: All Gram + (cocci and rods) Gram - cocci spirochetes penicillinase sensitive! ```

Answer 16

Methicillin, oxacillin, naficillin bulky R group to block beta-lactamase access to beta-lactam ring "use naf for staph" (except MRSA, which has altered PBP's)

Answer 17

Ampicillin, amoxicillin, aminopenicillins (w/ lactase inhibitor) AMinoPenicillins are AMPed up penicillins amOxicillin has greater Oral bioavailability than ampicillin good po can cause GI upset ``` spectrum: penicillinase sensitive! ampicillin/amoxicillin HELPS kill enterococci (H influenzae H pylori E coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella enterococci) ``` Adverse rxns: pseudomembranous colitis MORs: penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring

Answer 18

Peperacillin, ticarcillin (w/ lactamase inhibitor) extended spectrum clinical use: Pseudomonas gram negative rods penicillinase sensitive!

Answer 19

CAST Clavulanic Acid Sulbactam Tazobactam often added to penicillin antibiotics to protect from beta-lactamase (penicillinase) destruction

Answer 20

generations 1-5 beta lactic drugs bactericidal less susceptible to penicillinases organisms typically not covered by 1-4th generation cephalosporins are LAME: Listeria Atypical (chlamydia, mycoplasma) MRSA Enterococci --exception: ceftaroline (5th gen cephalosporin) covers MRSA

Answer 21

1st gen: cefazolin, cephalexin ``` covers: gram + cocci and PEcK: Proteus mirabilis E coli Klebsiella pneumoniae --Cefazolin prior to surgery to prevent Staph aureus wound infections ```

Answer 22

ceFAclor, ceFOXitin, ceFURoxime (Fake fox fur) ``` covers: gram + cocci and HENS PEcK H influenzae Enterobacter aerogenes Neisseria spp Serrate marcescens Proteus mirabilis E coli Klebsiella pneumoniae ```

Answer 23

ceftriaxone, cefotaxime, ceftazidime treats serious Gram negative infections resistant to other beta lactams Ceftriaxone: meningitis, gonorrhea, disseminated Lyme disease Ceftazidime: Pseudomonas

Answer 24

Cefepime treats gram negative organisms with increased activity against Pseudomonas and gram + organisms

Answer 25

Ceftaroline broad gram positive and gram neg organism coverage, including MRSA --does not cover Pseudomonas!!

Answer 26

Aztreonam narrow spectrum aerobic gram negative rods only for penicillin-allergic pts and those w/ renal insufficiency

Answer 27

Imipenem, Meropenem, Ertapenem, Doripenem ``` Wide spectrum gram + cocci gram neg rods anaerobes (reserve for resistant, life-threatening organisms) significant side effects (CNS toxicity) ``` Imipenem is always given w/ Cilastatin (to lower inactivation of drug in renal tubules) "w/ imipenem, the kill is lastin' with cilastatin"

Answer 28

bactericidal (except bacteriostatic vs C difficile) not susceptible to beta-lactamases ``` covers: narrow gram positive cocci serious, multidrug-resistnat organisms incl **MRSA, S epidermis, sensitive Enterococcus species, C difficile ``` ``` well tolerated but NOT trouble free: Nephrotoxicity Ototoxicity Thrombophlebitis diffuse flushing- red man syndrome (pretreat w/ antihistamines and slow infusion) ``` MOR: "pay back 2 D-ala's for VANdalizing vancomycin"

Answer 29

target the bacterial ribosome (70s made of 30s + 50s) -have to be influxed; can be effluxed "Buy AT 30, CCel at 50" 30s inhibitors: A= Aminoglycosides (bactericidal) T- tetracyclines 50s inhibitors: C= Chloramphenicol, Clindamycin E= Erythromycin (macrolides) L= Linezolid (variable) all are reversible except aminoglycosides (bactericidal)

Answer 30

protein synthesis inhibitor bactericidal irreversible inhibition of initiation complex via binding 30s subunit misreading of mRNA blocks translocation requires O₂ for uptake (ineffective against anaerobes) "GNATS caNNOT kill anaerobes in A-MIN(oglycosides) ``` Gentamicin Neomycin Amikacin Tobramycin Streptomycin ``` IV (poor oral) distribute through total body water ``` very good against E coli and pseudomonas systemic, severe, rapidly progressing infections (severe GNRs) synergistic w/ beta-lactams Neomycin for bowel surgery ``` ``` therapeutic levels are close to toxicity (where it accumulates) NNOT: Nephrotoxicity Neuromuscular block Ototoxicity (esp w/ loop diuretics) Teratogenic ```

Answer 31

Protein synthesis inhibitors Tetracycline Doxycycline Minocycline broad spectrum gram +/- accumulates intracellularly good for Rickettsia and Chlamydia, acne adverse effects: abnormal bone and tooth development (not <8yo) superinfections- fungal photosensitivity contraindicated in pregnancy chelates w/ divalent cations (don't consume milk/iron/antacids)

Answer 32

protein synthesis inhibitors via block of translocation (macroSLIDES) erythromycin azithromycin clarithromycin ``` spectrum: medium spectrum GP and some GN atypical pneumonias (mycoplasma, chlamydia, Legionella) STIs (chlamydia) B pertussis ``` ``` adverse rxns: drug interactions due to inhibition of P450 metabolism MACRO: gi Motility issues Arrhythmia (prolonged QT) acute Cholestatic hepatitis Rash eOsinophilia ```

Answer 33

protein synthesis inhibitor broad spectrum: treats meningitis (H influenzae, Neisseria meningitidis, Streptococcus pneumoniae) treats Rocky Mountain Spotted Fever (Rickettsia rickettsia) ``` limited use due to high toxicity, but cheap bone marrow toxicity anemia (dose dependent) aplastic anemia (dose independent) gray baby syndrome (premature infants) ```

Answer 34

protein synthesis inhibitors Clindamycin spectrum: narrow spectrum gram + cocci (penicillin alternative) anaerobes ABOVE the diaphragm- Bactericides spp, C perfringens) in aspiration pneumonia, lung abscesses, oral infections acne invasive Group A strep (strep pyogenes) adverse rxns: severe diarrhea pseudomembranous colitis (C diff overgrowth) fever

Answer 35

protein synthesis inhibitor Quinupristin Dalfopristin reserved for life threatening VRE

Answer 36

protein synthesis inhibitor Linezolid gram +, specifically MRSA and VRE adverse effects: bone marrow suppression (esp thrombocytopenia) peripheral neuropathy serotonin syndrome

Answer 37

``` Clindamycin, chloramphenicol Rifampin Isoniazid Metronidazole Erythromycin Sulfonamides, streptogramins ```

Answer 38

folic acid metabolism and reduction (DNA methylation) targeted because bac make their own folic acid and humans don't (but bac can get folic acid from a pustule!! so not helpful there) MOA: sulfonamides inhibit dihydropteroate synthase (DHPS) Trimethoprims inhibit dihydrofolate reductase --- selective toxicity bacteriostatic w/ delayed onset of action (5-6hrs) synergistic w/ other drugs in same pathway ``` Toxicity: moderately safe renal damage- crystalluria hematopoeitc system (anemia) hypersensitivity rxns drug interactions (displacement from albumin eg warfarin) Kernicterus in neonates GI upset common ``` earliest antibiotics- lots of resistance; not really used alone anymore sulfonamides trimethoprim

Answer 39

antimetabolite- inhibit folate synthesis sulfamethoxazole SMX sulfisozazole sulfadiazine ``` gram positive gram negative Nocardia Chlamydia SMX for simle UTI ``` add trimethoprim in combo w/ sulfonamide for sequential block of folate synthesis TMP Treats Marrow Poorly- can cause megaloblastic anemia, leukopenia, granulocytopenia)

Answer 40

fluoroquinolone metronidazole nitroimidazole inhibit DNA gyrase and TopoIV selective toxicity (humans don't have gyrase) bactericidal and rapid!!! many organisms resistant to ahminoglycosides and penicillins are sensitive to fluoroquinolone

Answer 41

important drug group! DNA gyrate inhibitors (induces supercoils) bactericidal -floxacin's (Ciprofloxacin) spectrum: gram neg rods of UTIs and GI tracts (incl pseudomonas) Neisseria some gram + organisms ``` do not take w/ antacids! (chelates metals) "fluoroquinolones hurt attachments to your bones" (cartilage, tendons) leg cramps/myalgias GI upset superinfection skin rashes HA, dizziness contraindicated in pregnancy ```

Answer 42

DNA metabolism inhibitor - toxic free radicals that damage bac DNA - has to be reduced to be active (good for anaerobic) bactericidal anti-protozoal anti-parasitic treats anaerobic infection BELOW the diaphragm (vs clindamycin above)- pseudomembranous colitis, severe amebiasis, trichomoniasis ``` "GET GAP on the Metro w/ Metronidazole!" treats: Giardia Entamoeba Trichomonas Gardnerella vaginalis Anaerobes (bactericides, C diff) h Pylori (used w/ PPI and clarithromycin for triple therapy) ``` adverse rxns: disulfiram-like rxn w/ alcohol (severe flushing, tachy, hypotension) HA Metallic taste

Answer 43

urinary antiseptic similar MOA to metronidazole but often only bacteriostatic uses: UTIs, esp in pts allergic to sulfa drugs adverse rxns: moderate GI upset hypersensitivity (hemolytic anemia) neuropathies

Answer 44

2nd generation- Ciprofloxacin 3rd generation- Levofloxacin 4th generation- Moxifloxacin

Answer 45

polymyxins daptomycin interact w/ cell membrane

Answer 46

cell membrane disrupter used topically due to high toxicity

Answer 47

cell membrane disrupter bactericidal against GRAM POSITIVE (like vancomycin) -also active against MRSA, VRE, and Linezolid mild adverse rxns rare eosinophilic pneumonia rhabdomyolysis myopathy lung surfactant inactivates drug restricted use

Answer 48

``` bactericidal: immune compromised, mixed infection, severe infection penicillins cephalosporins vancomycin ahminoglycosides fluoroquinolone rifampin polymyxins, daptomycin ``` ``` bacteriostatic: community setting when pts are immunocompetent some broad spectrum and can give rise to superinfecitons sulfonamides trimethoprim tetracyclines macrocodes clindamycin chloramphenicol ```

Answer 49

inadequate concentration of Ab at site or decreased activity site of infection problems (foreign body, pus) host factors resistance superinfection

Answer 50

``` aerobic gram postiive cocci clusters and pairs (staphylo= grape-like coccus= sphere) blood agar + Chocolate agar + MacConkey agar - catalase positive coagulase positive (often hemolytic and golden) clumping factor positive (binds to fibrinogen --> fibrin (clumping; protection from phagocytosis) ``` virulence factors: cell wall: Protein A!! (binds Fc receptor of IgG's; prevents Ab-mediated phagocytosis) also peptidoglycan, teichoic acids, caps, clumping factor!!!, fibronectin, PB2a!! enzymes: catalase, coagulase, hemolysis, lipase, beta-lactamase toxins: Enterotoxin A1, Exfoliatin A-B, TSST-1

Answer 51

capsule inhibits phagocytosis- clumps and localizes in clusters- gets bigger than the phagocyte

Answer 52

adhesion molecs that stick out of staph to attache to epi layers, particularly nasal/pharyngeal cells

Answer 53

hemolysins: alpha, beta, delta gamma hemolysis cause RBC lysis (all of these cause beta hemolysis) cause tissue damage ``` Pantun-Valentine Leucocidin: WBC lysis protection from phagocytosis invasive skin disease sever invasive disease ```

Answer 54

Exfoliatin A and B: 2 immunologically distinct toxins w/ identical effects bind to GM4 glycolipids (infants) separation at granular cell layer (desmosomes) -the skin exfoliates but it's a very superficial layer Scalded skin syndrome!!

Answer 55

Enterotoxins (enteric): heat and acid stable proteins 30-40% of Staph aureus strains PREFORMED toxin in contaminated food causes vomiting and diarrhea when ingested -mediated by cytokine release! (mast cells) -most common cause of food poisoning!!) Enterotoxins B and C associated w/ TSS due to focal infection

Answer 56

TSST-1 superantigen that stimulates cytokines results in endothelial leakage Binds to MHC II and TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α --> shock Toxic shock syndrome: acute fever, erythroderma (intense rash) shock (hypotension, multi-system involvement) ``` risk factors for TSS: exposure to TSS-containing staph aureus organism growth under conditions that promote toxin production no pre-existing Ab to toxin(s) genetically predisposed ```

Answer 57

normal flora in most humans staph aureus: NOSE some skin, throat, vagina coagulase-negative staph: SKIN some nose, throat

Answer 58

altered cell wall permeability antibiotic-altering enzymes altered protein targets altered metabolism

Answer 59

all staph aureus produce coagulase and nuclease, but MRSA strains carry the mega gene - codes for altered PBP2A - decreases beta-lactam binding and cell wall inhibition - primary mech for methicillin resistance

Answer 60

Vancomycin inhibits cross-polymerization in peptidoglycan vancomycin intermediate staph aureus VISA MIC is 4-8 ug/mL increased number of PG layers vancomycin resistant staph aureus VRSA MIC >=16 ug/nL van A gene from Enterococcus

Answer 61

the phenomenon that has been noted worldwide of slightly increasing vancomycin MIC's still within the susceptible range, but assoc w/ tx failures the higher the MIC, the higher the rate of therapeutic failure

Answer 62

positive test looks like a D shows exposure to erythromycin has induced clindamycin resistance

Answer 63

furunculosis = boils cellulitis- mild to severe also lymphadenitis- local lymph node abscess bet tx- pop and drain; Ab's are 2ndary

Answer 64

staph is uncommon cause of local respiratory spread: otitis sinusitis pneumonia (cystic fibrosis) generally a single deep focus -occasionally doesn't localize well and causes disseminated septicemia

Answer 65

osteomyelitis w/ hematogenous spread local bone abscess staph is most common cause

Answer 66

does not localize often assoc w/: endocarditis or thrombophlebitis

Answer 67

phagocytosis is major host defense impeded by: protein A Pantun-Valentine Leukocidin localizing factors (clumping, coagulase factors)

Answer 68

sex-linked recessive neutrophil defect most common neutrophil defect impaired hydrogen peroxide-mediated intracellular killing- can get chronic infections that just don't heal

Answer 69

leukocyte syndrome - T cell disorder Hyper IgE poor neutrophil chemotaxis/cytotaxis get cold abscesses ``` FATED: coarse Facies, cold (nonin amed) staphylococcal Abscesses, retained primary Teeth, IgE, Dermatologic problems (eczema). ```

Answer 70

scalded skin syndrome: AKA Ritter's disease caused by Exotoxin A and B in granular cell layer blisters are superficial, pts/kids still in pain you can tx and help kids develop antibody if you have pre-existing antibody, you'll get local toxin production (Bullous impetigo) if you don't, you'll get systemic toxin (Ritter's/Scalded skin/ scarlet fever, depending on age) Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which destroys epidermal-dermal junction). Characterized by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis G that heals completely. ⊕ Nikolsky sign. Seen in newborns and children, adults with renal insuf chancy. scarlet fever: older child Erythematous, sandpaper-like rash with fever and sore throat --strawberry tongue in young children older children have fewer skin receptors, so milder disease bullous impetigo: young infants, often in diaper area localized infections that give you local bulls disease; don't get systemic disease ----transplacental antibody protects from systemic disease

Answer 71

localizing factors: coagulase clumping factor protein A cause local infection abscesses- can give bacteremia disseminated infection, deep localized infection toxins: Enterotoxins: give rise to FOOD POISONING, tss TSST-1 give rise to TSS, staph scarlet fever Exfoliatin give rise to STAPH SCARLET FEVER, SCALDED SKIN SYNDROME

Answer 72

``` catalase negative (no bubbles) hemolytic behavior depends on strain (ex viridans is alpha hemolytic) immunologic: -Lancefield groups A-U -M and T proteins ```

Answer 73

lancefield groups = C-carbohydrate of cell wall Group A = beta hemolysis (s. pyogenes)- throat Group B= beta or none hemolysis (S agalactiae)- vagina Group D= alpha hemolysis (E faecalis)- GI

Answer 74

strep pneumoniae- optochin sensitive strep viridans- optochin resistant

Answer 75

GAS = strep pyogenes beta-hemolytic catalase negative penicillin susceptible virulence factors: many M proteins (antibodies provide type-specific immunity) attachment factors: pili (adhesion to epi cells), fibrontectin-binding protein spreading factors!!!: streptokinase, hyaluronidase, DNase Toxins: pyogenic exotoxins Necrotizing factors: protease

Answer 76

use pili to adhere to different epithelial cells thinly keratinized squamous epi: throat (pharyngitis/rheumatic fever) perineum (anus, vagina) skin: superficial: impetigo (nephritis) invasive: cellulitis, necrotizing fasciitis, TSS

Answer 77

M proteins stick out of cell wall- it's the major virulence factor for S pyogenes --phagocytes ingest/kill strains w/o M protein very far variable "A" region gives you 120 different M proteins --it has a neg charge to repel phagocytes core of the antibody can't get to it because you've got fibrinogen binding to it; so it can't be opsonized to be phagocytized but if you have proper antibody to M protein- strep is eaten/killed by PMNs --antibody protection is serotype specific

Answer 78

Streptomycin O -hemolytic, cardiotoxic Streptomycin S -hemolytic, cytotoxic Pyrogenic exotoxins A,B,C -superantigens! cause fever, rash, Strep TSS ``` spreading factors: streptokinase -activates plasminogen, lyses fibrin hyaluronidase -dissolves ground sub DNAase -dissolves DNA proteinase -proteolytic destruction ```

Answer 79

clindamycin is better tx for severe strep infections, even though it's not penicillin-resistant beta-lactams: bactericidal (only kill actively growing organisms) fail to kill large inoculum or stationary-phase organisms may stimulate toxin production and release! ``` clindamycin: bacteriostatic kills (w/ WBCs) all phases decreases toxin and enzyme production increases opsonization improved clinical efficacy ```

Answer 80

symptoms referable to throat over 10million acute pharyngitis cases/yr strep pyogenes- most common cause of bacterial pharyngitis (M proteins attach to pharyngeal) BUT 2/3 of sore throats are caused by viruses -strep much less likely in a pt w/ cough, runny nose, or <3yo- probably shouldn't culture these pts because you might find strep + as part of normal flora (not sickness) ``` tender lymph nodes = STREP close contact = STREP cough = VIRUS runny nose = VIRUS <3yo = VIRUS ``` also bad culture = bad text results

Answer 81

``` suppurative (pus): otitis media sinusitis parapharyngeal abscesses cervical adenines pneumonia ``` ``` non-suppurative: acute rheumatic fever (only certain M proteins and certain humans) Post-strep reactive arthritis PSGN PANDAS?? ``` toxic: scarlet fever TSS

Answer 82

nonsuppurative complication of strep pharyngitis -onset 3-6 weeks after infection inflammation of heart valve, skin, joints, CNS S pyogenes not recovered from site inflammation best model: autoimmune disease - Rheumatic strains: M3 and M18 associated ARF - Genetic predisposition: FHx, HLA and B cell alloantigen assoc's - Hypothesis: genetically programmed abnormal immune response to a common infection common recurrence w/ re-infection high ASO titers imply greater risk -can be prevented via therapy of acute infection JONES criteria - polyarthritis - endocardidits - nodules - erythema marginatum - Sydenham chorea

Answer 83

nonsuppurative complication of S pyogenes -only certain M types (nephritogenic) onset 2-4 weeks after infection inflammation of kidney/glomerulus S pyogenes not recovered from site of inflammation best model: immune complex disease -results in low complement levels

Answer 84

small joints as well as big ones and axial NSAID Unresponsive evidence of recent strep infection

Answer 85

ASO and ADB titers: will be positive in 15-20% of asymptomatic/normal children usually not elevated in acute disease only perform in children where strep is plausible for current illness -eg rheumatic fever of PSGN

Answer 86

superficial: impetigo ``` invasive: perineal -perianal -vaginitis (common in prepubertal girls) myositis necrotizing fasciitis cellulitis ``` toxic: Scarlet fever TSS

Answer 87

impetigo: honey-crusted lesions- usually around mouth frequent in tropical areas often assoc w/ acute post-strep nephritis cellulitis: only certain strains, tends to be ~superficial; spreading factors= hyaluronidase, DNase, streptokinase Necrotizing fasciitis: rapidly progressive classic (but not sensitive_ features: -blistering, painful, TSS, rash failure to improve w/ antibiotics -F/U on presumed cellulitis tx response within hours imaging not sensitive -MRI best; not delay surgery if NF suspected often requires early surgical exploration to assess may be staph or strep- culture and Ab choice is important -Vancomycin + Clindamycin + ? Meropenem)

Answer 88

you get scarlet fever if you don't have antibody superficial erythroderma (sunburn like skin) strawberry tongue conjunctivae not usually involved

Answer 89

Hypotension or shock + 2 or more: ``` renal impairment DIC liver impairment ARDS scarlet fever rash soft tissue necrosis ```

Answer 90

can be perianal or vulvovaginal infection Group A strep is most common cause of vaginitis in pre-pubertal girl different T and emm types

Answer 91

AKA Group B strep ``` gram postiive cocci weakly hemolytic lipotechoic acid- causes adherence M,T,R proteins absent polysaccharide capsule (anti-phagocytic) -6 serotypes -antibody against capsules mediates protection; antibody is serotype specific ``` major site of colonization is female genital tract -if they're recently infected and then give birth the baby won't have time to acquire Ab, so baby gets Group B strep- sepsis, pneumonia, etc (high mortality)

Answer 92

colonize normal GI tract adults: nosocomial infections- UTI, bacteremia, line sepsis, endocarditis children: nosocomial bacteria inherent resistance to cephalosporins, penicillin, ahminoglycosides, tmp/smx, clindamycin inducible transferable high level vancomycin resistance (VRE)

Answer 93

strep pneumo: encapsulated pathogen most common cause of bacterial pneumonia ``` strep viridans: many species non-lancefield typable nl flora in pharynx -causes dental caries and endocarditis ```

Answer 94

emerging pathogen usually alpha or non-hemolytic, but may be beta-hemolytic "butterscotch" odor normal upper respiratory, intestinal, and vaginal flora clinical presentation: brain abscesses resp infections -orbital cellulitis (most common cause in kids!!), peritonsillar abscess, penumonia human bites less common: -osteomyelitis, septic arthritis, liver abscess, myositis usually susceptible to penicillin! becoming more common in children

Answer 95

bacteria found in the intestine diarrhea is major cause of global mortality -cause by Enterobacteriaceae and Vibrionaceae US- from ingesting contaminated food/drink extra intestinal disease- pneumonia, sepsis, meningitis, UTI must overcome host defenses- gastric acidity, intestinal motility, local Ab, nl gut flora

Answer 96

Salmonella Shigella E coli Yersinia spp Vibrionaceae, campylobacter, helicobacter are distantly related to enterobacteriaceae all are gram negative bacilli Vibrio (curved rods) Campylobacter (gull-winged or S shaped) otherwise, look similar

Answer 97

LPS in outer membrane of all gram neg bac H antigens flagellar protein antigens assoc w/ motel organisms not all enterics have this ``` K antigens capsular polysaccharide not found in all strains usually assoc w/ increased virulence most significant when organism produces extra intestinal infections (eg bacteremias) ```

Answer 98

Lipid A: endotoxin toxic part of LPS similar but not identical among all gram neg's core polysaccharides: constant region of LPS within a genus O antigens: repeating subunits of oligosaccharides of LPS variable within a genus helps species identification

Answer 99

stool exam to differentiate non-inflamm, watery diarrhea from inflammatory diarrhea vol, smell, texture gram stain, methylene blue stain for fecal leukocytes wet mount for motility media and culture conditions biochemical rxns -all Enterics are oxides negative, ferment glucose Vibrios are oxidase positive API strips for species ID serological differentiation- usually limited to preliminary grouping Toxin assays or gene probes mostly for epidemiology rapid test kits are now available

Answer 100

plasmids many enterics have medically-relevant plasmids -toxins -adherence -invasive factors (Type 3 secretion system) bacteriophage conversion genes of a bacteriophage can change the phenotype of the bacterium it lysogenizes chromosome very dynamic variability, partly due to transposable elements that carry genes encoding virulence determinants and antibiotic resistances pathogenicity islands specific DNA regions found only in chromosomes of pathogenic strains encode virulence factors (invasion genes, toxins)

Answer 101

copious watery no blood or pus no tissue invasion Small intestine likely: ETEC, EPEC, campylobacter

Answer 102

scant volume blood pus or mucus present tissue invasion large intestine likely: Shigella, EIEC, campylobacter

Answer 103

lasting more than 14 days likely: EPEC

Answer 104

copious vol some blood, pus invasion ileum, colon likely: salmonella, campylobacter, Yersiniae

Answer 105

copious vol like liquid blood no leukocytes or invasion large intestine likely: EHEC

Answer 106

don't usually cause disease in healthy individuals usually assoc w/ extrainestinal sites, and in immunocompromised pts vibrio vulnificus septicemia is 50% fatal in these pts

Answer 107

not mutually exclusive primarily toxigenic- Vibrio cholerae, ETEC, EHEC primarily invasive- Salmonella or both mech's used Shigella dysenteriae

Answer 108

Exotoxin- usually a protein secreted out of cell by organism Enterotoxin- exotoxin that has specific effects on the intestine Endotoxin- LPS- Lipid A + O antigen

Answer 109

generally speaking... small intestine: secretory diarrhea large intestine: inflammatory diarrhea Stomach: H pylori SI: V cholerae, ETEC, Salmonella, Yersinia, Campylobacter LI: Shigella, EHEC

Answer 110

relative infectivity main correlation is that organisms that are more sensitive to acid (eg vibrios) have higher infective doses -these are more likely to be transmitted by food or water low infective doses -more likely to be transmitted directly person to person Shigella- as low as 10-100 Salmonella- anywhere from 100- 10^5 Vibrio, ETEC- 10^8 but may be 10^4 in foods that neutralize stomach acidity

Answer 111

Vibrio cholerae Enterotoxigenic E colic (ETEC) Enteropathogenic E coli (EPEC) Enterohemoryhagic E coli (EHEC)

Answer 112

``` cholera- profuse, watery diarrhea cause by an enterotoxin prototype for toxigenic diarrheas no tissue invasion affects small intestine ``` classification: frequently cause by organisms of serotype O1 clinical symptoms: intubation 2-5 days abrupt onset of diarrhea, abdominal cramps, some vomiting no fever mild to SEVERE watery diarrhea- up to 15-20L/day severe dehydration, BP drop, vascular collapse death if untreated pathogenesis colonization of small bowel and toxin production both require factors encoded by different lysogenic phages- Bacteriophage conversion is important!! colonization requires surface-expressed adherence factor TCP pilus, which is also the coat protein of a phage encoding cholera toxin CTX toxin production genes encoded as part of phage genome CTX this phage uses TCP pilus as its receptor toxin structure and function prototype A-B type toxin B subunit binds to cell surface receptors of enterocytes A subunit then enters cytoplasm, transfers ADP-ribose from NAD to a regulatory G protein increased Cl- secretion decreased Na absorption net secretion of fluid into gut lumen Cytotonic (does NOT kill the cell)- an intoxicated enterocyte continues secretion until it's replaced naturally epidemiology currently in 7th pandemic, mostly Asia and Africa endemic on Indian subcontinent Most US cases imported from endemic areas mode of transmission: fecal/oral, generally through contaminated foods environmental reservoir- aquatic environments Tx aimed to restore fluid and electrolyte loss mild- oral rehydration w/ salt/sugar solns ORS: isotonic Na/K, Cl, citrate or bicarb buffer, and glucose severe- IV rehydration w/ Ringers lactate + KCl Antibiotics shorten course, number/vol of stools, and number of Vibrios excreted in stool, and may help reduce carrier state

Answer 113

non-invasive enteric bacteria Halophilic (salt loving) inhabits marine and estuarine environments causes 3 major syndromes: gastroenteritis (most common) wound infections septicemia assoc w/ eating raw or undercooked shellfish ``` disease: usually acute diarrhea abdominal cramps N/V common occasionally bloody stools- produces hemolysin and is mildly invasive ```

Answer 114

can cause gastroenteritis usually from ingestion of contaminated seafood/oysters proceed to extra intestinal infections in immunocompromised pts, w/ high fatality rates also infects wounds

Answer 115

E coli is nl in human colon and is most abundant facultative anaerobe in feces ETEC: traveler's diarrhea -worldwide -heat-labile and heat-stable toxins EPEC: watery, persistent diarrhea -infants < 1 yo -attaching and effacing (AE) EHEC bloody, dysentery diarrhea -developed -AE, shiva-like cytotoxin

Answer 116

ETEC leading cause of traveler's diarrhea in adults -important in children's diarrhea in developing countries ``` symptoms: acute onset watery diarrhea no blood or pus rarely have low-grade fever abdominal cramps vomiting can be severe, cholera-like, even in adults ``` tx: usually supportive- replace fluids and salt acute onset, self-limiting nature Antibiotics (even prophylactic) not usually recommended Bismuth subsalicylate (pepto-Bismol) helps relieve symptoms and shorten duration Pathogenesis toxigenic diarrhea- no tissue invasion 2 types of toxins: heat labile entereotoxin- same MOA as cholera heat stable enterotoxin- small peptide toxin that activates guanylate cyclase, raising cGMP levels, leads to increased fluid secretion must be able to colonize small intestine- express fibril adhesions adhesion overcomes peristalsis effect

Answer 117

EPEC predominantly seen in infants < 1yo (childcare outbreaks) occasional adult outbreaks large inoculate needed ``` symptoms: watery stools no blood or mucus no tissue invasion vomiting, low grade fever common may be prolonged relapse is common ``` tx: restore hydration usually responds rapidly to antibiotic therapy pathogenesis intimately adhere to enterocyte surface a TYPE 3 SECRETION SYSTEM secretes the translocated-intimin receptor, initiating the characteristic "ATTACHING AND EFFACING LESION" -microvilli destruction, pedestal formation probably interferes w/ absorption, leading to diarrhea

Answer 118

cause structural damage to intestine usually produce inflammatory diarrhea (frequent, low-vol mucoid or bloody stools), tenesmus, fever, or severe abdominal pain stools may have leukocytes and gross or occult blood fecal leukocytes- indicative of colonic damage M cells play major role in tissue invasion (antigen-sampling cells that overly the lymphoid follicles of the gut; major initial targets of entry of invasive pathogens) ``` Shigella spp-- prototypic; dysentery Salmonella enterica; gastroenteritis (typhoid fever) Campylobacter Yersina spp- Yersinosis Helicobacter pylori ```

Answer 119

Shigellosis, bacterial dysentery classification: based on O antigen grouping: Group A: S dysenteriae type 1 causes epidemic dysentery Group B: S flexneri most common in developing world (US male homosexuals) -Groups A and B have haver incidence of dysentery Group C: S boydii rare in us; primarily in India Group D: S sonnei most prevalent in US mildest disease, usually watery diarrhea pathogenesis: watery diarrhea is Enterotoxins secretes effector proteins through Type 3 secretory system entry via M cells, uptake by macrophages Induce apoptosis and inflammation invade basal side of epi cells lyse the vacuole grow in cyto spread directly into neighboring cells inflammatory response increases local spread and severity of symptoms, but ultimately enables pt to clear infection ---only S dysenteriae type 1 make cytotoxic Shiga toxin clinical symptoms All shigella can cause dysentery, but severity decreases down the groups intubation 1-4 days (up to 8 w/ S dysenteriae) initial fever, malaise, vomiting followed by watery diarrhea progress to frank dysentery, freq small stools w/ blood and mucus, cramps, and tenesmus up to 20 stools/day LOW infectious dose- 10-100 organisms very acid resistant, survive stomach humans only known reservoir- no known animal host fecal/oral person-to-person transmission w/ four F's: food, fingers, feces, flies tx: supportive, restore fluid balance milder cases usually self-limiting Ab tx of severe cases shortens duration of symptoms and shedding of bacteria

Answer 120

Gastroenteritis and Typhoid fever invasive enter across intestinal mucosa, can cause both GI and systemic disease not host adapted (vs shigella)- move easily between environment, animals, and humans- Gastroenteritis -2nd leading bac cause of gastroenteritis Typhoid fever- from highly human-host adapted serovars classification 2500 different servers differentiated by O and H antigen combinations currently only 2 species recognized- all pathogenic Salmonella belongs to Salmonella enteric subspecies enterica Enteritidis and Typhimurium are most common serovars affecting humans Epidemiology, transmission fecal-oral typhoid- only transmitted by humans non-typhoidal salmonellosis is zoonotic- animals are important sources (poultry, eggs, contaminated fresh produce) pathogenesis entry via oral route invasion of M cells, leading to transient bacteremia uptake by mononuclear phagocytes, where Salmonella multiply clinical symptoms and tx: Gastroenteritis most common febrile food poisoning presents 24-48hrs after ingestion N/V, HA, followed by chills, fever, cramps, and watery diarrhea self-limiting mostly don't require Ab tx Septicemia prolonged fever, generally w/o diarrhea dx by multiple positive blood cultures highly invasive serovars such as Cholerasuis Typhoid (enteric) fever S typhi and S paratyphi inoculum-dependent intubation period days-weeks constipation or inflammatory diarrhea then stepwise increase in temp over several days to high fever untreated, continues 6-8 weeks colonization of gallbladder can lead to carrier state or intestinal perforation tx w/ antibiotics immunity not good immunity against Salmonella due to different serovars infection w/ 1 doesn't usually induce protection against a subsequent infection Typhoid vaccine w/ purified Vi polysaccharid effective in adults and children >2yo

Answer 121

Yersinosis invasive enteric bac 3 human pathogenic app: Y Pestis Y enterocolitica Y pseudotuberculosis only last 2 are enteric pathogens- causing food borne illness, and zoonotic infections from domestic animals occasional cause of infections acquired from blood transfusions due to ability to grow at low temp often assoc w/ eating undercooked pork, dairy products ``` pathogenesis: low grade fever watery diarrhea some w/ blood fecal leukocytes infects terminal ileum often prod RLQ pain mimicking appendicitis ``` ``` complications reactive arthritis (Reiters syndrome) most often w/ HLA-B27 positive pts ``` Antibiotics not shown to have major impact on outcome, but due to invasiveness and capacity to cause serious illness, infections usually tx w/ antibiotics

Answer 122

food-borne gastroenteritis invasive most common cause of gastroenteritis in Western world ``` pathogen and disease C jejuni and C coli small, curved, gram neg rods catalase and oxidase positive prefer microaerophilic and increased temp for culture- grow best on enriched media w/ antimicrobials that inhibit other intestinal bacteria low dose inoculum ``` ``` symptoms diarrhea fever abdominal cramping half of pts have bloody stools fetal leukocytes may be present ``` ``` complications (rare): Guillain-Barre syndrome- demyelinating degenerative nerve disease, may be due to antibody response against oligosaccharides of O antigen cross reacting w/ sphingolipids on nerve cells Reiters syndrome (autoimmune reactive arthropathy) frequently occurs w/ HLA-B27 positive pts ``` pathogenesis not well understood 3 factors influence disease- invasiveness, enterotoxin production, and cytotoxin production terminal ileum and proximal colon are sites of invasion motility and chemotaxis are important factors in colonization of gut epidemiology and transmission peak during WARM months person-person transmission is rare outbreaks due to contaminated milk or water sporadic cases assoc w/ young pets w/ diarrhea, improper handling of raw poultry, or eating undercooked poultry highest in infants; peaks again in young adults males lowest rates for adults- reflects some immunity more severe inflammatory diarrhea in industrialized countries vs milder watery diarrhea in developing nations- reflects levels of prior exposure to organism ``` tx supportive, fluid replacement antibiotics in severe cases Erythromycin or quinolone Fluroquinolones resistance is emerging due to overuse of related antibiotics in poultry industry ```

Answer 123

gastric and duodenal ulcers, gastric cancer invasive similar to campylobacter THE MOST common human bacterial pathogen, infecting more than half the world's pop pathogen and disease primary habitat- human gastric mucosa colonizes mucus layer of stomach; doesn't invade epithelium curved, highly motile, microaerophilic Gram neg rods- strong urease activity isolated on campy agar w/o antibiotics H pylori infection causes mucosal inflammation in virtually every pt, w/ epi cell damage and neutrophil infiltration (chronic gastritis, may be asymptomatic) causes reduction in acid secretion- leads to gastric atrophy, progressing to gastric carcinoma responsible for nearly all duodenal ulcers and 70% of gastric ulcers Pathogenesis/virulence factors high motility- rapid penetration of gastric mucus to reach less acidic environment of gastric epithelium powerful urease production- creases ammonia to further raise pH severity of disease correlates w/ strains that have a pathogenicity island encoding potential virulence genes- vacuolating cytotoxin? autoimmune response postulated- molecular mimicry (like campy)- LPS contains Lewis X and Y blood group antigens epidemiology and transmission typically acquired in childhood, is lifelong w/o tx decreasing in industrialized countries (standard of living) fecal/oral person-person suggested prevalence increases w/ overcrowding and low socioeconomic status genetic disposition for ability to be colonized- some never colonized predicted to disappear without intervention, but over a century ``` clinical dx "gold standard" histo exam of multiple biopsy specimens w/ special stains, followed by culture and isolation of organism rapid urease tests breath tests- 13C urea- given w/ meal ELISA tests for IgG ``` testing and tx NIH recommends tx only for pts w/ peptic ulcers (to prevent antibiotic resistance) successful tx means relief of symptoms and ulcer healing, preventing long-term sequelae tx- combo of antisecretory agents and antimicrobials- triple therapy recommended PPI + Bismuth + tetracycline for 14 days some failures due to antibiotic resistance

Answer 124

nutritional advantages -avoid competition for space and nutrients (Facultative vs obligate) protected site from the antimicrobial actions of immune system avoid innate and humoral defenses could lay dormant for decades and emerge in immunosuppressed conditions protected dissemination around the body Shigella can spread cell-cell in epi monolayers Salmonella can disseminate outside of intestine to systemic sites inside phagocytes

Answer 125

both: the reorganization of the actin cytoskeleton results in changes at membrane surface, allowing bac uptake Zipper: tight interaction between bac cell surface ligands and host cell receptors --> closure of host cell surface around bacterium ex. parasite-induced phagocytosis into phagocytes receptor-mediated phagocytosis of macrophages coiling phagocytosis Trigger: bacterial products induce the cell surface to ruffle, projecting membrane extensions that surround bacteria products secreted by type 3 secretory systems of Salmonella and Shigella induce this type of uptake

Answer 126

professional phagocytes- modifies internal compartment through acquiring proteins and makers of endosomes- continue maturation and acquire lysosome markers formation of phagolysosome- main job to kill microbes, degrade molecs, and present antigen to immune sys -harsh phagocyte environment and slow growth of some intracellular pathogens contribute to chronicity of many infections antimicrobial defenses of professional phagocytes- NADPH oxidase- causes reactive oxygen species production -some developed ways to prevent assembly of NADPH oxidase complex inducible NO synthase produces NO, which targets many intracellular pathogens -dormancy is a consequence of the continuous NO production oxygen-independent effector molecs broad-spectrum antimicrobial peptides -reduce conc's of Fe available to intracellular pathogens to levels non-compatible w/ life -low pH within phagolysosomes

Answer 127

escape from vacuole non-fusogenic organisms fusogenic orgnaisms intracellular bacterial of non-professional phagocytes

Answer 128

Escape: Listeria lyses the phagocytic vacuole, escaping into cytosol in the cytosol, Listeria polymerizes actin to propel itself within cytosol also allows bac to invade neighboring cells w/o ever going extracellular advantages: access to large nutrients, and minimize exposure to antimicrobials in vesicles ``` host defenses: cytosolic antimicrobial peptides, and NO synthase can target them cytotoxic CD8 T cells can lyse infected cells expressing MHC class 1 molecs in assoc w/ microbial peptides ```

Answer 129

contained in membrane-bound compartments that avoid degradation pathway ultimately linked to lysosomal function advantages: bac can remain viable inside phagosome also avoids processing of bac antigens that would lead to immune sys activation via MHC class 2 presentation host defenses: many cause long-term infections via formation of granulomas these lesions develop over months after infection, and consist of activated macrophages and T cells granulomas contain these infectious agents by maintaining balance between organism growth and antimicrobial host defenses

Answer 130

Coxiella burnetii- obligate intracellular Gram neg bacterium only intracellular pathogen to reside within phagolysosome phagosome matures through endocytic pathway eventually acquires lysosome properties pathogen-containing vacuole acidifies organism is not cytopathic, reaching very high numbers within a single vacuole

Answer 131

non-professional phagocytes like endothelial cells- limited phagocytic and bactericidal activity cells w/o lysosomes- erythrocytes (Bartonella does this)

Answer 132

intracellular location causes failure of some antibiotics for some tx of infected hosts intracellular antibiotic activity depends on: penetration of euk membrane sub cellular localization deleterious interactions w/ the intracellular milieu, incl pH antibiotic susceptibility of intracellular pathogen Amino glycosides and macrocodes: weak bases concentrated inside lysosomes by pH dependent mech -preferential localization to lysosomes and partial inactivation by acidic pH-- major disadvantage beta-lactams -lack of peptidoglycan in cell wall and intracellular lifestyle of chlamydiae may explain poor activity of beta-lactams

Answer 133

signs and symptoms: acute onset of watery diarrhea (no mucus or blood) +/- vomiting (often precedes diarrhea) Nausea intestinal cramping (from hyper motility) myalgias, low-grade fever, HA, malaise

Answer 134

fast on fast off short intubation period prolonged shading in stool (often asymptomatic)- high transmissibility very stable (can persist on contaminated surfaces) seasonal transmission: person to person fecal-oral -nosocomial in healthcare, day care, cruise ships -esp where pts are incontinent- psych, nursing home, etc food borne waterborne

Answer 135

``` US- think morbidity 2nd most common cause of illness 1-2 episodes/child/yr hospitalizations from dehydration ---big burden of disease w/ hospitalizations and healthcare costs ``` worldwide- think mortality 6-7 episodes/child/yr deaths from dehydration

Answer 136

viruses cause >75% of gastroenteritis of known etiology many different virus families: - Caliciviruses (norovirus, saprovirus) - Rotavirus - Enteric adenoviruses - Astroviruses multiple serotypes of each diarrhea virus

Answer 137

local infection of intestinal epi cells malabsorption due to virus killing mature enterocytes local villus ischemia leading to diarrhea --shortened, blunted villi viral enterotoxin changing the transepithelial fluid balance

Answer 138

``` specific viral dx is not needed or useful in most situations useful in: outbreaks immune compromised hosts severe disease ``` difficult to dx by traditional methods: difficult to grow in culture EM difficult to interpret, labor intensive serology can only tell exposure viral antigen only available for some viruses multiplex RT-PCR detection of viral nucleic acid in stool -overly sensitive, but is tested in correct clinical setting

Answer 139

rehydration and electrolyte correction -oral rehydration Na, K, bicarb, glucose -IV fluids if severe no antibiotics!! can prolong host's transmissibility time ``` prevention: hygiene (hand washing, food prep) sanitation (toilets, diapers, water supply) environmental cleaning isolation of pts vaccines (rotavirus available) ```

Answer 140

many human serotypes G2.4 Sydney is currently most important in US outbreaks variants arise by mutation or recombination

Answer 141

small round ssRNA virus cup shaped indentations naked, non-enveloped viral-encoded protease cleaves viral polyproteins - necessary for viral replication - potential drug target difficult to grow in culture

Answer 142

1/3 asymptomatic but still contagious/shedding virus N/V, watery diarrhea, cramping malaise, HA, myalgia, low-grade fever occasionally dehydration, esp in: young children elderly immunocompromised quickest on, quickest off incubation: 15hrs-2 days duration: 1-2 days most common cause of diarrheal outbreaks in adults -2nd most common in young children has replaced rotavirus as #1 in areas where rotavirus vaccine is in use ``` sources: person-person (fecal oral) contaminated surfaces food borne (esp shellfish) waterborne ``` seasonality: year round, but winter predominance shedding: 10 million/mL infectious dose: 10-100 viruses common cause of outbreaks on cruise ships, hospitals, and nursing homes

Answer 143

immunity is short lived ~6 months due to strain diversity and antigenic shift some lucky hosts are innately resistant - FUT2 gene required for virus to bind to intestinal cells - FUT2 -/- are resistant dx: antigen tests newly viable, but RT-PCR is more sensitive tx: currently- only rehydration effective vaccines would have to cover many serotypes

Answer 144

rota= wheel 11 double stranded RNA genome segments -each segment encodes one viral protein VP non-enveloped, but 3 protein shells: outer capsid layer -acid stability; VP7 with VP4 spikes inner capsid layer VP6 innermost core: VP2 classification: serotypes depend on VP7 and VP4 on outer capsid layer 12 major genotypes Groups based on immunologic assay to the inner capsid layer --Group A: frequent human infection; most important human group

Answer 145

reassortment: allows introduction of segments from animal rotavirus into human rotavirus, causing epidemics replication: uncoated virus enters ER, then pinched out into intestine to get its outer shell -NSP4, a secreted non-structural protein ``` pathogenesis: affects small intestine replicates in villus epi cells mononuclear inflammation villus shortening, stunting Mech causing diarrhea is unclear high viral titers shed in stool, esp in NICU ```

Answer 146

NSP4 destabilizes membranes, leading to cell death mobilizes intracellular Ca- activating signal transduction pathway to transport from ER Cl secretion and water follows ? activation of enteric NS

Answer 147

up to 50% of infections are asymptomatic symptomatic: abrupt onset fever and vomiting, followed by diarrhea -stools are explosive, watery, non bloody -frequently leads to dehydration in children symptoms last 4-8 days, self-limited incubation period: 1-3 days peak viral shedding on day 3, can be prolonged >3 weeks epidemiology: common in infants and young children fecal-oral transmission remain on infected surfaces seasonality: predominant fall/WINTER/spring year round in tropics high risk groups: immunocompromised, malnourished, elderly

Answer 148

Rotavirus is the single most important cause of severe infantile gastroenteritis worldwide!!!!! peak 3 mo-2yo --can lead to life-threatening dehydration in infants poor skin turgor sunken eyes mucus membranes dry treatable by oral/IV rehydration preventable by available rotavirus vaccines

Answer 149

Dx: antigen detection ELISA in stool Rotazyme, "diaper dipstick" PCR tx: no effective antiviral therapy available rehydration and electrolyte correction- paramount probiotics may decrease freq and duration immunology: evidence of IgM, IgG, and IgA cellular immune response repeated infections may occur (2nd generally milder) symptomatic infection is less common in pts <6mo (protective IgA breast feeding) chronic infection in cellular immune deficiencies, transplant pts

Answer 150

RotaTeq (RV5): Pentavalent live bovine Rotarix (RV1): Monovalent live human US children hospitalized for rotavirus has decreased by 85%

Answer 151

non-enveloped, icosahedral double stranded DNA virus most commonly cause URI, pharyngitis, conjunctivitis (Pink eye), pneumonia, hemorrhagic cystitis Serotypes 40,41!! cause gastroenteritis ``` 2-22% of pediatric gastroenteritis peak incidence 2yo no seasonality incubation 3-10 days fecal-oral transmission ``` often asymptomatic watery diarrhea, then vomiting lasting 5-12 days!! -less dehydration than rotavirus low grade fever re-infections can occur can cause persistent, severe infection in immunocompromised hosts ``` dx EM antigen immunoassays PCR difficult to grow in culture ``` tx: no antiviral available rehydration no vaccine available

Answer 152

virology: small non-enveloped single stranded RNA virus star shaped capsomers can be grown in viral culture Trypsin necessary to activate infectivity in gut 7 serotypes identified epidemiology 2-8% of diarrheal disease in children excreted for prolonged periods in immunocompromised person-person and food borne spread outbreaks in daycares, nursing homes, cafeterias, and nursing homes

Answer 153

chlamydia- most common notifiable disease in US >1.5 million gonorrhea- 2nd most syphillis- 20% increase over 2014 for primary and secondary all of these have increased

Answer 154

Neisseria gonorrheoeae Neisseria meningitidis Moraxella catarrhalis morphology- all gram neg diplococci individual cocci are kidney-shaped

Answer 155

specificity = negativity in health - accounting for false positives - testing 100 healthy pts, how many of them will have have a negative test? sensitivity= positivity in disease - accounting for false negatives - testin 100 dz pts, how many would have a positive test? Gold standard- best test that tells you pts have that infection an vice versa

Answer 156

advantages: low cost suitable for variety antimicrobial susceptibility can be performed indicated in pts who have exposure Hx, significant gonococcal infection, complaints, or clinical findings men: urethra, pharynx, retum women: cervix, pharynx, rectum, vagina, Bartholin's or Skene's glands

Answer 157

in infection- should be GN diplococci INSIDE PMNs seeing them outside you'd be suspicious for normal flora but if you took oral culture and did gram stain- you might get positive culture of commensal diplococci after teeth cleaning

Answer 158

amplified tests- NAATS -PCR non amplified tests -DNA probe gram stain smear doesn't tell you if bug is alive, it tells you the bug is present doesn't tell you bug's resistance either

Answer 159

Gram stain -GN diplococci in neutrophils sensitivity good for M, bad for F (still have infection and won't test positive) specificity good for both caveat- gram stain not sufficient to detect asymptomatic, endocervical, pharyngeal, or rectal infections

Answer 160

strictly aerobic- but have to give organism increased CO₂ (not a regular incubator)- both N gonorrhoeae and N meningitidis; can use a jar w/ lit candle to the side can use nitrate as e- acceptor when grown under anaerobic conditions complex growth requirements GOLD STANDARD- 3 steps if you find GN diplococci to dx Neisseria Gonorrhoeae oxidase positive (colonies turn black) 2 kinds of media: chocolate agar- blood agar that's been heated to release heme and other things ---Neisseria grows on chocolate agar but not regular blood agar; but also grows the normal flora Thayer-Martin chocolate agar has antibiotics- kills of nl flora and allows Neisseria to grow look for sugar fermentation of Neisseria;

Answer 161

suggestive: mucopurulent endocervical or urethral exudate sexual exposure presumptive: (one) growth or non-culture lab test definitive: (both) Isolation of Neisseria gonorrhoeae from sites of exposure by future and demonstration of appropriate growth characteristics confirmation of isolates by biochem, enzymatic, serologic, or nucleic acid testing -Adults NAATs preferred for sexual assault regardless of penetration - Children - culture is preferred for intra boys or all extra genital specimens - NAATS can be used as alternative for vaginal/urine from girls

Answer 162

obligate human pathogen high degree of infectivity many asymptomatic carriers (F>>M) almost exclusively transmitted by sexual contact eye infection in neonates born from infected mothers (preventable) sexual abuse is most frequent cause of gonococcal infection in preadolescents not uniform across the US spiked during WW2 and the sexual revolution, but it's starting to increase now because of vancomycin resistance

Answer 163

direct- mucosal and glandular structures (urethritis, pharyngitis, cervicitis, proctitis, etc) distal- bacteremia (dermatitis, arthritis, endocarditis, meningitis, perihepatitis, etc) very uncommon, but more likely the longer this is in the pt

Answer 164

incubation 2-5 days urithritis: pain/burning during urination purulent discharge assoc w/ PMN influx and shedding of epithelial cells dysuria most common complication of acute epididymitis

Answer 165

primary site of infection: cervix, urethra symptomatic disease within 10 days: cervicitis, urethritis vaginal discharge, dysuria ~50% F asymptomatic sending infection in up to 45% PID, fallopian tube scarring, infertility, ectopic pregnancy ``` disseminated infection: up to 3% swelling and pain in joints rash gonococcal conjunctivitis frequently serum resistant ``` can cause neonatal conjunctivitis -exposed during passage through infected birth canal eyelids become puffy, red, tender discharge can cause corneal perforation and destruction of deeper eyes structures antibiotic drops routine used

Answer 166

pili initiate binding to epi cells undergo antigenic variation and phase variation -within a single person you can see different types of pili-- which aids in their resistance Opa proteins opaque appearance of colonies important for intimate attachment undergo antigenic variation and phase generation antigenic variation: single cell can give rise to structurally and anti genetically different daughter cells while still retaining biological function up to a million different pili variants ---cured pts can be re-infected despite a strong antibody response --this is a big reason why we can't conquer gonorrhea yet

Answer 167

third generation cephalosporins- ceftriaxone or cefimine AND azithromycin or doxycycline (fluoroquinolone no longer recommended in US- widespread resistance) pts treated for gonorrhea should also be treated for chlamydia trachoma's all known sexual partners should be treated prophylaxis: instillation of 1% silver nitrate 1% tetracycline or 0.5% erythromycin into eyes at birth

Answer 168

obligate intracellular pathogen gram negative cocci --cannot make own ATP human pathogens: C trachoma's C psittaci C pneumoniae highly infectious, but rarely kill their host among most prevalent pathogens in world

Answer 169

obligate intracellular bacteria C trachoma's and C pneumonia are obligate human pathogens C psittaci infects animals- birds multiply in specialized endosome depending on host cell for ATP and nutrients spread to other cells by extracellular route very simple organism- elementary bodies see inclusion bodies on Giemsa stain, Lugol stain, immunofluorescence staining,

Answer 170

``` highly infectious attachment factors (adhesions) inhibit phagolysosome fusion heat-labile toxin may cause latent infections ```

Answer 171

short survival outside of host infections recently linked to atherosclerosis, arthritis, heart disease, and Alzheimer's trachomatis- direct person-person contact psittaci- aerosols from infected birds pneumoniae- aerosols from infected humans

Answer 172

adults males: urethritis leading to other complications adult F: acute urethral syndrome, cervicitis leading to other complications incidence is much higher in F; likely due to asymptomatic presentation not uniform across US

Answer 173

culture, antigen detection or DNA hybridization PCR serology

Answer 174

sexually transmitted many asymptomatic carriers (75% of women; 50% men) urethritis in men urethritis, cervicitis, and salpingitis in women purulent urethral discharge will contain PMNs but no chlamydia! on gram stain

Answer 175

occurs in both infants and adults most common cause of neonatal conjunctivitis in US mucopurulent conjunctivitis 7-12 days after delivery may disseminate and cause pneumonia

Answer 176

antibiotics to infected pregnant women: Erythromycin or Amoxicillin for 7-14 days neonatal ocular prophylaxis doesn't prevent perinatal transmission tx of infants w/ chlamydial conjunctivitis and/or pneumonia -Erythromycin for 10-14 days

Answer 177

STI caused by serovariants L1-L3 infection begins as small ulcer and disseminates to inguinal lymph nodes possible complications: peritonitis in F ulcerative colitis in M most prevalent in Africa and S America

Answer 178

use condoms or diaphragm CDC recommendations: Azithromycin single dose Doxycycline- 7 days all sexual partners should be tx

Answer 179

reproduce by transverse vision pathogenic treponema cannot be cultured in vitro- difficult to study T palladium remains motile 3-6 days Leptospira grows aerobically -uses long chain fatty acids as E source and urea as N source

Answer 180

``` ssp pallidum: Syphilis systemic STI worldwide sexually active; and congenital newborns ``` ``` ssp pertunue: Yaws localized nonvenereal transmitted tropics all ages ``` ``` ssp endemicum: Bejel localized nonvenereal transmitted desert all ages ```

Answer 181

4 defined stages 1 and 2- infection is transmissible by blood lesions are highly infectious latent and 3- infection is NOT transmissible by blood lesions are caused by immune mediated destruction of tissues 30% of pts w/ untreated syphilis develop clinical tertiary syphilis --25% of these pts go on to die

Answer 182

starts w/ lesion spreads to different organ antibody/inflammatory response causes a lot of destruction in tissue incubation 3 weeks primary syphilis 2-6 weeks asymptomatic period 2-24 weeks secondary syphilis 2-6 weeks latent syphilis asymptomatic for 3-30 years tertiary syphilis 25% of t. pallidum heal spontaneously if it's local systemic- skin lesions (rash), mucus membranes, lymph nodes, CNS 30% of untreated pts develop tertiary syphilis and 25% die

Answer 183

primary lesion or "chancre" develops at the site of inoculation chancre: progresses from macule to papule to ulcer -typically painless, indurated, and has clean base -highly infectious -heals spontaneously within 3-6 weeks -multiple lesions can occur regional lymphadenopathy: classically rubbery, painless, bilateral serologic tests for syphilis may not be positive during early primary syphilis

Answer 184

it's a gram neg bacillus chancroid ulcers- but typically multiple PAINFUL (vs non painful syphilis) ulcers

Answer 185

2ndary lesions occur several weeks after primary chancre may persist for weeks-months primary and secondary stages may overlap mucocutanous lesions most common ``` clinical manifestations: rash 75-100% lymphadenopathy malaise mucous patches condylomata lata alopecia liver and kidney involvement can occur splenomegaly occasionally present ``` serologic tests are highest in titer during 2ndary stage!!

Answer 186

host suppresses infection, but no lesions are clinically apparent only evidence is a positive serologic test!! may occur between 1 and 2ndary stages, between 2ndary relapses, and after 2ndary categories: early latent < 1 yr duration late latent >= 1 yr

Answer 187

approx 30% of untreated pts progress to tertiary 1-20 yrs rare because of widespread availability and use of antibiotics manifestations: Gummatous lesions Cardiovascular syphilis

Answer 188

occurs when T pallidum invades CNS may occur at any stage of syphilis can be asymotpmatic clinical manifestations: syphilitic meningitis, meningovascular syphilis, and ocular involvement neuro involvement can occur decades after infection, and is rarely seen --general paresis, TABES DORSALIS, and ocular involvement

Answer 189

infection in utero w/ Treponema pallidum wide spectrum only severe cases clinically apparent at birth infant/young child <2yo hepatosplenomegaly, rash, condyloma lata (wart like genital lesions), snuffles, jaundice, pseudo paralysis, anemia, edema (nephrotic syndrome and/or malnutrition) older child: stigmata (interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, HUTCHINSON TEETH, saddle nose, rhagades, Clutton joints

Answer 190

humoral (antibody) response not very protective extremely useful for dx ``` cell mediated (T cell) response very important in immunity to reinfection and protection against tertiary syphilis probably responsible for some of the damage seen in tertiary syphilis (eg gummas) ```

Answer 191

rapid plasma reagin RPR card (non-treponemal based test) Fluorescent Treponemal Antibody FTA test (treponemal based test to detect whether pt has antibodies against T pallidum) lots of reasons a false positive may happen

Answer 192

goals: enhancement of public health services and interventions prioritization of evidence-based, culturally competent interventions accountable services and interventions ``` strategies: improve surveillance and outbreak response improve clinical and partner services mobilization of affected communities training and staff development research and development ```

Answer 193

use of condoms prompt and adequate tx parenteral penicillin G- NO clinical resistance alternatively, doxycycline or tetracycline F/U on sources of infections and contacts NOTE- azithromycin resistance has now been found, mainly in organisms from homosexual men

Answer 194

rxn that develops 2-24 hrs after Penicillin tx in pts infected w/ Spirochetes (syphilis, Lyme disease) most common in pts w/ 2ndary syphilis 90% rare in late syphilis ``` symptoms: fever chills HA N general joint aches general muscle aches tachycardia ``` pts w/ general paresis or a high CSF cell count are likely to develop serious disorders- seizures or strokes reduction of penicillin dose does NOT decrease likelihood of occurrence may indicate coexistent syphilis in pts treated for other conditions w/ antibiotics active against syphilis This rxn should be explained to the pt before tx

Answer 195

primary/initial/acute infection when exposed --> ``` during infection- lytic replication making virus particles --disease --or transmit- called shedding significant infectious particles released nuclear and cytoplasmic inclusions cytomegalic cells and syncytia formation ``` viral will undergo latency virus isn't producing particles -this is why herpes viruses stay with you for life genome persists in nucleus of specific cells, reactivation of latent infection is source of majority of disease

Answer 196

Herpesviridae divided into 3 broad subfamilies = clinical syndromes alpha herpes virus think neurons beta myeloid lineage cells gamma B cells/ myeloid and transform cells- think atypical cells

Answer 197

morphology- they all look the same big linear dsDNA genomes (some unique long and unique short segments UL US) have both lytic and latent phases of replication specific glycoproteins will determine what cell that virus can get into

Answer 198

Herpes Simplex Virus-1 HSV1 HSV2 Varicella-Zoster Virus VZV grow RAPIDLY and lyse infected cells (12-24 hrs) establish latent infections in NEURONS of Peripheral NS, primarily SENSORY nerve ganglia

Answer 199

Human Cytomegalovirus CMV Human Herpes Virus-6 HHV6 (HHV7) grow very slowly (80-120 hrs) and infect wide variety of cell types est latent infections in cells of MYELOID lineage and endothelial cells

Answer 200

Epstein-Barr virus EBV Kaposi's Sarcoma-associated Herpesvirus KSV or KSHV grow very slowly (80-120 hrs) and infect a wide variety of cell types est latency in B CELLS, ENDOTHELIAL CELLS, capable of TRANSFORMING these cells eBv- think "B" cells Kaposi's- think purplish lesions

Answer 201

virus receptors= immune response target replication = targets for treatment virus entry packing of viral DNA = helps w/ diagnostics

Answer 202

``` Attachment and entry- dump capsid (linear dsDNA into nucleus) ``` forms an episome (circle) 3 gene expression events- immediate early, early, and late capsid is transported through ER, Golgi, then exported

Answer 203

mediate cellular tropism- causes attachment to cell membrane and determines what virus can get into which cell targets of the adaptive immune response!! (T and B cells recognize these and attack) exposure to a virus via close contact allows attachment/entry: ``` oral or genital mucosa, abraded skin body fluids (HSV1,2, CMV, HHV6, EBV, and KSHV) ``` blood transfusions or organ transplant (BMT, SOT) (CMV!!!, HHV6, EBV, KSHV) respiratory secretions (VZV only)

Answer 204

1- Immediate early IE sets up environment conducive for viral replication 2- Early E encode replication enzymes (viral DNA polymerase initiates replication- each virus has a different DNA polymerase) 3- Late encode structural proteins for assembly to get out uses genome replication rolling circle replication to lop off new genomes; can make a lot quickly capsidation process inside the nucleus, then rolling DNA -not 100% perfect, so you get intracellular inclusions which help make the dx

Answer 205

HSV-1 and HHV-8 make TK (alpha and gamma) CMV doesn't make TK (beta) acyclovir is dependent on a TK to be activated- these are prodrugs that need to be phosphorylated to shut off virus replication (does not happen in normal human cell) --cannot tx CMV w/ acyclovir --use broad spectrum Ganciclovir for beta herpesvirus Ganciclovir- uses a different initial phosphorylation event works in beta viruses --side effects and worry of CMV resistance causes us to avoid using it regularly but still some cases of resistance, so you'd use cidofovir or foscarnet that just use cellular kinases to activate, but they have lots of side effects

Answer 206

Intranuclear: acidophilic: Cowdry Type A (HSV, VZV) basophilic: "owl eyes"- CMV Intranuclear and intracytoplasmic: HHV6, CMV

Answer 207

host response determines extent of disease innate immune responses: important for controlling acute/lytic infections IFN/cytokine production NK cell activities adaptive immune responses: important in acute but also preventing latency neutralizing antibodies CD4+ and CD8+ T cell functions Herpesvirus countermeasures the host responses during an acute infection - blocks interferons, dendritic cell maturation, complement activation, and NK function - mimetics and decoy receptors, interfere w/ antigen presentation

Answer 208

latency- est latency in nerve nucleus doesn't kill but hurts nerve; commonly reactivates back to where it came from (rarely, travels to brain and causes encephalitis) HSV-1 latency- trigeminal ganglion commonly assoc w/ oral herpes HSV-2 latency- lumbar sacral ganglion commonly assoc w/ genital herpes

Answer 209

HSV pathogenesis: HSV invades through breaks in integument initially get a papule (infect cells at/above basal layer and lyse) vesicle (lysis of many cells w/ cytokines and inflammation--> fluid production) pustule (subsequent leukocyte response) scab (dried pustule) --only when it scabs over that you're no longer infectious

Answer 210

2 types of HSV: type 1- above the belt type 2- below the belt --distinction is decreasing share only 50% genetic relatedness usually typed w/ monoclonal antibodies labile (enveloped)- spreads by close contact

Answer 211

usually Type 1 HSV >90% are seroposeivie by 50yo -acquired in childhood (after maternal Ab clears) and another peak after puberty most have minor illness 20% have systemic/viremic symptoms classic canker sore reactivation typically self-limited herpetic GINGIOVOSTOMATITIS- diffuse inflammation of gums (bad primary infection or immunosuppressed) unusual presentation of HSV1 -responds to antiviral therapy older pts- severe pharyngitis you get type 2 on the mouth from oral-genital contact

Answer 212

HSV adenovirus streptococcus EBV (infectious mono)

Answer 213

prodrome of sensory symptoms (hours) shortened court compared to 1st episode rarely is systemic fever and sun exposure are recognized triggers antiviral tx is NOT standard of care minimal illness w/ reactivation indicates pre-existing immunological memory CD8 T cell are important for controlling the viruses

Answer 214

Herpetic keratitis (purulent, inflammatory eyes) ``` HSV encephalitis (necrosis, hemorrhage, edema of brain) fever, HA focal CNS findings (deficit, seizure) encephalopathy/AMS -CSF: mononuclear cells/ HSV DNA -Imaging MRI give High Dose Acyclovir ```

Answer 215

HSV-2 > HSV-1 3:2 most pts have minor illness the first episode of HSV-2 20% have significant symptoms illness peaks 7-10 days heals next 1-2 weeks 1-1.5 days shortened by EARLY antiviral therapy recurrent: shortened version of 1st episode mean 3-4 recurrences/yr; declines over time psychosocial significance antiviral therapy decreases morbidity minimal, but effective w/ prophylaxis

Answer 216

``` usually w/ first episode: urethritis meningitis (HSV2) yeast (candida) superinfection (vaginitis) perianal/perirectal disease ``` shedding: similar to oral major source of spread (asymptomatic) -during a flair up, contact is typically painful so you avoid sex during then anyway

Answer 217

severe local disease- oral or genital neonatal HSV- often severe/fatal important role for antiviral therapy! most severe in pts w/ defective T cell immunity (incl newborns and transplant pts) --high index of suspicion: chronic ulcer, crusted lesion, or mouth sores

Answer 218

Varicella Zoster- reactivation Chickenpox- primary

Answer 219

spreads by droplets from varicella (chickenpox) or by formites (spread via touch) from a case of herpes zoster virus infection via conjunctiva and upper resp tract replication in primary lymph nodes- primary viremia replicates in liver and spleen goes to sensory ganglia (typically dorsal root ganglia from skin- remains there for life) and undergoes latency- secondary viremia can reactivate in infected skin- rash (rarely, can infect NS)

Answer 220

kid- mild "crops of vesicles at varying ages"- some vesicles, papule, and ulcerated/crusted over-- CLASSIC for varicella/chiceknpox (vs smallpox- all the same stage) mild symptoms for 3-5 days infectious just prior to onset until scabbing peak incidence at grade school age

Answer 221

mainly clinical Dx- PCR prevention: childhood immunization any susceptible adult immunized, ESP MED PERSONNEL

Answer 222

bacterial superinfection 2% adult infection- often severe infection in immunocompromised children encephalitis congenital

Answer 223

reactivation of VZV typically unilateral (bilateral- less likely zoster) reactivation of a single dorsal root ganglia nerve cell explains the dermatomal pattern characteristic of herpes Zoster prodrome: abnormal sensation/pain in determatomal distribution (~3-7 days) (pain precedes rash) dermatomal vesicular rash variable pain (increases w/ age) post-herpetic neuralgia (weeks-yrs) therapy within 3-4 days- Acyclovir --increases w/ age because CD8 T cell response decreases w/ age

Answer 224

immediate pain/rash (increase w/ age) ``` secondary infection eye involvement motor deficit encephalitis post-herpetic neuralgia!!! -severe in immunocompromised ```

Answer 225

VZV-specific T-Cell Mediated Immunity (VZV-CMI) declines w/ age (or immune suppression) reactivation in sensory ganglia occurs intermittently; normally surpassed or lessened by VZV-CMI if VZV-CMI is below threshold, VZV will propagate, cause ganglionitis (pain), and descend in nerve to cause a dermatomal rash (w/ pain)

Answer 226

a vaccine, like the varicella vaccine, only more potent -recommended for all immune competent pts >60yo prevents cases and pain of HZ prevents 67% of POST-HERPETIC NEURALGIA

Answer 227

cytomegalovirus CMV CD34+ bone marrow progenitors circulating monocytes endothelial cells tissue-renewing stem cells? inflammatory stimuli can reactivate the virus w/o disease -pretty frequent, esp in hospital prophylactic therapy for pts at risk for CMV infection (transplant pts and donor/recipient serologic status)

Answer 228

``` perinatal- from maternal shedding of + mother --birth canal --milk --10% of exposed infants are infected ``` outcome if infected: mild, "virus"-like illness (term baby) prolonged CMV shedding maternal antibody via placenta protects infants for several months from severe herpesvirus infection toddler: infected by playmates -urine, saliva, prolonged shedding illness is mild adolescence: CMV shed in saliva and genital secretions -sexual transmission is common "CMV mononucleosis syndrome"

Answer 229

IgM anti-CMV antibody --implies you had a recent infection PCR tissue or see tissue intranuclear inclusions

Answer 230

in an immune compromised host severe end organ disease + viremia: wide tropism risk factors: degree of immune suppression age (premature infant, elderly) donor has latent CMV and recipient doesn't ``` disseminated CMV: tx: Ganciclovir (NOT acyclovir) resistant virus- Foscarnet prevention: screen organ donors screen blood products/tx blood use prophylactic antivirals check pts regularly for viremia early tx before symptoms ```

Answer 231

a lot of kids are exposed, but 90% don't develop disease- reflects maternal immune status symptomatic disease: 10% jaundice, enlarged liver/spleen, microcephaly, low plts) 10-20% mortality; others w/ sequelae asymptomatic disease: 90%

Answer 232

beta herpesvirus (along w/ CMV) Roseola (6th disease)- HHV6 and 7 HHV6 antibody in newborns declines until 5mo, then approaches 100% by 2yo - -in saliva of adults and children - -genital tracts of women at term - -spread occurs early (once maternal Ab is gone) from caretakers and playmates HHV7 antibody rises more slowly through 4yo and from teens to 30yo

Answer 233

infects cells at back of throat (tonsillar tissue)- 6mo to 2yo HHV6/7 infects B and T cells and becomes latent in similar cells or precursors both viruses cause a persistent lytic infection in salivary glands

Answer 234

high fever 3-7 days (>104) - looks good otherwise!! - may have minor symptoms - -relatively common cause of febrile seizure and rash Rash appears as fever ends abruptly!! -may occur w/o fever maculopapular rash starts on trunk --> face, neck, extremities; 1-2 days dx: clinical, esp tempo of events!! tx: for immune compromised host, tx w/ same antivirals effective against CMV

Answer 235

febrile seizures ``` in immune compromised: bone marrow suppression colitis encephalitis hepatitis pneumonitis organ rejfection ```

Answer 236

gamma herpesvirus "infectious mononucleosis" acute infection: viral capsid antigen VCA early antigen EA --typically develop antibodies to VCA and EA latent infection: infects native B cells for latency- for life! encodes 9 latency-associated proteins ---ex helps maintain viral genome and turn on latent genes Epstein-Barr nuclear antigen EBNA --having EBNA means you've probably had EBV for a while and not an acute infection

Answer 237

found everywhere- 97% adults have antibody childhood- like any other minor illness; unexplained fever adolescnece- infectious mononucleosis ``` patho: EBV enters mucosal cells in pharynx B cells infected; travel throughout body -lymph nodes, spleen, tonsils, liver T cells destroy infected B cells--> symptoms!! ``` associated w/ malignancies, but no evidence they're direct causes - -first human virus to be assoc w/ cancer - -tumors contain EBV genome and express characteristic EBV gene sets - -most tumors appear to have cofactors

Answer 238

fever, malaise, fatigue adenopathy pharyngitis hepatosplenomegaly atypical lymphocytes (activated T cells killing B cells) Heterophil antibodies (antibodies to other animal antigens; infected B cells are making weird antibodies) ``` dx is clinical heterophile ("likes foreign") antibody -"monospot" is rapid test atypical lymphocytes (abnl cyto) specific EBV serology ```

Answer 239

HHV8 gammaherpesvirus purplish violatious vascular lesions endemic from Africa that can affect non-immune compromised pts can cause oropharyngeal problems down to lungs; variety of mucosal surfaces results from HIV immune dysfunction HHV8 is latent in B cells periodically shed asymptomatically in saliva main significance: as a cause of sentinel malignancy (Kaposi sarcoma) at the beginning of the HIV epidemic discovered because 50% of untreated (MSM) HIV pts developed rare tumor -considered an STI Tx: lowering immune suppression operationally most successful by treating HIV Chemotherapy

Answer 240

``` Rotavirus -segmented dsRNA genomes -use genetic reassortment to produce vaccine RotaTeq (live-attenuated) Rotarix (live-attenuated) -vaccinate ASAP in child ``` HPV -doesn't grow well in tissue culture Gardacil and Cervarix (recombinant DNA expression of L1 proteins--> VLPs; these are subunit particles; not live attenuated) -vaccinate 11-12 yo's before becoming sexually active Varicella/Zoster high risk contraindication for most live-attenuated viruses (incl VZV): immunosuppression/ leukemia low risk contraindication: pregnancy (DON'T GIVE LIVE ATTENUATED ANYTHING TO A PREGNANT WOMAN) Varicella- kids Zoster- adults