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143 Cards in this Set
- Front
- Back
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Mechanism of action of sulfonamides
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competitively inhibit dihydropteroate synthetase, effectively blocking the addition of p-aminobenzoic acid in the second step of folate synthesis
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Mechanism of action of antimicrobial antifolates work
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inhibit biosynthesis of purines and pyrimidines by inhibiting dihydrofolate reductase (DHFR)
ex: trimethoprim aka diaminopyrimidines |
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why sulfonamides are selectively toxic to microbes
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humans don't synthesize folate and don't have this enzyme; we obtain it from the diet
-microbes are impermeable to folic acid; humans actively transport it |
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why antimicrobial antifolates are selectively toxic to microbes
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1. both microbes and humans use DHFR (isofunctional enzymes
2. structure of microbe DHFR is different even though it carries out the same mechanism 3. trimethoprim only inhibits microbe enzyme 4. toxic to microbes at a much lower concentration |
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Microbe resistance to sulfonamides
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-reduction in permeavility to sulfonamides
**mutation in dihydropteroate synthetase -increase in dihydropteroate synthetase -increase in PABA (substrate with which drug competes) |
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microbe resistance to antimicrobial antifolates
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-overproduction of DHFR
-reduced susceptibility of DHFR to trimethoprim |
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Who is Paul Ehrlich?
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Father of chemotherapy and immunology. Formulated the principles for discovering anti-infectives
1. believed that synthetic compounds can cure infections 2. raise chemotherapeutic index 3. Magic bullet: receptor theory of selective toxicity = selective targeting 4. drug resistance is usually a characteristic of infecting organism |
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chemotherapeutic index
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-ratio of maximum tolerated to minimum effective dose, ie dose to harm/dose to cure
-higher is better! |
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Prontosil
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Domagk theorized that dyes can function as drugs.
active in vivo against strep. pneumonae metabolism of prontosil liberates the sulfanilamide (SA) which is the active agent |
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sulfonamide toxicity
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-high rate of reactions in patients with AIDS
-allergic reaction to drug can be treated -NEVER given to newborns because can cause kernicterus due to deposition of bilirubin: drug causes dissociation of bilirubin with albumin (carrying protein) so that free bilirubin binds to intracellular proteins. **serum bilirubin in child given sulfonamides will be LOW |
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trimethoprim toxicity
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rare; rash, nausea
folate deficiency in nutritionally deprived patients (megaloblastic anemia, thrombocytopenia, neutropenia) |
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trimethoprim-sulfamethoaxazole (advantages)
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cotrimoxazole, bactrim, septra
combination chemotherapy blocking both folate synthesis and DHFR --synergism --broadened spectrum of activity --decreased likelihood of resistance --decreased dosage of each favors lower toxicity --bacteriocidal rather than bacteriostatic |
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clinical use of cotrimoxazole (TMP/SMX)
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1. Chronic and recurrent urinary tract infections
2. otitis media 3. shigellosis 4. chronic bronchitis 5. pneumocystis carinii 6. typhoid fever 7. MRSA |
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fansidar
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pyrimethoprim (diaminopyrimidine) + sulfonamide
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Alexander Fleming
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penicillin discovery
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Chain and Florey
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identified the active ingredient of penicillin mold
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B-lactam antibacterioal characteristics
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1. bactericidal
2. time-dependent killing: not dependent on concentration but on maintaining the minimum inhibitory concentration over dosing interval 3. post antibiotic effect for gram positives: suppression of bacterial growth persists after short exposure |
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B-lactam selective toxicity
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bacteria have cell walls
1. D-ala-D-ala 2. have transpepdidase |
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Penicilin G spectrum of activity
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gram positive strep
oral anaerobes |
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B-lactams: mechanism of action
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1. inhibit cross-linking of peptidoglycan strands catalyzed by a transpeptidase
2. autolysins play a role through continues dissolution of old cell wall in the absense of synthesis of new cell wall 3. not always lethal; sometimes just changes morphology of bacteria to render it ineffective |
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Penicillin Binding Protein
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enzymes to which penicillins bind; located in bacterial cell membrane, include transpeptidases, function varies
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bacterial resistance of penicillin
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1. alteration in PBP site
2. reduced permeability 3. B-lactamase: constitutive and periplasmic in many gram negatives, opens ring |
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B-lactamase inhibitors
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clavulanate
sulbactam tazobactam (given with B-lactams) |
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Augmentin
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clavulanate + amoxicillin
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B-lactamase inhibitor limitaions
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only active against Class A; except Tazobactam has Class C and D activity
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Penicillin's adverse effects
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-hypersensitivity--anaphylactic reaction is rare, but serious and fast (use skin testing)
-toxic: gastrointestinal symptoms are common |
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problems with Penicillin G
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-short half-life
-unstable to gastric acidity -inactivation by B-lactamase -spectrum poor for gram negatives -allergenicity |
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LPS
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conserved among gram negative bacteria; Lipid A is the most toxic moiety, faces periplasmic space...
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Quellung reaction
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homologous antibody that helps detect a capsule by causing it to swell
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# deaths by diarrhea
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1.7 million per year (was 5 million in 1980)
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classification of diarrheal diseases
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acute
--secretory: viral and bacterial --invasive: mostly bacterial chronic (>2-3 weeks) --mostly parasitic travelers' diarrhea |
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normal stool size
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from normal intake of 2 L, stool should be <200 ml
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pathophysiological mechanisms for diarrhea
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1. decreased absorption of fluid
-inhibited/defective absorption -luminal presence of osmotically active agents -decreased contact time 2. increased secretion of fluid -stimulated anion secretion from crypt cells |
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distribution of microflora in GI
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-most ingested organisms are killed before or in the stomach
-e.coli, lactobacilli found in small bowel -majority of resident flora is found after the ileocecal junction |
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intestinal host defenses
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gastric acid, digestive enzymes, mucus, epithelium (tight junctions), bile acids, indigenous microflora, peristalsis
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most acute diarrhea is caused by X
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gram negative rods
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Is enterotoxigenic E. coli (ETEC) common?
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-most frequent bacterial cause of acute diarrhea in children living in the developing world and travelers' diarrhea
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enteropathogenic (EPEC
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X
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enterohemorrhagic (EHEC)
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X
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mechanism of Vibrio cholerae O1 and O139 and ETEC
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secrete toxin --> activate cAMP or cGMP --> increase anion secretion and decrease absorption
Cl secretion, Na/Cl secretion no impairment of Na-glucose pump absorption no mucosal damage --cholera toxin/e. coli heat stable enterotoxin |
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Shigella dysenteriae disease
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low inoculum required (10-100)
bacteria pass through small bowel, invade mucosal cells in large bowel, causing pus, RBC, mucus in stool, fever, abdominal cramping --destructive to mucosal cells |
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non-typhoid Salmonella
salmonella typhi |
X
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campylobacter jejuni
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X
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Yersinia enterocolitica
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X
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Clostridium difficile
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X
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virulence factors of bacterial diarrheal pathogens
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1- enterotoxigenic bacteria
V. cholerae, ETEC, EHEC attachment to mucosal cells in the intestine by pili or other mechanisms 2- invasive bacteria -Shigella, Campylobacter, Salmonella, C. difficile, Yersinia, Listeria |
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inoculum sizes for bacterial diarrheas
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cholera and enterotoxigenic E. coli:
10^5-6 organisms Shigella and enterohemorrhagic E. coli: 10^1-2 organisms |
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comparison of CJD to "new variant"
-age of onset -duration of disease -early signs -later cerebellar signs electrocephagraphic periodic complexes -pathology |
29 yrs vs. 60 yrs
14 months vs. 5 psychiatric abnormalities, sensory symptoms vs. dementia, myoclonus 100% vs. 40% 0% vs. 94% diffuse amyloid plaques vs. sparse plaque in 10% |
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contrast enterotoxigenic and invasive diarrhea:
-diarrhea -major site of disease -major defect -character of fecal loss -primary Rx |
-severe vs. moderate
-small bowel vs. colon -increased secretion vs. inflammation -isotonic electrolyte solution vs. can also include + mucus, blood, pus (dysentery) -rehydration vs. antimicrobials |
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diagnosis of bacterial diarrheas
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-stool culture
-identification of toxin (serology) -blood cultures -antibody response -antigen detection (ELISA) -DNA probes -PCR |
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V. cholerae O1 and O39--characteristics of disease
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most severe of all diarrheas, death can occur in 12-24 hours after onset, stool rate > 1L per hour
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electrolyte content of cholera stool
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isotonic fluid
similar to plasma no red cells or protein large loss of HCO3 is most dangerous because it can result in metabolic acidosis |
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diagnosis of ETEC
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diagnosed via molecular methods to detect toxin
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diagnosis of cholera
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plated on TCES media and forms yellow colonies (very easy to detect)
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therapy for cholera and ETEC
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ORS based on the discovered coupling of Na and glucose includes equal amounts of Na and glucose; also includes K, citrate, Cl
delivery of tetracycline reduces amout of time needed with ORS (IV not available where cholera is most likely) |
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vibrio parahaemolyticus
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--gram negative rod
--grows well in sea water --found in undercooked fish --increase in cases in the summer --illness is mild: nausea, vomitting, low grade fever --no evidence of antibiotic effect --diagnosis on same TCBS agar --mechanism not well understood |
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vibrio vulnificus
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--organisms live in sea water
--causes blood stream infection through seafood or swimming with wounds --usually occurs in patients with underlying severe liver disease --high mortality rate (difficult to treat) |
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diagnosis of shigella
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stool culture: non-lactose fermenting
serology: detects antibodies to the O antigens (not commonly used) |
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M. Leprae: tuberculoid vs. lepromatous leprosy
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tub: 1) strong immune response with activated marcophages and lymphocytes 2)only a few bacilli are present 3) granulomatous reaction 4) reactive lepromin test
lep: 1) weak immune response; 2) bacilli multiply abundantly within macrophages causing swelling of macrophages 3) sheets of macrophages 4) non-reactive lepromin (skin) test |
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unique features of M. leprae
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only mycobacterium that regularly involves nerves
prefers cooler parts of body armadillos are a resevoir |
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unique characteristics of M. tuberculosis
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epidemic wave can last 100's of years (sharp rise, peak, and gradual decline)
most prevalent in crowded impoverished communities |
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Ramanujan
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brilliant mathemetician born in 1887, died of TB in 1920 in Cambridge
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mycobacteria
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acid-fast due to high lipid content of cell walls (mycolic acid)
obligate aerobes hard to detect in tissue, slow to grow in culture capacity to survive intracellularly no endospores or capsules; Gram positive |
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transmission of TB
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person-to-person by small airborne droplet nuclei produced when a person coughs, sneezes, speaks that disperse uniformly throughout enclosed space
-regular surgical masks may not protect (guinea pig experiment) |
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primary TB
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inhaled nuclei land in middle or lower lung fields b/c receive the greatest volume of air --> nuclei implant on respiratory bronchioles/alveoli --> bacilli elicit a non-specific PMN response --> alv. macrophages engulf mycobacteria --> bacilli remain viable and multiply --> macrophages process and present antigens to T-helper lymphocytes --> lymph. release lymphokines which attract and activate macrophages --> blood-borne monocytes enter lesion and form a granuloma --> some infected macrophages are transported to the lymphatics
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Ghon focus
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lesion produced where the first infection with the TB bacilli
Ghon complex also involves regional lymph nodes then throughout the body |
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# people infected with TB in the world
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2 BILLION
over 90% heal (granulomas calcify, have a positive skin test, viable bacilli remain) |
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Simon Foci
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some bacilli are transported to lung apices b/c regional O2 tension in upper lobes is greatest and relative lymphostasis (lower blood flow)
apical scars are common in tuberculin+ people and harbor more bacilli than other parts of the lung |
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progressive primary TB
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5-10% of patients; rapid enlargement of the primary complex that can erode into a blood vessel, bronchus, or pleura
can eventually cause MILIARY TB: thousands of small nodules (larger in the apex) spread througout lungs resulting from bacilli spread by the bloodstream |
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outcomes of primary TB
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95% heal
5% develop progressive primary TB: TB BRONCHOPNEUMONIA is spready by the airways TB EMPYEMA erodes into pleural space MILIARY TB is spread via blood stream |
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post-primary TB
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reactivation of previously healed TB (Simon focus): begins in posterior segment of upper lobe in 1.4-2.4% of untreated PPD+ patients over 5 years
OR reinfection of a previously infected individual **CAVITATION is the HALLMARK can also have bronchopneumonia, miliary, empyema during this stage, or also Massive hemorrhage or healed cavity=aspergilloma |
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Directly Observed Therapy
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health care workers go to patients' homes and watch them take their medication to reduce development of resistance
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HIV and TB
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usually diagnosed 6 months before opportunistic infections
more often extrapulmonary when it involves the lungs, it's non-cavitary, poorly developed granuloma drug resistant negative PPD *more like lecromatous leprosy TB is now an AIDS defining illness both diseases affect common demographic downward trend in TB ended in 1985 and reversed in 1986 *TB is the leading cause of death in individuals who carry the AIDS virus |
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Mycobacteria vs. Nocardia
Resevoir Host Range Route Clinical Cell Wall Microbiology Host Defense Evasion |
table
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AFB smear
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incubate microbes with carbol fuchsin dye --> use acid alcohol to decolorize, and mycobacteria will retain red color because of mycolic acid --> counterstain so background will be blue/green
aka Ziehl-Neelson, acid-fast bacilli -rapid diagnostic, non-specific, low sensitivity -requires decontamination |
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fluorochrome stain
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non-specific acid fast stain
requires concentration of specimen still not very sensitive, even in active TB |
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mycobacterial diagnosis: culture
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more sensitive than smear, but takes WEEKS to grow, often special conditions are required
-necessary for species identification, drug susceptibility testing, monitoring response to Rx |
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rapid diagnosis of TB
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nucleic acid amplification
-positive test strongly supports dx of TB -negative test does not exclude TB |
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diagnosis of leprosy
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examine for erythematous or hypopigmented skin lesions with associated sensory loss, palpably enlarged peripheral nerves
-perform skin smear or biopsy -PCR-based diagnostic |
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Non-Tuberculous Mycobacteria (NTM)
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-free-living environmental organisms
-opportunistic pathogens 4 clinical scenarios: -lymphadenitis -inhalational pulmonary disease -disseminated disease -skin infection after inoculation |
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Mycobacterium avium complex (MAC)
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3 clinical syndromes: lymphadenitis, pulmonary disease (solitary nodule or fibrocavitary), disseminated infection with AIDS (entry via GI)
largely diagnosis of exclusion |
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hot tub lung
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hypersensitivity pneumonitis caused by reaction to MAC in hot tub water
subacute onset of SOB, cough, fever |
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Mycobacterium marinum
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-inhabits aquatic and marine environments
-chronic ulceronodular skin disease is an occupational hazard of fishermen "fish tank granuloma" |
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Mycobacterium ulcerans
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presumed aquatic environmental organism
the only toxin-producing mycobacterium etiologic agent of Buruli ulcer (chronic painless cutaneous ulcer) |
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rapidly-growing Mycobacteria
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form colonies in <7 days
M. abscessus, M. chelonae, and M. fortuitum ubiquitous in home and hospital opportunistic pathogens: surgical site, implant-associated, pulmonary infection, disseminated in immunocompromised patients -require cooler temp for growth, can grow on normal plates |
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Nocardia
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aerobic, Gram+ filamentous rod
ubiquitous in soil, decaying vegetation no person-to-person -cutaneous nocardiosis in immunocompetent host: cellulitis, abscess, lymphocutaneous -pulmonary & disseminated nocardiosis: immuno-compromised, difficult to diagnose |
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Similarities of M. tuberculosis and Nocardia
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-both Mycobacteria
-cavitary lung disease with risk for dissemination in immunocompromised -both affect persons with impaired CMI -both acid fast |
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Differences of M. tuberculosis and Nocardia
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-Noc can be cultured on blood agar
-Noc is filamentous -Noc is ubiquitous -M. tb causes latent infection and gives postitive PPD -M. tb has a slower generation time -M. tb has longer mycolates and is more resistant to decolorization |
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life cycle of Chlamydia
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BIPHASIC lifecycle: elementary body is inert, infectious phase-->then fuse with phagosome-->reorganize (loosen cell membrane)-->replicate-->condensation-->extrusion
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unique features of Chlamydia
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obligate intracellular orgs
possess inner and outer membranes, but no peptidoglycan layer can't make own ATP biphasic life cycle |
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Chlamydia trachomatis division
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D-K serovars cause genital infections and conjunctivitis
L1-L3 serovars" LGV A-C serovars: trachoma (eye infection not seen in US) **all infect non-ciliated columnar epithelial cells, one infection confers little protection against reinfection |
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Chlamydia trachomatis D-K disease processes
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men: urethritis, epididymitis
women: urethritis, mucopurulent cervicitis, PID, ectopic preg men and women: pharyngitis, pneumonia, proctitis, conjunctivitis |
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Chlamydia in the US (epidemiology)
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estimated 3-4 million new cases annually
most frequently reported STD in US highest reporting in women (15-18) and AA population high prevalence of co-infection in partners perinatal transmission results in neonatal conjunctivitis |
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LGV pathogenesis
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worldwide distribution, higher prevalence in tropical areas
strains are more invasive aggressive systemic disease primary: painless genital lesion secondary: regional lymphadenopathy (buboes--painful) + systemic symptoms tertiary: genital elephantiasis, strictures, fistulas, frozen pelvis |
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Chlamydia trachomatis A-C: Trachoma
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chronic keratoconjunctivitis
leading cause of preventable blindness in the world transmitted hand to eye, via flies endemic in Africa, Asia, Middle East chronic follicular conjunctival inflammation --> conjunctival scarring --> entropion --> corneal abrasions and opacification --> blindness |
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Chlamydia trachomatis: Diagnosis
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must be cultivated in tissue cell cultures, but this is a non-sensitive method
for D-K and L1-L3, NAATs are preferred diagnostic trachoma is usually a clinical diagnosis |
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Chlamydia pneumoniae
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same life cycle as C. trachomatis
common cause of upper and lower resp infections bacterial cause of "atypical pneumonia" (similar to mycoplasm and legionella), diffuse rather than lobular 7-10% of community-acquired pneumonia is caused by C. pneumonia |
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Chlamydia psittaci
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common in birds
causes severe "atypical pneumonia," FUO, splenomegaly, malaise culture is DANGEROUS--serologic diagnosis or PCR |
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Chlamydia: Treatment
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tetracyclines (doxy) and macrolides (azithromycin) are effective against all
drug resistance is RARE |
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Mycoplasma: general characteristics
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lack cell wall
TINY can grow on specialized agar (difficult) |
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Mycoplasma pneumoniae
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another common bact. cause of "atypical pneumonia" (non-severe)
rarely diagnosed because no commercial test is available |
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Mycoplasma genitalium
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causes urethritis and cervicitis
unknown prevalence, no commercial test smallest prokaryote capable of self-replication |
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anaerobic pathogens: general characteristics
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do not usually cause disease alone
infection is usually related to a breach in a mucus membrane pathogenesis depends on: -virulence factors -mechanisms of abscess formation (poor blood supply and tissue negrosis favor their growth) -bacterial synergy |
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Where do we find Gram negative anaerobes?
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mouth--in saliva and gingival scrapings
stomach/upper intestine: few bc of gastric acid distal ileum/colon: 10^12/gm of stool vagina: 10^6/gm of secretions |
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What are the common infections caused by anaerobes?
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abdomen: peritonitis, abdominal abscess, appendicitis
head & neck: sinusitis, otitis, peridontitis lung: empeyema, aspiration pneumonia skin/soft tissue: diabetic foot infections, cutaneous abscess, gas gangrene, bite wound infections CNS: brain abscess, epidural abscess |
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Bacteroides fragilis
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anaerobic Gram-negative bacilli
part of normal GI flora resistant to penicillins due to production of B-lactamases (need to use inhibitors) has a CAPSULE which by itself provokes abscesses |
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Prevotella sp.
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anaerobic Gram-negative bacilli
part of normal oral and vaginal flora cause of aspiration pneumonia, lung abscesses, sinusitis, bite wounds, brain abscesses |
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Fusobacterium sp.
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long, thin Gram-negative rods
virulent LPS (similar to Enterobact) associated with oral, pulmonary, and intracranial infections increasing penicillin resistance |
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Virulence factors of Gram-negative anaerobes
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Superoxide dismutase: defends against O2 free radicals and enhances aerotolerance
proteases: cause tissue damage and promote spread capsule: inhibits phagocytosis, promotes adherence and abscess formation **LPS is les virulent than aerobes EXCEPT for Fusobacterium |
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Host risk factors predisposing to anaerobe infections
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**diabetes
broad-spectrum antibiotic use disrupts balance malignancy previous surgery (scar tissue, poor vascularization) immunodeficiency |
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Anaerobic infections: diagnosis
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primarily on symptoms & medical history
FOUL smell is a late feature (specific, but not sensitive) clues=tissue necrosis and gas production + culture grows nothing specimens for culture must be devoid of normal flora--get to the lab ASAP! |
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Anaerobic infections: treatment
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antibiotic therapy is largely empiric: clindamycin, metronidazole, B-lactam w/ lactamase inhibitor, cephalosporins, carbapenems, chloremphenicol
need to cover aerobic AND anaerobic pathogens surgery is often needed to clear necrotic tissue and wounds should be left open |
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Fournier's Gangrene
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bacterial infection of the skin that affects genitals and perineum
develops when a wound becomes infected POLYMICROBIAL anaerobic player: Bacteroides **surgical emergency |
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Ludwig's Angina
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progressive cellulitis of connective tissues of the floor of the mouth and neck
>50% of cases demonstrate polymicrobial infection (Strep, Bacillus, Prevotella, FUSO) |
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Which Gram-negative anaerobe is most likely to be found in intra-abdominal abscesses?
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Bacteroides fragilis
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Which virulence factor enhances aerotolerance and defends against O2 free radicals?
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Superoxidase dismutase
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Treponema pallidum: pathogenesis
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spirochete penetrates abraded skin
disseminates within hours to days through lymphatics or blood to ANY organ divides every 30 hours as few as ~10 spirochetes can establish infection "the great imitator" |
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primary syphilis
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~3 weeks before ulcer appears
chancre - single papule at the site of inoculation ulcer is painless heals without therapy neutrophils --> CD8 + CD4 create ulcer --> clear infection from site |
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secondary syphilis
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2 to 8 weeks afterchancre
as a result of multiplication and dissemination of the spirochete skin manifestations are most common and look like anything |
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latent syphilis
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when secondary manifestations are under control of immune system
early latency-1st year-pt can have relapses and is still infectious late latency-host is immune to relaplse and reinfection |
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tertiary syphilis
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30-60% of untreated patients develop late manifestations
gummatous: benign-like lesions usually affecting the skin and bones, but can occur in any organ cardiovascular: endarteritis obliterans of the vasa vasorum of the aorta neurosyphilis: usually occurs >10 years after primary infection, can be meningovascular (strokes) or parenchymatous (general paresis, psychosis) histopathology ressembles mycobacterial disease, so special antibody stain is needed (doesn't grow on culture) |
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diagnosis of syphilis
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-direct visualization via darkfield microscopy (gold standard; could be negative in 30% of cases)
-serology: non-specific tests that are very sensitive (RPR and VDRL), positive test needs to be confirmed with a treponemal test (MHA-TP, FTA-ABS) |
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congenital syphilis
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can occur at any stage of syphilis
infection in the fetus occurs after the 4th month manifestations: rhinitis, rash, splenomegaly, anemia, osteochondritis |
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syphilis: therapy
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penicillin; dose depends on stage
ALL partners need to be treated make sure to test for other STIs as well |
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klebsiella granulomatis
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causes Granuloma Inguinale Donovanosis
rare in the US; common in SE Asia & Africa painless progressive ulcerative lesions Dx via tissue biopsy treated with Doxycycline |
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chancroid
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caused by Haemophilus ducreyi
painful genital ulcer & tender suppurative inguinal adenopathy |
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Yersinia pestis
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-Gram negative coccobacillus
-bipolar staining (like a safety pin) -facultative intracellular bacterium -majority of cases in Africa -rodent hosts live with fleas that seem to be resistant from clinical manifestations of infection, moves from rural to urban env. |
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Plague: pathogenesis/clinical manifestations
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-Yersinia infection by flea bite: bubonic plague
-infection by aerosol: pneumonic plague -either route: septicemic plague -rapid spread and growth in tissues and blood -high case fatality rate -extensive tissue necrosis without extensive inflammation b/c bacteria suppress leukocyte function (Yops, LcrV); LPS activates systemic inflammatory responses, coagulation and fibrinolytic pathways (sepsis) -flea bites skin then defecates so that when human scratches the bite, the Yersinia enter the wound and drain to the local lymph node to cause hyperplasia and necrosis (bubo) -enlarging lymph node eventually erupts -causes high fever, headache, chills, malaise in 2-6 days -cure in 3-5 days |
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septicemic plague
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-Yersinia invasion of blood without buboes
-high frequency of death related to endotoxin and cytokine release that causes typical Gram-negative sepsis (ARDS) -complications include endophthalmitis, meningitis, tissue abscesses |
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Yersinia pestis: virulence mechanisms
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-flea vector and inhalation bypass primary host defenses
-secondary host defenses: PMNs engulf and kill Y. pestis, BUT Y. pestis survives in and kills macrophages, LPS drives infl response -virulence a result of plasmids that help degrade tissue barriers, inactivate complement, and stimulates IL-10 **generally promoting the bacteria to survive by suppressing the inflammatory response |
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Why has there been a reemergence of tick-borne diseases?
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increase in habitat suitability for deer ticks
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hard-body ticks
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deer, lonestar, dog ticks
have 4 life stages; adult stage has sexual differentiation -at each stage the tick has only one meal -needle-like appendage inoculates the host with saliva which may contain inf. organisms |
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Borrelia burgdorferi
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causes Lyme disease
-spirochetes that are narrow but long, promoting ability to twist into tissue -obligate parasite -maintained in small mammals that do not experience disease -bimodal distribution: cases occur in early Summer and late fall |
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Lyme disease
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3 potential states
1st stage: elicits chronic inflammation around tick bite (bulls eye lesion) w/in 7 days, sometimes fever early disseminated: fever, multiple erythema migrans, cranial nerve VII palsy, meningitis, cardiac arrhythmias, arthritis late stage: oligoarticular arthritis, chronic pain, lethargy (usually not responsive to antibiotics) |
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post Lyme disease syndrome
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probably does not represent active bacterial infection
absense of and lack of progression to concomitant objective clinical signs lab tests show persistence of symptoms is independent of serologic tests no substantive response to treatment |
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Lyme disease pathogenesis
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OspA-adhesin for borreliae in tick midgut
OspC-inportant for transmission from tick salivary gland and infection in human -abundant lipoprotiens that interact with TLR and induce host proinflammatory cytokine and chemokine production |
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Lyme disease: diagnosis and treatment
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diagnosis: history of tick exposure, residence in an endemic area, serologic (immunoassay, western blot)
treatment: localized or disseminated infection with no cardiac or neurologic involvement-amoxicillin; with neur or card involvement-IV ceftriaxone Vaccine no longer produced prevention: avoid bites and remove ticks early |
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Tick-borne rickettsial diseases
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obligate intracellular bacteria with Gram negative cell wall, lack genes for glycolysis
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Rocky Mountain Spotted Fever: pathogensis
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5% of those infected will die
-cell enters endothelial cell, escape endothelial cell, kills the cell--> lymphohistiocitic vasculitis (chronic inflammation) |
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Rocky Mountain Spotted Fever: clinical manifestations
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-fever, headach, myalgias, rash (macular-->maculopapular-->petechial)
-shock and multi-organ failure -GI system -renal system-acute tubular necrosis secondary to hypotension -Cardiopulmonary system-edema -CNS-meningoencephalitis |
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Rocky Mountain Spotted Fever: diagnosis and treatment
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risk of death increases 5x after 5 days of illness
-skin biopsy with R. rickettsii antigen -PCR -serologic confirmation not useful until at least day '7 treatment: doxycycline, tetracycline (chloramphenicol associated with increased mortality) |
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What are the viral properties that facilitate infection of the GI tract?
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-resistance to low pH in the stomach
-resistance to detergents (bile) -resistance to proteases (small intestine) |
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Viruses that replicate in the GI tract and cause gastroenteritis
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adenovirus, CALICIVIRUS (norovirus-negative strand, no envelope), Astrovirus, ROTAVIRUS (dsRNA, segmented, no envelope), Coronavirus, Torovirus
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