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67 Cards in this Set
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Aerobic, gram-positive cocci
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Major players: staphylococcus aureus, streptococcus pyogenes, streptococcus pneumoniae, enterococcus. Also important: staphylococcus epidermis, streptococcus agalactiase
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aerobic, gram positive bacilli
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Also important: listeria monocytogenes, bacilus cereus, bacilus anthracis
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anaerobic, gram positive bacilli
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Major players: clostridium difficille. Also important: clostridium perfringens, clotridium tetani, clostridium botulinum
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aerobic, gram neg cocci
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major players: neisseria meningitidis, neisseria gonorrhoeae
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aerobic, gram neg bacilli
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major players (enterobacteriaceae): escherichia coli, salmonella enteritidis, shigella species. Also important: salmonella typhi, yersinia pestis. Major players (non-enterobacteriaceae): campylobacter jejuni, helicobacter pylori, psudommonas aeruginosa, haemophilus influenzae, legionella pneumophila, vibrio cholerae, bordetella pertussis
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anaerobic, gram neg bacilli
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bactoides fragilis
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spirochetes
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borrelia burgdorferi, treponema pallidum
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chlamydiaceae
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chlamydia trachomatis
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mycobacteriaceae
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mycobacterium tuberculosis
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others
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rickettsia rickettsii
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streptococcus pyogenes
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Group A strep, small gram-pos coccus, catalase neg., beta-hemolysis, growth as whtie colonies on enriched blood agar, bacitracin sensitive, PYR-positive. Virulence factors: exotoxins, M protein (antigenically variable and immunodominant, accounts for recurrent streptococcal pharyngitis), capsule, hyaluronidase, C5a peptidase, streptokinase (catalyzes activation of plasmin to lyse blood clots), streptodornase (DNase, helps solubilize pus because DNA sticky), lipoteichoic acid and F-protein. Lab diag with direct antigen tests ('rapid strep test'), anti-streptolysin O or anti-DNAse B titer
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streptococcus pyogenes clinical
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"1. pharyngitis and tonsilitis (""strep throat"")occurs within several days of acquisition of organism; chief symptoms: sore throat, fever, malaise, headache, abdominal pain; physical signs: erythmatous posterior pharynx +/- exudate (acute inflamm response with neutrophils), cervical lymphadenopathy. 2. other suppurative diseases: puerperal sepsis, pneumoania, bacterimia, septicemia (sepsis, mortality approaching 40%). 3. Cutaneous & soft tissue infections: pyoderma (impertigo: contagious pyoderma with superficial yellow weeping-crusty lesions), erysipelas, cellulitis, necrotizing fasciitis ('flesh-eating bacteria', a medical emergency, scarlet fever (results from infection with strain lysogenized with temperate bacteriphase encoding for pyrogenic exotoxin). POST-INFECTION SEQUELAE: 1) ACUTE RHEUMATIC FEVER manifested by Carditis (heart inflammation), Polyarthritis, Subcutaneous skin nodules, Chorea (Sydenham's chorea), Erythema marginatum. 2) ACUTE GLOMERULONEPHRITIS manifested by dark smoky urine with RBCs and WBCs, renal failure, deposition of immune complexes in kidney, morbidity due to renal failure, most often seen in developing world. 3) STREPTOCOCCAL TOXIC SHOCK SYNDROME: systemic toxicity due to production of pyrogenic exotoxins (superantigen stimulation of T-cells).
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streptococcus pyogenes treatments
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1. Group A Pharyngitis: oral penicillin or intramuscular benzathine penicilline (GAS is not resistant, but treatment failure may occur due to neighboring oral flora secreting b-lactamases); alternatives: erythromycin, clindamycin, cephalexin (oral cephalosporin). 2. Acute rheumatic Fever: salicylates and coritocosteroids for acute symptom reduction and control of long-term sequelae; prophylactic antibiotics. 3. Acute post-streptococcal glomerulonephritis: sodium restriction, diuretics, anticonvulsants.
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streptococcus agalactiae characteristics and lab diag
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Group B strep, gram-pos coccus, pairs and chains, beta-or non-hemolytic, catalase-neg, bacitracin resistant, virulence factor: sialic acid-containing anti-phagocytic capsules. Antibodies against capsular polysaccharide type is protective. Identify by PCR, routine culture.
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streptococcus agalactiae epi, diseases and treatments
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EPI: Colonizes lower GI and GU tract, transient vaginal colonization (10-30%), maternal-fetal spread in utero (leading cause of neonatal infection, risk factors: prematurity, prolonged-reupture of chorioamniotic membranes, teen pregnancy). DISEASES: Disseminated infection both maternal (bacterimia) and newborn (sepsis, CNS-meningitis); Neonatal pneumonia, urinary tract infection mostly during pregnancy. TREATMENTS: penicillin; chemoprophylaxis for vaginally/rectally colonized women during late pregnancy; peripartum treatment of neonates with antibiotics for deliveries involving premature rupture of membranes (>18h) or signs of infection (fever); future prospect for polyvalent capsular polysaccharide protein conjugate vaccine.
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streptococcus pneumoniae
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respiratory tract infection. gram-pos cocci, encapsulated, alpha-hemolytic, catalase neg, bile salt soluble, optichin sensitive (good diag). 91 unique types known EPI: coommon commensal colonization in healthy people. most common cause of resp. infection. Disease occurs most commonly in non-immune <2yr old or >65yr. Usu req predispositions: estachian tube dysfunction, aspiration of nasopharyngeal contents or antecedent viral disruption of nasal mucosa, inability to produce Ab, defective clearance of opsonized bacteria. CLINICAL DISEASES: res. tract local -- acute otitis media, sinusitis, lobar pneumonia (most prominent cause of); invasive systemic -- septicemia, meningitis. TREATMENT: recent widespread (10%-80%) penicillin resistance due to accumulation of mutations in penicillin binding proteins, often confers resistance to other lactam antibiotics. Freq. occurs on strains already resistant to other oral antibiotics, few treatment options. Vaccines problemetic b/c 91 distinct CPSs and young and old mount poor antibody responses.
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haemophilus influenzae
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respiratory tract infection. gram-neg, nonmotile pleomorphic coccobacillus encapsulated (in Type B). Identification by unique growth requirements: aerobic growth requiring hemin (aka factor X) and NAD (aka factor V). Classify as Type B (can be controlled by immunization) or Non-typeable (lacking CPS and more sensitive to complement) EPI: 2nd most common cause of resp. tract infect. CLINICAL DISEASES: Type B -- otitis media, sinusitis, pneumonia (pediatric), bacteremia, cellulitis, epiglotitis, meningitis; Non-typeable: sinusitis (inflamm of paranasal sinuses), leading cause of acute otitis media (inflamm of middle ear), conjunctivitis (pink eye) and pneumonia (adult). TREATMENT: ~70-80% remain sensitive to penicillins; cephalosporins remain effective; CPS-conjugated to diphtheria toxoid vaccine (Hib) almost eliminated disease source.
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neisseria meningitidis
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respiratory tract infection. gram-neg, diplococcal encapsulated. serogroup Classification based on capsular polysacc, clinically important are A (large outbreaks), sporadic cases in B (no vaccine) and C, Y, and W135. DIAG: isolation by culture on chocolate blood agar from normally sterile site (blood, CSF), distinguish from other neisseria by oxidation of glucose and maltose but not sucrose or lactose. EPI: colonize posterior nasopharynx of humans, up to 20% in normal individ carriers, but disease manifested elsewhere! Often high incidence in young adults and in conditions that promote transmission. DISEASES: 1. Meningococcemia: fulminant meningococcal septicemia, emergency (characterized by hemorrhages into skin, aka Petechiae) 2. Meningococcal meningitis -- also complication of bactermic spread but lacks overwhelming sepsis and thus treatable and prolonged, manifestations similar to acute bacterial meningitis caused by organisms including fever, altered mental status, headache, nausea, vomiting, and photophobia. VACCINE: conjugated vaccine for A, C, Y, W-135.
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bordetella pertussis
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respiratory tract infection. aerobic, gram-neg coccobacilli, localized infection on ciliated surfaces of upper respitatory tract. DIAG by fluorescent Ab from nasopharyngeal swab or culture in Bordet-Gengou medium. produces several exotosins (pertussis toxin -- mediate binding to epithelial cells and blocking immune effector activity, adenylate cyclase toxin, and trachael cytotoxin -- inhibits cilliary beating). Marked lymphocytosis caused by pertussis toxin is hallmark of disease. EPI: highly contagious. stages -- 1. catarrhal stage (indistinguishable from viral upper respiratory infection or URI, 2. paroxysmal stage (episodic coughing), 3. convalescent stage (100-day cough). TREATMENT: diag often runs late in course so treatment does little except limit transmission, treat with erythromycin. Immunization with DTaP (diphtheria, tetatnus, acellular pertussis vaccine) very effective.
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pseudomonas aeruginosa
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respiratory tract infection. gram-neg rod, aerobic, minimal growth requirements, motile with polar flagella, some form mucoid colonies on culture plates, pigments, easy to Identify, oxidase positive, sweet odor. Virulence factors: adhesins, elastases, protease, phospholipase, exotoxins injected into host cells. EPI: widely distributed in moist environment, not common as host flora, intrinsically resistant to many antibiotics, antiseptics; person-to-person spread unusual. Takes advantage of compromised host defense (CF patients, burn victims, corneal damage, poor neutrophil function). Able to form biofilms that populate catheters. DISEASES: nocosomial pneumonia, chronic infection with CF, hot tub foliculitis, infected burns, otitis externa (swimmer's ear), corneal ulcers, bacteremi: catheter infections, neutropenic patients. TREATMENTS: few drugs, synergistic antibiotics, address underlying problem (CF), no vaccine.
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legionella pneumophilia
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respiratory tract infection. gram-neg motile, small coccobacilli, requires buffered charcoal-yeast extract for culture, non-fermentative, intracellular pathogen can survive in macrophages in intracellular vacuole (Dot/icm genes required). DIAG: fluorescent Ab stain or urine antigen detection. EPI: common in bodies of water, infections often asymptomatic or flu-like (Pontiac fever), elderly/decreased cellular immunity (Ab not important)/pulmonary function at risk, correlates with tobacco/alcohol heavy use. No person-to-person spread. DISEASES: 1. Pontiac fever: acute, short-lived, self-limiting, flu-like, non-fatal; 2. Legionnaire's disease: 2-10 days incubation, cough, high fever, pneumonia, multi-organ symptoms with cardiac, neuromuscular, renal, and GI complications, mortality >15%. TREATMENT: antibiotics (need to be able to penetrate intracellularly)-- macrolides (azithromycin) or quinolones (ciprofloxacin, levofloxacin), NOt beta-lactams; monitor potable water as preventive.
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acute/suppurative inflammation
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innate immune--infiltration of *neutrophils* and macrophages; triggered by extracellular bacteria, "pyrogenic" bacteria, gram-pos cocci and gram-neg rods. Outcomes: normal healing (usually), abscess formation (e.g. in staphylococci, klebsiella); progression to chronic inflammation. Can occur in clinically acute time course with extracellular organisms or clinically chronic time course (walled off abscesses) with hard-to-eradicate extracellular organisms.
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mononuclear/interstitial inflammation
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infiltration of lymphocytes, plasma cells, macrophages; often triggered by viruses, intracellular bacteria/parasites, spirochetes, any infectious process persisting a long time. Can occur in clinically acute time course (NK cells infiltrate, ex. In acute viral pneumonia, acute viral meningitis); can occur in clinicall chronic time course (e.g. tuberculosis, chronic fungal infections, chronic osteomyelitis)
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Granulomatous inflammation
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collection of "activated" macrophages (aka "epitheloid cells, "large cells, abundant pink cytoplasm, often fused to form giant cells). Macrophage activation by CD4+ T cells via IFNgamma to form granuloma that walls off infection. Elicited by: intracellular -- mycobacteria (TB*****, especially in CASEATING GRANULOMA but also may be in non-caseating granuloma) and fungi (histoplasma, aspergillus) and worms (schistosoma). Granuloma can occur due to non-immune mechs, but in context of infection, think poorly degrdable intracellular pathogen. In AIDS, see cannot form granulomas against mycobcterium due to defective CD4T. Microscopically differentiate from caseous necrosis (activated macrophages and lymphocytes in granuloma) from abscess (neutrophils).
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Necrosis
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morphological feature: loss of nuclei, very eosinophilic (pink on H&E). 1. liquefactive necrosis: pus; abscess center; 2. caseous necrosis (see in TB): dead cells and granular debris, surrounded by granulomatous inflammation.
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Cytopathic-Cytoproliferative changes
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can be very distinctive when induced by viruses. Features: viral inclusions in nucleus/cytoplasm (CMV); cell fusion (e.g. measles virus); epithelial cell proliferation (human papillomavirus -warts)
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Tissue necrosis
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necrosis prominent, but lack of inflammatory cells. Can be caused by bacterial toxins (e.g. clostridum perfringens), viruses (herpes viruses), parasites (e.g. entamoeba histolytica)
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eosinophilia
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presence of eosinophils means worm infection (in context of infection). Look for eosinophils in granulomatous inflammation.
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penicillin
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only good for group A strep
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resistance to beta-lactams
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1. beta-lactamse production, 2. low affinity penicilin binding proteins, 3. decreased permeability, 4. efflux pumps.
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Cephalosporins
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beta-lactam, do not cover enterococcus; higher generation means poorer gram-pos coverage and better gram-neg coverage. GI toxicity - C difficile colitis.
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Carbapenems
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beta-lactam, super drugs, last line of defense against gram-neg, penetrates OprD porins of many gram-neg rods.
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Monobactams
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beta-lactam, active against Gram neg. aerobic bacteria, no gram-pos coverage, used exclusively for pepole allergic to penicillin.
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Vancomycin
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inhibits cell wall synthesis by binding to muramyl L-Lys-D-Ala-D-Ala. Excellent gram-pos coverage (staph and strep). Used for MRSA and other beta-lactam resistant gram-pos organisms.
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macrolides
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think atypical bacterial organisms: legionella, bordatella pertussis, chlamydia. Inhibits riboome protein synthesis. Resistance from efflux or ribosome mutations.
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clindamycin (Lincosamide)
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inhibits 50S ribosomal protein synthesis -- kills bacterial in stationary phase, inhibits toxin production. Good for gram positive activitya gainst staphylococcus aureus and streptococci.
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fluoroquinolones
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"--floxacin," inhibits DNA gyrase.
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aminoglycosides
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inhibits 30S ribosomal protein synthesis. Resistance: inactivated by acetylation.
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trimethoprim/Sulfamethaxazole
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Bactrim. Acts by inhibiting folate metabolism. Hypersensitivity. Broad spectrum aerobic activity, both grampos and gramneg. Pneumocystis and nocardia.
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Metronidazole
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Flagyl, unknown mech. Treats C. difficile colitis.
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synercid
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Staphylococcus aureus
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gram-pos, predominant nocosomial bacteria, colonies turn golden, all staphylococci catalase positive, coagulase positive (distinguish from s. epidermis and s. hemolyticus), ineffective immmunity from prior exposure. CLINICAL DISEASES: wide variety of skin (abscesses), life threatening diseases; food intoxication -- heat stable enterotoxins consumed resulting in rapid (2-6h) onset of symptoms such as emesis and diarrhea; Toxic Shock Syndrome -- due to TSS1 (superantigen) or endotoxin B or C -- key hallmark: palm and sole desquamation ; Staphylococcal scaleded skin syndrome; wound infection; more disseminated disease (bactermia, endocarditis, intraveneous catheter infection, septic arthritis, seeding of bone to cause osteomyelitis); usually not what you think of for pneumonia, but when it does, very serious. Methicillin Resistance defined by presence of mecA gene, gives resistance to all beta-lactam antibiotics. ~50% of Nosocomial MRSA susceptible only to vancomycin. Vancomycin resistance arose from vanA operon.
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staphylococcus epidermidis
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gram-pos, coagulase neg. skin flora, common contaminant, catheter or device-related infections (biofilms)
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bacteroides fragilis
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example of GI pathogen, gram-neg rod, grows in presence of bile-esculin. HOST RESPONSE: may breach gut wall, cause peritonitis. Acute inflmmatory response with neutrophil influx induces abscess formation, central necrosis and walling off of infection. Treat with metronidazole (Flagyl) and surgical drainage of abscess.
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heliobacter pylori
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gram neg curved rod, highly motile flagella, colonzes stomach and duodenum; resides in thick mucus lining of stomach (protection from acid and immune), strong association of H. pylori infection with gastritis, peptic ulcers, gastric adenocardcinoma. High urease activity produces ammonia from urea to neutralize acid. Dsecretes CagA into host by type IV secretion aparatus; vacA encodes vacuolating cytotoxin that erodes gastric epithelial. DIAG: urase (best), oxidase, catalase; EPI: oral-fecal transmission most likely, most infected individuals asymptomatic (1/3 of world infected); ubiquitous, correlates with socioeconomic status, infection persists for life unless treated; DISEASES: gastritis, gastric ulcers, duodenal ulcers, increased risk of gastric acdnocarcinoma, gastric MALT B-cell lymphoma (rare). TREATMENT: sample regimen -- combo of macrolide and amoxicillin plus H+ pump inhibitor omeprazole).; no vaccine.
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enterococcus
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gram positive cocci in singles, apirs and chains. facultative anaerobe, major habitat is GI of humans and other animals. Two major species E. faecalis (encountered more frequently) and E. faecium (accounts for more multi-resistant strains). Gut colonization precedes disease in susceptible hosts; host factors (debilitation) rather than virulence is primary determinant of pathogensis; ability to exist as biofilm important to catheter related infection and difficulty in eradication with antibiotics. EPI: second most common cause of nosocomial infection. CLINICAL: urinary tract infection (able to adhere to renal epithelium), bacterimia/septicemia (esp. catheter associated), endocarditis (able to adhere to heart valves), intra-abdominal/pelvic infections; catheters major contributing factor. TREATMENT: mult-resistance, increasing dependence on vancomycin and cephalosporins in ICUs have selected for rapid increase in VRE in these settings, also cephalosporin resistance. Nothing left to treat! ampicillin is drug of choice for sensitive strains. no vaccine.
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mycobacteria general
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neither gram-pos nor gram-neg, recognize by acid-fast staining, resistant to desiccation, slowest replicating medically-important bacteria
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mycobacterium tuberculosis
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facultative intracellular pathogen, replicate in vesicles wtihin macrophages, phagocytosed by by alveolar macrophages and transported to regional lymph nodes, prevents fusion of phagocytic vesicles with lysosomes; Th1 type response is critical for control; mycobacteria-specific CD4 T cells produce IFN-gamma to activate macrophages, which increase TNF-alpha production and promotes lysosomal fusion and killing of pathogen; tuberculosis common patients with deficient CD4+ T cell responses; CD8 T cells and innate immune also important; immune response characterized by granulomatous inflammation EPI: infects 2 billion worldwide, most are asymptomatic but have 10% lifetime risk of reactivation; risk factors include homelessness, urban poverty, malnutrition, crowding and alcoholism; rates of disease higher in prison inmates, healthcare workers, immigrants from regions with high rates of endemic TB. CLINICAL: latent tuberculosis infection -- no evidence of primary infection beyond positive PPD, no evidence of active tuberculosis on chest x-ray, not contagious, could show calcifieed lesions which are not active infection. If no treatment, could lead to Reactivation of Tuberculosis -- 3-4% risk of reactivation during first year after infection, 5-15% lifetime risk of reactivation, 8% annual risk of reactivation in AIDS patients, don't understand causes of reactivation; reactivation most common in apex of lung, caseous necrosis wand formation of cavities; symptoms of pulmonary tuberculosis: local pulmonary symptoms (cough and sputum production, shortness of breath), prominent systemic symptoms: fever, chills, nigh tsweats, fatigue, weight loss; highly contagious. Primary Progressive Tuberculous Pneumonia -- local disease following initial infection, without latency. Miliary tuberculosis: more extreme, truly overwhelmes immune system leading to progressive, dissminated hematogenous tuberculosis, systemic disease, often fatal. Extrapulmonary tuberculosis: direct spread along mucosal surfaces -- GI tuberculosis, laryngeal tuberculosis, direct extension into pleura space, lymphohematogenous spread... DIAG: Tuberculin skin test -- intracutaneous injection of standardized quantity of purified protein (PPD) antigen, tests for delayed-type hypersensitivity reaction to PPD, results generally converts to positive 3-9 weeks after exposure; reactivity remains positive but can revert to negative witha dvancing age and waning cellular immunity; positive TST in absence of symptoms/chest xray evidence of disease indicates LTBI. False positives can result from exposure to environmental mycobactteria, recent BCG vaccination. False negatives due to weakened cellular immune response, malnutrition or chronic disease (even from TB itself!), AIDS. Interferon-gamma release assays are a diagnosis not affected by vaccination with BCG. Can use acid-fast staining or DNA probes. TREATMENT: isoniazid (INH) inhibits cell wall; Rifampin inhibits RNA pol; Pyrazinamide inhibits cell wall. Use mult-drug regiments for active disease. Transmission is airborne, protection requires N95 respirator mask. VACCINE: BCG derived from M. bovis by prolonged passage in vitro, attenuated by mutations; limited efficacy provides incomplete protection against tuberculosis, can cause disaease in immunocompromised; used in much of world but not in US.
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nontuberculous mycobacteria
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mycobacterium leprae
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human papillomavirus
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non-enveloped DNA virus, infect skin and mucosal epithelia. "high-risk" types are primary risk factor for cancer (primary risk factor for cervical cancer); low-risk typse cause benign warts. HPV vaccine. Express E6 and E7, which inactivate p53 and pRB.
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influenza viruses (orthomyxovirus)
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neg strand RNA viruses. (Influenza B infects only humans, mostyly children, mild disease, minor epidemics; Influenza C only infects humans, minor respiratory symptoms, rare) Influenza A: highly variable, infects humans, birds, hroses, seals; most prevalent human virus, cause of most human epidemics and all pandemics. BASICS: enveloped virus, viral membrane proteins -- Hemagglutinin (HA) binds to sialic acid for entry, most important component of flu vaccine, mechanism depends on acidic pH of endosome; Neuraminidase (NA) cleaves sialic acid to allow virion releas and entry, target of some antivirals; M2 integral membrane ion channel, target for antivirals. Segmented 8-piece RNA genome makes easy for antigenic shift (recombination by co-infection of cell with 2 viruses). For past 30 years, H1N1 and H3N2 have been circulating in humans as seasonal flu. Swin flu has avian, swine, and human genetic components. CLINICAL FINDINGS: respiratory transmission and replicates in respiratory epitheium; incubation per. 1-4days; abrupt onset of fever, myalgia, sore throat, nonproductive cough, generalized muscle aches/malaise; viremia rare, shed in respiratory secretions for 5-10days; otitis freq in children; antibody/cell mediated immunity 1-2wks; repair of respiratory damage >1month. Secondary bacterial pneumonia is leading cause of death from influenza (S. aureus esp.) TREATMENTS: Trivalent influenza vaccine -- composedof representative influenza B, influenza A H1 and influenza A H3 formalin-inactivated whole viruses; Subunit vaccine: surface glycoproteins from whole virus, used in young children, immunocompromised; FluMist: live-attenuated influenza consists of cold-adapted influenza virus that grows well only in nasal mucosa, not recommended for young children/elderly/pregnant/immunocompromised; amantadine and rimantadine inhibit M2 ionchannel.
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Herpesviruses
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dsDNA, genes required for txn and replication in tegument layer, envelope contiains multiple glycoproteins for entry and immun evasion, large genomes (150-229kB). Tend to cause chronic and latent infections. Classification: alpha herpes viruses (neurotropic, include HSV-1, HSV-2, VZV); gamma herpesviruses (lymphotropic, nclude EBV and HHV-8); beta herpes viruses (neither neurotropic or lymphotropic, include CMV, HHV-6, HHV-7). All herpesviruses transmit human-tohuman without other intermediate, except for Herpes B virus (transmitted to humans from monkey bites). Replication: tegument proteins initiate synthesis ofimmediate-early (IE) genes, IE proteins activate Early promoters, Early proteins stimulate viral DNA replication and late genes, Late proteins form virus structure. Many interfere with MHCI antigen presentation. CD4 and CD8 T cells critical for controlling herpesvirus infections; Ab somewhat effective; complement useless.
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Herpes Simplex Virus I
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dsDNA genome, remains episomal. Virus entry (generalizable for herpesviruses): glycoproteins bind cell surface, enter by fusion of virus envelop with plasma membrane or by endocytosis followed by membrane fusion from within endocytic vesicle; inner layer of tegument proteins and/or perhaps capsid itself attach to microtubules to be transported to nucleus. gC and gE enable virus to evade Ab and complement. Infect epidermal cells through microscopic skin breaks, replicates in these cells and spread to sensory neurnos innervating these structures (travel along microtubules to neuron nucleus). Can be lytic or latent, reactivation by fever, stress, UV, trauma to nerve, immunocompromisatioed patients prone. DIAG: PCR, Tzanck smear EPI: classically associated with oral lesions, also causes ~40% genital lesions. CLINICAL: Herpes labialis -- fever blisters or cold sores on gums, inside cheeks, tongue and lips, encephalitis -- life-threatening infection of brain (hallmark: focal findings, virus remains localized to one or both temporal lobes) gives headache, fever, confusion; keratitis -- infection of cornea, leading cause of eye transplants in U.S. In immunocompromised patients, find locally invasive mucocutaneous herpes, HSV infection may be extensive at usual sites or may appear at unusual sites, particularly mouth and esophagus. TREATMENT: important to treat (acyclovir or valacyclovir-- GTP mimic terminates replication) HSV encephalitis and immunocompromised patients. Vaccines under dev.
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Herpes Simplex 2
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dsDNA genome, remains episomal. Infect epidermal cells through microscopic skin breaks, replicates in these cells and spread to sensory neurnos innervating these structures (travel along microtubules to neuron nucleus). Can be lytic or latent, reactivation by fever, stress, UV, trauma to nerve, immunocompromisatioed patients prone. DIAG: PCR CLINICAL: genital herpes, neonatal herpes. TREATMENT: important to treat (acyclovir or valacyclovir -- GTP mimic terminates replication) neonatal herpes and immunocomprmomised patients. Vaccines under dev.
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Cytomegalovirus
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CLNICAL: Congenital infection -- 95% asymptomatic at birth, but by age 2-5 15% have hearing defects; 5% symptomatic (mostly are primary infetions) -- microcephaly, small for gestational age, born premature, damaged retina, hepatosplenomegaly, jaudice, death. Other ages: almost all asymptomatic in normal host; if symptomatic: Mononucleosis syndrome (atypical lymphocytosis in blood smear, fatigue, and mild hepatitis, difers from EBV in that no swollen lymph glands and no sore throat. In Transplant patients: prolonged fever, leukopenia, thrombocytopenia, mild hepatitis, pneumonia, atypical lymphocytews usu. not present in immunocompromised patient. HIV patient: retinitis, enteritis, encephalitis, neuropathies (manifested as pain in legs, leg weakness, difficulty controlling bowel/bladder) in advsnced HIV. TREATMENT: no treatment for newborn, damage already done. Other ages: ganciclovir inhibits viral DNA replication (treat for patient with HIV, transplant, any life-threatening) No vaccine.
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Epsteine-Barr virus
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gamma (lymphotrophic) herpesvirus. Highly specialized to infect B cells. Infects epithelial cells in pharynx and tongue (productive infection), then B cells as site of latency. CD21 (CR2) is cell receptor for EBV; glycoprotein gp320 binds CD21 and gp42 binds to MHCII as co-rec; genome is episomal in B cells and replicates during cell division. CD8 T cells form the atypical lymphocytes (and are important for control. B cell lymphomas occur in some patients with defects on T cell immunity. Immune evasion proteins: BCRF1 (IL-10-like activity reducing CD8T cells and stimulates B cell growth to expand pool for infetion), EBNA1 inhibits EBV antigen process ing proteasome. EPI: Peak incidence in 2-5 and young adults; seroprevalence 90% infected by age 20; most infections prior toteen are asymptomatic, virus may be present in saliva for years after infection; spread by contact with oral secretions. CLINICAL: Infectious mononucleosis -- mainly young adults, fever 2-4 weeks, fatigue, swollen lymph glands in neck and often generalized, splenomegaly, hepatitis, rash, oral hairy leukoplakia (in HIV, EBV growing in tongue epithelial cells), distinguish symptoms from CMV by sore throat and swollen tonsils. EBV-associated malignancies: post-transplant lymphoproliferative disorder (uncontrolled B cell prolif leading to B cell lymphoma in transplant organ, bone marrow, and other sites, highest risk EBV D+R-; Burkitt's lymphoma: B cell tumor of the jaw in equatorial africa; Nasopharyngeal carcinoma in China. Other complications of EBV: abnormal antibodies produced to cause autoimmune hemolytic anemia, thrombocytopenia; splenic rupture; central nervous system infection (encephalitis, Guillain-Barre syndrome; progressive infection leading to death seen in males with X-linked recessive lymphoproliferative syndrome. DIAG: heterophile antibody test ("monospot", mono patients have nonspecific antibodies that agglutinate sheep or horse erythrocytes); lymphocytosis >50% (normal is 30%) with >20% atypical lymphocytes; EBV-specific Ab assays can distinguish acute, past, or no infection; Treatment: No specific antiviral therapy for EBV, no vaccines; post-transplant lymphoproliferative disorder treat with Rituximab (monoclonal Ab targets B cells); Infectious mononucleosis treat with steroids to reduce swelling.
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Varicella Zoster virus
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neurotropic; enters via oral cavity, replicates in oral cavity and infects lymphocytes in bloodstream, which carry virus to epidermal cells, spread to neurons to establish latency. EPI: causes chickenpox (= varicella) in first infection (widespread lesions), and localicalized infection (zoster, aka shingles) in reactivation of virus in previously infected patient, infection of skin follows dermatomal distribution of nerve supply. Chickenpox common childhood infection, usu. occur by age 3. Zoster increasingly common after >60 and in immunocompromised patients. CLINICAL: Varicella -- fever 100-103deg.F 3-5 days, itchy rash begins on trunk and face spreading to entire body, lasts ~5d, infection can be severe (pneumonia and encephalitis can lead to death), most severe in adults (250 deaths/year in USA); chickenpox rash will have lesions at diff stages at any time, whereas smallpox rash all lesions at same stage of development. Varicella complications -- bacterial superinfection of skin (cellulitis), often by staphylococcus or streptococcus; encephalitis due to VZV spread to brain; pneumonia; hepatitis (usu. mild); perinatal infection, can be fatal. ZOSTER -- shingles is unilateral vesicular rash following dermatomal distribution of a sensory nerve, does not cross midline, recurrences can occur in diff dermatomes but unusual to occur in same dermatome. Zoster complications: severe pain in infected dermatome, can continue after rash (called post-herpetic neuralgia); can cause serious visual problems due to eye infection; granulomatous angiitis: complication develops 6mo after zosters, refers to inflammation of major arteries that supply brain, presents as stroke involving side of body opposite to side involved in zoster. DIAG: clinical grounds alone often sufficient; PCR vesicles or spinal fluid for suspected VZV encephalitis. TREATMENT: Acyclovir or Valacyclovir (similar to mech as HSV by inhibiition of VZV DNA synthesis), treatment shortens course of chicken pox in children but smal benefit; treatment reduces severity of acute pain in shingles but does not prevent post-herpetic neuralgia; treatment of varicella and zoster may save life of immunocompromised. Very good live vaccine for preventin chickenpox, recommended for children and suscepible healthcare workers, immunize again as adlescents; recently approved for preventing zoster in >60 group.
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Human Herpes virus6
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respiratory syncytial virus
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a respiratory tract virus of the paramyxovirus family, enveloped, neg-sense ssRNA surrounded by nucleocapsid, able to produce formation of syncytial cells, G glycoprotein mediates attachment and F glycoprotein mediates fusion and syncytium formation. Contains RNA-dep RNA polymerase. Antigenic types A and B. EPI: humans only source of infection, predictable annual community outbreaks involving nearly 50% of all families with children, virtually all children ifnected by 2-3yr; adults usu. get localized infection to upperairway. Adult infections: frequent and mild influenza-like illness, but seriosu in elderly (2-4% of pneumonia deaths among elderly) and patients with congestive heart failure, bronchiopulmonary insufficiency, imune supression. Major concern for nosocomial infections. CLINICAL: most are symptomatic in children -- bronchiolitis** (up to 90% of RSV), pneumonia, tracheobronchitis, croup; Upper respiratory tract infection -- cough, rhinitis, pharyngitis, fever; Lower respiratory tract infection: expiratory wheezing, air trapping tachpnea, dyspnea, rales, rhonchi, retractions, nasal flaring, grunting, hypoxemia, irritability, dehydration, respiratory distress, hyperexpansion of lungs, hypercapnia (CO2 retention), other -- otitis, vomiting, conjunctivitis, duration 10-14d. In adults, suspect RSV who present with fever and pulmonary infiltrates. TREATMENT: usu. just supportive, no vaccine, can give palivizumab (humanized mouse monoclonal Ab.) to high-risk children.
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parainfluenza virus
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paramyxovirus family, respiratory tract virus, enveloped, nonsegmented ssRNA genome (genomically stable), possess hemagglutinin, neuraminidase, and F protein. Serotypes 1, 2, 3, 4, each antigenically stable, different seasonality and frequencies and epidemic patterns. EPI: second only to RSV as important cause of LRI in infants/children, ersponsible for 15-20% of all nonbacterial respiratory diseases causing hospitalization. CLINIC: Virus 1 and 2 strongly associated with Croup -- begins as a URI with rhinorrhea, sore throat, mild cough; within 1-2 days have varying degrees of inspiratory stridor with supraclavicular and suprasternal retractions, worsening barking cough, and hoarseness due to obstruction in region of larynx and subglottic trachea, symptoms exacerbated at night. No viremia. Reinfection common. but tend to be less severe.
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Adenoviruses
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nonenveloped (stable in environment, allows fecal transmission), dsDNA, icosahedral capsid of hexon and penton capsomers, with fibers projecting from capsid and containing viral attachment proteins; penton base and fiber are toxic to cells and carry type-specific Ag. ~100 serotypes, 51 known to affect humans, characterized by ubiquity and perisstance in host tissues serotypes 1-5, 7, 8, 21 are important respiratory agents. EPI: totally unpredictable, endemic in U.S., infections most common in children 6mo-5yr, grade school and junior high; epidemics in military recruits, spread by respiratory and fecal route. CLINICAL: major associations with pharyngitis, conjunctivitis***, and pharyngoconjunctival fever.
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Rhinoviruses
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piconavirus family (small RNA virus), ssRNA genome, >100serotypes, EPI: associated with common cold (fever uncommon); most commonly identified virus from persons experiencing acute respiratory illness, seen in all age groups; more serious disease may give flu-like symptoms and role in asthma exascerbations under investigations.
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Coronaviruses
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enveloped, positive-sense ssRNA, accounts for 10-30% of common colds.
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Human Metapneumovirus
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neg. sense, ssRNA, enveloped. EPI: humans only source of infection. Tramsmission simlar to other respiratory viruses, epidemiology and linical manifestations similar to RSV (leading cause of brhonchiolitis in infants and causes pneumonia and croup. Linked to severe acute respiratory diseases in children, elderly, and those with cardiopulmonary diseae, and immunocompromised.
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Hepatitis A
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picornavirus, positive strand RNA genome, single serotype worldwide EPI: affects 1.4million worldwide annually, causes about 40% of acute cases of hepatitis, spread via fecal-oral route. Shellfish is an important source of infection because act as filter feeders, concentrate virus from contaminated water. CLINICAL: causes only acute infection, self-limited illness, no association with cancer, symptoms similar to acute HBV infection (fever, fatigue, malaise, anorexia, pruritus, nauseea, vomiting, RUQ ab; adult infection usually silent/subclinical in children
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Hepatitis B
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