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Respiratory Bacterial Infections. Dr Amin Aqel Respiratory system. In lower respiratory system usually no permanent residents are present. Bordetella pertussis Basics. Aerobic, small, Gram negative encapsulated coccobacillus Specific to Humans Colonizes the respiratory tract
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Respiratory Bacterial Infections Dr AminAqel Respiratory system
In lower respiratory system usually no permanent residents are present
Bordetella pertussis Basics • Aerobic, small, Gram negative encapsulated coccobacillus • Specific to Humans • Colonizes the respiratory tract • Whooping Cough (Pertussis) • Bordetella parapertussis is the most closely related to Bordetella pertussis . • It can cause a milder pertussis-like disease in humans http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm http://microvet.arizona.edu/Courses/MIC420/lecture_notes/bordetella_pertussis/ gram_pertussis.html
Transmission • Very Contagious • Transmission occurs via respiratory droplets • Outbreaks first described in the 16th Century • Major cause of childhood fatality prior to vaccination http://www.ratbags.com/rsoles/history/2000/12december.htm http://www.universityscience.ie/imgs/scientists/whoopingcough.gif
Virulence Steele, R.W. Pertussis: Is Eradication Achievable. Pediatric Annals. Aug 2004. 33(8):525-534
Adhesions • Filamentous hemagglutinin • Pertactin • Fimbriae http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpg http://www.my-pharm.ac.jp/~yishibas/research/Pertussis1.jpg
Toxins • Pertussis Toxin: Colonizing factor and endotoxin • Adenylate Cyclase Toxin: Invasive toxin, Impairment of immune effector cells • Tracheal cytotoxin: inhibits cilia movement • Dermonecrotic toxin: vasoconstriction and ischemic necrosis www.ibl.fr/u447/u447.htm
Pertussis Pathogenesis • Primarily a toxin-mediated disease • Bacteria attach to cilia of respiratory epithelial cells • produce toxins that paralyze the cilia, and cause inflammation of the respiratory tract • Inflammation will interferes with clearance of pulmonary secretions • Pertussis antigens allow evasion of host defenses (lymphocytosis promoted but impaired chemotaxis)
Pertussis Infection and Clinical Features • Incubation period 4-21 days • 3 Stages • 1st Stage- Catarrhal Stage 1-2 weeks • 2nd Stage- Paroxysmal Stage 1-6 weeks • 3rd Stage- Convalescent Stage weeks-months http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf
Diagnosis • Isolation by culture • PCR • Direct fluorescent antibody • Serological testing Treatment • Antibiotic therapy • Erythromycin • Azithromycin and clarithromycin • Trimethoprim-sulfamethoxazole http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg
Pertussis Vaccine • 1st Pertussis vaccine- whole cell • Acellular vaccine now used • Combination vaccines http://www.tdh.state.tx.us/immunize/providers.htm http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html
Corynebacterium Species • General characteristics • Found as free-living saprophytes in fresh and salt water, in soil and in the air • Members of the usual flora of humans and animals(often dismissed as contaminants) • Often called “diphtheroids” • Corynebacterium diphtheriae isthe most significant pathogen • Other species may cause infections in the immunocompromised hosts
General Characteristics • Morphology • Gram-positive, non–spore-forming rods, Non-motile; noncapsulate • Arrange in palisades:“L-V” shape; “Chinese characters” • Pleomorphic: “club-ends” or coryneform • Beaded, irregular staining • Metachromatic granules (often near the poles) give the rod a beaded appearance. • Strains of this genus contain short mycolic acid in the cell wall. .
C. diphtheriae: Agent of Diphtheria • Toxigenic Corynebacterium diphtheriae • Worldwide distribution but rare in places where vaccination programs exist • Exotoxin, Diphtheria toxin, as the virulence factor • Not all C. diphtheriae strains produce toxin • Toxin is produced by certain strains • Toxin is antigenic
C. diphtheriae Pathogenesis and Immunity C. diphtheriae occurs in the respiratory tract, in wounds, or on the skin of infected persons or normal carriers. It is spread by droplets or skin contact. Portal of entry: respiratory tract or skin abrasions. Diphtheria bacilli colonize and grow on mucous membranes, and start to produce toxin, which is then absorbed into the mucous membranes, and even spread by the bloodstream. Local toxigenic effects: elicit inflammatory response and necrosis of the faucial mucosa cells-- formation of "pseudo-membrane“ (composed of bacteria, lymphocytes, plasma cells, fibrin, and dead cells), causing respiratory obstruction. Systemic toxigenic effects: necrosis in heart muscle, liver, kidneys and adrenals. Also produces neural damage.
ToxigenicCorynebacteriumdiphtheriae • Toxin consists of two fragments(heat labile) • A: Active fragment • Inhibits protein synthesis • Leads to cell/tissue death • B: Binding • Binds to specific cell membrane receptors • Mediates entry of fragment A into cytoplasm of host cell
Clinical Forms of Diphtheria Bull-neck appearance • Respiratory • Acquired by droplet spray or hand to mouth contact • Non-immunized individuals are susceptible • Non-respiratory • Systemic • Skin and cutaneous forms
Diphtheria Respiratory disease–diphtheria Incubation period–2 to 5 days Symptoms: sore throat, fever, malaise Toxin is produced locally, usually in the pharynx or tonsils Toxin causes tissue necrosis, can be absorbed to produce systemic effects Forms a tough, thick, adherent grey to white pseudo-membrane which may cause suffocation (WBC + RBCs +organism +fibrin +dead cells)
Treatment • Infected patients treated with anti-toxin and antibiotics • Anti-toxin produced in horses • Antibiotics have no effect on circulating toxin, but prevent spread of the toxin by bacteial killing • Penicillin drug of choice, erythromycin • Prevention: DPT immunization
Laboratory Diagnosis Microscopic morphology Gram-positive, non–spore-forming rods, club-shaped, can be beaded Appear in palisades and give "Chinese letter" arrangement Produce metachromatic granules or “Babes’ Ernst” bodies (food reserves) which stain more darkly than remainder of organism Corynebacterium diphtheriae gram stain
Laboratory Diagnosis:Cultural Characteristics Loeffler's slant used to demonstrate pleomorphism and metachromatic granules ("Babes’ Ernst bodies“) Growth on Serum Tellurite or modified Tinsdale exhibits brown or grayish→ to black halos around the colonies Blood agar plate, grey translucent colonies Small zone of b- hemolysis also seen Tellurite: tellurium dioxide (TeO2).
Laboratory Diagnosis Toxigenicity testing Elek test Immunodiffusion test Organisms are streaked on media with low Fe content to maximize toxin production. protease peptone agar + serum (horse or bovine) 1 and 4 positive