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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 - PowerPoint PPT Presentation
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Dr Amin AqelRespiratory system
Respiratory Bacterial Infections
In lower respiratory system usually no permanent residents are present
Bordetella pertussis Basics
Aerobic, small, Gram negative encapsulated coccobacillus
Specific to HumansColonizes 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
TransmissionVery ContagiousTransmission occurs via respiratory dropletsOutbreaks first described in the 16th CenturyMajor cause of childhood fatality prior to
vaccination
http://www.ratbags.com/rsoles/history/2000/12december.htmhttp://www.universityscience.ie/imgs/scientists/whoopingcough.gif
Virulence
Steele, R.W. Pertussis: Is Eradication Achievable. Pediatric Annals. Aug 2004. 33(8):525-534
AdhesionsFilamentous hemagglutininPertactinFimbriae
http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpghttp://www.my-pharm.ac.jp/~yishibas/research/Pertussis1.jpg
ToxinsPertussis Toxin: Colonizing factor and
endotoxinAdenylate Cyclase Toxin: Invasive toxin,
Impairment of immune effector cellsTracheal cytotoxin: inhibits cilia
movementDermonecrotic toxin: vasoconstriction and
ischemic necrosis
www.ibl.fr/u447/u447.htm
Pertussis Pathogenesis
Primarily a toxin-mediated diseaseBacteria attach to cilia of respiratory
epithelial cellsproduce toxins that paralyze the cilia, and
cause inflammation of the respiratory tractInflammation will interferes with clearance of
pulmonary secretionsPertussis antigens allow evasion of host
defenses (lymphocytosis promoted but impaired chemotaxis)
Pertussis Infection and Clinical Features
Incubation period 4-21 days3 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
DiagnosisIsolation by culturePCRDirect fluorescent antibodySerological testing
TreatmentAntibiotic therapy
ErythromycinAzithromycin and clarithromycinTrimethoprim-sulfamethoxazole
http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg
Pertussis Vaccine1st Pertussis vaccine- whole cellAcellular vaccine now usedCombination vaccines
http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html
http://www.tdh.state.tx.us/immunize/providers.htm
Corynebacterium SpeciesGeneral 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 is the most significant
pathogenOther species may cause infections in the
immunocompromised hosts
General CharacteristicsMorphology
Gram-positive, non–spore-forming rods, Non-motile; noncapsulate
Arrange in palisades:“L-V” shape; “Chinese characters”
Pleomorphic: “club-ends” or coryneform
Beaded, irregular stainingMetachromatic 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 diphtheriaeWorldwide distribution but rare in places where
vaccination programs exist
Exotoxin, Diphtheria toxin, as the virulence factorNot all C. diphtheriae strains produce toxinToxin is produced by certain strainsToxin 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.
Toxigenic Corynebacterium diphtheriae
Toxin consists of two fragments (heat labile)A: Active fragment
Inhibits protein synthesis Leads to cell/tissue death
B: BindingBinds to specific cell membrane receptorsMediates entry of fragment A into cytoplasm of host
cell
Clinical Forms of Diphtheria
RespiratoryRespiratoryAcquired by droplet spray
or hand to mouth contactNon-immunized
individuals are susceptible
Non-respiratoryNon-respiratorySystemicSkin and cutaneous forms
Bull-neck appearance
Diphtheria
Respiratory disease–diphtheriaIncubation 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 antibioticsAnti-toxin produced in horsesAntibiotics have no effect on circulating toxin, but
prevent spread of the toxin by bacteial killingPenicillin drug of choice, erythromycin
Prevention: DPT immunization
Laboratory Diagnosis
Microscopic morphologyGram-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 seenTellurite: tellurium dioxide (TeO2).
Laboratory Diagnosis
Toxigenicity testingElek 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
Streptococcus pyogenes in chains
Bacillus anthracis
TB/ Löwenstein–Jensen medium
Pseudomonas/ Pigments in Nutrient Agar