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Corynaebacterium Diphtheriae

Corynaebacterium Diphtheriae. Dr. Qurat-Ul-Ain Senior Demonstrator Microbiology, KEMU, Lahore. Corynebacterium diphtheriae. Introduction. Klebs--1883 discovered Loefflers--1884 cultured Also known as KLB Emil von Behring- 1890 produced antitoxin Awarded nobel prize.

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Corynaebacterium Diphtheriae

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  1. Corynaebacterium Diphtheriae Dr. Qurat-Ul-Ain Senior Demonstrator Microbiology, KEMU, Lahore

  2. Corynebacteriumdiphtheriae

  3. Introduction • Klebs--1883 discovered • Loefflers--1884 cultured • Also known as KLB • Emil von Behring- 1890 produced antitoxin • Awarded nobel prize Emil Von Behring

  4. Morphology • Gram positive bacilli. 3-6 μ x 0.5-0.8 μ. • v or k or L shape. • Chinese letter pattern, angular arrangement, palisade arrangement • Metachromatic granules. volutin granules, polymetaphosphate energy storage depots • Alberts stain – green and bluish black • Nonmotile noncapsulated, nonsporing • pleomorphic

  5. Corynebacterium Biotypes • C diphtheriaegravis • C diphtheriaeintermedius • C diphtheriaemitis • Helpful for epidemiological tracing • Culture identified by biochemical tests.

  6. Transmission and Risk factors • solely among humans • spread by droplets • secretions • direct contact • Poor nutrition • Crowded or unsanitary living conditions • Low vaccine coverage among infants and children • Immunity gaps in adults

  7. Virulence Factors 1. Diphtheria toxin !!! • blocks protein synthesis 2. Dermonecrotic toxin • sphingomyelinase • increases vascular permeability 3. Hemolysin 4. Cord factor -Toxic trehalose • corynemycolic acid, corynemyolenic acid

  8. Pathogenesis • Part A • Active site • N terminal • Enzyme • Part B • Binding site • Binds to membrane receptor • Bound receptor internalized • Endosome • Hydrolysed by protease • Disulfide broken • Part A released

  9. Clinical Features/ Types of Diphtheria • Incubation period 2-5 days (range, 1-10 days) • May involve any mucous membrane • Classified based on site of infection

  10. Pharyngeal and Tonsillar Diphtheria • Insidious onset • Exudate spreads within 2-3 days and may form adherent membrane • Membrane may cause respiratory obstruction • Pseudomembrane: fibrin, bacteria, and inflammatory cells, no lipid • Fever usually not high but patient appears toxic

  11. Clinical classification i) Malignant (hypertoxic) diphtheria Signs: severe toxemia and adenitis, lymph glands swelling in the neck Complications: death-circulatory failure, paralytic sequelae ii) Septic diphtheria:Signs: ulceration with pseudomembrane formation and cellulites (gangrene around pm) iii) Hemorrhagic diphtheriaSigns: local and general bleeding from edge of psudomembrane, conjunctival, epistaxis and purpura

  12. COVERS tonsils, uvula, palate nasopharynx larynx. Pseudomembrane • CONTAINS • bacteria • lymphocytes • plasma cells • fibrin • dead cells

  13. Cutaneous Diphtheria

  14. Systemic complications • Nerves • toxic peripheral neuropathy • paralysis of short nerves • mouth, eye, facial extremities • Cardiac • Congestive heart failure • high amount of toxin 48-72 hours • Low amount of toxin 2-6 weeks

  15. Diphtheria Antitoxin • Produced in horses • First used in the U.S. in 1891 • Used only for treatment of diphtheria • Neutralizes only unbound toxin • Lifetime of Ab: 15 days – 3 weeks, wait 3-4 weeks before giving toxoid. Only given once.

  16. Diphtheria Toxoid • Formalin-inactivated diphtheria toxin • Schedule Three or four doses + booster Booster every 10 years • Efficacy Approximately 95% • Duration Approximately 10 years • Should be administered with tetanus toxoid as DTaP, DT, Td, or Tdap

  17. Schedule i) primary immunization – - infants and children - 3 doses, 4-6 weeks - 4th dose after a year - booster at school entry ii) Booster immunization - adults - Td toxoids used (traveling adults may need more) Shick test-to test sensitivity (allergic reaction)

  18. Diphtheria and Tetanus ToxoidsAdverse Reactions • Local reactions (erythema, induration) • Exaggerated local reactions (Arthus-type) • Fever and systemic symptoms not common • Severe systemic reactions rare

  19. Schick test • Be used to ascertain population risk This test involves the injection of a minute amount of the diphtheria toxin under the skin. The absence of a reaction indicates immunity.

  20. Control • Immunization diphtheria toxoid • Schick test • check for antibodies • Passive immunity • Antibodies • Antibiotics • Penicillin & erythromcyin

  21. DIAGNOSIS • Clinical: Muscle weakness, edema and a pseudomembranous material in the upper respiratory tract characterizes diphtheria. • Laboratory: Tellurite media is the agar of choice for isolation of Corynebacteria, which produce jet black colonies

  22. DiphtheriaLaboratory diagnosis • Rapid diagnosis required • Differentiate from commensals • “diphteroids” • nose & throat • Throat swabs (confirmatory) • Blood Tellurite

  23. Specialized media Tellurite: black colonies Not diagnosticallly significant .tellurite inhibits many organisms but not C. diphtheriae Loeffler serum: best colonial morphology Dextrose horse serum (1887) now Dextrose beef serum

  24. Blood tellurite • Selective & differential medium • Corynebacteria are resistant to tellurite • Reduced to tellurium • Forms deposit in colonies • Colonies appear dark

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