Diphtheria

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    • Corynebacteria
      • small, slender, pleomorphic, gram-positive rods of distinctive morphology
      • stain unevenly
      • non- motile and unencapsulated
      • they do not form spores. (MCQ)
      • Most species are facultative anaerobes . (MCQ)
      • grow aerobically on standard laboratory media such as blood agar.
      • Corynebacterium diphtheriae
        • found in the throat and nasopharynx of carriers
        • organism is primaiily spread by respiratory droplets
      • exotoxin
        • inhibits eukaryotic protein synthesis. . (MCQ)
        • a heat-labile polypeptide that is composed of two fragments, A and B.
        • Fragment B
          • binds to susceptible cell membranes
          • mediates the delivery of fragment A to its target . (MCQ)
        • fragment A
          • catalyzes a reaction between NAD+  and the eukaryotic polypeptide chain elongation factor, EF-21 . (MCQ)
        • toxin is encoded on a b-corynephage . (MCQ)
          • only those strains in which the phage is integrated into the C. diphtheriae chromosome produce toxin.
        • Toxin gene expression is also regulated by environmental conditions . (MCQ)
          • Low iron conditions induce toxin expression
          • high iron condtions repress toxin production.
      • Clinical significance
        • Upper respiratory tract infection
          • Pseudomembrane . (MCQ)
            • produces a distinctive thick, grayish, adherent exudate (pseudomem- brane)
            • composed of cell debris from the mucosa and inflammatory products
            • It coats the throat and may extend into the nasal passages or downward in the respiratory tract
            • the exudate sometimes obstructs the airways, even leading to suffocation.
          • major clinical effects involve the heart and peripheral nerves
            • Cardiac conduction defects and myocarditis may lead to congestive heart failure and permanent heart damage . (MCQ)
            • Neuritis of cranial nerves and paralysis of muscle groups, such as those that control move- ment of the palate or the eye, are seen late in the disease. . (MCQ)
        • Cutaneous diphtheria
          • A puncture wound or cut in the skin can result in introduction of C. diphtheriae into the subcutaneous tissue
          • lead to a chronic, nonhealing ulcer with a gray membrane
        • Immunity:
          • Diphtheria toxin is antigenic and stimulates the production of antibodies that neutralize the toxin’s activity
          • Formalin treatment of the toxin produces a toxoid that retains the antigenic-ity but not the toxicity of the molecule . (MCQ)
          • Toxoid is used for immunization against the disease
        • Laboratory identification
          • definitive diagnosis requires isolation of the organism
          • organism  is tested for virulence using an immunologic precipitin reaction to demonstrate toxin production.
          • Tinsdale agar. (MCQ)
            • C. diphtheriae can be isolated most easily from this selective medium
            • contains potassium tellurite, an inhibitor of other respiratory flora . (MCQ)
            • organism produces several distinctive black colonies with halos . (MCQ)
          • C. diphtheriae distinctive morphology when stained with methylene blue. . (MCQ)
            •  has characteristic bands and reddish (polychromatic) granules . (MCQ)
            • Granules are seen in thin, sometimes club-shaped rods that appear in clumps, sugges- tive of Chinese characters or picket fences . (MCQ)
            • This presentation is often referred to as a “palisade arrangement” of cells. . (MCQ)
        • Treatment:
          • requires prompt neutralization of toxin, followed by eradication of the organism.
          • A single dose of horse serum antitoxin . (MCQ)
            • inactivates any circulating toxin
            • it does not affect toxin already bound to a cell-surface receptor.
            • Serum sickness caused by a reaction to the horse protein may cause complications in approximately 10 percent of patients
          • Antibiotic treatment includes erythromycin or penicillin . (MCQ)


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