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Corynebacterium diphtheriae. Biological Features. Aerobic, Gram + , Noncapsulated, rods Gray-black colonies on tellurite 亚碲酸盐 medium Metachromatic granules. Chinese-letter morphology in Gram stain. Electron micrograph of corynebacteriophage ß, which carries tox. Transmission.
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Biological Features • Aerobic, Gram+, Noncapsulated, rods • Gray-black colonies on tellurite亚碲酸盐medium • Metachromatic granules
Electron micrograph of corynebacteriophage ß, which carries tox
Transmission • solely among humans • spread by droplets • secretions • direct contact
Risk factors • Poor nutrition • Crowded or unsanitary living conditions • Low vaccine coverage among infants and children • Immunity gaps in adults
Pathogenesis of diphtheria • Early stages:Sore throat. Low fever. Swollen neck glands. • Late stages:Airway obstruction and breathing difficulty. Shock
Diphtheria Toxin (DT) • Cleaved to yield A/B fragment, joined by S-S bond- A (catalytic domain) - B (transmembrane and receptor binding domains)
Diphtheria Toxin (DT) • Receptor - heparin-binding epidermal growth factor - rich on cardiac cells and nerve cells • Toxin diffuses throughout body via blood- Cardiac, neurologic complications - Heart/respiratory damage, paralysis
Schematic diagram of the diphtherial intoxication of a sensitive eukaryotic cell.
Thick grey ‘pseudomembrane’ composed of fibrin, epithelial cells, bacteria and polymorph neutrophils • Pseudomembrane may cause blockage, suffocation
The cervical lymph nodes enlarge causing oedema of the neck (a classical condition of ‘bullneck’)
Epidemiology • Largely controllednow by vaccination • However, factors such as poverty and other social factors have led to diphtheria being an endemic/epidemic in many regions of the world
Immunity • Immunization of animals with altered toxin, producing antitoxin, was first done in 1890, 1st used in humans in 1891 • Toxin-antitoxin introduced by Theobald Smith in 1909, used little • Toxoidintroduced in 1923, now widely used
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.
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
Control • Sanitary: Reduce carrier rate by use of vaccine. • Immunological: A vaccine (DPT) prepared from an alkaline formaldehyde inactivated toxin (i.e. toxoid) is required. Passive immunization with antitoxin can be used for patients. • Chemotherapeutic: Penicillin, erythromycin or gentamicin are drugs of choice.
Prospect For therapy of tumors !! tumor Ab DT