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 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)

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 Diphtheria Toxin (DT)

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’)

Largely controlled now 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 Epidemiology

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 Toxoid introduced 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

Elek immunodiffusion test.

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 Ab DT tumor tumors !!