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

AbDT

tumor

tumors !!