Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Diphtheria causes a thick covering in the back of the throat. It can lead to difficulty breathing, heart failure, paralysis, and even death. CDC recommends vaccines for infants, children, teens and adults to prevent diphtheria. The presentation consists of basic concepts regarding the bacteria and its infection. It has explanation in detail about signs and symptoms of Diptheria

1. Corynebacterium
diphtheriae
A paradigm of the toxigenic
infectious diseases
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2. Edwin Klebs
In 1883, Klebs demonstrated that
Corynebacterium diphtheriae was the
agent of diphtheria

3. Introduction
By 1888, Roux and Yersin showed that animals injected with sterile filtrates
of C diphtheriae developed symptoms similar to that of human diphtheria;
this demonstrated that a potent exotoxin was the major virulence factor.
Alexandre Yersin Pierre Paul Émile Roux

4. General Characters
• It is also known as the Klebs-Löffler bacillus
• Gram-positive, highly pleomorphic organisms with no particular arrangement
• Special stains like Albert’s stain and Ponder's stain are used to demonstrate the
metachromatic granules formed in the polar regions

5. General Characters
• It is also known as the Klebs-Löffler bacillus
• Gram-positive, highly pleomorphic organisms with no particular arrangement
• Special stains like Albert’s stain and Ponder's stain are used to demonstrate the
metachromatic granules formed in the polar regions

6. General Characters
• Corynebacterium diphtheriae is a nonmotile, noncapsulated, club-shaped, gram-positive
bacillus
• Toxigenic strains are lysogenic for one of a family of corynebacteriophages that carry the
structural gene for diphtheria toxin, tox
• Corynebacterium diphtheriae is classified into biotypes (mitis, intermedius, and gravis)
according to colony morphology on tellurite containing media, as well as into lysotypes
based upon corynebacteriophage sensitivity

7. Classification
• Long Rods
• curved shaped
• pleomorphic
• Prominent granules
• greyish black, opaque
colonies
• Glycogen and starch
fermentation
• Paralytic and epidemic
• Short Rods
• Uniform Staining
• Few or no granules
• May be pleomorphic
• gray colony, dark center
shining
• Non-hemolytic
• Hemorrhagic and epidemic
• Long-barred forms,
clubbed end
• Poor Granulation
• Very pleomorphic
• gray, opaque glossy,
smooth surface, poached
egg colonies,
• Obstructive and Endemic

8. DIphtheria
• Diphtheria is most commonly an infection of the
upper respiratory tract and causes
• Fever
• sore throat
• malaise
• A thick, gray-green fibrin membrane, the
pseudomembrane, often forms over the site(s) of
infection as a result of the combined effects of
• bacterial growth
• toxin production
• necrosis of underlying tissue
• host immune response

9. Diseases
• Symptoms of pharyngeal diphtheria vary
from mild pharyngitis to hypoxia due to
airway obstruction by the pseudomembrane
• The involvement of cervical lymph nodes may
cause swelling of the neck (bull neck
diphtheria), and the patient may have a fever
(≥ 103 °F)
• The skin lesions in cutaneous diphtheria are
usually covered by a gray-brown
pseudomembrane
• Life-threatening systemic complications,
principally loss of motor function (e.g.,
difficulty in swallowing) and congestive heart
failure, may develop as a result of the action
of diphtheria toxin on peripheral motor
neurons and the myocardium.
There are two types of clinical diphtheria: nasopharyngeal and cutaneous.

10. Pathogenesis
The pathogenesis of diphtheria is based upon two primary determinants:
1. the ability of a given strain of C diphtheriae to colonize in the nasopharyngeal cavity and/or
on the skin
2. its ability to produce diphtheria toxin

11. Pathogenesis
• The structural gene for diphtheria toxin, tox, is
carried by a family of closely related
corynebacteriophages
• The regulation of diphtheria tox expression is
mediated by an iron-activated repressor, DtxR,
which is encoded on the C diphtheriae genome
• When iron become the growth limiting
diphtheria toxin is synthesized and secreted at
maximal rates

12. Pathogenesis
• Diphtheria toxin is extraordinarily potent: as little as 100 to 150 ng/kg of body weight is
lethal
• Diphtheria toxin is composed of a single polypeptide chain of 535 amino acids
• Intoxication of a single eukaryotic cell by diphtheria toxin can lead to complete irreversible
inhibition of protein synthesis (by binding to elongation factor – 2, EF-2)

13. Diagnosis
• laboratory confirmation of toxigenic C diphtheriae in throat or lesion cultures
• Sterile cotton-tipped applicators are used to swab the pharyngeal tonsils or their beds.
• Swabs may be inserted through both nares to collect nasopharyngeal samples for culture. Since
diphtheritic lesions are often covered with a pseudomembrane, the surface of the lesion may
have to be carefully exposed before swabbing
• The most common in vitro assay for toxigenicity is the Elek immunodiffusion test
• This test is based on the double diffusion of diphtheria toxin and antitoxin in an agar medium.
• A sterile, antitoxin-saturated filter paper strip is embedded in the culture medium, and C
diphtheriae isolates are streak-inoculated at a 90° angle to the filter paper
• The production of diphtheria toxin can be detected within 18 to 48 hours by the formation of a
toxin-antitoxin precipitin band in the agar

14. Elek immunodiffusion test
• Sterile filter paper impregnated with diphtheria antitoxin is imbedded in agar culture
medium. Isolates of C diphtheriae are then streaked across the plate at an angle of 90° to
the antitoxin strip. Toxigenic C diphtheriae is detected because secreted toxin diffuses from
the area of growth and reacts with antitoxin to form lines of precipitin.

15. Signs and symptoms
• The symptoms of diphtheria usually begin two to seven days after infection
• fever of 38 °C (100.4 °F) or above, chills, fatigue, bluish skin coloration (cyanosis), sore
throat, hoarseness, cough, headache, difficulty swallowing, painful swallowing, difficulty
breathing, rapid breathing, foul-smelling and bloodstained nasal discharge, and
lymphadenopathy
• Within two to three days, diphtheria may destroy healthy tissues in the respiratory system
• Dead tissue forms a thick, gray coating that can build up in the throat or nose. This thick
gray coating is called a “pseudomembrane.”
• It can cover tissues in the nose, tonsils, voice box, and throat, making it very hard to
breathe and swallow.
• Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral
nerve palsies

16. Signs and symptoms
An adherent, dense,
grey
pseudomembrane
covering the tonsils is
classically seen in
diphtheria.
A diphtheria skin lesion
on the leg
Diphtheria can cause a
swollen neck, sometimes
referred to as a bull neck

17. Control
• The control of diphtheria depends upon adequate immunization with diphtheria toxoid:
ormaldehyde-inactivated diphtheria toxin that remains antigenically intact
• Immunization against diphtheria should begin in the second month of life with a series of
three primary doses spaced 4 to 8 weeks apart, followed by a fourth dose approximately 1
year after the last primary inoculation
• Diphtheria toxoid is widely used as a component in the DPT (diphtheria, pertussis, tetanus)
vaccine.
• Diphtheria vaccine is usually combined at least with tetanus vaccine (Td) and often with
pertussis (DTP, DTaP, TdaP) vaccines, as well.
• The adult population should be reimmunized with diphtheria toxoid every 10 years

18. Control
• Although antibiotics (e.g., penicillin and erythromycin) are used as part of the treatment of
patients who present with diphtheria, prompt passive immunization with diphtherial
antitoxin is most effective in reducing the fatality rate
• The long half-life of specific antitoxin in the circulation is an important factor in ensuring
effective neutralization of diphtheria toxin; however, to be effective, the antitoxin must
react with the toxin before it becomes internalized into the cell.
• Metronidazole, Erythromycin, Procaine penicillin G, rifampin or clindamycin
• diphtheria toxin spreads through the blood and can lead to potentially life-threatening
complications that affect other organs, such as the heart and kidneys. Damage to the heart
caused by the toxin affects the heart's ability to pump blood or the kidneys' ability to
clear wastes. It can also cause nerve damage, eventually leading to paralysis.

19. Immunization coverage

20. How did they make diphtheria antitoxin?