 General characteristic :

 - is gram-positive club-shaped rod (coryneform)

 often occuring in V and L shaped arrangements
 sometimes in clumps called “Chinese character”
 causes diphthria through upper respiratory
 colonization and elaboration of a potent exotoxin
Classification
3 morphological types of C. diphtheriae are found on
tellurite containing media:
△ Mitis ['maitɪs]– black colonies with a
gray periphery
△ Gravis – large, gray colonies
△ Intermedius – small, dull gray to black.
All produce an immunologically identical toxin

Mitis Gravis Intermedius

 Diphtheria exotoxin :
- is a potent A-B (two component) exotoxin
- the B component binding to specific cell membrane
receptor required to trigger uptake of the A-B
component by the cell
- component A is an enzyme (ADP ribosyl
transferase)
which ADP ribosylates elongation factor 2 (EF2)
inhibiting nascent peptide chain movement, thus
shutting down protein synthesis
- estimates suggest the enzymatic activity
of one molecule of toxin can effectively shut
down an entire cell
- is produced only in strain of C. diptheriae,
which are stably infected (lysogenized) by
beta-corynephage
- the DNA of the bacteriophage resides in the
bacterial cell (tox + cells) and directs synthesis
of the toxin
- toxin production occurs at low iron
concentration
- primary target cells of the toxin include upper
respiratory tract , heart and nerve cells
- in its inactivated form (toxoid), is a
component
of the diphtheria and tetanus toxoids and
pertussis (DPT) vaccine
- begins as mild pharyngitis with slight fever
and
chills
- spreads up to the nasopharynx or down to the
larynx and trachea
- the bacteria themselves do not disseminate
but elaborate the diphtheria exotoxin which
circulates(toxaemia) and causes additional
symptom such as hoarseness and stridor
- results in a firmly adherent, dirty gray,
spreading pseudomembrane, composed of
inflammatory necrosis, fibrin, epithelial cells,
neutrophils, monocytes and bacteria
- causes cervical adenitis and edema, which, in
severe cases, may produce the characteristic
“bull neck” appearance
- has the following complications :
- asphyxiation from the psudomembrane
- myocarditis and, occasionally, more severe
cardiotoxicity
- paralysis of the soft palate and more severe
neuropathies
- staining : gram, neisser
- culture on two special media :
- tellurite-containing medium; C. diphtheriae
imports and reduces tellurite,turning the
colony gray to black
- Loeffler coagulated serum medium;
C.diphtheriae produces many
metachromatically staining volutin granules
- requires demonstration of toxin production
which done with :
- agar diffusion Elek test (in vitro)
- in vivo test
- tissue culture cells test
- treatment is with antitoxin (ADS) and antibiotics
- prevention is by proper vaccination with toxoid
in DTP followed by Td (tetanus and diphtheria
toxoids) boosters.
- vaccination does not prevent colonization, but
has resulted in greatly reduced colonization
rates
right arm left arm

toxin heated-toxin
24-48 h 6d 24-48 h 6 d
+ + - - positive
- - - - negative
+ - + - pseudo-reaction
+ + + - combine-reaction
 Positive: when the test results in a wheal of 5–10 mm diameter,
reaching its peak in 4–7 days. The control arm shows no
reaction. This indicates that the subject lacks antibodies against
the toxin and hence is susceptible to the disease.
 Pseudo-positive: when there is only a red colored inflammation
(erythema) and it disappears within 4 days. This happens on
both the arms since the subject is immune but hypersensitive to
the toxin.
 Negative reaction: Indicates that the person is immune
 Combined reaction: Initial picture is like that of the pseudo-
reaction but the erythema fades off after 4 days only in the
control arm. It progresses on the test arm to a typical positive.
The subject is interpreted to be both susceptible and
hypersensitive