Diphtheria (page 2)
This chapter has 4 pages
© Kenneth Todar, PhD
Human Disease
CDC describes diphtheria as an upper respiratory tract illness
characterized
by sore throat, low-grade fever, and an adherent membrane of the
tonsil(s),
pharynx, and/or nose. Diphtheria is a rapidly developing, acute,
febrile
infection which involves both local and systemic pathology. A local
lesion
develops in the upper respiratory tract and involves necrotic injury to
epithelial cells. As a result of this injury, blood plasma leaks into
the
area and a fibrin network forms which is interlaced with with
rapidly-growing
C.
diphtheriae cells. This membranous network, called a pseudomembrane,
covers over the site of
the local lesion leading to respiratory distress, even suffocation.

Figure
3. Diphtheria pseudomembrane. CDC.
The diphtheria bacilli do not tend to invade tissues below or away
from
the surface epithelial cells at the site of the local lesion. However,
at this
site
they produce the toxin that is absorbed and disseminated through lymph
channels and blood to the susceptible tissues of the body. Degenerative
changes in these tissues, which include heart, muscle, peripheral
nerves,
adrenals, kidneys, liver and spleen, result in the systemic pathology
of
the disease.
Pathogenicity
The pathogenicity of Corynebacterium diphtheriae includes two
distinct phenomena:
1. Invasion of the local tissues of the throat, which
requires
colonization and subsequent bacterial proliferation. Little is known
about
the adherence mechanisms of C. diphtheriae, but the bacteria
produce several types of pili. The diphtheria toxin, as well, may be
involved in colonization of the throat.
2. Toxigenesis: bacterial production of the toxin. The
diphtheria
toxin causes the death eucaryotic cells and tissues by inhibition
protein
synthesis in the cells. Although the toxin is responsible for the
lethal
symptoms of the disease, the virulence of C. diphtheriae cannot
be attributed to toxigenicity alone, since a distinct invasive phase
apparently
precedes toxigenesis. However, it has not been ruled out that the
diphtheria
toxin plays an essential role in the colonization process due to
short-range
effects at the colonization site.
Three strains of Corynebacterium
diphtheriae are recognized,
gravis,
intermedius
and mitis. They are listed here by falling order of the
severity
of the disease that they produce in humans. All strains produce the
identical
toxin and are capable of colonizing the throat. The differences in
virulence
between the three strains can be explained by their differing abilities
to produce the toxin in rate and quantity, and by their differing
growth
rates.
The gravis strain has a generation time (in vitro) of 60 minutes;
the
intermedius strain has a generation time of about 100 minutes; and the
mitis stain has a generation time of about 180 minutes. The faster
growing
strains typically produce a larger colony on most growth media. In the
throat (in vivo), a faster growth rate may allow the organism to
deplete
the local iron supply more rapidly in the invaded tissues, thereby
allowing
earlier or greater production of the diphtheria toxin. Also, if the
kinetics
of toxin production follow the kinetics of bacterial growth, the faster
growing variety would achieve an effective level of toxin before the
slow
growing varieties.

Figure
4. Corynebacterium diphtheriae
colonies on blood
agar. CDC.
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