Diphtheria

dr. Tjatur Winarsanto SpPD

2011

Definition
Diphtheria is an acute, toxinmediated disease caused by
toxigenic Corynebacterium
diphtheriae .
Its a very contagious and
potentially life-threatening
bacterial disease.

Definition
Its a localized infectious disease,
which usually attacks the throat
and nose mucous membrane

Definition
Common symptoms: malaise, sore
throat, anorexia, and low-grade
fever.
Typical sign:
formation

specific

membrane

In serious cases, it can attack the

heart and nerves.

Etiology
Diphtheria
is
caused
by
Corynebacterium
diphtheriae,
a
bacterium, a bacillus.
C. diphtheriae is an aerobic grampositive bacillus.
Pleomorphic, club-end
Non-spore-forming
Non-acid-fast
Non-motile
5

Etiology
The major virulence determinant is
an exotoxin, diphtheria toxin. After
binding to the host cells, the active
subunit will interrupt the protein
synthesis of the target host cell
and results in cell death.
Toxoid made from diphtheria toxin
can be used as vaccine.

Etiology
The bacteria can be killed by mild
heating(58 for 10 minutes) and
sensitive to UV or sunlight.
Resistance to damage from drying,
be cultured from the floor dust for
5 weeks or longer, once the floor
dust was contaminated.

Epidemiology
Sources of infection
Patients
and
asymptomatic
carriers
Patients:
Transmission time is
variable, usually persist 12 days
or less, and seldom more than 4
weeks, without antibiotics.

Epidemiology
Sources of infection
Asymptomatic
carriers
(even
important): 1% in population, but
may be up to 10-20% during
outbreaks in the past. Most of
them were transient carriers (less
than 2 weeks), but chronic
carriers may shed organisms for
6 months or more.
9

Epidemiology
Transmission
Transmission
is
most
often
person-to-person spread from the
respiratory tract (by small droplet
when coughing or sneezing).
Rarely,
transmission may occur
from skin lesions or articles soiled
with discharges from lesions of
infected persons.
10

Pathogenesis and
pathology
Susceptible persons may acquire
toxigenic diphtheria bacilli in the
nasopharynx, skin, middle ear or
anterior nares.

11

Pathogenesis and
pathology
The organism produces a toxin that
inhibits cellular protein synthesis
and is responsible for local tissue
destruction and pseudomembrane
formation.

12

Pathogenesis and
pathology
The pseudomembrane consists of
coagulated
fibrin,
inflammatory
cells, destructed mucous tissues
and bacteria.
The pseudomembrane in larynx,
trachea or bronchia may have the
potential for airway obstruction.

13

Pathogenesis and
pathology
The toxin produced at the site of the
pseudomembrane is absorbed into
the
bloodstream
and
then
distributed to the tissues of the body.
The toxin is responsible for the major
complications of myocarditis and
neuritis, and can also cause low
platelet counts (thrombocytopenia)
and protein in the urine (proteinuria).
14

Clinical manifestations
The incubation period of diphtheria is
2-4 days (range, 1-7 days).
This disease can involve almost any
mucous membrane.
The major sign is pseudomembrane.
The
typical
pseudomembrane
is
adherent to the tissue, and forcible
attempts to remove it cause bleeding.
Pseudomembrane.
15

Clinical manifestations
For
clinical
purposes,
it
is
convenient to classify diphtheria
into four categories depending on
the
site
of
disease
(or
pseudomembrane).

16

Pharyngeal diphtheria
Its the most common type, >80%.
The sites of infection
tonsils and the pharynx.

are

the

Infection at these sites is usually

associated
with
substantial
systemic absorption of toxin.

17

Pharyngeal diphtheria
Mild type
Symptoms: malaise, sore throat,
anorexia, and low-grade fever.

Within 2-3 days, small patches of

white pseudomembrane on the
tonsils are found.

Often occurs in outbreaks and is

easily misdiagnosed.
18

Pharyngeal diphtheria
Ordinary type
Symptoms: malaise, sore throat,
anorexia, vomiting and middlegrade fever.
Typical
adherent,
bluishor
greyish-white
pseudomembrane
forms on the congested tonsils.
With lymph nodes enlargement in
the submandibular areas of neck.
19

Pharyngeal diphtheria
Grave type
Serious
early symptoms, highgrade fever.
Skin becomes pale, tachycardia,
blood pressure may be normal or
slightly depressed (Shock).

20

Pharyngeal diphtheria
Grave type
Large,
thick pseudomembrane,
and greyish-green or black in
color if there has been bleeding,
covering the tonsils, uvula, and
some soft palate, odoriferous in
mouth.
With enlarged lymph nodes in the
submandibular areas of neck.
21

Pharyngeal diphtheria
Extra-grave type
Tachycardia, tachypnea, depressed
blood pressure. Highly congested
tonsils and pharynx.
The
pseudomembrane is larger
than that of grave type, black in
color.
Extensive
pseudomembrane
formation may result in respiratory
obstruction.
22

Pharyngeal diphtheria
Extra-grave type
Patients develop marked edema of
the submandibular areas and the
anterior
neck
along
with
lymphadenopathy,
giving
a
characteristic bullneck appearance.
Complications,
include myocarditis
and thrombocytopenia may occur.
May even die within 6 to 10 days.

23

Laryngeal diphtheria
Laryngeal diphtheria can be either
an extension of the pharyngeal form
(often) or the only site involved
(rarely).
Symptoms include mild fever (with
little absorption of toxin), dyspnea,
hoarseness, and a barking cough.
The pseudomembrane can lead to
airway obstruction, coma, and death.
24

Anterior nasal diphtheria

The onset is indistinguishable from
that of the common cold and is
usually
characterized
by
a
mucopurulent
nasal
discharge
(containing both mucus and pus)
which may become blood-tinged.
A white pseudomembrane usually
forms on the nasal septum.

25

Anterior nasal diphtheria

The clinical symptoms of this
disease is usually fairly mild
because of apparent poor systemic
absorption of toxin in this location,
and can be terminated rapidly by
antitoxin and antibiotic therapy.

26

Cutaneous and Other site

diphtheria
Skin infections are quite common in
the tropics and are probably
responsible for the high levels of
natural immunity found in these
populations.

27

Cutaneous and Other site

diphtheria
Skin infections may be manifested
by a scaling rash or by ulcers with
clearly demarcated edges and
pseudomembrane.
In general, the severity of the skin
disease appears to be less than in
other forms of infection.

28

Cutaneous and Other site

diphtheria
Other sites of involvement include
the mucous membranes of the
conjunctiva and vaginal area, as
well as the external auditory canal.

29

Laboratory findings
Routine examination

Leukocytosis,
10~20
G/L,
neutrophil is dominant.
Low
platelet
count
(thrombocytopenia), rise profiles
of the serum enzyme tests and
proteinuria were found in serious
cases.
30

Laboratory findings
Bacteriological examinations
Smear
and gram stain can found C.
diphtheriae, but can not identify from
the diphtheroids.
Fluorescent
antibody-stain can found
toxigenic C. diphtheriae, favourable for
early diagnosis, but definitive diagnosis
(false positive).
C. diphtheriae can be cultured from the
swabs from nose, pharynx or other sites.

31

Laboratory findings
Immunological examinations

Schick test (not to be used any

more), positive result supports
diagnosis
Specific
antibody
detection.
Positive
results
deny
the
diagnosis since it is a protective
antibody.
32

Complications
Most complications of diphtheria,
including death, are attributable to
effects of the toxin.
The severity of the disease and
complications are generally related
to the extent of local disease.
The most frequent complications of
diphtheria are myocarditis and
neuritis.
33

Complications
Myocarditis

Present
as
abnormal
cardiac
rhythms and can occur early in
the course of the illness or weeks
later, and can lead to heart failure
and abrupt deterioration (sudden
death).
If myocarditis occurs early, it is
often fatal.
34

Complications
Neuritis

Most neuritis often affect motor

nerves and usually recovers
completely.
Paralysis of the soft palate is
most frequent during the third
week of illness.

35

Complications
Neuritis

Eye muscles, limbs, and

diaphragm paralysis can occur
after the fifth week.
Secondary pneumonia and
respiratory failure may result
from diaphragmatic paralysis.

36

Diagnosis
Clinical diagnosis is usually made based on the
epidemiological data and clinical presentation
since it is imperative to begin presumptive
therapy quickly.
Gram
stain
of
material
from
the
pseudomembrane can be helpful when trying
to confirm the clinical diagnosis.
Culture of the lesion is even important to
confirm the clinical diagnosis. It is critical to
take a swab of the pharyngeal area, especially
any discolored areas, ulcerations, and tonsillar
crypts.

37

Diagnosis
If diphtheria bacilli are isolated,
they must be tested for toxin
production by ELISA or Elek test.
If toxin test is positive, the
definitive diagnosis can be made.
The presence of staphylococci and
streptococci
do
not
rule
out
diphtheria.

38

Differential diagnosis
Streptococcal pharyngitis
The pus covering on the tonsils
sometimes is misunderstood as
the
pseudomembrane
of
diphtheria. Its usually yellow in
color, and easy to remove.

39

Differential diagnosis
Oral candidiasis
The oral candidiasis often occurs
in infants. The general conditions
of such patients are very well.
The membrane is very white, and
easy to remove

40

Differential diagnosis
Infectious
mononucleosis
and
Vincents angina
Sometimes also have things like
membranes on the surface of
tonsils or pharynx. However, they
can be remove without bleeding
of the tissues.

41

Prognosis
The overall case-fatality rate for
diphtheria is about 5%, with higher
death rates (up to 20%) in persons
<5 and >40 years of age.

42

Treatments
Strict isolation
Use antitoxin and antibiotics for
neutralization
of
free
toxin,
elimination
of
further
toxin
production and to control local
infection.
Use
supportive
interventions
during disintoxication.

43

Treatments
General measures
Relax on bed for more than 3
weeks, 4-6 weeks for patients
with myocarditis.
Provide
adequate energy and
nutriments

44

Treatments
Diphtheria antitoxin

Diphtheria antitoxin, produced in

horses.
It will not neutralize toxin that is
already fixed to tissues, but will
neutralize circulating toxin.
Early
use
will
prevent
progression of disease.
The earlier, the better.
45

Treatments
Diphtheria antitoxin
Dose: 3-5104 U for early (<3-4d)
and mild or ordinary patients; 610 104 U for later (>3-4d) or
grave patients; reduce in larynx
diphtheria
1-2104 U is given intravenously
and
the
rest
is
given
intramuscularly.
46

Treatments
Diphtheria antitoxin
The patient must be tested for
sensitivity before antitoxin is
given.
Respiratory
support and airway
maintenance
should
also
be
administered
as
needed.
(Pseudomembrane shedding often
happens during disintoxication)
47

Treatments
Antibiotics
Prevention
of
further
production.
Control local infection.
Reduction of transmission.

toxin

48

Treatments
Antibiotics
Procaine
penicillin
G
daily,
intramuscularly (300,000 U/day for those
weighing 10 kg or less and 600,000 U/day
for those weighing more than 10 kg) for
7-10 days.
Erythromycin orally or by injection (40-50
mg/kg/day; maximum, 2 gm/day) for 14
days.
The disease is usually not contagious 48
hours after antibiotics are used.
49

Preventions
Management of infection sources
Isolation
of patients (>7d), or
elimination
of
the
organism
should be documented by two
consecutive
negative
cultures
after therapy is completed.

50

Preventions
Management of infection sources
Persons
with
suspected
diphtheria
should
be
given
antibiotics
and
antitoxin
in
adequate dosage and placed in
isolation
(7d)
after
the
provisional clinical diagnosis is
made and appropriate cultures
are obtained.
51

Preventions
Management of infection sources
For
close contacts, especially
household contacts, a diphtheria
booster, appropriate for age,
should be given. Antitoxin 10002000 U, intramuscularly

52

Preventions
Management of infection sources
Contacts
should also receive
antibioticsbenzathine penicillin
G or a 7- to 10-day course of oral
erythromycin.
Interruption of the transmission
routes
by
disinfections
of
discharges
and
articles
of
patients
53

Preventions
Protect
the
susceptibles
by
vaccination
The effective measure
Primary
series (DTP, multivalent
vaccine) given at age of 3, 5, 6
months.
Boosters (DTP) given at 15 months
and 4-6 years old, and booster
(DT) every 10 years after then.
54

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56

Pharyngeal diphtheria

57

Pharyngeal diphtheria

58

Pharyngeal diphtheria

59

Pharyngeal diphtheria

60

Pharyngeal diphtheria

61

Laryngeal diphtheria

62

Cutaneous (skin)
diphtheria

63