Download Pharyngeal diphtheria

Diphtheria (白喉)
Peng Xiaomou (彭晓谋)
The Third Affiliated Hospital
1
Definition
Diphtheria is an acute, toxin-mediated
disease caused by toxigenic
Corynebacterium diphtheriae (白喉棒状
杆菌).
It’s a very contagious and potentially
life-threatening bacterial disease.
2
Definition
It’s a localized infectious disease, which
usually attacks the throat and nose
mucous membrane
3
Definition
Common symptoms: malaise, sore
throat, anorexia, and low-grade fever.
Typical sign: specific membrane
formation (pseudomembrane,伪膜, in
Greek diphthera, meaning leather, as
tough as leather)
In serious cases, it can attack the heart
and nerves.
4
Definition
Because of widespread immunization,
diphtheria is very rare in China (no case
was reported in recent years).
It is re-emerging in some areas of the
world where immunization practices are
lax.
5
Etiology
Diphtheria is caused by
Corynebacterium diphtheriae, a
bacterium, a bacillus.
6
Etiology
C. diphtheriae is an aerobic grampositive bacillus.
 Pleomorphic, club-end
 Non-spore-forming
 Non-acid-fast
 Non-motile
7
Etiology
Culture of the organism requires
selective media, tellurite agar or
Loeffler’ serum slants under aerobic
conditions.
8
Etiology
If isolated, the organism must be
distinguished in the laboratory from
other Corynebacterium species that
normally inhabit the nasopharynx and
skin (e.g., diphtheroids).
9
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.
10
Etiology
There are three biotypes — gravis,
intermedius, and mitis. The most severe
clinical type of this disease is associated
with the gravis biotype, but any strain
may produce toxin.
11
Etiology
Toxin production occurs only when the
bacillus is itself infected by a specific
virus (bacteriophage, a lysogenic phage) carrying the genetic information
for the toxin (toxin gene).
12
Etiology
Only toxigenic strains can cause severe
disease. So, all isolates of C. diphtheriae
should be tested by the laboratory for
toxigenicity (ELISA or the Elek tests).
13
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.
14
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.
15
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.
16
Epidemiology
Transmission


Transmission is most often person-toperson 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.
17
Epidemiology
Susceptibility



The susceptibility are influenced by
widespread immunization in
childhood and immunity obtained
after infection.
Children of 2-10 years old before
widespread immunization.
The unimmunized or inadequately
immunized adults after widespread
immunization.
18
Epidemiology
Susceptibility

The susceptibility can be
demonstrated by Schick’s test
(dermal test, positive result implies
sensitiveness or no resistance to the
disease) or ELISA (serologic assay).
19
Epidemiology
Epidemical features

Diphtheria occurs worldwide, but
clinical cases are more prevalent in
temperate zones, and in
socioeconomic conditions of poor
personal hygiene, crowding and
limited access to medical care.
20
Epidemiology
Epidemical features


Diphtheria most frequently occurs
during the autumn and winter or
early in the spring.
Children were subjected to this
disease in the past, but the
unimmunized or inadequately
immunized adults now.
21
Epidemiology
22
Epidemiology
23
Pathogenesis and pathology
Susceptible persons may acquire
toxigenic diphtheria bacilli in the
nasopharynx, skin, middle ear or
anterior nares.
24
Pathogenesis and pathology
The organism produces a toxin that
inhibits cellular protein synthesis and is
responsible for local tissue destruction
and pseudomembrane formation.
25
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.
26
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.
27
Pathogenesis and pathology
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).
28
Pathogenesis and pathology
The rapidity of onset, the severity of
disease, and the ultimate outcome are
determined by the site of infection, the
virulence of the strain and the status of
host immunization, in actual, by the site
and magnitude of the local lesions
(pseudomembrane).
29
Clinical manifestations
The incubation period of diphtheria is 24 days (range, 1-7 days).
This disease can involve almost any
mucous membrane.
30
Clinical manifestations
The major sign is pseudomembrane. The
typical pseudomembrane is adherent to
the tissue, and forcible attempts to
remove it cause bleeding.
Pseudomembrane.
31
Clinical manifestations
For clinical purposes, it is convenient to
classify diphtheria into four categories
depending on the site of disease (or
pseudomembrane).
32
Pharyngeal diphtheria
It’s the most common type, >80%.
The sites of infection are the tonsils and
the pharynx.
Infection at these sites is usually
associated with substantial systemic
absorption of toxin.
33
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.
34
Pharyngeal diphtheria
Ordinary type
 Symptoms: malaise, sore throat,
anorexia, vomiting and middle-grade
fever.
 Typical adherent, bluish- or greyishwhite pseudomembrane forms on the
congested tonsils.
 With lymph nodes enlargement in the
submandibular areas (颌下区) of neck.
35
Pharyngeal diphtheria
Grave type
 Serious early symptoms, high-grade
fever.
 Skin becomes pale, tachycardia,
blood pressure may be normal or
slightly depressed (Shock).
36
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.
37
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.
38
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.
39
Pharyngeal diphtheria
Extra-grave type
 Complications, include myocarditis
and thrombocytopenia may occur.
 May even die within 6 to 10 days.
40
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.
41
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.
42
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.
43
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.
44
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.
45
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.
46
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.
47
Laboratory findings
Bacteriological examinations

Smear and gram stain can found C.
diphtheriae, but can not identify from
the diphtheroids.
48
Laboratory findings
Bacteriological examinations

Fluorescent antibody-stain can found
toxigenic C. diphtheriae, favourable
for early diagnosis, but definitive
diagnosis (false positive).
49
Laboratory findings
Bacteriological examinations

C. diphtheriae can be cultured from
the swabs from nose, pharynx or
other sites.
50
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.
51
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.
52
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.
53
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.
54
Complications
Neuritis


Eye muscles, limbs, and diaphragm
paralysis can occur after the fifth
week.
Secondary pneumonia and respiratory
failure may result from diaphragmatic
paralysis.
55
Complications
Other complications

Include otitis media and respiratory
insufficiency due to airway
obstruction, especially in infants.
56
Diagnosis
Clinical diagnosis is usually made based
on the epidemiological data and clinical
presentation since it is imperative to
begin presumptive therapy quickly.
57
Diagnosis
Gram stain of material from the
pseudomembrane can be helpful when
trying to confirm the clinical diagnosis.
58
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.
59
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.
60
Diagnosis
In patients with negative culture and
prior antibiotic therapy, the
presumptive diagnosis (推定诊断) may
be confirmed with evidences:
(1) isolation of the C. diphtheriae from
culturing of close contacts, and/or (2) a
low or non-protective diphtheria
antibody titer in sera (<0.1 I.U.) or
Schick test (-).
61
Differential diagnosis
Dyspnea

Acute laryngitis; foreign body in trachea;
laryngeal edema
Pseudomembrane




Streptococcal pharyngitis (链球菌性咽炎)
Oral candidiasis (口腔念珠菌病)
Infectious mononucleosis (传染性单核细胞增
多症)
Vincent’s angina (奋森咽峡炎)
62
Differential diagnosis
Streptococcal pharyngitis
 The pus covering on the tonsils
sometimes is misunderstood as the
pseudomembrane of diphtheria. It’s
usually yellow in color, and easy to
remove.
63
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
64
Differential diagnosis
Infectious mononucleosis and Vincent’s
angina
 Sometimes also have things like
membranes on the surface of tonsils
or pharynx. However, they can be
remove without bleeding of the
tissues.
65
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.
66
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.
67
Treatments
General measures


Relax on bed for more than 3 weeks,
4-6 weeks for patients with
myocarditis.
Provide adequate energy and
nutriments
68
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.
69
Treatments
Diphtheria antitoxin


Dose: 3-5×104 U for early (<3-4d)
and mild or ordinary patients; 6-10
×104 U for later (>3-4d) or grave
patients; reduce in larynx diphtheria
1-2×104 U is given intravenously and
the rest is given intramuscularly.
70
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)
71
Treatments
Antibiotics



Prevention of further toxin production.
Control local infection.
Reduction of transmission.
72
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.
73
Treatments
Antibiotics

The disease is usually not contagious
48 hours after antibiotics are used.
74
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.
75
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 (临时临床
诊断) is made and appropriate
cultures are obtained.
76
Preventions
Management of infection sources

For close contacts, especially
household contacts, a diphtheria
booster, appropriate for age, should
be given. Antitoxin 1000-2000 U,
intramuscularly
77
Preventions
Management of infection sources

Contacts should also receive
antibiotics—benzathine penicillin G or
a 7- to 10-day course of oral
erythromycin.
78
Preventions
Interruption of the transmission routes
by disinfections of discharges and
articles of patients
79
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.
80
Summary of the definition
Acute, communicable, toxin-mediated,
sometime life-threatening bacterial
disease
Preventable with widespread
immunization
81
Summary of the definition
Pseudomembrane usually in the throat
or nose
The typical pseudomembrane is
adherent to the tissue, and forcible
attempts to remove it cause bleeding.
82
83
84
Pharyngeal diphtheria
85
Pharyngeal diphtheria
86
Pharyngeal diphtheria
87
Pharyngeal diphtheria
88
Pharyngeal diphtheria
89
Laryngeal diphtheria
90
Cutaneous (skin) diphtheria
91