Title: Diphtheria (??)
1Diphtheria (??)
- Peng Xiaomou (???)
- The Third Affiliated Hospital
2Definition
- Diphtheria is an acute, toxin-mediated disease
caused by toxigenic Corynebacterium diphtheriae
(??????). - Its a very contagious and potentially
life-threatening bacterial disease.
3Definition
- Its a localized infectious disease, which
usually attacks the throat and nose mucous
membrane
4Definition
- Common symptoms malaise, sore throat, anorexia,
and low-grade fever. - Typical sign specific membrane formation
(pseudomembrane,??, in Greek diphthera, meaning
leather, as tough as leather) - In serious cases, it can attack the heart and
nerves.
5Definition
- 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.
6Etiology
- Diphtheria is caused by Corynebacterium
diphtheriae, a bacterium, a bacillus.
7Etiology
- C. diphtheriae is an aerobic gram-positive
bacillus. - Pleomorphic, club-end
- Non-spore-forming
- Non-acid-fast
- Non-motile
8Etiology
- Culture of the organism requires selective media,
tellurite agar or Loeffler serum slants under
aerobic conditions.
9Etiology
- If isolated, the organism must be distinguished
in the laboratory from other Corynebacterium
species that normally inhabit the nasopharynx and
skin (e.g., diphtheroids).
10Etiology
- 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.
11Etiology
- 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.
12Etiology
- 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).
13Etiology
- 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).
14Etiology
- 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.
15Epidemiology
- 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.
16Epidemiology
- 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.
17Epidemiology
- 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.
18Epidemiology
- 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.
19Epidemiology
- Susceptibility
- The susceptibility can be demonstrated by
Schicks test (dermal test, positive result
implies sensitiveness or no resistance to the
disease) or ELISA (serologic assay).
20Epidemiology
- 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.
21Epidemiology
- 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.
22Epidemiology
23Epidemiology
24Pathogenesis and pathology
- Susceptible persons may acquire toxigenic
diphtheria bacilli in the nasopharynx, skin,
middle ear or anterior nares.
25Pathogenesis and pathology
- The organism produces a toxin that inhibits
cellular protein synthesis and is responsible for
local tissue destruction and pseudomembrane
formation.
26Pathogenesis 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.
27Pathogenesis 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.
28Pathogenesis 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).
29Pathogenesis 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).
30Clinical manifestations
- The incubation period of diphtheria is 2-4 days
(range, 1-7 days). - This disease can involve almost any mucous
membrane.
31Clinical manifestations
- The major sign is pseudomembrane. The typical
pseudomembrane is adherent to the tissue, and
forcible attempts to remove it cause bleeding. - Pseudomembrane.
32Clinical manifestations
- For clinical purposes, it is convenient to
classify diphtheria into four categories
depending on the site of disease (or
pseudomembrane).
33Pharyngeal diphtheria
- Its the most common type, gt80.
- The sites of infection are the tonsils and the
pharynx. - Infection at these sites is usually associated
with substantial systemic absorption of toxin.
34Pharyngeal 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.
35Pharyngeal diphtheria
- Ordinary type
- Symptoms malaise, sore throat, anorexia,
vomiting and middle-grade fever. - Typical adherent, bluish- or greyish-white
pseudomembrane forms on the congested tonsils. - With lymph nodes enlargement in the submandibular
areas (???) of neck.
36Pharyngeal diphtheria
- Grave type
- Serious early symptoms, high-grade fever.
- Skin becomes pale, tachycardia, blood pressure
may be normal or slightly depressed (Shock).
37Pharyngeal 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.
38Pharyngeal 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.
39Pharyngeal diphtheria
- Extra-grave type
- Patients develop marked edema of the
submandibular areas and the anterior neck along
with lymphadenopathy, giving a characteristic
bullneck appearance.
40Pharyngeal diphtheria
- Extra-grave type
- Complications, include myocarditis and
thrombocytopenia may occur. - May even die within 6 to 10 days.
41Laryngeal 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.
42Anterior 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.
43Anterior 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.
44Cutaneous 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.
45Cutaneous 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.
46Cutaneous 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.
47Laboratory findings
- Routine examination
- Leukocytosis, 1020 G/L, neutrophil is dominant.
- Low platelet count (thrombocytopenia), rise
profiles of the serum enzyme tests and
proteinuria were found in serious cases.
48Laboratory findings
- Bacteriological examinations
- Smear and gram stain can found C. diphtheriae,
but can not identify from the diphtheroids.
49Laboratory findings
- Bacteriological examinations
- Fluorescent antibody-stain can found toxigenic C.
diphtheriae, favourable for early diagnosis, but
definitive diagnosis (false positive).
50Laboratory findings
- Bacteriological examinations
- C. diphtheriae can be cultured from the swabs
from nose, pharynx or other sites.
51Laboratory 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.
52Complications
- 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.
53Complications
- 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.
54Complications
- 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.
55Complications
- Neuritis
- Eye muscles, limbs, and diaphragm paralysis can
occur after the fifth week. - Secondary pneumonia and respiratory failure may
result from diaphragmatic paralysis.
56Complications
- Other complications
- Include otitis media and respiratory
insufficiency due to airway obstruction,
especially in infants.
57Diagnosis
- Clinical diagnosis is usually made based on the
epidemiological data and clinical presentation
since it is imperative to begin presumptive
therapy quickly.
58Diagnosis
- Gram stain of material from the pseudomembrane
can be helpful when trying to confirm the
clinical diagnosis.
59Diagnosis
- 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.
60Diagnosis
- 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.
61Diagnosis
- In patients with negative culture and prior
antibiotic therapy, the presumptive diagnosis
(????) 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
(lt0.1 I.U.) or Schick test (-).
62Differential diagnosis
- Dyspnea
- Acute laryngitis foreign body in trachea
laryngeal edema - Pseudomembrane
- Streptococcal pharyngitis (??????)
- Oral candidiasis (??????)
- Infectious mononucleosis (??????????)
- Vincents angina (?????)
63Differential 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.
64Differential 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
65Differential 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.
66Prognosis
- The overall case-fatality rate for diphtheria is
about 5, with higher death rates (up to 20) in
persons lt5 and gt40 years of age.
67Treatments
- 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.
68Treatments
- General measures
- Relax on bed for more than 3 weeks, 4-6 weeks for
patients with myocarditis. - Provide adequate energy and nutriments
69Treatments
- 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.
70Treatments
- Diphtheria antitoxin
- Dose 3-5104 U for early (lt3-4d) and mild or
ordinary patients 6-10 104 U for later (gt3-4d)
or grave patients reduce in larynx diphtheria - 1-2104 U is given intravenously and the rest is
given intramuscularly.
71Treatments
- 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)
72Treatments
- Antibiotics
- Prevention of further toxin production.
- Control local infection.
- Reduction of transmission.
73Treatments
- 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.
74Treatments
- Antibiotics
- The disease is usually not contagious 48 hours
after antibiotics are used.
75Preventions
- Management of infection sources
- Isolation of patients (gt7d), or elimination of
the organism should be documented by two
consecutive negative cultures after therapy is
completed.
76Preventions
- 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.
77Preventions
- Management of infection sources
- For close contacts, especially household
contacts, a diphtheria booster, appropriate for
age, should be given. Antitoxin 1000-2000 U,
intramuscularly
78Preventions
- Management of infection sources
- Contacts should also receive antibioticsbenzathin
e penicillin G or a 7- to 10-day course of oral
erythromycin.
79Preventions
- Interruption of the transmission routes by
disinfections of discharges and articles of
patients
80Preventions
- 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.
81Summary of the definition
- Acute, communicable, toxin-mediated, sometime
life-threatening bacterial disease - Preventable with widespread immunization
82Summary 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.
83Gram staining
84Neisser staining
85Pharyngeal diphtheria
86Pharyngeal diphtheria
87Pharyngeal diphtheria
88Pharyngeal diphtheria
89Pharyngeal diphtheria
90Laryngeal diphtheria
91Cutaneous (skin) diphtheria