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Diphtheria (??)

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Title: Diphtheria (??)


1
Diphtheria (??)
  • Peng Xiaomou (???)
  • The Third Affiliated Hospital

2
Definition
  • Diphtheria is an acute, toxin-mediated disease
    caused by toxigenic Corynebacterium diphtheriae
    (??????).
  • Its a very contagious and potentially
    life-threatening bacterial disease.

3
Definition
  • Its a localized infectious disease, which
    usually attacks the throat and nose mucous
    membrane

4
Definition
  • 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.

5
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.

6
Etiology
  • Diphtheria is caused by Corynebacterium
    diphtheriae, a bacterium, a bacillus.

7
Etiology
  • C. diphtheriae is an aerobic gram-positive
    bacillus.
  • Pleomorphic, club-end
  • Non-spore-forming
  • Non-acid-fast
  • Non-motile

8
Etiology
  • Culture of the organism requires selective media,
    tellurite agar or Loeffler serum slants under
    aerobic conditions.

9
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).

10
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.

11
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.

12
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).

13
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).

14
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.

15
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.

16
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.

17
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.

18
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.

19
Epidemiology
  • 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).

20
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.

21
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.

22
Epidemiology
23
Epidemiology
24
Pathogenesis and pathology
  • Susceptible persons may acquire toxigenic
    diphtheria bacilli in the nasopharynx, skin,
    middle ear or anterior nares.

25
Pathogenesis and pathology
  • The organism produces a toxin that inhibits
    cellular protein synthesis and is responsible for
    local tissue destruction and pseudomembrane
    formation.

26
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.

27
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.

28
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).

29
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).

30
Clinical manifestations
  • The incubation period of diphtheria is 2-4 days
    (range, 1-7 days).
  • This disease can involve almost any mucous
    membrane.

31
Clinical manifestations
  • The major sign is pseudomembrane. The typical
    pseudomembrane is adherent to the tissue, and
    forcible attempts to remove it cause bleeding.
  • Pseudomembrane.

32
Clinical manifestations
  • For clinical purposes, it is convenient to
    classify diphtheria into four categories
    depending on the site of disease (or
    pseudomembrane).

33
Pharyngeal 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.

34
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.

35
Pharyngeal 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.

36
Pharyngeal diphtheria
  • Grave type
  • Serious early symptoms, high-grade fever.
  • Skin becomes pale, tachycardia, blood pressure
    may be normal or slightly depressed (Shock).

37
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.

38
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.

39
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.

40
Pharyngeal diphtheria
  • Extra-grave type
  • Complications, include myocarditis and
    thrombocytopenia may occur.
  • May even die within 6 to 10 days.

41
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.

42
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.

43
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.

44
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.

45
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.

46
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.

47
Laboratory 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.

48
Laboratory findings
  • Bacteriological examinations
  • Smear and gram stain can found C. diphtheriae,
    but can not identify from the diphtheroids.

49
Laboratory findings
  • Bacteriological examinations
  • Fluorescent antibody-stain can found toxigenic C.
    diphtheriae, favourable for early diagnosis, but
    definitive diagnosis (false positive).

50
Laboratory findings
  • Bacteriological examinations
  • C. diphtheriae can be cultured from the swabs
    from nose, pharynx or other sites.

51
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.

52
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.

53
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.

54
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.

55
Complications
  • Neuritis
  • Eye muscles, limbs, and diaphragm paralysis can
    occur after the fifth week.
  • Secondary pneumonia and respiratory failure may
    result from diaphragmatic paralysis.

56
Complications
  • Other complications
  • Include otitis media and respiratory
    insufficiency due to airway obstruction,
    especially in infants.

57
Diagnosis
  • Clinical diagnosis is usually made based on the
    epidemiological data and clinical presentation
    since it is imperative to begin presumptive
    therapy quickly.

58
Diagnosis
  • Gram stain of material from the pseudomembrane
    can be helpful when trying to confirm the
    clinical diagnosis.

59
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.

60
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.

61
Diagnosis
  • 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 (-).

62
Differential diagnosis
  • Dyspnea
  • Acute laryngitis foreign body in trachea
    laryngeal edema
  • Pseudomembrane
  • Streptococcal pharyngitis (??????)
  • Oral candidiasis (??????)
  • Infectious mononucleosis (??????????)
  • Vincents angina (?????)

63
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.

64
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

65
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.

66
Prognosis
  • 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.

67
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.

68
Treatments
  • General measures
  • Relax on bed for more than 3 weeks, 4-6 weeks for
    patients with myocarditis.
  • Provide adequate energy and nutriments

69
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.

70
Treatments
  • 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.

71
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)

72
Treatments
  • Antibiotics
  • Prevention of further toxin production.
  • Control local infection.
  • Reduction of transmission.

73
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.

74
Treatments
  • Antibiotics
  • The disease is usually not contagious 48 hours
    after antibiotics are used.

75
Preventions
  • 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.

76
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.

77
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

78
Preventions
  • Management of infection sources
  • Contacts should also receive antibioticsbenzathin
    e penicillin G or a 7- to 10-day course of oral
    erythromycin.

79
Preventions
  • Interruption of the transmission routes by
    disinfections of discharges and articles of
    patients

80
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.

81
Summary of the definition
  • Acute, communicable, toxin-mediated, sometime
    life-threatening bacterial disease
  • Preventable with widespread immunization

82
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.

83
Gram staining
84
Neisser staining
85
Pharyngeal diphtheria
86
Pharyngeal diphtheria
87
Pharyngeal diphtheria
88
Pharyngeal diphtheria
89
Pharyngeal diphtheria
90
Laryngeal diphtheria
91
Cutaneous (skin) diphtheria
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