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    Corynebacterium Diphtheriae

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    hercolanium
    Corynebacterium diphtheriae causes diphtheria, an infection characterized by a pseudomembrane in the throat or nose. The bacteria produces a toxin that can damage the heart and nerves. While most Corynebacterium species are harmless, C. diphtheriae is the only pathogenic one. Symptoms range from mild throat infection to severe airway obstruction. Treatment involves antibiotics, antitoxin, and supportive care. Active immunization through the DPT vaccine provides protection.

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    Corynebacterium Diphtheriae

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    hercolanium
    230 views21 pages
    Corynebacterium diphtheriae causes diphtheria, an infection characterized by a pseudomembrane in the throat or nose. The bacteria produces a toxin that can damage the heart and nerves. While most Corynebacterium species are harmless, C. diphtheriae is the only pathogenic one. Symptoms range from mild throat infection to severe airway obstruction. Treatment involves antibiotics, antitoxin, and supportive care. Active immunization through the DPT vaccine provides protection.

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    CORYNEBACTERIUM DIPHTHERIAE

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    Corynebacterium diphtheriae causes diphtheria, an infection characterized by a pseudomembrane in the throat or nose. The bacteria produces a toxin that can damage the heart and nerves. While most Corynebacterium species are harmless, C. diphtheriae is the only pathogenic one. Symptoms range from mild throat infection to severe airway obstruction. Treatment involves antibiotics, antitoxin, and supportive care. Active immunization through the DPT vaccine provides protection.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    230 views21 pages

    Corynebacterium Diphtheriae

    Uploaded by

    hercolanium
    Corynebacterium diphtheriae causes diphtheria, an infection characterized by a pseudomembrane in the throat or nose. The bacteria produces a toxin that can damage the heart and nerves. While most Corynebacterium species are harmless, C. diphtheriae is the only pathogenic one. Symptoms range from mild throat infection to severe airway obstruction. Treatment involves antibiotics, antitoxin, and supportive care. Active immunization through the DPT vaccine provides protection.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 21

    CORYNEBACTERIUM DIPHTHERIAE

    Mary Ann A. Wagas, MD,DPPS

    Corynebacterium diphtheriae

    Acute infection : Diphtheria Primary lesion is in the throat or nasopharynx & characterized by the presence of a grayish pseudomembrane composed of fibrin, leukocytes, necrotic epithelial cells & C. diphtheriae cells Exotoxin is released into the blood that damages the heart & neural cells by interfering in protein synthesis

    Corynebacterium diphtheriae

    Loffler isolated the organism in pure culture Roux & Yersin provided complete understanding of the pathogenesis of infection after discovering the exotoxin Most members of the genus are normal flora of the skin, naso- & oropharynx, urogenital tract & gastrointestinal tract C. diphtheriae is the only pathogenic species

    Corynebacterium diphtheriae: Morphology

    Pleomorphic Gram positive rods often with clubbed ends, in pairs or trios Cells are 1.5- 5um length by 0.5- 1.0um width Metachromatic (Babes-Ernst) granules accumulations of polyphosphates Non-capsulated, non-motile

    Corynebacterium diphtheriae: Physiology

    Aerobic & facultatively anaerobic Culture media: Loefflers agar


    used

    for primary isolation Enhances the formation of metachromatic granules Minute, grayish white glistening colonies grow in 12-24HR incubation at 37C Tellurite salts reduces the number of contaminants

    Corynebacterium diphtheriae: Physiology

    Tinsdales agar
    Selective

    medium, inhibits growth of other

    organism Allows differentiation from other Corynebacterium species by colony morphology

    3 major colonial types:


    Gravis Mitis Intermedius

    Corynebacterium diphtheriae: Physiology


    Gravis strains large, flat, gray to black with a dull surface Mitis strains medium-sized colonies, that are smaller, blacker, glossy & more convex Intermedius colonies very small & either smooth or rough C.diphtheriae are resistant to light, dessication & freezing; sensitive to a 1-minute exposure to 100C

    Antigenic Structure

    K antigen
    Responsible

    for the type specificity of C.

    diphtheriae Heat labile proteins in superficial layers of the wall Role in antibacterial immunity & hypersensitivity Major determinants of invasiveness & virulence: K antigen & glycolipid cord factor

    O antigen
    Heat

    stable Responsible for cross-reactivity with mycobacterium & nocardia

    Determinants of Pathogenecity

    Systemic disease is caused by strains producing exotoxin Toxin Synthesis


    Only

    strains that have been lysogenized with a bacteriophage carrying the tox gene produce diphtheria toxin Production is activated as organism enter death phase Low iron concentration in culture media promotes toxin synthesis

    Determinants of Pathogenecity
    Toxin Structure Fraction B (binding) moiety
    Mediates

    attachment of toxin to cells & transport of the toxin into cells for the biologic properties if the toxin

    Fraction A (active) moiety


    Responsible

    Determinants of Pathogenecity
    Mechanism of Action: Fraction A disrupts protein synthesis by catalyzing transfer of adenosinediphosphoribose (ADPR) moiety of Nicotinamide adenine dinucleotide (NAD) to the elongation factor-2 (EF-2) The ribosylation of EF-2 blocks polypeptide chain elongation

    Clinical Disease: Epidemiology

    Humans are the only natural hosts Very contagious & transmitted via aerosolized nasopharyngeal secretions In developing countries, where fewer infants are immunized, an estimated 1M deaths per year The marked decrease in incidence is due to successful active immunization programs Immunity declines with age

    Clinical Disease: Pathogenesis


    Incubation pd: 1-7 days Organisms usually localized to oropharynx

    Organisms multiply on epithelial cells, producing EXOTOXIN

    Formation of PSEUDOMEMBRANE over the tonsils, uvula, soft palate or pharyngeal wall

    Exotoxin is absorbed into the systemic circulation where it causes myocarditis & peripheral neuropathy

    Clinical Manifestations

    Initial symptoms : Pharyngitis or Tonsillitis Clinical manifestation depends on the location & extent of infection A) Anterior nasal diphtheria not very severe B) Tonsillar diphtheria most common presentation, causes sore throat with low grade fever & malaise C) Pharyngeal diphtheria more extensive pseudomembrane, which can obstruct airway & cause suffocation

    Clinical Manifestations

    Extra-Respiratory disease Skin Skin diphtheria


    appear

    as chronic, spreading, non-healing ulcers covered with grayish membrane Streptococcus pyogenes or Staphylococcus aureus may be present Mitis strains present

    Rarely conjunctiva, cornea, vagina & ear

    Complications

    Cardiac disease
    after the 2nd week of disease in 20% of patients Fatty myocardial degeneration
    Appear

    Neurologic symptoms
    in the 3rd 5th week of disease Cranial nerve involvement paralysis of soft palate, difficulty in swallowing & regurgitation Peripheral nerve involvement - polyneuritis
    Appear

    Laboratory Diagnosis

    Initial diagnosis clinical presentation Differential diagnosis :


    Infectious

    mononucleosis Streptococcal pharyngitis Leukemia with agranulocytosis

    Definitive diagnosis culture & isolation of organism

    Treatment

    Entails suppression of bacterial growth, neutralization of toxin & supportive measures Penicillin drug of choice Erythromycin in patients allergic to PCN Diphtheria antitoxin dose depend on severity
    20,000U

    mild case, 100,000U severe IM

    Supportive measures
    Tracheostomy

    for airway obstruction Full cardiovascular support for myocarditis

    Prevention

    Active immunization : diphtheria toxoid Primary of immunization started at 6-8weeks of life 0.5ml dose of diphtheria toxoid combined with tetanus toxoid & pertussis vaccine (DPT) given IM on 4 occasions the first 3doses at 48weeks interval, the forth dose at 6 to 12 months after the 3rd dose For 7yo & older, booster dose of tetanus & diphtheria toxoid (Td) should be given every 10 years

    Prophylaxis for Case Contacts

    All household contacts closely monitored Contact immunized within the previous 5yrs should receive booster dose of toxoid Unimmunized or inadequately immunized contacts should complete the immunization sequence & receive PCN or Erythromycin Passive immunization : 5,000-10,000U of antitoxin

    Establishment of Immune Status

    SCHICK Test
    Injection

    of 0.1ml purified toxin Intradermal to

    forearm Control injection to the other arm Positive test local inflammatory reaction 10mm diameter within 4-7 days, indicates absence of immunity to diphtheria Negative test antitoxin greater than 0.03U/ml, able to neutralize toxin & person is immune

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