Micro Cor Dip

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    Corynebacterium

    diphtheriae

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    A 4yr old boy was brought to the

    emergency ward with fever, sore throat

    and thick whitish tonsillar exudates with

    a white membrane around nasopharynx

    was demonstrated and there was cervical

    lymphadnopathy, pallor, tachycardia and

    dysnoea

    ?

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    a)what is your Provisional diagnosis ?

    (b) Describe the morphology and staining

    characters of the aetiological agent ?

    (c) Describe the pathogenesis?

    (d) Discuss the methods of toxigenicitytesting of the organism?

    (e) What immunoprophylactic measure willyou take for prevention of the disease?

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    The provisional diagnosis can be Faucial diphtheria

    caused by Corynebacterium diphtheriae

    What is diphtheriae ?

    Diphtheria is a bacterial infectious disease spreading

    from person to person by respiratory droplets from the

    throat through coughing and sneezing.

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    Word diphtheria comes from the Greek

    word for leather, which refers to the

    tough pharyngeal membrane that is the

    clinical hallmark of infection.

    Rarely, a similar disease can be cause

    by other Corynebacterium species: C.

    ulcerans, C. hemolyticum, and C.

    pseudotuberculosis.

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    HISTORY

    Diphtheria was first described by Hippocrates in the

    fifth century BC, and throughout history diphtheria

    has been a leading cause of death, primarily among

    children.

    The diphtheria bacterium was first identified in the

    1880s by F. Loeffler, and the antitoxin against

    diphtheria was later developed in the 1890s.

    The development of the first diphtheria toxoid

    vaccine occurred in the 1920s, by Von behring and

    its subsequent widespread use led to a dramatic

    decrease of diphtheria worldwide.

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    Describe the morphology and

    staining characters of the

    aetiological agent ?

    Gram- positive, slender rods with

    palisade or Chinese letters(V,L)

    arrangement with club shape at

    one or both ends composed of

    polymetaphosphate which serve

    as energy storage depots called

    Babes-Ernst granules or volutin

    or metachromatic granules

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    Staining with

    Methylene blue

    Special stains-

    Alberts,Neissers

    Ponders

    Metachromatic granules

    Media-Selective -

    Tellurite Blood Agar

    (McLeods Hoyles)

    raised, translucent,

    gray/black colonies

    Loefflers serum slo e

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    Diphtheria Clinical Features

    Incubation period 2-5 days

    (range, 1-10 days)

    May involve any mucous membrane

    Classified based on site of infection

    anterior nasal

    pharyngeal and tonsillar

    laryngeal

    cutaneous

    ocular

    enital

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    Infection may lead to respiratory

    disease, cutaneous disease or an

    asymptomatic carrier state.

    There are three biotypes of the

    bacterium (gravis, mitis, and

    intermedius) capable of producing

    diphtheria, though each biotype varies

    in the severity of disease it produces

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    Disease usually starts as a local

    infection of the mucous membranes

    causing a membranous pharyngitis.

    Local toxin effects result in

    degeneration of epithelial cells.

    Inflammation, edema, and production of

    a pseudomembrane composed of

    fibrin clots,leukocytes, and dead

    epithelial cells and microorganisms

    occurs in the throat.

    Extension of this pseudomembrane intothe larynx and trachea can lead toobstruction of the airway withsubsequent suffocation and death

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    BULL NECK

    Enlarged lymph

    nodes in the neck

    and neck swelling

    (producing a bull

    neck appearance)

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    The diphtheria toxin may be absorbed and disseminated

    via the blood and lymphatic system to other organs distan

    from the initial infection,

    Leads to more severe systemic sequelae (pathological

    conditions resulting from a prior disease, injury, or attack)

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    Exotoxin

    Strain widely used for toxin production ParkWilliams 8 strainIs a heat-labile polypeptide produced during

    lysogeny of a phage that carries the "tox

    geneInhibits protein synthesis by ADP-

    ribosylating elongation factor 2

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    Diphtheria toxin

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    Risk factors

    Include absent or incomplete immunization

    against diphtheria, overcrowded and/or

    unsanitary living conditions, a compromised

    immune system,

    Travel to areas where the disease is endemic,

    especially in individuals who have not obtained

    booster shots (vaccine).

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    Symptoms and Signs

    The symptoms and signs of respiratory diphtheria mayinitially be similar to a viral upper respiratory infection,

    however, the symptoms become more severe with the

    progression of the disease.

    The symptoms and signs of respiratory diphtheria may

    include the following:

    Sore throat ,Fever Hoarseness ,Difficulty

    swallowing,Malaise

    Weakness,Headache,Cough,Nasal discharge (that may

    contain pus or blood-tinged fluid)

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    The systemic manifestations of diphtheria are caused by

    the effects of the diphtheria toxin and its subsequent

    dissemination to other organs away from the initial area

    of infection.

    Commonly affected organs include the heart and

    nervous system, leading to complications such as

    inflammation of the heart (myocarditis), cardiac rhythm

    and conduction disturbances, muscle weakness,

    numbness (nerve), and vision changes.

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    Cutaneous diphtheria is characterized by an

    initially painful red lesion that eventually becomes

    a non-healing ulcer covered with a gray-brown

    membrane.

    Infection is only rarely associated with systemic

    complications.

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    Virulence tests In Vitro: EleksTest

    The organism is streaked

    on a plate containing low

    iron.

    A filter strip containing anti-

    toxin antibody is placed

    perpendicular to the streak

    of the organism.

    Diffusion of the antibody into

    the medium and secretion of

    the toxin into the medium

    occur.

    At the zone of equivalence,

    a precipitate will form.

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    Virulence tests :InVivo: Subcutaneous test

    Two guinea pigs of same wt. One

    acts as control with diphtheria

    antitoxin (18-24hrs)

    Diphtherial overnight culture is

    injected subcutaneously in to both

    If the stain is virulent the

    unprotected one wil die within four

    days

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    Treatment

    Includes diphtheria antitoxin, antibiotics,

    and supportive care .erythromycinor penicillin

    Patients with suspected diphtheria

    should be placed in isolation in order to

    prevent transmission.

    Active immunization is started at 6 week

    along wth PT,T(DPT)

    Three dose of 4-6 weeks intramuscular.

    Booster-18 months,5 yr.

    Passive immunization-500-1000 units

    Diptheria antitoxin

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