CLINICAL DIAGNOSIS

DEEPA BABIN TMC KOLLAM

Corynebacterium diphtheriae

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?

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 toxigenicity testing of the organism? 

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

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.

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 caused by other Corynebacterium species: C. ulcerans, C. hemolyticum, and C. pseudotuberculosis.

HISTORYDiphtheria 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.

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

 Staining  with Methylene blueSpecial stains-Alberts,Neisser’s Ponders

Metachromatic granules

Media-Selective -Tellurite Blood Agar (McLeod’s &Hoyle’s)– raised, translucent, gray/black colonies ,Loefflers serum slope

Diphtheria Clinical FeaturesIncubation period 2-5 days

(range, 1-10 days)May involve any mucous

membrane

Classified based on site of infectionanterior nasalpharyngeal and tonsillarlaryngealcutaneousoculargenital

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

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 into the larynx and trachea can lead to obstruction of the airway with subsequent suffocation and death

BULL NECK

Enlarged lymph nodes in the neck and neck swelling (producing a "bull neck“ appearance)

The diphtheria toxin may be absorbed and disseminated via the blood and lymphatic system to other organs distant from the initial infection,

Leads to more severe systemic sequelae (pathological conditions resulting from a prior disease, injury, or attack).

ExotoxinStrain widely used for toxin production Park Williams 8 strainIs a heat-labile polypeptide produced during lysogeny of  a phage that carries the "tox” gene Inhibits protein  synthesis  by  ADP-ribosylating elongation factor  2

Diphtheria toxin

By infected individuals and asymptomatic carriers (individuals who are infected but do not exhibit symptoms).

Transmission occurs via inhalation of airborne respiratory secretions or by direct contact with infected nasopharyngeal secretions or skin wounds.

Rarely, infection can be spread by contact with objects contaminated by an infected person.

TRANSMISSION

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).

Symptoms and Signs

The symptoms and signs of respiratory diphtheria may initially 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)

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.

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.

Virulence tests In Vitro: Elek’s Test

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.

Virulence tests :In Vivo: 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

Treatment Includes diphtheria antitoxin, antibiotics, and supportive care .erythromycin or penicillinPatients 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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