Diphtheria is a respiratory tract infection.
Agent of infection
Corynebacterium diphtheriae
Organism features
- Gram positive bacillus
- non capsulated, non sporing, non motile
- shows club shaped swellings
- fastidious
- aerobic bacteria
Special features
- Chinese letter (cuneiform) arrangement– When the bacterial cells divide, the daughter cells tend to lie at acute angles to each other (called snapping type of cell division). So they appear ass V- or L-shaped in smear.
- Metachromatic granules– Also called polar bodies or volutin granules. They are storage granules of the organim. these granules are gram positive (strongly stained)
Virulence factors
Diphtheria toxin (DT)
- It is the primary virulence factor
- DT is a polypeptide chainit has 2 fragments – A (active) and B (binding)
- It is phage coded
- The toxin production depends on iron concentration
- Toxoid is the form of toxin when virulence is lost, but is still antigenic
- Toxoid is used for vaccination.
Mechanism of action
↓ Fragment B binds to host cell receptors
↓ Helps in internalization of fragment A
↓ Fragment A causes ADP ribosylation of elongation factor 2 (EF-2)
↓ EF-2 inhibited
↓ inhibiton of translation (protein sysnthesis)
Pathogenesis
Bacilli are non-invasive; toxin is resposible for the pathogenesis
1. Respiratory diphtheria
- Most common form of Diphtheria
- Site: pharynx, tonsil, nose, larynx
- Diphtheria toxin elicits inflammatory response
- causes necrosis of epithelium and exudate formation
- leads to mucosal ulcer formation which is lined by a pseudomembrane coat
- it is strongly attached tto the mucosal base
- it bleeds on removal (true membranes can be easily separated)
- this coat is leathery and greyish white in apperance.
- it is composed of : inner fibrin band, surrounded by neutrophils, RBCs and bacteria
- this pseudomembrane can extend into larynx and the airways which can lead to airway obstruction (leads to asphyxia)
- Massive tonsillar swelling and neck edema presents as bull-neck appearance.
2. Cutaneous diphtheria
- Not toxin mediated (produced by organism itself)
- presents as punched out ulcerative lesions with necrosis
- pseudomembrane formation over them is rare
- mostly affect extremities
3. Systemic complications
- Neurologic manifestations: cranial nerve invovlement, peripheral neuropathy, ciliary paralysis
- Myocarditis: arrythmias, dilated cardiomyopathy
Lab diagnosis
Specimen
- throat swab containing the exudate
- portion of pseudomembane
- nose/skin specimens
Direct smear microscopy
Gram staining:
- Gram positive bacilli
- irregularly stained
- chinese letter arrangement
- Albert’s stain: green bacilli with bluish black metachromatic granules at poles