Diphtheria

An acute bacterial toxigenic infectious disease caused by gram-positive bacillus, Corynebacterium diphtheriae.

---

Epidemiology

• Source: Secretions and discharges (infected person or carriers)
• Transmission: Droplet, secretions, direct contact
  • Infection is spread solely among humans
• Portal of entry: Respiratory tract
• Incubation period: 2-5 days

---

Microbiology

Corynebacterium diphtheriae

Nonmotile, noncapsulated, club-shaped, Gram-positive bacillus

• Pathogenicity due to:
  • Ability to colonise nasopharyngeal cavity and/or skin
  • Diphtheria toxin

Macleod classification:

McLeod and Anderson classified diphtheria bacilli, based on the colony characteristics on Tellurite medium and other properties like biochemical reactions and severity of disease.

C. diphtheriae biotype	Colony appearance	Hemolysis	Glycogen & starch fermentation
Gravis	Daisy head	Variable	Fermenting
Intermedius	Frog egg	Non-hemolytic	Non-fermenting
Mitis	Poached egg	Hemolytic	Non-fermenting

---

Pathophysiology

Enter respiratory tract
↓
Proliferate and liberate powerful exotoxin
(Principal cause of systemic and local lesions)
↓
Necrosis of the epithelial cells
+
Liberation of serous and fibrinous material
↓
Forms a thick, gray-green fibrin membrane
Pseudomembrane
(composed of fibrin, bacteria, and inflammatory cells)

• Surrounding tissue: Inflamed and edematous
• Organs principally affected: Heart, kidney and myocardium

---

Presentation

Acute onset

• Fever, malaise and headache
• Toxic look

Clinical types (depends on the site of involvement):

• Respiratory diphtheria (M/C):
  • Faucial/tonsillopharyngeal diphtheria
  • Nasopharyngeal diphtheria
  • Laryngotracheal diphtheria
• Cutaneous diphtheria

Faucial/tonsillopharyngeal diphtheria:

M/C respiratory diphtheria

• Redness and swelling over the fauces
• Pseudomembrane
  • The exudates coalesce to form a greyish white pseudomembrane, which extends to surrounding areas.
  • Localised on posterior pharynx or tonsil
  • Wipes off easily, resulting in bleeding
  • Extends to become thick blue-white to grey-black and adherent
• Bull neck diphtheria (severe cases, involvement of cervical lymph nodes)
• Sore throat, dysphagia and muffled voice

Nasal diphtheria (mildest respiratory diphtheria):

• Unilateral/bilateral serosanguinous discharge from the nose (localised to septum/turbinates)
• Excoriation of upper lip

Laryngotracheal diphtheria:

• Preceded by Pharyngotonsillar Disease
• Membrane over the larynx leads to: Brassy cough, stridor, respiratory distress

Cutaneous diphtheria:

• Diphtheritic lesions in skin and conjunctiva
  • Secondary to previous skin lesion or infections
• Ulcer:
  • Surrounded by erythema
  • Covered by membrane

---

Complications

Respiratory failure (M/C)

• Due to occlusion of the airways by the membrane & loss of motor function (due to action of diphtheria toxin on peripheral motor neurons)

Myocarditis

• By 2^nd week of illness
• Can lead to: Congestive cardiac failure, arrhythmias → Sudden death

Diphtheric mono/polyneuropathy (loss of motor function due to action of diphtheria toxin on peripheral motor neurons):

• Palatal palsy (by 2^nd week of illness)
  • Clinically manifested as: Nasal twang & nasal regurgitation
• Ocular palsy (by 3^rd week of illness)
• Loss of accommodation (visual blurring, inability to read)
• Generalized polyneuritis (by 3^rd-6^th weeks of illness)

Renal complications:

• Oliguria
• Proteinuria

---

Diagnosis

High index of suspicion

• SGOT ↑
• CPK-MB ↑
• Troponin T (kit test)
• Urea, creatinine ↑

Rapid diagnosis:

• Culture: Albert stain
  • Swab from the oropharynx and larynx
• Primary isolation media: Loeffler agar, Mueller-Miller tellurite agar,
  or Tinsdale tellurite agar

Elek immunodiffusion test (M/C in vitro assay for toxigenicity):

• Based on the double diffusion of diphtheria toxin and antitoxin in an agar medium
• Procedure:
  • Sterile, antitoxin-saturated filter paper strip is embedded in the culture medium, and C diphtheriae isolates are streak-inoculated at a 90° angle to the filter paper.
  • Production of diphtheria toxin can be detected within 18-48 hours by the formation of a toxin-antitoxin precipitin band in the agar.

ECG (for cardiac complications):

• Findings:
  • T-wave inversion
  • Sinus tachycardia
  • 2° AV block

Differential diagnosis:

• Acute streptococcal membranous tonsillitis
  • High fever but are less toxic and the membrane is confined to the tonsils
• Viral (adenovirus) membranous tonsillitis
  • High fever, sore throat, membranous tonsillitis with normal leukocyte count
  • Self limited course of 4-8 days
• Herpetic tonsillitis
• Aphthous stomatitis
• Thrush
• Infectious mononucleosis
• Agranulocytosis
• Leukemia

---

Management

Goals of management:

1. Early detection
2. Isolation
3. Treatment

Treatment for cases:

1. Diphtheria antitoxin,  IM/IV
   • Dose: 20,000-100,000 units
   • Degree of protection offered by the diphtheria antitoxin is inversely proportional to the duration of clinical illness
   • Repeat doses may be given if clinical improvement is suboptimal.
2. Penicillin or Erythromycin  (5-6 days)
   • Actions:
     1. Terminate toxin production
     2. Limit proliferation of bacteria
     3. Prevent spread of organism to contacts
     4. Prevent the development of carriers

Treatment for carriers:

• Oral Erythromycin
  • 10-day course

Supportive therapy:

• Bed rest
  • 2-3 weeks
• Avoid sudden exertion
• Monitored for:
  • Airway obstruction and managed
    • Tracheostomy (if required)
  • Changes in rate and rhythm of heart
• Palatal palsy:
  • Nasogastric feeding.
• Generalized weakness due to polyneuritis:
  • Treated as for poliomyelitis or Guillain-Barre syndrome

Prevention:

Treatment should be followed by active immunization as clinical disease does not confer active immunity.