DIPHTHERIA

1. DIPHTHERIA
MITTAL PULKIT IM-565

2. Diphtheria (Corynebacterium diphtheriae)
Diphtherais Greek word for leather
Bull-neck appearance of diphtheritic
cervical lymphadenopathy

3. INTRODUCTION
 An acute toxic infection caused by Corynebacterium
diphtheriae and rarely toxigenic strains of Corynebacterium
ulcerans
 aerobic, nonencapsulated, non–spore-forming, mostly
nonmotile, pleomorphic, gram-positive bacilli
 Differentiation of C. diphtheriae from C. ulcerans is based on
urease activity, C. ulcerans is urease-positive
 Four C. diphtheriae biotypes - mitis, intermedius, belfanti,
gravis; differentiated by colonial morphology, hemolysis, and
fermentation reactions

4. INTRODUCTION
 Diphtheritic toxin production occurs only after acquisition of a
lysogenic Corynebacteriophage by either C. diphtheriae or C.
ulcerans, which encodes the diphtheritic toxin gene and
confers diphtheria-producing potential on these strains
 Demonstration of diphtheritic toxin production or potential
for toxin production by an isolate is necessary to confirm
disease
 The former is done in vitro using the agar immunoprecipitin
technique (Elek test) or in vivo with the toxin neutralization
test in guinea pigs, the latter by polymerase chain reaction
testing for carriage of the toxin gene
 Toxin is lethal in human beings in an amount 130μg/kg BW

5. EPIDEMIOLOGY
 Transmission: airborne respiratory droplets, direct contact
with respiratory secretions of symptomatic individuals, or
exudates from infected skin lesions
 Asymptomatic respiratory tract carriage is important in
transmission. Where diphtheria is endemic, 3-5% of healthy
individuals can carry toxigenic organisms
 Diphtheria is endemic in INDIA.
 Skin infection and skin carriage are silent reservoirs and
organisms can remain viable in dust or on fomites for up to
6 months
 Transmission through contaminated milk and an infected food
handler has been documented

6. EPIDEMIOLOGY
 Children aged 1-5yrs are commonly infected
 A herd immunity of 70% is required to prevent epidemics
 Contaminated objects like thermometers, cups, spoons, toys
and pencils can spread the disease
 Overcrowding, poor sanitation and hygiene, illiteracy, urban
migration and close contacts can lead to outbreak

7. PATHOGENESIS
Within the first few days of respiratory tract infection , a dense necrotic
coagulum of organisms, epithelial cells, fibrin, leukocytes and erythrocytes
forms, advances, and becomes a gray-brown, leather-like
adherent pseudomembrane . Removal is difficult and reveals a bleeding
edematous submucosa
The major virulence of the organism lies in its ability to produce the
potent 62-kd polypeptide exotoxin, which inhibits protein synthesis and
causes local tissue necrosis
Entry into nose or mouth
The organism remains in the superficial layers of skin lesions or respiratory tract
mucosa, inducing local inflammatory reaction

8.  Local effect of diphtheritic toxin:
 Paralysis of the palate and hypopharynx
 Pneumonia
 Systemic effects (Toxin absorption ):
 kidney tubule necrosis
 hypoglycemia
 myocarditis and/or demyelination of nerves
 Myocarditis:10-14 days
 Demyelination of nerves: 3-7 weeks

9. CLINICAL MANIFESTATIONS
 Influenced by the anatomic site of infection, the immune
status of the host and the production and systemic distribution
of toxin
 Incubation period: 1-6 days
 Classification (location):
 nasal
 pharyngeal
 tonsillar
 laryngeal or laryngotracheal
 skin, eye or genitalia

10. CLINICAL MANIFESTATIONS
 Nasal diphtheria: Infection of the anterior nares- more
common among infants, causes serosanguineous, purulent,
erosive rhinitis with membrane formation
 Shallow ulceration of the external nares and upper lip is
characteristic
 Unilateral nasal discharge is quite pathognomic of nasal
diphtheria
 Accurate diagnosis of nasal diphtheria delayed-paucity of
systemic signs and symptoms

11.  Tonsillar and pharyngeal diphtheria:
sore throat is the universal early symptom
 Only half of patients have fever and fewer have dysphagia,
hoarseness, malaise, or headache
 Mild pharyngeal injection unilateral or bilateral tonsillar
membrane formation extend to involve the uvula, soft
palate, posterior oropharynx, hypopharynx, or glottic areas
 Underlying soft tissue edema and enlarged lymph nodes: bull-
neck appearance

13.  Laryngeal diphtheria: At significant risk for suffocation
because of local soft tissue edema and airway obstruction by
the diphtheritic membrane
 Classic cutaneous diphtheria is an indolent, nonprogressive
infection characterized by a superficial, ecthymic, nonhealing
ulcer with a gray-brown membrane

14. Infection at Other Sites:
ear (otitis externa), the eye (purulent and ulcerative
conjunctivitis), the genital tract (purulent and ulcerative
vulvovaginitis) and sporadic cases of pyogenic arthritis
Diagnosis
 Clinical features
 Culture: from the nose and throat and any other
mucocutaneous lesion. A portion of membrane should be
removed and submitted for culture along with underlying
exudate
 Elek test: rapid diagnosis (16-24 hrs)

15.  Enzyme immunossay
 PCR for A or B portion of the toxic gene “tox”
 Hypoglycemia, glycosuria, BUN, or abnormal ECG for liver,
kidney and heart involvement
Differential diagnosis:
1. Common cold
2. Congenital syphilis snuffle
3. Sinusitis
4. Adenoiditis and foreign body in nose
5. Streptococcal pharyngitis
6. Infectious mononucleosis

16. COMPLICATIONS
1. Respiratory tract obstruction by pseudomembranes:
bronchoscopy or intubation and mechanical ventilation
2. Toxic Cardiomyopathy:
-in 10-25% of patients
-responsible for 50-60% of deaths
-the risk for significant complications correlates directly with the extent
and severity of exudative local oropharyngeal disease as well as delay in
administration of antitoxin
-Tachycardia out of proportion to fever
-prolonged PR interval and changes in the ST-T wave
-Elevation of the serum aspartate aminotransferase concentration closely
parallels the severity of myonecrosis

17. 3. Toxic Neuropathy:
 Acutely or 2-3 wk after: hypoesthesia and soft palate paralysis
 Afterwards weakness of the posterior pharyngeal, laryngeal, and facial
nerves : a nasal quality in the voice, difficulty in swallowing and risk for
aspiration
 Cranial neuropathies (5th wk): oculomotor and ciliary paralysis-
strabismus, blurred vision, or difficulty with accommodation
 Symmetric polyneuropathy (10 days to 3 mo): motor deficits with
diminished deep tendon reflexes
 Monitoring for paralysis of the diaphragm muscle
Recovery from the neuritis is often slow but usually
complete. Corticosteroids are not recommended.

18. TREATMENT
1. Antitoxin:
 Mainstay of therapy
 Neutralizes only free toxin, efficacy diminishes with elapsed time
 Antitoxin is administered as a single empirical dose of 20,000-120,000 U
based on the degree of toxicity, site and size of the membrane, and
duration of illness
2. Antimicrobial therapy
 Halt toxin production, treat localized infection and prevent transmission
of the organism to contacts
 erythromycin (40-50 mg/kg/day 6 hrly [PO] or [IV]), aqueous
crystalline penicillin G (100,000-150,000 U/kg/day 6 hrly IV or [IM]),
or procaine penicillin (25,000-50,000 U/kg/day 12 hrly IM) for 14 days

19.  Elimination of the organism should be documented by
negative results of at least 2 successive cultures of specimens
from the nose and throat (or skin) obtained 24 hr apart after
completion of therapy
 Prognosis: depends on the virulence of the organism
(subspecies gravis), patient age, immunization status, site of
infection and speed of administration of the antitoxin
 The case fatality rate of almost 10% for respiratory tract
diphtheria
 At recovery, administration of diphtheria toxoid is indicated to
complete the primary series or booster doses of immunization,
because not all patients develop antibodies to diphtheritic
toxin after infection

20. PREVENTION
Asymptomatic Case Contacts:
 Antimicrobial prophylaxis -erythromycin (40-50 mg/kg/day divided qid
PO for 10 days) or a single injection of benzathine penicillin G
(600,000U IM for patients <30 kg, 1,200,000U IM for patients ≥30 kg)
 Diphtheria toxoid vaccine-to immunized individuals who have not
received a booster dose within 5 yr. Children who have not received their
4th dose should be vaccinated. Those who have received fewer than 3
doses of diphtheria toxoid or who have uncertain immunization status are
immunized with an age-appropriate preparation on a primary schedule
Asymptomatic Carriers:
 Same+Repeat cultures are performed about 2 wk after completion of
therapy. if results are positive, an additional 10-day course of oral
erythromycin should be given and follow-up cultures performed