1. D iphtheria Sorokhan V.D.

, MD, PhD Bukovinian State Medical University Department of

infectious diseases and epidemiology
2. Definition

C . diphtheriae infection is typically characterized by a local inflammation, usually in the

upper respiratory tract, associated with toxin-mediated cardiac and neural disease.

3. Etiology

Corynebacteria are gram-positive, catalase-positive, aerobic or facultatively anaerobic,

generally nonmotile rods.

4. Pathophysiology The toxin is a single polypeptide with an active (A) domain, a binding
(B) domain, and a hydrophobic segment known as the T domain, which helps release the active
part of the polypeptide into the cytoplasm. T he toxin is responsible for many of the clinical
manifestations of the disease.
5. Pathophysiology In most cases, C diphtheriae infection grows locally and elicits toxin
rather than spreading hematogenously. The characteristic membrane of diphtheria is thick,
leathery, grayish-blue or white and composed of bacteria, necrotic epithelium, macrophages, and
fibrin. The membrane firmly adheres to the underlying mucosa; forceful removal of this
membrane causes bleeding. The membrane can spread down the bronchial tree, causing
respiratory tract obstruction and dyspnea.
6. Epidemiology

Humans are the only known reservoir for the disease. The primary modes of
dissemination are by airborne respiratory droplets, direct contact with droplets, or
infected skin lesions. Asymptomatic respiratory carrier states are believed to be important
in perpetuating both endemic and epidemic disease. Immunization reduces the likelihood
of carrier status.

7. Pathology
o At autopsy, the heart is pale brown, soft, and enlarged, with a characteristic
streaky appearance.
o Neutral fat accumulations are observed in approximately 50% of patients, with
extensive hyaline degeneration and necrosis with inflammatory changes.
o The coronary vessels, valves, endocardial surfaces, and epicardial surfaces are
unaffected.
o In fatal cases, the kidneys demonstrate interstitial edema and necrosis at autopsy.
8. Mortality/Morbidity

Mortality rates are highest at the extremes of age and in insufficiently immunized
persons. However, even partial immunization confers a reduced risk of severe disease.
Death usually occurs within the first week, either from asphyxia or heart disease.

9. History

Following an incubation period of 2-4 days, patients typically report upper respiratory
tract symptoms (eg, nasal discharge, sore throat). The posterior pharynx and tonsillar
pillars are most often involved. Onset is often sudden, with low-grade fevers, malaise,
and membrane development on one or both tonsils, with extension to other parts of the
respiratory system. The toxic effect in the myocardium characteristically occurs within 12 weeks following onset of infection, often when the upper respiratory tract symptoms
are improving. Manifestations are due to arrhythmias and congestive heart failure (CHF).

10. History

Neurological symptoms can occur immediately or after several weeks. Bulbar symptoms
generally occur within the first 2 weeks after disease onset and can range from mild
symptoms (eg, difficulty swallowing) to bilateral symmetric paresis of the palatal and
ocular muscles. The bulbar symptoms may remit or progress to paralysis of the proximal
and then distal skeletal muscles over the next 30-90 days. Although recovery can be very
slow, patients generally regain complete neurologic function. Secondary complications
include aspiration from bulbar paralysis and bronchopneumonia from respiratory muscle
dysfunction.

11. Physical

The membrane usually is grayish-white, although it can become blackish or greenish with
necrosis.

12. Physical

Respiratory signs :

The extent of disease correlates with the severity of symptoms. Extension of the
membrane to the posterior pharyngeal wall, soft palate, or nasopharynx is associated with
profound malaise, weakness, cervical adenopathy, and swelling, which can distort the
airway and cause stridor.

13. Physical

Cardiac signs :

Subtle evidence of myocarditis may occur in many patients, but 10-25% of patients
develop clinical cardiac dysfunction.

 14. Physical

Nervous system signs :

Signs of cranial nerve dysfunction can occur within a few days of disease onset, with
paralysis of the soft palate and posterior pharyngeal wall causing dysphagia and
regurgitation.

Although the motor component is usually affected most severely, both sensory and motor
nerves are affected by the peripheral neuritis that occurs later.

The symptoms start in the proximal muscle groups of the extremities and spread distally.

15. Physical

Skin signs :

C . diphtheriae can cause skin infections with nonhealing ulcers.

A vesicle or pustule develops initially and progresses to one or more punched-out lesions
that measure from a few millimeters to several centimeters, with curved elevated
margins.

The lesions are initially painful and may be covered with eschar.

After a few weeks, the lesions become painless and often have a serosanguineous
exudate.

16. Differential Diagnoses

Amyloidosis, Bacterial p haryngitis, Candidiasis , Viral p haryngitis, Dilated c

ardiomyopathy, Bacterial p neumonia, Infectious m ononucleosis , Upper r espiratory i
nfection , Infective e ndocarditis , Peritonsillar a bscess

17. Workup
o The diagnoses of C . diphtheriae infection can be confirmed definitively by
culture on blood agar or selective tellurite media, which inhibits the growth of
normal oral flora; C . diphtheriae develops a black colony with a characteristic
gray-brown halo.
o Traditionally, toxin production was demonstrated by injecting toxin material into
mice and watching to see if they died.
18. Medication

For C . diphtheriae infection, the therapy is antitoxin and antibiotic treatment. Many
antibiotics are effective, including penicillin, erythromycin, clindamycin, rifampin, and
tetracycline.

19. Diphtheria antitoxin (DAT)

o Dose given depends on site of infection and length of time patient is
symptomatic :
o Laryngeal or pharyngeal disease of <48 h duration: 20,000-40,000 U IV over 60
min .
o Nasopharyngeal infection: 40,000-60,000 U IV .
o Extensive disease of >3 d duration or any patient with neck swelling: 80,000100,000 U IV . May be given IM for mild-to-moderate disease
o Test all patients with a 1:10-1:100 dilution of DAT SC; if an immediate reaction
occurs, administer epinephrine; hypersensitivity to horse serum not
contraindication to antitoxin injection; desensitize subjects with increasing doses
of diluted DAT
20. Antibiotics
o Erythromycin - 500 mg PO/IV q6h for 14 d if tolerated .
o Vancomycin - 1 g IV infused over 1 h q12h .
o Rifampin - 600 mg PO qd or divided bid .
21. Prevention

C hildhood immunization is the prevention method of choice.

Diphtheria/tetanus/pertussis (DTP) vaccine, given at ages 2, 4, and 6 months; at age 1518 months; and at least 5 years later (age 4-6 y) is the immunization regimen
recommended.

22. Tests for self-control

Which statement about diphtheria is correct?

o diphtheria is a lower respiratory tract illness
o diphtheria is characterized by sore throat, high fever , and an adherent membrane
on the tonsils , pharynx , and/or nasal cavity

o a milder form of diphtheria can be restricted to the skin

o diphtheria is an acute toxin-mediated disease caused by nondiphtherial
corynebacteria
23. Tests for self-control

Corynebacterium diphtheriae are:

o gram-negative, catalase-negative, aerobic or facultatively anaerobic, generally
nonmotile rods
o gram-positive, catalase-negative, anaerobic or facultatively anaerobic, generally
motile rods
o gram-negative, catalase-positive, anaerobic or facultatively anaerobic, generally
motile rods
o gram-positive, catalase-positive, aerobic or facultatively anaerobic, generally
nonmotile rods

24. Tests for self-control

Diphtheria is:
o anthroponosis
o zoonosis
o anthropozoonosis

25. Tests for self-control

Corynebacterium diphtheriae are transmitted by:

o sexual route
o transmissive route
o air-borne route
o parenteral route
o food-borne route

 26. Tests for self-control

Corynebacterium diphtheriae gain entry to the body through

o upper respiratory tract
o skin
o genital tract
o eyes
o all mentioned above

27. Tests for self-control

Which statement about characteristic membrane of diphtheria is correct?

o membrane is thin, leathery, grayish-blue or white
o membrane of diphtheria is composed of virus, necrotic epithelium, macrophages,
and fibrin
o the membrane softly adheres to the underlying mucosa
o forceful removal of this membrane causes bleeding
o the membrane can not spread down the bronchial tree, causing respiratory tract
obstruction and dyspnea

28. Tests for self-control

The toxin-induced manifestations of diphtheria involve mainly:

o heart, brain, liver
o heart, kidneys, peripheral nerves
o heart, liver, peripheral nerves
o all mentioned above

29. Tests for self-control

The incubation period of diphtheria is:

o 1-2 days
o 2-4 days
o 3-6 days
o 4-8 days
30. Tests for self-control

Which statement about respiratory signs of diphtheria is correct?

o patients typically report lower respiratory tract symptoms (eg, cough)
o the posterior pharynx and tonsillar pillars are seldom involved
o onset is often gradual, with low-grade fevers, malaise, and membrane
development on one or both tonsils, with extension to other parts of the
respiratory system
o the membrane usually is grayish-white, although it can become blackish or
greenish with necrosis

31. Tests for self-control

Which statement about respiratory signs of diphtheria is incorrect?

o nasal infection may present as serosanguineous or seropurulent drainage
o with tonsillar and pharyngeal infection, exudates coalesce to form the
characteristic pseudomembrane of diphtheria
o t he extent of disease does not correlate with the severity of symptoms.
o edema and membrane formation require intubation