Diphtheria

DR.MASHUK
Diphtheria
❑ Introduction
❖ Diphtheria is an acute toxin-mediated disease caused by Corynebacterium
diphtheriae. Three biotypes (ie, mitis, gravis, intermedius), each capable of
causing diphtheria, are differentiated by colonial morphology, hemolysis,
and fermentation reactions.
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❑ Types
❖ There are two types of diphtheria-
⮚ Respiratory -Respiratory diphtheria involves the nose, throat and tonsils.
⮚ Cutaneous- Cutaneous diphtheria involves the skin.
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❑ Transmission
❖ Direct person- to-person transmission by intimate respiratory and physical
contact. Cutaneous lesions are important in transmission.
❖ Incubation period: 2–5 days.
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❑ Risk factors
❖ Cutaneous diphtheria is most often associated with the homeless and those
with poor personal and community hygiene.
❖ Poor living conditions and lack of immunisation, especially where there is
not an immunisation programme, increase risk.
❖ Adults are at risk as they lose protection from childhood vaccines unless
they have boosters. 70% of older adults are at risk.
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❑ Pathophysiology
❖ Diphtheria organisms usually remain in the superficial layers of skin
lesions or respiratory mucosa, inducing local inflammatory reaction. The
organism's major virulence lies in its ability to produce the potent
polypeptide exotoxin, which inhibits protein synthesis and causes local
tissue necrosis.
❖ Diphtheriae toxin, which is secreted by toxigenic strains of C diphtheriae,
is a single polypeptide . Toxigenic strains of C diphtheriae carry the tox
structural gene found in lysogenic corynebacteriophages beta-tox +,
gamma-tox +, and omega-tox +.
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❖ 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 adherent
pseudomembrane. Removal is difficult and reveals a bleeding edematous
submucosa. Paralysis of the palate and hypopharynx is an early local effect
of the toxin. Toxin absorption can lead to necrosis of kidney tubules,
thrombocytopenia, cardiomyopathy, and demyelination of nerves.
Because cardiomyopathy and demyelination of nerves can occur 2-10
weeks after mucocutaneous infection.
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❖ In the classic description of diphtheria, the primary focus of infection is
the tonsils or pharynx in more then 90% of patients; the nose and larynx
are the next most common sites. After an average incubation period of 2-4
days, local signs and symptoms of inflammation develop. Fever is rarely
higher than 39°C.
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❑ Clinical presentation
❖ Severity of disease due to C diphtheriae depends on the site of infection,
the immunization status of the patient, and the dissemination of toxin
(which is influenced by administration of antitoxin). Initial infection
usually is localized and is categorized by the site of involvement.
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❖Tonsils and pharynx: Tonsillar and pharyngeal diphtheria are most
common; symptoms begin with a sore throat. Fever, if it occurs, is
usually lower than 102°F, and malaise, dysphagia, tachycardia and
headache are prominent features. In tonsillar bed pseudomembranes is
formed which looks like greyish-green membranes with well defined edge.
⮚ In individuals with diphtheria infection who are not immune, membrane
formation begins after the 2-day to 5-day incubation period and grows to
involve the pharyngeal walls, tonsils, uvula, and soft palate. The
membrane may extend to the larynx and trachea, causing airway
obstruction and eventual suffocation.
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⮚ Underlying tissue of the throat and neck becomes edematous, and
lymphadenopathy develops. Marked edema of the neck may lead to a
bull-neck appearance with a distinct collar of swelling; the patient
throws the head back to relieve pressure on the throat and larynx. Erasure
edema associated with pharyngeal diphtheria obliterates the angle of the
jaw, the borders of the sternocleidomastoid muscle, and the medial border
of the clavicles. Swallowing may be made difficult by unilateral or
bilateral paralysis of the muscles of the palate.
⮚ If toxin production is unopposed by antitoxin and severe disease occurs,
early localized signs and symptoms give way to circulatory collapse,
respiratory failure, coma, and death.
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❖ Larynx: In a minority of patients, the larynx is the initial site of infection,
with initial presenting symptoms similar to laryngotracheobronchitis from
other causes. Initial hoarseness may progress to loss of voice and severe
respiratory tract obstruction. Initially, nasal diphtheria may present as a
common viral upper respiratory tract infection. A foul odor may develop
with nasal discharge, excoriation of nose and pseudomembranes over
nasal septum. This form of diphtheria is most common in infants.
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❖ Skin: Cutaneous diphtheria may occur at one or more sites, usually
localized to areas of previous mild trauma or bruising. It is more common
in tropical climates. Pain, tenderness, and erythema at the site of infection
progress to ulceration with sharply defined borders and formation of a
brownish gray membrane.
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❖ Other sites: Additional sites of infection have included the external ear, the
eye (usually the palpebral conjunctivae), and the genital mucosa.
Septicemia caused by C diphtheriae is rare but universally fatal.
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❑ Clinical feature(In short way)
⮚ Sore throat .
⮚ Hoarseness of voice.
⮚ Dysphagia .
⮚ Cervical lympadenopathy .
⮚ A thick, gray membrane covering throat and tonsils(green membrane on
the tonsils).
⮚ Dyspnoea.
⮚ Nasal discharge.
⮚ Fever and chills.
⮚ Malaise.
⮚ Myocarditis .
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❑ Diagnostic criteria
❖ Greyish-green pseudomembrane
❖ Sore throat
❖ Myocarditis+neuritis
❖ Positive culture
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❑ Differential Diagnoses
⮚ Epiglottitis.
⮚ Herpes Simplex Virus Infection.
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❑ Investigations
⮚ Bacterial culture(throat swab).
⮚ CBC
⮚ BUN, Sr.creatinine.
⮚ Polymerase chain reaction.
⮚ ECG in cardiac cases/Echo
Diphtheria
❑ Management
❑ General measures
❖ Barrier nursing is required. The disease can be spread by contact with
clothing and bedlinen.
❖ Cutaneous lesions should be thoroughly cleaned with soap and water.
Antitoxin is of no value for cutaneous diphtheria,
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❑ Pharmacological
❖ Antitoxin should be given within 48 hours of the onset of symptoms,
which can be before bacteriological confirmation:
▫ Myocarditis can treat with corticosteroids like prednisolone 1-2
mg/kg/day for 2 wks but it doesn’t show any good response.
▫ The antitoxin is derived from horse serum and so reactions are common
and sensitivity testing is necessary.
▫ Dosage is determined by the site of infection, and severity.
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❖ Neutralisation of toxin: Antitoxin single dose(ADS i.v inj 10000 and
20000 IU amp).
⮚ 1.Mild nasal or pharyngeal- 40,000 units.
⮚ 2.Moderate pharyngeal- 80,000 units.
⮚ 3.Severe pharyngeal or laryngeal- 120,000 units.

❖ Test for sensitivity must be performed prior to administartion.

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❖ Benzylpenicillin IV is followed by oral penicillin V for 10 to 14
days(600mg i.v 6hourly). Erythromycin(50mg/kg/day in 4 divided dose
for 7 to 10days) is used with penicillin allergy.
❖ Patients should be immunised in the convalescent stage because clinical
infection does not always induce adequate levels of antitoxin. They should
receive a complete course or a reinforcing dose according to their age and
immunisation history.
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❑ Management of contacts
⮚ Swab all close contacts, treating with antibiotics and confining to home
those with positive cultures.
⮚ Contacts need treatment to eliminate both incubating disease and to
prevent carriage to others.
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❑ The recommended regimen for close contacts is either:
❖ A single dose of IM benzylpenicillin 600,000 units for children less than 6
years old or 1.2 million units for anyone of 6 years or older.
❖ Or, 7 days' erythromycin 125 mg every 6 hours for children under 2 years
of age, or 250 mg every 6 hours for children aged 2 to 8 years, or 250 mg
or 500 mg every 6 hours for anyone over 8 years of age.
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❑ Complications
❖ Paralysis:
This often involves the muscles of the palate and the hypopharynx is seen
in 10-20% of patients, beginning as early as the first 10 days of illness.
❖ Difficulty swallowing and nasal speech:
These are often the first signs of neurological involvement.
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❖ Involvement of other cranial nerves:
This may be delayed until as late as 7 weeks after infection and produce
oculomotor paralysis and blurred vision. Diffuse, usually bilateral, motor
function deficits resulting from involvement of the anterior horn cells of
the spinal cord may be seen as late as 3 months after initial disease, with
progression of weakness either from proximal-to-distal regions or, more
commonly, from distal-to-proximal regions.
❖ Diaphragmatic paralysis:
This will result if the phrenic nerve is involved. This may occur at any
time between the 1st and 7th weeks of illness.
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❖ Cardiac complications:
These may arise during the first 10 days of the illness or they may be
delayed for 2 or 3 weeks by which time pharyngeal disease is subsiding:
The first sign of cardiac involvement is tachycardia disproportionate to the
degree of fever. Fever is rarely above 39°C.
⮚ Heart block of first, second or third degree may be seen.
⮚ Atrioventricular dissociation and ventricular tachycardia can develop and
congestive heart failure may result.
⮚ Echocardiogram may demonstrate dilated or hypertrophic cardiomyopathy.
⮚ In patients who survive, cardiac muscle regeneration and interstitial
fibrosis lead to recovery of normal cardiac function, unless toxic damage
has led to a permanent arrhythmia.
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❖ Airway obstruction:
This is caused by the diphtheritic membrane and peripharyngeal oedema
causing the 'strangling', and emergency tracheostomy may be required.
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❑ Prognosis
⮚ Overall there is a 5-10% mortality rate, but it is up to 20% in those
younger than 5 years and older than 40 years.
⮚ Recovery is slow and particular caution should be advised after
myocarditis.
⮚ Complete recovery from neurological damage is usual in those who
survive.
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❑ Prevention
❖ Diphtheria Vaccination.
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❑ Available vaccines
❖ Diphtheria vaccines are available in 2 strengths according to dose of
toxoid:
⮚ High-dose - vaccines contain >30 IU of diphtheria toxoid and are used to
achieve satisfactory primary immunisation of children - as in DTaP
vaccine (capital D = high-dose).
⮚ Low-dose - vaccines contain only 2 IU of toxoid and are used for primary
immunisation of those aged over 10 years and for subsequent boosters
(lower case d signifies low-dose as in dTaP).
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❖ Monovalent diphtheria vaccine is not available. Vaccination should
only given as a component of the following combination products:
⮚ Diphtheria/tetanus/acellular pertussis/inactivated polio/Haemophilus
influenzae type b vaccines (DTaP/IPV/ Hib).
⮚ Diphtheria/tetanus/acellular pertussis/inactivated polio vaccines
(DTaP/IPV or dTaP/IPV).
⮚ Tetanus/ diphtheria/inactivated polio (Td/IPV).