DIPHTHERIA

Amuja Precious O.
CLI/2017/037
OUTLINE
• Introduction
• History
• Aetiology
• Epidemiology
• Pathogenesis
• Clinical manifestations
• Diagnosis
• Management
• Prevention
• References
Introduction
• Diphtheria is an acute infectious disease caused by
toxigenic strains of Corynebacterium diptheriae.
• It is a serious bacterial infection that usually affects the
mucous membranes of the nose and throat.
• In the past, the disease was called a killer disease
because there was no treatment.
• It was the cause of high mortality especially in children.
History
• Named in 1826 by French physician Pierre Bretonneau.
• The name was derived from Greek word “diphthera” which
means leather. This is because of the characteristic formation of
the gray, leathery, sheath-like membrane that grows on the
tonsils and throat.
• In 1884, Friedrich Loeffler discovered the causative organism.
• In 1890s, the physician Emil von Behring developed an antitoxin
that did not kill the bacterium, but neutralized the toxic poison it
releases into the body.
• The first successful vaccine for diphtheria was developed in
1913 by Behring.
Aetiology
• Diphtheria is caused by Corynebacterium diphtheriae and
less commonly by toxigenic strains of Corynebacterium
ulcerans.
• They are aerobic, nonencapsulated, non–spore-forming,
mostly nonmotile, pleomorphic, Gram-positive bacilli.
• Differentiation of C. diphtheriae from C. ulcerans is based on
urease activity, because C. ulcerans is urease-positive.
• Their pathogenicity is associated with the production of
powerful exotoxin, the diphtheria toxin by which they produce
the local and systemic effects of the disease.
Aetiology

• Four strains/biotypes of C. diphtheriae have been associated

with manifest disease namely: Gravis, Mitis, Belfanti,
Intermedius.
• They are differentiated by their colonial morphology, hemolysis,
and fermentation reactions.
• The intermedius strain is known to account for most of the
systemic manifestations of the disease because of its propensity
for a higher level of exotoxin elaboration.
• C. ulcerans is frequently associated with cutaneous diphtheria
but also occasionally cause respiratory symptoms.
Aetiology
EPIDEMIOLOGY
• Diphtheria was once a major cause of mortality globally,
particularly in urban areas with crowded living conditions
and poor sanitation. However, widespread vaccination
has reduced its incidence in many parts of the world.
• It remains endemic in certain regions of the world where
vaccination coverage is low or interrupted, particularly in
sub-Saharan Africa and Southeast Asia.
• Periodic outbreaks may occur in these regions especially
among unvaccinated or under-vaccinated populations.
EPIDEMIOLOGY
• Diphtheria can affect individuals of any age, but it is most
common in children under the age of 5 years who have not
been fully vaccinated. Older adults who have not received
booster vaccinations may also be at risk, particularly in areas
where vaccination coverage is low.
• In the 1920s, more than 125,000 diphtheria cases, with 10,000
deaths, were reported annually in the United States. With
widespread use of diphtheria toxoid in the United States after
World War II, incidence declined steadily through the late
1970s. Since then, ≤5 cases have occurred annually in the
United States,
EPIDEMIOLOGY
• In Nigeria, there was an outbreak in Borno, north-eastern
Nigeria in 2011 with a total of 98 cases, and 21 deaths
(case fatality ratio was 21.4%).
• Since December 2022, Nigeria has been dealing with a
severe outbreak of Diphtheria, resulting in 471 deaths,
over 7,400 confirmed cases and 12,000 suspected cases
as of 28 September 2023 affecting 21 of the 36 states and
the FCT.
EPIDEMIOLOGY
Mode of transmission
• Diphtheria is spread from person to person, usually
through respiratory droplets like from coughing or
sneezing.
• Can also be transmitted directly to susceptible persons
from infected cutaneous lesions.
• Transmission by objects (cups, thermometers, toys etc.)
contaminated by the nasopharyngeal secretions of
patients is also possible.
RISK FACTORS
• The risk factors for diphtheria include;
1) Inadequate vaccination coverage
2) Lack of access to healthcare services
3) Overcrowded living conditions
4) Poor hygiene practices
5) Travel to endemic regions
6) Immunodeficiency/ Underlying health conditions
PATHOGENESIS
The pathogenesis of diphtheria is primarily driven by the production and effects of the
diphtheria toxin, which is elaborated by the bacterium, Corynebacterium diphtheriae.
The pathogenic mechanism involve:
• Colonization: C. diphtheriae typically colonizes the mucous membranes of the
upper respiratory tract, particularly the throat and tonsils. It can also colonize other
mucosal surfaces, such as the skin and conjunctiva.
• Toxin Production: Certain strains of C. diphtheriae carry a bacteriophage (a virus
that infects bacteria) that encodes the gene for the diphtheria toxin. When the
bacterium is infected with the bacteriophage, it can produce and release the toxin
into the surrounding tissues.
PATHOGENESIS
• Toxin Action: The diphtheria toxin is a 62 kDa
polypeptide exotoxin composed of two subunits (A and B)
• The B fragment binds to a receptor on the surface of the
susceptible host cell, which proteolytically cleaves the
membrane lipid layer enabling segment A to enter.
• Fragment A inhibits an amino acid transfer from RNA
translocase to the ribosomal amino acid chain, thus
inhibiting protein synthesis and causing tissue necrosis.
PATHOGENESIS
 Local effect of diphtheric toxin:
• Paralysis of the palate and hypopharynx.
• Pseudomembrane formation: a thick, grayish membrane
composed of dead tissue, bacteria, inflammatory cells,
and fibrin. This pseudomembrane can adhere to the
mucosal surfaces of the throat, tonsils, and nearby
structures, leading to airway obstruction and difficulty
breathing.
PATHOGENESIS
 Systemic effects (Toxin absorption):
• Myocarditis: May occur any time but frequent from end of
first week to 5–6 weeks. Signs of myocarditis are: cardiac
arrhythmia , cardiomegaly , muffled heart sound,
congestive cardiac failure.
• Renal tubular necrosis.
• Neuropathy (demyelination of nerves).
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
 Pharyngotonsillar
 Laryngeal or laryngotracheal
 Skin, eye or genitalia
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.
CLINICAL MANIFESTATIONS
 Pharyngotonsillar diphtheria (faucial)
• Sore throat is the universal early symptom.
• Other symptoms include fever, dysphagia, malaise, or
headache.
• Unilateral or bilateral tonsillar pseudomembrane
formation, may extend to involve the uvula, soft palate,
posterior oropharynx, hypopharynx, or glottic areas.
• Underlying soft tissue edema and cervical
lymphadenopathy: characteristic "bull-neck appearance".
CLINICAL MANIFESTATIONS
 Laryngeal diphtheria
• There's a significant risk of suffocation because of local
soft tissue edema and airway obstruction by the
dislodged diptheritic membrane.
• Hoarseness and a worsening stridor are the symptoms.
CLINICAL MANIFESTATIONS
 Cutaneous diphtheria
• Is an indolent, nonprogressive infection characterized by
a superficial, ecthymic, nonhealing ulcer with a gray-
brown membrane.
• Extremities are more often affected than the trunk or
head. Pain, tenderness, erythema, and exudate are
typical.
CLINICAL MANIFESTATIONS
 Infection at Other Sites
• C. diphtheriae occasionally causes mucocutaneous
infections at other sites, such as the ear (otitis externa),
the eye (purulent and ulcerative conjunctivitis), and the
genital tract (purulent and ulcerative vulvovaginitis).
Diagnosis
The diagnosis of diphtheria involves a combination of clinical evaluation, and
aboratory testing,.
• Clinical evaluation
a) Detailed history (including symptoms, recent travel, exposure to individuals with
diphtheria, vaccination status, and any underlying health conditions).
b) Physical examination with particular attention to the upper respiratory tract.
• Laboratory Testing
a) Culture: collect specimens from the throat, nasopharynx, or other affected sites
for bacterial culture.
b) Toxin detection: Test clinical specimens or bacterial isolates for the presence of
the diphtheria toxin using specialized assays, such as the Elek test or enzyme-
linked immunosorbent assay (ELISA). These tests detect the toxin produced by
Corynebacterium diphtheriae and can help confirm the diagnosis of diphtheria.
Differential diagnosis
 Faucial Diphtheria
• Acute streptococcal pharyngitis
– Absence of a gray, thick pseudomembrane which is
characteristic of diphtheria.
• Oral thrush
– Thrush is typically easily scraped off, unlike the
pseudomembrane of diphtheria.
• Infectious mononucleosis
– Presence of atypical lymphocytes on a blood smear and a
positive Monospot test.
• Agranulocytosis
– Profound neutropenia, absence of pseudomembrane.
• Viral membranous tonsillitis.
– Viral etiology confirmed through specific viral testing, typically
less severe systemic symptoms compared to diphtheria.
Differential diagnosis
 Laryngeal diphtheria
• Croup
– neck X-ray may show the "steeple sign.
– Gradual onset with preceding upper respiratory infection
symptoms, absence of pseudomembrane.
• Laryngotracheobronchitis
– neck and chest X-rays may show subglottic narrowing.
– More severe progression from croup, no pseudomembrane,
and typical viral etiology.
• Peritonsillar abscess
– Unilateral swelling and abscess formation, absence of
pseudomembrane, localized to tonsillar region.
• Retropharyngeal abscess
– Pain with neck extension, prominent posterior pharyngeal
swelling, and absence of pseudomembrane.
• Foreign body.
– History of sudden onset, focal findings on imaging, no
infectious signs or pseudomembrane.
 Differential diagnosis
 Nasal diphtheria
• Common cold
– Clear to yellow nasal discharge, absence of the characteristic
grayish pseudomembrane seen in diphtheria.
• Snuffle (syphilitic rhinitis)
– Associated with congenital syphilis, presence of other stigmata
of congenital syphilis, such as skin rash, hepatosplenomegaly,
and bone abnormalities.
• Foreign body
– Unilateral symptoms, foul-smelling discharge, and history of
foreign body insertion, no pseudomembrane.
MANAGEMENT

The broad principles of management include:

• Neutralization of free circulating toxin by administration of
antitoxin
• Antibiotics to eradicate bacteria
• Supportive and symptomatic treatment
• Management of complications
MANAGEMENT
 Antitoxin:
• Hyper-immune diphtheria antitoxin serum of equine origin.
• Mainstay of therapy.
• Neutralizes only free toxin, efficacy diminishes with elapsed time
• Antitoxin is administered as a single empirical dose of 20,000- 40000 units
IV or IM.
 Antimicrobial therapy
• Halts 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
• 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 (serotype
gravis is the most virulent), patient age, immunization status, site of
infection and speed of administration of the antitoxin.
• The case fatality rate is 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.
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
VACCINE
• Active immunization in early infancy with DTaP vaccine
containing diphtheria, tetanus toxoid as well as acellular
pertussis at weeks 6, 10 and 14.
• WHO recommends a 3-dose series of diphtheria toxoid-
containing vaccines in the first year of life beginning at 6
weeks of age and advises that 3 booster doses of
diphtheria toxoid-containing vaccine are provided during
childhood and adolescence to ensure long-term
protection.
References
• Illustrated Textbook of Pediatrics - Md. Salim Shakur
• Nelson Textbook of Paediatrics
• Paediatrics and Child Health in a Tropical Region -
Azubuike & Nkanginieme
• Medscape
• https://ncdc.gov.ng/diseases/factsheet/68
• https://www.who.int/emergencies/disease-outbreak
• Diphtheria is a serious bacterial infection. It can cause
severe complications like heart inflammation, kidney
damage, and nerve issues.
• Risk factors include poor vaccination, hygiene,
overcrowding, and travel to endemic regions.
• Treatment involves quick administration of antitoxin and
antibiotics.
• Prevention relies on DTaP vaccination, stressing early
detection and public health efforts to control outbreaks.