|A 10-year old male child was
brought to the hospital emergency with high fever and chills,
malaise, sore throat, headache, dysphagia and dyspnea. On
examination cervical lymphadenopathy was noted along with
grayish white membrane in the throat.
What is your diagnosis?
Clinically, this appears to be a case of pharyngeal or faucial
diphtheria. Differential diagnoses include peritonsillar abscess,
pharyngitis, epiglottitis, infectious mononucleosis, vincent's
angina, oropharyngeal candidiasis and herpes simplex virus infection.
What is pseudomembrane?
A thick, gray, leathery pseudomembrane composed of a mixture of
dead cells, fibrin, RBCs, WBCs, and organisms forms locally (tonsillar,
pharyngeal) or widely covering the entire tracheobronchial tree.
The membrane may cover the tonsils, soft palate, oropharynx,
nasopharynx, and uvula. Attempts at scraping the pseudomembrane
causes bleeding of the underlying mucosa.
What is the specimen collected and how is the condition
diagnosed with the aid of laboratory?
Nasopharyngeal or pharyngeal swabs must be carefully collected
using sterile cotton swabs. At least two sample must be collected,
one for microscopy and the other for smear. Smear may also be
taken from nose and beneath the membrane but care must be taken
not to bleed. Microscopic examination includes a Gram stained
smear. If diphtheria is suspected and gram positive bacilli are
seen, a special staining technique such as Albert's should be
performed. Other way of demonstrating diphtheria bacilli include
Immunofluorescent staining. Since microscopy does not provide
confirmatory results, culture must be performed. The specimen
should be inoculated on Blood agar. If diphtheria is suspected,
Loeffler's serum slope and Potassium tellurite agar, Blood
tellurite agar (Hoyle's agar/McLeod's agar) or Tinsdale agar should be used. The
culture plates should be inoculated at 37oC for 24-48 hours. Selective media may be incubated for 48 hours. If Corynebacterium diphtheriae is identified by biochemical tests,
its biotype (gravis, mitis, or intermedius) is determined and the toxigenicity
test must be performed using in-vivo or in-vitro methods.
What is your observation?
Gram stained smear reveals few pus cells and gram positive
club-shaped bacilli in Chinese letter pattern.
smear reveals green coloured bacilli in L, V or chinese letter
arrangement with few bluish black metachromatic granules throughout
the bacilli and especially more so at the bacilli. Blood agar
revealed small, greyish, smooth, non-hemolytic colonies. Upon
further incubation colonies have dull granular center and
glistening periphery and a lighter ring at the edge, resembling
frog's egg. Tellurite containing medium showed small black colonies
with a black halo.
White-grayish colonies are obtained in six hours on Loeffler's serum slope.
It is catalase positive, ferments glucose and maltose but not
sucrose in Hiss serum water, reduces nitrate but does not
hydrolyze urea. Neither glycogen nor starch is fermented.
What is your identification?
The organism isolated is Corynebacterium diphtheriae of the
What is the pathogenesis of diphtheria?
Asymptomatic carriers or patients with active infections are chief
source of infection. Fomites used by children also serves to
Infections occur via respiratory droplets or contact with
nasopharyngeal secretions. Overcrowding, poor health, and
substandard living conditions facilitate the spread of the
disease. C. diphtheriae is not an invasive organism. It infects
the superficial layers of the respiratory tract causing local
tissue inflammatory reaction followed by tissue necrosis. The
occurrence of systemic disease depends on the production of a
potent exotoxin by tox+ strains. Only the strains lysogenised by
beta phage can produce the toxin. Expression of the gene is
regulated by the bacterial host and is iron dependent. Increased
toxin production occurs in the presence of low concentrations of
iron. The diphtheria toxin is a
62,000-dalton polypeptide composed of two fragments (A and B). The
B fragment binds to a receptor on a susceptible cell and undergoes proteolytic cleavage, thus facilitating the entry of segment A,
which inhibits peptide chain elongation by inactivating EF-2. The
process ultimately functions to inhibit protein synthesis in
mammalian cells. Paralysis of the palate and hypopharynx is an
early local effect of the toxin. The locally produced toxin is then carried via lymphatics and blood vessels to susceptible tissues. It exhibits a
predilection for the myocardium and the cells of the nervous
system. Toxin absorption can lead to necrosis of kidney tubules,
thrombocytopenia, cardiomyopathy, and demyelination of nerves. Rarely, non-toxigenic strains have caused invasive
Which are the various types of diphtheria?
The site of infection can be faucial, laryngeal, nasal, otitic,
conjunctival, genital or cutaneous. Faucial type is the commonest
type and may vary from mild catarrhal inflammation to widespread
involvement. In malignant or hypertoxic diphtheria, there is
severe toxemia with marked submandibular cervical lymphadenopathy (bull neck). Death may
occur due to circulatory failure and paralytic sequelae may occur
in those who recover. Septic diphtheria manifests as ulceration,
cellulitis and even gangrene around pseudomembrane. Hemorrhagic
diphtheria is characterized by bleeding from the edge of the
membrane, epistaxis, conjunctival hemorrhage, purpura and
Which are the various complications of diphtheria?
Asphyxia can occur due to mechanical obstruction by the
pseudomembrane and its aspiration can suffocate the patient to
death. Infection with the gravis strain is associated with higher
mortality rates. Myocarditis can lead to acute circulatory
collapse. Other complications include cardiac dilatation and
failure, mycotic aneurysm, endocarditis, rhythm disturbances ,
secondary bacterial pneumonia, cranial nerve dysfunction and
peripheral neuropathy, total paralysis, septicemia, septic
arthritis, osteomyelitis and death.
Which are the toxigenicity tests?
After isolation of C.diphtheriae, it should be tested for toxin
production. It can be detected by in-vitro or in-vivo methods. In
vitro-methods include Elek's gel precipitation and tissue culture
toxicity test. In-vivo methods involve neutralization of toxin in
animal model (guinea pig) challenge test.
Polymerase chain reaction (PCR) can detect DNA sequence encoding
the A subunit of toxigenic strain.
How is this condition treated?
All cases are promptly isolated and universal precautions are used
to limit the number of possible contacts. Immediate airway
management is followed by the removal of membrane. Horse-derived
diphtheria antitoxin (20,000-1,00,000 units depending on the
severity) is administered to neutralize the toxin in circulation.
Antibiotics such as penicillin or erythromycin is used for the
eradication of organisms, which serves to limit the amount of
toxin production. Erythromycin has been shown to be slightly
superior in the eradication of the carrier state and throat
cultures should be repeated in two weeks as relapses are known to
How is diphtheria prevented?
Applied home Next
Diphtheria prophylaxis can be active, passive or combined. Active
immunization using diphtheria toxoid is given to the unvaccinated
(as DTP or DTaP in children) or as DT or Td (tetanus toxoid and a
low dose of diphtheria) to the traveler. It is a part of the
national immunization schedule in India to immunize infants, where
it is given in three doses of DPT are given at intervals of 4-6
weeks and followed by a fourth dose a year later. A booster dose
may be given every five years. Schick test was used in the
past to determine if a subject needed to be immunized. Passive
immunization involves subcutaneous administration of 500-1000
units of anti-diphtheritic serum as an emergency measure to the
exposed unvaccinated susceptible individuals. Such people should
be followed up with active immunization. Combined immunization
consists of administration of the first dose of diphtheria toxoid
on one arm and anti-diphtheritic serum on the other arm, which is
followed up by full course of active immunization.