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These three organisms are from widely differing taxonomic groups
but are linked by being important diseases of childhood that are
mediated by toxins and can be prevented by childhood immunization
Diphtheria is caused by Corynebacterium diphtheriae that contain
a bacteriophage encoding diphtheria toxin. The toxin kills cells by
interrupting protein synthesis, acting on the myocardium to cause
myocarditis and on the peripheral nervous system to cause neuropathy
and paralysis. The severity of infection is directly related
to the degree of toxin production. Cutaneous infection is often
Corynebacterium diphtheriae is transmitted by the respiratory
route or following direct contact with cutaneous lesions.
Clinical features and management
Infection of the skin, nasopharynx or larynx may occur; the severity
of disease is related to the extent of the infection. A rare cause
of sore throat, it causes inflammation and necrosis giving a green-
black 'pseudomembrane' on the posterior wall of the pharynx,
which can cause respiratory obstruction. Management is based on
isolation and treatment with antitoxin and erythromycin. Intensive
care support may be required.
Corynebacterium diphtheriae is isolated using specialist media (e.g.
Hoyle's) and identified by biochemical tests and confirmed by 16s
rRNA sequencing. The toxin gene is detected by nucleic acid
amplification test (NAAT).
Prevention and control
Diphtheria is prevented by childhood vaccination with a toxoid
). Immunity is long-lasting but boosters for adults
at extra risk may be required (e.g. laboratory staff). Contacts of
cases must be identified and given antibiotic prophylaxis, vaccination
and/or specific antitoxin.
Epidemiology and pathogenesis
Infection occurs in wounds that are deep enough to produce anaerobic
conditions. Clostridium tetani produces tetanospasmin, which
prevents release of the inhibitory transmitter ?-aminobutyric acid
(GABA), thereby resulting in muscle spasms. Neonatal tetanus,
which may occur if the umbilical stump is contaminated after
delivery, is an important cause of death in developing countries.
Tetanus is now rare in developed countries, usually being found
in the elderly in whom immunity has declined. The disease may
follow a trivial gardening injury.
Spastic paralysis and muscle spasms may develop at the site of the
lesion and if untreated become generalized. Perioral muscle spasm
(risus sardonicus) and spinal spasm (opisthotonus) may develop.
Spasms are painful, may be stimulated by light or sudden noise
and may compromise respiration so that secondary bacterial pneumonia
may develop. Diagnosis is based on history and clinical
features; isolation of the organism is not diagnostic.
Treatment and prevention
Treatment is with muscle relaxants and the use of human tetanus
hyperimmune immunoglobulin and antibiotics to limit further
toxin activity. Ventilation and treatment of secondary pneumonia
may be required.
Infants are protected by passive immunity if their mothers are
vaccinated. The disease is prevented by childhood immunization
and boosters are given at school entry and every 10-15 years.
Unvaccinated patients with tetanus-prone wounds should receive
antibiotics and human tetanus immunoglobulin, followed by a
course of vaccination.
Bordetella pertussis and B. parapertussis can cause whooping
cough. In the absence of an adequate vaccination campaign, epidemics
of whooping cough occur in children every 4 years. Asymptomatic
or unrecognized infection in adolescents and young adults
maintains the cycle of infection in the human population.
Bordetella pertussis express fimbriae that aid their adhesion and
produce a number of exotoxins that include pertussis toxin, adenyl
cyclase and tracheal cytotoxin. There is a complex interaction with
the cells of the respiratory tract that produces thickened bronchial
secretions and paroxysmal cough. Complications include:
- secondary respiratory tract infection;
- apnoea following coughing spasms;
- raised intracranial pressure.
A 2-week, cold-like illness occurs before the characteristic cough
is heard - repeated, prolonged coughing fits followed by an inspiratory
whoop that may be absent in very young children and adults.
Coughing may be associated with vomiting and subconjunctival
haemorrhage; this phase can last for up to 3 months. Infection can
be complicated by secondary pneumonia and otitis media.
Specimens for culture are obtained using a pernasal swab, but the
organism is difficult to isolate and NAATs are more likely to
achieve a diagnosis.
Erythromycin is thought to decrease infectivity and shorten symptoms
if given early during the catarrhal phase. Symptomatic
support and early treatment of secondary infections is the mainstay
Prevention and control
An acellular vaccine is given as part of the childhood vaccination