Diphtheria, tetanus and pertussis

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 (see Immunization).

Corynebacterium diphtheriae
Pathogenesis
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 asymptomatic.

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.

Laboratory diagnosis
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 (see Immunization). 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.

Tetanus
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.

Clinical features
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 spp.
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.

Pathogenesis
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.

Clinical features
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.

Laboratory diagnosis
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.

Treatment
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 of treatment.

Prevention and control
An acellular vaccine is given as part of the childhood vaccination scheme.