Diphtheria is an infectious disease caused primarily by toxigenic strains of Corynebacterium diphtheriae, a Gram-positive, non-spore-forming bacterium. The organism can colonise the mucous membranes of the nose and throat and, less commonly, the skin. The defining pathological feature of classical respiratory diphtheria is production of diphtheria toxin, an exotoxin that inhibits protein synthesis in susceptible host cells. Respiratory disease can produce a characteristic adherent pseudomembrane over the tonsils, pharynx, larynx or nasal passages.
The word derives from the Greek diphthera, meaning leather or hide, referring to the tough membrane associated with the disease. Although highly preventable through vaccination, Diphtheria remains clinically important because severe toxin-mediated disease can develop rapidly and may cause airway obstruction, cardiac injury and neurological complications.
Transmission occurs predominantly through respiratory droplets and close contact with infected respiratory secretions. Direct contact with infected skin lesions can transmit some forms of disease, while asymptomatic or mildly symptomatic carriers can also contribute to transmission. After entering the body, toxigenic bacteria adhere to epithelial surfaces and multiply locally; systemic illness is largely caused by absorption of toxin rather than widespread bacterial invasion. The incubation period is commonly a few days, although timing varies. Antimicrobial treatment reduces bacterial carriage and transmission, while antitoxin is directed against circulating toxin. Because toxin already bound to tissues cannot readily be neutralised, prompt treatment is important when respiratory diphtheria is clinically suspected.
Respiratory Diphtheria typically begins with symptoms resembling an upper respiratory infection, including sore throat, malaise, low-grade fever and cervical lymph-node enlargement. A grey or white adherent pseudomembrane may develop over the throat and can bleed if forcibly removed. Marked neck swelling can occur in severe disease and is sometimes referred to as a “bull neck” appearance. Laryngeal involvement can cause hoarseness, stridor and potentially life-threatening airway obstruction. Nasal disease may cause discharge and irritation. Because the membrane and systemic toxicity can distinguish severe disease from an uncomplicated sore throat, clinical recognition remains important even where vaccination has made the disease uncommon.
Diphtheria toxin is responsible for many of the serious complications. The toxin inactivates elongation factor 2 through ADP-ribosylation, disrupting protein synthesis and causing cell injury. Cardiac involvement can produce myocarditis, arrhythmias and conduction abnormalities, and neurological complications can include cranial-nerve dysfunction and peripheral neuropathy. Renal injury and other systemic effects can occur in severe illness. The severity of disease depends on factors including toxin production, anatomical site, host immunity and timing of treatment. Death can result from airway obstruction, cardiac complications or systemic toxicity, which explains why suspected disease requires urgent medical management rather than routine treatment as an ordinary respiratory infection.
Diagnosis is based on clinical suspicion together with laboratory confirmation. Samples may be collected from the nose, throat or relevant skin lesions for culture and molecular or other laboratory testing. Demonstrating C. diphtheriae does not by itself establish that the isolate is producing clinically important toxin, so toxin testing is important when appropriate. Because waiting for laboratory confirmation can delay treatment, suspected respiratory diphtheria is generally managed urgently while investigations proceed. Public-health authorities are involved because identification of a case can require contact tracing, testing, antimicrobial prophylaxis, assessment of vaccination status and measures to interrupt transmission.
Treatment of suspected Diphtheria can involve diphtheria antitoxin, appropriate antibiotics, respiratory support and careful monitoring for complications. Antitoxin neutralises unbound toxin and is therefore most useful when administered promptly. Antibiotics help eradicate the organism and reduce transmission but do not substitute for antitoxin in toxin-mediated disease. Airway management can be particularly challenging when a thick pseudomembrane obstructs the upper airway. Patients generally require isolation appropriate to the infection and public-health guidance. Close contacts may need antimicrobial prophylaxis and assessment for immunity, because exposure can occur even when the original patient has relatively limited symptoms.
Vaccination is the principal method of preventing Diphtheria. Modern vaccines use a chemically inactivated form of diphtheria toxin known as a toxoid, which stimulates protective antitoxin antibodies without causing toxin-mediated disease. Protection can decline with time, so booster doses are used in many immunisation programmes. Vaccination substantially reduces disease incidence but does not eliminate the possibility of importation or outbreaks, particularly where population immunity is inadequate. The disease can recur in individuals who have not been adequately immunised, and previous infection does not necessarily provide reliable lifelong protection. Maintaining high vaccination coverage therefore remains important even in countries where cases are uncommon.
Diphtheria should be distinguished from non-toxigenic C. diphtheriae carriage and from infections caused by other Corynebacterium species. A sore throat with a membrane has several possible differential diagnoses, so laboratory and clinical assessment are important. Cutaneous Diphtheria produces chronic or ulcerative skin lesions and is epidemiologically and clinically different from classical respiratory disease. Historically, Diphtheria was a major cause of childhood illness and death before widespread immunisation, and the development of antitoxin and toxoid vaccination transformed its public-health impact. Its continued significance lies in the combination of efficient transmission, potent toxin, potentially severe complications and the availability of highly effective prevention.
