Overview
Serious bacterial infection of the throat and nose causing a characteristic membrane. Can be fatal due to airway obstruction or toxin-mediated heart and nerve damage. Preventable by DTP vaccination.
Symptoms
Symptoms | Frequency | Severity | Onset |
|---|---|---|---|
| Dysphagia | 75% | Moderate | Early |
| Fever | 70% | Mild | Early |
| Malaise | 85% | Mild | Early |
| Sore throat | 90% | Moderate | Early |
| Headache | 50% | Mild | Early |
| Loss of appetite | 65% | Mild | Early |
| Nausea | 30% | Mild | Early |
| Nasal congestion | 8% | Mild | Early |
| Edema | 25% | Moderate | Peak |
| Shortness of breath | 25% | Severe | Peak |
| Swollen lymph nodes | 70% | Moderate | Peak |
| Cough | 40% | Mild | Peak |
| Vomiting | 15% | Mild | Peak |
| Hypotension | 10% | Severe | Late |
| Paralysis | 5% | Severe | Late |
| Tachycardia | 20% | Moderate | Late |
| Blurred vision | 8% | Mild | Late |
| Paresthesia | 10% | Mild | Late |
| Fatigue | 80% | Mild | Any phase |
| Skin ulcer | 20% | Moderate | Any phase |
Transmission
Overview
Serious bacterial infection affecting the mucous membranes of the throat and nose.
Overview
Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae transmitted via respiratory droplets. It produces a potent exotoxin causing local pseudomembrane formation and systemic cardiotoxic and neurotoxic effects. Once a leading cause of childhood death, it is now rare where vaccination coverage is high. Resurgence has been documented in Yemen (2017–2020), Southeast Asia, and among unvaccinated populations.
Emergency Signs
Seek emergency care immediately if:
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Severe throat pain with visible grayish membrane
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Difficulty breathing, stridor (high-pitched breathing), or drooling
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Neck swelling ("bull neck") with difficulty swallowing
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Rapid heart rate with chest pain (myocarditis)
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Any neurological symptoms: double vision, difficulty swallowing, facial weakness
Detailed Symptoms
Most common signs and symptoms
Pharyngeal/tonsillar diphtheria (most common):
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Sore throat, low-grade fever, malaise
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Characteristic grayish-white pseudomembrane on tonsils/pharynx — bleeds when removed
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"Bull neck" appearance from cervical lymphadenopathy and soft tissue edema
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Nasal voice and dysphagia
Laryngeal diphtheria:
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Hoarseness, croup-like cough
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Stridor — risk of complete airway obstruction and suffocation
Cutaneous diphtheria:
- Chronic, non-healing skin ulcers with gray membrane; more common in tropical regions
Toxic complications (from exotoxin):
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Myocarditis (usually onset 1–2 weeks after infection)
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Neuropathy (bulbar palsy, respiratory paralysis, peripheral neuropathy)
Knowing the symptoms is the first step to a quick response.
Course of Disease
Typical disease course (pharyngeal/tonsillar):
- Incubation period: 2–5 days.
- Onset: Sore throat, low-grade fever, malaise. Cervical lymphadenopathy ("bull neck" in severe cases).
- Pseudomembrane formation (days 2–3): Tough, gray-white pseudomembrane on tonsils/pharynx. Bleeds on attempted removal. May extend to larynx causing stridor and airway compromise.
- Toxin-mediated complications (weeks 1–6):
- Myocarditis: conduction abnormalities, heart failure (week 1–2).
- Neuropathy: palatal weakness, nasal voice, difficulty swallowing (week 3–5). Peripheral motor neuropathy (week 5–7).
- Recovery: Gradual with antibiotics + antitoxin. Pseudomembrane sloughs within days of treatment.
Note: Cutaneous diphtheria (skin ulcers) is generally milder with less systemic toxicity but serves as a reservoir.
Diagnosis
How this disease is identified
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Clinical diagnosis: characteristic pseudomembrane in throat in a febrile patient with toxicity signs
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Culture: C. diphtheriae from membrane or throat swab — confirmatory; takes 24–48 hours
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PCR: rapid detection of tox gene (confirms toxigenicity)
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Elek test or ELISA: confirms toxin production from isolate
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Notify public health authorities immediately — diphtheria is a quarantinable disease in many countries
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Screen close contacts; culture all household contacts
Treatment
Available treatment methods
Treatment is urgent and should not await laboratory confirmation:
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Diphtheria Antitoxin (DAT): equine antitoxin — administered as early as possible (20,000–100,000 IU depending on severity)
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neutralizes circulating toxin. Premedicate with antihistamines
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desensitization may be required.
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Antibiotics: erythromycin or penicillin G for 14 days — eliminate the organism and reduce toxin production
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Airway management: early intubation or tracheotomy may be necessary for laryngeal diphtheria
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Cardiac monitoring: ECG monitoring for myocarditis
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beta-blockers/pacemaker for arrhythmias
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Strict isolation: until two negative cultures ≥24 hours apart after antibiotics completion
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Active immunization: during convalescence (natural infection may not confer immunity)
Most cases are effectively treated with early diagnosis.
Prevention Details
How to protect yourself
Diphtheria toxoid vaccination is highly effective:
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Primary series: DTP at 2, 4, 6 months; booster at 15–18 months and 4–6 years
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Adult boosters: Td or Tdap every 10 years
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Outbreak control: ring vaccination and chemoprophylaxis (erythromycin/penicillin) for close contacts
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Travelers to endemic areas should ensure vaccination is current Endemic regions include Yemen, Pakistan, India, Indonesia, Philippines, and parts of Sub-Saharan Africa
Preparation is the best protection.
Travel Advice
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Ensure DTP/Td/Tdap vaccination is current; receive booster if last dose >10 years ago.
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High-risk destinations: Yemen, parts of Southeast Asia (Philippines, Indonesia, India), Papua New Guinea, Sub-Saharan Africa
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Travelers to refugee camps or crowded, low-vaccination settings face elevated risk.
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Close contact with local populations in endemic areas increases transmission risk.
How common is it?
Statistics and geographic data
Global diphtheria cases decreased dramatically with vaccination: from >100,000/year in 1980s to ~8,000 in 2020. However, recent resurgence in Yemen (>30,000 cases, 2017–2020 due to civil war-related vaccine collapse), India, Indonesia, and among European migrants. Most countries maintain <5% of cases. Waning adult immunity is a growing concern — antibody levels decline below protective threshold in ~50% of adults >40 years.
Risk Factors
Who is most at risk
The risk of diphtheria is primarily determined by vaccination status and proximity to endemic or outbreak settings. The following factors increase the likelihood of infection and/or severe disease:
Risk factors for infection:
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Incomplete or absent vaccination: The dominant risk factor globally. In the 1990s outbreak in the former Soviet Union (>150,000 cases, >5,000 deaths), the majority of cases occurred in adults whose childhood vaccine-induced immunity had waned without booster doses.
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Living in or traveling to endemic areas: Regions with DTP3 coverage <80%, particularly sub-Saharan Africa, South Asia, and Southeast Asia
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Crowded living conditions: Military barracks, refugee camps, prisons, homeless shelters — outbreaks propagate rapidly in overcrowded settings with poor hygiene
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Close contact with a case or carrier: Household contacts of a diphtheria case have a secondary attack rate of 2–5% even in partially immunized populations
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Low socioeconomic status and poor hygiene: Both respiratory and cutaneous diphtheria are diseases of poverty
Risk factors for severe disease and death:
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Age: CFR is highest in children <5 years (up to 20%) and adults >40 years (up to 20–30%). The relatively lower CFR in older children and young adults (3–5%) reflects both immune maturity and lower membrane burden.
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Delayed antitoxin administration: Every day of delay after day 2 of illness increases mortality. Antitoxin given on day 1 is associated with ~1% CFR; by day 4+, CFR exceeds 15%.
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Extensive membrane: Membrane involving the larynx, trachea, or extending across the entire pharynx carries higher risk of airway obstruction and systemic toxicity.
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Bull-neck (severe cervical edema): Indicates massive toxin production and correlates with higher rates of myocarditis and neuropathy.
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Biotype: C. diphtheriae biotype gravis has historically been associated with more severe disease, though this correlation is not absolute.
Populations at increased risk in high-income countries:
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Adults aged >50 years (waning immunity, inadequate booster uptake — serological studies show 30–60% are below protective antibody levels)
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Immigrants and refugees from low-coverage countries
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Homeless populations (cutaneous diphtheria)
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Healthcare workers in contact with cases
Complications Details
Potential complications
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Myocarditis: 10–25% of cases; onset 1–2 weeks after infection; can cause heart failure, heart block, ventricular arrhythmias — most common cause of death
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Neuropathy: bulbar palsy (difficulty swallowing/speaking), peripheral neuritis, respiratory muscle paralysis (weeks to months after infection) — can be fatal
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Airway obstruction: from membrane extension into larynx/trachea — can cause asphyxiation
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Renal failure: tubular necrosis from toxin
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Thrombocytopenia: from toxin-mediated platelet destruction
Recovery & Outlook
Expected outcomes and recovery
With antitoxin + antibiotics: CFR 5–10%.
Without treatment: CFR 30–50%.
Complications determining prognosis:
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Myocarditis: 10–25% of cases, may be fatal. Can occur 1–2 weeks after onset.
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Neuropathy: cranial nerve palsies (palatal, oculomotor), peripheral polyneuropathy (3–7 weeks post-onset). Usually reversible over weeks to months.
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Airway obstruction: from pseudomembrane extension. May require tracheostomy.
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Renal tubular necrosis (rare).
Recovery: With treatment, most patients recover fully within 4–6 weeks. Myocarditis carries the worst prognosis.