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Causative Agent

Corynebacterium diphtheriae, toxigenic strains

Incubation Period

2 - 5 days (range 1-10 days)

Infectious Period

Up to 2 - 4 weeks after onset of illness


Close contact of nasopharyngeal secretions of case or asymptomatic human carrier or from skin lesion exudate.


Diphtheria has been eradicated from Singapore as a result of the comprehensive coverage of the childhood immunization programme. In a 2008-2010 MOH serosurvey, virtually all children below 17 years of age possessed antitoxin immunity against diphtheria (99.4%). An isolated case reappeared in 1992 in a 41 year old male with multiple co-morbid conditions. Corynebacterium diphtheriae var gravis was isolated from his blood. He subsequently died from septicaemia secondary to bacterial endocarditis.

The disease is still endemic in many countries (see below) but rare in developed countries despite waning immunity.

Presentation depends on sites of infection: anterior nasal, tonsillar/pharyngeal, laryngeal, cutaneous, ocular or genital. Any mucosal site can be involved.

Symptomatic infection results from 2 factors:

  • Local non-invasive inflammation of the respiratory tract or skin; and
  • Local and systemic effects of a potent diphtheria exotoxin.


  • Sore throat, fever and malaise.
  • Thick greyish pseudomembrane on tonsils extending to soft palate.
  • Cervical lymphadenopathy and oedema (“bull neck”).


  • Can be direct extension from pharyngeal form or the only site of involvement.
  • Fever, hoarseness, barking cough
  • Can lead to airway obstruction, coma, death

Cutaneous diphtheria

  • Primary chronic, non-healing ulcers with a dirty gray membrane
  • Systemic toxicity is rare.
  • Diphtheritic skin infection induces a brisk antibody response and is therefore immunizing.

Potential complications

Absorption and dissemination of the toxin leads to remote complications like myocarditis, endocarditis, neuritis, otitis media, respiratory compromise and death.

  • Throat and nasopharyngeal swabs: need to alert laboratory to suspected diagnosis so that selective culture media can be used (Loffler's or Tindale's).
  • ECG to detect conduction block.

A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis.

  • Antitoxin should be administered without delay if the diagnosis is seriously suspected (dose 20,000 - 100,000 units depending on severity).
  • Procaine penicillin G 25,000 to 50,000 units/kg per day for children and 1.2 million units/day for adults given IM in two divided doses.
  • Erythromycin (40 to 50 mg/kg per day, up to a maximum of 2 grams/day IV) is recommended until the patient can swallow comfortably. At that point, oral penicillin V (125 to 250 mg four times daily) can be used.
  • Respiratory isolation (for pharyngeal/laryngeal diphtheria) until 2 negative cultures (taken 24 hours apart) after stopping antibiotics.
  • Patients should be given diphtheria toxoid immunisation since infection does not confer immunity.
  • Patients who continue to harbour the organism after treatment should receive  an additional 10-day course of oral erythromycin and should submit samples for follow-up cultures.

Management of close contacts

  • Take cultures from throat and nasal swabs.
  • Prophylactic antibiotics with either penicillin or erythromycin.
  • A single dose of benzathine penicillin G (600,000 units IM for persons <6  years of age and 1.2 million units IM for persons ≥6 years of age) or a 7 to 10- day course of oral erythromycin (40 mg/kg per d for children and 1 g/d for adults) has been recommended.
  • Immunization or booster shots depending on immunization history.
  • Antitoxin if contacts develop signs and symptoms of diphtheria.

  • Respiratory isolation of suspected pharyngeal/laryngeal cases.
  • Routine childhood vaccination: primary immunisation at 3, 4 and 5 months (DPT); first booster (DPT) before school entry at 18 months, with a second booster (either Td or Tdap) at 10-11 years (Primary V). See Appendix 2.
  • Notification of all childhood immunisations to the National Immunisation Registry, Health Promotion Board, and post-vaccination adverse reactions to the Pharmacovigilance Branch, Health Sciences Authority.

  • Countries with endemic diphtheria include Asia/Oceania – Afghanistan, Bangladesh, Cambodia, China, India, Indonesia, Iran, Iraq, Laos, Mongolia, Burma (Myanmar), Nepal, Pakistan, Philippines, Syria, Thailand, Turkey, Vietnam, and Yemen; Africa – Algeria, Egypt, and the countries in sub- Saharan region; Americas – Brazil, Dominican Republic, Ecuador, and Haiti; and Europe – Albania and all countries of the former Soviet Union.
  • Adults travelling to endemic areas should receive booster Td vaccine if their vaccination has lapsed for more than 10 years.


  1. Lin, RV, Lin CSC, Yew FS, et al. Corynebacterium diphtheriae endocarditis in an adult with congenital heart disease: a case report. J Trop Med Hyg 1994; 97: 189-92.
  2. Liew F, Ang LW, Cutter J et al. Evaluation on the effectiveness of the national childhood immunisation programme in Singapore, 1982-2007. Ann Acad Med Singapore 2010; 39:532-10.

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