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Overview
Diphtheria is an infection caused by Corynebacterium diphtheriae and is characterised by sore throat, fever, neck pain, cervical lymphadenopathy, and a thick greyish pseudomembrane on the tonsils.
Disease epidemiology
The disease is endemic in many countries globally. In countries where diphtheria is endemic, between 3% to 5% of healthy persons may carry the organism asymptomatically and can serve as important reservoirs.
In Singapore, diphtheria vaccination is part of the National Childhood Immunisation Programme and has been mandatory since 1977. An isolated case in 2017 involving a 23-year-old Bangladeshi migrant worker was believed to have acquired the infection in Singapore. Screening of his immediate contacts was negative. Prior to this, the last local case of diphtheria was reported in 1992.
The Case Fatality Rate (CFR) for respiratory diphtheria is 5% to 10% even with treatment, with higher death rates (up to 20%) among persons younger than 5 years and older than 40 years of age. Before treatment was available, the disease was fatal in up to half of cases.
Pathogen(s)
Toxin-producing strains of Corynebacterium diphtheriae. Four biotypes: gravis, intermedius, mitis and belfanti.
Transmission
Diphtheria primarily transmits through direct deposition of infectious respiratory particles (IRPs) such as when an infected person coughs or sneezes. It can also spread via contact with contaminated surfaces such as when IRPs settle on surfaces or transfer through direct contact (e.g. handshake) before reaching the mouth, nose or eyes. Diphtheria also transmits via direct contact with exudate from discharging skin lesions.
Incubation period: Typically 2 to 5 days; ranging from 1 to 10 days.
Infectious period: The infectious period is variable and depends on how long organisms remain present in discharges and skin lesions. Usually this is 2 to 4 weeks after onset of illness. Seldom, for respiratory diphtheria, the infectious period may be more than 4 weeks. Rarely, chronic carriers may shed organisms for 6 months or more.
Clinical features
The presentation of diphtheria depends on the site of involvement. It usually involves the mucous membranes of the upper respiratory tract, skin, and rarely, other mucous membranes (any mucosal site can be involved).
The main clinical forms of diphtheria are:
Respiratory diphtheria: Commonly presents with sore throat, fever and malaise. In moderate to severe cases, cervical lymphadenopathy and marked oedema can result in a “bull neck” appearance. The classic lesion is a thick greyish pseudomembrane on the tonsils that extends to the soft palate. Extensive pseudomembrane formation can lead to airway obstruction, respiratory failure and death.
Cutaneous diphtheria: Chronic, non-healing ulcer with dirty grey membrane, covered with eschar – a hard brownish-grey membrane. Commonly occurs on exposed limbs (legs). Systematic toxicity is rare.
Other sites of involvement include the mucous membranes of the conjunctiva and vulvovaginal area, as well as the external auditory canal.
Complications of diphtheria infection are due to absorption and dissemination of toxin, and include myocarditis, arrhythmia, heart failure, polyneuropathies, respiratory failure, and death.
Risk factors
All persons who are unvaccinated or partially vaccinated.
Diagnosis
Detection of C. diphtheriae in respiratory or cutaneous specimen through isolation or positive for toxin production by polymerase chain reaction (PCR).
Treatment and management
Treatment should be started immediately after a clinical diagnosis is made and cultures are obtained. Diphtheria antitoxin is the specific treatment for respiratory diphtheria. Antibiotics are administered for both respiratory and cutaneous diphtheria to help eliminate the organism and prevent spread. Patients should still be vaccinated against diphtheria since infection does not confer immunity.
Precaution, prevention, and control
Isolation measures
Standard, droplet, and contact (for cutaneous diphtheria) precautions apply during management of the patient. Droplet precautions should be instituted until 2 negative cultures from both throat and nose (at least 24 hours apart), and at least 24 hours after cessation of antimicrobial therapy. Asymptomatic carriers should receive prophylactic antibiotics.
Contact management
Cultures from the throat and nasal swabs should be obtained from close contacts. Close contacts should receive prophylactic antibiotics, and immunisation or booster shots depending on their immunisation history. Contacts should also be monitored closely and given antitoxin if they develop signs and symptoms of diphtheria.
Vaccination
Vaccination against diphtheria is compulsory under Singapore law.
The National Childhood Immunisation Schedule recommends:
3 doses of DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine) at 2 months, 4 months and 6 months of age.
1 booster dose of DTaP at 18 months of age.
1 booster dose of Tdap (Tetanus- diphtheria- acellular pertussis) at 10 to 11 years of age.
The National Adult Immunisation Schedule recommends:
Tdap vaccine for adults with certain medical conditions, with no history of previous vaccination or if their last vaccination was at least 10 years ago.
One dose of Tdap vaccination for pregnant women during 16 to 32 weeks of each pregnancy for protection of the infant against pertussis, regardless of the interval since the previous Tdap vaccination.
Notification
Diphtheria is a legally notifiable disease in Singapore.
Who should notify:
Medical practitioners
Laboratories
When to notify:
On clinical suspicion/ laboratory confirmation
How to notify:
Please refer to the Infectious Disease Notification for more information.
Notification timeline:
As soon as possible. No later than 24 hours.
Resources
Please refer to the Weekly Infectious Diseases Bulletin for the number of diphtheria cases in Singapore.
For more information on diphtheria, please refer to the World Health Organization website.
For general travel advisory, please refer to Health Advice for Travellers.