Diphtheria is a contagious infectious disease that primarily affects the upper respiratory tract (respiratory diphtheria), and it is characterized by sore throat, fever, and an adherent membrane (pseudomembrane) on the tonsils and nasopharynx. Diphtheria can also affect the skin and cause localized skin infections (cutaneous diphtheria). Severe infection with diphtheria can lead to systemic involvement and can affect other organ systems as well, such as the heart and nervous system, sometimes leading to death. Diphtheria is caused by the bacterium Corynebacterium diphtheriae.
Diphtheria was first described by Hippocrates in the fifth century BC, and throughout history diphtheria has been a leading cause of death, primarily among children. The diphtheria bacterium was first identified in the 1880s by F. Loeffler, and the antitoxin against diphtheria was later developed in the 1890s. The development of the first diphtheria toxoid vaccine occurred in the 1920s, and its subsequent widespread use led to a dramatic decrease of diphtheria worldwide.
Though the implementation of vaccination programs has significantly decreased the incidence of diphtheria, serious outbreaks may still occur when vaccination rates wane. One such outbreak occurred in the 1990s in the Russian Federation and the Newly Independent States of the former Soviet Union, in which the World Health Organization (WHO) reported more than 157,000 cases and 5,000 deaths. Though still endemic in many parts of the world, respiratory diphtheria in the United States is currently a rare disease that has largely been eliminated through effective vaccination programs.
Diphtheria Causes and Risk Factors
Diphtheria is caused by the bacterium Corynebacterium diphtheriae, a gram-positive bacillus. There are three biotypes of the bacterium (gravis, mitis, and intermedius) capable of producing diphtheria, though each biotype varies in the severity of disease it produces. The Corynebacterium diphtheriae bacterium causes disease by invading the tissues lining the throat and producing diphtheria toxin, a substance which destroys the tissue and leads to the development of the adherent pseudomembrane characteristic of respiratory diphtheria. The diphtheria toxin may be absorbed and disseminated via the blood and lymphatic system to other organs distant from the initial infection, leading to more severe systemic sequelae (pathological conditions resulting from a prior disease, injury, or attack). Cutaneous diphtheria is usually caused by non-toxin-producing organisms, thereby typically causing a milder form of the disease.
Diphtheria is transmitted by infected individuals and asymptomatic carriers (individuals who are infected but do not exhibit symptoms). Transmission occurs via inhalation of airborne respiratory secretions or by direct contact with infected nasopharyngeal secretions or skin wounds. Rarely, infection can be spread by contact with objects contaminated by an infected person.
Risk factors for the development of diphtheria include absent or incomplete immunization against diphtheria, overcrowded and/or unsanitary living conditions, a compromised immune system, and travel to areas where the disease is endemic, especially in individuals who have not obtained booster shots (vaccine).
Diphtheria Symptoms and Signs
The symptoms and signs of respiratory diphtheria may initially be similar to a viral upper respiratory infection, however, the symptoms become more severe with the progression of the disease. Generally speaking, individuals exposed to diphtheria begin to experience symptoms between two to five days after the initial infection, though some individuals may not experience any symptoms at all (asymptomatic). The symptoms and signs of respiratory diphtheria may include the following:
- Sore throat
- Difficulty swallowing
- Nasal discharge (that may contain pus or blood-tinged fluid)
- Enlarged lymph nodes in the neck and neck swelling (producing a "bull neck" appearance)
- Difficulty breathing
As respiratory diphtheria progresses, individuals may develop the classic adherent thick, gray membrane (pseudomembrane) forming over the lining tissue of the tonsils, pharynx, and/or nasal cavity. Extension of this pseudomembrane into the larynx and trachea can lead to obstruction of the airway with subsequent suffocation and death.
The systemic manifestations of diphtheria are caused by the effects of the diphtheria toxin and its subsequent dissemination to other organs away from the initial area of infection. Commonly affected organs include the heart and nervous system, leading to complications such as inflammation of the heart (myocarditis), cardiac rhythm and conduction disturbances, muscle weakness, numbness (nerve), and vision changes.
Cutaneous diphtheria is characterized by an initially painful red lesion that eventually becomes a non-healing ulcer covered with a gray-brown membrane. This mild localized infection is only rarely associated with systemic complications.
When to Seek Medical Care for Diphtheria
As mentioned above, the initial symptoms of diphtheria may be similar to those of a viral upper respiratory infection (a cold). However, there are certain symptoms and conditions which should warrant a visit to your health-care provide for further evaluation should they develop:
- Severe sore throat or the inability to swallow
- Neck swelling
- Difficulty breathing
- Chest pain
- Extreme weakness or numbness
- Exposure to someone with known or suspected diphtheria
- Fever in individuals with a compromised immune system.
In order to establish the diagnosis of diphtheria, the isolation of Corynebacterium diphtheriae in culture media is required. Determining the presence of diphtheria toxin can also serve to confirm the diagnosis. Diagnostic testing to isolate the bacterium requires obtaining cultures from the nose and throat of individuals suspected of having diphtheria. Furthermore, if diphtheria is suspected in a patient, anyone who has had close contact with that individual should also have cultures obtained. Determining the presence of diphtheria toxin can be accomplished by testing in specialized laboratories. If diphtheria infection is confirmed, the Centers for Disease Control and Prevention (CDC) should be notified.
Diphtheria Treatment and Medications
The mainstays of treatment for diphtheria include diphtheria antitoxin, antibiotics, and supportive care. If diphtheria is suspected in a patient, treatment (antibiotics and antitoxin) should be initiated as soon as possible, even before confirmatory diagnostic test results are available, in order to improve the chances of a favorable outcome. Patients with suspected diphtheria should be placed in isolation in order to prevent transmission of the disease to others.
The effective treatment of diphtheria involves the early administration of diphtheria antitoxin, which neutralizes the circulating diphtheria toxin and reduces the progression of the disease. It is not effective against toxin that has already bound to body tissue. Diphtheria antitoxin is derived from horses, and it is only available from the Centers for Disease Control and Prevention (CDC). Individuals who are asymptomatic carriers and those with localized cutaneous diphtheria do not generally require antitoxin but are treated with antibiotics.
Antibiotics are also recommended in the treatment of diphtheria. The prompt administration of either erythromycin or penicillin can eradicate the bacteria and halt the production of further diphtheria toxin. The administration of antibiotics also assists in preventing the transmission of diphtheria to others. Antibiotics are also recommended for asymptomatic carriers of Corynebacterium diphtheriae and to those who come in close contact with individuals suspected or known to have diphtheria.
Supportive measures may also be necessary in the treatment of diphtheria. Airway obstruction from the pseudomembrane may necessitate the insertion of a breathing tube to prevent suffocation and death. Cardiac monitoring is necessary to manage potential cardiac rhythm or conduction disturbances. Consultation with cardiologists, neurologists, pulmonologists, and infectious disease specialists may also be necessary.
Appropriate outpatient follow-up must be arranged upon discharge from a hospital. A health-care provider will need to monitor the patient's progress, especially if they have experienced cardiac or neurologic complications during the course of illness. Nasopharyngeal cultures should be repeated post-treatment to make sure the bacterium has been eradicated, and their immunization schedule for diphtheria should be updated, if not previously done.
Universal immunization is the best measure to prevent diphtheria. The diphtheria toxoid vaccine, which is generally combined with the tetanus and pertussis vaccine, is currently recommended for administration to infants, adolescents, and adults. Immunization for infants and children consists of five DTaP vaccinations generally given at 2, 4, and 6 months, with the fourth dose being administered between 15-18 months, and the fifth dose at 4-6 years of age. Because immunity to diphtheria wanes over time, booster shots are recommended. The adult form of the vaccine, Tdap, is recommended for adolescents 11 or 12 years of age, or in place of one Td booster in older adolescents and adults 19-64 years of age. Whereas diphtheria primarily affected younger children in the pre-vaccination era, an increasing proportion of cases today occur in unvaccinated or inadequately immunized adolescents and adults, a problem which underscores the importance of keeping a current immunization schedule.
The prognosis for diphtheria depends on the severity of the disease and the presence of systemic involvement. Cardiac involvement and bacteremia (blood infection) are especially associated with a poor prognosis. The fatality rate for respiratory diphtheria is between 5%-10%, although it appears to be higher in patients less than 5 years of age and older than 40 years of age (~20%). Airway obstruction leading to suffocation and cardiac complications are the most commons causes of death.
The prognosis for treated cutaneous diphtheria is good, with complications and death only occurring rarely.