Diphtheria

  • Medical Author:
    Charles Patrick Davis, MD, PhD

    Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

  • Medical Editor: Jerry R. Balentine, DO, FACEP
    Jerry R. Balentine, DO, FACEP

    Jerry R. Balentine, DO, FACEP

    Dr. Balentine received his undergraduate degree from McDaniel College in Westminster, Maryland. He attended medical school at the Philadelphia College of Osteopathic Medicine graduating in1983. He completed his internship at St. Joseph's Hospital in Philadelphia and his Emergency Medicine residency at Lincoln Medical and Mental Health Center in the Bronx, where he served as chief resident.

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Diphtheria facts

  • Diphtheria is an infectious disease caused by bacteria that usually produce exotoxins that damage human tissue.
  • The initial symptoms of diphtheria are flu-like but worsen to include fever, swallowing problems, hoarseness, enlarged lymph nodes, coughing, and shortness of breath; some patients may have skin involvement, producing skin ulcers.
  • The history of diphtheria dates back to Hippocrates; once the organisms were identified and found to produce exotoxins, the development of vaccines have markedly reduced diphtheria worldwide.
  • The cause of diphtheria is an infection by Corynebacterium species; the most severe infections are due to those Corynebacterium strains that produce exotoxins.
  • The highest risk factor for developing diphtheria is not getting immunized against the disease; other factors include crowding, immunosuppression, and direct or indirect contact with an infected individual.
  • Diphtheria is diagnosed by the patient's history and physical examination; culture of Corynebacterium from the patient yields a definitive diagnosis although patient should be treated if diphtheria is even suspected.
  • The treatment of diphtheria involves early administration of antibiotics; the use of antitoxin, made in horses, is done to neutralize Corynebacterium exotoxin that has not bound to human tissue.
  • Complications of diphtheria include heart-rhythm problems, sepsis, organ damage, and breathing problems that can be severe enough to cause death.
  • If treated appropriately and early in the infection, the prognosis for diphtheria is usually good; however, if complications develop, the prognosis decreases, especially if sepsis and/or cardiac involvement occurs.
  • It is possible to prevent diphtheria; the main way is to appropriately vaccinate individuals with one of the four major vaccine types available.

What is diphtheria?

Diphtheria is an infectious disease caused by the Corynebacterium species of bacteria and is most often associated with a sore throat, fever, and the development of an adherent membrane on the tonsils and/or nasopharynx. Severe infections can affect other organ systems such as the heart and the nervous system. In addition, some patients with diphtheria can also have skin infections. Exotoxin produced by the bacteria is an important component in causing diphtheria's more severe symptoms.

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What are the symptoms and signs of diphtheria?

Initially the symptoms of diphtheria may be similar to a viral upper respiratory infection but symptoms worsen over about two to five days. The symptoms may include: 

As the disease progresses, an adherent membrane (pseudomembrane) may begin to cover the tonsils, pharynx, and/or nasal tissues. If untreated, the pseudomembrane can extend into the larynx and trachea and obstruct the airway; this can lead to death.

Cutaneous diphtheria symptoms include initial reddish lesions that are painful and that may develop into nonhealing ulcers. Some ulcers may be covered by a gray-colored membrane.

What is the history of diphtheria?

Diphtheria has been infecting humans for centuries. Hippocrates produced the first documented description of diphtheria in the fifth century BC. The disease has been a leader in causing death, especially in children, for many centuries. The bacteria were first identified in the 1880s by F. Loffler. In the 1890s, exotoxins were discovered. The first diphtheria toxoid vaccine was produced in the 1920s. Vaccination programs have decreased the incidence of diphtheria worldwide, however, when vaccination rates drop, infection rates of diphtheria rise and, occasionally, serious outbreaks of the disease occur. For example, in the 1990s, an epidemic in Russia caused about 5,000 deaths according to the World Health Organization's (WHO) statistics, and from about 1993-2003, Latvia reported 101 deaths from diphtheria.

Before the diphtheria vaccination program, there were 100,000 to 200,000 cases of diphtheria each year in the U.S., leading to approximately 15,000 to 20,000 deaths. According to the CDC, less than five cases have been reported in the U.S. in the last 10 years.

What causes diphtheria?

The cause of diphtheria is bacterial species termed Corynebacterium diphtheriae, a gram-positive bacillus that usually produces exotoxins. There are four main strains (biotypes) of C. diphtheriae: gravis, intermedius, mitis, and belfanti. The strain termed intermedius is most often associated with exotoxin production although all three strains are capable of producing exotoxin. The organisms easily invade the tissue lining the throat, and during that invasion, they produce exotoxins that destroy the tissue and lead to the development of a pseudomembrane. Non-toxin-producing strains and other Corynebacterium species such as C. ulcerans can still cause infection, but infection is less severe and sometimes remains only in the skin (cutaneous infection).

What are risk factors for diphtheria?

Because human carriers or symptomatic individuals are the main reservoir for infection, situations such as overcrowding (dormitories, institutional housing, poor living conditions), incomplete immunization, and people who are immunocompromised are at higher risk for getting diphtheria. Diphtheria is transmitted by inhalation of airborne droplets or by direct contact with infected patients by mucous secretions or skin ulcerations. Some people may carry the bacteria in their respiratory tracts (termed carriers) but do not exhibit disease. However, such individuals can still transmit the organisms to uninfected individuals.

How do physicians diagnose diphtheria?

Preliminary diagnosis of diphtheria is usually made from the patient's history and physical exam and the presence of a pseudomembrane formation in the throat. Confirmation is based on isolation of the organism from swab specimens taken from the throat or from skin lesions. However, because diphtheria can be lethal, the CDC recommends immediate treatment if diphtheria suspected; do not wait for laboratory confirmation.

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What is the treatment for diphtheria?

There are two treatment strategies that are used for patients diagnosed with diphtheria. Both are most effective when utilized early in the disease process. The first treatment is antibiotics. The CDC recommends erythromycin as the first-line therapy for patients older than 6 months of age. For patients who are younger or who cannot take erythromycin, the CDC recommends intramuscular penicillin. Patients usually become noninfectious after about 48 hours of antibiotic treatment and should be held in isolation until that time to prevent spread of the disease.

The second treatment is administration of diphtheria antitoxin. However, this antitoxin is only available from the CDC. Diphtheria antitoxin reduces the progression of the disease by binding diphtheria toxin that has not yet attached to the body's cells. The antitoxin is derived from horses, so recipients should not be treated if they are allergic. Your doctor will make the decision if you need only antibiotics or antibiotics plus antitoxin based on your symptoms, immunization status, and disease progression.

What are possible complications of diphtheria?

The worst possible complication of diphtheria is respiratory failure or death due to pseudomembrane formation that blocks the airway. Other possible complications include cardiac problems such as rhythm disturbances, myocarditis, heart block, secondary pneumonia, septic shock, and infection of other organs such as the spleen, central nervous system, or heart tissue.

What is the prognosis of diphtheria?

The prognosis of diphtheria ranges from good to poor, depending upon how early in the infection the patient is treated, and how the patient responds to treatment. If the patient develops sepsis or bacteremia, or if there's cardiac involvement, the prognosis is usually poor. The mortality (death) rate is highest in patients less than 5 years old and in patients that are older than 40. The average rate of death from is about 5%-10%.

Is it possible to prevent diphtheria? Is there a diphtheria vaccine?

It is possible to prevent diphtheria; the most effective way is to vaccinate people (infants, see below) early in their lives and to prevent infected individuals from coming in contact with uninfected people. In addition, individuals who are carriers of the bacteria can be treated with antibiotics to eliminate the bacteria and thus reduce the chance of carriers transmitting bacteria to others.

There are vaccines available to protect individuals from diphtheria and all formulations contain toxoid concentrations that stimulate antibody production against diphtheria toxin (D or d). These toxoid vaccinations also may contain acellular pertussis (aP or ap) and tetanus (T) vaccine. They are as follows: DTaP, Tdap, DT, and Td. DTaP is the childhood vaccine while Tdap is the adult vaccine. Perhaps the most important vaccine is DTaP, given at 2 months, 4 months, 6 months, 15-18 months, and 4-6 years of age.

DT does not contain pertussis and is given to children who have reacted to pertussis vaccine; Td is a vaccine for adolescents and adults given every 10 years as a booster for tetanus. Tdap has several formulations; the CDC in 2012 recommended that Tdap formulations be used as a booster to cover pertussis instead of just the Td formulation against tetanus and diphtheria only.

The side effects of these vaccines are usually mild such as pain or soreness at the injection site and/or a mild fever. These effects usually go away within a day. However, some patients do develop more severe symptoms; although this is infrequent, patients that do so should be aware of the reaction and inform any medical caregiver that they may have an allergy (for example, an allergy to tetanus or pertussis vaccine).

Medically reviewed by Robert Cox, MD; American Board of Internal Medicine with subspecialty in Infectious Disease

REFERENCES:

Lo, Bruce M. "Diphtheria." Medscape.com. Dec. 11, 2013. <http://emedicine.medscape.com/article/782051-overview>.

United States. Centers for Disease Control and Prevention. "Diphtheria." May 13, 2013. <http://www.cdc.gov/diphtheria/>.

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Reviewed on 3/22/2016
References
Medically reviewed by Robert Cox, MD; American Board of Internal Medicine with subspecialty in Infectious Disease

REFERENCES:

Lo, Bruce M. "Diphtheria." Medscape.com. Dec. 11, 2013. <http://emedicine.medscape.com/article/782051-overview>.

United States. Centers for Disease Control and Prevention. "Diphtheria." May 13, 2013. <http://www.cdc.gov/diphtheria/>.

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