A bottle of diphtheria antitoxin, produced by the United States Hygienic Laboratory and dated May 8, 1895
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Diphtheria

Diphtheria is an upper respiratory tract illness characterized by sore throat, low-grade fever, and an adherent membrane of the tonsil(s), pharynx, and/or nose. A milder form of diphtheria can be limited to the skin. It is caused by Corynebacterium diphtheriae, an aerobic Gram-positive bacterium. more...

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Diphtheria is a highly contagious disease spread by direct physical contact or breathing the secretions of those infected. Diphtheria was once quite common, but has now largely been eradicated in developed nations (in the United States for instance, there have been fewer than 5 cases a year reported since 1980, as the DPT (Diphtheria-Tetanus-Pertussis) vaccine is given to all school children). Boosters of the vaccine are recommended for adults because the benefits of the vaccine decrease with age; they are particularly recommended for those travelling to areas where the disease has not been eradicated yet.

Signs and symptoms

The respiratory form has an incubation time of 1-4 days. Symptoms include fatigue, fever, a mild sore throat and problems swallowing. Children infected have symptoms that include nausea, vomiting, chills, and a high fever, although some do not show symptoms until the infection has progressed further.

Low blood pressure may develop in some patients. Longer-term effects include cardiomyopathy and peripheral neuropathy (sensory type).

Diagnosis

Laboratory criteria

  • Isolation of Corynebacterium diphtheriae from a clinical specimen, or
  • Histopathologic diagnosis of diphtheria

Case classification

  • Probable: a clinically compatible case that is not laboratory confirmed and is not epidemiologically linked to a laboratory-confirmed case
  • Confirmed: a clinically compatible case that is either laboratory confirmed or epidemiologically linked to a laboratory-confirmed case

Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

Treatment

The disease may remain manageable, but in more severe cases lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require a tracheotomy. In addition, an increase in heart rate may cause cardiac arrest. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases will be put in ICUs (Intensive Care Units) at hospitals and be given a diphtheria anti-toxin and bactericidal drugs such as penicillin and erythromycin. Bed rest is important and physical activity should be limited, especially in cases where there is inflammation of the heart muscles. Recovery is generally slow.

Epidemiology

Diphtheria remains a serious disease, with 5-10% percent fatality and up to 20% in children younger than 5 or adults older than 40. Outbreaks, though very rare, still can occur worldwide, even in developed nations. After the breakup of the old Soviet Union in the late 1980s, vaccination rates fell so low that there was an explosion of diphtheria cases. In 1991 there were 2,000 cases of diphtheria in Russia and its newer independent states. By 1998 there were as many as 200,000 cases, with 5,000 deaths, according to Red Cross estimates. This was so great an increase that it was cited in the Guinness Book of World Records as "most resurgent disease".

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Diphtheria
From Gale Encyclopedia of Medicine, 4/6/01 by Rebecca J. Frey

Definition

Diphtheria is a potentially fatal, contagious disease that usually involves the nose, throat, and air passages, but may also infect the skin. Its most striking feature is the formation of a grayish membrane covering the tonsils and upper part of the throat.

Description

Like many other upper respiratory diseases, diphtheria is most likely to break out during the winter months. At one time it was a major childhood killer, but it is now rare in developed countries because of widespread immunization. Since 1988, all confirmed cases in the United States have involved visitors or immigrants. In countries that do not have routine immunization against this infection, the mortality rate varies from 1.5-25%.

Persons who have not been immunized may get diphtheria at any age. The disease is spread most often by droplets from the coughing or sneezing of an infected person or carrier. The incubation period is two to seven days, with an average of three days. It is vital to seek medical help at once when diphtheria is suspected, because treatment requires emergency measures for adults as well as children.

Causes & symptoms

The symptoms of diphtheria are caused by toxins produced by the diphtheria bacillus, Corynebacterium diphtheriae (from the Greek for "rubber membrane"). In fact, toxin production is related to infections of the bacillus itself with a particular bacteria virus called a phage (from bacteriophage; a virus that infects bacteria). The intoxication destroys healthy tissue in the upper area of the throat around the tonsils, or in open wounds in the skin. Fluid from the dying cells then coagulates to form the telltale gray or grayish green membrane. Inside the membrane, the bacteria produce an exotoxin, which is a poisonous secretion that causes the life-threatening symptoms of diphtheria. The exotoxin is carried throughout the body in the bloodstream, destroying healthy tissue in other parts of the body.

The most serious complications caused by the exotoxin are inflammations of the heart muscle (myocarditis) and damage to the nervous system. The risk of serious complications is increased as the time between onset of symptoms and the administration of antitoxin increases, and as the size of the membrane formed increases. The myocarditis may cause disturbances in the heart rhythm and may culminate in heart failure. The symptoms of nervous system involvement can include seeing double (diplopia), painful or difficult swallowing, and slurred speech or loss of voice, which are all indications of the exotoxin's effect on nerve functions. The exotoxin may also cause severe swelling in the neck ("bull neck").

The signs and symptoms of diphtheria vary according to the location of the infection:

Nasal

Nasal diphtheria produces few symptoms other than a watery or bloody discharge. On examination, there may be a small visible membrane in the nasal passages. Nasal infection rarely causes complications by itself, but it is a public health problem because it spreads the disease more rapidly than other forms of diphtheria.

Pharyngeal

Pharyngeal diphtheria gets its name from the pharynx, which is the part of the upper throat that connects the mouth and nasal passages with the voice box. This is the most common form of diphtheria, causing the characteristic throat membrane. The membrane often bleeds if it is scraped or cut. It is important not to try to remove the membrane because the trauma may increase the body's absorption of the exotoxin. Other signs and symptoms of pharyngeal diphtheria include mild sore throat, fever of 101-102°F (38.3-38.9°C), a rapid pulse, and general body weakness.

Laryngeal

Laryngeal diphtheria, which involves the voice box or larynx, is the form most likely to produce serious complications. The fever is usually higher in this form of diphtheria (103-104°F or 39.4-40°C) and the patient is very weak. Patients may have a severe cough, have difficulty breathing, or lose their voice completely. The development of a "bull neck" indicates a high level of exotoxin in the bloodstream. Obstruction of the airway may result in respiratory compromise and death.

Skin

This form of diphtheria, which is sometimes called cutaneous diphtheria, accounts for about 33% of diphtheria cases. It is found chiefly among people with poor hygiene. Any break in the skin can become infected with diphtheria. The infected tissue develops an ulcerated area and a diphtheria membrane may form over the wound but is not always present. The wound or ulcer is slow to heal and may be numb or insensitive when touched.

Diagnosis

Because diphtheria must be treated as quickly as possible, doctors usually make the diagnosis on the basis of the visible symptoms without waiting for test results.

In making the diagnosis, the doctor examines the patient's eyes, ears, nose, and throat in order to rule out other diseases that may cause fever and sore throat, such as infectious mononucleosis, a sinus infection, or strep throat. The most important single symptom that suggests diphtheria is the membrane. When a patient develops skin infections during an outbreak of diphtheria, the doctor will consider the possibility of cutaneous diphtheria and take a smear to confirm the diagnosis.

Laboratory tests

The diagnosis of diphtheria can be confirmed by the results of a culture obtained from the infected area. Material from the swab is put on a microscope slide and stained using a procedure called Gram's stain. The diphtheria bacillus is called Gram-positive because it holds the dye after the slide is rinsed with alcohol. Under the microscope, diphtheria bacilli look like beaded rod-shaped cells, grouped in patterns that resemble Chinese characters. Another laboratory test involves growing the diphtheria bacillus on a special material called Loeffler's medium.

Treatment

Diphtheria is a serious disease requiring hospital treatment in an intensive care unit if the patient has developed respiratory symptoms. Treatment includes a combination of medications and supportive care:

Antitoxin

The most important step is prompt administration of diphtheria antitoxin, without waiting for laboratory results. The antitoxin is made from horse serum and works by neutralizing any circulating exotoxin. The doctor must first test the patient for sensitivity to animal serum. Patients who are sensitive (about 10%) must be desensitized with diluted antitoxin, since the antitoxin is the only specific substance that will counteract diphtheria exotoxin. No human antitoxin is available for the treatment of diphtheria.

The dose ranges from 20,000-100,000 units, depending on the severity and length of time of symptoms occurring before treatment. Diphtheria antitoxin is usually given intravenously.

Antibiotics

Antibiotics are given to wipe out the bacteria, to prevent the spread of the disease, and to protect the patient from developing pneumonia. They are not a substitute for treatment with antitoxin. Both adults and children may be given penicillin, ampicillin, or erythromycin. Erythromycin appears to be more effective than penicillin in treating people who are carriers because of better penetration into the infected area.

Cutaneous diphtheria is usually treated by cleansing the wound thoroughly with soap and water, and giving the patient antibiotics for 10 days.

Supportive care

Diphtheria patients need bed rest with intensive nursing care, including extra fluids, oxygenation, and monitoring for possible heart problems, airway blockage, or involvement of the nervous system. Patients with laryngeal diphtheria are kept in a croup tent or high-humidity environment; they may also need throat suctioning or emergency surgery if their airway is blocked.

Patients recovering from diphtheria should rest at home for a minimum of two to three weeks, especially if they have heart complications. In addition, patients should be immunized against diphtheria after recovery, because having the disease does not always induce antitoxin formation and protect them from reinfection.

Prevention of complications

Diphtheria patients who develop myocarditis may be treated with oxygen and with medications to prevent irregular heart rhythms. An artificial pacemaker may be needed. Patients with difficulty swallowing can be fed through a tube inserted into the stomach through the nose. Patients who cannot breathe are usually put on mechanical respirators.

Prognosis

The prognosis depends on the size and location of the membrane and on early treatment with antitoxin; the longer the delay, the higher the death rate. The most vulnerable patients are children under age 15 and those who develop pneumonia or myocarditis. Nasal and cutaneous diphtheria are rarely fatal.

Prevention

Prevention of diphtheria has four aspects:

Immunization

Universal immunization is the most effective means of preventing diphtheria. The standard course of immunization for healthy children is three doses of DPT (diphtheria-tetanus-pertussis) preparation given between two months and six months of age, with booster doses given at 18 months and at entry into school. Adults should be immunized at 10 year intervals with Td (tetanus-diphtheria) toxoid. A toxoid is a bacterial toxin that is treated to make it harmless but still can induce immunity to the disease.

Isolation of patients

Diphtheria patients must be isolated for one to seven days or until two successive cultures show that they are no longer contagious. Children placed in isolation are usually assigned a primary nurse for emotional support.

Identification and treatment of contacts

Because diphtheria is highly contagious and has a short incubation period, family members and other contacts of diphtheria patients must be watched for symptoms and tested to see if they are carriers. They are usually given antibiotics for seven days and a booster shot of diphtheria/tetanus toxoid.

Reporting cases to public health authorities

Reporting is necessary to track potential epidemics, to help doctors identify the specific strain of diphtheria, and to see if resistance to penicillin or erythromycin has developed.

Key Terms

Antitoxin
An antibody against an exotoxin, usually derived from horse serum.
Bacillus
A rod-shaped bacterium, such as the diphtheria bacterium.
Carrier
A person who may harbor an organism without symptoms and may transmit it to others.
Cutaneous
Located in the skin.
Diphtheria-tetanus-pertussis (DTP)
The standard preparation used to immunize children against diphtheria, tetanus, and whooping cough. A so-called "acellular pertussis" vaccine (aP) is usually used since its release in the mid-1990s.
Exotoxin
A poisonous secretion produced by bacilli which is carried in the bloodstream to other parts of the body.
Gram's stain
A dye staining technique used in laboratory tests to determine the presence and type of bacteria.
Loeffler's medium
A special substance used to grow diphtheria bacilli to confirm the diagnosis.
Myocarditis
Inflammation of the heart tissue.
Toxoid
A preparation made from inactivated exotoxin, used in immunization.

Further Reading

For Your Information

    Books

  • Abzug, Mark J. "Infectious Diseases: Bacterial, Spirochetal, Protozoal, Metazoal, & Mycotic." In Handbook of Pediatrics, edited by Gerald B. Merenstein, et al. Norwalk, CT: Appleton & Lange, 1994.
  • Chambers, Henry F. "Infectious Diseases: Bacterial & Chlamydial." In Current Medical Diagnosis & Treatment 1997, edited by Lawrence M. Tierney, Jr., et al. Stamford, CT: Appleton & Lange, 1997.
  • "Childhood Infections: Bacterial Infections." In The Merck Manual of Diagnosis and Therapy, vol. II, edited by Robert Berkow, et al. Rahway, NJ: Merck Research Laboratories, 1992.
  • Mirza, Ayesha, and Russell W. Steele. "Diphtheria." In Conn's Current Therapy, edited by Robert E. Rakel. Philadelphia: W. B. Saunders Company, 1997.
  • Ogle, John W. "Infections: Bacterial & Spirochetal." In Current Pediatric Diagnosis & Treatment, edited by William W. Hay, Jr., et al. Stamford, CT: Appleton & Lange, 1997.
  • Simoes, Eric A. F., and Jessie R. Groothuis. "Immunization." In Current Pediatric Diagnosis & Treatment, edited by William W. Hay, Jr., et al. Stamford, CT: Appleton & Lange, 1997.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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