Diphtheria



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 in the early 2000s it is rare in developed countries because of widespread immunization.

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.

Demographics

Diphtheria is a reportable disease in many countries in the world. Since 1988, all confirmed cases in the United States involved visitors or immigrants. In countries that do not have routine immunization against this infection, the mortality rate varies from 1.5 to 25 percent.

Causes and 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 are 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 person is very weak. People 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 percent of all 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.

When to call the doctor

A doctor should be called whenever a case of diphtheria is suspected.

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 affected person'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 person 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 Gram-positive which means 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 person 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 people for sensitivity to animal serum. People who are sensitive (about 10%) must be desensitized with diluted antitoxin, since as of 2004 the antitoxin is the only specific substance that counteracts diphtheria exotoxin. No human antitoxin is available for the treatment of diphtheria.

The dose ranges from 20,000 to 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 people 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 an individual antibiotics for ten days.

Supportive care

Persons with diphtheria require bed rest with intensive nursing care, including extra fluids, oxygenation, and monitoring for possible heart problems, airway blockage, or involvement of the nervous system. People 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.

People recovering from diphtheria should rest at home for a minimum of two to three weeks, especially if they have heart complications. In addition, persons 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

People with diphtheria who develop myocarditis may be treated with oxygen and with medications to prevent irregular heart rhythms. An artificial pacemaker may be needed. Persons with difficulty swallowing can be fed through a tube inserted into the stomach through the nose. Persons 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 persons are children under the age of 15 years and those who develop pneumonia or myocarditis. Nasal and cutaneous diphtheria are rarely fatal.

Prevention

Prevention of diphtheria has four aspects: immunization, isolation of infected persons, identification and treatment of contacts, and reporting cases to health authorities.

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 ten-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 affected persons

Individuals with diphtheria must be isolated for one to seven days or until two successive cultures show that the individuals 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 persons with diphtheria 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 for tracking potential epidemics, to help doctors identify the specific strain of diphtheria, and to see if resistance to penicillin or erythromycin has developed.

Parental concerns

Parents in the United States should ensure that their children have full immunizations against diphtheria. Completion of the three-shot series initiates lifelong immunity from diphtheria.

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 possesses a gene for an abnormal trait without showing signs of the disorder. The person may pass the abnormal gene on to offspring. Also refers to a person who has a particular disease agent present within his/her body, and can pass this agent on to others, but who displays no symptoms of infection.

Cutaneous —Pertaining to the skin

Diphtheria-tetanus-pertussis (DTP) vaccine —The standard vaccine 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 that is carried in the bloodstream to other parts of the body.

Gram stain —A staining procedure used to visualize and classify bacteria. The Gram stain procedure allows the identification of purple (gram positive) organisms and red (gram negative) organisms. This identification aids in determining treatment.

Loeffler's medium —A special substance used to grow diphtheria bacilli to confirm the diagnosis.

Myocarditis —Inflammation of the heart muscle (myocardium).

Toxoid —A preparation made from inactivated exotoxin, used in immunization.

Resources

BOOKS

Diphtheria: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: ICON Health Publications, 2004.

Holmes, Randall K. "Diphtheria, Corynebacterial Infections and Anthrax." In Harrison's Principles of Internal Medicine , 15th ed. Edited by Eugene Braunwald et al. New York: McGraw-Hill, 2001, pp. 909–14.

Long, Sarah S. "Diphtheria (Corynebacterium diphtheriae)." In Nelson Textbook of Pediatrics , 17th ed. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2003, pp. 886–9.

Miller, Debbie S. Great Serum Race: Blazing the Iditarod Trail. New York: Walker & Company, 2002.

Salisbury, Gay. The Cruelest Miles: The Heroic Story of Dogs and Men in a Race against an Epidemic. New York: Norton, 2003.

PERIODICALS

Bertuccini, L., et al. "Internalization of non-toxigenic Corynebacterium diphtheriae by cultured human respiratory epithelial cells." Microbial Pathogenesis 37, no. 3 (2004): 111–8.

Clarke, P., et al. "DTP immunization of steroid treated preterm infants." Archives of Disease in Childhood: Fetal and Neonatal Edition 89, no. 5 (2004): F468–9.

Colgrove, J. "The power of persuasion: Diphtheria immunization, advertising, and the rise of health education." Public Health Rep 119, no. 5 (2004): 506–9.

Netterlid, E, et al. "Persistent itching nodules after the fourth dose of diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium." Vaccine 22, no. 27–28 (2004): 3698–706.

ORGANIZATIONS

American Public Health Association. 800 I Street, NW, Washington, DC 20001–3710. Web site: http://www.apha.org/.

Centers for Disease Control and Prevention. 1600 Clifton Road, Atlanta, GA 30333. Web site: http://www.cdc.gov.

Pan American Health Organization. 525 23rd St., NW, Washington, DC 20037. Web site: http://www.paho.org.

World Health Organization, Communicable Diseases. 20 Avenue Appia, 1211 Geneva 27, Switzerland. Web site: http://www.who.int/gtb/.

WEB SITES

"Diphtheria." MedlinePlus. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/001608.htm (accessed January 5, 2005).

"Diphtheria." World Health Organization. Available online at http://www.who.int/topics/diphtheria/en/ (accessed January 5, 2005).

"Diphtheria, Tetanus, and Pertussis." Centers for Disease Control and Prevention. Available online at http://www.cdc.gov/travel/diseases/dtp.htm (accessed January 5, 2005).

L. Fleming Fallon, Jr., MD, DrPH



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