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Diphtheria

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 101102°F (38.338.9°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 (103104°F or 39.440°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. 90914.

Long, Sarah S. "Diphtheria (Corynebacterium diphtheriae)." In Nelson Textbook of Pediatrics, 17th ed. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2003, pp. 8869.

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): 1118.

Clarke, P., et al. "DTP immunization of steroid treated preterm infants." Archives of Disease in Childhood: Fetal and Neonatal Edition 89, no. 5 (2004): F4689.

Colgrove, J. "The power of persuasion: Diphtheria immunization, advertising, and the rise of health education." Public Health Rep 119, no. 5 (2004): 5069.

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. 2728 (2004): 3698706.

ORGANIZATIONS

American Public Health Association. 800 I Street, NW, Washington, DC 200013710. Web site: <www.apha.org/>.

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

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

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

WEB SITES

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

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

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

L. Fleming Fallon, Jr., MD, DrPH

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Diphtheria

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 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 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 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.

Resources

BOOKS

Chambers, Henry F. "Infectious Diseases: Bacterial & Chlamydial." In Current Medical Diagnosis and Treatment, 1998, edited by Stephen McPhee, et al., 37th ed. Stamford: Appleton & Lange, 1997.

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.

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Diphtheria

DIPHTHERIA

Diphtheria is a communicable disease caused by infection with Corynebacterium diphtheriae, typically presenting as respiratory tract infection in temperate climates and as cutaneous infection in the tropics. Clinical manifestations include pseudomembrane formation in the respiratory tract and soft tissue swelling of the neck ("bull neck"). Serious complications, primarily damage to the heart muscle and certain nerves that activate muscles, are due to diphtheria toxin, a potent toxin. Nontoxigenic strains can produce respiratory tract illness with pseudomembrane. Clusters of cases of invasive disease due to nontoxigenic strains, predominantly among persons with antecedent injection use, have been reported recently from several countries.

Vaccines composed of inactivated diphtheria toxindiphtheria toxicwere developed in the early twentieth century and have been widely used in most developed countries since the middle of the twentieth century. Prior to introduction of vaccination, diphtheria was a major cause of childhood mortality in the United States, but by the 1990s respiratory diphtheria has been virtually eliminated in the United States and in other countries with high levels of childhood vaccination for diphtheria. Nonetheless, the infection remains endemic in much of the developing world. In the 1990s, a massive resurgence of diphtheria occurred in the countries of the former Soviet Union. Factors contributing to the epidemic included low vaccination coverage among children, lack of routine adult booster vaccination, population movements, and multiple introductions from areas where diphtheria remained endemic.

In the World Health Organization's Expanded Programme on Immunization, diphtheria toxic is administered with tetanus toxic and pertussis vaccine (DTP) at 6, 10, and 14 weeks of age. Recommendations for subsequent doses vary among countries. In the United States, diphtheria toxic is routinely administered with tetanus toxic and acellular pertussis vaccine at 2, 4, and 6 months of age, with booster doses at 15 to 18 months and 4 to 6 years of age.

Diptheria antitoxin is the mainstay of treatment of diphtheria. Outcome improves with early diagnosis and treatment. Antimicrobial therapy with penicillin or erythromycin hastens elimination of the organism. Antimicrobial prophylaxis is recommended for those in close contact with diphtheria cases.

Melinda Wharton

Charles Vitek

(see also: Communicable Disease Control; Diphtheria Vaccine; Immunizations )

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diphtheria

diphtheria (dĬfthēr´ēə), acute contagious disease caused by Corynebacterium diphtheriae (Klebs-Loffler bacillus) bacteria that have been infected by a bacteriophage. It begins as a soreness of the throat with fever. The bacteria lodge in the mucous membranes of the throat, producing virulent toxins that destroy the tissue. The resultant formation of a tough gray membrane is one of the most dangerous aspects of diphtheria, since it can spread to the larynx and cause suffocation. Deaths from diphtheria often result from inflammation of the heart. Diphtheria usually occurs in children of preschool age. Treatment with antitoxin is begun as early as possible. Penicillin or erythromycin is also given, particularly to guard against complicating factors such as pneumonia or streptococcal infection. Diphtheria was once a common and dreaded disease with a high mortality rate; it is now rare in countries where infants are vaccinated (see vaccination). Underimmunization, however, can lead to epidemics such as the one in Russia during 1994–95.

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diphtheria

diphtheria (dif-theer-iă) n. an acute highly contagious infection, caused by the bacterium Corynebacterium diphtheriae, that generally affects the throat but occasionally affects other mucous membranes and the skin. Early symptoms are a sore throat, weakness, and mild fever; later, a soft grey membrane forms across the throat, constricting the air passages and causing difficulty in breathing and swallowing. Bacteria multiply at the site of infection and release a toxin into the bloodstream, which damages heart and nerves. An effective immunization programme has now made diphtheria rare in most Western countries (see also Schick test).

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Diphtheria

Diphtheria

What Is Diphtheria?

How Common Is Diphtheria?

Is Diphtheria Contagious?

What Are the Signs and Symptoms of Diphtheria?

How Is Diphtheria Diagnosed and Treated?

Can Diphtheria Be Prevented?

Resources

Diphtheria (dif-THEER-e-uh) is an infection of the lining of the upper respiratory tract (the nose and throat). It is a serious disease that can cause breathing difficulty and other complications, including death. Routine vaccination against diphtheria has made it rare in the United States.

KEYWORDS

for searching the Internet and other reference sources

Antitoxin

Corynebacterium diphtheriae

Epidemic

Respiratory infection

Vaccination

What Is Diphtheria?

Diphtheria is an infection caused by a bacterium called Corynebacterium diphtheriae (kor-ih-nee-bak-TEER-e-um dif-THEER-e-eye) that infects the upper respiratory tract. As the bacteria infect the nose, throat, or larynx (LAIR-inks, the voicebox), a distinctive thick membrane forms over the site of infection. The membrane can become large enough to interfere with a persons breathing and swallowing. Some strains of Corynebacterium diphtheriae also produce an exotoxin* that can cause arthritis and damage to the nerves and heart. Sepsis, a potentially serious spreading of infection (usually bacterial) through the bloodstream and body, can result from diphtheria, causing shock*, heart failure, and even death.

*exotoxin
(ek-so-TOK-sin) is a substance produced by bacteria that has harmful effects on the infected person.
*shock
is a serious condition in which blood pressure is very low and not enough blood flows to the bodys organs and tissues. Untreated, shock may result in death.

How Common Is Diphtheria?

Diphtheria infection occurs throughout the world and is common in developing regions of Africa, Asia, and South America where children often do not receive the diphtheria vaccine. Cases usually occur in winter and the cooler months of autumn and spring.

Diphtheria infection is extremely rare in the United States because of the widespread use of routine diphtheria vaccination during childhood. From 1980 through 2000, 51 cases of diphtheria were reported in the United States. However, a diphtheria epidemic* has affected the countries that make up the former Soviet Union; since 1990 more than 150,000 cases have been reported.

*epidemic
(eh-pih-DEH-mik) is an outbreak of disease, especially infectious disease, in which the number of cases suddenly becomes far greater than usual. Usually epidemics are outbreaks of diseases in specific regions, whereas worldwide epidemics are called pandemics.

A Canine Hero

In the winter of 1925, a diphtheria epidemic swept through Nome, Alaska. Antitoxin was located almost 1,000 miles away in the city of Anchorage. The only way to transport the medicine was by dog sled. A relay of sled-dog teams, with the last leg led by a dog named Balto, successfully carried the medicine through frigid Alaskan temperatures in time to save many lives. In honor of that achievement, a statue of Balto was erected in Central Park in New York City.

Is Diphtheria Contagious?

Diphtheria is highly contagious. An untreated person who has diphtheria can spread the infection for up to a month. Within 48 hours of receiving antibiotics, however, people infected with diphtheria are usually no longer contagious.

The bacteria that cause diphtheria are spread through the air in drops of moisture from the respiratory tract, often from coughing or sneezing. Sharing drinking glasses or eating utensils or handling soiled tissues or handkerchiefs that have been used by a person with the disease can also transmit the bacteria. A person can get diphtheria from someone who has symptoms of the disease or from someone who is just a carrier* of the bacteria.

*carrier
is a person who has in his body a bacterium or virus that he can transmit to other people without getting sick himself.

What Are the Signs and Symptoms of Diphtheria?

Within 5 days after becoming infected, a person typically begins to have symptoms of diphtheria. Early symptoms often include a severe sore throat, runny nose, mild fever, and swollen glands in the neck. People infected with diphtheria in the nose, throat, or larynx usually develop a thick membrane at the site of the infection. Membranes in the nose are often white, whereas those at the back of the throat are gray-green.

As diphtheria progresses, respiratory symptoms can become more severe and include difficulty breathing or swallowing and a bark-like cough. Sometimes inflammation and swelling in the throat and the diphtheria membrane itself can cause blockage of the upper airways, making emergency treatment necessary.

How Is Diphtheria Diagnosed and Treated?

Diphtheria is diagnosed when the membrane that signals the disease is seen in the nose or throat during an examination of someone with symptoms of the disease. The diagnosis is confirmed by taking a swab of the coating from underneath the membrane and performing a laboratory test that identifies diphtheria bacteria.

Hospitalized people who are known to have diphtheria are kept isolated to prevent the disease from spreading to others. Patients are treated in the hospital with antibiotics and diphtheria antitoxin*. The antitoxin, which is produced in horses, is given intravenously (directly into a vein).

*antitoxin
(an-tih-TOK-sin) counteracts the effects of a toxin, or poison, in the body. Antitoxins are produced to act against specific toxin, like those made by the bacteria that cause botulism or diphtheria.

In severe cases of diphtheria, patients may need a ventilator (VEN-tuh-lay-ter) to help with breathing or medication to treat complications of the disease, such as septic shock*, heart inflammation, or heart failure. After they leave the hospital, bed rest at home for several weeks is generally recommended. Members of the same household are usually given a diphtheria booster vaccine to protect against possible infection. Recovery from diphtheria often takes 4 to 6 weeks or more.

*septic shock
is shock due to overwhelming infection, and is characterized by decreased blood pressure, internal bleeding, heart failure, and, in some cases, death.

Complications of diphtheria include abnormal heart rhythms, arthritis, and neuritis*. Diphtheria is most dangerous for children under 5 and adults over 40. Death occurs in up to 10 percent of people with diphtheria who receive medical treatment; death rates are higher in some parts of the world where treatment is not readily available.

*neuritis
(nuh-RYE-tis) is an inflammation of the nerves that disrupts their function.

Can Diphtheria Be Prevented?

In the United States, immunization programs have been very effective in preventing diphtheria. The diphtheria vaccine is given in combination with vaccines for tetanus* and pertussis* (this is called the DTaP vaccine) as part of a childs routine immunizations. Four doses of the vaccine are given before 2 years of age. A first booster dose is given at 4 to 6 years of age when a child enters school. Additional booster doses are recommended every 10 years, in combination with a tetanus booster.

*tetanus
(TET-nus) is a serious bacterial infection that affects the bodys central nervous system.
*pertussis
(per-TUH-sis) is a bacterial infection of the respiratory tract that causes severe coughing.

Sometimes people have mild reactions to the vaccine, including a low-grade fever, tenderness at the injection site, and irritability. Very rarely, stronger reactions such as seizures* or allergic reactions can occur.

*seizures
(SEE-zhurs) are sudden bursts of disorganized electrical activity that interrupt the normal functioning of the brain, often leading to uncontrolled movements in the body and sometimes a temporary change in consciousness.

See also

Arthritis, Infectious

Public Health

Sepsis

Vaccination (Immunization)

Resources

Organizations

Immunization Action Coalition, 573 Selby Avenue, Suite 234, St. Paul, MN 55104. The Immunization Action Coalition provides information about infectious diseases and immunization.

Telephone 651-647-9009 http://www.immunize.org

U.S. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road Atlanta, GA 30333. The CDC provides information about infectious and other diseases, including diphtheria, at its website.

Telephone 800-311-3435 http://www.cdc.gov

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diphtheria

diph·the·ri·a / difˈ[unvoicedth]irēə; dip-/ • n. a highly contagious disease caused by the bacterium Corynebacterium diphtheriae and characterized by the formation of a breath-obstructing membrane in the throat and by a potentially fatal toxin in the blood. DERIVATIVES: diph·the·ri·al adj. diph·the·rit·ic / ˌdif[unvoicedth]əˈritik; ˌdip-/ adj.

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diphtheria

diphtheria Acute infectious disease characterized by the formation of a membrane in the throat which can cause asphyxiation; there is also release of a toxin which can damage the nerves and heart. Caused by a bacterium, Corynebacterium diphtheriae, which often enters through the upper respiratory tract, it is treated with antitoxin and antibiotics

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diphtheria

diphtheria infectious disease affecting chiefly the throat. XIX. — modL. — F. diphthérie (now diphtérie), substituted for earlier diphthérite, f. Gr. diphthérā, diphtherís skin, hide, piece of leather; so named on account of the tough membrane which forms on parts affected by the disease.

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diphtheria

diphtheriabarrier, carrier, farrier, harrier, tarrier •Calabria, Cantabria •Andrea • Kshatriya • Bactria •Amu Darya, aria, Zaria •Alexandria •Ferrier, terrier •destrier •aquaria, area, armamentaria, Bavaria, Bulgaria, caldaria, cineraria, columbaria, filaria, frigidaria, Gran Canaria, herbaria, honoraria, malaria, pulmonaria, rosaria, sacraria, Samaria, solaria, tepidaria, terraria •atria, gematria •Assyria, Illyria, Styria, SyriaLaurier, warrior •hypochondria, mitochondria •Austria •auditoria, ciboria, conservatoria, crematoria, emporia, euphoria, Gloria, moratoria, phantasmagoria, Pretoria, sanatoria, scriptoria, sudatoria, victoria, Vitoria, vomitoria •Maurya •courier, Fourier •currier, furrier, spurrier, worrier •Cumbria, Northumbria, Umbria •Algeria, anterior, bacteria, Bashkiria, cafeteria, criteria, cryptomeria, diphtheria, exterior, hysteria, Iberia, inferior, interior, Liberia, listeria, Nigeria, posterior, Siberia, superior, ulterior, wisteria •Etruria, Liguria, Manchuria, Surya

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Diphtheria

Diphtheria

Diphtheria is a potentially fatal, contagious bacterial 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.

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% to 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.

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 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 diphtheria gets its name from the pharynx, which is the part of the upper throat that connects the mouth and nasal passages with the larynx. 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 101102°F (38.338.9°C), a rapid pulse, and general body weakness.

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 (103104°F or 39.440°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.

The skin 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.

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 Loeffler's medium.

The most important treatment is prompt administration of diphtheria antitoxin. The antitoxin is made from horse serum and works by neutralizing any circulating exotoxin. The physician 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.

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.

Universal immunization is the most effective means of preventing diphtheria. The standard course of immunization for healthy children is three doses of DPT (diphtheria-tetanuspertussis) 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.

Diphtheria patients must be isolated for one to seven days or until two successive cultures show that they are no longer contagious. 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 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. In 1990, an outbreak of diphtheria began in Russia and spread within four years to all of the newly independent states of the former Soviet Union. By the time that the epidemic was contained, over 150,000 cases and 5000 deaths were reported. A vast public health immunization campaign largely confined the epidemic by 1999.

See also Bacteria and bacterial infection; Epidemics, bacterial; Public health, current issues

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Diphtheria

Diphtheria

Incidence of diphtheria

Diphtheria toxin

Symptoms

Treatment

Vaccine

Resources

Diphtheria is a serious disease caused by the bacterium Corynebacterium diptheriae. Usually, the bacteria initially infect the throat and pharynx. During the course of the infection, a membranelike growth appearing on the throat can obstruct breathing. Some strains of this bacterium release a toxin, a substance that acts as a poison in the body. This toxin, when released into the bloodstream, travels to other organs of the body and can cause severe damage.

Diphtheria was first formally described as a disease in 1826. In 1888, Corynebacterium diptheriae was identified as the cause of the disease. A few years later, researchers discovered the antitoxin, or antidote, to the diphtheria toxin. If the antitoxin is given to a person with diphtheria in the early stages of the infection, the antitoxin neutralizes the toxin. This treatment, along with an aggressive vaccination program, has virtually eliminated the disease in the United States. Other countries that do not have an aggressive vaccination program see numerous cases of diphtheria, many of which end in death.

Incidence of diphtheria

Since most children in the United States are vaccinated against diphtheria, the domestic incidence of the disease is very low. When diphtheria does occur, it tends to strike adults, because fewer adults than children have been immunized against the disease. In developing countries, where fewer than 10% of the children are vaccinated against diphtheria, about five thousand deaths are still caused each year by this disease. Diphtheria is highly contagious. The disease is prevalent in densely-populated areas, especially during the winter months when more people crowd together indoors. Transmission of the bacteria occurs when an infected person sneezes or coughs and a susceptible person breathes in the saliva or mucus droplets form the air.

Diphtheria toxin

Interestingly, diphtheria toxin is produced by strains of Corynebacterium diptheriae that have themselves been infected with a special type of virus called a bacteriophage. The particular bacteriophage that infects C. diptheriae carries with it the gene that produces the diphtheria toxin. Strains of C. diptheriae without the bacteriophage do not produce the toxin.

The diphtheria toxin consists of two subunits, A and B. The B subunit binds to the plasmamembrane of a cell. Once it is bound to the membrane, it pulls the A subunit into the cell. The A subunit is the active segment of the toxin, producing most of the effects. Once inside the cell, the A subunit disrupts protein synthesis; once this mechanism is disrupted, the cell cannot survive for long. Diphtheria toxin thus kills cells. Cells in the throat and respiratory tract are killed first; if the toxin spreads in the bloodstream to other organs such as the heart, kidney, and brainsevere and even fatal damage can result.

Symptoms

The incubation periodthe time from exposure to the bacteria to the first symptomsis one to seven days. The first symptoms of diphtheria are fatigue, a low-grade fever, and a sore throat. As the disease progresses, the throat swells, sometimes so much that the patient has noticeable neck swelling. The bacteria infect the throat first before spreading to the larynx (voice box) and trachea (windpipe). At the site of infection, the throat is red and sore. In reaction to the infection, the throat tissues release a discharge containing fibrous material and immune cells. This discharge covers the throat tissues and appears as a grayish, membranelike material. The throat and trachea continue to swell; if not relieved, the swelling may obstruct the airway, leading to death by suffocation.

Sometimes diphtheria bacteria infect the skin first. When this type of infection occurs, skin lesions appear. For reasons that are not clear, the diphtheria characterized by infection is more contagious than the disease characterized by respiratory infection. The skin-type of diphtheria is more common in tropical and sub-tropical countries.

Treatment

Diphtheria is treated with antibiotics and an antitoxin that can neutralize the toxin that has not yet bound to a cell membranes; it cannot neutralize the toxin that

KEY TERMS

Antitoxin A antidote to a toxin that neutralizes its poisonous effects.

Bacteriophage A virus that infects bacteria. When a bacteriophage that carries the diphtheria toxin gene infects diphtheria bacteria, the bacteria produce diphtheria toxin.

Schick test A test that checks for the presence of diphtheria antitoxin in the body.

Toxin A poisonous substance.

has already bound to and penetrated a cell. For this reason, antitoxin must be administered early in infection. In fact, some experts recommend giving doses of antitoxin if diphtheria is even suspected, since the additional time spent waiting for confirming lab results allows for more of the toxin to spread and penetrate the cells.

Vaccine

The diphtheria vaccine consists of a small amount of the toxin that has been altered so as not to cause toxic effects. The vaccine works by prompting the bodys immune system to make antitoxin against the altered vaccine toxin. The diphtheria toxin is combined with the tetanus toxin and the pertussis (whooping cough) toxin in one vaccine, abbreviated DPT. The DPT is given in four doses. In the United States, infants are given their first DPT dose at about six to eight weeks of age. If all four doses are administered before age four, the child should have a DPT booster before beginning kindergarten. This shot boosts the immunity to the disease.

A person can be tested for their immunity to diphtheria by the Schick test, which demonstrates the presence of antitoxin within the body. In this test, a small amount of diphtheria toxin is placed under the skin of the forearm. If the site develops a reaction such as redness or swellingthe person has not developed the antitoxin from a previous infection or a vaccine, and is therefore susceptible to diphtheria. If no reaction is present, the person had already developed the antitoxin. The Schick test is useful for adults who cannot find their immunization records or do not know if they had diphtheria in childhood.

See also Childhood diseases.

Resources

BOOKS

Hammonds, Evelyn Maxine. Childhoods Deadly Scourge: The Campaign to Control Diphtheria in New York City 18801930. Baltimore: Johns Hopkins, 2002.

Salisbury, Gay, and Salisbury, Lanie. The Cruelest Miles: The Heroic Story of Dogs And Men in a Race Against an Epidemic. New York: W.W. Norton, 2005.

OTHER

World Health Organization. Diphtheria. <http://www.who.int/mediacentre/factsheets/fs089/en/> (accessed November 25, 2006).

Kathleen Scogna

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Diphtheria

Diphtheria

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Diphtheria is an acute infectious illness affecting the throat and tonsils. In severe cases, suffocation may result and there may be complications involving the heart and nervous system. Diphtheria is caused by the bacterium Corynebacterium diphtheriae. In the past, diphtheria was a major killer, with children being especially susceptible. The introduction of mass immunization has made the disease rare in the industrialized world. However, immunity to diphtheria is lost over time. Those living in stable countries with high standards of public hygiene are unlikely to be at risk. The same cannot be said when health and political systems break down, or when childhood immunization is not universal. The re-emergence of diphtheria in the former Soviet Union in the 1990s resulted from a combination of these factors. The reintroduction of mass immunization eventually brought this epidemic under control. However, diphtheria remains a threat in countries where overcrowding, unsanitary conditions, and low levels of immunization are a fact of everyday life.

Disease History, Characteristics, and Transmission

C. diphtheriae is a Gram-positive bacillus. Bacilli are a group of bacteria characterized by their rodlike shape; Gram-positive refers to the way certain bacteria absorb stains applied for microscopic study of the organism. Most strains of C. diphtheriae produce a potent toxin that is responsible for the complications of diphtheria. There are two forms of the disease—respiratory diphtheria, which is the more common, and cutaneous diphtheria. The symptoms of respiratory diphtheria include painful tonsillitis and/or pharyngitis—inflammation of tonsils and/or throat. The voice may be hoarse and fever is often present. What distinguishes diphtheria from other throat infections is the presence of a pseudomembrane, a thick, bluish white or gray covering on the throat or tonsils that may develop greenish black patches. The pseudomembrane develops when the C. diphtheriae toxin kills cells within the mucous membrane lining the throat and tonsils. The membrane may spread downwards and can interfere with breathing, causing suffocation. At the same time, the neck tends to swell, giving the patient a characteristic “bull neck” appearance.

In 10 to 20% of cases, the toxin spreads to the heart and the peripheral nervous system. It can cause myocarditis, an inflammation of the heart muscle and heart valves, which may lead to heart failure in later life. In the nervous system, diphtheria toxin can cause paralysis, which could lead to respiratory failure. Even with prompt treatment, the death rate of respiratory diphtheria is 5 to 10%. Diphtheria tends to be more severe in children under five and in adults over 40.

Cutaneous diphtheria occurs when the bacterium infects bites or rashes and is more common in tropical regions. Again, a pseudomembrane forms at the site of the infection, and ulcers usually develop on the skin. However, the complications associated with respiratory diphtheria are far less common in the cutaneous form of the disease.

Diphtheria usually is transmitted by contact with droplets from the upper respiratory tract that are propelled into the air by the coughs and sneezes of infected individuals. It is highly infectious. People who are untreated remain infectious for two to three weeks. C. diphtheriae can also be spread by contaminated objects or food.

Scope and Distribution

Diphtheria was a major child killer in the eighteenth and nineteenth centuries. Now, thanks to mass immunization, it is rare in the United States and Western Europe. Before immunization there were 100 to 200 cases of diphtheria per 100,000 of the U.S. population; now there are only 0.001 cases per 100,000 of the population. In 1942, the year when immunization was introduced in the United Kingdom, there were 60,000 cases of diphtheria a year, of which around 4,000 proved fatal. Between 1937 and 1938 diphtheria was second only to pneumonia as a cause of death in childhood. With levels of immunization in the U.K. now reaching 94%, presently there are only very occasional cases. Several European countries have not seen a single case of diphtheria for many years.

Before the discovery of the vaccine, children were most at risk from diphtheria. Now all ages seem to be at risk and, although the risk is higher among those who have not been vaccinated, cases occur among those who have had the vaccine too, because immunity appears to decline over time. In the United States, Canada, and many countries in Western Europe, childhood vaccination beginning in the 1930s and 1940s led to a rapid reduction in cases. Where diphtheria does occur, it tends to be in an incompletely vaccinated, or unvaccinated person, of low socioeconomic status.

Diphtheria is found in temperate climates. As with any highly infectious disease, diphtheria is more commonly found in areas with poor sanitation and over-crowding. The disease is endemic in the former Soviet Union, the Indian subcontinent, Southeast Asia, and Latin America. In temperate regions, diphtheria is more common in the colder months of the year. In 2000, the World Health Organization (WHO) reported 30,000 cases of diphtheria worldwide, of which 3,000 were fatal.

Treatment and Prevention

Since diphtheria is so rare in developed countries, it may be difficult for physicians to recognize when it does occur. However, the presence of the pseudomembrane, together with heart rhythm abnormalities linked to the toxin, should alert a physician to the possibility of diphtheria. Ideally, the presence of C. diphtheriae should be confirmed in the laboratory (it requires special methods for its identification), but this should not delay the start of treatment. Diphtheria is treated with antitoxin, which neutralizes the toxin before it can do too much damage, and antibiotics. The antitoxin, which was discovered in 1888, has saved the lives of many children, since it causes the pseudo membrane to recede dramatically. Diphtheria antitoxin is prepared from the serum of horses that have been immunized against the disease, and it needs to be given within four days of the onset of symptoms. Erythromycin and penicillin are the two most commonly prescribed antibiotics for diphtheria. Hospitalization and isolation are essential when dealing with diphtheria—the latter to prevent others from being exposed to the infection. If breathing is obstructed by the pseudomembrane, a tracheostomy may be needed. This procedure involves cutting an artificial opening in the trachea, or windpipe, and inserting a tube so that the patient can breathe.

Immunization has been shown to be the best way of preventing the spread of diphtheria. A toxoid is an inactivated version of a bacterial toxin. It has been found to give an excellent immune response in diseases where bacterial toxins play an important role, such as diphtheria and tetanus.

Most countries use diphtheria toxoid in combination with tetanus toxoid and pertussis (whooping cough) vaccine (DTP vaccine) to protect children. DTP is given by injection. WHO recommends children receive three separate doses of DTP. One vaccination schedule administers the three primary doses as the age of six, ten, and 14 weeks, with a booster between 18 months and six years of age. However, there is considerable variation between countries as to the vaccine and vaccination schedule used. For example, in the United States the Centers for Disease Control (CDC) recommends the use of DTaP, rather than DTP, as the safer version offering lessened side effects. Some countries have been using a combination vaccine that includes vaccines against diphtheria, tetanus, pertussis, hepatitis B, and pneumonia.

Parents often worry that a vaccine may harm their child, and this is one reason that vaccine coverage is never universal (some parents always opt out). DTP can cause fever shortly after the child receives an injection and some complain of pain, redness, and swelling at the injection site. More severe reactions, such as convulsions or shock, occur occasionally. However, for the vast majority of children, the benefits of DTP far outweigh the risk. DTP is not usually given after six years of age. Older children and adults are offered a tetanusdiphtheria toxoid vaccine (Td) and, in 2005, a combination tetanus, diphtheria, and pertussis vaccine (Tdap) was approved for adolescents and adults in the United States. Booster injections may be needed every ten years to maintain immunity, where this might be important (for instance, if traveling to an area where diphtheria is endemic). There is evidence that immunity to diphtheria tends to wane over time.

Impacts and Issues

Like cholera, diphtheria has a long history. The disease was first described by the Greek physician Hippocrates (ca. 460–357 BC), and it was also mentioned in ancient Syrian and Egyptian texts. In seventeenth century Spain, epidemic diphtheria was known as “El Garatillo” or “The Strangler.” There were also significant epidemics in England in the 1730s and in Western Europe in the second half of the nineteenth century. Diphtheria was known in America from the eighteenth century and reached epidemic proportions in 1735, often killing whole families. At the start of the twentieth century, diphtheria was still one of the leading causes of death among infants and children. When the first data on the disease were gathered, in the 1920s, there were around 150,000 cases and 13,000 deaths each year.

Today, most physicians in the United States will never see a case of diphtheria. Though diphtheria, like tuberculosis, is highly infectious, it is likely to be endemic in less developed countries where there is poverty, overcrowding, malnutrition, and poor sanitation. Mass immunization is known to be an essential tool in the prevention of diphtheria. However, less developed countries tend not to have the access to vaccine supplies or the health infrastructure to achieve WHO's goal of a 95% immunization rate.

Moreover, diphtheria still has the ability to spread and cause significant illness and death, even in a modern society where it had previously been all but eradicated. This was demonstrated clearly by the outbreaks and epidemics of the disease that occurred in the former Soviet Union in the 1990s. During the first half of the twentieth century, diphtheria rates were high in the Soviet Union; inthe1950stherewerearound750,000casesinRussia alone, but, after this time, the Communist regime of the former Soviet Union developed an excellent record on immunization. By 1976, rates of the disease were practically zero and eradication was thought to be within reach. However, in 1977, the disease began to make a comeback, with rates increasing in all age groups rather than just among children. Rates peaked in 1984 and then began to decline thereafter, although they never returned to the low of 1976. Researchers for the Centers for Disease Control and Prevention (CDC) argue that the military may have contributed to the spread of diphtheria in the 1980s. Military service was universal and led to the housing of recruits, many of whom had not been immunized, in overcrowded conditions. Adult immunity, among those immunized many years earlier, appeared to be declining, accounting for adult cases of diphtheria. The immunization schedule among children was also less intense than previously, in part due to a campaign against immunization that found favor in a population increasingly distrustful of its government.

WORDS TO KNOW

ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).

ANTITOXIN: An antidote to a toxin that neutralizes its poisonous effects.

CUTANEOUS: Pertaining to the skin.

RE-EMERGENCE: Reemergence is when something that has been absent appears again.

The breakup of the Soviet Union in the late 1980s and early 1990s was the final event that set the stage for a new wave of diphtheria in the former Soviet Union. In 1990, diphtheria returned to Russia in force. There were over 1,000 cases reported from St Petersburg, Kaliningrad, Orlovskaya, and Moscow. The epidemic grew over the next few years and deaths occurred because of failures in a health care system facing economic crisis. Epidemic diphtheria became established in urban Russia, Ukraine, and Belarus. In 1993, 19,462 cases were reported of which 15,211 were in Russia, an increase of nearly 300% from the previous year. Many of these cases were, again, among adults. This was the first largescale diphtheria epidemic in a developed country for over three decades. At the peak of the epidemic, in 1995, there were over 50,000 cases reported in the region, compared to only 24 cases in the rest of Europe.

In 1994 and 1995, WHO, the United Nations Children's Fund, other agencies, and governments in the affected countries undertook massive efforts to vaccinate both children and adults. These efforts soon began to bring the epidemic under control, resulting in a 60% drop in cases by 1996. According to WHO data, gathered in 2000, incidence rates of diphtheria in Armenia, Estonia, Lithuania, and Uzbekistan were 0.5 to 1 per 100,000 of the population. In Russia and Tajikistan, rates were as high as 27 to 32 per 100,000 of the population. Fatality rates were 2 to 3% in Russia and Ukraine and 6 to 10 %in Armenia, Kazakhstan, Moldova, and Latvia. In Azerbaijan, Georgia, and Turkmenistan the death rate from diphtheria was 17 to 23%. By 2004, the number of cases reported to the WHO European region, which includes the former Soviet Union, was down to 176.

The CDC says that the outbreak of diphtheria in the former Soviet Union shows that adults can become vulnerable to childhood diseases again when immunization does not confer lifelong immunity. This condition applies in any other country where there is mass immunization against diphtheria. However, there have been no similar epidemics anywhere else in the Western world. It was probably the combination of factors in the Soviet Union at the time that set the scene for the epidemic. Added to the decline in both childhood and adult immunity was the political breakup of the Soviet Union and the formation of several new states. Economic pressures led to mass migrations of people from rural areas into the cities in Russia; many failed to find work and ended up sleeping in primitive or crowded conditions. Many diphtheria cases occurred in this group. Refugees fleeing from fighting in Georgia, Armenia, Azerbaijan, and Tajikistan were also at risk. People were on the move in the region on a scale never seen before. This powerful factor—not seen in neighboring nations—probably encouraged the spread of the disease. The success of mass vaccination in controlling the epidemic in the former Soviet Union reconfirms the importance of this primary tool for fighting diphtheria.

A WHO report of a diphtheria outbreak in Afghanistan illustrates the factors that increase the risk of the disease. Between June and August 2003, there were 50 cases of diphtheria, including three deaths, in a resettlement camp for internally displaced people in Kandahar. About 75% of the patients were ages five to 14. A mass immunization campaign for the 40,000 residents of the camp was launched in August 2003. The Ministry of Health was assisted by WHO and several other organizations, such as Médecins sans Frontières-Holland and the Red Cross, in provision of drugs, antitoxin, and vaccine supplies to help bring the outbreak under control.

Lessons learned from Russia and Afghanistan can be applied to other diseases and other countries. Improving living conditions, mass immunization, and establishing a health infrastructure within a stable political system are the ways in which highly infectious diseases can best be controlled.

Primary Source Connection

Advances in the treatment of diphtheria and many other infectious diseases (along with advances in the treatment of illnesses such as diabetes) have significantly changed the expectations of parents and communities in countries with advanced health care and public health capacity.

Russell Baker is a Pulitzer Prize-winning writer. The excerpt below is republished from his autobiography and allows readers some insights into the resignation and thinking of a time, less than a century ago in America, when disease “mostly with prayer, and early death was commonplace.”

IN CONTEXT: REAL-WORLD RISKS

The Coordinating Center for Infectious Diseases/Division of Bacterial and Mycotic Diseases states that diphtheria “circulation appears to continue in some settings even in populations with 80% childhood immunization rates. An asymptomatic carrier state exists even among immune individuals.”

Because immunity lessens over time “decennial booster doses are required to maintain protective antibody levels. Large populations of adults are susceptible to diphtheria in developed countries—[and] appear to be increasing in developing countries as well.”

SOURCE: Coordinating Center for Infectious Diseases/Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention (CDC)

See AlsoCholera; Médecins Sans Frontières (Doctors Without Borders).

BIBLIOGRAPHY

Books

Garrett, Laurie. The Coming Plague: Newly Emerging Diseases in a World out of Balance. London: Virago Press, 1995.

Wilson, Walter R., and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.

Periodicals

Vitek, C.R., and M. Wharton. “Diphtheria in the Former Soviet Union: Reemergence of a Pandemic Disease.” Emerging Infectious Diseases 4 (October-December 1998). This article is available online <http://www.cdc.gov/ncidod/eid/vol4no4/vitek.htm>

Web Sites

Health Protection Agency. “Diphtheria.” February 2, 2006. <http://www.hpa.org.uk/infections/topics_az/diphtheria/gen_info.htm> (accessed February 16, 2007).

Todar's Online Textbook of Bacteriology. “Diphtheria.” <http://textbookofbacteriology.net/diphtheria.html> (accessed February 16, 2007).

World Health Organization. “Diphtheria.” <http://www.who.int/topics/diphtheria/en/> (accessed February 16, 2007).

Susan Aldridge

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Diphtheria

Diphtheria

Diphtheria is a serious disease caused by the bacterium Corynebacterium diptheriae. Usually, the bacteria initially infect the throat and pharynx. During the course of the infection , a membrane-like growth appearing on the throat can obstruct breathing. Some strains of this bacterium release a toxin, a substance that acts as a poison in the body. This toxin, when released into the bloodstream, travels to other organs of the body and can cause severe damage.

Diphtheria was first formally described as a disease in 1826. In 1888, Corynebacterium diptheriae was identified as the cause of the disease. A few years later, researchers discovered the antitoxin, or antidote, to the diphtheria toxin. If the antitoxin is given to a person with diphtheria in the early stages of the infection, the antitoxin neutralizes the toxin. This treatment, along with an aggressive vaccination program, has virtually eliminated the disease in the United States. Other countries that do not have an aggressive vaccination program, have numerous cases of diphtheria, many of which end in death.


Incidence of diphtheria

Since most children in the United States are vaccinated against diphtheria, the domestic incidence of the disease is very low. When diphtheria does occur, it tends to strike adults, because fewer adults than children have been immunized against the disease. In developing countries, where less than 10% of the children are vaccinated against diphtheria, about one million deaths are caused each year by this disease. Diphtheria is highly contagious. The disease is prevalent in densely-populated areas, especially during the winter months when more people crowd together indoors. Transmission of the bacteria occurs when an infected person sneezes or coughs and a susceptible person breathes in the saliva or mucus droplets form the air.


Diphtheria toxin

Interestingly, diphtheria toxin is produced by strains of Corynebacterium diptheriae that have themselves been infected with a special type of virus called a bacteriophage . The particular bacteriophage that infects C. diptheriae carries with it the gene that produces the diphtheria toxin. Strains of C. diptheriae without the bacteriophage do not produce the toxin.

The diphtheria toxin consists of two subunits, A and B. The B subunit binds to the plasma membrane of a cell . Once it is bound to the membrane, it pulls the A subunit into the cell. The A subunit is the active segment of the toxin, producing most of the effects. Once inside the cell, the A subunit disrupts protein synthesis; once this mechanism is disrupted, the cell cannot survive for long. Diphtheria toxin thus kills cells. Cells in the throat and respiratory tract are killed first; if the toxin spreads in the bloodstream to other organs—such as the heart , kidney, and brain—severe and even fatal damage can result.


Symptoms

The incubation period—the time from exposure to the bacteria to the first symptoms—is one to seven days. The first symptoms of diphtheria are fatigue, a low-grade fever, and a sore throat. As the disease progresses, the throat swells, sometimes so much that the patient has noticeable neck swelling. The bacteria infect the throat first before spreading to the larynx (voice box) and trachea (windpipe). At the site of infection, the throat is red and sore. In reaction to the infection, the throat tissues release a discharge containing fibrous material and immune cells. This discharge covers the throat tissues and appears as a grayish, membrane-like material. The throat and trachea continue to swell; if not relieved, the swelling may obstruct the airway, leading to death by suffocation.

Sometimes diphtheria bacteria infect the skin first. When this type of infection occurs, skin lesions appear. For reasons that are not clear, the diphtheria characterized by infection is more contagious than the disease characterized by respiratory infection. The skin-type of diphtheria is more common in tropical and sub-tropical countries.


Treatment

Diphtheria is treated with an antitoxin that can only neutralize the toxin that has not yet bound to a cell membranes; it cannot neutralize the toxin that has already bound to and penetrated a cell. For this reason, antitoxin must be administered early in infection. In fact, some experts recommend giving doses of antitoxin if diphtheria is even suspected, since the additional time spent waiting for confirming lab results allows for more of the toxin to spread and penetrate the cells.


Vaccine

The diphtheria vaccine consists of a small amount of the toxin that has been altered so as not to cause toxic effects. The vaccine works by prompting the body's immune system to make antitoxin against the altered vaccine toxin. The diphtheria toxin is combined with the tetanus toxin and the pertussis (whooping cough ) toxin in one vaccine, abbreviated DPT. The DPT is given in four doses. In the United States, infants are given their first DPT dose at about six to eight weeks of age. If all four doses are administered before age four, the child should have a DPT "booster" before beginning kindergarten. This shot "boosts" the immunity to the disease.

A person can be tested for their immunity to diphtheria by the Schick test, which demonstrates the presence of antitoxin within the body. In this test, a small amount of diphtheria toxin is placed under the skin of the forearm. If the site develops a reaction—such as redness or swelling—the person has not developed the antitoxin from a previous infection or a vaccine, and is therefore susceptible to diphtheria. If no reaction is present, the person had already developed the antitoxin. The Schick test is useful for adults who cannot find their immunization records or cannot remember if they had diphtheria in childhood.

See also Childhood diseases.


Resources

periodicals

Kleinman, Lawrence C. "To End an Epidemic: Lessons From the History of Diphtheria." New England Journal of Medicine 326 (March 12, 1992): 773.

"Misfiring Magic Bullets (Report on Adverse Effect from Diphtheria-Pertussis-Tetanus and Rubella Vaccines)." Science News 140 (July 20, 1991): 45.

Peter, Georges. "Childhood Immunizations." New EnglandJournal of Medicine 327 (December 7, 1992): 25.


Kathleen Scogna

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antitoxin

—A antidote to a toxin that neutralizes its poisonous effects.

Bacteriophage

—A virus that infects bacteria. When a bacteriophage that carries the diphtheria toxin gene infects diphtheria bacteria, the bacteria produce diphtheria toxin.

Schick test

—A test that checks for the presence of diphtheria antitoxin in the body.

Toxin

—A poisonous substance.

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