DIPHTHERIA

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

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

Contents
1 Signs and symptoms
2 Diagnosis
2.1 Laboratory criteria
2.2 Case classification
3 Treatment
4 Epidemiology
5 History
6 Source

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

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

Diagnosis

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

Case classification
Probable: a clinically compatible case that is not laboratory confirmed and is not epidemiologically linked to a laboratory-confirmed case
Confirmed: a clinically compatible case that is either laboratory confirmed or epidemiologically linked to a laboratory-confirmed case
Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

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

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

Such statistics show that constant vigilance must be maintained even on largely eradicated diseases, especially since many of these diseases show growing resistance to drugs that have been used to fight them for decades.

From the CDC guidelines:

Cutaneous diphtheria should not be reported. Respiratory disease caused by nontoxigenic C. diphtheriae should be reported as diphtheria. All diphtheria isolates, regardless of association with disease, should be sent to the Diphtheria Laboratory, National Center for Infectious Diseases, CDC.

History
Diphtheria (dif-thir-ee-uh or often dip-thir-ee-uh) takes its name from the Greek word for "leather", dipthera, and was named in 1855 by French physician Armand Trousseau (1801-1867). This coinage alludes to the leathery, sheath-like membrane that grows on the tonsils, throat and in the nose.

Diphtheria was once one of the most dreaded diseases, with frequent large-scale outbreaks. From 1735-1740, a diphtheria epidemic in the New England colonies was said to have killed as much as 80% of the children under 10 years of age in some towns. In 1920s there were an estimated 100,000 to 200,000 cases a year of diphtheria in the United States, with 13,000 to 15,000 deaths. Children represented the large majority of cases and fatalities.

A bottle of diphtheria antitoxin, produced by the United States Hygienic Laboratory and dated May 8, 1895One of the first early effective treatments was discovered in the 1880s by U.S. physician Joseph O'Dwyer (1841-1898). O'Dwyer developed tubes that could be inserted into the throat to prevent victims from suffocating from the membrane sheath that grew and obstructed the airways. In the 1890s, the German physician Emil von Behring developed an anti-toxin that, although it did not kill the bacteria, neutralized the toxic poisons that the bacteria released into the body. For this (and his serum therapy for diphtheria), he won the first Nobel Prize in Medicine. (Americans William H. Park and Anna Wessels Williams also developed a diphtheria antitoxin in the 1890s.) Effective vaccines were not developed until the discovery and development of sulfa drugs following World War II.

Diphtheria was also prevalent in the British royal family during the late 19th century. Famous cases included a daughter and granddaughter of Britain's Queen Victoria. Princess Alice of Hesse (second daughter of Queen Victoria) died of diphtheria after she contracted it from her children in December of 1878 while nursing them. One of Princess Alice's own daughter, Princess Marie also died of diphtheria in November of 1878 when she was only four years old.

Sacagawea and Elisha Graves Otis were two famous people who died from diphtheria.

Diphtheria is an acute, toxin-mediated disease caused by Corynebacterium diphtheriae. The name of the disease is derived from the Greek diphthera, meaning leather hide. The disease was described in the 5th Century B.C. by Hippocrates, and epidemics were described in the 6th Century A.D. by Aetius. The bacterium
was first observed in diphtheritic membranes by Klebs in 1883 and cultivated by Löffler in 1884. Antitoxin was invented in the late 19th century, and toxoid was developed in the 1920s.

CORYNEBACTERIUM DIPHTHERIAE
C. diphtheriae is an aerobic gram-positive bacillus.Toxin production (toxigenicity) occurs only when the bacillus is itself infected (lysogenized) by a specific virus (bacteriophage) carrying the genetic information for the toxin (tox gene). Only toxigenic strains can cause severe disease. Culture of the organism requires selective media containing tellurite. If isolated, the organism must be distinguished in the laboratory from other Corynebacterium species that normally inhabit the nasopharynx and skin (e.g., diphtheroids).

There are three biotypes of C. diphtheriae — gravis, intermedius, and mitis. The most severe disease is associated with the gravis biotype, but any strain may produce toxin. All isolates of C. diphtheriae should be tested by the laboratory for toxigenicity.

PATHOGENESIS
Susceptible persons may acquire toxigenic diphtheria bacilli in the nasopharynx. The organism produces a toxin that inhibits cellular protein synthesis and is responsible for local tissue destruction and membrane formation. The toxin produced at the site of the membrane is absorbed into the bloodstream and distributed to the tissues of the body. The toxin is responsible for the major complications of myocarditis and neuritis and can also cause low platelet counts (thrombocytopenia) and protein in the urine (proteinuria).
Clinical disease associated with non-toxin-producing strains is generally milder. While rare severe cases have been reported, these may actually have been caused by toxigenic strains which were not detected due to inadequate culture sampling.

CLINICAL FEATURES
The incubation period of diphtheria is 2–5 days (range, 1–10 days).
Disease can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into a number of manifestations, depending on the site of disease.

ANTERIOR NASAL DIPHTHERIA
Diphtheria

What is diphtheria?
Diphtheria is a very contagious and potentially life-threatening infection that usually attacks the throat and nose. In more serious cases, it can attack the nerves and heart. Because of widespread immunization, diphtheria is very rare in the United States. However, some people are not adequately vaccinated, and cases still occur.

What is the infectious agent that causes diphtheria?
Diphtheria is caused by Corynebacterium diphtheriae, a bacterium. The bacterium produces a toxin (poison) that is carried in the bloodstream.

Where is diphtheria found?
Diphtheria is common in many parts of the world. Diphtheria bacteria live in the mouth, nose, throat, or skin of infected persons.

How do people get diphtheria?
Diphtheria spreads from person to person very easily. People get diphtheria by breathing in diphtheria bacteria after an infected person has coughed or sneezed. People also get diphtheria from close contact with discharges from an infected person's mouth, nose, throat, or skin.

What are the signs and symptoms of diphtheria?
Usually, diphtheria develops in the throat. Early symptoms are a sore throat and mild fever. A membrane that forms over the throat and tonsils can make it hard to swallow. The infection also causes the lymph glands and tissue on both sides of the neck to swell to an unusually large size. Some people can be infected but not appear ill. They can also spread the infection.

How soon after exposure do symptoms appear?
Symptoms usually appear 2 to 4 days after infection.

How is diphtheria diagnosed?
Diagnosis is by physician examination and throat culture.

Who is at risk for diphtheria?
Diphtheria is most common in areas where people live in crowded conditions with poor sanitation. Persons, especially children, who are not immunized or who did not receive adequate immunization are most at risk.

What complications can result from diphtheria?
If diphtheria is not properly treated, or not treated in time, the bacteria can produce a powerful toxin (poison). This poison can spread through the body and cause serious, often life-threatening complications. The diphtheria toxin can damage the heart muscles and cause heart failure or paralyze the breathing muscles. The membrane that forms over the tonsils can also move deeper into the throat and block the airway.

What is the treatment for diphtheria?
Diphtheria is a medical emergency. A delay in treatment can result in death or long-term heart disease. A person with diphtheria should be hospitalized until fully recovered. The person should be given a medicine (diphtheria antitoxin) to fight the diphtheria poison and antibiotics to fight the diphtheria bacteria. Some patients might need mechanical help in breathing (respirator).
Persons who have been in close contact with the patient should have throat cultures and be given antibiotics. They should be closely watched for possible symptoms. Close contacts who have not been immunized should receive a complete series of diphtheria shots. A booster vaccine can be given to persons who have been immunized before.

How common is diphtheria?
Diphtheria was once one of the most common causes of death in children. Since the introduction and widespread use of diphtheria vaccine, diphtheria has been rare in the United States. Between 1980 and 1995, 41 cases of diphtheria were reported to health authorities.
Diphtheria is still common in many other parts of the world, including the Caribbean and Latin America. During the last few years, large epidemics of diphtheria have occurred in the former Soviet republics. Outbreaks have also been reported in Algeria, China, and Ecuador. The majority of cases in many of these epidemics have been in adults and adolescents.

Is diphtheria an emerging infectious disease?
Yes. Diphtheria has re-emerged in the newly independent states of the former Soviet Union and in some other parts of the world at near-epidemic levels. The increases have generally been the result of failed public health and immunization programs in areas weakened by economic and social turmoil.
In the United States, the diphtheria threat is shifting from children to adults and adolescents. Cases are occurring in persons who have not been immunized or in vaccinated persons who did not receive periodic booster doses to maintain their immunity. Routine vaccination of both children and adults is essential to prevent the re-emergence of diphtheria in the United States.

How can diphtheria be prevented?
There is a vaccine for diphtheria. The diphtheria vaccine is usually given in a combination shot with tetanus and pertussis vaccines, known as DTP vaccine. A child should have received four DTP shots by 18 months of age, with a booster shot at age 4 years to 6 years. After that, diphtheria and tetanus boosters should be given every 10 years to provide continued protection.
As is the case with all immunizations, there are important exceptions and special circumstances. Health-care providers should have the most current information on recommendations about diphtheria vaccination.
This fact sheet is for information only and is not meant to be used for self-diagnosis or as a substitute for consultation with a health-care provider. If you have any questions about the disease described above, consult a health-care provider.