Diphtheria
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| ICD-10 | A30 |
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| ICD-9 | 032 |
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| eMedicine | {{{eMedicineSubj}}}/{{{eMedicineTopic}}} |
| DiseasesDB | {{{DiseasesDB}}} |
Diphtheria is an upper respiratory tract illness characterized by sore throat, low-grade fever, and an adherent membrane (a pseudomembrane) on 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.
Signs and symptoms
The respiratory form has an incubation period of 2-5 days. The onset of disease is usually gradual. 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. In 10% of cases, patients experience neck swelling. These cases are associated with a higher risk of death.
In addition to symptoms at the site of infection (sore throat), the patient may experience more generalized symptoms, such as listlessness, pallor, and fast heart rate. These symptoms are caused by the toxin released by the bacterium. Low blood pressure may develop in these patients. Longer-term effects of the diphtheria toxin include cardiomyopathy and peripheral neuropathy (sensory type)[1].
The cutaneous form of diphtheria is often a secondary infection of a preexisting skin disease. Signs of cutaneous diphtheria infection develop an average of 7 days after the appearance of the primary skin disease.
Diagnosis
The current definition of diphtheria used by the Centers for Disease Control and Prevention (CDC) is based on both laboratory and clinical criteria.
Laboratory criteria
- Isolation of Corynebacterium diphtheriae from a clinical specimen, or
- Histopathologic diagnosis of diphtheria.
Clinical criteria
- Upper respiratory tract illness with sore throat
- Low-grade fever, and
- An adherent membrane of the tonsil(s), pharynx, and/or nose.
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 intubation or 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 a hospital intensive care unit (ICU) and be given a diphtheria anti-toxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.
Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The CDC recommends either:
- Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
- Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg).
Patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin.
Epidemiology
Diphtheria remains a serious disease, with fatality rates between 5 and 10 percent in adults. In children under 5 years and adults over 40 years, the fatality rate may be as much as 20%. Outbreaks, though very rare, still occur worldwide, even in developed nations. After the breakup of the former Soviet Union in the late 1980s, vaccination rates in its constituent countries fell so low that there was an explosion of diphtheria cases. In 1991 there were 2,000 cases of diphtheria in the USSR. By 1998, according to Red Cross estimates, there were as many as 200,000 cases in the Commonwealth of Independent States, with 5,000 deaths. This was so great an increase that diphtheria 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.
The Schick test can be used to test susceptibility.
History
Diphtheria takes its name from the Greek word for “leather,” διφθερα (dipthera), and was named in 1826 by French physician Pierre Bretonneau. The name alludes to the leathery, sheath-like membrane that grows on the tonsils, throat and in the nose. The pronunciation /ˌdipˈθiɹˌi.ə/ was originally considered incorrect but has now become the most common way of saying the word, and is accepted as a correct form. While many writers today use the spelling "diptheria" which fits the modern pronunciation, this cannot be found in dictionaries.
Diphtheria was once one of the most dreaded diseases, with frequent large-scale outbreaks. A diphtheria epidemic in the New England colonies between 1735 and 1740 was said to have killed as many as 80% of the children under 10 years of age in some towns. In the 1920s there were an estimated 100,000 to 200,000 cases of diphtheria per year in the United States, with 13,000 to 15,000 deaths. Children represented the large majority of cases and fatalities.
One 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 antitoxin that, although it did not kill the bacteria, neutralized the toxic poisons that the bacteria released into the body. For this discovery and his development of a 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.) The first successful vaccine for diphtheria was developed in 1923. However, 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 daughters, Princess Marie, also died of diphtheria in November of 1878.
Sacagawea and Elisha Graves Otis also died from diphtheria.
ReferencesISBN links support NWE through referral fees
- The first version of this article was adapted from the CDC document "Diphtheria - 1995 Case Definition" at http://www.cdc.gov/epo/dphsi/casedef/diphtheria_current.htm. As a work of an agency of the U.S. Government without any other copyright notice it should be available as a public domain resource.
- Holmes RK, Diphtheria and other corynebacterial infections. in Harrison's Principles of Internal Medicine, 16th Ed. (2005)
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