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

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

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

Signs and symptoms

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

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

Diagnosis

Laboratory criteria

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

Case classification

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

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

Treatment

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

Epidemiology

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

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Availability of diphtheria antitoxin through an investigational new drug protocol - Notice to Readers
From Morbidity and Mortality Weekly Report, 5/21/04

Cases of respiratory diphtheria continue to occur sporadically among persons in the United States (1). Respiratory diphtheria is caused by toxigenic Corynebacterium diphtheriae (also, rarely, by toxigenic (C. ulcerans) and frequently manifests insidiously as a membranous nasopharyngitis of obstructive laryngotracheitis accompanied by a low-grade fever. Respiratory diphtheria most often affects unvaccinated or inadequately vaccinated persons, particularly those who travel to areas where diphtheria is endemic and those who come into close contact with travelers from such areas (1). Effective treatment of respiratory diphtheria includes early administration of an equine diphtheria antitoxin (DAT). Delay in DAT administration can lead to life-threatening respiratory obstruction, myocarditis, and other complications. To ensure quick access to DAT, CDC maintains a stock of DAT for release to U.S. physicians.

No manufacturer has sought U.S. licensure of a DAT product since 1996. In 1997, an equine DAT product manufactured by Pasteur Merieux (Lyons, France) was made available in the United States through a Food and Drug Administration (FDA)-approved Investigational New Drug (IND) protocol (2). Production of this product ceased in 2002, and remaining supplies at CDC will expire on May 30, 2004.

To ensure the continued availability of DAT in the United States, CDC has procured an equine DAT product from the Instituto Butantan in Brazil. CDC will provide this product to U.S. physicians under an FDA-approved IND protocol. U.S. physicians caring for patients with suspected respiratory diphtheria can obtain DAT by contacting the diphtheria duty officer at CDC's Bacterial Vaccine Preventable Disease Branch in the Epidemiology and Surveillance Division of the National Immunization Program (telephone, 404-639-8257) from 8 a.m. to 4:30 p.m. Eastern time or from the Emergency Operations Center (telephone, 770-488-7100) at all other times. The duty officer will discuss the case and protocol with the physician and, if indicated, DAT will be rushed from one of eight U.S. Public Health Service quarantine stations. Respiratory diphtheria is a reportable disease; physicians should report any suspected case of respiratory diphtheria promptly to their local and state health departments.

References

(1.) CDC. Fatal respiratory diphtheria in a U.S. traveler to Haiti--Pennsylvania, 2003. MMWR 2003;52:1285-6.

(2.) CDC. Availability of diphtheria antitoxin through an Investigational New Drug protocol. MMWR 1997;46:380.

COPYRIGHT 2004 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

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