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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Imported cutaneous diphtheria, Germany, 1997-2003
From Emerging Infectious Diseases, 2/1/05 by Andreas Sing

To the Editor: The March 2004 report by de Benoist et al. on the incidence of imported cutaneous diphtheria in the United Kingdom (1) prompted us to describe the situation of cutaneous diphtheria in Germany and to analyze the cases reported to the German Consiliary Laboratory on Diphtheria since its establishment at our institute in 1997. The laboratory provides advisory and diagnostic services mainly to microbiologic laboratories throughout Germany.

From 1997 to 2003, 6 cases of cutaneous infections caused by toxigenic Corynebacterium diphtheriae were documented (Table). None of these was accompanied by secondary diphtheria infection. Toxigenicity was determined by both dtx polymerase chain reaction and Elek test (2). As in the United Kingdom, all cases for which clinical information was available (N = 5) were imported. Three were found in tourists who had traveled to tropical countries: a 20-year-old diver had injured her heel after stepping on coral in Thailand; a 60-year-old tourist had a chronic ulcer develop in the thigh alter a trip to Indonesia (no history of an insect bite); and a 39-year-old traveler to Kenya returned with a purulent ear infection with no memory of trauma or insect bite. The remaining imported C. diphtheriae skin infections were reported in 2 Angolan children, 5 and 10 years of age, who were brought to Germany by a humanitarian organization for surgery on severe gun wounds to their lower extremities (foot and thigh with chronic osteomyelitis, respectively). To our knowledge, these reports are the first of cutaneous diphtheria in gunshot wounds in recent years. Moreover, in the patient with the thigh wound, C. diphtheriae was also isolated from a deep fistula, which suggests involvement of C. diphtheriae in the chronic osteomyelitis.

As in the United Kingdom, all cases of diphtheria reported since 1997 were caused by C. diphtheriae mitis. In 4 of 5 cutaneous diphtheria patients who had an available medical history, mixed infections with Staphylococcus aureus and Streptococcus pyogenes were found; 3 of 5 patients were not sufficiently vaccinated against diphtheria as recommended. Systemic symptoms, such as malaise and general weakness, developed in the 20-year-old Thailand tourist, although she had received a booster dose just before her travel. Cutaneous diphtheria must be expected even in vaccinated patients; for instance, among serum samples of 287 healthy German adults with a complete record of basic immunization against diphtheria, only 42.2% showed full serologic protection as indicated by antitoxin levels [greater than or equal to] 0.1 IU/mL (3).

As de Benoist et al. outline, cutaneous diphtheria might be difficult to diagnose because of its unspecific clinical appearance and the presence of mixed infections in chronic nonhealing skin lesions. Because of the nearly complete disappearance of cutaneous diphtheria in many parts of the western world, microbiologists lack experience in identifying C. diphtheriae grown from specimens. From 1997 to 2003, approximately one fifth of the strains sent to our Consiliary Laboratory on Diphtheria for species identification and toxin testing were either nondiphtheria Corynebacterium spp. or noncoryneform bacteria of different genera (including lactobacilli, Dermabacter hominis, and Propionibacterium acnes).

Clinicians (4) and microbiologists (5) should be aware of the possibility of cutaneous diphtheria in chronically infected skin lesions in patients returning from disease-endemic regions. Medical personnel should include this in civilian as well as military health services, since our cases indicate that toxigenic C. diphtheriae might affect not only travel-related skin injuries caused by leisure or tourist activities but also wounds in patients from war regions in diphtheria-endemic areas.

References

(1.) De Benoist AC, White JM, Efstratiou A, Kelly C, Mann G, Nazareth B, et al. Imported cutaneous diphtheria, United Kingdom. Emerg Infect Dis. 2004:10:511-3.

(2.) Sing A. Hogardt M. Bierschcnk S, Heesemann J. Detection of differences in the nucleotide and amino acid sequences of diphtheria toxin from Corynebacterium diphtheriae and Corynebacterium ulcerans causing extrapharyngeal infections. J Clin Microbiol. 2003:41:4848-51.

(3.) Hasselhorn HM, Nubling M, Tiller FW, Hofmann F. Factors influencing immunity against diphtheria in adults. Vaccine. 1998;16:70-5.

(4.) Bonnet JM, Begg NT. Control of diphtheria: guidance for consultants in communicable disease control. Commun Dis Public Health. 1999:2:242-9.

(5.) Efstratiou A, George RC. Laboratory guidelines for the diagnosis of infections caused by Corynebacterium diphtheriae and C. ulcerans. Commun Dis Public Health. 1999:2:250-7.

Address for correspondence: Andreas Sing, Max von Pettenkofer-Institut fur Hygiene und Medizinische Mikrobiologie, National Consiliary Laboratory on Diphtheria, Pettenkoferstrasse 9a, 80336 Munich, Germany: fax: 49-89-5160-5223; email: sing@m3401.mpk.med.uni-muenchen.de

Andreas Sing * and Jurgen Heesemann *

* Max von Pettenkofer-Institut fur Hygiene und Medizinische Mikrobiologie, Munich, Germany

COPYRIGHT 2005 U.S. National Center for Infectious Diseases
COPYRIGHT 2005 Gale Group

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