Diphtheria

What is Diphtheria?

Diphtheria is an upper respiratory tract illness characterized by sore throat, low fever, and an adherent membrane (a ''pseudomembrane'') on the tonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin. Uncommon consequences include myocarditis (about 20% of cases) and peripheral neuropathy (about 10% of cases). It is caused by ''Corynebacterium diphtheriae'', a facultative anaerobic Gram-positive bacterium.

Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations through widespread vaccination. In the United States for example, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007 there were only three cases as the DPT (''Diphtheria–Pertussis–Tetanus'') vaccine is recommended for all school-age children. Boosters of the vaccine are recommended for adults since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

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Diphtheria Mechanism

Diphtheria toxin consists of a single polypeptide. Proteolysis yields two fragments (A and B) which are held together by a disulfide bond. The toxin binds to EGF-like domain of Heparin-binding EGF-like growth factor (HB-EGF) through fragment B and is internalized with HB-EGF by receptor-mediated endocytosis.

The low pH in the late endosomes induce pore formation by fragment B as well as catalyses the release of catalytic fragment A into the cytosol. Diphtheria toxin catalyzes the ADP-ribosylation of, and inactivates, the elongation factor eEF-2. In this way, it acts to inhibit translation during eukaryotic protein synthesis. The toxin enters the host cell and is hydrolysed by a trypsin-like protease to give a fragment with enzymatic activity.

The toxin then transfers an ADP-ribose from NAD+ to a diphthamide residue, a modified histidine (amino acid), which is found within the EF-2 protein. EF-2 is needed for translocation of tRNA from the A-site to the P-site of the ribosome during translation. The ADP-ribosylation is reversible by administering high concentrations of nicotinamide, one of the reaction products.

Diphtheria toxin is only produced by C. diphtheriae when it is infected with a bacteriophage. The bacteriophage integrates a gene into the bacteria that causes the toxin to be produced.

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Diphtheria 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
  • high-grade fever, and
  • An adherent pseudomembrane 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.

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Diphtheria 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. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure.

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. 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.

In cases that progress beyond a throat infection, diphtheria toxin spreads through the bloodstream and can lead to potentially life-threatening complications that affect other organs of the body, such as the heart and kidneys. The toxin can cause damage to the heart that affects its ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. Up to 40% to 50% of those who don't get treated can die.

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Diphtheria 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, informally referred to as "bull neck." 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).

The cutaneous form of diphtheria is often a secondary infection of a preexisting skin disease. Signs of cutaneous diphtheria infection develop an average of seven days after the appearance of the primary skin disease.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Diphtheria" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.