Diphtheria
From DrugPedia: A Wikipedia for Drug discovery
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. It is caused by Corynebacterium diphtheriae, an aerobic Gram-positive bacterium.
Diphtheria causes the progressive deterioration of myelin sheaths in the central and peripheral nervous system leading to degenerating motor control and loss of sensation. Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Once quite common, diphtheria has largely been eradicated in developed nations through widespread vaccination. In the United States for instance, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007 there were only five cases as the DPT (Diphtheria–Pertussis–Tetanus) vaccine is given to all school 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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Mechanism
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.
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).
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.
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 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.
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 and 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.
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.
See also
- Bacterial diseases in India
- Anthrax
- Bacterial meningitis
- Cholera
- Gonorrhea
- Leprosy
- Plague
- Rickettsial diseases
- Syphilis
- Tuberculosis
- Yaws
Further reading
- Holmes RK, "Diphtheria and other corynebacterial infections". In Harrison's Principles of Internal Medicine, 16th Ed. (2005).
- "Antitoxin dars 1735 and 1740." The William and Mary Quarterly, 3rd Ser., Vol 6, No 2. p. 338.
- Shulman ST, "The History of Pediatric Infectious Diseases", Pediatric Research. Vol. 55, No. 1 (2004).
Original Source
This article was originally posted in Wikipedia.
--Jasjit 15:17, 29 August 2008 (IST)
