Diphtheria (Greek for “pair of leather scrolls”) is an upper respiratory tract illness with sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity (thus the comparison to leather scrolls). 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 systems leading to degenerating motor control and loss of sensation. Diphtheria is contagious and is spread by direct physical contact or breathing the aerosolized droplets of infected individuals. Diphtheria has largely been eradicated in developed nations, presumably through widespread vaccination. In the U.S. there were 52 reported cases of diphtheria between 1980 and 2000. Since 2000 there have been five cases. The DPT (Diphtheria–Pertussis–Tetanus) vaccine is given to all school children and boosters of the vaccine are recommended for adults since the benefits of the vaccine decrease with age without constant re-exposure. REvaccination is particularly recommended for those traveling to areas where the disease has not been eradicated. Not all doctors agree with vaccination, however this is a subject for another article.
Signs and Symptoms
The respiratory form of diptheria 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 swelling of the neck, a development associated with a higher risk of death. In addition the patient may experience more generalized symptoms, such as listlessness, pallor, and accelerated heart rate, all symptoms caused by the bacterial toxin. Low blood pressure may develop in these patients. Longer-term effects of the diphtheria toxin include cardiomyopathy and sensory peripheral neuropathy. Signs of cutaneous diphtheria infection develop an average of seven days after the appearance of the primary skin disease.The cutaneous form of diphtheria is often a secondary infection of a preexisting skin disease.
Diagnosis is made by both laboratory and clinical criteria. Isolation of Corynebacterium diphtheriae from a clinical specimen, or histopathologic diagnosis will sufffice for diagnosis at the laboratory level. Upper respiratory tract illness with sore throat, low-grade fever, and an adherent pseudomembrane of the tonsils, pharynx, and/or nose constitutes the clinical presentation.
In severe cases lymph nodes in the neck may swell, and breathing and swallowing will become difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or tracheotomy. Hyper sensitivity of the larynx may cause cardiac arrest around the intubation. 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 and be given the diphtheria antitoxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation. Antibiotics have not beeen demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin but are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The recommended antibiotid is Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 grams/d), or Procaine penicillin G given intramuscularly for 14 days (300,000 U/day 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 the 1920s there were an estimated 150,000 cases of diphtheria per year in the United States, causing 13,000 to 15,000 deaths. Children represented a large majority of these cases and fatalities. One of the most famous outbreaks of diphtheria was in Nome, Alaska. The famous 1925 serum run to Nome to deliver diphtheria antitoxin is now celebrated as the “Great Race of Mercy.” Twenty mushers and about 150 sled dogs relayed diphtheria antitoxin 674 miles by dog sled across Alaska in a record-breaking five and a half days, saving the small city of Nome and the surrounding communities from an epidemic. Diphtheria was prevalent in the British royal family during the late 19th century.
One of the first effective treatments for diphtheria was discovered in the 1880s by U.S. physician Joseph O’Dwyer (1841-1898). O’Dwyer developed tubes that were inserted into the throat, and prevented victims from suffocating due to the membrane sheath that grows over and obstructs airways. In the 1890s, Emil von Behring, a German physician, developed an antitoxin that did not kill the bacteria, but neutralized the toxic poisons that the bacteria releases into the body. von Behring discovered that animal blood has antitoxins and so he took the blood, removed the clotting agents and injected it into human patients. von Behring was awarded the first Nobel Prize in Medicine for his role in the discovery, and development of a serum therapy for diphtheria. The first successful vaccine for diphtheria was developed in 1913 by von Behring. Antibiotics against diphtheria were not available until the discovery and development of sulfa drugs following World War II.
The Schick test, invented between 1910 and 1911, is used to determine whether or not a person is susceptible to diphtheria. It was named after its inventor, Béla Schick (1877-1967), a Hungarian-born American pediatrician. A massive five-year campaign was coordinated by Dr. Schick. A vaccine was developed in the next decade, and deaths began declining in earnest in 1924.
Diphtheria has fatality rates between 8%. In children under 5 years and adults over 40 years, the fatality rate may be as high as 20%. Outbreaks, though very rare, still occur worldwide, even in developed nations. After the breakup of the Soviet Union in the late 80s, vaccination rates in its constituent countries fell so low that there were minor epidemics of diphtheria cases. In 1991 there were an estimated 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.