 Diphtheria
is an upper respiratory tract illness characterized by sore throat, low-grade
fever, and an adherent membrane (apseudo-membrane) on the tonsil(s), pharynx,
and/or nose. A milder form of diphtheria can be limited to the skin. It is
caused by Corynebacterium diphtheriae, a facultatively anaerobic Gram-positive
bacterium.
Diphtheria is a highly 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 wide-spread
vaccination. In the United States for instance, between 1980 and 2004 there have
been 57 reported cases of diptheria 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; they are
particularly recommended for those traveling to areas where the disease has not
been eradicated.
History
Diphtheria was named in 1826 by French physician Pierre Bretonneau. The name
alludes to the leathery, sheath-like membrane that grows on the tonsils, throat,
and in the nose. The pronunciation was originally considered incorrect, but has
become the most common way of saying the word, and is accepted as a correct
form. While many writers today use the spelling "diptheria" which fits the
modern pronunciation, this spelling is rarely found in dictionaries.
Diphtheria was once a dreaded disease, with frequent large-scale outbreaks. A
diphtheria epidemic in the New England colonies between 1735 and 1740 was said
to have killed as many as 80% of the children under 10 years of age in some
towns.
In the 1920s there were an estimated 100,000 to 200,000 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 trip made to get the antitoxin is now
celebrated by the Iditarod Trail Sled Dog Race.
Diphtheria was also prevalent in the British royal family during the late 19th
century. Famous cases included a daughter and granddaughter of Britain's Queen
Victoria. Princess Alice of Hesse (second daughter of Queen Victoria) died of
diphtheria after she contracted it from her children in December of 1878 while
nursing them. One of Princess Alice's own daughters, Princess May, also died of
diphtheria in November of 1878.
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, the German
physician Emil von Behring developed an antitoxin that did not kill the
bacteria, but neutralized the toxic poisons that the bacteria releases into the
body. von Behring was awarded the first Nobel Prize in Medicine for his role in
the discovery, and development of a serum therapy for diphtheria. (Americans
William H. Park and Anna Wessels Williams; and Pasteur Institute scientists
Emile Roux and Martin Chaillou also independently developed diphtheria antitoxin
in the 1890s.) The first successful vaccine for diphtheria was developed in
1923. However, antibiotics against diphtheria were not available until the
discovery and development of sulfa drugs following World War II.
Mechanism
Diphtheria toxin catalyzes the ADP-ribosylation of, and inactivates, eEF-2. In
this way, it acts to inhibit translocation during eukaryotic protein synthesis.
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 intubations or 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 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.
Epidemiology
Diphtheria is a serious disease, with fatality rates between 5% and 10%. In
children under 5 years and adults over 40 years, the fatality rate may be as
much as 20%. Outbreaks, though very rare, still occur worldwide, even in
developed nations. After the breakup of the former Soviet Union in the late
1980s, vaccination rates in its constituent countries fell so low that there was
an explosion of diphtheria cases. In 1991 there were 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. This
was so great an increase that diphtheria was cited in the Guinness Book of World
Records as "most resurgent disease".
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