Hippocrates recorded tetanus cases and discussed the condition in general terms as well, providing details of symptoms, the course of the disease, and treatment. Treatment regimens were many and varied, and largely ineffective. Aretaeus, writing some 700 years later, believed that onlookers' prayers for the death of the patient were useful; he pitied the attending physician's inability to afford relief. After an excellent clinical description of the disease, Aretaeus too urged a wide variety of therapeutic maneuvers.
Ancient clinical descriptions have not been bettered. Therapy has changed, but it is possible that the number of survivors "after the fourteenth day" may not have improved markedly. William Osler, writing in 1892, found 80 percent mortality within 4 days. Therapy had improved: The nasogastric tube enabled feeding and hydration; morphine provided sedation, and chloroform provided muscle relaxation. Osler emphasized antiseptic care of the wound. It is fair to say that from Hippocrates to Osler - and to today - there have been no changes in diagnostic techniques, and there has been only a small reduction in mortality rates in established cases. Tetanus is a disease that must be prevented, and prevention had to begin with isolation of the organism and advances in immunology.
The discovery of the tetanus organism was part of the microbiological revolution that proved the theory that specific organisms caused specific diseases. In 1884, Arthur Nicolaier produced tetanus-like symptoms and death by injecting soil samples into animals. He isolated a rod-shaped bacillus and suggested that it secreted a toxin resembling strychnine in its action. He did not isolate the organism in pure culture. Neither did D. Rosenbach in 1886, although he was able to produce classic tetanus in guinea pigs by injecting tissue from a fatal human case. He described the "drumstick" shapes and correctly deduced that these were terminal spores. It remained for Shibasaburo Kitasato to isolate the organism in pure culture, in 1889, from a fatal case in Berlin. He described the anaerobic culture requirements, confirmed
Nicolaier's observations, and concluded that the clinical effects were caused by a toxin. The study of tetanus toxin and antitoxin followed directly and in parallel with the research of Emil Behring and Kitasato on diphtheria toxin, a much more important disease.
Tetanus and diphtheria investigations provided the framework on which Behring built his understanding of the principles of serum therapy In an 1892 paper, he argued that the serum of a patient should contain material protective and curative for another individual with the disease. In a series of studies, he and others proved this point in animals but did not recommend serum use in humans until its mechanism was better understood. They noted that even if treatment of the animal began very early, at least 1,000 times as much antitoxin was needed to cure as to protect before infection, and that, as the symptoms became general, the antitoxin was useless in any amount.
The availability of horse antitoxin soon led to clinical trials, with widely varying results. Analysis eventually showed that antitoxin had to be given very early in the disease; that dosage -empirical at first - was critical; and that it was essentially useless once the toxin was fixed to neurons and the patient was symptomatic. Better understanding of wound care and more aseptic surgery accompanied the rising rate of successful use of antitoxin and a decreased death rate, especially in selected populations like soldiers.
Given that soldiers often have fought in well-manured farmland and do not have clean skins, and that until very recently armies lived in close proximity to horses used for transport and cavalry, it is not surprising that tetanus was a common problem in wounded soldiers. In 1808, for example, the rate of tetanus before immunization was 12.5 per 1,000; by contrast, the rate was only 0.04 per 1,000 in World War II.
World War I saw the general introduction of early, near-universal use of antitoxin, accompanied by meticulous debridement of wounds. The effect of these measures may be seen in the British army. Incidence was 8 per 1,000 wounded from August to October 1914. As improved wound management and routine antitoxin use developed, the rate fell to 1.5 per 1,000 wounded. World War I patients, perhaps because the antitoxin produced a forme fruste, had a syndrome of "local tetanus" - not fatal, and usually confined to one extremity. U.S. forces, entering the war in 1917, had the advantage of the experience of their allies and thus had an incidence of only 0.16 per 1,000 wounded. Allergic reactions to horse serum occurred, more commonly after repeated doses of antitoxin.
The practical use of formaldehyde to produce a toxoid (a formalin-inactivated antitoxin) was introduced for tetanus in 1927. As opposed to the passive immunity conferred by antitoxin, the toxoid produced an active immunity that would protect against tetanus. Later, the duration of immunity and the timing and effect of booster doses was worked out.
A fluid toxoid was in use because of its harmlessness and efficacy (although it caused more local reactions than does the modern aluminum phosphate absorbed vaccine). This tox-oid, a combined diphtheria-tetanus toxoid vaccine, was given to infants in parts of France in the late 1920s and, by regulation, to French soldiers in 1931.
Immunization with the much more epidemi-ologically important diphtheria toxoid began in the 1920s in parts of the United States and just before World War II in Britain. The absorbed tetanus toxoid was used by the armies of Britain, France, and Canada by 1939; the United States began its use in 1941. During World War II, the American army had 5 fatal tetanus cases (2 in nonimmunized patients) and 7 nonfatal cases (all in immunized patients) in over 500,000 wounded soldiers. The reaction rate to the immunization series of three doses was 21 per 100,000, none fatal.
After World War II, routine use of a combined vaccine of diphtheria and tetanus toxoids (DT) was urged for childhood immunization. Soon the triple vaccine, with pertussis added (DPT), became legally required for school admission in the United States. Childhood immunization programs in Europe vary but tend to be on similar schedules and under similar laws. Nonfatal anaphylactic reactions occur at a rate of 1-1.5 per 2 million doses. The benefit/risk ratio for tetanus immunization is thus extraordinarily good. A worldwide infant and child immunization campaign, coupled with a booster upon injury, would essentially eliminate the disease as a clinical entity.
Was this article helpful?
Studies show obesity may soon overtake tobacco as the leading cause of death in world. Who Else Could Use 101 'Everyday' Ways to Lose 10 Pounds or more and Keep it Off! You've been putting it off too long. Hey, everyone needs to lose weight from time to time. You're no different!