Antiquity Through The Seventeenth Century Typhoid fever has surely been a disease of human beings since prehistory, but for ancient physicians its nonspecific symptoms did not make it distinct from other illnesses. Hippocrates described a case of what appears to have been typhoid, and Caesar Augustus was cured of a fever with the characteristics of typhoid by the use of cold baths, a remedy that persisted well into the twentieth century.

Although meaningful reports from ancient and medieval times are lacking, the early mercantile and colonial enterprises of European expansion were clearly affected by typhoid epidemics. In the early seventeenth century, 6,500 out of 7,500 colonists at Jamestown, Virginia, died most likely from typhoid fever.

At about the same time this epidemic was occurring, the Belgian anatomist Adriaan van den Spieghel (Spigelius) described lesions in the lymphoid tissue of the small intestine of a patient who had died of a protracted fever, the first report of the characteristic pathological findings of typhoid. Later in the century, a British physician, Thomas Willis, cataloged the symptoms, signs, and course of a disease he called "putrid malignant fever," which was clearly typhoid.

Eighteenth Through Nineteenth Century In the mid-eighteenth century, the Frenchman Fran├žois Boissier de Sauvages consolidated a variety of ailments, including what Willis had called putrid malignant fever, into the term "typhus." In the 1830s, Pierre Louis, dissatisfied with the heterogeneity of the concept of typhus, proposed isolating a particular constellation of symptoms under the name "typhoid fever," or typhus-like fever. Later the American William W. Gerhard, studying an epidemic in Philadelphia, established typhoid fever as an entity independent of typhus, a term that now refers only to diseases caused by the rickettsial family of bacteria.

Though the illness now had a clinical definition, its mode of transmission was still in dispute. Somewhat earlier in the century, Pierre Bretonneau had argued that typhoid was contagious and that an attack conferred immunity. In the 1840s, the Englishman William Budd virtually inaugurated the science of epidemiology by his demonstration that typhoid was spread from infected individuals to new hosts by means of water and food. Budd's position was actively opposed by those who believed in spontaneous generation, and little was done to implement his recommendations of public health measures. As a result, the annual incidence in Europe at that time remained as high as 1 per 200 people.

Finally, in 1875 Budd's warnings were heeded, and the British Public Health Act was passed, radically improving sanitary practices. Within a decade, typhoid mortality was cut in half. This lesson was not lost on other developed nations who enacted sanitary laws of their own. Since that time, the incidence of typhoid in the developed world has steadily declined to its current annual rate of 1 case per 250,000 individuals.

This profound revolution in public health had begun before the microbial etiology of typhoid, or any other infection, had been established. Yet just 2 years after the Public Health Act was passed in England, the German Robert Koch demonstrated that a microorganism was the cause of anthrax; 3 years later his countrymen Carl Eberth and Edwin Klebs identified the typhoid bacillus in intestinal lymph nodes, making typhoid one of the earliest diseases for which a bacterial agent was known.

The next 2 decades saw an explosion of knowledge about the organism which was then called Eber-thella typhosa in honor of its discoverer. In 1884 Georg Gafiky succeeded in culturing the bacillus from lymph nodes, and shortly thereafter it was isolated from blood and stool.

Despite these rapid advances, therapeutic interventions against typhoid were lacking. During the Spanish-American War of 1898, one-fifth of the American army fell ill from typhoid fever, with a mortality six times the number of those who died of wounds. At about this time in England, Almroth Wright developed a vaccine of heat-killed bacilli, which reduced the attack rate among soldiers in India by 75 percent. Despite these impressive results, the vaccine was little used 2 years later in the South African (Boer) War, and the disastrous experience of the American army in the war against Spain was virtually repeated among British troops in South Africa.

Twentieth Century

Early in this century, both the British and American commands ordered mandatory typhoid immunization and better military sanitation. The effect a decade later was dramatic: During World War I, the typhoid attack rate was reduced from 1 in 5, to 1 in 2,000, and since then, perhaps for the first time in human history, typhoid has not played a major role in armed conflicts.

In 1906 George Soper, then a sanitary engineer for the New York Department of Health, was called upon to investigate an outbreak of typhoid. It had occurred in a summer home in Oyster Bay, a well-to-do town where the disease was unknown. Yet 6 of 11 people in the house had become ill. Soper determined that 3 weeks before the outbreak a new cook had been hired but had left after the first persons began falling ill. The cook's name was Mary Mallon, and she was destined to become inextricably linked with typhoid fever.

Four years earlier, Koch had proposed that a person might chronically shed the typhoid bacillus and thus infect others, yet remain healthy and unaffected by the disease. His carrier hypothesis lacked adequate supporting evidence and was doubted by many. It occurred to Soper, however, that the perplexing cluster of typhoid cases in Oyster Bay might be explained if the cook were a carrier.

Soper's investigations showed that over the previous 10 years inexplicable typhoid outbreaks had occurred in seven of the eight families for which Mary Mallon had worked. A year later, Soper located her working once again in a home where typhoid fever had just broken out. She was removed against her will to a hospital where culture of her stool proved that she was indeed shedding S. typhi in great numbers. After a 3-year detention on North Brother Island in Long Island Sound (a detention that raised many civil liberty questions), she was released on the promise that she would never again handle food. Five years later, however, she was found to be the source of an epidemic of 25 cases of typhoid that occurred at Women's Hospital in Manhattan. She was arrested and spent the rest of her life on North Brother Island. "Typhoid Mary" had established beyond scientific doubt that a carrier state existed in typhoid.

In 1933 Eberthella typhosa became Salmonella typhi, thereby joining a family of bacilli named after D. E. Salmon, who in the 1880s had discovered an organism (Salmonella cholerasuis) responsible for bacteremia in humans and diarrhea in swine. The discovery in 1948 of antibiotics active against S. typhi converted typhoid in the developed world from a rare but dread disease to just a rare one, acquired mainly by travel abroad.

On a global scale, however, there has been little evidence that typhoid is fading into obscurity. Although inexpensive vaccines place typhoid control within reach of those nations with limited health resources, the huge worldwide reservoir of carriers and the continuation of poor sanitation in endemic areas suggest that it will be some time before the developing nations can significantly reduce the incidence of typhoid fever.

Charles W. LeBaron and David W. Taylor

This chapter was written in the authors' private capacities. No official support or endorsement by the Centers for Disease Control is intended or should be inferred.

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