First typhoid inoculation. Army Medical School, March, 1909.
Images from the History of Medicine (NLM)
Symptoms and Causative Agent
Typhoid fever is a bacterial disease caused by Salmonella typhi. While rare in industrialized countries, typhoid fever is a significant threat in some low-income countries.
Symptoms of typhoid fever range from mild to serious and usually develop one to three weeks after exposure to the bacteria. Symptoms include fever, headache, nausea, constipation or diarrhea, loss of appetite, and a rose-colored rash on the body.
Typhoid fever symptoms are similar to those of other common gastrointestinal illnesses. The only way to know that a person is ill with typhoid is to have their blood or feces tested for Salmonella typhi.
Typhoid fever spreads from person to person via contaminated food and water. Transmission is via the fecal-oral route, meaning that contaminated feces (and sometimes urine) may enter water supplies or food supplies, which may then be consumed by and infect others. Salmonella typhi lives only in humans; there is no animal reservoir for the bacteria.
About 21 million cases of typhoid fever and 220,000 deaths occur annually worldwide.
Treatment and Care
Typhoid fever is found more commonly in densely populated areas where water supplies are vulnerable to contamination. Good water sanitation methods and proper storage and handling of food and water can help prevent spread of S. typhi.
Antibiotics are the only effective treatment for typhoid fever. Most patients improve after beginning antibiotic treatment, especially if the disease is detected early.
Typhoid fever may lead to intestinal bleeding and perforation. This in turn can cause severe abdominal pain, nausea, vomiting, and sepsis. Surgery may be needed to repair the intestinal damage.
Less common complications that can occur are inflammation of the heart muscle, inflammation of the lining of the heart and valves, pneumonia, inflammation of the pancreas, meningitis, kidney or bladder infections, and delirium.
Available Vaccines and Vaccination Campaigns
Two typhoid vaccines are licensed for use in the United States; these are typically reserved for people traveling to areas where typhoid fever is common or for people who may come into direct contact with the disease.
Ty21a is a live, attenuated vaccine given in oral capsule form. Within the first two years of vaccination, the vaccine is moderately effective at preventing disease. Three years after initial vaccination, the vaccine offers no protection. The minimum age for this vaccine is six years.
Vi capsular polysaccharide (ViCPS) is an injected subunit vaccine. In clinical trials, it reduced disease rates by nearly 66%, though effectiveness wanes after several years. The minimum age for this vaccine is two years.
Typhoid conjugate vaccine (TCV), not available in the United States, was approved for use in India in 2013 and in late 2017 was pre-qualified by the World Health Organization (WHO). This new vaccine may be given to infants six months of age and older. It offers protection for up to five years after immunization.
U.S. Vaccination Recommendations
Typhoid fever vaccination is neither required nor recommended for routine use in people who live in the United States. Vaccination with Ty21a or ViCPS may be recommended for travel to areas where there is a risk for typhoid infection. Travelers are usually advised to take the typhoid vaccine one to two weeks before departure.
TCV has recently been recommended by the WHO for control of typhoid fever because of its long-lasting immunological effects and its suitability even for very young children. Both Ty21a and ViCPS are also approved by the World Health Organization for typhoid fever control.
Anwar, E., Goldberg, E., Fraser, A., Acosta, C.J., Paul, M., Leibovici, L. Vaccines for preventing typhoid fever. The Cochrane Database of Systematic Reviews 1: CD001261. 2014. Accessed 01/25/2018.
Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Diseases. Typhoid Fever. Accessed 01/25/2018.
CDC. Typhoid Fever Vaccination. Accessed 01/25/2018.
The Mayo Clinic. Typhoid Fever. Accessed 01/25/2018.
Szu, S.C. Development of Vi conjugate - a new generation of typhoid vaccine. Expert Review of Vaccines 12 (11): 1273–86. November 2013. Accessed 01/25/2018.
World Health Organization. Typhoid Fever. Accessed 01/25/2018.
World Health Organization. Typhoid Fever Vaccines. Accessed 01/25/2018.
World Health Organization. Typhoid Fever Vaccines: Position Statement. March 2018. Accessed 4/2/2018.
Last update 03 April 2018
Timeline Entry: 1896
Basis for Typhoid Vaccination Is Established
As with many discoveries in medical history, several different researchers were working on the idea of protection against typhoid fever at the same time in the 1890s. In Germany, Richard Pfeiffer and Wilhelm Kolle in 1896 demonstrated that inoculation with killed typhoid bacteria resulted in human immunity against typhoid fever. Almroth E. Wright published a paper a few months later in 1897, in which he described a similar finding.
Reading before the Harvey Society of New York in February 1913, U.S. Army physician Frederick F. Russell stated that “The publication of Pfeiffer and Kolle’s investigations antedates Wright’s paper by some months,” giving credit for the demonstration of typhoid immunity via inoculation to Pfeiffer and Kolle. Wright, however, would be the first to develop an effective typhoid vaccine the following year. Russell developed the first U.S. typhoid fever vaccine in 1909.
In the November-December 1981 issue of Reviews of Infectious Diseases, Dieter H. M. Gröschel and Richard B. Hornick conducted a review of original literature related to typhoid vaccination and argued that Wright and Pfeiffer in particular should share the credit for the vaccine.See this item in the timeline
Timeline Entry: 1909
The Debut of "Typhoid Mary"
Mary Mallon was first referred to as “Typhoid Mary” by the New York American on June 20, 1909.
Mallon, an Irish immigrant who worked as a cook for wealthy New York families, first gained the attention of public health officials in 1906. A Long Island family for whom Mallon had worked as a cook had fallen ill with typhoid fever. Though Mallon was no longer with the family, officials trying to locate her discovered that other families she’d worked for had also developed typhoid fever. In one outbreak at a household of nine in Dark Harbor, Maine, in 1902, Mallon and Mr. Coleman Drayton, head of the household, were the only two not to fall ill (Drayton had contracted typhoid fever years before). Major George A. Soper of the United States Army, after investigating Mallon’s past some years later, noted that:
Mr. Drayton felt so grateful to the cook for the help which she gave him during the epidemic that at the end of the epidemic he made her a handsome present of money in addition to her wages, little thinking that the cause of the whole trouble lay at her door. – Typhoid Mary, Major George A. Soper, reprinted from the Military Surgeon, July 1919
Eventually, Mary Mallon became the first identified healthy carrier of typhoid: she carried the typhoid bacteria and spread them to others, but did not fall ill herself.
In 1907, Mallon was detained by the New York City Department of Health for three years, first at a hospital for contagious diseases in Manhattan, and then at Riverside Hospital on North Brother’s Island in the East River to be kept in isolation. She was released in 1910 under the conditions that she would no longer work as a cook and would take steps to prevent spreading typhoid. In 1915, however, Mallon was caught once again working as a cook (this time under the assumed name Mary Brown) after infecting 25 people with typhoid, one of whom died. Mallon was eventually sent back to North Brother Island and remained there for the next 23 years until her death in 1938.
Although the phrase “Typhoid Mary” is now used to describe a person or object that brings widespread death and destruction, the number of illnesses and deaths caused by Mary Mallon herself are often inflated. At the time of her death in 1938, she was officially blamed for 10 outbreaks totaling 51 cases of typhoid fever, and three deaths from the disease.See this item in the timeline
Timeline Entry: 1914
Typhoid Vaccination Becomes Commonplace in the United States
By 1914, typhoid vaccination had moved beyond military forces in the United States and into use for the general public.
Parke, Davis & Company sent the letter shown on the left to a Philadelphia physician to suggest the use of typhoid vaccine for travelers. The pamphlet referred to in the letter can also be viewed on the left.
The text of the letter reads as follows:
Dear Doctor:-See this item in the timeline
Your patients, many of them, will soon be leaving for their vacations and unless protected by vaccination they may incidentally be in some danger of contracting Typhoid Fever.
As a preventive of Typhoid Fever the value of Typhoid Vaccine is now well established. It has been used extensively in our own and other great armies with very satisfactory results. Consequently in the U.S. Army anti-typhoid vaccination of recruits is now compulsory.
It is a simple matter to use Typhoid Vaccine Prophylactic (P.D. & Co). Three doses are given, injected subcutaneously at ten-day intervals. It is offered in packages containing enough for the protective treatment of one person – three doses in three bulbs, three doses in three syringes or three doses in one graduated syringe. It may also be had in a larger package known as the “hospital size” and containing enough for ten persons.
The interesting and important subject of typhoid vaccination is presented concisely in the enclosed booklet which we commend to your careful attention and we shall be very glad to supply additional information if you desire it. Supplies of Typhoid Vaccine Prophylactic, (P.D. & Co.), may be obtained through pharmacists.
Very truly yours,
Parke, Davis & Co.