Typhoid fever — also known simply as typhoid[1] — is a common worldwide bacterial disease transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica enterica, serovar Typhi.[2]

The disease has received various names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever and pythogenic fever. The name typhoid means “resembling typhus” and comes from the neuropsychiatric symptoms common to typhoid and typhus.[3] Despite this similarity of their names, typhoid fever and typhus are distinct diseases and are caused by different species of bacteria.[4]

The impact of this disease fell sharply in the developed world with the application of 20th-century sanitation techniques.


Sanitation and hygiene are the critical measures that can be taken to prevent typhoid. Typhoid does not affect animals, and therefore, transmission is only from human to human. Typhoid can only spread in environments where human feces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid.

There are two vaccines licensed for use for the prevention of typhoid:[8] the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable Typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are 50% to 80% protective and are recommended for travellers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. There exists an older, killed-whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection).[8]

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin.[7][9] Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.[10][11][12] Cefixime is a suitable oral alternative.[13][14]

Typhoid fever, when properly treated, is not fatal in most cases. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology (Baron S et al.). Treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.[15]

When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases.[16] In some communities, however, case-fatality rates may reach as high as 47%.During the course of treatment of a typhoid outbreak in a local village in 1838, English country doctor William Budd, realised that the “poisons” involved in infectious diseases multiplied in the intestines of the sick, were present in their excretions, and could then be transmitted to the healthy through their consumption of contaminated water.[26] He proposed strict isolation as a method for containing such outbreaks in the future.[27] The medical and scientific communities did not identify the role of microorganisms in infectious disease until the work of Louis Pasteur.

Almroth Edward Wright, developed the first effective typhoid vaccine.
In 1880 Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. In 1884 pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberth’s findings, and the organism was given names such as Eberth’s bacillus, Eberthella typhi and Gaffky-Eberth bacillus. Today the bacillus that causes typhoid fever goes by the scientific name of Salmonella enterica enterica, serovar Typhi.

The British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully during the Boer War.[28] At that time typhoid often killed more soldiers at war than were lost due to enemy combat. He further developed his vaccine at a newly opened research department at St Mary’s Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood.

Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccines should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during the War.[29] The British Army was the only combatant at the outbreak of the war to be fully immunized against the bacteria, which meant that for the first time, casualties due to combat exceeded those from disease.[8]

In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wright’s typhoid vaccine for use with the US Army and two years later his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military.[30]

Lizzie van Zyl was a child inmate in a British-run concentration camp in South Africa who died from typhoid fever during the Boer War (1899–1902).
Most developed countries saw declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1908, the chlorination of drinking water was a significant step in the control of typhoid fever in the U.S. The first permanent disinfection of drinking water in the U.S. occurred on the Jersey City, New Jersey water supply. Credit for the decision to build the chlorination system has been given to John L. Leal[31] The chlorination facility was designed by George W. Fuller.[32] Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality. Today, the incidence of typhoid fever in developed countries is around 5 cases per 1,000,000 people per year.

A notable outbreak occurred in Aberdeen, Scotland in 1964. This was due to contaminated tinned meat sold at the city’s branch of the William Low chain of stores. No fatalities resulted.

An outbreak in the Democratic Republic of Congo in 2004–05 recorded more than 42,000 cases and 214 deaths.[16]

Around 430–424 BC, a devastating plague, which some believe to have been typhoid fever, killed one third of the population of Athens, including their leader Pericles. The balance of power shifted from Athens to Sparta, ending the Golden Age of Pericles that had marked Athenian dominance in the Greek ancient world. The ancient historian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak and modern academics and medical scientists consider epidemic typhus the most likely cause. In 2006 a study detected DNA sequences similar to those of the bacterium responsible for typhoid fever.[20]


Mary Mallon (“Typhoid Mary”) in a hospital bed (foreground). She was forcibly quarantined as a carrier of typhoid fever in 1907 for three years and then again from 1915 until her death in 1938.
The cause of the plague has long been disputed and other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.[21] The disease is most commonly transmitted through poor hygiene habits and public sanitation conditions; during the period in question, the whole population of Attica was besieged within the Long Walls and lived in tents.

Some historians believe that the English colony of Jamestown, Virginia, died out from typhoid. Typhoid fever killed more than 6000 settlers between 1607 and 1624.[22]

During the American Civil War, 81,360 Union soldiers died of typhoid or dysentery.[23] In the late 19th century, the typhoid fever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst year was 1891, when the typhoid death rate was 174 per 100,000 people.[24]

The most notorious carrier of typhoid fever—but by no means the most destructive—was Mary Mallon, also known as Typhoid Mary. In 1907, she became the first American carrier to be identified and traced. She was a cook in New York. She is closely associated with fifty-three cases and three deaths.[25] Public health authorities told Mary to give up working as a cook or have her gall bladder removed. Mary quit her job but returned later under a false name. She was detained and quarantined after another typhoid outbreak. She died of pneumonia after 26 years in quarantine.


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