Typhoid fever

Typhoid fever

Name = Typhoid fever

Caption = "Salmonella" typhi bacteria
DiseasesDB = 27829
ICD10 = ICD10|A|01|0|a|00
ICD9 = ICD9|002
MedlinePlus =
eMedicineSubj = oph
eMedicineTopic = 686
eMedicine_mult = eMedicine2|med|2331 | MeshID = D014435

Typhoid fever, also known as enteric fever, bilious fever, Yellow Jack or commonly just typhoid, [MedlinePlus|001332|Typhoid fever] is an illness caused by the bacterium "Salmonella enterica" serovar Typhi. Common worldwide, it is transmitted by the ingestion of food or water contaminated with feces from an infected person.cite book | author = Giannella RA | chapter = Salmonella | title = Baron's Medical Microbiology "(Baron S "et al", eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1221 | isbn = 0-9631172-1-1 ] The bacteria then perforate through the intestinal wall and are phagocytosed by macrophages. Salmonella Typhi then alters its structure to resist destruction and allow them to exist within the macrophage. This renders them resistant to damage by PMN's, complement and the immune response. The organism is then spread via the lymphatics while inside the macrophages. This gives them access to the Reticulo-Endothelial System and then to the different organs throughout the body.The organism is a Gram-negative short bacillus that is motile due to its peritrichous flagella. The bacteria grows best at convert|37|°C|°F|abbr=on|lk=on|disp=s – human body temperature.


Typhoid fever is characterized by a sustained fever as high as convert|40|°C|°F|abbr=on|lk=off, profuse sweating, gastroenteritis, and nonbloody diarrhea. Less commonly a rash of flat, rose-colored spots may appear. [CDCDiseaseInfo|typhoidfever_g]

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, there is a slowly rising temperature with relative bradycardia, malaise, headache and cough. A bloody nose (epistaxis) is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia, a decrease in the number of circulating white blood cells, with eosinopenia and relative lymphocytosis, a positive diazo reaction and blood cultures are positive for Salmonella Typhi or Paratyphi. The classic Widal test is negative in the first week.

In the second week of the infection, the patient lies prostrated with high fever in plateau around convert|40|°C|°F|abbr=on|lk=off and bradycardia (Sphygmo-thermic dissociation), classically with a dicrotic pulse wave. Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around 1/3 patients. There are rhonchi in lung bases. The abdomen is distended and painful in the right lower quadrant where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea-soup. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender and there is elevation of liver transaminases. The Widal reaction is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.

In the third week of typhoid fever a number of complications can occur:
* Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually non-fatal.
* Intestinal perforation in distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
* Encephalitis
* Metastatic abscesses, cholecystitis, endocarditis and osteitisThe fever is still very high and oscillates very little over 24 hours. Dehydration ensues and the patient is delirious (typhoid state). By the end of third week defervescence commences that prolongs itself in the fourth week.


Diagnosis is made by blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of Widal test and blood cultures.cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 ]


Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, Amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in developed countries. Prompt treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.

When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases.


Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and streptomycin is now common, and these agents have not been used as first line treatment now for almost 20 years. Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).

Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are therefore moving away from using ciprofloxacin as first line for treating suspected typhoid originating in India, Pakistan, Bangladesh, Thailand or Vietnam. For these patients, the recommended first line treatment is ceftriaxone.

There is a separate problem with laboratory testing for reduced susceptibility to ciprofloxacin: current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin (MIC 0.125–1.0 mg/l) would not be picked up by this method. [cite journal | title=Fluoroquinolone resistance in "Salmonella" Typhi (letter) | author=Cooke FJ, Wain J, Threlfall EJ | journal=Brit Med J | year=2006 | volume=333 | issue=7563 | pages=353–4 | doi = 10.1136/bmj.333.7563.353-b ] It not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent disc testing and cannot test for MICs.


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 therefore crucial to preventing typhoid.

There are two vaccines currently recommended by the World Health Organization for the prevention of typhoidcite journal |author= |title=Typhoid vaccines: WHO position paper |journal=Wkly. Epidemiol. Rec. |volume=83 |issue=6 |pages=49–59 |year=2008 |month=Feb |pmid=18260212 |doi= |url=http://www.who.int/wer/2008/wer8306/en/index.html] : these are the live, oral Ty21a vaccine (sold as "Vivotif Berna") and the injectable Vi capsular polysacharide vaccine (sold as "Typhim Vi"). Both are between 50 to 80% protective and are recommended for travelers to areas where typhoid is endemic. 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).


Flying insects feeding on feces may occasionally transfer the bacteria through poor hygiene habits and public sanitation conditions. Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease. According to statistics from the United States Center for Disease Control, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.

A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others. According to the Centers for Disease Control approximately 5% of people who contract typhoid continue to carry the disease after they recover. The most famous asymptomatic carrier was Typhoid Mary. She was a young cook that was responsible for infecting about 47 people during her lifetime, killing three of the infected. This was the first time a perfectly healthy person was known to be responsible for an "epidemic".

Many carriers of typhoid were locked into an isolation ward never to be released in order to prevent further typhoid cases. These people often deteriorated mentally, driven mad by the conditions they lived in. [BBC on Long Grove Hospital Surrey GB url: http://news.bbc.co.uk/today/hi/today/newsid_7523000/7523680.stm ]


With an estimated 16-33 million cases of annually resulting in 500,000 to 600,000 deaths in endemic areas, the World Health Organisation identifies typhoid as a serious public health problem. Its incidence is highest in children between 5 and 19 years old.cite web | title = Typhoid Fever | publisher = World Health Organisation | url = http://www.who.int/vaccine_research/diseases/diarrhoeal/en/index7.html | accessdate = 2007-08-28]

Heterozygous advantage

It is thought that cystic fibrosis may have risen to its present levels (1 in 1600 in UK) due to the heterozygous advantage that it confers against typhoid fever. The CFTR protein is present in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium.


Around 430–426 B.C., 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 ancient world. Ancient historian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak. The cause of the plague has long been disputed, with modern academics and medical scientists considering epidemic typhus the most likely cause. However, a 2006 study detected DNA sequences similar to those of the bacterium responsible for typhoid fever.cite journal | author=Papagrigorakis MJ, Yapijakis C, Synodinos PN, Baziotopoulou-Valavani E | title=DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens | journal=Int J Infect Dis | year=2006 | pages=206–14 | volume=10 | issue=3 | pmid=16412683 ] Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.cite journal |author=Shapiro B, Rambaut A, Gilbert M |title=No proof that typhoid caused the Plague of Athens (a reply to Papagrigorakis et al.) |journal=Int J Infect Dis |volume=10 |issue=4 |pages=334–5; author reply 335–6 |year=2006 |pmid=16730469 | doi = 10.1016/j.ijid.2006.02.006 ] 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.

In the late 19th century, 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 persons.cite web | title=1900 Flow of Chicago River Reversed | work=Chicago Timeline | url=http://www.chipublib.org/004chicago/timeline/riverflow.html | publisher = Chicago Public Library | accessdate=2007-02-08] 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; some believe she was the source of infection for several hundred people. She is closely associated with forty-seven cases and three deaths.cite web | title=Nova: The Most Dangerous Woman in America | url=http://www.pbs.org/wgbh/nova/typhoid/letter.html] 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.

In 1897, Almroth Edward Wright developed an effective vaccine. In 1909, Frederick F. Russell, a U.S. Army physician, developed an American typhoid vaccine 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.

Most developed countries saw declining rates of typhoid fever throughout first half of 20th century due to vaccinations and advances in public sanitation and hygiene. Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality. At the present time, incidence of typhoid fever in developed countries is around 5 cases per 1,000,000 people per year.

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

Famous typhoid victims

Famous people who have had the disease include:

* Abigail Adams, wife of former United States President John Adams
* Jean Baudrillard, cultural theorist, sociologist and philosopher
* Arnold Bennett, novelist
* Belle Boyd, female confederate spy
* Gonville Bromhead, Victoria Cross recipient for actions during Battle of Rorke's Drift
* John Buford
* Martha Bulloch, mother of Theodore Roosevelt
* Stephen A. Douglas, US politician
* Alexander Alexandrovich Friedman
* Mark Hanna, US politician
* Gerard Manley Hopkins, English poet
* Archduke Karl Ludwig of Austria
* Mary Henrietta Kingsley
* William Wallace Lincoln, son of Abraham Lincoln
* Joseph Lucas
* James Martin (Australian soldier), Youngest known ANZAC
* Frank McCourt, contracted typhoid fever during his childhood, but survived
* Albert of Saxe-Coburg-Gotha, British prince consort, Queen Victoria's husband
* Franz Schubert, composer
* Joseph Smith Jr., first Prophet of The Church of Jesus Christ of Latter Day Saints (also known as Mormons), contracted typhoid fever during childhood (7 years old), but survived
* Leland Stanford, Jr.
* Henry Frederick Stuart, Prince of Wales, original heir to the throne of James I of England
* Wilbur Wright

Fictional characters

* Ellen O'Hara, (Scarlett's mother from "Gone With the Wind"), Suellen O'Hara and Carreen O'Hara (Scarlett's sisters) suffer from Typhoid fever.
* Gilbert Blythe (of the Anne of Green Gables Series) almost dies of Typhoid fever in "Anne of the Island," by L.M. Montgomery.
* Walter Blythe (son of Anne and Gilbert Blythe in the latter Anne of Green Gables books)was in recovery of Typhoid in "Rilla of Ingleside" and is seen as the reason why he doesn't enlist at the onset of WWI.
* Johann "Hanno" Buddenbrook, in Thomas Mann's novel, "Buddenbrooks", dies of typhoid fever, and the book includes a long medical description of the disease and its effects.
* John H. Watson (Sherlock Holmes' famed companion) nearly died of Typhoid contracted in India, and returned to England for convalescence - where he first met the detective.


Further reading





External links


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