Classification & external resources

Salmonella typhi bacteria
ICD-10	A01.0
ICD-9	002
DiseasesDB	27829
eMedicine	oph/686  med/2331
MeSH	D014435

Typhoid fever, also known as enteric fever,^[1] is an illness caused by the bacterium Salmonella enterica serovar typhi. Common worldwide, it is transmitted by the fecal-oral route — the ingestion of food or water contaminated with feces from an infected person.^[2] The bacteria then multiply in the blood stream of the infected person and are absorbed into the digestive tract and eliminated with the waste.

Symptoms

Typhoid fever is characterized by a sustained fever as high as 40°C (104°F), profuse sweating, gastroenteritis, and diarrhea. Less commonly a rash of flat, rose-colored spots may appear.^[3]

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. Epistaxis is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia 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 40°C 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 osteitis

The 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

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.^[4]

Treatment

Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, 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. Vaccines for typhoid fever are available and are advised for persons traveling in regions where the disease is common (especially Asia, Africa and Latin America). Typhim Vi is an intramuscular killed-bacteria vaccination and Vivotif is an oral live bacteria vaccination, both of which protect against typhoid fever. Neither vaccine is 100% effective against typhoid fever and neither protects against unrelated typhus.

Resistance

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.^[5] 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.

Transmission

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 toileting 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.

Epidemiology

With an estimated 16-33 million cases of typhoid 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 the ages of 5 and 19 years.^[6]

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.

History

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.^[7] Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.^[8] 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.^[9] 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.^[10] 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.

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 0.5 cases per 100,000 people per year.

An outbreak in the Democratic Republic of Congo in 2004-05 recorded more than 42,000 cases and 214 deaths.^[6]

Famous typhoid victims

Famous people who have succumbed to the disease include:

• Abigail Adams, U.S. President John Adams's wife
• Albert of Saxe-Coburg-Gotha, British prince consort, Queen Victoria's husband
• John Buford
• Stephen A. Douglas
• Alexander Alexandrovich Friedman
• Mark Hanna
• K.B. Hedgewar, founder of Rashtriya Swayamsewak Sangh
• Archduke Karl Ludwig of Austria
• Tsar Nicholas II
• Mary Henrietta Kingsley
• Joseph Lucas
• Leland Stanford, Jr.
• Henry Frederick Stuart, Prince of Wales, original heir to the throne of James I of England
• Evangelista Torricelli
• Charles Trenet
• Godfrey Weitzel, major general in the Union army during the American Civil War
• Wilbur Wright
• Ignacio Zaragoza
• Belle Boyd the female confederate spy

See also

• Frederick F. Russell
• Typhoid Mary

References

Further reading

• Gale's Encyclopedia of Medicine, published by Thomas Gale in 1999, ISBN

External links

• www.netdoctor.co.uk. Article on typhoid fever for travelers. Retrieved on 17 december, 2004.
• United States Center for Disease Control and Prevention Listing
• Harrison, Noel G. (2007). www.healthsystem.virginia.edu. Historical exhibit on efforts by US Army to control typhoid fever. Retrieved on 4 July 2006.
• www.medicalnewstoday.com. Article on typhoid fever and the fall of Athens. Retrieved on 17 February 2006.

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