Typhoid: Background

Typhoid
Background
Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness caused
primarily by Salmonella enterica, subspecies enterica serovar typhi and, to a lesser extent,
related serovars paratyphi A, B, and C.
The protean manifestations of typhoid fever make this disease a true diagnostic challenge. The
classic presentation includes fever, malaise, diffuse abdominal pain, and constipation. Untreated,
typhoid fever is a grueling illness that may progress to delirium, obtundation, intestinal
hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with
long-term or permanent neuropsychiatric complications.
S typhi has been a major human pathogen for thousands of years, thriving in conditions of poor
sanitation, crowding, and social chaos. It may have responsible for the Great Plague of Athens at
the end of the Pelopennesian War. The name S typhi is derived from the ancient Greek typhos, an
ethereal smoke or cloud that was believed to cause disease and madness. In the advanced stages
of typhoid fever, the patient's level of consciousness is truly clouded. Although antibiotics have
markedly reduced the frequency of typhoid fever in the developed world, it remains endemic in
developing countries.
S paratyphi causes the same syndrome but appears to be a relative newcomer. It may be taking
over the typhi niche, in part, because of immunological naivete among the population and
incomplete coverage by vaccines that target typhi.
Note that some writers refer to the typhoid and paratyphoid fever as distinct syndromes caused
by the typhi versus paratyphi serovars, while others use the term typhoid fever for a disease
caused by either one. We use the latter terminology. We refer to these serovars collectively as
typhoidal salmonella.
What is typhoid fever? What is the history of typhoid fever?

Typhoid fever is an acute illness associated with fever that is most often caused by the
Salmonella typhi bacteria. It can also be caused by Salmonella paratyphi, a related bacterium that
usually leads to a less severe illness. The bacteria are deposited through fecal contamination in
water or food by a human carrier and are then spread to other people in the area. Typhoid fever is
rare in industrial countries but continues to be a significant public-health issue in developing
countries.
The incidence of typhoid fever in the United States has decreased since the early 1900s. Today,
approximately 5,700 cases are reported annually in the United States, mostly in people who
recently have traveled to endemic areas. This is in comparison to the 1920s, when over 35,000
cases were reported in the U.S. This improvement is the result of improved environmental
sanitation. Mexico and South America are the most common areas for U.S. citizens to contract
typhoid fever. India, Pakistan, and Egypt are also known high-risk areas for developing this
disease. Worldwide, typhoid fever affects more than 21 million people annually, with over
200,000 patients dying of the disease.
If traveling to endemic areas, you should consult with your health-care professional and discuss
if you should receive vaccination for typhoid fever.
How do patients get typhoid fever?

Typhoid fever is contracted by the ingestion of the bacteria in contaminated food or water.
Patients with acute illness can contaminate the surrounding water supply through stool, which
contains a high concentration of the bacteria. Contamination of the water supply can, in turn,
taint the food supply. About 3%-5% of patients become carriers of the bacteria after the acute
illness. Some patients suffer a very mild illness that goes unrecognized. These patients can
become long-term carriers of the bacteria. The bacteria multiply in the gallbladder, bile ducts, or
liver and passes into the bowel. The bacteria can survive for weeks in water or dried sewage.
These chronic carriers may have no symptoms and can be the source of new outbreaks of typhoid
fever for many years.
How do the bacteria cause disease, and how is it diagnosed?

After the ingestion of contaminated food or water, the Salmonella bacteria invade the small
intestine and enter the bloodstream temporarily. The bacteria are carried by white blood cells to
the liver, spleen, and bone marrow. The bacteria then multiply in the cells of these organs and
reenter the bloodstream. Patients develop symptoms, including fever, when the organism reenters
the bloodstream. Bacteria invade the gallbladder, biliary system, and the lymphatic tissue of the
bowel. Here, they multiply in high numbers. The bacteria pass into the intestinal tract and can be
identified for diagnosis in cultures from the stool tested in the laboratory. Stool cultures are
sensitive in the early and late stages of the disease but often must be supplemented with blood
cultures to make the definite diagnosis.
What are the symptoms of typhoid fever?

The incubation period is usually one to two weeks, and the duration of the illness is about four to
six weeks. The patient experiences
poor appetite;
abdominal pain;
headaches;
generalized aches and pains;
fever, often up to 104 F;

lethargy (usually only if untreated);
intestinal bleeding or perforation (after two to three weeks of the disease);
Diarrhea or constipation.
People with typhoid fever usually have a sustained fever as high as 103 F-104 F (39 C-40 C).
Chest congestion develops in many patients, and abdominal pain and discomfort are common.
The fever becomes constant. Improvement occurs in the third and fourth week in those without
complications. About 10% of patients have recurrent symptoms (relapse) after feeling better for
one to two weeks. Relapses are actually more common in individuals treated with antibiotics.
What is the treatment for typhoid fever, and what is the prognosis?
Typhoid fever is treated with antibiotics that kill the Salmonella bacteria. Prior to the use of
antibiotics, the fatality rate was 20%. Death occurred from overwhelming infection, pneumonia,
intestinal bleeding, or intestinal perforation. With antibiotics and supportive care, mortality has
been reduced to 1%-2%. With appropriate antibiotic therapy, there is usually improvement within
one to two days and recovery within seven to 10 days.
Several antibiotics are effective for the treatment of typhoid fever. Chloramphenicol was the
original drug of choice for many years. Because of rare serious side effects, chloramphenicol has
been replaced by other effective antibiotics. The choice of antibiotics needs to be guided by
identifying the geographic region where the organism was acquired and the results of cultures
once available. (Certain strains from South America show a significant resistance to some
antibiotics.) Ciprofloxacin (Cipro) is the most frequently used drug in the U.S. for non-pregnant
patients. Ceftriaxone (Rocephin), an intramuscular injection medication, is an alternative for
pregnant patients. Ampicillin (Omnipen, Polycillin, Principen) and trimethoprimsulfamethoxazole (Bactrim, Septra) are frequently prescribed antibiotics although resistance has
been reported in recent years. If relapses occur, patients are retreated with antibiotics.
The carrier state, which occurs in 3%-5% of those infected, can be treated with prolonged
antibiotics. Often, removal of the gallbladder, the site of chronic infection, will cure the carrier
state.
Can typhoid fever be prevented?

For those traveling to high-risk areas, vaccines are now available. The vaccine is usually not
recommended in the U.S. There are two forms of the vaccine available an oral and an injectable
form. The vaccination needs to be completed at least one week prior to travel and, depending on
the type of vaccine, only protects from two to five years. The oral vaccine is contraindicated in
patients with depressed immune system.
Two typhoid vaccines are currently recommended for use by:

1. An injectable polysaccharide vaccine based on the purified Vi antigen (known as Vi-PS and
vaccine) for persons aged two years and above;
2 A live attenuated oral Ty21a vaccine in capsule formulation for those over five years of
age.
WHO recommends the use of the Vi-PS and Ty21a vaccines to control endemic disease and for
outbreak control. WHO further recommends that all typhoid fever vaccination programmers
should be implemented in the context of other efforts to control the disease, including health
education, water quality and sanitation improvements, and training of health professionals in
diagnosis and treatment.
Several Vi polysaccharideprotein conjugate vaccine candidates are under development (or are
nationally licensed but not on the international market) and anticipated to be available in the
future for infant immunization.
REFERENCE:
United States. Centers for Disease Control and Prevention. "Typhoid Fever."
<http://www.cdc.gov/ncidod/dbmd/diseaseinfo/TyphoidFever_g.htm>.
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2. Christie AB. Infectious Diseases: Epidemiology and Clinical Practice. 4th ed. Edinburgh,
Scotland: Churchill Livingstone; 1987.
3. Raffatellu M, Chessa D, Wilson RP, Tkel C, Akelik M, Bumler AJ. Capsule-mediated
immune evasion: a new hypothesis explaining aspects of typhoid fever pathogenesis.
Infect Immun. 2006 Jan. 74(1):19-27.
4. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med. 2002 Nov 28.
347(22):1770-82.
5. de Jong HK, Parry CM, van der Poll T, Wiersinga WJ. Host-pathogen interaction in
invasive Salmonellosis. PLoS Pathog. 2012. 8(10):e1002933.
6. Ramsden AE, Mota LJ, Mnter S, Shorte SL, Holden DW. The SPI-2 type III secretion
system restricts motility of Salmonella-containing vacuoles. Cell Microbiol. 2007 Oct.
9(10):2517-29.
7. Gonzalez-Escobedo G, Gunn JS. Gallbladder epithelium as a niche for chronic
Salmonella carriage. Infect Immun. 2013 Aug. 81(8):2920-30.
8. Chiou CS, Wei HL, Mu JJ, Liao YS, Liang SY, Liao CH, et al. Salmonella enterica
serovar Typhi variants in long-term carriers. J Clin Microbiol. 2013 Feb. 51(2):669-72.

Typhoid: Background

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Typhoid

What is typhoid fever? What is the history of typhoid fever?

How do patients get typhoid fever?

How do the bacteria cause disease, and how is it diagnosed?

What are the symptoms of typhoid fever?

fever, often up to 104 F;

Can typhoid fever be prevented?

Two typhoid vaccines are currently recommended for use by:

1. Papagrigorakis MJ, Synodinos PN, Yapijakis C. Ancient typhoid epidemic reveals

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