What is typhoid fever?

Typhoid fever is an acute illness associated with fever that is most often caused by the Salmonella  typhibacteria. It
can also be caused bySalmonella paratyphi, a related bacterium that usually leads to a less severe illness. The
bacteria are deposited in water or food by a human carrier and are then spread to other people in the area.

The incidence of typhoid fever in the United States has markedly decreased since the early 1900s. Today,
approximately 400 cases are reported annually in the United States, mostly in people who recently havetraveled 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 13 million people annually, with over 500,000
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 multiplies 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 does 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 in 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,

 headaches,
 generalized aches and pains,

 fever,

 lethargy,

 diarrhea.

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.

How is typhoid fever treated, 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. Chloramphenicolwas 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),ampicillin (Omnipen, Polycillin, Principen), and trimethoprim-
sulfamethoxazole (Bactrim, Septra) are frequently prescribed antibiotics. 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.

For those traveling to high-risk areas, vaccines are now available.

Typhoid Fever At A Glance

 Typhoid fever usually is caused by Salmonellae typhi bacteria.

 Typhoid fever is contracted by the ingestion of contaminated food or water.
 Diagnosis of typhoid fever is made when the Salmonella bacteria is detected with a stool culture.
 Typhoid fever is treated with antibiotics.
 Typhoid fever symptoms are poor appetite, headaches, generalized aches and pains, fever, and lethargy.
 Approximately 3%-5% of patients become carriers of the bacteria after the acute illness.

Typhoid fever is a life-threatening illness caused by the bacterium Salmonella Typhi. In the United

States about 400 cases occur each year, and 75% of these are acquired while traveling
internationally. Typhoid fever is still common in the developing world, where it affects about 21.5
million persons each year.
Typhoid fever can be prevented and can usually be treated with antibiotics. If you are planning to
travel outside the United States, you should know about typhoid fever and what steps you can take to
protect yourself.

How is typhoid fever spread?

Salmonella Typhi lives only in humans. Persons with typhoid fever carry the bacteria in their
bloodstream and intestinal tract. In addition, a small number of persons, called carriers, recover from
typhoid fever but continue to carry the bacteria. Both ill persons and carriers shed SalmonellaTyphi in
their feces (stool). 

You can get typhoid fever if you eat food or drink beverages that have been handled by a person who
is shedding Salmonella Typhi or if sewage contaminated with Salmonella Typhi bacteria gets into the
water you use for drinking or washing food. Therefore, typhoid fever is more common in areas of the
world where handwashing is less frequent and water is likely to be contaminated with sewage. 

Once Salmonella Typhi bacteria are eaten or drunk, they multiply and spread into the bloodstream.
The body reacts with fever and other signs and symptoms.
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Where in the world do you get typhoid fever?

Typhoid fever is common in most parts of the world except in industrialized regions such as the United
States, Canada, western Europe, Australia, and Japan. Therefore, if you are traveling to the
developing world, you should consider taking precautions. Over the past 10 years, travelers from the
United States to Asia, Africa, and Latin America have been especially at risk.

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How can you avoid typhoid fever?

Two basic actions can protect you from typhoid fever:

1. Avoid risky foods and drinks.

2. Get vaccinated against typhoid fever.

It may surprise you, but watching what you eat and drink when you travel is as important as being
vaccinated. This is because the vaccines are not completely effective. Avoiding risky foods will also
help protect you from other illnesses, including travelers' diarrhea, cholera, dysentery, and hepatitis A.

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"Boil it, cook it, peel it, or forget it"

 If you drink water, buy it bottled or bring it to a rolling boil for 1 minute before you drink it.
Bottled carbonated water is safer than uncarbonated water.

 Ask for drinks without ice unless the ice is made from bottled or boiled water. Avoid popsicles
and flavored ices that may have been made with contaminated water.

 Eat foods that have been thoroughly cooked and that are still hot and steaming.

 Avoid raw vegetables and fruits that cannot be peeled. Vegetables like lettuce are easily
contaminated and are very hard to wash well.

 When you eat raw fruit or vegetables that can be peeled, peel them yourself. (Wash your
hands with soap first.) Do not eat the peelings.

 Avoid foods and beverages from street vendors. It is difficult for food to be kept clean on the
street, and many travelers get sick from food bought from street vendors.

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Getting vaccinated

If you are traveling to a country where typhoid is common, you should consider being vaccinated
against typhoid. Visit a doctor or travel clinic to discuss your vaccination options.

Remember that you will need to complete your vaccination at least 1-2 weeks (dependent upon
vaccine type) before you travel so that the vaccine has time to take effect. Typhoid vaccines lose
effectiveness after several years; if you were vaccinated in the past, check with your doctor to see if it
is time for a booster vaccination. Taking antibiotics will not prevent typhoid fever; they only help treat
it.

The chart below provides basic information on typhoid vaccines that are available in the United States.
 Table 1: Typhoid Vaccines Available in the United
States
Time immunization
Number of Time Minimum Age Booster
How should be completed
Vaccine Name Doses Between For Needed
Given by (before possible
Necessary Doses Vaccination Every...
exposure)

Ty21a (Vivotif 1 capsule 4 2 days 1 week 6 years 5 years

Berna, Swiss by mouth
Serum and
Vaccine
Institute)

ViCPS (Typhim Injection 1 N/A 2 weeks 2 years 2 years

Vi, Pasteur
Merieux)

The parenteral heat-phenol-inactivated vaccine (manufactured by Wyeth-Ayerst) has been

discontinued.

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What are the signs and symptoms of typhoid fever?

Persons with typhoid fever usually have a sustained fever as high as 103° to 104° F (39° to 40° C).
They may also feel weak, or have stomach pains, headache, or loss of appetite. In some cases,
patients have a rash of flat, rose-colored spots. The only way to know for sure if an illness is typhoid
fever is to have samples of stool or blood tested for the presence of Salmonella  Typhi.
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What do you do if you think you have typhoid fever?

If you suspect you have typhoid fever, see a doctor immediately. If you are traveling in a foreign
country, you can usually call the U.S. consulate for a list of recommended doctors.

You will probably be given an antibiotic to treat the disease. Three commonly prescribed antibiotics
are ampicillin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Persons given antibiotics usually
begin to feel better within 2 to 3 days, and deaths rarely occur. However, persons who do not get
treatment may continue to have fever for weeks or months, and as many as 20% may die from
complications of the infection.

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Typhoid fever's danger doesn't end when symptoms disappear

Even if your symptoms seem to go away, you may still be carrying Salmonella Typhi. If so, the illness
could return, or you could pass the disease to other people. In fact, if you work at a job where you
handle food or care for small children, you may be barred legally from going back to work until a
doctor has determined that you no longer carry any typhoid bacteria.
If you are being treated for typhoid fever, it is important to do the following:

Keep taking the prescribed antibiotics for as long as the doctor has asked you to take them.

Wash your hands carefully with soap and water after using the bathroom, and do not prepare or serve
food for other people. This will lower the chance that you will pass the infection on to someone else.

Have your doctor perform a series of stool cultures to ensure that no Salmonella Typhi bacteria remain
in your body.

Signs and symptoms

Typhoid fever is characterized by a slowly progressive fever as high as 40 °C (104 °F), profuse
sweating, gastroenteritis, and nonbloody diarrhea. Less commonly, a rash of flat, rose-colored spots may
appear.[4]

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 classicWidal test is negative in the first week.

In the second week of the infection, the patient lies prostrate with high fever in plateau around 40 °C
(104 °F) and bradycardia (sphygmothermic 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 a third of 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. (The major symptom of this fever is the fever usually rises in the afternoon up to the first and
second week.)

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 not fatal.
 Intestinal perforation in the 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 the fever has started reducing this (defervescence).
This carries on into the fourth and final week.

[edit]Cause

[edit]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
defecating and before handling food are an important component in controlling spread of the disease.
According to statistics from the United States Centers for Disease Control and Prevention (CDC),
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 CDC approximately 5% of people who contract typhoid continue to carry
the disease after they recover. The most famous asymptomatic carrier was Mary Mallon (commonly
known as "Typhoid Mary"), a young cook who was responsible for infecting at least 53 people with
typhoid, three of whom died from the disease.[5] Mallon was the first apparently perfectly healthy person
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.[6]

[edit]Heterozygous advantage
It has been hypothesized 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.[7] 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. However, the heterozygous
advantage hypothesis was proposed in one review in which the author himself writes, "Although
cellular/molecular evidence presently is not available for this hypothesis, the CF mutation may be one of
several mutations that have spread in European populations because they increased resistance to
infectious diseases." Since no molecular experimental evidence has been presented in support of this
theory, this theory is not accepted by the majority of the scientific community.

[8]
== Diagnosis of typhoid ==

Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of

salmonella antibodies against antigens O-somatic and H-flagellar). In epidemicsand 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 cultures of the
blood and stool.[9]

The Widal test is time consuming and often times when diagnosis is reached it is too late to start an
antibiotic regimen. Since an early diagnosis is key to a good prognosis, researches have recently
developed a new diagnostic method using PCR. The new PCR method still test blood cultures and is
highly sensitive but it allows results in eight hours versus several days as with the Widal test. see full test
at http://www.ann-clinmicrob.com/content/9/1/14 .[10]

The term "enteric fever" is a collective term that refers to typhoid and paratyphoid. [11]

[edit]Prevention

Main article:  Typhoid vaccine

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 preventing typhoid.
There are two vaccines currently recommended by the World Health Organization for the prevention of
typhoid:[12] these are the live, oral Ty21avaccine (sold as Vivotif Berna) and the injectable Typhoid
polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are
between 50% to 80% protective and are recommended for travelers to areas where typhoid is endemic.
Boosters are recommended every 5 years for the oral vaccine and every 2 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). [12]

[edit]Treatment

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[11]
[13]
 otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.[14][15]
[16]
 Cefixime is a suitable oral alternative.[17][18]

Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-

sulfamethoxazole, Amoxicillin andciprofloxacin, 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[citation needed]. In some communities, however, case-fatality rates may reach as high
as 47%.[citation needed]

[edit]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. [citation
needed]
 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 South America, India, Pakistan, Bangladesh, Thailand or Vietnam. For these
patients, the recommended first line treatment is ceftriaxone. It has also been suggested Azithromycin is
better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone.
[19]
 Azithromycin significantly reduces relapse rates compared with 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.[20] It is not certain how this problem can be solved, because most laboratories around the world
(including the West) are dependent on disc testing and cannot test for MICs.

[edit]Epidemiology

With an estimated 16–33 million cases of annually resulting in 216,000 deaths in endemic areas,
the World Health Organization identifies typhoid as a serious public health problem. Its incidence is
highest in children and young adults between 5 and 19 years old. [21]

[edit]History

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 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.
[22]
 Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived
DNA study.[23] 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.

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.
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 people. [24] The most
notorious carrier of typhoid fever—but by no means the most destructive—wasMary 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.

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 the first half of the 20th century
due to vaccinations and advances in public sanitation and hygiene. Antibiotics were introduced in clinical
practice in 1942, greatly reducing mortality. Today, 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.[21]

Typhoid fever was also known as suette milliaire in nineteenth-century France.