TABLE OF CONTENTS

CHAPTER I...................................................................................................1
INTRODUCTION...........................................................................................1
CHAPTER II.................................................................................................2
TINJUAN PUSTAKA.....................................................................................2
1. DEFINITION...........................................................................................2
2. ANATOMY...............................................................................................3
3. ETIOLOGY..............................................................................................7
4. PATHOPHYSIOLOGY.............................................................................8
5. RISK FACTORS.....................................................................................11
6. EPIDEMIOLOGY..................................................................................12
Mortality/Morbidity...................................................................................12
Race...........................................................................................................13
Sex.............................................................................................................13
Age.............................................................................................................13
CLINICAL PRESENTATION.....................................................................14
History.......................................................................................................14
7. LABORATORY STUDIES......................................................................22
8. IMAGING STUDIES.............................................................................25
9. HISTOLOGIC FINDINGS.....................................................................25
10. STAGING.............................................................................................26
11. TREATMENT.......................................................................................26
12. MEDICATION.....................................................................................27
13. FOLLOW UP.......................................................................................31
14. COMPLICATION................................................................................36
15. PROGNOSIS.......................................................................................39
REFERENCE................................................................................................41

CHAPTER I
INTRODUCTION
Typhoid fever is an acute systemic bacterial disease resulting from infection with
Salmonella typhi. The organism is a Gram-negative short bacillus that is motile due to its
peritrichous flagella. The bacterium grows best at 37 C/99 F human body
temperature. The organism gains access to the body through ingestion of food or water
that has been contaminated by infected feces or urine. Since it is eliminated in the stools
and urine of patients, the organism can find its way into food and water through sewage,
flies and the hands of the carriers handling raw fruits, vegetables and other food. And
other source of infection is the ingestion of oysters and shellfish harvested from polluted
water. And we consider the five Fs factors which are the Feces, Flies, Fumites, Food,
and Fingers which can be a way in getting the disease. Most of the affected and at risk of
the disease are those clients with an age of 30 years old. And most of the carriers of the
bacteria are those clients with an age of 50 yeas old and above especially women.
The onset of typhoid fever is gradual. During the first week of having the disease, the
signs and symptoms include fever, anorexia, myalgia, malaise, and headache. The patient
may not seek health care at this time since these are non specific symptoms. But at the
end of the first week, rose spot (a cluster of pink lesions that initially blanch with
pressure) may be found on the chest and abdomen. Without therapy, the temperature rises
steadily reaching its highest level, usually 40 0C 41 0C.
During this period of rising temperature, most patients suffer with a severe headache and
a non productive cough. During the second week, if the patient is not treated, the signs
and symptoms of the disease already include fever (40 0C specifically in the evening)
accompanied with chills and delirium, diaphoresis, weakness, abdominal pain, diarrhea,
and cough (crackles). And during the third week, the signs and symptoms include
persistent fever and body weakness. The impact of this disease falls sharply with the
application of modern sanitation techniques.

CHAPTER II
TINJUAN PUSTAKA
1. DEFINITION
Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness
caused primarily by Salmonella typhi. 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 one 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.1 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.2
2. ANATOMY
THE GASTROINTESTINAL SYSTEM
To aid in understanding the disease process, Anatomy and Physiology provides
the necessary information about the normal function of certain body components, its
structure and function. Anatomy and physiology are always related. Anatomy is the study
of the structure and shape of the body and body parts and their relationships to one
another. Physiology is the study of how the body pars work or function.

The gastrointestinal tract (GIT) consists of a hollow muscular tube starting from
the oral cavity, where food enters the mouth, continuing through the pharynx, esophagus,
stomach and intestines to the rectum and anus, where food is expelled. There are various
accessory organs that assist the tract by secreting enzymes to help break down food into
its component nutrients. Thus the salivary glands, liver, pancreas and gall bladder have
important functions in the digestive system. Food is propelled along the length of the GIT
by peristaltic movements of the muscular walls.

The primary purpose of the gastrointestinal tract is to break down food into
nutrients, which can be absorbed into the body to provide energy. First food must be
ingested into the mouth to be mechanically processed and moistened. Secondly, digestion
occurs mainly in the stomach and small intestine where proteins, fats and carbohydrates
are chemically broken down into their basic building blocks. Smaller molecules are then
absorbed across the epithelium of the small intestine and subsequently enter the

circulation. The large intestine plays a key role in reabsorbing excess water. Finally,
undigested material and secreted waste products are excreted from the body via
defecation (passing of faeces). In the case of gastrointestinal disease or disorders, these
functions of the gastrointestinal tract are not achieved successfully. Patients may develop
symptoms of nausea, vomiting, diarrhea, malabsorption, constipation or obstruction.
Gastrointestinal problems are very common and most people will have experienced some
of the above symptoms several times throughout their lives.

Basic structure
The gastrointestinal tract is a muscular tube lined by a special layer of cells, called
epithelium. The contents of the tube are considered external to the body and are in
continuity with the outside world at the mouth and the anus. Although each section of the
tract has specialized functions, the entire tract has a similar basic structure with regional
variations.

The wall is divided into four layers as follows:

Mucosa
The innermost layer of the digestive tract has specialized epithelial cells
supported by an underlying connective tissue layer called the lamina propria. The lamina
propria contains blood vessels, nerves, lymphoid tissue and glands that support the
mucosa. Depending on its function, the epithelium may be simple (a single layer) or
stratified (multiple layers).
Areas such as the mouth and esophagus are covered by a stratified squamous
(flat) epithelium so they can survive the wear and tear of passing food. Simple columnar
(tall) or glandular epithelium lines the stomach and intestines to aid secretion and
absorption. The inner lining is constantly shed and replaced, making it one of the most
rapidly dividing areas of the body. Beneath the lamina propria is the muscularis mucosa.
This comprises layers of smooth muscle which can contract to change the shape of the
6

lumen.
Submucosa
The submucosa surrounds the muscularis mucosa and consists of fat, fibrous
connective tissue and larger vessels and nerves. At its outer margin there is a specialized
nerve plexus called the submucosal plexus or Meissner plexus. This supplies the mucosa
and submucosa.
Muscularis Externa
This smooth muscle layer has inner circular and outer longitudinal layers of
muscle fibres separated by the myenteric plexus or Auerbach plexus. Neural innervations
control the contraction of these muscles and hence the mechanical breakdown and
peristalsis of the food within the lumen.
Serosa/mesentery
The outer layer of the GIT is formed by fat and another layer of epithelial cells
called mesothelium.

Layer
serosa

Duodenum
1st part serosa, 2nd - 4th

Jejunum
normal

Ileum
normal

adventitia

muscularis externa

longitudinal and circular

layers, with Auerbach's
(myenteric) plexus in
between

same as
duodenum

same as
duodenum

submucosa

Brunner's glands and

Meissner's (submucosal)
plexus

no BG

no BG

mucosa: muscularis
mucosae

normal

normal

normal

mucosa: lamina
propria

no PP

no PP

Peyer's patches

mucosa: intestinal
epithelium

simple columnar. Contains

goblet cells, Paneth cells

Similar to
duodenum

3. ETIOLOGY
S typhi has no nonhuman vectors. The following are modes of transmission:

Oral transmission via food or beverages handled by an individual who chronically

sheds the bacteria through stool or, less commonly, urine

Hand-to-mouth transmission after using a contaminated toilet and neglecting hand

hygiene

Oral transmission via sewage-contaminated water or shellfish (especially in the

developing world)3

An inoculum as small as 100,000 organisms causes infection in more than 50% of healthy
volunteers.4

4. PATHOPHYSIOLOGY
All pathogenic Salmonella species are engulfed by phagocytic cells, which then pass
them through the mucosa and present them to the macrophages in the lamina propria.
Nontyphoidal salmonellae are phagocytized throughout the distal ilium and colon. With
toll-like receptor (TLR)5 and TLR-4/MD2/CD-14 complex, macrophages recognize
pathogen-associated

molecular

patterns

(PAMPs)

such

as

flagella

and

lipopolysaccharides. Macrophages and intestinal epithelial cells then attract T cells and
neutrophils with interleukin 8 (IL-8), causing inflammation and suppressing the
infection.5,6
In contrast to the nontyphoidal salmonellae, S typhi enters the host's system primarily
through the distal ilium. S typhi has specialized fimbriae that adhere to the epithelium
over clusters of lymphoid tissue in the ilium (Peyer patches), the main relay point for
macrophages traveling from the gut into the lymphatic system. S typhi has a Vi capsular
antigen that masks PAMPs, avoiding neutrophil-based inflammation. The bacteria then
induce their host macrophages to attract more macrophages.5
It co-opts the macrophages' cellular machinery for their own reproduction 7 as it is carried
through the mesenteric lymph nodes to the thoracic duct and the lymphatics and then
through to the reticuloendothelial tissues of the liver, spleen, bone marrow, and lymph
nodes. Once there, the S typhi bacteria pause and continue to multiply until some critical
density is reached. Afterward, the bacteria induce macrophage apoptosis, breaking out
into the bloodstream to invade the rest of the body.6
The gallbladder is then infected via either bacteremia or direct extension of S typhi
infected bile. The result is that the organism re-enters the gastrointestinal tract in the bile
and reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the
stool and are then available to infect other hosts.6,2

10

5. RISK FACTORS
S typhi are able to survive a stomach pH as low as 1.5. Antacids, histamine-2 receptor
antagonists (H2 blockers), proton pump inhibitors, gastrectomy, and achlorhydria
decrease stomach acidity and facilitate S typhi infection.6
HIV/AIDS is clearly associated with an increased risk of nontyphoidal Salmonella
infection; however, the data and opinions in the literature as to whether this is true for S
typhi infection are conflicting. If an association exists, it is probably minor.8,9,10,11
Other risk factors for clinical S typhi infection include various genetic polymorphisms.
These risk factors often also predispose to other intracellular pathogens. For instance,
PARK2 and PACGR code for a protein aggregate that is essential for breaking down the
bacterial signaling molecules that dampen the macrophage response. Polymorphisms in
their shared regulatory region are found disproportionately in persons infected with
Mycobacterium leprae and S typhi.12
On the other hand, protective host mutations also exist. The fimbriae of S typhi bind in
vitro to cystic fibrosis transmembrane conductance receptor (CFTR), which is expressed
on the gut membrane. Two to 5% of white persons are heterozygous for the CFTR
mutation F508del, which is associated with a decreased susceptibility to typhoid fever, as
well as to cholera and tuberculosis. The homozygous F508del mutation in CFTR is
associated with cystic fibrosis. Thus, typhoid fever may contribute to evolutionary
pressure that maintains a steady occurrence of cystic fibrosis, just as malaria maintains
sickle cell disease in Africa.13,14
Environmental and behavioral risk factors that are independently associated with typhoid
fever include eating food from street vendors, living in the same household with someone
who has new case of typhoid fever, washing the hands inadequately, sharing food from
the same plate, drinking unpurified water, and living in a household that does not have a
toilet.15,12 As the middle class in south Asia grows, some hospitals there are seeing a large

11

number of typhoid fever cases among relatively well-off university students who live in
group households with poor hygeine.16 American clinicians should keep this in mind, as
members of this cohort often come to the United States for higher degrees.
6. EPIDEMIOLOGY
International
Typhoid fever occurs worldwide, primarily in developing nations whose sanitary
conditions are poor. Typhoid fever is endemic in Asia, Africa, Latin America, the
Caribbean, and Oceania, but 80% of cases come from Bangladesh, China, India,
Indonesia, Laos, Nepal, Pakistan, or Vietnam. 18 Within those countries, typhoid fever is
most common in underdeveloped areas. Typhoid fever infects roughly 21.6 million
people (incidence of 3.6 per 1,000 population) and kills an estimated 200,000 people
every year.19
In the United States, most cases of typhoid fever arise in international travelers. The
average yearly incidence of typhoid fever per million travelers from 1999-2006 by county
or region of departure was as follows:17

Canada - 0

Western Hemisphere outside Canada/United States - 1.3

Africa - 7.6

Asia - 10.5

India - 89 (122 in 2006)

Total (for all countries except Canada/United States) - 2.2

Mortality/Morbidity
With prompt and appropriate antibiotic therapy, typhoid fever is typically a short-term
febrile illness requiring a median of 6 days of hospitalization. Treated, it has few longterm sequelae and a 0.2% risk of mortality.17 Untreated typhoid fever is a life-threatening
illness of several weeks' duration with long-term morbidity often involving the central

12

nervous system. The case fatality rate in the United States in the pre-antibiotic era was
9%-13%.20
Race
Typhoid fever has no racial predilection.
Sex
Fifty-four percent of typhoid fever cases in the United States reported between 1999 and
2006 involved males.17
Age
Most documented typhoid fever cases involve school-aged children and young adults.
However, the true incidence among very young children and infants is thought to be
higher. The presentations in these age groups may be atypical, ranging from a mild febrile
illness to severe convulsions, and the S typhi infection may go unrecognized. This may
account for conflicting reports in the literature that this group has either a very high or a
very low rate of morbidity and mortality.16,21

13

CLINICAL PRESENTATION
History
A severe nonspecific febrile illness in a patient who has been exposed to S typhi should
always raise the diagnostic possibility of typhoid fever (enteric fever).
Classic typhoid fever syndrome
Typhoid fever begins 7-14 days after ingestion of S typhi. The fever pattern is stepwise,
characterized by a rising temperature over the course of each day that drops by the
subsequent morning. The peaks and troughs rise progressively over time.
Over the course of the first week of illness, the notorious gastrointestinal manifestations
of the disease develop. These include diffuse abdominal pain and tenderness and, in some
cases, fierce colicky right upper quadrant pain. Monocytic infiltration inflames Peyer
patches and narrows the bowel lumen, causing constipation that lasts the duration of the
illness. The individual then develops a dry cough, dull frontal headache, delirium, and an
increasingly stuporous malaise.2
At approximately the end of the first week of illness, the fever plateaus at 103-104F (3940C). The patient develops rose spots, which are salmon-colored, blanching, truncal,
maculopapules usually 1-4 cm wide and fewer than 5 in number; these generally resolve
within 2-5 days.2 These are bacterial emboli to the dermis and occasionally develop in
persons with shigellosis or nontyphoidal salmonellosis.22
During the second week of illness, the signs and symptoms listed above progress. The
abdomen becomes distended, and soft splenomegaly is common. Relative bradycardia
and dicrotic pulse (double beat, the second beat weaker than the first) may develop.
In the third week, the still febrile individual grows more toxic and anorexic with
significant weight loss. The conjunctivae are infected, and the patient is tachypneic with a
thready pulse and crackles over the lung bases. Abdominal distension is severe. Some
patients experience foul, green-yellow, liquid diarrhea (pea soup diarrhea). The individual
14

may descend into the typhoid state, which is characterized by apathy, confusion, and even
psychosis. Necrotic Peyer patches may cause bowel perforation and peritonitis. This
complication is often unheralded and may be masked by corticosteroids. At this point,
overwhelming toxemia, myocarditis, or intestinal hemorrhage may cause death.
If the individual survives to the fourth week, the fever, mental state, and abdominal
distension slowly improve over a few days. Intestinal and neurologic complications may
still occur in surviving untreated individuals. Weight loss and debilitating weakness last
months. Some survivors become asymptomatic S typhi carriers and have the potential to
transmit the bacteria indefinitely.16,23,24,2,6
Various presentations of typhoid fever

Incubation Week 1

Week 2

Week 3

Systemic
Stepladder

Week 4

Post

Recovery 10%-20% relapse; 3%fever

pattern or insidious

Very

Very common

commona

phase or 4%
death
(15%

onset fever

chronic

long-term

Very rare

Chills

Almost allc

Rigors

Uncommon

Anorexia

Almost all

Diaphoresis

Very common

of sequelae (extremely rare);

cases)

(RR=167; carriers)

Neurologic

Insomnia

neurologic

untreated gallbladder
b

Acute high fever

Malaise

carriers;

Almost all Almost all Typhoid

Very
common

state
(common)

15

cancer

Confusion/delirium

Commond Very
common

Psychosis

Very rare Common

Catatonia

Very rare

Frontal

headache

Very

(usually mild)

common

Meningeal signs

Raree

Parkinsonism

Very rare

Rare

Ear, nose, and throat

Coated tongue

Very
common

Sore throatf
Pulmonary
Mild cough

Common

Bronchitic cough

Common

Rales

Common

Pneumonia

Rare

Rare

(lobar)

Common
(basal)

Cardiovascular
Dicrotic pulse

Rare

Myocarditis

Rare

Pericarditis

Extremely

Common

rareg

16

Thrombophlebitis

Very rare

Gastrointestinal
Constipation

Very

Common

common
Diarrhea

Rare

Bloating

with

tympany

Common (pea soup)

Very
common
(84%) 30

Diffuse

mild

abdominal pain
Sharp

right

Very
common

lower

Rare

quadrant pain
Gastrointestinal

Very rare; Very common

hemorrhage

usually
trace

intestinal perforation

Rare

Hepatosplenomegaly

Common

Jaundice

Common

Gallbladder pain

Very rare

Urogenital
Urinary retention

Common

Hematuria

Rare

Renal pain

Rare

17

Musculoskeletal
Myalgias

Very rare

Arthralgias

Very rare

Rheumatologic
Arthritis (large joint) Extremely rare
Dermatologic
Rose spots

Rare

Miscellaneous
Abscess (anywhere)

Extremely Extremely Extremely

rare
Incubation Week 1

rare

rare

Week 2

Week 3

Systemic
Stepladder

Week 4

Post

Recovery 10%-20% relapse; 3%fever

pattern or insidious

Very

Very common

commona

onset fever

phase or 4%
death
(15%

chronic

long-term

neurologic

of sequelae (extremely rare);

untreated gallbladder
b

Acute high fever

Very rare

Chills

Almost allc

Rigors

Uncommon

Anorexia

Almost all

Diaphoresis

Very common

cases)

(RR=167; carriers)

Neurologic
Malaise

carriers;

Almost all Almost all Typhoid

18

cancer

Insomnia

Confusion/delirium

Very

state

common

(common)

Commond Very
common

Psychosis

Very rare Common

Catatonia

Very rare

Frontal

headache

Very

(usually mild)

common

Meningeal signs

Raree

Parkinsonism

Very rare

Rare

Ear, nose, and throat

Coated tongue

Very
common

Sore throatf
Pulmonary
Mild cough

Common

Bronchitic cough

Common

Rales

Common

Pneumonia

Rare

Rare

(lobar)

Common
(basal)

Cardiovascular
Dicrotic pulse

Rare

Myocarditis

Rare

Common

19

Pericarditis

Extremely
rareg

Thrombophlebitis

Very rare

Gastrointestinal
Constipation

Very

Common

common
Diarrhea

Rare

Bloating

with

tympany

Common (pea soup)

Very
common
(84%) 30

Diffuse

mild

abdominal pain
Sharp

right

Very
common

lower

Rare

quadrant pain
Gastrointestinal

Very rare; Very common

hemorrhage

usually
trace

intestinal perforation

Rare

Hepatosplenomegaly

Common

Jaundice

Common

Gallbladder pain

Very rare

Urogenital
Urinary retention

Common

Hematuria

Rare
20

Renal pain

Rare

Musculoskeletal
Myalgias

Very rare

Arthralgias

Very rare

Rheumatologic
Arthritis (large joint) Extremely rare
Dermatologic
Rose spots

Rare

Miscellaneous
Abscess (anywhere)

Extremely Extremely Extremely

rare

rare

rare

Very common: Symptoms occur in well over half of cases (approximately 65%-95%).
Very rare: Symptoms occur in less than 5% of cases.
Almostall: Symptoms occur in almost all cases.
Common: Symptoms occur in 35%-65% of cases.
Rare: Symptoms occur in 5%-35% of cases.

The clinical course of a given individual with typhoid fever may deviate from the above
description of classic disease. The timing of the symptoms and host response may vary
based on geographic region, race factors, and the infecting bacterial strain. The stepladder
fever pattern that was once the hallmark of typhoid fever now occurs in as few as 12% of
cases. In most contemporary presentations of typhoid fever, the fever has a steady
insidious onset.

21

Young children, individuals with AIDS, and one third of immunocompetent adults who
develop typhoid fever develop diarrhea rather than constipation. In addition, in some
localities, typhoid fever is generally more apt to cause diarrhea than constipation.
Atypical manifestations of typhoid fever include isolated severe headaches that may
mimic meningitis, acute lobar pneumonia, isolated arthralgias, urinary symptoms, severe
jaundice, or fever alone. Some patients, especially in India and Africa, present primarily
with neurologic manifestations such as delirium or, in extremely rare cases, parkinsonian
symptoms

or

Guillain-Barr

syndrome.

Other

unusual

complications

include

pancreatitis,25 meningitis, orchitis, osteomyelitis, and abscesses anywhere on the body.2

Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid
Fever2,26,27,28,29,30
Blank cells: No mention of the symptom at that phase was found in the literature.
Extremely rare: Symptoms have been described in occasional case reports.
7. LABORATORY STUDIES
The diagnosis of typhoid fever (enteric fever) is primarily clinical.
Importantly, the reported sensitivities of tests for S typhi vary greatly in the literature,
even among the most recent articles and respected journals.

Culture
o

The criterion standard for diagnosis of typhoid fever has long been culture
isolation of the organism. Cultures are widely considered 100% specific.

Culture of bone marrow aspirate is 90% sensitive until at least 5 days after
commencement of antibiotics. However, this technique is extremely
painful, which may outweigh its benefit.31

Blood, intestinal secretions (vomitus or duodenal aspirate), and stool

culture results are positive for S typhi in approximately 85%-90% of
patients with typhoid fever who present within the first week of onset.

22

They decline to 20%-30% later in the disease course. In particular, stool

culture may be positive for S typhi several days after ingestion of the
bacteria secondary to inflammation of the intraluminal dendritic cells.
Later in the illness, stool culture results are positive because of bacteria
shed through the gallbladder.
o

Multiple blood cultures (>3) yield a sensitivity of 73%-97%. Largevolume (10-30 mL) blood culture and clot culture may increase the
likelihood of detection.32

Stool culture alone yields a sensitivity of less than 50%, and urine culture
alone is even less sensitive. Cultures of punch-biopsy samples of rose
spots reportedly yield a sensitivity of 63% and may show positive results
even after administration of antibiotics. A single rectal swab culture upon
hospital admission can be expected to detect S typhi in 30%-40% of
patients. S typhi has also been isolated from the cerebrospinal fluid,
peritoneal fluid, mesenteric lymph nodes, resected intestine, pharynx,
tonsils, abscess, and bone, among others.

Bone marrow aspiration and blood are cultured in a selective medium (eg,
10% aqueous oxgall) or a nutritious medium (eg, tryptic soy broth) and are
incubated at 37C for at least 7 days. Subcultures are made daily to one
selective medium (eg, MacConkey agar) and one inhibitory medium (eg,
Salmonella-Shigella agar). Identification of the organism with these
conventional culture techniques usually takes 48-72 hours from
acquisition.

Table

Incubation
Bone

marrow

Week 1

Week 2

Week 3

Week 4

90% (may decrease after 5 d of antibiotics)

aspirate (0.5-1 mL)

Blood (10-30 mL), 40%-80%

~20%

Variable (20%-60%)

23

stool, or duodenal
aspirate culture
Urine

25%-30%, timing unpredictable

Polymerase chain reaction (PCR):35,36 PCR has been used for the diagnosis of
typhoid fever with varying success. Nested PCR, which involves two rounds of
PCR using two primers with different sequences within the H1-d flagellin gene of
S typhi, offers the best sensitivity and specificity. Combining assays of blood and
urine, this technique has achieved a sensitivity of 82.7% and reported specificity
of 100%. However, no type of PCR is widely available for the clinical diagnosis
of typhoid fever.

Specific serologic tests

o

Assays that identify Salmonella antibodies or antigens support the

diagnosis of typhoid fever, but these results should be confirmed with
cultures or DNA evidence.

The Widal test was the mainstay of typhoid fever diagnosis for decades. It
is used to measure agglutinating antibodies against H and O antigens of S
typhi. Neither sensitive nor specific, the Widal test is no longer an
acceptable clinical method.

Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect

enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M
(IgM) and IgG antibodies to S typhi polysaccharide, as well as monoclonal
antibodies against S typhi flagellin,37 are promising, but the success rates of
these assays vary greatly in the literature.

Other nonspecific laboratory studies

o

Most patients with typhoid fever are moderately anemic, have an elevated
erythrocyte sedimentation rate (ESR), thrombocytopenia, and relative
lymphopenia.

Most also have a slightly elevated prothrombin time (PT) and activated
partial thromboplastin time (aPTT) and decreased fibrinogen levels.

24

Circulating fibrin degradation products commonly rise to levels seen in

subclinical disseminated intravascular coagulation (DIC).

Liver transaminase and serum bilirubin values usually rise to twice the
reference range.

Mild hyponatremia and hypokalemia are common.

A serum alanine amino transferase (ALT)tolactate dehydrogenase

(LDH) ratio of more than 9:1 appears to be helpful in distinguishing
typhoid from viral hepatitis. A ratio of greater than 9:1 supports a
diagnosis of acute viral hepatitis, while ratio of less than 9:1 supports
typhoid hepatitis.38

8. IMAGING STUDIES

Radiography: Radiography of the kidneys, ureters, and bladder (KUB) is useful if

bowel perforation (symptomatic or asymptomatic) is suspected.

CT scanning and MRI: These studies may be warranted to investigate for

abscesses in the liver or bones, among other sites.

9. HISTOLOGIC FINDINGS
The hallmark histologic finding in typhoid fever is infiltration of tissues by macrophages
(typhoid cells) that contain bacteria, erythrocytes, and degenerated lymphocytes.
Aggregates of these macrophages are called typhoid nodules, which are found most
commonly in the intestine, mesenteric lymph nodes, spleen, liver, and bone marrow but
may be found in the kidneys, testes, and parotid glands. In the intestines, 4 classic
pathologic stages occur in the course of infection: (1) hyperplastic changes, (2) necrosis
of the intestinal mucosa, (3) sloughing of the mucosa, and (4) the development of ulcers.
The ulcers may perforate into the peritoneal cavity.

25

In the mesenteric lymph nodes, the sinusoids are enlarged and distended by large
collections of macrophages and reticuloendothelial cells. The spleen is enlarged, red, soft,
and congested; its serosal surface may have a fibrinous exudate. Microscopically, the red
pulp is congested and contains typhoid nodules. The gallbladder is hyperemic and may
show evidence of cholecystitis. Liver biopsy specimens from patients with typhoid fever
often show cloudy swelling, balloon degeneration with vacuolation of hepatocytes,
moderate fatty change, and focal typhoid nodules. Intact typhoid bacilli can be observed
at these sites.2,6

10. STAGING
The proper treatment approach to typhoid fever depends on whether the illness is
complicated or uncomplicated. Complicated typhoid fever is characterized by melena
(3% of all hospitalized patients with typhoid fever), serious abdominal discomfort,
intestinal perforation, marked neuropsychiatric symptoms, or other severe manifestations.
Depending on the adequacy of diagnosis and treatment, complicated disease may develop
in up to 10% of treated patients. Delirium, obtundation, stupor, coma, or shock demands a
particularly aggressive approach.

11. TREATMENT
11.1 Medical Care
If a patient presents with unexplained symptoms described in Table 1 within 60 days of
returning from an typhoid fever (enteric fever) endemic area or following consumption of
26

food prepared by an individual who is known to carry typhoid, broad-spectrum empiric

antibiotics should be started immediately. Treatment should not be delayed for
confirmatory tests since prompt treatment drastically reduces the risk of complications
and fatalities. Antibiotic therapy should be narrowed once more information is available.
Compliant patients with uncomplicated disease may be treated on an outpatient basis.
They must be advised to use strict handwashing techniques and to avoid preparing food
for others during the illness course. Hospitalized patients should be placed in contact
isolation during the acute phase of the infection. Feces and urine must be disposed of
safely.
11.2 Surgical Care
Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer
simple closure of the perforation with drainage of the peritoneum. Small-bowel resection
is indicated for patients with multiple perforations.
If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should
be resected. Cholecystectomy is not always successful in eradicating the carrier state
because of persisting hepatic infection.
11.3 Consultations
An infectious disease specialist should be consulted. Consultation with a surgeon is
indicated

upon

suspected

gastrointestinal

perforation,

serious

gastrointestinal

hemorrhage, cholecystitis, or extraintestinal complications (arteritis, endocarditis, organ

abscesses).
11.4 Diet
Fluids and electrolytes should be monitored and replaced diligently. Oral nutrition with a
soft digestible diet is preferable in the absence of abdominal distension or ileus.
11.5 Activity

27

No specific limitations on activity are indicated for patients with typhoid fever. As with
most systemic diseases, rest is helpful, but mobility should be maintained if tolerable.
The patient should be encouraged to stay home from work until recovery.

12. MEDICATION
12.1 Antibiotics
Definitive treatment of typhoid fever (enteric fever) is based on susceptibility. As a
general principle of antimicrobial treatment, intermediate susceptibility should be
regarded as equivalent to resistance. Between 1999 and 2006, 13% of S typhi isolates
collected in the United States were multidrug resistant.
Until susceptibilities are determined, antibiotics should be empiric, for which there are
various recommendations. The authors of this article consider the 2003 World Health
Organization (WHO) guidelines to be outdated. These recommend fluoroquinolone
treatment for both complicated and uncomplicated cases of typhoid fever, but 38% of S
typhi isolates taken in the United States in 2006 were fluoroquinolone resistant (nalidixic
acidresistant S typhi [NARST]), and the rate of multidrug resistance was 13%.
(Multidrug-resistant S typhi is, by definition, resistant to the original first-line agents,
ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.)
The particular sensitivity pattern of the organism in its area of acquisition should be the
major basis of empiric antibiotic choice. It may soon become necessary to treat all cases
presumptively for multidrug resistance until sensitivities are obtained.
Note that nalidixic acid is a nontherapeutic drug that is used outside of the United States
as a stand-in for fluoroquinolones in sensitivity assays. In the United States, it is still used
specifically for S typhi infection.39,17
12.2 History of antibiotic resistance

28

Chloramphenicol was used universally to treat typhoid fever from 1948 until the 1970s,
when widespread resistance occurred. Ampicillin and trimethoprim-sulfamethoxazole
(TMP-SMZ) then became treatments of choice. However, in the late 1980s, some S typhi
and S paratyphi strains (multidrug resistant [MDR] S typhi or S paratyphi) developed
simultaneous plasmid-mediated resistance to all three of these agents.
Fluoroquinolones are now recommended by most authorities for the treatment of typhoid
fever. They are highly effective against susceptible organisms, yielding a better cure rate
than cephalosporins. Unfortunately, resistance to first-generation fluoroquinolones is
widespread in many parts of Asia.
In recent years, third-generation cephalosporins have been used in regions with high
fluoroquinolone resistance rates, particularly in south Asia and Vietnam. Unfortunately,
sporadic resistance has been reported, so it is expected that these will become less useful
over time.39

12.3 Mechanisms of antibiotic resistance

The genes for antibiotic resistance in S typhi and S paratyphi are acquired from
Escherichia coli and other gram-negative bacteria via plasmids. The plasmids contain
cassettes of resistance genes that are incorporated into a region of the Salmonella genome
called an integron. Some plasmids carry multiple cassettes and immediately confer
resistance to multiple classes of antibiotics. This explains the sudden appearance of MDR
strains of S typhi and S paratyphi, often without intermediate strains that have lessextensive resistance.
The initial strains of antibiotic-resistant S typhi and S paratyphi carried chloramphenicol
acetyltransferase type I, which encodes an enzyme that inactivates chloramphenicol via
acetylation. MDR strains may carry dihydrofolate reductase type VII, which confers
resistance to trimethoprim. Interestingly, in areas where these drugs have fallen out of
use, S typhi has reverted to wild type, and they are often more effective than newer
agents.40,41,42,30
29

Resistance to fluoroquinolones is evolving in an ominous direction. Fluoroquinolones

target DNA gyrase and topoisomerase IV, bacterial enzymes that are part of a complex
that uncoils and recoils bacterial DNA for transcription.43 S typhi most commonly
develops fluoroquinolone resistance through specific mutations in gyrA and parC, which
code for the binding region of DNA gyrase and topoisomerase IV, respectively.
A single point mutation gyrA confers partial resistance. If a second gyrA point mutation is
added, the resistance increases somewhat. However, a mutation in parC added to a single
gyrA mutation confers full in vitro resistance to first-generation fluoroquinolones.
Clinically, these resistant strains show a 36% failure rate when treated with a firstgeneration fluoroquinolone such as ciprofloxacin.44 The risk of relapse after bacterial
clearance is higher in both partially and fully resistant strains than in fully susceptible
strains.18
The third-generation fluoroquinolone gatifloxacin appears to be highly effective against
all known clinical strains of S typhi both in vitro and in vivo. However, any two of a
number of gyrA mutations, when added to the parC mutation, confer full in vitro
resistance. Although such a combination has yet to be discovered in vivo, all of these
mutations exist in clinic strains, and it seems highly likely that a gatifloxacin-resistant
strain will be encountered clinically if selective pressure with fluoroquinolones continues
to be exerted.44
12.4 Geography of resistance
Among S typhi isolates obtained in the United States between 1999 and 2006, 43% were
resistant to at least one antibiotic.
Nearly half of S typhi isolates found in the United States now come from travelers to the
Indian subcontinent, where fluoroquinolone resistance is endemic (see Table 3). The rate
of fluoroquinolone resistance in south and Southeast Asia and, to some extent, in East
Asia is generally high and rising (see Table 3). Susceptibility to chloramphenicol, TMPSMZ, and ampicillin in these areas is rebounding. In Southeast Asia, MDR strains remain
predominant, and some acquired resistance to fluoroquinolones by the early 2000s.

30

The most recent professional guideline for the treatment of typhoid fever in south Asia
was issued by the Indian Association of Pediatrics (IAP) in October 2006. Although these
guidelines were published for pediatric typhoid fever, the authors feel that they are also
applicable to adult cases. For empiric treatment of uncomplicated typhoid fever, the IAP
recommends cefixime and, as a second-line agent, azithromycin. For complicated typhoid
fever, they recommend ceftriaxone. Aztreonam and imipenem are second-line agents for
complicated cases.45 The authors believe that the IAP recommendations have more
validity than the WHO recommendations for empiric treatments of typhoid fever in both
adults and children.
In high-prevalence areas outside the areas discussed above, the rate of intermediate
sensitivity or resistance to fluoroquinolones is 3.7% in the Americas (P =.132), 4.7% (P
=.144) in sub-Saharan Africa, and 10.8% (P =.706) in the Middle East. Therefore, for
strains that originate outside of south or Southeast Asia, the WHO recommendations may
still be validthat uncomplicated disease should be treated empirically with oral
ciprofloxacin and complicated typhoid fever from these regions should be treated with
intravenous ciprofloxacin.39,42,46,19,47
Antibiotic resistance is a moving target. Reports are quickly outdated, and surveys of
resistance may have limited geographic scope. Therefore, any recommendation regarding
antibiotic treatment must be taken with a grain of salt. In the authors' opinion, if the
origin of the infection is unknown, the combination of a first-generation fluoroquinolone
and a third-generation cephalosporin should be used.
Table 3. Antibiotic Recommendations by Origin and Severity
Table

Location

Severity

First-Line Antibiotics Second-Line Antibiotics

South Asia, East Asia 45 Uncomplicated Cefixime PO

Azithromycin PO

48, 40

Complicated

Ceftriaxone IV or

Aztreonam

IV

or

31

Cefotaxime IV

Imipenem IV

*Note that the combination of azithromycin and fluoroquinolones is not recommended

because it may cause QT prolongation and is relatively contraindicated.

13. FOLLOW UP
13.1 Further Inpatient Care

If treated with well-selected antibiotics, patients with typhoid fever (enteric fever)
should defervesce within 3-5 days. However, patients with complicated typhoid
fever should finish their course intravenously and should remain in the hospital if
unable to manage this at home.

Patients with complicated typhoid fever should be admitted through the acute
phase of the illness. Uncomplicated cases are generally treated on an outpatient
basis unless the patient is a public health risk or cannot be fully monitored outside
the home.

13.2 Further Outpatient Care

After discharge, patients should be monitored for relapse or complications for 3

months after treatment has commenced.

Five percent to 10% of patients treated with antibiotics experience relapse of

typhoid fever after initial recovery. Relapses typically occur approximately 1
week after therapy is discontinued, but relapse after 70 days has been reported. In
these cases, the blood culture results are again positive, and high serum levels of
H, O, and Vi antibodies and rose spots may reappear.
o

A relapse of typhoid fever is generally milder and of shorter duration than

the initial illness. In rare cases, second or even third relapses occur.
Notably, the relapse rate is much lower following treatment with the new
quinolone drugs, which have effective intracellular penetration.

32

S typhi and S paratyphi rarely develop antibiotic resistance during

treatment. If an antibiotic has been chosen according to sensitivities,
relapse should dictate a search for anatomic, pathologic, or genetic
predispositions rather than for an alternate antibiotic.

Previous infection does not confer immunity. In any suspected relapse,

infection with a different strain should be ruled out.

Depending on the antibiotic used, between 0% and 5.9% of treated patients

become chronic carriers. In some cases, the organism evades antibiotics by
sequestering itself within gallstones or Schistosoma haematobium organisms that
are infecting the bladder. From there, it is shed in stool or urine, respectively. If
present, these diseases must be cured before the bacterium can be eliminated.

Untreated survivors of typhoid fever may shed the bacterium in the feces for up to
3 months. Therefore, after disease resolution, 3 stool cultures in one-month
intervals should be performed to rule out a carrier state. Concurrent urinary
cultures should be considered.

13.3 Deterrence/Prevention

Travelers to endemic countries should avoid raw unpeeled fruits or vegetables

since they may have been prepared with contaminated water; in addition, they
should drink only boiled water.

In endemic countries, the most cost-effective strategy for reducing the incidence
of typhoid fever is the institution of public health measures to ensure safe
drinking water and sanitary disposal of excreta. The effects of these measures are
long-term and reduce the incidence of other enteric infections, which are a major
cause of morbidity and mortality in those areas.

13.4 Vaccines
In endemic areas, mass immunization with typhoid vaccines at regular intervals
considerably reduces the incidence of infections. Routine typhoid vaccination is not
recommended in the United States but is indicated for travelers to endemic areas, persons
with intimate exposure to a documented S typhi carrier (eg, household contact), and

33

microbiology laboratory personnel who frequently work with S typhi. Vaccines are not
approved for use children younger than 2 years.

Travelers should be vaccinated at least one week prior to departing for an endemic
area. Because typhoid vaccines lose effectiveness after several years, consultation
with a specialist in travel medicine is advised if the individual is traveling several
years after vaccination.

The only absolute contraindication to vaccination is a history of severe local or

systemic reactions following a previous dose. The typhoid vaccines available in
the United States have not been studied in pregnant women.

Currently, the 3 typhoid fever vaccines include injected Vi capsular

polysaccharide (ViCPS; Typhim Vi, Pasteur Merieux) antigen, enteric Ty21a
(Vivotif Berna, Swiss Serum and Vaccine Institute) live-attenuated vaccine, and
an acetone-inactivated parenteral vaccine (used only in members of the armed
forces). The efficacy of both vaccines available to the general public approaches
50%.
o

Vi capsular polysaccharide antigen vaccine is composed of purified Vi

antigen, the capsular polysaccharide elaborated by S typhi isolated from
blood cultures.

Primary vaccination with ViCPS consists of a single parenteral

dose of 0.5 mL (25 g IM) one week before travel. The vaccine
manufacturer does not recommend the vaccine for children
younger than 2 years. Booster doses are needed every 2 years to
maintain protection if continued or renewed exposure is expected.

Adverse effects include fever, headache, erythema, and/or

induration of 1 cm or greater. In a study conducted in Nepal, the
ViCPS vaccine produced fewer local and systemic reactions than
the control (the 23-valent pneumococcal vaccine). 55 Among school
children in South Africa, ViCPS produced less erythema and
induration than the control (bivalent vaccine).

34

A systemic review and meta-analysis of 5 randomized controlled

trials on the efficacy and safety of ViCPS versus placebo or
nontyphoid vaccine found a cumulative efficacy of 55% (95% CI,
30%-70%).

The efficacy of vaccination with ViCPS has not been studied

among persons from areas without endemic disease who travel to
endemic regions or among children younger than 5 years. ViCPS
has not been given to children younger than 1 year.

Questions concerning Vi typhoid vaccine effectiveness in young

children (ie, <5 y) have inhibited its use in developing countries.
Whether the vaccine is effective under programmatic conditions is
also unclear.

Sur et al conducted a phase IV effectiveness trial in slum-dwelling

residents aged 2 years or older in India to determine vaccine
protection. Participants (n=37,673) were randomly assigned to
receive a single dose of either Vi vaccine or inactivated hepatitis A
vaccine, according to geographic clusters. The mean rate of Vi
vaccine coverage was 61% and 60% for the hepatitis A vaccine.

Typhoid fever was diagnosed in 96 subjects in the hepatitis A

vaccine group compared with 34 in the Vi vaccine group (no more
than 1 episode was reported per individual). Protective effect for
typhoid with the Vi vaccine was 61% (P <0.001) compared with
the hepatitis A vaccine group. Children vaccinated while aged 2-5
years had an 80% protection level. Unvaccinated members of the
Vi vaccine clusters showed a protection level of 44%. The overall
protection level with all Vi vaccine cluster residents was 57%. The
authors concluded that the Vi vaccine was effective in young
children and protected unvaccinated neighbors of Vi vaccinees.56

Ty21a is an oral vaccine that contains live attenuated S typhi Ty21a strains
in an enteric-coated capsule. The vaccine elicits both serum and intestinal
antibodies and cell-mediated immune responses.

35

In the United States, primary vaccination with Ty21a consists of one

enteric-coated capsule taken on alternate days to a total of 4 capsules.
The capsules must be refrigerated (not frozen), and all 4 doses must be
taken to achieve maximum efficacy.

The optimal booster schedule has not been determined; however, the
longest reported follow-up study of vaccine trial subjects indicated that
efficacy continued for 5 years after vaccination. The manufacturer
recommends revaccination with the entire 4-dose series every 5 years
if continued or renewed exposure to S typhi is expected. This vaccine
may be inactivated if given within 3 days of antibiotics.

Adverse effects are rare. They include abdominal discomfort, nausea,

vomiting, fever, headache, and rash or urticaria.

The vaccine manufacturer of Ty21a recommends against use in

children younger than 6 years. It should not be administered to
immunocompromised persons; the parenteral vaccines present
theoretically safer alternatives for this group.

A systemic review and meta-analysis of 4 randomized controlled trials

on the efficacy and safety of Ty21a versus placebo or nontyphoid
vaccine found a cumulative efficacy of 51% (95% CI, 36%-62%).

The efficacy of Ty21a has not been studied among persons from areas
without endemic disease who travel to disease-endemic regions.

Acetone-inactivated parenteral vaccine is currently available only to members of

the US Armed Forces. Efficacy rates for this vaccine range from 75%-94%.
Booster doses should be administered every 3 years if continued or renewed
exposure is expected.
o

The parenteral heat-phenolinactivated vaccine (Wyeth-Ayerst) has been

discontinued.

No information has been reported concerning the use of one vaccine as a

booster after primary vaccination with a different vaccine. However, using
either the series of 4 doses of Ty21a or 1 dose of ViCPS for persons

36

previously vaccinated with parenteral vaccine is a reasonable alternative to

administration of a booster dose of parenteral inactivated vaccine.
o

A more effective vaccine may be on the horizon. An investigational

vaccine

using

ViCPS

conjugated

to

the

nontoxic

recombinant

pseudomonas exotoxin A (Vi-rEPA) has been studied in a randomized

controlled trial. The vaccine was given to children aged 2-5 years and
showed an efficacy of 89% (95% CI, 76%-97%) after 3.8 years. Vi-rEPA
has not been approved for use in the United States.
14. COMPLICATION

Neuropsychiatric manifestations (In the past 2 decades, reports from diseaseendemic areas have documented a wide spectrum of neuropsychiatric
manifestations of typhoid fever.)
o

A toxic confusional state, characterized by disorientation, delirium, and

restlessness, is characteristic of late-stage typhoid fever. In some cases, these
and other neuropsychiatric features dominate the clinical picture at an early
stage.

Facial twitching or convulsions may be the presenting feature. Meningismus

is not uncommon, but frank meningitis is rare. Encephalomyelitis may
develop, and the underlying pathology may be that of demyelinating
leukoencephalopathy. In rare cases, transverse myelitis, polyneuropathy, or
cranial mononeuropathy develops.

Stupor, obtundation, or coma indicates severe disease.

Focal intracranial infections are uncommon, but multiple brain abscesses have
been reported.57

Other less-common neuropsychiatric manifestations events have included

spastic paraplegia, peripheral or cranial neuritis, Guillain-Barr syndrome,
schizophrenialike illness, mania, and depression.

Respiratory
o

Cough

Ulceration of posterior pharynx

37

Occasional presentation as acute lobar pneumonia (pneumotyphoid)

Cardiovascular
o

Nonspecific electrocardiographic changes occur in 10%-15% of patients

with typhoid fever.

Toxic myocarditis occurs in 1%-5% of persons with typhoid fever and is a

significant cause of death in endemic countries. Toxic myocarditis occurs
in patients who are severely ill and toxemic and is characterized by
tachycardia,

weak

pulse

and

heart

sounds,

hypotension,

and

electrocardiographic abnormalities.
o

Pericarditis is rare, but peripheral vascular collapse without other cardiac

findings is increasingly described. Pulmonary manifestations have also
been reported in patients with typhoid fever.58

Hepatobiliary
o

Mild elevation of transaminases without symptoms is common in persons

with typhoid fever.

Jaundice may occur in persons with typhoid fever and may be due to
hepatitis, cholangitis, cholecystitis, or hemolysis.

Pancreatitis and accompanying acute renal failure and hepatitis with

hepatomegaly have been reported.59

Intestinal manifestations
o

The 2 most common complications of typhoid fever include intestinal

hemorrhage (12% in one British series) and perforation (3%-4.6% of
hospitalized patients).

From 1884-1909 (ie, preantibiotic era), the mortality rate in patients with
intestinal perforation due to typhoid fever was 66%-90% but is now
significantly lower. Approximately 75% of patients have guarding,
rebound tenderness, and rigidity, particularly in the right lower quadrant.

Diagnosis is particularly difficult in the approximately 25% of patients

with perforation and peritonitis who do not have the classic physical
findings. In many cases, the discovery of free intra-abdominal fluid is the
only sign of perforation.

38

Genitourinary manifestations
o

Approximately 25% of patients with typhoid fever excrete S typhi in their

urine at some point during their illness.

Immune complex glomerulitis60 and proteinuria have been reported, and

IgM, C3 antigen, and S typhi antigen can be demonstrated in the
glomerular capillary wall.

Nephritic syndrome may complicate chronic S typhi bacteremia associated

with urinary schistosomiasis.

Nephrotic syndrome may occur transiently in patients with glucose-6phosphate dehydrogenase deficiency.

Cystitis: Typhoid cystitis is very rare. Retention of urine in the typhoid

state may facilitate infection with coliforms or other contaminants.

Hematologic manifestations
o

Subclinical disseminated intravascular coagulation is common in persons

with typhoid fever.

Hemolytic-uremic syndrome is rare.61

Hemolysis

may

also

be

associated

with

glucose-6-phosphate

dehydrogenase deficiency.

Musculoskeletal and joint manifestations

o

Skeletal muscle characteristically shows Zenker degeneration, particularly

affecting the abdominal wall and thigh muscles.

Clinically evident polymyositis may occur.62

Arthritis is very rare and most often affects the hip, knee, or ankle.

Late sequelae (rare in untreated patients and exceedingly rare in treated patients)
o

Neurologic - Polyneuritis, paranoid psychosis, or catatonia63

Cardiovascular - Thrombophlebitis of lower-extremity veins

Genitourinary -Orchitis

Musculoskeletal

Periostitis, often abscesses of the tibia and ribs

Spinal abscess (typhoid spine; very rare)

39

15. PROGNOSIS

The prognosis among persons with typhoid fever depends primarily on the speed
of diagnosis and initiation of correct treatment. Generally, untreated typhoid fever
carries a mortality rate of 10%-20%. In properly treated disease, the mortality rate
is less than 1%.

An unspecified number of patients experience long-term or permanent

complications, including neuropsychiatric symptoms and high rates of
gastrointestinal cancers.

15.1 Patient Education

Because vigilant hand hygiene, vaccination, and the avoidance of risky foods and
beverages are mainstays of prevention, educating travelers before they enter a
disease-endemic region is important.

Because the protection offered by vaccination is at best partial, close attention to

personal, food, and water hygiene should be maintained. The US Centers for
Disease Control and Prevention dictum to "boil it, cook it, peel it, or forget it" is a
good rule in any circumstance. If disease occurs while abroad despite these
precautions, one can usually call the US consulate for a list of recommended
doctors.

40

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