Typhoid fever

From Wikipedia, the free encyclopedia

Jump to: navigation, search
For an unrelated disease with a similar name, see typhus. For a related disease which is
caused by two different bacteria, see Paratyphoid fever. For the character in the 2006 film
Elektra, see Typhoid (Elektra).
Typhoid Fever
Classification and external resources

Rose spots on the chest of a patient with typhoid fever due to

the bacterium Salmonella Typhi
ICD-10 A01.0
ICD-9 002
DiseasesDB 27829
eMedicine oph/686 med/2331
MeSH D014435

Typhoid fever, also known as typhoid,[1] is a common worldwide illness, transmitted by

the ingestion of food or water contaminated with the feces of an infected person, which
contain the bacterium Salmonella typhi.[2][3] The bacteria then perforate through the
intestinal wall and are phagocytosed by macrophages. 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.

This fever received various names, such as gastric fever, abdominal typhus, infantile
remittant fever, slow fever, nervous fever, pythogenic fever, etc. The name of "
typhoid " was given by Louis in 1829, as a derivative from typhus.

The impact of this disease falls sharply with the application of modern sanitation
techniques.

Contents
[hide]

• 1 Signs and symptoms

• 2 Cause
o 2.1 Transmission
o 2.2 Heterozygous advantage
• 3 Diagnosis of typhoid
• 4 Prevention
• 5 Treatment
o 5.1 Resistance
• 6 Epidemiology
• 7 History
o 7.1 Famous victims
o 7.2 In fiction
• 8 See also
• 9 References
o 9.1 Further reading

• 10 External links

[edit] 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 classic Widal 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 is thought that cystic fibrosis may have risen to its present levels (1 in 1600 in UK) due
to the heterozygous advantage that it confers against typhoid fever.[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.
[edit] 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
epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a
therapeutic trial time with chloramphenicol is generally undertaken while awaiting the
results of Widal test and cultures of the blood and stool.[8]

The term "enteric fever" is a collective term that refers to typhoid and paratyphoid.[9]

[edit] Prevention

Doctor administering a typhoid vaccination at a school in San Augustine County, Texas

It has been suggested that Typhoid vaccine be merged into this article or section.
(Discuss)

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.

A vaccine against typhoid fever was developed during World War II by Ralph Walter
Graystone Wyckoff.[10] There are two vaccines currently recommended by the World
Health Organization for the prevention of typhoid:[11] these are the live, oral Ty21a
vaccine (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).[11]
1939 conceptual illustration showing various ways that typhoid bacteria can contaminate
a water well (center)

[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[9][12] otherwise, a third-generation cephalosporin such as ceftriaxone or
cefotaxime is the first choice.[13][14][15] Cefixime is a suitable oral alternative.[16][17]

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

When untreated, typhoid fever persists for three weeks to a month. Death occurs in
between 10% and 30% of untreated cases[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.[18]
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.[19] 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

Incidence of typhoid fever

♦ Strongly endemic
♦ Endemic
♦ Sporadic cases

Death rates for typhoid fever in the U.S. 1906–1960

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.[20]

[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.[21] Other scientists have disputed the findings, citing serious
methodologic flaws in the dental pulp-derived DNA study.[22] 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.[23] The most notorious carrier of typhoid fever—but by no means the
most destructive—was Mary Mallon, also known as Typhoid Mary. In 1907, she became
the first American carrier to be identified and traced. She was a cook in New York. She is
closely associated with fifty-three cases and three deaths.[24] 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.[20]
Typhoid fever was also known as suette milliaire in nineteenth-century France.

Abstract
Until the last few years, chloramphenicol was recognized positively as the drug of choice
in the treatment of acute typhoid fever. Its hematotoxicity, as well as the recently
observed epidemic and the present endemic occurrence of S.typhi strains with R-factor-
mediated resistance to chloramphenicol in Mexico, India and South-East Asia, render the
clinical evaluation of new antibacterial agents extremely important. By means of a
literature review on controlled comparative trials, the value of thiamphenicol, ampicillin,
amoxycillin, furazolidone and co-trimoxazole as alternative drugs for the treatment of
acute typhoid fever is examined. Co-trimoxazole seems to be the drug of choice in the
treatment of acute typhoid fever. For the treatment of the chronic typhoid carrier
ampicillin is most frequently used, but amoxycillin and co-trimoxazole seem to be just as
effective.Bis vor wenigen Jahren war Chloramphenicol unumstritten das Mittel der Wahl
beim akuten Typhus abdominalis. Seine Hämotoxizität sowie das vor kurzem erstmals
beobachtete epidemische und z. Z. immer noch endemische Vorkommen von
Typhuserregern mit durch R-Faktor bewirkter Chloramphenicol-Resistenz in Mexiko,
Indien und Südostasien macht die klinische Erprobung neuer Chemotherapeutika
dringend notwendig. Anhand einer Literaturanalyse von kontrollierten Vergleichsstudien
wird der Wert von Thiamphenicol, Ampicillin, Amoxycillin, Furazolidon und Co-
trimoxazol als Alternativmittel untersucht. Co-trimoxazol scheint das Mittel der Wahl zu
sein. Für die Behandlung des Typhusdauerausscheiders wird Ampicillin am meisten
gebraucht, Amoxycillin und Co-trimoxazol scheinen jedoch gleich wirksam zu sein.

Fulltext Preview
Typhoid Fever: Treatment & Medication
Author: John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical
School; Consulting Staff, Department of Medicine and Infectious Disease Service,
Cambridge Health Alliance
Coauthor(s): Thomas Garvey, MD, JD, Chief, Medical Affiliated Services, Department
of Medicine, Lemuel Shattuck Hospital; Attending Physician, Chest Clinic, Lawrence
Memorial Hospital; Co-chair, Medical Advisory Committee for the Elimination of
Tuberculosis; Roberto Corales, DO, Medical Director, Principal Investigator, AIDS
Community Health Center; Steven K Schmitt, MD, Co-director of Infectious Disease
Fellowship Program, Department of Infectious Disease, The Cleveland Clinic Foundation
Contributor Information and Disclosures

Updated: Apr 8, 2010

• Print This

• Email This
• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• Multimedia

• References
• Keywords

Information from Industry

View efficacy data in the bacterial RTIs you see most Clinical success > 90% was
demonstrated in acute bacterial sinusitis, acute bacterial exacerbation of chronic
bronchitis, and in community-acquired pneumonia Learn more

Treatment
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
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.

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.

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).

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.

Activity

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.