Typhoid fever

Pathophysiology

Typhoid fever, also known as Salmonella typhi or commonly just typhoid, is a

common worldwide illness, transmitted by the ingestion of food or water contaminated with the
feces of an infected person. The bacteria then perforate through the intestinal wall and are
phagocytosed by macrophages. It is caused by the bacterium 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.

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.
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.

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 septicemia 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
(defervescence). This carries on into the fourth and final week.
Cause

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 Center for
Disease Control, the chlorination of drinking water has led to dramatic decreases in the
transmission of typhoid fever in the U.S.

A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms,

but capable of infecting others. According to the Centers for Disease Control approximately 5%
of people who contract typhoid continue to carry the disease after they recover. 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. 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.
Heterozygous advantage

It is thought that cystic fibrosis may have risen to its present levels (1 in 1600 in UK) due
to the heterozygous advantage that it confers against typhoid fever. The CFTR protein is present
in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR
protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium.

Diagnosis

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.

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

Prevention
 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.[ There are two vaccines currently recommended by the World Health
Organization for the prevention of typhoid: 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).

1939 conceptual illustration showing various ways that typhoid bacteria can contaminate a water
well (center)

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
ciprofloxacinotherwise; a third-generation cephalosporin such as ceftriaxone or cefotaxime is the
first choice. Cefixime is a suitable oral alternative.

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 in some communities; however, case-fatality rates may
reach as high as 47%.

The common treatment of Typhoid is Mucomelt-Forte which is the combination of

Cefixime with Acetylcysteine. Cefixime is the third generation cephalosporin antibiotic which
breaks the cell wall of bacteria that is Salmonella typhi and acetylcysteine neutralize the
endotoxin which is released by the bacteria as a waste product of metabolism.This endotoxin
cause rise in body temperature which is the main symptom of typhoid.

Resistance

Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and

streptomycin is now common, and these agents have not been used as first line treatment now for
almost 20 years Typhoid that is resistant to these agents is known as multidrug-resistant typhoid
(MDR typhoid).

Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent

and Southeast Asia. Many centers 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[ 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. 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.
Public Health Nursing Responsibility

 Teach members of the family how to report all symptoms to the attending physician
especially when patient is being cared at home. Teach, guide and suoervise members of
the family on nursing techniques which will contribute patient’s recovery

 Interpret to family nature of disease and need for practicing preventive and control
measures

Nursing Care

 Demonstrate to family how to give bedside care, such as tepid sponge bath, feeding,
changing linens, use of bedpan and mouth care.

 Any bleeding from the rectum, blood in stools, sudden acute abdominal pain,
restlessness, falling of temperature should be reported at once to the physician or the
patient should be brought at once to the hospital.

 Take vital signs and teach family member how to take and record same

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.

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.[ Other scientists
have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA
study. 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. 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 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.
Prepared by:
Brett Brian D. Atalan

BSN 3H