Typhoid Fever

Submitted by:
Bernadette Aban
Maricell Asis

Submitted to:
Mr. Prince Rener Pera

Typhoid fever is an acute illness associated with fever caused by the Salmonella typhi bacteria. It can also be caused
by Salmonella paratyphi, a related bacterium that usually causes 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, less than
500 cases are reported annually in the United States, mostly in people who recently have traveled to endemic areas.
This is in comparison to the 1920s, when over 35,000 cases were reported in the U.S. This improvement is the result
of improved environmental sanitation. Mexico and South America are the most common areas for U.S. citizens to
contract typhoid fever. India, Pakistan, and Egypt are also known high-risk areas for developing this disease.
Worldwide, typhoid fever affects more than 13 million people annually, with over 500,000 patients dying of the
disease.
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 need to 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, and
• diarrhea.
People with typhoid fever usually have a sustained fever as high as 103 to 104 degrees Fahrenheit (39 to 40 degrees
Celsius).
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 which kill the Salmonella bacteria. Prior to the use of antibiotics, the
fatality rate was 20%. Death occurred from overwhelming infection, pneumonia, intestinal bleeding, or intestinal
perforation. With antibiotics and supportive care, mortality has been reduced to 1%-2%. With appropriate antibiotic
therapy, there is usually improvement within one to two days and recovery within seven to 10 days.
Several antibiotics are effective for the treatment of typhoid fever. Chloramphenicol was the original drug of choice
for many years. Because of rare serious side effects, chloramphenicol has been replaced by other effective
antibiotics. The choice of antibiotics needs to be guided by identifying the geographic region where the organism
was acquired and the results of cultures once available. (Certain strains from South America show a significant
resistance to some antibiotics.) 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 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.

Causes of Typhoid Fever

• Poor sanitation, contaminated water and infected milk is main factors responsible for developing typhoid.
 • Flies contaminate the food with germs and people carrying the germs can also spread the disease if they
prepare or serve food.
• Wrong dietary habits and faulty style of living lead to accumulation of toxic waste in the body and
promotes typhoid fever.
• It is common in people who eat more meat and fleshy foods.
Natural remedies for Typhoid Fever
• Complete bed rest is essential.
• Patient should be kept on a liquid diet of orange, barley juice and milk. Orange juice especially hastens
recovery as it increases energy, promotes body resistance and increases urinary output. Administer warm
water enema regularly.
• Apply cold compress to head if temperature rises above 103 degree Fahrenheit. Or wrap the body and legs
twice with a sheet wrung in cold water and then cover it with a warm material. The pack should be kept for
an hour and renewed after every 3 hours. Hot water bottles may be applied to the sides of the body and feet.
• Fresh fruits and easily digestible foods can be given after temperature comes down to normal.
• Plain water or unsweetened lemon water can be used for drinking.
• Gradually start a well-balanced diet.

Treatment
Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin[5][6] otherwise, a
third-generation cephalosporin such as ceftriaxone Gramocef-Oor cefotaxime is the first choice.[7][8][9] Cefixime is a
suitable oral alternative.[10][11]
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. Though in some communities case-fatality rates may be as high as 47%.
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)
Third-generation cephalosporins and quinolones are drugs of choice for the treatment of typhoid fever
because they are less toxic and because many strains of Salmonella typhi often are resistant to
chloramphenicol

Treatment
Antibiotic therapy is the only effective treatment for typhoid and paratyphoid fevers. In the past, the drug of choice
was chloramphenicol (Chloromycetin). Doctors no longer commonly use it, however, because of severe side effects,
a high relapse rate and widespread bacterial resistance. In fact, the existence of antibiotic-resistant bacteria is a
serious and growing problem in the treatment of typhoid, especially in the developing world.
The pathophysiology of typhoid fever is complex and occurs through several stages.
Once, the bacteria(Salmonella typhi),survives the acidity of the stomach, it reaches the intestine and invades the
Payer`s patches of the intestinal wall.Payer`s patches are the clusters of cell primarily composed of Macrophages are
specialised cells that are essential to kill any bacteria.But, Salmonella Typhi is unaffected by these macrophages but,
start survive within the macrophage itself.
So , during this asymptomatic incubation period of 7-14 days, the bacteria spread throughout the reticuloendothelial
system of liver,spleen,gallbladder,and bone marrow.
The first week of symptomatic period is characterised by progressive elevation of temperature.
In the second week, the victim may experience abdominal pain, spleen enlargement and notice Rose spots on his
skin.
The third week is more intense as the bacteria start causing necrosis of the Payer`s patches of the intestine which
leads to perforation and bleeding.This is the terminal stage,if, left untreated, death is imminent.
That`s why,it is also called "enteric fever".Enteric which means, intestine.

PATHOPHYSIOLOGY

After ingestion by the host, Salmonella typhi invades through the gut and multiplies within the mononuclear
phagocytic cells in the liver, spleen, lymph nodes, and Peyer patches of the ileum.

After successfully passing through the stomach, any Salmonella subspecies may be phagocytized by the gut's
intraluminal dendritic cells, causing inflammation that leads to diarrhea. Its specialized fimbriae adhere to the
epithelium that overlies Peyer patches. Peyer patches are grossly visible aggregates of 5-100 lymphoid follicles in
the small bowel submucosa; these patches are larger and more numerous distally. They are the primary mechanism
for sampling antigens in the gut and initiating response. S enterica enters them via 1 of 3 pathways.

Intraluminal dendritic cells may infiltrate through the gut epithelium while carrying the bacterium. M cells may
transport it as well. Immobile and interspersed among regular enterocytes in Peyer patches, M cells are epithelial
cells that mature into professional phagocytes. They phagocytize bacteria such as S enterica and present them to
macrophages and T cells in the lamina propria. Most interestingly, S enterica may convert normally nonphagocytic
epithelial cells into bacterially-mediated endocytosis (BME).

In BME, Salmonella uses a type III secretion system—macromolecular channels those gram-negative bacteria such
as Salmonella insert into eukaryotic cells and intracellular membranes to inject virulence proteins—to inject proteins
SipA and SipC into the epithelial cell. These disrupt the normal brush border and force the cell to form membrane
ruffles. The ruffles engulf the bacilli and create vesicles that carry them across the epithelial cell cytoplasm and the
basolateral membrane. Salmonella pathogenicity island 1 (SPI-1) in the genome encodes the elements of BME.

In the submucosa, Salmonella enters macrophages via bacteria-triggered pinocytosis or via macrophage receptor–
mediated phagocytosis. The intravacuolar environment activates the PhoP/PhoQ regulon, leading to modification of
protein and lipopolysaccharide elements of the bacterial inner and outer membranes. Thus, Salmonella resists lysis
and decreases host pro-inflammatory signaling. The bacterium also produces homocysteine to inactivate nitric oxide
and enzymes against other microbicides. Finally, with the VI antigen, a polysaccharide capsule, S typhi and S
paratyphi further protect themselves from lysis within the macrophage and from neutrophils and complement
without. The infected macrophage provides Salmonella a vehicle safe from other elements of the immune system
and in which it can multiply and travel. It passes through the mesenteric lymph nodes into the thoracic duct and the
lymphatics beyond to seed the reticuloendothelial tissues—liver, spleen, bone marrow, and lymph nodes. In these
havens, it multiplies until some critical density is reached. It causes the apoptosis in the macrophages and enters the
bloodstream to attack the rest of the body. At this stage, the VI antigen comes into play. It forms a capsule to protect
the bacterium from complement and from phagocytic immune cells.

From blood or from the liver via bile ducts, it infects the gallbladder and reenters the gastrointestinal tract in the bile,
spreading to other hosts via stool. In addition, it occasionally invades the urinary tract and spreads via urine.

After primary intestinal infection, further seeding of the Peyer patches occurs through infected bile. They may
become hyperplastic and necrotic with infiltration of mononuclear cells and neutrophils, forming ulcers that may
hemorrhage through eroded blood vessels or perforate the bowel wall, causing peritonitis.

The host recognizes the invader with toll-like receptors 2, 4, and 5. These induce cytokines such as interferon alpha,
interleukin (IL)–12, and tumor necrosis factor-alpha, which recruit macrophages and cause the high fevers of the
disease. Macrophages and neutrophils suppress the active infection. Later, humoral and CD4 T-cell–mediated
immunity clears it.