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.