Typhoid fever is an infectious disease caused primarily by the bacterium Salmonella typhi, characterized by symptoms such as high fever, abdominal pain, and malaise, and predominantly occurs in areas with poor sanitation. The disease can be transmitted through contaminated food and water, with vaccination being a key prevention method. Treatment includes antibiotics and supportive care, though antibiotic resistance has become a significant concern.

1. Typhoid Fever

2. Definition
 An infectious feverish disease caused by the bacterium
Salmonella typhi(Salmonella enterica Serovar Typhi )
and less commonly by Salmonella
paratyphoid.
 It is characterized by Acute generalized infection of the
reticule endothelial system, intestinal lymphoid tissue,
and the gall bladder.
 The infection always comes from another human, either
an ill person or a healthy carrier of the bacterium. The
bacterium is passed on with water and foods and can
withstand both drying and refrigeration.

3. Brief History
 Thomas Willis who is credited with the first description of typhoid fever in
1659
 Alexandre Louis, a French Physician, first proposed the name “typhoid
fever”
 Carl Joseph Eberth who discovered the typhoid bacillus in 1880.
 Georges Widal who described the ‘Widal agglutination reaction’ of the
blood in 1896.
Carl Joseph Eberth

4. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families

5. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
3. By person
Age:
•Can effect any age. But peak incidence
is from 5-19 years
Sex:
•Male are at greater risk
Immunity:
•All ages are susceptible to infection.
Gastric acidity and intestinal immunity
provides some degree of immunity.

6. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
B. Determinants
1. Primary Determinants
•The aetiologic agent are;
•Salmonella Typhi
•Salmonella Para Typhi A and B
•S. typhi is the major cause of typhoid fever and has 3
antigens.
•O Antigens: somatic antigens
•H Antigens: Flagella Antigens
•Vi Antigens. Virulence antigen

7. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
2. Secondary Determinants
• Rainy Season
•Poor sanitation
•Open air defecation and urination
•Poor personal hygiene

8. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
C. Frequency
Typhoid fever occurs in all parts of the world where water
supplies and sanitation are Sub-standard.
The disease in now common in Developed countries
In UK, typhoid fever ha been brought very close to
eradication
Worldwide typhoid fever affects more than 6 million people
About 600,000 death occur annually due to typhoid
Due to the presence of all the factors responsible for spread
of disease in Pakistan, very much common
In Pakistan, it is endemic

9. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
2. Source of infection
A. Primary Sources
•Faces and urine of cases
and carriers.
•B. Secondary Sources
Contaminated
•Food
Water
Milk
Flies
Fingers

10. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
3. Mode of Transmission
•Faeco-oral route
•Urine-oral route
4. Reservoir of Infection
• Man is the only reservoir and may be
cases or carriers.

11. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
5. Portal of Entry
•Mouth
6. incubation period
•10-14 days

12. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
Clinical features
1. Invasion: (1st week)
Onset is insidious with headache, body ache, malaise, sore
throat and anorexia
Tongue coated with raw tips and edges
Step ladder fever: Low in the morning and gradually
increases in the night
Bronchitis: Cough
Relative Bradycardia

13. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
•In untreated cases:
•The temperature becomes high
•Spleen becomes palpable at the end of
first week
•Rose spots appear on the upper
abdomen and back in crops
2. Advanced (2nd week)

14. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
•Mild case: Toxemia abates, gradual fall of temperature.
•Severe case: Increased Toxemia, intestinal hemorrhage
and perforation may occur.
3. decline (3rd week)
•In a typical uncomplicated case fever subsides in 4 weeks.
4. Convalescence

15. Causes
1. Caused by the bacterium Salmonella Typhoid .
2. Ingestion of contaminated food or water.
3. Contact with an acute case of typhoid fever.
4. Water is contaminated where inadequate sewerage systems and poor
sanitation.
5. Contact with a chronic asymptomatic carrier.
6. Eating food or drinking beverages that handled by a person carrying the
bacteria.
7. Salmonella enteriditis and Salmonella typhimurium are other salmonella bacteria,
cause food poisoning and diarrhea.

16. How do bacteria cause disease?

17. Pathophysiology
 Ingestion of contaminated food and water (via Salmonella typhi )
 Invade small intestine and enter blood stream
 Carried by white blood cells in the liver spleen and bone marrow
 Multiply and reenter the blood stream
 Bacteria invade the gall bladder, biliary system and lymphatic tissue
of the bowel and multiply in high numbers
 Then pass into the intestinal tract and can be identified for diagnosis
in cultures from the stool tested in the laboratory

18. Symptoms
 No symptoms - if only a mild exposure; some people become
"carriers" of typhoid.
 Poor appetite,
 Headaches, Generalized aches and pains.
 Fever, Lethargy, Lethargy.
 Diarrhea.
 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.
 Constipation, mild vomiting, slow heartbeat.

19. Time frame
Occurs gradually over a few weeks after exposure to the
bacteria. Sometimes children suddenly become sick. The
condition may last for weeks or even a month or longer without
treatment.
First-Stage Typhoid Fever
The beginning stage is characterized by high fever, fatigue,
weakness, headache, sore throat, diarrhea, constipation,
stomach pain and a skin rash on the chest and abdominal area.
According to the Mayo Clinic, adults are most likely to
experience constipation, while children usually experience
diarrhea.

20. Second stage
Second-stage typhoid fever is characterized by
weight loss, high fever, severe diarrhea and severe
constipation. Also, the abdominal region may
appear severely distended.
Typhoid State
When typhoid fever continues untreated for more
than two or three weeks, the effected individual
may be delirious or unable to stand and move, and
the eyes may be partially open during this time. At
this point fatal complications may emerge

21. Diagnosis
1) Blood, bone marrow, or stool cultures test.
2) Widal test.
3) Slide agglutination.
4) Antimicrobial susceptibility testing.

22. Widal test
" A test involving agglutination of typhoid
bacilli when they are mixed with serum
containing typhoid antibodies from an
individual having typhoid fever; used to
detect the presence of Salmonella typhi and
S. paratyphoid."

23. How to read widal test report
 The highest dilution of the patient's serum in which
agglutinations occurs is noted, ex. if the dilution is 1 in
160 then the titer is 169.
 Agglutination in dilution up to <1 :60 is seen in normal
individuals.
 Agglutination in dilution 1 :160 is suggestive of Salmonella
infection.
 Agglutination in dilution of and more than 1 :320 is
confirmatory of Enteric fever .

24. Prevention
Two main typhoid fever prevention strategies:
1. Vaccination
First type of vaccine:
 Contains killed Salmonella typhi bacteria.
 Administered by a shot.
Second type of vaccine:
 Contains a live but weakened strain of the Salmonella bacteria that
causes
typhoid fever.
 Taken by mouth.

25. Cont..
• Be vaccinated against typhoid while traveling to a country where
typhoid is common.
• Need to complete your vaccination at least one week
before travel.
• Typhoid vaccines lose their effectiveness after several
years so check with your doctor to see if it is time for a
booster vaccination.
• Avoid food and drinks with poor hygiene and risks of
contamination..

26. Treatment and care.
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.
Rest is helpful, but mobility should be maintained if
tolerable.
• The patient should be encouraged to stay home from work
until recovery.

27. Treatment Cont.…
Consultations
 An infectious disease specialist or surgeon should be consulted.
Surgical Care
 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.

28. Medication
Antibiotics
 Antibiotics, such as ampicillin, chloramphenicol, fluoroquinolone
trimethoprim-sulfamethoxazole, Amoxicillin and ciprofloxacin etc
used totreat typhoid fever.
 Prompt treatment of the disease with antibiotics reduces the case-fatality
rate to approximately 1%

30. Fluoroquinolones
 Optimal for the treatment of typhoid fever.
 Relatively inexpensive, well tolerated and more rapidly and reliably
effective than the former first-line drugs, viz. chloramphenicol,
ampicillin,amoxicillin and trimethoprim-sulfamethoxazole.
 Rapid therapeutic response, i.e. clearance of fever and symptoms in three
to five days, and very low rates of post-treatment carriage.
Chloramphenicol
 Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth
by inhibiting protein synthesis.
 Oral administration gives slightly greater bio availability than
intramuscular (i.m.) or intravenous (i.v.) administration of the
succinate salt.
 The recommended dosage is 50 - 75 mg per kg per day for 14 days
divided into four doses per day, or for at least five to seven days
after defervescence.

31. Cephalosporins
 Ceftriaxone: 50-75 mg per kg per day one or two doses
 Cefotaxime: 40-80 mg per kg per day in two or three doses
 Cefoperazone: 50-100 mg per kg per day.
Amoxicillin (Trimox, Amoxil, Biomox)
 Interferes with synthesis of cell wall mucopeptides during active
multiplication, resulting in bactericidal activity against susceptible bacteria.
 At least as effective as chloramphenicol in rapidity of defervescence and
relapse rate.
 Usually given PO with a daily dose of 75-100 mg/kg tid (three times a day)
for 14 d.
Adult: 1 g PO q8
Pediatric: 20-50 mg/kg/d PO divided q8h for 14 d

32. Dexamethasone
 Prompt administration of high-dose dexamethasone reduces mortality
in patients with severe typhoid fever without increasing incidence of
complications, carrier states, or relapse among survivors.
 Initial dose of 3 mg/kg by slow i.v. infusion over 30 minutes.
 1 mg/kg 6 hourly for 2 days.
Antibiotic Resistance
 MDR is mediated by plasmid The genes for antibiotic resistance in
S typhi and S paratyphi are acquired into a region called an
integron from Escherichia coli and other gram-negative bacteria via
plasmids.
 Quinolone resistance is frequently mediated by single point mutations in
the quinolone-resistance–determining region of the gyrA gene.
 Nalidixic acid resistant: MIC of fluoroquinolones for these strains was 10
times that for fully susceptible strains.

33. Misdiagnosis
 Paratyphoid fever- similar to typhoid fever but usually less
severe.
 Paraenteric fever- a typhoid-like fever but not caused by
Salmonella.
 Gastroenteritis- mild case of typhoid fever may be mistaken
for gastroenteritis.
 Tuberculosis
 Q fever
 Rickettsial infections
 Acute diarrhea (type of Diarrhea)
 Viral Hepatitis
 Malaria

34. A. Distribution
1. By Time
Most common from July to September.
2. By Place
More common in place with:
•Poor Sanitation
•Poor housing
•Overcrowding
•Large Families
• A polysaccharide vaccine based on the purified Vi-antigen, known as Vi-PS
vaccine. This single-dose intramuscular or subcutaneous injectable Vi vaccine
provides about 70% protection against blood culture-confirmed typhoid fever for
at least 3 years.
• A live attenuated oral vaccine known as Ty21a, made with attenuated S. typhi
strain Ty2 and is available in capsules. A liquid formulation also used to be
available but now discontinued due to lack of demand for it. Extensive trials in
children in chile, Egypt and Indonesia showed protective efficacy of 33-67&
against blood-culture confirmed typhoid fever for the capsule Ty21a, and a fourth
dose of the vaccine increased the protective efficacy of he vaccine significantly.
In two trials in school-aged children's in chile, the capsule Ty21a vaccine had a
67& protective efficacy after three years and 62% protective after seven years.
Two typhoid vaccinations are currently
available