1. Definition
Typhoid fever (enteric fever) is a systemic bacterial infection caused mainly by Salmonella
enterica serovar Typhi. It is transmitted predominantly through the fecal–oral
route, usually by ingestion of food or water contaminated with feces from
an infected person or carrier.
Paratyphoid fever is caused by Salmonella Paratyphi A, B, or C.
2. Causative Organism
The main causative organism is:
- Salmonella Typhi
- Gram-negative bacillus
- Facultative anaerobe
- Motile
- Non-spore-forming
- Humans are the principal
reservoir.
Important antigens
O antigen: Somatic antigen associated with the bacterial cell wall.
H antigen: Flagellar antigen.
Vi antigen: Capsular/virulence antigen that helps the organism evade host immune
defenses.
3. Mode of Transmission
Typhoid is mainly transmitted by the fecal–oral route.
An infected person or chronic carrier excretes S. Typhi in feces.
If sanitation and hand hygiene are poor, the organism can contaminate drinking
water or food. When another person consumes the contaminated food or water,
infection can occur.
Major risk factors
- Unsafe drinking water
- Contaminated food
- Poor sanitation
- Poor hand hygiene
- Overcrowding
- Living in or traveling to endemic
areas
- Food prepared by an infected
carrier
- Lack of access to safe water and
sanitation
4. Pathophysiology
The pathophysiology can be remembered as:
Ingestion → Intestinal invasion → Macrophages → Lymph nodes → Bacteremia
→ Reticuloendothelial organs → Secondary bacteremia → Intestinal damage
Step-by-step
- A person consumes food or water
contaminated with S. Typhi.
- The bacteria pass through the
stomach and reach the small intestine.
- They invade the intestinal
mucosa, particularly through M cells overlying Peyer's patches.
- The bacteria are taken up by macrophages.
- Unlike many bacteria, S. Typhi
can survive and multiply within macrophages.
- The infected macrophages
transport the organisms to the mesenteric lymph nodes.
- The bacteria enter the
bloodstream, producing primary bacteremia.
- They reach the reticuloendothelial
system, particularly the:
- Liver
- Spleen
- Bone marrow
- The bacteria multiply in these
organs.
- They subsequently re-enter the
bloodstream, producing secondary bacteremia, which is responsible
for many systemic manifestations such as persistent fever, headache and
malaise.
- The bacteria can return to the
intestine through the biliary system.
- Repeated infection of Peyer's
patches causes inflammation, necrosis and ulceration.
- Severe ulceration may result in:
- Intestinal hemorrhage
- Intestinal perforation
- Peritonitis
5. Clinical Manifestations
🌡️ Early illness —
approximately Week 1
Symptoms commonly develop gradually and may include:
- Gradually increasing fever
- Headache
- Malaise
- Weakness
- Fatigue
- Loss of appetite
- Nausea
- Abdominal discomfort
- Sometimes cough
🌡️ Week 2
Fever may become persistent and high.
Other manifestations include:
- Persistent fever
- Headache
- Abdominal pain
- Abdominal distension
- Diarrhea or constipation
- Weakness
- Relative bradycardia may occur
- Rose spots may appear, usually on the trunk
Rose spots 🌹
These are small, faint, pink-colored macules that can occur on the trunk.
They are a classic feature but are not present in every patient.
⚠️ Week 3
Severe untreated disease may produce:
- Severe weakness
- Delirium
- Encephalopathy
- Intestinal hemorrhage
- Intestinal perforation
- Peritonitis
- Sepsis
6. Diagnosis
Diagnosis should be based on the clinical presentation plus
appropriate laboratory testing.
A. Blood Culture ⭐
Blood culture is an important diagnostic test for typhoid fever, especially during the early stage of
illness.
Ideally, cultures should be obtained before antibiotic treatment
whenever possible.
A positive culture demonstrating S. Typhi provides
microbiological confirmation.
B. Bone Marrow Culture
Bone marrow culture has higher sensitivity than blood culture,
including in some patients who have already received antibiotics.
However, it is invasive and therefore is not routinely required for every
patient.
C. Stool Culture
Stool culture may become positive later in the illness.
It is particularly useful for:
- Detecting intestinal shedding
- Identifying carriers
- Epidemiological investigation
D. Widal Test
The Widal test detects antibodies against:
- O antigen
- H antigen
However, the Widal test has significant limitations because of
false-positive and false-negative results.
Therefore:
⚠️ Widal test should not be used alone to confirm
acute typhoid fever.
Culture-based diagnosis is preferred where available.
E. Other Laboratory Findings
Possible findings include:
- Leukopenia or a normal/low white
blood cell count
- Mild elevation of liver enzymes
- Elevated inflammatory markers
- Abnormal renal function in severe
dehydration or systemic illness
7. Complications ⭐⭐⭐
Complications are more likely in severe or untreated disease,
particularly later in the illness.
Major complications include:
1. Intestinal Hemorrhage 🩸
Inflammation and ulceration of Peyer's patches can damage intestinal
blood vessels, resulting in gastrointestinal bleeding.
2. Intestinal Perforation 🕳️
Deep ulceration, particularly in the terminal ileum, can penetrate
through the intestinal wall and cause perforation.
This can lead to:
Perforation → Peritonitis → Sepsis → Septic shock
3. Peritonitis
Leakage of intestinal contents into the abdominal cavity following
perforation can cause severe peritonitis.
4. Sepsis
The infection can become systemic and produce severe inflammatory
response and organ dysfunction.
5. Septic Shock
Severe sepsis can cause profound hypotension and inadequate tissue
perfusion.
6. Encephalopathy / Delirium
Severe systemic infection may affect the central nervous system and cause
confusion, delirium or encephalopathy.
7. Hepatitis
Liver involvement may occur during systemic infection.
8. Cholecystitis
The gallbladder can become involved because S. Typhi can persist
in the biliary system.
9. Pancreatitis
Pancreatic involvement is an uncommon complication.
10. Relapse
Symptoms may return after apparent recovery, particularly if infection is
not completely eradicated.
11. Chronic Carrier State
Some individuals, especially those with gallbladder colonization, can
continue to excrete S. Typhi for a prolonged period despite having few
or no symptoms.
This is important epidemiologically because carriers can transmit
infection to others.
💊 8. Treatment Goals
The major goals of treatment are:
- Eradicate Salmonella Typhi.
- Reduce fever and other symptoms.
- Prevent intestinal hemorrhage and
perforation.
- Prevent sepsis and other systemic
complications.
- Correct dehydration and
electrolyte disturbances.
- Restore adequate nutrition.
- Prevent transmission to other
people.
- Prevent relapse.
- Eliminate chronic carriage when
present.
- Achieve complete clinical
recovery.
🔄 9. Treatment Flow
Suspected Typhoid
⬇️
Clinical assessment + appropriate cultures
⬇️
Assess severity and complications
⬇️
Mild / uncomplicated disease
Moderate disease
Severe / complicated disease
⬇️
Clinical improvement
⬇️
Complete prescribed antibiotic course
⬇️
Follow-up and assessment for relapse/carriage when indicated
💊 10. Pharmacological Treatment
A. Antibiotic Therapy ⭐⭐⭐
Antibiotic selection should be based on:
- Local antimicrobial resistance
patterns
- Culture and susceptibility
results
- Severity of disease
- Patient age
- Pregnancy status
- Allergy history
- Previous antibiotic exposure
Commonly used options include:
1. Azithromycin
A commonly used oral option for uncomplicated typhoid where
susceptibility is expected.
Mechanism: Inhibits bacterial protein synthesis by binding to the 50S ribosomal
subunit.
2. Ceftriaxone
A third-generation cephalosporin commonly used for moderate-to-severe
disease or when oral therapy is unsuitable.
Mechanism: Inhibits bacterial cell-wall synthesis.
It is administered parenterally.
3. Cefixime
An oral third-generation cephalosporin that may be used in selected
situations, depending on susceptibility and local guidelines.
4. Fluoroquinolones
Examples include:
- Ciprofloxacin
- Ofloxacin
However:
⚠️ Widespread resistance to fluoroquinolones is present
in many regions, so they should only be used when the organism is
demonstrated or strongly expected to be susceptible according to local guidance.
5. Older antibiotics
Historically used drugs include:
- Chloramphenicol
- Ampicillin/amoxicillin
- Co-trimoxazole
Because of widespread resistance and/or toxicity concerns, these are not
routine first choices and should generally be considered only when
susceptibility and current clinical guidelines support their use.
🌡️ B. Symptomatic and Supportive Pharmacotherapy
Paracetamol
Used for:
- Fever
- Headache
- Body aches
Avoid unnecessary NSAIDs in patients with significant gastrointestinal
bleeding risk.
ORS
Useful for patients with:
- Diarrhea
- Mild dehydration
- Fluid and electrolyte losses
IV fluids
Used when there is:
- Severe dehydration
- Inability to drink
- Shock
- Significant electrolyte
disturbance
🥗 11. Non-Pharmacological
Treatment
💧 Adequate Hydration
Encourage sufficient fluid intake when the patient can drink.
ORS can be used when diarrhea or dehydration is present.
🍲 Nutritional Support
Provide:
- Easily digestible food
- Adequate calories
- Adequate protein
- Small, frequent meals if appetite
is poor
🛌 Adequate Rest
Rest helps recovery and reduces physical stress during acute illness.
🧼 Hygiene
Very important to prevent transmission:
- Wash hands thoroughly after using
the toilet.
- Wash hands before preparing or
eating food.
- Use safe drinking water.
- Maintain proper sanitation.
- Handle food safely.
🚫 Prevent
Transmission
Patients and particularly suspected carriers should follow appropriate
hygiene and public-health advice.
Food handlers with typhoid require appropriate medical evaluation and
clearance according to local public-health regulations.
🎯 12. Treatment Goal — Easy Memory
Remember "ERADICATE":
⭐ 13. High-Yield Exam Points
- 🦠 Causative organism:
Salmonella Typhi
- 🚰 Transmission: Fecal–oral route
- 🧬 Major intestinal
site: Peyer's patches
- 🩸 Important diagnostic
test: Blood culture
- ⭐ Most sensitive culture: Bone marrow culture
- 🌹 Classic skin finding: Rose spots
- 🕳️ Major intestinal complications: Hemorrhage and perforation
- 💊 Antibiotic choice: Depends on severity and local
resistance/susceptibility
- 💧 Supportive treatment: Hydration + nutrition + rest
- 🧼 Prevention: Safe
water, sanitation, hand hygiene and vaccination where appropriate
- ⚠️ Do not rely on Widal alone for diagnosis.
- ⚠️ Complete the prescribed antibiotic course to reduce
treatment failure and relapse.