Typhoid Fever

Systemic infectious disease caused by Salmonella enterica serovar Typhi

Aetiology

Causative organism: Salmonella enterica serovar Typhi

Type: Gram-negative bacillus

Family: Enterobacteriaceae

Motility: Motile (flagella)

Antigenic structure:

O antigen (somatic)
H antigen (flagellar)
Vi antigen (capsular; virulence factor)

Mode of Transmission

Fecal–oral route

Ingestion of contaminated:

Water
Food

Chronic carriers (gallbladder colonization) play a key role

Pathophysiology

Ingestion of bacteria

Survival through gastric acid

Invasion of intestinal epithelium (Peyer’s patches)

Uptake by macrophages

Hematogenous dissemination

Seeding of liver, spleen, bone marrow

Secondary bacteremia → systemic manifestations

Clinical presentation

Incubation Period

7–14 days (range 3–30 days)

Clinical Stages

First Week

Gradually rising fever (“step-ladder” pattern)

Headache

Malaise

Relative bradycardia (Faget sign)

Constipation (more common in adults)

Second Week

Sustained high fever

Toxic appearance

Abdominal pain

Rose spots (faint salmon-colored macules on trunk)

Hepatosplenomegaly

Diarrhea (“pea soup” stool) may occur

Third Week

Severe illness

Intestinal complications:

Intestinal hemorrhage
Intestinal perforation

Delirium (“typhoid state”)

Fourth Week

Gradual recovery or complications

Investigations

Hematological and Biochemical Tests

(Supportive, not confirmatory)

Complete Blood Count (CBC)

Leukopenia (common)

Relative lymphocytosis

Mild anemia

Thrombocytopenia (occasionally)

Mechanism: Bone marrow suppression and reticuloendothelial involvement.

Liver Function Tests (LFTs)

Mild to moderate elevation of:

Disproportionately high alkaline phosphatase

Mild hyperbilirubinemia (rare)

⚠️ Transaminases are not as high as in viral hepatitis.

Microbiological Diagnosis (Definitive Diagnosis)

Blood Culture — Gold Standard (Early Disease)

Best test in the 1st week of illness

Sensitivity: ~40–80%

Requires:

Adequate blood volume
Collection before antibiotics

Why it works early:

During the first week, bacteremia is highest.

Stool Culture

Becomes positive in 2nd–3rd week

Reflects intestinal shedding

Useful for:

Carrier detection
Epidemiological studies

Urine Culture

Positive in later stages (3rd week)

Lower sensitivity

Supportive only

Bone Marrow Culture — Most Sensitive Test

Sensitivity >90%

Positive at any stage of illness

Less affected by prior antibiotic use

Indications:

Strong clinical suspicion

Negative blood cultures

Prior antibiotic exposure

⚠️ Invasive → not routinely done.

Serological Tests

Widal Test → detected starting on 5th days of fever

Detects antibodies against:

O antigen (early, IgM)

H antigen (later, IgG)

Interpretation:

Significant if:

Fourfold rise in titer (paired sera)
Or high single titer in endemic areas (1/320 titer)

Limitations:

False positives (previous infection, vaccination)

False negatives (early disease)

Low specificity and sensitivity

⚠️ Not confirmatory—use only as supportive evidence.

Rapid Serological Tests

(e.g., Typhidot, Tubex)

Faster results

Detect IgM/IgG

Variable accuracy

Useful where cultures unavailable

Management

Antibiotic Therapy

First Line (Fluoroquinolones)

Ciprofloxacin 500mg BID PO (7-14 days)
Ofloxacin 400mg BID PO (7-14 days)
Norfloxacin 400mg BID PO (7-14 days)

Second Line (3rd generation Cephalosporins)

Ceftriaxone 3-4gr/days (3-5 days)
Cefixime 20mg/kg/days (7-14 days)

Supportive Care

Hydration, antipyretics, diet (high calorie/protein).

Monitor for Complications

Surgical and specialist involvement if needed.

Prevention

Hygiene, sanitation, possibly vaccine in select populations.

Complications

Intestinal

Ileal perforation

Massive GI bleeding

Extraintestinal

Encephalopathy

Myocarditis

Pneumonia

Cholecystitis

Osteomyelitis

Relapse

Chronic carrier state