TYPHOID FEVER 

1. Definition

Typhoid fever (enteric fever) is a systemic febrile illness caused primarily by:

  • Salmonella Typhi
  • Salmonella Paratyphi A (paratyphoid – usually milder)

It is a faeco-oral transmitted, invasive intracellular infection affecting the reticuloendothelial system.


2. Epidemiology 

  • Endemic in South Asia (India, Pakistan, Bangladesh), Africa
  • Transmission: contaminated water, street food
  • Incubation: 7–14 days (range 3–60 days)
  • Humans are the only reservoir
  • Chronic carriage: ~1–5%


3. Microbiology & Pathogenesis

Organism

  • Gram-negative bacillus

Virulence Factors

  • Vi capsule (anti-phagocytic)
  • LPS endotoxin
  • Type III secretion system


Pathogenesis 

  1. Ingestion → survives gastric acid
  2. Invades terminal ileum (M cells)
  3. Replicates in macrophages
  4. Disseminates via lymphatics → liver, spleen, bone marrow
  5. Bacteraemia → systemic illness
  6. Re-infection of intestine → Peyer’s patch necrosis
  7. → Ulceration → haemorrhage or perforation


4. Clinical Features

Classic Time Course 

Week

Features

Week 1

Step-ladder fever, malaise, headache, dry cough, constipation

Week 2

High sustained fever, abdominal pain, rose spots, relative bradycardia

Week 3

Complications – perforation, haemorrhage, delirium

Week 4

Gradual recovery


Key Symptoms

  • Prolonged fever (>5 days)-Step-ladder fever refers to a gradually rising temperature (d/t Gradual systemic dissemination) over several days, where each day’s peak is slightly higher than the previous day
  • Headache
  • Abdominal pain
  • Constipation (adults) or diarrhoea (children)
  • Anorexia
  • Dry cough

Important Signs 

  • Relative bradycardia (Faget sign)

Normally:

  • For every ↑1°C rise in temperature
    → HR increases by ~10–15 bpm

If this does NOT happen → Relative bradycardia

  • Rose spots (salmon-coloured macules on trunk)
  • Coated tongue
  • Hepatosplenomegaly
  • Abdominal tenderness (RLQ)

5. Investigations

Blood Tests

Test

Finding

FBC

Leukopenia (classical), may be normal

LFT

Mild transaminitis

CRP

Elevated

U&E

Usually normal


Definitive Diagnosis

There is no single universally accepted formal “criteria” but diagnosis is based on:Compatible clinical syndrome + microbiological confirmation

Test

Sensitivity

Timing

Blood culture

60–80%

Week 1

Stool culture

Less sensitive early

Week 2+

Bone marrow culture

Highest sensitivity (~90%)

Any stage

Bone marrow culture remains positive even after antibiotics.


Widal Test

  • Detects O and H antibodies
  • Poor sensitivity/specificity
  • False positives (previous vaccination, past infection)
  • Not recommended in UK.

TYPHIDOT 

It is a rapid serological test used to detect antibodies against:

  • Salmonella enterica serovar Typhi

It detects IgM and IgG antibodies against outer membrane proteins (OMP).

IgM detectable from day 3–5 of fever

⚠ However:

  • False positives common in endemic areas
  • Cannot distinguish active vs recent infection reliably
  • Background IgG positivity common

Types of Tests

Test

Detects

Clinical Meaning

Typhidot

IgM + IgG

Acute vs past infection

Typhidot-M

IgM only

Early acute infection

Typhidot Combo

Rapid card test

Screening


6. Complications 

Gastrointestinal

  • Ileal perforation (week 3)
  • Massive lower GI bleed

Neurological

  • Delirium (“Typhoid state”)
  • Encephalopathy

Cardiovascular

  • Myocarditis
  • Shock

Others

  • Hepatitis
  • Osteomyelitis (esp. sickle cell)
  • DIC
  • Chronic carrier state

7. Chronic Carrier State

Organism persists in gallbladder.

Risk factors:

  • Gallstones
  • Female
  • Older age

Famous example: Typhoid Mary

Management:

  • Prolonged antibiotics
  • Cholecystectomy if persistent


8. Differential Diagnosis

Condition

Clue

Malaria

Travel + thrombocytopenia

Dengue

Severe myalgia + rash + low platelets

Brucellosis

Animal exposure

TB

Chronic course

Infective endocarditis

Murmur + emboli


9. Treatment 

Uncomplicated Typhoid

Due to rising resistance:

Drug

Duration

Ceftriaxone (IV)

7–14 days

Azithromycin

7 days

Ciprofloxacin

Only if sensitive


Severe Disease

  • IV Ceftriaxone
  • IV fluids
  • Manage complications surgically if perforation

XDR Typhoid 

Extensively drug-resistant strains 

Sensitive only to:

  • Azithromycin
  • Carbapenems

10. Prevention

  • Safe water
  • Hand hygiene
  • Vaccination

Vaccines

Type

Example

Duration

Oral live attenuated

Ty21a

3 years

Injectable polysaccharide

Vi vaccine

2–3 years

Indicated for travellers to endemic regions.


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