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 

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

Definitive Diagnosis

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

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

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

9. Treatment 

Uncomplicated Typhoid

Due to rising resistance:

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

Indicated for travellers to endemic regions.