Typhoid and Paratyphoid Fever (Enteric Fever)
Summary
Enteric Fever is a systemic, potentially fatal infection caused by the bacteria Salmonella enterica serovar Typhi (Typhoid) or Paratyphi A, B, C. It remains a major global health burden, particularly in South Asia. Transmission is fecal-oral via contaminated food/water. The bacteria invade the gut lymphoid tissue (Peyer's patches), disseminate via macrophages to the reticuloendothelial system (Liver/Spleen), and re-seed the gut, causing severe inflammation. The classic presentation involves a "step-ladder" fever, headache, and abdominal pain. Major complications include intestinal perforation and haemorrhage (usually in the 3rd week). Multidrug resistance (MDR) is widespread, necessitating third-generation cephalosporins or azithromycin as first-line therapy. [1,2]
Key Facts
- Travel History: The single biggest risk factor. >80% of imported cases in the West originate from the Indian Subcontinent (India, Pakistan, Bangladesh).
- Presentation: It is a systemic febrile illness, NOT just gastroenteritis. Constipation is often more prominent than diarrhoea in the first week.
- "Rose Spots": Faint salmon-coloured macules on the trunk (30% of cases).
- Faget's Sign: Relative bradycardia (pulse is slower than expected for the height of the fever).
- Carrier State: Bacteria can colonise the Gallbladder (forming bioflims on gallstones), turning patients into chronic carriers ("Typhoid Mary") who shed bacteria for years.
Clinical Pearls
Don't wait for the stool: In the first week of fever, stool cultures are often negative. Blood culture is the investigation of choice initially. Bone marrow culture is the most sensitive but rarely done.
The "Pea Soup" Diarrhoea: This classic description typically appears in Week 2 or 3. Don't rule out typhoid because the patient is constipated in Week 1.
Caution with NSAIDs: Avoid them. The Peyer's patches in the ileum are inflamed and friable. NSAIDs increase the risk of massive GI bleed.
Vaccination: Provides only ~50-70% protection. A vaccinated traveller can still get Typhoid. Never rule it out based on vaccination status.
Global Burden
- Incidence: 11-20 million cases/year. ~120,000 deaths.
- Endemic areas: South Asia, Southeast Asia, Sub-Saharan Africa.
Transmission
- Fecal-Oral: "Boil it, cook it, peel it, or forget it."
- Chronic Carriers: Food handlers often sources of outbreaks.
Mechanism of Invasion
- Ingestion: Bacteria survive stomach acid.
- Invasion: Cross intestinal epithelium via M-cells (Peyer's patches in terminal ileum).
- Dissemination: Engulfed by Macrophages but survive intracellularly. Carried to Liver, Spleen, Bone Marrow (Primary Bacteraemia - incubation 7-14 days).
- Replication: Multiply in RES (Reticuloendothelial System).
- Re-invasion: Dumped back into bloodstream (Secondary Bacteraemia - Symptomatic Phase) and bile.
- Ulceration: High bacterial load in bile re-infects Peyer's patches -> necrosis -> ulceration -> perforation.
Timeline "The Weeks"
Week 1 (Invasion)
Week 2 (Dissemination)
Week 3 (Complications)
Week 4 (Recovery)
- General: Toxic, exhausted, apathetic facies ("Typhoid state").
- Vitals: High fever + Relative Bradycardia.
- Abdomen: Distended, tender RLQ (swollen Peyer's patches). Spleen palpable.
- Skin: Search carefully for Rose spots.
Microbiology
- Blood Culture: Primary test. Positive in 60-80% (Week 1-2). Sensitivity drops in later weeks.
- Stool Culture: Positive from Week 2 onwards.
- Urine Culture: Positive Week 2-3.
- Bone Marrow Culture: Gold Standard. Sensitivity >90% even if on antibiotics. (Reserved for complex cases).
Bloods
- FBC: Leucopenia (Neutropenia) is classic (bacterial marrow suppression). Anaemia. Thrombocytopenia.
- LFTs: Transaminitis (Salmonella hepatitis is common). Elevated CRP.
Serology
- Widal Test: Historical. Detects O and H antigens. Low sensitivity/specificity. Generally NOT recommended in modern practice due to false positives.
Management Algorithm
SUSPECTED TYPHOID
(Fever + Travel)
↓
┌───────────┴───────────┐
MILD SEVERE
(Ambulatory) (Hospitalised)
(PO Meds) (Delirium/Shock)
↓ ↓
Azithromycin IV Ceftriaxone
(avoid Cipro (or Azithromycin)
unless sens + STEROIDS
proven)
1. Antibiotics
Resistance is dynamic. Ciprofloxacin (Fluoroquinolone) resistance is widespread in Asia ("NARST" strains).
- Empiric Treatment:
- Ceftriaxone (IV): 2g OD for 10-14 days. Drug of Choice for severe disease.
- Azithromycin (PO): 1g then 500mg daily for 7 days. Drug of Choice for uncomplicated disease.
- Extensively Drug Resistant (XDR) (Pakistan strain): Resistant to Ceftriaxone. Requires Meropenem or Azithromycin.
- Chloramphenicol: Historical. Rarely used now (toxicity/resistance).
2. Steroids
- Dexamethasone (High dose: 3mg/kg stat then 1mg/kg Q6H for 48h).
- Indication: ONLY for severe typhoid with shock or altered mental status. Shown to reduce mortality significantly. [3]
3. Supportive
- Fluids (IV/Oral).
- Antipyretics.
- Nutrition (Soft diet to protect ileum).
4. Surgery
- For ileal perforation. Repair vs Resection. High mortality.
5. Carrier Eradication
- High dose Ciprofloxacin or Amoxicillin for 4-6 weeks.
- Cholecystectomy if gallstones present (as bacteria persist in biofilm).
- Intestinal Perforation: 1-3%. Terminal ileum. Sudden pain -> Check Erect CXR (Pneumoperitoneum).
- Haemorrhage: Erosion of vessel in Peyer's patch.
- Cholecystitis.
- Osteomyelitis: Salmonella is a classic cause of osteomyelitis in Sickle Cell Disease.
- Untreated: Mortality 10-20%.
- Treated: Mortality less than 1%.
- Relapse: 5-10% (usually milder).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Typhoid Treatment | WHO | Use Fluoroquinolones with caution due to resistance. Azithromycin preferred PO. |
| Enteric Fever | IDSA / PHE | Ceftriaxone first line for inpatients. Add Azithromycin to cover XDR if returning from Pakistan. |
Landmark Studies
1. Jakarta Protocol (Dexamethasone Study, 1984)
- Intervention: High dose steroids in severe typhoid (shock/coma).
- Result: Mortality reduced from 56% to 10%.
- Impact: Standard of care for severe typhoid.
2. Gaskell et al. (2008)
- Topic: Fluoroquinolone resistance.
- Result: Demonstrated widespread resistance in South Asia. Shifted guidelines to Cephalosporins/Azithromycin.
What is Typhoid?
It is a serious bacterial infection caught from contaminated food or water mixed with sewage. It is common in India and Southeast Asia.
Is it just tummy bug?
No. It starts in the gut but spreads to the blood, liver, and spleen. It causes weeks of high fever and can make holes in the bowel if not treated.
Treatment
We treat it with strong antibiotics. You usually feel better within 3-5 days of starting them. You must finish the course to stop it coming back.
Am I contagious?
Yes. The bacteria are in your poo. You must wash hands thoroughly. You cannot prepare food for others until 3 stool samples show you are clear of the bacteria.
Primary Sources
- Wain J, et al. Typhoid fever. Lancet. 2015;385:1136-1145. PMID: 25458731.
- Bhan MK, et al. Typhoid and paratyphoid fever. Lancet. 2005;366:749-762. PMID: 16125594.
- Hoffman SL, et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med. 1984;310:82-88. PMID: 6361558.
Common Exam Questions
- Infectious Disease: "Returning traveller from India, fever + neutropenia relative bradycardia. Diagnosis?"
- Answer: Typhoid Fever.
- Microbiology: "Mechanism of carrier state?"
- Answer: Biofilm formation on gallstones.
- Pharmacology: "Treatment for severe typhoid with shock?"
- Answer: Ceftriaxone + Dexamethasone.
- Pathology: "Where does perforation occur?"
- Answer: Peyer's patches of the terminal ileum (anti-mesenteric border).
Viva Points
- Faget's Sign: Define it.
- Sickle Cell: Why osteomyelitis? Salmonella thrives in devitalised bone/infarcts, and sickle patients have functional asplenia (reduced clearance of encapsulated/intracellular bacteria).
- Widal Test: Why obsolete? Cross reacts with other salmonella, malaria, and prior vaccination.
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