Enteric Fever: Signs and Symptoms, Investigation, and Management
Signs and Symptoms
Fever is almost invariable in enteric fever, accompanied by non-specific symptoms including headache, constipation or diarrhea, dry cough, and relative bradycardia. 1
Core Clinical Features:
- Fever: Gradual onset over 3-7 days, present in virtually all cases 2
- Headache: Diagnostic accuracy of 75.5% 3
- Relative bradycardia: Diagnostic accuracy of 66% 3
- Gastrointestinal symptoms: Abdominal pain/discomfort (51% accuracy), diarrhea (55% accuracy), or constipation 3
- Constitutional symptoms: Malaise, myalgia, and chills 2
Important Clinical Pitfalls:
- Symptoms are highly non-specific and overlap with other febrile illnesses, making clinical diagnosis challenging 1, 4
- Meningism and other misleading symptoms may occur, potentially causing diagnostic confusion 1
- Laboratory findings are unreliable: Full blood count and liver function tests may be normal or deranged in almost any pattern 1
Complications (10-15% of patients):
- More likely if illness duration exceeds 2 weeks 1
- Gastrointestinal bleeding 1
- Intestinal perforation 1
- Typhoid encephalopathy 1, 5
- Myocardial dysfunction 5
- Secondary hemophagocytic lymphohistiocytosis 5
Investigation
Blood cultures have the highest yield within the first week of symptom onset and should be obtained immediately in suspected cases. 1
Recommended Diagnostic Approach:
Primary investigations:
- Blood culture: Sensitivity 40-80% (modern methods may be higher), highest yield in first week 1
- Stool culture: Sensitivity 35-65%, becomes positive after the first week 1
- Urine culture: Sensitivity 0-58%, also positive after first week 1
Secondary investigations:
- Bone marrow culture: Higher sensitivity than blood culture, but invasive 1
Critical Testing Considerations:
Antibiotic susceptibility testing requires special attention:
- Ciprofloxacin disc testing alone is unreliable for determining fluoroquinolone sensitivity 1
- Only consider the isolate fluoroquinolone-sensitive if also sensitive to nalidixic acid on disc testing 1
Tests NOT recommended:
- Widal test lacks sensitivity and specificity and should not be used 1
- Newer rapid serological tests (Typhidot, Typhidot-M, Tubex) have shown mixed results and are not yet reliable 1
Management
Intravenous ceftriaxone is now the preferred first-line empirical agent for unstable patients or those returning from Asia due to widespread fluoroquinolone resistance. 1
Empirical Treatment Algorithm:
For unstable patients or strong clinical suspicion:
- Start treatment empirically without waiting for culture results 1
- First-line: IV ceftriaxone (>70% of S. typhi and S. paratyphi imported to UK are fluoroquinolone-resistant; all 2006 isolates were ceftriaxone-sensitive) 1
Definitive Treatment Based on Susceptibility:
For fluoroquinolone-resistant isolates:
- Azithromycin: Suitable oral alternative for uncomplicated disease, relapse rate <3% 1
- Continue treatment for 14 days to reduce relapse risk 1
- Azithromycin is well-tolerated with no reported side effects 6
For fluoroquinolone-sensitive isolates:
- Fluoroquinolones remain most effective: Average fever clearance <4 days, cure rates >96%, low faecal carriage rates 1
- Relapse rates <8% 1
Alternative oral agents:
- Cefixime has high treatment failure rates (4-37.6%) and should be avoided as first-line 1
Special Considerations:
Severe cases:
Outpatient management:
- Uncomplicated enteric fever can be safely managed as outpatient with oral azithromycin 6
- Outpatients typically receive shorter antibiotic courses (median 7 days vs 11 days for inpatients) 6
- Careful monitoring is essential as treatment failure can occur 6
Emerging Resistance Concerns:
Critical resistance patterns:
- Extensively drug-resistant (XDR) enteric fever from Pakistan (since 2016) responds to only limited antibiotics 7
- Overall increase in antibiotic resistance in all endemic areas 7
- Treatment choice must be guided by local resistance patterns 2