What are the typical manifestations and treatment options for typhoid fever in a patient with a history of travel?

Typhoid Fever: Clinical Manifestations and Treatment

Clinical Presentation

Fever is almost invariable, occurring in 97-100% of cases, typically presenting as sustained high-grade fever with an insidious rather than abrupt onset. 1, 2

Cardinal Symptoms

• Fever: Present in nearly all cases, often sustained and high-grade, though the classic "step-ladder" pattern is not reliably present 1, 2
• Constitutional symptoms: Headache, malaise, myalgia, and anorexia are common presenting features 1, 2
• Gastrointestinal manifestations: Either constipation OR diarrhea may occur (both are possible), along with abdominal pain 1, 3
• Respiratory symptoms: Nonproductive dry cough is frequently reported 1, 2
• Relative bradycardia: High fever associated with paradoxical bradycardia occurs in approximately 57% of patients 2, 3

Critical Clinical Pitfall

Approximately half of malaria patients are afebrile on presentation, though almost all have a history of fever—absence of fever at the time of examination does not rule out typhoid fever. 1, 4

Atypical Presentations

• Meningism and other misleading neurological symptoms may occur 1
• Full blood count and liver function tests may be normal or deranged in almost any pattern 1
• Leukopenia is present in approximately one-third of cases 3

Timeline and Epidemiology

• Incubation period: 7-18 days (range: 3-60 days) 1, 2, 4
• Typical symptom duration before presentation: Average 7.9 days 3
• Highest incidence: South and Southeast Asia (>100 cases per 100,000 person-years), particularly India 1, 2
• High-risk populations: Travelers visiting friends and relatives in endemic areas, immunocompromised individuals, those with chronic liver disease, and malnourished children 2, 4

Serious Complications (10-15% of patients)

Complications are more likely if illness duration exceeds 2 weeks and include life-threatening manifestations that significantly impact mortality. 1, 4

Major Complications

• Intestinal perforation: Most commonly occurs in the ileum or jejunum, typically in the third week if untreated 2, 5
• Gastrointestinal bleeding: Can range from occult to massive lower GI hemorrhage 2, 5
• Typhoid encephalopathy: Presents with confusion, seizures, or reduced Glasgow coma scale 1, 2
• Septic shock and ARDS: Rare but potentially fatal complications requiring intensive care 6
• Acute liver failure: Exceptionally uncommon but rapidly progressive and life-threatening 7
• Hepatitis and cholestasis: Can present with jaundice, acholic stools, and elevated liver enzymes 7

Diagnostic Approach

Gold Standard Testing

Blood culture is the gold standard diagnostic test and must be obtained in all suspected cases, with the highest yield (40-80% sensitivity) occurring within the first week of symptom onset. 1, 2, 4, 8

Diagnostic Algorithm

• First week: Blood cultures have highest sensitivity (40-80%) 1, 4
• After first week: Stool (35-65% sensitivity) and urine cultures (0-58% sensitivity) become positive 1, 4
• If antibiotics already given or negative blood cultures: Bone marrow culture has higher sensitivity than blood culture 1, 4, 8
• Adjunctive tests: Duodenal fluid cultures may be beneficial 8

Critical Diagnostic Pitfall

The Widal test lacks sensitivity and specificity and is NOT recommended for diagnosis—serologic evidence alone is insufficient, and isolation of the organism is required for confirmation. 1, 4, 8

Treatment Recommendations

Empiric Therapy Indications

If there is strong suspicion of enteric fever and the patient's clinical condition is unstable, treatment should be started empirically after blood culture collection but before results are available. 1

First-Line Empiric Antibiotic Selection

For patients returned from Asia, intravenous ceftriaxone is now preferred as first-line empiric therapy due to increasing fluoroquinolone resistance (>70% of isolates imported into the UK are fluoroquinolone-resistant). 1, 9

Treatment Algorithm by Geographic Origin

• Travel from Asia (South/Southeast Asia):

  • First-line: IV ceftriaxone (third-generation cephalosporin) 1, 9, 7
  • Alternative if sensitive: Azithromycin or meropenem for extensively drug-resistant (XDR) strains 5, 7

• Travel from sub-Saharan Africa:

  • Ciprofloxacin remains an alternative if fluoroquinolone resistance rates are lower 1

• Once susceptibility confirmed:

  • Switch to ciprofloxacin if sensitive 1, 10
  • If resistant, use azithromycin as oral follow-on agent 1

Treatment Duration

• Standard duration: 2 weeks of antibiotic therapy 1

Critical Antibiotic Susceptibility Testing Pitfall

When testing isolates for antibiotic sensitivity, ciprofloxacin disc testing alone is unreliable—only if the organism is also sensitive to nalidixic acid on disc testing should the isolate be considered truly sensitive to fluoroquinolones. 1, 4

Adjunctive Therapy for Severe Complications

• High-dose dexamethasone: May decrease mortality in patients with septic shock, delirium, obtundation, or coma, though controlled studies in children are lacking and most data are >30 years old from developing countries 6

Vaccination Considerations

Vaccination provides incomplete protection (50-70% efficacy) against typhoid fever and does NOT protect against paratyphoid fever—vaccinated patients can still develop disease. 1, 9

Key Clinical Pearls for Emergency Management

• Include typhoid in differential diagnosis for any febrile patient from Latin America or with recent travel to endemic countries, particularly South/Southeast Asia 3
• Do not delay blood culture collection if antibiotics are being considered 4
• Monitor for complications including signs of intestinal perforation (acute abdomen), GI bleeding (melena, hematochezia), septic shock (hypotension, tachycardia), or encephalopathy (altered mental status) 2, 4, 6, 5
• Rising multidrug resistance: Be aware of extensively drug-resistant (XDR) strains responding only to azithromycin and carbapenems, particularly from Pakistan and Southeast Asia 5, 7