What are the clinical manifestations and treatment options for typhoid fever?

Clinical Manifestations of Typhoid Fever

Typhoid fever typically presents with sustained high-grade fever (present in 97-100% of cases), accompanied by malaise, headache, abdominal pain, and either constipation or diarrhea, with an insidious onset over 3-7 days following a 7-18 day incubation period. 1, 2, 3

Cardinal Clinical Features

Constitutional Symptoms

• Fever is the most consistent finding, occurring in 97-100% of patients, characteristically high-grade and sustained rather than intermittent 1, 3
• Malaise and myalgia are prominent constitutional symptoms that accompany the fever 1, 2
• Headache occurs in approximately 29-33% of cases and can be severe 1, 3, 4
• Anorexia is commonly reported 1

Gastrointestinal Manifestations

• Abdominal pain presents in 38-41% of patients 1, 3, 4
• Diarrhea occurs in 35-36% of cases, though constipation may also be present 1, 3, 4
• Vomiting can occur as part of the clinical presentation 1
• Febrile gastroenteritis is a particularly frequent manifestation in pediatric patients (52% of children) 3

Other Clinical Signs

• Relative bradycardia (pulse-temperature dissociation) may be present, though not reliably 1
• Nonproductive cough can occur 1
• The classic "step-ladder" fever pattern is not reliably present in all cases and should not be used to rule out typhoid 1

Timeline and Disease Progression

Incubation and Onset

• Incubation period: 7-18 days (range 3-60 days) 1, 2
• Onset pattern: Insidious rather than abrupt, with gradual fever development over 3-7 days 1, 2
• Average symptom duration before diagnosis is approximately 10 days 3

Complications (If Untreated)

• Intestinal perforation typically occurs in the third week of disease, most commonly in the ileum or jejunum 1
• Gastrointestinal bleeding can range from minor to massive hemorrhage requiring endoscopic intervention 1, 5
• Encephalopathy is a rare but serious complication 1
• Septic shock can develop in severe cases 1

Laboratory and Diagnostic Findings

Hematologic Changes

• Leucopenia is not a consistently helpful diagnostic marker 3
• Lymphopenia and thrombocytopenia may be present and can help differentiate from other febrile illnesses 6

Microbiologic Diagnosis

• Blood culture is the gold standard, with highest yield in the first week of symptoms 1
• Bone marrow culture remains a reference standard method despite low sensitivity of blood culture 2
• The Widal test alone is insufficient for diagnosis and should not be relied upon 1

High-Risk Populations

• Travelers from endemic areas, particularly South and Southeast Asia (>100 cases per 100,000 person-years) 1, 4
• Immunocompromised individuals are at higher risk for severe disease 1
• Patients with chronic liver disease have increased susceptibility 1
• Malnourished children are more vulnerable to severe manifestations 1

Critical Clinical Pearls

• Absence of fever at presentation does not rule out typhoid if there is a history of fever 1
• Symptoms can be altered by previous antimicrobial use, making diagnosis more challenging 2
• In developed countries, typhoid is mostly seen in returning travelers or associated with foodborne outbreaks 1
• Life-threatening complications can arise in the second week of untreated illness 2

Treatment Considerations

Empiric antibiotic therapy should be initiated after culture collection in patients with clinical features of sepsis, severe illness with documented fever ≥38.5°C in travelers from endemic areas, or signs of septic shock or encephalopathy. 1

Antibiotic Options

• Azithromycin is a recommended first-line option 1, 2
• Ciprofloxacin is effective but should be avoided for cases originating from South Asia due to high resistance rates (46% resistance reported) 1, 7, 2, 4
• Third-generation cephalosporin (ceftriaxone) for severe cases or when fluoroquinolone resistance is suspected (only 0.6-2% resistance) 1, 2, 3, 4
• Treatment choice must be guided by local resistance patterns 1, 2

Critical Pitfalls to Avoid

• Do not miss complications such as intestinal perforation, gastrointestinal bleeding, or septic shock 1
• Do not delay empiric treatment in severely ill patients while awaiting culture results 1
• Do not use ciprofloxacin empirically for patients with travel history to Pakistan or South Asia due to widespread resistance 2, 4