What is the etiology and clinical manifestation of typhoid fever?

Typhoid Fever: Etiology and Clinical Manifestation

Etiology

Typhoid fever is a systemic infectious disease caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi), transmitted through the fecal-oral route via contaminated food and water. 1, 2

• The bacterium is acquired by ingestion of contaminated food and water, with humans serving as the only reservoir 3, 4
• Transmission occurs primarily in areas with inadequate sanitation and poor hygiene practices 2
• The incubation period ranges from 7-18 days (with extremes of 3-60 days) after exposure 5
• In the United States, 79% of cases are travel-related, with the highest risk among travelers to South and Southeast Asia, particularly the Indian subcontinent 6, 5
• Laboratory workers handling S. Typhi cultures represent an occupational risk group 6

Key Epidemiologic Context

• The disease affects 11-21 million people annually worldwide, causing 0.12-0.16 million deaths 3
• In the U.S., an average of 237 cases are reported annually, with a median patient age of 22 years 6
• Paratyphoid fever (caused by S. Paratyphi) presents similarly but is typically milder, with no available vaccine 6, 1

Clinical Manifestations

Classic Presentation

The hallmark clinical features include sustained high-grade fever (present in 97-100% of cases), headache, malaise, and gastrointestinal symptoms, though the onset is typically insidious over 3-7 days rather than abrupt. 7, 5

Constitutional Symptoms

• Fever: High-grade and sustained, present in 97-100% of cases; the classic "step-ladder" pattern is not reliably present 7, 5
• Headache: A prominent early symptom 7, 5
• Malaise and myalgia: Common constitutional features 5
• Anorexia: Frequently reported 5
• Relative bradycardia: May occur despite high fever 5

Gastrointestinal Manifestations

• Abdominal pain: Diffuse tenderness is common 8
• Vomiting: Occurs frequently, particularly in early disease 7, 5
• Bowel pattern changes: Either constipation or diarrhea may occur 5
• Nonproductive cough: Can be present 5

Disease Progression and Complications

If untreated, typhoid fever can progress to life-threatening complications, typically in the third week of illness. 5

Severe Complications

• Intestinal perforation: Most commonly occurs in the ileum or jejunum during the third week if untreated 5
• Gastrointestinal bleeding: A serious complication requiring urgent intervention 5
• Encephalopathy: Develops in 10-15% of patients, manifesting as altered mental status 7, 5
• Acute liver failure: Rare but can present with hepatocellular and cholestatic patterns, elevated ammonia, and rapid clinical deterioration 8
• Septic shock: Can occur in severe cases 5

Extraintestinal Manifestations

• Hepatobiliary involvement: Hepatitis, cholestasis, and rarely acute liver failure with jaundice and acholic stools 8
• Cardiovascular complications: Can occur in severe disease 3
• Pulmonary manifestations: Respiratory involvement may develop 3
• Central nervous system complications: Beyond encephalopathy, other neurologic sequelae are possible 3
• Transient immunosuppression: CD4+ lymphopenia can occur, potentially leading to opportunistic infections like oropharyngeal candidiasis 4

Atypical Presentations

Many mild and atypical infections occur, and the absence of fever at initial presentation does not rule out typhoid fever if there is a history of recent fever. 5

• Immunocompromised patients, those with chronic liver disease, and malnourished children may present with more severe disease 5
• Returning travelers may present early in the disease course with nonspecific symptoms 5

Laboratory Findings

• Leukocytosis or leukopenia: Variable white blood cell counts 8
• Lymphopenia and thrombocytopenia: Can help differentiate from other febrile illnesses 9
• Elevated liver enzymes: Mixed hepatocellular and cholestatic patterns may occur 8
• Blood culture: Gold standard for diagnosis, with highest yield in the first week of symptoms 5

Critical Clinical Pearls

• The typical onset is insidious over 3-7 days, not abrupt 5
• Fever may be absent at presentation despite a clear history of fever 5
• Always consider malaria first in febrile travelers from tropical areas, as it can be rapidly fatal 9
• Dengue fever can present identically and co-exists in the same endemic regions 9