Typhoid Fever

Typhoid fever is a systemic infection caused by Salmonella enterica serotype Typhi (and a milder, related illness, paratyphoid fever, caused by Salmonella Paratyphi), transmitted via the fecal oral route through contaminated food or water.

It remains a significant cause of febrile illness in many low and middle income settings with limited access to safe water and sanitation.

Following ingestion, the organism invades the intestinal mucosa, is taken up by macrophages, and disseminates systemically via the lymphatic and reticuloendothelial system, ultimately seeding the gallbladder, liver, spleen, and Peyer's patches of the terminal ileum, the latter accounting for the classic intestinal complications of later disease.

The illness classically evolves over several weeks if untreated, though this classic staged progression is less reliably seen with prompt antibiotic treatment.

• Week 1: a stepwise, progressively rising fever, headache, malaise, and abdominal discomfort, with relative bradycardia (a pulse rate lower than would be expected for the degree of fever) sometimes noted, though this sign is inconsistent.

• Week 2: sustained high fever, abdominal pain and distension, hepatosplenomegaly, and, in a minority of patients, rose spots, faint, blanching, salmon colored macules typically on the trunk, though these are often subtle and easily missed, particularly on darker skin.

• Week 3: the period of highest risk for major complications, including intestinal hemorrhage and perforation from ulceration of the Peyer's patches (presenting with sudden deterioration, peritonism, and shock), and encephalopathy ("typhoid state," with confusion, obtundation, or coma).

Other recognized features include constipation (perhaps more classically taught, though diarrhea is at least as common in practice), a coated tongue, and, less commonly, myocarditis and cholecystitis.

A chronic carrier state, in which the organism persists asymptomatically in the gallbladder (particularly in the presence of gallstones) with ongoing intermittent fecal shedding, is an important public health consideration, since carriers can transmit infection despite having no active symptoms themselves.

• Blood culture is the mainstay of diagnosis, with sensitivity highest in the first week of illness before antibiotic treatment; multiple sets improve diagnostic yield.
• Bone marrow culture offers higher sensitivity than blood culture, particularly later in the illness or after antibiotics have already been started, though it is more invasive and reserved for cases where blood culture is negative but suspicion remains high.
• Stool and urine culture may be positive, particularly later in the illness, and are useful for identifying chronic carriers.
• Widal serology (assessing antibody response to Salmonella O and H antigens) is widely available but has limited sensitivity and specificity, with significant potential for both false positive and false negative results, and should be interpreted cautiously and ideally alongside culture rather than relied upon in isolation.
• FBC often shows a relative or absolute leukopenia (in contrast to many other bacterial infections, which more typically cause leukocytosis), alongside anemia and, sometimes, thrombocytopenia in more severe disease.
• LFTs are frequently mildly deranged, reflecting hepatic involvement.

Differentials include malaria (essential to actively exclude in any febrile returned traveler or resident of an endemic area), other causes of prolonged fever including tuberculosis and brucellosis, rickettsial disease, and other causes of an acute abdomen where intestinal perforation is suspected.

• Antibiotic choice is increasingly guided by local resistance patterns, given the substantial and growing global burden of multidrug resistant and, in some regions, extensively drug resistant typhoid.
• Third generation cephalosporins (ceftriaxone) or azithromycin are commonly used first line options in many settings given rising fluoroquinolone resistance, with fluoroquinolones (ciprofloxacin) remaining effective in areas without significant resistance.
• Treatment duration is typically around 7 to 14 days depending on the specific agent used and clinical response, with a longer course generally required for more severe or complicated disease.
• Intestinal perforation, a surgical emergency, requires urgent surgical intervention alongside broad spectrum antibiotics covering the resulting mixed enteric and anaerobic peritoneal contamination, following the same general principles as any perforated viscus.
• Encephalopathy or profound toxemia (typhoid state) may benefit from adjunctive high dose corticosteroids alongside antibiotics, based on trial evidence in this specific severe subgroup, though this is reserved for genuinely severe disease rather than used routinely.
• Supportive care, including careful attention to hydration and nutrition, is important throughout the illness course.
• Chronic carriers require a prolonged antibiotic course, and, where gallstones are present and thought to be perpetuating the carrier state, cholecystectomy may be required to achieve eradication.
• Prevention includes safe water and food hygiene, and typhoid vaccination (available as both injectable and oral live attenuated formulations), recommended for travelers to endemic areas and, in some settings, incorporated into routine immunization programs for at risk populations.

Referral: infectious disease input for treatment failure, suspected multidrug resistant infection, or complicated disease; surgery urgently for suspected intestinal perforation.