Enteric Fever (Typhoid Fever)

Essentials of Diagnosis

• Gradual onset of headache, sore throat, cough, and either diarrhea or constipation

• Rose spots, relative bradycardia, splenomegaly, and abdominal distention and tenderness

• Leukopenia; blood, stool, and urine cultures positive for Salmonella

General Considerations

• Can be caused by any Salmonella species, including S typhi (typhoid fever) and non-typhoidal strains, especially S paratyphi subtype A in the United States

• Infection begins when organisms breach the mucosal epithelium of the intestines

  • Having crossed the epithelial barrier, organisms invade and replicate in macrophages in Peyer patches, mesenteric lymph nodes, and the spleen

  • Serotypes other than typhi usually do not cause invasive disease, presumably because they lack the necessary human-specific virulence factors

  • Bacteremia occurs, and the infection then localizes principally in the lymphoid tissue of the small intestine

  • Peyer patches become inflamed and may ulcerate, with involvement greatest during the third week of disease

  • The organism may disseminate to the lungs, gallbladder, kidneys, or central nervous system

• May have a long incubation period (6–30 days)

Symptoms and Signs

Prodromal stage

• Increasing malaise, headache, cough, and sore throat

• Abdominal pain and constipation are often present while the fever ascends in a stepwise fashion

• During the early prodrome, physical findings are few

• There may be marked constipation

Later stage

• After about 7–10 days, the fever reaches a plateau and the patient is much more ill, appearing exhausted and often prostrated

• Marked constipation may develop into "pea soup" diarrhea

• Splenomegaly, abdominal distention and tenderness, relative bradycardia, dicrotic pulse, and occasionally meningismus appear

• The rash (rose spots) commonly appears during the second week of disease

  • The individual spot, found principally on the trunk, is a pink papule 2–3 mm in diameter that fades on pressure

  • It disappears in 3–4 days

Differential Diagnosis

• Brucellosis

• Tuberculosis

• Infective endocarditis

• Q fever and other rickettsial infections

• Other causes of acute diarrhea

• Viral hepatitis

• Lymphoma

• Adult Still disease

• Malaria

Laboratory Tests

• Best diagnosed by isolation of the organism from blood culture, which is positive in the first week of illness in 80% of patients who have not taken antibiotics

• Cultures of bone marrow occasionally are positive when blood cultures are not

• Stool culture is not reliable because it may be positive in gastroenteritis without typhoid fever

Medications

• Ciprofloxacin, 500 mg twice daily orally or 400 mg twice daily intravenously for 5–7 days (10–14 days for severe typhoid)

• Azithromycin, 500 mg once daily orally for 7 days (for uncomplicated disease; not recommended for severe disease)

• Ceftriaxone, 2 g once daily intravenously for 10–14 days for severe typhoid

• Dexamethasone

  • 3 mg/kg over 30 min intravenously, then 1 mg/kg every 6 hours for eight doses

  • Reduces mortality in patients with severe typhoid fever (eg, those with delirium, coma, shock)

• Resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole has spread globally

Follow-Up

• Follow-up examination, with blood cultures for fever, since relapse can occur

Complications

• Complications occur in about 30% of untreated cases and account for 75% of all deaths

• Intestinal hemorrhage, manifested by a sudden drop in temperature and signs of shock followed by dark or fresh blood in the stool, or intestinal perforation, accompanied by abdominal pain and tenderness, is most likely to occur during the third week

Prevention

• Immunization is not always effective but should be provided for household contacts of a typhoid carrier, for travelers to endemic areas, and during epidemic outbreaks

• A multiple-dose oral vaccine and a single-dose parenteral vaccine are available

• Adequate waste disposal and protection of food and water supplies from contamination are important public health measures to prevent salmonellosis

• Carriers must not be permitted to work as food handlers

Prognosis

• Mortality rate is about 2% in treated cases

• With complications, the prognosis is poor

• Relapses occur in 5–10% of cases; these are treated the same as primary infection

• A residual carrier state frequently persists in spite of therapy

When to Refer

• Report to the public health department to trace contacts or carriers

• Refer early to an infectious disease specialist

When to Admit

• For intravenous antibiotics or supportive care