Typhoid fever

Typhoid fever presents as fever that gradually increases over several days. Diarrhea occurs in about 50% of cases. Constipation was common in the pre-antibiotic era. Hepatomegaly and splenomegaly may be present. Bradycardia and rose spots are usually absent according to more recent case series.

CASES/YEAR
3,900 (US); 27,000,000 (Global)
CATEGORY
AGENT TYPE
Bacteria
OTHER NAMES
Enteric fever; Salmonella typhi infection; Paratyphoid fever (S. paratyphi infection);
ACUITY
Acute-Severe
INCUBATION
10-14 days (range of 5-21 days); [Harrison ID, p. 539]
INITIAL SYMPTOMS
Fever that gradually increases over several days; [CDC Travel] Fever, headache, relative bradycardia, splenomegaly, cough, rose spots, and diarrhea or constipation; [CCDM] Constipation early & diarrhea late in disease; [Merck Manual, 1593-4]
PRECAUTIONS
Standard; "Use Contact Precautions for diapered or incontinent persons for the duration of illness or to control institutional outbreaks." [CDC 2007 Guideline for Isolation Precautions] "Personal hygiene, particularly hand hygiene before and after all patient contacts, will minimize risk for transmitting enteric pathogens to patients." [ACIP, 2011]
COMMENTS
FINDINGS:
Initial symptoms are fever, myalgia, abdominal pain, headache, cough, and sore throat. Leukopenia and leukocytosis may occur, but the WBC count is usually normal. Diarrhea occurs in about 50% of cases. Constipation was common in the pre-antibiotic era. Hepatomegaly and splenomegaly may be present. Bradycardia and rose spots are usually absent according to more recent case series. [ID, p. 625-7] Rose spots are uncommon in uncomplicated disease. The spots are maculopapular, 2-3 mm in diameter, mainly on the trunk, blanch with pressure, and disappear in 3-5 days. Coagulation abnormalities are common in the laboratory but not clinically. [PPID, p. 1370-1] Rose spots are pink, blanching lesions that appear in crops on the chest and abdomen in about 10% of patients; they appear during the second week and resolve in 2 to 5 days. Uncommon symptoms include dysuria, nonproductive cough, and epistaxis. [Merck Manual, p. 1593] In patients with light skin color, rose spots are seen in about 25% of cases. Intestinal hemorrhage occurs in about 3% of cases in the developing world. Relapses occur in about 15%-20% of cases. [CCDM, p. 654] Typhoid fever and paratyphoid fever are "clinically indistinguishable." [Harrison ID, p. 539] "Rapid serologic tests have demonstrated only moderate accuracy to diagnose typhoid. Additionally, these are designed to detect Salmonella enterica serotype Typhi only." [CDC Travel, p. 623]

COMPLICATIONS:
Serious complications include intestinal hemorrhage and perforation that usually occur 2-3 weeks into the illness. [CDC Travel, p. 365] Possible complications include blood in stool, cholecystitis, intestinal perforation, pneumonia, osteomyelitis, endocarditis, meningitis, skin abscesses, glomerulitis, genitourinary tract infection, and shock. [Merck Manual, p. 1594] Intestinal hemorrhage and perforation are the major complications seen in patients with disease lasting more than 2 weeks. Endocarditis is rare. Meningitis occurs mainly in infants and children. Brain abscesses occur in adults, but rarely. Epididymitis has been reported. [ID, p. 625-7] Intestinal perforation occurs in 0.5% to 1% of patients. [Guerrant, p. 123] Other complications are septic shock, bleeding diathesis, hepatitis (with or without jaundice) and abscesses (brain, liver, and spleen). [Cohen, p. 1004t] Septic arthritis occurs rarely. CNS infections can cause extraocular palsies. [Guerrant, p. 123]

EPIDEMIOLOGY:
Patients and carriers are sources of infection by contaminating food and water with feces or urine. The hands of carriers are usually the source of milk contamination. Sewage-contaminated oysters and other shellfish are sources of infection. Other contaminated foods have included raw fruit and vegetables and frozen fruit. "About 10% of untreated typhoid fever patients discharge bacilli for 3 months after onset of symptoms. . . . International travelers to endemic areas are also at risk, as are individuals with gastric achlorhydria." [CCDM, p. 656] There are about 350 cases/year (culture-confirmed) in the USA and an estimated 26 million cases and 215,000 deaths per year worldwide. [CDC Travel, p. 364] Flies may carry bacteria from feces to food. Transmission by the fecal-oral route may occur among children playing and among adults through sexual contact. [Merck Manual, p. 1260] Case fatality rate is <1% in industrialized countries, but is 15-20% without antibiotic treatment. [Cecil, p. 1943]

PREVENTION:
"Both vaccines protect 50%-80% of recipients. To maintain immunity, booster doses of the oral vaccine are required every 5 years, and booster doses of the injected vaccine are required every 2 years. . . . Live-attenuated Ty21a vaccine should not be used among immunocompromised. . . . Microbiologists and others who work frequently with S. Typhi should be vaccinated with either of the two licensed and available vaccines." [ACIP, 2011] ACIP recommends the vaccine for travelers to areas with increased risk of Typhi. [CDC Travel, p. 366]
DIAGNOSTIC
Culture of blood (early), urine and feces (after first week) and bone marrow (most sensitive); Serology (Widal) not useful; [CCDM] Serology not sens & not spec.; [ABX Guide] Blood cultures are 40% to 80% sensitive. [PPID, p. 1372]
SCOPE
Risk is greatest for travelers to southern Asia (80% of reported cases in US travelers); Other high-risk areas are Africa & Southeast Asia; At lower risk are the Caribbean, East Asia & South America; [CDC Travel]
SIGNS & SYMPTOMS
  • >arthralgia
  • >fatigue, weakness
  • >fever
  • >myalgia
  • >relative bradycardia
  • E epistaxis
  • E pharyngitis
  • G abdominal pain
  • G blood in stool
  • G constipation
  • G diarrhea
  • G fecal leukocytes
  • G hepatomegaly
  • G jaundice
  • G liver function test, abnormal
  • G nausea, vomiting
  • H anemia
  • H hemolysis
  • H leukocytosis
  • H leukopenia
  • H lymphadenopathy
  • H splenomegaly
  • H thrombocytopenia
  • N confusion, delirium
  • N headache
  • N lethargy
  • N seizure
  • O conjunctivitis, acute
  • R cough
  • S papules or plaques
  • S pustule
  • S rash (exanthem)
  • U pyuria
  • *acute renal failure
  • *ARDS
  • *arthritis
  • *bleeding tendency
  • *brain abscess or lesion
  • *endocarditis
  • *epididymo-orchitis
  • *glomerulonephritis
  • *hepatitis
  • *meningitis
  • *myocarditis
  • *osteomyelitis
  • *pancreatitis
  • *paralysis
  • *parotitis
  • *pericarditis
  • *peripheral neuropathy
  • *pneumonia
  • *pneumonitis
  • *rhabdomyolysis
  • *sepsis
  • *shock
  • *stupor, coma
  • *weight loss
ANTIMICROBIC

Yes

VACCINE

Yes

ENTRY
Ingestion, Sexual Contact
SOURCE
Person-to-Person, Human Fecal-Oral, Eating Contaminated Food, Eating Contaminated or Infected Meat, Eating Infected or Toxin-Containing Fish, Eating Contaminated Mollusks or Crustacean, Eating Unpasteurized Milk or Cheese, Eating Contaminated Produce, Waterborne (Ingesting, Inhaling, or Swimming)
RESERVOIR
Cattle, Goats and Sheep, Fish and Shellfish, Human
RISK FACTORS
  • Care for patients (fecal-oral pathogens)
  • Consume unpasteurized milk/cheese
  • Eat undercooked meat or fish
  • Fail to complete immunizations
  • Ingest infectious agents in food/water
  • Travel to endemic area
  • Victim--water/food release
  • Work in a medical or research lab
REFERENCES FOR CASES/YEAR
1. (US) Published in MMWR 2011= 390; Use correction factor of 10 for reported diseases: 390 X 10 = 3900;
2. (Global) About 27 million cases of typhoid fever and 210,000 deaths/year; [CCDM, p. 655]