• Clinical science

Typhoid fever, Paratyphoid fever (Enteric fever)

Abstract

Typhoid and paratyphoid fever are infectious diseases caused by the bacteria Salmonella typhi and Salmonella paratyphi. Transmission occurs via the fecal-oral route. The incubation period is typically 7–21 days, although it may be as long as 30 days. Typhoid and paratyphoid fever classically have three clinical stages. In the first week of symptoms, body temperature rises gradually and relative bradycardia as well as diarrhea or constipation may occur. The second week of illness is characterized by persistent fever, rose-colored spots on the abdomen, nonspecific abdominal pain, and profuse diarrhea. During the third week, complications such as hepatosplenomegaly, intestinal bleeding, and/or perforation with secondary bacteremia and peritonitis may occur. Symptoms begin to subside in the fourth week. Pathogen detection in blood and stool cultures confirms the diagnosis. The treatment of choice includes fluoroquinolone antibiotics such as ciprofloxacin. Up to 6% of patients become chronic carriers after symptoms have resolved.

Epidemiology

  • Globally, there are an estimated ∼ 22 million cases occur per year.
    • Mainly in underdeveloped areas with poor sanitation
    • In the United States, approx. 300 culture-confirmed cases of typhoid fever and 100 cases of paratyphoid fever are reported annually, mostly in individuals who have traveled to endemic regions.

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Humans are the main reservoir for Salmonella typhi!

Salmonella have flagella, which allow them to swim like a salmon. References:[3]

Pathophysiology

Lifecycle

  1. Oral uptake of pathogen
  2. Distal ileum: migration into the Peyer patches
  3. Infection of macrophages → nonspecific symptoms
  4. Spread from macrophages to the bloodstream: septicemia → systemic disease
  5. Migrates back to intestine → excretion in feces

References:[3][4]

Clinical features

General

  • Incubation period: 5–30 days (most commonly 7–14 days)
  • If left untreated, three different disease stages, each lasting a week, classically occur.
  • After 3 weeks of disease: slow regression of symptoms; patients may become chronic Salmonella carriers (see “complications” below)

Typhoid fever is a systemic disease; it is not limited to the gastrointestinal system!

Typhoid fever must always be considered in the case of persistent fever of unknown origin and a history of travel to an endemic region!

Progression of illness

Week 1

Week 2

Week 3

  • Clinical features of week 2
  • Additional possible complications include:

References:[3][1]

Diagnostics

Blood culture is the most important diagnostic tool at disease onset, as stool cultures are often negative despite active infection!

References:[3][1]

Treatment

References:[5]

Complications

Chronic Salmonella carrier

  • Definition: positive stool cultures 12 months after overcoming the disease
  • Incidence: up to 6% of the patients become chronic carriers
  • Presentation: typically asymptomatic
  • Treatment: fluoroquinolones (e.g., ciprofloxacin) administered for at least 1 month
  • Chronic carriers are not allowed to work in the food industry.
  • Increased risk for cholangiocarcinoma (bile duct cancer)

References:[5]

We list the most important complications. The selection is not exhaustive.

Prevention

Food and water

Vaccination

  • Indication: The WHO recommends typhoid fever vaccination to those traveling to high-risk areas (East and Southeast Asia, Latin America, Africa).
  • Administration: A parenteral, inactivated vaccine and an oral, live vaccine are available for active immunization, and both provide similar levels of protection.
    • Inactivated vaccine: one intramuscular injection containing Vi polysaccharide, ideally administered at least 10 days before traveling
    • Live-attenuated vaccine: oral ingestion of capsules containing live attenuated S. typhi; ideally administered at least 10 days before traveling

Overcoming an infection with Salmonella typhi/paratyphi does not confer lifelong immunity!
Vaccination is not entirely protective!

Reporting requirements

Legislation varies from state to state. However, in general, physicians must report cases of typhoid/paratyphoid fever to their state's department of health.

References:[5][6][7]