Typhoid Fever

Typhoid fever, also known simply as typhoid, is a disease caused by the bacterium Salmonella enterica serotype Typhi, also known as Salmonella typhi. The disease manifests with a range of symptoms, from mild to severe, typically beginning six to 30 days after exposure.

Typhoid fever is most common in less developed regions with inadequate water sanitation and is transmitted through the ingestion of food or water contaminated with the faeces of an infected person.

Humans are the exclusive carriers of S. Typhi, and the disease is particularly prevalent in areas such as India, sub-Saharan Africa, and Southeast Asia.

Causative agent: Salmonella enterica serological variant Typhi (shown under a microscope with flagellar stain)

Signs and Symptoms

Typhoid fever typically progresses through three distinct stages if left untreated, each lasting about a week. In the first week, symptoms include a gradually increasing fever, relative bradycardia (Faget sign), malaise, headache, and cough. A quarter of cases may present with epistaxis (bloody nose) and abdominal pain.

In the second week, the fever reaches a plateau around 40°C (104°F), with bradycardia and delirium. Rose spots may appear on the lower chest and abdomen, and the spleen and liver often enlarge and become tender.

The third week can bring severe complications such as intestinal haemorrhage or perforation, dehydration, respiratory diseases, and neuropsychiatric symptoms. The fever remains high, and the patient may become delirious.

A 1939 conceptual illustration showing various ways that typhoid bacteria can contaminate a water well (centre)

Diagnosis

Diagnosis can be made through blood, bone marrow, or stool cultures, and with the Widal test, which detects antibodies against Salmonella antigens. Rapid diagnostic tests like Tubex, Typhidot, and Test-It have shown moderate accuracy. The Widal test is prone to false positives and negatives and can be time-consuming, while rapid tests offer quicker results but may not be quantitative.

Widal test card

Prevention

Sanitation and hygiene are very important in preventing typhoid fever. Vaccination is also an essential preventive measure, particularly for travellers to endemic regions. Two vaccines are widely used: the live, oral Ty21a vaccine and the injectable typhoid polysaccharide vaccine (Vi antigen vaccine). Both vaccines are effective and recommended for people travelling to areas where typhoid is prevalent.

Doctor administering a typhoid vaccination at a school in San Augustine County, Texas, 1943

Treatment

Oral Rehydration Therapy

Oral rehydration therapy is a simple yet effective method to prevent deaths from dehydration, a common complication of typhoid fever.

Antibiotics

Antibiotics are the primary treatment for typhoid fever, with options including azithromycin, fluoroquinolones (e.g., ciprofloxacin), and third-generation cephalosporins (e.g., ceftriaxone). However, antibiotic resistance is an increasing challenge, particularly in regions such as South Asia and Southeast Asia. Multidrug-resistant typhoid is treated with alternative antibiotics like azithromycin and ceftriaxone.

Surgery

In severe cases of intestinal perforation, surgery may be required. The preferred surgical method is the simple closure of the perforation with peritoneal drainage. In cases of multiple perforations, small-bowel resection may be necessary.

History

The understanding and treatment of typhoid fever have evolved significantly over the centuries. Early descriptions of the disease date back to the Plague of Athens, and significant milestones include the discovery of the causative bacterium by Karl Joseph Eberth in 1880 and the development of the first effective typhoid vaccine by British bacteriologist Almroth Edward Wright in 1896. The introduction of antibiotics in the mid-20th century revolutionised the treatment of typhoid fever, although the rise of antibiotic resistance remains a significant concern.

Mary Mallon ("Typhoid Mary") in a hospital bed (foreground): She was forcibly quarantined as a carrier of typhoid fever in 1907 for three years and then again from 1915 until her death in 1938.

Epidemiology

Typhoid fever remains a significant global health issue, with the highest incidence in developing countries. Efforts to combat typhoid include improving water sanitation, promoting hygiene, and widespread vaccination, especially in endemic regions. The disease's historical impact and ongoing challenges highlight the importance of continued public health initiatives and research to prevent and treat typhoid fever effectively.

Typhoid fever incidence; most common in Asia, Africa, Central and South America

Self-assessment MCQs (single best answer)

What bacterium causes typhoid fever?

score 0 / 1. running total: 0 / 0

How is typhoid fever most commonly transmitted?

score 0 / 1. running total: 0 / 0

Which of the following is a common symptom in the first week of typhoid fever?

score 0 / 1. running total: 0 / 0

What is the preferred initial treatment for typhoid fever?

score 0 / 1. running total: 0 / 0

Which diagnostic test for typhoid fever detects antibodies against Salmonella antigens?

score 0 / 1. running total: 0 / 0

What is a major complication that can occur in the third week of untreated typhoid fever?

score 0 / 1. running total: 0 / 0

Which vaccine for typhoid fever is administered orally?

score 0 / 1. running total: 0 / 0

What historical figure is known for being a carrier of typhoid fever?

score 0 / 1. running total: 0 / 0

Which region has the highest incidence of typhoid fever?

score 0 / 1. running total: 0 / 0

What is a common preventive measure against typhoid fever, especially for travellers to endemic areas?

score 0 / 1. running total: 0 / 0