How Typhoid Develops in Humans

Typhoid Fever, also known as enteric fever is a potentially fatal multisystemic illness caused by Salmonella enterica subspecies called Salmonella typhi and Salmonella paratyphi (A, B, and C). These etiologic agents of typhoid fever have no known host except humans and are transmitted through feco-oral route, most commonly, food or water borne transmission which results from fecal contamination by I’ll or asymptomatic chronic carriers. Healthcare workers may occasionally acquire typhoid fever after exposure to infected patients or during the processing of infected clinical specimens and culture.

Host Risk Factors for Developing Typhoid Fever 

The development of severe disease which occurs in 10% to 15% of patients depend on the host factors, strain virulence of the bacteria, and the choice if antibiotics used for treatment. Some of the host factors include

  • Conditions that reduce stomach acidity like use of antacid, H. Pylori infection, and achlohydric disease
  • Conditions that decrease intestinal integrity like inflammatory bowel disease, previous gastrointestinal surgery and alteration of intestinal flora by antibiotics use
  • Immuno suppression like HIV
  • Less than 1 year of age (infants)
  • Previous exposure to typhoid fever
  • Vaccination against typhoid fever

Classic symptoms of typhoid include fever, malaise, diffuse abdominal pain, and constipation. Neurological manifestations can also occur which include meningitis, Guillain Barrè syndrome, neuritis, and neuropsychiatric symptoms described as muttering delirium or coma vigil (in which patient picks at bedclothes or imaginary objects).

Gastrointestinal bleeding and intestinal perforation mostly occur in the third and fourth week of the illness as a result of hyperplasia, ulceration and necrosis of the ileocecal payer’s patches which is the initial site of Salmonella growth in the intestines.

How Typhoid Fever Develops in Humans

Humans may acquire Salmonella species after ingestion of contaminated food or water. This micro organisms then find their way through the gastrointestinal tract as the food is being digested.

Normally, all pathogenic organisms including Salmonella species that are found in the gastrointestinal tract are destroyed by gastric acid in the stomach or engulfed by phagocytic cells in the gastrointestinal tract which then presents them through the mucosa to the macrophages and epithelial cells of the gastrointestinal tract. These cells attract T-helper cells and neutrophils with interleukin 8 which cause inflammation and subsequent suppressing of the infection.

Ingested Salmonella species that survive exposure to gastric acid and the phagocytes of the gastrointestinal tract penetrate the small intestinal epithelium, enter the lymphoid tissues of the payer’s patches (where it multiplies)  and disseminate to the blood stream from there through the lymphatic system. The organism is able to penetrate the bowel mucosa either  through an antigen called M-cell or through direct penetration into the epithelial cells (this process is called bacteria-mediated endocytosis).

The Salmonella is able to survive antimicrobial attack by the macrophages through the altering of its outer membrane surface proteins (which are what trigger macrophages to act in the first place). This altered bacteria membrane surface can resist antimicrobial activities in the body by altering the host cell signalling mechanism.

Once the Salmonella species is in the blood stream, they are able to spread throughout the entire body via the lymphatics and reticuloendothelial tissues in the liver, spleen, lymph nodes and bone marrows. At this stage of incubation, there are still no signs and symptoms of the infection yet.

Subsequent signs and symptoms of typhoid like fever and abdominal pains results from the secretion of cytokines by macrophages in the blood in response to the recognised bacteria Now present in the blood stream and body tissues.

The Salmonella can cause destruction of the tissues of the body where it is present, which is what gives rise to other signs and symptoms as well as complications of the disease.

Clinical Detection of Typhoid in Humans 


Because the clinical presentation of typhoid fever is relatively non-specific, differential diagnoses needs to be considered in any febrile person. This is where a comprehensive history taking and physical examination of the presenting symptoms is crucial to rule other possible causes of the clinical presentation.

Other infections that can mimic typhoid fever include

  • Malaria
  • Prodrome of viral hepatitis
  • Yellow fever
  • Quartan fever
  • Brucellosis
  • Dengue fever
  • Rickettsial infection
  • Leptospirosis
  • Bebesiosis
  • Amoebic liver abscess
  • Schistosomiasis
  • Tuberculosis
  • Acute HIV infection

Available Laboratory Test 

  • Blood cultures to isolate Salmonella typhi and Salmonella paratyphi.
  • Serologic tests like widal test which is non-specific to determine the titre values of host and flagella antibodies.
  • Newer ELISA kits like typhidot test which detects immunoglobulin M antibodies to the outer membrane proteins of Salmonella species.
  • Imaging studies like ultrasound scan although not used for routine diagnosis can be helpful in identifying uncommon complications like intestinal perforation or splenic abscess if suspected.

Typhoid fever can be effectively treated with appropriate antibiotics treatment and prevention of the disease is possible through vaccination and improved environmental sanitation and personal hygiene.