Typhoid fever is a serious bacterial infection caused by Salmonella Typhi, a bacterium spread through contaminated water and food. It affects an estimated 9 million people worldwide each year and kills about 110,000, with the heaviest burden in parts of South Asia, Southeast Asia, and sub-Saharan Africa. Unlike common food poisoning, typhoid invades the bloodstream and can affect multiple organs if untreated.
How the Infection Spreads Through the Body
Salmonella Typhi enters your body through your mouth, typically from drinking contaminated water or eating food prepared with it. Once the bacteria reach your small intestine, they attach to the cells lining the gut wall and essentially trick those cells into absorbing them. The bacteria force the cell membrane to ruffle and fold inward, pulling the organisms inside like a Trojan horse.
From there, the bacteria multiply inside the gut lining and then travel to nearby lymph nodes. Within days, they spill into the bloodstream and spread throughout the body, settling in the liver, spleen, and bone marrow. This is what sets typhoid apart from ordinary Salmonella food poisoning, which typically stays in the gut. Typhoid becomes a whole-body infection, which is why the symptoms are so much more severe and last so much longer.
Symptoms and How They Progress
After exposure, there’s a quiet incubation period of 10 to 14 days (sometimes as short as 6 or as long as 30) before symptoms appear. The illness comes on gradually, not all at once.
The first sign is usually a fever that climbs in a staircase pattern, rising a little higher each day until it reaches 38 to 40°C (about 100 to 104°F) by the third or fourth day. Along with the fever, most people experience fatigue, headache, and loss of appetite. Abdominal symptoms are common too: pain, bloating, and either constipation or diarrhea. One unusual feature is that your heart rate may not speed up the way it normally would with a high fever, a quirk doctors call relative bradycardia.
Some patients develop “rose spots,” small pinkish-red spots 2 to 4 millimeters across, mostly on the chest and abdomen. These appear in fewer than one in four cases, so their absence doesn’t rule out typhoid. Without treatment, fever can persist for weeks, and the risk of dangerous complications rises significantly.
Serious Complications
The most common complication is delirium or confusion, reported in roughly 27% of typhoid cases in a recent global analysis published in The Lancet Infectious Diseases. This reflects how deeply the infection affects the whole body, not just the gut.
The most feared complication is intestinal perforation, where the infection erodes through the wall of the small intestine. This occurs in about 1.7% of cases, but it carries a fatality rate of around 16%. When the intestine perforates, bacteria spill into the abdominal cavity, causing a surgical emergency. This is why early treatment matters so much: antibiotics dramatically reduce the chance of reaching this stage.
How Typhoid Is Diagnosed
Blood culture is the primary diagnostic tool. A sample of your blood is placed in a growth medium to see if Salmonella Typhi grows from it. This confirms the diagnosis and also allows doctors to test which antibiotics the bacteria respond to, which is increasingly important given rising drug resistance.
Bone marrow cultures are more sensitive, picking up the bacteria about 80% of the time and remaining accurate even if you’ve already started antibiotics. However, they’re more invasive and not routinely used unless blood cultures come back negative in a patient who still looks like they have typhoid. The Widal test, an older blood test that looks for antibodies, is no longer recommended because it produces too many false positives.
Treatment and Drug Resistance
Typhoid fever is treated with antibiotics, and most people improve within a few days of starting the right one. The challenge is that the “right one” has become a moving target. An extensively drug-resistant (XDR) strain first identified in Pakistan in 2016 has changed the treatment landscape. This strain resists five commonly used antibiotics: ampicillin, chloramphenicol, ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftriaxone. Among samples from people infected with this strain in the United States, 89% were resistant to all five drugs.
This XDR strain has been found in travelers returning from Pakistan and neighboring countries, and even in people who never left the United States, suggesting local transmission. It means doctors now need to confirm which drugs the bacteria are susceptible to before committing to a treatment plan, rather than relying on a standard prescription. For drug-resistant cases, treatment options narrow considerably, and hospitalization may be needed.
Chronic Carriers
Most people clear the infection completely after treatment. But about 2 to 5% of typhoid patients never fully eliminate the bacteria, becoming chronic carriers who can shed Salmonella Typhi in their stool for a year or more, sometimes for life.
The bacteria persist primarily in the gallbladder. During the bloodstream phase of the infection, organisms pass from the liver into the bile ducts and settle in the gallbladder, where they form biofilms: dense, protective colonies that coat surfaces and resist both the body’s immune defenses and antibiotics. The bacteria are remarkably well-adapted to survive in bile, a fluid that would kill most other organisms. Up to 90% of chronic carriers also have gallstones, which provide additional surfaces for bacterial biofilms to anchor to and make eradication even harder.
Chronic carriers pose a public health risk because they can contaminate food and water without knowing they’re infected. The most famous example, “Typhoid Mary” in early 20th-century New York, infected dozens of people while working as a cook, never showing symptoms herself.
Vaccines and Prevention
Three types of typhoid vaccine exist, and their effectiveness varies considerably. The oldest oral vaccine (Ty21a) has a cumulative efficacy of about 43% over one to five years. The injectable polysaccharide vaccine (ViPS) does somewhat better at 57% over one to three years. Neither is particularly impressive.
The newer typhoid conjugate vaccine (TCV) is a significant step forward. A single dose provides about 83% protection over the first one to two years in children, and effectiveness remains around 78% four years later. During a large outbreak in Hyderabad, Pakistan, TCV showed 95% effectiveness against confirmed typhoid in children aged 6 months to 10 years. This vaccine can also be given to younger children, starting at 6 months of age, which the older vaccines cannot.
Beyond vaccination, typhoid prevention comes down to water and sanitation. The bacteria spread through the fecal-oral route: sewage contaminating drinking water, an infected food handler who doesn’t wash their hands, raw produce washed in unsafe water. In areas with reliable water treatment and sanitation, typhoid is rare. In places without those systems, vaccines and careful food and water hygiene are the primary defenses. If you’re traveling to a high-risk area, drinking only bottled or boiled water, avoiding raw foods, and getting vaccinated before you leave all reduce your risk substantially.