What is typhoid fever?

Typhoid fever is a disease caused by a microbe called Salmonella enterica subspecies enterica serovar Typhi, or Salmonella Typhi (S. Typhi).

This bacterium is different from the Salmonella bacteria that can cause food poisoning if you eat undercooked chicken. That Salmonella is called non-typhoidal.

S. Typhi is a typhoidal microbe and causes typhoid when it leaves your gut and enters your bloodstream. You can catch it if you don’t wash your hands after using the loo or drink unsanitary water. Symptoms include high fever, diarrhoea, fatigue and sometimes rashes.

Typhoid causes 100,000 deaths per year, largely in low-and-middle-income countries, with 9 million cases globally. The UK is not an endemic region, meaning the disease is not commonly found here, but cases are on the rise. Most UK cases occur when returning from travel to endemic countries like Pakistan and India.

How is typhoid fever spread and what is a healthy carrier?

Some people unknowingly carry S. Typhi, often without symptoms, and can spread these microbes to others.

A well-known example is Typhoid Mary. An Irish American cook in the 19th Century, Mary Mallon unintentionally infected the wealthy families she cooked for, transmitting typhoid at a time when we didn’t know what caused the disease and there was no treatment.

The puzzle of what caused typhoid was pieced together by an ‘epidemic fighter’, George Soper. George was determined to understand why these families had fallen ill. He discovered the common denominator: Typhoid Mary and the peach ice cream she made them.

Mary was what we now call a ‘healthy carrier’, a healthy individual carrying and spreading infectious microbes to others. To this day, it’s what makes some typhoid cases in the UK so difficult to track down, and why scientists are working to better understand this microbe.

Why is Salmonella Typhi so hard to study and track down?

S. Typhi is difficult to study because it can only survive in humans, it can be spread by people without symptoms and is genetically flexible.

The human-restriction of S. Typhi is a doubled-edged sword. If we cure typhoid in humans, we’ve cured it full stop. But we also can’t easily study S. Typhi in mouse models since it’s not adapted to this environment. These barriers to studying S. Typhi make it more difficult to find effective treatments for typhoid.

Secondly, S. Typhi is difficult to study because it can be spread by healthy carriers. Like Typhoid Mary, these individuals become infected with S. Typhi but fail to clear the microbe, so it persists in the individual. Asymptomatic, these carriers are hard to detect and can carry the bacteria for many years. In non-endemic countries like the UK, carriage is an important risk factor. Since S. Typhi is less common, these ‘invisible’ carriers pose a risk of disease transmission.

Thirdly, S. Typhi is tricky to decipher because it is genetically flexible. It rearranges fragments within its circular genome, flipping, cutting and moving sections around. These are not direct changes to the bacterium’s DNA, but larger, structural changes that can alter how genes work. Equipped with this genetic flexibility, S. Typhi strongly adapts to specific environments, like humans.

Using science to detect Salmonella Typhi in the UK

Alice Nisbet is a 3rd year PhD student on the Microbes, Microbiomes and Bioinformatics programme. Working in Dr Gemma Langridge’s group, Alice studies S. Typhi and the closely related bacterium Salmonella Paratyphi A, which causes paratyphoid fever. The two diseases are jointly known as enteric fever.

Collaborating with the UK Health Security Agency (UKHSA), the government agency responsible for health security in England, Alice is looking at all the cases of enteric fever in the UK over the past 20 years to identify carriers for further analysis. Since enteric fever is a notifiable disease in England, samples taken from patients are sent to the Gastrointestinal Bacteria Reference Unit, where the bacteria are sequenced to identify and track cases.

While the majority of cases are associated with foreign travel to endemic regions, cases with no travel history are observed and potentially signal spread by carrier patients. If healthy carriers handle food as part of their job, they have a higher risk of passing the disease on to someone else.

Tracking down people who carry typhoid is difficult and relies on ability and willingness to give repeat samples. Alice explains, “If a carrier gave a sample in 2020 due to illness, became ill again in 2025 and gave another sample, you might assume it was a different infection. However, bacterial genetic material can reveal clues. If there are few genetic differences in both samples, that would suggest it’s the same microbe that’s been carried within the patient for 5 years.”

When samples are received, healthcare specialists and researchers ask questions like ‘Are there samples from other family members?’ and ‘Did they travel together?’. If samples keep coming in, then connections can be formed between the cases. Carriers are often connectors but very expensive to track down. A study in 2006 suggested it cost an estimated £17, 315 to detect a probable  carrier.

There were 702 cases of enteric fever in the UK in 2024, an 8% increase from 2023. This is a rising burden on healthcare and limited treatment options in some cases.

Here at the Quadram Institute, in collaboration with UKHSA, retrospective identification of carrier patients is part of the detective work Alice does.

“I investigate whether there are genetic components of S. Typhi that could be associated with carriage, or if there are any metabolic differences – changes in the way bacteria convert food into energy – seen in carriage samples, alongside identifying what kind of changes we see over the course of carriage.”

To carry out this work, Alice uses genetics, bioinformatics and builds metabolic models.

Defining the factors causing carriage in S. Typhi and S. Paratyphi A is key to help carriers get rid of the bacterium and prevent spread to other potential carriers.

What’s next for typhoid research?

Research into Salmonella Typhi will help us tackle growing cases in the UK and in endemic countries too, where this research will be applicable to a significant number of samples and cases.

Alice reflects, “The more we learn and understand about S. Typhi through research, the more we can do to address this public health issue.”