This first-of-it-kind enteric fever surveillance study combined multi-team collaborations.

A collaborative study combining expertise from the Quadram Institute, UK Health Security Agency (UKHSA) and Public Health Wales sheds light on enteric fever cases between 2004-2023, revealing that cases have risen post-pandemic.

2.7% of cases constitute carriage, the phenomenon where healthy individuals carry and spread the disease unknowingly, increasing the enteric fever burden in England and Wales.

Salmonella Typhi and the closely related bacteria Salmonella Paratyphi A and B cause enteric fever, a major disease causing 100,000 deaths annually, largely in low-and-middle-income countries, including India.

The UK is not an endemic region, meaning the disease is not commonly found here in its acute (symptomatic) form, but cases are on the rise, reaching a peak of 652 cases in 2023. Carriage is a particular threat since cases are largely ‘invisible’ and difficult to identify.

The most famous case of carriage is that of Typhoid Mary, who unintentionally infected the families she cooked for in early 20th Century New York. It took many months to identify Mary as the cause because she herself experienced no symptoms and the concept of healthy carriage was in its infancy.

UKHSA undertakes surveillance of enteric fever in England and Wales, sequencing the causal bacteria and collecting demographic and behavioural details relevant for infection.

Using this data, researchers carried out the first wide-scale study looking at enteric fever trends and carriage estimates. The last carriage estimates date from the 1900s when enteric fever was much more prevalent in the country.

Now, the modern day genomic survey suggests it will continue to be complex to identify carriage. The findings suggest there is no genetic signature in the causative pathogen predisposing them to cause carriage infections. This complicates how we can track potential carriers and reduce transmission of this global health issue in England and Wales. Instead, factors linked to individuals’ immune systems, age and travel history likely dictate whether an individual will become a carrier.

The researchers identified that elderly patients and those without foreign travel have higher risk of carriage. This data will enable public health bodies to target these higher risk individuals to identify modern day ‘Typhoid Marys’.

Retrospective identification of carriage is generally difficult since it relies on patients giving multiple samples, presenting with symptoms at some point and shedding the bacteria in their samples.

Dr Marie Anne Chattaway, Unit Head of UKHSA’s Gastrointestinal Reference Unit states:

This study represents an important step forward in understanding the hidden burden of asymptomatic carriage in enteric fever in England and Wales. By applying genomic analysis to long-term surveillance data from the Gastrointestinal Bacterial Reference Unit, alongside enhanced surveillance data, we have been able to explore carriage at a scale not previously possible. Crucially, this work highlights how integrated surveillance, combined with strong cross-agency collaboration, can provide new insights to support more targeted public health interventions.

Alice Nisbet, a postgraduate student in Dr Langridge’s group at the Quadram Institute adds:

Alongside supporting future public health action, we hope this work can guide future research on typhoidal Salmonella carriage. By shifting focus towards examining the immune profiles of carrier patients and the functional capacity of carriage isolates, future work will help to better characterise this neglected condition, advancing both our understanding and management of it.

Dr Gemma Langridge’s group at the Quadram Institute collaborated with the UKHSA’s Gastrointestinal Bacterial Reference Unit, Travel Health and International Health Regulations Team and Statistics Modelling and Economics Department, alongside the Gastrointestinal, Emerging and Zoonotic Infections sector of Public Health Wales to produce this surveillance study.

Read more in the paper published in PLOS Neglected Tropical Diseases.