Genomic study reveals challenges in identifying modern-day ‘Typhoid Marys’

People who unknowingly carry and spread enteric fever are difficult to identify, according to a new study that analysed more than 20 years of cases in England and Wales.

Researchers from the Quadram Institute, UK Health Security Agency (UKHSA) and Public Health Wales used genomic and surveillance data from 2004–2023 to investigate how often carriage occurs and what factors may increase the risk. The study [1] was published in PLOS Neglected Tropical Diseases.

Enteric fever is caused by Salmonella Typhi and the related bacteria Salmonella Paratyphi A and B. While the disease is not endemic in the UK, cases have increased in recent years, reaching a peak of 652 cases in 2023.

The study found that around 2.7% of cases involved carriage, where individuals continue to harbour and potentially spread the bacteria without symptoms. These silent infections make it challenging for public health teams to identify and prevent further transmission.

The researchers compared bacterial genomes from cases across two decades and found no genetic signature in the pathogen that predicted whether someone would become a carrier. Instead, factors linked to the individual, including age, immune response and travel history, appear to influence carriage risk.

The phenomenon is often associated with the historic case of ‘Typhoid Mary’, an asymptomatic carrier in early 20th-century New York who unknowingly transmitted typhoid fever to people she cooked for.

Dr Marie Anne Chattaway, Unit Head at UKHSA’s Gastrointestinal Reference Unit, said:

“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, alongside enhanced surveillance information, we have been able to explore carriage at a scale not previously possible.”

She added that combining surveillance approaches could help support more targeted public health interventions.

Alice Nisbet, a postgraduate researcher at the Quadram Institute, said:

“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 better characterise this neglected condition.”

The researchers say understanding why some individuals become long-term carriers will be key to improving disease control strategies, both in the UK and globally.

More information online

1. The typhoid Mary legacy: Genomic epidemiology uncovers contemporary carriage dynamics across two decades of enteric fever surveillance in England and Wales published in PLOS Neglected Tropical Diseases