Real-time whole-genome sequencing for the surveillance of Listeria monocytogenes, France

Real-time whole-genome sequencing for the surveillance of Listeria monocytogenes in France

Listeria monocytogenes is the bacterium responsible for listeriosis(1), a rare (approximately 400 cases annually) but serious foodborne infection that primarily affects individuals with compromised immune systems: the elderly, pregnant women, newborns, and immunocompromised individuals. It can be fatal in one out of every five cases. The article “Real-Time Whole-Genome Sequencing for the Surveillance of Listeria monocytogenes, France,” published this month in the journal Emerging Infectious Diseases¹ describes the application of a method for characterizing Listeria strains based on whole-genome sequencing—developed by the National Reference Center—to the routine surveillance of human listeriosis.

Santé publique France conducts epidemiological surveillance of listeriosis in collaboration with the National Reference Center for Listeria (Institut Pasteur in Paris), which performs microbiological testing of strains. The goal is to detect clusters of cases as early as possible in order to identify the source of contamination and implement control measures.

Mathieu Tourdjman

3 Questions for Mathieu Tourdjman, Head of the Infectious Diseases Division

As with most bacteria that cause foodborne infections, there is a wide variety of Listeria strains. Having effective tools to distinguish between these strains is key to efficiently identifying patients infected by the same strain—known as clusters—who are highly likely to have been infected from a common source, which we must then identify to reduce the risk of infecting others. In other words, the more effective the method, the more efficiently the source of contamination can be identified: this will therefore help reduce the number of patients and limit the associated human and economic costs.
Until recently, pulsed-field gel electrophoresis was considered the gold standard for distinguishing between Listeria strains. Although this technique has undeniably contributed to resolving many outbreaks, it is far less powerful than whole-genome analysis for differentiating Listeria strains. The CNR for Listeria has developed a genome sequencing technique called Core-Genome Multilocus Sequence Typing (cgMLST) that allows for the distinction between strains in cases where electrophoresis cannot. Such a level of discrimination therefore enables more precise identification of clustered cases and improves our ability to identify the sources of contamination in patients.

Over a two-year period, from 2015 to 2016, both methods were used in parallel on 2,743 strains of Listeria monocytogenes of human, food, and environmental origin.
During this period, the genomic sequencing technique identified nearly four times as many clusters as those identified by electrophoresis, identified the source of contamination more frequently, and at an earlier stage—that is, before outbreaks affected a large number of people.
The source of contamination was identified in nearly 20% of clustered cases, and prolonged contamination of food production sites was detected. In some cases, contamination had been present for several months or even years without having been detected. Today, as soon as two patients are found to have the same strain, an investigation is systematically conducted.

Given the clear superiority of this genome sequencing technique, it has already replaced electrophoresis for routine surveillance of listeriosis since the beginning of 2017.
The application of genome sequencing to listeriosis surveillance thus serves as a model for many other infectious diseases: more outbreaks are identified, and at the same time, sources of contamination are identified earlier and these outbreaks are smaller. This technique should help producers improve Listeria risk control.
Given the low annual number of listeriosis cases, this disease—for which there has historically been a highly effective surveillance system in France—has served as a prototype for the routine application of sequencing. In the future, such surveillance is expected to be extended to many other infectious diseases, such as salmonellosis, shigellosis, and meningitis.

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(1) Listeriosis has been a reportable disease since 1999.

Moura A, Tourdjman M, Leclercq A, Hamelin E, Laurent E, Fredriksen N, et al. Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France. Emerg Infect Dis. 2017 Aug [date cited].