Pediatric Hemolytic Uremic Syndrome Associated with Shiga Toxin-Producing Escherichia coli: A Review of 10 Years of Surveillance in France, 2007–2016.
Shiga toxin-producing Escherichia coli (STEC) are bacteria that cause diarrhea, which is often bloody, and can lead to hemolytic uremic syndrome (HUS) in 5 to 15% of cases. HUS is the leading cause of acute kidney failure in young children. It is a rare but serious disease, often leaving lasting effects. Infection can result from consuming contaminated food or water, contact with a contaminated animal or environment, or person-to-person transmission.
Since 1996, pediatric HUS has been subject to surveillance in France, coordinated by Santé publique France.
The article recently published in Eurosurveillance by Santé publique France and its partners describes the main findings of this surveillance in France between 2007 and 2016.
3 Questions for Mathias Bruyand, Santé publique France
Since 1996, surveillance of HUS in children under 15 has been based on a network of pediatric departments in hospitals. Pediatricians report cases to Santé publique France on a voluntary basis.
The objectives of this surveillance are to describe the spatial and temporal trends of pediatric HUS, the characteristics of cases and the STEC strains affecting them, and to detect outbreaks in order to guide control and prevention measures.
The National Reference Center and its associated laboratory screen stool samples for STEC strains. These strains undergo routine detailed characterization and comparison via whole-genome sequencing at the NRC, which allows for the identification of clusters of strains sharing the same characteristics. When the NRC detects a cluster, it notifies Santé publique France, which initiates an epidemiological investigation to determine whether there is a link between the cases. If an epidemiological link is identified between the cases, an alert is issued and an investigation team is deployed to precisely identify the source of the outbreak, enabling the implementation of control and prevention measures.
Between 2007 and 2016, 1,215 cases of pediatric HUS were reported, representing an incidence rate of 1.0 cases per 100,000 person-years. On average, 116 cases were reported each year. The median age at diagnosis was 30 months.
The highest incidence rate was observed in 2011 (1.3 cases per 100,000 person-years), after which it declined through 2016 (1.0 cases per 100,000 person-years). Seasonal patterns were observed each year (with the majority of cases reported in the summer), as well as spatial heterogeneity (the regions of Lower Normandy and Franche-Comté were the most affected).
The STEC O157 serogroup, historically the most common, peaked in 2011 (37 cases) before declining through 2016 (7 cases). This serogroup is highly virulent and often associated with the onset of hemolytic uremic syndrome (HUS).
Two serogroups have clearly emerged: O26 since 2010 (28 cases in 2016) and O80 since 2012 (18 cases in 2016).
Four foodborne STEC HUS outbreaks were detected in France during this period. The first involved STEC O104 and was linked to the consumption of sprouted seeds. This outbreak, which caused 7 cases of HUS in France (6 adults and 1 child), resulted in several thousand cases across Europe, primarily in Germany, including several dozen deaths*. The three other outbreaks in France involved STEC O157 and were linked to the consumption of ground beef (2 outbreaks) and raw-milk Camembert (1 outbreak).
Finally, two outbreaks linked to human-to-human transmission were detected in daycare centers: one in Brittany involving a strain of STEC O111 and one in southern France involving a strain of STEC O26.
In conclusion, the main measures to prevent STEC infections must be reiterated; in particular, the consumption of raw-milk cheese (or raw milk) should be avoided in young children, and ground beef should be cooked thoroughly.
The description of the strains affecting the cases allowed us to demonstrate that STEC serogroups evolved during the study period.
An unexpected increase in the number of reported HUS cases may raise suspicion of an outbreak even before microbiological data are available. Conversely, if cases linked to an outbreak are few in number and spread over a relatively long period of time or a large geographic area, epidemiological surveillance alone may fail to detect the event. WGS
technology allows for the highly detailed characterization of STEC strains in routine settings and enables their comparison. This makes it possible to detect clusters, including small ones that are spread out over time or space.
Isolating STEC strains and sequencing them takes a few weeks; therefore, microbiological surveillance complements epidemiological surveillance, which allows for case reporting as soon as HUS is diagnosed.
In conclusion, this surveillance system, which combines epidemiological data on cases with microbiological data on strains, enables the detection of emerging serogroups. This was the case, for example, with the STEC O104 outbreak linked to sprouted seeds: it was the first HUS outbreak caused by STEC O104 observed in France and Europe.
* King LA, Nogareda F, Weill FX, Mariani-Kurkdjian P, Loukiadis E, Gault G, et al. Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011. Clin Infect Dis. 2012;54(11):1588-94. https://doi.org/10.1093/cid/cis255 PMID: 22460976
[1] Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing Escherichia coli, an overview of 10 years of surveillance in France, 2007 to 2016. Bruyand M, Mariani-Kurkdjian P, Le Hello, Simon, King, L and Van Cauteren D et al. and French Hospital Network for the Surveillance of Paediatric HUS, Eurosurveillance, 24, 1800068 (2019), https://doi.org/10.2807/1560-7917.ES.2019.24.8.1800068ec of sprouted seeds: this was the first STEC O104 HUS outbreak observed in France and Europe.