Sporadic Shiga Toxin-Producing Escherichia coli-Associated Pediatric Hemolytic Uremic Syndrome, France, 2012–2021
Sporadic cases of pediatric hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli, France, 2012–2021
Shiga toxin-producing Escherichia coli (STEC) bacteria cause a variety of symptoms, ranging from mild diarrhea to bloody diarrhea, and put patients at increased risk of serious complications, including hemolytic uremic syndrome (HUS). HUS caused by STEC infection can occur at any age, although it mainly affects children under the age of 5 and the elderly. Over the past decade, several outbreaks of foodborne STEC-HUS have received widespread media coverage. For children, this illness remains a significant public health risk in France. Although ruminants (cows, sheep, goats, etc.) are the main reservoir of STEC bacteria, it is difficult to determine the source of contamination in sporadic infections due to the multiple possible modes of contamination (consumption of contaminated food or water, contact with ruminants or their contaminated environment, contact with an infected person, etc.).
Identifying geographic areas where there is a higher risk of sporadic STEC-HUS will help improve our understanding of the environmental risk factors associated with these geographic disparities. This was the objective of the study conducted by Santé publique France, in partnership with the National Reference Center (Centre national de référence, CNR) for E. coli at the Institut Pasteur and its affiliated laboratory at the Robert Debré University Hospital (Centre Hospitalier Universitaire Robert Debré), which was recently published in the journal Emerging Infectious Diseases [1].
3 questions for: Gabrielle Jones, Infectious Diseases Division, Santé publique France
First of all, it should be reiterated that this disease remains a significant public health risk for children in France. Although these infections have the potential to cause epidemics, only 3% of STEC-HUS cases reported in France between 2007 and 2016 were part of an epidemic; the majority were sporadic cases with a highly diverse geographic distribution. Our goal was therefore to identify areas with a higher risk of sporadic STEC-HUS at a fine geographic scale. We used pediatric HUS surveillance data from a 10-year period, 2012 to 2021.
These data were drawn from reports submitted to Santé publique France by clinicians from the surveillance network and analyses conducted at the National Reference Centre for E. coli. This study focused on sporadic cases; therefore, all cases of pediatric HUS linked to an outbreak were excluded from the analysis. Based on these data, we were able to describe the temporal and geographic patterns of these infections.
The primary objective of this study was to describe the temporal trends and geographic distribution of these sporadic cases of pediatric HUS. The secondary objective was to identify space-time clusters and describe geographic areas where there is a higher risk of pediatric HUS, using the statistical approach of space-time scanning. This analysis confirmed the existence of geographic disparities in the risk of sporadic pediatric HUS in France and identified three areas in particular with a higher risk: the eastern half of the Auvergne-Rhône-Alpes region and, to a lesser extent, the Bourgogne-Franche-Comté region, as well as Brittany and Normandy.
Geographic differences in the incidence of pediatric HUS have been observed since surveillance began in 1996. However, there has never been an in-depth analysis using statistical methods that covers a study period of several years and employs a finer geographic scale.
This type of spatiotemporal analysis is important for confirming the observed differences, describing how they change, and improving our characterization of them. It then becomes possible to inform our understanding by studying the origins of the observed diversity, particularly environmental risk factors such as ruminant livestock density (cows, goats, sheep, etc.), the classification of rural and urban areas, water sources, and so on.
This is the first spatiotemporal analysis of sporadic pediatric HUS in France to contribute to a better understanding of the epidemiological situation. These results are useful for epidemiological surveillance, as they will improve the detection and investigation of epidemics and help shape research questions aimed at deepening our knowledge of the risk factors associated with the observed geographic disparities.
Within the framework of epidemiological surveillance, the results generated by this study will be incorporated into a planned study that will use the same space-time scanning approach to detect epidemics of pediatric HUS in France.
These results are also essential for designing additional studies to explore the reasons for the observed geographic differences in risk. Such differences suggest that conditions for the transmission of STECs are favorable in the most affected geographic areas. Studies like these will help improve our understanding of the geographic risk factors associated with a higher risk of sporadic STEC-HUS, and could lead to changes in public health and prevention measures for these infections. This might involve expanding communication efforts or adapting prevention messages to focus on specific risks or target specific populations. However, this will require identifying potential risk factors through further studies.
STEC Surveillance: A robust surveillance system
Since 1996, Santé publique France has coordinated the surveillance of pediatric (affecting children under 15 years of age) hemolytic uremic syndrome (HUS) in France. The agency also plays a role in the prevention of this disease. This clinical and microbiological surveillance system relies on a stable network of volunteer specialized hospital units, which allows Santé publique France to maintain a high level of comprehensive case capture. Over the 10-year period covered by the Jones et al. study, there have been advancements in the microbiological aspects of surveillance, particularly due to improved characterization of isolates, meaning genetically related strains and epidemics can be detected.
In 2022, the number of pediatric HUS cases (n=253) reported to Santé publique France was the highest since surveillance began. The incidence was the highest on record (2.2 cases per 100,000 children under 15 years of age), affecting all age groups and the majority of regions. As in previous years, children under 3 years of age are the most commonly affected, with an incidence of 6.8 per 100,000 children.
It should be noted that this increase in 2022 was partly due to the occurrence of several outbreaks, one of which was large—59 confirmed or probable cases—and linked to the consumption of frozen pizzas.
