Sporadic cases of pediatric hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli, France, 2012–2021
Sporadic Shiga Toxin-Producing Escherichia coli-Associated Pediatric Hemolytic Uremic Syndrome, France, 2012–2021
Pediatric hemolytic-uremic syndrome
thematic dossier
Shiga toxin-producing Escherichia coli (STEC) bacteria cause a range of symptoms, from mild diarrhea to bloody diarrhea, and are associated with an increased risk of serious complications, including hemolytic uremic syndrome (HUS). HUS caused by STEC infection can occur at any age, but it primarily affects children under 5 and the elderly. Over the past decade, several foodborne STEC-HUS outbreaks have received extensive media coverage. This syndrome remains a significant public health risk for children in France. While ruminants (cows, sheep, goats, etc.) are the primary reservoir of STEC bacteria, determining the source of contamination for sporadic infections is difficult due to the multiple possible modes of transmission (consumption of contaminated food or water, contact with ruminants or their contaminated environment, person-to-person transmission following contact with an infected individual, etc.).
Identifying geographic areas with a higher risk of sporadic STEC-associated HUS will help improve understanding of the environmental risk factors associated with geographic disparities. This is the objective of the study conducted by Santé publique France, in partnership with the National Reference Center (CNR) for E. coli, located at the Institut Pasteur, and its associated laboratory at the Robert Debré University Hospital, which has just been published in the journal Emerging Infectious Diseases [1].
3 questions for: Gabrielle Jones, Infectious Diseases Directorate, Santé publique France
First, it is important to note that this syndrome remains a significant public health risk for children in France. Although these infections have the potential to cause outbreaks, only 3% of HUS-STEC cases reported in France between 2007 and 2016 were associated with an outbreak; the majority were sporadic cases exhibiting significant geographic heterogeneity. Hence our objective to identify, at a fine geographic scale, the areas with a higher risk of sporadic STEC-associated HUS.
We analyzed pediatric HUS surveillance data over a 10-year period, from 2012 to 2021. These data were derived from reports submitted to Santé publique France by clinicians in the surveillance network and from analyses conducted at the CNR E. coli. This study focused on sporadic cases; that is, all cases of pediatric HUS linked to an outbreak were excluded from the analysis. Using these data, it was possible to describe the occurrence of these infections over time and space.
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 spatiotemporal clusters and describe geographic areas with a higher risk of pediatric HUS, using a spatiotemporal scanning statistical approach.
This analysis confirmed the existence of geographic disparities in the risk of sporadic pediatric HUS in France and identified, in particular, three areas with a higher risk: the eastern half of the Auvergne-Rhône-Alpes region and, to a lesser extent, the regions of Bourgogne-Franche-Comté, Brittany, and Normandy.
Geographical differences in the incidence of pediatric HUS have been observed since surveillance began in 1996. However, there has never been an in-depth statistical analysis covering a multi-year study period and at a finer geographical scale. Such a spatiotemporal analysis is important for confirming these differences, describing their evolution, and better characterizing them. This can inform research into the causes of the observed heterogeneity, particularly environmental risk factors such as ruminant density (cows, goats, sheep, etc.), rural-urban classification, water sources, and so on.
This is the first spatiotemporal analysis of sporadic pediatric HUS in France, contributing to a better understanding of the epidemiological situation. These results are relevant for epidemiological surveillance, as they improve the detection and investigation of outbreaks, and help guide research questions aimed at improving knowledge of the risk factors associated with the observed geographic disparities.
As part of epidemiological surveillance, the results generated by this study will be incorporated into a planned study exploring the same spatiotemporal scanning approach for detecting pediatric HUS outbreaks in France.
These results are also essential for designing complementary studies aimed at exploring the causes of the observed geographic differences in risk. Indeed, these differences suggest conditions favorable for STEC transmission in the most affected geographic areas.
Such studies will help improve our understanding of the geographic risk factors associated with a higher risk of sporadic STEC-HUS and could lead to the adaptation of public health and prevention measures for these infections. For example, strengthening communication or tailoring prevention messages to target specific risks or populations. However, this requires identifying potential risk factors through further studies.
[1] Jones G, Mariani-Kurkdjian P, Cointe A, Bonacorsi S, Lefèvre S, Weill F, et al. Sporadic Shiga Toxin–Producing Escherichia coli–Associated Pediatric Hemolytic Uremic Syndrome, France, 2012–2021. Emerg Infect Dis. 2023;29(10):2054-2064.
Surveillance of STEC: A Robust Surveillance System
Since 1996, Santé publique France has coordinated the surveillance of pediatric hemolytic uremic syndrome (HUS) (in children under 15 years of age) in France. The agency also contributes to the prevention of this disease. This clinical and microbiological surveillance system relies on a stable network of volunteer specialized hospital units, enabling Santé publique France to maintain a high level of case coverage. Over the 10-year period covered by the study by G. Jones et al., the microbiological component has evolved, particularly through improved characterization of isolates, enabling the detection of genetically related strains and outbreaks.
In 2022, the number of pediatric HUS cases (n=253) reported to Santé publique France was the highest since surveillance began. Consequently, the incidence was the highest ever observed (2.2 cases per 100,000 children under 15 years of age), across all age groups and in the majority of regions. As in previous years, children under 3 years of age were the most affected, with an incidence of 6.8 per 100,000 children.
It should be noted that this increase in 2022 is partly due to the occurrence of several outbreaks, including a large-scale one—59 confirmed or probable cases—linked to the consumption of frozen pizzas.
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