Sporadic Shiga Toxin-Producing Escherichia coli-Associated Paediatric Haemolytic Uraemic Syndrome, France, 2012–2021

Cas sporadiques de syndrome hémolytique et urémique pédiatriques liés à Escherichia coli productrices de shigatoxines, France, 2012-2021

Publié le 22 janvier 2024

Shiga toxin-producing Escherichia coli (STEC) bacteria cause a variety of symptoms, ranging from simple diarrhoea to bloody diarrhoea, and expose patients to an increased risk of serious complications, including haemolytic uraemic syndrome (HUS). HUS due to 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 food-borne STEC-HUS have received wide 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 to improve our knowledge of the environmental risk factors associated with the geographic disparities. This was the objective of the study carried out by Santé publique France, in partnership with the National Reference Centre (Centre national de référence, CNR) for E. coli, at the Institut Pasteur, and its associated laboratory at the Robert Debré Teaching 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

What was your approach, and what was the study period you used to identify the geographic areas at most risk of paediatric haemolytic uraemic syndrome (HUS)?

First of all, it should be reiterated that this illness remains a significant public health risk for children in France. Although these infections have epidemic potential, only 3% of STEC-HUS cases reported in France between 2007 and 2016 were part of an epidemic, the majority being sporadic cases with highly diverse geographic distribution. Our goal was therefore to identify areas where there is a higher risk of sporadic STEC-HUS at a fine geographic scale. We used paediatric HUS surveillance data from a 10-year period, 2012 to 2021.

These data were drawn from reports made to Santé publique France by clinicians from the surveillance network and analyses carried out at the National Reference Centre for E. coli. This work focused on sporadic cases, so all cases of paediatric HUS connected to an epidemic were excluded from the analysis. Based on these data, we were able to describe the temporal and geographic occurrence of these infections.

The primary objective of this study was to describe the temporal trends and geographic distribution of these sporadic cases of paediatric HUS. The secondary objective was to identify space-time clusters and describe geographic areas where there is a higher risk of paediatric HUS, using the statistical approach of space-time scanning. This analysis confirmed the existence of geographic disparities in the risk of sporadic paediatric HUS in France and identified three areas in particular with a higher risk: the eastern half of the Auvergne-Rhône-Alps region and, to a lesser extent, the Bourgogne-Franche-Comté region, and Brittany and Normandy.

How will the identification of these spatiotemporal aggregates contribute to improving our understanding of the environmental risk factors associated with the geographic disparities of STEC-HUS in France?

Geographic differences in the incidence of paediatric HUS have been observed since surveillance was implemented in 1996. However, there has never been an in-depth analysis using statistical methods, looking at a study period of several years and using a finer geographic scale.

This kind of spatiotemporal analysis is important to confirm the differences observed, describe how they change and improve how we characterise them. It is then possible to inform our thinking by studying the origin of the diversity observed, especially environmental risk factors such as ruminant livestock density (cows, goats, sheep, etc.), the classification of rural and urban areas, water sources, etc.

Do your results open up potential research avenues or prospects that could affect epidemiological surveillance?

This is the first spatiotemporal analysis of sporadic paediatric HUS in France to contribute to an improved understanding of the epidemiological situation. These results are useful for epidemiological surveillance as they will improve the detection and investigation of epidemics and help to shape research questions that aim to deepen our knowledge of the risk factors implied by the geographic disparities observed.

Within the framework of epidemiological surveillance, the results generated by this study will be incorporated into a planned study that will look at using the same space-time scanning approach to detect epidemics of paediatric 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 favourable in the most affected geographic areas. Studies like these will help to improve our knowledge of the geographic risk factors associated with a higher risk of sporadic STEC-HUS, and could result in changes to public health and prevention measures for these infections. This might mean expanding communication or adapting prevention messages focused on certain risks or targeting certain populations. However, this will involve identifying potential risk factors through additional studies.

STEC surveillance: A robust surveillance system

Since 1996, Santé publique France has coordinated the surveillance of paediatric (affecting children under 15 years of age) haemolytic uraemic 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 specialised hospital units, which allows Santé publique France to maintain a good level of exhaustive capture regarding the cases. Over the 10-year period covered by the Jones et al study, there have been developments in the microbiological side of surveillance, in particular due to improved characterisation of isolates, meaning genetically related strains and epidemics can be detected.

In 2022, the number of paediatric HUS cases (n=253) reported to Santé publique France was the highest since surveillance began. The incidence was the highest observed on record (2.2 cases per 100,000 children <15 years old), which applied to all age groups and in the majority of regions. As in previous years, children under 3 years are the most commonly affected with an incidence of 6.8/100,000 children.

It should be restated that this increase in 2022 was partly due to the occurrence of several epidemics, one of which was large – 59 confirmed or probable cases – and linked to the consumption of frozen pizzas.

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