Marc Lecuit

About

An integrative approach to understand and fight infectious encephalitis in children

An encephalitis is an acute inflammation of the central nervous system associated with neurologic dysfunction. The most common etiologies are infections by bacteria or viruses. In Asia, infectious encephalitis is major public health concern, as acute encephalitis are among the most frequent and severe causes of pediatric hospitalization (dengue virus, Japanese encephalitis virus, EV71 virus). Despite extensive microbiological investigations and the use of the most advanced molecular biology-based assays, encephalitis etiologies remain unknown in close to half of cases.

The SEAe (SouthEast Asia encephalitis) program has been launched to address the public health and research issues raised by infectious encephalitis in Southeast Asia. This major inter-organizational and multidisciplinary initiative involves so far four Southeast Asian countries (Cambodia, Laos, Vietnam and Myanmar), and France. It has the following objectives:

To strengthen hospital capacities to improve diagnosis and care for patients with encephalitis
To fill-in the biomedical knowledge gaps regarding encephalitis (e.g. pathophysiology, long‐term sequelae, …)
To gather comprehensive data on well-characterized and unusual pathogens responsible for encephalitis
To identify previously unknown pathogens responsible for encephalitis
To identify and analyze factors related to clusters of encephalitis cases, integrating human health, animal health and environment through a One Health approach
To provide reliable information and a sustainable regional and sub-regional surveillance network to clinicians and public health authorities that will help better define prevention policies, vaccination strategy, and build preparedness to emerging infectious risks

Clinical activities

The workpackage on clinical and epidemiological studies is responsible for the rigorous identification and inclusion of infectious encephalitis cases, the collection and storage of clinical data and biological samples for microbiological diagnosis. Training of medical personnel in clinical sites participating to the study is an important aspect of this workpackage mission. Identification of clusters of cases unusual by their numbers, the causative pathogen, or the clinical presentation, will trigger field investigations conducted in collaboration with the partners involved in the third component (see below). The prospective follow-up of survivors one year after discharge will document the long-term neurologic sequelae associated with acute encephalitis.

Diagnosis activities

The laboratory diagnosis, will improve the microbiological diagnosis of known pathogens by strengthening capacities in selected clinical sites and national collaborative centers, in order to provide the clinicians with state-of-the-art and timely laboratory diagnosis for the microorganisms accessible to treatment. In order to establish a harmonized diagnostic strategy, molecular diagnostic tools will be implemented allowing the detection of dozens of infectious agents known to be responsible for encephalitis in Southeast Asia. This will extend to the detection and characterization of new or unusual pathogens in the samples of unknown etiology by using a combined approach: pan-generic PCRs, cell cultures, electron microscopy, High Throughput Sequencing (HTS).

Field Investigations

The project will also document and analyze collective and environmental risk factors related to encephalitis cases in order to improve the understanding of human infectious encephalitis epidemiology in Southeast Asia, integrating potential environmental, epidemiological and sociological factors, and provide adapted surveillance, control and outbreak investigation methodologies. Indeed, recognizing the essential link between human, animal (domestic animal and wildlife) and environmental health, and the threat of disease transmission, field investigations using an interdisciplinary “One Health” approach is crucial to a better understanding of the epidemiology of diseases and, by extension, their control.

Partners