The Threat of Infectious Encephalitis in Southeast Asia: SouthEast Asia Encephalitis Project

Background:

Encephalitis is defined as an acute inflammation of the central nervous system associated with neurologic dysfunction. The most common etiologies are infections by either viruses or bacteria although parasites and fungi can also be occasionally detected, especially in immunocompromised patients. Because of high mortality and long-term neurological sequelae, encephalitis is of public health concern worldwide. Reported incidences range between 3.5 and 7.4 cases per 100,000 patient-years with higher incidences in children than adults. Various encephalitis outbreaks have recently emerged in Asia such as the fatal outbreak of enterovirus 71 (EV71) that occurred in mid-2012 in Cambodia affecting very young children (most below 3 years, all below 12 years). In Asia where many of the possible etiologies are of major public health concerns (i.e. dengue, Japanese encephalitis, West Nile virus, EV71), acute encephalitis is among the most frequent and severe causes of pediatric hospitalization.

Despite extensive microbiological investigations and the use of the most advanced molecular biology-based assays, no pathogen is identified for a significant proportion of encephalitis patients in both industrialized and developing countries (28-85% of cases remain unconfirmed). Previous studies support the hypothesis that unknown and sometimes new emerging infectious agents may be responsible for cases of currently unknown etiology and strongly argue for an intensive effort to identify and characterize them. This hypothesis is also strengthened by the recent apparent increase in emerging infectious diseases, many of which have been linked to human activities that impact the environment and to the spreading of pathogens to new geographic regions. From this perspective, the Southeast Asian region, a particularly significant biodiversity hotspot, is at high risk for new pathogen emergence. Indeed, growing human populations, increasing urbanization and frequent contact with wildlife and domesticated animals have created novel opportunities for the emergence of pathogens such as SARS at the end of 2002, and highly facilitated the spread of infectious diseases such as H5N1 high-pathogenicity avian influenza virus since 2004, and H1N1 pandemic influenza virus in 2009. The population in developing Southeast Asian countries is particularly at risk for the circulation of emerging or reemerging infectious agents and for this reason the surveillance and investigation of acute encephalitis syndrome in this region is of utmost public health importance, both locally and globally.

Surveillance and diagnostic capabilities for encephalitis remain poor and still suffer from serious shortcomings in most Southeast Asian countries and beyond. Although the burden of non-infectious encephalitis in this region remains to be ascertained, the best laboratories only identify etiological infective agents in less than half of patients. Moreover, because of the absence of reliable microbiological diagnostic capacity in the majority of public referral hospitals, local clinicians have to treat acute encephalitis syndromes mostly empirically, with little evaluation of the effectiveness of their clinical approach. Even if some of the most common causes of acute encephalitis syndrome may be vaccine-preventable, systematic data regarding the contribution of these diseases are lacking and no reliable data are available to define the burden of these infections, to describe the full clinical spectrum and characteristics of acute central nervous system infections, and to develop diagnostic and therapeutic algorithms to improve patient care. Besides, whatever the nature and magnitude of the encephalitis burden in Southeast Asia and the criteria used to assess it (i.e. morbidity, mortality, handicap, impact on families' budget or livelihood), this burden is borne principally by underprivileged populations with limited access to prevention and health care.

Project partners The proposed project is an ambitious and multidisciplinary research consortium associating: (i) national health authorities in Cambodia, Lao PDR, Vietnam and Myanmar; (ii) local major university and clinical sites (national hospitals and provincial health centers); (iii) key French stakeholders of life and health sciences with research activities carried out in the Southeast Asian region such as: Institut Pasteur and the Institut Pasteur International Network, Institut National de la Santé et de la Recherche Médicale (Inserm), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut de Recherche pour le Développement (IRD) - Aix-Marseille University - Ecole des Hautes Etudes en Santé Publique (EHESP); and (iv) teams from the Southeast Asian Wellcome Trust Oxford University Major Overseas Programme.