Observational study on the clinical epidemiology of infectious acute encephalitis syndrome including Nipah virus disease, Bangladesh: BASE cohort study protocol.

introductionNipah virus (NiV) is a bat-transmitted paramyxovirus causing recurrent, high-mortality outbreaks in South and South-East Asia. As a WHO priority pathogen, efforts are underway to develop therapies like monoclonal antibodies and small-molecule antivirals, which require evaluation in clinical trials. However, trial design is challenging due to limited understanding of NiV's clinical characteristics. Given the rarity of NiV infections, strategies targeting improved outcomes for the broader acute encephalitis syndrome (AES) patient population, including those with NiV, are essential for advancing therapeutic research. To address these gaps, we designed the Bangladesh AES cohort study to characterise the patient population, clinical features, treatment practices, common aetiologies and outcomes in patients presenting with AES, including NiV infection, as a clinical characterisation study to inform the design of clinical trials for NiV and AES more broadly. METHODS AND ANALYSIS: This prospective cohort study will be conducted in Bangladesh, a NiV endemic country with annual outbreaks. In collaboration with the ongoing NiV surveillance programme in Bangladesh, we aim to enrol up to 2000 patients of all ages presenting with AES at three tertiary care hospitals within the Nipah belt. Patients who provide informed consent to participate will be monitored throughout their hospital stay until 90 days post enrolment. Data will be systematically collected through interviews and medical record reviews at several time points: on the day of enrolment, day 3, day 7, the day of critical care admission (if applicable), discharge day and 90 days post enrollment. Additionally, a portion of the cerebrospinal fluid collected under the concurrent NiV surveillance protocol will be tested for an array of viral and bacterial pathogens responsible for encephalitis at the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory. ETHICS AND DISSEMINATION: The study received ethical approval from the Oxford Tropical Research Ethics Committee, University of Oxford, UK (OxTREC Ref: 576-23) and the institutional review board of icddr,b, Bangladesh (icddr,b protocol number: 24016). By characterising the AES patient population, this study will generate essential evidence on key clinical parameters, which will be pivotal in optimising the design of clinical trials for potential interventions aimed at improving outcomes in patients with AES, including those with NiV disease. Findings will be shared with participating hospitals, patients and relevant government stakeholders. Results will also be disseminated through conference presentations and peer-reviewed publications. CLINICAL TRIAL NUMBER: Not applicable (this is an observational study).