Nipah 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.

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.

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.

Not applicable (this is an observational study).

Artemisinin-based combination therapies (ACTs) remain the WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of artemisinin resistance (ART-R) threatens ACT efficacy. ART-R is phenotypically expressed as delayed parasite clearance, which can facilitate ACT partner drug resistance. ART-R has been causally linked to specific mutations in the Pfkelch13 gene.

The systematic review and associated meta-analysis aim to determine the correlation between Pfkelch13 (alleles present in the Kelch13 gene region of the P. falciparum parasite) genotypes and clinical and parasitological response to ACTs from a globally representative data set pooling individual patient data (IPD) from eligible published and unpublished studies. The eligibility criteria include Pfkelch13 genotyping results at baseline complemented by individually linked parasitological and clinical assessments following artemisinin-based treatment. The data will be curated, standardised and analysed using this proposed statistical analysis plan (SAP), adhering to PRISMA-IPD (PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Our SAP will apply hierarchical modelling to assess the effect of the P. falciparum parasite Pfkelch13 mutations on parasite clearance half-life and therapeutic efficacy across different regions. This will include study sites as random effects in the model and potential predictors such as age, sex, baseline parasite load and other potential effect modifiers as fixed effects. This analysis will enhance the understanding of the influence of Pfkelch13 mutations on malaria treatment outcomes.

Data were obtained with informed consent and ethical approvals from the relevant countries and were pseudonymised before curation in the Infectious Diseases Data Observatory (IDDO)/WorldWide Antimalarial Resistance Network (WWARN) repository. Data ownership remains with contributors. This IPD meta-analysis met the Oxford Tropical Research Ethics Committee criteria for waiving ethical review, as it is a secondary analysis of existing pseudonymised data. The resulting peer-reviewed publication and conference proceedings will help strengthen and enhance the efficiency of ART-R surveillance and response and support policy decisions.

CRD42019133366.