Following the first known outbreak in Malaysia in 1998-99, annual localised outbreaks occur in India and Bangladesh causing encephalitis and respiratory failure with 70% mortality.

The relatively small number of cases makes testing therapeutic interventions for NiV disease challenging because of limited clinical data to inform therapeutic trial methodologies, and because trials will be inadequately powered.

Instead, the incidence of acute meningoencephalitis is high: therefore, we have adopted a syndromic approach and initiated an observational cohort study of acute encephalitis in Bangladesh to prepare for trials evaluating potential therapeutic candidates.

In parallel we are collecting available information on the pathophysiology of NiV disease and candidate treatments and generating pathways to test and make new interventions available and affordable.

Characterising disease

Nipah is a highly lethal zoonotic paramyxovirus that can infect humans through contact with infected bats, pigs, or humans, or by consuming contaminated raw date palm sap. It causes a rapidly progressive illness that affects the respiratory and central nervous systems, including respiratory distress and encephalitis, with a very high case-fatality ratio.  Due to limited data from human cases and insights from animal experiments, our understanding of the natural history and pathogenesis of Nipah virus disease remains insufficient. 

We are therefore collecting available information on disease presentation and physiopathology, as well as generating new evidence on disease characterisation and outcomes that will allow to design new intervention strategies.

Systematic review on pathogenesis of Henipavirus infection:

Integrating data from human cases, naturally infected animals, and laboratory experiments is crucial for a comprehensive understanding of henipavirus pathogenesis, identifying knowledge gaps, potential therapeutic targets, and prognostic markers related to disease severity and progression. The objective of this review is to summarise existing evidence on the pathogenesis of Henipavirus infection in humans, other animals and experimental animal models to support selection of potential therapeutic candidates and strategies for interventions.

The PROSPERO registered review protocol can be found here: (CRD42023463537).

Bangladesh Acute encephalitis syndrome cohort study (BASE cohort):

ISARIC, in collaboration with partners in Nipah-endemic countries including icddr,b in Dhaka, Bangladesh, the Institute of Epidemiology Disease Control and Research (IEDCR), the Bangladesh Ministry of Health, and the US Centers for Disease Control and Prevention, initiated an observational study in three tertiary care hospitals located within the Nipah belt in Bangladesh, which have ongoing Nipah virus surveillance.

This study is designed to describe the patient population, clinical features, clinical course from initial stages to its full manifestation, treatment practices, and clinical outcomes of patients who come to hospitals with AES including NiV infection, with the ultimate goal to inform the design of clinical trials of new treatments for NiV specifically and acute encephalitis syndrome more broadly.

Working alongside the NiV surveillance programme currently ongoing in Bangladesh, we will enrol up to 2000 patients of all ages coming to selected study hospitals with AES. We will explain the benefits and potential risks of the study and invite patients to take part in the study. The study staff will follow each study participant during their hospital stay and up to 90 days post-discharge. Discussions with the patient and medical record reviews will be used to record demographic and clinical data on the day they join the study, day 3, day 7, the day of critical care admission (as relevant), the day they leave the study and on 90 days after leaving the study. An aliquot of the cerebrospinal fluid (CSF) collected under the concurrent NiV surveillance protocol will be tested for common viral and bacterial pathogens causing AES in the icddr,b laboratory.

Developing methodologies

The death rate in patients with confirmed NiV infection is very high and efforts are underway to develop treatments that target NiV. These potential new treatments will need be evaluated for safety and efficacy in clinical trials. Work is needed to describe and estimate key clinical parameters to improve understanding of the disease which can improve the design of clinical trials of potential treatments. Since NiV infection is rare, interventions aimed at improving patient outcomes in the broader group of patients with acute encephalitis syndrome (AES), including NiV infection, is more practical. By focusing on encephalitis—which represents the main clinical presentation in NiV disease patients (97% in India, 90% in Bangladesh, 88% in Singapore, 64% in the Philippines, and 55% in Malaysia)—and testing therapeutic strategies for all-cause encephalitis in endemic regions, we can potentially enhance the management and outcomes of the disease broadly. Previous trials have failed to improve encephalitis outcomes, but by incorporating NiV-specific interventions into a wider syndromic strategy, this approach not only tackles a major health issue in a patient-centred way, but also offers a viable method for managing low NiV caseloads and enhancing clinical research capabilities to adapt to changing epidemiological patterns.

We will utilize data from the ongoing systematic review of Henipavirus pathogenesis and the BASE cohort study to identify key clinical parameters for designing clinical trials for potential treatment. Subsequently, we will assemble a consultation group comprising clinicians, statisticians, clinical researchers, patients, public health officials, regulators, and ethics boards to gather their insights on the trial design for all-cause encephalitis.)

More details on our approach to NiVD can be found in this paper.

Improving treatment

Currently, the clinical management of encephalitis patients, including those affected by NiV, primarily focuses on supportive care. This includes the administration of oxygen, fluids, nutritional support, and resuscitation, when necessary, along with symptomatic treatments such as antipyretics, anticonvulsants, and interventions for complications like raised intracranial pressure, hypoglycaemia, and shock. Empirical treatment often begins with antibiotics (e.g., intravenous ceftriaxone), antivirals (e.g., intravenous acyclovir), and steroids. Patients showing signs of severe deterioration, such as decreased consciousness, uncontrolled seizures, haemodynamic instability, or multiorgan failure, are considered for transfer to intensive care units (ICU) or more specialized centres. However, improving outcomes for NiV patients remains challenging due to the variability in the availability of standardized supportive care and timely ICU access in endemic regions. Advancing knowledge to guide clinical care and improve outcomes for isolated NiV cases and small clusters will also be good preparation for a potential larger epidemic in the future.

Systematic review of Henipavirus therapeutic candidates:

No therapeutics have been licensed to data against NiV to date, and only few candidates are in development. To progress effectively, we need therapeutic candidates to advance through pre-clinical research, early human safety testing, and manufacturing so that they can be tested clinically, and also clinical trial protocols to ensure a coordinated and standardised assessment of their clinical safety and efficacy.  We conducted this systematic review to assess the evidence for the safety and efficacy of therapeutic options (monoclonal antibodies and small molecules) for Nipah virus and other henipaviral diseases to support candidate prioritisation for further evaluation in clinical trials.

Our findings showed that at present, there is sufficient evidence to trial only m102.4 and remdesivir (singly and/or in combination) for prophylaxis and early treatment of Nipah virus disease.

This is the most detailed systematic review and analysis of the Nipah virus therapeutics landscape to date, including all available in vivo and related in vitro data on the safety, efficacy, and pharmacokinetics of monoclonal antibodies and small molecules with the specific aim of supporting prioritisation for clinical trials. We also present a roadmap for how in vivo development of Nipah therapeutics could be strengthened to achieve greater equity, efficiency, and effectiveness.

The details of the review methods and results can be found here.

Use case and TPP development

Developing safe and effective therapeutic agents to treat acute NiVD and its acceptance by the end-users (clinicians and patients) is crucial for improving survival rates and reducing associated morbidity and mortality, and long-term disability. However, to design and select therapeutics that achieve these objectives, we need to first define the clinical circumstances in which a therapeutic might be used and the therapeutic goal (use-cases) and the desired characteristics of the therapeutic product (the Target Product Profile – TPP) to guide down-selection and prioritization of candidate products for clinical trials. 

Defining use-cases of potential therapeutic options as illustrated in the Figure is essential to support the development of the TPP that serves as a guide for drug developers and other actors in the clinical development pathway, indicating the necessary and suitable characteristics for future therapeutic candidates after consultation with key stakeholders and end-users.

Therefore, our objectives for this work are: 1) to define the use-cases for potential NiVD therapeutics, and 2) to understand country public health decision-makers, end-users’ (healthcare providers), and patients’ and survivors’ expectations on potential NiV therapies to inform R&D.

Figure: Potential interventions for Nipah virus disease

Figure: Potential interventions for Nipah virus disease

ISARIC, CEPI and ICMR workshop on Nipah medical counter measures:

ISARIC, in partnership with the Indian Council of Medical Research (ICMR) and the Coalition for Epidemic Preparedness Innovations (CEPI), organized a workshop focusing on the use cases of Nipah medical countermeasures, including vaccines, monoclonal antibodies, and small molecule therapeutics. The two-day workshop was held on April 23rd and 24th in New Delhi. Participants of the workshop included academic scientists from endemic countries and globally, representatives from the health ministries of India and Bangladesh, members of the Western Pacific Region Immunisation Technical Advisory Group, representatives from regional and global regulatory agencies, and representatives from product development companies.

 The first day included discussions on the WHO Southeast Asia Regional Strategy for the Prevention and Control of Nipah Virus Infection and review of Nipah virus disease. The second day specifically focused on defining use cases for Nipah medical countermeasures based on various scenarios, such as limited, amplified, and extended outbreaks, using assumptions specific to each.

To identify the use cases for medical countermeasures against Nipah, a three-step analytical process called the 7Ws (what, why, where, within, when, to whom, by whom) approach was utilized. This methodology strives to align with the WHO Evidence Considerations for Vaccine Policy (ECVP) as closely as possible.

Removing barriers

Identifying and evaluating therapeutic interventions for Nipah Virus Disease (NiVD) face three distinct challenges: epidemiological, operational, and market/policy-related. 

First, the epidemiological challenge arises from the disease’s low incidence and unpredictable outbreaks, even in endemic areas like Bangladesh, making traditional phase III efficacy trials unfeasible. Secondly, operational challenges are evident in the limited research infrastructure and clinical capacity in outbreak regions, which complicates the conduct of clinical trials and hinders timely diagnosis and research involvement. Lastly, the market and policy challenges reflect a lack of financial incentives for private sector investment in NiVD therapeutics due to the minimal number of cases and the insufficient public and private investments in R&D, resulting in a failure to develop new therapeutics or attract necessary partnerships for advancing drug development

To overcome the epidemiological, operational and market and policy challenges posed by NiVD and to effectively evaluate potential interventions for improving patient outcomes, a coordinated, public health-focused approach must be adopted that maximizes the chance of identifying and progressing the best therapeutic options in a timely way, and emphasizes transparency and equitable access to interventions for NiV-affected communities. 

We propose a model similar to the West Africa Lasa fever Consortium (WALC) to generate essential elements of a pathway to develop and make available new treatments to those in need. This model includes laying out a clinical development plan that is regulatory-compliant, clinically meaningful, and context-specific, as well as strengthening research sites’ capacity to meet regulatory quality standards (good clinical practices and good clinical laboratory practices) and ensuring good participatory practice for trials (GPP). Moreover, the model recognizes the need for involving key stakeholders both in NiV-endemic countries and internationally and establish an end-to-end partnership and financing structure in which all actors commit to the collective end goal of equitable access to effective treatments.

Developing value proposition and ensuring access to Nipah therapeutics:

To effectively respond to the urgent public health needs for NiV therapeutics, a comprehensive approach is required that includes securing funding from both international and regional sources, advocacy to policy makers and global stakeholders, and the development of a clinical trial platform embedded in the local health system that serves as the central asset around which value is created. The value proposition should be informed by a robust assessment of the risk of future outbreaks and the economic, societal, and health impacts that such outbreaks could generate. A partnership between drug developers and the trial sites platform should be defined upfront to serve public health goals, leveraging different capabilities and financing opportunities towards ultimate availability and access. Having pre-established agreements in place for availability and pricing will avoid repeating the inequalities seen in cases like Ebola and COVID-19.

Stigma Scale

Due to the potential impact of stigma on outbreak control and community cohesion, rapidly assessing and addressing stigma is a key component of a coordinated outbreak response and pandemic preparedness efforts. There is currently no cross-culturally validated and widely used tool for measuring stigma associated with infectious disease outbreaks, including Nipah virus. A proactive cross-outbreak approach to stigma survey development could overcome this limitation. It would also allow for assessment of the types and severity of stigma associated with Nipah virus in Bangladesh which is currently undetermined. ISARIC and icddr,b are collaborating to develop and validate a survey to assist with recognition and reduction of Nipah-related stigma. This project involves the following three phases: 

  1. Systematic review and stakeholder interviews
  2. Co-development of scale: Iterative development through feedback rounds with experts and piloting with community members. 
  3. Survey administration: the finalised survey will be administered to relevant community members.

 Better understanding stigma associated with Nipah virus is the first step to addressing any potential stigma, which is beneficial both for affected communities and outbreak control. 

The completed systematic review of outbreak-related stigma scales is available here.


Nipah Virus Therapeutics: A Systematic Review to Support Prioritisation for Clinical Trials (Preprint)

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Nipah virus disease: what can we do to improve patient care?

We propose a regionally led, patient-centred, and public health-centred, end-to-end framework that articulates a public health vision and a roadmap for research, development, manufacturing, and access towards the goal of improving patient outcomes. This framework includes co-creating a regulatory-compliant, clinically meaningful, and context-specific clinical development plan and establishing quality standards in clinical care and research capabilities at sites where the disease occurs. The Learn more

Public health vision led by ISARIC partners aims to tackle Nipah virus

15 January 2024: In a new paper published in The Lancet Infectious Diseases, researchers based in Bangladesh, Oxford and Geneva call for a comprehensive public health framework to counter Nipah virus and other neglected infectious diseases with pandemic potential.


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