Researchers from PSI and the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) have published a new review in The Lancet Microbe outlining the key clinical characteristics and pathogenesis of Nipah virus disease.
Nipah virus, which has recently caused an outbreak in West Bengal, India, is a highly infectious pathogen that is primarily spread from animals to humans. It was first identified in 1998 following an outbreak among pig farmers in Malaysia and Singapore. Subsequent outbreaks in the early 2000s were linked to bats transmitting the virus through contamination of raw date palm sap, a popular delicacy in Bangladesh and India. The virus can also spread from person to person, particularly through close physical contact and exposure to respiratory secretions or other bodily fluids of an infected individual, most often within households or healthcare settings.
Although the virus has so far been confined to South and South-East Asia, its widespread animal reservoirs and potential for human-to-human transmission have led to the World Health Organization identifying it as a threat to global health security.
Current understanding of the clinical characteristics and pathogenesis of Nipah virus disease remains limited. This lack of robust evidence presents significant challenges for the design of trials evaluating potential vaccines and therapeutic candidates, progressing through the research and development pipelines. As a result, there is no systematic approach to improving patient care, and disease management is currently restricted to supportive treatment.
To address these gaps, researchers conducted a systematic review of 59 studies reporting on 717 cases of Nipah virus disease. The aim was to identify the key clinical features and underlying disease mechanisms associated with infection.
Key findings include:
- Evidence of neurological involvement in 71% of patients who underwent brain imaging
- Neurological symptoms were common, with 70% of patients presenting with headache, 65% with confusion, and 62% with altered consciousness
- Respiratory symptoms were also frequently reported, with 45% of patients presenting with cough and 58% experiencing breathing difficulties
- Pulmonary abnormalities in 80% of patients who had imaging performed, consistent with viral pneumonitis or acute respiratory distress.
- High case-fatality rate of 69%, with more than a quarter of survivors experiencing persistent neurological deficits
- Differences in clinical presentation were observed between Nipah virus strains: infections caused by the Bangladesh/India strain (NiV-B) showed more frequent respiratory involvement and higher mortality than those caused by the Malaysia strain (NiV-M).
In addition to these findings, the review makes several recommendations to strengthen future outbreak responses. The authors found that viral RNA is detectable in the bloodstream between four and ten days after symptom onset, and in the central nervous system from around five days after symptom onset. This underscores a narrow window for effective antiviral intervention and highlights the need for therapeutic agents capable of crossing the blood-brain barrier and penetrating multiple tissues to effectively treat the infection.
The review also identifies a critical lack of post-mortem examinations, largely due to cultural, religious, and biosafety concerns. The authors suggest alternative approaches to address this gap, including minimally invasive tissue sampling, verbal autopsies, and non-invasive imaging techniques.
Lead author Dr Md Zakiul Hassan, DPhil Candidate in Clinical Medicine at PSI and Associate Scientist at icddr,b, said “This review highlights missed opportunities to generate reliable evidence on the clinical features of Nipah virus disease due to inadequate and incomplete data, inconsistency in reporting, and a lack of agreed terminology. It underscores the need for a coordinated research response across affected countries, with harmonised research methods and universally applicable tools, to support the development and optimisation of clinical trials for potential treatments.”
Co-author Professor Piero Olliaro, Professor of Poverty Related Infectious Diseases at PSI and ISARIC Director of Science, added that “Despite gaps in the available evidence, these data still provide useful information to guide the design of future clinical studies, such as the timing of intervention, the need to account for distinct disease phenotypes, and the selection of clinically-meaningful and patient-relevant endpoints beyond mortality.”