Nipah virus (NiV) is a WHO Blueprint priority zoonotic paramyxovirus (genus Henipavirus) causing severe encephalitis and/or respiratory disease with a case fatality rate of 40–75%. [1-2] First identified in Malaysia in 1998, outbreaks continue in Bangladesh and India, with no approved vaccines or therapeutics. [3-4] The virus is classified as a BSL-4 pathogen. [5]
1. History
- Exposure history is paramount: Travel to or residence in endemic regions (Malaysia, Bangladesh, India — particularly Kerala, West Bengal) [6-7]
- Contact with Pteropus fruit bats, pigs, horses, or their excreta [8-9]
- Consumption of raw date palm sap (major transmission route in Bangladesh) [10-11]
- Close contact with a confirmed or suspected NiV patient — touching, feeding, nursing, or exposure to body fluids [12-13]
- Incubation period: Median 9.5–10 days (range 4–21 days) [5][12]
- Prodrome: 3–4 days of fever, headache, myalgia, dizziness, nausea/vomiting [14-15]
- Progression to altered sensorium, respiratory distress, seizures
- Ask about occupation (pig farming, abattoir work), recent funeral attendance (corpse-to-person transmission documented), and known outbreak clusters [3][11]
2. Alarm Features
- Rapidly declining consciousness or GCS deterioration
- Segmental myoclonus, areflexia, hypotonia — brainstem involvement signs [14]
- Abnormal doll's-eye reflex and tachycardia — independently associated with mortality [14]
- Intractable hypotension/bradycardia suggesting myocarditis [16]
- Acute respiratory distress (bilateral infiltrates, ARDS) [12][16]
- Seizures (39.2% of cases) [1]
- Viremia detectable on diagnosis — associated with 100% fatality in one series [17]
- Clustering of encephalitis cases in a community or healthcare setting should trigger immediate public health alert [7]
3. Medications
- No approved antiviral therapy exists [3-4]
- Ribavirin: Only therapeutic with human outbreak data; associated with 36% mortality reduction in the Malaysian outbreak (open-label, historical controls) — used on compassionate basis. No statistically significant benefit confirmed in the 2018 Kerala outbreak [3][16][18]
- Remdesivir: Protective in African green monkey challenge model when initiated within 24 hours of exposure (IV, 12-day course); no human efficacy data [19-20]
- Favipiravir: Fully protective in hamster model; no human data [21]
- m102.4 monoclonal antibody: Phase 1 safety data in humans; targets henipavirus G glycoprotein; compassionate use protocol developed for future outbreaks; dosing: single 20 mg/kg IV dose (or two doses 48 hours apart for established disease) [18][20]
- Supportive care remains the standard: mechanical ventilation, vasopressors, seizure management, ICP management [3][22]
- Empiric acyclovir should be started pending HSV encephalitis exclusion [23]
The following figure illustrates the antiviral drug targets in the NiV life cycle, including fusion inhibitors and RdRp inhibitors:
4. Diet
- Avoid raw date palm sap — primary zoonotic transmission route in Bangladesh; bats contaminate sap collection pots [10-11][25]
- Avoid consumption of fruits partially eaten by bats or fallen fruit in endemic areas
- No specific dietary management once infected; standard ICU nutrition protocols apply
- Hydration management per encephalitis/ARDS protocols
5. Review of Systems
- Neurologic: Headache, dizziness, altered sensorium, confusion, hallucinations, focal deficits, seizures, drowsiness [14][23]
- Respiratory: Cough, dyspnea, respiratory distress (prominent in Bangladesh strain NiV-B) [12][26]
- Cardiovascular: Palpitations, chest pain (myocarditis) [16]
- GI: Nausea, vomiting (27–42.6%), abdominal pain [1][14]
- Constitutional: Fever (80–100%), myalgia (47%), fatigue [1][10]
- Other: Increased salivation (noted in Bangladesh surveillance) [10]
6. Collateral History and Family History
- Critical to obtain: Contact history with any febrile encephalitis patient in the preceding 3 weeks
- Household members, caregivers, and healthcare workers are at highest risk for person-to-person transmission [12-13]
- Spouses of case patients had 14% infection rate vs. 1.3% for other close family members [13]
- Duration of exposure >48 hours and exposure to body fluids significantly increase transmission risk [13]
- Funeral attendance and body preparation of deceased NiV patients — documented transmission route [3]
- No hereditary predisposition identified; family clustering reflects shared exposure
7. Risk Factors
- Geographic: Residence in or travel to Bangladesh, India (Kerala, West Bengal), Malaysia, Singapore, Philippines [6-7]
- Occupational: Pig farming, abattoir work, veterinary work [14][23]
- Behavioral: Consumption of raw date palm sap, contact with bat-contaminated fruit [10-11]
- Healthcare exposure: Nosocomial transmission is well-documented; healthcare workers caring for NiV patients without adequate PPE [12][27]
- Close contact: Touching, feeding, or nursing infected patients; exposure to respiratory secretions or body fluids [13]
- Seasonal: Outbreaks in Bangladesh peak December–April (date palm sap harvesting season) [10][25]
- Age ≥45 years with respiratory symptoms — highest predicted reproduction number (R₀ = 1.1) [13]
8. Differential Diagnosis
- Japanese encephalitis — historically confused with NiV in Malaysia; distinguished by MRI pattern (deep gray matter involvement vs. NiV's white matter lesions) and epidemiology (mosquito-borne, rice paddy exposure) [28-29]
- Herpes simplex encephalitis — temporal lobe predominance on MRI; CSF HSV PCR positive [30]
- Cerebral malaria — travel history, peripheral smear, rapid diagnostic test
- Bacterial meningitis/encephalitis — CSF Gram stain, culture, higher WBC counts
- Other arboviral encephalitides — West Nile, Eastern equine, dengue; serology-based diagnosis [30]
- Autoimmune encephalitis — subacute onset, psychiatric features, anti-NMDAR antibodies [30]
- Hendra virus — closely related henipavirus; Australia; horse exposure [8]
- Influenza-associated encephalopathy
- Rabies — animal bite history, hydrophobia
- Atypical pneumonia (if respiratory-predominant presentation) — Legionella, Mycoplasma, COVID-19
9. Past Medical History
- No specific comorbidities identified as major risk modifiers, though healthcare availability and quality affect outcomes [2]
- Prior NiV infection: Relapsed encephalitis occurs in 7.5% of acute encephalitis survivors; late-onset encephalitis in 3.4% of initially non-encephalitic cases, at a mean interval of 8.4 months [31]
- Immunosuppression status should be assessed (may affect viral clearance)
- Document vaccination history (to exclude vaccine-preventable encephalitides)
10. Physical Exam
- Vitals: Fever (80–100%), hypertension and tachycardia (brainstem dysfunction), or bradycardia and hypotension (myocarditis) [14][16]
- Neurologic:
- Reduced level of consciousness (55%) [14]
- Segmental myoclonus (32%) — distinctive finding [14]
- Areflexia and hypotonia (56% had reduced reflexes) [14]
- Nuchal rigidity (28%), cerebellar signs (9%) [15]
- Abnormal doll's-eye reflex — poor prognostic sign [14]
- Focal neurologic deficits, cranial nerve palsies
- Respiratory: Tachypnea, crackles (bilateral infiltrates in ~82% on CXR in Kerala outbreak) [16]
- Cardiovascular: Signs of myocarditis — muffled heart sounds, gallop rhythm
- No exanthem typically seen
11. Lab Studies
- Confirmatory: Real-time RT-PCR (gold standard) — specimens: throat/nasal swab, blood, urine, CSF. Requires BSL-3 or BSL-4 laboratory [5][12][26]
- Serology: IgM capture ELISA (useful as primary screening tool; 99.3% specificity, 100% sensitivity); IgG ELISA for convalescent/seroprevalence studies [26][32]
- CSF: Pleocytosis in ~75% (mean ~40 cells/mm³, lymphocytic), elevated protein (mean 69 mg/dL), normal glucose. CSF virus isolation correlates with mortality [14-15][33]
- CBC: Lymphopenia (common), thrombocytopenia (30%) [14][23]
- Chemistry: Hyponatremia (45%), elevated AST (42%), elevated ALT (33%) [14][23]
- Prognostic: Detectable viremia at diagnosis → 100% fatality; IgG positivity at diagnosis → better survival [17]
- Standard encephalitis workup to exclude mimics: HSV PCR, arboviral serologies, blood cultures, malaria smear
12. Imaging
- MRI Brain (preferred modality):
- Acute encephalitis: Multiple discrete 2–7 mm high-signal lesions on T2/FLAIR in subcortical and deep white matter of cerebral hemispheres; cortical and brainstem lesions also seen; no mass effect or edema [28][34-35]
- Lesions represent microinfarctions from small vessel vasculitis [28][35]
- DWI: Restricted diffusion (hyperintense) in acute phase, decreasing over time [29][34]
- Leptomeningeal enhancement in some cases [29]
- Relapsed encephalitis: Confluent cortical gray matter involvement — distinct from acute pattern [31][35]
- MRI is more sensitive than CSF examination for detecting disease [14]
The following MRI demonstrates the characteristic findings in acute versus relapsed Nipah encephalitis:
- CT Brain: Usually normal in acute phase — insufficient sensitivity [14]
- Chest X-ray: Bilateral interstitial infiltrates (common, especially NiV-B strain); may present as atypical pneumonia pattern [16][23]
13. Special Tests
- RT-LAMP assay (reverse transcription loop-mediated isothermal amplification): More sensitive than RT-PCR; potential for rapid point-of-care use in outbreak settings [3]
- Virus isolation: Vero cell culture with syncytial cell formation — requires BSL-4; not routinely attempted due to biosafety risk [14]
- Whole genome sequencing: For phylogenetic analysis and strain identification (Malaysia vs. Bangladesh lineage) [12][36]
- EEG: Nonspecific diffuse slowing; periodic complexes correlate with severity and poor outcome [14]
- SPECT: Shows evolution from focal hyperperfusion to hypoperfusion in relapsed cases [31]
- No validated clinical scoring system specific to NiV exists; GCS for encephalitis severity monitoring
14. ECG
- ECG indicated to evaluate for myocarditis — a recognized clinical prototype [16]
- Look for: Sinus bradycardia, ST-segment changes, conduction abnormalities, low voltage
- Tachycardia (sinus) is common and associated with brainstem dysfunction and poor prognosis [14]
- Continuous cardiac monitoring recommended in all hospitalized cases
15. Assessment
Three overlapping clinical phenotypes: [16]
- Encephalitis (most common, ~83%) — progressive brainstem dysfunction with high mortality
- Acute respiratory distress syndrome — prominent in Bangladesh strain (NiV-B)
- Myocarditis — hemodynamic instability requiring vasopressors
- Spectrum ranges from asymptomatic infection to rapidly fatal encephalitis [1][8]
- Case fatality rate: 40–75% overall; up to 91% in some outbreaks (Kerala 2018); 86% in recent Bangladesh outbreaks [12][17]
- Mortality predictors: Coma, abnormal doll's-eye reflex, tachycardia, hypertension, vomiting, segmental myoclonus, CSF virus isolation, viremia at diagnosis [14][17][33]
- Survivors: 53% full recovery, 15% persistent neurologic deficits [14]
- Relapsing/late-onset encephalitis: Unique complication occurring months after initial infection in 3.4–7.5% [31]
The following figure from an NEJM study illustrates person-to-person transmission dynamics in Bangladesh, showing that a minority of cases drive most transmission events:
16. Treatment Plan
Initial Stabilization
- Airborne isolation room immediately [37]
- ABCs with full PPE; intubation and mechanical ventilation for ARDS or GCS ≤8
- Vasopressor support for myocarditis-related hemodynamic instability [16]
- Seizure management with standard anticonvulsants
- Empiric IV acyclovir until HSV encephalitis excluded [23]
- ICP monitoring and management as indicated
Antiviral Therapy (compassionate/investigational)
- Ribavirin — may be considered on compassionate basis; limited evidence [3]
- Remdesivir — strongest preclinical evidence (NHP model); may be considered if available within 24 hours of exposure [19-20]
- m102.4 monoclonal antibody — available through compassionate use protocols in some settings; 20 mg/kg IV [18]
- Contact WHO, CDC, or national health authority for access to investigational therapeutics [22]
Supportive Care
- Intensive supportive therapy is the current standard of care [3]
- Mechanical ventilation (lung-protective strategy for ARDS)
- Hemodynamic support, renal replacement therapy as needed
- Nutritional support, DVT prophylaxis, stress ulcer prophylaxis
17. Disposition
- All confirmed or suspected NiV cases require ICU-level care in an airborne infection isolation room [37]
- Immediate notification of local/state public health authorities and CDC [37]
- NiV is a nationally notifiable condition and a potential bioterrorism agent
- Contact tracing of all exposed individuals within 21 days [12][37]
- Quarantine of high-risk contacts for 21 days (maximum incubation period)
- Transfer to a facility with BSL-4 diagnostic capability and high-containment clinical care if not available locally
- Specialist consultation: Infectious disease, neurology, critical care, pulmonology
Infection Control (per CDC): [37]
- Suspected stable patients: N95/PAPR + fluid-resistant gown + face shield/goggles + gloves
- Confirmed or unstable patients: Impermeable gown/coverall + N95/PAPR + double gloves with extended cuffs + boot covers + apron
- Minimize personnel entering the room; maintain entry log [37]
- Avoid aerosol-generating procedures when possible; if necessary, perform in negative-pressure room [37]
18. Follow Up / Return Precautions
- Survivors require long-term neurologic follow-up — 15% have persistent neurologic deficits [14]
- Monitor for relapsed encephalitis (7.5% of survivors) and late-onset encephalitis (3.4% of initially mild/asymptomatic cases) — can occur months after initial infection [31]
- Serial MRI if new neurologic symptoms develop post-recovery
- Clearance of virus from oropharyngeal space begins around day 16–20 post-illness onset — informs isolation duration [17]
- Return precautions for discharged contacts: Seek immediate care for fever, headache, altered mental status, respiratory symptoms, or myalgia within 21 days of exposure
- Psychological support for survivors and families given high mortality among contacts
- Public health follow-up: Continued surveillance of bat populations and date palm sap harvesting practices in endemic areas [10][25]
References
1. A Systematic Review of Case Reports on Mortality, Modes of Infection, Diagnostic Tests, and Treatments for Nipah Virus Infection. — Alla D, Shah DJ, Adityaraj N, et al. Medicine. 2024.
2. The Rising Threat of Nipah Virus: A Highly Contagious and Deadly Zoonotic Pathogen. — Ganguly A, Mahapatra S, Ray S, et al. Virology Journal. 2025.
3. Medical Countermeasures Against Henipaviruses: A Review and Public Health Perspective. — Gómez Román R, Tornieporth N, Cherian NG, et al. The Lancet. Infectious Diseases. 2022.
4. Therapeutic Intervention Strategies for Nipah Virus Infection: A Scoping Review. — Kusuma IY, Tayeb BA, Zidan MJ, et al. Infectious Diseases. 2026.
5. An Emerging Zoonotic Disease to Be Concerned About - A Review of the Nipah Virus. — Paliwal S, Shinu S, Saha R. Journal of Health, Population, and Nutrition. 2024.
6. Nipah Virus, an Emerging Zoonotic Disease Causing Fatal Encephalitis. — Alam AM. Clinical Medicine. 2022.
7. Nipah Virus in South Asia: From Emergence to Enduring Preparedness' Challenges. — Gupta N, Gkrania-Klotsas E, Drexler JF, et al. Clinical Microbiology and Infection : The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2026.
8. Nipah Virus Infection. — Ang BSP, Lim TCC, Wang L. Journal of Clinical Microbiology. 2018.
9. Henipavirus Zoonosis: Outbreaks, Animal Hosts and Potential New Emergence. — Li H, Kim JV, Pickering BS. Frontiers in Microbiology. 2023.
10. Tackling a Global Epidemic Threat: Nipah Surveillance in Bangladesh, 2006-2021. — Satter SM, Aquib WR, Sultana S, et al. PLoS Neglected Tropical Diseases. 2023.
11. Transmission of Human Infection With Nipah Virus. — Luby SP, Gurley ES, Hossain MJ. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2009.
12. Outbreak Investigation of Nipah Virus Disease in Kerala, India, 2018. — Arunkumar G, Chandni R, Mourya DT, et al. The Journal of Infectious Diseases. 2019.
13. Transmission of Nipah Virus — 14 Years of Investigations in Bangladesh. — Nikolay B, Salje H, Hossain MJ, et al. The New England Journal of Medicine. 2019.
14. Clinical Features of Nipah Virus Encephalitis among Pig Farmers in Malaysia. — Goh KJ, Tan CT, Chew NK, et al. The New England Journal of Medicine. 2000.
15. Emerging Viral Infections of the Central Nervous System: Part 2. — Tyler KL. Archives of Neurology. 2009.
16. Clinical Manifestations of Nipah Virus-Infected Patients Who Presented to the Emergency Department During an Outbreak in Kerala State in India, May 2018. — Chandni R, Renjith TP, Fazal A, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2020.
17. Insights Into the Acute Phase of Nipah Virus Infection: Clinical Features, Viral Detection, and Humoral Immune Response. — Satter SM, Sultana S, Choudhury SS, et al. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. 2025.
18. Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Human Monoclonal Antibody Targeting the G Glycoprotein of Henipaviruses in Healthy Adults: A First-in-Human, Randomised, Controlled, Phase 1 Study. — Playford EG, Munro T, Mahler SM, et al. The Lancet. Infectious Diseases. 2020.
19. Remdesivir (GS-5734) Protects African Green Monkeys From Nipah Virus Challenge. — Lo MK, Feldmann F, Gary JM, et al. Science Translational Medicine. 2019.
20. Therapeutics for Nipah Virus Disease: A Systematic Review to Support Prioritisation of Drug Candidates for Clinical Trials. — Chan XHS, Haeusler IL, Choy BJK, et al. The Lancet. Microbe. 2025.
21. Favipiravir (T-705) Protects Against Nipah Virus Infection in the Hamster Model. — Dawes BE, Kalveram B, Ikegami T, et al. Scientific Reports. 2018.
22. Improving Clinical Care of Patients in Nipah Outbreaks: Moving Beyond 'Compassionate Use'. — Hassan MZ, Rojek A, Olliaro P, Horby P. The Lancet Regional Health. Southeast Asia. 2025.
23. Outbreak of Nipah-Virus Infection Among Abattoir Workers in Singapore. — Paton NI, Leo YS, Zaki SR, et al. Lancet. 1999.
24. Advancements in Nipah virus treatment: Analysis of current progress in vaccines, antivirals, and therapeutics. — Mishra G, Prajapat V, Nayak D. Immunology. 2024.
25. Nipah Virus Dynamics in Bats and Implications for Spillover to Humans. — Epstein JH, Anthony SJ, Islam A, et al. Proceedings of the National Academy of Sciences of the United States of America. 2020.
26. Nipah Virus: An Overview of the Current Status of Diagnostics and Their Role in Preparedness in Endemic Countries. — Garbuglia AR, Lapa D, Pauciullo S, Raoul H, Pannetier D. Viruses. 2023.
27. The Role of Infection Prevention and Control in the Mitigation of Human-to-Human Transmission of Nipah Virus: A Systematic Review. — Pritchard S, Hornsey E. Antimicrobial Resistance and Infection Control. 2025.
28. Viral Encephalitis: Familiar Infections and Emerging Pathogens. — Whitley RJ, Gnann JW. Lancet. 2002.
29. Nipah Viral Encephalitis or Japanese Encephalitis? MR Findings in a New Zoonotic Disease. — Lim CC, Sitoh YY, Hui F, et al. AJNR. American Journal of Neuroradiology. 2000.
30. Acute Viral Encephalitis. — Tyler KL. The New England Journal of Medicine. 2018.
31. Relapsed and Late-Onset Nipah Encephalitis. — Tan CT, Goh KJ, Wong KT, et al. Annals of Neurology. 2002.
32. Development of Nipah Virus-Specific IgM & IgG ELISA for Screening Human Serum Samples. — Shete AM, Jain R, Mohandas S, et al. The Indian Journal of Medical Research. 2022.
33. High Mortality in Nipah Encephalitis Is Associated With Presence of Virus in Cerebrospinal Fluid. — Chua KB, Lam SK, Tan CT, et al. Annals of Neurology. 2000.
34. Nipah Virus Encephalitis: Serial MR Study of an Emerging Disease. — Lim CC, Lee KE, Lee WL, et al. Radiology. 2002.
35. MR Imaging Features of Nipah Encephalitis. — Sarji SA, Abdullah BJ, Goh KJ, Tan CT, Wong KT. AJR. American Journal of Roentgenology. 2000.
36. Nipah Virus Outbreak in Kerala State, India Amidst of COVID-19 Pandemic. — Yadav PD, Sahay RR, Balakrishnan A, et al. Frontiers in Public Health. 2022.
37. Post-Travel Evaluation to Rule Out Viral Special Pathogen Infection. — Catherine Brown, Mary J. Choi, Susan McLellan, and Trevor Shoemaker CDC Yellow Book. 2025.