Nipah Virus Infection

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]

• 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]

• 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]

• 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:

• 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

• 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]

• 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

• 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]

• 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

• 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)

• 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

• 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

• 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]

• 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

• 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

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:

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

• 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]

• 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]

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