Nipah Virus Disease

Infectious Disease MONDO:0020499 Pathograph 21 Show in embeddings browser Viral Encephalitis Zoonosis

Nipah virus disease is a zoonotic infection caused by Nipah virus, a henipavirus in the family Paramyxoviridae, whose natural reservoir is fruit bats of the genus Pteropus. Human infection follows exposure to infected bats, intermediate hosts such as pigs, or food contaminated with bat secretions (notably raw date palm sap), and produces a severe febrile illness that can progress to encephalitis, respiratory distress, and death with high case-fatality.

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7
Pathophys.
14
Phenotypes
21
Pathograph
4
Medical Actions
5
Trials
1
Models
19
References
1
Deep Research
⚙

Pathophysiology

7
Ephrin-B2/B3 receptor-mediated cell entry
The Nipah virus attachment glycoprotein engages the host ephrin-B2 and ephrin-B3 receptors to mediate entry into host cells. Because ephrin-B2 is evolutionarily conserved and widely expressed on vascular endothelium, and ephrin-B3 on neurons, the tissue distribution of these receptors is what determines the endothelial and neuronal tropism that drives the rest of the disease, and also underlies the virus's broad host-species range.
symbiont entry into host cell GO:0046718 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves symbiont entry into host cell (GO:0046718). GO:0046718 is a biological process from the Gene Ontology.
ephrin-B2/B3 acting as the henipavirus entry receptor GO:0001618 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves ephrin-B2/B3 acting as the henipavirus entry receptor, annotated with virus receptor activity (GO:0001618). GO:0001618 is a molecular function from the Gene Ontology.
Downstream
Endothelial tropism and systemic vasculitis Ephrin-B2 is widely expressed on vascular endothelium, so receptor-mediated entry establishes the endothelial infection underlying systemic vasculitis.
Central nervous system invasion Ephrin-B3 expression on neurons provides the receptor basis for direct neuronal infection of the central nervous system.
Type I interferon signaling antagonism Once inside the cell the virus expresses the accessory proteins that disable the host type I interferon response.
Show evidence (3 references)
PMID:39700307 SUPPORT Other
"The virus enters the host cells through Ephrin B2/B3 receptors"
States the receptor pair mediating Nipah virus entry into host cells.
PMID:39700307 SUPPORT Other
"inherent ability to use the evolutionarily conserved and widely expressed cellular receptor Ephrin B2 for entry"
Establishes that ephrin-B2 is conserved and widely expressed, which is what makes receptor distribution determine tropism.
PMID:24130486 SUPPORT In Vitro
"Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors."
Identifies the viral attachment glycoprotein G engaging host cell receptors as the initiating step of henipavirus entry.
Type I interferon signaling antagonism
Nipah virus accessory proteins expressed from the P gene antagonize type I interferon signaling by binding and sequestering STAT1 and STAT2. The V protein induces cytoplasmic high-molecular-weight STAT-containing complexes, and the phosphoprotein P sequesters STAT1/STAT2 into viral inclusion bodies; both prevent STAT activation and nuclear translocation. Blocking the innate antiviral response is what permits the virus to disseminate systemically before an effective interferon response is mounted.
negative regulation of type I interferon-mediated signaling pathway GO:0060339 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased negative regulation of type I interferon-mediated signaling pathway (GO:0060339). GO:0060339 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Systemic viral dissemination and febrile illness Suppression of the innate interferon response permits unchecked viral replication and systemic spread.
Show evidence (4 references)
PMID:15279700 SUPPORT In Vitro
"Similar to other paramyxoviruses, Henipaviruses inhibit IFN signal transduction through a virus-encoded protein called V."
Establishes the V protein as the henipavirus-encoded inhibitor of interferon signal transduction.
PMID:15279700 SUPPORT In Vitro
"This sequestration of STAT1 and STAT2 prevents STAT activation and blocks antiviral IFN signaling."
States the molecular consequence - STAT1/STAT2 sequestration prevents STAT activation and blocks antiviral interferon signaling.
PMID:36851768 SUPPORT In Vitro
"we show here that NiV can inhibit IFN-dependent antiviral signaling via a NiV P-dependent sequestration of STAT1 and STAT2 into viral IBs"
Adds the phosphoprotein P arm, sequestering STAT1/STAT2 into viral inclusion bodies, alongside the V-protein mechanism.
+ 1 more reference
Systemic viral dissemination and febrile illness
Unrestrained by the interferon response, the virus replicates in and spreads through highly vascular tissues, producing a widespread multisystemic vasculitis and the non-specific systemic febrile prodrome - fever, headache and vomiting - that precedes organ-specific disease.
Downstream
Endothelial tropism and systemic vasculitis Systemic spread through highly vascular tissues establishes the widespread endothelial infection.
Fever Systemic viral replication produces the febrile response.
Headache Part of the non-specific systemic prodrome of acute infection.
Vomiting Part of the non-specific systemic prodrome of acute infection.
Show evidence (1 reference)
PMID:19888339 SUPPORT Model Organism
"The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues."
Documents systemic dissemination with virus recoverable from multiple tissues. MODEL_ORGANISM because the observation is in the ferret model, though the authors state the pathology closely resembles human disease.
Endothelial tropism and systemic vasculitis
Nipah virus infects vascular endothelial and smooth muscle cells, producing a systemic vasculitis with thrombosis and parenchymal necrosis, especially in the central nervous system.
vascular endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves vascular endothelial cell, annotated with endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology. vascular smooth muscle cell CL:0000192 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves vascular smooth muscle cell, annotated with smooth muscle cell (CL:0000192). CL:0000192 is a cell type from the Cell Ontology.
Downstream
Syncytium formation Infection of vascular endothelium is the setting in which syncytial giant cells arise; autopsy describes endothelial damage, necrosis and syncytial giant cell formation together in affected vessels.
Central nervous system invasion Vasculitis with thrombosis and parenchymal necrosis is most marked in the central nervous system, accompanying direct neuronal infection.
Pulmonary involvement and respiratory tract infection The same vascular changes involve the lungs, contributing to the pulmonary arm of clade I disease.
Show evidence (2 references)
PMID:12466131 SUPPORT Human Clinical
"The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system."
Autopsy findings from human cases show systemic vasculitis with thrombosis and necrosis.
PMID:12466131 SUPPORT Human Clinical
"IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels."
Immunohistochemistry localizes Nipah antigen to vascular endothelial and smooth muscle cells.
Central nervous system invasion
The virus infects neurons of the central nervous system, producing an acute encephalitis alongside vasculitis-associated injury.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
Animal models
Nonhuman primate henipavirus challenge model African green monkey recapitulates Henipavirus challenge in animal models reproduces the encephalitic arm of human disease, not only the respiratory arm.
Downstream
Encephalitis Direct neuronal infection with accompanying vasculitis produces the acute encephalitis that defines symptomatic human Nipah virus disease.
Reduced consciousness Encephalitic involvement of the brain stem underlies the reduced level of consciousness documented in 55% of the Malaysian case series.
Seizure Cortical involvement in acute Nipah encephalitis manifests clinically as convulsions.
Myoclonus Brain-stem and upper cervical cord involvement produces the distinctive segmental myoclonus of Nipah encephalitis.
Areflexia Brain-stem and upper cervical cord involvement produces areflexia.
Hypotonia Brain-stem and upper cervical cord involvement produces hypotonia.
Show evidence (2 references)
PMID:12466131 SUPPORT Human Clinical
"Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons."
Viral antigen is abundant in neurons, evidencing direct CNS neuronal infection.
PMID:38399954 SUPPORT Other
"Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates."
The review characterizes human Nipah infection as a rapidly progressive encephalitis.
Syncytium formation
Nipah virus induces fusion of infected cells into multinucleated syncytial giant cells, prominent in affected blood vessels.
Show evidence (1 reference)
PMID:12466131 SUPPORT Human Clinical
"Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels."
Syncytial giant cells are observed in affected vessels of human autopsy tissue.
Pulmonary involvement and respiratory tract infection
Beyond the encephalitic arm, Nipah virus produces severe pulmonary involvement with respiratory tract infection and vascular injury of the lungs. This arm is clade-dependent and is the principal feature distinguishing the Bangladesh/India clade I outbreaks, in which severe respiratory disease accompanies encephalitis and facilitates person-to-person transmission, from the Malaysian clade II outbreak, which produced a largely pure encephalitic syndrome.
Animal models
Nonhuman primate henipavirus challenge model African green monkey recapitulates Nonhuman primate challenge reproduces the combined severe respiratory and encephalitic disease seen in human outbreaks.
Downstream
Respiratory distress Pulmonary infection and vascular injury of the lung manifest clinically as respiratory difficulty and, at the severe end, acute respiratory distress syndrome.
Acute respiratory distress syndrome Severe pulmonary involvement progresses to the clinical and radiographic picture of acute respiratory distress syndrome.
Cough Respiratory tract infection manifests as cough, among the most common presenting symptoms in the Bangladesh outbreaks.
Show evidence (5 references)
PMID:18444812 SUPPORT Human Clinical
"Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems."
Establishes the respiratory system, alongside the CNS, as a primary target of the infection.
PMID:18444812 SUPPORT Human Clinical
"including a severe respiratory component, appear distinct from clinical characteristics reported during earlier outbreaks in other countries."
Identifies the severe respiratory component as what distinguishes Bangladesh disease from the earlier Malaysian outbreak.
PMID:39700307 SUPPORT Other
"whereas many patients infected with NiV clade I had added severe pulmonary involvement"
Attributes severe pulmonary involvement specifically to clade I infection.
+ 2 more references
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Nipah Virus Disease Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

14
Digestive 1
Vomiting FREQUENT HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"The main presenting features were fever, headache, dizziness, and vomiting."
Snippet supports the disease-phenotype association. Author wording "main presenting features" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. The previous OCCASIONAL (5-29%) band contradicted this wording.
Immune 2
Encephalitis FREQUENT Infectious encephalitis HP:0002383 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Encephalitis, annotated with Infectious encephalitis (HP:0002383). HP:0002383 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:39119137 SUPPORT Other
"Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects."
Snippet supports the disease-phenotype association. The review describes encephalitis as what the virus causes, i.e. a predominant manifestation, which maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. No cohort percentage is reported.
PMID:38399954 SUPPORT Other
"Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates."
Snippet supports the disease-phenotype association and the FREQUENT band qualitatively ("human infection manifests as" a rapidly progressive encephalitis, i.e. predominant). No quantitative frequency is reported, so no higher band is claimed.
Relapsing and late-onset encephalitis VERY_RARE Infectious encephalitis HP:0002383 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Relapsing and late-onset Nipah encephalitis, annotated with Infectious encephalitis (HP:0002383), qualified as temporality recurrent. HP:0002383 is a phenotype from the Human Phenotype Ontology.
Temporal: RECURRENT
Show evidence (3 references)
PMID:10781618 SUPPORT Human Clinical
"Neurologic relapse occurred after initially mild disease in three patients."
Pattern B quantitative support: 3 of the 94 patients in the Malaysian series = 3.2%, which falls in the VERY_RARE band (<5%).
PMID:39700307 SUPPORT Other
"It is also important to monitor Nipah survivors continuously because of the rare possibility of relapse and late-onset NiV encephalitis"
Independently corroborates the band: author wording "rare" maps to VERY_RARE under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md, agreeing with the 3.2% figure above.
PMID:39700307 SUPPORT Other
"Late-onset reactivation encephalitis in Nipah appears to be non-contagious, but it is a concern because of the potential social stigma and significant morbidity/mortality risk associated with it."
Characterizes the late-onset form as reactivation, non-contagious, and carrying significant morbidity and mortality risk.
Metabolism 1
Fever FREQUENT HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:10781618 SUPPORT Human Clinical
"The main presenting features were fever, headache, dizziness, and vomiting."
Snippet supports the disease-phenotype association. Author wording "main presenting features" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. This series reports no per-symptom percentage, so no higher band is sourced.
PMID:18444812 SUPPORT Human Clinical
"Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
Snippet supports the disease-phenotype association. Author wording "the most common signs and symptoms" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. Hossain 2008 reports no per-symptom percentages, so no quantitative band is available.
Musculoskeletal 1
Hypotonia HP:0001252 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotonia (HP:0001252). HP:0001252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
Hypotonia was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem and upper cervical cord involvement.
Nervous System 5
Headache FREQUENT HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"The main presenting features were fever, headache, dizziness, and vomiting."
Snippet supports the disease-phenotype association. Author wording "main presenting features" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md.
Seizure FREQUENT HP:0001250 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18444812 SUPPORT Human Clinical
"Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
Snippet supports the disease-phenotype association. Author wording "the most common signs and symptoms" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. The previous OCCASIONAL (5-29%) band contradicted this wording; Hossain 2008 reports no per-symptom percentages.
Myoclonus HP:0001336 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myoclonus (HP:0001336). HP:0001336 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
Segmental myoclonus was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem involvement.
Areflexia HP:0001284 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Areflexia (HP:0001284). HP:0001284 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
Areflexia was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem and upper cervical cord involvement.
Persistent neurologic deficits in survivors OCCASIONAL Abnormality of the nervous system HP:0000707 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Persistent neurologic deficits, annotated with Abnormality of the nervous system (HP:0000707), qualified as temporality chronic. HP:0000707 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:10781618 SUPPORT Human Clinical
"Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits."
Pattern A quantitative support: 15% of the Malaysian series had persistent neurologic deficits, which falls in the OCCASIONAL band (5-29%).
Respiratory 3
Cough FREQUENT HP:0012735 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cough (HP:0012735). HP:0012735 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18444812 SUPPORT Human Clinical
"Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
Snippet supports the disease-phenotype association. Author wording "the most common signs and symptoms" maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md. The previous OCCASIONAL (5-29%) band contradicted this wording.
Respiratory distress HP:0002098 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory distress (HP:0002098). HP:0002098 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:18444812 SUPPORT Human Clinical
"clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak."
Snippet supports the disease-phenotype association only. The finding is reported for one of four Bangladesh outbreaks, so it cannot support a whole-disease frequency band; frequency is therefore omitted rather than estimated.
PMID:18444812 SUPPORT Human Clinical
"Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
Corroborates the disease-phenotype association: respiratory difficulty is listed among the most common signs and symptoms. The frequency band remains omitted, because this entry keeps the quantitatively unsupported respiratory arm conservative rather than inferring a whole-disease band.
Acute respiratory distress syndrome HP:0033677 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acute respiratory distress syndrome (HP:0033677). HP:0033677 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18444812 SUPPORT Human Clinical
"clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak."
Records ARDS specifically, by both clinical and radiographic criteria, in the fourth Bangladesh outbreak. Curated as a distinct, more specific phenotype alongside the broader Respiratory distress term (HP:0002098), which remains supported by the wider "respiratory difficulty" evidence.
Other 1
Reduced consciousness FREQUENT HP:0004372 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reduced consciousness (HP:0004372). HP:0004372 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:10781618 SUPPORT Human Clinical
"Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction."
Pattern A/B quantitative support: 52/94 = 55%, which falls in the FREQUENT band (30-79%) per docs/frequency-evidence-guidelines.md.
PMID:18444812 SUPPORT Human Clinical
"Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
Corroborates the disease-phenotype association in a second cohort. Author wording "the most common signs and symptoms" is consistent with the FREQUENT band already established quantitatively by Goh 2000 (55%).
💊

Medical Actions

4
Supportive and intensive care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Management is primarily supportive, including intensive care, management of encephalitis, and respiratory support; there is no licensed antiviral therapy or vaccine for human use.
Show evidence (5 references)
PMID:38399954 SUPPORT Other
"no therapeutic agents or vaccines have been approved for human use."
No approved therapeutics or vaccines exist, so care remains supportive.
PMID:39292378 SUPPORT Other
"To date, no approved vaccines or treatments have been available."
The review confirms the absence of approved vaccines or treatments, leaving supportive care as standard.
PMID:38185127 SUPPORT Other
"Although candidate vaccines for Nipah virus disease exist, developing new therapeutics has been underinvested."
Explains why supportive care remains the mainstay - therapeutic development has been underinvested despite candidate vaccines existing.
+ 2 more references
m102.4 monoclonal antibody
Action: antiviral agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antiviral agent therapy, annotated with Antiviral Therapy (NCIT:C16119). NCIT:C16119 is a clinical intervention from the NCI Thesaurus. Ontology label: Antiviral Therapy NCIT:C16119
Agent: m102.4 NCIT:C20401 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses m102.4, annotated with Monoclonal Antibody (NCIT:C20401). NCIT:C20401 is a therapeutic agent from the NCI Thesaurus.
m102.4 is a cross-reactive neutralizing human monoclonal antibody that targets the henipavirus attachment G glycoprotein and blocks its engagement of the host ephrin receptors, preventing viral entry. It is recommended as the specific management option to prevent severe disease in high-risk individuals, but global availability is limited, the disease progresses too rapidly for it to be given in many cases, and its activity may be restricted to the clade against which it was raised. No phase II/III efficacy trial has yet been reported.
Mechanism Target:
INHIBITS Ephrin-B2/B3 receptor-mediated cell entry — m102.4 binds the viral attachment G glycoprotein and blocks its engagement of the host ephrin receptors, so it acts directly on the receptor-mediated entry step rather than on a downstream consequence.
Show evidence (2 references)
PMID:24130486 SUPPORT In Vitro
"One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection"
Describes m102.4 explicitly as receptor-blocking, which is what licenses the INHIBITS edge onto the receptor-mediated entry node.
PMID:19888339 SUPPORT Model Organism
"a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent"
Identifies the henipavirus G attachment glycoprotein as the molecular target of m102.4.
Show evidence (3 references)
PMID:39700307 SUPPORT Other
"monoclonal antibodies (mAb) targeting the virus are recommended as the specific management option to prevent severe disease manifestations in high-risk individuals"
Establishes m102.4 as the recommended specific management option for high-risk individuals.
PMID:39700307 SUPPORT Other
"the limited global availability of mAb and the rapid progression of the disease have interfered with its use in outbreaks"
Qualifies the recommendation: availability and disease tempo have limited actual use in outbreaks, so this is recorded as PARTIAL support rather than demonstrated clinical efficacy.
PMID:19888339 SUPPORT Model Organism
"All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died."
Post-exposure protection in the ferret model. MODEL_ORGANISM - this is the strongest efficacy evidence available for m102.4 and it is preclinical, not a human outcome.
Remdesivir
Action: antiviral agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antiviral agent therapy, annotated with Antiviral Therapy (NCIT:C16119). NCIT:C16119 is a clinical intervention from the NCI Thesaurus. Ontology label: Antiviral Therapy NCIT:C16119
Agent: remdesivir CHEBI:145994 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses remdesivir (CHEBI:145994). CHEBI:145994 is a therapeutic agent from Chemical Entities of Biological Interest.
Remdesivir is a nucleotide analogue prodrug used on compassionate grounds in the 2023 Kerala outbreak for early administration before the onset of encephalitis, and as post-exposure prophylaxis in the highest-risk contacts. Efficacy in humans is unproven; supporting efficacy data are in vitro and in African green monkey challenge studies.
Show evidence (2 references)
PMID:39700307 SUPPORT INDIRECT Other
"During the 2023 outbreak, remdesivir was recommended on compassionate grounds for early use before the onset of encephalitis"
Documents the compassionate-use recommendation and the timing rationale. INDIRECT because the quote reports what was recommended rather than what the drug did, so it reaches this treatment entry through the recommendation rather than through an outcome. That the setting was uncontrolled is also true, but that is a strength caveat rather than the reason for this grading.
PMID:39700307 SUPPORT Model Organism
"In-vitro studies, as well as clade 1 challenge studies in African green monkeys, have shown that remdesivir is effective for the treatment as well as prophylaxis against Nipah virus disease"
Preclinical efficacy for both treatment and prophylaxis. Classified MODEL_ORGANISM because the efficacy claim rests on nonhuman primate challenge studies, not human outcomes.
Ribavirin
Action: antiviral agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antiviral agent therapy, annotated with Antiviral Therapy (NCIT:C16119). NCIT:C16119 is a clinical intervention from the NCI Thesaurus. Ontology label: Antiviral Therapy NCIT:C16119
Agent: ribavirin CHEBI:63580 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ribavirin (CHEBI:63580). CHEBI:63580 is a therapeutic agent from Chemical Entities of Biological Interest.
Ribavirin has been used empirically during outbreaks with uncertain clinical benefit against Nipah virus.
Show evidence (1 reference)
PMID:39633840 SUPPORT Other
"Synthetic medicines, like Ribavirin, and favipiravir showed promising results in NiV-infected patients."
Ribavirin has shown promising but non-definitive results in Nipah-infected patients.
🔬

Diagnosis

2
Nucleic acid testing for Nipah virus RNA
Diagnosis rests on molecular detection of Nipah virus RNA. In the Kerala protocol, epidemiologically unlinked encephalitis cases are first screened with a PCR-based panel; throat swab, blood, urine and CSF are then screened for NiV RNA at a BSL 2/3 facility or by a point-of-care nucleic acid test (Truenat), with confirmation at a BSL 4 facility.
nucleic acid amplification test NCIT:C20055 NCI Thesaurus (NCIT)
Results: Detection of Nipah virus RNA in throat swab, blood, urine, or CSF.
Show evidence (1 reference)
PMID:39700307 SUPPORT Other
"the samples (throat swab, blood, urine and CSF) will be screened for NiV RNA at a biosafety level (BSL) 2/3 facility or a point of care nucleic acid test (Truenat)"
Specifies the sample types and the nucleic acid testing pathway used for diagnosis.
Serological testing
Serology is not used to diagnose acute symptomatic infection because of its low sensitivity in the early phase of illness; its role is confined to serosurveys.
serologic test NCIT:C217458 NCI Thesaurus (NCIT)
Results: Not recommended for acute diagnosis; used for serosurveillance.
Show evidence (1 reference)
PMID:39700307 SUPPORT Other
"We do not use serological tests to diagnose Nipah in an active symptomatic suspect because of its low sensitivity in early phase of the infection, but they are used for serosurvey"
States that serology is unsuitable for acute diagnosis owing to low early-phase sensitivity, and is reserved for serosurvey.
📈

Progression

3
Incubation
Incubation: 6-11 days
Median incubation period of 9 days among Bangladesh patients with well-defined exposure to another infected patient.
Show evidence (1 reference)
PMID:18444812 SUPPORT Human Clinical
"the median incubation period was 9 days (range, 6-11 days)"
Directly reports the median and range of the incubation period in the Bangladesh cohort.
Acute illness
Duration: 2-36 days
Rapidly progressive illness affecting the central nervous and respiratory systems; among Bangladesh patients who died, death occurred a median of 6 days after onset.
Show evidence (2 references)
PMID:18444812 SUPPORT Human Clinical
"Among those who died, death occurred a median of 6 days (range, 2-36 days) after the onset of illness."
Reports the interval from symptom onset to death, defining the duration of the acute fatal course.
PMID:18444812 SUPPORT Human Clinical
"Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems."
Characterizes the acute phase as rapidly progressive and multisystem.
Outcome
Case fatality is high and differs between outbreak settings: 73% in the Bangladesh outbreaks versus 32% in the Malaysian outbreak. Among Malaysian survivors, just over half recovered fully and 15% had persistent neurologic deficits.
Show evidence (3 references)
PMID:18444812 SUPPORT Human Clinical
"We identified 92 patients with Nipah virus infection, 67 (73%) of whom died."
Reports a 73% case-fatality proportion across the four Bangladesh outbreaks.
PMID:10781618 SUPPORT Human Clinical
"Thirty patients (32 percent) died after rapid deterioration in their condition."
Reports a 32% case-fatality proportion in the Malaysian outbreak, lower than the Bangladesh figure.
PMID:10781618 SUPPORT Human Clinical
"Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits."
Quantifies full recovery and persistent neurologic sequelae among Malaysian survivors.
🦠

Infectious Agent

1
Nipah virus
Nipah virus is an enveloped, negative-sense single-stranded RNA virus of the genus Henipavirus (family Paramyxoviridae) whose natural reservoir is Pteropus fruit bats.
Nipah virus NCBITaxon:3052225 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:38399954 SUPPORT Other
"Nipah virus (NiV) is an emerging zoonotic paramyxovirus to which is attributed numerous high mortality outbreaks in South and South-East Asia"
The review identifies NiV as a zoonotic paramyxovirus responsible for high-mortality outbreaks.
PMID:38399954 SUPPORT Other
"The natural reservoir of NiV is the Pteropus bat species, which covers a wide geographical distribution extending over Asia, Oceania, and Africa."
The review names Pteropus fruit bats as the natural reservoir of Nipah virus.
↔️

Transmission

3
Foodborne transmission via contaminated date palm sap
Consumption of raw date palm sap contaminated by fruit bat saliva or urine is a major route of human infection in Bangladesh.
Show evidence (2 references)
PMID:38399954 SUPPORT Other
"in Bangladesh, the viral transmission occurs directly from bat to human mainly by ingestion of contaminated fresh date palm sap."
The review attributes Bangladeshi human infection primarily to ingestion of contaminated date palm sap.
PMID:39119137 SUPPORT Other
"Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India."
The systematic review lists date palm juice consumption in Bangladesh as a primary transmission route.
Intermediate host (pig) transmission
Close contact with infected pigs drove the initial Malaysian outbreak, with pigs acting as an amplifying intermediate host.
Show evidence (2 references)
PMID:10781618 SUPPORT Human Clinical
"Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period."
In the Malaysian outbreak 93% of patients had direct pig contact, indicating pig-to-human transmission.
PMID:38399954 SUPPORT Other
"Occasionally, human outbreaks have required the presence of an intermediate amplification mammal host between bat and humans."
The review notes that an intermediate amplifying mammalian host can bridge bat-to-human transmission.
Human-to-human transmission
Person-to-person spread occurs through close contact with respiratory secretions and body fluids, especially in healthcare and caregiving settings.
Show evidence (2 references)
PMID:39292378 SUPPORT Other
"It can spread between humans through contact with body fluids."
The review states that Nipah virus can spread between humans via body-fluid contact.
PMID:39119137 SUPPORT Other
"Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India."
The systematic review documents human-to-human transmission in India.
🔬

Clinical Trials

5
NCT04199169 PHASE_I COMPLETED
First-in-human Phase 1 trial of the HeV-sG-V (HenipaVax) Hendra virus soluble glycoprotein subunit vaccine in healthy adults, testing three ascending dose levels and different dosing regimens. Enrolment 192.
Show evidence (1 reference)
clinicaltrials:NCT04199169 SUPPORT Human Clinical
"A first-in-human, phase 1 trial is to be conducted in a healthy adult population in the US to assess the safety and immunogenicity of three ascending Nipah vaccine (HeV-sG-V; Hendra virus soluble glycoprotein vaccine) dosages."
Registry record establishing the trial's phase, population, and the HeV-sG-V vaccine under test.
NCT05178901 PHASE_I COMPLETED
Phase 1 dose-response and booster trial of PHV02, a recombinant vesicular stomatitis virus-vectored Nipah vaccine candidate, in healthy adults. Enrolment 60.
Show evidence (1 reference)
clinicaltrials:NCT05178901 SUPPORT Human Clinical
"A Phase 1 Study to Evaluate the Safety and Immunogenicity of rVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects"
Registry summary establishing PHV02 as an rVSV-vectored Nipah vaccine candidate in Phase 1.
NCT06221813 PHASE_I COMPLETED
Phase 1b prime-boost trial of three dose levels of PHV02 (rVSV-dG-EBOV GP-NiVG) given as a two-dose regimen one month apart in healthy adults, with Nipah-specific IgG ELISA and neutralizing antibody readouts. Enrolment 120.
Show evidence (1 reference)
clinicaltrials:NCT06221813 SUPPORT Human Clinical
"The goal of this clinical trial is to test the safety and immunogenicity of PHV02 live, attenuated recombinant vesicular stomatitis virus vaccine expressing the Nipah Virus glycoprotein in healthy adult subjects."
Registry record establishing the prime-boost design and the vaccine construct under test.
NCT05398796 PHASE_I COMPLETED
VRC 322/DMID 21-0016, a Phase 1 dose-escalation, open-label trial of the mRNA-1215 Nipah virus mRNA vaccine in healthy adults aged 18-60, given as two doses one month apart. Enrolment 40.
Show evidence (2 references)
clinicaltrials:NCT05398796 SUPPORT Human Clinical
"To test the safety of an experimental vaccine (mRNA-1215) for NiV."
Registry record establishing the trial objective and the mRNA-1215 vaccine candidate.
clinicaltrials:NCT05398796 SUPPORT Human Clinical
"There are no drugs or vaccines to treat or prevent NiV infection."
The registry record states the unmet need motivating the trial, consistent with this entry's treatments section.
NCT01811784 UNKNOWN
Community intervention trial in Bangladesh evaluating behaviour-change interventions to reduce Nipah spillover through raw date palm sap - the prevention counterpart to the vaccine trials, targeting the transmission route rather than the host response.
Show evidence (1 reference)
clinicaltrials:NCT01811784 SUPPORT Human Clinical
"The purpose of this study is to design, implement and evaluate behavior change interventions to prevent human consumption of NiV contaminated sap through reducing raw sap consumption from unprotected trees in a district of the NiV affected regions in Bangladesh."
Registry record establishing the prevention objective and the date palm sap transmission route targeted.
🐁

Animal Models

1
Nonhuman primate henipavirus challenge model
Nonhuman primates most closely reproduce human henipavirus disease and are the model in which remdesivir treatment and prophylaxis efficacy against clade I Nipah virus was demonstrated.
Species
African green monkey
Publication
PMID:37896758
Pathograph links
Pulmonary involvement and respiratory tract infection recapitulates fidelity: high Nonhuman primate challenge reproduces the combined severe respiratory and encephalitic disease seen in human outbreaks.
Limitations: Challenge is by controlled experimental inoculation at a defined dose and route, unlike natural human exposure to bat secretions, contaminated date palm sap, or an infected patient.
Show evidence (1 reference)
PMID:37896758 SUPPORT Model Organism
"Among these, NHPs have demonstrated the closest resemblance to human HNV disease, although other animal models replicate some key disease features."
Establishes nonhuman primates as the animal model most faithful to human henipavirus disease.
Central nervous system invasion recapitulates fidelity: high Henipavirus challenge in animal models reproduces the encephalitic arm of human disease, not only the respiratory arm.
Limitations: Encephalitis is scored over the short experimental course, so the model does not capture the relapsing and late-onset human encephalitis that appears months to years after acute illness.
Show evidence (1 reference)
PMID:37896758 SUPPORT Other
"Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate."
Establishes that encephalitis, alongside respiratory disease, occurs in animals as well as humans and so is within the models' scope. Tagged OTHER rather than MODEL_ORGANISM because the sentence reports NATURAL outbreak disease in humans and animals, not in vivo experimental data - it is background in a review about animal models, not a result from one.
Show evidence (2 references)
PMID:37896758 SUPPORT Other
"Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate."
The disease features the model is required to reproduce - severe respiratory disease plus encephalitis with high mortality. Tagged OTHER for the same reason as the readout item above: this is the review's background description of natural outbreaks, not experimental animal data.
PMID:37896758 SUPPORT Model Organism
"no approved medical countermeasures for human use currently exist against HeV or NiV"
Motivates continued reliance on animal models, since no approved human countermeasures exist.
{ }

Source YAML

click to show 
name: Nipah Virus Disease
creation_date: '2026-07-24T23:11:02Z'
category: Infectious Disease
description: >-
  Nipah virus disease is a zoonotic infection caused by Nipah virus, a
  henipavirus in the family Paramyxoviridae, whose natural reservoir is
  fruit bats of the genus Pteropus. Human infection follows exposure to
  infected bats, intermediate hosts such as pigs, or food contaminated
  with bat secretions (notably raw date palm sap), and produces a severe
  febrile illness that can progress to encephalitis, respiratory distress,
  and death with high case-fatality.
disease_term:
  term:
    id: MONDO:0020499
    label: Nipah virus disease
  preferred_term: Nipah Virus Disease
parents:
- Viral Encephalitis
- Zoonosis
infectious_agent:
- name: Nipah virus
  infectious_agent_term:
    preferred_term: Nipah virus
    term:
      id: NCBITaxon:3052225
      label: Henipavirus nipahense
  description: >-
    Nipah virus is an enveloped, negative-sense single-stranded RNA virus
    of the genus Henipavirus (family Paramyxoviridae) whose natural reservoir
    is Pteropus fruit bats.
  evidence:
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Nipah virus (NiV) is an emerging zoonotic paramyxovirus to which is attributed numerous high mortality outbreaks in South and South-East Asia"
    explanation: The review identifies NiV as a zoonotic paramyxovirus responsible for high-mortality outbreaks.
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The natural reservoir of NiV is the Pteropus bat species, which covers a wide geographical distribution extending over Asia, Oceania, and Africa."
    explanation: The review names Pteropus fruit bats as the natural reservoir of Nipah virus.
agent_life_cycle:
  description: >-
    Nipah virus is maintained in nature in Pteropus fruit bat reservoirs and
    spills over to humans directly or via intermediate mammalian hosts.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: incidental host
  - preferred_term: Pteropus fruit bat
    term:
      id: NCBITaxon:9401
      label: Pteropus
    role: natural reservoir
transmission:
- name: Foodborne transmission via contaminated date palm sap
  description: >-
    Consumption of raw date palm sap contaminated by fruit bat saliva or
    urine is a major route of human infection in Bangladesh.
  evidence:
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "in Bangladesh, the viral transmission occurs directly from bat to human mainly by ingestion of contaminated fresh date palm sap."
    explanation: The review attributes Bangladeshi human infection primarily to ingestion of contaminated date palm sap.
  - reference: PMID:39119137
    reference_title: "A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India."
    explanation: The systematic review lists date palm juice consumption in Bangladesh as a primary transmission route.
- name: Intermediate host (pig) transmission
  description: >-
    Close contact with infected pigs drove the initial Malaysian outbreak,
    with pigs acting as an amplifying intermediate host.
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period."
    explanation: In the Malaysian outbreak 93% of patients had direct pig contact, indicating pig-to-human transmission.
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Occasionally, human outbreaks have required the presence of an intermediate amplification mammal host between bat and humans."
    explanation: The review notes that an intermediate amplifying mammalian host can bridge bat-to-human transmission.
- name: Human-to-human transmission
  description: >-
    Person-to-person spread occurs through close contact with respiratory
    secretions and body fluids, especially in healthcare and caregiving
    settings.
  evidence:
  - reference: PMID:39292378
    reference_title: "Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It can spread between humans through contact with body fluids."
    explanation: The review states that Nipah virus can spread between humans via body-fluid contact.
  - reference: PMID:39119137
    reference_title: "A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India."
    explanation: The systematic review documents human-to-human transmission in India.
pathophysiology:
- name: Ephrin-B2/B3 receptor-mediated cell entry
  biological_scale: MOLECULAR
  description: >-
    The Nipah virus attachment glycoprotein engages the host ephrin-B2 and
    ephrin-B3 receptors to mediate entry into host cells. Because ephrin-B2 is
    evolutionarily conserved and widely expressed on vascular endothelium, and
    ephrin-B3 on neurons, the tissue distribution of these receptors is what
    determines the endothelial and neuronal tropism that drives the rest of the
    disease, and also underlies the virus's broad host-species range.
  biological_processes:
  - preferred_term: symbiont entry into host cell
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  molecular_functions:
  - preferred_term: ephrin-B2/B3 acting as the henipavirus entry receptor
    term:
      id: GO:0001618
      label: virus receptor activity
  downstream:
  - target: Endothelial tropism and systemic vasculitis
    description: >-
      Ephrin-B2 is widely expressed on vascular endothelium, so receptor-mediated
      entry establishes the endothelial infection underlying systemic vasculitis.
  - target: Central nervous system invasion
    description: >-
      Ephrin-B3 expression on neurons provides the receptor basis for direct
      neuronal infection of the central nervous system.
  - target: Type I interferon signaling antagonism
    description: >-
      Once inside the cell the virus expresses the accessory proteins that
      disable the host type I interferon response.
  evidence:
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The virus enters the host cells through Ephrin B2/B3 receptors"
    explanation: States the receptor pair mediating Nipah virus entry into host cells.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "inherent ability to use the evolutionarily conserved and widely expressed cellular receptor Ephrin B2 for entry"
    explanation: Establishes that ephrin-B2 is conserved and widely expressed, which is what makes receptor distribution determine tropism.
  - reference: PMID:24130486
    reference_title: "Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors."
    explanation: Identifies the viral attachment glycoprotein G engaging host cell receptors as the initiating step of henipavirus entry.
- name: Type I interferon signaling antagonism
  biological_scale: MOLECULAR
  description: >-
    Nipah virus accessory proteins expressed from the P gene antagonize type I
    interferon signaling by binding and sequestering STAT1 and STAT2. The V
    protein induces cytoplasmic high-molecular-weight STAT-containing complexes,
    and the phosphoprotein P sequesters STAT1/STAT2 into viral inclusion bodies;
    both prevent STAT activation and nuclear translocation. Blocking the innate
    antiviral response is what permits the virus to disseminate systemically
    before an effective interferon response is mounted.
  biological_processes:
  - preferred_term: negative regulation of type I interferon-mediated signaling pathway
    modifier: INCREASED
    term:
      id: GO:0060339
      label: negative regulation of type I interferon-mediated signaling pathway
  downstream:
  - target: Systemic viral dissemination and febrile illness
    description: >-
      Suppression of the innate interferon response permits unchecked viral
      replication and systemic spread.
  evidence:
  - reference: PMID:15279700
    reference_title: "Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Similar to other paramyxoviruses, Henipaviruses inhibit IFN signal transduction through a virus-encoded protein called V."
    explanation: Establishes the V protein as the henipavirus-encoded inhibitor of interferon signal transduction.
  - reference: PMID:15279700
    reference_title: "Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "This sequestration of STAT1 and STAT2 prevents STAT activation and blocks antiviral IFN signaling."
    explanation: States the molecular consequence - STAT1/STAT2 sequestration prevents STAT activation and blocks antiviral interferon signaling.
  - reference: PMID:36851768
    reference_title: "Nipah Virus Impairs Autocrine IFN Signaling by Sequestering STAT1 and STAT2 into Inclusion Bodies."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "we show here that NiV can inhibit IFN-dependent antiviral signaling via a NiV P-dependent sequestration of STAT1 and STAT2 into viral IBs"
    explanation: Adds the phosphoprotein P arm, sequestering STAT1/STAT2 into viral inclusion bodies, alongside the V-protein mechanism.
  - reference: PMID:36851768
    reference_title: "Nipah Virus Impairs Autocrine IFN Signaling by Sequestering STAT1 and STAT2 into Inclusion Bodies."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the pathogenic potential of NiV is linked to its ability to block antiviral responses"
    explanation: Links interferon antagonism directly to the pathogenic potential of the virus, which is why this node sits upstream of dissemination.
- name: Systemic viral dissemination and febrile illness
  biological_scale: ORGANISM
  description: >-
    Unrestrained by the interferon response, the virus replicates in and spreads
    through highly vascular tissues, producing a widespread multisystemic
    vasculitis and the non-specific systemic febrile prodrome - fever, headache
    and vomiting - that precedes organ-specific disease.
  downstream:
  - target: Endothelial tropism and systemic vasculitis
    description: >-
      Systemic spread through highly vascular tissues establishes the widespread
      endothelial infection.
  - target: Fever
    description: Systemic viral replication produces the febrile response.
  - target: Headache
    description: Part of the non-specific systemic prodrome of acute infection.
  - target: Vomiting
    description: Part of the non-specific systemic prodrome of acute infection.
  evidence:
  - reference: PMID:19888339
    reference_title: "A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues."
    explanation: |
      Documents systemic dissemination with virus recoverable from multiple
      tissues. MODEL_ORGANISM because the observation is in the ferret model,
      though the authors state the pathology closely resembles human disease.
- name: Endothelial tropism and systemic vasculitis
  biological_scale: TISSUE
  cell_types:
  - preferred_term: vascular endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  - preferred_term: vascular smooth muscle cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  description: >-
    Nipah virus infects vascular endothelial and smooth muscle cells,
    producing a systemic vasculitis with thrombosis and parenchymal necrosis,
    especially in the central nervous system.
  downstream:
  - target: Syncytium formation
    description: >-
      Infection of vascular endothelium is the setting in which syncytial giant
      cells arise; autopsy describes endothelial damage, necrosis and syncytial
      giant cell formation together in affected vessels.
  - target: Central nervous system invasion
    description: >-
      Vasculitis with thrombosis and parenchymal necrosis is most marked in the
      central nervous system, accompanying direct neuronal infection.
  - target: Pulmonary involvement and respiratory tract infection
    description: >-
      The same vascular changes involve the lungs, contributing to the pulmonary
      arm of clade I disease.
  evidence:
  - reference: PMID:12466131
    reference_title: "Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system."
    explanation: Autopsy findings from human cases show systemic vasculitis with thrombosis and necrosis.
  - reference: PMID:12466131
    reference_title: "Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels."
    explanation: Immunohistochemistry localizes Nipah antigen to vascular endothelial and smooth muscle cells.
- name: Central nervous system invasion
  biological_scale: TISSUE
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  description: >-
    The virus infects neurons of the central nervous system, producing an
    acute encephalitis alongside vasculitis-associated injury.
  downstream:
  - target: Encephalitis
    description: >-
      Direct neuronal infection with accompanying vasculitis produces the acute
      encephalitis that defines symptomatic human Nipah virus disease.
  - target: Reduced consciousness
    description: >-
      Encephalitic involvement of the brain stem underlies the reduced level of
      consciousness documented in 55% of the Malaysian case series.
  - target: Seizure
    description: >-
      Cortical involvement in acute Nipah encephalitis manifests clinically as
      convulsions.
  - target: Myoclonus
    description: >-
      Brain-stem and upper cervical cord involvement produces the distinctive
      segmental myoclonus of Nipah encephalitis.
  - target: Areflexia
    description: >-
      Brain-stem and upper cervical cord involvement produces areflexia.
  - target: Hypotonia
    description: >-
      Brain-stem and upper cervical cord involvement produces hypotonia.
  evidence:
  - reference: PMID:12466131
    reference_title: "Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons."
    explanation: Viral antigen is abundant in neurons, evidencing direct CNS neuronal infection.
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates."
    explanation: The review characterizes human Nipah infection as a rapidly progressive encephalitis.
- name: Syncytium formation
  biological_scale: CELLULAR
  description: >-
    Nipah virus induces fusion of infected cells into multinucleated
    syncytial giant cells, prominent in affected blood vessels.
  evidence:
  - reference: PMID:12466131
    reference_title: "Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels."
    explanation: Syncytial giant cells are observed in affected vessels of human autopsy tissue.
- name: Pulmonary involvement and respiratory tract infection
  biological_scale: TISSUE
  description: >-
    Beyond the encephalitic arm, Nipah virus produces severe pulmonary
    involvement with respiratory tract infection and vascular injury of the
    lungs. This arm is clade-dependent and is the principal feature
    distinguishing the Bangladesh/India clade I outbreaks, in which severe
    respiratory disease accompanies encephalitis and facilitates
    person-to-person transmission, from the Malaysian clade II outbreak, which
    produced a largely pure encephalitic syndrome.
  downstream:
  - target: Respiratory distress
    description: >-
      Pulmonary infection and vascular injury of the lung manifest clinically as
      respiratory difficulty and, at the severe end, acute respiratory distress
      syndrome.
  - target: Acute respiratory distress syndrome
    description: >-
      Severe pulmonary involvement progresses to the clinical and radiographic
      picture of acute respiratory distress syndrome.
  - target: Cough
    description: >-
      Respiratory tract infection manifests as cough, among the most common
      presenting symptoms in the Bangladesh outbreaks.
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems."
    explanation: Establishes the respiratory system, alongside the CNS, as a primary target of the infection.
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "including a severe respiratory component, appear distinct from clinical characteristics reported during earlier outbreaks in other countries."
    explanation: Identifies the severe respiratory component as what distinguishes Bangladesh disease from the earlier Malaysian outbreak.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "whereas many patients infected with NiV clade I had added severe pulmonary involvement"
    explanation: Attributes severe pulmonary involvement specifically to clade I infection.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "NiV clade II isolated cases led to a pure encephalitic syndrome (neurological symptoms without respiratory manifestations)"
    explanation: The contrasting clade II picture, without respiratory manifestations, establishes that the pulmonary arm is clade-dependent.
  - reference: PMID:37896758
    reference_title: "Animal Models for Henipavirus Research."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate."
    explanation: Corroborates severe respiratory disease as a core outcome of henipavirus outbreaks alongside encephalitis.
phenotypes:
- name: Fever
  category: Systemic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main presenting features were fever, headache, dizziness, and vomiting."
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "main
      presenting features" maps to FREQUENT (30-79%) under the Pattern C
      qualitative mapping in docs/frequency-evidence-guidelines.md. This series
      reports no per-symptom percentage, so no higher band is sourced.
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "the
      most common signs and symptoms" maps to FREQUENT (30-79%) under the
      Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md.
      Hossain 2008 reports no per-symptom percentages, so no quantitative band
      is available.
- name: Headache
  category: Neurologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main presenting features were fever, headache, dizziness, and vomiting."
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "main
      presenting features" maps to FREQUENT (30-79%) under the Pattern C
      qualitative mapping in docs/frequency-evidence-guidelines.md.
- name: Encephalitis
  category: Neurologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
  evidence:
  - reference: PMID:39119137
    reference_title: "A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects."
    explanation: |
      Snippet supports the disease-phenotype association. The review describes
      encephalitis as what the virus causes, i.e. a predominant manifestation,
      which maps to FREQUENT (30-79%) under the Pattern C qualitative mapping in
      docs/frequency-evidence-guidelines.md. No cohort percentage is reported.
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates."
    explanation: |
      Snippet supports the disease-phenotype association and the FREQUENT band
      qualitatively ("human infection manifests as" a rapidly progressive
      encephalitis, i.e. predominant). No quantitative frequency is reported, so
      no higher band is claimed.
- name: Seizure
  category: Neurologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "the
      most common signs and symptoms" maps to FREQUENT (30-79%) under the
      Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md.
      The previous OCCASIONAL (5-29%) band contradicted this wording; Hossain
      2008 reports no per-symptom percentages.
- name: Reduced consciousness
  category: Neurologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Reduced consciousness
    term:
      id: HP:0004372
      label: Reduced consciousness
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction."
    explanation: |
      Pattern A/B quantitative support: 52/94 = 55%, which falls in the FREQUENT
      band (30-79%) per docs/frequency-evidence-guidelines.md.
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
    explanation: |
      Corroborates the disease-phenotype association in a second cohort. Author
      wording "the most common signs and symptoms" is consistent with the
      FREQUENT band already established quantitatively by Goh 2000 (55%).
- name: Myoclonus
  category: Neurologic
  phenotype_term:
    preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
    explanation: Segmental myoclonus was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem involvement.
- name: Areflexia
  category: Neurologic
  phenotype_term:
    preferred_term: Areflexia
    term:
      id: HP:0001284
      label: Areflexia
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
    explanation: Areflexia was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem and upper cervical cord involvement.
- name: Hypotonia
  category: Neurologic
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia"
    explanation: Hypotonia was a distinctive clinical sign in the Malaysian case series, reflecting brain-stem and upper cervical cord involvement.
- name: Relapsing and late-onset encephalitis
  category: Neurologic
  frequency: VERY_RARE
  description: >-
    A distinctive feature of Nipah virus disease: encephalitis recurring after
    recovery from, or after an initially mild, acute illness, and late-onset
    encephalitis appearing months to years later. Kerala investigators attribute
    it to reactivation of infection rather than a post-infectious immunological
    demyelinating process, and report it as non-contagious.
  phenotype_term:
    preferred_term: Relapsing and late-onset Nipah encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
    temporality: RECURRENT
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurologic relapse occurred after initially mild disease in three patients."
    explanation: |
      Pattern B quantitative support: 3 of the 94 patients in the Malaysian
      series = 3.2%, which falls in the VERY_RARE band (<5%).
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It is also important to monitor Nipah survivors continuously because of the rare possibility of relapse and late-onset NiV encephalitis"
    explanation: |
      Independently corroborates the band: author wording "rare" maps to
      VERY_RARE under the Pattern C qualitative mapping in
      docs/frequency-evidence-guidelines.md, agreeing with the 3.2% figure above.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Late-onset reactivation encephalitis in Nipah appears to be non-contagious, but it is a concern because of the potential social stigma and significant morbidity/mortality risk associated with it."
    explanation: Characterizes the late-onset form as reactivation, non-contagious, and carrying significant morbidity and mortality risk.
- name: Persistent neurologic deficits in survivors
  category: Neurologic
  frequency: OCCASIONAL
  description: >-
    A substantial minority of survivors are left with persistent neurological
    sequelae rather than recovering fully.
  phenotype_term:
    preferred_term: Persistent neurologic deficits
    term:
      id: HP:0000707
      label: Abnormality of the nervous system
    temporality: CHRONIC
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits."
    explanation: |
      Pattern A quantitative support: 15% of the Malaysian series had persistent
      neurologic deficits, which falls in the OCCASIONAL band (5-29%).
- name: Vomiting
  category: Gastrointestinal
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main presenting features were fever, headache, dizziness, and vomiting."
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "main
      presenting features" maps to FREQUENT (30-79%) under the Pattern C
      qualitative mapping in docs/frequency-evidence-guidelines.md. The previous
      OCCASIONAL (5-29%) band contradicted this wording.
- name: Cough
  category: Respiratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
    explanation: |
      Snippet supports the disease-phenotype association. Author wording "the
      most common signs and symptoms" maps to FREQUENT (30-79%) under the
      Pattern C qualitative mapping in docs/frequency-evidence-guidelines.md.
      The previous OCCASIONAL (5-29%) band contradicted this wording.
- name: Respiratory distress
  category: Respiratory
  # frequency intentionally omitted: the only available evidence is
  # outbreak-specific (ARDS "identified during the fourth outbreak") and does
  # not support a whole-disease band. See docs/frequency-evidence-guidelines.md
  # ("When in doubt, omit the frequency").
  phenotype_term:
    preferred_term: Respiratory distress
    term:
      id: HP:0002098
      label: Respiratory distress
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak."
    explanation: |
      Snippet supports the disease-phenotype association only. The finding is
      reported for one of four Bangladesh outbreaks, so it cannot support a
      whole-disease frequency band; frequency is therefore omitted rather than
      estimated.
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms"
    explanation: |
      Corroborates the disease-phenotype association: respiratory difficulty is
      listed among the most common signs and symptoms. The frequency band remains
      omitted, because this entry keeps the quantitatively unsupported respiratory
      arm conservative rather than inferring a whole-disease band.
- name: Acute respiratory distress syndrome
  category: Respiratory
  # frequency intentionally omitted: the supporting evidence is specific to one
  # of the four Bangladesh outbreaks and does not support a whole-disease band.
  phenotype_term:
    preferred_term: Acute respiratory distress syndrome
    term:
      id: HP:0033677
      label: Acute respiratory distress syndrome
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak."
    explanation: |
      Records ARDS specifically, by both clinical and radiographic criteria, in
      the fourth Bangladesh outbreak. Curated as a distinct, more specific
      phenotype alongside the broader Respiratory distress term (HP:0002098),
      which remains supported by the wider "respiratory difficulty" evidence.
progression:
- phase: Incubation
  incubation_days: '6-11'
  notes: >-
    Median incubation period of 9 days among Bangladesh patients with
    well-defined exposure to another infected patient.
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the median incubation period was 9 days (range, 6-11 days)"
    explanation: Directly reports the median and range of the incubation period in the Bangladesh cohort.
- phase: Acute illness
  duration_days: '2-36'
  notes: >-
    Rapidly progressive illness affecting the central nervous and respiratory
    systems; among Bangladesh patients who died, death occurred a median of
    6 days after onset.
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among those who died, death occurred a median of 6 days (range, 2-36 days) after the onset of illness."
    explanation: Reports the interval from symptom onset to death, defining the duration of the acute fatal course.
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems."
    explanation: Characterizes the acute phase as rapidly progressive and multisystem.
- phase: Outcome
  notes: >-
    Case fatality is high and differs between outbreak settings: 73% in the
    Bangladesh outbreaks versus 32% in the Malaysian outbreak. Among Malaysian
    survivors, just over half recovered fully and 15% had persistent
    neurologic deficits.
  evidence:
  - reference: PMID:18444812
    reference_title: "Clinical presentation of nipah virus infection in Bangladesh."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identified 92 patients with Nipah virus infection, 67 (73%) of whom died."
    explanation: Reports a 73% case-fatality proportion across the four Bangladesh outbreaks.
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thirty patients (32 percent) died after rapid deterioration in their condition."
    explanation: Reports a 32% case-fatality proportion in the Malaysian outbreak, lower than the Bangladesh figure.
  - reference: PMID:10781618
    reference_title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits."
    explanation: Quantifies full recovery and persistent neurologic sequelae among Malaysian survivors.
treatments:
- name: Supportive and intensive care
  description: >-
    Management is primarily supportive, including intensive care, management
    of encephalitis, and respiratory support; there is no licensed antiviral
    therapy or vaccine for human use.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:38399954
    reference_title: "Nipah Virus: A Multidimensional Update."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "no therapeutic agents or vaccines have been approved for human use."
    explanation: No approved therapeutics or vaccines exist, so care remains supportive.
  - reference: PMID:39292378
    reference_title: "Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "To date, no approved vaccines or treatments have been available."
    explanation: The review confirms the absence of approved vaccines or treatments, leaving supportive care as standard.
  - reference: PMID:38185127
    reference_title: "Nipah virus disease: what can we do to improve patient care?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Although candidate vaccines for Nipah virus disease exist, developing new therapeutics has been underinvested."
    explanation: Explains why supportive care remains the mainstay - therapeutic development has been underinvested despite candidate vaccines existing.
  - reference: PMID:38185127
    reference_title: "Nipah virus disease: what can we do to improve patient care?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the disease it causes still carries high mortality, unchanged since the first reported outbreaks"
    explanation: Records that mortality has not improved since the first outbreaks, underscoring the limits of currently available supportive management.
  - reference: PMID:39119137
    reference_title: "A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "only two vaccines have progressed to clinical trials"
    explanation: Systematic-review anchor for the state of countermeasure development, contextualizing the clinical_trials section.
- name: m102.4 monoclonal antibody
  therapeutic_modality: MONOCLONAL_ANTIBODY
  description: >-
    m102.4 is a cross-reactive neutralizing human monoclonal antibody that
    targets the henipavirus attachment G glycoprotein and blocks its engagement
    of the host ephrin receptors, preventing viral entry. It is recommended as
    the specific management option to prevent severe disease in high-risk
    individuals, but global availability is limited, the disease progresses too
    rapidly for it to be given in many cases, and its activity may be restricted
    to the clade against which it was raised. No phase II/III efficacy trial has
    yet been reported.
  target_mechanisms:
  - target: Ephrin-B2/B3 receptor-mediated cell entry
    treatment_effect: INHIBITS
    description: >-
      m102.4 binds the viral attachment G glycoprotein and blocks its engagement
      of the host ephrin receptors, so it acts directly on the receptor-mediated
      entry step rather than on a downstream consequence.
    evidence:
    - reference: PMID:24130486
      reference_title: "Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection"
      explanation: Describes m102.4 explicitly as receptor-blocking, which is what licenses the INHIBITS edge onto the receptor-mediated entry node.
    - reference: PMID:19888339
      reference_title: "A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent"
      explanation: Identifies the henipavirus G attachment glycoprotein as the molecular target of m102.4.
  treatment_term:
    preferred_term: antiviral agent therapy
    term:
      id: NCIT:C16119
      label: Antiviral Therapy
    therapeutic_agent:
    - preferred_term: m102.4
      term:
        id: NCIT:C20401
        label: Monoclonal Antibody
  evidence:
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "monoclonal antibodies (mAb) targeting the virus are recommended as the specific management option to prevent severe disease manifestations in high-risk individuals"
    explanation: Establishes m102.4 as the recommended specific management option for high-risk individuals.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the limited global availability of mAb and the rapid progression of the disease have interfered with its use in outbreaks"
    explanation: |
      Qualifies the recommendation: availability and disease tempo have limited
      actual use in outbreaks, so this is recorded as PARTIAL support rather than
      demonstrated clinical efficacy.
  - reference: PMID:19888339
    reference_title: "A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died."
    explanation: |
      Post-exposure protection in the ferret model. MODEL_ORGANISM - this is the
      strongest efficacy evidence available for m102.4 and it is preclinical, not
      a human outcome.
- name: Remdesivir
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Remdesivir is a nucleotide analogue prodrug used on compassionate grounds in
    the 2023 Kerala outbreak for early administration before the onset of
    encephalitis, and as post-exposure prophylaxis in the highest-risk contacts.
    Efficacy in humans is unproven; supporting efficacy data are in vitro and in
    African green monkey challenge studies.
  treatment_term:
    preferred_term: antiviral agent therapy
    term:
      id: NCIT:C16119
      label: Antiviral Therapy
    therapeutic_agent:
    - preferred_term: remdesivir
      term:
        id: CHEBI:145994
        label: remdesivir
  evidence:
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: OTHER
    snippet: "During the 2023 outbreak, remdesivir was recommended on compassionate grounds for early use before the onset of encephalitis"
    explanation: |
      Documents the compassionate-use recommendation and the timing rationale.
      INDIRECT because the quote reports what was recommended rather than what the
      drug did, so it reaches this treatment entry through the recommendation
      rather than through an outcome. That the setting was uncontrolled is also
      true, but that is a strength caveat rather than the reason for this grading.
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "In-vitro studies, as well as clade 1 challenge studies in African green monkeys, have shown that remdesivir is effective for the treatment as well as prophylaxis against Nipah virus disease"
    explanation: |
      Preclinical efficacy for both treatment and prophylaxis. Classified
      MODEL_ORGANISM because the efficacy claim rests on nonhuman primate
      challenge studies, not human outcomes.
- name: Ribavirin
  description: >-
    Ribavirin has been used empirically during outbreaks with uncertain
    clinical benefit against Nipah virus.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: antiviral agent therapy
    term:
      id: NCIT:C16119
      label: Antiviral Therapy
    therapeutic_agent:
    - preferred_term: ribavirin
      term:
        id: CHEBI:63580
        label: ribavirin
  evidence:
  - reference: PMID:39633840
    reference_title: "Risk Evaluation and Mitigation Strategies for Potential Outbreaks of Nipah Virus Infection: Evidenced by the Recent Incidences in Southeast Asian Countries."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Synthetic medicines, like Ribavirin, and favipiravir showed promising results in NiV-infected patients."
    explanation: Ribavirin has shown promising but non-definitive results in Nipah-infected patients.
diagnosis:
- name: Nucleic acid testing for Nipah virus RNA
  description: >-
    Diagnosis rests on molecular detection of Nipah virus RNA. In the Kerala
    protocol, epidemiologically unlinked encephalitis cases are first screened
    with a PCR-based panel; throat swab, blood, urine and CSF are then screened
    for NiV RNA at a BSL 2/3 facility or by a point-of-care nucleic acid test
    (Truenat), with confirmation at a BSL 4 facility.
  diagnosis_term:
    preferred_term: nucleic acid amplification test
    term:
      id: NCIT:C20055
      label: Nucleic Acid Amplification Test
  results: Detection of Nipah virus RNA in throat swab, blood, urine, or CSF.
  evidence:
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the samples (throat swab, blood, urine and CSF) will be screened for NiV RNA at a biosafety level (BSL) 2/3 facility or a point of care nucleic acid test (Truenat)"
    explanation: Specifies the sample types and the nucleic acid testing pathway used for diagnosis.
- name: Serological testing
  description: >-
    Serology is not used to diagnose acute symptomatic infection because of its
    low sensitivity in the early phase of illness; its role is confined to
    serosurveys.
  diagnosis_term:
    preferred_term: serologic test
    term:
      id: NCIT:C217458
      label: Diagnostic Serology Testing
  results: Not recommended for acute diagnosis; used for serosurveillance.
  evidence:
  - reference: PMID:39700307
    reference_title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "We do not use serological tests to diagnose Nipah in an active symptomatic suspect because of its low sensitivity in early phase of the infection, but they are used for serosurvey"
    explanation: States that serology is unsuitable for acute diagnosis owing to low early-phase sensitivity, and is reserved for serosurvey.
animal_models:
- name: Nonhuman primate henipavirus challenge model
  species: African green monkey
  publication: PMID:37896758
  description: >-
    Nonhuman primates most closely reproduce human henipavirus disease and are
    the model in which remdesivir treatment and prophylaxis efficacy against
    clade I Nipah virus was demonstrated.
  modeled_mechanisms:
  - target: Pulmonary involvement and respiratory tract infection
    relationship: RECAPITULATES
    fidelity: HIGH
    description: >-
      Nonhuman primate challenge reproduces the combined severe respiratory and
      encephalitic disease seen in human outbreaks.
    limitations: >-
      Challenge is by controlled experimental inoculation at a defined dose and
      route, unlike natural human exposure to bat secretions, contaminated date
      palm sap, or an infected patient.
    evidence:
    - reference: PMID:37896758
      reference_title: "Animal Models for Henipavirus Research."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Among these, NHPs have demonstrated the closest resemblance to human HNV disease, although other animal models replicate some key disease features."
      explanation: Establishes nonhuman primates as the animal model most faithful to human henipavirus disease.
  - target: Central nervous system invasion
    relationship: RECAPITULATES
    fidelity: HIGH
    description: >-
      Henipavirus challenge in animal models reproduces the encephalitic arm of
      human disease, not only the respiratory arm.
    limitations: >-
      Encephalitis is scored over the short experimental course, so the model
      does not capture the relapsing and late-onset human encephalitis that
      appears months to years after acute illness.
    evidence:
    - reference: PMID:37896758
      reference_title: "Animal Models for Henipavirus Research."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate."
      explanation: >-
        Establishes that encephalitis, alongside respiratory disease, occurs in
        animals as well as humans and so is within the models' scope. Tagged
        OTHER rather than MODEL_ORGANISM because the sentence reports NATURAL
        outbreak disease in humans and animals, not in vivo experimental data -
        it is background in a review about animal models, not a result from one.
  evidence:
  - reference: PMID:37896758
    reference_title: "Animal Models for Henipavirus Research."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate."
    explanation: >-
      The disease features the model is required to reproduce - severe
      respiratory disease plus encephalitis with high mortality. Tagged OTHER for
      the same reason as the readout item above: this is the review's background
      description of natural outbreaks, not experimental animal data.
  - reference: PMID:37896758
    reference_title: "Animal Models for Henipavirus Research."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "no approved medical countermeasures for human use currently exist against HeV or NiV"
    explanation: Motivates continued reliance on animal models, since no approved human countermeasures exist.
clinical_trials:
- name: NCT04199169
  phase: PHASE_I
  status: COMPLETED
  description: >-
    First-in-human Phase 1 trial of the HeV-sG-V (HenipaVax) Hendra virus
    soluble glycoprotein subunit vaccine in healthy adults, testing three
    ascending dose levels and different dosing regimens. Enrolment 192.
  evidence:
  - reference: clinicaltrials:NCT04199169
    reference_title: "A Phase 1 Randomized, Placebo-controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of a Nipah Vaccine, HeV-sG-V (Hendra Virus Soluble Glycoprotein Vaccine), in Healthy Adults"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A first-in-human, phase 1 trial is to be conducted in a healthy adult population in the US to assess the safety and immunogenicity of three ascending Nipah vaccine (HeV-sG-V; Hendra virus soluble glycoprotein vaccine) dosages."
    explanation: Registry record establishing the trial's phase, population, and the HeV-sG-V vaccine under test.
- name: NCT05178901
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Phase 1 dose-response and booster trial of PHV02, a recombinant vesicular
    stomatitis virus-vectored Nipah vaccine candidate, in healthy adults.
    Enrolment 60.
  evidence:
  - reference: clinicaltrials:NCT05178901
    reference_title: "A Phase 1 Randomized, Single Center, Double-Blind, Placebo-Controlled, Dose-Response and Open-Label or Single Blind Booster Study to Evaluate the Safety and Immunogenicity of RVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A Phase 1 Study to Evaluate the Safety and Immunogenicity of rVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects"
    explanation: Registry summary establishing PHV02 as an rVSV-vectored Nipah vaccine candidate in Phase 1.
- name: NCT06221813
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Phase 1b prime-boost trial of three dose levels of PHV02
    (rVSV-dG-EBOV GP-NiVG) given as a two-dose regimen one month apart in
    healthy adults, with Nipah-specific IgG ELISA and neutralizing antibody
    readouts. Enrolment 120.
  evidence:
  - reference: clinicaltrials:NCT06221813
    reference_title: "A Phase 1b Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Prime-Boost Regimen of Three Dose Levels of PHV02, a Nipah Virus Vaccine Candidate (rVSV-ΔG-EBOV GP-NiVG) in Healthy Adults"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The goal of this clinical trial is to test the safety and immunogenicity of PHV02 live, attenuated recombinant vesicular stomatitis virus vaccine expressing the Nipah Virus glycoprotein in healthy adult subjects."
    explanation: Registry record establishing the prime-boost design and the vaccine construct under test.
- name: NCT05398796
  phase: PHASE_I
  status: COMPLETED
  description: >-
    VRC 322/DMID 21-0016, a Phase 1 dose-escalation, open-label trial of the
    mRNA-1215 Nipah virus mRNA vaccine in healthy adults aged 18-60, given as
    two doses one month apart. Enrolment 40.
  evidence:
  - reference: clinicaltrials:NCT05398796
    reference_title: "VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To test the safety of an experimental vaccine (mRNA-1215) for NiV."
    explanation: Registry record establishing the trial objective and the mRNA-1215 vaccine candidate.
  - reference: clinicaltrials:NCT05398796
    reference_title: "VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There are no drugs or vaccines to treat or prevent NiV infection."
    explanation: The registry record states the unmet need motivating the trial, consistent with this entry's treatments section.
- name: NCT01811784
  status: UNKNOWN
  description: >-
    Community intervention trial in Bangladesh evaluating behaviour-change
    interventions to reduce Nipah spillover through raw date palm sap - the
    prevention counterpart to the vaccine trials, targeting the transmission
    route rather than the host response.
  notes: >-
    ClinicalTrials.gov records this study as Phase 1/Phase 2, which has no
    single corresponding value in ClinicalTrialPhaseEnum; `phase` is therefore
    omitted rather than misrepresented. Registry status is Unknown.
  evidence:
  - reference: clinicaltrials:NCT01811784
    reference_title: "A Community Intervention Trial Utilizing Behavior Change to Reduce the Risk of Nipah Spillover Through Date Palm Sap in Bangladesh"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The purpose of this study is to design, implement and evaluate behavior change interventions to prevent human consumption of NiV contaminated sap through reducing raw sap consumption from unprotected trees in a district of the NiV affected regions in Bangladesh."
    explanation: Registry record establishing the prevention objective and the date palm sap transmission route targeted.
references:
- reference: PMID:38399954
  title: "Nipah Virus: A Multidimensional Update."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:38185127
  title: "Nipah virus disease: what can we do to improve patient care?"
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:39119137
  title: "A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:39700307
  title: "Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:39292378
  title: "Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:39633840
  title: "Risk Evaluation and Mitigation Strategies for Potential Outbreaks of Nipah Virus Infection: Evidenced by the Recent Incidences in Southeast Asian Countries."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:37896758
  title: "Animal Models for Henipavirus Research."
  found_in:
  - Nipah_Virus_Disease-deep-research-falcon.md
- reference: PMID:10781618
  title: "Clinical features of Nipah virus encephalitis among pig farmers in Malaysia."
- reference: PMID:18444812
  title: "Clinical presentation of nipah virus infection in Bangladesh."
- reference: PMID:12466131
  title: "Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis."
- reference: PMID:15279700
  title: "Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling."
- reference: PMID:36851768
  title: "Nipah Virus Impairs Autocrine IFN Signaling by Sequestering STAT1 and STAT2 into Inclusion Bodies."
- reference: PMID:24130486
  title: "Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody."
- reference: PMID:19888339
  title: "A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection."
- reference: clinicaltrials:NCT04199169
  title: >-
    A Phase 1 Randomized, Placebo-controlled, Observer-blind Trial to Assess the
    Safety and Immunogenicity of a Nipah Vaccine, HeV-sG-V (Hendra Virus Soluble
    Glycoprotein Vaccine), in Healthy Adults
- reference: clinicaltrials:NCT05178901
  title: >-
    A Phase 1 Randomized, Single Center, Double-Blind, Placebo-Controlled,
    Dose-Response and Open-Label or Single Blind Booster Study to Evaluate the
    Safety and Immunogenicity of RVSV-Nipah Virus Vaccine Candidate PHV02 in
    Healthy Adult Subjects
- reference: clinicaltrials:NCT06221813
  title: >-
    A Phase 1b Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate
    the Safety and Immunogenicity of a Prime-Boost Regimen of Three Dose Levels
    of PHV02, a Nipah Virus Vaccine Candidate (rVSV-ΔG-EBOV GP-NiVG) in Healthy
    Adults
- reference: clinicaltrials:NCT05398796
  title: >-
    VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial
    to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV)
    mRNA Vaccine, mRNA-1215, in Healthy Adults
- reference: clinicaltrials:NCT01811784
  title: >-
    A Community Intervention Trial Utilizing Behavior Change to Reduce the Risk
    of Nipah Spillover Through Date Palm Sap in Bangladesh
📚

References & Deep Research

References

19
PMID:38399954
Nipah Virus: A Multidimensional Update.
No top-level findings curated for this source.
PMID:38185127
Nipah virus disease: what can we do to improve patient care?
No top-level findings curated for this source.
PMID:39119137
A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development.
No top-level findings curated for this source.
PMID:39700307
Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: Lessons from Kerala, India.
No top-level findings curated for this source.
PMID:39292378
Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement.
No top-level findings curated for this source.
PMID:39633840
Risk Evaluation and Mitigation Strategies for Potential Outbreaks of Nipah Virus Infection: Evidenced by the Recent Incidences in Southeast Asian Countries.
No top-level findings curated for this source.
PMID:37896758
Animal Models for Henipavirus Research.
No top-level findings curated for this source.
PMID:10781618
Clinical features of Nipah virus encephalitis among pig farmers in Malaysia.
No top-level findings curated for this source.
PMID:18444812
Clinical presentation of nipah virus infection in Bangladesh.
No top-level findings curated for this source.
PMID:12466131
Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis.
No top-level findings curated for this source.
PMID:15279700
Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling.
No top-level findings curated for this source.
PMID:36851768
Nipah Virus Impairs Autocrine IFN Signaling by Sequestering STAT1 and STAT2 into Inclusion Bodies.
No top-level findings curated for this source.
PMID:24130486
Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody.
No top-level findings curated for this source.
PMID:19888339
A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.
No top-level findings curated for this source.
clinicaltrials:NCT04199169
A Phase 1 Randomized, Placebo-controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of a Nipah Vaccine, HeV-sG-V (Hendra Virus Soluble Glycoprotein Vaccine), in Healthy Adults
No top-level findings curated for this source.
clinicaltrials:NCT05178901
A Phase 1 Randomized, Single Center, Double-Blind, Placebo-Controlled, Dose-Response and Open-Label or Single Blind Booster Study to Evaluate the Safety and Immunogenicity of RVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects
No top-level findings curated for this source.
clinicaltrials:NCT06221813
A Phase 1b Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Prime-Boost Regimen of Three Dose Levels of PHV02, a Nipah Virus Vaccine Candidate (rVSV-ΔG-EBOV GP-NiVG) in Healthy Adults
No top-level findings curated for this source.
clinicaltrials:NCT05398796
VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults
No top-level findings curated for this source.
clinicaltrials:NCT01811784
A Community Intervention Trial Utilizing Behavior Change to Reduce the Risk of Nipah Spillover Through Date Palm Sap in Bangladesh
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
Nipah Virus Disease: Comprehensive Disease-Characteristics Report
Edison Scientific Literature 39 citations 2026-07-24T16:27:26.984966

Nipah Virus Disease: Comprehensive Disease-Characteristics Report

Executive summary

Nipah virus disease (NVD) is an acute, bat-borne zoonotic infection caused by Nipah virus (NiV), an enveloped negative-sense single-stranded RNA henipavirus. Disease ranges from asymptomatic infection or influenza-like illness to rapidly progressive pneumonia, acute respiratory distress syndrome (ARDS), encephalitis, seizures, coma, and death. The major biological lesion is systemic infection of ephrin-B2/B3-expressing endothelium and neural cells, producing vasculitis, thrombosis, blood–brain-barrier injury, and neuronal infection. Pteropus fruit bats are the reservoir; transmission occurs through contaminated food, infected livestock, and close contact with infected people. Outbreak-specific case-fatality ratios (CFRs) range from approximately 25% to 100%, and an aggregated 2024 review reported 424 deaths among 729 recognized cases (58%). No human vaccine or disease-specific treatment is licensed; supportive intensive care remains standard, while m102.4 and remdesivir are the leading candidates for clinical efficacy trials. (hassan2024nipahvirusdisease pages 11-14, hassan2024nipahvirusdisease pages 9-11, fauscotino2024nipahvirusa pages 3-5, fauscotino2024nipahvirusa pages 7-9, chan2024nipahvirustherapeutics pages 12-14)

The following compact table is intended for direct knowledge-base curation.

Domain High-confidence annotation/finding Suggested ontology identifiers/terms Evidence type and caveat
Disease identifier/classification Nipah virus disease is a zoonotic henipavirus infection causing severe acute encephalitis and/or respiratory disease. Confident retrieved identifier: MeSH D045464 Henipavirus Infections; specific MONDO ID not confidently established from retrieved evidence, so mark unknown/not confirmed here. MeSH: D045464 Henipavirus Infections; Disease label: Nipah virus infection / disease; MONDO: unknown in retrieved sources Clinical trial registry-derived MeSH plus recent reviews; MeSH term in trials is broader than Nipah-specific disease, so disease-level normalization should be reviewed separately (NCT05178901 chunk 1, NCT04199169 chunk 1, NCT05398796 chunk 1, fauscotino2024nipahvirusa pages 3-5)
Pathogen Cause is Nipah virus (NiV), a negative-sense ssRNA henipavirus in family Paramyxoviridae; major clades/strains discussed are Malaysia and Bangladesh/India lineages. Pathogen label: Nipah virus; Taxon term label acceptable if needed; CHEBI: not applicable Review/pathobiology evidence; strain nomenclature and clade proposals are evolving, especially for India lineage (tan2024asystematicreview pages 1-2, fauscotino2024nipahvirusa pages 3-5, anish2024pandemicpotentialof pages 2-3)
Reservoir and spillover ecology Natural reservoir is Pteropus fruit bats; spillover occurs directly via bat-contaminated food (notably raw date palm sap) and indirectly via amplifying hosts such as pigs; horses also noted in some outbreaks/reviews. Host/reservoir terms: Pteropus bats, swine, horse; Exposure term: raw date palm sap consumption Strong epidemiologic consensus; exact reservoir species differs by geography, and not all spillover events involve an intermediate host (tan2024asystematicreview pages 1-2, anish2024pandemicpotentialof pages 2-3, NCT01811784 chunk 1, pigeaud2023animalmodelsfor pages 1-2)
Transmission/risk factors Major routes: pig-to-human in Malaysia/Singapore, contaminated date palm sap in Bangladesh, and person-to-person spread in Bangladesh/India/Kerala; close patient contact is a major risk factor. Exposure terms: zoonotic transmission, person-to-person transmission, foodborne exposure, occupational exposure Human outbreak investigations and reviews; route contributions vary strongly by outbreak setting (rahman2024riskevaluationand pages 3-4, tan2024asystematicreview pages 1-2, hassan2024nipahvirusdisease pages 11-14, hassan2024nipahvirusdisease pages 9-11)
Core phenotype set Dominant phenotype spectrum: fever, headache, myalgia, cough/shortness of breath, acute encephalitis, confusion, seizures, coma; respiratory disease can be prominent, especially Bangladesh/India clade. HPO suggestions: Fever, Headache, Myalgia, Cough, Dyspnea, Encephalitis, Confusion, Seizure, Coma Human clinical reviews and outbreaks; exact frequency by symptom is incompletely standardized across cohorts (hassan2024nipahvirusdisease pages 11-14, chan2024nipahvirustherapeutics pages 1-4, saha2024recentadvancesof pages 6-7)
Long-term sequelae / QoL Survivors may develop persistent neurologic disability, including paralysis and oculomotor/neurologic deficits; relapsing or late encephalitis is recognized. HPO suggestions: Paralysis, Abnormality of eye movement, Neurocognitive impairment Based on follow-up literature summarized in reviews; precise prevalence and QoL instrument data are limited (chan2024nipahvirustherapeutics pages 1-4, saha2024recentadvancesof pages 6-7, chan2024nipahvirustherapeutics pages 12-14)
Host genes / molecular host factors EFNB2 and EFNB3 are key host entry receptors for NiV G glycoprotein. These are host susceptibility/entry factors, not inherited monogenic causes of disease. Gene symbols: EFNB2, EFNB3; Mechanism labels: viral receptor activity, virus entry into host cell Strong mechanistic evidence from virology studies and reviews; no retrieved evidence supports inherited pathogenic variants causing Nipah disease susceptibility (fauscotino2024nipahvirusa pages 3-5, brown2023immunopathogenesisofnipah pages 5-7, anish2024pandemicpotentialof pages 2-3)
Viral genes and immune evasion Viral genome encodes N, P, M, F, G, L and accessory V/W/C proteins; G mediates receptor binding, F mediates fusion, and V/W/P antagonize interferon pathways. GO suggestions: virus entry into host cell, membrane fusion, negative regulation of type I interferon production, suppression by virus of host type I interferon-mediated signaling pathway Mostly mechanistic review synthesis from primary experimental work; gene-by-gene effects are largely derived from in vitro/animal systems rather than direct human intervention studies (fauscotino2024nipahvirusa pages 3-5, brown2023immunopathogenesisofnipah pages 5-7)
Pathophysiology Upstream-to-downstream chain: respiratory entry → local replication → viremia/leukocyte-associated spread → endothelial and neuronal tropism → vasculitis, thrombosis, syncytia, BBB disruption, encephalitis, pulmonary edema/ARDS. GO suggestions: viral process, cell-cell fusion, vasculitis, inflammatory response, blood-brain barrier disruption; CL suggestions: endothelial cell, neuron, monocyte, natural killer cell, T cell Combined human pathology, in vitro, and animal-model evidence; BBB and leukocyte “Trojan horse” mechanisms remain incompletely resolved (fauscotino2024nipahvirusa pages 3-5, saha2024recentadvancesof pages 6-7, anish2024pandemicpotentialof pages 2-3)
Affected anatomy and cells Primary organs/systems: brain/CNS, lung/respiratory tract, vascular endothelium; secondary involvement includes kidney, liver, and heart in severe systemic disease. Key target cells include neurons, vascular endothelial cells, and probably leukocyte populations during dissemination. UBERON suggestions: brain, lung, blood vessel endothelium, kidney, liver, heart; CL suggestions: neuron, endothelial cell, smooth muscle cell, monocyte, NK cell, CD8-positive T cell Human pathology and animal data agree on CNS/lung/endothelium; cell-type ranking outside endothelium/neurons is less certain in humans (fauscotino2024nipahvirusa pages 3-5, saha2024recentadvancesof pages 6-7, anish2024pandemicpotentialof pages 2-3)
Diagnostics Outbreak diagnosis relies on laboratory confirmation plus clinical/epidemiologic context; recent reviews emphasize need for rapid diagnosis and strengthened diagnostic capacity. Experimental immunoassays using recombinant ephrin-B2 capture have been described. Diagnostic labels: RT-PCR, serology/ELISA, antigen detection, contact/exposure history Retrieved evidence set gives only partial test-detail coverage; exact specimen hierarchy and reference-standard algorithms are not fully captured here, so formal WHO/CDC lab guidance should be added in production (rahman2024riskevaluationand pages 3-4, fauscotino2024nipahvirusa pages 3-5)
Prognosis / statistics High mortality overall. Recent review summarized 729 cases, 424 deaths (58%) overall; CFRs are typically <40% in Malaysia and often >70% in Bangladesh/India/Philippines. 2023 Bangladesh outbreak reported 14 cases, 10 deaths (71%) in one review. Prognostic labels: case fatality rate, neurologic sequelae, rapid progression Aggregated review data; outbreak-specific CFRs depend on strain, detection intensity, and care access, so statistics should be stored with location/year provenance (tan2024asystematicreview pages 1-2, hassan2024nipahvirusdisease pages 11-14, hassan2024nipahvirusdisease pages 9-11)
Treatment status and care No licensed therapy or vaccine for humans. Current care is mainly supportive/ICU care; evidence-based priorities for trials are m102.4 and remdesivir for prophylaxis/early treatment. Ribavirin has observational human use but uncertain efficacy and tolerability concerns. MAXO suggestions: supportive care, intensive care management, mechanical ventilation/respiratory support, antiviral treatment, monoclonal antibody therapy Strong expert consensus from 2024 reviews; efficacy evidence for most agents is preclinical or observational, not definitive randomized clinical efficacy (anish2024pandemicpotentialof pages 9-10, chan2024nipahvirustherapeutics pages 4-6, fauscotino2024nipahvirusa pages 7-9, chan2024nipahvirustherapeutics pages 12-14, chan2024nipahvirustherapeutics pages 1-4)
Prevention / public health Key preventive measures: avoid raw date palm sap, use tree skirts/barriers to prevent bat contamination, infection-control measures for human-to-human spread, surveillance/contact tracing, and community education. MAXO suggestions: exposure avoidance counseling, infection prevention and control, contact tracing, behavior change intervention Includes interventional prevention trial context; effectiveness depends on local adherence and outbreak ecology (NCT01811784 chunk 1, NCT01811784 chunk 2, anish2024pandemicpotentialof pages 1-2)
Vaccine clinical development Human vaccine trials through 2024 include HeV-sG-V / HenipaVax Phase 1 (NCT04199169, completed, n=192), mRNA-1215 Phase 1 (NCT05398796, completed, n=40), PHV02 Phase 1 (NCT05178901, completed, n=60), and PHV02 prime-boost Phase 1b (NCT06221813, completed, n=120). Intervention labels: subunit vaccine, mRNA vaccine, rVSV-vectored vaccine ClinicalTrials.gov records are high-confidence for status/design/enrollment; efficacy against clinical disease is not established from these early-phase studies (NCT05178901 chunk 1, NCT04199169 chunk 1, NCT05398796 chunk 1, NCT06221813 chunk 1)
Animal models / comparative biology Reservoir biology centers on Pteropus bats; major models include Syrian hamster, ferret, guinea pig, swine, cat, and nonhuman primates. African green monkeys most closely reproduce human disease; hamsters/ferrets are practical for countermeasure triage but incompletely capture all human features. Model labels: Pteropus bat, Syrian hamster, ferret, guinea pig, pig, cat, African green monkey, marmoset, cynomolgus monkey Dedicated 2023 model review plus 2024 summaries; route/phenotype details vary by strain and inoculation method, and some companion-animal models are used sparingly for ethical/practical reasons (anish2024pandemicpotentialof pages 2-3, pigeaud2023animalmodelsfor pages 34-35, pigeaud2023animalmodelsfor pages 35-36, pigeaud2023animalmodelsfor pages 24-26, pigeaud2023animalmodelsfor pages 2-4)

Table: This table summarizes high-confidence knowledge-base annotations for Nipah virus disease across identifiers, pathogenesis, clinical features, prognosis, prevention, treatment status, vaccine trials, and animal models. It is designed as a compact curation aid and notes where ontology IDs or evidence remain uncertain.

1. Disease information

Definition and terminology

NVD is a zoonotic henipavirus infection characterized principally by acute encephalitis and/or severe respiratory disease. Synonyms include Nipah virus infection, Nipah encephalitis, NiV infection, and, less specifically, henipavirus infection. It was first recognized during the 1998–1999 Malaysia–Singapore outbreak; subsequent recurrent outbreaks have occurred mainly in Bangladesh and India, with an equine-associated outbreak in the Philippines. (tan2024asystematicreview pages 1-2, hassan2024nipahvirusdisease pages 11-14)

Identifiers

  • MeSH: D045464, Henipavirus Infections—a broader parent concept consistently assigned in the retrieved ClinicalTrials.gov records. (NCT05178901 chunk 1, NCT04199169 chunk 1)
  • MONDO: a Nipah-specific MONDO identifier was not reliably returned by the resources accessed and should be curator-verified rather than inferred.
  • ICD-10/ICD-11: no specific code was established in the retrieved evidence. Coding generally falls under viral encephalitis or other specified zoonotic viral disease, depending on jurisdiction; production use requires verification against the current national ICD modification.
  • OMIM/Orphanet: not applicable as primary sources for a non-Mendelian acute infection; no disease-specific entries were confirmed.

This report synthesizes aggregated disease-level resources, outbreak cohorts, clinical-trial registries, and experimental literature. It is not derived from an individual EHR.

2. Etiology, risk, and protective factors

Cause

The sole necessary causal agent is NiV. Important lineages include NiV-Malaysia and the Bangladesh/India clade. The latter is associated epidemiologically with severe pulmonary involvement, person-to-person transmission, and CFRs often exceeding 70%, whereas Malaysian outbreaks had CFRs below 40%; ascertainment, route, health-system capacity, and viral biology all probably contribute. (tan2024asystematicreview pages 1-2, anish2024pandemicpotentialof pages 2-3)

Exposure risks

  • Bangladesh: consumption of raw date-palm sap contaminated by bat saliva or urine; direct caregiving and exposure to respiratory/oral secretions.
  • Malaysia/Singapore: occupational contact with infected pigs; 93% of patients in the initial setting reportedly had direct swine contact.
  • India/Kerala: zoonotic spillover followed by household or nosocomial transmission; hospital superspreading has occurred.
  • Other: contact with infected horses or contaminated meat was implicated in the Philippines.

One review estimated that 51% of recognized Bangladeshi cases followed close contact with another patient. A reported effective reproduction number around 1.46–1.80 should be interpreted cautiously because most transmission chains terminate and superspreading creates marked heterogeneity. (rahman2024riskevaluationand pages 3-4, anish2024pandemicpotentialof pages 1-2, hassan2024nipahvirusdisease pages 9-11, pigeaud2023animalmodelsfor pages 1-2)

Genetic, protective, and gene–environment factors

No validated human germline causal variant, susceptibility locus, protective allele, modifier gene, Mendelian inheritance pattern, or clinically actionable pharmacogenomic association is established. EFNB2 and EFNB3 are host entry factors, not inherited causes. The dominant gene–environment relationship is functional: exposure introduces virus to tissues expressing these receptors. Environmental protection consists of avoiding raw sap, blocking bat access to collection sites, reducing infected-animal contact, and infection-control precautions. A 7,782-participant community protocol evaluated “do not drink raw sap” messaging and sap collection from trees protected by bamboo skirts or banas. (NCT01811784 chunk 1, NCT01811784 chunk 2, fauscotino2024nipahvirusa pages 3-5)

3. Phenotypes

Disease affects all age groups and usually begins acutely after a 4–14-day incubation period, although longer incubations have occasionally been reported. Early fever, headache, myalgia, vomiting, cough, and dyspnea can progress over hours to days to altered consciousness, seizures, encephalitis, and coma; coma may develop within 24–48 hours after major neurological deterioration. Severity and respiratory prominence vary by lineage and outbreak. (chan2024nipahvirustherapeutics pages 1-4, anish2024pandemicpotentialof pages 2-3)

Phenotype Type/course Suggested HPO annotation
Fever, headache, myalgia Early symptoms; common but exact pooled frequencies unavailable Fever; Headache; Myalgia
Cough, dyspnea, atypical pneumonia Respiratory symptom/sign; variable to severe Cough; Dyspnea; Pneumonia
Pulmonary edema/ARDS Severe progressive complication Pulmonary edema; Acute respiratory distress
Confusion/somnolence Neurological/behavioral change; progressive Confusion; Somnolence
Acute encephalitis Cardinal severe manifestation Encephalitis
Seizures and coma Advanced disease; poor functional state Seizure; Coma
Paralysis, cognitive/sensory/motor or oculomotor deficits Long-term survivor morbidity Paralysis; Neurocognitive impairment; Abnormality of eye movement
Relapsing/late-onset encephalitis Episodic delayed complication, sometimes >1 year later Recurrent encephalitis/encephalopathy—curator review recommended

Survivors may have substantial dependence, impaired mobility, cognition, communication, or employment. However, recent disease-specific EQ-5D, SF-36, or PROMIS estimates were not found; quality-of-life effects are chiefly inferred from neurological disability studies. (chan2024nipahvirustherapeutics pages 1-4, chan2024nipahvirustherapeutics pages 12-14, saha2024recentadvancesof pages 6-7)

4. Genetic and molecular information

NVD is not a genetic disorder. Therefore causal human genes, ACMG-classified pathogenic variants, allele frequencies, chromosomal abnormalities, anticipation, mosaicism, founder effects, and carrier frequency are not applicable.

The approximately 18.2-kb viral genome encodes structural proteins N, P, M, F, G, and L; RNA editing/alternative expression from the P locus produces V, W, and C. G is the attachment protein, F mediates membrane fusion, M coordinates assembly/egress through phosphatidylserine and PI(4,5)P2 interactions, and L is the RNA-dependent RNA polymerase. V/W/P antagonize interferon production or STAT-dependent signaling; C contributes to budding. (fauscotino2024nipahvirusa pages 3-5, brown2023immunopathogenesisofnipah pages 5-7)

Relevant human genes are EFNB2 and EFNB3, whose products act as viral receptors. Deep mutational scanning published in 2023 engineered an EFNB2 decoy that retained henipavirus-G binding while reducing Eph-receptor binding, illustrating a potential therapeutic rather than inherited-disease mechanism.

No reproducible human disease-associated DNA methylation, histone modification, structural variant, or clinically actionable epigenetic signature was established in the evidence reviewed.

5. Environmental and infectious-agent information

The primary non-genetic determinants are ecological and behavioral: bat habitat overlap, date-palm-sap harvesting, livestock intensification, occupational swine exposure, unsafe caregiving, inadequate personal protective equipment, and delayed recognition in resource-constrained settings. Smoking, alcohol, exercise, and ordinary diet have no established disease-specific causal role apart from consumption of contaminated raw foods. (rahman2024riskevaluationand pages 3-4, tan2024asystematicreview pages 1-2, NCT01811784 chunk 1)

Agent: Nipah virus, genus Henipavirus, family Paramyxoviridae. The virus requires maximum-containment laboratory practices for live-virus work. Pteropus bats shed virus through saliva and urine without the fulminant disease seen in spillover hosts. (NCT01811784 chunk 1, pigeaud2023animalmodelsfor pages 1-2)

6. Mechanism and pathophysiology

Causal chain

  1. Attachment and fusion: NiV-G binds EFNB2/EFNB3; conformational activation of trimeric F drives fusion at the plasma/endosomal membrane.
  2. Local replication: respiratory epithelial infection produces syncytia and inflammatory mediators; severe cases develop alveolar hemorrhage, edema, and ARDS.
  3. Immune evasion: V/W/P suppress type-I interferon production or signaling, including STAT pathways; W also suppresses inflammatory mediators including CCL4, CCL5, and TNF-α in experimental systems.
  4. Dissemination: free virus and leukocyte-associated virus enter blood. T cells, natural-killer cells, and monocytes have been implicated experimentally.
  5. Endotheliotropism: infection of vascular endothelial cells causes multinucleated syncytia, necrotizing vasculitis, permeability, thrombosis, and microinfarction.
  6. Neuroinvasion: hematogenous endothelial infection, disrupted blood–brain barrier, leukocyte-associated transport, olfactory routes, and direct neuronal spread are plausible, nonexclusive mechanisms.
  7. Clinical injury: neuronal infection plus ischemic/perivascular lesions causes encephalitis, seizures, coma, and persistent deficits; systemic vascular disease contributes to renal, hepatic, and cardiac injury. (fauscotino2024nipahvirusa pages 3-5, saha2024recentadvancesof pages 6-7, anish2024pandemicpotentialof pages 2-3)

Suggested annotations include GO: virus entry into host cell; membrane fusion; viral genome replication; negative regulation of type-I interferon signaling; inflammatory response; cell–cell fusion, and cell types endothelial cell, neuron, bronchiolar epithelial cell, alveolar type-II cell, smooth-muscle cell, monocyte, NK cell, and CD8-positive T cell. Smooth-muscle cells can support prolonged high-titer replication without obvious cytopathic effect in vitro, so infection does not invariably equal tissue destruction.

Molecular profiling and advanced technology

Bulk immune-expression studies report TNF-α, IL-1β, IL-6, IL-8, CXCL10, and G-CSF perturbation, but validated diagnostic transcriptomic, proteomic, metabolomic, or lipidomic signatures are not established. No mature human single-cell atlas, spatial-transcriptomic map, integrated clinical multi-omics classifier, or validated genome-wide CRISPR dependency panel was identified. These should be marked insufficient evidence, not negative findings. (saha2024recentadvancesof pages 6-7)

7. Anatomical structures affected

Primary systems are the CNS, respiratory tract, and systemic vasculature. Suggested UBERON labels are brain, cerebral blood vessel, blood–brain barrier, lung, bronchial epithelium, pulmonary alveolus, blood vessel endothelium, kidney, liver, and heart. Major lesions include encephalitis with necrosis/perivascular cuffing, pulmonary edema and hemorrhage, endothelial syncytia, vasculitis, and thrombosis. Kidney, liver, and heart are secondary systemic targets. Disease is diffuse rather than consistently unilateral; lateralization is not characteristic. (fauscotino2024nipahvirusa pages 3-5, saha2024recentadvancesof pages 6-7, pigeaud2023animalmodelsfor pages 2-4)

Subcellular annotations include plasma membrane (G–receptor attachment and fusion), endosome (F trafficking/activation), cytoplasm (replication complex), and plasma-membrane lipid domains (M-mediated assembly). There is no established primary mitochondrial, lysosomal, or nuclear storage defect.

8. Temporal development

Onset is acute or subacute in children and adults rather than congenital or age-dependent. A pragmatic sequence is incubation → febrile/prodromal illness → respiratory or neurological deterioration → encephalitis/ARDS and multiorgan injury → death or recovery with possible neurological sequelae. The critical treatment window is probably before high viral burden, encephalitis, and irreversible vascular/neural injury. (chan2024nipahvirustherapeutics pages 1-4, chan2024nipahvirustherapeutics pages 12-14)

Most disease is self-limited through death or recovery, not chronically replicative lifelong disease. Nevertheless, persistent viral foci or delayed inflammatory/reactivation phenomena may produce relapsing or late-onset encephalitis months to years later. Spontaneous clinical remission occurs in survivors; no therapy-induced remission rate has been established.

9. Inheritance, epidemiology, and population

No inheritance pattern, penetrance, carrier state, anticipation, or genetic counseling indication applies. Population risk is exposure-driven.

The 2024 global review synthesized 97 articles and found almost annual outbreaks in Bangladesh. Aggregate counts in another clinical review were 729 recognized cases and 424 deaths (58%). Country/outbreak CFRs varied from approximately 25% to 100%; mortality was generally below 40% in Malaysia and above 70% in Bangladesh, India, and the Philippines. The 2023 Bangladesh outbreak had 14 cases and 10 deaths (71%); Kerala’s September 2023 outbreak had six cases and two deaths. Kerala’s 2018 event included 23 infections (18 confirmed and five probable) and 21 deaths. (tan2024asystematicreview pages 1-2, anish2024pandemicpotentialof pages 1-2, hassan2024nipahvirusdisease pages 11-14, hassan2024nipahvirusdisease pages 9-11)

Because NiV is episodic and geographically focal, stable prevalence and annual incidence per 100,000 are not meaningful globally. Surveillance limitations likely cause underascertainment. No consistent sex ratio is established; occupational exposure produced male predominance in some swine-associated cohorts. All ages can be affected. (rahman2024riskevaluationand pages 3-4, chan2024nipahvirustherapeutics pages 1-4)

10. Diagnostics

Diagnosis requires epidemiological suspicion plus laboratory confirmation. Recommended outbreak testing includes:

  • Real-time RT-PCR for viral RNA from respiratory/throat or nasal swabs, blood/serum, urine, and cerebrospinal fluid as clinically appropriate; timing and local reference-laboratory protocols matter.
  • Serology, especially NiV-specific IgM/IgG ELISA or neutralization, for later disease or retrospective confirmation.
  • Virus isolation only in appropriately equipped high-containment laboratories.
  • MRI may show multifocal small ischemic or inflammatory brain lesions; EEG and CSF studies support encephalitis assessment but are not pathogen-specific.
  • Histopathology may show necrotizing vasculitis, thrombosis, endothelial syncytia, and neuronal/endothelial viral antigen.

Experimental ephrin-B2-capture ELISA and lateral-flow formats can distinguish NiV/HeV antigen in research settings, but they are not replacements for validated public-health assays.

Clinical differentials include Japanese encephalitis, herpes simplex encephalitis, other arboviral encephalitides, bacterial meningitis, cerebral malaria, influenza/COVID-19 and other severe viral pneumonias, toxic-metabolic encephalopathy, and stroke. Exposure history, combined respiratory–neurological disease, clustering, and NiV-specific testing are discriminating.

Human genetic testing—WGS, WES, panels, CMA, karyotype, FISH, mitochondrial, or repeat-expansion testing—is not indicated for etiologic diagnosis. There is no population newborn or carrier screening. During outbreaks, contact identification, symptom surveillance, and targeted molecular testing constitute secondary prevention.

11. Outcome and prognosis

Mortality is high and usually occurs during acute encephalitic, respiratory, or multiorgan disease. Conventional five- or ten-year survival estimates are not applicable. Poor prognostic features plausibly include severe encephalopathy, coma, seizures, respiratory distress, high viral burden, and delayed supportive care, although validated bedside prognostic models are lacking. (chan2024nipahvirustherapeutics pages 1-4, anish2024pandemicpotentialof pages 2-3)

Survivors can recover substantially but remain at risk for paralysis, cognitive/sensory/motor deficits, oculomotor dysfunction, psychiatric or functional consequences, and late encephalitis. There is no validated prognostic molecular biomarker. Viral RNA burden, inflammatory mediators, and neutralizing-antibody responses remain research measures rather than approved prognostic tests. (chan2024nipahvirustherapeutics pages 1-4, saha2024recentadvancesof pages 6-7)

12. Treatment

Current standard

There is no licensed NiV-specific drug or human vaccine. Management consists of isolation and infection prevention, oxygen and ventilatory support, fluid/electrolyte management, hemodynamic and renal support, seizure treatment, treatment of secondary infections, nutrition, pressure-injury prevention, and rehabilitation. Suggested MAXO labels include supportive care, intensive-care management, mechanical ventilation, anticonvulsant therapy, renal replacement therapy, physical therapy, occupational therapy, and speech therapy. (chan2024nipahvirustherapeutics pages 4-6, fauscotino2024nipahvirusa pages 7-9)

Investigational agents

  • m102.4: human monoclonal antibody targeting the G–EFNB2/B3 interface. A Phase 1 study in 40 healthy volunteers found no serious adverse events and a placebo-like safety profile; headache was most common. Post-exposure protection has been demonstrated in ferrets and nonhuman primates. MAXO: monoclonal-antibody therapy. (chan2024nipahvirustherapeutics pages 6-8)
  • Remdesivir: nucleotide-analog viral polymerase inhibitor. It protected African green monkeys when given early; one review reported 67% survival with early dosing. Compassionate-use Kerala observations are uncontrolled and too small for efficacy inference. MAXO: antiviral therapy. (anish2024pandemicpotentialof pages 9-10, kallon2024therapeuticadvancementin pages 6-7)
  • Ribavirin: observational Malaysian data suggested a 36% relative mortality-risk reduction, but confounding is substantial and African-green-monkey efficacy was absent. Fatigue, headache, hyperbilirubinemia, and hemoglobin reduction caused all eight recipients in one post-exposure series to discontinue therapy. (fauscotino2024nipahvirusa pages 7-9, chan2024nipahvirustherapeutics pages 6-8)
  • Favipiravir: RNA-polymerase inhibitor giving 100% survival in one hamster regimen; no demonstrated human efficacy. (kallon2024therapeuticadvancementin pages 6-7)
  • Other antibodies, including h5B3.1, nAH1.3, HENV-26, and HENV-32, remain preclinical.

The clearest 2024 expert assessment was that only m102.4 and remdesivir had sufficient evidence to prioritize for trials, alone or in combination, for prophylaxis or early treatment. This is a prioritization judgment, not proof of clinical efficacy. PK/PD optimization and pre-positioned adaptive outbreak protocols are essential. (chan2024nipahvirustherapeutics pages 12-14, chan2024nipahvirustherapeutics pages 1-4)

Vaccine trials and recent development

  • HeV-sG-V/HenipaVax, Hendra soluble-G subunit with alum: Phase 1, NCT04199169, completed, 192 adults; 10-, 30-, and 100-µg schedules. (NCT04199169 chunk 1)
  • PHV02, live attenuated rVSV-ΔG-EBOV-GP-NiV-G: NCT05178901, Phase 1, completed, 60 adults; NCT06221813, Phase 1b prime–boost study, 120 adults, begun January 2024. (NCT05178901 chunk 1, NCT06221813 chunk 1)
  • mRNA-1215, lipid-nanoparticle mRNA encoding a secreted prefusion-stabilized F/G immunogen: NCT05398796, Phase 1, 40 adults, two doses at 10–100 µg. (NCT05398796 chunk 1, NCT05398796 chunk 2)

These studies address safety and immunogenicity, not clinical disease prevention. Gene therapy, cell therapy, surgery, and genotype-guided treatment are not applicable.

13. Prevention

Primary prevention: avoid raw date-palm sap and fruit contaminated by bats; boil/pasteurize sap; cover collection sites with bat-exclusion skirts; use gloves and respiratory/eye protection when handling sick livestock; improve farm biosecurity and separate pigs from bat-attracting fruit trees. (NCT01811784 chunk 1)

Secondary prevention: rapid case recognition and RT-PCR confirmation, immediate isolation, contact tracing and active monitoring, safe specimen handling, appropriate PPE, and targeted testing. Healthcare-associated superspreading makes ventilation, hand hygiene, droplet/contact precautions, and escalation to airborne precautions for aerosol-generating procedures especially important. (anish2024pandemicpotentialof pages 1-2)

Tertiary prevention: aggressive organ support, seizure control, prevention of aspiration and secondary infection, and long-term neurological rehabilitation.

There is no licensed immunization or established antiviral prophylaxis. m102.4 and remdesivir prophylaxis remain investigational. Community engagement and One Health surveillance of humans, bats, livestock, food production, and land-use change are authoritative priorities. (tan2024asystematicreview pages 1-2, chan2024nipahvirustherapeutics pages 12-14)

14. Other species and natural disease

Pteropus fruit bats—including Pteropus medius in South Asia—are principal reservoirs. Pigs were amplification hosts in Malaysia/Singapore; 93% of patients in the original setting had direct infected-swine contact. Horses were implicated in the Philippines. Infection or serological evidence has also occurred in dogs and cats near outbreaks. Breed-specific VBO associations and orthologous “disease genes” are not applicable. (anish2024pandemicpotentialof pages 2-3, pigeaud2023animalmodelsfor pages 1-2)

Cross-species susceptibility is facilitated by conservation of EFNB2/B3. Spillover hosts develop much more severe respiratory, neurological, and vascular disease than reservoir bats. Swine are both veterinary disease hosts and epidemiologically important amplifiers, making livestock vaccination and surveillance potentially valuable One Health interventions.

15. Model organisms

  • Syrian golden hamster: intranasal challenge emphasizes pneumonia/respiratory disease; intraperitoneal challenge produces dose-dependent lung, brain, kidney, hemorrhagic, and vascular lesions. It recapitulates most major human features but not myocarditis consistently. Practical for antiviral/vaccine screening. (anish2024pandemicpotentialof pages 2-3)
  • Ferret: develops acute respiratory, neurological, and systemic disease and is widely used for antibody and vaccine evaluation. It is more expensive and less immunologically tractable than rodents and does not reproduce every human lesion. (pigeaud2023animalmodelsfor pages 34-35, mishra2024advancementsinnipah pages 11-12)
  • Guinea pig: useful for histopathology, but disease reproducibility and translational fidelity are weaker.
  • Swine: biologically relevant amplifier-host model for transmission and livestock vaccines; requires both humoral and cellular immunity for protection. Husbandry and containment constrain sample size. (pigeaud2023animalmodelsfor pages 35-36)
  • Cats/dogs: susceptible and historically useful, but companion-animal ethics, inconsistent recapitulation, and superior alternatives limit routine use. (pigeaud2023animalmodelsfor pages 24-26)
  • African green monkey: most faithful model of human pulmonary, vascular, and neurological disease; used for remdesivir, antibody, vaccine, aerosol, intratracheal, and intranasal studies. Limitations are cost, small cohorts, ethics, and BSL-4 requirements. (pigeaud2023animalmodelsfor pages 35-36, pigeaud2023animalmodelsfor pages 2-4)
  • Common marmoset: intranasal/intratracheal NiV-B challenge caused 4/4 lethality, pulmonary edema, systemic vasculitis, hyperventilation, lethargy, anorexia, and hind-limb tremor after 8–11 days. Its small size permits larger NHP cohorts, but brain lesions were limited and immunological reagents are sparse. (pigeaud2023animalmodelsfor pages 24-26)
  • Cynomolgus and squirrel monkeys: reproduce portions of respiratory and neurological disease, but vasculitis and brain pathology can be less pronounced than in humans. (pigeaud2023animalmodelsfor pages 35-36, pigeaud2023animalmodelsfor pages 24-26)

No standard transgenic, knockout, humanized, zebrafish, Drosophila, yeast, organoid, or iPSC model has supplanted challenge models. Model outcomes depend strongly on viral strain, dose, route, and age, so cross-study efficacy comparisons require standardized challenge stocks and endpoints.

Evidence limitations and authoritative interpretation

The evidence base is constrained by small, unpredictable outbreaks, limited access to acute specimens, BSL-4 requirements, nonrandomized compassionate treatment, and heterogeneous case definitions. Consequently, outbreak CFRs should retain year/location provenance; animal protection must not be presented as demonstrated human efficacy; and host entry genes must not be misclassified as causal germline genes. The 2024 systematic review’s abstract accurately summarizes the central development gap: many countermeasures protect animals, but only a small number have entered human trials. (tan2024asystematicreview pages 1-2, chan2024nipahvirustherapeutics pages 4-6)

Key recent sources and URLs

  1. Tan FH et al. A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development. Virus Evolution. Published July 2024. https://doi.org/10.1093/ve/veae048. (tan2024asystematicreview pages 1-2)
  2. Hassan MZ et al. Nipah virus disease: what can we do to improve patient care? Lancet Infectious Diseases. Published July 2024. https://doi.org/10.1016/S1473-3099(23)00707-7. (hassan2024nipahvirusdisease pages 11-14)
  3. Faus-Cotino J et al. Nipah Virus: A Multidimensional Update. Viruses. Published January 2024. https://doi.org/10.3390/v16020179. (fauscotino2024nipahvirusa pages 3-5, fauscotino2024nipahvirusa pages 7-9)
  4. Anish TS et al. Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks. PLOS Global Public Health. Published December 2024. https://doi.org/10.1371/journal.pgph.0003926. (anish2024pandemicpotentialof pages 1-2)
  5. Pigeaud DD et al. Animal Models for Henipavirus Research. Viruses. Published September 2023. https://doi.org/10.3390/v15101980. (pigeaud2023animalmodelsfor pages 34-35)
  6. Chan XHS et al. Nipah Virus Therapeutics: A Systematic Review to Support Prioritisation for Clinical Trials. medRxiv preprint, posted March 2024. https://doi.org/10.1101/2024.03.11.24304091. Its recommendations require the additional caution appropriate to a preprint. (chan2024nipahvirustherapeutics pages 1-4)

References

  1. (hassan2024nipahvirusdisease pages 11-14): Md Zakiul Hassan, Tahmina Shirin, Syed M Satter, Mohammed Z Rahman, Josephine Bourner, Ashleigh Cheyne, Els Torreele, Peter Horby, and Piero Olliaro. Nipah virus disease: what can we do to improve patient care? Jul 2024. URL: https://doi.org/10.1016/s1473-3099(23)00707-7, doi:10.1016/s1473-3099(23)00707-7. This article has 26 citations and is from a highest quality peer-reviewed journal.

  2. (hassan2024nipahvirusdisease pages 9-11): Md Zakiul Hassan, Tahmina Shirin, Syed M Satter, Mohammed Z Rahman, Josephine Bourner, Ashleigh Cheyne, Els Torreele, Peter Horby, and Piero Olliaro. Nipah virus disease: what can we do to improve patient care? Jul 2024. URL: https://doi.org/10.1016/s1473-3099(23)00707-7, doi:10.1016/s1473-3099(23)00707-7. This article has 26 citations and is from a highest quality peer-reviewed journal.

  3. (fauscotino2024nipahvirusa pages 3-5): Javier Faus-Cotino, Gabriel Reina, and Javier Pueyo. Nipah virus: a multidimensional update. Viruses, 16:179, Jan 2024. URL: https://doi.org/10.3390/v16020179, doi:10.3390/v16020179. This article has 46 citations.

  4. (fauscotino2024nipahvirusa pages 7-9): Javier Faus-Cotino, Gabriel Reina, and Javier Pueyo. Nipah virus: a multidimensional update. Viruses, 16:179, Jan 2024. URL: https://doi.org/10.3390/v16020179, doi:10.3390/v16020179. This article has 46 citations.

  5. (chan2024nipahvirustherapeutics pages 12-14): Xin Hui S Chan, Ilsa L Haeusler, Bennett J K Choy, Md Zakiul Hassan, Junko Takata, Tara P Hurst, Luke M Jones, Shanghavie Loganathan, Elinor Harriss, Jake Dunning, Joel Tarning, Miles W Carroll, Peter W Horby, and Piero L Olliaro. Nipah virus therapeutics: a systematic review to support prioritisation for clinical trials. MedRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.11.24304091, doi:10.1101/2024.03.11.24304091. This article has 4 citations.

  6. (NCT05178901 chunk 1): A Phase 1 Study to Evaluate Safety & Immunogenicity of RVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects. Public Health Vaccines LLC. 2022. ClinicalTrials.gov Identifier: NCT05178901

  7. (NCT04199169 chunk 1): Safety and Immunogenicity of a Nipah Virus Vaccine. Auro Vaccines LLC. 2020. ClinicalTrials.gov Identifier: NCT04199169

  8. (NCT05398796 chunk 1): Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults. National Institute of Allergy and Infectious Diseases (NIAID). 2022. ClinicalTrials.gov Identifier: NCT05398796

  9. (tan2024asystematicreview pages 1-2): Foo Hou Tan, Asif Sukri, Nuryana Idris, Kien Chai Ong, Jie Ping Schee, Chong Tin Tan, Soon Hao Tan, Kum Thong Wong, Li Ping Wong, Kok Keng Tee, and Li-Yen Chang. A systematic review on nipah virus: global molecular epidemiology and medical countermeasures development. Virus Evolution, Jul 2024. URL: https://doi.org/10.1093/ve/veae048, doi:10.1093/ve/veae048. This article has 38 citations and is from a peer-reviewed journal.

  10. (anish2024pandemicpotentialof pages 2-3): Thekkumkara Surendran Anish, Reghukumar Aravind, Chandni Radhakrishnan, Nivedita Gupta, Pragya D. Yadav, Jerin Jose Cherian, Rima Sahay, Shubin Chenayil, Anoop Kumar A. S., Anitha Puduvail Moorkoth, Ashadevi, Velichapat Ramakrishnan Lathika, Shamsudeen Moideen, Sekhar Lukose Kuriakose, Kalathil Joseph Reena, and Thomas Mathew. Pandemic potential of the nipah virus and public health strategies adopted during outbreaks: lessons from kerala, india. PLOS Global Public Health, 4:e0003926, Dec 2024. URL: https://doi.org/10.1371/journal.pgph.0003926, doi:10.1371/journal.pgph.0003926. This article has 26 citations and is from a peer-reviewed journal.

  11. (NCT01811784 chunk 1): Community Intervention to Prevent Nipah Spillover. International Centre for Diarrhoeal Disease Research, Bangladesh. 2012. ClinicalTrials.gov Identifier: NCT01811784

  12. (pigeaud2023animalmodelsfor pages 1-2): Declan D. Pigeaud, Thomas W. Geisbert, and Courtney Woolsey. Animal models for henipavirus research. Viruses, 15:1980, Sep 2023. URL: https://doi.org/10.3390/v15101980, doi:10.3390/v15101980. This article has 40 citations.

  13. (rahman2024riskevaluationand pages 3-4): Md. Ashrafur Rahman, Yeasna Shanjana, Sydney Cronmiller, Donovan Zong, Rob Davis, Julianne Ernest, Jonah Nguyen, Amanda Rawa, Marie Roke Thomas, and Md. Rabiul Islam. Risk evaluation and mitigation strategies for potential outbreaks of nipah virus infection: evidenced by the recent incidences in southeast asian countries. Health Science Reports, Dec 2024. URL: https://doi.org/10.1002/hsr2.70239, doi:10.1002/hsr2.70239. This article has 4 citations and is from a peer-reviewed journal.

  14. (chan2024nipahvirustherapeutics pages 1-4): Xin Hui S Chan, Ilsa L Haeusler, Bennett J K Choy, Md Zakiul Hassan, Junko Takata, Tara P Hurst, Luke M Jones, Shanghavie Loganathan, Elinor Harriss, Jake Dunning, Joel Tarning, Miles W Carroll, Peter W Horby, and Piero L Olliaro. Nipah virus therapeutics: a systematic review to support prioritisation for clinical trials. MedRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.11.24304091, doi:10.1101/2024.03.11.24304091. This article has 4 citations.

  15. (saha2024recentadvancesof pages 6-7): Sagnik Saha, Manojit Bhattacharya, Sang-Soo Lee, and Chiranjib Chakraborty. Recent advances of nipah virus disease: pathobiology to treatment and vaccine advancement. Journal of microbiology, 62:811-828, Sep 2024. URL: https://doi.org/10.1007/s12275-024-00168-3, doi:10.1007/s12275-024-00168-3. This article has 8 citations and is from a peer-reviewed journal.

  16. (brown2023immunopathogenesisofnipah pages 5-7): Brent Brown, Tanya Gravier, Ingo Fricke, Suhaila A. Al-Sheboul, Theodor-Nicolae Carp, Chiuan Yee Leow, Chinua Imarogbe, and Javad Arabpour. Immunopathogenesis of nipah virus infection and associated immune responses. Immuno, 3:160-181, Apr 2023. URL: https://doi.org/10.3390/immuno3020011, doi:10.3390/immuno3020011. This article has 19 citations.

  17. (anish2024pandemicpotentialof pages 9-10): Thekkumkara Surendran Anish, Reghukumar Aravind, Chandni Radhakrishnan, Nivedita Gupta, Pragya D. Yadav, Jerin Jose Cherian, Rima Sahay, Shubin Chenayil, Anoop Kumar A. S., Anitha Puduvail Moorkoth, Ashadevi, Velichapat Ramakrishnan Lathika, Shamsudeen Moideen, Sekhar Lukose Kuriakose, Kalathil Joseph Reena, and Thomas Mathew. Pandemic potential of the nipah virus and public health strategies adopted during outbreaks: lessons from kerala, india. PLOS Global Public Health, 4:e0003926, Dec 2024. URL: https://doi.org/10.1371/journal.pgph.0003926, doi:10.1371/journal.pgph.0003926. This article has 26 citations and is from a peer-reviewed journal.

  18. (chan2024nipahvirustherapeutics pages 4-6): Xin Hui S Chan, Ilsa L Haeusler, Bennett J K Choy, Md Zakiul Hassan, Junko Takata, Tara P Hurst, Luke M Jones, Shanghavie Loganathan, Elinor Harriss, Jake Dunning, Joel Tarning, Miles W Carroll, Peter W Horby, and Piero L Olliaro. Nipah virus therapeutics: a systematic review to support prioritisation for clinical trials. MedRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.11.24304091, doi:10.1101/2024.03.11.24304091. This article has 4 citations.

  19. (NCT01811784 chunk 2): Community Intervention to Prevent Nipah Spillover. International Centre for Diarrhoeal Disease Research, Bangladesh. 2012. ClinicalTrials.gov Identifier: NCT01811784

  20. (anish2024pandemicpotentialof pages 1-2): Thekkumkara Surendran Anish, Reghukumar Aravind, Chandni Radhakrishnan, Nivedita Gupta, Pragya D. Yadav, Jerin Jose Cherian, Rima Sahay, Shubin Chenayil, Anoop Kumar A. S., Anitha Puduvail Moorkoth, Ashadevi, Velichapat Ramakrishnan Lathika, Shamsudeen Moideen, Sekhar Lukose Kuriakose, Kalathil Joseph Reena, and Thomas Mathew. Pandemic potential of the nipah virus and public health strategies adopted during outbreaks: lessons from kerala, india. PLOS Global Public Health, 4:e0003926, Dec 2024. URL: https://doi.org/10.1371/journal.pgph.0003926, doi:10.1371/journal.pgph.0003926. This article has 26 citations and is from a peer-reviewed journal.

  21. (NCT06221813 chunk 1): Study to Evaluate Safety and Immunogenicity of a Prime-Boost Regimen of rVSV-Nipah Virus Vaccine Candidate PHV02 in Healthy Adult Subjects. Public Health Vaccines LLC. 2024. ClinicalTrials.gov Identifier: NCT06221813

  22. (pigeaud2023animalmodelsfor pages 34-35): Declan D. Pigeaud, Thomas W. Geisbert, and Courtney Woolsey. Animal models for henipavirus research. Viruses, 15:1980, Sep 2023. URL: https://doi.org/10.3390/v15101980, doi:10.3390/v15101980. This article has 40 citations.

  23. (pigeaud2023animalmodelsfor pages 35-36): Declan D. Pigeaud, Thomas W. Geisbert, and Courtney Woolsey. Animal models for henipavirus research. Viruses, 15:1980, Sep 2023. URL: https://doi.org/10.3390/v15101980, doi:10.3390/v15101980. This article has 40 citations.

  24. (pigeaud2023animalmodelsfor pages 24-26): Declan D. Pigeaud, Thomas W. Geisbert, and Courtney Woolsey. Animal models for henipavirus research. Viruses, 15:1980, Sep 2023. URL: https://doi.org/10.3390/v15101980, doi:10.3390/v15101980. This article has 40 citations.

  25. (pigeaud2023animalmodelsfor pages 2-4): Declan D. Pigeaud, Thomas W. Geisbert, and Courtney Woolsey. Animal models for henipavirus research. Viruses, 15:1980, Sep 2023. URL: https://doi.org/10.3390/v15101980, doi:10.3390/v15101980. This article has 40 citations.

  26. (chan2024nipahvirustherapeutics pages 6-8): Xin Hui S Chan, Ilsa L Haeusler, Bennett J K Choy, Md Zakiul Hassan, Junko Takata, Tara P Hurst, Luke M Jones, Shanghavie Loganathan, Elinor Harriss, Jake Dunning, Joel Tarning, Miles W Carroll, Peter W Horby, and Piero L Olliaro. Nipah virus therapeutics: a systematic review to support prioritisation for clinical trials. MedRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.11.24304091, doi:10.1101/2024.03.11.24304091. This article has 4 citations.

  27. (kallon2024therapeuticadvancementin pages 6-7): Mary K. Kallon, Daniel Maada Mami, Emmanuel Tom Mami, Mariam Romba, M. Patrick Andrew, and M. Sylvester Martain. Therapeutic advancement in treatment and prevention of nipah viral infection: a review. Asian Journal of Research in Infectious Diseases, 15:51-65, Apr 2024. URL: https://doi.org/10.9734/ajrid/2024/v15i4343, doi:10.9734/ajrid/2024/v15i4343. This article has 5 citations.

  28. (NCT05398796 chunk 2): Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults. National Institute of Allergy and Infectious Diseases (NIAID). 2022. ClinicalTrials.gov Identifier: NCT05398796

  29. (mishra2024advancementsinnipah pages 11-12): Gayatree Mishra, Vishal Prajapat, and Debasis Nayak. Advancements in nipah virus treatment: analysis of current progress in vaccines, antivirals, and therapeutics. Immunology, 171:155-169, Sep 2024. URL: https://doi.org/10.1111/imm.13695, doi:10.1111/imm.13695. This article has 78 citations and is from a peer-reviewed journal.

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