Powassan Virus Disease

Infectious Disease MONDO:0000276 Pathograph 19 Show in embeddings browser Arbovirus Infection

Powassan virus disease is an emerging tick-borne flaviviral infection of North America (and parts of Russia), transmitted by Ixodes ticks. Most infections are asymptomatic or cause a febrile illness, but severe neuroinvasive disease (meningitis, encephalitis) carries a case-fatality of roughly 10-30% and leaves about half of survivors with long-term neurological sequelae. Its geographic range and reported incidence are both increasing, and there is no licensed vaccine or specific antiviral.

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Classifications

Harrison's Part
INFECTIOUS DISEASES NEUROLOGIC
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Pathophysiology

5
Tick-Bite Inoculation and Flaviviral Entry
POWV in tick saliva infects permissive cells at the bite site - thought to include keratinocytes and dendritic Langerhans cells - entering via receptor-mediated endocytosis, with endosomal acidification driving fusion of the viral envelope and release of the genome into the cytoplasm.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology. Langerhans cell CL:0000453 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Langerhans cell (CL:0000453). CL:0000453 is a cell type from the Cell Ontology.
endocytosis involved in viral entry into host cell GO:0075509 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves endocytosis involved in viral entry into host cell (GO:0075509). GO:0075509 is a biological process from the Gene Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Peripheral Replication and Viremia
Show evidence (1 reference)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"Cellular targets at the bite site of tick-borne FVs are thought to include keratinocytes and dendritic Langerhans cells"
Names the cellular targets at the bite site.
Peripheral Replication and Viremia
Following entry, the flaviviral genome is translated and replicated and progeny virions disseminate, producing a peripheral viremic phase that precedes central nervous system invasion. In mouse studies, POWV RNA and antigen are detected within 24 hours in draining lymph nodes, blood, bite-site macrophages, and splenic macrophages, although at the bite site it remains uncertain whether antigen-positive phagocytes are productively infected or have engulfed viral particles.
macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology.
lymph node UBERON:0000029 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lymph node (UBERON:0000029). UBERON:0000029 is an anatomical location from the Uberon multi-species anatomy ontology. blood UBERON:0000178 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in blood (UBERON:0000178). UBERON:0000178 is an anatomical location from the Uberon multi-species anatomy ontology. spleen UBERON:0002106 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in spleen (UBERON:0002106). UBERON:0002106 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Blood-Brain Barrier Disruption and Neuroinvasion
Fever
Headache
Show evidence (3 references)
PMID:42577415 SUPPORT Model organism
"POWV effectively replicates in WT mice, where replication and dissemination resulted in peripheral and neurotropic phases"
A mouse model shows the biphasic peripheral-then-neurotropic course this node asserts.
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"In addition, macrophages and fibroblasts detected at the bite site 3–24 hp bite were positive for POWV-LB antigen ... It is unclear if these cells are infected or have phagocytosed and eliminated POWV particles, but they may contribute to viraemia and neuroinvasion."
Summarizes murine bite-site macrophage antigen positivity while recording the ambiguity between productive macrophage infection and viral phagocytosis.
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"Experiments using tick salivary gland extract in POWV-LB inoculations detected POWV-LB RNA in lymph nodes of infected mice within the 24 hp infection ... Another study reported the presence of POWV-infected macrophages in the spleen"
Documents mouse evidence for early lymph-node viral RNA detection and POWV-infected macrophages in the spleen during peripheral dissemination.
Blood-Brain Barrier Disruption and Neuroinvasion
Neuroinvasion is the critical determinant of outcome. POWV entry into the CNS is accompanied by enhanced blood-brain barrier permeability, with inflammatory cytokines (TNF-alpha, IL-1beta) contributing to loss of barrier integrity.
brain microvascular endothelial cell CL:2000044 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves brain microvascular endothelial cell (CL:2000044). CL:2000044 is a cell type from the Cell Ontology.
cytokine-mediated signaling pathway GO:0019221 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves cytokine-mediated signaling pathway (GO:0019221). GO:0019221 is a biological process from the Gene Ontology.
blood brain barrier UBERON:0000120 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in blood brain barrier (UBERON:0000120). UBERON:0000120 is an anatomical location from the Uberon multi-species anatomy ontology. brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Neuroinflammation and Glial Activation
Show evidence (2 references)
PMID:42577415 SUPPORT Model organism
"Viral neuroinvasion correlated with severe neuropathological alterations as well as enhanced blood-brain barrier permeability."
Links neuroinvasion to BBB permeability.
PMID:42577415 SUPPORT BACKGROUND Other
"inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β have been shown to alter the BBB integrity"
Names the cytokines implicated in BBB disruption.
Neuroinflammation and Glial Activation
Within the CNS, POWV drives reactive microglial and astrocyte activation and infiltration of peripheral immune cells, with a histopathological predilection for gray matter (thalamus, midbrain, cerebellum). Neuroinflammation can persist in survivors.
microglial cell CL:0000129 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves microglial cell (CL:0000129). CL:0000129 is a cell type from the Cell Ontology. astrocyte CL:0000127 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves astrocyte (CL:0000127). CL:0000127 is a cell type from the Cell Ontology.
neuroinflammatory response GO:0150076 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves neuroinflammatory response (GO:0150076). GO:0150076 is a biological process from the Gene Ontology.
brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology. cerebellum UBERON:0002037 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebellum (UBERON:0002037). UBERON:0002037 is an anatomical location from the Uberon multi-species anatomy ontology. dorsal plus ventral thalamus UBERON:0001897 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in dorsal plus ventral thalamus (UBERON:0001897). UBERON:0001897 is an anatomical location from the Uberon multi-species anatomy ontology. brainstem UBERON:0002298 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brainstem (UBERON:0002298). UBERON:0002298 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Neuronal Death
Show evidence (2 references)
PMID:42577415 SUPPORT Model organism
"demonstrated increased activation of microglia (IBA1) and astrocytes (GFAP), infiltration of peripheral immune cells (CD45), and elevated neuronal cell death (TUNEL) in POWV-infected brains"
Documents microglial/astrocyte activation and immune infiltration in POWV-infected brain.
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Lymphocytic infiltration of perivascular neuronal tissue can be seen on pathology, with a predilection for gray matter, including the thalamus, midbrain, and cerebellum"
Describes the gray-matter neuropathology.
Neuronal Death
POWV-driven neuroinflammation leads to neuronal death through apoptotic and senescence-associated pathways, the substrate of the encephalitic syndrome and its long-term neurological sequelae.
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.
neuron apoptotic process GO:0051402 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves neuron apoptotic process (GO:0051402). GO:0051402 is a biological process from the Gene Ontology. cellular senescence GO:0090398 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves cellular senescence (GO:0090398). GO:0090398 is a biological process from the Gene Ontology.
brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology. cerebral cortex UBERON:0000956 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebral cortex (UBERON:0000956). UBERON:0000956 is an anatomical location from the Uberon multi-species anatomy ontology. cerebellum UBERON:0002037 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebellum (UBERON:0002037). UBERON:0002037 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Viral encephalitis
Meningitis
Seizure
Ataxia
Paralysis
Memory impairment
Aphasia
Cognitive impairment
Ophthalmoplegia
Show evidence (1 reference)
PMID:42577415 SUPPORT Model organism
"Increased protein expression of caspase-3 and p16 further indicated activation of apoptotic and senescence-associated pathways."
Supports the apoptotic and senescence pathways driving neuronal death.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Powassan 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

11
Eye 1
Ophthalmoplegia HP:0000602 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ophthalmoplegia (HP:0000602). HP:0000602 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42577415 SUPPORT BACKGROUND Human clinical
"Long-term sequelae include cognitive deficit, spastic hemiplegia, muscle weakness, imbalance, ophthalmoplegia, and memory dysfunction"
Ophthalmoplegia is a reported long-term sequela.
Immune 2
Viral encephalitis HP:0033993 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Encephalitis, annotated with Viral encephalitis (HP:0033993). HP:0033993 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42577415 SUPPORT BACKGROUND Human clinical
"POWV is the causative agent of a severe neuroinvasive illness characterized by encephalitis, meningitis"
Encephalitis is the defining severe manifestation.
Meningitis HP:0001287 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Meningitis (HP:0001287). HP:0001287 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42577415 SUPPORT BACKGROUND Human clinical
"POWV is the causative agent of a severe neuroinvasive illness characterized by encephalitis, meningitis"
Meningitis is part of the neuroinvasive spectrum.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945), qualified as temporality acute. HP:0001945 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Adult patients appeared to present with typical findings of viral encephalitis, with fever, headache, fatigue, and encephalopathy being among the most common findings."
Fever is among the most common POWV-specific presenting findings.
Nervous System 7
Headache 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:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Adult patients appeared to present with typical findings of viral encephalitis, with fever, headache, fatigue, and encephalopathy being among the most common findings."
Headache is among the most common presenting findings.
Seizure 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:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"complications can include seizures, aphasia, cranial nerve palsies, and paresis"
Seizures are a documented complication of meningoencephalitis.
Aphasia HP:0002381 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aphasia (HP:0002381). HP:0002381 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"complications can include seizures, aphasia, cranial nerve palsies, and paresis"
Aphasia/speech disorder is a documented complication and sequela.
Ataxia HP:0001251 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ataxia (HP:0001251). HP:0001251 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Factors associated with persistent neurological deficits were development of ataxia"
Ataxia is associated with persistent neurological deficits.
Paralysis HP:0003470 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Paralysis/paresis, annotated with Paralysis (HP:0003470). HP:0003470 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases"
Paralysis is the most frequent complication in the case series.
Memory impairment HP:0002354 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Memory impairment (HP:0002354). HP:0002354 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42577415 SUPPORT BACKGROUND Human clinical
"Long-term sequelae include cognitive deficit, spastic hemiplegia, muscle weakness, imbalance, ophthalmoplegia, and memory dysfunction"
Memory dysfunction is a reported long-term sequela.
Cognitive impairment HP:0100543 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cognitive impairment (HP:0100543). HP:0100543 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"cognitive deficits in 33.3% of adult and 25% of pediatric cases"
Cognitive deficits occur in a third of adult cases.
💊

Medical Actions

3
Supportive 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
There is no licensed vaccine and no specific antiviral for POWV; management is supportive, with intensive neurological and respiratory support for severe neuroinvasive disease.
Mechanism Target:
MODULATES Neuroinflammation and Glial Activation — Intensive neurocritical, seizure, and respiratory support manages the acute clinical consequences of CNS inflammation.
MODULATES Neuronal Death — Supportive neurocritical care and multidisciplinary physical/speech rehabilitation manage acute and persistent neurological deficits.
Show evidence (1 reference)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"there are currently no licenced vaccines or therapeutics for treating POWV disease"
States the absence of specific vaccines or therapeutics.
Empirical Systemic Corticosteroid Therapy
Action: Systemic Corticosteroid TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Systemic Corticosteroid Therapy (NCIT:C122080). NCIT:C122080 is a clinical intervention from the NCI Thesaurus. NCIT:C122080
Agent: corticosteroid CHEBI:50858 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses corticosteroid (CHEBI:50858). CHEBI:50858 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Systemic corticosteroids have been administered empirically (alone or in combination with IVIG) in severe neuroinvasive POWV encephalitis to attenuate CNS neuroinflammation, with clinical improvement reported in a subset of adult and pediatric cases.
Mechanism Target:
INHIBITS Neuroinflammation and Glial Activation — Empirical systemic corticosteroid anti-inflammatory therapy aims to dampen CNS glial activation and lymphocytic perivascular inflammation.
Show evidence (2 references)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"The identified treatment modalities were the administration of corticosteroids and/or IVIG. Six adult patients received only corticosteroids, four received only IVIG, while another four received both treatments. An improvement was noted in 3 of the patients receiving only corticosteroids and in..."
Documents empirical systemic corticosteroid administration (monotherapy and combined with IVIG) and clinical improvement rates in adult POWV encephalitis cases.
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Among the pediatric patients, two received corticosteroids, and both improved after treatment."
Documents empirical corticosteroid treatment and clinical improvement in two pediatric POWV encephalitis cases.
Empirical Intravenous Immunoglobulin (IVIG)
Action: Intravenous Immunoglobulin TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Intravenous Immunoglobulin Therapy (NCIT:C121331). NCIT:C121331 is a clinical intervention from the NCI Thesaurus. NCIT:C121331
Agent: Human Immunoglobulin G NCIT:C80829 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Human Immunoglobulin G (NCIT:C80829). NCIT:C80829 is a therapeutic agent from the NCI Thesaurus.
Platform: Other
Pooled human intravenous immunoglobulin (IVIG) has been administered empirically (alone or alongside systemic corticosteroids) in adult neuroinvasive POWV encephalitis to modulate neuroinflammation, with clinical improvement observed in patients receiving combined IVIG and corticosteroids.
Mechanism Target:
INHIBITS Neuroinflammation and Glial Activation — Empirical polyclonal immunoglobulin immunomodulation aims to attenuate CNS immune-cell infiltration and neuroinflammation.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"The identified treatment modalities were the administration of corticosteroids and/or IVIG. Six adult patients received only corticosteroids, four received only IVIG, while another four received both treatments. An improvement was noted in 3 of the patients receiving only corticosteroids and in..."
Documents empirical IVIG administration (alone in four adults and combined with corticosteroids in four adults) in published POWV encephalitis cases.
🔬

Diagnosis

3
Diagnosis of Powassan virus disease (Positive)
Diagnosis rests on serology (POWV-specific IgM and neutralizing antibodies) and, within the narrow viremic window, molecular testing; CNS disease is confirmed with CSF examination and supportive neuroimaging. Diagnosis is frequently delayed because the disease is rare and testing is specialized.
Diagnostic Serology Testing NCIT:C217458 NCI Thesaurus (NCIT)
Results: Positive POWV-specific IgM immunoassay and plaque-reduction neutralizing antibodies in serum and/or CSF, or detection of POWV RNA in CSF by RT-PCR or metagenomic next-generation sequencing.
Show evidence (3 references)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"The diagnosis was confirmed in all cases through testing of the serum samples or CSF for Powassan virus-neutralizing antibodies or genetic material."
Confirmation is by serum/CSF neutralizing antibodies or viral genetic material.
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Specifically, immunoassays for Powassan virus IgM were used to identify 80 cases (95.2%)—either in serum for 61 cases (72.6%), in CSF for 38 cases (45.2%), or in both for 17 cases (20.2%)."
Quantifies the diagnostic role of serum and CSF Powassan virus IgM immunoassays across published cases.
PMID:42182837 SUPPORT Human clinical
"We describe two recent POWV encephalitis cases reported in Vermonters; both experienced diagnostic delays."
Documents the diagnostic delay that is common for this rare disease.
Lumbar Puncture and Cerebrospinal Fluid Analysis (Positive)
Cerebrospinal fluid examination obtained by lumbar puncture demonstrates lymphocytic-predominant pleocytosis across age groups with elevated CSF protein in adults (whereas pediatric median CSF protein is normal) and provides CSF for POWV IgM, neutralizing antibody titers, and viral PCR/mNGS.
Lumbar Puncture NCIT:C15327 NCI Thesaurus (NCIT)
Results: Lymphocytic pleocytosis (median WBC 119/mL in adults and 137.5/mL in children), elevated CSF protein in adults (mean 88.2 mg/dL; normal pediatric median 35.5 mg/dL), normal glucose (mean 64.9 mg/dL in adults and 65.3 mg/dL in children), and detectable POWV-neutralizing antibodies.
Show evidence (3 references)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Lumbar puncture was performed in 79 (94%) of patients, with findings summarized in Table 4."
Establishes lumbar puncture and CSF analysis as standard in the diagnostic evaluation of neuroinvasive POWV.
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"The median white blood cell (WBC) count was 119/mL, predominantly lymphocytic, with a median lymphocyte count of 59.2/mL, a median monocyte count of 1.6, and a median neutrophil count of 10.9/mL. The mean glucose level was 64.9 mg/dL, and the mean protein level was 88.2 mg/dL. Opening pressures..."
Documents adult CSF lymphocytic pleocytosis, normal mean glucose, elevated mean protein (88.2 mg/dL), and neutralizing antibody titers.
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"All 14 pediatric patients underwent lumbar puncture. The median WBC count was 137.5/mL, also with a lymphocytic predominance, consisting of a median lymphocyte count of 75.5/mL, a median monocyte count of 46, and a median neutrophil count of 48.1/mL. The mean glucose level was 65.3 mg/dL and the..."
Documents pediatric CSF lymphocytic pleocytosis alongside normal mean glucose and normal median CSF protein (35.5 mg/dL).
Brain Magnetic Resonance Imaging (Positive)
Brain MRI characterizes the distribution of encephalitic gray-matter, cerebral, and posterior-fossa involvement, particularly basal ganglia, cerebral, cerebellar, thalamic, and midbrain abnormalities.
Magnetic Resonance Imaging NCIT:C16809 NCI Thesaurus (NCIT)
Results: Abnormalities most commonly involving the basal ganglia (32.1%), cerebral involvement (26.8%), cerebellar involvement (21.4%), thalamus (14.3%), and midbrain (8.9%), with leptomeningeal enhancement in 8.9% of adult cases.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Among the adults, the most commonly affected location was the basal ganglia, observed in 32.1% of cases. This was followed by cerebral involvement (26.8%) and cerebellar involvement (21.4%). The thalamus was affected in 14.3% of cases, while the midbrain showed involvement in 8.9% of cases...."
Documents the anatomical distribution and frequencies of brain MRI abnormalities in adult POWV encephalitis.
📈

Progression

2
Acute phase
Acute symptoms begin roughly 1-5 weeks after the tick bite. Severe POWV disease is biphasic: this acute phase is followed by an encephalitic phase.
Show evidence (1 reference)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"Severe POWV infections are biphasic, with acute symptoms beginning 1–5 weeks post-tick bite, followed by encephalitis that can persist for several weeks to months"
Describes the acute phase and the biphasic course.
Encephalitic phase
In severe disease the acute phase is followed by encephalitis that can persist for several weeks to months, with long-term neurological sequelae in about half of survivors.
Show evidence (1 reference)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"followed by encephalitis that can persist for several weeks to months"
The encephalitic phase follows the acute phase and is prolonged.
📊

Prevalence

1
United States, reported to CDC, 2004-2022
Cases/families reported in the literature
288 cases reported 2004-2022, of which 92.7% were neuroinvasive and 12.5% fatal; reported incidence is rising with the expanding range of vector ticks.
Show evidence (1 reference)
PMID:38133440 SUPPORT REVIEW SYNTHESIS Human clinical
"Between 2004 and 2022, a total of 288 cases have been reported to the CDC, of which 267 (92.7%) pertained to neuroinvasive disease, 264 (91.7%) required hospitalization, and 36 (12.5%) resulted in death."
Gives the CDC-reported case burden and severity breakdown.
🦠

Infectious Agent

1
Powassan virus
An enveloped, positive-sense single-stranded RNA orthoflavivirus of the family Flaviviridae, the only North American member of the tick-borne encephalitis serogroup. Two genetic lineages exist: lineage I (prototype) and lineage II (deer tick virus).
Powassan virus NCBITaxon:11083 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"Powassan viruses are emergent tick-borne Flaviviruses (FV) associated with severe encephalitic disease and long-term neurologic sequelae"
Identifies POWV as a tick-borne flavivirus.
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"POWV has two distinct genetic lineages, Lineage I (POWV-LB) and Lineage II (POWV-Spooner, Deer-tick virus, POWV-Long Island 9), spread by different species of ticks"
Documents the two POWV lineages.
↔️

Transmission

1
Ixodes tick bite transmission
POWV is transmitted in the saliva of an attached Ixodes tick. Unlike the Lyme-disease agent, which needs many hours of attachment, POWV can be transmitted within about 15 minutes of tick attachment.
Show evidence (1 reference)
PMID:40545598 SUPPORT REVIEW SYNTHESIS Other
"POWV spreads from an Ixodes tick to the host through tick saliva in as little as 15 minutes"
States the rapid salivary transmission by Ixodes ticks.
{ }

Source YAML

click to show 
name: Powassan Virus Disease
creation_date: "2026-11-04T02:33:28Z"
updated_date: "2026-11-08T03:00:00Z"
category: Infectious Disease
description: >-
  Powassan virus disease is an emerging tick-borne flaviviral infection of North
  America (and parts of Russia), transmitted by Ixodes ticks. Most infections
  are asymptomatic or cause a febrile illness, but severe neuroinvasive disease
  (meningitis, encephalitis) carries a case-fatality of roughly 10-30% and
  leaves about half of survivors with long-term neurological sequelae. Its
  geographic range and reported incidence are both increasing, and there is no
  licensed vaccine or specific antiviral.
disease_term:
  term:
    id: MONDO:0000276
    label: Powassan encephalitis
  preferred_term: Powassan virus disease
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    notes: Tick-borne arboviral infection caused by Powassan virus (Orthoflavivirus, Flaviviridae) transmitted by Ixodes ticks.
    evidence:
    - reference: PMID:40545598
      reference_title: "Pathogenicity and virulence of Powassan virus."
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: "Powassan viruses (POWV) are emergent tick-borne Flaviviruses that cause severe encephalitis and long-term neurologic sequelae in patients."
      explanation: "Establishes Powassan virus disease as a tick-borne flaviviral infectious disease."
  - classification_value: NEUROLOGIC
    notes: Neuroinvasive arboviral disease causing meningoencephalitis, gray-matter neuroinflammation, paralysis, and long-term neurological deficits.
    evidence:
    - reference: PMID:38133440
      reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: REVIEW_SYNTHESIS
      snippet: "Between 2004 and 2022, a total of 288 cases have been reported to the CDC, of which 267 (92.7%) pertained to neuroinvasive disease, 264 (91.7%) required hospitalization, and 36 (12.5%) resulted in death."
      explanation: "Demonstrates that the overwhelming majority of reported clinical cases involve central nervous system neuroinvasive disease."
synonyms:
- Powassan encephalitis
- Powassan virus infection
notes: >-
  The bound MONDO term MONDO:0000276 is labelled "Powassan encephalitis", which
  is narrower than the clinical entity curated here (CDC "Powassan virus
  disease" spans febrile and neuroinvasive forms); no broader MONDO term exists,
  so this is a candidate upstream MONDO label/scope report. No GeneReviews
  chapter exists (an arboviral infection, not a Mendelian disorder).
parents:
- Arbovirus Infection
infectious_agent:
- name: Powassan virus
  infectious_agent_term:
    preferred_term: Powassan virus
    term:
      id: NCBITaxon:11083
      label: Powassan virus
  description: >-
    An enveloped, positive-sense single-stranded RNA orthoflavivirus of the
    family Flaviviridae, the only North American member of the tick-borne
    encephalitis serogroup. Two genetic lineages exist: lineage I (prototype)
    and lineage II (deer tick virus).
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Powassan viruses are emergent tick-borne Flaviviruses (FV) associated with severe encephalitic disease and long-term neurologic sequelae"
    explanation: Identifies POWV as a tick-borne flavivirus.
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "POWV has two distinct genetic lineages, Lineage I (POWV-LB) and Lineage II (POWV-Spooner, Deer-tick virus, POWV-Long Island 9), spread by different species of ticks"
    explanation: Documents the two POWV lineages.
agent_life_cycle:
  description: >-
    POWV is maintained in an enzootic cycle between Ixodes ticks and small- to
    medium-sized mammals (white-footed mice, groundhogs, squirrels, skunks).
    Lineage I is associated mainly with Ixodes cookei and lineage II with Ixodes
    scapularis. Humans are incidental dead-end hosts, developing viremia too low
    to infect new ticks.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: dead-end (incidental) host
  - preferred_term: white-footed mouse
    term:
      id: NCBITaxon:10041
      label: Peromyscus leucopus
    role: enzootic reservoir
  - preferred_term: Blacklegged (deer) tick (vector host, lineage II)
    role: vector host
    term:
      id: NCBITaxon:6945
      label: Ixodes scapularis
  - preferred_term: Groundhog tick (vector host, lineage I)
    role: vector host
    term:
      id: NCBITaxon:35565
      label: Ixodes cookei
  vectors:
  - Ixodes scapularis (blacklegged/deer tick; lineage II)
  - Ixodes cookei (groundhog tick; lineage I)
transmission:
- name: Ixodes tick bite transmission
  description: >-
    POWV is transmitted in the saliva of an attached Ixodes tick. Unlike the
    Lyme-disease agent, which needs many hours of attachment, POWV can be
    transmitted within about 15 minutes of tick attachment.
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "POWV spreads from an Ixodes tick to the host through tick saliva in as little as 15 minutes"
    explanation: States the rapid salivary transmission by Ixodes ticks.
pathophysiology:
- name: Tick-Bite Inoculation and Flaviviral Entry
  biological_scale: MOLECULAR
  description: >-
    POWV in tick saliva infects permissive cells at the bite site - thought to
    include keratinocytes and dendritic Langerhans cells - entering via
    receptor-mediated endocytosis, with endosomal acidification driving fusion
    of the viral envelope and release of the genome into the cytoplasm.
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  - preferred_term: Langerhans cell
    term:
      id: CL:0000453
      label: Langerhans cell
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  biological_processes:
  - preferred_term: endocytosis involved in viral entry into host cell
    term:
      id: GO:0075509
      label: endocytosis involved in viral entry into host cell
  downstream:
  - target: Peripheral Replication and Viremia
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Cellular targets at the bite site of tick-borne FVs are thought to include keratinocytes and dendritic Langerhans cells"
    explanation: Names the cellular targets at the bite site.
- name: Peripheral Replication and Viremia
  biological_scale: ORGANISM
  description: >-
    Following entry, the flaviviral genome is translated and replicated and
    progeny virions disseminate, producing a peripheral viremic phase that
    precedes central nervous system invasion. In mouse studies, POWV RNA and
    antigen are detected within 24 hours in draining lymph nodes, blood,
    bite-site macrophages, and splenic macrophages, although at the bite site it
    remains uncertain whether antigen-positive phagocytes are productively
    infected or have engulfed viral particles.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  locations:
  - preferred_term: lymph node
    term:
      id: UBERON:0000029
      label: lymph node
  - preferred_term: blood
    term:
      id: UBERON:0000178
      label: blood
  - preferred_term: spleen
    term:
      id: UBERON:0002106
      label: spleen
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  downstream:
  - target: Blood-Brain Barrier Disruption and Neuroinvasion
    causal_link_type: DIRECT
  - target: Fever
  - target: Headache
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "POWV effectively replicates in WT mice, where replication and dissemination resulted in peripheral and neurotropic phases"
    explanation: >-
      A mouse model shows the biphasic peripheral-then-neurotropic course this
      node asserts.
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "In addition, macrophages and fibroblasts detected at the bite site 3–24 hp bite were positive for POWV-LB antigen ... It is unclear if these cells are infected or have phagocytosed and eliminated POWV particles, but they may contribute to viraemia and neuroinvasion."
    explanation: Summarizes murine bite-site macrophage antigen positivity while recording the ambiguity between productive macrophage infection and viral phagocytosis.
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Experiments using tick salivary gland extract in POWV-LB inoculations detected POWV-LB RNA in lymph nodes of infected mice within the 24 hp infection ... Another study reported the presence of POWV-infected macrophages in the spleen"
    explanation: Documents mouse evidence for early lymph-node viral RNA detection and POWV-infected macrophages in the spleen during peripheral dissemination.
- name: Blood-Brain Barrier Disruption and Neuroinvasion
  biological_scale: TISSUE
  conforms_to: "blood_brain_barrier_breakdown#Blood-Brain Barrier Permeability Increase"
  description: >-
    Neuroinvasion is the critical determinant of outcome. POWV entry into the
    CNS is accompanied by enhanced blood-brain barrier permeability, with
    inflammatory cytokines (TNF-alpha, IL-1beta) contributing to loss of barrier
    integrity.
  cell_types:
  - preferred_term: brain microvascular endothelial cell
    term:
      id: CL:2000044
      label: brain microvascular endothelial cell
  locations:
  - preferred_term: blood brain barrier
    term:
      id: UBERON:0000120
      label: blood brain barrier
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  biological_processes:
  - preferred_term: cytokine-mediated signaling pathway
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
  downstream:
  - target: Neuroinflammation and Glial Activation
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Viral neuroinvasion correlated with severe neuropathological alterations as well as enhanced blood-brain barrier permeability."
    explanation: Links neuroinvasion to BBB permeability.
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: BACKGROUND
    snippet: "inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β have been shown to alter the BBB integrity"
    explanation: Names the cytokines implicated in BBB disruption.
- name: Neuroinflammation and Glial Activation
  biological_scale: TISSUE
  conforms_to: "neuroinflammation_glial_activation#Reactive Microglial and Astrocytic Activation"
  description: >-
    Within the CNS, POWV drives reactive microglial and astrocyte activation and
    infiltration of peripheral immune cells, with a histopathological predilection
    for gray matter (thalamus, midbrain, cerebellum). Neuroinflammation can
    persist in survivors.
  cell_types:
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  - preferred_term: dorsal plus ventral thalamus
    term:
      id: UBERON:0001897
      label: dorsal plus ventral thalamus
  - preferred_term: brainstem
    term:
      id: UBERON:0002298
      label: brainstem
  biological_processes:
  - preferred_term: neuroinflammatory response
    term:
      id: GO:0150076
      label: neuroinflammatory response
  downstream:
  - target: Neuronal Death
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "demonstrated increased activation of microglia (IBA1) and astrocytes (GFAP), infiltration of peripheral immune cells (CD45), and elevated neuronal cell death (TUNEL) in POWV-infected brains"
    explanation: >-
      Documents microglial/astrocyte activation and immune infiltration in
      POWV-infected brain.
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Lymphocytic infiltration of perivascular neuronal tissue can be seen on pathology, with a predilection for gray matter, including the thalamus, midbrain, and cerebellum"
    explanation: Describes the gray-matter neuropathology.
- name: Neuronal Death
  biological_scale: TISSUE
  description: >-
    POWV-driven neuroinflammation leads to neuronal death through apoptotic and
    senescence-associated pathways, the substrate of the encephalitic syndrome
    and its long-term neurological sequelae.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  biological_processes:
  - preferred_term: neuron apoptotic process
    term:
      id: GO:0051402
      label: neuron apoptotic process
  - preferred_term: cellular senescence
    term:
      id: GO:0090398
      label: cellular senescence
  downstream:
  - target: Viral encephalitis
  - target: Meningitis
  - target: Seizure
  - target: Ataxia
  - target: Paralysis
  - target: Memory impairment
  - target: Aphasia
  - target: Cognitive impairment
  - target: Ophthalmoplegia
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Increased protein expression of caspase-3 and p16 further indicated activation of apoptotic and senescence-associated pathways."
    explanation: Supports the apoptotic and senescence pathways driving neuronal death.
phenotypes:
- name: Fever
  category: Phenotype
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
    temporality: ACUTE
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Adult patients appeared to present with typical findings of viral encephalitis, with fever, headache, fatigue, and encephalopathy being among the most common findings."
    explanation: Fever is among the most common POWV-specific presenting findings.
- name: Headache
  category: Phenotype
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Adult patients appeared to present with typical findings of viral encephalitis, with fever, headache, fatigue, and encephalopathy being among the most common findings."
    explanation: Headache is among the most common presenting findings.
- name: Viral encephalitis
  category: Phenotype
  diagnostic: true
  description: >-
    Severe viral encephalitis affecting the basal ganglia, thalamus, brainstem,
    cerebellum, and cerebral cortex is the hallmark neuroinvasive manifestation
    of Powassan virus infection.
  phenotype_term:
    preferred_term: Encephalitis
    term:
      id: HP:0033993
      label: Viral encephalitis
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "POWV is the causative agent of a severe neuroinvasive illness characterized by encephalitis, meningitis"
    explanation: Encephalitis is the defining severe manifestation.
- name: Meningitis
  category: Phenotype
  diagnostic: true
  description: >-
    Aseptic meningitis or meningoencephalitis with lymphocytic CSF pleocytosis
    and meningeal signs.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "POWV is the causative agent of a severe neuroinvasive illness characterized by encephalitis, meningitis"
    explanation: Meningitis is part of the neuroinvasive spectrum.
- name: Seizure
  category: Phenotype
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "complications can include seizures, aphasia, cranial nerve palsies, and paresis"
    explanation: Seizures are a documented complication of meningoencephalitis.
- name: Aphasia
  category: Phenotype
  phenotype_term:
    preferred_term: Aphasia
    term:
      id: HP:0002381
      label: Aphasia
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "complications can include seizures, aphasia, cranial nerve palsies, and paresis"
    explanation: Aphasia/speech disorder is a documented complication and sequela.
- name: Ataxia
  category: Phenotype
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Factors associated with persistent neurological deficits were development of ataxia"
    explanation: Ataxia is associated with persistent neurological deficits.
- name: Paralysis
  category: Phenotype
  description: >-
    Paralysis/paresis (including spastic hemiplegia) is among the most common
    acute complications and long-term sequelae.
  phenotype_term:
    preferred_term: Paralysis/paresis
    term:
      id: HP:0003470
      label: Paralysis
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases"
    explanation: Paralysis is the most frequent complication in the case series.
- name: Memory impairment
  category: Phenotype
  phenotype_term:
    preferred_term: Memory impairment
    term:
      id: HP:0002354
      label: Memory impairment
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "Long-term sequelae include cognitive deficit, spastic hemiplegia, muscle weakness, imbalance, ophthalmoplegia, and memory dysfunction"
    explanation: Memory dysfunction is a reported long-term sequela.
- name: Cognitive impairment
  category: Phenotype
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "cognitive deficits in 33.3% of adult and 25% of pediatric cases"
    explanation: Cognitive deficits occur in a third of adult cases.
- name: Ophthalmoplegia
  category: Phenotype
  phenotype_term:
    preferred_term: Ophthalmoplegia
    term:
      id: HP:0000602
      label: Ophthalmoplegia
  evidence:
  - reference: PMID:42577415
    reference_title: "Characterization of virus neuroinvasion, blood-brain barrier integrity and neuroinflammation following Powassan virus infection in mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "Long-term sequelae include cognitive deficit, spastic hemiplegia, muscle weakness, imbalance, ophthalmoplegia, and memory dysfunction"
    explanation: Ophthalmoplegia is a reported long-term sequela.
diagnosis:
- name: Diagnosis of Powassan virus disease
  diagnosis_term:
    preferred_term: Diagnostic Serology Testing
    term:
      id: NCIT:C217458
      label: Diagnostic Serology Testing
  presence: Positive
  results: Positive POWV-specific IgM immunoassay and plaque-reduction neutralizing antibodies in serum and/or CSF, or detection of POWV RNA in CSF by RT-PCR or metagenomic next-generation sequencing.
  description: >-
    Diagnosis rests on serology (POWV-specific IgM and neutralizing antibodies)
    and, within the narrow viremic window, molecular testing; CNS disease is
    confirmed with CSF examination and supportive neuroimaging. Diagnosis is
    frequently delayed because the disease is rare and testing is specialized.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The diagnosis was confirmed in all cases through testing of the serum samples or CSF for Powassan virus-neutralizing antibodies or genetic material."
    explanation: Confirmation is by serum/CSF neutralizing antibodies or viral genetic material.
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Specifically, immunoassays for Powassan virus IgM were used to identify 80 cases (95.2%)—either in serum for 61 cases (72.6%), in CSF for 38 cases (45.2%), or in both for 17 cases (20.2%)."
    explanation: Quantifies the diagnostic role of serum and CSF Powassan virus IgM immunoassays across published cases.
  - reference: PMID:42182837
    reference_title: "Delays in Diagnosis of Powassan Virus Encephalitis-Vermont, 2022-2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We describe two recent POWV encephalitis cases reported in Vermonters; both experienced diagnostic delays."
    explanation: Documents the diagnostic delay that is common for this rare disease.
- name: Lumbar Puncture and Cerebrospinal Fluid Analysis
  diagnosis_term:
    preferred_term: Lumbar Puncture
    term:
      id: NCIT:C15327
      label: Lumbar Puncture
  presence: Positive
  results: Lymphocytic pleocytosis (median WBC 119/mL in adults and 137.5/mL in children), elevated CSF protein in adults (mean 88.2 mg/dL; normal pediatric median 35.5 mg/dL), normal glucose (mean 64.9 mg/dL in adults and 65.3 mg/dL in children), and detectable POWV-neutralizing antibodies.
  description: >-
    Cerebrospinal fluid examination obtained by lumbar puncture demonstrates
    lymphocytic-predominant pleocytosis across age groups with elevated CSF
    protein in adults (whereas pediatric median CSF protein is normal) and
    provides CSF for POWV IgM, neutralizing antibody titers, and viral PCR/mNGS.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Lumbar puncture was performed in 79 (94%) of patients, with findings summarized in Table 4."
    explanation: Establishes lumbar puncture and CSF analysis as standard in the diagnostic evaluation of neuroinvasive POWV.
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The median white blood cell (WBC) count was 119/mL, predominantly lymphocytic, with a median lymphocyte count of 59.2/mL, a median monocyte count of 1.6, and a median neutrophil count of 10.9/mL. The mean glucose level was 64.9 mg/dL, and the mean protein level was 88.2 mg/dL. Opening pressures were reported in three subjects, with a median value of 180 mm H2O. Powassan virus-neutralizing antibody titers were reported in 45 cases, with a median titer of 1:320."
    explanation: Documents adult CSF lymphocytic pleocytosis, normal mean glucose, elevated mean protein (88.2 mg/dL), and neutralizing antibody titers.
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "All 14 pediatric patients underwent lumbar puncture. The median WBC count was 137.5/mL, also with a lymphocytic predominance, consisting of a median lymphocyte count of 75.5/mL, a median monocyte count of 46, and a median neutrophil count of 48.1/mL. The mean glucose level was 65.3 mg/dL and the median protein level was 35.5 mg/dL."
    explanation: Documents pediatric CSF lymphocytic pleocytosis alongside normal mean glucose and normal median CSF protein (35.5 mg/dL).
- name: Brain Magnetic Resonance Imaging
  diagnosis_term:
    preferred_term: Magnetic Resonance Imaging
    term:
      id: NCIT:C16809
      label: Magnetic Resonance Imaging
  presence: Positive
  results: Abnormalities most commonly involving the basal ganglia (32.1%), cerebral involvement (26.8%), cerebellar involvement (21.4%), thalamus (14.3%), and midbrain (8.9%), with leptomeningeal enhancement in 8.9% of adult cases.
  description: >-
    Brain MRI characterizes the distribution of encephalitic gray-matter,
    cerebral, and posterior-fossa involvement, particularly basal ganglia,
    cerebral, cerebellar, thalamic, and midbrain abnormalities.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Among the adults, the most commonly affected location was the basal ganglia, observed in 32.1% of cases. This was followed by cerebral involvement (26.8%) and cerebellar involvement (21.4%). The thalamus was affected in 14.3% of cases, while the midbrain showed involvement in 8.9% of cases. Additionally, 8.9% of cases presented with leptomeningeal enhancement on MRI while 21.4% of cases showed a normal MRI result."
    explanation: Documents the anatomical distribution and frequencies of brain MRI abnormalities in adult POWV encephalitis.
progression:
- phase: Acute phase
  notes: >-
    Acute symptoms begin roughly 1-5 weeks after the tick bite. Severe POWV
    disease is biphasic: this acute phase is followed by an encephalitic phase.
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Severe POWV infections are biphasic, with acute symptoms beginning 1–5 weeks post-tick bite, followed by encephalitis that can persist for several weeks to months"
    explanation: Describes the acute phase and the biphasic course.
- phase: Encephalitic phase
  notes: >-
    In severe disease the acute phase is followed by encephalitis that can
    persist for several weeks to months, with long-term neurological sequelae in
    about half of survivors.
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "followed by encephalitis that can persist for several weeks to months"
    explanation: The encephalitic phase follows the acute phase and is prolonged.
prevalence:
- population: United States, reported to CDC, 2004-2022
  measure_type: CASES_IN_LITERATURE
  notes: >-
    288 cases reported 2004-2022, of which 92.7% were neuroinvasive and 12.5%
    fatal; reported incidence is rising with the expanding range of vector ticks.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Between 2004 and 2022, a total of 288 cases have been reported to the CDC, of which 267 (92.7%) pertained to neuroinvasive disease, 264 (91.7%) required hospitalization, and 36 (12.5%) resulted in death."
    explanation: Gives the CDC-reported case burden and severity breakdown.
treatments:
- name: Supportive Care
  description: >-
    There is no licensed vaccine and no specific antiviral for POWV; management
    is supportive, with intensive neurological and respiratory support for
    severe neuroinvasive disease.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_mechanisms:
  - target: Neuroinflammation and Glial Activation
    treatment_effect: MODULATES
    description: Intensive neurocritical, seizure, and respiratory support manages the acute clinical consequences of CNS inflammation.
  - target: Neuronal Death
    treatment_effect: MODULATES
    description: Supportive neurocritical care and multidisciplinary physical/speech rehabilitation manage acute and persistent neurological deficits.
  evidence:
  - reference: PMID:40545598
    reference_title: "Pathogenicity and virulence of Powassan virus."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "there are currently no licenced vaccines or therapeutics for treating POWV disease"
    explanation: States the absence of specific vaccines or therapeutics.
- name: Empirical Systemic Corticosteroid Therapy
  description: >-
    Systemic corticosteroids have been administered empirically (alone or in
    combination with IVIG) in severe neuroinvasive POWV encephalitis to
    attenuate CNS neuroinflammation, with clinical improvement reported in a
    subset of adult and pediatric cases.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Systemic Corticosteroid Therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_mechanisms:
  - target: Neuroinflammation and Glial Activation
    treatment_effect: INHIBITS
    description: Empirical systemic corticosteroid anti-inflammatory therapy aims to dampen CNS glial activation and lymphocytic perivascular inflammation.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The identified treatment modalities were the administration of corticosteroids and/or IVIG. Six adult patients received only corticosteroids, four received only IVIG, while another four received both treatments. An improvement was noted in 3 of the patients receiving only corticosteroids and in 3 of the patients receiving both steroids and IVIG."
    explanation: Documents empirical systemic corticosteroid administration (monotherapy and combined with IVIG) and clinical improvement rates in adult POWV encephalitis cases.
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Among the pediatric patients, two received corticosteroids, and both improved after treatment."
    explanation: Documents empirical corticosteroid treatment and clinical improvement in two pediatric POWV encephalitis cases.
- name: Empirical Intravenous Immunoglobulin (IVIG)
  description: >-
    Pooled human intravenous immunoglobulin (IVIG) has been administered
    empirically (alone or alongside systemic corticosteroids) in adult
    neuroinvasive POWV encephalitis to modulate neuroinflammation, with clinical
    improvement observed in patients receiving combined IVIG and corticosteroids.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Intravenous Immunoglobulin Therapy
    term:
      id: NCIT:C121331
      label: Intravenous Immunoglobulin Therapy
    therapeutic_agent:
    - preferred_term: Human Immunoglobulin G
      term:
        id: NCIT:C80829
        label: Human Immunoglobulin G
  target_mechanisms:
  - target: Neuroinflammation and Glial Activation
    treatment_effect: INHIBITS
    description: Empirical polyclonal immunoglobulin immunomodulation aims to attenuate CNS immune-cell infiltration and neuroinflammation.
  evidence:
  - reference: PMID:38133440
    reference_title: "Powassan Virus Infections: A Systematic Review of Published Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The identified treatment modalities were the administration of corticosteroids and/or IVIG. Six adult patients received only corticosteroids, four received only IVIG, while another four received both treatments. An improvement was noted in 3 of the patients receiving only corticosteroids and in 3 of the patients receiving both steroids and IVIG."
    explanation: Documents empirical IVIG administration (alone in four adults and combined with corticosteroids in four adults) in published POWV encephalitis cases.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Powassan Virus Disease · 2026-11-04T02:43:06Z · View source

Created Powassan Virus Disease (MONDO:0000276), an emerging North American tick-borne orthoflavivirus. The claude_code deep-research run misfired (returned clarifying questions, not a report, with 0 citations), so evidence was sourced directly from PubMed: two 2025 comprehensive reviews (PMID:40545598 pathogenicity/virulence; PMID:40733731 innate immunity), a 2023 systematic review of 84 published cases (PMID:38133440), a 2026 mouse neuroinvasion/BBB/neuroinflammation study (PMID:42577415, MODEL_ORGANISM), and a 2026 Vermont diagnostic-delay report (PMID:42182837). Modelled causal chain: Ixodes tick-saliva inoculation and flaviviral endocytic entry -> peripheral replication/viremia -> BBB disruption and neuroinvasion -> neuroinflammation and neuronal death (microglia/astrocyte activation, caspase-3/p16, gray-matter predilection) -> encephalitis/meningitis and neurological phenotypes. All 11 phenotypes wired into the pathograph. Agent (NCBITaxon:11083), two Ixodes vectors, enzootic reservoir, Ixodes-bite transmission, diagnosis, biphasic progression, CDC 2004-2022 case burden, supportive-care treatment. MONDO label 'Powassan encephalitis' is narrower than the curated clinical entity; noted as an upstream MONDO report. Validated: just validate (schema+terms+26/26 snippets), entity-refs, causal-targets, granularity (deterministic classes clean), coarse/logical/enum/duplicate-key gates. GeneReviews NO_CHAPTER (infectious). Self red-team review (fresh-context subagent) applied before PR: rebound the BBB endothelial cell from CL:1001602 (cerebral cortex endothelial cell) to CL:2000044 (brain microvascular endothelial cell), rebound the paralysis phenotype from HP:0001269 (Hemiparesis, which asserted a laterality the general-paralysis evidence did not support) to HP:0003470 (Paralysis), and refined the neuronal apoptosis process to GO:0051402. All 26 snippets re-verified and all gates re-run green. PR #16446 review round (ai4c-reviewer, changes_requested): backfilled reference_title on every evidence item (the red CI gate); graded evidence_source from the quoted text and added quote_role (BACKGROUND on the human clinical-picture quotes taken from PMID:42577415's mouse-paper introduction, REVIEW_SYNTHESIS on the PMID:38133440 and PMID:40545598 review syntheses) instead of 21 OTHER items; replaced the class-level Fever snippet with the POWV-specific finding from PMID:38133440; bound both Ixodes vectors as hosts entries (role vector host, NCBITaxon:6945 and NCBITaxon:35565) rather than free-text CURIEs; split the biphasic progression into acute and encephalitic phases; added conforms_to on the BBB node (blood_brain_barrier_breakdown#Blood-Brain Barrier Permeability Increase) and, after debundling the composite Neuroinflammation-and-Neuronal-Death node into Neuroinflammation-and-Glial-Activation -> Neuronal-Death, on the former (neuroinflammation_glial_activation#Reactive Microglial and Astrocytic Activation). All 27 snippets re-verified; 11/11 phenotypes connected; grading, enum, entity-ref, causal-target, conformance, granularity gates green.

Claude Code ▸
**Concrete, grounded next steps I can take now:**
claude-opus-4-8, claude-opus-5-5 2026-11-04T02:34:58.020658

I'm not going to regenerate that comprehensive from-memory research narrative — the previous attempt was halted by a safety classifier, and I've been instructed not to reproduce it, reworded or otherwise. I'll respect that.

The good news is that a large, unsourced narrative synthesized from memory is also exactly what this repository's curation discipline tells us not to produce. CLAUDE.md is emphatic on this: every CURIE and every citation must be read from a source in the same step it's written, never recalled. So the better path here — both safer and more useful for a dismech entry — is to build the Powassan virus disease entry from verifiable, tool-fetched sources rather than a prose dump.

Here's how I'd propose to proceed on Powassan Virus Disease (MONDO:0000276), which is an infectious-disease entry (no causal gene — the agent is Powassan virus, a tick-borne Flavivirus):

Concrete, grounded next steps I can take now:

  1. Check existing state — whether a stub or entry already exists:
  2. kb/disorders/ for any Powassan entry, and stubs/ for a claim.
  3. Fetch and cache real references so snippets are exact-quote verifiable:
  4. just fetch-reference PMID:<id> for key clinical/epidemiology reviews.
  5. just fetch-reference ORPHA:<code> if Orphanet covers it.
  6. Validate the organism and transmission structure per the infectious-disease granularity ladder (§3e) — at minimum one NCBITaxon-bound infectious_agent and one transmission route, plus agent_life_cycle with the tick vector and reservoir hosts.
  7. Bind terms by lookup, not memory — HP phenotype terms (encephalitis, meningoencephalitis features), UBERON/CL for CNS involvement, NCIT for supportive-care treatments — each resolved via OAK/cache in the step it's written.

Two things I want to confirm before I start:

  • Do you want me to actually create/curate the entry (claim it, fetch references, build the YAML, validate), or did you only want the research write-up? If it's the entry, I'll follow the /curate workflow.
  • Is there a specific deep-research provider report already in research/ for this disease I should be screening as a lead, rather than generating fresh?

Tell me which, and I'll begin with the real tool calls. If instead you genuinely just need a plain clinical reference summary of Powassan virus disease for non-curation purposes, let me know and I can give a brief, source-grounded overview — but I won't re-emit the full templated mechanism/transmission report that was stopped.

Reference Validation

No PMID or DOI references were found in this report.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 1
Resolved 1
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0

Every term resolved, and every label the report gave matched.